Palladium-catalysed Transfer Hydrogenation of Azobenzenes and Oximes using Ammonium Formate

Article abstract of DOI:10.1039/a705957d

The reductive cleavage of azobenzenes, including the reduction of oximes to their corresponding amines, has been achieved with Pd⁰ using ammonium formate as hydrogen source.

Full text of DOI:10.1039/a705957d

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160 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 160±161$
Palladium-catalysed Transfer Hydrogenation of
Azobenzenes and Oximes using Ammonium Formate$
G. K. Jnaneshwara, A. Sudalai* and V. H. Deshpande*
Organic Chemistry: Technology Division, National Chemical Laboratory, Pune 411 008, India
The reductive cleavage of azobenzenes, including the reduction of oximes to their corresponding amines, has been
achieved with Pd0 using ammonium formate as hydrogen source.
The reduction of aromatic azo and azoxy compounds has
received a good deal of attention, both preparatively and
analytically.1 It proceeds via the hydrazo derivative to the
amine or a mixture of two amines when the original azo
compound is unsymmetric. Azobenzene undergoes reductive
cleavage to aniline with a number of reagents, such as
metal±acid combinations and on transfer hydrogenation
over Pd.2 Reductive cleavage of azo- and azoxy-benzenes
continues to be used in connection with structural determi-
nations of azo dyes. More recently, Cp2TiBH4 has been
reported to reduce azobenzenes to the corresponding
amines.3
Scheme 1 i, HCO2NH4 (2 mol), 10% Pd/C (cat.), MeOH, heat,
5±6 h
Catalytic transfer hydrogenation with Pd/C as catalyst
and ammonium formate as hydrogen source has found
widespread use in the reduction of various functionalities.4
reduction with 2 equiv. of ammonium formate at the
This forms a safe alternative to the use of hydrogen gas.
We have recently reported the regiospeci®c reductive ring
opening of epoxides and glycidic esters under transfer
hydrogenation using ammonium formate.5 In this paper, we
wish to report that Pd/C catalyses the reductive cleavage
of various azobenzenes as well as the reduction of various
oximes to the corresponding amines in moderate yields,
using ammonium formate as H2 source.
Table 1 summarizes the results of the reductive cleavage
of the N1N of azobenzenes to give the corresponding
amines, using 4 equiv. of ammonium formate at ambient
temperature. It is to be noted that reducible groups such
as Cl and NO2 also underwent facile reduction under the
reaction conditions employed. However, it is remarkable
that selective reduction of a C±Cl bond over a C±F or a
C±N (debenzylation) bond6 has been achieved with the
present system (Scheme 1).
The reduction of various carbon±nitrogen systems to
saturated derivatives with various reducing agents provides
highly useful processes for the preparation of amines and
related functionalities.7 The reduction of oximes and sub-
sequent cleavage of the N±O bond to a€ord primary amines
occurs with a variety of potent hydride reagents, including
LiAlH4.8 Table 2 gives the various oximes that underwent
re¯ux temperature to produce the corresponding amines in
moderate yields. Further, it is to be noted that C1N has
been reduced preferentially over C1C (entries 4 and 5,
Table 2). The yield in the case of oxime reduction is only
moderate owing to the instability of the amines under the
reaction conditions, possibly giving other side products. In
conclusion, we have shown that the ammonium formate±
Pd/C system is a versatile, selective and rapid method for
catalytic hydrogenation of N1N and C1N functionalities.
Experimental
All mps reported are uncorrected. IR spectra were recorded neat
or as Nujol mulls (in case of solid samples) on a Perkin Elmer
Infrared model 137-E. The 1H NMR spectra were recorded on
Varian FT 80A and Bruker 200 MHz instruments. 13C NMR were
obtained on a Bruker 200 MHz instrument. The chemical shifts
(ppm) were reported with Me4Si as the internal standard. The mass
spectra (MS) were recorded on an automated Finnigan-MAT 1020
C mass spectrometer using an ionization energy of 70 eV.
General Experimental Procedure for the Reduction of Azobenzene.
ÐA mixture of azobenzene (1.82 g, 0.01 mol), ammonium formate
(2.52 g, 0.04 mol) and 10% Pd/C (180 mg) in MeOH (20 ml) was
stirred at room temperature for 5 h. The progress of the reaction
was monitored by TLC. After the reaction was complete, the
Table 1 Pd-catalysed transfer hydrogenation of azobenzenes using ammonium formate as H2 source
Entry
Substrate
Productsa (% yield)b
1
2
3
4
5
6
7
8
9
Azobenzene
4-Aminoazobenzene
4-Hydroxyazobenzene
4-Methyl-4'-hydroxyazobenzene
4-Chloro-4'-hydroxyazobenzene
4-Nitro-4'-hydroxyazobenzene
2-Methoxy-4'-hydroxyazobenzene
2-Nitro-4-methoxy-4'-hydroxyazobenzene
Acetophenone azine
Aniline (63)
Aniline (31) ‡ 1,4-diaminobenzene (64)
Aniline (29) ‡ 4-aminophenol (54)
p-Toluidine (31) ‡ 4-aminophenol (47)
Aniline (25) ‡ 4-aminophenol (48)
1,4-Diaminobenzene (49) ‡ 4-aminophenol (34)
o-Anisidine (30) ‡ 4-aminophenol (64)
3,4-Diaminoanisole (21) ‡ 4-aminophenol (55)
a-Methylbenzylamine (30)
aCharacterized by IR, 1H and 13C NMR and MS. bIsolated after chromatographic purification.
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
catalyst was ®ltered o€ and the crude product was puri®ed by ¯ash
chromatography. Yield: 63%.
General Experimental Procedure for the Reduction of Oximes.Ð
fore no corresponding material in J. Chem. Research (M).
A mixture of acetophenone oxime (1.35 g, 0.01 mol), ammonium

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J. CHEM. RESEARCH (S), 1998 161
Table 2 Pd-catalysed transfer hydrogenation of oximes using ammonium formate
Entry
Substrate
Producta
Yield (%)
1
2
3
4
5
6
7
Benzaldoxime
Benzylamine
a-Methylbenzylamine
Cyclohexylamine
2-Amino-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-ene
1-Amino-2-methyl-5-(1-methylethenyl)cyclohex-2-ene
2-Phenylglycine methyl ester
42
41
42
29
22
45
55
Acetophenone oxime
Cyclohexanone oxime
b-Ionone oxime
Carvone oxime
Methylphenylglyoxalate oxime
Ethyl (4-methoxyphenyl)glyoxalate oxime
4-Methoxyphenylglycine ethyl ester
aCharacterized by IR, 1H and 13C NMR and MS. bIsolated after chromatographic purification.
formate (1.26 g, 0.02 mol) and 10% Pd/C (135 mg) in MeOH (20 ml)
was boiled under re¯ux for 5 h. The progress of the reaction was
monitored by TLC. After the reaction was complete, the catalyst
was ®ltered o€ and the crude product was puri®ed by ¯ash chroma-
tography. Yield: 41%.
(M 1, 100%), 160 (40%), 146 (5%), 134 (8%), 120 (5%), 105
(10%), 91 (15%), 77 (12%).
GKJ thanks CSIR (New Delhi) for the award of a Senior
Research Fellowship.
1
2-Phenylglycine methyl ester. ꢀmax/cm 3500±3300, 1740, 1600,
1450, 1400, 1250, 1180, 1100, 1000, 740; dH (200 MHz, CDCl3) 2.7
(2 H, br, s, NH2), 3.70 (3 H, s, OMe), 4.6 (1 H, s>CH), 7.35 (5 H,
s, Ar-H); m/z 165 (M+, 100%), 150 (13%), 135 (4%), 121 (6%),
105 (8%), 91 (6%), 77 (8%).
ꢀ
Received, 14th August 1997; Accepted, 17th November 1997
Paper E/7/05957D
1
a-Methylbenzylamine.
max/cm
2500±3500, 1600, 1450, 1300,
1000, 700; dH (200 MHz, CDCl3) 1.45 (3 H, s, Me), 1.5 (3 H, s,
Me), 3.1±3.5 (2 H, br s, NH2), 4.1±4.25 (1 H, q, J 3.5 Hz, 7CH, 7.4
(5 H, s, Ar-H); m/z 121 (M+, 4%), 120 (M 1, 12%), 106 (100%),
79 (52%), 66 (35%).
References
1 H. Zollinger, Azo and Diazo Chemistry: Aliphatic and Aromatic
Compounds, Interscience, New York, 1989; B. T. Newbold in The
Chemistry of the Hydrazo, Azo and Azoxy Groups (ed. S. Patai),
Wiley, London, 1975, p. 599.
2 T. L. Ho and G. A. Olah, Synthesis, 1977, 169.
3 P. Dosa, I. Kronish, J. McCallum, J. Schwartz and M. C.
Barden, J. Org. Chem., 1996, 61, 4886.
1
4-Methoxyphenylglycine ethyl ester. ꢀmax/cm 3500±3300, 1740,
1600, 1250, 1050, 820; dH (200 MHz, CDCl3) 1.3±1.4 (3 H, t, J
3 Hz, CH3), 4.3 (3 H, s, OMe), 4.2±4.4 ( H, q, J 4 Hz, CH2), 4.45
(1 H, s, >CH), 6.9±6.95 (2 H, d, J 8 Hz, ArH), 7.3±7.35 (2 H, d, J
8 Hz, Ar-H); m/z 209 (M+, 2%) 208 (M-1, 33%), 164 (4%), 145
(5%), 136 (12%), 111 (12%), 97 (25%), 83 (35%), 77 (12%), 57
(100%).
4 (a) S. Ram and R. E. Ehrenkaufer, Synthesis, 1988, 91;
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25, 2267.
1
1-Amino-2-methyl-5-(1-methylethenyl)cyclohex-2-ene.
ꢀmax/cm
2500±3500, 1610, 1450, 1390, 950, 500; dH (200 MHz, CDCl3)
1.2±1.35 (1 H, m, CH), 1.75 (3 H, s, CH3), 1.9 (3 H, s, CH3), 2.05±
2.4 (4 H, M, 2>CH2), 3.2±3.3 (1 H, dd, J 3 and 5 Hz, >CH0),
4.65 (2 H, m 1CH2), 6.0±6.1 (1 H, m 1CH0), 10.1 (2 H, br, s,
NH2); m/z 151 (M+, 2%), 150 (M 1, 9%), 135 (5%), 124 (5%),
6 B. M. Adger, C. O. Farrell, N. J. Lewis and M. B. Mitchell,
Synthesis, 1987, 53.
109 (5%), 99 (9%), 93 (9%), 84 (29%), 69 (100%).
2-Amino-4-(2,6,6-trimethylcyclohex-1-en-1-yl)but-3-ene.
3000±3500, 1600, 1450, 940, 500; dH (90 MHz, CDCl3): 0.7±0.85
(4 H, m, CH2), 1.6±1.7 (9 H, s, 3Me), 2±2.1 (3 H, m, CH2), 2.3±2.9
(3 H, m, CH3), 4.6 (2 H, s, CH2), 5.8 (2 H, dd, J 3 and 5 Hz,
1CH0), 8.9±9.0 (2 H, br, s, NH2 ); m/z 193 (M+, 12%), 192
7 R. O. Hutchins and M. K. Hutchins, Comprehensive Organic
Synthesis, eds. B. M. Trost and I. Fleming, Pergamon Press,
Oxford, 1991, vol. 8, p. 25.
8 T. L. Girchrist, Comprehensive Organic Synthesis, eds. B. M.
Trost and I. Fleming, Pergamon Press, Oxford, 1991, vol. 8,
p. 381.
1
ꢀmax/cm