Platinum catalysed hydrolytic amidation of unactivated nitriles

Article abstract of DOI:10.1016/S0040-4039(00)00181-7

The platinum(II) complex, [(Me₂PO··H··OPMe₂)PtH(PMe₂OH)], efficiently catalyses the direct conversion of unactivated nitriles to N- substituted amides with both primary and secondary amines. Possible mechanisms for this reaction are discussed and evidence for initial amidine formation is reported. Isolated yields vary from 51-89%. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00181-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2467–2470
Platinum catalysed hydrolytic amidation of unactivated nitriles
∗
,†
Christopher J. Cobley, Marco van den Heuvel, Abdelilah Abbadi
and
∗
Johannes G. de Vries
DSM-Research, Department of Fine Chemicals, PO Box 18, 6160 MD Geleen, The Netherlands
Received 5 January 2000; accepted 25 January 2000
Abstract
The platinum(II) complex, [(Me2PO··H··OPMe2)PtH(PMe2OH)], efficiently catalyses the direct conversion of
unactivated nitriles to N-substituted amides with both primary and secondary amines. Possible mechanisms for this
reaction are discussed and evidence for initial amidine formation is reported. Isolated yields vary from 51–89%.
©
2000 Elsevier Science Ltd. All rights reserved.
Keywords: homogeneous catalysis; nitriles; amides; platinum compounds.
The preparation of amides is one of the most important synthetic transformations in organic synthesis.
Most syntheses are based on the reaction between an activated carboxylic acid and an amine or
1
–3
ammonia. So far, few methods have been found to make the amide bond catalytically without the aid
4
,5
of stoichiometric activating agents. For this reason we have turned our attention to the use of nitriles as
they are intrinsically more reactive than carboxylic acids. We were triggered by the work of Ghaffar and
Parkins who used tris-dimethylphosphinito platinum hydride (1) as a catalyst for the selective hydration
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of nitriles to the amides (Scheme 1). Most impressive are the high turnover numbers (up to 50 000) and
the rate of the reaction (1 485 mol/mol.h) achieved for the hydrolysis of acrylonitrile.
Scheme 1.
∗
Corresponding author. Fax: +31-46-4767604; e-mail: arachem@worldonline.nl (A. Abbadi), hans-jg.vries-de@dsm-
group.com (J. G. de Vries)
†
Present address: AraChem Contract Research & Custom Synthesis, PO Box 2021, 6020 AA Budel, The Netherlands.
0
040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00181-7
tetl 16461

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It occurred to us that in view of the fact that the reaction is not retarded by the presence of pyridines, use
of nucleophiles other than water, such as amines, should proceed equally well (Scheme 2). N-Substituted
amides have previously been prepared from nitriles and amines, however these methods lack generality
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and require severe reaction conditions such as extremely high temperatures or catalysts such as strong
8
9
acids and strong bases. Hence, the reaction of acetonitrile with propylamine and water in DME at
60°C in an autoclave, catalysed by 0.1 mol% of tris-dimethylphosphinite platinum hydride (1), gave the
1
amide in 57% isolated yield after 24 h. The reaction is very fast initially and could also be performed
with catalyst amounts as low as 0.02 mol%. However, build-up of ammonia pressure occurs and this may
well be the reason that the reaction slows down appreciably afterwards. In addition, some black material
precipitates at the end of the reaction which suggests that catalyst decomposition also plays a role.
Scheme 2.
We investigated the scope of this new reaction to some extent (Table 1) and found it to work
equally well for both primary and secondary amines. All experiments were performed with unactivated
alkylnitriles; benzonitrile gave only benzamide in these reactions. In the case of succinonitrile, the use of
two equivalents of primary amine (entries 11 and 12) resulted in the formation of bisamides.
Table 1
Platinum catalysed hydrolytic amidation of nitriles
The mechanism of the reaction is still unclear (Scheme 3). It is possible that the nitrile is rapidly
hydrolysed to the amide, which then goes on to react further with the alkylamines. Indeed, in each case,
the only observable side product was the unsubstituted amide, the result of nitrile hydrolysis. However,

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it is also conceivable that the substituted amines react initially with the nitrile to form amidines, which
then further hydrolyse to the amides.
Scheme 3.
1
0
Metal-catalysed formation of amidines from the reaction between nitriles and amines has previously
been reported and indeed, for reactions performed in the absence of water, amidines have been detected.
Specifically, when n-propylamine is reacted with acetonitrile the major products formed are the mono-
1
1
and bisamidines, 2 and 3 (Scheme 4). This seems to strongly support the latter mechanism.
Scheme 4.
An interesting extension to this finding results when 2-amino-ethanol is reacted with propionitrile.
1
1
The initial formation of amidine 4 occurs, which subsequently undergoes ring-closure to form the final
product, 2-ethyl-2-oxazoline 5; no other products being visible by GC analysis (Scheme 5).
Scheme 5.
In summary, we have found that the platinum(II) complex 1 acts as an efficient homogeneous catalyst
for the direct conversion of nitriles to N-substituted amides.
Typical experimental procedure: the amine (0.110 mol), nitrile (0.121 mol) and water (0.220 mol)
were dissolved in 10 ml of dimethoxyethane in an autoclave. Catalyst 1 (0.110 mmol, 0.1 mol%) was
added and the mixture was heated under N for the time given in Table 1. After cooling, the mixture was
2
dried over Na SO and concentrated by rotary evaporation. The crude product was purified by spinning
2
4
band distillation for acetamides or by column chromatography (CH Cl /2% MeOH/1% NEt ) for the
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2
3
1
2
remainder.

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References
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1. Observed by GC–MS analysis using a Cp sil 8 CB-MS, 30 m×0.25 mm Df=1.0 µm, injection temp.: 250°C, column
temperature program: 5 min at 50°C (rate 7.5°C/min) 28 min at 250°C (rate 25°C/min) 30 min at 280°C, split: 1:50, flow:
He 1.2 ml/min, injection volume: 1.0 µl.
2. All products are known compounds that show satisfactory GC–MS and NMR spectral data.