A Convenient New Synthesis of 1-Cyanobenzotriazole and Its Use as a C-Cyanating Reagent

Full text of DOI:10.1021/jo9717548

J . Org. Chem. 1998, 63, 401-402
401
Sch em e 1
A Con ven ien t New Syn th esis of
1-Cya n oben zotr ia zole a n d Its Use a s a
C-Cya n a tin g Rea gen t
Terry V. Hughes, Stephen D. Hammond, and
Michael P. Cava*
Department of Chemistry, The University of Alabama, Box
870336, Tuscaloosa, Alabama 35487-0336
Received September 19, 1997
In tr od u ction
Sch em e 2
The formation of a carbon-carbon bond by the intro-
duction of a cyano group is a fundamental process in
organic synthesis. Most often, this is accomplished by
nucleophilic attack of a cyanide ion (CN-) at an electro-
philic carbon. A few reagents are known, however, that
behave as cyano cation (CN+) equivalents on treatment
with a carbanion. These include tosyl cyanide,1,2 2-chlo-
robenzyl thiocyanate,3 thiocyanogen,4 and most impor-
tant, cyanogen chloride.5 In searching for additional CN+
synthons, our attention focused upon the known 1-cy-
anobenzotriazole (1), which is already known to effect the
cyanation of amines and thiols.6,7 We now report a new
and convenient synthesis of 1, as well as the first
examples of its use as a C-cyanation reagent.
Resu lts a n d Discu ssion
1-Cyanobenzotriazole (1) has been prepared previously
only by the reaction of the benzotriazole anion with either
cyanogen chloride or cyanogen bromide, both of which
are highly toxic and irritating reagents.6,8-10 We have
now found that it may be conveniently prepared by a
simple and safe two-step process. Thus, reaction of
benzotriazole (2) with commercial 5% sodium hypochlo-
rite affords 1-chlorobenzotriazole (3) in quantitative yield,
as previously reported (Scheme 1).11,12 Treatment of 3
with sodium cyanide in acetonitrile under mild condi-
tions, followed by sublimation of the crude product, gave
pure cyano compound 1 in 70% yield. Purification of the
nonvolatile residue afforded the known imine 4, which
is a byproduct formed in the reaction of benzotriazole
anion with BrCN.6
The formation of 4 is consistent with the formation of
the benzotriazole anion as an intermediate in our pro-
cedure. Consequently, the likely mechanism for the
reaction is that shown in Scheme 2, in which ClCN is
indeed formed as the other transient intermediate. The
alternate possibility of a direct attack of CN- at either
N-1 or N-3 of 3 seems unlikely and, furthermore, would
not explain the formation of 4.
The utility of 1 as a cyanating reagent was tested by
reacting it with a series of arylacetonitrile anions to give
the corresponding arylmalonitriles in fair to good yields.
(1) Kahne, D.; Collum, D. Tetrahedron Lett. 1981, 22, 5011-5014.
(2) Van Leusen, A. M.; J agt, J . C. Tetrahedron Lett. 1970, 12, 967-
970.
(3) Davis, W. A.; Cava, M. P. J . Org. Chem. 1983, 48, 2774-2775.
(4) Boltze, K.-H.; Dell, H.-D. Liebigs Ann. Chem. 1967, 709, 63-69.
(5) Wheland, R. C.; Martin, E. L. J . Org. Chem. 1975, 40, 3101-
3109.
Exp er im en ta l Section
Gen er a l. Meth od s. Melting points are uncorrected. 1H
NMR were obtained at 360 MHz. Unless otherwise noted,
materials were obtained from commercial suppliers and used
without purification.
1-Ch lor oben zotr ia zole (3). A 5% NaOCl solution (com-
mercial bleach, 1280 mL, 0.96 mol) was added dropwise to a
solution of benzotriazole (95.84 g, 0.80 mol) in 50% AcOH (384
mL) with stirring. After the addition was complete, the solution
was stirred for 2 h and filtered, and the precipitate was washed
with H2O (∼3 L) until the washings were neutral. The solid
was dried in vacuo to give 1-chlorobenzotriazole 3 (119.41 g, 97%)
as white crystals: mp 103-105 °C (lit.12 mp 104-106 °C); 1H
NMR (CDCl3) δ 8.09 (d, 1H, J ) 8.39 Hz), 7.62 (m, 2H), 7.46 (m,
1H).
(6) Katritzky, A. R.; Brzezinski, J . Z.; Lam, J . N. Rev. Roum. Chim.
1991, 36, 573-580.
(7) For further examples of benzotriazole as a synthetic auxiliary
see: (a) Katritzky, A. R.; Lan, X. Chem. Soc. Rev. 1994, 23, 363-373.
(b) Katritzky, A. R.; Yang, Z.; Cundy, D. J . Aldrichim. Acta 1994, 27,
31. (c) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445.
(8) Hermes, M. E.; Marsh, F. D. J . Am. Chem. Soc. 1967, 89, 4760-
4764.
(9) Sheludyakov, V. D.; Sheludyakova, S. V.; Kuznetsova, M. G.;
Silkina, N. N.; Mironov, V. F. Zh. Obshch. Khim. 1980, 50, 875-881.
(10) Purygin, P. P.; Pan’Kov, S. V. Zh. Org. Khim. 1995, 31, 934-
936.
(11) Rees, C. W.; Storr, R. C. J . Chem. Soc., Chem. Commun. 1968,
1305-1306.
(12) Rees, C. W.; Storr, R. C. J . Chem. Soc. C 1969, 1474-1476.
1-Cya n oben zotr ia zole (1). A solution of NaCN (7.95 g, 160
mmol), 1-chlorobenzotriazole (24.56 g, 160 mmol), and CH3CN
(640 mL) was stirred for 3 h in an ice bath. The solution was
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402 J . Org. Chem., Vol. 63, No. 2, 1998
Notes
Ta ble 1. Ar ylm a lon on itr iles fr om Ar yla ceton itr iles
and the mixture was stirred for 15 min. This solution was
syringed into a solution of 1-cyanobenzotriazole (0.86 g, 6.00
mmol) in THF (5 mL) at 0 °C under nitrogen, and the reaction
mixture was stirred overnight. A solution of NH4Cl (3 mL) was
added, and the solvent was evaporated. The residue was
dissolved in benzene (50 mL) and extracted with 10% NaOH
(4 × 40 mL). The aqueous extracts were combined, cooled in
an ice bath and acidified to pH 1 with concd HCl and extracted
with CH2Cl2 (3 × 50 mL), and the combined extracts were dried
over anhyd Na2SO4 and evaporated. The residue was purified
via a short column (CH2Cl2) to give the corresponding arylma-
lononitrile (Table 1).
Ar
% yield
mp (°C)
lit.3 mp °C
phenyl
4-bromophenyl
2-chlorophenyl
3,4-(methylenedioxy)phenyl
1-naphthyl
66
65
52
30
52
67-68
68-69
85-86
86-87
59-60
131-133
166-167
60-62
131-133
165-166
then allowed to slowly warm to rt and stirred for 24 h. The
solvent was then removed and the resulting residue sublimed
(70 °C, 2 mmHg) to give 1-cyanobenzotriazole (1) (16.08 g, 70%)
as white crystals: mp ) 73.4-74.8 °C (lit.8 mp ) 74-76 °C); 1H
NMR (CDCl3) δ 8.22 (d, 1H, J ) 8.32 Hz), 7.79 (m, 2H), 7.62 (m,
1H). Column chromatography of the nonvolatile residue on silica
gel (hexane/EtOAc, 2:1) followed by crystallization (CH2Cl2/
hexane) gave bis(benzotriazol-1-yl)methylimine (4) as white
Ack n ow led gm en t. The authors are grateful for the
support of S.D.H., who participated in the NSF Summer
Undergraduate Research Program at The University of
Alabama. We also thank the National Science Founda-
tion for a grant (CHE-9612350) in partial support of this
work.
1
needles. The properties of 4 (mp, H NMR, MS) were in accord
with those previously reported.6
Gen er a l P r oced u r e for Ar yla ceton itr ile Cya n a tion . To
a solution of LDA (4.5 mmol) in THF (10 mL) at 0 °C under
nitrogen was added the arylacetonitrile (3 mmol) in THF (5 mL),
J O9717548