Deepika
Tyagi‡
,
Rohit K.
Rai‡
,
Ambikesh D.
Dwivedi
,
Shaikh M.
Mobin
and
Sanjay K.
Singh
*
Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology (IIT) Indore, Khandwa Road, Indore 452 017, India. E-mail: sksingh@iiti.ac.in; Tel: +91 731 2438 730
First published on 11th November 2014
A highly active phosphine-free ruthenium-arene complex, [(η6-C6H6)RuCl2(C6H5NH2)], exhibits excellent catalytic performance for a one-pot conversion of aldehydes to primary amides at low temperature (60 °C), in water and without any inert gas protection. The reported catalyst performed exceptionally well for a huge range of aldehydes, including aromatic, heteroaromatic, aliphatic and conjugated systems, with a high tolerance for other functional groups. The development of such highly active catalysts using simple reagents will offer new opportunities for the development of improved phosphine-free catalytic systems for this and other related catalytic reactions.
Moreover, the ability to perform organic reactions in water, which is cheap, safe and most importantly environment friendly, is in high demand and essentially required.12 Notably, two recent reports have demonstrated a synthesis of amides from aldoxime rearrangements in water, using metal-arene complexes [(η6-C6Me6)RuCl2{P(NMe2)3}] and [(η5-C5Me5)Ir(H2O)3][OTf3]2 (shown in Fig. 1).5,8 Cadierno et al. demonstrated that the complex [(η6-C6Me6)RuCl2{P(NMe2)3}] provides high yields of amides, through aldoxime rearrangement in water, but requires a high reaction temperature (100 °C) and protection by an inert atmosphere.5 However, the iridium complex, [(η5-C5Me5)Ir(H2O)3][OTf3]2, reported by Li et al. exhibited high activity for amide formation in water without inert gas protection, but it also operates only at a very high temperature (110 °C).8
Fig. 1 Metal-arene complex-based active catalysts for amide synthesis from aldoxime rearrangement in water. |
Therefore, in light of the above, we focused our efforts on developing a highly efficient catalyst without phosphine ligands for a one-pot synthesis of primary amides from aldehydes at a lower reaction temperature, under aqueous-aerobic conditions. Here, we report a highly efficient and selective catalyst based on an arene-ruthenium complex with a readily available aniline ligand, [(η6-arene)RuCl2(C6H5NH2)] (η6-arene = C6H6 ([Ru]-2a) and C10H14 ([Ru]-2b)) (Fig. 1), for the one-pot conversion of aldehydes with a broad range of aromatic, heteroaromatic, aliphatic and conjugated systems to amides in water, without inert gas protection, and most importantly at a lower reaction temperature (60 °C).
Chemical formula | C24H26Cl4N2O2Ru2 |
Fw | 718.41 |
T (K) | 150(2) |
Wavelength (Å) | 0.71073 |
Cryst syst, space group | Triclinic, P |
Cryst size (mm) | 0.33 × 0.26 × 0.21 |
a (Å) | 8.0036(3) |
b (Å) | 8.7265(3) |
c (Å) | 18.6255(7) |
α (°) | 76.921(3) |
β (°) | 85.191(3) |
γ (°) | 74.312(3) |
V (Å3) | 1219.56(8) |
Z | 2 |
ρ calcd (g cm−3) | 1.956 |
μ (mm−1) | 11.704 |
F(000) | 712 |
θ range (°) | 2.97–25.00 |
Index ranges | −9 ≤ h ≤ 9; −10 ≤ k ≤ 10;−22 ≤ l ≤ 22 |
Completeness to θmax | 99.8% |
No. of data collected/unique data | 11690/4285 [Rint = 0.1943] |
Absorption correction | Semi-empirical from equivalents |
No. of params/restraints | 297/0 |
Refinement method | Full-matrix least-squares on F2 |
Goodness of fit on F2 | 1.047 |
R 1 [I > 2σ(I)] | 0.0829 |
wR2 [I > 2σ(I)] | 0.2091 |
Largest diff peak and hole (e Å−3) | 2.989 and −4.032 |
Scheme 1 The synthesis of ruthenium-arene complexes [(η6-arene)RuCl2(C6H5NH2)] ([Ru]-2a and [Ru]-2b). |
The structure of the complex [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) was further confirmed by single-crystal X-ray diffraction analysis of suitable crystals of [Ru]-2a, grown by slow evaporation of a solution of [Ru]-2a in a methanol–dichloromethane (2:1) mixture. The complex [Ru]-2a crystallizes in the triclinic P space group, where two crystallographically independent molecules have been observed in the unit cell of [Ru]-2a (Fig. 2, Fig. S1,†Table 1, and Tables S1 and S2 in the ESI†). An ORTEP view of a single molecule of the complex [Ru]-2a and selected bond lengths and angles are given in Fig. 2. The Ru centre in complex [Ru]-2a exhibits the usual piano-stool geometry, with the nitrogen atom of aniline and two chloride ligands as the legs. The η6-coordinated benzene ring in the complex [Ru]-2a is almost planar and the ruthenium centre is displaced by 1.662 Å from the centroid of the benzene ring. Both the Ru–nitrogen bond distances (2.158 Å) and the Ru–chlorine bond distances (2.431 Å) were within the expected bonding distances for ruthenium arene complexes.16 The angles between the legs, Cl–Ru–Cl (88.48°) and Cl–Ru–N (82.87°), and the angles between the legs and the centroid of the η6-C6H6 ring (CCt) (126.5°–133.7°) are comparable with other similar complexes.16 Moreover, the Ru1–N1–C7 and Ru2–N2–C19 angles of 117.7(4)° and 117.8(5)°, respectively, indicated an away placement of the phenyl ring of aniline from the Ru centre.
Entry | Catalyst | Base | T (°C)/time (h) | Conv./sel. (%)b |
---|---|---|---|---|
a Conditions: benzaldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv.), [Ru] (5 mol%), NaHCO3 (1.3 equiv.), H2O (8 mL). b Determined by 1H NMR. c Reactions were performed under a N2 atmosphere. d [Ru] (2.5 mol%), TON 25.3 (5 h) (in parentheses: selectivity at 24 h). e Ref. 5. f Ref. 8. g Cat. (1.5 mol%), with p-chlorobenzaldehyde as the substrate. h Ref. 6b. i Reaction was performed in toluene. j Ref. 6e. k Ref. 10. l Reaction was performed in DMSO–H2O. m Isolated yields. | ||||
1 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 60/5 | 99/99 |
2 | [(η6-C10H14)RuCl2(C6H5NH2)] ([Ru]-2b) | NaHCO3 | 60/5 | 99/65 |
3 | [{(η6-C6H6)RuCl2}2] ([Ru]-1a) | NaHCO3 | 60/5 | 99/54 |
4 | [{(η6-C10H14)RuCl2}2] ([Ru]-1b) | NaHCO3 | 60/5 | 99/84 |
5c | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 80/4 | 99/99 |
6c | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 60/5 | 99/99 |
7 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 50/5 | 96/99 |
8 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 40/5 | 94/92 |
9 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | K2CO3 | 60/5 | 99/91 |
10 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaOH | 60/5 | 98/98 |
11 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | KOH | 60/5 | 95/85 |
12 | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | Na2CO3 | 60/5 | 92/77 |
13d | [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) | NaHCO3 | 60/5 | 99/64(83) |
14e | [(η6-C6Me6)RuCl2{P(NMe2)3}] | NaHCO3 | 100/7 | 88m |
15f,g | [(η5-C5Me5)Ir(H2O)3][OTf3]2 | Na2CO3 | 110/12 | 85m |
16h,i | [terpyRu(PPh3)Cl2] | NaHCO3 | Reflux/17 | 88m |
17i,j | [Ru(DMSO)4Cl2] | NaHCO3 | Reflux/6 | 24m |
18k,l | Pd(OAc)2 | Cs2CO3 | 100/15 | 98m |
Most importantly, the complex [Ru]-2a not only exhibits higher catalytic performance even at a lower temperature (60 °C) in comparison to other catalysts, it also exhibits excellent stability in an aerobic environment. It is worth mentioning here that removal of the N2 gas protection, does not exhibit any adverse effect on the catalytic performances of the studied complexes (Table 2, entries 1 and 6). Use of inert gas was considered in previous reports to be essential for the catalytic conversion of aldehydes to amides.5 Therefore, we performed all of the catalytic reactions under aerobic conditions without any inert gas protection. The optimal reaction conditions for the catalytic conversion of aldehydes to amides are: a substrate/catalyst/NH2OH·HCl/NaHCO3 ratio of 100/5/130/130; H2O as the solvent; a reaction temperature 60 °C; and without any inert gas protection. The generality and scope of complex [Ru]-2a were then explored using a wide range of aldehydes (entries 1–18, Table 3 and entries 1–7, Table 4), including aromatic, heteroaromatic, aliphatic and conjugated systems, and the results obtained are summarized in Tables 3 and 4.
Entry | Substrate | Product | Time (h) | Conv./sel. (%) | TONd/TOFe |
---|---|---|---|---|---|
a Conditions: aldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv.), [Ru]-2a (5 mol%), NaHCO3 (1.3 equiv.), H2O (8 mL). b Conversion and selectivity were determined by 1H NMR. c Reaction was performed in a H2O–methanol mixture (10:1 v/v). d TON = turnover number. e TOF = turnover frequency (h−1). | |||||
1 | 5 | 99/99 | 19.60/3.92 | ||
2 | 5 | 99/60 | 11.88/2.37 | ||
3 | 5 | 99/84 | 16.63/3.32 | ||
4 | 5 | 99/99 | 19.60/3.92 | ||
5 | 5 | 99/86 | 17.02/3.40 | ||
6 | 5 | 99/56 | 11.08/2.21 | ||
7 | 5 | 99/55 | 10.89/2.17 | ||
8 | 5 | 99/90 | 17.82/3.56 | ||
9 | 5 | 99/91 | 18.01/3.60 | ||
10 | 5 | 99/45 | 8.91/1.78 | ||
11 | 5 | 99/73 | 14.45/2.89 | ||
12 | 5 | 99/23 | 4.55/0.91 | ||
24 | 99/80 | 15.84/0.66 | |||
13 | 24 | 99/93 | 18.41/0.76 | ||
14 | 5 | 99/60 | 11.88/2.38 | ||
24 | 99/90 | 17.82/0.74 | |||
15 | 5 | 99/90 | 17.82/3.56 | ||
16 | 5 | 99/92 | 18.21/3.64 | ||
17 | 24 | 99/99 | 19.60/0.81 | ||
18c | 24 | 99/99 | 19.60/0.81 |
Entry | Substrate | Product | Time (h) | Conv./Sel. (%) | TONc/TOFd |
---|---|---|---|---|---|
a Conditions: aldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv.), [Ru]-2a (5 mol%), NaHCO3 (1.3 equiv.), H2O (8 mL). b Conversion and selectivity were determined by 1H NMR. c TON = turnover number. d TOF = turnover frequency (h−1). | |||||
1 | 24 | 99/65 | 12.87/0.536 | ||
2 | 24 | 99/74 | 14.65/0.61 | ||
3 | 5 | 99/99 | 19.60/3.92 | ||
4 | 5 | 99/92 | 18.81/3.76 | ||
5 | 5 | 99/86 | 17.03/3.40 | ||
6 | 5 | 99/99 | 19.60/3.92 | ||
7 | 5 | 99/99 | 19.60/3.92 |
As observed for benzaldehyde, complex [Ru]-2a exhibits a high catalytic performance, >99% conversion and good selectivity, for almost all of the substituted aromatic aldehydes used to synthesize the corresponding primary amides, regardless of the position and electronic behavior of the substituents on the phenyl ring (Table 3). However, aromatic aldehydes with electron donating substituents (entries 13–17, Table 3) displayed a high selectivity in comparison to those with electron withdrawing substituents (entries 2–12, Table 3). Among the substrates with electron withdrawing substituents, the –NO2 substituted aromatic aldehydes exhibited very low selectivity in the amide formation due to the strong electron withdrawing nature of the –NO2 group, which retards the rearrangement of the aldoxime intermediate into the corresponding amide (Table 3, entry 12).11d Moreover, as expected, the ortho-substituted (entries 2,6, Table 3) aromatic aldehydes showed a lower activity in comparison to the corresponding meta- and para-substituted aromatic aldehydes, presumably due to steric effects (entries 3–5,7–8, Table 3). In comparison to –Me substituted aromatic aldehydes (Table 3, entries 15–16), with the 2-OMe substituted aromatic aldehyde (Table 3, entry 13) there is a possibility of coordination of the resulting aldoxime, as O,N chelation, to the metal centre thereby preventing the rearrangement of the aldoxime to the corresponding amide, which may be responsible for the long reaction period used (24 h) to generate 2-methoxybenzamide.19 As an extreme case, aromatic (e.g. salicylaldehyde) and heteroaromatic (e.g. pyridine-2-carboxaldehyde) aldehydes which are highly coordinating in nature, remain completely unreactive.17 It is worth mentioning here that the complex [Ru]-2a exhibits a high tolerance towards various labile functional groups, such as halides (entries 2–9, Table 3), nitro groups (entries 10–12, Table 3) and thioethers (entry 17, Table 3). The tolerance towards sulfur containing substrates is worth noting as sulfur species can poison homogeneous catalysts. Moreover, the complex [Ru]-2a could be advantageously used to synthesize ferrocenecarboxamide (entry 18, Table 3) from ferrocenecarboxaldehyde in higher yields and at a lower temperature (60 °C), when compared to the classical two-step method for its synthesis which uses harmful reagents such as thionyl chloride.18 In addition, heteroaromatic aldehydes, furyl (entry 1, Table 4) and thienyl (entry 2, Table 4) aldehydes, and α,β-unsaturated aldehydes (entries 3–4, Table 4) having conjugated olefin-carbonyl conjugated bonds, can also be converted to the corresponding primary amides. Further exploration with aliphatic aldehydes (CH3(CH2)nCHO, n = 2,4) (entries 5–6, Table 4) and cyclohexanecarboxaldehyde (entry 7, Table 4) revealed that [Ru]-2a exhibits an exceptionally high catalytic activity (selectivities 86%–99%) for the transformation of these aldehyde substrates into the corresponding amides. Almost all of the aldehydes exhibit high conversions and selectivities in the transformation to the corresponding amides, the only byproduct observed is aldoxime, which is also an intermediate for the aldehyde to amide conversion,7 for those aldehyde substrates having a poor selectivity. Moreover, pure crystals of the amides, in most of the cases, could be isolated by cooling the reaction mixture to 0 °C after completion of the reaction, and the identity of the isolated amides were analyzed by NMR spectroscopy (Fig. S2, ESI†).
To elucidate the reaction mechanism, we monitored the catalytic reaction by 1H NMR spectroscopy using benzaldehyde as the representative aldehyde substrate. As shown in Fig. 3, the benzaldoxime formed in the early stages of the catalytic cycle is slowly consumed to generate benzamide. To our surprise, benzonitrile was not observed, which was considered to be an important intermediate in the aldoxime rearrangement process. So the classical pathway of hydration of a benzonitrile intermediate by water can be discarded, instead aldoxime assisted hydration of benzonitrile may be the plausible pathway.8,19 To further demonstrate the above assumption, a reaction of benzonitrile was attempted in water at 60 °C in the presence of the [Ru]-2a catalyst, but no conversion was observed. However, under analogous reaction conditions, hydration of benzonitrile can be facilitated in the presence of butylaldoxime to yield benzamide, which further supports the alternative pathway for the hydration of benzonitrile (Schemes 2 and S1, ESI†).
Fig. 3 Plot of the time-dependent reaction progress for the catalytic conversion of benzaldehyde to benzamide in the presence of [Ru]-2a, in water at 60 °C. |
Dissociation of the ancillary ligands from the metal complex has previously been reported to generate a catalytically active species.20 Therefore, the possible structural changes in the [Ru]-2a catalyst, such as the dissociation of aniline, during the catalytic reaction were studied by 1H NMR and mass spectrometry, using the substrate 3-chlorobenzaldehyde at a substrate to catalyst ratio (S/C) of 6:1. While characterizing the catalyst recovered after the catalytic reaction using 1H NMR, we observed that the peaks corresponding to the ruthenium bound aniline were missing. Moreover, the mass spectrum of the recovered catalyst exhibits peaks corresponding to only [(η6-C6H6)RuCl(OH2)] (m/z 232.9285) and [(η6-C6H6)RuCl] (m/z 214.9190), whereas those corresponding to [(η6-C6H6)RuCl(C6H5NH2)] were absent (Fig. S3, ESI†). The observed 1H NMR and mass spectral data indicates that, presumably, replacement of the aniline ligand is the first step in the catalytic reaction, to provide a vacant coordination site for subsequent coordination of aldoxime to the ruthenium metal centre (Scheme 2).20 Comparing the catalytic performance of [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) with the corresponding arene-ruthenium dimer [{(η6-C6H6)RuCl2}2], it is easy to understand that the presence of aniline has a positive effect on the observed enhanced catalytic performance of the [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) catalyst, and presumably this is accounted for by the easy replacement of aniline with aldoxime. To further address the question of whether aniline is working as a base or a co-catalyst, we performed a reaction in the absence of base and observed >99% conversion but with only 94% selectivity for the amide. These results indicated that presumably the free aniline may act as a base or co-catalyst without coordination to the ruthenium centre. However, using aniline as an additive may retard the catalytic reaction due to it undergoing condensation with the aldehyde and preventing the formation of the crucial aldoxime intermediate. Moreover, surprisingly, free aniline in the crude reaction mixture could not be detected by either 1H NMR or mass spectrometry.
Footnotes |
† Electronic supplementary information (ESI) available: Experimental and spectral data for the amides. Structural data for [Ru]-2a. CCDC 995119. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4qi00115j |
‡ These authors contributed equally. |
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