2020
T. A. Khan et al.
LETTER
Table 1 Dehydration of Aldoximes to Nitriles with DMDTC
H
i
CN
Entry Oxime
R
Nitrile
Yield
Ar
N-OH
Ar
(%)10,11
6
5
5-6a, Ar = C6H5, 70%
1
2
2a
2b
2c
2d
2e
2f
Ph
4a
4b
4c
4d
4e
4f
88
92
89
87
89
93
80
93
70
63
81
80
85
75
92
O
5-6b, Ar = H2C
C6H,469%
4-MeOC6H4
2-MeOC6H4
2,5-(MeO)2C6H3
3,4-(MeO)2C6H3
3,4,5-(MeO)2C6H2
4-ClC6H4
O
H
C
3
CN
N-OH
i
4
MeO
MeO
5
8, 90%
7
H
C
6
CN
7
2g
2h
2i
4g
4h
4i
N-OH
i
8
4-(NMe2)C6H4
4-NO2C6H4
2-HOC6H4
9
10, 90%
9
10
11
12
13
14
15
2j
4j
Scheme 2 Reagents and conditions: (i) DMDTC (1.1 mmol), Et3N
(5.0 mmol), dioxane, 90 °C.
2k
2l
C6H5CH2
4k
4l
n-C7H15
2m
2n
2o
(CH3)2CH
4m
4n
References
C6H5(CH3)CH
(1) (a) North, M. In Comprehensive Organic Functional Group
Transformations; Katritzky, A. R.; Meth-Cohn, O.; Rees, C.
W., Eds.; Pergamon: Oxford, 1995, 617–618. (b) Tennant,
G. In Comprehensive Organic Chemistry, Vol. 2; Barton, D.
H. R.; Ollis, W. D., Eds.; Pergamon: Oxford, 1979, Chap. 8,
534–535. (c) Luo, F.-T.; Jeevanandam, A. Tetrahedron Lett.
1998, 39, 9455. (d) Yamada, H. Chimia 1993, 47, 69.
(e) Crossby, J.; Moiller, J.; Parratt, J. S.; Turner, N. J. J.
Chem. Soc., Perkin Trans. 1 1994, 1679. (f) Cohen, M. A.;
Sawden, J.; Turner, N. J. Tetrahedron Lett. 1990, 31, 7223.
(2) (a) Friedrich, K.; Wallensfels, K. In The Chemistry of the
Cyano Group; Rappaport, Z., Ed.; Wiley-Interscience: New
York, 1970, 67. (b) Fatiadi, A. J. In Preparation and
Synthetic Application of Cyano Compounds; Patai, S.;
Rappaport, Z., Eds.; Wiley: New York, 1983, 1057.
(c) Miller, J. S.; Manson, J. L. Acc. Chem. Res. 2001, 34,
563. (d) Wang, E.-C.; Lin, G.-J. Tetrahedron Lett. 1998, 39,
4047. (e) Medwid, J. B.; Paul, R.; Baker, J. S.; Brockman, J.
A.; Du, M. T.; Hallett, W. A.; Hanifin, J. W.; Hardy, R. A.
Jr.; Tarrant, M. E.; Torley, L. W.; Wrenn, S. J. Med. Chem.
1990, 33, 1230. (f) Judkins, B. D.; Allen, D. G.; Cook, T. A.;
Evans, B.; Sardharwala, T. E. Synth. Commun. 1996, 26,
4351.
HO-N
C
C
N
H
4o
4p
16
17
18
19
20
21
2p
2q
2r
2s
2t
2-Thienyl
76
83
84
87
97
76
2-(5-Methyl)furyl
4q
2-(1-N-Methylpyrrolyl) 4r
3-(Indolyl) 4s
3-(1-N-Methylindolyl) 4t
3-Pyridyl 4u
2u
fragmentation prone O-substituted aldoxime thioester 3
which would collapse under reaction conditions to gener-
ate nitrile 4, carbon dioxide and methylmercaptan.
In conclusion, the methodology reported herein demon-
strates dimethyl dithiocarbonate to be an efficient dehy-
drating agent for conversion of a range of aldoximes to the
corresponding nitriles and offers a useful alternative to the
existing methodologies due to its simplicity and high
yields.
(3) (a) Katritzky, A. R.; Zhang, G. F.; Fan, W. Q. Org. Prep.
Proced. Int. 1993, 25, 315. (b) Larock, R. C.
Comprehensive Organic Transformations; VCH: New
York, 1989. (c) Ishihara, K.; Furuya, Y.; Yamamoto, H.
Angew. Chem. Int. Ed. 2002, 41, 2983. (d) Choi, E.; Lee,
C.; Na, Y.; Chang, S. Org. Lett. 2002, 4, 2369. (e) Yang, S.
H.; Chang, S. Org. Lett. 2001, 3, 4209; and references
therein. (f) Sharghi, H.; Sarvari, M. H. Synthesis 2003, 243.
(g) Sharghi, H.; Sarvari, M. H. Tetrahedron 2002, 58,
10323. (h) Bandgar, B. P.; Makone, S. S. Synlett 2003, 262.
(i) Boruah, M.; Konwar, D. J. Org. Chem. 2002, 67, 7138.
(j) DeLuca, L.; Giacomelli, G.; Porcheddu, A. J. Org. Chem.
2002, 67, 6272. (k) Fukuzawa, S.-i..; Yamaishi, Y.; Furuya,
H.; Terao, K.; Iwasaki, F. Tetrahedron Lett. 1997, 38, 7203.
(l) Meshram, H. M. Synthesis 1992, 943. (m) Villemin, D.;
Lalaoni, M.; Ben Alloum, A. Chem. Ind. (London) 1991,
Acknowledgment
TAK thanks DST, New Delhi for junior research fellowship. Finan-
cial assistance under DST project is also acknowledged.
Synlett 2004, No. 11, 2019–2021 © Thieme Stuttgart · New York