A new efficient method for the conversion of aldehydes into nitriles using ammonia and hydrogen peroxide

Article abstract of DOI:10.1016/S0040-4039(00)01168-0

Aldehydes were converted into the corresponding nitriles by a homogeneous reaction with ammonia and aqueous hydrogen peroxide in the presence of copper salts or complexes under mild conditions. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01168-0

Tetrahedron Letters 41 (2000) 6749±6752
A new ecient method for the conversion of aldehydes into
nitriles using ammonia and hydrogen peroxide
Mark B. Erman,* Joe W. Snow and Melissa J. Williams
Millennium Specialty Chemicals, PO Box 389, Jacksonville, FL 32201, USA
Received 27 June 2000; accepted 13 July 2000
Abstract
Aldehydes were converted into the corresponding nitriles by a homogeneous reaction with ammonia and
aqueous hydrogen peroxide in the presence of copper salts or complexes under mild conditions. # 2000
Elsevier Science Ltd. All rights reserved.
Keywords: nitriles; aldehydes; ammonia; hydrogen peroxide; catalysis; copper.
The conversion of aldehydes (1) into the corresponding nitriles (2) is a functional group
transformation of signi®cant practical importance, especially in the ®ne chemical industry. The
most widely used general method is based on the dehydration of aldoximes, and although
numerous protocols already exist, new variants continue to appear.1 5 A few methods are known
which involve various transformations of other N-substituted azomethine derivatives of aldehydes,
such as N,N-dialkylhydrazones,6,7 O-2,4-dinitrophenyloximes,8 imines with 1-amino-4,6-diphenyl-
2-pyridone.9 The relatively high cost of hydroxylamine, substituted hydrazines, etc. has stimulated
development of methods based on the oxidative dehydrogenation of ammonia-derived
azomethines (3) using persulfates,10,11 nickel peroxide,12 iodine,13 and oxygen in the presence of
Cu catalysts14 17 as oxidants under relatively mild conditions (Scheme 1).
Scheme 1. (a) R=Me2CˆCHCH2CH2CMeˆCH±; (b) PhCHˆCH±; (c) Ph±; (d) p-MeOPh±; (e) 3,4-methylenedioxy-
phenyl; (f) MeCHˆCH±CHˆCH±; (g) Me2CˆCHCH2CH2CH(Me)CH2±; (h) n-C10H21±
From economic and environmental standpoints, the oxygen-based methods14 17 seem more
attractive than the others,10 13 although they have technical drawbacks which limit their practical
applicability. For example, some reports14,15 use molar ratio copper:substrate of 1:1 or greater.
Other procedures16,17 use a large excess of ammonia and very dilute solutions.
* Corresponding author. Tel: 1 904 9242766; fax: 1 904 9242743; e-mail: merman@aromachem.com
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01168-0

6750
Hydrogen peroxide is another environmentally friendly and inexpensive oxidant. However, we
found no indication in the literature that hydrogen peroxide can be used for this transformation.
Moreover, unsuccessful attempts to use hydrogen peroxide have been described.18 28 For exam-
ple, it is known that aldehydes react with ammonia and hydrogen peroxide to form aminohy-
droperoxides or aminoperoxides, not nitriles.18,19 Nitriles themselves react readily with hydrogen
peroxide in the presence of bases giving amides in high yields (the Radziszewski reaction).20 23
Both a,b-unsaturated aldehydes and nitriles can be epoxidized by hydrogen peroxide.24,25 In the
presence of nitriles, hydrogen peroxide epoxidizes non-activated double bonds (the Payne epox-
idation).26,27 Also, some amounts of the Baeyer±Villiger oxidation products could always be
expected on contacting aldehydes and hydrogen peroxide.28
Our primary goal was the conversion of citral (1a) into geranyl nitrile (2a)Ða case where all the
above mentioned reactions could be anticipatedÐand chances to obtain nitrile (2a) seemed extremely
poor. Nevertheless, dropwise addition of 50% aqueous hydrogen peroxide (CAUTION! strong
oxidizer)18 to a mixture of aldehyde (1a), 29.4% aqueous ammonium hydroxide, and a catalytic
Table 1
Cu-catalyzed conversion of aldehydes to nitriles with ammonia and 50% hydrogen peroxide in i-PrOHa

6751
amount of cuprous chloride in DMF or i-PrOH gave nitrile (2a) in about 10% yield. A signi®cant
improvement (50% yield) was observed when both hydrogen peroxide and ammonium hydroxide
were added dropwise simultaneously to the other reagents.
Yet better results (Table 1, method A) were obtained when starting aldehyde (1a) (0.38 mol)
was also added parallel with hydrogen peroxide (1.4 mol) and ammonium hydroxide (0.44±0.49
mol) to a stirred mixture of copper catalyst (0.01 mol) and 300 ml of i-PrOH at 17±30ꢀC (the
reaction was noticeably exothermic, so some cooling was necessary). Importantly, the addition
rates were selected so as to always maintain low concentrations of all starting reagents and
intermediate azomethine (3a) in the course of the reaction. Speci®cally, ammonium hydroxide
was added for about 3 hours, and the addition of aldehyde (1a) and hydrogen peroxide
commenced almost simultaneously with ammonium hydroxide and was ®nished in 2.5 and
4 hours, respectively. Other aldehydes (1b±h) were converted similarly. After a conventional
work-up, the products were puri®ed by distillation or crystallization.
In method B, gaseous ammonia (2.5±2.8 mol) was passed for 3 hours into a solution of 4 g of
cuprous chloride in 800 ml of i-PrOH, while 1.5 mol of aldehyde (1), and 3.35 mol of 50%
hydrogen peroxide were added dropwise for 2.5 and 4 hours, respectively. Both procedures A and
B were optimized with respect to the conversion of aldehyde (1a) into nitrile (2a) only, which
explains the relatively lower yields of other a,b-unsaturated and aromatic nitriles. Poor yields of
aliphatic nitriles (2g,h) may be due to the slow rate of oxidative dehydrogenation of the
corresponding azomethines (3g,h).
In the case of a,b-unsaturated aldehydes, the formation of small amounts of retro-aldol
by-products was observed by GLC, for instance 6-methyl-5-hepten-2-one from aldehyde (1a) or
benzaldehyde (and benzonitrile) from (1b). Also, small amounts of carboxylic acids and acetone
were formed due to the direct oxidation of starting aldehydes and i-PrOH solvent, respectively.
The requirement for a signi®cant excess of hydrogen peroxide over the aldehyde raised a
legitimate suspicion that the real oxidant is oxygen formed in the copper-catalyzed decomposition
of hydrogen peroxide. However, control experiments starting with aldehyde (1a) and using air or
oxygen instead of hydrogen peroxide gave practically no nitrile (2a), so hydrogen peroxide
remains the most likely actual oxidant. There is not enough data yet to discuss the mechanistic
aspects of the reaction, and even the intermediacy of azomethines (3) has not been proven. The
reaction certainly deserves more detailed study.
Regardless of its mechanism, the reaction of aldehydes with ammonia and hydrogen peroxide
in the presence of copper catalysts presents a new, convenient and ecient method for obtaining
nitriles.
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