**5. Organic synthesis in the presence of illuminated semiconductors**

Although semiconductor materials like as TiO2 have been extensively applied in the environmental field in order to mineralize organic pollutants, their application as tool for the organic synthesis has been also investigated. Recently, some reviews on this field have been published (Gambarotti, 2010; Pastori, 2009; Shiraishi, 2008; Anpo & Kamat, 2010). Herein we report some examples taken from the literature which can be used to take a view on the recent state of the art.

### **5.1 TiO2 in organic photosynthesis**

The selective oxidation of hydrocarbons under mild conditions is an important industrial and scientific challenge because relatively cheap feedstocks are converted into highly valueadded products.

#### **5.1.1 Synthesis of phenol derivatives**

Phenol is an highly important chemical intermediate because it is used in a large number of different sectors including the production of phenolic resins, caprolactam, aniline, alkylphenols, diphenols, and salicylic acid (Weber et al., 2005). It is produced from benzene mainly through the cumene process (Hock process). Currently, in the USA and Western Europe, about 20 % of the total benzene production is consumed for the synthesis of phenol (Weissermel & Arpe, 1997). In the last years interests have aroused for the direct production of phenol from benzene, despite these proposed processes are still not effective and competitive if compared with the classic procedures (Bal et al., 2006; Guo et al., 2009; Tani et al., 2005; Tlili et al., 2009). Among them, photocatalytic processes, in particular based on the use of semiconductors, gained attention both in industriy and academy as an economically and environmentally favourable approach (Chen et al., 2009). Recently, Molinari and coworkers reported the direct benzene conversion to phenol in a hybrid photocatalytic membrane reactor (Molinari et al., 2009a). The authors used TiO2 Degussa P25 as catalyst to promote the oxidation of benzene to phenol in water under UV irradiation (λ = 366 nm, power = 6.0 mW cm-2). The particularity was the adoption of a membrane reactor having two compartments, one containing the aqueous phase, in which TiO2 and benzene were

Semiconductors in Organic Photosynthesis 93

activity of TiO2 in the anatase form performing the oxidation of benzene in water under 300 W Xe-arc lamp irradiation for 24 h. The catalyst indicated with TiO2@MCF consists of TiO2 crystals incorporated in the MCF structure. Such crystals had a size of 9 nm, lower than the corresponding ones of the simply TiO2 (16 nm). The surface area (SBET) of TiO2@MCF (29.5 wt % of TiO2) was 637 m2g-1. In order to increase the hydrophobicity of the catalyst, TiO2@MCF was treated with triethoxymethylsilane (TMS) getting the material TiO2@MCF/CH3 (TiO2 wt %: 21.7, SBET: 450 m2g-1). Finally, the methylsilyl groups grafted on the TiO2 surface were selectively removed by post UV-irradiation treatment obtaining the catalyst TiO2@MCF/CH3/UV (TiO2 wt %: 23.3, SBET: 491 m2g-1). The authors found that TiO2@MCF had better performances than TiO2 with regard to both the phenol yield (YP, mmol phenol / g TiO2) and the phenol selectivity (SP, %). In particular YP increased from about 10 mmol/g TiO2 for TiO2 to about 35 mmol/g TiO2 for TiO2@MCF. Similarly an increase of SP was observed (from 15.8 to 22.2 %). Upon silylating TiO2@MCF, a reduction of the catalytic performance is experienced (YP is lower than the correspond value of TiO2, while SP remains practically similar to the value of TiO2@MCF, essentially because the active TiO2 surface sites were blocked by the methylsilyl groups in TiO2@MCF/CH3. The removal of such groups by UV irradiation allows to recover the catalytic properties. In fact TiO2@MCF/CH3/UV gave a YP

O- OH

h+ H2O

O

above 50 mmol/g TiO2 while SP is about 35 %.

O2

O2 -

e-

vis. light

TiO2

Fig. 9. Proposed mechanism for the photooxidation of benzene

e-

SPR effect

Au filled states

The photocatalytic activity of TiO2 can be modified by depositing noble metal nanoparticles on the particles surface. This is the case of the work of Zheng et al (Zheng et al., 2011). The authors developed a noble-metal plasmonic photocatalyst effective for the oxidation of benzene to give phenol under visible light irradiation. Three different noble metal were used: Pt, Au and Ag. Between them Au@TiO2 microsphere having 2 wt % of Au showed the best catalytic

e-

empty states

dispersed, and the other one containing the organic phase, consisting on benzene, whose role was to remove phenol, produced during the photocatalysis, from the aqueous phase. The membrane was a hydrophobic polypropylene porous flat sheet. The authors claimed that the system allowed the production of the phenol and its separation, although the formation of intermediate oxidation by-products, like benzoquinone, hydroquinone and other oxidized molecules was observed.

Recently Zhang et al. (Zhang et al., 2011) reported the selective photocatalytic conversion of benzene to phenol by using titanium oxide nanoparticles incorporated in hydrophobically modified mesocellular siliceous foams (MCF) as shown in Fig. 8.

Fig. 8. Titanium oxide entrapped in the cagelike mesopores of hydrophobically modified MCF for the hydroxylation of benzene

Generally, the hydroxyl radicals generated during the photo-illumination of the TiO2 crystals are highly reactive and unselective causing a large formation of secondary by-products. The main characteristic of this method is based on the hydrophobicity of the MCF, for that benzene is preferentially attracted into the hydrophobic mesopores while the more hydrophilic phenol is rapidly release from the cavity before it undergoes further oxidation. In this way an increase in the selectivity is obtained. In particular, the authors compared the catalytic activity of three materials (TiO2@MCF, TiO2@MCF/CH3, TiO2@MCF/CH3/UV) with the corresponding

dispersed, and the other one containing the organic phase, consisting on benzene, whose role was to remove phenol, produced during the photocatalysis, from the aqueous phase. The membrane was a hydrophobic polypropylene porous flat sheet. The authors claimed that the system allowed the production of the phenol and its separation, although the formation of intermediate oxidation by-products, like benzoquinone, hydroquinone and

Recently Zhang et al. (Zhang et al., 2011) reported the selective photocatalytic conversion of benzene to phenol by using titanium oxide nanoparticles incorporated in hydrophobically

Fig. 8. Titanium oxide entrapped in the cagelike mesopores of hydrophobically modified

Generally, the hydroxyl radicals generated during the photo-illumination of the TiO2 crystals are highly reactive and unselective causing a large formation of secondary by-products. The main characteristic of this method is based on the hydrophobicity of the MCF, for that benzene is preferentially attracted into the hydrophobic mesopores while the more hydrophilic phenol is rapidly release from the cavity before it undergoes further oxidation. In this way an increase in the selectivity is obtained. In particular, the authors compared the catalytic activity of three materials (TiO2@MCF, TiO2@MCF/CH3, TiO2@MCF/CH3/UV) with the corresponding

other oxidized molecules was observed.

MCF for the hydroxylation of benzene

modified mesocellular siliceous foams (MCF) as shown in Fig. 8.

activity of TiO2 in the anatase form performing the oxidation of benzene in water under 300 W Xe-arc lamp irradiation for 24 h. The catalyst indicated with TiO2@MCF consists of TiO2 crystals incorporated in the MCF structure. Such crystals had a size of 9 nm, lower than the corresponding ones of the simply TiO2 (16 nm). The surface area (SBET) of TiO2@MCF (29.5 wt % of TiO2) was 637 m2g-1. In order to increase the hydrophobicity of the catalyst, TiO2@MCF was treated with triethoxymethylsilane (TMS) getting the material TiO2@MCF/CH3 (TiO2 wt %: 21.7, SBET: 450 m2g-1). Finally, the methylsilyl groups grafted on the TiO2 surface were selectively removed by post UV-irradiation treatment obtaining the catalyst TiO2@MCF/CH3/UV (TiO2 wt %: 23.3, SBET: 491 m2g-1). The authors found that TiO2@MCF had better performances than TiO2 with regard to both the phenol yield (YP, mmol phenol / g TiO2) and the phenol selectivity (SP, %). In particular YP increased from about 10 mmol/g TiO2 for TiO2 to about 35 mmol/g TiO2 for TiO2@MCF. Similarly an increase of SP was observed (from 15.8 to 22.2 %). Upon silylating TiO2@MCF, a reduction of the catalytic performance is experienced (YP is lower than the correspond value of TiO2, while SP remains practically similar to the value of TiO2@MCF, essentially because the active TiO2 surface sites were blocked by the methylsilyl groups in TiO2@MCF/CH3. The removal of such groups by UV irradiation allows to recover the catalytic properties. In fact TiO2@MCF/CH3/UV gave a YP above 50 mmol/g TiO2 while SP is about 35 %.

Fig. 9. Proposed mechanism for the photooxidation of benzene

The photocatalytic activity of TiO2 can be modified by depositing noble metal nanoparticles on the particles surface. This is the case of the work of Zheng et al (Zheng et al., 2011). The authors developed a noble-metal plasmonic photocatalyst effective for the oxidation of benzene to give phenol under visible light irradiation. Three different noble metal were used: Pt, Au and Ag. Between them Au@TiO2 microsphere having 2 wt % of Au showed the best catalytic

Semiconductors in Organic Photosynthesis 95

(Liu et al., 2010). Indeed, it has been reported that water molecules undergo spontaneous dissociative adsorption on clean anatase {001} forming hydrogen peroxide and peroxyl

More complex functionalizations of aromatic hydrocarbons have also been promoted by TiO2. For example the perfluoroalkylation of arenes and α-methylstyrene derivatives in acetonitrile using titanium oxide as photocatalyst and in presence of alcohols and NaBF4 has been reported (Eq. 4, Iizuka & Yoshida, 2009). The electrons in the conduction band of TiO2 can reduce the perfluoroalkyl iodide forming a perfluoroalkyl radical and iodide ion. The resulting radical reacts with the arene forming an arenium radical, which is successively oxidized to the corresponding arenium cation by the action of the holes providing at the end the product. Different alcohols were considered. The best performances were obtained with methanol and ethanol while 2-propanol gave lower conversions and selectivities in the desidered products. Both alcohol and NaBF4 may act as modulators of the red-ox network in

Heterocyclic compounds have also been synthesized through the use of TiO2. Shiraishi and co-workers investigated a one-pot synthesis of benzimidazoles by simultaneous photocatalytic and catalytic reactions on Pt@TiO2 nanoparticles (Shiraishi et al., 2010). A number of *ortho*-arylenediamines were converted to their corresponding benzimidazoles by Pt@TiO2 catalyzed reaction with different alcohols at 303 K for 30 min under UV irradiation (xenon lamp, 2 kW; light intensity, 18.2 Wm-2 at 300 – 400 nm) using, in some cases, MeCN as co-solvent. A comparison between Pt@TiO2 and a commercial TiO2 similar to Degussa P25 (JRC-TIO-4 TiO2 from the Catalyst Society of Japan with a anatase/rutile = 8:2) was reported, showing a significant improvement in both conversions (> 99%) and yields (generally above 80 % with different cases where the yield was above 95 %) after using Pt@TiO2 (Eq. 5). The UV-light excite TiO2 creating e-/h+ pairs. The hole pairs oxidize the alcohol to the corresponding aldehyde on the surface of the TiO2. The aldehyde spontaneously condense with the arylenediamine forming an imine intermediate, which undergoes cyclization furnishing a benzimidazoline. This last one is finally fast oxidized to the product by the catalytic action of Pt. In this way Pt@TiO2 has a double role: it works as *photocatalyst* in the oxidation of the alcohol and works as *catalyst* (due the presence of Pt) in the conversion of the benzimidazoline to the benzimidazole. Indeed, if Pt were not present the fast step from **5** to **2** (Eq. 6) would not be possible, allowing the shifting of the equilibrium **4**-**5** toward **4**. So, a further aldehyde molecule would condense giving the

(4)

radicals which are then involved in the degradative process (Selloni, 2008).

**5.1.2 Other hydrocarbon functionalizations** 

particular reducing the hole-electron recombination process.

diimine **3** which finally furnishes the by-product **6**.

performance (Au > Pt >> Ag) giving high yield (above 60 %) and selectivity (about 90 %). Such results were obtained irradiating the reacting mixture (phenol (0.06 g) dissolved in 50 mL of deionized water (50 mL) with benzene (0.07 mL) and the catalyst (50 mg)) with a 300 W Xe arc lamp for a variable time (up to 5 h). No reaction was observed when metal-free TiO2 microspheres were used because the visible light ( ≥ 400 nm) cannot excite TiO2 (band-gap 3.2 eV). In Fig. 9 it is shown the mechanism proposed by the authors to explain the photooxidation of benzene into phenol in the presence of an initial amount of phenol under visible light irradiation. An initial concentration of phenol is of paramount importance and the higher is the concentration, the higher are the yield and the selectivity. The O2 involved in the mechanism is the oxygen already dissolved in the reacting mixture because this was not purged with nitrogen. The visible light excites the electrons in the Au nanoparticles to move fast toward the conduction band minimum of the TiO2 where they are withdrawn by the O2 so reducing it. The phenoxy ions are oxidized to phenoxy free radicals through the release of electrons to the electron-depleted Au nanoparticles. The phenoxy radicals are finally involved in the oxidation of the benzene to phenol becoming phenoxy ions again. The importance of this work relies on the possibility of a modulation of the catalytic properties of the TiO2 by depositing different noble metals on the base of the different spectral characteristic of the light and with regard to a wider class of organic substrates.

Toluene is another aromatic hydrocarbon having relevancy in the industry. It is mainly converted to benzene by catalytic dealkylation and sometimes it is used for production of xylenes by transalkylation and disproportionation (Weber et al., 2005). The oxidation of toluene with O2 to produce benzaldehyde throughout TiO2 photocatalytic reactions has been investigated by different authors in the last years. Recently Ouidri and Khalaf (Ouidri & Khalaf, 2009) reported the oxidation of toluene by using TiO2-pillared montmorillonite in acetonitrile or water or mixture of them and irradiating the reaction mixture by a 125 W Hg lamp for 1 h. The authors found that reactions performed in water gave the higher yield of benzaldehyde. Furthermore, the catalyst prepared according to this protocol showed a superior catalytic activity than the Degussa P25. The authors explained this experimental evidence with the higher capacity of the TiO2-pillared montmorillonite to adsorb toluene compared with the Degussa P25. The presence of the catalyst is mandatory for the effectiveness of the process.

A further method is described by Cao et al. (Cao et al., 2011) who prepared TiO2 hollow spheres by the hydrothermal reaction between TiF4 and H2O. Such material was used in the photocatalytic oxidation of toluene to give benzaldehyde in water under irradiation with a light of 310 nm. The TiO2 spheres had a diameter of about 1 m as shown by the FESEM and TEM images. The SBET was in the range of 6.6 – 19 m2g-1 while the anatase crystals size was in the range of 31 – 56 nm depending on the reaction time adopted for the synthesis (hydrothermal time). Such crystals covered the surface of the hollow spheres exposing the {001} face. The authors found that the conversion of toluene gradually increased from 9.0 % to 21 %, when the hydrothermal time was increased from 20 min to 6 h while the selectivity was about 90 %. In particular the catalytic activity was in the following order: TiO2-20 min < TiO2- 40 min << TiO2-6 h < TiO2-12 h < TiO2-72 h. The TiO2-72 h microspheres showed activity two times higher than the commercial Degussa P25. As this last one has a SBET of 45 m2g-1 (higher than 6.6 m2g-1 associated to the TiO2-72h) and the {101} facets are more developed than that of TiO2-72 h, the difference in the reactivity could be ascribed to the wider {001} facets in TiO2- 72h. The superior catalytic activity of the {001} facets has been already documented for different reactions in particular with regard to the degradation processes of water pollutants

performance (Au > Pt >> Ag) giving high yield (above 60 %) and selectivity (about 90 %). Such results were obtained irradiating the reacting mixture (phenol (0.06 g) dissolved in 50 mL of deionized water (50 mL) with benzene (0.07 mL) and the catalyst (50 mg)) with a 300 W Xe arc lamp for a variable time (up to 5 h). No reaction was observed when metal-free TiO2 microspheres were used because the visible light ( ≥ 400 nm) cannot excite TiO2 (band-gap 3.2 eV). In Fig. 9 it is shown the mechanism proposed by the authors to explain the photooxidation of benzene into phenol in the presence of an initial amount of phenol under visible light irradiation. An initial concentration of phenol is of paramount importance and the higher is the concentration, the higher are the yield and the selectivity. The O2 involved in the mechanism is the oxygen already dissolved in the reacting mixture because this was not purged with nitrogen. The visible light excites the electrons in the Au nanoparticles to move fast toward the conduction band minimum of the TiO2 where they are withdrawn by the O2 so reducing it. The phenoxy ions are oxidized to phenoxy free radicals through the release of electrons to the electron-depleted Au nanoparticles. The phenoxy radicals are finally involved in the oxidation of the benzene to phenol becoming phenoxy ions again. The importance of this work relies on the possibility of a modulation of the catalytic properties of the TiO2 by depositing different noble metals on the base of the different spectral characteristic of the light

Toluene is another aromatic hydrocarbon having relevancy in the industry. It is mainly converted to benzene by catalytic dealkylation and sometimes it is used for production of xylenes by transalkylation and disproportionation (Weber et al., 2005). The oxidation of toluene with O2 to produce benzaldehyde throughout TiO2 photocatalytic reactions has been investigated by different authors in the last years. Recently Ouidri and Khalaf (Ouidri & Khalaf, 2009) reported the oxidation of toluene by using TiO2-pillared montmorillonite in acetonitrile or water or mixture of them and irradiating the reaction mixture by a 125 W Hg lamp for 1 h. The authors found that reactions performed in water gave the higher yield of benzaldehyde. Furthermore, the catalyst prepared according to this protocol showed a superior catalytic activity than the Degussa P25. The authors explained this experimental evidence with the higher capacity of the TiO2-pillared montmorillonite to adsorb toluene compared with the Degussa P25. The presence of the catalyst is mandatory for the

A further method is described by Cao et al. (Cao et al., 2011) who prepared TiO2 hollow spheres by the hydrothermal reaction between TiF4 and H2O. Such material was used in the photocatalytic oxidation of toluene to give benzaldehyde in water under irradiation with a light of 310 nm. The TiO2 spheres had a diameter of about 1 m as shown by the FESEM and TEM images. The SBET was in the range of 6.6 – 19 m2g-1 while the anatase crystals size was in the range of 31 – 56 nm depending on the reaction time adopted for the synthesis (hydrothermal time). Such crystals covered the surface of the hollow spheres exposing the {001} face. The authors found that the conversion of toluene gradually increased from 9.0 % to 21 %, when the hydrothermal time was increased from 20 min to 6 h while the selectivity was about 90 %. In particular the catalytic activity was in the following order: TiO2-20 min < TiO2- 40 min << TiO2-6 h < TiO2-12 h < TiO2-72 h. The TiO2-72 h microspheres showed activity two times higher than the commercial Degussa P25. As this last one has a SBET of 45 m2g-1 (higher than 6.6 m2g-1 associated to the TiO2-72h) and the {101} facets are more developed than that of TiO2-72 h, the difference in the reactivity could be ascribed to the wider {001} facets in TiO2- 72h. The superior catalytic activity of the {001} facets has been already documented for different reactions in particular with regard to the degradation processes of water pollutants

and with regard to a wider class of organic substrates.

effectiveness of the process.

(Liu et al., 2010). Indeed, it has been reported that water molecules undergo spontaneous dissociative adsorption on clean anatase {001} forming hydrogen peroxide and peroxyl radicals which are then involved in the degradative process (Selloni, 2008).

#### **5.1.2 Other hydrocarbon functionalizations**

More complex functionalizations of aromatic hydrocarbons have also been promoted by TiO2. For example the perfluoroalkylation of arenes and α-methylstyrene derivatives in acetonitrile using titanium oxide as photocatalyst and in presence of alcohols and NaBF4 has been reported (Eq. 4, Iizuka & Yoshida, 2009). The electrons in the conduction band of TiO2 can reduce the perfluoroalkyl iodide forming a perfluoroalkyl radical and iodide ion. The resulting radical reacts with the arene forming an arenium radical, which is successively oxidized to the corresponding arenium cation by the action of the holes providing at the end the product. Different alcohols were considered. The best performances were obtained with methanol and ethanol while 2-propanol gave lower conversions and selectivities in the desidered products. Both alcohol and NaBF4 may act as modulators of the red-ox network in particular reducing the hole-electron recombination process.

(4)

Heterocyclic compounds have also been synthesized through the use of TiO2. Shiraishi and co-workers investigated a one-pot synthesis of benzimidazoles by simultaneous photocatalytic and catalytic reactions on Pt@TiO2 nanoparticles (Shiraishi et al., 2010). A number of *ortho*-arylenediamines were converted to their corresponding benzimidazoles by Pt@TiO2 catalyzed reaction with different alcohols at 303 K for 30 min under UV irradiation (xenon lamp, 2 kW; light intensity, 18.2 Wm-2 at 300 – 400 nm) using, in some cases, MeCN as co-solvent. A comparison between Pt@TiO2 and a commercial TiO2 similar to Degussa P25 (JRC-TIO-4 TiO2 from the Catalyst Society of Japan with a anatase/rutile = 8:2) was reported, showing a significant improvement in both conversions (> 99%) and yields (generally above 80 % with different cases where the yield was above 95 %) after using Pt@TiO2 (Eq. 5). The UV-light excite TiO2 creating e-/h+ pairs. The hole pairs oxidize the alcohol to the corresponding aldehyde on the surface of the TiO2. The aldehyde spontaneously condense with the arylenediamine forming an imine intermediate, which undergoes cyclization furnishing a benzimidazoline. This last one is finally fast oxidized to the product by the catalytic action of Pt. In this way Pt@TiO2 has a double role: it works as *photocatalyst* in the oxidation of the alcohol and works as *catalyst* (due the presence of Pt) in the conversion of the benzimidazoline to the benzimidazole. Indeed, if Pt were not present the fast step from **5** to **2** (Eq. 6) would not be possible, allowing the shifting of the equilibrium **4**-**5** toward **4**. So, a further aldehyde molecule would condense giving the diimine **3** which finally furnishes the by-product **6**.

Semiconductors in Organic Photosynthesis 97

successful radical sources, the high regio- and chemoselectivity and the simple experimental conditions. The well known Friedel–Crafts aromatic substitutions are unfavored when carried out on aromatic substrates bearing electron withdrawing groups. 6-Membered mono and poli *N*-heteroaromatic bases behave as electron poor substrates toward "classic" ionic electrophylic substitutions and only carbon atoms in b-position to nitrogen are suitable of substitution. However the reaction rate is much lower than the one carried out on benzenesystems. Otherwise C-centered radicals show nuchleophilic character and easily react with deactivated bases reproducing most of the Friedel–Crafts aromatic substitutions, but with opposite reactivity and selectivity. One of the main goal of the free-radical nucleophilic substitution is represented by the almost total absence of by-product formation during the reaction. In fact only catalytic amount of catalysts or initiators, depending on the reaction types, are needed to promote the reactions, whereas the classic Friedel–Crafts protocol needs stoichiometric quantity of Lewis acids. TiO2 photocatalysis offers an alternative to the free-radical functionalization of heteroaromatic bases in the presence of classic metalperoxide system (Gambarotti et al., 2010; Augugliaro et al., 2010). Caronna and co-workers reported the carboxyamidation of bases in the presence of H2O2 or air under sunlight (Eq. 8 a) (Caronna et al., 2003; Caronna et al., 2007a). A similar protocol has been successfully applied to the etherification of bases, affording, in the case of 1,3,5-trioxane and 1,3 dioxolane, a green-route to heteroaromatic aldehydes (Eq. 8 b) (Caronna et al., 2005). Moreover, in the presence of aliphatic aldehydes the bases are both acylated and alkylated (Caronna et al., 2007b). Particularly, it is interesting the fact that under the reaction conditions, the decarbonylation rate of the acyl radical intermediate is extraordinarily high, and good conversion to the corresponding alkyl derivatives are obtained also with primary

N

N

N

Recently Selvam reported the synthesis of quinaldines from photocatalytic conversion of aniline and its derivatives in ethanol under mild conditions in the presence TiO2 or Au-TiO2 (Eq. 9) (Selvam & Swaminathan, 2010). The authors found that Au-TiO2 has superior catalytic properties compared to TiO2. Using Au-TiO2, after only 4 hours of photoirradiation at 365 nm the yield of quinaldine was about 75 % with a 10 % yield of 2,3 dimethylindole and 5% yield of other by-products, whereas, with TiO2 the yield of quinaldine was about 50 % after 6h with 15 % of 2,3-dimethylindole. The presence of water reduces drastically the yield of quinaldine (5 % yield with a 96/4 ethanol-water

O R

N

O O

O N

hydrolysis

N

R

N

N

O H (8)

N

N CONH2

TiO2

H2O2

H2O2

TiO2

H2O2

H+

h

H+

h

H +

h

+ +

N

aldehydes (Eq. 8 c).

**a)**

**b)**

**c)**

ratio).

N

+

+

N

N

N

N

H NH2 O

O O O

R H

O TiO2

A similar approach for the synthesis of benzimidazoles and indazole has been reported (Selvam & Swaminathan, 2010). The authors found that 2-nitrophenyl azide, in the presence of different alcohols, undergoes a combined redox reaction and condensation after irradiation in the presence of TiO2, giving 2-alkylbenzimidazoles as the main product, whereas, using 2-nitrobenzyl azide, the reduced amine does not react with aldehyde but undergoes cyclization to form indazole. The photoactivity was significantly enhanced by doping TiO2 with Ag or Pt especially under solar light irradiation. In this case, for example, the yield of 2-methylbenzimidazole increased from 85 % by using Degussa P25 to 98 % with both Ag-TiO2 and Pt-TiO2 (Eq. 7)

The substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals, commonly reported as "Minisci Reaction" (Minisci et al., 1986), is one of the main general reactions of this class of aromatic compounds as a result of the large variety of

h ( > 300nm) Pt@TiO2 N2 - 303 K

R1

**2**

N

(5)

(6)

(7)

82 - 99 % yield

H

N O

NO2

, 4H+ - H2O

N

NH OH

H N

N

H2

H N H N R2

NH2

NH2 R1 + R2 OH

TiO2 TiO2 (e-

NH2 NH2

TiO2 TiO2 (e-

2e-

N - H2O

N3

3 3

NO2

H N , h+) <sup>h</sup>

**a**

+

NH2

+ N2

N

The substitution of protonated heteroaromatic bases by nucleophilic carbon-centered radicals, commonly reported as "Minisci Reaction" (Minisci et al., 1986), is one of the main general reactions of this class of aromatic compounds as a result of the large variety of

OH

H N

, 2H<sup>+</sup> <sup>N</sup>

+ **a** - H2O

4e-

NO2

OH <sup>O</sup> 6H 6h <sup>+</sup> <sup>+</sup>

Pt 2e-

**1**

both Ag-TiO2 and Pt-TiO2 (Eq. 7)

OH O -2H+ 2h+

, h+) <sup>h</sup>

O - H2O


N


N

A similar approach for the synthesis of benzimidazoles and indazole has been reported (Selvam & Swaminathan, 2010). The authors found that 2-nitrophenyl azide, in the presence of different alcohols, undergoes a combined redox reaction and condensation after irradiation in the presence of TiO2, giving 2-alkylbenzimidazoles as the main product, whereas, using 2-nitrobenzyl azide, the reduced amine does not react with aldehyde but undergoes cyclization to form indazole. The photoactivity was significantly enhanced by doping TiO2 with Ag or Pt especially under solar light irradiation. In this case, for example, the yield of 2-methylbenzimidazole increased from 85 % by using Degussa P25 to 98 % with

O

NH2 N

**4 5**

N N

<sup>6</sup> <sup>3</sup>

O

successful radical sources, the high regio- and chemoselectivity and the simple experimental conditions. The well known Friedel–Crafts aromatic substitutions are unfavored when carried out on aromatic substrates bearing electron withdrawing groups. 6-Membered mono and poli *N*-heteroaromatic bases behave as electron poor substrates toward "classic" ionic electrophylic substitutions and only carbon atoms in b-position to nitrogen are suitable of substitution. However the reaction rate is much lower than the one carried out on benzenesystems. Otherwise C-centered radicals show nuchleophilic character and easily react with deactivated bases reproducing most of the Friedel–Crafts aromatic substitutions, but with opposite reactivity and selectivity. One of the main goal of the free-radical nucleophilic substitution is represented by the almost total absence of by-product formation during the reaction. In fact only catalytic amount of catalysts or initiators, depending on the reaction types, are needed to promote the reactions, whereas the classic Friedel–Crafts protocol needs stoichiometric quantity of Lewis acids. TiO2 photocatalysis offers an alternative to the free-radical functionalization of heteroaromatic bases in the presence of classic metalperoxide system (Gambarotti et al., 2010; Augugliaro et al., 2010). Caronna and co-workers reported the carboxyamidation of bases in the presence of H2O2 or air under sunlight (Eq. 8 a) (Caronna et al., 2003; Caronna et al., 2007a). A similar protocol has been successfully applied to the etherification of bases, affording, in the case of 1,3,5-trioxane and 1,3 dioxolane, a green-route to heteroaromatic aldehydes (Eq. 8 b) (Caronna et al., 2005). Moreover, in the presence of aliphatic aldehydes the bases are both acylated and alkylated (Caronna et al., 2007b). Particularly, it is interesting the fact that under the reaction conditions, the decarbonylation rate of the acyl radical intermediate is extraordinarily high, and good conversion to the corresponding alkyl derivatives are obtained also with primary aldehydes (Eq. 8 c).

Recently Selvam reported the synthesis of quinaldines from photocatalytic conversion of aniline and its derivatives in ethanol under mild conditions in the presence TiO2 or Au-TiO2 (Eq. 9) (Selvam & Swaminathan, 2010). The authors found that Au-TiO2 has superior catalytic properties compared to TiO2. Using Au-TiO2, after only 4 hours of photoirradiation at 365 nm the yield of quinaldine was about 75 % with a 10 % yield of 2,3 dimethylindole and 5% yield of other by-products, whereas, with TiO2 the yield of quinaldine was about 50 % after 6h with 15 % of 2,3-dimethylindole. The presence of water reduces drastically the yield of quinaldine (5 % yield with a 96/4 ethanol-water ratio).

Semiconductors in Organic Photosynthesis 99

titanyl nitrate and urea into a muffle furnace at 400 °C. The fast evaporation of water was followed by a smouldered combustion of the titanyl nitrate (acting as precursor of Ti) in ammonia atmosphere (acting as fuel) obtained by the decomposition of the urea to NH3 and CO2. Different N-doped solid catalysts were prepared changing the precursor/fuel ratio. The oxidations were performed in aqueous solutions and without bubbling oxygen, obtaining yields of *p*-anisaldehyde of 25 % under sunlight and 30 % under laboratory light source in 7 hours. Despite the absence of oxygen, these results are comparable to that reported by Palmisano, who used a home-prepared TiO2 as well as TiO2 Merck (100 % anatase) and Degussa P25 (Palmisano et al., 2007b). In this work, 10 % yields of *p*-anisaldehyde was obtained in the presence of TiO2 Merck or Degussa P25 and 30 - 40 % yields in the presence of

home-made catalyst (depending on its amount, phase constitution and morphology).

photo-catalyst both with regard the yield (> 99%) and the reaction time (10 h).

increasing the surface area and consequently enhancing the reaction rate.

32 nm TiO2 (1 mol %) CH2Cl2 h 15 W

As described before, TiO2 is undoubtedly the most commonly used catalyst in organic photosynthesis. It is often metal-doped, in order to increase the wavelength radiation adsorption, and supported over inert materials (silica or zeolites), with the unique scope of

In the last decades, several other inorganic semiconductors have been investigated for the development of innovative organic photosynthetic strategies, including metal sulfides (ZnS and CdS) (Kisch, 2001), metal oxides (ZrO2, ZnO, V2O5, SnO2, Sb2O4, CeO2, WO3 and Sn/Sb

One of the reasons, which often make TiO2 the photocatalyst of choice, is the higher protocol efficiency usually observed, in terms of both conversion and selectivity, when it is compared with other semiconductors. This is, for example, the case for the selective photoactivated radical addition of tertiary amines to electron deficient alkenes such as ,-unsaturated lactones (Marinković & Hoffmann, 2001, 2003), conducted in the presence of TiO2, ZnS or SiC. When reacting the *N*-methylpyrrolidine, the best results were achieved with TiO2 (Eq.

OAc

(11)

OH

+ Ac2O

**5.2 Other semiconductors in organic photosynthesis** 

mixed oxides) (Maldotti et al., 2002a), and polyoxometalates.

More recently Chen described the photo-catalytic acetylation of 2-phenylethanol by acetic anhydride in the presence of TiO2 nanoparticles (Chen, 2011). The synthesis was performed by suspending TiO2 nanoparticles (32 nm grade) in H2O2 (30 % wt) for 30 min. under UV light (254 nm, 15 W) and then concentrating it in order to photoactivate the TiO2 surface (Eq. 11). The solid was suspended in a solution of 2-phenylethanol in CH2Cl2 and irradiated for 10 h. The authors investigated the effects of the oxidant (O2, *t*-butyl hydroperoxide, H2O2) finding that hydrogen peroxide was the most effective (99 % conversion) despite, even in absence of oxidant, a 88 % conversion was obtained. Moreover, different solvents were used finding that CH2Cl2 was the best one (> 99% conversion after 10 h) while reactions performed in toluene, hexane, ether, THF, acetone, ethyl acetate and CH3CN gave lower or null conversions also during longer times. A screening of different TiO2 catalyst (anatase, rutile) having different morphological parameters as well as other oxides like as Y2O3, WO3, ZrO2, was also carried out, finding that 32 nm TiO2 (anatase/rutile = 4/1) was the optimal

$$\underbrace{\stackrel{\text{NH}\_2}{\bigtimes}}\_{\text{R}} + \underbrace{\text{C}\_{\text{2}\text{H}\_5\text{OH}}}\_{\text{Au-TiO}\_2} \xrightarrow[\text{Au-TiO}\_2]{\text{hv (h} > 300\,\text{nm})} \underset{\text{R}}{\bigtimes}\_{\text{R}} \tag{9}$$

The partial oxidation of alcohols for the production of fine and specialty chemicals represents a further field of investigation having high scientific and industrial impact. The use of TiO2 to promote the oxidation of alcohols to the corresponding aldehydes has been investigated by different authors in the last years. Pillai and Sahle–Demessie described the oxidation of various primary and secondary alcohols to aldehydes in a gas-phase photochemical reactor with immobilized TiO2 (Pillai & Sahle–Demessie, 2002). Enache reported the solvent-free oxidation of primary alcohols to aldehydes using Au-Pd/ TiO2 catalysts without light irraditation (Enache et al., 2006).

Molinari investigated the photooxidation of geraniol to citral (Eq. 10), which is used in perfumes, flavourings and in the manufacture of other chemicals (Molinari et al, 2009b).

In this work, dispersions of Degussa P25 TiO2 in CH3CN containing geraniol (0.01 M) were irradiated by UV-light ( > 320 nm), at room temperature and under 760 Torr of O2 for different times (up to 140 min). The formation of citral occurs as consequence of the adsorption of the geraniol on the surface of the TiO2 forming an alkoxide ion, RCH2O- . This latter is then oxidized to its corresponding alkoxide radical RCH2O and finally to the aldehyde RCHO by the direct electron transfer to the positive holes. Hence, the mechanism proposed by the authors is not based on the intervention of the hydroxyl radicals and it is supported by some ESR experiments. Furthermore, the experiments showed that water has negative effect on the oxidation of the -OH group of geraniol. In fact, water reduces the adsorption of the alcohol on the TiO2 photoactive surface both due to the increase of the polarity which keep the geraniol preferentially in the solution and also due the competitive adsorption of water on the TiO2. Finally, this inhibits the direct electron transfer from geraniol to the electron holes of TiO2 reducing its catalytic effect. In order to investigate the effect of the nature of alcohol, the authors compared the reactivity of geraniol with that of *trans*-2-penten-1-ol, an allylic alcohol similar to geraniol but with a shorter chain of carbon atoms. As expected, *trans*-2-penten-1-ol is adsorbed on TiO2 much better than geraniol and hence higher amount of aldehyde is obtained. Furthermore, if primary aliphatic alcohol with chains of the same lengths are considered like as citronellol (as corresponding of geraniol) and 1-pentanol (as corresponding of *trans*-2-penten-1-ol), it is observed that each primary alcohol is always better adsorbed than the corresponding allylic alcohol getting an increase of the yield of aldehyde.

The conversion of *p*-anisyl alcohol to *p*-anisaldehyde, an important intermediate for pharmaceutical industry, through the use of N-doped mesoporous titania (meso-TiO2-xNx) under sunlight as well as UV-lamp irradiation has been reported (Sivaranjani & Gopinath, 2011). The catalyst was prepared by a SCM technique introducing an aqueous solution of

h ( > 300nm)

N2

The partial oxidation of alcohols for the production of fine and specialty chemicals represents a further field of investigation having high scientific and industrial impact. The use of TiO2 to promote the oxidation of alcohols to the corresponding aldehydes has been investigated by different authors in the last years. Pillai and Sahle–Demessie described the oxidation of various primary and secondary alcohols to aldehydes in a gas-phase photochemical reactor with immobilized TiO2 (Pillai & Sahle–Demessie, 2002). Enache reported the solvent-free oxidation of primary alcohols to aldehydes using Au-Pd/ TiO2

Molinari investigated the photooxidation of geraniol to citral (Eq. 10), which is used in perfumes, flavourings and in the manufacture of other chemicals (Molinari et al, 2009b).

P25 TiO2 MeCN

In this work, dispersions of Degussa P25 TiO2 in CH3CN containing geraniol (0.01 M) were irradiated by UV-light ( > 320 nm), at room temperature and under 760 Torr of O2 for different times (up to 140 min). The formation of citral occurs as consequence of the adsorption of the geraniol on the surface of the TiO2 forming an alkoxide ion, RCH2O-

latter is then oxidized to its corresponding alkoxide radical RCH2O and finally to the aldehyde RCHO by the direct electron transfer to the positive holes. Hence, the mechanism proposed by the authors is not based on the intervention of the hydroxyl radicals and it is supported by some ESR experiments. Furthermore, the experiments showed that water has negative effect on the oxidation of the -OH group of geraniol. In fact, water reduces the adsorption of the alcohol on the TiO2 photoactive surface both due to the increase of the polarity which keep the geraniol preferentially in the solution and also due the competitive adsorption of water on the TiO2. Finally, this inhibits the direct electron transfer from geraniol to the electron holes of TiO2 reducing its catalytic effect. In order to investigate the effect of the nature of alcohol, the authors compared the reactivity of geraniol with that of *trans*-2-penten-1-ol, an allylic alcohol similar to geraniol but with a shorter chain of carbon atoms. As expected, *trans*-2-penten-1-ol is adsorbed on TiO2 much better than geraniol and hence higher amount of aldehyde is obtained. Furthermore, if primary aliphatic alcohol with chains of the same lengths are considered like as citronellol (as corresponding of geraniol) and 1-pentanol (as corresponding of *trans*-2-penten-1-ol), it is observed that each primary alcohol is always better adsorbed than the corresponding allylic alcohol getting an increase

The conversion of *p*-anisyl alcohol to *p*-anisaldehyde, an important intermediate for pharmaceutical industry, through the use of N-doped mesoporous titania (meso-TiO2-xNx) under sunlight as well as UV-lamp irradiation has been reported (Sivaranjani & Gopinath, 2011). The catalyst was prepared by a SCM technique introducing an aqueous solution of

Au-TiO2 <sup>R</sup> <sup>N</sup>

O

O2 h > 320 nm) (10)

(9)

. This

NH2

catalysts without light irraditation (Enache et al., 2006).

OH

of the yield of aldehyde.

+ C2H5OH

R

titanyl nitrate and urea into a muffle furnace at 400 °C. The fast evaporation of water was followed by a smouldered combustion of the titanyl nitrate (acting as precursor of Ti) in ammonia atmosphere (acting as fuel) obtained by the decomposition of the urea to NH3 and CO2. Different N-doped solid catalysts were prepared changing the precursor/fuel ratio. The oxidations were performed in aqueous solutions and without bubbling oxygen, obtaining yields of *p*-anisaldehyde of 25 % under sunlight and 30 % under laboratory light source in 7 hours. Despite the absence of oxygen, these results are comparable to that reported by Palmisano, who used a home-prepared TiO2 as well as TiO2 Merck (100 % anatase) and Degussa P25 (Palmisano et al., 2007b). In this work, 10 % yields of *p*-anisaldehyde was obtained in the presence of TiO2 Merck or Degussa P25 and 30 - 40 % yields in the presence of home-made catalyst (depending on its amount, phase constitution and morphology).

More recently Chen described the photo-catalytic acetylation of 2-phenylethanol by acetic anhydride in the presence of TiO2 nanoparticles (Chen, 2011). The synthesis was performed by suspending TiO2 nanoparticles (32 nm grade) in H2O2 (30 % wt) for 30 min. under UV light (254 nm, 15 W) and then concentrating it in order to photoactivate the TiO2 surface (Eq. 11). The solid was suspended in a solution of 2-phenylethanol in CH2Cl2 and irradiated for 10 h. The authors investigated the effects of the oxidant (O2, *t*-butyl hydroperoxide, H2O2) finding that hydrogen peroxide was the most effective (99 % conversion) despite, even in absence of oxidant, a 88 % conversion was obtained. Moreover, different solvents were used finding that CH2Cl2 was the best one (> 99% conversion after 10 h) while reactions performed in toluene, hexane, ether, THF, acetone, ethyl acetate and CH3CN gave lower or null conversions also during longer times. A screening of different TiO2 catalyst (anatase, rutile) having different morphological parameters as well as other oxides like as Y2O3, WO3, ZrO2, was also carried out, finding that 32 nm TiO2 (anatase/rutile = 4/1) was the optimal photo-catalyst both with regard the yield (> 99%) and the reaction time (10 h).

$$\begin{array}{cccc} \underset{\scriptstyle \leqslant \searrow \hspace{0.1cm} \text{\$\mathord{\bf M\\${}\_{2}}\$}}{\Longarrow \hspace{0.1cm} \text{\$\mathord{\bf M\\${}\_{2}}\$}} & \underset{\scriptstyle \geqslant \mathtt{0.1cm} \text{\$\mathop{\bf T\\${}\_{2}}\$}}{\Longarrow \hspace{0.1cm} \text{\$\mathop{\bf T\\${}\_{2}}\$}} & \underset{\scriptstyle \geqslant \mathtt{0.1cm}}{\longarrow \hspace{0.1cm} \text{\$\mathop{\bf T\\${}\_{2}}\$}} \end{array}$$

#### **5.2 Other semiconductors in organic photosynthesis**

As described before, TiO2 is undoubtedly the most commonly used catalyst in organic photosynthesis. It is often metal-doped, in order to increase the wavelength radiation adsorption, and supported over inert materials (silica or zeolites), with the unique scope of increasing the surface area and consequently enhancing the reaction rate.

In the last decades, several other inorganic semiconductors have been investigated for the development of innovative organic photosynthetic strategies, including metal sulfides (ZnS and CdS) (Kisch, 2001), metal oxides (ZrO2, ZnO, V2O5, SnO2, Sb2O4, CeO2, WO3 and Sn/Sb mixed oxides) (Maldotti et al., 2002a), and polyoxometalates.

One of the reasons, which often make TiO2 the photocatalyst of choice, is the higher protocol efficiency usually observed, in terms of both conversion and selectivity, when it is compared with other semiconductors. This is, for example, the case for the selective photoactivated radical addition of tertiary amines to electron deficient alkenes such as ,-unsaturated lactones (Marinković & Hoffmann, 2001, 2003), conducted in the presence of TiO2, ZnS or SiC. When reacting the *N*-methylpyrrolidine, the best results were achieved with TiO2 (Eq.

Semiconductors in Organic Photosynthesis 101

Alkanes too were shown to undergo partial oxidation, when illuminated in the presence of silica-supported vanadium oxide, affording the corresponding carbonylic products in good

Supported polyoxometalates based on tungsten afforded high photocatalytic activity in the oxidation of different substrates. (*n*-Bu4N)4W10O32 (TBADT), supported on silica by impregnation procedure, was successfully employed at room temperature and atmospheric pressure to promote by irradiation ( > 300 nm) the aerobic oxidation of cyclohexane to a 1:1 mixture of cyclohexanol and cyclohexanone (Molinari et al., 1999), while under analogous conditions cyclohexene was converted to the corresponding cyclohexenyl hydroperoxide with 90 % of selectivity (Molinari et al., 2000). This decatungstate was also immobilized on a mesoporous MCM-41-type material, which allows to obtain a better dispersion of the semiconductor, and the new material was tested in the oxidation of the cyclohexane for comparison with the silica supported material (Maldotti et al., 2002b). These studies showed the key role of the solid matrix in controlling the ketone/alcohol ratio of the products. In fact, the higher surface area of the mesoporous material favored the conversion of cyclohexanol to the corresponding cyclohexanone, affording a higher final ratio

Another tungsten-based heteropolyoxometalate supported on amorphous silica (H3PW12O40/SiO2) was successfully used for the selective aerobic photocatalytic oxidation of benzylic alcohols to the corresponding aldehydes and ketones, with yields up to 97 % (Farhadi et al., 2005). Even more interesting, in spite of the higher reactivity of carbonylic derivatives, no overoxidation was observed, and no traces of carboxylic acids were found in

> H3PW12O40-SiO2 / h O2 / CH3CN / r.t.

If we exclude the conversion of CO2 into more useful hydrogenated chemicals, which is however characterized by low energy conversion efficiencies, the main application of the

Being the most powerful reducing semiconductor, CdS usually provides highest yield and selectivity by converting nitro-benzenes into corresponding anilines, if compared with the common TiO2 (Maldotti et al., 2000). Nevertheless, it requires UV light to be activated, this

Very recently, Pfitzner and coworkers (Füldner et al., 2011) have reported that the blue light irradiation of PbBiO2*X* (*X* = Cl or Br), in the presence of triethanolamine (TEOA) as an electron donor, provides the selective and complete reduction of nitrobenzene derivatives to their corresponding anilines (Eq. 15). By replacing bismuth with antimony in the oxide halide no conversion was observed. The same unreactivity resulted by operating in the presence of PbBiO2I. The authors suggest that the different catalytic activity should be ascribed to multiple factors, including the crystal structures and their optical and redox properties. Photocatalyst recycling experiments showed that sonication of PbBiO2*X* before

photoinduced reduction reaction is the transformation of nitro-aromatic derivatives.

Ar R

O

(14)

yields with only traces of COx (Tanaka et al., 2000).

Ar R

OH

R = H, aryl, alkyl

reuse was essential to retain its activity up to five catalytic cycles.

ketone/alcohol (2.4).

the final products (Eq. 14).

**5.2.2 Reduction reactions** 

limiting the range of applications.

12 a), while the reaction of *N*-methylpiperidine led to a different product distribution (Eq. 12 b). In particular, TiO2 favoured the selective formation of product **A**, deriving from a classical Michael addition, while ZnS promoted the formation of product **B** in poor yields, probably because of its less oxidative properties.

<sup>O</sup> <sup>O</sup> OMent H N <sup>O</sup> <sup>O</sup> OMent H N H h semiconductor <sup>O</sup> <sup>O</sup> OMent H N <sup>O</sup> <sup>O</sup> OMent H N H <sup>O</sup> <sup>O</sup> OMent H N **A B a) b)** h semiconductor (12)

Another significative example is furnished by the selective synthesis of 2-methylpiperazine from *N*-(β-hydroxtpropyl)-ethylenediamine by means of semiconductor-zeolite composite photocatalysts (Subba Rao & Subrahmanyam, 2002). Also in this case, zeolites modified with semiconductors ZnO and CdS were not very effective, while TiO2-zeolites composites considerably facilitated the intramolecular cyclization (Eq. 13).

$$\times \stackrel{\mathsf{H}}{\smile} \stackrel{\mathsf{H}}{\smile} \stackrel{\mathsf{H}}{\frown} \stackrel{\mathsf{h}^{\mathsf{V}}}{\rightharpoonup} \stackrel{\mathsf{h}^{\mathsf{V}}}{\smile} \stackrel{\mathsf{h}^{\mathsf{V}}}{\smile} \stackrel{\mathsf{H}}{\smile} \tag{13}$$

Nevertheless, in many cases inorganic semiconductors different from TiO2 have recently allowed to afford new and intriguing photosynthetic approaches. In this section we aim to show a few very recent examples of the application of these photocatalysts for selective oxidation, reduction and C-C bond forming reactions.

#### **5.2.1 Oxidation reactions**

One of the main drawbacks in semiconductor catalyzed photoxidations in the presence of O2 is the low selectivity in the desired product. In fact, in many cases the photomineralization of the substrate occurs, leading to the formation of CO2.

A successful route to overcome this limitation is to employ the semiconductor, usually in the form of metal oxide, fixed or dispersed on a suitable inorganic support. Additional advantages in the use of semiconductors in their heterogenized form are the availability of wide range of supports and the easy recovery and recycle of the catalyst. Once again, TiO2 is often the first choice, but in many cases other metal oxides provide better results.

Highly dispersed (Men+O)-Si binary oxides, prepared by both conventional impregnation and sol-gel procedures, have been widely employed under irradiation for the aerobic oxidation of alkanes and alkenes (Maldotti, 2002a). Propylene was converted to different oxidized species, varying the final product on the basis of the photocatalyst of choice: the corresponding epoxide in the presence of ZnO-SiO2 (Yoshida et al., 1999), acetaldehyde with V2O5-SiO2 (Tanaka et al., 1986), a mixture of both by means of CrOx-SiO2 (Murata et al., 2001).

12 a), while the reaction of *N*-methylpiperidine led to a different product distribution (Eq. 12 b). In particular, TiO2 favoured the selective formation of product **A**, deriving from a classical Michael addition, while ZnS promoted the formation of product **B** in poor yields,

> h semiconductor

h semiconductor

Another significative example is furnished by the selective synthesis of 2-methylpiperazine from *N*-(β-hydroxtpropyl)-ethylenediamine by means of semiconductor-zeolite composite photocatalysts (Subba Rao & Subrahmanyam, 2002). Also in this case, zeolites modified with semiconductors ZnO and CdS were not very effective, while TiO2-zeolites composites

h

TiO2-zeolite <sup>N</sup>

NH2

Nevertheless, in many cases inorganic semiconductors different from TiO2 have recently allowed to afford new and intriguing photosynthetic approaches. In this section we aim to show a few very recent examples of the application of these photocatalysts for selective

One of the main drawbacks in semiconductor catalyzed photoxidations in the presence of O2 is the low selectivity in the desired product. In fact, in many cases the photomineralization

A successful route to overcome this limitation is to employ the semiconductor, usually in the form of metal oxide, fixed or dispersed on a suitable inorganic support. Additional advantages in the use of semiconductors in their heterogenized form are the availability of wide range of supports and the easy recovery and recycle of the catalyst. Once again, TiO2 is

Highly dispersed (Men+O)-Si binary oxides, prepared by both conventional impregnation and sol-gel procedures, have been widely employed under irradiation for the aerobic oxidation of alkanes and alkenes (Maldotti, 2002a). Propylene was converted to different oxidized species, varying the final product on the basis of the photocatalyst of choice: the corresponding epoxide in the presence of ZnO-SiO2 (Yoshida et al., 1999), acetaldehyde with V2O5-SiO2

often the first choice, but in many cases other metal oxides provide better results.

(Tanaka et al., 1986), a mixture of both by means of CrOx-SiO2 (Murata et al., 2001).

<sup>O</sup> <sup>O</sup> OMent H

<sup>O</sup> <sup>O</sup> OMent H N

**A B**

H

H N <sup>O</sup> <sup>O</sup> OMent H

N H (12)

(13)

N H

N

N

considerably facilitated the intramolecular cyclization (Eq. 13).

OH

oxidation, reduction and C-C bond forming reactions.

of the substrate occurs, leading to the formation of CO2.

H N

probably because of its less oxidative properties.

<sup>O</sup> <sup>O</sup> OMent H

**a)**

**b)**

**5.2.1 Oxidation reactions** 

<sup>O</sup> <sup>O</sup> OMent H

Alkanes too were shown to undergo partial oxidation, when illuminated in the presence of silica-supported vanadium oxide, affording the corresponding carbonylic products in good yields with only traces of COx (Tanaka et al., 2000).

Supported polyoxometalates based on tungsten afforded high photocatalytic activity in the oxidation of different substrates. (*n*-Bu4N)4W10O32 (TBADT), supported on silica by impregnation procedure, was successfully employed at room temperature and atmospheric pressure to promote by irradiation ( > 300 nm) the aerobic oxidation of cyclohexane to a 1:1 mixture of cyclohexanol and cyclohexanone (Molinari et al., 1999), while under analogous conditions cyclohexene was converted to the corresponding cyclohexenyl hydroperoxide with 90 % of selectivity (Molinari et al., 2000). This decatungstate was also immobilized on a mesoporous MCM-41-type material, which allows to obtain a better dispersion of the semiconductor, and the new material was tested in the oxidation of the cyclohexane for comparison with the silica supported material (Maldotti et al., 2002b). These studies showed the key role of the solid matrix in controlling the ketone/alcohol ratio of the products. In fact, the higher surface area of the mesoporous material favored the conversion of cyclohexanol to the corresponding cyclohexanone, affording a higher final ratio ketone/alcohol (2.4).

Another tungsten-based heteropolyoxometalate supported on amorphous silica (H3PW12O40/SiO2) was successfully used for the selective aerobic photocatalytic oxidation of benzylic alcohols to the corresponding aldehydes and ketones, with yields up to 97 % (Farhadi et al., 2005). Even more interesting, in spite of the higher reactivity of carbonylic derivatives, no overoxidation was observed, and no traces of carboxylic acids were found in the final products (Eq. 14).

$$\bigotimes\_{\mathsf{Ar}}^{\mathsf{O}\mathsf{H}} \overbrace{\mathsf{R}^{\mathsf{H}} \overbrace{\mathsf{H}\_{3}\mathsf{PW}\_{12}\mathsf{O}\_{40}\mathsf{SiO}\_{2}/\mathsf{h}\mathsf{v}}}^{\mathsf{O}\mathsf{H}} \overbrace{\mathsf{H}^{\mathsf{O}}}^{\mathsf{O}\mathsf{H}\mathsf{H}\_{3}\mathsf{CN}/\mathsf{h}\mathsf{v}}^{\mathsf{O}} \overbrace{\mathsf{R}^{\mathsf{O}}}^{\mathsf{O}} \tag{14}$$

#### **5.2.2 Reduction reactions**

If we exclude the conversion of CO2 into more useful hydrogenated chemicals, which is however characterized by low energy conversion efficiencies, the main application of the photoinduced reduction reaction is the transformation of nitro-aromatic derivatives.

Being the most powerful reducing semiconductor, CdS usually provides highest yield and selectivity by converting nitro-benzenes into corresponding anilines, if compared with the common TiO2 (Maldotti et al., 2000). Nevertheless, it requires UV light to be activated, this limiting the range of applications.

Very recently, Pfitzner and coworkers (Füldner et al., 2011) have reported that the blue light irradiation of PbBiO2*X* (*X* = Cl or Br), in the presence of triethanolamine (TEOA) as an electron donor, provides the selective and complete reduction of nitrobenzene derivatives to their corresponding anilines (Eq. 15). By replacing bismuth with antimony in the oxide halide no conversion was observed. The same unreactivity resulted by operating in the presence of PbBiO2I. The authors suggest that the different catalytic activity should be ascribed to multiple factors, including the crystal structures and their optical and redox properties. Photocatalyst recycling experiments showed that sonication of PbBiO2*X* before reuse was essential to retain its activity up to five catalytic cycles.

Semiconductors in Organic Photosynthesis 103

method for the in situ regeneration of nicotinamide (NAD) co-factor, on which depend the activity of many enzymes. In fact, the high cost of NAD often limits the industrialization potentials of many promising enzymatic processes. The overall schematic mechanism, which regulates this photobioreactor, is reported in Fig. 10. In the photocatalytic cycle, the W2Fe4Ta2O17 upon band-gap excitation by visible light ( > 420 nm) promotes electrons to the conduction band, which are in turn easily transferred to an organometallic Rh complex. The latter, after undergoing hydrogen abstraction from the aqueous medium, transfers

Among semiconductor photocatalysts, Ru(II)polypyridine complexes are attracting increasing interest because of their stability at room temperature and enhanced photoredox properties (Narayanam & Stephenson, 2011). In particular, Ru(bpy)3Cl2 has been widely employed, as its irradiation with visible light leads to the excited species Ru(bpy)32+ \*, which in turn can be employed as strong single electron oxidant and reductant, depending upon reaction conditions. Besides classical oxidative reactions introducing oxygen atoms and reductive hydrogenations, Ru(bpy)3Cl2 has found large use in the photocatalytic promotion

Irradiation of aryl enones, in the presence of a mixture of Ru(bpy)3Cl2, *i-*Pr2NEt and LiBF4 in acetonitrile, allowed to develop a highly diasteroselective intramolecular [2 + 2] cycloaddition reaction, which, in all the examples reported, led to the formation of the corresponding *cis*-cyclobutanes (Eq. 17) (Ischay & al., 2008). In the reaction mechanism, *i*-Pr2NEt has the role to reduces the excited species Ru(bpy)32+ \* to Ru(bpy)3+, which seems to be the real initiator of the process, while LiBF4, being a Lewis acid, favours the solubility of

The same system was applied to promote the intermolecular homo-dimerization of aryl enones (Eq. 18) and the crossed intermolecular cyloaddition (Eq. 19) (Du & Yoon, 2009).

CH3CN - visible light

Ru(bpy)3Cl2 / *i*-Pr2NEt/LiBF4

CH3CN - visible light

Ru(bpy)3Cl2 / *i*-Pr2NEt/LiBF4

CH3CN - visible light

More recently, a photoredox strategy based on Ru(bpy)3Cl2 photocatalyst was successfully employed both for the selective -trifluoromethylation upon in situ or pre-generated enolsilanes and silylketenes (Eq. 20) (Pham et al., 2011) and to promote an oxidation/[3 + 2] cycloaddition/aromatization cascade reaction (Zou et al., 2011), the latter leading to the

Ar

Ar

Ar

O

O

O

R

Ar

Ar

Alk

(17)

(18)

(19)

O

O H H

O H H

H H

R R

H H

Ru(bpy)3Cl2 / *<sup>i</sup>*-Pr2NEt/LiBF4 Ar Ar

Ar

Alk

O O

R R

O O

+

R

O O

+

electrons and hydride to NAD+, forming NADH.

**5.2.3 C-C bond forming reactions** 

of C-C bond formation.

Ru complex in acetonitrile.

Ar

Ar

$$\bigcap\_{\lambda=440\text{ nm}/20\text{ h}}^{\mathsf{NO\_2}} \xrightarrow[\lambda=440\text{ nm}/20\text{ h}]{\mathsf{NO\_2}} \tag{15}$$

Anilines can be also obtained in 50 % yields and complete selectivity by photoreduction of aryl azides catalyzed by CdS or CdSe nanoparticles (Warrier et al., 2004). The reaction, which occurs under very mild conditions (room temperature, atmospheric pressure, neutral pH and aqueous medium), requires the presence of sodium formate as sacrificial electron donor (Eq. 16).

The high efficiency of this photocatalyzed reduction is attributed to the large driving force for electron transfer to the azide, which in turn arises from the much more negative potential of excited CdS nanoparticles electrons relative to the azide reduction potential. More recently, the same photocatalytic approach was successfully applied to the reduction of aryl azide-terminated, self-assembled monolayers on gold to the corresponding arylamine species (Radhakrisham et al., 2006).

Fig. 10. Schematic diagram of photocatalyst W2Fe4Ta2O17 mediated bioreactor for the enzymatic synthesis of L-glutamate.

Photoreduction has been also applied to the design of a novel photobioreactor capable to couple a redox enzyme biocatalysis (Glutamate Dehydrogenase) with the new visible-light active heterogeneous photocatalyst W2Fe4Ta2O17 for the production of L-glutamate (Park et al., 2008). The idea arises from the necessity to develop an efficient and industrially feasible

NO2 NH2

PbBiO2*X* / TEOA nm / 20 h

Anilines can be also obtained in 50 % yields and complete selectivity by photoreduction of aryl azides catalyzed by CdS or CdSe nanoparticles (Warrier et al., 2004). The reaction, which occurs under very mild conditions (room temperature, atmospheric pressure, neutral pH and aqueous medium), requires the presence of sodium formate as sacrificial electron

N3 NH2

CdS

h

HCO2Na CO2

The high efficiency of this photocatalyzed reduction is attributed to the large driving force for electron transfer to the azide, which in turn arises from the much more negative potential of excited CdS nanoparticles electrons relative to the azide reduction potential. More recently, the same photocatalytic approach was successfully applied to the reduction of aryl azide-terminated, self-assembled monolayers on gold to the corresponding

[Rh-complex-H]+


NADH


NAD+

Glutamate Dehydrogenase


H2O

NH4 +

[Rh-complex]2+

Fig. 10. Schematic diagram of photocatalyst W2Fe4Ta2O17 mediated bioreactor for the

Photoreduction has been also applied to the design of a novel photobioreactor capable to couple a redox enzyme biocatalysis (Glutamate Dehydrogenase) with the new visible-light active heterogeneous photocatalyst W2Fe4Ta2O17 for the production of L-glutamate (Park et al., 2008). The idea arises from the necessity to develop an efficient and industrially feasible

donor (Eq. 16).

arylamine species (Radhakrisham et al., 2006).

+2e-

[Rh-complex] +H+

h W2Fe4Ta2O17

enzymatic synthesis of L-glutamate.

e -

VB

CB

> 99 %

(15)

(16)

method for the in situ regeneration of nicotinamide (NAD) co-factor, on which depend the activity of many enzymes. In fact, the high cost of NAD often limits the industrialization potentials of many promising enzymatic processes. The overall schematic mechanism, which regulates this photobioreactor, is reported in Fig. 10. In the photocatalytic cycle, the W2Fe4Ta2O17 upon band-gap excitation by visible light ( > 420 nm) promotes electrons to the conduction band, which are in turn easily transferred to an organometallic Rh complex. The latter, after undergoing hydrogen abstraction from the aqueous medium, transfers electrons and hydride to NAD+, forming NADH.

#### **5.2.3 C-C bond forming reactions**

Among semiconductor photocatalysts, Ru(II)polypyridine complexes are attracting increasing interest because of their stability at room temperature and enhanced photoredox properties (Narayanam & Stephenson, 2011). In particular, Ru(bpy)3Cl2 has been widely employed, as its irradiation with visible light leads to the excited species Ru(bpy)3 2+ \*, which in turn can be employed as strong single electron oxidant and reductant, depending upon reaction conditions. Besides classical oxidative reactions introducing oxygen atoms and reductive hydrogenations, Ru(bpy)3Cl2 has found large use in the photocatalytic promotion of C-C bond formation.

Irradiation of aryl enones, in the presence of a mixture of Ru(bpy)3Cl2, *i-*Pr2NEt and LiBF4 in acetonitrile, allowed to develop a highly diasteroselective intramolecular [2 + 2] cycloaddition reaction, which, in all the examples reported, led to the formation of the corresponding *cis*-cyclobutanes (Eq. 17) (Ischay & al., 2008). In the reaction mechanism, *i*-Pr2NEt has the role to reduces the excited species Ru(bpy)32+ \* to Ru(bpy)3 +, which seems to be the real initiator of the process, while LiBF4, being a Lewis acid, favours the solubility of Ru complex in acetonitrile.

The same system was applied to promote the intermolecular homo-dimerization of aryl enones (Eq. 18) and the crossed intermolecular cyloaddition (Eq. 19) (Du & Yoon, 2009).

$$\mathbf{^{Ar}} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \quad \mathbf{^{Ar}} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{\bullet} \bigvee\_{$$

$$\underbrace{\text{G}}\_{\text{Ar}} \underbrace{\text{G}}\_{\text{R}} + \underbrace{\text{G}}\_{\text{R}} \underbrace{\text{G}}\_{\text{Ar}} \underbrace{\text{G}}\_{\text{Ar} \underbrace{\text{G} \text{M} \text{(bpy)} \text{s}}\_{\text{C} \text{ (dủ} \text{ (e)} \text{lb} \text{ (fủ)}}}\_{\text{H}} \underbrace{\text{G}}\_{\text{Ar}} \underbrace{\text{G}}\_{\text{B}} \underbrace{\text{G}}\_{\text{Ar}} \underbrace{\text{G}}\_{\text{Ar}} \tag{18}$$

$$\underbrace{\text{Od}}\_{\text{Ar}} \underbrace{\text{Od}}\_{\text{Ar}} + \underbrace{\text{Od}}\_{\text{Alk}} \underbrace{\text{Na}(\text{bp}\text{y})\_3 \text{Cl}\_2 / \text{Ar}\_2 \text{NEtM} \text{lBF}\_4}\_{\text{CH}\_3\text{CN} - \text{visible light}} + \underbrace{\text{Od}}\_{\text{Ar}} + \underbrace{\text{Od}}\_{\text{Alk}} \tag{19}$$

More recently, a photoredox strategy based on Ru(bpy)3Cl2 photocatalyst was successfully employed both for the selective -trifluoromethylation upon in situ or pre-generated enolsilanes and silylketenes (Eq. 20) (Pham et al., 2011) and to promote an oxidation/[3 + 2] cycloaddition/aromatization cascade reaction (Zou et al., 2011), the latter leading to the

Semiconductors in Organic Photosynthesis 105

In the last decades a growing interest has been devoted to the development of photocatalytic processes both in the homogeneous and in the heterogeneous phase. Particularly, concerning the heterogeneous systems, great interest has aroused the use of photosensitive semiconductors as catalysts for organic processes, due to their ease to use, recycle and low environmental impact. Although most of the actual applications are restricted to the decomposition of organic pollutants, semiconductors are becoming more and more important for the development of new photocatalyzed organic protocols, as an alternative to the conventional metal-catalyzed thermal processes. Generally, TiO2 has a dominant role in all the semiconductor-phtocatalyzed applications, including the organic synthesis, however, in the last decades many others transition metals photocatalysts, have been developed. Actually, in the scientific landscape, big challenges are represented by the reduction of energy consumption and environmental impact, and photocatalysis could be one of the

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**6. Conclusions** 

**7. References** 

winning answers in the chemistry field.

452, ISSN: 1521-3773

ISSN 1566-7367

548X

formation of pyrrolo[2,1-]isoquinolines from ethyl 2-(3,4-dihydroisoquinolin-2(1*H*-yl) acetate (Eq. 21)

$$\mathsf{R}' \underset{\mathsf{R}''}{\bigotimes\_{\mathsf{R}''}^{\mathsf{I}\mathsf{S}\mathsf{H}\_3}}^{\mathsf{OSVR}\_3} + \quad \mathsf{C}\mathsf{F}\_3^{\mathsf{I}} \underset{\mathsf{T}\mathsf{H}\mathsf{F}\cdot\mathsf{H}\_2\mathsf{O}\cdot\mathsf{s}\mathsf{s}\mathsf{s}\mathsf{s}\mathsf{H}\mathsf{e}\ \mathsf{I}\mathsf{g}\mathsf{H}\mathsf{t}} \quad \mathsf{R}' \underset{\mathsf{R}''}{\bigotimes\_{\mathsf{R}''}^{\mathsf{I}\mathsf{S}\mathsf{F}\_3}}^{\mathsf{O}}\tag{20}$$

$$\left\| \underset{\bullet}{\bigotimes\_{\bullet}^{\mathsf{N}}} \right\|\_{\bullet} \lesssim\_{\epsilon} \sum\_{\mathsf{M}} \underbrace{\underset{\bullet}{\bigotimes\_{\bullet}^{\mathsf{N}} \in \mathsf{C}^{\mathsf{N}} \times \mathsf{C}^{\mathsf{N}}}{\mathsf{C}^{\mathsf{N}} \cdot \mathsf{C}^{\mathsf{N}} \cdot \mathsf{C}^{\mathsf{N}}}}\_{\mathsf{M}} \approx \underbrace{\sum\_{\mathsf{N}} \sum\_{\mathsf{N}} \epsilon\_{\mathsf{N}}}\_{\mathsf{N}}$$

We have already reported the photocatalytic activity of tetrabutylammonium decatungstate salt ((*n*-Bu4N)4W10O32) in selective photoxidations. TBADT has been also used by Albini and coworkers to promote the photocatalytic radical conjugate addition of electron-poor olefins by cycloakanes (Eq. 22) (Dondi et al., 2006) and the acylation of ,-unsaturated nitriles, ketones and esters (Eq. 23) (Esposti et al., 2007), affording the desired products in good yields.

CH3CN / h <sup>+</sup> <sup>O</sup> O (*n-*Bu4N)4W10O32 (22) C CH3CN / h 6H13 H O + EWG EWG C6H13 O EWG EWG (*n-*Bu4N)4W10O32 (23)

 The same group has recently shown that irradiated TBADT can also effectively catalyze the alkylation at position 2 of 1,3-benzodioxoles, making this moiety more biological active and enzyme-specific (Eq. 24) (Ravelli et al., 2011).

$$\bigotimes\_{\mathsf{R}} \bigotimes\_{\mathsf{O}}^{\mathsf{O}} \bigotimes\_{\mathsf{R}^{4}}^{\mathsf{O}} \bigvee\_{\mathsf{R}^{2}}^{\mathsf{R}^{3}} \bigvee\_{\mathsf{EWG}}^{\mathsf{R}^{4}} \xrightarrow[\mathsf{C}\mathsf{A}\_{3}\mathsf{ON}/\mathsf{M}\_{1}\mathsf{O}\_{\mathsf{Z}}]\_{\mathsf{R}}} \star\_{\mathsf{R}} \bigotimes\_{\mathsf{R}} \bigotimes\_{\mathsf{R}^{2}}^{\mathsf{R}^{2}} \bigvee\_{\mathsf{R}^{4}}^{\mathsf{R}^{2}} \bigvee\_{\mathsf{R}^{4}}^{\mathsf{R}^{2}} \tag{24}$$

Another significative example of potentials of semiconductor photocatalysis is represented by the artificial photosynthesis design, that is the fixation of CO2 molecules to afford higher organic compounds (Hoffmann et al., 2011).

For example, many studies have concentrated on the fixation of CO2 in carboxylic acids to produce intermediates in key cellular processes. Recently Guzman and Martin have reported that a glyoxylate can be methylated to produce the corresponding lactate, directly involved in the reductive tricarboxylic acid cycle, by photocatalytic fixation of CO2 mediated by ZnS (Guzman & Martin, 2010).

Nevertheless, it has been recently outlined (Yang et al., 2010) that many results reported in the literature and related to these studies could be influenced by the presence of carbon residues left over from the synthesis of metal oxide semiconductors. In other words, there could be experimental artefacts affecting reports and final conclusions, so that more investigations in the field of artificial photosynthesis is still mandatory.
