**1. Introduction**

238 Current Trends in X-Ray Crystallography

Velders, A. H.; Kooijman, H.; Spek, A. L.; Haasnoot, J. G.; de Vos, D. & Reedijk, J. (2000).

Velders, A. H.; Van der Schilden, K.; Hotze, A. C. G.; Reedijk, J.; Kooijman, H. & Spek, A. L.

Wada, T.; Fujihara, T.; Tomori, M.; Ooyama, D. & Tanaka, K. (2004). Strong Interaction

Complexes. *Bulletin of the Chemical Society of Japan*, Vol.77, No.4, pp. 741-749 Zhou, Y.; Xiao, H.-P.; Kang, L.-C.; Zuo, J.-L.; Li, C.-H. & You, X.-Z. (2009). Synthesis and

pp. 2966-2967

*Transactions*, No.3, pp. 448-455

Strong Differences in the in Vitro Cytotoxicity of Three Isomeric Dichlorobis(2 phenylazopyridine)ruthenium(II) Complexes. *Inorganic Chemistry*, Vol.39, No.14,

(2004). Dichlorobis(2-phenylazopyridine)ruthenium(II) Complexes: Characterisation, Spectroscopic and Structural Properties of Four Isomers. *Dalton* 

between Carbonyl and Dioxolene Ligands Caused by Charge Distribution of Ruthenium-Dioxolene Frameworks of Mono- and Dicarbonylruthenium

Characterization of Neutral Iron(II) and Ruthenium(II) Complexes with the Isocyanotriphenylborate Ligand. *Dalton Transactions*, No.46, pp. 10256-10262

> Functionalization of metal complexes by introduction of functional groups has been recognized to be important toward the development of further functionality of metal complexes, including ion sensing, molecular recognition, and selective catalysis.

> Convergence of functional groups into certain direction and appropriate spatial arrangement can be achieved by coordination of metal ions to ligands with those groups to perform novel functions that cannot be achieved by organic ligand molecules for themselves. This strategy allows us to access multifunctional molecules more easily than that with well-designed organic molecules in terms of synthetic availability.

> Ruthenium complexes bearing chelating pyridylamine ligands are robust enough to hold those ligands in the coordination spheres for the convergence of functional groups attached to the ligands and to maintain their appropriate spatial geometry. We have used tris(2 pyridylmethyl)amine (TPA) and its derivatives which coordinate to the ruthenium ion as tetradentate ligands. Introduction of functional groups to the 6-position of pyridine rings of TPA can provide additional functionality for ruthenium-TPA complexes (Figure 1). The concept, i.e., the introduction of amide groups at the 6-positions of pyridine rings in TPA, has been originally introduced by Masuda and coworkers to construct a hydrophobic and sterically protected environment in copper complexes by using pivaloylamide groups (Harata *et al*., 1994, 1995, 1998; Wada *et al.*, 1998). They have succeeded in a number of important metal complexes in bioinorganic chemistry. Inspired by their works, we have developed our concept to functionalize ruthenium-TPA complexes by introducing various functional groups via amide linkages. In our case, the ruthenium complexes bearing trisubstituted TPA is not suitable for functionalization due to its large steric crowding. Therefore we have applied bisamide and monoamide-TPA as ligands. In this chapter, we will present an overview of a chemistry of ruthenium complexes bearing bisamide-TPA and monoamide-TPA as ligands and their characteristics.

### **2. Convergence of hydrophobic functional groups in the coordination sphere of ruthenium complexes**

According to the strategy mentioned above, we introduced hydrophobic groups to TPA toward molecular recognition based on van der Waals interactions in the coordination

Ruthenium(II)-Pyridylamine Complexes Having Functional Groups via Amide Linkages 241

dihedral angles between the amide moieties and the amide-linked pyridine rings are 13.4º for the coordinated amide group and 4.3º for the uncoordinated group, respectively. Compared to those dihedral angles, the naphthalene rings show larger dihedral angels with respect to the amide moieties (39.3° for the coordinated amide and 45.6° for the uncoordinated amide). The coordinated amide oxygen and the uncoordinated amide N-H hydrogen forms the intramolecular hydrogen bond with the distance of 3.036(6) Å for O1N6 to converge the two naphthyl groups. The two naphthalene rings are close enough

C29-C34 and other interatomic distance are listed in Table 1, and are almost parallel to each other with the dihedral angle of 5.9º, indicating the formation of a face-to-face

interaction (Figure 3a) (Hunter & Sanders, 1990; Janiak, 2000). Complex **2** bearing two 2 naphthyl groups exhibits almost the same structural features as those of **1** (Figure 2b). Dihedral angles between the amide-linked pyridine ring and the amide plane were calculated to be 10.4 and 20.7° for the coordinated and the uncoordinated ones, respectively. The distortion between the amide planes and the naphthalene rings (20.6° for the coordinated amide and 20.0° for the uncoordinated amide) are smaller than those observed for **1**, probably due to the lack of steric hindrance derived from the peri hydrogen atoms in **1**. The distance of the hydrogen bond between the coordinated amide oxygen and the

Fig. 2. Crystal structures of the cationic moieties of (a) **1**, (b) **2**, (c) **3**, and (d) **4** with 50% probability thermal ellipsoids. Hydrogen atoms except the amide N-H ones are omitted for

interactions as represented by the shortest contact of 3.36(1) Å for


to form intramolecular

clarity.


sphere of Ru(II) complexes. The TPA derivatives synthesized were those having 1-naphtyl, 2-naphtyl, and isobutyl groups via amide linkages (*N*,*N*-bis(6-(1-naphthoylamide)-2 pyridylmethyl)-*N*-(2-pyridylmethyl)amine = (1-Naph)2-TPA, *N*,*N*-bis(6-(2-naphthoylamide)-2-pyridylmethyl)-*N*-(2-pyridylmethyl)amine = (2-Naph)2-TPA, *N*,*N*-bis(6-(isobutyrylamide)-2-pyridylmethyl)-*N*-(2-pyridyl-methyl)amine = (Isob)2-TPA, *N*-(6-(1 naphthoylamide)-2-pyridylmethyl)-*N*,*N*-bis(2-pyridylmethyl)amine = 1-Naph-TPA) and their Ru(II) complexes ([RuCl((1-Naph)2-TPA)]PF6 (**1**), [RuCl((2-naph)2TPA)]PF6 (**2**), [RuCl((Isob)2-TPA)]PF6, (**3**), [RuCl((1-Naph)-TPA)(DMSO)]PF6 (**4**)) were also prepared, respectively (Figure 1) (Kojima *et al.*, 2000, 2004a, 2005).

Fig. 1. Structures of Ru-bisamide-TPA and Ru-monoamide-TPA complexes

#### **2.1 Crystal structures of ruthenium(II) complexes bearing TPA with 1-naphthyl, 2-naphthyl, and isopropyl groups via amide linkages**

The crystal structures of **1-3** are shown in Figure 2. Those Ru(II)-bisamide-TPA complexes have basically the same coordination environment around the Ru(II) centers. The bisamide-TPA ligands in those complexes coordinate to the Ru(II) ions as pentadentate ligands by the chelation involving three pyridine nitrogen atoms, one tertiary amino nitrogen, and one amide oxygen. Besides those, one chloride ion binds to the Ru(II) center at the *trans* position to the unsubstituted pyridine ring, providing distorted octahedral environments of the Ru(II) complexes. The amide oxygen coordinates to the *trans* site to the tertiary amino nitrogen to afford an asymmetric geometry of the complex. The substituted pyridine rings are located at *trans* positions to each other, and the N-H hydrogen atoms of the uncoordinated amide moiety forms intramolecular hydrogen bonding with the coordinated oxygen atom. The hydrophobic groups were converged and fixed into one direction due to the intramolecular hydrogen bond between two amide arms.

In the structure of **1** (Figure 2a), the bond lengths between the Ru(II) center and the nitrogen atoms of the substituted pyridines are different from the Ru(II) complexes with unsubstituted TPA, reflecting the asymmetric coordination environment due to the coordination of amide oxygen (1.992(5) Å for Ru1-N3 and 2.125(5) Å for Ru1-N4). The

sphere of Ru(II) complexes. The TPA derivatives synthesized were those having 1-naphtyl, 2-naphtyl, and isobutyl groups via amide linkages (*N*,*N*-bis(6-(1-naphthoylamide)-2 pyridylmethyl)-*N*-(2-pyridylmethyl)amine = (1-Naph)2-TPA, *N*,*N*-bis(6-(2-naphthoylamide)-2-pyridylmethyl)-*N*-(2-pyridylmethyl)amine = (2-Naph)2-TPA, *N*,*N*-bis(6-(isobutyrylamide)-2-pyridylmethyl)-*N*-(2-pyridyl-methyl)amine = (Isob)2-TPA, *N*-(6-(1 naphthoylamide)-2-pyridylmethyl)-*N*,*N*-bis(2-pyridylmethyl)amine = 1-Naph-TPA) and their Ru(II) complexes ([RuCl((1-Naph)2-TPA)]PF6 (**1**), [RuCl((2-naph)2TPA)]PF6 (**2**), [RuCl((Isob)2-TPA)]PF6, (**3**), [RuCl((1-Naph)-TPA)(DMSO)]PF6 (**4**)) were also prepared,

respectively (Figure 1) (Kojima *et al.*, 2000, 2004a, 2005).

Fig. 1. Structures of Ru-bisamide-TPA and Ru-monoamide-TPA complexes

**2-naphthyl, and isopropyl groups via amide linkages** 

the intramolecular hydrogen bond between two amide arms.

**2.1 Crystal structures of ruthenium(II) complexes bearing TPA with 1-naphthyl,** 

The crystal structures of **1-3** are shown in Figure 2. Those Ru(II)-bisamide-TPA complexes have basically the same coordination environment around the Ru(II) centers. The bisamide-TPA ligands in those complexes coordinate to the Ru(II) ions as pentadentate ligands by the chelation involving three pyridine nitrogen atoms, one tertiary amino nitrogen, and one amide oxygen. Besides those, one chloride ion binds to the Ru(II) center at the *trans* position to the unsubstituted pyridine ring, providing distorted octahedral environments of the Ru(II) complexes. The amide oxygen coordinates to the *trans* site to the tertiary amino nitrogen to afford an asymmetric geometry of the complex. The substituted pyridine rings are located at *trans* positions to each other, and the N-H hydrogen atoms of the uncoordinated amide moiety forms intramolecular hydrogen bonding with the coordinated oxygen atom. The hydrophobic groups were converged and fixed into one direction due to

In the structure of **1** (Figure 2a), the bond lengths between the Ru(II) center and the nitrogen atoms of the substituted pyridines are different from the Ru(II) complexes with unsubstituted TPA, reflecting the asymmetric coordination environment due to the coordination of amide oxygen (1.992(5) Å for Ru1-N3 and 2.125(5) Å for Ru1-N4). The dihedral angles between the amide moieties and the amide-linked pyridine rings are 13.4º for the coordinated amide group and 4.3º for the uncoordinated group, respectively. Compared to those dihedral angles, the naphthalene rings show larger dihedral angels with respect to the amide moieties (39.3° for the coordinated amide and 45.6° for the uncoordinated amide). The coordinated amide oxygen and the uncoordinated amide N-H hydrogen forms the intramolecular hydrogen bond with the distance of 3.036(6) Å for O1N6 to converge the two naphthyl groups. The two naphthalene rings are close enough to form intramolecular - interactions as represented by the shortest contact of 3.36(1) Å for C29-C34 and other interatomic distance are listed in Table 1, and are almost parallel to each other with the dihedral angle of 5.9º, indicating the formation of a face-to-face - interaction (Figure 3a) (Hunter & Sanders, 1990; Janiak, 2000). Complex **2** bearing two 2 naphthyl groups exhibits almost the same structural features as those of **1** (Figure 2b). Dihedral angles between the amide-linked pyridine ring and the amide plane were calculated to be 10.4 and 20.7° for the coordinated and the uncoordinated ones, respectively. The distortion between the amide planes and the naphthalene rings (20.6° for the coordinated amide and 20.0° for the uncoordinated amide) are smaller than those observed for **1**, probably due to the lack of steric hindrance derived from the peri hydrogen atoms in **1**. The distance of the hydrogen bond between the coordinated amide oxygen and the

Fig. 2. Crystal structures of the cationic moieties of (a) **1**, (b) **2**, (c) **3**, and (d) **4** with 50% probability thermal ellipsoids. Hydrogen atoms except the amide N-H ones are omitted for clarity.

Ruthenium(II)-Pyridylamine Complexes Having Functional Groups via Amide Linkages 243

A Ru(II) complex having a monoamide-TPA ligand has been also synthesized employing (1- Naph)-TPA as a ligand. The crystal structure of the cation moiety of **4** is presented in Figure 2d. The (1-Naph)-TPA ligand coordinates to the Ru(II) center as a tetradentate ligand without the coordination of its amide oxygen as observed in Ru(II)-bisamide-TPA complexes mentioned above. The amide-substituted pyridine ring occupies the *trans* position to one of the unsubstituted pyridine rings. The chloride anion binds to the Ru(II) ion at the *trans* site to the tertiary amino group; the DMSO molecule binds to Ru(II) ion with the S atom at the *trans* site to the unsubstituted pyridine ring. The intramolecular hydrogen bond can be observed between the N-H group of the amide moiety and the chloride ligand (Cl1N5, 3.135(3) Å). Complex **4** shows a larger dihedral angle between the amide plane

As an important characteristics of the Ru(II)-bisamide-TPA complexes **1 – 3**, the coordinated amide moiety can exhibit reversible deprotonation and protonation, as depicted in Scheme 1, to regulate the redox potential of the RuII/RuIII couple of the ruthenium center: The redox potential can be reversibly controlled in the range of ~500 mV (500 mV for **1**, 450 mV for **2**,

Scheme 1. Reversible deprotonation and protonation of the coordinated amide moiety.

The convergence of functional groups to form hydrophobic environments in the coordination sphere of Ru(II) complexes has been achieved by introduction of

& Hirota interactions in coordination spheres to regulate the stereochemistry of Ru

such as acetyl acetone (Hacac), dibenzoylmethane (Hdbm), and benzoyl acetone (Hbac). The

[Ru(acac)((1-Naph)2-TPA)]PF6 (**5**), [Ru(dbm)((1-Naph)2-TPA)]PF6 (**6**), and [Ru(bac)((1- Naph)2-TPA)]PF6 (**7Me** and **7Ph**) as depicted in Figure 1 (Kojima *et al*., 2004b). In those complexes, in contrast to the case of **1**, the (1-Naph)2-TPA ligand coordinates to the Ru(II)

bidentate monoanionic ligands. Both of the amide oxygens in the (1-Naph)2-TPA ligand direct to the opposite sides from the metal center and both of the amide N-H hydrogens

**-diketonato complexes and** 


**-diketonato ligands** 

and CH/



Nishio



and the 1-naphthyl group of 57.65(4)º than those (39.3° and 45.6°) of **1**.

and 480 mV for **3**) in CH3CN.

**2.2 Crystal structures of ruthenium(II)-TPA-**

reactions between **1** and

**intramolecular rearrangement of coordination geometry of** 

naphthoylamide groups to the TPA ligand. Then, the ability to form

presence of 2,6-lutidine as a base to afford corresponding

center as a tetradentate ligand by the TPA moiety, and the

centers has been examined using the Ru(II)-(1-Naph)2-TPA complex (**1**) and


Table 1. Interatomic Distances (Å) for Intramolecular –Interactions in **1** and **2**.

Fig. 3. Intramolecular -interactions between two naphthalene rings of (a) **1** and (b) **2**.

uncoordinated amide N-H moiety is 2.977(3) Å (O1N6). Two naphthalene rings were converged with the shortest contact of 3.398(4) Å for C27-C38. However, two naphthalene rings of **2** show a larger dihedral angle of 27.1º than that (5.9°) of **1**, indicating a sort of edgeto-face - interaction (Figure 3b and Table 1). In this complex, the 2-naphthyl groups exhibit fluxional behavior and the thermodynamic parameters of the - interaction has been estimated to be *H*° = –2.3 kJ mol–1; thus, *G*° = –0.9 kJ mol–1 and *S*° = –7.7 J mol–1 K–1 at 233 K in CD3CN.

Concerning the crystal structure of **3** having two isopropyl groups (Figure 2c), two substituted pyridine rings occupy the *trans* sites to each other with the intramolecular hydrogen bond between the coordinated amide oxygen and the N-H hydrogen of the uncoordinated amide moiety (3.041(6) Å) in a similar manner to those in **1** and **2**. This observation suggests that the formation of the intramolecular hydrogen bond provides the asymmetric coordination environments of those complexes and convergence of the naphthalene rings to form intramolecular van der Waals interactions.

C20C33 3.68(1) C26C32 3.699(4) C24C34 3.65(1) C26C39 3.528(4) C24C35 3.50(1) C26C40 3.496(4) C24C40 3.43(1) C27C31 3.466(4) C25C35 3.63(1) C27C37 3.596(4) C25C40 3.59(1) C27C38 3.398(4)

C26C38 3.69(1) C26C39 3.57(1) C27C31 3.61(1) C28C32 3.64(1) C28C33 3.563(9) C29C33 3.65(1) C29C34 3.36(1)

Table 1. Interatomic Distances (Å) for Intramolecular

Fig. 3. Intramolecular

to-face


at 233 K in CD3CN.


–

interactions between two naphthalene rings of (a) **1** and (b) **2**.

interaction (Figure 3b and Table 1). In this complex, the 2-naphthyl groups

uncoordinated amide N-H moiety is 2.977(3) Å (O1N6). Two naphthalene rings were converged with the shortest contact of 3.398(4) Å for C27-C38. However, two naphthalene rings of **2** show a larger dihedral angle of 27.1º than that (5.9°) of **1**, indicating a sort of edge-

been estimated to be *H*° = –2.3 kJ mol–1; thus, *G*° = –0.9 kJ mol–1 and *S*° = –7.7 J mol–1 K–1

Concerning the crystal structure of **3** having two isopropyl groups (Figure 2c), two substituted pyridine rings occupy the *trans* sites to each other with the intramolecular hydrogen bond between the coordinated amide oxygen and the N-H hydrogen of the uncoordinated amide moiety (3.041(6) Å) in a similar manner to those in **1** and **2**. This observation suggests that the formation of the intramolecular hydrogen bond provides the asymmetric coordination environments of those complexes and convergence of the

exhibit fluxional behavior and the thermodynamic parameters of the

naphthalene rings to form intramolecular van der Waals interactions.

Interactions in **1** and **2**.


interaction has

A Ru(II) complex having a monoamide-TPA ligand has been also synthesized employing (1- Naph)-TPA as a ligand. The crystal structure of the cation moiety of **4** is presented in Figure 2d. The (1-Naph)-TPA ligand coordinates to the Ru(II) center as a tetradentate ligand without the coordination of its amide oxygen as observed in Ru(II)-bisamide-TPA complexes mentioned above. The amide-substituted pyridine ring occupies the *trans* position to one of the unsubstituted pyridine rings. The chloride anion binds to the Ru(II) ion at the *trans* site to the tertiary amino group; the DMSO molecule binds to Ru(II) ion with the S atom at the *trans* site to the unsubstituted pyridine ring. The intramolecular hydrogen bond can be observed between the N-H group of the amide moiety and the chloride ligand (Cl1N5, 3.135(3) Å). Complex **4** shows a larger dihedral angle between the amide plane and the 1-naphthyl group of 57.65(4)º than those (39.3° and 45.6°) of **1**.

As an important characteristics of the Ru(II)-bisamide-TPA complexes **1 – 3**, the coordinated amide moiety can exhibit reversible deprotonation and protonation, as depicted in Scheme 1, to regulate the redox potential of the RuII/RuIII couple of the ruthenium center: The redox potential can be reversibly controlled in the range of ~500 mV (500 mV for **1**, 450 mV for **2**, and 480 mV for **3**) in CH3CN.

Scheme 1. Reversible deprotonation and protonation of the coordinated amide moiety.

#### **2.2 Crystal structures of ruthenium(II)-TPA--diketonato complexes and**

**intramolecular rearrangement of coordination geometry of -diketonato ligands**  The convergence of functional groups to form hydrophobic environments in the coordination sphere of Ru(II) complexes has been achieved by introduction of naphthoylamide groups to the TPA ligand. Then, the ability to form - and CH/Nishio & Hirota interactions in coordination spheres to regulate the stereochemistry of Ru centers has been examined using the Ru(II)-(1-Naph)2-TPA complex (**1**) and -diketones, such as acetyl acetone (Hacac), dibenzoylmethane (Hdbm), and benzoyl acetone (Hbac). The reactions between **1** and -diketones have been performed in ethylene glycol at 100ºC in the presence of 2,6-lutidine as a base to afford corresponding -diketonato complexes, [Ru(acac)((1-Naph)2-TPA)]PF6 (**5**), [Ru(dbm)((1-Naph)2-TPA)]PF6 (**6**), and [Ru(bac)((1- Naph)2-TPA)]PF6 (**7Me** and **7Ph**) as depicted in Figure 1 (Kojima *et al*., 2004b). In those complexes, in contrast to the case of **1**, the (1-Naph)2-TPA ligand coordinates to the Ru(II) center as a tetradentate ligand by the TPA moiety, and the -diketonato ligands bind to it as bidentate monoanionic ligands. Both of the amide oxygens in the (1-Naph)2-TPA ligand direct to the opposite sides from the metal center and both of the amide N-H hydrogens

Ruthenium(II)-Pyridylamine Complexes Having Functional Groups via Amide Linkages 245

interactions of (a) **5**, (b) **6**, and (c) **7Me**.

interactions in **5**, **6**, and **7Me**.

interactions

5 6 7**Me**

C41C14 3.59 C51C7 3.46 C41C21 3.38 C41C22 3.62 C51C8 3.45 C41C22 3.41 C41C23 3.45 C51C9 3.66 C41C31 3.51 C41C32 3.34 C52C9 3.66 C41C32 3.66 C41C33 3.52 C52C10 3.31 C41C40 3.64

O3N5 2.79 O2N5 2.87 O3N5 2.87 O3N6 2.85 O2N6 2.92 O3N6 2.92

The structure of **7Me** has been determined as shown in Figure 4c. The methyl group of the bac ligand is also included between the two naphthyl groups as observed in the structure of

–

interactions CH/

Fig. 5. Intramolecular CH/

interactions

hydrogen bonds

CH/  and -

Table 2. Interatomic distances (Å) for intramolecular

–

 C52C16 3.42 C53C11 3.35 C53C12 3.43 C53C13 3.62 C53C15 3.69 C54C14 3.59 C51C32 3.36 C51C33 3.48 C52C33 3.47

form intramolecular hydrogen bonds with one of the oxygen atoms of the -diketonato ligand.

In the structure of **5** (Figure 4a), one of the methyl group of the acac ligand is sandwiched between the two naphthalene rings of the (1-Naph)2-TPA ligand and forms CH/ interactions with the shortest distance of 3.34 Å for C41C32 (Table 2 and Figure 5a). The formation of the CH/ interactions is also demonstrated in solution by 1H NMR measurements in CD2Cl2. The singlet assigned to the included methyl protons of the acac ligand shows a large upfield shift to = –0.27 ppm compared to that of the nonincluded methyl group ( = 1.86 ppm) due to the shielding by the electrons of the naphthalene rings.

Crystal structure of **6** shows inclusion of one of the two phenyl groups of the dbm ligand in the hydrophobic cavity made of the two 1-naphthyl groups (Figure 4b). Close contact can be observed between the included phenyl ring of dbm and the naphthalene rings to form intramolecular - interactions (Table 2). The dihedral angles between the included phenyl ring of the dbm ligand and the two naphthalene rings are estimated to be 11.3(7)º and 62.4(8)º, indicating that one of the - interactions between them is a face-to-face type and the other isedge-to face (Figure 5b). In 1H NMR measurements in CD2Cl2, large upfield shifts of signals assigned to the included phenyl protons compared to those of the nonincluded phenyl group are observed at = 5.54, 6.12, 6.50 ppm. This observation indicates the insertion of the phenyl ring into the two naphthalene rings even in solution.

Fig. 4. ORTEP drawings of (a) **5** and (b) **6** with 50 % probability thermal ellipsoids and (c) **7Me** with 30 % probability thermal ellipsoid.

In the structure of **5** (Figure 4a), one of the methyl group of the acac ligand is sandwiched

with the shortest distance of 3.34 Å for C41C32 (Table 2 and Figure 5a). The formation of the

Crystal structure of **6** shows inclusion of one of the two phenyl groups of the dbm ligand in the hydrophobic cavity made of the two 1-naphthyl groups (Figure 4b). Close contact can be observed between the included phenyl ring of dbm and the naphthalene rings to form

ring of the dbm ligand and the two naphthalene rings are estimated to be 11.3(7)º and

the other isedge-to face (Figure 5b). In 1H NMR measurements in CD2Cl2, large upfield shifts of signals assigned to the included phenyl protons compared to those of the nonincluded

Fig. 4. ORTEP drawings of (a) **5** and (b) **6** with 50 % probability thermal ellipsoids and (c)

 interactions is also demonstrated in solution by 1H NMR measurements in CD2Cl2. The singlet assigned to the included methyl protons of the acac ligand shows a large upfield shift

interactions (Table 2). The dihedral angles between the included phenyl

= 1.86 ppm) due to the

interactions between them is a face-to-face type and

= 5.54, 6.12, 6.50 ppm. This observation indicates the


interactions

form intramolecular hydrogen bonds with one of the oxygen atoms of the

between the two naphthalene rings of the (1-Naph)2-TPA ligand and forms CH/

= –0.27 ppm compared to that of the nonincluded methyl group (


insertion of the phenyl ring into the two naphthalene rings even in solution.

electrons of the naphthalene rings.

ligand.

CH/

to 

shielding by the

intramolecular


phenyl group are observed at

**7Me** with 30 % probability thermal ellipsoid.

62.4(8)º, indicating that one of the

Fig. 5. Intramolecular CH/ and -interactions of (a) **5**, (b) **6**, and (c) **7Me**.


Table 2. Interatomic distances (Å) for intramolecular –interactions in **5**, **6**, and **7Me**.

The structure of **7Me** has been determined as shown in Figure 4c. The methyl group of the bac ligand is also included between the two naphthyl groups as observed in the structure of

Ruthenium(II)-Pyridylamine Complexes Having Functional Groups via Amide Linkages 247

electronic effect is not a determining factor of the regioselectivity of **7Me**. The reaction of **1** with an equimolar mixture of Hacac and Hdbm has been examined to evaluate the steric effect of methyl and phenyl groups on the selective conversion to **7Me**. After the reaction in ethylene glycol at 100 ºC for 24 h, complexes **5** and **6** were obtained in the ratio of 4.8:1. This accessibility of the methyl group in the hydrophobic cavity of the complex suggests that the steric effect may contribute to the regioselectivity. However, the complete conversion of **6** to **5** has not been observed unlike the intramolecular rearrangement from **7Ph** to **7Me**. Therefore, the conversion from **7Ph** to **7Me** is supposed to be consequences of both the steric effect and


hydrophobic cavity of the Ru(II)-(1-Naph)2-TPA complex, even though superior

generally accepted (Steed & Atwood, 2000). The introduction of the 1-naphtyl groups attached to the TPA ligand via amide linkage has allowed us to regulate the stereochemistry of the ruthenium complex by selective inclusion of the methyl group of the bac ligand by

CH/ interaction observed here can be attributed to the polarization of the C-H bond of the methyl group of the bac ligand bound to the positively charged Ru(II) center, making the C-H bond more acidic to strengthen the interaction between the positively polarized hydrogen

Ferrocene is a well-known redox-active molecule and has been introduced to many kinds of functional molecules. Among those, ferrocene-containing ligands have been reported on their multiple redox behavior and mixed-valence states toward a construction of redoxresponsive functional molecules. Thus, we have prepared ferrocene-appended TPA derivatives (*N*-(6-ferrocenoylamide-2-pyridylmethyl)-*N*,*N*-bis(2-pyridylmethyl)amine = Fc-TPA, and *N*,*N*-bis(6-ferrocenoylamide-2-pyridylmethyl)-*N*-(2-pyridylmethyl)amine = Fc2- TPA) and their Ru(II) complexes. We have focused on intramolecular magnetic interactions between the Fe(III) center in the ferrocenium moiety and the Ru(III) center upon oxidation.

**3.1 Crystal structures of a ferrocene-appended TPA derivative and its ruthenium(II)** 


In the crystal of Fc-TPA (Figure 7a), two adjacent molecules form intermolecular hydrogen bonds with each other between the amide N-H and one of unsubstituted pyridine rings (3.042(2) Å for N2N5', 160.5º for N2–H1'–N5'). An intermolecular C-HO hydrogen bond is also found between the amide oxygen and one of unsubstituted pyridine ring (3.334(2) Å

ring and a substituted cyclopentadienyl (Cp) ring, a nonsubstituted Cp ring and adjacent pyridine rings, and a substitute pyridine ring and nonsubstituted pyridine ring (3.325(4) Å for C14C7, 3.638(3) Å for C19C1, 3.618(4) Å for C22C4, 3.257(3) Å for C12-C28; Figure


**3. Ferrocene-appended TPA derivatives and their ruthenium complexes: Intramolecular magnetic interactions between ruthenium and iron centers** 

interactions over


interactions to that obtained by CH/


interactions are observed between a pyridine

interaction as well as the steric effect. The preference of

interactions in the

interactions is

the thermodynamic preference of CH/

thermodynamic stability gained by

virtue of the intramolecular CH/

atom and the negatively charged

**induced by oxidations** 

(Kojima *et al.*, 2008)

for C21O1; Figure 8a). Intermolecular

**complex** 

8b). The

**5** (Table 2 and Figure 5c). Although the single crystal of **7Ph** could not be obtained, the van der Waals interaction between the substituents of bac and naphthalene rings has been indicated by large upfield shift of the methyl signal of **7Me** and those of the phenyl signals of **7Ph** in their 1H NMR spectra.

The formation of CH/ and - interactions in the hydrophobic cavity made of the two naphthyl groups in the Ru(II) coordination sphere has been demonstrated for **5** with acac having two methyl groups and **6** with dbm having two phenyl groups, respectively. Then, the selectivity between - and CH/ interactions has been examined by using an asymmetric -diketone, Hbac, which has both methyl and phenyl groups. After the reaction of **1** with Hbac for 3 h at 100 ºC in ethylene glycol, all the starting material was consumed and a mixture of **7Me** and **7Ph** was obtained at the ratio of 1.8 to 1, accompanying the dissociation of the amide oxygen in **1**. This observation indicates no kinetic selectivity in the coordination mode of the bac ligand to the Ru(II) ion. However, continuous heating of this mixture of the two isomers gave only **7Me** due to the selective conversion of **7Me** to **7Ph**, indicating that **7Me** is thermodynamically more favored relative to **7Ph**. The reaction rate of the conversion from **7Me** to **7Ph** has been revealed to be independent of the Hbac concentration. This result indicates that the isomerization reaction proceeds as a onedirectional intramolecular rearrangement. Kinetic analysis of the rearrangement in light of Arrhenius equation has been made to determine the activation energy to be 52 kJ mol–1. A proposed reaction mechanism involving a putative transition state is described in Figure 6 (Kojima *et al.*, 2004b). This intramolecular rearrangement is assumed to proceed without bond rupture and the transition state should involve weakened coordination bonds for the bac ligand.

Fig. 6. A proposed reaction mechanism of the selective intramolecular rearrangement from **7Me** to **7Ph** in ethylene glycol.

We have also examined whether the selectivity of **7Me** is derived from electronic or steric effect. According to PM3 calculation, the two oxygen atoms of bac exhibits no significant difference in its negative charges (–0.466 for Ph-C*O*- and –0.476 for Me-C*O*-), suggesting the

**5** (Table 2 and Figure 5c). Although the single crystal of **7Ph** could not be obtained, the van der Waals interaction between the substituents of bac and naphthalene rings has been indicated by large upfield shift of the methyl signal of **7Me** and those of the phenyl signals of

naphthyl groups in the Ru(II) coordination sphere has been demonstrated for **5** with acac having two methyl groups and **6** with dbm having two phenyl groups, respectively. Then,

of **1** with Hbac for 3 h at 100 ºC in ethylene glycol, all the starting material was consumed and a mixture of **7Me** and **7Ph** was obtained at the ratio of 1.8 to 1, accompanying the dissociation of the amide oxygen in **1**. This observation indicates no kinetic selectivity in the coordination mode of the bac ligand to the Ru(II) ion. However, continuous heating of this mixture of the two isomers gave only **7Me** due to the selective conversion of **7Me** to **7Ph**, indicating that **7Me** is thermodynamically more favored relative to **7Ph**. The reaction rate of the conversion from **7Me** to **7Ph** has been revealed to be independent of the Hbac concentration. This result indicates that the isomerization reaction proceeds as a onedirectional intramolecular rearrangement. Kinetic analysis of the rearrangement in light of Arrhenius equation has been made to determine the activation energy to be 52 kJ mol–1. A proposed reaction mechanism involving a putative transition state is described in Figure 6 (Kojima *et al.*, 2004b). This intramolecular rearrangement is assumed to proceed without bond rupture and the transition state should involve weakened coordination bonds for the

Fig. 6. A proposed reaction mechanism of the selective intramolecular rearrangement from

We have also examined whether the selectivity of **7Me** is derived from electronic or steric effect. According to PM3 calculation, the two oxygen atoms of bac exhibits no significant difference in its negative charges (–0.466 for Ph-C*O*- and –0.476 for Me-C*O*-), suggesting the


interactions in the hydrophobic cavity made of the two

interactions has been examined by using an

**7Ph** in their 1H NMR spectra. The formation of CH/

the selectivity between

asymmetric

bac ligand.

**7Me** to **7Ph** in ethylene glycol.

 and -

> -

and CH/

electronic effect is not a determining factor of the regioselectivity of **7Me**. The reaction of **1** with an equimolar mixture of Hacac and Hdbm has been examined to evaluate the steric effect of methyl and phenyl groups on the selective conversion to **7Me**. After the reaction in ethylene glycol at 100 ºC for 24 h, complexes **5** and **6** were obtained in the ratio of 4.8:1. This accessibility of the methyl group in the hydrophobic cavity of the complex suggests that the steric effect may contribute to the regioselectivity. However, the complete conversion of **6** to **5** has not been observed unlike the intramolecular rearrangement from **7Ph** to **7Me**. Therefore, the conversion from **7Ph** to **7Me** is supposed to be consequences of both the steric effect and the thermodynamic preference of CH/ interactions over - interactions in the hydrophobic cavity of the Ru(II)-(1-Naph)2-TPA complex, even though superior thermodynamic stability gained by - interactions to that obtained by CH/ interactions is generally accepted (Steed & Atwood, 2000). The introduction of the 1-naphtyl groups attached to the TPA ligand via amide linkage has allowed us to regulate the stereochemistry of the ruthenium complex by selective inclusion of the methyl group of the bac ligand by virtue of the intramolecular CH/ interaction as well as the steric effect. The preference of CH/ interaction observed here can be attributed to the polarization of the C-H bond of the methyl group of the bac ligand bound to the positively charged Ru(II) center, making the C-H bond more acidic to strengthen the interaction between the positively polarized hydrogen atom and the negatively charged -electron cloud of the naphthyl group.
