**Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling**

Makoto Hashimoto, Yuta Murai, Geoffery D. Holman and Yasumaru Hatanaka

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/48730

### **1. Introduction**

120 Hydrogenation

Tetrahedron Letters. 44: 8501-8503.

Activity. Tetrahedron. 61: 2217-2231.

Molecular Catalysis A: Chemical. 273: 102-108.

Chemical. 173: 185-221.

Letters. 45: 3215-3217.

Chemical. 324: 9-14.

284: 165-175.

Organometallics. 26: 4357-4360.

Synthesis of Paroxetine. J. Am. Chem. Soc. 129: 290-291.

Formate. Tetrahedron Letters. vol.35. no.46: 8549-8650.

Complexes. Coordination Chemistry Reviews. 248: 2201-2237.

[43] Solladié-Cavallo A, Roje M, Baram A, Šunjić E (2003) Partial Hydrogenation of Substituted Pyridines and Quinolines: A Crucial Role of the Reaction Conditions.

[44] Ito M, Sakaguchi A, Kobayashi Ch, Ikariya T (2007) Chemoselective Hydrogenation of Imides Catalyzed by Cp\*Ru(PN) Complexes and Its Application to the Asymmetric

[45] Molnár Á, Sárkány A, Varga M (2001) Hydrogenation of Carbon–Carbon Multiple Bonds: Chemo-, Regio- and Stereo-Selectivity. Journal of Molecular Catalysis A:

[46] Ranu B C, Sarkar A (1994) Regio- and Stereoselectlve Hydrogenation of Conjugated Carbonyl Compounds via Palladium Assisted Hydrogen Transfer by Ammonium

[47] Ikawa T, Sajiki H, Hirota K (2005) Highly Chemoselective Hydrogenation Method Using Novel Finely Dispersed Palladium Catalyst on Silk-Fibroin: Its Preparation and

[48] Sahoo S, Kumar Pr, Lefebvre F, Halligudi S B (2007) Immobilized Chiral Diamino Ru Complex as Catalyst for Chemo- and Enantioselective Hydrogenation. Journal of

[49] Fujita K, Kitachuji Ch, Furukawa Sh, Yamaguchi R (2004) Regio- and Chemoselective Transfer Hydrogenation of Quinolines Catalyzed by a Cp\*Ir Complex. Tetrahedron

[50] Clapham S E, Hadzovic A, Morris R H (2004) Mechanisms of the H2-Hydrogenation and Transfer Hydrogenation of Polar Bonds Catalyzed by Ruthenium Hydride

[51] Chaplin A B, Dyson P J (2007) Catalytic Activity of Bis-phosphine Ruthenium(II)-Arene Compounds: Chemoselective Hydrogenation and Mechanistic Insights.

[52] Verdolino V, Forbes A, Helquist P, Norby P-O, Wiest O (2010) On the Mechanism of the Rhodium Catalyzed Acrylamide Hydrogenation. Journal of Molecular Catalysis A:

[53] Haddad N, Qu B, Rodriguez S, van den Veen L, Reeves D C, Gonnella N C, Lee H, Grinberg N, Ma Sh, Krishnamurthy Dh, Wunberg T (2011) Catalytic Asymmetric Hydrogenation of Heterocyclic Ketone-Derived Hydrazones, Pronounced Solvent Effect

[54] Bridier B, Pérez-Ramírez J (2011) Selectivity Patterns in Heterogeneously Catalyzed Hydrogenation of Conjugated Ene-yne and Diene Compounds. Journal of Catalysis.

[55] Balázsik K, Szőri K, Szőllősi G, Bartók M (2011) New Phenomenon in Competitive Hydrogenation of Binary Mixtures of Activated Ketones Over Unmodified and Cinchonidine-Modified Pt/alumina Catalyst. Catalysis Communications. 12: 1410-1414.

on the Inversion of Configuration. Tetrahedron Letters. 52: 3718-3722.

### **1.1. Photoaffinity labeling**

Elucidation of protein functions on the basis of structure–activity relationships can reveal the mechanisms of homeostasis functions in life and is one of the greatest interests of scientists. In the human body, many proteins are activated and/or inactivated by ligands to maintain homeostasis. Understanding the mechanism of molecular interactions between small bioactive ligands and proteins is an important step in rational drug design and discovery.

Photoaffinity labeling, which is one of the most familiar approaches for chemical biology analysis, was initiated using diazocarbonyl derivatives in 1962 (Singh et al., 1962). Many researchers have subsequently tried to establish alternative approaches for the direct identification of target proteins for the bioactive small ligands. These approaches are based on the affinity between the ligand and the target protein *(Figure 1)*. Several reviews are published for the recent applications of photoaffinity labeling (Tomohiro et al., 2005; Hashimoto & Hatanaka, 2008).

To archive photoaffinity labeling, researchers have to prepare photoaffinity labeling ligands. The native ligands must be modified by photoreactive compounds (photophores) by organic synthesis.

© 2012 Hashimoto et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Hashimoto et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 123

**O C**

**F3C**

**C**

phenyldiazirine

**N**

**N**

**F3C**

**Figure 2.** Photophores and their reactive intermediates following irradiation

**N**

**N3**

(precursor)

Reactive intermediate

**<sup>O</sup>** Photophore

*1.2.2. Synthesis of trifluoromethylphenyldiazirine (TPD)* 

al., 2006 & 2007).

photoaffinity labeling.

Comparative irradiation studies of these three photophore types in living cells suggested that the irradiation needed for the generation of active species from azide and benzophenone caused cell death because long irradiation times are needed to incorporate the photophores into cell membrane surface biomolecules. By contrast, a carbene precursor – trifluoromethylphenyldiazirine (TPD) – did not cause cell death in the generation of active species (Hashimoto et al., 2001). Never-the-less, benzophenones (such as those attached to secretase) are sometimes preferred for photoaffinity labeling experiments in vitro (Fuwa et

**C**

nitrene biradical **carbene**

<280 nm ~350 nm 360 nm

**C**

arylazide benzophenone triflioromethyl

There are more several steps involved in the the constructions of the TPD skeleton than are needed for synthesis of other photophores. Synthesis of the TPD three-membered ring

Although TPD is commercially available many are very expensive (1200 USD/0.5g for the simple TPD). In many previous synthetic routes the functional groups, which can be connected to ligands, tags and isotopes, should be pre-installed onto the benzene ring before constructions of three membered rings. The repeated construction of a diazirine moiety for each derivative is a drawback for application of the photophore for

required at least five steps from the corresponding aryl halide derivatives (Figure 3).

**Figure 1.** Schematic representation of photoaffinity labeling

### **1.2. Photophore synthesis and their properties**

### *1.2.1. Selections of photophores*

It is important which photophores are used for effective photoaffinity labeling (Figure 2). Typically, aryl azide, benzophenone, or trifluoromethylphenyldiazirine (TPD) have been used.

Aryl azides are photoactivated below a wavelength of 300 nm, which sometimes causes damage to biomolecules. In addition, these generate nitrenes (Platz, 1995) as active species and these sometimes rearrange to ketimines as undesired side products (Karney & Borden, 1997).

Benzophenones are photoreactivated with light over 350 nm and generate reactive triplet carbonyl states (Galardy et al., 1973). These regenerate ground-state carbonyl compounds and so benzophenone ligands are reusable for other photolabeling experiments, although the photophores sometimes need long photoirradiation times for labeling.

TPD, with a three membered ring and nitrogen-nitrogen double bond, are also photoreactivated with light over 350 nm. These generate carbenes, which are more highly reactive species than other photophores, and rapidly form cross-links to biomolecules with short photoirradiation times (Smith & Knowles, 1973). It has been reported that the photolysis of diazirines can cause diazo isomerization, giving undesired intermediates in photoaffinity labeling. Diazo isomerization can be suppressed by introduction of a trifluoromethyl group into a diazirinyl three-membered ring (Brunner et al., 1980; Nassal, 1983).

**Figure 2.** Photophores and their reactive intermediates following irradiation

**Figure 1.** Schematic representation of photoaffinity labeling

*Identify ligand binding site and amino acid residue*

*photophore*

*ligand*

amino acid

+

*biomolecules*

**1.2. Photophore synthesis and their properties** 

It is important which photophores are used for effective photoaffinity labeling (Figure 2). Typically, aryl azide, benzophenone, or trifluoromethylphenyldiazirine (TPD) have been

*h*

*crosslinking*

*Identify ligand utilized biomolecule(s)*

Aryl azides are photoactivated below a wavelength of 300 nm, which sometimes causes damage to biomolecules. In addition, these generate nitrenes (Platz, 1995) as active species and these sometimes rearrange to ketimines as undesired side products (Karney & Borden,

Benzophenones are photoreactivated with light over 350 nm and generate reactive triplet carbonyl states (Galardy et al., 1973). These regenerate ground-state carbonyl compounds and so benzophenone ligands are reusable for other photolabeling experiments, although

TPD, with a three membered ring and nitrogen-nitrogen double bond, are also photoreactivated with light over 350 nm. These generate carbenes, which are more highly reactive species than other photophores, and rapidly form cross-links to biomolecules with short photoirradiation times (Smith & Knowles, 1973). It has been reported that the photolysis of diazirines can cause diazo isomerization, giving undesired intermediates in photoaffinity labeling. Diazo isomerization can be suppressed by introduction of a trifluoromethyl group into a diazirinyl three-membered ring (Brunner et al., 1980; Nassal,

the photophores sometimes need long photoirradiation times for labeling.

*1.2.1. Selections of photophores* 

used.

1997).

1983).

Comparative irradiation studies of these three photophore types in living cells suggested that the irradiation needed for the generation of active species from azide and benzophenone caused cell death because long irradiation times are needed to incorporate the photophores into cell membrane surface biomolecules. By contrast, a carbene precursor – trifluoromethylphenyldiazirine (TPD) – did not cause cell death in the generation of active species (Hashimoto et al., 2001). Never-the-less, benzophenones (such as those attached to secretase) are sometimes preferred for photoaffinity labeling experiments in vitro (Fuwa et al., 2006 & 2007).

### *1.2.2. Synthesis of trifluoromethylphenyldiazirine (TPD)*

There are more several steps involved in the the constructions of the TPD skeleton than are needed for synthesis of other photophores. Synthesis of the TPD three-membered ring required at least five steps from the corresponding aryl halide derivatives (Figure 3).

Although TPD is commercially available many are very expensive (1200 USD/0.5g for the simple TPD). In many previous synthetic routes the functional groups, which can be connected to ligands, tags and isotopes, should be pre-installed onto the benzene ring before constructions of three membered rings. The repeated construction of a diazirine moiety for each derivative is a drawback for application of the photophore for photoaffinity labeling.

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 125

considerations directed our synthesis strategies towards derivatizations on the benzene ring after constructions of the trifluoromethyl diazirinyl ring (post-functional derivatizations). During the course of the studies, applications of hydrogenations to the TPD derivatives for post-functional synthesis are very important in associated derivatizations. However, the diazirinyl group consists of a nitrogen-nitrogen double bond in the structure and could be easily hydrogenated under the certain conditions. In this chapter, we would like to present a comprehensive summary for the hydrogenations that are compatible with or incompatible with the reaction conditions used for the trifluoromethylphenyl diazirinyl derivative. These

considerations lead to effective post-functional derivatization approaches.

hydrogenations of carbon-iodine bond in iodoarene are chemoselective.

F3C

H

**functional synthesis of TPD derivatives** 

condition at atmospheric pressure (Fig.5).

H2 - Pd/C TEA

CH3OH < 50 min

**1 2**

N

OH

N

**Pd/C** 

F3C

I

**2. Selective hydrogenation methods over diazirinyl moiety for post-**

**2.1. Selective hydrogenation of carbon-iodine bond to carbon-hydrogen bond with H2-**

It has been reported that hydrogenation of diazirinyl compounds under H2-Pd/C at atmospheric pressure caused diazirinyl moiety reduction to diaziridine and further reduction of diaziridine moiety over a long time of treatment. Ambroise et al. found that

This occurs selectively over other easily reducible functional groups using Pd/C (10 mol%) under a hydrogen atmosphere, in the presence of triethylamine and within an hour (Ambroise et al., 2000). The selective hydrogenations can be applied for TPD derivatives. The iodoarene TPD derivative (**1**) was subjected to hydrogenation under the H2-Pd/C

N

H2 - Pd/C

complex mixtures due to reduction of diazirine

additional 60 min

OH

N

**Figure 5.** Selective hydrogenation of iodoarene TPD derivatives (**1**). Selectivity for carbon- iodine bond

Detailed analysis revealed that the hydrogenation of carbon-iodine bond proceeded in parallel to the consumption of the starting material for 50 min. The hydrodeiodinated product (**2**) was subjected to further hydrogenolysis at the diazirinyl nitrogen-nitrogen double and compound **2** was completely consumed within an additional hour of hydrogenation. The chemoselective hydrogenation was applied to the synthesis of radiolabeled tritium TPD compounds from the corresponding iodoarene derivatives

to carbon-hydrogen bonds (**2**) occurs on Pd/C under a hydrogen atmosphere

**Figure 3.** Synthesis of trifluoromethylphenyldiazirine derivatives

### *1.2.3. Post-functional synthesis of TPD derivatives*

Our breakthrough work on "post-functional" adaptation of diazirinyl compounds (Hatanaka et al., 1994, a & b) revealed that the trifluoromethyl-substituted three-membered ring was stable under many organic reaction conditions. Although the 3- (trifluoromethyl)diazirinyl moiety is categorized as an alkyl substituent, polarization means that the quaternary carbon atom is slightly positively charged, so the moiety is less activated towards electrophilic aromatic substitution than its unsubstituted counterpart (Hashimoto et al., 2006). We first selected the m-methoxy- substituted TPD (Fig. 4 R = OCH3) as the mother skeleton, because: 1) the methoxy group strongly activates for electrophilic aromatic substitution, 2) the orientation of the substitution favors the o-position against the methoxy group, because the p-position is sterically hindered by the 3-(trifluoromethyl)diazirinyl moiety, and 3) demethylation of *m*-methoxy-TPD was easier than for *p*-methoxy-TPD, and realkylation of phenol derivative after demethylation was utilized for introduction of the tag.

**Figure 4.** Post-functional synthesis of trifluoromethylphenyldiazirine derivatives

It is somewhat difficult to derivatize unsubstituted TPD (Fig. 4, R=H) as this is less susceptible to aromatic substitution than *m*-methoxy TPD. It would need harsh conditions for the substitutions on aromatic ring. For example, the formylation with dichloromethyl methyl ether was performed using titanium chloride in dichloromethane for the 3-methoxy diazirine at 0 °C while the unsubstituted TPD did not afford formyl derivatives under the same condition. It is only archived when the trifluoromethanesulfonic acid, which is stronger acid than titanium chloride, was used as promoter for the reaction. These considerations directed our synthesis strategies towards derivatizations on the benzene ring after constructions of the trifluoromethyl diazirinyl ring (post-functional derivatizations). During the course of the studies, applications of hydrogenations to the TPD derivatives for post-functional synthesis are very important in associated derivatizations. However, the diazirinyl group consists of a nitrogen-nitrogen double bond in the structure and could be easily hydrogenated under the certain conditions. In this chapter, we would like to present a comprehensive summary for the hydrogenations that are compatible with or incompatible with the reaction conditions used for the trifluoromethylphenyl diazirinyl derivative. These considerations lead to effective post-functional derivatization approaches.

124 Hydrogenation

R

tag.

F3C

**R1**

C

N

R

N

**Figure 3.** Synthesis of trifluoromethylphenyldiazirine derivatives

**Figure 4.** Post-functional synthesis of trifluoromethylphenyldiazirine derivatives

Photophore

Electrophiles introducible

It is somewhat difficult to derivatize unsubstituted TPD (Fig. 4, R=H) as this is less susceptible to aromatic substitution than *m*-methoxy TPD. It would need harsh conditions for the substitutions on aromatic ring. For example, the formylation with dichloromethyl methyl ether was performed using titanium chloride in dichloromethane for the 3-methoxy diazirine at 0 °C while the unsubstituted TPD did not afford formyl derivatives under the same condition. It is only archived when the trifluoromethanesulfonic acid, which is stronger acid than titanium chloride, was used as promoter for the reaction. These

**<sup>C</sup> F3C**

*Preparable in large scale*

**N**

R = OCH3 or H

**R**

**N**

Our breakthrough work on "post-functional" adaptation of diazirinyl compounds (Hatanaka et al., 1994, a & b) revealed that the trifluoromethyl-substituted three-membered ring was stable under many organic reaction conditions. Although the 3- (trifluoromethyl)diazirinyl moiety is categorized as an alkyl substituent, polarization means that the quaternary carbon atom is slightly positively charged, so the moiety is less activated towards electrophilic aromatic substitution than its unsubstituted counterpart (Hashimoto et al., 2006). We first selected the m-methoxy- substituted TPD (Fig. 4 R = OCH3) as the mother skeleton, because: 1) the methoxy group strongly activates for electrophilic aromatic substitution, 2) the orientation of the substitution favors the o-position against the methoxy group, because the p-position is sterically hindered by the 3-(trifluoromethyl)diazirinyl moiety, and 3) demethylation of *m*-methoxy-TPD was easier than for *p*-methoxy-TPD, and realkylation of phenol derivative after demethylation was utilized for introduction of the

**Br <sup>C</sup> F3C**

1) Mg, then F3CC(O)N

2) NH2OH HCl

3) TsCl, Et3N 4) NH3 (gas)

5) MnO2 (activated)

**N**

C

N

R

N

F3C

**R2**

R

**N**

*1.2.3. Post-functional synthesis of TPD derivatives* 

**derivatization**

### **2. Selective hydrogenation methods over diazirinyl moiety for postfunctional synthesis of TPD derivatives**

#### **2.1. Selective hydrogenation of carbon-iodine bond to carbon-hydrogen bond with H2- Pd/C**

It has been reported that hydrogenation of diazirinyl compounds under H2-Pd/C at atmospheric pressure caused diazirinyl moiety reduction to diaziridine and further reduction of diaziridine moiety over a long time of treatment. Ambroise et al. found that hydrogenations of carbon-iodine bond in iodoarene are chemoselective.

This occurs selectively over other easily reducible functional groups using Pd/C (10 mol%) under a hydrogen atmosphere, in the presence of triethylamine and within an hour (Ambroise et al., 2000). The selective hydrogenations can be applied for TPD derivatives. The iodoarene TPD derivative (**1**) was subjected to hydrogenation under the H2-Pd/C condition at atmospheric pressure (Fig.5).

**Figure 5.** Selective hydrogenation of iodoarene TPD derivatives (**1**). Selectivity for carbon- iodine bond to carbon-hydrogen bonds (**2**) occurs on Pd/C under a hydrogen atmosphere

Detailed analysis revealed that the hydrogenation of carbon-iodine bond proceeded in parallel to the consumption of the starting material for 50 min. The hydrodeiodinated product (**2**) was subjected to further hydrogenolysis at the diazirinyl nitrogen-nitrogen double and compound **2** was completely consumed within an additional hour of hydrogenation. The chemoselective hydrogenation was applied to the synthesis of radiolabeled tritium TPD compounds from the corresponding iodoarene derivatives

(Ambroise et al., 2001) (Fig. 6). The synthesis of compounds with isotope incorporation has also been studied with other photophores including phenylazides and benzophenones (Faucher et al., 2002).

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 127

**2.2. Selective hydrogenation of carbon-nitrogen double bonds (imines, Schiff's** 

Imine (Schiff's base) TPD derivatives have been readily prepared from aldehyde (**9**) and primary amine (**10**). Catalytic hydrogenations of imines with H2-Pd/C were potentially available to afford amines, but side reactions at the nitrogen-nitrogen double bond on TPD derivatives prevented use of these catalytic hydrogenations. Hydride reductions for imines are acceptable for TPD derivatives and sodium cyanoborohydride has been used for the

F3C

O2N O

N

H

<sup>N</sup> <sup>O</sup> <sup>O</sup> <sup>N</sup>

H

complex mixtures

biotin

N

Although this type of reaction is distinct from hydrogenation, we would like to briefly summarize reductions with hydride for use in TPD derivatization. NaBH4 or LiAlH4, which were most common hydride sources, were compatible for TPD derivative chemistry that involved reduction of carbonyl groups. However those reduction reagents that incorporated a cofactor (ie CoCl2, NiCl2 etc) promoted destruction of the diazirinyl ring (Hashimoto,

Hydrazones derivatives of TPD (**13**) have been prepared with moderate yield from the corresponding TPD acetophenone (**12**) using hydrazine hydrate (1.5 eq). In early stages the acetophenone moieties were more reactive for the nucleophilic substitution with hydrazine

N

OCH3

reduction of C=N bond

N

hydrate than the reaction involving reduction of the diazirinyl group to diaziridines.

F3C

**Figure 9.** Selective TPD hydrazone formation (**13**) from acetophenone derivative (**12**)

H2NN

reductive amination leading to (**11**) (Fig. 8) (Daghish et al., 2002).

NaCNBH3

**10**

CH3OH rt, 32h

H2N <sup>O</sup> <sup>O</sup> <sup>N</sup>

**Figure 8.** Reductive amination of TPD derivative (**9**) with biotin derivative (**10**)

**9 11 (**60%)

H

biotin

Many other hydride sources were compatible with TPD derivatizations.

NH2NH2 - H2O

CH3OH rt, 12h

**12 13** (63%)

**bases, reductive amination)** 

unpublished results).

N

OCH3

N

F3C

O

F3C

O2N O

N

O

H

N

**Figure 6.** Selective tritiations of iodoarene TPD derivatives (**1, 3** and **4**) for carbon-iodine bond to carbon-tritium bond on Pd/C under tritium atmosphere. Parentheses are isolated yields.

Sammelson et al. performed selective hydrogenation for iodoarene derivative (**7**) over the chloroarene and trifluoromethyldiazirinyl group in the synthesis of photoreactive fipronil (**8**) using Pd/C under a H2 or 3H2 atmosphere. The resulting compound was a high-affinity probe for GABA receptor (Sammelson and Casida, 2003) (Fig. 7).

**Figure 7.** Selective hydrogenation or tritiations of carbon-iodine bond over carbon-chlorine bond and trifluoromethyldiazirinyl group of **7** with Pd/C under hydrogen or tritium atmosphere.

### **2.2. Selective hydrogenation of carbon-nitrogen double bonds (imines, Schiff's bases, reductive amination)**

126 Hydrogenation

(Faucher et al., 2002).

F3C

I

N

R

**1** R = CH2OH **3** R = COOH **4** R = CH2NH2

N

(Ambroise et al., 2001) (Fig. 6). The synthesis of compounds with isotope incorporation has also been studied with other photophores including phenylazides and benzophenones

F3C

3H

**[**

**[**

**[**

N

**3H]-2** R = CH2OH (68%)

**3H]-5** R = COOH (64%)

**3H]-6** R = CH2NH2 (65%)

N

N

<sup>N</sup> <sup>R</sup>

N

Cl

**[**

F3C

CF3

**3H]-8** R = 3H

R

Cl

R

N

**Figure 6.** Selective tritiations of iodoarene TPD derivatives (**1, 3** and **4**) for carbon-iodine bond to

Sammelson et al. performed selective hydrogenation for iodoarene derivative (**7**) over the chloroarene and trifluoromethyldiazirinyl group in the synthesis of photoreactive fipronil (**8**) using Pd/C under a H2 or 3H2 atmosphere. The resulting compound was a high-affinity

> 3H2 - Pd/C TEA

> > EtOAc 1 h

**7 8** R = H (45%)

**Figure 7.** Selective hydrogenation or tritiations of carbon-iodine bond over carbon-chlorine bond and

trifluoromethyldiazirinyl group of **7** with Pd/C under hydrogen or tritium atmosphere.

carbon-tritium bond on Pd/C under tritium atmosphere. Parentheses are isolated yields.

3H2 - Pd/C TEA

> EtOAc 1 h

probe for GABA receptor (Sammelson and Casida, 2003) (Fig. 7).

I

Cl

N

N

N

<sup>N</sup> <sup>I</sup>

Cl

F3C

CF3

Imine (Schiff's base) TPD derivatives have been readily prepared from aldehyde (**9**) and primary amine (**10**). Catalytic hydrogenations of imines with H2-Pd/C were potentially available to afford amines, but side reactions at the nitrogen-nitrogen double bond on TPD derivatives prevented use of these catalytic hydrogenations. Hydride reductions for imines are acceptable for TPD derivatives and sodium cyanoborohydride has been used for the reductive amination leading to (**11**) (Fig. 8) (Daghish et al., 2002).

**Figure 8.** Reductive amination of TPD derivative (**9**) with biotin derivative (**10**)

Although this type of reaction is distinct from hydrogenation, we would like to briefly summarize reductions with hydride for use in TPD derivatization. NaBH4 or LiAlH4, which were most common hydride sources, were compatible for TPD derivative chemistry that involved reduction of carbonyl groups. However those reduction reagents that incorporated a cofactor (ie CoCl2, NiCl2 etc) promoted destruction of the diazirinyl ring (Hashimoto, unpublished results).

Many other hydride sources were compatible with TPD derivatizations.

Hydrazones derivatives of TPD (**13**) have been prepared with moderate yield from the corresponding TPD acetophenone (**12**) using hydrazine hydrate (1.5 eq). In early stages the acetophenone moieties were more reactive for the nucleophilic substitution with hydrazine hydrate than the reaction involving reduction of the diazirinyl group to diaziridines.

**Figure 9.** Selective TPD hydrazone formation (**13**) from acetophenone derivative (**12**)

The selective reduction of the carbon-nitrogen double bond in hydrazone to form carbonnitrogen single bond was not archived under various conditions (alcoholic KOH with reflux, t-BuOK-DMSO at room temperature, or t-BuOK-toluene with reflux). Instead the side reaction involving loss of the diazirinyl group occurred (Hashimoto, unpublished results). (Fig. 9)

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 129

CHO

N

OCH3

N

0 °C, 1h **<sup>17</sup>** (73%)

N

OCH3

N

conversions from benzyl carbonyl to methylene are very smooth and afforded the product (**18**) in very high yield without breaking the diazirinyl ring. (Fig. 12) (Hashimoto et al. 2003

F3C

F3C

**12 18** (96%)

**Figure 11.** Synthesis of benzaldehyde TPD derivative (**17**) with Friedel-Crafts alkylation, followed by

Cl2CHOCH3

TiCl4

**Figure 12.** Transfer hydrogenation of TPD acetophenone derivative (**12**) with triethylsilane and

(C2H5)3SiH CF3COOH

rt, 1h

A sequence of reactions involving Friedel-Crafts acylation followed by reduction of the benzyl carbonyl to methylene enables us to stereocontrol synthesis of trifluoromethyldiazirinyl homo- and bishomo- phenylalanine derivatives. Synthesis of homo-phenylalanine has been reported using various methodologies including enzymatic methods (Zhao et al., 2002), Suzuki-coupling (Barfoot, et al., 2005), diastereoselective Michel addition (Yamada et al., 1998) and catalytic asymmetric hydrogenation (Xie, et al., 2000). These methods require the preparation of special reagents or precursors for the asymmetric synthesis of both enantiomers, especially aromatic compounds. Therefore one has to spend time and effort on establishment of TPD derivatizations without

Amino acids are one of the most popular precursors and easily available compounds for stereo controlled synthesis using the asymmetric center. Friedel-Crafts reactions between

& 2004)

F3C

hydrolysis from m-methoxy TPD (**14**)

N

OCH3

N

**14**

N

OCH3

N

trifluoroacetic acid

O

F3C

decomposition of diazirine.

### **2.3. Selective hydrogenation of carbon-oxygen double bonds (carbonyl and carboxyl) for the TPD derivatives.**

Many methods for the reduction of carbon-oxygen double bonds have been reported. The carbonyl groups, which can be introduced by Friedel-Crafts acylation, are one of the most important synthetic methods for the post-functional synthesis. Friedel-Crafts reactions of TPD derivatives are not attainable because the trifluoromethyldiazirinyl moiety has slight electron withdrawing properties (due to polarity of the quaternary carbon, which is connected directly to benzene ring). Furthermore the diazirinyl moiety was not stable over 25 °C in the presence of Lewis acids, which are the conditions generally used for catalysis in Friedel-Crafts reaction (Moss et al., 2001). TPD derivatives (**14** and **15**) can react at room temperature with the reactive acyl donor acetyl chloride when using aluminum chloride to introduce acetyl moiety (**12** and **16**) (Hashimoto et al., 2003, 2004) (Fig. 10) .

**Figure 10.** Friedel-Crafts acetylation of TPD derivatives (**14** and **15**) with acetyl chloride and aluminum chloride.

On the other hand incorporation of less active acyl donors such as dichloromethyl methyl ether has to use stronger the Lewis acid, TiCl4. These conditions allow reaction with compound **14** to proceed (Hashimoto et al. 1997). Dichloromethane was used as solvent in early synthesis of this type but dichloromethyl methyl ether can also be used as solvent. This has enabled improvement in the yield of compound **17**. (Fig. 11)

Hydrogenation of the Friedel-Crafts acylated products has been studied. Clemmensen reduction, Wolff-Kishner reduction and catalytic hydrogenation with Pd/C cannot be applied to synthesis of TPD derivative as these conditions lead to breakage of the diazirinyl moiety.

During the course of these trial screening reactions, it was found that transfer hydrogenation with triethylsilane in trifluoroacetic acid could be applied to TPD derivatives (**12**). The conversions from benzyl carbonyl to methylene are very smooth and afforded the product (**18**) in very high yield without breaking the diazirinyl ring. (Fig. 12) (Hashimoto et al. 2003 & 2004)

128 Hydrogenation

(Fig. 9)

chloride.

F3C

N

rt, 2h **<sup>14</sup>** R = CH3

OR

**15** R = (CH2)10CO2H

N

moiety.

**carboxyl) for the TPD derivatives.** 

The selective reduction of the carbon-nitrogen double bond in hydrazone to form carbonnitrogen single bond was not archived under various conditions (alcoholic KOH with reflux, t-BuOK-DMSO at room temperature, or t-BuOK-toluene with reflux). Instead the side reaction involving loss of the diazirinyl group occurred (Hashimoto, unpublished results).

**2.3. Selective hydrogenation of carbon-oxygen double bonds (carbonyl and** 

introduce acetyl moiety (**12** and **16**) (Hashimoto et al., 2003, 2004) (Fig. 10) .

F3C

has enabled improvement in the yield of compound **17**. (Fig. 11)

CH3COCl

CHCl3

Many methods for the reduction of carbon-oxygen double bonds have been reported. The carbonyl groups, which can be introduced by Friedel-Crafts acylation, are one of the most important synthetic methods for the post-functional synthesis. Friedel-Crafts reactions of TPD derivatives are not attainable because the trifluoromethyldiazirinyl moiety has slight electron withdrawing properties (due to polarity of the quaternary carbon, which is connected directly to benzene ring). Furthermore the diazirinyl moiety was not stable over 25 °C in the presence of Lewis acids, which are the conditions generally used for catalysis in Friedel-Crafts reaction (Moss et al., 2001). TPD derivatives (**14** and **15**) can react at room temperature with the reactive acyl donor acetyl chloride when using aluminum chloride to

**Figure 10.** Friedel-Crafts acetylation of TPD derivatives (**14** and **15**) with acetyl chloride and aluminum

O

N

OR

**12** R = CH3 (93%)

**16** R = (CH2)10CO2H (73%)

N

On the other hand incorporation of less active acyl donors such as dichloromethyl methyl ether has to use stronger the Lewis acid, TiCl4. These conditions allow reaction with compound **14** to proceed (Hashimoto et al. 1997). Dichloromethane was used as solvent in early synthesis of this type but dichloromethyl methyl ether can also be used as solvent. This

Hydrogenation of the Friedel-Crafts acylated products has been studied. Clemmensen reduction, Wolff-Kishner reduction and catalytic hydrogenation with Pd/C cannot be applied to synthesis of TPD derivative as these conditions lead to breakage of the diazirinyl

During the course of these trial screening reactions, it was found that transfer hydrogenation with triethylsilane in trifluoroacetic acid could be applied to TPD derivatives (**12**). The

**Figure 11.** Synthesis of benzaldehyde TPD derivative (**17**) with Friedel-Crafts alkylation, followed by hydrolysis from m-methoxy TPD (**14**)

**Figure 12.** Transfer hydrogenation of TPD acetophenone derivative (**12**) with triethylsilane and trifluoroacetic acid

A sequence of reactions involving Friedel-Crafts acylation followed by reduction of the benzyl carbonyl to methylene enables us to stereocontrol synthesis of trifluoromethyldiazirinyl homo- and bishomo- phenylalanine derivatives. Synthesis of homo-phenylalanine has been reported using various methodologies including enzymatic methods (Zhao et al., 2002), Suzuki-coupling (Barfoot, et al., 2005), diastereoselective Michel addition (Yamada et al., 1998) and catalytic asymmetric hydrogenation (Xie, et al., 2000). These methods require the preparation of special reagents or precursors for the asymmetric synthesis of both enantiomers, especially aromatic compounds. Therefore one has to spend time and effort on establishment of TPD derivatizations without decomposition of diazirine.

Amino acids are one of the most popular precursors and easily available compounds for stereo controlled synthesis using the asymmetric center. Friedel-Crafts reactions between aromatics and a side chain of aspartic acid (Asp) or glutamic acid (Glu) are some of the key reactions for asymmetric synthesis for both homo- or bishomo- phenylalanine enantiomers' skeletons. (Reifenrath, et al. 1976; Nordlander et al., 1985; Melillo et al., 1987; Griesbeck & Heckroth, 1997; Xu et al., 2000; Lin et al., 2001)

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 131

F3C

D

13C]-**<sup>12</sup>** [1-13C-1,1-D2]-**<sup>18</sup>**

F3C

D

13C

D

D

N

N

CD3

[1,1,2,2,2-D5]-**18**

OCH3

N

OCH3

N

*2.3.1. Selective hydrogenation of carbon-oxygen double bonds with stable isotope labeling* 

**Figure 14.** Synthesis of stable isotope labeled TPD derivatives with transfer hydrogenation

CD3 O

[2,2,2-D3]-**12**

incorporated photoreactive fatty acid derivatives. (Murai et al. 2010)

The -position of the carbonyl groups was susceptible to very fast hydrogen-deuterium exchange using sodium hydroxide (NaOH) and methanol-OD (CH3OD) at room temperature. There are no serious decrements of deuterium incorporation with various work up to synthesis [2,2,2-D3]-**12**. After that, ionic hydrogenation with Et3SiD and trifluoroacetic acid afforded 5 deuterium incorporated TPD derivatives ([1,1,2,2,2-D5]-**18**). (Fig. 14). These synthetic methodologies have also been applied to synthesis of deuterium

OCH3

2004)

F3C

F3C

O

N

N

OCH3 **12**

N

CH3

**14** rt, 2h OCH3

13COCl

F3C

F3C

13C O

N

[

N

N

OCH3

(C2H5)3SiD CF3COOH

rt, 1h

(C2H5)3SiD CF3COOH

rt, 1h

N

CH2Cl2

NaOH CH3OD

rt, 10min

N

Established methods for the post-functional synthesis (described in the previous section) have facilitated the preparation of stable isotope labeled TPD. Stable isotopes act as a tag for the exogenous ligand derivatives on mass spectrometry. The methodologies will be very useful for the field of photoaffinity labeling to detect the labeled components. Friedel-Crafts acylation with 1-13C acetyl chloride, which is a relatively inexpensive reagent compared with other 13C labeled compounds, afforded 13C labeled acetophenone derivative ([13C]-**12**) in moderate yield. Hydrogenations by deuterium atom of the acetophenone has been applied using various conditions. Deuterium was effectively introduced to the methylene moiety by deuterium labeled triethylsilane (Et3SiD) and unlabeled trifluoroacetic acid (CF3COOH) to afford [1-13C-1, 1-D2]-**18**). It is not necessary to use deuterium labeled trifluoroacetic acid for the deuteration. (Hashimoto & Hatanaka,

It has been reported that synthesis of homophenylalanine using a Friedel-Crafts reaction of Asp anhydride (*N*-unprotected or *N*-protected) with AlCl3 requires use of large excesses of aromatics and reflux in organic solvent for long durations (Xie, et al., 2000). These synthesis conditions cannot apply the equivalent condition of amino acid and TPD derivatives. Furthermore, the diazirinyl ring did not tolerate heating in the presence of Lewis acids. After Friedel-Crafts acylation, the constructed benzyl carbonyl group was hydrogenated to methylene under H2-Pd/C, which is not suitable for TPD derivatives. These difficulties were overcome Friedel-Crafts acylation of TPD derivative (**14**) and side chain derivatives of Asp (**19**) or Glu (**20**) using trifluoromethanesulfonic acid followed by ionic hydrogenation of benzylcarbonyl group to methylene with triethylsilane - trifluoroacetic acid. After constructions of the homo- (**23**) or bishomo- (**24**) phenylalanine skeletons, removal of the protective groups afforded TPD containing homo- (**25**) or bishomo- (**26**) phenylalanine while maintaining the stereochemistry of starting Asp or Glu (Murai et al., 2009; Murashige et al. 2009) (Fig. 13).

**Figure 13.** Stereo controlled synthesis of homo- (**25**) and bishomo- (**26**) phenylalanine TPD derivatives from m-methoxy TPD (**14**) and optically pure Asp (**19**) or Glu (**20**) derivatives

### *2.3.1. Selective hydrogenation of carbon-oxygen double bonds with stable isotope labeling*

130 Hydrogenation

2009) (Fig. 13).

**14**

N

OCH3

F3C

TFAHN OCH3

O

n

N

OCH3

N

+

N

F3C

Heckroth, 1997; Xu et al., 2000; Lin et al., 2001)

aromatics and a side chain of aspartic acid (Asp) or glutamic acid (Glu) are some of the key reactions for asymmetric synthesis for both homo- or bishomo- phenylalanine enantiomers' skeletons. (Reifenrath, et al. 1976; Nordlander et al., 1985; Melillo et al., 1987; Griesbeck &

It has been reported that synthesis of homophenylalanine using a Friedel-Crafts reaction of Asp anhydride (*N*-unprotected or *N*-protected) with AlCl3 requires use of large excesses of aromatics and reflux in organic solvent for long durations (Xie, et al., 2000). These synthesis conditions cannot apply the equivalent condition of amino acid and TPD derivatives. Furthermore, the diazirinyl ring did not tolerate heating in the presence of Lewis acids. After Friedel-Crafts acylation, the constructed benzyl carbonyl group was hydrogenated to methylene under H2-Pd/C, which is not suitable for TPD derivatives. These difficulties were overcome Friedel-Crafts acylation of TPD derivative (**14**) and side chain derivatives of Asp (**19**) or Glu (**20**) using trifluoromethanesulfonic acid followed by ionic hydrogenation of benzylcarbonyl group to methylene with triethylsilane - trifluoroacetic acid. After constructions of the homo- (**23**) or bishomo- (**24**) phenylalanine skeletons, removal of the protective groups afforded TPD containing homo- (**25**) or bishomo- (**26**) phenylalanine while maintaining the stereochemistry of starting Asp or Glu (Murai et al., 2009; Murashige et al.

**Figure 13.** Stereo controlled synthesis of homo- (**25**) and bishomo- (**26**) phenylalanine TPD derivatives

**<sup>24</sup>** n = 2 (95%) H2N OH

**<sup>20</sup>** n = 2, Glu (73%) TFAHN OCH3

F3C

TfOH 0 °C, 1h

O

N

OCH3

**25** n = 1 (94%) **26** n = 2 (90%)

N

O

n

F3C

O n

OCH3

**21** n = 1 (70%) **22** n = 2 (73%)

(C2H5)3SiH CF3COOH

rt, 1h

N

N

from m-methoxy TPD (**14**) and optically pure Asp (**19**) or Glu (**20**) derivatives

**23** n = 1 (80%)

TFAHN OCH3

O

O

n

Cl

**19** n = 1, Asp (70%)

NaOH CH3OH

rt, 2h

Established methods for the post-functional synthesis (described in the previous section) have facilitated the preparation of stable isotope labeled TPD. Stable isotopes act as a tag for the exogenous ligand derivatives on mass spectrometry. The methodologies will be very useful for the field of photoaffinity labeling to detect the labeled components. Friedel-Crafts acylation with 1-13C acetyl chloride, which is a relatively inexpensive reagent compared with other 13C labeled compounds, afforded 13C labeled acetophenone derivative ([13C]-**12**) in moderate yield. Hydrogenations by deuterium atom of the acetophenone has been applied using various conditions. Deuterium was effectively introduced to the methylene moiety by deuterium labeled triethylsilane (Et3SiD) and unlabeled trifluoroacetic acid (CF3COOH) to afford [1-13C-1, 1-D2]-**18**). It is not necessary to use deuterium labeled trifluoroacetic acid for the deuteration. (Hashimoto & Hatanaka, 2004)

**Figure 14.** Synthesis of stable isotope labeled TPD derivatives with transfer hydrogenation

The -position of the carbonyl groups was susceptible to very fast hydrogen-deuterium exchange using sodium hydroxide (NaOH) and methanol-OD (CH3OD) at room temperature. There are no serious decrements of deuterium incorporation with various work up to synthesis [2,2,2-D3]-**12**. After that, ionic hydrogenation with Et3SiD and trifluoroacetic acid afforded 5 deuterium incorporated TPD derivatives ([1,1,2,2,2-D5]-**18**). (Fig. 14). These synthetic methodologies have also been applied to synthesis of deuterium incorporated photoreactive fatty acid derivatives. (Murai et al. 2010)

### **2.4. Selective hydrogenation of carbon-carbon double bonds for the TPD derivatives**

The synthetic strategies for the Wittig reaction, followed by hydrogenation are amongst the major methods for carbon elongation derivatizations. These synthetic methods have not been compatible with synthesis of the TPD derivatives. This is because conditions for establishment for the selective hydrogenation (reduction) for the carbon-carbon double bond over that for nitrogen- nitrogen double bond on TPD are not easily achieved.

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 133

bonds in TPD have been established. Very strict conditions are necessary as the important nitrogen-nitrogen double bond can easily be lost. The establishments of a range of hydrogenation methods, together with the limitations of these methods that are described in this review, will facilitate further progress in the post-functional preparations of TPD. These chemical considerations could generate further widespread use of these biochemically ideal

*Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Japan* 

*Department of Biology and Biochemistry, University of Bath; Claverton Down, Bath BA2 7AY,* 

*Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama,* 

This research was partially supported by a Ministry of Education, Science, Sports and Culture Grant-in-Aid for Scientific Research in a Priority Area, 18032007 and for Scientific

Ambroise, Y.; Mioskowski, C.; Djéga-Mariadassou, G. & Rousseau, B. (2000). Consequences of affinity in heterogeneous catalytic reactions: highly chemoselective hydrogenolysis of

Barfoot, C. W.; Harvey, J. E.; Kenworthy, M. N.; Kilburn, J. P.; Ahmed, M. & Taylor, R. J. K. (2005). Highly functionalised organolithium and organoboron reagents for the

Faucher, N.; Ambroise, Y.; Cintrat, J. -C.; Doris, E.; Pillon, F. & Rousseau, B. (2002). Highly

chemoselective hydrogenolysis of iodoarenes. *J. Org. Chem.* 67, 932-934.

preparation of enantiomerically pure α-amino acids. *Tetrahedron*, 61, 3403-3417. Brunner, J.; Senn, H. & Richards, F. M. (1980). 3-Trifluoromethyl-3-phenyldiazirine. A new carbene generating group for photolabeling reagents. *J. Biol. Chem.* 255, 3313–3318 Daghish, M.; Hennig, L.; Findeisen, M.; Giesa, S., Schumer, F.; Hennig, H.; Beck-Sickinger, A. G. & Welzel, P. (2002) Tetrafunctional photoaffinity labels based on Nakanishi's *m*nitroalkoxy-substituted phenyltrifluoromethyldiazirine. *Angew. Chem. Int. Ed.* 41, 2293-

photoaffinity labels.

**Author details** 

Geoffery D. Holman

Yasumaru Hatanaka

**Acknowledgement** 

**4. References** 

2297

Research (C), 19510210, 21510219 (M.H.).

iodoarenes. *J. Org. Chem.* 65, 7183-7186.

*U.K.* 

*Japan* 

Makoto Hashimoto and Yuta Murai

We found Wilkinson's catalyst, chlorotris(triphenylphosphine)rhodium(I) in methanol has specificity for the target reaction. The alkene containing TPD derivatives (**27**-**29**), which are synthesized from Wittig reaction for TPD aldehyde (**17**) and stable ylides, were subjected to hydrogenation with H2-Wilkinson's catalyst at atmospheric pressure. It was observed that 25mol% of Wilkinson's catalyst required for complete hydrogenation. The , -unsaturated ester (**27**), nitrile (**28**) and aldehyde (**29**) were also hydrogenated under these conditions. The aldehyde carbonyl group conversion to primary alcohol (**33**) was only partially complete. (Fig. 15)

**Figure 15.** Synthesis of , -unsaturated carbonyl TPD derivatives and their hydrogenation with Wilkinson's catalyst

The hydrogenation of **27** and **28** with deuterium gas allowed effective incorporation of the deuterium atom intro these compounds (Hashimoto et al., 2007).

### **3. Conclusions**

Hydrogenations are very important for post-functional synthesis of TPD compounds.

It is very important for synthesis of TPD compounds that a range of hydrogenation methods are investigated. Selective hydrogenations in the presence of nitrogen-nitrogen double bonds in TPD have been established. Very strict conditions are necessary as the important nitrogen-nitrogen double bond can easily be lost. The establishments of a range of hydrogenation methods, together with the limitations of these methods that are described in this review, will facilitate further progress in the post-functional preparations of TPD. These chemical considerations could generate further widespread use of these biochemically ideal photoaffinity labels.

### **Author details**

132 Hydrogenation

(Fig. 15)

F3C

Wilkinson's catalyst

CHO

**17**

N

OCH3

Ph3P=CHR

F3C

N

R

**27** R = COOEt (95%, 83 : 17) **28** R = CN (94%, 69 : 31) **29** R = CHO (40%, 74 : 26)

OCH3

F3C

H2 (Ph3P)3RhCl (25mol%)

> CH3OH rt, 10h

N

R

OCH3

**30** R = COOEt (76%) **31** R = CN (68%) **32** R = CHO (40%)

**33** R = CH2OH (18% from **29**)

N

N

CH2Cl2 rt, 1h

N

**3. Conclusions** 

**derivatives** 

**2.4. Selective hydrogenation of carbon-carbon double bonds for the TPD** 

bond over that for nitrogen- nitrogen double bond on TPD are not easily achieved.

**Figure 15.** Synthesis of , -unsaturated carbonyl TPD derivatives and their hydrogenation with

Hydrogenations are very important for post-functional synthesis of TPD compounds.

deuterium atom intro these compounds (Hashimoto et al., 2007).

The hydrogenation of **27** and **28** with deuterium gas allowed effective incorporation of the

It is very important for synthesis of TPD compounds that a range of hydrogenation methods are investigated. Selective hydrogenations in the presence of nitrogen-nitrogen double

The synthetic strategies for the Wittig reaction, followed by hydrogenation are amongst the major methods for carbon elongation derivatizations. These synthetic methods have not been compatible with synthesis of the TPD derivatives. This is because conditions for establishment for the selective hydrogenation (reduction) for the carbon-carbon double

We found Wilkinson's catalyst, chlorotris(triphenylphosphine)rhodium(I) in methanol has specificity for the target reaction. The alkene containing TPD derivatives (**27**-**29**), which are synthesized from Wittig reaction for TPD aldehyde (**17**) and stable ylides, were subjected to hydrogenation with H2-Wilkinson's catalyst at atmospheric pressure. It was observed that 25mol% of Wilkinson's catalyst required for complete hydrogenation. The , -unsaturated ester (**27**), nitrile (**28**) and aldehyde (**29**) were also hydrogenated under these conditions. The aldehyde carbonyl group conversion to primary alcohol (**33**) was only partially complete.

Makoto Hashimoto and Yuta Murai

*Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo, Japan* 

Geoffery D. Holman

*Department of Biology and Biochemistry, University of Bath; Claverton Down, Bath BA2 7AY, U.K.* 

#### Yasumaru Hatanaka

*Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan* 

### **Acknowledgement**

This research was partially supported by a Ministry of Education, Science, Sports and Culture Grant-in-Aid for Scientific Research in a Priority Area, 18032007 and for Scientific Research (C), 19510210, 21510219 (M.H.).

### **4. References**


Fuwa, H.; Hiromoto, K.; Takahashi, Y.; Yokoshima, S.; Kan, T.; Fukuyama, T.; Iwatsubo,T.; Tomita, T. & Natsugari, H. (2006). Synthesis of biotinylated photoaffinity probes based on arylsulfonamide γ-secretase inhibitors, *Bioorg. Med. Chem. Lett.*16, 4184–4189.

Selective Hydrogenation and Transfer Hydrogenation for Post-Functional Synthesis of Trifluoromethylphenyl Diazirine Derivatives for Photoaffinity Labeling 135

Lin, W.; He, Z.; Zhang, H.; Zhang, X.; Mi, A. & Jiang, Y. (2001). Amino acid anhydride hydrochlorides as acylating agents in Friedel-Crafts reaction: a practical synthesis of L-

Melillo, D. G.; Larsen, R. D.; Mathre, D. J.; Shukis, W. F.; Wood, A. W. & Colleluori, J. R. (1987). Practical enantioselective synthesis of a homotyrosine derivative and (*R,R*)-4 propyl- 9-hydroxynaphthoxazine, a potent dopamine agonist. *J. Org. Chem.* 52, 5143-

Moss, R. A.; Fedé, J. –M. & Yan S. (2001). SbF5-mediated reactions of oxafluorodiazirines.

Murai, Y.; Hatanaka, Y.; Kanaoka, Y. & Hashimoto, M. (2009). Effective synthesis of optically active 3-phenyl-3-(3-trifluoromethyl) diazirinyl bishomophenylalanine derivatives,

Murai, Y.; Takahashi, M.; Muto, Y.; Hatanaka, Y. & Hashimoto, M. (2010). Simple deuterium introduction at α-position of carbonyl in diazirinyl derivatives for photoaffinity

Murashige, R.; Y. Murai, Y.; Hatanaka, Y. & Hashimoto, M. (2009). Effective synthesis of optically active trifluoromethyldiazirinyl homophenylalanine and aroylalanine derivatives with Friedel-Crafts reactions in triflic acid. *Biosci. Biotechnol. Biochem.* 73,

Nassal, M. (1983). 4-(1-Azi-2,2,2-trifluoroethyl)benzoic acid, a highly photolabile carbene generating label readily fixable to biochemical agents. *Liebigs Ann. Chem.* 1510– 1523. Nordlander, J. E.; Payne, M. J.; Njoroge, F. G.; Vishwanath, V. M.; Han, G. R.; Laikos, G. D. & Balk, M. A. (1985) A short enantiospecific synthesis of 2-amino-6,7-dihydroxy- 1,2,3,4-

Platz, M. S. (1995). Comparison of phenylcarbene and phenylnitrene. *Acc. Chem. Res.* 28,

Reifenrath, W. G.; Bertelli, D. J.; Micklus M. J. & Fries, D. S. (1976). Stereochemistry of friedel-crafts addition of phthalylaspartic anhydride to benzene. *Tetrahedron Lett.* 17,

Sammelson, R. E. & Casida, J, E. (2003). Synthesis of a tritium-labeled, fipronil-based, highly potent, photoaffinity probe for the GABA receptor. *J. Org. Chem.* 68, 8075-8079. Singh, A.; Thornton, E. R. & Westheimer, F. H. (1962). The photolysis of diazoacetyl-

Smith, R. A. G. & Knowles, J. R. (1973). Aryldiazirines. potential reagents for photolabeling

Tomohiro, T.; Hashimoto, M. & Hatanaka, Y. (2005). Cross-linking chemistry and biology: development of multifunctional photoafnity probes. Chemical Record, 5, 385–395 Yamada, M.; Nagashima, N.; Hasegawa, J. & Takahashi, S. (1998). A highly efficient asymmetric synthesis of methoxyhomophenylalanine using michael addition of

tetrahydronaphthalene (ADTN). *J. Org. Chem.* 1985, 50, 3619-3622.

chymotrypsin. *J. Biol. Chem.* 237, PC3006-PC3008.

phenethylamine. *Tetrahedron Lett.* 39, 9019-9022.

of biological receptor sites. *J. Am. Chem. Soc.* 95, 5072–5073.

homophenylalanine. *Synthesis* 7, 1007-1009.

5150.

1377-1380.

487–492.

1959-1962.

*Org. Lett.* 3, 2305–2308.

*Heterocycles* 79, 359-364.

labeling. *Heterocycles*, 82, 909 - 915.


Lin, W.; He, Z.; Zhang, H.; Zhang, X.; Mi, A. & Jiang, Y. (2001). Amino acid anhydride hydrochlorides as acylating agents in Friedel-Crafts reaction: a practical synthesis of Lhomophenylalanine. *Synthesis* 7, 1007-1009.

134 Hydrogenation

128.

123.

47, 3391–3394.

Fuwa, H.; Hiromoto, K.; Takahashi, Y.; Yokoshima, S.; Kan, T.; Fukuyama, T.; Iwatsubo,T.; Tomita, T. & Natsugari, H. (2006). Synthesis of biotinylated photoaffinity probes based

Galardy, R. E.; Craig, L. C. & Printz, M. P. (1973). Benzophenone triplet: a new photochemical probe of biological ligand-receptor interactions. *Nat. New Biol.* 242, 127–

Griesbeck, A. G. & Heckroth, H. (1997). A simple approach to �-amino acids by acylationof

Hashimoto, M.; Kanaoka, Y. & Hatanaka, Y. (1997). A versatile approach for functionalization of 3-aryl-3-trifluoromethyldiazirine photophore. *Heterocycles*, 46, 119-

Hashimoto, M.; Yang, J. & Holman, G. D. (2001). Cell-surface recognition of biotinylated membrane proteins requires very long spacer arms : An example from glucose-

Hashimoto, M.; Hatanaka, Y. & Nabeta, K. (2003). Effective synthesis of a carbon-linked diazirinyl fatty acid derivative via reduction of the carbonyl group to methylene with

Hashimoto, M. & Hatanaka, Y. (2004). Simple synthesis of deuterium and 13C labeled triuoromethyl phenyldiazirine derivatives as stable isotope tags for mass

Hashimoto, M.; Kato, Y. & Hatanaka, Y. (2006) Simple method for the introduction of iodolabel on (3-triuoromethyl) phenyldiazirine for photoaffinity labeling. *Tetrahedron Lett.*

Hashimoto, M.; Kato, Y. & Hatanaka, Y. (2007). Selective hydrogenation of alkene in (3 trifluoromethyl) phenyldiazirine photophor with Wilkinson's catalyst for photoaffinity

Hashimoto, M. & Hatanaka, Y. (2008). Recent progress in diazirine-based photoaffinity

Hatanaka, Y.; Hashimoto, M.; Kurihara, H.; Nakayama, H. & Kanaoka, Y. (1994a). A novel family of aromatic diazirines for photoaffinity labeling. *J. Org. Chem.* 59, 383–387. Hatanaka, Y.; Hashimoto, M.; Nakayama, H. & Kanaoka, Y. (1994b). Syntheses of nitrosubstituted aryl diazirines. An entry to chromogenic carbene precursors for

Karney, W. L. & Borden, W. T. (1997). Why does o-fluorine substitution raise the barrier to

on arylsulfonamide γ-secretase inhibitors, *Bioorg. Med. Chem. Lett.*16, 4184–4189. Fuwa, H.; Takahashi, Y.; Konno, Y.; Watanabe, N.; Miyashita, H.; Sasaki, M.; Natsugari,H.; Kan, T.; Fukuyama, T.; Tomita, T. & Iwatsubo, T. (2007). Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic γ-

secretase inhibitors. *ACS Chem. Biol.* 2, 408–418.

transporter probes. *CHEMBIOCHEM* 2, 52-59.

spectrometry. *Chem. Pharm. Bull.* 52, 1385—1386.

labeling. *Chem. Pharm. Bull.* 55, 1540-1543.

photoaffinity labeling. *Chem. Pharm. Bull.* 42, 826–831.

ring expansion of phenylnitrene? *J. Am. Chem. Soc.* 119, 3347–3350.

labeling. *Eur. J. Org. Chem.* 2513–2523

arenes with *N*-acyl aspartic anhydrides. *Synlett* 11, 1243-1244.

triethylsilane and trifluoroacetic acid. *Heterocycles* 59, 395-398.


Xie, Y.; Lou, R.; Li, Z.; Mi, A. & Jiang, Y. (2000). DPAMPP in catalytic asymmetric reactions: enantioselective synthesis of L-homophenylalanine. *Tetrahedron: Asymm.* 11, 1487-1494.

**Chapter 6** 

© 2012 Liprandi et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Liprandi et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Terminal and Non Terminal** 

**Catalyzed by Some** *d8*

Juan Badano and Mónica Quiroga

http://dx.doi.org/10.5772/47742

**1. Introduction** 

**Alkynes Partial Hydrogenation** 

**and Heterogeneous Systems** 

Additional information is available at the end of the chapter

conversion and selectivity to the *(Z)*-alkene [3-5].

increases when the temperature decreases using a Ni catalyst [20].

**Metal Complexes in Homogeneous** 

Domingo Liprandi, Edgardo Cagnola, Cecilia Lederhos,

 **Transition** 

The synthesis and manufacture of food additives, flavours and fragrances, as well as pharmaceutical, agrochemical and petrochemical substances, examples of fine and

Regarding alkyne partial hydrogenation, the main goal is to avoid hydrogenation to single bond and in the case of non-terminal alkynes is to give priority to the highest possible

These kind of reactions are carried out by means of a catalytic process where control over conversion and selectivity can be exerted in different ways, e.g.: by varying a) the active species or b) the support, and/or by adding c) a promoter / a poison / a modifier, and finally, and not less important, by modifying the reaction temperature. Examples of factor b) are: mesoporous [6] and siliceous [7] materials, a pumice [8], carbons [9], and hydrotalcite [3]. Cases of factor c) are the typical Lindlar catalyst (palladium heterogenized on calcium carbonate poisoned by lead acetate or lead oxide, Pd-CaCO3-Pb) [10] and the presence of quinoline and triphenylphosphine [11,12]. Research on factors a) and c) include bi-elemental systems such as Ni-B, Pd-Cu, etc. [13-19]. An example of the effect of the reaction temperature is a paper by Choi and Yoon, who found that the selectivity to *(Z)*-alkene

industrial chemicals, are closely related to selective alkyne hydrogenation [1,2].


**Chapter 6** 

**Terminal and Non Terminal Alkynes Partial Hydrogenation Catalyzed by Some** *d8*  **Transition Metal Complexes in Homogeneous and Heterogeneous Systems** 

Domingo Liprandi, Edgardo Cagnola, Cecilia Lederhos, Juan Badano and Mónica Quiroga

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/47742

### **1. Introduction**

136 Hydrogenation

Xie, Y.; Lou, R.; Li, Z.; Mi, A. & Jiang, Y. (2000). DPAMPP in catalytic asymmetric reactions: enantioselective synthesis of L-homophenylalanine. *Tetrahedron: Asymm.* 11, 1487-1494. Xu, Q.; Wang, G.; Wang, X.; Wu, T.; Pan, X.; Chan, A. S. C. & Yang, T. (2000). The synthesis of L-(+)-homophenylalanine hydrochloride. *Tetrahedron: Asymm*. 11, 2309-2314. Zhao, H.; Luo, R. G.; Wei, D. & Malhotra, S. V. (2002). Concise synthesis and enzymatic

resolution of L-(+)-homophenylalanine hydrochloride, *Enantiomer*, 7, 1-3.

The synthesis and manufacture of food additives, flavours and fragrances, as well as pharmaceutical, agrochemical and petrochemical substances, examples of fine and industrial chemicals, are closely related to selective alkyne hydrogenation [1,2].

Regarding alkyne partial hydrogenation, the main goal is to avoid hydrogenation to single bond and in the case of non-terminal alkynes is to give priority to the highest possible conversion and selectivity to the *(Z)*-alkene [3-5].

These kind of reactions are carried out by means of a catalytic process where control over conversion and selectivity can be exerted in different ways, e.g.: by varying a) the active species or b) the support, and/or by adding c) a promoter / a poison / a modifier, and finally, and not less important, by modifying the reaction temperature. Examples of factor b) are: mesoporous [6] and siliceous [7] materials, a pumice [8], carbons [9], and hydrotalcite [3]. Cases of factor c) are the typical Lindlar catalyst (palladium heterogenized on calcium carbonate poisoned by lead acetate or lead oxide, Pd-CaCO3-Pb) [10] and the presence of quinoline and triphenylphosphine [11,12]. Research on factors a) and c) include bi-elemental systems such as Ni-B, Pd-Cu, etc. [13-19]. An example of the effect of the reaction temperature is a paper by Choi and Yoon, who found that the selectivity to *(Z)*-alkene increases when the temperature decreases using a Ni catalyst [20].

© 2012 Liprandi et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 Liprandi et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Besides, transition metal complexes are a group of substances widely used as catalysts that could be considered as a new active species or as a metal conditioned by its ligands, a kind of "poison" or a modifier for the metal atom [21].

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 139

as the stationary phase using chloroform for [PdCl2(TDA)2] and chloroform/methanol (5/1 vol/vol) for [RhCl(TDA)3] as the corresponding eluting solvents. All the aliquots were tested to determine the presence of free TDA by thin layer chromatography. After drying the TDA-

In each preceding complex preparation, a blank experiment, using only the corresponding salt and solvent, was run verifying that there was no product obtained from them at all.

Anchoring of the complexes was carried out on -alumina (Ketjen CK 300), previously calcinated in air at 773 K for 3 h, or on RX3 (NORIT), a pelletized commercial carbon, by means of the incipient wetness technique. The solvents used for impregnation were as follows: a) chloroform for [PdCl2(TDA)2] and b) chloroform-methanol 5/1 (vol/vol) for [RhCl(TDA)3] using a suitable concentration to obtain 0.3 wt % M (M = Pd or Rh). Then,

In order to check for a possible leaching of the immobilized complexes, each freshsupported system was subjected to a 100-hour run in the corresponding reaction solvent at 353 K. After the tests, none Pd or Rh metal was detected in the remaining solution by Atomic Absorption spectroscopy, thus revealing a strong complex adherence to each support. In this respect, the constancy of M/Al or M/C atomic ratios obtained by XPS before and after the mentioned tests (see Table 2), ratifies that there was no leaching at all and that

The presence and weight percent of metal (Pd or Rh), chlorine and nitrogen elements were evaluated for each pure complex on a C- and H-free base, according to standard methods [36-39] to determine the stoichiometric ratios of the main atoms and to give a minimum

XPS spectra were carried out to evaluate: a) the electronic state of atoms, b) the atomic ratios, for the pure complexes and for the supported complexes before and after the reaction and (c) the atomic ratios M/Al or M/C (where M = Pd or Rh) for the supported complexes before and after reactions. This was done to get each pure complex minimum formula and some insight in the way the complexes were immobilized on the supports; verifying at the same time that the coordination compounds were maintained after anchoring (fresh catalysts) and after the catalytic evaluations (run catalysts) with the final purpose of

solvents were let evaporate in a desiccator at 298 K, until constant mass was verified.

the complexes species remained anchored on both supports.

demonstrating that the complexes are the real catalytic active species.

free solution in a rotary evaporator each complex, in solid state, was obtained.

**2.2. Blank test** 

**2.3. Complexes immobilization** 

**2.4. Complexes characterization** 

*2.4.2. X-Ray photoelectron spectroscopy (XPS)* 

*2.4.1. Elemental composition* 

formula for each complex.

These coordination compounds, used as catalysts, have gained increasing importance for such reactions [22-28] because they allow getting higher activities and selectivities, even under mild conditions of temperature and pressure [29-33].

The d8 metals, e.g. Rh(I), Ir(I), Pd(II), Ni(II) and Pt(II), form complexes for which the square planar geometry is specially favoured. They are important in catalysis as the central atom can increase its coordination number by accepting ligands in the apical sites [34] or by interacting with the support. These complexes have also the ability to dissociate molecular dihydrogen, and stabilize a variety of reaction intermediates through coordination as ligands in relatively stable but reactive complexes. This is made possible by promoting rearrangements within their coordination spheres [35].

On the other hand, regarding the physical condition, the desired product can be obtained in homogeneous or heterogeneous systems. The latter, in the context of transition metal complexes used as catalysts, have some practical-economical benefits as follows: a) the easy and cheap way in which the catalyst is removed from the remaining solution after ending the hydrogenation reaction; b) the main product does not need further purification due to a possible contamination with a heavy metal compound when no complex leaching is detected; and lastly, c) there is no need for a costly temperature control.

The purpose of this chapter is to illustrate, based on results already published, the previous ideas using: a) 1-heptyne and 3-hexyne as the substrates to be partially hydrogenated, examples of terminal and non-terminal alkynes respectively, b) [PdCl2(NH2(CH2)12CH3)2] and [RhCl(NH2(CH2)12CH3)3] as the catalytic species with coordination spheres having tridecylamine as an electron-donating **σ** ligand and chloride as an electron-withdrawing **σ/π** ligand and Pd(II) and Rh(I) as the central atoms respectively and c) -Al2O3 Ketjen CK 300 and RX3, a commercial carbonaceous material from NORIT, as supports for the heterogeneous catalytic tests.

Last but not least, the complex catalytic performances are compared, at the same operational conditions, against those obtained with the Lindlar catalyst which is accepted as a standard one.

### **2. Experimental**

### **2.1. Complexes preparation and purification**

[PdCl2(TDA)2] and [RhCl(TDA)3] (TDA = NH2(CH2)12CH3) were prepared in a glass equipment with agitation and reflux in a purified argon atmosphere using tridecylamine (TDA) and PdCl2 or RhCl3 according to the case. [PdCl2(TDA)2] (yellow-orange) was obtained at 338 K after 4.0 h with a molar ratio TDA/PdCl2 = 2, while [RhCl(TDA)3] (yellow) was got at 348 K after 4.5 h with a molar ratio TDA/RhCl3 = 6 using toluene and carbon tetrachloride as solvents respectively. The purification was made by column chromatography with silica gel as the stationary phase using chloroform for [PdCl2(TDA)2] and chloroform/methanol (5/1 vol/vol) for [RhCl(TDA)3] as the corresponding eluting solvents. All the aliquots were tested to determine the presence of free TDA by thin layer chromatography. After drying the TDAfree solution in a rotary evaporator each complex, in solid state, was obtained.

### **2.2. Blank test**

138 Hydrogenation

catalytic tests.

**2. Experimental** 

Besides, transition metal complexes are a group of substances widely used as catalysts that could be considered as a new active species or as a metal conditioned by its ligands, a kind

These coordination compounds, used as catalysts, have gained increasing importance for such reactions [22-28] because they allow getting higher activities and selectivities, even

The d8 metals, e.g. Rh(I), Ir(I), Pd(II), Ni(II) and Pt(II), form complexes for which the square planar geometry is specially favoured. They are important in catalysis as the central atom can increase its coordination number by accepting ligands in the apical sites [34] or by interacting with the support. These complexes have also the ability to dissociate molecular dihydrogen, and stabilize a variety of reaction intermediates through coordination as ligands in relatively stable but reactive complexes. This is made possible by promoting

On the other hand, regarding the physical condition, the desired product can be obtained in homogeneous or heterogeneous systems. The latter, in the context of transition metal complexes used as catalysts, have some practical-economical benefits as follows: a) the easy and cheap way in which the catalyst is removed from the remaining solution after ending the hydrogenation reaction; b) the main product does not need further purification due to a possible contamination with a heavy metal compound when no complex leaching is

The purpose of this chapter is to illustrate, based on results already published, the previous ideas using: a) 1-heptyne and 3-hexyne as the substrates to be partially hydrogenated, examples of terminal and non-terminal alkynes respectively, b) [PdCl2(NH2(CH2)12CH3)2] and [RhCl(NH2(CH2)12CH3)3] as the catalytic species with coordination spheres having tridecylamine as an electron-donating **σ** ligand and chloride as an electron-withdrawing **σ/π** ligand and Pd(II) and Rh(I) as the central atoms respectively and c) -Al2O3 Ketjen CK 300 and RX3, a commercial carbonaceous material from NORIT, as supports for the heterogeneous

Last but not least, the complex catalytic performances are compared, at the same operational conditions, against those obtained with the Lindlar catalyst which is accepted as a standard one.

[PdCl2(TDA)2] and [RhCl(TDA)3] (TDA = NH2(CH2)12CH3) were prepared in a glass equipment with agitation and reflux in a purified argon atmosphere using tridecylamine (TDA) and PdCl2 or RhCl3 according to the case. [PdCl2(TDA)2] (yellow-orange) was obtained at 338 K after 4.0 h with a molar ratio TDA/PdCl2 = 2, while [RhCl(TDA)3] (yellow) was got at 348 K after 4.5 h with a molar ratio TDA/RhCl3 = 6 using toluene and carbon tetrachloride as solvents respectively. The purification was made by column chromatography with silica gel

of "poison" or a modifier for the metal atom [21].

under mild conditions of temperature and pressure [29-33].

rearrangements within their coordination spheres [35].

**2.1. Complexes preparation and purification** 

detected; and lastly, c) there is no need for a costly temperature control.

In each preceding complex preparation, a blank experiment, using only the corresponding salt and solvent, was run verifying that there was no product obtained from them at all.

### **2.3. Complexes immobilization**

Anchoring of the complexes was carried out on -alumina (Ketjen CK 300), previously calcinated in air at 773 K for 3 h, or on RX3 (NORIT), a pelletized commercial carbon, by means of the incipient wetness technique. The solvents used for impregnation were as follows: a) chloroform for [PdCl2(TDA)2] and b) chloroform-methanol 5/1 (vol/vol) for [RhCl(TDA)3] using a suitable concentration to obtain 0.3 wt % M (M = Pd or Rh). Then, solvents were let evaporate in a desiccator at 298 K, until constant mass was verified.

In order to check for a possible leaching of the immobilized complexes, each freshsupported system was subjected to a 100-hour run in the corresponding reaction solvent at 353 K. After the tests, none Pd or Rh metal was detected in the remaining solution by Atomic Absorption spectroscopy, thus revealing a strong complex adherence to each support. In this respect, the constancy of M/Al or M/C atomic ratios obtained by XPS before and after the mentioned tests (see Table 2), ratifies that there was no leaching at all and that the complexes species remained anchored on both supports.

### **2.4. Complexes characterization**

### *2.4.1. Elemental composition*

The presence and weight percent of metal (Pd or Rh), chlorine and nitrogen elements were evaluated for each pure complex on a C- and H-free base, according to standard methods [36-39] to determine the stoichiometric ratios of the main atoms and to give a minimum formula for each complex.

### *2.4.2. X-Ray photoelectron spectroscopy (XPS)*

XPS spectra were carried out to evaluate: a) the electronic state of atoms, b) the atomic ratios, for the pure complexes and for the supported complexes before and after the reaction and (c) the atomic ratios M/Al or M/C (where M = Pd or Rh) for the supported complexes before and after reactions. This was done to get each pure complex minimum formula and some insight in the way the complexes were immobilized on the supports; verifying at the same time that the coordination compounds were maintained after anchoring (fresh catalysts) and after the catalytic evaluations (run catalysts) with the final purpose of demonstrating that the complexes are the real catalytic active species.

A Shimadzu ESCA 750 Electron Spectrometer coupled to a Shimadzu ESCAPAC 760 Data System was used. The C 1s line was taken as an internal standard at 285.0 eV so as to correct possible deviations caused by electric charge on the samples. The superficial electronic states of the atoms were studied according to the position of the following peak maxima: Rh 3d5/2 and Pd 3d5/2, N 1s for the TDA molecule and Cl 2p3/2 for the complexes in any condition. In order to ensure that there was no modification on the electronic state of the species, the sample introduction was made according to the operational procedure reported elsewhere [40]. Exposing the samples to the atmosphere for different periods of time confirmed that there were no electronic modifications. Determination of the atomic ratios x/Metal (x = N, Cl) and Metal/Z (Z = Al or C, depending on the support) were made by comparing the areas under the peaks after background subtraction and corrections due to differences in escape depths [41] and in photoionization cross sections [42].

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 141

between 0.2 and 0.7 relative pressure corresponds to the mesopore range of porosity. The wider porosity, macropores (Vmacro) and part of the mesopores (with diameter from 7.5 to 50 nm), was determined by mercury porosimetry, using a Carlo Erba 2000 porosimeter. This equipment reaches a maximum pressure of 196 MPa, which allows estimating the volume of pores with a diameter longer than 7.5 nm. The addition of the mesopore volumes determined from N2 adsorption isotherm and by mercury porosimetry gives the total mesopore volume (Vmeso) [46]. Finally, with the BET equation applied to the N2 adsorption

This information can be used to know the support profitable sites where the complexes can be located and the concentration of the substrates would turn out augmented by a

The catalytic runs were made using 100 mL of a 2 % v/v alkyne in toluene solution, in a PTFE-coated batch stainless steel stirred tank reactor, operated at 600 rpm during 120 min. The weight of the supported complex catalysts was 0.075 g in all cases. In the catalytic evaluation of the unsupported complexes, a suitable mass of these ones was used to provide the same amount of metal (Pd or Rh) as in the corresponding supported catalysts. The same criterion was used for the Lindlar catalyst. Every catalytic test was carried out in triplicate at

Detection of possible diffusional limitations during the catalytic runs was taken into account according to the procedures described in the literature [47-48]. External diffusional limitations were examined by varying the stirring velocity in the range of 180-1400 rpm. Conversion and selectivity constancy verified above 500 rpm allows to say that this type of limitation was absent at the selected rotatory speed. On the other hand, intraparticle mass transfer limitations were considered by crushing the heterogenised complex catalyst up to ¼ the original size and using the obtained samples to carry out the partial hydrogenation reactions. Conversion and selectivity values, equal to those obtained with the uncrushed heterogenised catalyst, permitted to state that this type of limitation was also absent in the physical operational conditions of our work. Last but not least, the catalyst cylinders were properly treated and weighted after the end of reactions. The difference in the mass of catalyst cylinders (before and after the test reactions) was not appreciable within the experimental error of the analytical balance method, meaning that there was no mass loss from the cylinders. Thus, it can be considered that the attrition effect was absent or was negligible enough to play a role in determining an additional mass transfer limitation. The analysis of reactants and products was

made by gas chromatography, using a FID and a CP WAX 52 CB capillary column. The following substrates and conditions were used to perform the catalytic tests:

 1-heptyne (a terminal alkyne) partial hydrogenation was used to evaluate the catalytic performance of both complexes in homogeneous condition and anchored on -Al2O3 at 303 K with a 1-heptyne/Pd or Rh molar ratio equal to 7.3 103 and 7.0 103, respectively.

isotherm at 77 K it is possible to evaluate the specific surface area.

P = 150 kPa with a relative experimental error of about 3 %.

*2.4.5. Catalytic runs* 

physicochemical adsorption process favouring the partial hydrogenation.

### *2.4.3. Infrared spectroscopy (FTIR and IR)*

Pure complexes and TDA IR spectra were taken, in the 4100-900 cm-1 range, to determine the presence of tridecylamine as a ligand in the complexes coordination spheres. The analysis was carried out using the TDA characteristic normal wavenumbers [43-45]. Besides, pure [PdCl2(TDA)2] IR spectra was also taken and analyzed, below 600 cm-1, with the purpose to elucidate if the obtained complex was the cis or trans isomer, and consequently to be able to assign a correct local site symmetry for this species.

The high wavenumber spectra were taken in a Shimadzu FTIR 8101/8101M single beam spectrometer; the equipment has a Michelson type optical interferometer. Two chambers are available to improve the quality of the spectra. The first one has a pyroelectric detector made of a high sensitivity LiTaO element, and the other has an MCT detector and the possibility to create a controlled N2 (or dry air) atmosphere. On the other hand due to the low detector sensitivity below 500 cm-1, a Perkin-Elmer 580 B double beam spectrometer was also used.

All the samples were dried at 353 K and were examined either in potassium bromide or cesium iodide disks in a concentration ranging from 0.5 to 1 wt% to ensure non-saturated spectra [41].

### *2.4.4. Supports characterization*

The porosity of the supports was characterized by physical adsorption of N2 (77 K) and CO2 (273 K). Gas adsorption is useful to calculate specific surface area and pore volume. The use of both adsorptives (N2 and CO2) allows estimating the pore volume distribution of pores up to about 7.5 nm diameter [46]. By applying the Dubinin-Raduskevich equation to the CO2 adsorption isotherm at 273 K, the volume of micropores with a diameter less than 0.7 nm (Vmicro) can be obtained. On the other hand, the volume of supermicropores (Vsupermicro), diameter ranging from 0.7 to 2 nm, is obtained by subtraction of Vmicro from the volume calculated by applying the Dubinin-Raduskevich method to the N2 adsorption isotherm at 77 K [46]. The volume of mesopores with diameter between 2 and 7.5 nm was calculated from the N2 adsorption isotherm at 77 K. In this respect, the volume of gas adsorbed between 0.2 and 0.7 relative pressure corresponds to the mesopore range of porosity. The wider porosity, macropores (Vmacro) and part of the mesopores (with diameter from 7.5 to 50 nm), was determined by mercury porosimetry, using a Carlo Erba 2000 porosimeter. This equipment reaches a maximum pressure of 196 MPa, which allows estimating the volume of pores with a diameter longer than 7.5 nm. The addition of the mesopore volumes determined from N2 adsorption isotherm and by mercury porosimetry gives the total mesopore volume (Vmeso) [46]. Finally, with the BET equation applied to the N2 adsorption isotherm at 77 K it is possible to evaluate the specific surface area.

This information can be used to know the support profitable sites where the complexes can be located and the concentration of the substrates would turn out augmented by a physicochemical adsorption process favouring the partial hydrogenation.

### *2.4.5. Catalytic runs*

140 Hydrogenation

A Shimadzu ESCA 750 Electron Spectrometer coupled to a Shimadzu ESCAPAC 760 Data System was used. The C 1s line was taken as an internal standard at 285.0 eV so as to correct possible deviations caused by electric charge on the samples. The superficial electronic states of the atoms were studied according to the position of the following peak maxima: Rh 3d5/2 and Pd 3d5/2, N 1s for the TDA molecule and Cl 2p3/2 for the complexes in any condition. In order to ensure that there was no modification on the electronic state of the species, the sample introduction was made according to the operational procedure reported elsewhere [40]. Exposing the samples to the atmosphere for different periods of time confirmed that there were no electronic modifications. Determination of the atomic ratios x/Metal (x = N, Cl) and Metal/Z (Z = Al or C, depending on the support) were made by comparing the areas under the peaks after background subtraction and corrections due to differences in escape

Pure complexes and TDA IR spectra were taken, in the 4100-900 cm-1 range, to determine the presence of tridecylamine as a ligand in the complexes coordination spheres. The analysis was carried out using the TDA characteristic normal wavenumbers [43-45]. Besides, pure [PdCl2(TDA)2] IR spectra was also taken and analyzed, below 600 cm-1, with the purpose to elucidate if the obtained complex was the cis or trans isomer, and consequently to be able to

The high wavenumber spectra were taken in a Shimadzu FTIR 8101/8101M single beam spectrometer; the equipment has a Michelson type optical interferometer. Two chambers are available to improve the quality of the spectra. The first one has a pyroelectric detector made of a high sensitivity LiTaO element, and the other has an MCT detector and the possibility to create a controlled N2 (or dry air) atmosphere. On the other hand due to the low detector sensitivity below 500 cm-1, a Perkin-Elmer 580 B double beam spectrometer was also used.

All the samples were dried at 353 K and were examined either in potassium bromide or cesium iodide disks in a concentration ranging from 0.5 to 1 wt% to ensure non-saturated spectra [41].

The porosity of the supports was characterized by physical adsorption of N2 (77 K) and CO2 (273 K). Gas adsorption is useful to calculate specific surface area and pore volume. The use of both adsorptives (N2 and CO2) allows estimating the pore volume distribution of pores up to about 7.5 nm diameter [46]. By applying the Dubinin-Raduskevich equation to the CO2 adsorption isotherm at 273 K, the volume of micropores with a diameter less than 0.7 nm (Vmicro) can be obtained. On the other hand, the volume of supermicropores (Vsupermicro), diameter ranging from 0.7 to 2 nm, is obtained by subtraction of Vmicro from the volume calculated by applying the Dubinin-Raduskevich method to the N2 adsorption isotherm at 77 K [46]. The volume of mesopores with diameter between 2 and 7.5 nm was calculated from the N2 adsorption isotherm at 77 K. In this respect, the volume of gas adsorbed

depths [41] and in photoionization cross sections [42].

assign a correct local site symmetry for this species.

*2.4.4. Supports characterization* 

*2.4.3. Infrared spectroscopy (FTIR and IR)* 

The catalytic runs were made using 100 mL of a 2 % v/v alkyne in toluene solution, in a PTFE-coated batch stainless steel stirred tank reactor, operated at 600 rpm during 120 min. The weight of the supported complex catalysts was 0.075 g in all cases. In the catalytic evaluation of the unsupported complexes, a suitable mass of these ones was used to provide the same amount of metal (Pd or Rh) as in the corresponding supported catalysts. The same criterion was used for the Lindlar catalyst. Every catalytic test was carried out in triplicate at P = 150 kPa with a relative experimental error of about 3 %.

Detection of possible diffusional limitations during the catalytic runs was taken into account according to the procedures described in the literature [47-48]. External diffusional limitations were examined by varying the stirring velocity in the range of 180-1400 rpm. Conversion and selectivity constancy verified above 500 rpm allows to say that this type of limitation was absent at the selected rotatory speed. On the other hand, intraparticle mass transfer limitations were considered by crushing the heterogenised complex catalyst up to ¼ the original size and using the obtained samples to carry out the partial hydrogenation reactions. Conversion and selectivity values, equal to those obtained with the uncrushed heterogenised catalyst, permitted to state that this type of limitation was also absent in the physical operational conditions of our work. Last but not least, the catalyst cylinders were properly treated and weighted after the end of reactions. The difference in the mass of catalyst cylinders (before and after the test reactions) was not appreciable within the experimental error of the analytical balance method, meaning that there was no mass loss from the cylinders. Thus, it can be considered that the attrition effect was absent or was negligible enough to play a role in determining an additional mass transfer limitation. The analysis of reactants and products was made by gas chromatography, using a FID and a CP WAX 52 CB capillary column.

The following substrates and conditions were used to perform the catalytic tests:

 1-heptyne (a terminal alkyne) partial hydrogenation was used to evaluate the catalytic performance of both complexes in homogeneous condition and anchored on -Al2O3 at 303 K with a 1-heptyne/Pd or Rh molar ratio equal to 7.3 103 and 7.0 103, respectively.

	- 3-hexyne (a non-terminal alkyne) partial hydrogenation was used to evaluate the catalytic performance of [RhCl(TDA)3] in homogeneous condition and anchored on RX3 at 275, 290 and 303 K with a 3-hexyne/Rh molar ratio equal to 8.1 103.

Terminal and Non Terminal Alkynes Partial Hydrogenation

Binding energies (eV) Atomic ratios (at/at)

N/M Cl/M M/Al or C

Cl 2p3/2

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 143

N 1s

pure[49] 338.2 401.9 198.3 2.00 1.99 - -Al2O3 fresh [49] 338.3 401.7 198.2 2.01 2.00 0.09 -Al2O3 runa [49] 338.2 402.0 198.1 1.99 1.99 0.09 RX3 fresh [53] 338.4 401.9 198.2 2.02 2.00 0.10 RX3 runb 338.3 402.0 198.3 2.01 1.99 0.10

pure[49] 307.1 402.1 198.1 3.00 1.01 - -Al2O3 fresh[49] 307.2 402.2 198.3 2.99 1.02 0.05 -Al2O3 runa [49] 307.1 402.2 198.2 2.99 0.99 0.05 RX3 fresh [52] 307.1 401.9 198.0 3.00 1.02 0.06 RX3 runb 307.0 402.0 198.0 2.99 1.00 0.06

indicate that these elements appear in the proportion **Pd:Cl:N equal to 1:2:2 and Rh:Cl:N equal to 1:1:3. These numbers are equal to those obtained via Elemental Composition** 

> M 3d5/2

**Table 2.** XPS binding energies and XPS atomic ratios for pure, fresh and run heterogenized Pd or Rh

On the other hand, Figure 1 shows the pure TDA, [PdCl2(TDA)2] and [RhCl(TDA)3] FTIR spectra, while Figure 2 depicts the pure [PdCl2(TDA)2] IR spectrum in the range below 600 cm-1. As observed at high wavenumbers in Figure 1, the following characteristic peaks of a primary aliphatic amine [44], are present: (A) NH2 "stretching" (3600-3100 cm-1), CH "stretching" (3000-2800 cm-1), (B) NH2 "bending" (1700-1600 cm-1), CH "bending" (1500-1300 cm-1) and (C) CN "stretching" (1200-1000 cm-1). In particular, labels A, B and C, related to the nitrogen atom, are taken as a reference because they are sensitive to its environment. Besides Figure 1 shows that [PdCl2(TDA)2] and [RhCl(TDA)3] FTIR peaks globally agree with those corresponding to pure TDA. **Anyhow, differences are found in the labelled wavenumbers indicated above: A, B and C as they show a slight shift to lower frequencies with respect to the pure ligand, meaning an interaction between the nitrogen lone pair and the Pd or Rh atom. This argument is reinforced by the fact that when a primary amine is bonded, the NH2 stretching peak is considerably different in shape and intensity from the original NH2 band [45], as seen in the shown spectra. This information confirms that the** 

**TDA molecule is one of the ligands in the complexes coordination spheres**.

typical of centre-symmetric species [54].

The IR spectrum presented in Figure 2 shows the peaks corresponding to the Pd-ligand vibrations for the pure complex. **[PdCl2(TDA)2] can be considered as the trans-isomer** because of the presence of single peaks, which obey the principle of mutual exclusion,

**results.** 

[PdCl2(TDA)2]

[RhCl(TDA)3]

complexes.

a 1-heptyne partial hydrogenation b 3-hexyne partial hydrogenation

Complex Condition

### *2.4.6. Atomic absorption spectroscopy*

The possible presence of M (Rh or Pd), provoked by a solvent leaching effect in each solution after catalytic evaluation of the heterogeneous systems, was analyzed by means of the Atomic Absorption technique.

### **3. Results and discussion**

### **3.1. Pd or Rh complex minimum formula**


Table 1 shows M (Pd or Rh), N and Cl elemental composition on a C- and H- free base, as well as Cl/M and N/M molar ratios obtained for the pure complexes.

**Table 1.** M (Pd or Rh), N and Cl (on a C- and H-free base) elemental composition and Cl/M and N/M molar ratios for the pure complexes.[49]

The **Pd:Cl:N and Rh:Cl:N** molar ratios for the pure complexes calculated from the weight percent values (Table 1) and the molar masses of these elements, can be expressed as ca. **1:2:2 and 1:1:3** respectively.

Additionally, Table 2 presents the M 3d5/2, N 1s and Cl 2p3/2 peaks binding energies (BE), and the atomic ratios N/M, Cl/M for the pure and for the fresh and run supported complexes, obtained by XPS.

Table 2 also includes the superficial molar ratio M/Al or M/C for the heterogenized complexes. XPS binding energies for the pure substances are in accordance with the literature values [50,51]; showing that Pd or Rh, N and Cl are present in the corresponding products obtained after the synthesis and purification stages. Besides, the electronic states of these atoms may be considered as follows: a) **n+ for Pd or Rh, with n = 2 and n close to 1 respectively**; this is based on data in Table 2 and the literature values 338.3 eV for [PdCl2(NH3)2] and ranging from 307.3 to 308.5 eV for Rh(I) [50,51]; b) **-3 for N but as an ammonium-like nitrogen** as the 1s binding energies in Table 2 fall within the values found in the literature (400.9 to 402 eV [50,51]) corresponding to a NH4+ species; **this information suggests a bonding character for the N lone pair towards an electrophilic centre, in this case the Pd or Rh atom**; and c) **-1 for Cl as in a chloride compound** because the 2p3/2 binding energies in Table 2 are included within the literature values (197.9 to 198.5 eV [50,51]). At the same time, from the mentioned table, the atomic ratios for each complex


indicate that these elements appear in the proportion **Pd:Cl:N equal to 1:2:2 and Rh:Cl:N equal to 1:1:3. These numbers are equal to those obtained via Elemental Composition results.** 

a 1-heptyne partial hydrogenation

142 Hydrogenation

*2.4.6. Atomic absorption spectroscopy* 

the Atomic Absorption technique.

**3. Results and discussion** 

molar ratios for the pure complexes.[49]

**1:2:2 and 1:1:3** respectively.

complexes, obtained by XPS.

**3.1. Pd or Rh complex minimum formula** 

 3-hexyne (a non-terminal alkyne) partial hydrogenation was used to evaluate the catalytic performance of [RhCl(TDA)3] in homogeneous condition and anchored on RX3

The possible presence of M (Rh or Pd), provoked by a solvent leaching effect in each solution after catalytic evaluation of the heterogeneous systems, was analyzed by means of

Table 1 shows M (Pd or Rh), N and Cl elemental composition on a C- and H- free base, as

Complex Elemental Composition (weight %) Atomic ratios

[PdCl2(TDA)2] 52.0 34.3 13.7 1.99 2.00 [RhCl(TDA)3] 56.9 19.6 23.5 1.00 3.04 **Table 1.** M (Pd or Rh), N and Cl (on a C- and H-free base) elemental composition and Cl/M and N/M

The **Pd:Cl:N and Rh:Cl:N** molar ratios for the pure complexes calculated from the weight percent values (Table 1) and the molar masses of these elements, can be expressed as ca.

Additionally, Table 2 presents the M 3d5/2, N 1s and Cl 2p3/2 peaks binding energies (BE), and the atomic ratios N/M, Cl/M for the pure and for the fresh and run supported

Table 2 also includes the superficial molar ratio M/Al or M/C for the heterogenized complexes. XPS binding energies for the pure substances are in accordance with the literature values [50,51]; showing that Pd or Rh, N and Cl are present in the corresponding products obtained after the synthesis and purification stages. Besides, the electronic states of these atoms may be considered as follows: a) **n+ for Pd or Rh, with n = 2 and n close to 1 respectively**; this is based on data in Table 2 and the literature values 338.3 eV for [PdCl2(NH3)2] and ranging from 307.3 to 308.5 eV for Rh(I) [50,51]; b) **-3 for N but as an ammonium-like nitrogen** as the 1s binding energies in Table 2 fall within the values found in the literature (400.9 to 402 eV [50,51]) corresponding to a NH4+ species; **this information suggests a bonding character for the N lone pair towards an electrophilic centre, in this case the Pd or Rh atom**; and c) **-1 for Cl as in a chloride compound** because the 2p3/2 binding energies in Table 2 are included within the literature values (197.9 to 198.5 eV [50,51]). At the same time, from the mentioned table, the atomic ratios for each complex

M Cl N Cl/M N/M

at 275, 290 and 303 K with a 3-hexyne/Rh molar ratio equal to 8.1 103.

well as Cl/M and N/M molar ratios obtained for the pure complexes.

b 3-hexyne partial hydrogenation

**Table 2.** XPS binding energies and XPS atomic ratios for pure, fresh and run heterogenized Pd or Rh complexes.

On the other hand, Figure 1 shows the pure TDA, [PdCl2(TDA)2] and [RhCl(TDA)3] FTIR spectra, while Figure 2 depicts the pure [PdCl2(TDA)2] IR spectrum in the range below 600 cm-1. As observed at high wavenumbers in Figure 1, the following characteristic peaks of a primary aliphatic amine [44], are present: (A) NH2 "stretching" (3600-3100 cm-1), CH "stretching" (3000-2800 cm-1), (B) NH2 "bending" (1700-1600 cm-1), CH "bending" (1500-1300 cm-1) and (C) CN "stretching" (1200-1000 cm-1). In particular, labels A, B and C, related to the nitrogen atom, are taken as a reference because they are sensitive to its environment. Besides Figure 1 shows that [PdCl2(TDA)2] and [RhCl(TDA)3] FTIR peaks globally agree with those corresponding to pure TDA. **Anyhow, differences are found in the labelled wavenumbers indicated above: A, B and C as they show a slight shift to lower frequencies with respect to the pure ligand, meaning an interaction between the nitrogen lone pair and the Pd or Rh atom. This argument is reinforced by the fact that when a primary amine is bonded, the NH2 stretching peak is considerably different in shape and intensity from the original NH2 band [45], as seen in the shown spectra. This information confirms that the TDA molecule is one of the ligands in the complexes coordination spheres**.

The IR spectrum presented in Figure 2 shows the peaks corresponding to the Pd-ligand vibrations for the pure complex. **[PdCl2(TDA)2] can be considered as the trans-isomer** because of the presence of single peaks, which obey the principle of mutual exclusion, typical of centre-symmetric species [54].

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 145

orbitals are taken into account to explain metal-ligand bonding according to their symmetry properties. In this respect, the (n-1)d and ns metal atomic orbitals are those that match best the energy of the TASO/MOs. Based on this, complex antibonding MOs have considerably more metal character while complex bonding MOs have more ligand character; with the former lying higher in energy. On the other hand, tetra-coordinated palladium(II) and rhodium(I) (*d8* species) complexes have a square-planar geometry [55]. On this background

Knowing that [PdCl2(TDA)2] and [RhCl(TDA)3] have a D2h and C2v local site symmetries respectively and taking the main rotation axis along the z cartesian axis, the Angular Overlap Model (AOM) [56] can be used to predict the HOMO-LUMO frontier orbitals in an

Non-bonding (dxy), antibonding double degenerate 2e\*<sup>π</sup> ((dxz, dyz)\*), e\*<sup>σ</sup> ((dz2)\*) and 3e\*σ ((dx2–y2)\*) [49]. Assigning the eight electrons to this scheme, it turns out that (dz2)\* (z direction) and (dx2-y2)\* (x and y directions) are the HOMO and LUMO frontier

Non-bonding (dxy), antibonding double-degenerate e\*<sup>π</sup> ((dxz, dyz)\*), 7/4 e\*<sup>σ</sup> ((dz2)\*) and 9/4 e\*σ ((dx2–y2)\*). Assigning the eight electrons to this scheme, it turns out that (dz2)\* (z direction) and (dx2-y2)\* (x and y directions) are the HOMO and LUMO frontier orbitals,

The Rh(I) complex HOMO-LUMO frontier orbitals lie higher in energy than those corresponding to the Pd(II) complex because of the lower oxidation number of the central atom. The HOMO is useful to produce the cleavage of the H–H bonding, generating hydrogen atoms and the LUMO is available to receive electron density from the substrate molecule, weakening the C–C triple bond; both concepts are key factors during the catalytic

The approximate molecular size of the metal complexes can be estimated in order to study structural aspects related to their location in the supports porosity. This can be done taking into account the square planar geometry, typical covalent radii, a 109.5° C–C–C angle and

The lengths TDA–Pd–TDA and Cl–Pd–Cl are ca. 4 and 0.7 nm, respectively.

The lengths TDA–Rh–TDA and Cl–Rh–TDA are ca. 4 and 2.3 nm, respectively.

Table 3 presents the BET surface area and the pore volume distribution for both supports.

and knowing that [PdCl2(TDA)2] is the trans isomer two facts can be considered:

i. HOMO-LUMO Electron Configurations

increasing order of energy for each case:

cycle leading to the hydrogenation of the substrate.

**3.3. Supported Pd and Rh complexes structures** 

[PdCl2(TDA)2]

[RhCl(TDA)3]

respectively.

ii. Complexes Dimensions

basic trigonometry. [PdCl2(TDA)2]

[RhCl(TDA)3]

orbitals, respectively.

**Figure 1.** FTIR spectra corresponding to pure TDA, [PdCl2(TDA)2] and [RhCl(TDA)3].[49]

**Figure 2.** IR spectrum below 600 cm-1 for pure [PdCl2(TDA)2]. [54]

*At this point, the complex minimum formula, on the basis of the preceding Elemental Composition, XPS and FTIR arguments, can be expressed by [PdCl2(TDA)2] or [RhCl(TDA)3].* 

### **3.2. Palladium and rhodium local site symmetries, HOMO-LUMO electron configurations and complexes dimensions**

Molecular orbitals with symmetries corresponding to the irreducible representations of the molecular point group automatically satisfy the Fock equation. For complex species the terminal atom symmetry orbital (TASO)/molecular orbitals (MO) and the metal atomic orbitals are taken into account to explain metal-ligand bonding according to their symmetry properties. In this respect, the (n-1)d and ns metal atomic orbitals are those that match best the energy of the TASO/MOs. Based on this, complex antibonding MOs have considerably more metal character while complex bonding MOs have more ligand character; with the former lying higher in energy. On the other hand, tetra-coordinated palladium(II) and rhodium(I) (*d8* species) complexes have a square-planar geometry [55]. On this background and knowing that [PdCl2(TDA)2] is the trans isomer two facts can be considered:

i. HOMO-LUMO Electron Configurations

Knowing that [PdCl2(TDA)2] and [RhCl(TDA)3] have a D2h and C2v local site symmetries respectively and taking the main rotation axis along the z cartesian axis, the Angular Overlap Model (AOM) [56] can be used to predict the HOMO-LUMO frontier orbitals in an increasing order of energy for each case:

[PdCl2(TDA)2]

144 Hydrogenation

**Figure 1.** FTIR spectra corresponding to pure TDA, [PdCl2(TDA)2] and [RhCl(TDA)3].[49]

*At this point, the complex minimum formula, on the basis of the preceding Elemental Composition,* 

)

Wavenumber (cm-1

Molecular orbitals with symmetries corresponding to the irreducible representations of the molecular point group automatically satisfy the Fock equation. For complex species the terminal atom symmetry orbital (TASO)/molecular orbitals (MO) and the metal atomic

**3.2. Palladium and rhodium local site symmetries, HOMO-LUMO electron** 

*XPS and FTIR arguments, can be expressed by [PdCl2(TDA)2] or [RhCl(TDA)3].* 

**Figure 2.** IR spectrum below 600 cm-1 for pure [PdCl2(TDA)2]. [54]

**configurations and complexes dimensions** 

Transmittance (a.u.)

Non-bonding (dxy), antibonding double degenerate 2e\*<sup>π</sup> ((dxz, dyz)\*), e\*<sup>σ</sup> ((dz2)\*) and 3e\*σ ((dx2–y2)\*) [49]. Assigning the eight electrons to this scheme, it turns out that (dz2)\* (z direction) and (dx2-y2)\* (x and y directions) are the HOMO and LUMO frontier orbitals, respectively.

[RhCl(TDA)3]

Non-bonding (dxy), antibonding double-degenerate e\*<sup>π</sup> ((dxz, dyz)\*), 7/4 e\*<sup>σ</sup> ((dz2)\*) and 9/4 e\*σ ((dx2–y2)\*). Assigning the eight electrons to this scheme, it turns out that (dz2)\* (z direction) and (dx2-y2)\* (x and y directions) are the HOMO and LUMO frontier orbitals, respectively.

The Rh(I) complex HOMO-LUMO frontier orbitals lie higher in energy than those corresponding to the Pd(II) complex because of the lower oxidation number of the central atom. The HOMO is useful to produce the cleavage of the H–H bonding, generating hydrogen atoms and the LUMO is available to receive electron density from the substrate molecule, weakening the C–C triple bond; both concepts are key factors during the catalytic cycle leading to the hydrogenation of the substrate.

ii. Complexes Dimensions

The approximate molecular size of the metal complexes can be estimated in order to study structural aspects related to their location in the supports porosity. This can be done taking into account the square planar geometry, typical covalent radii, a 109.5° C–C–C angle and basic trigonometry.


### **3.3. Supported Pd and Rh complexes structures**

Table 3 presents the BET surface area and the pore volume distribution for both supports.


Terminal and Non Terminal Alkynes Partial Hydrogenation

[49] 1-heptyne/Pd = 7.3 103 and 1-

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 147

Based on the ideas of the previous paragraph it can be stated that the anchored complexes maintain the local site symmetries around the central atoms, that is D2h for [PdCl2(TDA)2]

Besides, as the longest dimension of the coordination compounds is the same for both complexes, and according to the Al2O3 or RX3 distribution pore sizes (Table 3), it can be concluded that the species can be located only in the meso and macropores (2–7.5 and 7.5–50 nm respectively) for both supports, thus occupying ca. 88 % and 43 % of the support total

1-heptene and n-heptane were the only products detected by GC during the catalytic runs using: (1) commercial Lindlar catalyst, (2) [PdCl2(TDA)2] or [RhCl(TDA)3] (homogeneous condition), and (3) [PdCl2(TDA)2] or [RhCl(TDA)3] supported on -Al2O3 (heterogeneous condition) at 303 K, 150 kPa and 2 % v/v 1-heptyne/toluene solution. In Figures 4 and 5, the conversion (Xe) and the selectivity (Se) to 1-heptene versus 1-heptyne total conversion (XT)

**Figure 4.** Conversion to 1-heptene vs. 1-heptyne total conversion for: Lindlar catalyst, [PdCl2(TDA)2],

0 10 20 30 40 50 60 70 80 90 100 1-heptyne Total Conversion (%)

It can be seen, from Figure 4, that the catalytic systems show an initial part with an almost 45° linear slope. From that part onwards, all the systems show a similar profile shape, with increasing conversion to 1-heptene up to a maximum value, after which this variable falls.

The selectivity plots displayed in Figure 5 show a plateau-shaped behaviour in a very important range of 1-heptyne total conversion followed then by a decreasing tendency.

and C2v for [RhCl(TDA)3], with the same HOMO-LUMO electron configurations.

*3.4.1. 1-heptyne partial hydrogenation (terminal alkyne)* 

[PdCl2(TDA)2]/ -Al2O3, [RhCl(TDA)3], [RhCl(TDA)3]/ -Al2O3.

are plotted for all of the catalytic systems.

[RhCl(TDA)3]-Alum [RhCl(TDA)3]-Hom Lindlar [PdCl2(TDA)2]-Hom [PdCl2(TDA)2]-Alum

pore volume, respectively.

**3.4. Catalytic tests** 

heptyne/Rh = 7.0 103.

Conversion to 1-heptene (%)

**Table 3.** BET surface area and supports pore volume distributions.[53]

According to this information it can be remarked that RX3 possesses a SBET that is 7.84 times greater than the -Al2O3 surface area. Besides, -Al2O3 can be considered basically a mesoporous support, while RX3 has a pore volume distribution in the range of micro, supermicro and macro pores.

On the other hand, XPS results of binding energies and atomic ratios for the anchored complexes, Table 1, show that: a) Cl/M and N/M atomic ratios are equal to those obtained for the pure complexes and in total accordance with the elemental composition results for the pure complexes; and b) there is a constancy of the M 3d5/2, N 1s and Cl 2p3/2 XPS BEs with respect to the corresponding values for the pure complexes, meaning that their electronic states remain unchanged. Item a) indicates that the supported complexes may be considered as tetra-coordinated, maintaining its chemical identity after anchoring, and item b) suggests that the metal (Pd or Rh) is not in contact with the support surface. In this way, as the inductive influence of the hydrocarbon chain on the nitrogen atom is exerted up to the second/third carbon atom, the immobilization of the complexes takes place via a physicochemical interaction between the last part of the TDA molecule and the alumina or carbon basal planes, i.e. an anchoring showing a kind of "table" arrangement as seen in Figure 3.

**Figure 3.** [PdCl2(TDA)2] and [RhCl(TDA)3] anchored on -Al2O3 or RX3, "a" indicates the TDA carbon chain portion involved in the adsorption process.

Based on the ideas of the previous paragraph it can be stated that the anchored complexes maintain the local site symmetries around the central atoms, that is D2h for [PdCl2(TDA)2] and C2v for [RhCl(TDA)3], with the same HOMO-LUMO electron configurations.

Besides, as the longest dimension of the coordination compounds is the same for both complexes, and according to the Al2O3 or RX3 distribution pore sizes (Table 3), it can be concluded that the species can be located only in the meso and macropores (2–7.5 and 7.5–50 nm respectively) for both supports, thus occupying ca. 88 % and 43 % of the support total pore volume, respectively.

### **3.4. Catalytic tests**

146 Hydrogenation

Figure 3.

Sample SBET

supermicro and macro pores.

(m2 g–1)

Vmicro (mL g–1) [<0.7 nm]

**Table 3.** BET surface area and supports pore volume distributions.[53]

Vsupermicro (mL g–1) [0.7-2 nm]


According to this information it can be remarked that RX3 possesses a SBET that is 7.84 times greater than the -Al2O3 surface area. Besides, -Al2O3 can be considered basically a mesoporous support, while RX3 has a pore volume distribution in the range of micro,

On the other hand, XPS results of binding energies and atomic ratios for the anchored complexes, Table 1, show that: a) Cl/M and N/M atomic ratios are equal to those obtained for the pure complexes and in total accordance with the elemental composition results for the pure complexes; and b) there is a constancy of the M 3d5/2, N 1s and Cl 2p3/2 XPS BEs with respect to the corresponding values for the pure complexes, meaning that their electronic states remain unchanged. Item a) indicates that the supported complexes may be considered as tetra-coordinated, maintaining its chemical identity after anchoring, and item b) suggests that the metal (Pd or Rh) is not in contact with the support surface. In this way, as the inductive influence of the hydrocarbon chain on the nitrogen atom is exerted up to the second/third carbon atom, the immobilization of the complexes takes place via a physicochemical interaction between the last part of the TDA molecule and the alumina or carbon basal planes, i.e. an anchoring showing a kind of "table" arrangement as seen in

**Figure 3.** [PdCl2(TDA)2] and [RhCl(TDA)3] anchored on -Al2O3 or RX3, "a" indicates the TDA carbon

chain portion involved in the adsorption process.

Vmeso (mL g–1) [2-7.5 nm]

Vmacro (mL g–1) [7.5-50 nm]

### *3.4.1. 1-heptyne partial hydrogenation (terminal alkyne)*

1-heptene and n-heptane were the only products detected by GC during the catalytic runs using: (1) commercial Lindlar catalyst, (2) [PdCl2(TDA)2] or [RhCl(TDA)3] (homogeneous condition), and (3) [PdCl2(TDA)2] or [RhCl(TDA)3] supported on -Al2O3 (heterogeneous condition) at 303 K, 150 kPa and 2 % v/v 1-heptyne/toluene solution. In Figures 4 and 5, the conversion (Xe) and the selectivity (Se) to 1-heptene versus 1-heptyne total conversion (XT) are plotted for all of the catalytic systems.

**Figure 4.** Conversion to 1-heptene vs. 1-heptyne total conversion for: Lindlar catalyst, [PdCl2(TDA)2], [PdCl2(TDA)2]/ -Al2O3, [RhCl(TDA)3], [RhCl(TDA)3]/ -Al2O3.[49] 1-heptyne/Pd = 7.3 103 and 1 heptyne/Rh = 7.0 103.

It can be seen, from Figure 4, that the catalytic systems show an initial part with an almost 45° linear slope. From that part onwards, all the systems show a similar profile shape, with increasing conversion to 1-heptene up to a maximum value, after which this variable falls.

The selectivity plots displayed in Figure 5 show a plateau-shaped behaviour in a very important range of 1-heptyne total conversion followed then by a decreasing tendency.

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 149

Besides, depending on the central element or the physical condition two new trends can be

*From these tendencies, it can be stated that the best combination is the Rh(I) complex heterogeneous system, which is in the first place in the general trend and the worst option is the Lindlar catalyst.*

*(Z)*-3-hexene, *(E)*-3-hexene and n-hexane were the only products detected by GC during the reaction tests using the catalytic systems: (1) commercial Lindlar catalyst (2) [RhCl(TDA)3] (homogeneous condition) , and (3) [RhCl(TDA)3]/RX3 (heterogeneous condition) at 275, 290 and 303 K, 150 kPa and 2 % v/v 3-hexyne/toluene solution. In Figure 6(a) the conversions to *(Z)-*3-hexene and *(E)-*3-hexene are shown as a function of the 3-hexyne total conversion for the Lindlar catalyst and for Rh(I) homogeneous and heterogeneous complex for the three temperatures, while Figure 6(b), for the sake of clarity, is presented at the optimum temperature 303 K. It can be noted the predominant formation of the *(Z)-*alkene stereoisomer, the desired product. In this respect, it can be seen in Figure 6, that all of the catalytic systems show again an initial part with an almost linear slope, which takes a value of 45° for the [RhCl(TDA)3]/RX3 catalyst. After that initial part, all of the systems have a similar shape with an increasing 3-hexyne total conversion, showing a maximum value of conversion to *(Z)-*3-hexene. There was also a relatively low amount of the side products: *(E)-*3-hexene formed either as initial product or via *Z E* isomerization, and n-hexane (not plotted in Figure 6 because of the low values obtained and for the sake of clarity) produced either by hydrogenation of the alkyne or the alkene isomers [7,57]. Last but not least, [RhCl(TDA)3]/RX3 showed the lowest conversion values to the *(E)* isomer and to the alkane. In Figure 7, a detail from Figure 6, it can be observed that, for a given catalytic system, the variation of conversion to *(Z)-*3-hexene vs. 3-hexyne total conversion follows an increasing tendency as the temperature is raised. However, it can be noted that the performance of Rh(I) complex heterogeneous system is slightly sensitive to temperature changes while the homogeneous system and the Lindlar catalyst are considerably sensitive to temperature

For a given temperature, the [RhCl(TDA)3]/RX3 system shows the highest conversions to *(Z)-*3-hexene at the highest 3-hexyne total conversions (maximum value: X*(Z)* = 95.0% at XT =

In Figure 8 the selectivity to *(Z)*-3-hexene vs. the 3-hexyne total conversion values are presented. The selectivity plots show an initial plateau-shaped behaviour followed by a marked decreasing tendency for the increasing 3-hexyne total conversion. The [RhCl(TDA)3]/RX3 system allows to obtain a practically constant value of a very high selectivity (not lower than 98.5%) up to a very high 3-hexyne total conversion (ca. 85%); after

99.8%), followed by [RhCl(TDA)3] and then by the Lindlar catalyst.

**Physical Condition: Heterogeneous systems are better than Homogeneous systems** 

**Central Element: Rh systems are better than Pd systems** 

*3.4.2. 3-hexyne Partial Hydrogenation (Non-Terminal Alkyne)* 

written:

changes.

**Figure 5.** Selectivity to 1-heptene vs. 1-heptyne total conversion for: Lindlar catalyst, [PdCl2(TDA)2], [PdCl2(TDA)2]/ -Al2O3, [RhCl(TDA)3], [RhCl(TDA)3]/ -Al2O3.[49] 1-heptyne/Pd = 7.3 103 and 1 heptyne/Rh = 7.0 103.

On the other hand, high selectivities to 1-heptene (Se), which are obtained up to 50 min of reaction time, and their corresponding conversions to 1-heptene (Xe) and 1-heptyne total conversions (XT), are presented in Table 4.


**Table 4.** Selectivity and conversion to 1-heptene and 1-heptyne total conversion values for the catalytic systems up to 50 min of reaction. 1-heptyne/Rh = 7.0 103 and 1-heptyne/Pd = 7.3 103.

With this information, trends and selection of the best catalytic systems are drawn taking into account two factors: a) high selectivity values to 1-heptene and b) the range of 1 heptyne total conversion in which the high selectivity values are maintained.

A general trend, based on the better catalytic performances (Table 4), can be established for the involved systems:

### **[RhCl(TDA)3]/Al2O3 > [PdCl2(TDA)2]/Al2O3 > [RhCl(TDA)3] > [PdCl2(TDA)2] >> Lindlar**

*From this trend, it can be stated that [PdCl2(TDA)2] and [RhCl(TDA)3] in heterogeneous or homogeneous conditions are better options than the Lindlar catalyst for the 1-heptyne partial hydrogenation under mild operational conditions.* 

Besides, depending on the central element or the physical condition two new trends can be written:

#### **Central Element: Rh systems are better than Pd systems**

148 Hydrogenation

heptyne/Rh = 7.0 103.

Selectivity to 1-heptene (%)

the involved systems:

conversions (XT), are presented in Table 4.

[RhCl(TDA)3]-Alum [RhCl(TDA)3]-Hom Lindlar [PdCl2(TDA)2]-Hom [PdC2l(TDA)2]-Alum

*hydrogenation under mild operational conditions.* 

**Figure 5.** Selectivity to 1-heptene vs. 1-heptyne total conversion for: Lindlar catalyst, [PdCl2(TDA)2], [PdCl2(TDA)2]/ -Al2O3, [RhCl(TDA)3], [RhCl(TDA)3]/ -Al2O3.[49] 1-heptyne/Pd = 7.3 103 and 1-

0 10 20 30 40 50 60 70 80 90 100 1-heptyne Total Conversion (%)

On the other hand, high selectivities to 1-heptene (Se), which are obtained up to 50 min of reaction time, and their corresponding conversions to 1-heptene (Xe) and 1-heptyne total

Catalytic System Condition Se (%) Xe (%) XT (%)

Homogeneous 92 59.4 66.5

Homogeneous 92 54.0 67.9

[RhCl(TDA)3] Heterogeneous 92-93 73.6 80.0

[PdCl2(TDA)2] Heterogeneous 95 64.3 68.0

Lindlar Heterogeneous 92 43.2 47.1 **Table 4.** Selectivity and conversion to 1-heptene and 1-heptyne total conversion values for the catalytic

With this information, trends and selection of the best catalytic systems are drawn taking into account two factors: a) high selectivity values to 1-heptene and b) the range of 1-

A general trend, based on the better catalytic performances (Table 4), can be established for

**[RhCl(TDA)3]/Al2O3 > [PdCl2(TDA)2]/Al2O3 > [RhCl(TDA)3] > [PdCl2(TDA)2] >> Lindlar**  *From this trend, it can be stated that [PdCl2(TDA)2] and [RhCl(TDA)3] in heterogeneous or homogeneous conditions are better options than the Lindlar catalyst for the 1-heptyne partial* 

systems up to 50 min of reaction. 1-heptyne/Rh = 7.0 103 and 1-heptyne/Pd = 7.3 103.

heptyne total conversion in which the high selectivity values are maintained.

#### **Physical Condition: Heterogeneous systems are better than Homogeneous systems**

*From these tendencies, it can be stated that the best combination is the Rh(I) complex heterogeneous system, which is in the first place in the general trend and the worst option is the Lindlar catalyst.*

### *3.4.2. 3-hexyne Partial Hydrogenation (Non-Terminal Alkyne)*

*(Z)*-3-hexene, *(E)*-3-hexene and n-hexane were the only products detected by GC during the reaction tests using the catalytic systems: (1) commercial Lindlar catalyst (2) [RhCl(TDA)3] (homogeneous condition) , and (3) [RhCl(TDA)3]/RX3 (heterogeneous condition) at 275, 290 and 303 K, 150 kPa and 2 % v/v 3-hexyne/toluene solution. In Figure 6(a) the conversions to *(Z)-*3-hexene and *(E)-*3-hexene are shown as a function of the 3-hexyne total conversion for the Lindlar catalyst and for Rh(I) homogeneous and heterogeneous complex for the three temperatures, while Figure 6(b), for the sake of clarity, is presented at the optimum temperature 303 K. It can be noted the predominant formation of the *(Z)-*alkene stereoisomer, the desired product. In this respect, it can be seen in Figure 6, that all of the catalytic systems show again an initial part with an almost linear slope, which takes a value of 45° for the [RhCl(TDA)3]/RX3 catalyst. After that initial part, all of the systems have a similar shape with an increasing 3-hexyne total conversion, showing a maximum value of conversion to *(Z)-*3-hexene. There was also a relatively low amount of the side products: *(E)-*3-hexene formed either as initial product or via *Z E* isomerization, and n-hexane (not plotted in Figure 6 because of the low values obtained and for the sake of clarity) produced either by hydrogenation of the alkyne or the alkene isomers [7,57]. Last but not least, [RhCl(TDA)3]/RX3 showed the lowest conversion values to the *(E)* isomer and to the alkane.

In Figure 7, a detail from Figure 6, it can be observed that, for a given catalytic system, the variation of conversion to *(Z)-*3-hexene vs. 3-hexyne total conversion follows an increasing tendency as the temperature is raised. However, it can be noted that the performance of Rh(I) complex heterogeneous system is slightly sensitive to temperature changes while the homogeneous system and the Lindlar catalyst are considerably sensitive to temperature changes.

For a given temperature, the [RhCl(TDA)3]/RX3 system shows the highest conversions to *(Z)-*3-hexene at the highest 3-hexyne total conversions (maximum value: X*(Z)* = 95.0% at XT = 99.8%), followed by [RhCl(TDA)3] and then by the Lindlar catalyst.

In Figure 8 the selectivity to *(Z)*-3-hexene vs. the 3-hexyne total conversion values are presented. The selectivity plots show an initial plateau-shaped behaviour followed by a marked decreasing tendency for the increasing 3-hexyne total conversion. The [RhCl(TDA)3]/RX3 system allows to obtain a practically constant value of a very high selectivity (not lower than 98.5%) up to a very high 3-hexyne total conversion (ca. 85%); after

that, the selectivity decays to a value ca. 82 %. Meanwhile, in the case of [RhCl(TDA)3] and the Lindlar catalyst, high values of selectivities (ca. 89.4 and ca. 94.2 respectively) were obtained for lower 3-hexyne total conversions up to ca. 44%; then both systems show a monotonously decreasing profile shape, which is more pronounced in the case of the Lindlar catalyst.

Terminal and Non Terminal Alkynes Partial Hydrogenation

(3)

303 K

(3)

(2)

275 K 290 K

290 K 303 K

(1) (2)

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 151

40 50 60 70 80 90 100

3-hexyne Total Conversion (% )

0 10 20 30 40 50 60 70 80 90 100

3-hexyne Total Conversion (%)

**Figure 8.** Selectivity to *(Z)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar, (2) [RhCl(TDA)3], (3)

To reinforce the conclusions given in the previous paragraphs, some relevant conversion

Considering Figures 6, 7 and 8 and Table 5 the different catalytic systems can be ordered in a descendent X*(Z)*production as follows: [RhCl(TDA)3]/RX3 > [RhCl(TDA)3] >> Lindlar catalyst. Finally, for each system the higher the temperature the higher the selectivity and the higher the conversion to the *(Z)-* isomer, although the [RhCl(TDA)3]/RX3 system behaves as the less

and selectivity values for diverse reaction conditions are summarized in Table 5.

303 K

**Figure 7.** Conversion to *(Z)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3 (a detail of Figure 6 in the zone where the three systems present

275 K

(1)

290 K

275 K

the most remarkable differences).[54] 3-hexyne/Rh = 8.1 103.

 Lindlar 275 K Lindlar 290 K Lindlar 303 K Homog 275 K Homog 290 K Homog 303 K RX3 275 K RX3 290 K RX3 303 K

[RhCl(TDA)3]/RX3; (●) 275 K, (▲) 290 K, (♦) 303 K.[54] 3-hexyne/Rh = 8.1 103.

30

50

sensitive catalyst to that variable.

60

70

Selectivity to (Z)-3-hexene (%)

80

90

100

40

50

60

Conversion to (Z)-3-hexene (%)

70

80

90

100

**Figure 6.** (a) Conversion to *(Z)-*3-hexene and to *(E)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3; filled square/open square 275 K, filled triangle/open triangle 290 K, filled diamond/open diamond 303 K. Open symbols: *(E)*-3-hexene, solid symbols *(Z)*-3-hexene.[54] 3-hexyne/Rh = 8.1 103.

(b) Conversion to *(Z)-*3-hexene and to *(E)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3; at the optimum temperature 303 K. Open symbols: *(E)*-3-hexene, solid symbols *(Z)*-3-hexene.[54] 3-hexyne/Rh = 8.1 103.

Lindlar catalyst.

that, the selectivity decays to a value ca. 82 %. Meanwhile, in the case of [RhCl(TDA)3] and the Lindlar catalyst, high values of selectivities (ca. 89.4 and ca. 94.2 respectively) were obtained for lower 3-hexyne total conversions up to ca. 44%; then both systems show a monotonously decreasing profile shape, which is more pronounced in the case of the

(a)

**Figure 6.** (a) Conversion to *(Z)-*3-hexene and to *(E)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3; filled square/open square 275 K, filled triangle/open triangle 290 K, filled diamond/open diamond 303 K. Open symbols: *(E)*-3-hexene, solid

(b)

(b) Conversion to *(Z)-*3-hexene and to *(E)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3; at the optimum temperature 303 K. Open symbols:

symbols *(Z)*-3-hexene.[54] 3-hexyne/Rh = 8.1 103.

*(E)*-3-hexene, solid symbols *(Z)*-3-hexene.[54] 3-hexyne/Rh = 8.1 103.

**Figure 7.** Conversion to *(Z)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar catalyst, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3 (a detail of Figure 6 in the zone where the three systems present the most remarkable differences).[54] 3-hexyne/Rh = 8.1 103.

**Figure 8.** Selectivity to *(Z)-*3-hexene vs. 3-hexyne total conversion for: (1) Lindlar, (2) [RhCl(TDA)3], (3) [RhCl(TDA)3]/RX3; (●) 275 K, (▲) 290 K, (♦) 303 K.[54] 3-hexyne/Rh = 8.1 103.

To reinforce the conclusions given in the previous paragraphs, some relevant conversion and selectivity values for diverse reaction conditions are summarized in Table 5.

Considering Figures 6, 7 and 8 and Table 5 the different catalytic systems can be ordered in a descendent X*(Z)*production as follows: [RhCl(TDA)3]/RX3 > [RhCl(TDA)3] >> Lindlar catalyst. Finally, for each system the higher the temperature the higher the selectivity and the higher the conversion to the *(Z)-* isomer, although the [RhCl(TDA)3]/RX3 system behaves as the less sensitive catalyst to that variable.


Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 153

According to the Atomic Orbital Model (AOM) mentioned in Section 3.2, the (dz2)\* and (dx2 y2)\* are the HOMO/LUMO frontiers orbitals, respectively. The former, along the z axis with a high electron density, is ready to overlap with the hydrogen σ antibonding orbital, thus favouring H-H bond breaking and the latter, an empty orbital extended on the xy plane, is available to receive electron density from the substrate molecule triple bond, thus weakening its π bonds. These two factors, that are important in the hydrogenation catalytic cycle, will be particularly favoured in this case as the complex antibonding orbitals have considerably more metal than ligand character with a relatively high energy because of the

On the other hand, the complex bonding molecular orbitals have a predominant character from the TASO/MOs of the ligands in the coordination sphere constituted by tridecylamine (an electron donating σ species) and chloride (an electron-withdrawing σ/π species) in a 3/1 ratio what means a net electronic enrichment on the Rh atom, a fact that will also contribute to the H-H bond rupture. Besides, the TDA ligand presents another remarkable feature related to the Dispersion forces which are relevant when the TDA/solvent interaction is analyzed. This is important as soon as the TDA molecule is released, due to the trans-effect, and it is simultaneously stabilized by the solvent via a solvatation process, a fact that is

Besides, the presence of a support, either -Al2O3 or RX3, can favour the catalytic process by activating some extra substrate molecules (1-heptyne or 3-hexyne) because of their interactions with the support surface via Acid/Base Lewis or Dipersion forces for -Al2O3 or RX3 respectively. In any case, this situation turns out to be an important factor as it makes the alkyne (1-heptyne or 3-hexyne) concentration around the supported complex higher

Finally, the high selectivity values could be explained considering the interaction between the substrate triple or double bond (alkyne or alkene) with the complex species LUMO frontier orbital, and, additonally, for the heterogeneous system, with the support chemical sites. For both factors the stronger the interaction, the more favourable the hydrogenation process, but in each case a triple bond will give place to the strongest interaction. Thus, the selectivity to 1-heptene or *(Z)-*3-hexene will be kept in a very high value inasmuch as the alkyne concentration is high enough to consider the alkene hydrogenation negligible, after

On the other hand, regarding that [RhCl(NH2(CH2)12CH3)3] anchored on -Al2O3 or RX3 is the optimum catalyst, some practical-economical benefits can be mentioned: a) the easy and cheap way in which the catalyst is removed from the remaining solution after ending the hydrogenation reaction; b) the main product does not need further purification due to a possible contamination with a heavy metal compound as no complex leaching was detected; and lastly, c) there is no need for a costly temperature control due to the mild operational

greatly favoured because of the long hydrocarbon chain of the TDA ligand.

low oxidation state of the central element.

than in the bulk solution.

that the situation is reversed.

*3.5.2. Practical considerations* 

conditions.

**Table 5.** 3-hexyne total conversion (XT), conversions to *(Z)-*3-hexene (X*(Z)*) and selectivities to *(Z)-*3 hexene (S*(Z)*), *(E)-*3-hexene (S*(E)*) and n-hexane (Sn) for the following catalysts: Lindlar, [RhCl(TDA)3] complex unsupported and anchored on RX3. 3-hexyne/Rh = 8.1 103.

*It can be remarked that for the 3-hexyne (non-terminal alkyne) partial hydrogenation, [RhCl(TDA)3] is a much better option than the Lindlar catalyst to obtain the desired product.* 

### **3.5. The optimum catalytic system for both test reactions**

#### *3.5.1. Chemical considerations*

Based on the information obtained from the previous sections, it can be concluded that [RhCl(TDA)3], supported either on -Al2O3 or on RX3 in a "table" arrangement structure (Section 3.3), is the best option to carry out the 1-heptyne or 3-hexyne partial hydrogenation to obtain high conversion values. As it was said in Section 3.2, this complex has a d8 central element with a combination of ligands L'/L = 3 (L' = TDA, L = Cl), with a square planar geometry associated to a C2v local site symmetry. This type of coordination compound, at some point of the reaction mechanism, has to release one of the coordination sphere ligands; in this respect, the trans-effect series indicates that the labile ligand is TDA opposite to the Cl ligand. Some features related to the central atom, the TDA ligand, the complex coordination number, the site symmetry and the supported condition, could explain this optimum performance.

According to the Atomic Orbital Model (AOM) mentioned in Section 3.2, the (dz2)\* and (dx2 y2)\* are the HOMO/LUMO frontiers orbitals, respectively. The former, along the z axis with a high electron density, is ready to overlap with the hydrogen σ antibonding orbital, thus favouring H-H bond breaking and the latter, an empty orbital extended on the xy plane, is available to receive electron density from the substrate molecule triple bond, thus weakening its π bonds. These two factors, that are important in the hydrogenation catalytic cycle, will be particularly favoured in this case as the complex antibonding orbitals have considerably more metal than ligand character with a relatively high energy because of the low oxidation state of the central element.

On the other hand, the complex bonding molecular orbitals have a predominant character from the TASO/MOs of the ligands in the coordination sphere constituted by tridecylamine (an electron donating σ species) and chloride (an electron-withdrawing σ/π species) in a 3/1 ratio what means a net electronic enrichment on the Rh atom, a fact that will also contribute to the H-H bond rupture. Besides, the TDA ligand presents another remarkable feature related to the Dispersion forces which are relevant when the TDA/solvent interaction is analyzed. This is important as soon as the TDA molecule is released, due to the trans-effect, and it is simultaneously stabilized by the solvent via a solvatation process, a fact that is greatly favoured because of the long hydrocarbon chain of the TDA ligand.

Besides, the presence of a support, either -Al2O3 or RX3, can favour the catalytic process by activating some extra substrate molecules (1-heptyne or 3-hexyne) because of their interactions with the support surface via Acid/Base Lewis or Dipersion forces for -Al2O3 or RX3 respectively. In any case, this situation turns out to be an important factor as it makes the alkyne (1-heptyne or 3-hexyne) concentration around the supported complex higher than in the bulk solution.

Finally, the high selectivity values could be explained considering the interaction between the substrate triple or double bond (alkyne or alkene) with the complex species LUMO frontier orbital, and, additonally, for the heterogeneous system, with the support chemical sites. For both factors the stronger the interaction, the more favourable the hydrogenation process, but in each case a triple bond will give place to the strongest interaction. Thus, the selectivity to 1-heptene or *(Z)-*3-hexene will be kept in a very high value inasmuch as the alkyne concentration is high enough to consider the alkene hydrogenation negligible, after that the situation is reversed.

### *3.5.2. Practical considerations*

152 Hydrogenation

50

120

Reaction

Lindlar

[RhCl(TDA)3]

[RhCl(TDA)3]/RX3

Lindlar

[RhCl(TDA)3]

[RhCl(TDA)3]/RX3

*3.5.1. Chemical considerations* 

optimum performance.

complex unsupported and anchored on RX3. 3-hexyne/Rh = 8.1 103.

*is a much better option than the Lindlar catalyst to obtain the desired product.* 

**3.5. The optimum catalytic system for both test reactions** 

time (min) Catalyst T (K) XT (%) X*(Z)* (%) S*(Z)* (%) S*(E)* (%) Sn (%)

**Table 5.** 3-hexyne total conversion (XT), conversions to *(Z)-*3-hexene (X*(Z)*) and selectivities to *(Z)-*3 hexene (S*(Z)*), *(E)-*3-hexene (S*(E)*) and n-hexane (Sn) for the following catalysts: Lindlar, [RhCl(TDA)3]

*It can be remarked that for the 3-hexyne (non-terminal alkyne) partial hydrogenation, [RhCl(TDA)3]* 

Based on the information obtained from the previous sections, it can be concluded that [RhCl(TDA)3], supported either on -Al2O3 or on RX3 in a "table" arrangement structure (Section 3.3), is the best option to carry out the 1-heptyne or 3-hexyne partial hydrogenation to obtain high conversion values. As it was said in Section 3.2, this complex has a d8 central element with a combination of ligands L'/L = 3 (L' = TDA, L = Cl), with a square planar geometry associated to a C2v local site symmetry. This type of coordination compound, at some point of the reaction mechanism, has to release one of the coordination sphere ligands; in this respect, the trans-effect series indicates that the labile ligand is TDA opposite to the Cl ligand. Some features related to the central atom, the TDA ligand, the complex coordination number, the site symmetry and the supported condition, could explain this

275 48 44 92 3 5 290 53 49 93 3 4 303 57 53 93 4 3

275 76 61 79 13 8 290 81 64 80 13 7 303 82 69 84 13 3

275 87 85 98 2 0.3 290 89 87 98 2 0.3 303 92 90 98 1.5 0.5

275 60 46 77 6 17 290 66 45 68 9 23 303 73 44 61 11 28

275 94 55 58 21 21 290 98 58 59 20 21 303 98 62 64 20 16

275 99.9 82 82 9 9 290 99.9 81 81 8 11 303 99.9 82 82 8 10

> On the other hand, regarding that [RhCl(NH2(CH2)12CH3)3] anchored on -Al2O3 or RX3 is the optimum catalyst, some practical-economical benefits can be mentioned: a) the easy and cheap way in which the catalyst is removed from the remaining solution after ending the hydrogenation reaction; b) the main product does not need further purification due to a possible contamination with a heavy metal compound as no complex leaching was detected; and lastly, c) there is no need for a costly temperature control due to the mild operational conditions.

### **4. Conclusions**

Experimental results demonstrate that [PdCl2(NH2(CH2)12CH3)2] and [RhCl(NH2(CH2)12CH3)3], *d8* transition metal complexes, can be used as catalysts to partially hydrogenate 1-heptyne and 3-hexyne (terminal and non-terminal alkynes respectively) in homogeneous and heterogeneous systems (-Al2O3 and RX3 as supports) at mild operational conditions (P = 150 kPa and T up to 303K) with very good catalytic performances even better than the Lindlar catalyst. Analyses based on Elemental Composition, XPS, IR, Atomic Absorption Spectroscopy show that the active catalytic species is the complex itself in each case, with a minimum formula as written above.

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 155

[3] Mastalir A, Király Z (2003) Pd nanoparticles in hydrotalcite: mild and highly selective

[4] Marín-Astorga N, Pecchi G, Fierro JLG, Reyes P (2003) Alkynes hydrogenation over Pd-

[5] Semagina N, Kiwi-Minsker L (2009) Palladium Nanohexagons and Nanospheres in

[6] Choudary BM, Kantam ML, Reddy NM, Rao KK, Haritha Y, Bhaskar V, Figueras F, Tuel A (1999) Hydrogenation of acetylenics by Pd-exchanged mesoporous materials. App.

[7] Li F, Yi X, Fang W (2009) Effect of Organic Nickel Precursor on the Reduction Performance and Hydrogenation Activity of Ni/Al2O3 Catalysts. Catal. Lett. 130:335-340. [8] Gruttadauria M, Noto R, Deganello G, Liotta LF (1999) Efficient semihydrogenation of the C-C triple bond using palladium on pumice as catalyst. Tetrahedron Lett. 40:2857-

[9] Lennon D, Marshall R, Webb G, Jackson SD (2000) The effects of hydrogen concentration on propyne hydrogenation over a carbon supported palladium catalyst studied under

[10] Lindlar H, Dubuis R, Jones FN, McKusick FC (1973) Palladium catalyst for partial

[11] Yu J, Spencer JB (1998) Discovery that quinoline and triphenylphosphine alter the

[12] Nijhuis TA, van Koten G, Kapteijn F, Moulijn JA (2003) Separation of kinetics and masstransport effects for a fast reaction: the selective hydrogenation of functionalized

[13] Huang W, Li A, Lobo RF, Chen JG (2009) Effects of Zeolite Structures, Exchanged Cations, and Bimetallic Formulations on the Selective Hydrogenation of Acetylene Over

[14] Badano JM, Quiroga M, Betti C, Vera C, Canavese S, Coloma-Pascual F (2010) Resistence To Sulfur And Oxygenated Compounds Of Supported Pd, Pt, Rh, Ru

[15] Nijhuis TA, van Koten G, Moulijn JA (2003) Optimized palladium catalyst systems for selective liquid-phase hydrogenation of functionalized alkynes. App. Catal. A: Gen. 238:

[16] Chen JG, Qi S-T, Humbert MP, Menning CA, Zhu Y-X (2010) Rational design of lowtemperature hydrogenation catalysts: Theoretical predictions and experimental

[17] Shiju RN, Guliants VV (2009) Recent developments in catalysis using nanostructured

[18] Volpe MA, Rodríguez P, Gigola CE (1999) Preparation of Pd/Pb/α-Al2O3 catalysts for selective hydrogenation using PbBu4: the role of metal-support boundary atoms and the

electronic properties of hyfrogenation catalysts. Chem. Comm. 1103-1104

catalysts for alkyne semihydrogenation. J. Catal. 220: 372-381.

Selective Alkyne Hydrogenation. Catal. Lett. 127 (3–4):334-338.

continuous flow conditions. Stud. Surf. Sci. Catal. 130: 245-250.

reduction of acetylenes. Org. Synth. Coll. 5: 880.

Zeolite-Supported Catalysts. Catal. Lett. 130: 380-385.

verification. Acta Phys. Chim. Sin. 26 (4): 869-876.

formation of a stable surface complex. Catal. Lett. 61: 27-32

materials. Appl. Catal. A: Gen. 356: 1-17.

alkynes. Catal. Today 79–80: 315-321.

Catalysts. Catal. Lett. 137: 35-44.

supported catalysts. Catal. Lett. 91 (1–2):115-121.

Catal. A; Gen. 181:139-144.

2858.

259-271.

Tetracoordinated electron-rich transition elements, as well as the presence and the relative quantity of a good electron donating ligand such as NH2(CH2)12CH3 with a long-chain hydrocarbon substituent and the heterogeneous condition, contribute to obtain a catalytic system with a high activity and selectivity performance. According to this and supported by experimental results, the optimum catalyst turns out to be [RhCl(NH2(CH2)12CH3)3] supported either on -Al2O3 or RX3. This behaviour can be understood in terms of Coordination Sphere parameters, Complex Dimensions, Local Site Symmetry, HOMO/LUMO frontier orbitals and some Support features

### **Author details**

Domingo Liprandi1,\*, Edgardo Cagnola1, Cecilia Lederhos2, Juan Badano2 and Mónica Quiroga1,2 *1Inorganic Chemistry, Departament of Chemistry, Faculty of Chemical Engineering, National University of Litoral (UNL), Santa Fe, Argentina, 2Institute of Catalysis and Petrochemistry Research, INCAPE (CONICET- UNL), Santa Fe, Argentina* 

### **Acknowledgement**

UNL and CONICET financial supports are greatly acknowledged.

### **5. References**


<sup>\*</sup> Corresponding Author

[3] Mastalir A, Király Z (2003) Pd nanoparticles in hydrotalcite: mild and highly selective catalysts for alkyne semihydrogenation. J. Catal. 220: 372-381.

154 Hydrogenation

**4. Conclusions** 

formula as written above.

**Author details** 

**Acknowledgement** 

**5. References** 

Corresponding Author

 \*

*Argentina* 

frontier orbitals and some Support features

*University of Litoral (UNL), Santa Fe, Argentina,* 

Juan Badano2 and Mónica Quiroga1,2

App.Catal. A: Gen. 280:17-46.

Wiley-VCH, Darmstadt, p 375

Domingo Liprandi1,\*, Edgardo Cagnola1, Cecilia Lederhos2,

UNL and CONICET financial supports are greatly acknowledged.

Experimental results demonstrate that [PdCl2(NH2(CH2)12CH3)2] and [RhCl(NH2(CH2)12CH3)3], *d8* transition metal complexes, can be used as catalysts to partially hydrogenate 1-heptyne and 3-hexyne (terminal and non-terminal alkynes respectively) in homogeneous and heterogeneous systems (-Al2O3 and RX3 as supports) at mild operational conditions (P = 150 kPa and T up to 303K) with very good catalytic performances even better than the Lindlar catalyst. Analyses based on Elemental Composition, XPS, IR, Atomic Absorption Spectroscopy show that the active catalytic species is the complex itself in each case, with a minimum

Tetracoordinated electron-rich transition elements, as well as the presence and the relative quantity of a good electron donating ligand such as NH2(CH2)12CH3 with a long-chain hydrocarbon substituent and the heterogeneous condition, contribute to obtain a catalytic system with a high activity and selectivity performance. According to this and supported by experimental results, the optimum catalyst turns out to be [RhCl(NH2(CH2)12CH3)3] supported either on -Al2O3 or RX3. This behaviour can be understood in terms of Coordination Sphere parameters, Complex Dimensions, Local Site Symmetry, HOMO/LUMO

*1Inorganic Chemistry, Departament of Chemistry, Faculty of Chemical Engineering, National* 

*2Institute of Catalysis and Petrochemistry Research, INCAPE (CONICET- UNL), Santa Fe,* 

[1] Chen B, Dingerdissen U, Krauter JGE, Lansink Rotgerink HGJ, Móbus K, Ostgard DJ, Panste P, Riermeir TH, Seebald S, Tacke T, Trauthwein H (2005) New developments in hydrogenation catalysis particularly in synthesis of fine and intermediate chemicals.

[2] Elsevier CJ, Kluwer AM (2007) Homogeneous hydrogenation of alkynes and dienes. In: de Vries JG, Elsevier CJ (eds) Handbook of homogeneous hydrogenation. vol 1, ch 14.


[19] Zhang W, Li L, Du Y, Wang X, Yang P (2009) Gold/Platinum Bimetallic Core/Shell Nanoparticles Stabilized by a Fréchet-Type Dendrimer: Preparation and Catalytic Hydrogenations of Phenylaldehydes and Nitrobenzenes. Catal. Lett. 127 (3–4): 429-436.

Terminal and Non Terminal Alkynes Partial Hydrogenation

Catalyzed by Some *d8* Transition Metal Complexes in Homogeneous and Heterogeneous Systems 157

[35] Halpern J (1968) in: Homogeneous Catalysis. American Chemical Society: Chap. 1. [36] Kolthoff IM, Sandell EB, Meehan EJ, Bruckenstein S (1969) Quantitative Chemical

[38] Vogel AI (1951) A Text Book of Quantitative Inorganic Analysis, Longmans, Green and

[39] Livingstone S, in: Bailar JC Jr, Emeléus H., Nyholm R, Trotman-Dickenson AF (Eds.) (1973) The Chemistry of Ruthenium, Rhodium, Palladium, Osmium, Iridium and

[40] Mallat T, Petrov J, Szabó S, Sztatisz J (1985) Palladium–cobalt catalyst: phase structure and activity in liquid phase hydrogenations. Reac. Kinet. Catal. Lett. 29: 353-361.

[43] Nakamoto K (1986) Infrared and Raman Spectra of Inorganic and Coordination

[44] Silverstein RM, Clayton Basler G, Morril TC, Spectrometric Identification of Organic

[46] Rodríguez-Reinoso F, Linares-Solano A (1988) in: Chemistry and Physics of Carbon,

[47] Holland FA, Chapman FS (1976) Liquid Mixing and Processing in Stirred Tanks,

[49] Quiroga M, Liprandi D, Cagnola E, L'Argentière P (2007) 1-heptyne semihydrogenation catalyzed by palladium or rhodium complexes. Influence of: metal atom, ligands and

[50] Wagner CD, Riggs WM, Davis RD, Moulder JF (1978). In Handbook of X-ray Photoelectron Spectroscopy. Muilenberg. G.E., Ed. Perkin-Elmer: Eden Preirie, MN. [51] NIST X-ray Photoelectron Spectroscopy Database NIST Standard Reference Database 20, Version 3.5 (Web Version), National Institute of Standards and Technology, USA,

[52] Liprandi DA, Cagnola EA, Paredes JF, Badano JM, Quiroga M E (2012) A High (Z)/(E) Ratio Obtained During the 3-Hexyne Hydrogenation with a Catalyst Based on a Rh(I)

[53] L'Argentiere P, Quiroga M, Liprandi D, Cagnola E., Román Martínez MC, Díaz Auñón JA, Salinas Martínez de Lecea C. (2003) Activated carbon heterogenized [PdCl2(NH2(CH2)12CH3)2] for the selective hydrogenation of 1-heptyne. Catal. Lett. 87:

[54] Liprandi DA, Cagnola E A, Quiroga M E, L'Argentière PC (2009) Influence of the Reaction Temperature on the 3-Hexyne Semi-Hydrogenation Catalyzed by a

[55] Cotton FA, Wilkinson G (1988) Advanced Inorganic Chemistry, fifth ed, John Wiley and

Complex Anchored on a Carbonaceous Support. Catal. Lett. 142: 231–237.

Palladium(II) Complex. Catal. Lett. 128: 423–433

Sons, New York, pp 901-902.

Platinum, Comprehensive Inorganic Chemistry, Pergamon Press, Oxford.

[41] Borade R, Sayari A, Adnot A, Kaliaguine S (1990) J. Phys. Chem. 94: 5989.

[45] Pouchert CJ (1981) The Aldrich Library of Infrared Spectra Ed. (III): 1562 D.

[48] Le Page JF (1978) Catalyse de Contact, Editions Technip, Paris, Chap 2.

the homo/heterogeneous condition. Appl. Catal. A: Gen. 326:121–129.

[42] Scofield JH (1976) J. Electron. Spectrosc. Relat. Phenom. 8: 129.

Compounds, 4th Ed., Wiley, New York, parts I and III.

Compounds, 5th Ed. Wiley, New York, 1991, chapter III.

Vol. 21, Walker PL Jr. (Ed) ,Marcel Dekker, New York p1.

Reinhold, New York, Chap 5.

2007.

97 – 101.

Analysis, fourth ed., Interscience Publishers, New York. [37] Anderson SN, Basolo F (1963) Inorg. Synth. 7: 214-220.

Co, London.


hexyne. J. Catal. 279: 66-74.

667: 197-208.

Tod. 93-95: 445-450.

Chem. 197 (1-2): 37-50.

Gen. 274: 205-212.

152.

Technol .Biotechnol. 71: 285-290.

Ind. Eng. Chem. Res. 41: 4906-4910

alkynes. J. Molec. Catal. A: Chem. 178: 21-26.

Tetrahedron Lett. 29 (43): 5545-5548.

alkenes and 4-alkynes. Tetrahedron 58: 3911-3922.

[19] Zhang W, Li L, Du Y, Wang X, Yang P (2009) Gold/Platinum Bimetallic Core/Shell Nanoparticles Stabilized by a Fréchet-Type Dendrimer: Preparation and Catalytic Hydrogenations of Phenylaldehydes and Nitrobenzenes. Catal. Lett. 127 (3–4): 429-436. [20] Choi J, Yoon NM (1996) An excellent nickel boride catalyst for the cis-selective

[21] Crespo-Quesada M, Dykeman RR, Laurenczy G, Dyson PJ, Kiwi-Minsker L (2011) Supported nitrogen-modified Pd nanoparticles for the selective hydrogenation of 1-

[22] Costa M, Pelagatti P, Pelizzi C, Rogolino D (2002) Catalytic activity of palladium(II) complexes with tridentate nitrogen ligands in the hydrogenation of alkenes and

[23] de Wolf E, Spek AL, Kuipers BWM, Philipse AP, Meeldijk JD, Bomans PHH, Frederik P.M., Deelman B.J., van Koten G. (2002) "Fluorous derivatives of [Ru(COD)(dppe)]BX4 (X=F, Ph): synthesis, physical studies and application in catalytic hydrogenation of 1-

[24] Edvrard D, Groison K, Mugnier Y, Harvey PD (2004) The Pd4(dppm)4(H)22+ cluster: a precatalyst for the homogeneous hydrogenation of alkynes. Inorg. Chem. 43: 790-796. [25] Frediani P, Giannelli C, Salvini A, Ianelli S (2003) Ruthenium complexes with 1,1' biisoquinoline as ligands. Synthesis and hydrogenation activity. J. Organomet. Chem.

[26] Kerr JM, Suckling CJ (1988) Selective hydrogenation by novel palladium(II) complex.

[27] Park JW, Chung YM, Suh YW, Rhee HK (2004) Partial hydrogenation of 1,3 cyclooctadiene catalyzed by palladium-complex catalysts inmobilized on silica. Catal.

[28] Santra PK, Sagar P (2003) Dihydrogen reduction of nitroaromatics, alkenes, alkynes using Pd(II) complexes both in normal and high pressure conditions. J. Molec. Catal. A:

[29] L'Argentière PC, Cagnola EA, Cañón MG, Liprandi DA, Marconetti DV (1998), A nickel tetra-coordinated complex as catalyst in heterogeneous hydrogenation. J. Chem.

[30] Quiroga ME, Cagnola EA, Liprandi DA, L'Argentière PC (1999) Supported Wilkinson's complex used as a high active hydrogenation catalyst. J. Mol. Catal. A: Chem. 149: 147-

[31] Liprandi DA, Quiroga ME, Cagnola EA, L'Argentière PC (2002) A new more sulfurresistannt rhodium complex as an alternative to the traditional Wilkinson's catalyst.

[32] Cagnola EA, Quiroga ME, Liprandi DA, L'Argentière PC (2004) Immobilized Rh, Ru, Pd and Ni complexes as catalysts in the hydrogenation of cyclohexene. Appl. Catal.. A:

[33] Hamilton CA, Jackson SD, Kelly GJ, Spence R, Bruin D (2002) Competitive Reactions in

Alkyne Hydrogenation. App. Catal. A: Gen. 237: 201-209.

[34] Bailar J C, (ed) (1975) Comprehensive Inorganic Chemistry. Vol 3, p. 1234.

semihydrogenation of acetylenes. Tetrahedron Lett. 37 (7): 1057-1060.


[56] Purcell KF, Kotz JC (1977) Inorganic Chemistry, Holt-Saunders International Editions: Philadelphia, pp 543-549.

**Chapter 7** 

© 2012 Maccarrone et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Maccarrone et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Kinetic Study of the Partial Hydrogenation of** 

M. Juliana Maccarrone, Gerardo C. Torres, Cecilia Lederhos, Carolina Betti,

Selective hydrogenation reactions are industrially used for the partial hydrogenation of unsaturated organic compounds in order to form more stable products or intermediate materials for different processes. The production of final organic products of high added value or intermediate compounds for the synthesis of fine chemicals is both of industrial and academic importance [1]. Alkenes are much appreciated products used in the food industry (flavours), the pharmaceutical industry (sedatives, anesthetises, vitamins) and in the perfumes industry (fragrances). They are also used for the production of biologically

The partial hydrogenation of acetylenic compounds using homogeneous or heterogeneous metallic catalysts provides a very viable and economically feasible way for the obtaining of these olefinic compounds. Selective catalysts and optimum operational conditions are necessary in order to avoid the complete hydrogenation of the unsaturated bond. Certain transition metals anchored on different solids have demonstrated to be very active and selective catalysts for this type of reaction. They also have the advantage that they can be operated under milder reaction conditions. It is well documented that palladium is a highly active catalyst for hydrogenation [3]. In this sense, Lindlar catalyst (Pd/CaCO3, 5 wt % of Pd modified with Pb(OAc)2) has been used since 1952 as an excellent commercial catalyst for this type of reactions [4]. The argued reasons for the differences in reactivity of Pd indicate that when the metal is electron deficient it becomes less active because alkynes are more

During decades a lot of research has been carried out modifying this type of catalysts in order to increase the activity and selectivity: different supports as alumina, coal, silica [5-7] have been tried while modified palladium [8], or nanoparticles of Pd have also been

Juan M. Badano, Mónica Quiroga and Juan Yori

active compounds [2], resins, polymers and lubricants, etc.

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/48699

**1. Introduction** 

weakly adsorbed [5].

**1-Heptyne over Ni and Pd Supported on Alumina** 

[57] Papp A, Molnár A, Mastalir A (2005) Catalytic investigation of Pd particles supported on MCM-41 for the selective hydrogenations of terminal and internal alkynes. Appl. Catal. A: Gen. 289: 256-266.
