Heterocyclization of ethyl esters of 2-chloro-3-substituted aminoacrylic acids with o-phenylenediamine [4]

Full text of DOI:10.1023/A:1016004027096

Chemistry of Heterocyclic Compounds, Vol. 38, No. 4, 2002
HETEROCYCLIZATION OF ETHYL
ESTERS OF 2-CHLORO-3-SUBSTITUTED
AMINOACRYLIC ACIDS WITH
o-PHENYLENEDIAMINE
F. I. Guseinov, N. A. Yudina, R. N. Burangulova, T. Ya. Ryzhikova, and R. Zh. Valiullina
Keywords: carbonyl-substituted chloroenamines, 5,6,13,14-tetrahydro[1,2,4,5]pyrazino[1,2-a]-
quinoxaline-6,14-dione, o-phenylenediamine, heterocyclization.
The heterocyclization of carbonyl-substituted chloroenamines with bifunctional nucleophilic reagents
features participation of the enamine carbon atoms. It is interesting that the carbonyl group is not altered in this
process [1, 2]. We have shown that the reaction of carboethoxychloroenamines 3 with o-phenylenediamine takes an
unusual course, in which all three electrophilic sites are involved, leading to condensed heterocycle 4. Enamines 3a-c
were obtained by the reaction of enolate 1 with the corresponding amine hydrochloride salts 2 in chloroform at
1
13
room temperature. The H and C NMR spectra show that enamines 3 are obtained as a single isomer. The X-ray
diffraction structural analysis data for analogous enamines [3] suggest that enamines 3 have Z-configuration.
O
Cl
EtO
H
NR R
EtO
ONa +
R
1
R
2
NH HCl
a–c
.
1
2
Cl
–
NaCl
2
O
1
3a–c
Z-isomer
O(CH
1
2
1
2
1
2
2
, 3 a R = H, R = Me, b R = H, R = Ph, c R + R = –(CH
2
)
2
2
2
) –
Heterocyclization of enamines 3 with o-phenilenediamine proceeds when boiling reaction mixture in the
polar solvents. The yield of desired products is only 10-25%. The highest yield is obtained using the
morpholino-substituted enamine 3c. Benzimidazole and other substances which failed to be isolated individually
were formed alongside with heterocycle 4 in the reaction course.
1
2
H
N
1
4
NH2
13
O
15
N
N
1
1
3
+
+
H
2
10
H
N
H
NH2
N
7
9
8
1
6
1
2
3
5
H
O
6
N 5
H
4
4
_
_________________________________________________________________________________________
Kazan State Technological University, 420015 Kazan, Russia; e-mail: eltos@kai.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 561-563, April, 2002. Original article submitted
October 25, 2001.
4
96
0009-3122/02/3804-0496$27.00©2002 Plenum Publishing Corporation

Ethyl Ester of 2-Chloro-3-methylaminoacrylic Acid (3a). A mixture of enolate 1 (17.25 g, 0.1 mol)
and methylamine hydrochloride 2a (0.1 mol) in chloroform (100 ml) was stirred at room temperature for 8 h.
The NaCl precipitate was filtered off and the solvent was removed from the filtrate. Distillation of the residue
1
gave enamine 3a in 80% yield; bp 63-65°C (0.09 mm Hg). H NMR spectrum (CDCl
3
, 100 MHz), δ, ppm: 1.15
(
3H, t, Me); 2.88 (3H, d, Me); 4.05 (2H, q, OCH ); 6.68 (1H, br. d, NH); 8.05 (1H, d, N=CH). IR spectrum,
2
-1
ν, cm : 1710 (C=O), 3260 (NH). Found, %: Cl 21.65; N 8.54. C
6
H
10ClNO . Calculated, %: Cl 21.71; N 8.56.
2
Ethyl Ester of 2-Chloro-3-phenylaminoacrylic Acid (3b) was obtained analogously in 87% yield;
1
mp 91°C (acetonitrile). H NMR spectrum (CDCl
3
, 100 MHz), δ, ppm: 1.32 (3H, t, Me); 4.30 (2H, q, OCH
2
);
7
.10 (5H, m, Ph); 8.15 (1H, d, N=CH). Found, %: Cl 15.70; N 6.19. C11
2
H12ClNO . Calculated, %: Cl 15.74;
N 6.21.
Ethyl Ester of 2-Chloro-3-morpholinoacrylic Acid (3c) was obtained analogously in 85% yield;
1
mp 86°C. H NMR spectrum (CDCl
3
), δ, ppm: 1.18 (3H, t, Me); 3.60 (8H, d, –(CH
2
CH
2
) O–); 4.05 (2H, q,
2
OCH
2
); 7.00 (1H, s, N=CH). Found, %: Cl 14.08; N 5.54. C10
H
14ClNO
2
. Calculated, %: Cl 14.12; N 5.57.
5
,6,13,14-Tetrahydroquinoxalino[1,2,4,5]pyrazino[1,2-a]quinoxaline-6,14-dione (4). A mixture of
corresponding enamine 3a-c (0.005 mol) and o-phenylenediamine (0.5 g, 0.005 mol) in propan-2-ol (30 ml) was
heated at reflux for 48 h. The resultant red precipitate was filtered off, washed with acetone, and dried in
1
vacuum. H NMR spectrum, δ, ppm: 6.91 (2H, s, =CH–N); 7.23 (4H, m, Ar); 7.72 (4H, m, Ar); 11.93 (2H, s,
1
3
NH). C NMR spectrum, δ, ppm: 88.25 (d, =CHN), 115.10, 120.81, 123.01, 124.91, 128.29 (Ar); 14.78
-1
(
C
=C–N), 155.45 (C=O). IR spectrum, ν, cm : 1630 (C=N), 1690 (C=O). Found, %: C 68.01; H 3.75; N 17.56.
H N
18 12 4
O . Calculated, %: C 68.35; H 3.79; N 17.72. After removal of the solvent, an additional amount of
2
benzimidazole was obtained in 40% yield; mp 169°C (170.5°C [4]).
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1
2
.
.
F. I. Guseinov, N. A. Yudina, and G. J. Klimentova, in: Abstracts of the 36-th IUPAC Congress, Geneva
(
1997), p. 476.
F. I. Guseinov and N. A. Judina, in: Abstracts of the 7-th International Kyoto Conference in New
Aspects of Organic Chemistry, Kyoto, Japan (1997), p. 287.
F. I. Guseinov, Chemical Sciences Doctoral Dissertation, Moscow (1999).
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3
4
.
.
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97