Reactions of substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acid esters with halogens

Article abstract of DOI:10.1023/A:1012354223760

Substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acid esters react with chlorine and bromine to give the corresponding 4-halo-2,3,7-triazabicyclo[3.3.0]oct-2-ene-4-carboxylates. Heating of the latter to 120°C under reduced pressure leads to elimination of nitrogen molecule and formation of 6-halo-3-azabicyclo[3.1.0]hexane-6-carboxylates.

Full text of DOI:10.1023/A:1012354223760

Russian Journal of Organic Chemistry, Vol. 37, No. 1, 2001, pp. 128 135. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 1, 2001,
pp. 137 143.
Original Russian Text Copyright
2001 by Molchanov, Stepakov, Kostikov.
Reactions of Substituted 2,3,7-Triazabicyclo[3.3.0]oct-3-ene-
4-carboxylic Acid Esters with Halogens*
A. P. Molchanov, A. V. Stepakov, and R. R. Kostikov
St. Petersburg State University, Universitetskii pr. 2, St. Petersburg, 198904 Russia
e-mail: mol@am1391.spb.edu
Received January 19, 2000
Abstract Substituted 2,3,7-triazabicyclo[3.3.0]oct-3-ene-4-carboxylic acid esters react with chlorine and
bromine to give the corresponding 4-halo-2,3,7-triazabicyclo[3.3.0]oct-2-ene-4-carboxylates. Heating of the
latter to 120 C under reduced pressure leads to elimination of nitrogen molecule and formation of 6-halo-
3-azabicyclo[3.1.0]hexane-6-carboxylates.
1-Halogen-substituted cyclopropanecarboxylic acid
esters are synthesized most frequently by reactions
of geminal dihalocyclopropanes with organolithium
compounds and subsequent treatment of 1-halocyclo-
propyllithium with carbon dioxide [1], by reactions
of diazo compounds with -haloacrylic acid esters [2],
and by reactions of diazohaloacetic acid esters with
unsaturated compounds [3]. In the present com-
munication we report on the synthesis of 1-halo-1-
cyclopropanecarboxylates via thermal elimination of
nitrogen from dihydropyrazoles [4].
1-Substituted 7-aryl-6,8-dioxo-2,3,7-triazabicyclo-
[3.3.0]oct-3-ene-4-carboxylic acid esters Ia In were
obtained from the corresponding diazoacetates and
N-substituted maleimides [5]. The reactions of esters
I with chlorine in chloroform at 0 C gave 69 84% of
7-aryl-4-chloro-6,8-dioxo-2,3,7-triazabicyclo[3.3.0]-
oct-2-ene-4-carboxylates as mixtures of endo (IIa IIg)
and exo isomers (IIIa IIIg) at a ratio of (7 10):1
(Scheme 1). The reaction mixtures obtained from
esters Ia Ie also contained some amount (up to 10%)
of cyclopropane derivatives formed by elimination of
nitrogen from the corresponding dihydropyrazoles.
corresponding signal of exo isomers IIIa IIIe was
observed in a stronger field (at 3.43 ppm). The H
1
NMR spectra of compounds IIf and IIg having no
substituent in the bridgehead position contain a signal
from the 1-H proton at 6.3 6.5 ppm. The position
of this signal is typical of protons on C3 in 4,5-di-
hydro-3H-pyrazoles. The 5-H signal is located at
4.0 4.2 ppm. The corresponding signals of exo
isomers IIIf and IIIg are observed at 6.5 6.8 and
3.8 4.0 ppm, respectively. In the 13C NMR spectrum
of ester IIe the C4 signal appears at
105.4 ppm.
The UV spectra of IIb, IIe, and IIf areCcharacterized
by absorption in the region 320 330 nm, which also
supports their structure.
The reaction with chlorine of ester Ih having
an electron-donor methoxy group in the aromatic ring
is accompanied by chlorination of the aromatic sub-
stituent. As a result, a 3.5:1 mixture of endo and exo
isomers IIh and IIIh is formed. The structure of
compounds IIh and IIIh was proved by the elemental
analyses (Table 1) and spectral data (Table 2).
Heating of pyrrolopyrazoles IIa IIh and IIIa IIIh
at 120 C under reduced pressure resulted in elimina-
tion of nitrogen and formation of substituted 6-chloro-
bicyclo[3.1.0]hexane-6-carboxylic acid esters as mix-
tures of endo (IVa IVh) and exo isomers (Va Vh)
Pure endo isomers IIa, IIb, IId, and IIe were
isolated by crystallization. The structure of esters
IIa IIg was derived from the data of elemental
analysis and spectral measurements (Tables 1, 2).
1
in up to 87% yield. H NMR study of the reaction
1
Compounds IIa IIe showed in the H NMR spectra
mixtures showed that thermolysis of endo isomers
II gives only endo-cyclopropanes IV, whereas from
exo isomers III mixtures of isomeric cyclopropanes
IV and V are obtained. Thus thermolysis of isomeric
mixture II/III is accompanied by considerable
increase of the fraction of endo isomer IV in the
a singlet from 5-H in the region 3.6 3.8 ppm; the
____________
*
This study was financially supported by the Ministry of
Education of the Russian Federation (project no. 97-0-9.4-18)
and by the INTAS program (grant no. 961325).
1070-4280/01/3701-0128$25.00 2001 MAIK Nauka/Interperiodica

REACTIONS OF SUBSTITUTED 2,3,7-TRIAZABICYCLO[3.3.0]OCT-3-ENE-. . .
129
Scheme 1.
I, R1 = Et, R2 = Me, R3 = 4-MeC6H4 (a); R1 = R2 = Me, R3 = 3,4-Me2C6H3 (b); R1 = R2 = Me, R3 = 4-MeC6H4 (c); R1 = R2 =
Me, R3 = 3-CF3C6H4 (d); R1 = R2 = Me, R3 = 4-BrC6H4 (e); R1 = Et, R2 = H, R3 = cyclo-C6H11 (f); R1 = Et, R2 = H, R3 =
3-ClC6H4 (g); R1 = Et, R2 = H, R3 = 4-MeOC6H4 (h); R1 = Me, R2 = 4-ClC6H4, R3 = 4-ClC6H4 (i); R1 = Me, R2 = 4-ClC6H4,
R3 = Ph (j); R1 = Me, R2 = 4-ClC6H4, R3 = 4-MeC6H4 (k); R1 = Me, R2 = R3 = 4-MeC6H4 (l); R1 = Me, R2 = 3-NO2C6H4,
R3 = 4-ClC6H4 (m); R1 = R2 = Me, R3 = 3,4-Cl2C6H3 (n); II V, R1 = Et, R2 = Me, R3 = 4-MeC6H4, Hlg = Cl (a); R1 = R2 = Me,
R3 = 3,4-Me2C6H3, Hlg = Cl (b); R1 = R2 = Me, R3 = 4-MeC6H4, Hlg = Cl (c); R1 = R2 = Me, R3 = 3-CF3C6H4, Hlg = Cl (d);
R1 = R2 = Me, R3 = 4-BrC6H4, Hlg = Cl (e); R1 = Et, R2 = H, R3 = cyclo-C6H11, Hlg = Cl (f); R1 = Et, R2 = H, R3 = 3-ClC6H4,
Hlg = Cl (g); R1 = Et, R2 = H, R3 = 3-Cl-4-MeOC6H3 (h); IV, V, R1 = Me, R2 = R3 = 4-ClC6H4, Hlg = Cl (i); R1 = Me, R2 =
4-ClC6H4, R3 = Ph, Hlg = Cl (j); R1 = Me, R2 = 4-ClC6H4, R3 = 4-MeC6H4, Hlg = Cl (k); VI, R1 = Et, R2 = Me, R3 = 4-MeC6H4,
Hlg = Br; VII, VIII, R1 = Et, R2 = Me, R3 = 4-MeC6H4, Hlg = Br (a); R1 = Me, R2 = 4-ClC6H4, R3 = Ph, Hlg = Br (b); R1 = Me,
R2 = R3 = 4-MeC6H4, Hlg = Br (c); R1 = Me, R2 = 4-ClC6H4, R3 = 4-MeC6H4, Hlg = Br (d); R1 = Me, R2 = 3-NO2C6H4, R3 =
4-ClC6H4, Hlg = Br (e); R1 = R2 = Me, R3 = 3,4-Cl2C6H3, Hlg = Br (f).
products. Pure endo isomers IVa, IVb, and IVd IVg
and exo isomer Ve were isolated by column chromato-
graphy. Compounds Ii Ik having an aromatic substit-
uent on C1 reacted with chlorine in dichloroethane at
0 C to afford directly endo-cyclopropane carboxylates
IVi IVk. Presumably, the initially formed dihydro-
pyrazole with an aryl group in the bridgehead position
is unstable, and it loses nitrogen even at 0 C. The
structure of products IV and V was confirmed by the
data of elemental analysis (Table 1) and spectral
measurements (Tables 2, 3). In the IR spectra of these
compounds we observed an ester carbonyl band at
1720 cm . The position of the 5-H signal in the H
NMR spectra of IV and V strongly depends on the
R2 substituent: when R2 = Me, it is located at 3.4
3.5 ppm for endo isomers IVa IVk and 2.8 2.9 ppm
for exo isomers Va Vk; when R2 = Ar, the 5-H signal
shifts downfield to 4.0 ppm due to deshielding effect
of the benzene ring.
[3.3.0]oct-2-ene-4-carboxylate (VI). Heating of VI at
120 C under reduced pressure resulted in elimination
of nitrogen and formation of a mixture of endo and
exo isomers VIIa and VIIIa at a ratio of 1:3.
By reactions of pyrrolopyrazoles Ij In with
bromine in acetic acid at 70 C we obtained mixtures
of endo- and exo-6-bromo-2,4-dioxo-3-azabicyclo-
[3.1.0]hexane-6-carboxylates VIIb VIIf and VIIIb
VIIIf. The ratio of endo and exo isomers was 2.3
(VIIb/VIIIb), 0.7 (VIIc/VIIIc), 0.9 (VIId/VIIId),
1.1 (VIIe/VIIIe), and 12 (VIIf/VIIIf). The structure
of brominated cyclopropanes VII and VIII was estab-
lished on the basis of their elemental compositions
and spectral data. The signal from the CH proton of
1
1
1
the cyclopropane ring in the H NMR spectra of endo
isomers VIIa VIIf was observed in a weaker field
relative to the corresponding signal of the exo isomers
due to deshielding effect of the cis-bromine atom, ,
ppm: 3.58 (VIIa), 3.90 4.10 (VIIb VIIe), 3.43
(VIIf) and 2.85 (VIIIa), 3.42 3.60 (VIIIb VIIIe),
2.90 (VIIIf).
Treatment of ester Ia with bromine in chloroform
at 60 C gave a mixture of products from which we
isolated by crystallization 36% of ethyl exo-4-bromo-
1-methyl-6,8-dioxo-7-(4-tolyl)-2,3,7-triazabicyclo-
Our results suggest a mechanism involving electro-
philic substitution of hydrogen at the nitrogen atom
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001

130
MOLCHANOV et al.
Table 1. Yields, melting points, and elemental analyses of compounds II VIII and XIII
Found, %
Calculated, %
H
Compound
no.
Yield,
%
mp,
C
Formula
C
H
N
C
N
IIa
IIb
IIc/IIIc
IId
IIe
IIf/IIIf
IIg/IIIg
IIh/IIIh
IVa
IVb
IVc/Vc
IVd
IVe
IVf
IVg
IVh
IVi
IVj
IVk
Ve
69
68
84
70
71
78
83
79
73
76
81
73
73
72
59
77
94
88
91
14
36
61
76
72
81
69
63
91
89
52
64
68
72
94
86
73
44
48
82
98 99a
96 98a
55.01
55.07
53.91
46.37
41.89
51.47
47.01
46.67
59.86
59.61
58.64
50.01
45.18
56.18
51.12
50.18
53.71
58.67
59.44
45.04
48.97
52.61
52.51
58.92
53.61
47.18
41.32
57.82
50.59
59.13
60.04
52.94
45.84
55.39
52.64
51.14
45.63
61.58
51.38
4.43
4.32
4.33
2.71
2.51
5.72
3.15
3.56
5.07
5.01
4.53
2.99
3.03
6.00
3.63
3.71
3.04
3.49
4.02
2.99
4.29
4.33
3.07
4.32
3.48
2.79
2.75
5.87
4.70
4.01
4.26
3.04
3.01
3.63
3.21
3.15
3.12
5.02
3.49
11.88
11.94
12.34
10.52
10.31
12.69
11.59
10.61
4.27
4.19
4.31
3.65
3.58
4.46
4.09
3.69
3.03
3.46
3.31
3.51
10.25
3.69
C16H16ClN3O4
C16H16ClN3O4
C15H14ClN3O4
C15H11ClF3N3O4
C14H11BrClN3O4
C14H18ClN3O4
C14H11Cl2N3O4
C15H13Cl2N3O5
C16H16ClNO4
C16H16ClNO4
C15H14ClNO4
C15H11ClF3NO4
C14H11BrClNO4
C14H18ClNO4
C14H11Cl2NO4
C15H13Cl2NO5
C19H12Cl3NO4
C19H13Cl2NO4
C20H15Cl2NO4
C14H11BrClNO4
C16H16BrN3O4
C16H16BrNO4
C19H13BrClNO4
C21H18BrNO4
C20H15BrClNO4
C19H12BrClN2O6
C14H10BrCl2NO4
C14H17N3O4
54.94
54.94
53.66
46.22
41.96
51.30
47.20
46.64
59.73
59.73
58.55
49.80
45.12
56.10
51.23
50.29
53.73
58.46
59.42
45.12
48.74
52.46
52.48
58.89
53.54
47.58
41.31
57.73
50.63
58.95
60.20
52.60
46.18
55.46
52.59
50.92
45.71
61.34
51.51
4.58
4.58
4.17
2.82
2.75
5.50
3.09
3.37
4.98
4.98
4.55
3.04
2.95
6.01
3.35
3.63
2.82
3.33
3.71
2.95
4.06
4.37
2.99
4.24
3.37
2.52
2.48
5.84
4.67
3.89
4.38
3.13
2.77
3.32
3.13
3.05
3.07
4.83
3.43
12.02
12.02
12.52
10.78
10.49
12.83
11.80
10.88
4.36
4.36
4.55
3.87
3.76
4.67
4.27
3.91
3.29
3.59
3.47
3.76
10.66
3.82
111 112a
102 104a
109 111a
101 103a
116 118a
120 122a
97 98
114 115
131 133
103 104
151 153
116 118
82 83
205 207
179 181
201 202
207 209
112 113
118 120
87 89
149 152
109 111
141 143
98 99
163 165
155 157
164 165
194 196
216 218
202 203
215a
VI
VIIa/VIIIa
VIIb/VIIIb
VIIc/VIIIc
VIId/VIIId
VIIe/VIIIe
VIIf/VIIIf
XIIIa
XIIIb
XIIIc
XIIId
XIIIe
XIIIf
XIIIg
XIIIh
XIIIi
3.14
2.88
2.72
5.83
3.22
3.27
3.12
5.84
3.23
3.44
21.69
17.90
14.54
14.37
12.95
11.44
13.84
12.99
17.08
10.43
13.17
11.86
21.99
17.71
14.72
14.03
13.14
11.53
13.86
13.15
16.96
10.66
13.41
12.02
C10H11N3O4
C14H11N3O4
C15H13N3O4
C14H10ClN3O4
C14H10BrN3O4
C14H10FN3O4
C14H10ClN3O4
C14H10N4O6
C15H12BrN3O5
C16H15N3O4
C15H12ClN3O5
222 224
147 149
210 212
211 213
128 130
221 223
XIIIj
XIIIk
XIIIl
a
With decomposition.
with formation of N-halogen derivative IX, homo-
lytic cleavage of the Hlg N bond in IX, and reaction
of allylic radical X with the second halogen molecule
to give isomeric products II and III (Scheme 2).
The reduction of chlorocyclopropanes IVi IVk
with zinc in glacial acetic acid was nonstereospecific
and yielded endo/exo-isomeric methyl cyclopropane-
carboxylates XIa XIc and XIIa XIIc at a ratio of
1:1 (Scheme 3). The H NMR spectra of mixtures
XI/XII contained doublets from the cyclopropane ring
protons at 3.2 and 2.9 ppm (J = 8 Hz) and 3.5 and
3.0 ppm (J = 3 Hz) for the endo and exo isomers,
1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001

REACTIONS OF SUBSTITUTED 2,3,7-TRIAZABICYCLO[3.3.0]OCT-3-ENE-. . .
131
Table 2. IR and 1H NMR spectra of compounds II VIII and XIII
Comp.
no.
1
IR spectrum, , cm
1H NMR spectrum, , ppm (J, Hz)
IIa
1030, 1110, 1140, 1250, 1300, 1380 s, 1450, 1520, 7.28 d (2H, 8), 7.15 d (2H, 8), 4.42 q (2H, 7), 3.74 s
1720 v.s, 3050 (1H), 2.40 s (3H), 2.01 s (3H), 1.42 t (3H, 7)
910, 1020, 1110, 1140, 1250, 1300, 1380 s, 1460, 7.28 6.98 (3H), 4.01 s (3H), 3.75 s (1H), 2.29 s (6H),
1510, 1720 v.s, 3050 2.01 s (3H)
940, 1050, 1110, 1140, 1260, 1310, 1380 s, 1450, 7.33 7.06 (4H), 4.05 s (3H), 3.75 s (1H), 2.42 s (3H),
1510, 1720 v.s, 3050 2.03 s (3H)
IIb
IIca
IId
IIeb
IIfa
900, 1010, 1100, 1140, 1180 s, 1330, 1370, 1460, 7.75 7.45 (4H), 4.04 s (3H), 3.81 s (1H), 2.02 s (3H)
1490, 1720 v.s, 3050
890, 1020, 1080, 1110, 1130, 1260, 1380 s, 1460, 7.63 d (2H, 8), 7.15 d (2H, 8), 4.03 s (3H), 3.75 s
1490, 1720 v.s, 3050
910, 1040, 1110, 1150, 1270, 1300, 1370 s, 1400, 6.31 d (1H, 8), 4.32 m (2H), 3.98 d (1H, 8), 3.76 m
1460, 1720 v.s, 2940 s (1H), 2.06 1.09 (15H)
IIga, c 910, 1020, 1050, 1110, 1240, 1300, 1370 s, 1440, 7.61 7.22 (4H), 6.52 d (1H, 8), 4.35 m (2H), 4.23 d
1480, 1590, 1730 v.s, 3050 (1H, 8), 1.30 t (3H, 7)
910, 1030, 1070, 1100, 1270 s, 1380, 1440, 1510 s, 7.33 7.15 (3H), 6.47 d (1H, 8), 4.35 m (2H), 4.19 d
1720 v.s, 3050 (1H, 8), 3.88 s (3H), 1.30 t (3H, 7)
870, 930, 970, 1030, 1060, 1150, 1260, 1290, 1390 s, 7.26 d (2H, 8), 7.17 d (2H, 8), 4.36 q (2H, 7), 3.45 s
1460, 1520, 1730 v.s, 3050 (1H), 2.40 s (3H), 1.65 s (3H), 1.38 t (3H, 7)
880, 940, 990, 1010, 1080, 1140, 1170, 1280 s, 1380 s, 7.25 m (1H), 7.03 m (2H), 3.93 s (3H), 3.46 s (1H),
1450, 1510, 1720 v.s, 2960, 3050 2.29 s (6H), 1.64 s (3H)
890, 940, 1040, 1110, 1140, 1260, 1300, 1380 s, 1450, 7.27 d (2H, 8), 7.18 d (2H, 8), 3.92 s (3H), 3.46 s
1520, 1720 v.s, 3050 (1H), 2.39 s (3H), 1.65 s (3H)
(1H), 2.01 s (3H)
IIha
IVa
IVb
IVc
IVd
IVe
IVf
920, 990, 1020, 1080, 1140 s, 1250, 1300, 1330, 7.0 7.52 (4H), 3.94 s (3H), 3.51 s (1H), 1.67 s (3H)
1380 s, 1460, 1500, 1720 v.s, 3050
900, 990, 1020, 1080, 1140, 1260, 1290 s, 1380 s, 7.61 d (2H, 8), 7.20 d (2H, 8), 3.95 s (3H), 3.49 s
1440, 1490, 1730 v.s, 3050
(1H), 1.66 s (3H)
900, 970, 990, 1020, 1050, 1120, 1270 s, 1370 s, 1460, 4.30 q (2H, 7), 3.91 m (1H), 3.18 s (2H), 2.06 m
1720 v.s, 2940 s
(2H), 1.82 m (2H), 1.60 m (1H), 1.34 t (3H, 7),
1.5 m (3H)
IVg
IVh
960, 1030, 1070, 1260 s, 1390, 1420, 1450, 1470, 7.42 7.19 (4H), 4.38 q (2H, 7), 3.41 s (2H), 1.37 t
1510 s, 1720 v.s, 3050 (3H, 7)
960, 1030, 1070, 1260 s, 1390, 1420, 1450, 1470, 7.37 d (1H, 3), 7.18 d.d (1H, 6, 3), 6.99 d (1H, 6),
1510 s, 1740 v.s, 3050
4.35 q (2H, 7), 3.93 s (3H), 3.41 s (2H), 1.38 t
(3H, 7)
IVi
IVj
IVk
Ve
910, 1020, 1090, 1160, 1250, 1290, 1380 s, 1490 s, 7.48 7.27 (8H), 4.03 s (1H), 3.57 s (3H)
1600, 1720 v.s, 3050
920, 980, 1020, 1090, 1160, 1250, 1290, 1380 s, 7.52 7.31 (9H), 4.04 s (1H), 3.57 s (3H)
1500 s, 1600, 1720 v.s, 3050
920, 980, 1020, 1090, 1160, 1250, 1290, 1380 s, 1440, 7.45 s (4H), 7.28 d (2H, 8), 7.17 d (2H, 8), 4.02 s
1520, 1720 v.s, 3050
900, 990, 1020, 1080, 1140, 1260, 1290 s, 1380 s, 7.59 d (2H, 8), 7.18 d (2H, 8), 3.81 s (3H), 2.86 s
1440, 1490, 1720 v.s, 3050 (1H), 1.83 s (3H)
930, 1110, 1140, 1260, 1380 s, 1450, 1520, 1720 v.s, 7.23 d (2H, 8), 7.07 d (2H, 8), 4.30 m (2H), 3.58 s
3050 (1H), 2.38 s (3H), 1.97 s (3H), 1.25 t (3H, 7)
(1H), 3.56 s (3H), 2.40 s (3H)
VId
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MOLCHANOV et al.
Table 2. (Contd.)
Comp.
no.
1
IR spectrum, , cm
1H NMR spectrum, , ppm (J, Hz)
VIIaa 1020, 1090, 1120, 1280, 1380 s, 1450, 1520, 1720 v.s, 7.25 d (2H, 8), 7.08 d (2H, 8), 4.35 q (2H, 7), 3.39 s
3050 (1H), 2.37 s (3H), 1.63 s (3H), 1.38 t (3H, 7)
VIIba 840, 910, 1020, 1100, 1160, 1290, 1380 s, 1440, 1500, 7.51 7.23 (9H), 3.98 s (1H), 3.54 s (3H)
1600, 1720 v.s, 2970
VIIca 840, 910, 1030, 1100, 1160, 1290, 1380 s, 1440, 1520, 7.45 7.12 (8H), 3.95 s (1H), 3.50 s (3H), 2.46 2.37
1720 v.s, 2960
(6H)
VIIda 850, 910, 1020, 1100, 1290, 1380 s, 1440, 1520, 1600, 7.48 7.09 (8H), 3.97 s (1H), 3.54 s (3H), 2.40 s (3H)
1720 v.s, 2950
VIIea 840, 880, 910, 1020, 1100, 1160, 1280, 1380 s, 1440, 8.36 m (2H), 7.95 d (1H, 3), 7.88 d (1H, 3), 7.73 t
1500, 1540, 1720 v.s, 2960
(1H, 3), 7.62 t (1H, 3), 7.46 m (2H), 7.33 d
(1H, 3), 7.22 d (1H, 3), 4.09 s (1H), 3.56 s (3H)
VIIf
870, 920, 1040, 1080, 1140, 1260, 1290, 1380 s, 1480, 7.54 m (2H), 7.26 m (1H), 3.92 s (3H), 3.43 s (1H),
1590, 1720 v.s, 2950 1.64 s (3H)
XIIIa 900, 950, 1040, 1090, 1170, 1330 s, 1460, 1610, 15.22 br.s (1H), 4.35 q (2H, 7), 3.86 m (1H),
1730 v.s, 2950, 3410 2.02 m (3H), 1.80 1.55 (4H), 1.31 t (3H, 7)
XIIIb 890, 1020 s, 1120, 1160, 1250, 1320 s, 1370, 1450, 14.15 br.s (1H), 4.41 q (2H, 7), 3.63 q (2H, 7),
1600, 1720 v.s, 3040, 3400 1.42 t (3H, 7), 1.20 t (3H, 7)
XIIIc 1030, 1090, 1110, 1240, 1320 s, 1360 s, 1730 v.s, 15.44 br.s (1H), 7.52 7.30 (5H), 4.40 q (2H, 7),
3040, 3400 1.34 t (3H, 7)
XIIId 1035 s, 1090, 1110, 1235, 1320 s, 1360 s, 1730 v.s, 15.40 br.s (1H), 7.32 d (2H, 8), 7.26 d (2H, 8), 4.40 q
3030, 3400 (2H, 7), 2.37 s (3H), 1.34 t (3H, 7)
XIIIe 1035 s, 1095, 1235, 1320 s, 1355 s, 1495, 1735 v.s, 15.50 br.s (1H), 7.60 d (2H, 8), 7.44 d (2H, 8), 4.40 q
3040, 3400 (2H, 7), 1.34 t (3H, 7)
XIIIf 1030, 1080, 1110, 1240, 1320, 1360, 1490, 1730 v.s, 15.50 br.s (1H), 7.73 d (2H, 8), 7.38 d (2H, 8), 4.40 q
3040, 3400 (2H, 7), 1.34 t (3H, 7)
XIIIg 940, 1030, 1080, 1110, 1160, 1250, 1320, 1360, 1450, 15.40 br.s (1H), 7.52 7.21 (4H), 3.50 q (2H, 7),
1510, 1600, 1740 v.s, 3050, 3400 1.36 t (3H, 7)
XIIIh 930, 1030, 1070, 1120, 1160, 1240, 1320, 1380, 1450, 15.48 br.s (1H), 7.59 7.39 (4H), 4.40 q (2H, 7),
1510, 1610, 1730 v.s, 3050, 3400 1.34 t (3H, 7)
XIIIi 1030, 1120, 1240, 1320, 1345 s, 1530, 1730 v.s, 3035, 15.53 br.s (1H), 8.39 d (2H, 9), 7.73 d (2H, 9), 4.41 q
3395 (2H, 7), 1.35 t (3H, 7)
XIIIj 1030 s, 1095, 1250, 1320 s, 1355 s, 1730 v.s, 3030, 15.43 br.s (1H), 7.20 s (1H), 7.18 d (1H, 8), 7.12 d
3400
(1H, 8), 4.38 q (2H, 7), 2.35 s (3H), 2.09 s (3H),
1.36 t (3H, 7)
XIIIk 1035 s, 1090, 1110, 1260, 1300, 1320, 1480, 1500, 15.43 br.s (1H), 7.66 d (1H, 2), 7.42 d.d (1H, 7, 2),
1735 v.s, 3040, 3400
7.28 d (1H, 7), 4.40 q (2H, 7), 3.91 s (3H), 1.34 t
(3H, 7)
XIIIl 900, 1040, 1090, 1110, 1170, 1250, 1330, 1360, 1450, 15.41 br.s (1H), 7.44 d (1H, 3), 7.26 d.d (1H, 9, 3),
1500, 1590, 1720 v.s, 3050, 3400 7.04 d (1H, 9), 4.53 q (2H, 7), 1.49 t (3H, 7)
a
b
c
Mixture of endo and exo isomers.
13C NMR spectrum, C, ppm: 169.6, 167.9, 164.8, 132.9, 130.1, 128.1, 123.8, 105.4, 103.6, 55.7, 51.5, 10.2.
13C NMR spectrum, C, ppm: 167.4, 165.2, 163.2, 134.6, 131.2, 130.0, 129.4, 126.2, 121.2, 104.4, 95.7, 64.9, 45.1, 13.6.
13C NMR spectrum, C, ppm: 169.9, 169.4, 163.1, 139.9, 130.4, 128.4, 126.4, 101.3, 94.8, 65.2, 57.1, 21.6.
d
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REACTIONS OF SUBSTITUTED 2,3,7-TRIAZABICYCLO[3.3.0]OCT-3-ENE-. . .
133
Scheme 2.
respectively. Compounds XIa XIc and XIIa XIIc
were identical to those reported previously [6]. Non-
stereospecific reduction of bromocyclopropanes with
zinc was also reported in [7].
substitution of hydrogen in the aromatic ring by
bromine to afford product XIIIj. Introduction of
bromine into the aromatic ring was also observed for
compound Iv at 70 C, whereas at 20 C pyrrolopyra-
zole XIIIk is formed.
As shown above, compounds Ij In having a sub-
stituent in the bridgehead position react with bromine
in acetic acid at 70 C to give isomeric bromocyclo-
propanes VIIb VIIf and VIIIb VIIIf. On the other
hand, bromination of compounds If and Io Iv (which
lack substituent on C1) in acetic acid or chloroform
on heating yields pyrrolopyrazoles XIIIa XIIIl
(Scheme 4). The sane products were obtained by the
action of triethylamine on chlorinated compounds IIf,
IIg, and IIh. The structure of compounds XIIIa XIIIl
is confirmed by their elemental analyses and IR and
EXPERIMENTAL
The IR spectra were obtained on a UR-20 spectro-
1
photometer from 2% solutions in chloroform. The H
NMR spectra were recorded on a Bruker AM-300
instrument (300 MHz) from 2% solutions in CDCl3
or DMSO-d6.
Ethyl 4-chloro-1-methyl-6,8-dioxo-7-(4-tolyl)-
2,3,7-triazabicyclo[3.3.0]oct-2-ene-4-carboxylate
1H NMR spectra (Tables 1, 2). In the IR spectra of (IIa). A stream of gaseous chlorine was passed at
1
XIIIa XIIIl we observed absortion at 3400 cm due
0 C through a solution of 0.35 g (1.1 mmol) of com-
pound Ia in 30 ml of dry chloroform until saturation
( 1 min). The solvent was removed under reduced
pressure at room temperature, and the residue was
recrystallized from methanol. Yield of IIa 0.31 g
to stretching vibrations of the NH bond, and their
1H NMR spectra contain a signal at
15.5 ppm
belonging to the NH proton. The reaction of com-
pound Ih with bromine at 70 C is accompanied by
Scheme 3.
R3 = Ph (a), 4-MeC6H4 (b), 4-ClC6H4 (c).
Scheme 4.
If, XIIIa, R3 = cyclo-C6H11; Io, XIIIb, R3 = Et; Ip, XIIIc, R3 = Ph; Iq, XIIId, R3 = 4-MeC6H4; Ir, XIIIe, R3 = 4-ClC6H4;
Is, XIIIf, R3 = 4-BrC6H4; It, XIIIg, R3 = 4-FC6H4; IIg, XIIIh, R3 = 3-ClC6H4; Iu, XIIIi, R3 = 4-NO2C6H4; XIIIj, R3
4-CH3O-3-BrC6H3; Iv, XIIIk, R3 = 2,4-Me2C6H3; IIh, XIIIl, R3 = 3-Cl-4-MeOC6H3.
=
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001

134
MOLCHANOV et al.
1
Table 3. Chemical shifts of some protons in the H NMR
spectra of compounds IIIa IIIh, Vb Ve, VIIIa VIIIf,
, ppm (J, Hz)
with a solution of Na2SO3, the organic phase was
separated, dried over MgSO4, and evaporated, and
the residue was recrystallized from methanol. Yield
of ester VI 0.27 g (36%).
Ethyl 6-bromo-1-methyl-2,4-dioxo-3-(4-tolyl)-
3-azabicyclo[3.1.0]hexane-6-carboxylate (isomeric
mixture VIIa/VIIIa). Ester VI, 0.20 g (0.5 mmol),
was heated at 130 C under a residual pressure of
20 mm until nitrogen no longer evolved (4 min). The
resulting material was cooled and recrystallized from
methanol. Yield of VIIa/VIIIa 0.11 g (61%).
Methyl 6-bromo-3-(3,4-dichlorophenyl)-1-
methyl-2,4-dioxo-3-azabicyclo[3.1.0]hexane-6-car-
boxylate (VIIf). A mixture of 0.7 g (2 mmol) of com-
pound In and 1.6 g of bromine in 20 ml of glacial
acetic acid was heated for 5 h at 70 C. The solvent
and excess bromine were distilled off, and a mixture
of diethyl ether and hexane (1:1) was added to the
residue for crystallization. The precipitate was filtered
off and recrystallized from ethanol. Yield of ester VIIf
0.5 g (63%). Isomer ratio VIIf:VIIIf 12:1 (before
recrystallization). Esters VIIb VIIe and VIIIb VIIIe
were synthesized in a similar way; according to the
1H NMR data, the isomer ratio was 2.3 (VIIb/VIIIb),
4.1 (VIIc/VIIIc), 0.9 (VIId/VIIId), 1.1 (VIIe/VIIIe).
Methyl 1-(4-chlorophenyl)-3-phenyl-3-azabicy-
clo[3.1.0]hexane-6-carboxylate (XIa/XIIa). A mix-
ture of 62 mg (0.25 mmol) of chlorocyclopropane IVj
and 0.7 g of zinc dust in 15 ml of glacial acetic acid
was heated for 1 h. The mixture was cooled and fil-
tered, acetic acid was removed from the filtrate under
reduced pressure, the residue was dissolved in chloro-
form, the chloroform solution was filtered, washed
with a 10% solution of Na2CO3, dried over MgSO4,
and evaporated, and the residue was purified by
column chromatography on silica gel (eluent hexane
ether, 1 : 2 by volume). Yield of XIa/XIIa 69%.
Isomeric mixtures XIb/XIIb and XIc/XIIc were
isolated in 71% and 75% yield, respectively.
Compound no.
5-H
COOCH3
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
Vb
3.43 s
3.42 s
3.43 s
3.45 s
3.43 s
3.88 s
3.88 s
3.89 s
3.91 s
3.89 s
6.52 d (J = 8)a
6.78 d (J = 8)a
6.83 d (J = 8)a
2.83 s
3.88 d (J = 8)
4.02 d (J = 8)
4.04 d (J = 8)
3.83 s
Vc
2.84 s
3.82 s
3.82 s
3.81 s
Vd
2.88 s
Ve
2.86 s
VIIIa
2.85 s
4.24 q (J = 7),b
1.21 t (J = 7)
3.87 s
VIIIb
VIIIc
VIIId
VIIIe
VIIIf
3.46 s
3.42 s
3.44 s
3.60 s
2.90 s
3.86 s
3.86 s
3.88 s
3.80 s
a
1-H.
C2H5.
b
(71%). Esters IIb IIg and IIIb IIIg were obtained
in a similar way.
Ethyl 6-chloro-1-methyl-2,4-dioxo-3-(4-tolyl)-3-
azabicyclo[3.1.0]hexane-6-carboxylate (IVa). Com-
pound IIa, 0.20 g (0.57 mmol), was heated at 120 C
under a residual pressure of 20 mm until nitrogen no
longer evolved (5 min). The resulting material was
cooled and recrystallized from methanol. Yield of
ester IVa 0.134 g. Compounds IVb IVg were ob-
tained in a similar way.
Methyl 6-chloro-1-(4-chlorophenyl)-2,4-dioxo-
3-phenyl-3-azabicyclo[3.1.0]hexane-6-carboxylate
(IVj). A stream of dry gaseous chlorine was passed
at 0 C through a solution of 0.3 g (0.78 mmol) of
compound Ij in 30 ml of anhydrous 1,2-dichloro-
ethane until saturation ( 2 min). The solvent was
evaporated at room temperature, and the residue was
recrystallized from ethanol. Yield of ester IVj 0.27 g
(88%). Compounds IVi and IVk were obtained by
a similar procedure.
Ethyl 7-cyclohexyl-6,8-dioxo-3,3,7-triazabicyclo-
[3.3.0]octa-1(5),3-diene-4-carboxylate (XIIIa).
A solution of 230 mg (0.8 mmol) of compound If and
0.2 ml of bromine in 10 ml of chloroform was heated
for 3 h. The mixture was cooled and washed with
a solution of Na2S2O3, the organic phase was se-
parated, dried over MgSO4, and evaporated, and the
residue was recrystallized from hexane acetone. Yield
of ester XIIIa 210 mg (91%). Compounds XIIIb and
XIIIg were synthesized in a similar way.
Ethyl 4-bromo-1-methyl-6,8-dioxo-7-(4-tolyl)-
2,3,7-triazabicyclo[3.3.0]oct-2-ene-4-carboxylate
(VI). A mixture of 0.6 g (2 mmol) of compound Ia
and 1.6 g of bromine in 30 ml of dry chloroform was
Ethyl 6,8-dioxo-7-phenyl-3,3,7-triazabicyclo-
[3.3.0]octa-1(5),3-diene-4-carboxylate (XIIIc).
A mixture of 1 g (3.5 mmol) of compound Ip and
heated for 3 h. The mixture was cooled and treated 1 ml of bromine in 30 ml of acetic acid was heated
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 1 2001

REACTIONS OF SUBSTITUTED 2,3,7-TRIAZABICYCLO[3.3.0]OCT-3-ENE-. . .
135
for 2 h at 60 70 C. The mixture was cooled and
poured into 100 ml of water, and the precipitate was
filtered off, washed with a solution of Na2S2O3 and
water, and recrystallized from aqueous ethanol. Yield
of XIIIc 0.5 g (52%). Esters XIIId XIIIf and XIIIi
XIIIk were synthesized in a similar way.
Ethyl 7-(3-chlorophenyl)-6,8-dioxo-3,3,7-tri-
azabicyclo[3.3.0]octa-1(5),3-diene-4-carboxylate
(XIIIh). A mixture of 70 mg (0.2 mmol) of compound
IIg and 40 mg of triethylamine in 7 ml of chloroform
was stirred for 2 h. The mixture was washed with
10% hydrochloric acid, and the organic phase was
dried over MgSO4. The solvent was evaporated, and
the residue was recrystallized from methanol. Yield
of ester XIIIh 60 mg (86%). Compound XIIIl was
obtained in a similar way.
2. Walborsky, H.M. and Impastato, F.J., J. Am. Chem.
Soc., 1959, vol. 81, no. 21, pp. 5835 5837;
Walborsky, H.M., Barash, L., Yuong, A.E., and
Impastato, F.J., J. Am. Chem. Soc., 1961, vol. 83,
no. 11, pp. 2517 2525; Walborsky, H.M. and
Yuong, A.E., J. Am. Chem. Soc., 1964, vol. 86,
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3. Schollkopf, U., Gerhart, F., Reetz, M., Frasnelli, H.,
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