2-Acylamino-3-chloroacrylonitriles, promising reagents for heterocyclization

Article abstract of DOI:10.1023/B:RUJO.0000034944.88382.28

2-Acylamino-3-chloroacrylonitriles prepared by treating available N-(1,2,2-trichloroethyl)amides of carboxylic acids with sodium cyanide readily undergo cyclization in the presence of excess hydrazine hydrate. The cyclization products, 5-amino-4-acylaminopyrazoles, were applied to the synthesis of new imidazo[4,5-c]pyrazole and pyrazolo[1,5-a]pyrimidine derivatives.

Full text of DOI:10.1023/B:RUJO.0000034944.88382.28

Russian Journal of Organic Chemistry, Vol. 40, No. 2, 2004, pp. 219-220. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 2, 2004,
pp. 247-248.
Original Russian Text Copyright Ó 2004 by Popil’nichenko, Brovarets, Drach.
.
2-Acylamino-3-chloroacrylonitriles, Promising Reagents
for Heterocyclization
S. V. Popil’nichenko, B. S. Brovarets, and B. S. Drach
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
Kiev, 02094 Ukraine
Received July 24, 2003
Abstract—2-Acylamino-3-chloroacrylonitriles prepared by treating available N-(1,2,2-trichloroethyl)amides of
carboxylic acids with sodium cyanide readily undergo cyclization in the presence of excess hydrazine hydrate. The
cyclization products, 5-amino-4-acylaminopyrazoles, were applied to the synthesis of new imidazo[4,5-ñ]pyrazole
and pyrazolo[1,5 à]pyrimidine derivatives.
ethyl)amides of aromatic acids Ia and Ib with sodium
cyanide afforded a mixture of Z- and E isomers of
2 acylamino-3-chloroacrylonitriles IIa and IIb that
without isolation could be used for cyclization at
treatment with hydrazine hydrate along the following
scheme.
Substituted acrylonitriles of a general formula
Cl2C=C(NHCOR)CºN are important reagents for
various cyclocondensations [1–4]. Yet heterocyclizations
of their analogs with a single chlorine atom in the b-
position with respect to the cyano group were not studied.
We established that a reaction of N-(1,2,2- trichloro-
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R = Ph (a), 4-MeC6H4 (b).
The structure of cyclization products IIIa, b is consistent
with the data of H NMR and IR spectra. It was also
the series of nitrogen-containing heterocyles will be
reported in more detail elsewhere.
1
confirmed by conversions IIIb ’ IV and IIIb ’ V. The
prospects of application of the promising reagents IIa, b
and their analogs to the synthesis of new derivatives from
N-(5-Amino-1H-pyrazol-4-yl)benzamide (IIIa). To
a solution of 0.98g (20 mmol) of sodium cyanide in 5 ml
of water at cooling to –10°C was added within 30 min
1070-4280/04/4002-0219Ó2004 MAIK “Nauka/Interperiodica”

220
POPIL’NICHENKO et al.
while vigorous stirring a solution of 2.53 g (10 mmol) of
N-(1,2,2-trichloroethyl)benzamide [1] in 5 ml of dioxane.
The mixture was stirred for 2 h more at –10...–5°C, then
25 ml of water was added, the precipitate was filtered
off, washed with water, and dissolved in 30 ml of
methanol. To the methanol solution was added 1.00 ml
(20 mmol) of hydrazine hydrate. The mixture was left
standing for 72 h at 20–25°C, the methanol was removed
in a vacuum, the residue was treated with water, filtered
off, and recrystallized from aqueous ethanol, 1:2. Yield
of compound IIIa 0.45 g (45%), mp 221–223°C.
Found,%: C 59.03; H 4.89; N 27.33. C10H10N4O.
Calculated, %: C 59.40; H 4.98; N 27.71.
recrystallized from aqueous ethanol, 1:1. Yield of
compound IV 0.22 g (55%), mp 209–210°C. 1H NMR
spectrum, d, ppm: 2.40 s (3H, CH3), 7.30 d (2H, H arom),
7.98 d (2H, H arom), 8.15s (1H,C3H), 10.23 s (1H, N–
H). The proton signal of another N–H bond was not
observed. Found, %: C 66.49; H 4.93; N 28.14. C11H10N4.
Calculated, %: C 66.65; H 5.09; N.26.
N-(5,7-Dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-
4-methylbenzamide (V). To a solution of 0.43 g (2
mmol) of compound IIIb in 30 ml of toluene was added
0.21 ml (2 mmol) of acetylacetone, the mixture was
refluxed for 10 h, the most of solvent was removed in a
vacuum, the precipitate was filtered off, and recrystallized
from toluene. Yield of compound V 0.40 g (72%), mp
N-(5-Amino-1H-pyrazol-4-yl)methylbenzamide
(IIIb) was synthesized in the same way as compound
IIIa from 2.66 g (20 mmol) of p-toluic acid N-(1,2,2-
trichloroethyl)amide [1]. After the reaction with sodium
cyanide the precipitate was filtered off, washed with
water, and dried in a vacuum desiccator over phosphorus
pentoxide to obtain 1.15 g of a mixture of geometrical
isomers of substituted acrylonitrile IIb in a ratio ~3:1
according to relative intensity of signals in the 1H NMR
spectrum at 7.49 and 7.40 ppm (C3H) and also at 10.56
and 10.12 ppm (N–H). Inasmuch as this isomer mixture
under common conditions suffered fast tarring it was
immediately dissolved in 30 ml of methanol and treated
with hydrazine hydrate as described above. Yield of
compound IIIb 0.56 g (50%), mp 252–254°C after
recrystallization from aqueous ethanol, 1:2. IR spectrum,
–1
160–162°C. IR spectrum, n, cm : 1660 (C=O), 3440 (NH
1
associated). H NMR spectrum, d, ppm: 2.39 s (3H,
CH3C6H4 ), 2.52 s (3H, CH3), 2.68 s (3H, CH3), 6.88 s
(1H, C6H), 7.33 d (2H, H arom), 7.96 d (2H, H arom),
8.42 s (1H, C2H), 10.07 s (1H, NHCO). Found, %:
C 68.38; H 5.65; N 19.83. C16H16N4O. Calculated, %:
C 68.55; H 5.75; N.99.
IR spectra were registered on spectrometer Specord
M-80 from samples pelletized with KBr. 1H NMR spectra
were registered on Varian VXR-300 instrument from
solutions of compounds in DMSO d6, internal reference
TMS.
REFERENCES
1. Drach, B.S., Brovarets, V.S., and Smolii, O.B., Sintezy
azotsoderzhashchikh geterotsiklicheskikh soedinenii na
osnove amidoalkiliruyushchikh agentov (Syntheses of
Nitrogen-Containing Heterocyclic Compounds on the base
ofAmidoalkilating Reagents), Kiev: Naukova Dumka, 1992,
p. 81.
–1
n, cm : 1640 (C=O), 3200–3440 (NH, NH2 associated}
1H NMR spectrum, d, ppm: 2.36 s (3H, CH3), 4.69 s
(2H, NH2), 7.32 d (2H, H arom), 7.66 s (1H, C3H), 7.82 d
(2H, H arom), 9.52 s (N1H), 11.42 br.s (1H, NHCO).
Found,%: C 61.05; H 5.46; N 25.73. C11H12N4O.
Calculated, %: C61.11; H 5.59; N 25.91.
2. Brovarets, V.S., Pil’o, S.G., Chernega,A.N., Romanenko, E.A.,
and Drach, B.S., Zh. Obshch. Khim.,1999, vol. 69, p. 1946.
5-p-Tolyl-1,4(6)-dihydroimidazo[4,5-c]pyrazole
(IV). A mixture of 0.43 g (2 mmol) of compound IIIb,
5 ml of anhydrous benzene, and 0.5 ml of thionyl chloride
was heated at 40–50°C for 20 h. The volatile substances
were removed in a vacuum, the residue was treated with
5 ml of ethanol, the precipitate was filtered off and
3. Pil’o, S.G., Brovarets, V.S., Vinogradova, T.K., Golovchen-
ko, A.V., and Drach, B.S., Zh. Obshch. Khim., 2002, vol. 72,
p. 1818.
4. Pil’o, S.G., Brovarets, V.S., Romanenko, E.A., and Drach, B.S.,
Zh. Obshch. Khim., 2002, vol. 72, p. 1828.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004