Reactions of methyl 4-aminofurazan-3-carboximidate with nitrogen-containing nucleophiles

Article abstract of DOI:10.1023/A:1012412220493

Methyl 4-aminofurazan-3-carboximidate reacts with aromatic amines and hydrazines to give the corresponding amidines and amidrazones. The reaction of the title compound with o-phenylenediamine yields 3-amino-4-(2-benzimidazolyl)furazan, and with acylhydraz

Full text of DOI:10.1023/A:1012412220493

Russian Journal of Organic Chemistry, Vol. 37, No. 5, 2001, pp. 717 720. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 5, 2001,
pp. 755 758.
Original Russian Text Copyright
2001 by Sergievskii, Pirogov, Mel’nikova, Tselinskii.
Reactions of Methyl 4-Aminofurazan-3-carboximidate
*
with Nitrogen-Containing Nucleophiles
A. V. Sergievskii, S. V. Pirogov, S. F. Mel’nikova, and I. V. Tselinskii
St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 198013 Russia
e-mail: svpi@yandex.ru
Received April 7, 2000
Abstract Methyl 4-aminofurazan-3-carboximidate reacts with aromatic amines and hydrazines to give the
corresponding amidines and amidrazones. The reaction of the title compound with o-phenylenediamine yields
2
3
-amino-4-(2-benzimidazolyl)furazan, and with acylhydrazines N -acyl-4-aminofurazan-3-carbohydrazides
are formed. The latter undergo thermal intramolecular cyclization with formation of 3-amino-4-(1,2,4-triazol-
-yl)furazan derivatives containing various substituents in position 5 of the triazole ring.
3
In continuation of our studies on the applicability
of a new synthon of the 1,2,5-oxadiazole series,
methyl 4-aminofurazan-3-carboximidate (I) [1], for
preparation of various polycyclic structures possessing
a 3-amino-1,2,5-oxadiazole fragment, we examined
its behavior in reactions with some aromatic amines,
aromatic hydrazines, and acylhydrazines. Easy reac-
tions of carboximidate I with hydrazides derived
from heterocyclic acids [1] led us to presume that
analogous reactions are possible with aliphatic carbo-
hydrazides containing various functional groups. In
fact, heating of a mixture of compound I with alkane-
carbohydrazide in alcohol resulted in formation of
substituted carboxamidrazones II IV in good yields
(Fig. 1). An analogous pattern was observed in the
C NMR spectrum: there were two signals from the
1
3
carbonyl carbon atoms, eight signals from carbon
atoms of the furazan ring, two amidine carbon signals,
and two signals from the methylene group (Fig. 2).
However, we failed to assign these signals to parti-
cular isomers because of the lack of appropriate model
compounds.
A fairly strong molecular ion peak with m/z 267
Irel = 40%) was observed in the mass spectrum of
(
IV. The fragment ion peak with m/z 249 corresponds
to elimination of water from the molecular ion.
A similar pattern was observed in the mass spectra
of amidrazones II, III, and V. This allowed us to
presume easy intramolecular cyclization of compounds
II V into furazanyl-1,2,4-triazole derivatives. Indeed,
heating of II V at a temperature exceeding their
melting point by 5 10 C resulted in elimination of
water and formation of 3-amino-(1,2,4-triazol-3-yl)-
furazans VI IX (Scheme 2).
(
Scheme 1). According to the NMR data, amidrazones
1
II IV exist as two isomers, A and B. The H NMR
spectrum of compound IV contains signals from
protons of two NH and two NH groups of the amid-
2
razone moiety, four protons of two NH groups in
2
the furazan ring, and protons of the methylene group
Scheme 1.
II, R = OMe; III, R = (CH ) OH; IV, R = 4-aminofurazan-3-yl.
2
4
_
___________
*
This study was financially supported by the Russian Founda-
tion for Basic Research (project no. 99-03-33085a).
1
070-4280/01/3705-0717$25.00 2001 MAIK Nauka/Interperiodica

7
18
SERGIEVSKII et al.
Scheme 2.
II, VI, R = CH OCH ; III, VII, R = (CH ) OH; IV, VIII, R = 4-aminofurazan-3-ylmethyl; V, IX, R = 4-methylfurazan-3-yl.
2
3
2 5
Scheme 3.
X, R = Cl; XI, R = NO2.
3
-Amino-4-(1,2,4-triazol-3-yl)furazans VI IX are
diamine stops at the stage of formation of amidine
XII which does not undergo cyclization for steric
reasons. o-Phenylenediamine reacts with I to give
substituted benzimidazole XIII in more than 70%
yield (Scheme 4). o-Aminophenol failed to react with
carboximidate I, presumably because of the lower
basicity (nucleophilicity) of the amino group.
NH acids, and they readily form salts on treatment
with aqueous alkalies. The methoxy group in carbox-
imidate I can be replaced by nitrogen-containing
nucleophiles to give amidines or amidrazones. If the
latter contain reactive groups and/or there are no steric
hindrances, subsequent intramolecular cyclization is
possible. The reactions of I with para-substituted
phenylhydrazines result in formation of amidrazones
X and XI (Scheme 3). The reaction with p-phenylene-
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
1
a Bruker DPX-300 spectrometer using DMSO-d as
6
solvent and internal reference. The IR spectra were
measured on a Perkin Elmer Spectrum 1000 instru-
ment from thin films on KBr support. The mass
spectra were run on a Varian CH-6 spectrometer.
Compound V was synthesized by the procedure
reported in [1].
Typical procedure for reactions of methyl
-aminofurazan-3-carboximidate (I) with aliphatic
4
carbohydrazides. A mixture of 0.5 g (3.52 mmol)
of carboximidate I and 3.52 mmol of appropriate
hydrazide in 20 ml of alcohol was refluxed for 12 h.
The mixture was cooled, and the precipitate was
filtered off, washed with alcohol (2 5ml) and water
(
2 5ml), dried at 60 C, and recrystallized from
alcohol.
2
N -(Methoxymethylcarbonyl)-4-aminofurazan-3-
carboxamide hydrazone (II). Yield 85%, mp 201
1
2
(
(
02 C. H NMR spectrum, , ppm: 10.32 and 10.24
1H, NH), 6.98 and 6.75 (4H, 2NH ), 4.33 and 3.98
2
1
3
1
2
2H, CH ), 3.34 and 3.33 (3H, CH ). C NMR spec-
Fig. 1. H NMR spectrum of N -(4-aminofurazan-3-
ylmethylcarbonyl)-4-aminofurazan-3-carboxamide hydra-
zone (IV).
2
3
trum, C, ppm: 170.22 (C O), 165.56 (furazan),
154.80, 154.20, 140.74, 139.92, 136.91, 70.98 and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

REACTIONS OF METHYL 4-AMINOFURAZAN-3-CARBOXIMIDATE
719
Scheme 4.
6
9.57 (CH ), 58.77 and 58.48 (CH ). Mass spectrum,
136.45, 60.69 (CH OH), 34.15 ( CH ), 32.36 (CH ),
2 2 2
2
3
+
+
m/z: 214 M , 196 [M H O] . Found, %: C 33.75;
H 4.41; N 39.32. C H N O . Calculated, %: C 33.64;
25.36 (CH ), 25.17 (CH ). Mass spectrum, m/z: 256
2
2 2
+
+
M , 238 [M H O] . Found, %: C 42.08; H 5.89;
6
10
6
3
2
H 4.67; N 39.25. M 214.
N 32.73. C H N O . Calculated, %: C 42.18; H 6.25;
9
16
6
3
2
N 32.81. M 256.
N -(6-Hydroxyhexanoyl)-4-aminofurazan-3-car-
2
boxamide hydrazone (III). Yield 80%, mp 189
N -(4-Aminofurazan-3-ylmethylcarbonyl)-4-
aminofurazan-3-carboxamide hydrazone (IV).
Yield 73%, mp 223 224 C (from alcohol). Mass
1
1
1
4
1
90 C (from alcohol). H NMR spectrum, , ppm:
0.2 and 9.79 (1H, NH), 6.75 and 6.30 (4H, 2NH2),
.30 br (1H, OH), 3.40 (2H, CH ), 2.20 t (2H, CH ),
+
+
spectrum, m/z: 267 M , 249 [M H O] . Found, %:
2
2
2
1
3
.63 1.52 m (6H, 3CH2). C NMR spectrum, C,
C 31.79; H 4.81; N 47.57. C H N O . Calculated, %:
7
9
9
3
ppm: 173.79, 168.53, 155.09, 154.71, 140.66, 138.63,
C 31.46; H 3.37; N 47.19. M 267.
1
3
2
Fig. 2. C NMR spectrum of N -(4-aminofurazan-3-ylmethylcarbonyl)-4-aminofurazan-3-carboxamide hydrazone (IV).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

7
20
SERGIEVSKII et al.
2
Typical procedure for synthesis of 1,2,4-triazoles
N -(4-Chlorophenyl)-4-aminofurazan-4-carbox-
amide hydrazone (X). Yield 79%, mp 165 C
VI IX. N-Acylcarboxamidrazone II V, 0.75 g, was
heated on a metal bath to 5 10 C above its melting
point, kept for 1 2 min at that temperature, and
cooled. The melt was dissolved in 20% aqueous
sodium hydroxide, the undissolved material was fil-
tered off, and the filtrate was acidified to pH 1 by
adding concentrated hydrochloric acid. The precipitate
was filtered off and dried in air.
1
(decomp.). H NMR spectrum, , ppm: 8.95 s (1H,
NH), 7.25 d (2H, Harom), 6.95 d (2H, Harom), 6.43 s
(2H, NH ), 6.41 s (2H, NH ). C NMR spectrum, C,
ppm: 154.63 (furazan), 144.74 (amidrazone), 140.85
(furazan), 135.53, 129.05, 121.82, 113.41 (C H ).
Found, %: C 42.52; H 3.75; Cl 14.08; N 33.99.
M 252. C H N OCl. Calculated, %: C 42.78; H 3.59;
1
3
2
2
6
4
+
9
9
6
3
-Amino-4-(5-methoxymethyl-1,2,4-triazol-3-yl)-
Cl 14.03; N 33.26. M 252.
1
2
furazan (VI). Yield 70%, mp 189 190 C. H NMR
spectrum, , ppm: 6.70 s (2H, NH ), 4.64 s (2H,
N -(4-Nitrophenyl)-4-aminofurazan-4-carbox-
2
amide hydrazone (XI). Yield 88%, mp 279 280 C
1
3
1
CH ), 3.36 s (3H, OCH ). C NMR spectrum, C,
2
3
(decomp.). H NMR spectrum, , ppm: 9.85 s (1H,
ppm: 155.55 (furazan), 155.33 and 150.66 (triazole),
39.35 (furazan), 64.99 (CH ), 58.42 (CH ). Found,
: C 36.53; H 4.78; N 42.61. M 196. C H N O .
6 8 6 2
Calculated, %: C 36.74; H 4.11; N 42.84. M 196.
NH), 8.12 d (2H, Harom), 7.03 d (2H, Harom), 6.78 s
1
3
1
%
2 3
(2H, NH ), 6.40 s (2H, NH ). C NMR spectrum, C,
2 2
+
ppm: 154.74 (furazan), 150.68 (amidrazone), 140.84
furazan), 138.11, 138.05, 126.30, 111.11 (Carom).
(
+
3
-Amino-4-[5-(5-hydroxypentyl)-1,2,4-triazol-3-
Found, %: C 41.05; H 3.94; N 37.31. M 263.
1
yl]furazan (VII). Yield 80%, mp 156 157 C. H
C H N O . Calculated, %: C 41.06; H 3.45; N 37.26.
9
9
7
3
NMR spectrum, , ppm: 14.3 br (1H, NH), 6.40 s
M 263.
2
(
2
2H, NH ), 4.33 br (1H, OH), 3.39 s (2H, CH ),
.80 s (2H, CH ), 1.73 1.36 m (6H, 3CH ). C NMR
2 2
2
2
3-Amino-N -(4-aminophenyl)furazan-4-carbox-
amidine (XII). A mixture of 0.5 g (3.5 mmol) of
compound I and 0.4 g (3.5 mmol) of p-phenylenedi-
amine in 10 ml of alcohol was refluxed for 3 days.
The mixture was cooled, and the precipitate was
filtered off and dried in air. Yield 0.63 g (83%),
mp 177 C (from alcohol). H NMR spectrum, , ppm:
6.75 d (2H, Harom), 6.70 s (2H, NH ), 6.58 d (2H,
Harom), 6.55 s (2H, NH ), 4.9 s (2H, NH ). Found, %:
C 50.24; H 5.44; N 39.48. M 218. C H N O. Cal-
1
3
spectrum, C, ppm: 173.79, 168.53, 155.09, 154.71,
1
3
40.66, 138.63, 136.45, 60.69 (CH OH), 34.15 (CH ),
2 2
2.36 (CH ), 25.36 (CH ), 25.17 (CH ). Found, %:
2
2
2
+
C 45.48; H 5.12; N 35.21. M 238. C H N O . Cal-
9
14
6
2
1
culated, %: C 45.37; H 5.92; N 35.27. M 238.
-(4-Aminofurazan-3-yl)-5-(4-aminofurazan-3-
ylmethyl)-1,2,4-triazole (VIII). Yield 60%, mp 180
3
2
2
2
1
+
1
3
1
1
81 C. IR spectrum, , cm : 3617, 3534, 3455, 3344,
194, 3041, 2896, 2784, 1640, 1602, 1552, 1532,
461, 1439, 1401, 1357, 1279, 1245, 1172, 1131,
9 10 6
culated, %: C 49.54; H 4.58; N 38.53. M 218.
-Amino-4-(2-benzimidazolyl)furazan (XIII).
A mixture of 0.5 g (3.5 mmol) of compound I and
.35 g (3.5 mmol) of o-phenylenediamine in 10 ml
3
1
049, 1007, 975, 892, 860, 795, 769, 718, 690. H
NMR spectrum, , ppm: 14.72 br (1H, NH), 6.42 s
2H, NH ), 6.35 s (2H, NH ), 4.36 s (2H, CH ).
0
(
2
2
2
of ethanol was refluxed for 20 h. The mixture was
cooled, and the precipitate was filtered off, washed
with alcohol (2 5 ml), and dried in air. Yield 0.42 g.
An additional amount (0.08 g) can be isolated by
dilution of the filtrate with water. Overall yield 71%,
1
3
C NMR spectrum, C, ppm: 156.97 and 156.07
furazan), 144.94 (triazole), 21.10 (CH ). Found, %:
(
2
+
C 33.52; H 3.16; N 50.35. M 249. C H N O . Cal-
7
7
9
2
culated, %: C 33.74; H 2.83; N 50.59. M 249.
1
3
-(4-Aminofurazan-3-yl)-5-(4-methylfurazan-3-
mp 264 265 C (from alcohol). H NMR spectrum, ,
yl)-1,2,4-triazole (IX). Yield 75%, mp 214 215 C.
ppm: 13.6 s (1H, NH), 7.7 m (2H, Harom), 7.3 m (2H,
1
3
1
Harom), 6.8 s (2H, NH2).
C NMR spectrum, C,
ppm: 155.60 and 138.63 (furazan), 140.31 (imidazole),
42.71, 134.34, 124.28, 122.85, 119.67, 112.20
H NMR spectrum, , ppm: 16.11 br (1H, NH), 6.50 s
1
3
(
2H, NH ), 2.70 s (3H, CH ). C NMR spectrum, C,
2 3
1
ppm: 153.33, 151.42, 9.34 (CH ). Found, %: C 36.02;
3
+
(Carom). Found, %: C 53.76; H 2.98; N 34.92. M 201.
H 2.76; N 47.95. C H N O . Calculated, %: C 35.90;
7
6
8
2
C H N O. Calculated, %: C 53.73; H 3.51; N 34.81.
H 2.58; N 47.85.
9
7
5
M 201.
Typical procedure for reaction of carboximidate
I with aromatic hydrazines. A mixture of equimolar
amounts of compound I and substituted phenylhydra-
zine in alcohol was refluxed for 5 h. The mixture was
cooled, and the precipitate was filtered off, washed
with cold alcohol (10 ml) and water (10 ml), and
dried in air.
REFERENCE
1. Tselinskii, I.V., Mel’nikova, S.F., Pirogov, S.V., and
Sergievskii, A.V., Russ. J. Org. Chem., 1999, vol. 35,
no. 2, pp. 296 300.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001