Reactions of 2-aryl-4-arylidene-4H-oxazol-5-ones with 3-amino-1,2,4- triazole, 5-aminotetrazole, and 2-aminobenzimidazole

Article abstract of DOI:10.1007/s11172-005-0200-0

The reactions of 3-amino-1,2,4-triazole, 5-aminotetrazole, and 2-aminobenzimidazole with 2-aryl-4-arylidene-4H-oxazol-5-ones (azlactones) were studied. The electron-releasing properties of the azole ring were demonstrated to influence the reaction pathway

Full text of DOI:10.1007/s11172-005-0200-0

Russian Chemical Bulletin, International Edition, Vol. 53, No. 12, pp. 2845—2849, December, 2004
2845
Reactions of 2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones with
3ꢀaminoꢀ1,2,4ꢀtriazole, 5ꢀaminotetrazole, and
2ꢀaminobenzimidazole
ꢀ
V. A. Chebanov, S. M. Desenko, S. A. Kuzmenko, V. A. Borovskoy,
V. I. Musatov, and Yu. V. Sadchikova
Scientific and Technological Corporation "Institute for Single Crystals," National Academy of Sciences of Ukraine,
60 prosp. Lenina, 61001 Kharkov, Ukraine.
Fax: +38 (057) 340 9343. Eꢀmail: chebanov@isc.kharkov.com
The reactions of 3ꢀaminoꢀ1,2,4ꢀtriazole, 5ꢀaminotetrazole, and 2ꢀaminobenzimidazole
with 2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones (azlactones) were studied. The electronꢀreleasing
properties of the azole ring were demonstrated to influence the reaction pathway of azlactones
with aminoazoles. The structures of the resulting compounds were established by 1H and
13C NMR spectroscopy using spinꢀspin decoupling and the nuclear Overhauser effect.
Key words: aminoazoles, 2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones, Nꢀ[2ꢀarylꢀ1ꢀ(azolꢀ5ꢀ
ylcarbamoyl)vinyl]aroylamides, Nꢀ(7ꢀarylꢀ5ꢀoxoꢀ4,5,6,7ꢀtetrahydroazolo[1,5ꢀa]pyrimidinꢀ6ꢀ
yl)aroylamides, cyclocondensation, NMR spectroscopy.
Arylideneoxazolones attract interest primarily as inꢀ
termediates, which combine the properties of acid anꢀ
hydrides and unsaturated carbonyl compounds and can
react with substances containing labile hydrogen atoms,
for example, with water,1 alcohols,2—4 amines,5—7 and
hydrogen halides.8,9 However, data on their reactions with
1,3ꢀdinucleophiles are lacking.
As part of continuing studies of the reactions of
aminoazoles with α,βꢀunsaturated carbonyl compounds,
we examined the reactions of 2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀ
oxazolꢀ5ꢀones 1—7 (Scheme 1) with 3ꢀaminoꢀ1,2,4ꢀ
triazole (8), 5ꢀaminotetrazole (9), and 2ꢀaminobenzimidꢀ
azole (24).
Compounds 10—20 remained unchanged upon reꢀ
fluxing both in pure DMF and in the presence of piperiꢀ
dine or triethylamine. Heterocyclization of triazole deꢀ
rivatives 10, 13, and 14 into the corresponding Nꢀ(5ꢀoxoꢀ
4,5,6,7ꢀtetrahydroꢀ1,2,4ꢀtriazolo[1,5ꢀa]pyrimidinꢀ6ꢀ
yl)benzamides 21—23 was performed by heating their soꢀ
lutions in DMF in the presence of acetic acid. Under
these conditions, acylaminotetrazoles 15—20 did not unꢀ
dergo cyclization.
Compounds 21—23 were also prepared by the direct
reactions of azlactones 1, 4, and 5, respectively, with
3ꢀaminoꢀ1,2,4ꢀtriazole (8) in DMF in the presence of
catalytic amounts of acetic acid. The addition of acetic
acid to the reaction mixtures of 5ꢀaminotetrazole (9) with
azlactones 1—6 has no effect on condensation, and the
reactions also afforded aroylamides 15—20 as the only
products.
The starting azlactones 1—7 were prepared by the reꢀ
actions of Nꢀaroyl derivatives of hippuric acid with aroꢀ
matic aldehydes.5,10
We found that heating of azlactones 1—6 with amines
8 and 9 in DMF led to the oxazolone ring opening givꢀ
ing rise to Nꢀ[2ꢀarylꢀ1ꢀ(1,2,4ꢀtriazolꢀ5ꢀylcarbamoyl)viꢀ
nyl]aroylamides 10—14 and Nꢀ[2ꢀarylꢀ1ꢀ(tetrazolꢀ5ꢀ
ylcarbamoyl)vinyl]aroylamides 15—20, respectively. Unꢀ
der analogous conditions, the reactions of arylideneꢀ
oxazolones 1—4, 6, and 7 with 2ꢀaminobenzimidazole 24
did not stop at acylation and afforded 1,2,3,4ꢀtetraꢀ
The difference in the reactivity of aminoazoles 8, 9,
and 24 with respect to arylideneoxazolones can be attribꢀ
utable to the fact that the triazole and tetrazole rings
possess much stronger electronꢀwithdrawing properties
than the benzimidazole fragment. This leads to a decrease
in the electron density on the reaction centers of aminoꢀ
azoles 8 and 9 and, correspondingly, to a decrease in their
nucleophilicity.
hydropyrimido[1,2ꢀa]benzimidazolꢀ2ꢀones
26—31.
1
Nꢀ[1ꢀ(Benzimidazolꢀ2ꢀylcarbamoyl)ꢀ2ꢀ(2ꢀmethoxyꢀ
phenyl)vinyl]benzamide 25 was isolated by performing
the reaction of azlactone 3 with amine 24 at room temꢀ
perature. Heating of 25 in DMF gave imidazopyrimꢀ
idine 28.
The compounds were identified by H and 13C NMR
spectroscopy. The 1H NMR spectra of compounds 10—20
show singlets of the ethylene proton at δ 7.6—7.8 and
singlets of the CH groups of the triazole ring (for comꢀ
pounds 10—14) at δ 7.3. In addition, the NMR spectra
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2730—2733, December, 2004.
1066ꢀ5285/04/5312ꢀ2845 © 2004 Springer Science+Business Media, Inc.

2846
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Chebanov et al.
Scheme 1
8, 10—14: X = CH
9, 15—20: X = N
Compound
R
R´
1, 10, 15, 21, 26
2, 11, 16, 27
3, 12, 17, 25, 28
4, 13, 18, 22, 29
5, 14, 19, 23
6, 20, 30
Ph
Ph
Ph
Ph
Ph
Ph
3,4ꢀ(MeO)2C6H3
2ꢀMeOC6H4
2,4,5ꢀ(MeO)3C6H2
4ꢀNO2C6H4
2ꢀMeOC6H4
4ꢀMeOC6H4
4ꢀMeOC6H4
2ꢀMeC6H4
7, 31
have signals for the protons of three NH groups at δ 10.2,
11.8, and 13.5, multiplets for the aromatic protons, and
signals of other functional groups. The assignment of the
signals of the amino groups was made based on analysis of
the experimental data on the deuterium exchange.
The 13C NMR spectrum of compound 16 shows sigꢀ
nals for all C nuclei present in the molecule (see the
Experimental section).
In addition to the signals of the terminal substituents
and aromatic protons, the 1H NMR spectra of compounds
21—31 have signals for the methine protons and two amino
groups. The signal of the C(3)H group (δH 5.7—5.8) apꢀ
pears as a doublet of doublets, and the signals of C(4)H
(δH 5.5—6.5) and the exocyclic amino group (δH 7.5—9)
appear as doublets. It should be noted that this set of
signals in the 1H NMR spectra corresponds both to strucꢀ
tures 21—31 and compounds 32, which could be generꢀ
ated in the case of the opposite direction of the reaction.
The structures of compounds 21—31 were unambiguꢀ
ously established using spinꢀspin decoupling and the
nuclear Overhauser effect. It was found that suppression
of the doublet of the exocyclic amino group or the douꢀ
blet of C(4)H leads to a change in the multiplicity of the
signal for C(3)H. In turn, suppression of the doublet of
doublets of C(3)H changes the multiplicities of the sigꢀ
nals of both the amino group and C(4)H. The nuclear
Overhauser effect measurements demonstrated that
C(3)H, C(4)H, and the proton of the exocyclic secondary
amino group are in spatial proximity to each other. Addiꢀ
tional irradiation at the resonance frequency of C(3)H

Reactions of 2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004 2847
Nꢀ[2ꢀ(3,4ꢀDimethoxyphenyl)ꢀ1ꢀ(1,2,4ꢀtriazolꢀ3ꢀylcarbaꢀ
moyl)vinyl]benzamide (11). The yield was 61%, m.p. 255—256 °C.
Found (%): N, 17.85. C20H19N5O4. Calculated (%): N, 17.80.
1H NMR, δ: 3.48 and 3.51 (both s, 3 H each, OMe); 7.35 (s,
1 H, N=CH—N); 7.69 (s, 1 H, C=CH); 7.38—8.27 (m, 8 H,
Ar); 10.25, 11.78, and 13.47 (all s, 1 H each, ArCONH,
CONH, N—NH).
Nꢀ[1ꢀ(1,2,4ꢀTriazolꢀ3ꢀylcarbamoyl)ꢀ2ꢀ(2,4,5ꢀtrimethoxyꢀ
phenyl)vinyl]benzamide (13). The yield was 58%, m.p.
215—217 °C. Found (%): N, 16.51. C21H21N5O5. Calcuꢀ
lated (%): N, 16.54. 1H NMR, δ: 3.48, 3.49, and 3.51 (all s,
3 H each, OMe); 7.33 (s, 1 H, N=CH—N); 7.71 (s, 1 H, C=CH);
6.92—7.92 (m, 7 H, Ar); 10.22, 11.82, and 13.45 (all s, 1 H each,
ArCONH, CONH, N—NH).
Nꢀ[2ꢀ(4ꢀNitrophenyl)ꢀ1ꢀ(1,2,4ꢀtriazolꢀ3ꢀylcarbamoyl)viꢀ
nyl]benzamide (14). The yield was 67%, m.p. 221—222 °C.
Found (%): N, 22.19. C18H14N6O4. Calculated (%): N, 22.21.
1H NMR, δ: 7.41 (s, 1 H, N=CH—N); 7.80 (s, 1 H, C=CH);
7.36—8.30 (m, 9 H, Ar); 10.22, 11.75, and 13.44 (all s, 1 H each,
ArCONH, CONH, N—NH).
Nꢀ[2ꢀPhenylꢀ1ꢀ(tetrazolꢀ5ꢀylcarbamoyl)vinyl]benzamide
(15). A mixture 5ꢀaminotetrazole (9) (0.85 g, 0.01 mol) and
azlactone 1 (0.01 mol) was heated until a homogenous mixture
formed. Then three drops of DMF were added, and the mixture
was heated until a precipitate formed (~5 min). After cooling of
the reaction mixture, acetone (5 mL) was added. The precipiꢀ
tate was filtered off and washed with hot acetone. The yield
was 54% (0.18 g), m.p. 243—245 °C. Found (%): N, 25.19.
C17H14N6O2. Calculated (%): N, 25.14. 1H NMR, δ: 7.70 (s,
1 H, C=CH); 6.85—8.17 (m, 10 H, Ar); 10.01, 11.95, and 15.41
(all s, 1 H each, ArCONH, CONH, N—NH).
causes an increase in the integral intensities of the signals
of C(4)H and NH, whereas double resonance at the freꢀ
quency of the signal of the endocyclic amino group does
not change the integral intensities of the signals for other
protons.
The 13C NMR spectrum of compound 27 is also conꢀ
sistent with the proposed structure.
The aboveꢀmentioned spectroscopic data provide eviꢀ
dence that the reactions of arylideneoxazolones 1—7 with
3ꢀaminoꢀ1,2,4ꢀtriazole (8) and 2ꢀaminobenzimidazole
(24) afford compounds 21—31, whereas an alternative
pathway giving rise to imidazopyrimidines 32 does not
take place.
To summarize, the reaction of aminoazoles with
2ꢀarylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones provides a conveꢀ
nient approach to the synthesis of both Nꢀ[2ꢀarylꢀ1ꢀ
(azolylcarbamoyl)vinyl]aroylamides and Nꢀ(7ꢀarylꢀ5ꢀ
oxoꢀ4,5,6,7ꢀtetrahydroazolo[1,5ꢀa]pyrimidinꢀ6ꢀyl)aroylꢀ
amides or Nꢀ(4ꢀarylꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydropyrimiꢀ
do[1,2ꢀa]benzimidazolꢀ3ꢀyl)aroylamides.
Experimental
The 1H and 13C NMR spectra were recorded on a Varian
Mercury VXꢀ200 spectrometer (200 MHz for 1H and 50 MHz
for 13C) in DMSOꢀd6 with Me4Si as the internal standard. The
deuterium exchange was carried out with the use of methanolꢀ
d4. The purity of the compounds was checked by TLC on Silufol
UVꢀ254 plates using chloroform, ethyl acetate, or their mixtures
as the solvents. The melting points were measured on a Kofler
hotꢀstage apparatus.
2ꢀArylꢀ4ꢀarylideneꢀ4Hꢀoxazolꢀ5ꢀones 1—7 were synthesized
according to a known procedure.5,10 The melting points and
spectroscopic characteristics of compounds 1—7 are identical to
the data published in the literature.11—14
Nꢀ[2ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀ(1,2,4ꢀtriazolꢀ3ꢀylcarbaꢀ
moyl)vinyl]benzamide (12). A mixture of 3ꢀaminoꢀ1,2,4ꢀtriazole
(8) (0.84 g, 0.01 mol) and azlactone 3 (3.10 g, 0.01 mol) was
heated until a homogeneous mixture formed. Then three drops
of DMF were added and the mixture was heated until a precipiꢀ
tate formed (~5 min). After cooling of the reaction mixture,
acetone (5 mL) was added. The precipitate was filtered off and
washed with hot acetone. The yield was 57% (2.25 g), m.p.
257—258 °C. Found (%): N, 19.29. C19H17N5O3. Calculated
(%): N, 19.27. 1H NMR, δ: 3.43 (s, 3 H, OMe); 7.38 (s, 1 H,
N=CH—N); 7.73 (s, 1 H, C=CH); 7.35—8.29 (m, 9 H,
Ar); 10.20, 11.76, and 13.43 (all s, 1 H each, ArCONH,
CONH, N—NH).
Compounds 16—20 were prepared analogously.
Nꢀ[2ꢀ(3,4ꢀDimethoxyphenyl)ꢀ1ꢀ(tetrazolꢀ5ꢀylcarbamoyl)viꢀ
nyl]benzamide (16). The yield was 78%, m.p. 259—260 °C.
Found (%): N, 25.19. C17H14N6O2. Calculated (%): N, 25.14.
1H NMR, δ: 3.46 and 3.48 (both s, 3 H each, OMe); 7.69 (s,
1 H, C=CH); 6.95—8.15 (m, 8 H, Ar); 10.10, 12.08, and 15.15
(all s, 1 H each, ArCONH, CONH, N—NH). 13C NMR, δ:
55.0, 55.5 (OMe); 111.6 (CH=C); 124.2 (CH=C); 112.8, 126.0,
127.7, 128.1 131.5 (oꢀCHAr, mꢀCHAr); 133.3 (pꢀCHAr); 164.5,
166.0 (C=O); 125.8, 132.5 (ipsoꢀCAr), 148.3, 150.1, 151.5 (quaꢀ
ternary C).
Nꢀ[2ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀ(tetrazolꢀ5ꢀylcarbamoyl)viꢀ
nyl]benzamide (17). The yield was 61%, m.p. 261—263 °C.
Found (%): N, 23.10. C18H16N6O3. Calculated (%): N, 23.07.
1H NMR, δ: 3.41 (s, 3 H, OMe); 7.65 (s, 1 H, C=CH);
6.78—8.06 (m, 9 H, Ar); 9.95, 12.03, and 15.35 (all s, 1 H each,
ArCONH, CONH, N—NH).
Nꢀ[1ꢀ(Tetrazolꢀ5ꢀylcarbamoyl)ꢀ2ꢀ(2,4,5ꢀtrimethoxypheꢀ
nyl)vinyl]benzamide (18). The yield was 63%, m.p. 208—210 °C.
Found (%): N, 25.19. C20H20N6O5. Calculated (%): N, 25.14.
1H NMR, δ: 3.50, 3.51, and 3.56 (all s, 3 H each, OMe); 7.61 (s,
1 H, C=CH); 6.81—7.88 (m, 7 H, Ar); 10.05, 11.98, and 15.50
(all s, 1 H each, ArCONH, CONH, N—NH).
Compounds 10, 11, 13, and 14 were synthesized analoꢀ
gously.
Nꢀ[2ꢀPhenylꢀ1ꢀ(1,2,4ꢀtriazolꢀ3ꢀylcarbamoyl)vinyl]benzamide
(10). The yield was 63%, m.p. 212—213 °C. Found (%): N, 21.05.
C18H15N5O2. Calculated (%): N, 21.01. 1H NMR, δ: 7.30 (s,
1 H, N=CH—N); 7.65 (s, 1 H, C=CH); 7.21—8.32 (m, 10 H,
Ar); 10.18, 11.69, and 13.42 (all s, 1 H each, ArCONH,
CONH, N—NH).
Nꢀ[2ꢀ(4ꢀNitrophenyl)ꢀ1ꢀ(tetrazolꢀ5ꢀylcarbamoyl)viꢀ
nyl]benzamide (19). The yield was 68%, m.p. 254—255 °C.
Found (%): N, 25.89. C17H13N7O4. Calculated (%): N, 25.85.
1H NMR, δ: 7.13 (s, 1 H, C=CH); 6.87—8.09 (m, 9 H,
Ar); 10.03, 12.01, and 15.46 (all s, 1 H each, ArCONH,
CONH, N—NH).

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Russ.Chem.Bull., Int.Ed., Vol. 53, No. 12, December, 2004
Chebanov et al.
Nꢀ[2ꢀ(2ꢀMethoxyphenyl)ꢀ1ꢀ(tetrazolꢀ5ꢀylcarbamoyl)vinyl]ꢀ
4ꢀmethoxybenzamide (20). The yield was 65%, m.p. 244—246 °C.
Found (%): N, 21.32. C19H18N6O4. Calculated (%): N, 21.31.
1H NMR, δ: 3.53 and 3.65 (both s, 3 H each, OMe); 7.01 (s,
1 H, C=CH); 6.91—8.10 (m, 8 H, Ar); 10.06, 11.97, and 15.55
(all s, 1 H each, ArCONH, CONH, N—NH).
Nꢀ[7ꢀ(4ꢀNitrophenyl)ꢀ5ꢀoxoꢀ4,5,6,7ꢀtetrahydroꢀ1,2,4ꢀtriꢀ
azolo[1,5ꢀa]pyrimidinꢀ6ꢀyl]benzamide (23). A. Glacial acetic acid
(two drops) was added to a mixture of azlactone 5 (0.30 g,
0.01 mol) and 3ꢀaminoꢀ1,2,4ꢀtriazole (8) (0.84 g, 0.01 mol) in
DMF (0.1 mL), and the mixture was heated for 10 min. The
precipitate that formed was filtered off and washed with propanꢀ
2ꢀol. The yield was 34% (0.13 g), m.p. 268—270 °C.
B. Glacial acetic acid (two drops) was added to a solution
of Nꢀ[2ꢀ(4ꢀnitrophenyl)ꢀ1ꢀ(1,2,4ꢀtriazolꢀ3ꢀylcarbamoyl)viꢀ
nyl]benzamide (12) (0.38 g, 0.01 mol) in DMF (0.2 mL) and the
reaction mixture was heated for 15 min. The precipitate that
formed was filtered off and washed with propanꢀ2ꢀol. The yield
was 40% (0.15 g), m.p. 268—270 °C.
Found (%): N, 22.19. C18H14N6O4. Calculated (%):
N, 22.21. 1H NMR, δ: 5.62 (dd, 1 H, C(3)H, J = 7.4 Hz, J =
6.8 Hz); 5.89 (d, 1 H, C(4)H, J = 7.4 Hz); 7.80 (s, 1 H,
N=CH—N); 6.47—7.79 (m, 9 H, Ar); 8.21 (d, 1 H, NH, J =
6.8 Hz); 12.04 (br.s, 1 H, N(1)H).
B. A solution of Nꢀ[1ꢀ(benzimidazolꢀ2ꢀylcarbamoyl)ꢀ2ꢀ
(2ꢀmethoxyphenyl)vinyl]benzamide (23) (0.41 g, 0.01 mol) in
DMF (0.3 mL) was heated for 15 min and then cooled, after
which acetone (5 mL) was added and the reaction mixture was
kept at room temperature for one day. The precipitate that
formed was filtered off and washed with acetone. The yield
was 75%, m.p. 257—258 °C.
Found (%): N, 13.60. C24H20N4O3. Calculated (%):
N, 13.58. 1H NMR, δ: 3.57 (s, 3 H, OMe); 5.69 (dd, 1 H,
C(3)H, J = 8.2 Hz, J = 7.2 Hz); 6.26 (d, 1 H, C(4)H, J =
8.2 Hz); 6.78—7.65 (m, 13 H, Ar); 8.02 (d, 1 H, NH, J =
7.2 Hz); 11.84 (br.s, 1 H, N(1)H).
Compounds 26, 27, and 29—31 were synthesized according
to the procedure A.
Nꢀ[2ꢀOxoꢀ4ꢀphenylꢀ1,2,3,4ꢀtetrahydrobenz[6,7]imidꢀ
azo[1,2ꢀa]pyrimidinꢀ3ꢀyl]benzamide (26). The yield was 58%,
m.p. 223—225 °C. Found (%): N, 14.63. C23H18N4O2. Calcuꢀ
lated (%): N, 14.65. 1H NMR, δ: 5.70 (dd, 1 H, C(3)H, J =
7.5 Hz, J = 7.5 Hz); 6.12 (d, 1 H, C(4)H, J = 7.5 Hz); 6.89—7.90
(m, 14 H, Ar); 8.20 (d, 1 H, NH, J = 7.5 Hz); 11.75 (br.s,
1 H, N(1)H).
Nꢀ[4ꢀ(3,4ꢀDimethoxyphenyl)ꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydroꢀ
benz[6,7]imidazo[1,2ꢀa]pyrimidinꢀ3ꢀyl]benzamide (27). The yield
was 84%, m.p. 257—258 °C. Found (%): N, 12.64. C25H22N4O4.
1
Compounds 21 and 22 were synthesized according to the
methods A and B, respectively.
Calculated (%): N, 12.66. H NMR, δ: 3.45 and 3.65 (both s, 3
H each, OMe); 5.67 (dd, 1 H, C(3)H, J = 7.6 Hz, J = 7.6 Hz);
6.10 (d, 1 H, C(4)H, J = 7.6 Hz); 6.40—7.81 (m, 12 H, Ar); 8.22
(d, 1 H, NH, J = 7.6 Hz); 11.96 (br.s, 1 H, N(1)H). 13C NMR,
δ: 55.7, 56.0 (OMe); 53.2 (C(4)); 55.2 (C(3)); 110.2, 112.1,
Nꢀ(5ꢀOxoꢀ7ꢀphenylꢀ4,5,6,7ꢀtetrahydroꢀ1,2,4ꢀtriazoꢀ
lo[1,5ꢀa]pyrimidinꢀ6ꢀyl)benzamide (21). The yield was 42%, m.p.
263—265 °C. Found (%): N, 21.04. C18H15N5O2. Calcuꢀ
lated (%): N, 21.01. 1H NMR, δ: 5.66 (dd, 1 H, C(3)H, J =
7.6 Hz, J = 7.6 Hz); 5.91 (d, 1 H, C(4)H, J = 7.6 Hz); 7.78 (s,
1 H, N=CH—N); 6.50—7.75 (m, 10 H, Ar); 8.18 (d, 1 H, NH,
J = 7.6 Hz); 12.02 (br.s, 1 H, N(1)H).
Nꢀ[5ꢀOxoꢀ7ꢀ(2,4,5ꢀtrimethoxyphenyl)ꢀ4,5,6,7ꢀtetrahydroꢀ
1,2,4ꢀtriazolo[1,5ꢀa]pyrimidinꢀ6ꢀyl)benzamide (22). The yield
was 38%, m.p. 265—267 °C. Found (%): N, 16.57. C21H21N5O5.
Calculated (%): N, 16.54. 1H NMR, δ: 3.66, 3.67, and 3.75
(all s, 3 H each, OMe); 5.68 (dd, 1 H, C(3)H, J = 7.2 Hz, J =
6.4 Hz); 5.95 (d, 1 H, C(4)H, J = 7.2 Hz); 8.01 (s, 1 H,
N=CH—N); 6.68—8.15 (m, 7 H, Ar); 9.61 (d, 1 H, NH, J =
6.4 Hz); 11.55 (br.s, 1 H, N(1)H).
112.5, 118.0, 119.0, 121.9, 122.6, 128.3, 129.0 (oꢀCHAr
,
mꢀCHAr); 132.8 (pꢀCHAr); 167.1, 167.3 (C=O); 127.9, 134.1
(ipsoꢀCAr); 132.8, 142.1, 147.9, 149.1, 149.5 (quaternary C).
Nꢀ[2ꢀOxoꢀ4ꢀ(2,4,5ꢀtrimethoxyphenyl)ꢀ1,2,3,4ꢀtetrahydroꢀ
benz[6,7]imidazo[1,2ꢀa]pyrimidinꢀ3ꢀyl]benzamide (29). The yield
was 56%, m.p. 216—218 °C. Found (%): N, 11.90. C26H24N4O5.
Calculated (%): N, 11.86. 1H NMR, δ: 3.37, 3.83, and 3.84
(all s, 3 H each, OMe); 5.88 (dd, 1 H, C(3)H, J = 7.4 Hz, J =
7.2 Hz); 6.05 (d, 1 H, C(4)H, J = 7.4 Hz); 6.67—8.81 (m, 11 H,
Ar); 9.83 (d, 1 H, NH, J = 7.2 Hz); 11.84 (br.s, 1 H, N(1)H).
Nꢀ[4ꢀ(2ꢀMethoxyphenyl)ꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydroꢀ
benz[6,7]imidazo[1,2ꢀa]pyrimidinꢀ3ꢀyl]ꢀ4ꢀmethoxybenzamide
(30). The yield was 60%, m.p. 220—221 °C. Found (%): N, 12.65.
C25H22N4O4. Calculated (%): N, 12.66. 1H NMR, δ: 3.52 and
3.71 (both s, 3 H each, OMe); 5.65 (dd, 1 H, C(3)H, J = 7.6 Hz,
J = 7.6 Hz); 6.22 (d, 1 H, C(4)H, J = 7.6 Hz); 6.70—7.74
(m, 12 H, Ar); 7.76 (d, 1 H, NH, J = 7.6 Hz); 11.69 (br.s,
1 H, N(1)H).
Nꢀ[4ꢀ(4ꢀMethoxyphenyl)ꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydroꢀ
benz[6,7]imidazo[1,2ꢀa]pyrimidinꢀ3ꢀyl]ꢀ2ꢀmethylbenzamide (31).
The yield was 62%, m.p. 219—220 °C. Found (%): N, 13.16.
C25H22N4O3. Calculated (%): N, 13.14. 1H NMR, δ: 2.25 (s,
3 H, Me); 3.71 (s, 3 H, OMe); 5.10 (dd, 1 H, C(3)H, J = 7.3 Hz,
J = 7.6 Hz); 5.58 (d, 1 H, C(4)H, J = 7.6 Hz); 6.13—7.65 (m,
12 H, Ar); 8.90 (d, 1 H, NH, J = 7.3 Hz); 11.65 (br.s,
1 H, N(1)H).
Nꢀ[1ꢀ(Benzimidazolꢀ2ꢀylcarbamoyl)ꢀ2ꢀ(2ꢀmethoxyphenyl)viꢀ
nyl]benzamide (25). A mixture of azlactone 3 (0.28 g, 0.01 mol)
and 2ꢀaminobenzimidazole 22 (0.13 g, 0.01 mol) in DMF
(0.3 mL) was kept at room temperature for 12 h. The precipitate
that formed was filtered off and washed with a small amount of
acetone. The yield was 56%, m.p. 279—280 °C. Found (%):
1
N, 13.56. C24H20N4O3. Calculated (%): N, 13.58. H NMR, δ:
3.85 (s, 3 H, OMe); 7.49 (s, 1 H, C=CH); 6.80—8.10 (m,
13 H, Ar); 9.96, 12.12, and 15.62 (all s, 1 H each, ArCONH,
CONH, N=C—NH).
Nꢀ[4ꢀ(2ꢀMethoxyphenyl)ꢀ2ꢀoxoꢀ1,2,3,4ꢀtetrahydroꢀ
benz[6,7]imidazo[1,2ꢀa]pyrimidinꢀ3ꢀyl]benzamide
(28).
A. A mixture of 2ꢀaminobenzimidazole (22) (0.13 g, 0.01 mol)
and azlactone 3 (0.28 g, 0.01 mol) was heated until a melt
formed and then DMF (0.1 mL) was added. The reaction mixꢀ
ture was heated for 7 min and then cooled, after which acetone
(5 mL) was added and the reaction mixture was kept at room
temperature for one day. The precipitate that formed was filꢀ
tered off and washed with acetone. The yield was 84%, m.p.
257—258 °C.
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Received February 18, 2004;
in revised form July 23, 2004