Na2SO3/SOCl2, an efficient reagent for the dehydration of aldoximes to nitriles

Article abstract of DOI:10.1080/10426500307896

Aldoximes undergo rapid dehydration with sodium sulfite, thionyl chloride, under mild reaction condition to afford nitriles in excellent isolated yields. Dehydration reactions were performed in solvent and under solvent free conditions.

Full text of DOI:10.1080/10426500307896

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Phosphorus, Sulfur, and Silicon and the Related
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Na 2 SO 3 /SOCl 2 , an Efficient Reagent for the
Dehydration of Aldoximes to Nitriles
Ali Reza Kiasat a , Foad Kazemi a & Forogh. Khosravian a
a Shahid Chamran University, Ahvaz, Iran
Published online: 27 Oct 2010.
To cite this article: Ali Reza Kiasat , Foad Kazemi & Forogh. Khosravian (2003) Na 2 SO 3 /SOCl 2 , an Efficient Reagent for
the Dehydration of Aldoximes to Nitriles, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:6, 1377-1383, DOI:
10.1080/10426500307896
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Phosphorus, Sulfur, and Silicon, 178:1377–1383, 2003
C
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390200693
Na2SO3/SOCl2, AN EFFICIENT REAGENT FOR THE
DEHYDRATION OF ALDOXIMES TO NITRILES
Ali Reza Kiasat, Foad Kazemi, and Forogh. Khosravian
Shahid Chamran University, Ahvaz, Iran
(Received October 24, 2002; accepted December 3, 2002)
Aldoximes undergo rapid dehydration with sodium sulfite, thionyl chlo-
ride, under mild reaction condition to afford nitriles in excellent isolated
yields. Dehydration reactions were performed in solvent and under sol-
vent free conditions.
Keywords: Aldoxime; nitrile; solid state; thionyl chloride
Nitriles are of particular interest in preparative organic chemistry
due to their rich chemistry.1 They serve as useful precursors for the
synthesis of amines, carboxylic acids, amides, ketones, and hetrocyclic
compounds such as tetrazoles, thiazoles, oxazoles, 2-oxazolines, and 1,3-
3
diarylimidazoles.1 It also has been well documented that the cyano
group itself is present in HIV protease inhibitors, 5-lipoxygenase in-
hibitors, and many other bioactive significant molecules.3 They usu-
ally are prepared by nucleophilic substitution with the cyanide an-
ion or by regenerating the cyano group via oxidation, rearrangement,
or elimination.2 The most efficient route reported so far is based on
the dehydration of aldoximes into the corresponding nitriles. A great
variety of reagents have emerged as a result of sustained efforts by
13
chemists to discover new and mild methods to effect this conversion.2
However, many of these methods met with some limitations, including
low yields, laborious procedures, expensive or not readily accessible
reagents, harsh reaction conditions, use of aqueous medium, necessary
presence of a PTC, need for the addition of an acid or a base, tedious
work-up, or, perhaps, most importantly, a lack of generality for both the
Authors acknowledge the partial support of this work by Shahid Chamran Ahvaz
University Research Council.
Address correspondence to Ali Riza Kiasat, Chemistry Department, College of Science,
Shahid Chamran University, Ahvaz, Iran.
1377

1378
A. R. Kiasat et al.
aliphatic and aromatic aldoximes. Reagents like triethylamine-sulfur
dioxide and sulfuryl chloride fluoride allow the rapid and mild dehy-
dration of aldoximes. However, the preparation of the reagents is in-
convenient ( 70 C).5 Effective conversion of aldoximes to nitriles with
zeolites (CsX)8 requires high temperature (350 C) whereas montmo-
rillonite KSF and Envirocat EPZG9 require very long reaction time
(12–24 h). The reagent like phosgene,4 diphosgene,7 and triphosgene10
are hazardous to use. Consequently, it seems that there is a still great
demand for a new and efficient method. In our development of new
methods for functional group transformation,14 we especially are inter-
ested in developing the application of a modified form of thionyl chloride
in organic synthesis.14h,i Now we report on conditions whereby various
types of nitriles can be conveniently synthesized from the correspond-
ing aldoximes under mild nonaqueous reaction conditions by sodium
sulfite/thionyl chloride in solvent and under solvent free conditions in
high isolated yields.
RESULTS AND DISCUSSION
The reagent was easily prepared by the reaction of thionyl chlo-
ride with stiochiometric amount of sodium sulfite at room tem-
perature. At first, (I) is probably formed, this kind of mecha-
nism has been proposed in the reaction of thionyl chloride and
polyvinylpyrrolidone,14h 1,4-diazabicyclo[2.2.2]octane,14i N-methyl-
pyrolidone,15 or N, N-dimethylformamide.16 Representative aldoximes
were treated with (I) in CH2Cl2 at room temperature or reflux con-
ditions. The reaction proceeded, probably via O-substituted aldoxime
(II), which then underwent fragmentation to afford the corresponding
nitriles in high yield (Scheme 1).
The effects of other solvents such as CCl4, n-hexane, ether, and
THF also were studied, but in comparison with CH2Cl2 the reac-
tion times were longer and the yields were considerably lower. The
procedure turned out to be general for a range of structurally di-
verse aldoximes. Aliphatic and aromatic aldoximes with electron-
withdrawing or electron-donating groups, were cleanly, easily, and
efficiently dehydrated and afforded the corresponding nitriles as the

Dehydration of Aldoximes to Nitriles
1379
SCHEME 1
exclusive products in short reaction time periods and in excellent
yields. The scope and generality of this process is illustrated with
several examples and the results are summarized in Table I. The
structure of all the products were settled from their analytical and
1
spectral (IR, H NMR) data and by direct comparison with authentic
18
samples.7,17
Recently, while exploring the scope and utility of solid-phase condi-
tions in organic synthesis, we observed that the no solvent conditions
are also effective for the dehydration of aldoxime. The required time
for complete conversion of aldoximes to the corresponding nitriles by
this simplified procedure were lower than in the solvent mediated proce-
dure. For example, when 4-nitro benzaldoxime was reacted with sodium
sulfite/thionyl chloride, monitoring of the reaction by TLC showed that
in the absence of solvent the reaction was finished after 10 min at 0 C
but in refluxing CH2Cl2 the reaction was not completed after 90 min
(Table I, entry 6).
This procedure was compatible with substitutes such as hydroxyl
and ether. The reaction of 4-hydroxy benzaldoxime, for example, clearly
furnished the product 4-cyano phenol in 98% isolated yield (Table I,
entry 7).
The advantage of using Na2SO3/SOCl2 as reagent for the dehydra-
tion of aldoximes is shown by comparing our results with those previ-
ously reported in the literature (Table II).
Compared to some previously reported reagents with major or minor
drawbacks, several noteworthy features of this system are apparent:
the easy work-up procedure, availability of the reagent, operational
simplicities, and use of inexpensive reagent. It also is not worthy that
attempts to perform the dehydration with thionyl chloride alone were
not successful due to its very high reactivity and mixture of unidentified
products were obtained.

1380

Dehydration of Aldoximes to Nitriles
1381
TABLE II Comparison of Some Results Obtained from the Reaction of
Aldoximes with Na2SO3/SOCl2 with Those Reported from Other Methods
Benzaldoxime
p-Methoxy benzaldoxime
Cinemaldoxime
Time Temp. Yield
Time Temp. Yield Time Temp.
Yield
(%)
Method
(h)
( C)
(%)
(h)
( C)
(h)
( C)
(%)
Aa
Bb
Cc
Dd
Ee
0.08
0.66
24
16
48
0
98
92
81
81
60
0.17
0.83
24
15
78
0
94
85
60
70
90
0.05
0.66
24
—
—
0
r.t.
100
—
91
88
50
—
—
r.t.
100
120
70
r.t.
100
120
70
—
aThe present method (solvent free procedure).
bDobco/SOCl2 was used.
ct-BuMe2SiCl/imidazole was used.13
dMontmorillonite KSF was used.9
eOrtho ester CH3C(OEt)3, H+ was used.12
CONCLUSION
We believe that the present procedure for dehydration of aldoximes
provides an easy, mild, efficient, versatile and general methodology for
the preparation of nitriles from different classes of aldoximes, and we
feel that it may be a suitable addition to methodologies already present
in the literature.
EXPERIMENTAL
General
IR spectra were recorded on a Shimadzo 450 spectrophotometer;
1
and HNMR spectra in CDCl3 on a Bruker Avance DPX instrument
(250 MHz). Sodium sulfite and thionyl chloride were purchased from
Fluka Company. Aldoximes were purchased from Fluka and Merck or
were prepared in our laboratory from the corresponding aldehydes ac-
cording to known procedures.19 Products were characterized by compar-
ison of their physical data, IR, and 1H NMR spectra with authentic sam-
ples. The purity determination of the products and reaction monitoring
were accomplished by TLC on silica gel polygram SILG/UV 254 plates.
General Procedure for the Conversion of Aldoximes
to Nitriles with Na2SO3/SOCl2 in CH2Cl2
To a suspension solution of sodium sulfite (1.5 mmol, 0.189 g) in anhy-
drous CH2Cl2 (3 ml), was added a solution of freshly distilled thionyl

1382
A. R. Kiasat et al.
chloride (1.5 mmol, 0.179 g) in CH2Cl2 (2 ml). The heterogeneous mix-
ture was stirred for about 3 min at ambient temperature. To the reaction
mixture, aldoxime (1 mmol) was slowly added and stirred at room tem-
perature or under reflux conditions for 7–40 min. The progress of the re-
action was followed by TLC until no starting material could be detected.
After cooling to ambient temperature, the product was then filtered and
the residue washed thoroughly with CH2Cl2 (5 ml). Evaporation of sol-
vent under reduced pressure furnished the desired nitrile in 87–98%
isolated yields.
General Procedure for the Conversion of Aldoximes
to Nitriles with Na2SO3/SOCl2 under Solvent
Free Conditions
Fine powdered sodium sulfite (1.5 mmol, 0.189 g) was mixed with the
freshly distilled thionyl chloride (1.5 mmol, 0.179 g) in a 25 ml round-
bottomed flask. To the resulting powder, aldoxime (1 mmol) was slowly
added and stirred at 0 C for 1–30 min. The progress of the reaction
was followed by TLC until no starting material could be detected. The
mixture was shaken with CH2Cl2 (5 ml), and filtered. The residue was
washed with CH2Cl2 and the solvent evaporated under reduced pres-
1
sure to afford the TLC and HNMR pure products in 87–98% isolated
yields.
REFERENCES
[1] a). G. Tennant, Comprehensive Organic Chemistry, edited by D. Barton, D. W. Ollis,
and I. O. Sutherland (Pergamon Press, Oxford 1979), vol. 2, p. 528. b) K. V. N. S.
Srinivas, E. Bolla Reddy, and Das Biswanath. Synlett, 4, 625 (2002).
[2] A. Kamal, M. Arifuddin, and V. Rao, Synth. Commun., 28, 4507 (1998).
[3] G. Lai, N. K. Bhamare, and W. K. Anderson, Synlett, 2, 230 (2001).
[4] H. Babad and A. G. Zeiler, Chemical Review, 75 (1973).
[5] G. A. Olah and Y. D. Vanker, Synthesis, 9, 702 (1978).
[6] S. Kim and K. Y. Yi, Tetrahedron Lett., 27, 1925 (1986).
[7] K. Mai and G. Patil, Synthesis, 12, 1037 (1986).
[8] M. Narayanrao, P. Kumar, and K. Garyali, Org Prep Proced Int., 230 (1989).
[9] B. P. Bandger, S. R. Jagtap, S. B. Ghodeshwar, and P. P. Wadgaonkar, Synth Com-
mun., 25, 2993 (1995).
[10] D. P. Sabu, Indian J Chem., 32B, 385 (1993).
[11] B. P. Bandgar, V. S. Sadavarte, and K. R. Sabu, Synth. Commun., 29, 3409 (1999).
[12] M. Rogic, J. F. Van Paooen, K. P. Klein, and T. P. J. Demmin, Org. Chem., 39, 3424
(1974).
[13] M. O. Marciales, L. Pifiero, L. Ufret, W. Algarin, and J. Morales, Synth. Commun.,
28, 2807 (1998).

Dehydration of Aldoximes to Nitriles
1383
[14] a) F. Kazemi, A. R. Kiasat, and S. Ebrahimi, Phosphorus, Sulfur, and Silicon, 176,
135 (2001); b) F. Kazemi and A. R. Kiasat, Synthetic Commun., 32, 2255 (2002);
c) F. Kazemi, A. R. Kiasat, and S. Ebrahimi, Synthetic Commun., 32, 2483 (2002);
d) F. Kazemi, A. R. Kiasat, and S. Ebrahimi, J. Chem. Research (S), 176 (2002);
e) B. Tamami and A. R. Kiasat, Synthetic Commun., 28, 1275 (1998); f) B. Tamami
and A. R. Kiasat, J. Chem Research, 454 (1998), g) B. Tamami and A. R. Kiasat,
Synthetic Commun., 30, 235 (2000); h) B. Tamami and A. R. Kiasat, J. Chem Re-
search, 444 (1999); i) F. Kazemi and A. R. Kiasat, Indian Journal of Chemistry,
Section B (2002).
[15] F. Hiashi and J. Nishi, J. Polymer Science. Part A: Polymer Chemistry, 701 (1986).
[16] M. S. Newman and P. K. Sujeeth, J. Org. Chem., 4367 (1978).
[17] a). A. Saednya, Synthesis, 9, 748 (1983); b). B. Das, C. Ramesh, and P.
Madhusudhan, Synlett, 11, 1599 (2000).
[18] Fluka Handbook of Fine Chemicals, (1999–2000).
[19] A. I. Vogel, A Textbook of Practical Organic Chemistry (Elbs and Longmann, 1978),
4th ed.