Five-membered 2,3-dioxo heterocycles: XLIV. Reaction of 3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones with o-phenylenealamines

Article abstract of DOI:10.1023/A:1019679526434

The reaction of (Z)-3-phenacylidene-1,2,3,4-tetrahydroquinoxalin-2-ones with oxalyl chloride gives 3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones which react with o-phenylenediamine to afford 8-aryl-6,7,9,14,15,16-hexahydroquinoxalino[1

Full text of DOI:10.1023/A:1019679526434

Russian Journal of Organic Chemistry, Vol. 38, No. 5, 2002, pp. 738 743. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 5, 2002,
pp. 775 779.
Original Russian Text Copyright
2002 by Maslivets, Mashevskaya, Kol’tsova, Duvalov, Feshin.
Five-Membered 2,3-Dioxo Heterocycles:
XLIV.* Reaction of 3-Aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]-
quinoxaline-1,2,4-triones with o-Phenylenediamines**
1
1
2
A. N. Maslivets , I. V. Mashevskaya , S. V. Kol’tsova ,
1
2
A. V. Duvalov , and V. P. Feshin
1
Perm State University, ul. Bukireva 15, Perm, 614600 Russia
e-mail: info@psu.ru
2
Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences,
Perm, Russia
Received March 11, 2001
Abstract The reaction of (Z)-3-phenacylidene-1,2,3,4-tetrahydroquinoxalin-2-ones with oxalyl chloride gives
3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones which react with o-phenylenediamine to
afford 8-aryl-6,7,9,14,15,16-hexahydroquinoxalino[1,2-a]pyrrolo[2,3-b][1,5]benzodiazepine-6,7,15-triones.
The structure of products formed by reaction of
o-phenylenediamine with substituted 2,3-dihydropyr-
role-2,3-diones fused to aza heterocycles through the
a bond is determined mainly by the substituent in
position 4 of the dihydropyrrole ring. Reactions of
o-phenylenediamine with 4-unsubstituted, 4-dialkyl-
carbamoyl-, and 4-phenyl-2,3-dihydropyrrole-2,3-di-
ones [2 4] fused to isoquinoline [2, 3], phenanthridine
[3], or 1,3-oxazine ring [4] begin with nucleophilic
attack on the carbonyl group in position 2 (path a)
or 3 (path b) of the pyrrole ring with subsequent
recyclization either to quinoxalin-2-ones and then to
pyrroloquinoxalines (path a) or to pyrrolobenzimid-
azoles (path b) [2 4]. By contrast, 4-aroyl-2,3-di-
hydropyrrole-2,3-diones, fused through the a bond to
2-oxo-1,4-benzoxazine ring, react with o-phenylene-
diamine via primary nucleophilic addition at C5 of the
pyrrole ring, followed by recyclization with opening
of the benzoxazine ring [5].
account our previous data on the direction of primary
nucleophile addition to compounds I (at C5 of the
pyrrole ring) and on reactions of monocyclic substi-
tuted 4-acyl-2,3-dihydropyrrole-2,3-diones with the
same nucleophile [7], we expected formation of dif-
ferent products. Therefore, we performed a detailed
study of the reaction, and its results were interpreted
with the aid of quantum-chemical methods.
Compounds Ic, Id, and Ig were synthesized by the
procedure described in [1] from (Z)-3-phenacylidene-
1,2,3,4-tetrahydroquinoxalin-2-ones IIc, IId, and IIg,
respectively, and oxalyl chloride. 3-Aroyl-1,2,4,5-
tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones
Ia Ig reacted with o-phenylenediamine in anhydrous
dioxane on heating for a short time (1 5 min) under
reflux. The products were 8-aryl-6,7,9,14,15,16-hexa-
hydroquinoxalino[1,2-a]pyrrolo[2,3-b][1,5]benzodi-
azepine-6,7,15-triones IIIa IIIg (Scheme 1, Table 1)
which were formed in almost quantitative yields via
successive nucleophilic attack by the amino groups of
the reagent on C5 and carbonyl carbon atom of the
aroyl fragment in position 4 of the pyrrole ring. The
same ptoducts were also obtained when the reaction
was carried out at 0 C, and their yield did not change
to an appreciable extent.
In continuation of our studies on nucleophilic trans-
formations of 4-acyl-2,3-dihydropyrrole-2,3-diones,
fused through the a bond to 2-oxoquinoxaline moiety,
namely 3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quino-
xaline-1,2,4-triones Ia Ig [6], the latter were brought
into reaction with o-phenylenediamine. Taking into
____________
*
Compounds IIIa IIIg are dark red high-melting
crystalline substances, which are almost insoluble in
common organic solvents, poorly soluble in DMF and
DMSO, and insoluble in water. They give a negative
For communication XLIII, see [1].
**
This study was financially supported by the Russian Founda-
tion for Basic Research (projects nos. 01-03-32641 and
02-03-96411).
1070-4280/02/3805-0738$27.00 2002 MAIK Nauka/Interperiodica

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XLIV.
739
Scheme 1.
R1 = R2 = R3 = H (a); R1 = R2 = H, R3 = Me (b); R1 = R2 = H, R3 = OMe (c); R1 = R2 = H, R3 = NO2 (d); R1 = R3 = H,
R2 = Ph (e); R1 = H, R2 = Ph, R3 = Me (f); R1 = NO2, R2 = R3 = H (g).
Table 1. Yields, melting points, and elemental analyses of compounds Ic, Id, Ig, IIc, IId, IIg, and IIIa IIIj
Found, %
H
Calculated, %
H
Comp.
no.
Yield,
%
mp, C (solvent)
Formula
C
N
C
N
Ic
Id
Ig
IIc
IId
IIg
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
92
87
83
84
75
82
95
89
92
85
93
80
90
87
92
79
203 205 (dichloroethane)
290 292 (dichloroethane)
267 269 (dichloroethane)
238 240 (DMSO)
298 299 (DMSO)
294 296 (DMSO)
385 387 (DMF)
65.69
59.78
59.25
69.40
62.04
62.97
70.76
71.27
68.45
64.63
74.51
74.67
64.64
63.56
69.12
63.79
3.41
2.42
2.43
4.73
3.37
3.48
3.90
4.24
3.20
3.01
4.12
4.40
2.99
3.29
2.95
2.55
7.99
11.04
11.17
9.31
C19H12N2O5
C18H9N3O6
C18H9N3O6
C17H14N2O3
C16H11N3O4
C16H11N3O4
C24H16N4O3
C25H18N4O3
C25H18N4O4
C24H15N5O5
C30H20N4O3
C31H22N4O3
C25H14N5O5
C24H15N5O5
C31H16N5O5
C31H15N6O7
65.52
59.50
59.50
69.45
62.20
62.20
70.75
71.25
68.02
64.66
74.53
74.70
64.66
63.58
69.14
63.81
3.45
2.48
2.48
4.80
3.59
3.59
3.93
4.26
3.23
3.02
4.14
4.42
3.02
3.31
2.97
2.57
8.05
11.57
11.57
9.53
13.41
13.04
13.62
13.17
12.87
15.06
11.47
11.23
15.07
15.43
13.00
14.40
13.59
13.59
13.64
13.19
12.90
15.09
11.49
11.25
15.09
15.45
13.01
14.41
369 370 (DMF)
312 314 (DMSO)
328 330 (DMSO)
317 319 (DMF)
315 317 (DMSO)
338 340 (DMF)
302 304 (DMSO)
299 301 (DMSO)
305 307 (DMSO)
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740
MASLIVETS et al.
Table 2. IR and 1H NMR spectra of compounds Ic, Id, Ig, IIc, IId, IIg, and IIIa IIIg
Comp.
no.
1
IR spectrum, , cm
1H NMR spectrum, , ppm
Ic
3080 (N5 H), 1774 (C1 O), 1742 (C2 O),
1698 (C4 O), 1636 (3-C O)
Id
3070 (N5 H), 1783 (C1 O), 1740 (C2 O),
1699 (C4 O), 1666 (3-C O)
Ig
3115 (N5 H), 1789 (C1 O), 1741 (C2 O),
1660 (C4 O), 1625 (3-C O)
IIc
IId
IIg
3160 (N1 H), 3040 br (N4 H), 1687 3.77 s (3H, CH3O), 6.86 s (1H, CH ), 6.85 7.97 m (8H, Harom),
(C2 O), 1606 br (CH C O)
11.81 s (1H, 1-H), 13.45 s (1H, 4-H)
3200 (N1 H), 3040 br (N4 H), 1698 6.86 s (1H, CH ), 7.10 7.50 m (4H, Harom), 8.30 d (4H, Harom
,
(C2 O), 1608 br (CH C O)
AB system), 12.10 s (1H, 1-H), 13.93 s (1H, 4-H)
3160 (N1 H), 3020 br (N4 H), 1701
(C2 O), 1610 br (CH C O)
IIIa 3050 br (N H); 1685 (C6 O); 1670, 1656 6.90 s (1H, 14-H), 7.15 7.80 m (11H, Harom), 7.96 d (2H, o-H in
(C7 O, C15 O)
Ph, J = 7.3 Hz), 12.58 br.s (2H, 9-H, 16-H)
IIIb 3110 br (N H), 1680 (C6 O), 1670 (C7 O, 2.35 s (3H, CH3), 6.87 s (1H, 14-H), 7.21 7.57 m (10H, Harom),
C15 O)
7.85 d (2H, o-H in Tol, J = 8.2 Hz), 12.55 br.s (2H, 9-H,
16-H)
IIIc 3120 br (N H), 1670 (C6 O), 1660 (C7 O, 3.65 s (3H, CH3O), 6.92 s (1H, 14-H), 7.05 7.92 m (12H, Harom),
C15 O)
12.11 br.s (2H, 9-H, 16-H)
IIId 3110 br (N H), 1694 (C6 O), 1671 (C7 O,
C15 O)
IIIe 3040 br (N H); 1698 (C6 O); 1686, 1670
(C7 O, C15 O)
IIIf 3070 br (N H), 1686 (C6 O), 1665 (C7 O, 2.36 s (3H, CH3), 6.65 d (1H, o-H in Ph, J = 7.3 Hz), 6.90 s (1H,
C15 O)
14-H), 7.10 7.67 m (14H, Harom), 7.90 d (2H, o-H in Tol, J =
8.2 Hz, 12.55 br.s (2H, 9-H, 16-H)
IIIg 3080 br (N H), 1697 (C6 O), 1680 (C7 O,
C15 O)
test for enolic hydroxy group with an alcoholic solu-
tion of iron(III) chloride.
substituted 4-aroyl-5-arylaminopyrrol-2-ones, products
of arylamine addition at C5 of 4-aroyl-2,3-dihydropyr-
role-2,3-diones [8].
The IR spectra of compounds IIIa IIIg (Table 2)
contain absorption bands due to stretching vibrations
of the NH groups (a broad band in the region 3040
1
The IR and H NMR parameters of compounds
IIIa IIIg agree well with those reported for substi-
tuted 1-aryl-1,2,3,5,10,10a-hexahydropyrrolo[2,3-b]-
[1,5]benzodiazepine-2,3-diones [7], which were ob-
tained by reaction of o-phenylenediamine with mono-
cyclic 4-acyl-1-aryl-2,3-dihydropyrrole-2,3-diones
via successive nucleophilic attack first at C5 and then
at the acyl carbonyl carbon atom of the substituent in
position 4.
1
3110 cm ) lactam C6 O carbonyl group (1680
1
1698 cm ), and ketone C7 O and amide carbonyl
1
1
C15 O groups (1656 1686 cm ). In the H NMR
spectra of IIIa IIIg (Table 2) we observed signals
from protons in the aromatic rings and CH3 and CH3O
groups attahced thereto, a singlet from the secondary
amino group proton N14H at
6.87 6.92 ppm,
and a downfield broadened signal from protons of the
amide group N16H (in IIIa IIIc) and enamino group
N9 at 12.11 12.58 ppm. The position of the N14H
signal is very consistent with our previous data for
The UV spectra of 0.0003 M solutions of IIIa,
IIIb, and IIIe in dioxane (see Experimental) are
characterized by the presence of two absorption bands
above 300 nm, max, nm (log ): IIIa: 341 (3.83), 432
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XLIV.
741
Fig. 1. Charges on atoms (in the numerator) and coefficients of 2pz-AO in the LUMO (in the denominator) of molecule Ia.
(3.81); IIIb: 348 (3.81), 428 (3.80); IIIe: 340 (3.78),
427 (3.77). The UV spectra of IIIa, IIIb, and IIIe are
very similar to each other and also to those of model
compounds, substituted 1,4-diaryl-10a-methoxycar-
bonyl-1,2,3,5,10,10a-hexahydropyrrolo[2,3-b][1,5]-
benzodiazepine-2,3-diones IVa IVe [6] and 1-butyl-
4,10-diphenyl-1,2,3,5,10,10a-hexahydropyrrolo[2,3-b]-
[1,5]benzodiazepine-2,3-dione (V). The structure of
compound V was proved by the X-ray diffraction data
[8]. Compounds IVa IVe and V display two absorp-
and the greatest contribution to the lowest unoccupied
molecular orbital (LUMO) is that from 2pz-AO of C3a.
This means that just the latter atom should be attacked
by nucleophile under conditions of orbital control.
Presumably, in the first reaction stage o-phenylene-
diamine adds at C3a of pyrroloquinoxalinetriones I to
give 3a-(o-aminophenylamino)-3-benzoyl-2-hydroxy-
1,3a,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,4-di-
ones VI, as was reported in [1] for reactions of I with
monofunctional nucleophiles. The subsequent nucleo-
philic attack by the second amino group can be
directed at the carbonyl carbon atom of the hetero-
ring (C4) or aroyl fragment (C13). Figure 2 shows the
results of calculation of charges on atoms in molecule
VIa, performed by the above procedure with full
geometry optimization. It is seen that the C13 atom is
the most electron-deficient; moreover, the contribution
of its 2pz-AO to the LUMO is the largest. Obviously,
these factors are responsible for the attack of C13 by
the second amino group of o-phenylenediamine,
which leads to closure of benzodiazepine ring.
tion bands in the UV spectra,
348 355 nm
(log 3.85 3.88) and 417 418 nmm(alxog 3.83 3.93)
(IVa IVe) [7]; 351 (log 3.76) and 460 nm
(log 3.83) (V) [9].
EXPERIMENTAL
IV, X = Y = H (a); X = H, Y = Me (b); X = Cl, Y = H (c);
X = Br, Y = H (d); X = NO2, Y = H (e).
The IR spectra were recorded on a UR-20 spectro-
1
photometer in mineral oil. The H NMR spectra were
In order to explain the direction of primary nucleo-
philic attack on compounds Ia Ig we performed AM1
semiempirical quantum-chemical calculations of
molecule Ia with full geometry optimization using
GAUSSIAN-94W software [10]. The results are
shown in Fig. 1. According to the calculations, the
most electron-deficient atoms are C1, C2, C4, and C13,
obtained on RYa-2310 (60 MHz), Bruker WP-80-54
(80 MHz), and Bruker AM-300 (400 MHz) spectrom-
eters using DMSO-d6 as solvent and HMDS or TMS
as internal reference. The UV spectra were measured
on a Specord UV-Vis instrument in dioxane. The
mass spectrum was run on an MKh-1320 spectrometer
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002

742
MASLIVETS et al.
Fig. 2. Charges on atoms in molecule VIa.
(70 eV). The purity of the products was checked by
TLC on Silufol plates; spots were visualized with
iodine vapor.
a solution of 0.01 mol of o-phenylenediamine in
20 ml of anhydrous dioxane. The mixture was re-
fluxed for 3 min, and the precipitate was filtered off.
3-Aroyl-1,2,4,5-tetrahydropyrrolo[1,5-a]quino-
xaline-1,2,4-triones Ic, Id, and Ig. To a solution of
0.01 mol of compound II in 50 ml of dry chloroform
we added a solution of 0.01 mol of oxalyl chloride in
10 ml of dry chloroform. The mixture was refluxed
for 2 h, cooled, and the precipitate was filtered off.
REFERENCES
1. Pimenova, E.V., Maslivets, A.N., Khamatgaleev, R.A.,
and Andreichikov, Yu.S., Russ. J. Org. Chem., 1996,
vol. 32, no. 9, pp. 1357 1360.
2. Mikhailovskii, A.G., Shklyaev, V.S., and Aleksand-
rov, B.B., Khim. Geterotsikl. Soedin., 1990, no. 6,
pp. 808 810.
8-Aryl-6,7,9,14,15,16-hexahydroquinoxalino-
[1,2-a]pyrrolo[2,3-b][1,5]benzodiazepine-6,7,15-
triones IIIa IIIg. To a solution of 0.01 mol of com-
pound I in 50 ml of anhydrous dioxane we added
3. Mikhailovskii, A.G. and Shklyaev, V.S., Khim.
Geterotsikl. Soedin., 1994, no. 7, pp. 946 949.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 3 2002

FIVE-MEMBERED 2,3-DIOXO HETEROCYCLES: XLIV.
743
4. Kollenz, G., Kriwets, G., Ott, W., and Ziegler, E.,
Justus Liebigs Ann. Chem., 1977, nos. 11 12,
pp. 1964 1968.
9. Terpetschnig, E., Ott, W., Kollenz, G., Peters, K.,
Peters, E.-N., and von Schnering, H.G., Monatsh.
Chem., 1988, vol. 119, no. 3, pp. 367 378.
5. Maslivets, A.N., Mashevskaya, I.V., and Andreichi-
kov, Yu.S., Russ. J. Org. Chem., 1995, vol. 31, no. 4,
pp. 569 572.
6. Mashevskaya, I.V., Makhmudov, R.R., Aleksandro-
va, G.A., Golovnina, O.V., Duvalov, A.V., and
Maslivets, A.N., Khim.-Farm. Zh., 2001, vol. 35,
no. 4, pp. 20 21.
7. Maslivets, A.N., Smirnova, L.I., Ivanenko, O.I., and
Andreichikov, Yu.S., Russ. J. Org. Chem., 1995,
vol. 31, no. 4, pp. 563 568.
8. Maslivets, A.N., Smirnova, L.I., and Andreichi-
kov, Yu.S., Zh. Org. Khim., 1989, vol. 25, no. 8,
pp. 1748 1753.
10. Frisch, M.J., Trucks, G.W., Schlegel, H.B.,
Gill, P.M.W., Johnson, B.G., Robb, M.A.,
Cheeseman, J.R., Keith, T., Petersson, G.A.,
Montgomery, J.A., Raghavachari, K., Al-La-
ham, M.A., Zakrzewski, V.G., Ortiz, J.V., Fores-
man, J.B., Cioslowski, J., Stefanov, B.B., Nanayak-
kara, A., Challacombe, M., Peng, C.Y., Ayala, P.Y.,
Chen, W., Wong, M.W., Andres, J.L., Re-
plogle, E.S., Gomperts, R., Martin, R.L., Fox, D.J.,
Binkley, J.S., Defrees, D.J., Baker, J., Stewart, J.P.,
Head-Gordon, M., Gonzalez, C., and Pople, J.A.,
Gaussian 94, Revision E.3, Pittsburgh: Gaussian,
1995.
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