Phosphine-free ruthenium-arene complex for low temperature one-pot catalytic conversion of aldehydes...

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Rai, A. D. Dwivedi, M. M. Shaikh and S. K. Singh, Inorg. Chem. Front., 2014, DOI: 10.1039/C4QI00115J.

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1

Phosphine-free ruthenium-arene complex for low temperature one-pot catalytic conversion 1

of aldehydes to primary amides in water† 2

Deepika Tyagia‡

, Rohit K. Raia‡

, Ambikesh D. Dwivedia, Shaikh M. Mobin

a, Sanjay K. Singh

a* 3

4

Abstract 5

Highly active phosphine free ruthenium-arene complex, [(η6-C6H6)RuCl2(C6H5NH2)], exhibit ex-6

cellent catalytic performance for one-pot conversion of aldehydes to primary amides at low tem-7

perature (60 °C), in water and without any inert gas protection. The reported catalyst performed 8

exceptionally well for a huge range of aldehydes, ranging from aromatic, heteroaromatic, aliphat-9

ic and conjugated systems, with high tolerance to other functional groups. The development of 10

such highly active catalysts using simple reagents will offer new opportunities for the develop-11

ment of improved phosphine-free catalytic systems for this and other related catalytic reactions. 12

13

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View Article OnlineDOI: 10.1039/C4QI00115J


2

Introduction 1

Amide bonds are not only abundantly observed in nature, as a major component of proteins and 2

natural products, but they are also the key functional groups in synthetic organic chemistry owing 3

to their numerous applications in pharmaceuticals and other industries.1-3

The classical method 4

for amide synthesis is remarkably general where amide linkage is formed by coupling carboxylic 5

acids and their derivatives with amines.4 However, these reactions are regarded as expensive and 6

wasteful method due to the use of toxic and/or expensive reagents, poor functional group toler-7

ance, and generate wastes which may raise potential environmental threats.4 Not surprisingly, the 8

development of an atom efficient and waste-free process for amide synthesis using environment 9

friendly components is considered as the top challenge for organic chemistry.2 Therefore, im-10

proved methodologies for amide bond formation are in great demand. In this context, aldehydes, 11

which are easily available in nature, have been identified as important starting materials. Signifi-12

cant efforts have been made to develop one-pot methodology for the synthesis of amides from 13

aldehydes, via a metal-catalysed rearrangement of aldoxime.3 In recent years, several such cata-14

lytic reactions have been accomplished using various catalytic systems, e.g. Ru, Rh, Ir, Pd, Cu, 15

Fe, Zn, In and Sc, that facilitate an atom-economical approach of amide formation.5-11

16

Moreover, performing organic reactions in water, which is cheap, safe and most im-17

portantly environment friendly, is highly demanding and essentially required.12

Notably, two re-18

cent reports have demonstrated the synthesis of amides from aldoxime rearrangements in water 19

using metal-arene complexes [(η6-C6Me6)RuCl2{P(NMe2)3}] and [(η

5-C5Me5)Ir(H2O)3][OTf3]2 20

(as shown in Figure 1).5,8

Cadierno et al demonstrated that the complex [(η6-21

C6Me6)RuCl2{P(NMe2)3}] exhibit high yields of amides, by aldoxime rearrangement in water, 22

but needs high reaction temperature (100 °C) and inert atmosphere protection.5 However, the 23

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iridium complex, [(η5-C5Me5)Ir(H2O)3][OTf3]2, reported by Li et al exhibited high activity for 1

amide formation in water without an inert gas protection, but it also operates only at very high 2

temperature (110 °C).8 3

Fig. 1 Metal-arene complexes based active catalysts for amide synthesis from aldoxime rear-

rangement in water.

Therefore, in light of above, we focused our efforts to develop a highly efficient catalyst 4

having a non-phosphine ligand for one-pot synthesis of primary amide from aldehyde at lower 5

reaction temperature, under aqueous-aerobic atmosphere. Here, we report a highly efficient and 6

selective catalyst based on arene-ruthenium complex with readily available aniline ligand, [(η6-7

arene)RuCl2(C6H5NH2)] (η6-arene = C6H6 ([Ru]-2a) and C10H14 ([Ru]-2b)) (Figure 1), for one-8

pot conversion of aldehydes with a broad range of aromatic, heteroaromatic, aliphatic and conju-9

gated systems to amides in water, without inert gas protection, and most importantly at lower re-10

action temperature (60 °C). 11

Experimental 12

Materials and instrumentations. All reactions were performed, without inert gas protection, 13

using the chemicals of higher purity purchased from Aldrich and Alfa Aesar. Ruthenium arene 14


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precursors, [{(η6-C6H6)RuCl2}2] and [{(η

6-C10H14)RuCl2}2], were synthesized according to the 1

literature procedure.13,14

Catalytic reactions were monitored by thin layer chromatography (TLC) 2

method. 1H NMR (400 MHz),

13C NMR (100 MHz), and

19F NMR (376.5 MHz) spectra were 3

recorded at 298 K using CDCl3 and DMSO-d6 as solvent on a Bruker Avance 400 spectrometer. 4

Chemical shifts in ppm are relative to tetramethylsilane (TMS) as external standard which are 5

relative to the center of the singlet at 7.26 ppm for CDCl3 and 2.50 ppm for DMSO-d6 in 1H 6

NMR, and to the center of the triplet at 77.0 ppm for CDCl3 and 39.50 ppm for DMSO-d6 in 13

C 7

NMR. Coupling constant J values are reported in Hertz (Hz), and the splitting patterns are desig-8

nated as follows: s, singlet; d, doublet; t, triplet; m, multiplet; br., broad. Single crystal X-ray 9

structural studies of complex, [Ru]-2a, were done using Agilent Technologies Supernova CCD 10

system. The elemental analysis was carried out with the Thermo Scientific FLASH 200 elemental 11

analyzer. High-resolution mass spectra (HRMS) was recorded on a micrOTF-Q II mass spec-12

trometer. 13

General procedure for the synthesis of complexes 14

(a) Preparation of complex [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a). [{(η

6-C6H6)RuCl2}2] 15

(0.250 g, 0.5 mmol), aniline (95 μl, 1.05 mmol) were taken in a round bottom flask with metha-16

nol (100 ml) as a solvent, the reaction mixture was stirred for 15 minutes at room temperature 17

then refluxed the reaction mixture for 24 hours. After 24 hours brown colored solution obtained 18

was dried over rotavapour, the precipitate was washed with diethyl ether, filtered through a cru-19

cible then collected in a round bottom flask by dissolving it in dichloromethane and methanol 20

solvent and again evaporated on rotavapour and dried the solvents in vacuo. The brown precipi-21

tate of the catalyst obtained was washed with hexane solution 4-5 times to remove excess of ani-22

line. The precipitate was crystallized from the dichloromethane/methanol solvent mixture. Identi-23


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ty of resulting complex was assessed using 1H NMR,

13C NMR, Mass spectroscopy, CHN ele-1

mental analysis and single crystal XRD study. Yield: 82 % (0.280 g). 1H NMR (400 MHz, 2

CDCl3): δ (ppm) = 7.45-7.36 (m, 5H), 5.35 (s, 6H), 4.87(br, 2H), 13

C NMR (100 MHz, DMSO-3

d6): δ (ppm) = 148.84, 128.84, 115.65, 113.88, 87.68. HRMS (ESI) m/z calculated for [[(η6-4

C6H6)RuCl2(C6H5NH2)] – Cl]: 307.649 [M+], found 305.255 [M+], Anal. Calcd.: C, 41.99; H, 5

3.82; N, 4.08. Found: C, 41.98; H, 3.79; N, 4.08. 6

(b) Preparation of complex [(η6-C10H14)RuCl2(C6H5NH2)] ([Ru]-2b): Using identical condi-7

tions of ([Ru]-2a) preparation, [(η6-C10H14)RuCl2(C6H5NH2)] complex was prepared by taking 8

the Ru (p-cymene) dimer [{(η6-C10H14)RuCl(μ-Cl)}2] (0.306 g, 0.5 mmol) and aniline (95 μl, 1.05 9

mmol) with 100 ml of methanol as solvent. Yield: 85 % (0.339 g). 1H NMR (400 MHz, CDCl3): 10

δ (ppm) = 7.37 (s, 5H), 7.22 (br., 1H), 5.02 (d, 2H, J = 5.5Hz), 4.91 (d, 2H, J = 5.5Hz), 4.88 (br., 11

1H), 2.86-2.79 (m, 1H), 2.11 (s, 3H), 1.20 (d, 6H, J = 8Hz), 13

C NMR (100 MHz, CDCl3): δ 12

(ppm) = 145.36, 129.51, 125.55, 120.40, 103.51, 95.68, 81.74, 79.67, 30.49, 22.02, 18.58. HRMS 13

(ESI) m/z calculated for [[(η6-C10H14)RuCl2(C6H5NH2)] – Cl]: 364.040 [M

+], found 364.034 14

[M+], Anal. Calcd.: C, 48.2; H, 5.30; N, 3.51. Found: C, 47.7; H, 5.27; N, 3.64. 15

General procedure for catalytic synthesis of amides from aldehydes. To the stirred solution of 16

ruthenium (II) complex [(η6-C10H14)RuCl2(C6H5NH2)] [Ru]-2a (0.017 g, 0.05 mmol, 5 mol%, 17

dissolved in 3 ml of water), added primary aldehyde (1 mmol), hydroxyl ammonium chloride 18

(0.090 g, 1.3 mmol), NaHCO3 (0.109 g, 1.3 mmol), and 5 ml water (water/methanol in ratio 10:1, 19

v/v in case of ferrocenecarboxaldehyde) in a round bottom flask in open air condition and the re-20

action mixture was stirred at 60 °C for 5-24 hours. After this time the reaction mixture was ex-21

tracted with dichloromethane solvent at least 5-6 times, the organic layer of extract was dried 22

with sodium sulfate to remove moisture then evaporated the solvent under reduced pressure 23


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which led to give the corresponding amide. The conversion and selectivity of corresponding am-1

ide were determined with 1H,

13C and

19F NMR spectrum. 2

Single crystal X-ray diffraction Studies. Single crystal X-ray structural studies of [Ru]-2a were 3

performed on a CCD Agilent Technologies (Oxford Diffraction) SUPER NOVA diffractometer. 4

Data were collected at 150(2) K using graphite-monochromated Mo Kα radiation (λα = 0.71073 5

Å). The strategy for the Data collection was evaluated by using the CrysAlisPro CCD software. 6

The data were collected by the standard ‘phi-omega’ scan techniques, and were scaled and re-7

duced using CrysAlisPro RED software. The structures were solved by direct methods using 8

SHELXS-97, and refined by full matrix least-squares with SHELXL-97, refining on F2.15

The 9

positions of all the atoms were obtained by direct methods. All non-hydrogen atoms were refined 10

anisotropically, except the solvent molecules (O111 and O222) which are refined isotropically. 11

The remaining hydrogen atoms were placed in geometrically constrained positions, and refined 12

with isotropic temperature factors, generally 1.2Ueq of their parent atoms. The crystal and re-13

finement data are summarized in Table 1. Bond lengths and bond angles are summarized in Table 14

S1 and S2 (†ESI). The CCDC number 995119 contains the supplementary crystallographic data 15

for [Ru]-2a. This data can be obtained free of charge via www.ccdc.cam.ac.uk (or from the 16

Cambridge Crystallographic Data Centre, 12 union Road, Cambridge CB21 EZ, UK; Fax: (+44) 17

1223-336-033; or [email protected]). 18

Results and Discussion 19

Synthesis of complexes and crystal structure. Mononuclear complexes, [(η6-20

C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) and [(η6-C10H14)RuCl2(C6H5NH2)] ([Ru]-2b), are obtained in 21

high yields by treating the methanol solutions of the respective ruthenium-arene dimers precur-22

sors, [{(η6-arene)RuCl2}2] (η

6-arene = C6H6 ([Ru]-1a), C10H14 ([Ru]-1b)) with aniline under re-23


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fluxing condition (Scheme 1). The isolated complexes [Ru]-2a and [Ru]-2b are soluble in polar 1

solvents such as dichloromethane, chloroform, methanol and water, whereas insoluble in petrole-2

um ethers and hexane. Identity of the complexes has been established by NMR, elemental analy-3

sis and ESI mass (details are given in the Experimental Section and Supporting Information). In 4

the 1H NMR of complex [Ru]-2a, η

6-C6H6 resonates at 5.35 ppm as a sharp singlet. Aromatic 5

protons of C6H5NH2 were significantly down shielded and resonate as multiplet at 7.45-7.36 ppm 6

for five protons of the phenyl ring of aniline, whereas NH2 protons shows a broad singlet at 4.87 7

ppm. In the 13

C NMR of complex [Ru]-2a, η6-C6H6 resonates at 87.68 ppm (DMSO-d6). 8

Scheme 1. 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 con-9

firmed by single-crystal X-ray diffraction analysis of suitable crystals of [Ru]-2a, grown by slow 10

evaporation of the solution of [Ru]-2a in methanol/dichloromethane (2:1) mixture. The complex 11

[Ru]-2a crystallizes in triclinic P-1 space group, where two crystallographically independent 12

molecules have been observed in the unit cell of [Ru]-2a (Figure 2, Figure S1, Table 1 and Ta-13

bles S1-S2, †ESI). An ORTEP view of the single molecule of the complex [Ru]-2a and selected 14


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bond lengths and angles, is shown in Figure 2. The Ru centre in complex [Ru]-2a exhibits the 1

usual piano-stool geometry with the nitrogen atom of aniline and two chloride ligands as legs. 2

The η6-coordinated benzene ring in the complex [Ru]-2a is almost planar and the ruthenium cen-3

tre is displaced by 1.662 Å from the centroid of the benzene ring. Both the Ru−nitrogen bond dis-4

tances (2.158 Å) and the Ru−chlorine bond distances (2.431 Å) were within expected bonding 5

distances for ruthenium arene complexes.16

The angles between the legs, Cl-Ru-Cl (88.48°) and 6

Cl-Ru-N (82.87°), and those between the legs and the centroid of the η6-C6H6 ring (CCt) (126.5° – 7

133.7°) are comparable with other similar complexes.16

Moreover, the Ru1-N1-C7 and Ru2-N2-C19 8

angles of 117.7(4)° and 117.8(5)°, respectively, indicated the away placement of the phenyl ring 9

of aniline from the Ru centre. 10

Fig. 2 ORTEP view of the complex [Ru]-2a (50% probability thermal ellipsoids). Hydrogen at-

oms are omitted for clarity. Selected bond lengths (Å), and bond angles (deg): Ru1-Cav 2.1758,

Ru1-Cl1 2.4242(15), Ru1-Cl2 2.4329(18), Ru1-N1 2.162(7), N1-C7 1.448(9); Cl1-Ru1-Cl2 88.35(6),

Cl1-Ru1-N1 82.26(15), Cl2-Ru1-N1 82.99(18), Ru1-N1-C7 117.7(4).


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Table 1. Crystal Data and Structure Refinement Details for Complex [Ru]-2a

chemical formula C24H26Cl4N2O2Ru2

fw 718.41

T (K) 150(2)

Wavelength (Å) 0.71073

cryst syst, space group Triclinic, P -1

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, deg 76.921(3)

β, deg 85.191(3)

γ, deg 74.312(3)

V, Å3 1219.56(8)

Z 2

calcd, g cm-3

1.956

μ, mm-1

11.704

F(000) 712

range, deg 2.97 - 25.00

index ranges -9 ≤ h ≤ 9; -10 ≤ k ≤ 10; -22 ≤ l ≤ 22

completeness to max 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

R1 [I > 2(I)] 0.0829

wR2 [I > 2(I)] 0.2091

largest diff peak and hole, e Å-3

2.989 and -4.032

1


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Catalytic activities of the complexes. The catalytic activity of complexes [Ru]-2a and [Ru]-2b 1

for the synthesis of aldehydes to amides in water was evaluated by using benzaldehyde as model 2

substrate and hydroxylamine hydrochloride as NH2 source (Table 2). Previous recent reports with 3

analogous catalytic reactions were performed at ≥ 100 °C using NaHCO3 or Na2CO3 base in wa-4

ter (Table 2, entries 14-15) or in other organic solvents (Table 2, entries 16-18).5,6b,6e,8,10

We 5

thought to bring down the reaction temperature, and treated benzaldehyde with NH2OH·HCl in 6

water at 80 °C and under N2 atmosphere in the presence of [Ru]-2a catalysts. Surprisingly, com-7

plex [Ru]-2a displayed high yields (>99%) for the formation of benzamide (Table 2, entry 5). It 8

is a worthy noting superior catalytic performance of the complex [Ru]-2a, as previously reported 9

active catalyst, [(η6-C6H6)RuCl2{P(NMe2)3}], exhibits a drastic loss in the catalytic yield to 10

~55% even with a minor decrease in the reaction temperature to 80 °C.5 The above results led us 11

to further evaluate the catalytic performance of the complex [Ru]-2a for the synthesis of amide 12

from aldehyde at lower temperature (< 80 °C). Interestingly, the catalytic synthesis of benzamide 13

from benzaldehyde proceeds well even at reaction temperature as low as 40 °C, however, with a 14

little loss in yields. The average reaction yields for the conversion of benzaldehyde to benzamide 15

were >99 % at 80 °C (Table 2, entry 5), >99% at 60 °C (Table 2, entry 1 and 6), 95 % at 50 °C 16

(Table 2, entry 7) and 86 % at 40 °C (Table 2, entry 8). At the optimized reaction temperature of 17

60 °C, catalytic performance of other catalytic analogues of [Ru]-2a, such as [Ru]-2b (Table 2, 18

entry 2), [Ru]-1a (Table 2, entry 3), and [Ru]-1b (Table 2, entry 4) were also examined, but the 19

complex [Ru]-2a outperform than other. Moreover, compared to other bases used for the studied 20

catalytic reaction, NaHCO3 promoted the high performance of the catalysts (Table 2, entries 9-21

12). Moreover, catalytic activity of the [Ru]-2a catalyst was also evaluated by lowering the cata-22

lyst loading down to 2.5 mol%, and observed appreciable high catalytic performance (after 5 h of 23


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reaction, TON = 25.3 and TOF = 5.1 h-1

) for the conversion of aldehydes to primary amides. (Ta-1

ble 2, entries 13). 2

Table 2. Reaction optimization for the catalytic one-pot conversion of benzaldehyde to ben-

zamide in water.a,b

Entry Catalyst Base T (ᵒC)/Time (h) Conv./Sel. (%)

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 [(η

6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) NaHCO3 80/4 99/99

6c [(η

6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) NaHCO3 60/5 99/99



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


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13d [(η

6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) NaHCO3 60/5 99/64(83)

14e [(η

6-C6Me6)RuCl2{P(NMe2)3}] NaHCO3 100/7 88

m

15f,g

[(η5-C5Me5)Ir(H2O)3][OTf3]2 Na2CO3 110/12 85

m

16h,i

[terpyRu(PPh3)Cl2] NaHCO3 reflux/17 88m

17i,j

[Ru(DMSO)4Cl2] NaHCO3 reflux/6 24m

18k Pd(OAc)2 Cs2CO3 100/15 98

m

aConditions: benzaldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv), [Ru] (5 mol%), NaHCO3 (1.3 equiv),

H2O (8 mL). bDetermined by

1H NMR.

cReactions performed under a N2 atmosphere.

d[Ru] (2.5

mol%), TON 25.3 (5h), (in parentheses: selectivity at 24 h). eRef. 5.

fRef. 8.

gCat. (1.5 mol%), with p-

chlorobenzaldehyde substrate. hRef. 6b.

iin toluene.

jRef. 6e.

kRef. 10.

lin DMSO-H2O.

mYields.

Most importantly the complex [Ru]-2a not only exhibits high catalytic performance even 1

at lower temperature (60 °C) in comparison to others, it exhibit excellent stability towards aero-2

bic environment. It is worthy to mention here that removing the N2 gas protection, does not ex-3

hibit any adverse effect on the catalytic performances of the studied complexes (Table 2, entries 1 4

and 6), which was considered (in previous reports) to be essential for the catalytic conversion of 5

aldehydes to amides.5 Therefore, we performed all the catalytic reactions under aerobic condition 6

without any inert gas protection. The optimal reaction conditions for the catalytic conversion of 7

aldehyde to amide are substrate/catalyst/NH2OH·HCl/NaHCO3 ratio of 100/5/130/130; in H2O 8

(solvent); reaction temperature 60 °C, without any inert gas protection. The generality and the 9

scope of the complex [Ru]-2a were then explored using a wide range of aldehydes (entries 1-18, 10

Table 3 and entries 1-7, Table 4), ranging from aromatic, heteroaromatic, aliphatic and conjugat-11

ed systems, and the results obtained are summarized in Table 3 and Table 4. 12


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Table 3. Scope and generality for aromatic and heteroaromatic aldehydesa,b

Entry Substrate Product Time (h) Conv./Sel. (%) TONd/TOF

e

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


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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

aConditions: aldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv), [Ru]-2a (5 mol%), NaHCO3 (1.3

equiv), H2O (8 mL). bConversion and selectivity is determined by

1H NMR.

cin H2O-methanol

mixture (10:1 v/v). dTON = turnover number.

eTOF = turnover frequency (h

-1).

As observed for benzaldehyde, complex [Ru]-2a exhibits high catalytic performance, 1

>99% conversion and good selectivity, for almost all of the substituted aromatic aldehydes to 2

corresponding primary amides, regardless of the position and electronic behavior of the substitu-3

tions on the phenyl ring (Table 3). However, aromatic aldehydes having electron donating sub-4

stituents (entries 13-17, Table 3) displayed high selectivity in comparison to those having elec-5

tron withdrawing substituents (entries 2-12, Table 3). Among the substrates having electron 6

withdrawing substituents, the -NO2 substituted aromatic aldehydes exhibited very low selectivity 7

to amide formation due to the strong electron withdrawing nature of -NO2 group which retard the 8

rearrangement of aldoxime intermediate into corresponding amide (Table 3, entry 12).11d

Moreo-9


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ver, as expected, the ortho- substituted (entries 2,6, Table 3) aromatic aldehydes showed a lower 1

activity in comparison to the corresponding meta- and para- substituted aromatic aldehydes, pre-2

sumably due to steric effect (entries 3-5,7-8, Table 3). For instance, in comparison to -Me substi-3

tuted aromatic aldehyde (Table 3, entries 15-16), in 2-OMe substituted aromatic aldehyde (Table 4

3, entry 13) there is possibility of coordination of the resulting aldoxime, as O,N chelation, with 5

the metal centre thereby preventing the rearrangement of aldoxime to corresponding amides, 6

which may be responsible for a long reaction period (24 h) to generate 2-methoxybenzamide.19

7

For an extreme case, the aromatic (salicylaldehyde) and heteroaromatic (pyridine-2-8

carboxyldehyde), which are highly coordinating in nature, remains completely unreactive.17

It is 9

worth mentioning here that the complex [Ru]-2a exhibits high tolerance towards various labile 10

functional groups such as halides (entries 2-9, Table 3), nitro (entries 10-12, Table 3) and thi-11

oether (entry 17, Table 3). The tolerance towards sulfur containing substrates is worthy nothing 12

as sulfur species can poison the homogeneous catalysts. Moreover, the complex [Ru]-2a could be 13

advantageously used to synthesis ferrocenecarboxamide (entry 18, Table 3) in higher yields from 14

ferrocenecarboxaldehyde at lower temperature (60 °C), in contrast to the classical two-step meth-15

od for its synthesis using harmful reagents such as thionyl chloride.18

Moreover, heteroaromatic 16

aldehydes, furyl (entry 1, Table 4), and thienyl (entry 2, Table 4) and α,β–unsaturated aldehydes 17

(entries 3-4, Table 4) having conjugated olefin-carbonyl conjugated bonds can also be converted 18

to the corresponding primary amides. Further exploration with aliphatic (CH3(CH2)nCHO, n = 19

2,4) (entries 5-6, Table 4) and cyclohexanecarboxaldehyde (entry 7, Table 4), [Ru]-2a exhibits 20

exceptionally high catalytic transformation (selectivities 86 % ~ 99 %) of these aldehyde sub-21

strates also corresponding amide. Almost all the aldehydes exhibit high conversions and selec-22

tivities for corresponding amides, the only byproduct observed is aldoxime, which is also an in-23


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termediate for aldehyde to amide conversion,7 for those aldehyde substrates having poor selec-1

tivities. Moreover, the purified crystals of amides, in most of the cases, can also be isolated by 2

cooling the reaction mixture to 0 °C, after the completion of the reaction, and the identity of the 3

isolated amides were also analyzed by NMR spectroscopy (Fig. S2, †ESI). 4

Table 4. Scope and generality for aliphatic, heterocyclic and conjugated aldehydesa,b

Entry Substrate Product Time (h) Conv./Sel. (%) TONc/TOF

d

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

aConditions: aldehyde (1.0 mmol), NH2OH·HCl (1.3 equiv), [Ru]-2a (5 mol%), NaHCO3 (1.3

equiv), H2O (8 mL). bConversion and selectivity is determined by

1H NMR.

cTON = turnover num-

ber. dTOF = turnover frequency (h

-1).


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Fig. 3 Time-dependent reaction progress for the catalytic conversion of benzaldehyde to ben-

zamide in the presence of [Ru]-2a, in water at 60 °C.

To elucidate the reaction mechanism, we monitored the catalytic reaction by 1H NMR 1

spectroscopy by using benzaldehyde as the representative aldehyde substrate. As shown in Fig. 3, 2

the formation of benzaldoxime in early stages of the catalytic cycle is slowly consumed to gener-3

ate benzamide. To our surprise, benzonitrile was not observed, which is considered to be an im-4

portant intermediate in the aldoxime rearrangement process. So the classical way of hydration of 5

benzonitrile intermediate by water can be discarded, instead aldoxime assisted hydration of ben-6

zonitrile may be the plausible pathway.8,19

Further to demonstrate the above assumption, the reac-7

tion of benzonitrile was carried out in water at 60 °C in the presence of [Ru]-2a catalyst, but 8

showed no conversion. However, under the analogous reaction condition hydration of benzo-9

nitrile can be facilitated in the presence of butylaldoxime to yield benzamide, which further sup-10

ports the alternative pathway for the hydration of benzonitrile (Scheme 2 and S1, †ESI). 11


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Scheme 2. Plausible mechanism for the catalytic conversion of aldehyde to primary amide.

Dissociation of the ancillary ligands from the metal complex has previously been reported 1

to generate catalytically active species.20

Therefore, the possible structural changes in the [Ru]-2a 2

catalyst, such as dissociation of aniline, during the catalytic reaction, using the substrate 3-3

chlorobenzaldehyde at the substrate to catalyst ratio (S/C) of 6:1, was studied by 1H NMR and 4

mass spectrometry. While characterizing the catalyst recovered after the catalytic reaction using 5

1H NMR, we observed that the peaks corresponding to the ruthenium bound aniline was missing. 6

Moreover, in mass spectra of the recovered catalyst exhibits peaks corresponding to only [(η6-7

C6H6)RuCl(OH2)] (m/z 232.9285) and [(η6-C6H6)RuCl] (m/z 214.9190), whereas those corre-8


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sponding to [(η6-C6H6)RuCl(C6H5NH2)] was absent (Fig. S3, †ESI). The observed

1H NMR and 1

mass spectral data indicates that, presumably, the replacement of the aniline ligand is the first 2

step in the catalytic reaction to provide a vacant coordination site for further coordination of ald-3

oxime to the ruthenium metal centre (Scheme 2).20

Comparing the catalytic performance of [(η6-4

C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) with the corresponding arene-ruthenium dimer [{(η6-5

C6H6)RuCl2}2], it is easy to understand that presence of aniline has a positive effect on the ob-6

served enhanced catalytic performance of [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a) catalyst, pre-7

sumably, this accounts for the easy replacement of aniline with aldoxime. Further to address the 8

question if aniline is working as a base or a co-catalyst, we performed reaction in the absence of 9

base and observed >99 % conversion but with only 94 % selectivity for amide. These results in-10

dicated that presumably the free aniline may act as a base or co-catalyst without coordination to 11

the ruthenium centre. However, using aniline as additive may retard the catalytic reaction by un-12

dergoing condensation with aldehyde and preventing the formation of the crucial aldoxime in-13

termediate. Moreover, surprisingly, free aniline in crude reaction mixture could not be detected 14

by either 1

H NMR or mass spectra. 15

Conclusions 16

In conclusion, we demonstrated a new highly efficient catalytic system based on a phosphine-free 17

ruthenium-arene complex, [(η6-C6H6)RuCl2(C6H5NH2)] ([Ru]-2a), for one-pot primary amide 18

synthesis from aldehydes at remarkably lower temperature (as low as 60 °C, superior than other 19

related reports operated at 100-110 °C). Moreover, the reported method is environmentally sus-20

tainable too, as all the reactions are performed in water and without inert gas protection. Advan-21

tageously, the reported complex displayed wide generality and tolerance for reactive/unprotective 22

functional groups of aldehyde substrates. The current report will offer new opportunities for the 23


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development of improved phosphine-free catalytic systems for this and other related catalytic re-1

actions. 2

Acknowledgements 3

Financial support from IIT Indore and CSIR, New Delhi (01(2722)/13/EMR-II) is acknowledged. 4

SIC IIT Indore is acknowledged for instrumentation facilities. D.T. and R.K.R. thank UGC, New 5

Delhi and CSIR, New Delhi, respectively, for their fellowships. 6

Notes and references 7

a Discipline of Chemistry, School of Basic Sciences, Indian Institute of Technology (IIT) Indore, 8

Khandwa Road, Indore 452 017, India. Tel: +91 731 2438 730; E-mail: [email protected] 9

‡These authors contributed equally. 10

†Electronic Supplementary Information (ESI) available: [Experimental and spectral data of am-11

ides. Structural data of [Ru]-2a (CCDC deposition Number is 995119)]. 12

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Table of Content

A simple and highly efficient catalytic system based on phosphine-free ruthenium arene complex

for aqueous-phase one-pot direct synthesis of primary amides from aldehydes and hydroxylamine

hydrochloride, with high tolerance to other reactive functional groups, at lower reaction tempera-

ture (60 °C) and without inert gas protection.


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Phosphine-free ruthenium-arene complex for low temperature one-pot catalytic conversion of aldehydes...

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Transcript of Phosphine-free ruthenium-arene complex for low temperature one-pot catalytic conversion of aldehydes...