Thermolytic transformations of 5-aryl-4-quinoxalin-2-ylfuran-2,3-diones in the presence of n-cyano compounds

Article abstract of DOI:10.1007/s10593-012-1144-6

6-Aryl-5-quinoxalinyl-1,3-oxazin-4-ones were obtained by thermolysis of 5-aryl-4-quinoxalinylfuran-2,3-diones in the presence of tert-butylcyanamide, 4-morpholinecarbonitrile, and N-cyanobenzamide.

Full text of DOI:10.1007/s10593-012-1144-6

Chemistry of Heterocyclic Compounds, Vol. 48, No. 9, December, 2012 (Russian Original Vol. 48, No. 9, September, 2012)
THERMOLYTIC TRANSFORMATIONS OF
5-ARYL-4-QUINOXALIN-2-YLFURAN-2,3-DIONES
IN THE PRESENCE OF N-CYANO COMPOUNDS
N. Yu. Lisovenko1*, D. D. Nekrasov1, and V. I. Karmanov2
6-Aryl-5-quinoxalinyl-1,3-oxazin-4-ones were obtained by thermolysis of 5-aryl-4-quinoxalinylfuran-
2,3-diones in the presence of tert-butylcyanamide, 4-morpholinecarbonitrile, and N-cyanobenzamide.
Keywords: aroyl(imidoyl)ketenes, N-cyano compounds, 1,3-oxazin-4-ones, [4+2] cycloaddition.
Aroylketenes, generated from 4-unsubstituted 5-arylfuran-2,3-diones, enter into a Diels–Alder reaction
with N-cyano compounds [1-3], where the aroylketene fragment acts as diene, while the C≡N bond of the
N-cyano compound acts as dienophile.
The presence of the quinoxaline fragment at the position 4 of the 5-arylfuran-2,3-dione molecule in
thermolytic reactions leads to the corresponding aroyl(imidoyl)ketenes, which have alternative paths for
cycloaddition at the aroylketene or imidoylketene fragment. In the absence of reaction partners they undergo
intermolecular dimerization, where one molecule of the ketene acts as diene through the conjugated
imidoylketene bond system while another acts as dienophile through the C=C bond of the aroylketene fragment
[4]. In the presence of active dienophiles, cycloaddition takes place at the aroylketene fragment of the
aroyl(imidoyl)ketene [5, 6].
The possibility of aroyl(imidoyl)ketenes generated from 5-aryl-4-quinoxalinylfuran-2,3-diones
undergoing cycloaddition in both directions was investigated by us for the case of N-cyano compounds
containing substituents with various electronic effects at the cyano group.
Substituted 6-aryl-5-quinoxalinyl-1,3-oxazin-4-ones 2a-f (Tables 1, 2) were obtained by the thermolysis
of furandiones 1a,b with commercially available tert-butylcyanamide, 4-morpholinecarbonitrile, and N-cyano-
benzamide.
Compounds 2a-f are evidently formed as a result of [4+2] cycloaddition of the aroylketene fragment of
the aroyl(imidoyl)ketenes A, generated from the furandiones 1a,b, at the C≡N bond of the N-cyanoamide
reagent.
In the IR spectra of the obtained compounds, the absence of absorption bands characteristic of the
ketone carbonyl in the aroyl fragment makes it possible to rule out the formation of the isomeric structure 3.
_______
*To whom correspondence should be addressed, e-mail: lisovn@mail.ru.
1Perm State National Research University, 15 Bukireva St., Perm 614990, Russia.
2Institute of Technical Chemistry, Ural Branch, Russian Academy of Sciences, 3 Acad. Koroleva St., Perm
614013, Russia e-mail: info@itch.perm.ru.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1456-1459, September, 2012.
Original article submitted May 29, 2011.
0009-3122/12/4809-1357©2012 Springer Science+Business Media New York
1357

The reaction of benzoylketene, generated from 5-phenylfuran-2,3-diones, with compounds containing a
C≡N bond has been modelled by the semiempirical SCF-MO-LCAO method in the MNDO-PM3
approximation, indicating that the reaction proceeds by a pseudopericyclic mechanism [7]. It can be supposed
that compounds 2a-f will be formed by a similar mechanism.
N
N
Ar
N
N
Ar
N
N
Ar

RCN
O
O
O
O
O
–CO
C
O
N
O
Ar
R
Ar
Ar
A
1a,b
2a–f
RCN
Ar
N
O
O
Ar
N
R
N
3
1 a Ar = Ph, b Ar = 4-MeC6H4; 2 a Ar = Ph, R = t-BuNH; b Ar = 4-MeC6H4, R = t-BuNH; c Ar = Ph, R = morpholin-4-yl;
d Ar = 4-MeC6H4, R = morpholin-4-yl; e Ar = Ph, R = PhCONH; f Ar = 4-MeC6H4, R = PhCONH
Unlike tert-butylcyanamide, 4-morpholinecarbonitrile, and N-cyanobenzamide, aliphatic and aromatic
nitriles do not react with aroyl(imidoyl)ketenes A. In the course of the reaction only the dimers 4a,b were
isolated, with physicochemical characteristics matching those of previously obtained samples [4].
N
N
Ar
COAr
N
N
Ar

RCN
O
OCOAr
O
1a,b
C
O
–CO
Ar
N
N
Ar
A
4a,b
R = Me, 4-EtOC6H4, 2,4-(EtO)2C6H3, 4-Me2NC6H4
This is probably explained by the fact that the reaction of aroyl(imidoyl)ketenes with unsaturated
compounds is a [4+2] cycloaddition with inverse electron demands in comparison with usual Diels–Alder
reactions. Therefore, only cyanides in which the C≡N bond is activated by strong electron-donating groups enter
into reactions with aroyl(imidoyl)ketenes.
Thus, investigation of the thermolytic transformations of furan-2,3-diones in the presence of N-cyano
compounds has demonstrated the regiospecific nature of such reactions. In the course of the reaction only the
products from dienophile cycloaddition at the aroylketene fragment of the aroyl(imidoyl)ketenes (substituted
1,3-oxazin-4-ones) are formed. Estimation of the reactivity of compounds containing C≡N bonds in
intermolecular cycloaddition with ketenes showed that the reaction only occurs with cyano compounds
activated by strong electron-donating groups.
1358

TABLE 1. The Physicochemical Characteristics of the Synthesized
Compounds
Found, %
——————
Calculated, %
Com-
pound
Empirical
formula
Mp, С
(solvent)
Yield, %
С
Н
N
C28H24N4O2
C30H28N4O2
C28H22N4O3
C30H26N4O3
C31H20N4O3
C33H24N4O3
74.99
74.98
75.66
75.61
72.68
72.71
73.51
73.45
74.91
74.99
75.52
75.56
5.34
5.39
5.95
5.92
4.77
4.79
5.38
5.34
4.11
4.06
4.60
4.61
12.47
12.49
11.70
11.76
12.16
12.11
11.49
11.42
11.31
11.28
10.61
10.68
275-276
(MeCN)
277-279
(MeCN)
180-181
(PhMe)
231-233
(PhMe)
243-245
(PhMe)
194-196
(PhMe)
76
87
78
75
60
67
2а
2b
2c
2d
2e
2f
EXPERIMENTAL
The IR spectra were recorded in vaseline oil on an FSM-1201 spectrometer. The 1H NMR spectra were
obtained in CDCl3 on a Mercury 300 Plus instrument (300 MHz) with HMDS as internal standard (δ 0.05 ppm).
Elemental analysis was performed on an automatic LECO CHNS-932 analyzer. The melting points were
determined on a PTP-2 instrument. The chemical purity of the compounds and the progress of the reactions
were monitored by TLC on Silufol UV-254 plates with 5:2 hexane–EtOAc as eluent and with detection by
iodine vapor.
2-tert-Butylamino-6-phenyl-5-(3-phenylquinoxalin-2-yl)-4H-1,3-oxazin-4-one (2a). A solution of
furandione 1a (378 mg, 1 mmol) and tert-butylcyanoamide (98 mg, 1 mmol) in absolute p-xylene (15 ml) was
refluxed for 30 min, the solvent was evaporated, and the residue was recrystallized.
Compounds 2b-f were synthesized similarly to compound 2a.
2-tert-Butylamino-6-(4-methylphenyl)-5-[3-(4-methylphenyl)quinoxalin-2-yl]-4H-1,3-oxazin-4-one
(2b). This compound was obtained from the furandione 1b and tert-butylcyanoamide.
2-(Morpholin-4-yl)-6-phenyl-5-(3-phenylquinoxalin-2-yl)-4H-1,3-oxazin-4-one (2c). This compound
was obtained from the furandione 1a and 4-morpholinecarbonitrile.
6-(4-Methylphenyl)-5-[3-(4-methylphenyl)quinoxalin-2-yl]-2-(morpholin-4-yl)-4H-1,3-oxazin-4-one
(2d). This compound was obtained from the furandione 1b and 4-morpholinecarbonitrile.
TABLE 2. The Spectral Characteristics of the Synthesized Compounds
IR spectrum,
Com-
pound
1Н NMR spectrum, , ppm
, cm-1
1668 (СON),
3220 (br., NH)
1.40 (9Н, s, C(СН3)3); 6.99–8.18 (14Н, m, H Ar); 8.32 (1Н, s, NH)
2a
2b
1664 (СON),
3219 (br., NH)
1.44 (9Н, s, C(СН3)3); 2.26 (3Н, s, СН3); 2.37 (3Н, s, СН3);
7.00-8.20 (12Н, m, H Ar); 8.33 (1Н, s, NH)
1668 (СОN)
1674 (СОN)
3.74 (8H, br. s, 4CH2 morpholine); 7.11–8.21 (14Н, m, H Ar)
2c
2.26 (3Н, s, СН3); 2.37 (3Н, s, СН3);
2d
3.74 (8H, br. s, 4CH2 morpholine); 7.06-8.20 (12Н, m, H Ar)
1662 (СОN),
3228 (br., NH)
7.49-8.23 (19Н, m, H Ar); 11.88 (1Н, s, NН)
2e
2f
1666 (СОN),
3231 (br., NH)
2.45 (3Н, s, СН3); 2.52 (3Н, s, СН3); 7.25–8.02 (17Н, m, H Ar);
11.63 (1Н, s, NH)
1359

N-[4-Oxo-6-phenyl-5-(3-phenylquinoxalin-2-yl)-4H-[1,3]oxazin-2-yl]benzamide (2e). This compound
was obtained from the furandione 1a and N-cyanobenzamide.
N-{6-(4-Methylphenyl)-4-oxo-5-[3-(4-methylphenyl)quinoxalin-2-yl]-4H-[1,3]oxazin-2-yl}benzamide
(2f). This compound was obtained from the furandione 1b and N-cyanobenzamide.
The work was carried out with financial support from the Ministry of Education of Perm Region
(project MIG).
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