Organic reactions in water: Highly rapid CAN mediated one-pot synthesis of nitriles from aldehydes under mild conditions

Article abstract of DOI:10.1055/s-2003-36779

A variety of aliphatic and aromatic nitriles were prepared from the corresponding aldehydes in high yield in a direct one pot and rapid process using ceric ammonium nitrate (CAN) in amonia-water under mild conditions.

Full text of DOI:10.1055/s-2003-36779

262
LETTER
Organic Reactions in Water: Highly Rapid CAN Mediated One-Pot Synthesis
of Nitriles from Aldehydes under Mild Conditions
H
ighly Rapid CA
.
N
M
ediated
P
One-Pot Synt
.
Nitri
B
les andgar,* S. S. Makone
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Vishnupuri,
Nanded-431 606, India
Fax +91(2462)29245; E-mail: bandgar_bp@yahoo.com
Received 2 December 2002
conditions,9 have limited applications10,11 or may lead to
Abstract: A variety of aliphatic and aromatic nitriles were prepared
formation of explosive NI3⋅NH3.13 Therefore, there are
from the corresponding aldehydes in high yield in a direct one pot
and rapid process using ceric ammonium nitrate (CAN) in amonia-
water under mild conditions.
still improvements to be made for the transformation of
aldehydes to nitriles.
We describe here a very simple, general and direct method
for the preparation of aliphatic as well as aromatic nitriles
from corresponding aldehydes using NH3/CAN in water
under mild conditions (0 °C) (Equation 1).
Key words: ceric ammonium nitrate (CAN), aldehydes, nitriles,
organic reactions in water
Preparation of nitriles from the corresponding aldehydes
is an important functional group transformation in organic
synthesis.1 Many methods involve aldoxime dehydration
through a two-step process. The aldoximes prepared ini-
tially by condensation of hydroxylamine hydrochloride
with various aldehydes are subjected to dehydration
which is effected by a variety of reagents,2 to generate ni-
triles. Of those one-pot preparative methods developed in
recent years, many are mainly limited to aromatic alde-
hydes and often give unsatisfactory yields. Other
methods3 which involve direct conversion of aldehydes
into nitriles without isolation of nitrogen-containing inter-
mediates and are applicable to both aromatic and aliphatic
aldehydes often involve expensive reagents or hazardous
reagents. In most cases, aromatic aldehydes are preferably
converted to aromatic nitriles, whereas the transformation
of enolizable aliphatic aldehydes often gives unsatisfacto-
ry yields of aliphatic nitriles. The problem can be some-
what circumvented by using less available reagents4 such
as sulfimide or non-conventional approaches5 such as mi-
crowaves and IR.
Equation 1
A variety of aliphatic, aromatic heterocyclic, α,β-unsatur-
ated aldehydes (Table 1) and carbohydrate aldehydes
(Equation 2) was converted into nitriles, when reacted
with liquid NH3 in water in the presence of CAN at 0 °C.
Progress of the reaction can be monitored by TLC and
high conversion is achieved within 15 minutes.
The use of ammonia combined with an appropriate oxi-
dant is an expedient method for the transformation of ali-
phatic and aromatic aldehydes to their corresponding
nitriles. Different reagents developed to effect this con-
version are: NH3/O2/CuCl2⋅2H2O/MeONa in MeOH,6
NH3/Pb(OAc)4 in dry benzene,7 NH3/I2/MeONa in
MeOH,8 NH3/S8/NaNO2,9 NH3/KI/MeONa in MeOH on
electrooxidation,10 NH3/H2O2/CuCl in 2-propanol,11 NH3/
I2 in THF–water.12 However, these methods are not gen-
eral and have some limitations. The first three methods
provide moderate yields of nitriles from aromatic alde-
hydes and very poor yields of nitriles from aliphatic and
α,β-unsaturated aldehydes; whereas others involve com-
plex procedures,7 lead to by-products,8,10 involve extreme
Equation 2
By comparison with the closely related methods8,10 our
method exhibited distinct advantages. Firstly, we utilized
aqueous ammonia instead of ammonia gas and the opera-
tion of such a reaction using our method thus became sim-
ple and efficient. Secondly, we omitted MeONa in the
reaction media so that the complication of side reactions
(e.g. formation of methyl ester) found in previous meth-
ods is avoided. These two small changes improved the
yields of nitriles to a great extent, especially in the prepa-
ration of p-nitrobenzonitrile (92%), furonitrile (82%), cin-
namononirile (97%) and aliphatic nitriles (87–90%). It is
also noted that our method is ideal for water-soluble sub-
strates, such as the corbohydrate aldehyes shown in Equa-
tion 2. Thus, 2-deoxy-D-ribose was treated with CAN in
ammonia water at 0 °C for 15 minutes to give a 97% yield
Synlett 2003, No. 2, Print: 31 01 2003.
Art Id.1437-2096,E;2002,0,02,0262,0264,ftx,en;D19702ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Highly Rapid CAN Mediated One-Pot Synthesis of Nitriles
263
In summary, the direct conversion of aldehydes into ni-
triles presented in this paper provides a simple, practical
and general methodology. This environmentally benign
procedure is especially useful for the transformation of
water-soluble carbohydrate aldehydes (Equation 2).
Table 1 Transformation of Aldehydes to Nitriles Using CAN in
Ammonia Water
Entry Substrate
Product
Yield (%)a,b
1
2
3
4
5
6
H3CCH2CHO
H3CCH2CN
H3C(CH2)2CN
H3C(CH2)4CN
H3C(CH2)5CN
H3C(CH2)7CN
89
88
90
89
87
90
H3C(CH2)2CHO
H3C(CH2)4CHO
H3C(CH2)5CHO
H3C(CH2)7CHO
General Procedure
A suspension of an aldehyde (5 mmol) in aq ammonia (10 mL,
30%) is stirred for 5 min at r.t., resulting in formation of a turbid so-
lution. To this turbid solution CAN (5 mmol) is added with constant
stirring at 0 °C. After completion of the reaction (TLC, disappear-
ance of reddish-brown color of reaction mixture in 10–15 min) solid
products are collected by simple filtration, whereas liquid products
are obtained by usual work-up by extraction with ethyl acetate.
7
8
94
93
92
80
85
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Synlett 2003, No. 2, 262–264 ISSN 0936-5214 © Thieme Stuttgart · New York

264
B. P. Bandgar, S. S. Makone
LETTER
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