A novel system for the synthesis of nitriles from aldehydes using aqueous ammonia and sodium dichloroiodate

Article abstract of DOI:10.1016/j.tetlet.2008.02.046

A simple and mild method for the conversion of varieties of aldehydes to the corresponding nitriles using aqueous ammonia and aqueous sodium dichloroiodate reagent at room temperature is discussed. Advantages of this system are short reaction time, easy work-up and moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2008.02.046

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Tetrahedron Letters 49 (2008) 2213–2215
A novel system for the synthesis of nitriles from aldehydes
using aqueous ammonia and sodium dichloroiodate
Vikas N. Telvekar *, Kavit N. Patel, Harish S. Kundaikar, Hemchandra K. Chaudhari
Department of Pharmaceutical Sciences and Technology, University Institute of Chemical Technology, Matunga, Mumbai 400 019, India
Received 20 December 2007; revised 26 January 2008; accepted 11 February 2008
Available online 13 February 2008
Abstract
A simple and mild method for the conversion of varieties of aldehydes to the corresponding nitriles using aqueous ammonia and
aqueous sodium dichloroiodate reagent at room temperature is discussed. Advantages of this system are short reaction time, easy
work-up and moderate to good yields.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Sodium dichloroiodate solution; Aqueous ammonia; Aldehydes; Nitriles
A number of methods are known for the conversion of
CHO
CN
aldehydes into nitriles from the corresponding aldehydes
via dehydration of aldoximes or using reagents such as tri-
methylsilyl azide,1 triazidochlorosilane,2 sodium azide and
aluminium chloride.3 There are several methods developed
using a combination of ammonia such as NH3/O2/
CuCl2Á2H2O/MeONa in MeOH,4 NH3/Pb(OAc)4 in dry
benzene,5 NH3/I2 in THF–water,6 NH3/NBS in water7
and recently NH3/IBX in acetonitrile.8 Despite these, there
is still scope for alternative reagent systems for the prepa-
ration of nitriles from aldehydes.
Our group has been working extensively on the develop-
ment of novel methodologies under mild reaction condi-
tions using various hypervalent iodine reagents.9 Sodium
dichloroiodate is commercially available in 50% water solu-
tion,10 and reported only for the iodination of the aromatic
ring at 40–70 °C for 72 h.11
aqueous NaICl2, aqueous NH3
4 hr, rt.
Scheme 1. Preparation of nitrile using aq NaICl2 and NH3.
aqueous ammonia and aqueous sodium dichloroiodate
solution was stirred at room temperature (25 °C). The
starting material was consumed within 4 h as indicated
by TLC analysis. After work-up and purification by silica
gel column chromatography, benzonitrile was isolated in
90% yield. To the best of our knowledge, there is no report
on the use of aqueous NaICl2 solution in aqueous ammo-
nia for the direct conversion of aldehydes to nitriles. No
iodination of aromatic ring was observed at room
temperature.
Encouraged by these results, we subjected various aro-
matic and aliphatic aldehydes to the reaction conditions
and the results are presented in Table 1.12 The results
clearly indicate that ether, acetyl and ester groups are sta-
ble to the conditions (Table 1, entries 4–7). Pyridine-3-alde-
hyde was converted into 3-cyano pyridine in good yield
(Table 1, entry 8). Aliphatic aldehydes also underwent this
transformation smoothly; however, a slower reaction rate
was observed; pentanal (Table 1, entry 12), hexanal (Table
We observed that this aqueous 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,
*
Corresponding author. Tel.: +91 22 24145616; fax: +91 22 24145614.
E-mail address: vikastelvekar@rediffmail.com (V. N. Telvekar).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.02.046

2214
V. N. Telvekar et al. / Tetrahedron Letters 49 (2008) 2213–2215
Table 1
Synthesis of nitriles from aldehydes using sodium dichloroiodate solution and aqueous ammoniaa
Entry
1
Substrateb
Product
Time (h)
4
Yieldc (%)
90
CHO
CN
CHO
CN
2
6
92
CN
CN
CHO
CHO
3
4
6
5
90
87
H3CO
H3CO
CHO
CN
5
6
7
7
85
83
H3CO
CH3
H3CO
CH3
CN
CHO
O
O
O
O
CHO
CN
7
7
85
H3CO
H3CO
O
O
CHO
CN
8
9
5
6
9
90
88
87
N
N
CHO
CN
CN
CHO
10
11
12
9
9
86
85
H3C
H3C
CHO
H3C
H3C
CN
CN
CN
CHO
CHO
13
9
6
86
88
H3C
H3C
CN
CHO
14d
H
H
CH3
CH3
CHO
CN
15d
6
90
H
CH3
CH2-Ph
H
CH3
CH2-Ph
a
Reaction conditions: substrate (4.7 mmol), aqueous sodium dichloroiodate (2.0 equiv, 2.0 M), aqueous ammonia (15 mL), rt.
Starting compounds were prepared by standard literature procedures.
Isolated yields after column chromatography. Structures confirmed by comparison of IR and 1H NMR with those of authentic materials.
Optical purity confirm by chiral HPLC analysis and optical rotations matches with literature values.13
b
c
d

V. N. Telvekar et al. / Tetrahedron Letters 49 (2008) 2213–2215
2215
2. Elmorsy, S. S.; El-Ahl, A. A. S.; Soliman, H.; Amer, F. A.
Tetrahedron Lett. 1995, 36, 2639.
3. Suzuki, H.; Nakaya, C. Synthesis 1992, 641.
4. Brackman, W.; Smith, P. J. Recl. Trev. Chem. 1963, 82, 757.
5. Parameswaram, K. N.; Friedman, O. M. Chem. Ind. (London) 1965,
988.
6. Talukdar, S.; Hsu, J. L.; chou, T. C.; Fang, J. M. Tetrahedron Lett.
2001, 42, 1103.
1, entry 13) were converted to the corresponding nitriles in
good yields. Double bonds were not affected under these
reaction conditions (Table 1, entries 9–11).
Optically active aldehydes, R-2-methyl-3-phenylprop-
anal and R-2-phenylpropanal were subjected to reaction
conditions, after column purification corresponding opti-
cally active R-nitriles were obtained, with optical purity
>99%, determined by chiral HPLC analysis (Table 1,
entries 14 and 15).
7. Bandgar, B. P.; Makone, S. S. Synth. Commun. 2006, 36, 1347.
8. Arote, N. D.; Bhalerao, D. S.; Akamanchi, K. G. Tetrahedron Lett.
2007, 48, 3651.
In conclusion, a novel method has been developed for
the direct conversion of aldehydes to the corresponding
nitriles using aqueous sodium dichloroiodate solution 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.
9. (a) Telvekar, V. N.; Arote, N. D.; Herlekar, O. P. Synlett 2005, 2495;
(b) Telvekar, V. N.; Rane, R. M. Tetrahedron Lett. 2007, 48, 6051.
10. Dark red or brown liquid, stable at room temperature, which has
specific gravity 2.26, miscible in acetic acid, light sensitive and cause
sensitization by inhalation or through skin contact.
11. (a) William, T.; Einar O. I.; Trygve G.; U.S. Patent RE38,856E, 2005;
(b) Bernstein, J.; Kathryn, A. L.; U.S. Patent 3,666,799, 1972.
12. General experimental procedure: To a stirred solution of aldehyde
(1.0 equiv, 4.7 mmol) in aqueous ammonia (15 mL of a 28–30%
solution, Sp. gravity = 0.89) was added the NaICl2 (2.0 equiv, 2.0 M).
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 with
H2O (1 Â 20 mL). The organic layer was dried over Na2SO4 and
concentrated in vacuo. The residue obtained was purified by silica gel
column chromatography (10% EtOAc–hexane) to afford pure nitriles.
13. Enders, D.; Plant, A.; Backhaus, D.; Reinhold, U. Tetrahedron 1995,
51, 10699.
Acknowledgement
V.N.T., K.N.P., H.S.K. and H.K.C. thank UGC, India,
for financial support as well as Rishichem. Research Pvt.
Ltd for providing us aqueous NaICl2 solution.
References and notes
1. Nishiyama, K.; Oba, M.; Watanabe, A. Tetrahedron 1987, 43, 693.