Novel system for the synthesis of nitriles from aldehydes using aqueous ammonia and [bis(trifluoroacetoxy)iodo]benzene

Article abstract of DOI:10.1080/00397910902985549

A simple and mild method for the conversion of varieties of aldehydes to the corresponding nitriles using aqueous ammonia and trivalent hypervalent iodine reagent, [bis(trifluoroacetoxy)iodo]benzene, at room temperature is discussed. Advantages of this system are short reaction time, easy workup, and moderate to good yields. Copyright Taylor & Francis Group, LLC.

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Novel System for the Synthesis of Nitriles
from Aldehydes Using Aqueous Ammonia
and [Bis(Trifluoroacetoxy)iodo]benzene
Vikas N. Telvekar a , Rajesh A. Rane a & Tejal V. Namjoshi a
a Department of Pharmaceutical Sciences and Technology ,
University Institute of Chemical Technology, University of Mumbai ,
Matunga, Mumbai, India
Published online: 03 Feb 2010.
To cite this article: Vikas N. Telvekar , Rajesh A. Rane & Tejal V. Namjoshi (2010)
Novel System for the Synthesis of Nitriles from Aldehydes Using Aqueous Ammonia and
[Bis(Trifluoroacetoxy)iodo]benzene, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 40:4, 494-497, DOI: 10.1080/00397910902985549
To link to this article: http://dx.doi.org/10.1080/00397910902985549
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Synthetic Communications1, 40: 494–497, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902985549
NOVEL SYSTEM FOR THE SYNTHESIS OF NITRILES
FROM ALDEHYDES USING AQUEOUS AMMONIA AND
[BIS(TRIFLUOROACETOXY)IODO]BENZENE
Vikas N. Telvekar, Rajesh A. Rane, and Tejal V. Namjoshi
Department of Pharmaceutical Sciences and Technology, University Institute
of Chemical Technology, University of Mumbai, Matunga, Mumbai, India
A simple and mild method for the conversion of varieties of aldehydes to the corresponding
nitriles using aqueous ammonia and trivalent hypervalent iodine reagent, [bis(trifluoroace-
toxy)iodo]benzene, at room temperature is discussed. Advantages of this system are short
reaction time, easy workup, and moderate to good yields.
Keywords: Aldehydes; aqueous ammonia; [bis(trifluoroacetoxy)iodo]benzene; nitriles
INTRODUCTION
A number of methods are known for the conversion of aldehydes into nitriles
from the corresponding aldehydes via dehydration of aldoximes or use of reagents
such as trimethylsilyl azide,[1] triazidochlorosilane,[2] sodium azide, and aluminium
chloride.[3] There are several methods developed using a combination of ammonia
with other compounds, such as NH3=O2=CuCl2 Á 2H2O=MeONa in MeOH, NH3=
Pb(OAc)4 in dry benzene,[4] NH3=I2 in tetrahydrofuran (THF)–water,[5] NH3=N-
bromosuccinimide (NBS) in water,[6] and NH3=O-iodoxy benzoic acid (IBX) in acet-
onitrile.[7] Although most of these methods are satisfactory, the use of more complex,
hazardous reagents such as Pb(OAc)4 and potentially explosive reagents such as IBX,
as well as sometimes tedious workup and longer reaction time, means that there is still
scope for alternative reagent systems for the preparation of nitriles from aldehydes.
Our group has been working extensively to develop novel methodologies under
mild reaction conditions using various hypervalent iodine reagents.[8,9] [Bis(trifluor-
oacetoxy)iodo]benzene is commercially available as a colorless crystalline solid. It is
fairly stable and can be kept without refrigeration for a long period of time with light
protection and is reported for the synthesis of N-arylated and N-alkylated
heterocyclic fused aromatic compounds,[10] synthesis of pyrrolidinone and lactone
skeletons,[11] oxidative deprotection of dithiane containing alkaloids,[12] and direct
a-hydroxylation of ketones.[13]
Received January 31, 2009.
Address correspondence to Vikas N. Telvekar, Department of Pharmaceutical Sciences and
Technology, University Institute of Chemical Technology, University of Mumbai, Matunga, Mumbai
400019, India. E-mail: vikastelvekar@rediffmail.com
494

NOVEL SYNTHESIS OF NITRILES FROM ALDEHYDES
495
Scheme 1. Preparation of nitrile from aldehyde.
We observed that this reagent could be used in combination with aqueous
ammonia at room temperature for the direct conversion of aldehydes to the
corresponding nitriles. For our initial studies, benzaldehyde was chosen as model
substrate (Scheme 1).
A mixture of benzaldehyde, aqueous ammonia, and [bis(trifluoroacetoxy)
iodo]benzene [PhI(OOCCF3)2] was stirred at room temperature (25ꢀC). The starting
material was consumed within 30 min as indicated by thin-layer chromatography
(TLC). After workup and purification by silica-gel column chromatography,
benzonitrile was isolated in 92% yield. To the best of our knowledge, there is no
report on the use of [bis(trifluoroacetoxy)iodo]benzene in aqueous ammonia for
direct conversion of aldehydes to nitriles.
RESULTS AND DISCUSSION
Encouraged by these results, we subjected various aromatic and aliphatic
aldehydes to the reaction condition using [bis(trifluoroacetoxy)iodo]benzene, and
the results are presented in Table 1. The results clearly indicate that ether, acetyl,
and ester groups are stable in these conditions (Table 1, entries 4–7). Aliphatic
aldehydes also underwent this transformation smoothly; pentanal and hexanal
(Table 1, entries 12 and 13) were converted to the corresponding nitriles in good
yields. Double bonds were not affected under these reaction conditions (Table 1,
entries 9 and 10). Under similar reaction conditions, benzyaldehyde was successfully
converted into nitrile by using [bis(acetoxy)iodo]benzene, but reaction time was
increased to 3 h.
In conclusion, a novel method has been developed for the direct conversion of
aldehydes to the corresponding nitriles using [bis(trifluoroacetoxy)iodo]benzene in
combination with aqueous ammonia at room temperature. The method is mild
and gave good to excellent yields of nitriles in the case of both aliphatic and aromatic
substrates.
GENERAL PROCEDURE
PhI(OOCCF3)2 (1.2 equiv, 5.4 mmol) was added to a stirred solution of
aldehyde (1.0 equiv, 4.5 mmol) in aqueous ammonia (15 mL of a 28–30% solution,
sp. gravity 0.89). The resultant mixture was stirred at rt until the starting material
had been completely consumed (TLC). The reaction mixture was diluted with water
and extracted with chloroform (2 Â 20 mL). The combined organic layer was washed
successively with 10% aq. sodium bisulfite solution (2 Â 15 mL) 10% aq. NaHCO3
(2 Â 15 mL), and finally H2O (1 Â 20 mL). The organic layer was dried over Na2SO4

496
V. N. TELVEKAR, R. A. RANE, AND T. V. NAMJOSHI
Table 1. Synthesis of nitriles from aldehydes using [bis(trifluoroacetoxy)iodo]benzene and aqueous
ammoniaa
Entry
1
Substrateb
Product
Time (min)
30
Yield (%)c
92
2
35
90
3
4
36
30
84
86
5
6
40
40
85
90
7
40
85
8
9
35
30
95
85
10
11
35
40
82
82
12
13
45
45
80
82
aReaction conditions: substrate (4.5 mmol), [bis(trifluoroacetoxy)iodo]benzene (1.2 equiv, 5.4 mmol),
aqueous ammonia (15 mL), rt.
bStarting compounds were prepared by standard literature procedures.
cIsolated yields after column chromatography. Structures were confirmed by comparison of IR and
1H NMR with those of authentic materials.

NOVEL SYNTHESIS OF NITRILES FROM ALDEHYDES
497
and concentrated in vacuo. The residue obtained was purified by silica-gel column
chromatography (10% EtOAc–hexane) to afford pure nitriles.
ACKNOWLEDGMENT
We gratefully acknowledge the University Grants Commission, India, for
financial support under the scheme of a UGC major research project.
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