Totally selective dry microwave assisted amide synthesis by hydration of nitrile using silica supported MnO2 reagent

Article abstract of DOI:10.1081/SCC-120004268

An easy, facile and efficient method for nitrile hydrolysis is developed using the combination of a silica supported MnO₂ reagent and microwave irradiation under dry reaction conditions.

Full text of DOI:10.1081/SCC-120004268

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TOTALLY SELECTIVE DRY MICROWAVE ASSISTED AMIDE
SYNTHESIS BY HYDRATION OF NITRILE USING SILICA
SUPPORTED MnO2 REAGENT
Bhushan M. Khadilkar a & Virendra R. Madyar a
a Applied Organic Chemistry Laboratory, University Department of Chemical Technology,
University of Mumbai, Matunga, Mumbai, 400 019, India
Version of record first published: 16 Aug 2006.
To cite this article: Bhushan M. Khadilkar & Virendra R. Madyar (2002): TOTALLY SELECTIVE DRY MICROWAVE ASSISTED AMIDE
SYNTHESIS BY HYDRATION OF NITRILE USING SILICA SUPPORTED MnO2 REAGENT, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 32:11, 1731-1734
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SYNTHETIC COMMUNICATIONS, 32(11), 1731–1734 (2002)
TOTALLY SELECTIVE DRY MICROWAVE
ASSISTED AMIDE SYNTHESIS BY
HYDRATION OF NITRILE USING
SILICA SUPPORTED MnO2 REAGENT
*
Bhushan M. Khadilkar and Virendra R. Madyar
Applied Organic Chemistry Laboratory, University
Department of Chemical Technology, University of
Mumbai, Matunga, Mumbai 400 019, India
ABSTRACT
An easy, facile and efficient method for nitrile hydrolysis
is developed using the combination of a silica supported
MnO2 reagent and microwave irradiation under dry reaction
conditions.
The use of dry reaction (or solvent-free reactions) technology is
becoming very popular as it has many advantages: reduced pollution, low
cost, and simplicity in process and in handling. These factors are especially
very important in industry.
Recently, an informative review[1] by Toda et al. clearly pointed out
the superiority of the solvent-free or the use of dry reaction conditions in
chemical synthesis. The use of dry reaction conditions using supported solid
*Corresponding author.
1731
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1732
KHADILKAR AND MADYAR
reagent with that of microwave technology has found immense application
in organic group transformation reactions.[2–8]
Hydration of nitrile to amide can be achieved by many different
methods such as refluxing nitrile in the presence of strong acidic[9,10] and
basic conditions,[11] by Ritter reaction,[12] under basic H2O2 in DMSO[13] or
basic H2O2 in PTC conditions[14] or by enzymatic routes.[15,16] Cook et al.[17]
has reported selective hydrolysis of nitriles to amide at room temperature
using unsupported MnO2 and in dichloromethane. Cheng-Ting et al.[18] has
reported the use of MnO2 deposited on silica gel using an aqueous prepara-
tion of the reagent. The method required an excess of MnO2 and the reaction
time was much higher except in a few cases. Also, they have used hydrocar-
bons as solvents to carry out hydration of nitriles to amides. Thus, most of
these methods show some or other drawback such as the use of strong acidic
or basic medium, excessive use of organic solvents, elaborate procedures, less
selectivity (hydration of amide to acid) or in some cases very long reaction
time—several hours to days.
We report here a rapid solid state microwave assisted hydration of
nitrile to amide (Scheme 1). To the best of our knowledge, this is the first
report of nitrile hydration to amide under solvent free or dry reaction con-
ditions using silica supported MnO2 and microwave heating. In our labora-
tory we have successfully prepared silica supported MnO2 under microwave
irradiation and it showed good activity for benzylic oxidation (Table 1).[19]
We got complete selectivity toward amide and good yields for nitriles.
The silica supported MnO2 could be reused for at least three times.
Reactivation of the reagent before reuse was done by simply air drying
after each run.
To investigate the role of silica support in the nitrile hydration reac-
tion, we prepared unsupported MnO2 by the similar procedure as reported
in our earlier work.[19] MnO2, when used in a stoichiometric ratio for the
benzonitrile hydration, gave about 19% yield of benzamide under micro-
wave irradiation, and, surprisingly, failed to show any reusability. This
clearly points out the importance of silica gel as a support in nitrile hydra-
tion reactions under these conditions.
Some of the amides such as pyridinecarboxamide, nicotinamide and
piperazinamide, prepared by our procedure in good yields, have immense
utility in the pharmaceutical industry.
Scheme 1.

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AMIDE SYNTHESIS BY HYDRATION OF NITRILE
1733
Table 1. Microwave Promoted Hydration of Nitrile Using MnO2/SiO2
Under ‘‘Dry’’ Reaction Conditions
Entry
No.
MW
(min)
Yield*
(%)
M.p. (ꢀC)
(Lit.[20]
Substrate
Benzonitrile
2-Aminobenzonitrile
4-Hydroxybenzonitrile
4-Acetylbenzonitrile
2-Chlorobenzonitrile
4-Cyanobenzaldehyde
2-Cyanopyridine
)
1
2
3
4
5
6
7
8
9
14
6
12
14
4
6
4
8
2
65
–4101121(0112–14)
124–126 (127–28)
53
45
99
41
81
78
84
160–162 (162)
188–189 (190–91)
138–140(142)
157–160(160)
108–110 (107–9)
128 (129–130)
188–190(192)
3-Cyanopyridine
2-Cyanopiperazine
*% Isolated yield. All products show satisfactory physical and spectral data.
In all cases, unreacted nitrile were recovered and recycled.
Substrate ¼ 0.01 mole; MnO2/SiO2 ¼ 0.01 mole (5 g).
EXPERIMENTAL
In a typical procedure, benzonitrile 1.03 g (0.01 mole) was stirred with
10ml of diethylether and 5 g of silica supported MnO 2 (2 mmol MnO2 per g
of SiO2). Dry powder obtained after removal of diethyl ether was trans-
ferred into a beaker and irradiated in a domestic microwave oven (IFB,
750W output) for 14 min (7 cycles of 2 min each). After the microwave
irradiation the mixture was washed with 25 ml of hot methanol, and the
methanol was removed to obtain the mixture of benzamide and unreacted
benzonitrile. The unreacted benzonitrile was recovered from the mixture by
washing with 10ml of petroleum ether and then recycled. The benzamide
was obtained as pure white crystals. The progress of the reaction was mon-
itored by TLC using (benzene–ethyl acetate 9 : 1) as eluant.
CONCLUSION
In conclusion, a clean, safe and efficient method for the selective
hydration of nitriles using silica supported manganese dioxide reagent
under microwave assisted dry reaction conditions has been carried out.
Thus, by coupling microwave technology and methodologies such as dry
reaction conditions in combination with solid supported reagents, we have
developed an environmentally benign hydrolysis of nitrile to amide.

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KHADILKAR AND MADYAR
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Received in the Netherlands May 9, 2001