Pyrano[4,3-d]pyrimidinium salts : 22. Reactions of 1,3-dimethyl-2,4- dioxopyrano[4,3-d]pyrimidinium salts with hydrazine

Article abstract of DOI:10.1007/s11172-008-0232-3

Reactions of 5-aryl- and 5,7-diaryl-1,3-dimethyl-2,4-dioxopyrano[4,3-d] pyrimidinium salts with hydrazine were studied. In the former case, the reaction products were the 6-amino-1,3-dimethyl-2,4-dioxopyrido[4,3-d]pyrimidinium salts. 5,7-Diarylpyrano[4,3-d]pyrimidinium salts were transformed into either the corresponding pyridinium salts or 1H-pyrimido-[5,4-d][1,2]diazepine-2,4(3H, 9H)-diones, depending on the hydrazine concentration and the reaction time.

Full text of DOI:10.1007/s11172-008-0232-3

Russian Chemical Bulletin, International Edition, Vol. 57, No. 8, pp. 1754—1759, August, 2008
1754
Pyrano[4,3ꢀd]pyrimidinium salts
2.* Reactions of 1,3ꢀdimethylꢀ2,4ꢀdioxopyrano[4,3ꢀd]pyrimidinium salts with hydrazine
V. V. Kostrub, E. B. Tsupak, Yu. N. Tkachenko, and M. A. Shevchenko
Department of Chemistry, Southern Federal University,
7 ul. Zorge, 344090 RostovꢀonꢀDon, Russian Federation.
Phone: +7 (863) 297 5154. Eꢀmail: dastr@yandex.ru
Reactions of 5ꢀarylꢀ and 5,7ꢀdiarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxopyrano[4,3ꢀd]pyrimidinium salts
with hydrazine were studied. In the former case, the reaction products were the 6ꢀaminoꢀ
1,3ꢀdimethylꢀ2,4ꢀdioxopyrido[4,3ꢀd]pyrimidinium salts. 5,7ꢀDiarylpyrano[4,3ꢀd]pyrimidinium
salts were transformed into either the corresponding pyridinium salts or 1Hꢀpyrimidoꢀ
[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdiones, depending on the hydrazine concentration and the
reaction time.
Key words: pyrano[4,3ꢀd]pyrimidinium salts, recyclization, 6ꢀaminoꢀ2,4ꢀdioxopyridoꢀ
[4,3ꢀd]pyrimidinium salts, 1Hꢀpyrimido[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdiones.
The nucleophilic substitution reaction at the O atom
of the pyrylium ring is one of the most important properꢀ
ties of pyrylium cations. Recyclization of pyrylium and
benzo[c]pyrylium salts into pyridines and isoquinolines,
respectively, were reviewed.2,3 Recently,1 we have found
that treatment of the pyrano[4,3ꢀd]pyrimidinium salts with
ammonia and primary amines gives, as in the case of
benzo[c]pyrylium salts, the corresponding pyrido[4,3ꢀd]ꢀ
pyrimidines and pyrido[4,3ꢀd]pyrimidinium salts. These
reactions open up a simple route to novel fused systems
containing the uracil ring, which is believed to impart
biological activity to many relevant compounds.
hydrazine leads to Nꢀaminoisoquinolinium derivatives,
while the reaction with a great excess of the nucleophile
gives benzoꢀ2,3ꢀdiazepines.6,7
5ꢀArylꢀ and 5,7ꢀdiarylꢀ2,4ꢀdioxopyrano[4,3ꢀd]pyriꢀ
midinium salts were prepared according to earlier developed
Scheme 1
Proceeding further in the investigation of the recyclizaꢀ
tion of pyrano[4,3ꢀd]pyrimidinium salts under the action
of nitrogen nucleophiles, we studied their reactions with
hydrazine.
The pathway of the reactions of benzo[c]pyrylium salts
with hydrazine is known to depend on the presence or
the absence of a substituent in the pyrylium ring and
on the substituent nature. 1,3ꢀDialkylbenzo[c]pyrylium
perchlorates in the presence of hydrazine were transformed
into Nꢀaminoisoquinolinium cations4, while reactions of
1ꢀarylbenzo[c]pyrylium salts result in their recyclization
into benzoꢀ2,3ꢀdiazepines.5 3ꢀ and 4ꢀFunctionalized
benzo[c]pyrylium cations behave in a more complicated
way and the reaction outcome depends on both the
substituent nature and the hydrazine concentration. For
instance, heating of 3ꢀethoxyꢀ and 4ꢀcyanobenzo[c]ꢀ
pyrylium perchlorates with an equimolar amount of
1—3: Ar = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
–
3: R = H; X– = ClO4
4, 5: R = Ar´ = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c);
5: Ar = Ph, X– = Br–
* For Part 1, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1720—1725, May, 2008.
1066ꢀ5285/08/5708ꢀ1754 © 2008 Springer Science+Business Media, Inc.

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1755
procedures.1 For instance, 5ꢀaroylꢀ1,3,6ꢀmethyluracils
1a—c were transformed into 5ꢀaroylꢀ6ꢀ(2ꢀmorpholinoꢀ
ethenyl)pyrimidineꢀ2,4(1H,3H)ꢀdiones 2a—c and further,
under the action of HClO4, into the target 5ꢀarylꢀ1,3ꢀdiꢀ
methylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀpyrano[4,3ꢀd]pyrimidiꢀ
nium perchlorates 3a—c. Condensation of 5ꢀbenzoylꢀ
1,3,6ꢀtrimethyluracil 1a with aromatic aldehydes leads
to 6ꢀ(2ꢀarylethenyl)ꢀ5ꢀphenylpyrimidineꢀ2,4(1H,3H)ꢀ
diones 4a—c, which easily undergo cyclization into
7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,2H,3H,4Hꢀ
pyrano[4,3ꢀd]pyrimidinium bromides 5a—c (Scheme 1).
We found that heating of 5ꢀarylpyrano[4,3ꢀd]pyrimiꢀ
dinium perchlorates 3a—c with hydrazine results in their
recyclization into 6ꢀaminoꢀ5ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium cations 6a—c,
regardless of the hydrazine concentration or the reaction
time (Scheme 2).
Scheme 3
Scheme 2
Ar´ = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
nonequivalent protons of the endocyclic CH2 group. An
analogous methylene group in diazepine hydrobromides 7
is manifested as doublets at δ 2.79—2.90 and 4.67—4.75
(J = 14.12—14.13 Hz). The nonequivalence of the methꢀ
ylene protons is probably due to the nonplanar structure
of the diazepine ring in compounds 7 and 8 and to the
high energy barrier to its conformational changes. The acid
proton in hydrobromides 7 absorbs at 3375—3380 cm–1
.
Treatment of salts 5a—c with excess hydrazine for 30 min
gave 6ꢀaminoꢀ7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium bromides 9a—c
(Scheme 4).
The Nꢀamino group in 6ꢀaminoꢀ5,7ꢀdiarylpyridoꢀ
[4,3ꢀd]pyrimidinium salts 9 absorbs at 3250—3300 and
3285—3350 cm–1. In the 1H NMR spectra, its protons are
manifested as singlets at δ 6.32—6.39, which disappear
upon deuteration. The singlet at δ 7.92—7.99 relates to
the H(8) proton.
By analyzing experimental data, we assumed that
reactions of pyrano[4,3ꢀd]pyrimidinium salts with hydrꢀ
azine involve intermediate formation of a diazepine ring
from the pyrylium one and recyclization of the former in
the presence of excess hydrazine into an Nꢀaminoꢀ
pyridinium ring. This assumption is confirmed by isolaꢀ
tion of 6ꢀaminopyrido[4,3ꢀd]pyrimidinium bromides 9
in 70—80% yields upon heating of diazepine hydroꢀ
bromides 7 with an equimolar amount of hydrazine for
30 min (Scheme 5).
Ar = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
The structures of compounds 6a—c were determined
from their IR and 1H NMR spectra. The IR spectra show
absorption peaks of the amino group at 3245—3260 and
3325—3350 cm–1. In the 1H NMR spectra, the Nꢀamino
group is manifested as a broadened singlet (δ 7.16—7.19,
2 H) that disappears upon deuteration.
When heated for a short time with an equimolar
amount of hydrazine, 5,7ꢀdiarylpyrano[4,3ꢀd]pyrimidiꢀ
nium bromides 5a—c undergo recyclization into 8ꢀarylꢀ
1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimido[5,4ꢀd][1,2]diazeꢀ
pineꢀ2,4(3H,9H)ꢀdione hydrobromides 7a—c, which
are transformed into free bases 8a—c under the action of
water (Scheme 3).
The presence of the diazepine ring is confirmed by
doublets at δ 2.97—3.03 and 4.33—4.42 (J = 13.20—13.50 Hz)
1
in the H NMR spectra of compounds 8, which persist
upon deuteration. We assigned them to the signals for

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Kostrub et al.
Scheme 4
Scheme 5
Ar´ = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
salt 9a is more stable (by 18.3 kcal mol–1) than the
diazepinium cation in hydrobromide 7a.
The transformation can be represented as recyclization
in which hydrazine molecules serve as both nucleophiles
and nucleofuges. Apparently, the reaction proceeds
through the formation of intermediate dihydrazone A,
which undergoes the closure of a pyridine ring upon elimiꢀ
nation of the hydrazine molecule (Scheme 6).
In the proposed reaction scheme, the nucleophile may
attack either the C(5) or C(8) atom because both pathꢀ
ways lead to intermediate A.
The driving force of the reaction is the formation of
the aromatic pyridinium ion, which is more stable than
diazepine. This was confirmed by HF/6ꢀ311G* calculaꢀ
tions8 of the total energies of pyrimido[5,4ꢀd][1,2]ꢀ
diazepine hydrobromide 7a and 6ꢀaminopyrido[4,3ꢀd]ꢀ
pyrimidinium bromide 9a. Indeed, pyridinium cation in
Thus, we studied reactions of 5ꢀarylꢀ and 5,7ꢀdiarylꢀ
pyrano[4,3ꢀd]pyrimidinium salts with hydrazine. We
found that 5ꢀarylpyrano[4,3ꢀd]pyrimidinium perchlorates
yield 6ꢀaminopyrido[4,3ꢀd]pyrimidinium salts, regardless
of the reaction conditions. At the same time, 5,7ꢀdiarylꢀ
pyrano[4,3ꢀd]pyrimidinium salts can yield both pyrimidoꢀ
[5,4ꢀd][1,2]diazepines and 6ꢀaminopyrido[4,3ꢀd]pyrimiꢀ
dinium salts, depending on the reaction time and the
hydrazine concentration. The formation of 6ꢀaminoꢀ
pyrido[4,3ꢀd]pyrimidinium salts is preceded by recyclizaꢀ
tion of the 5,7ꢀdiarylpyrano[4,3ꢀd]pyrimidinium salt into
pyrimido[5,4ꢀd][1,2]diazepinium salts.
Scheme 6

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1757
5ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀ
pyrano[4,3ꢀd]pyrimidinium perchlorate (3b). Yield 4.20 g (94%),
colorless crystals, m.p. 238—240 °C (AcOEt). Found (%):
C, 40.56; H, 2.50; Br + Cl, 25.62. C15H12BrClN2O7. Calculated
Experimental
IR spectra were recorded on a Specord IRꢀ71 spectrophoꢀ
tometer (Nujol). 1H NMR spectra were recorded on Bruker
Avance DPXꢀ250 and Varian Unityꢀ300 instruments in CDCl3,
DMSOꢀd6, and CDCl3 + CF3COOH with HMDS as the internal
standard. Compounds 1a—c were prepared as described earlier.9
5ꢀAroylꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀmorpholinoethenyl)pyrimidineꢀ
2,4(1H,3H)ꢀdiones 2 (general procedure). A mixture of 5ꢀaroylꢀ
1,3,6ꢀtrimethylpyrimidineꢀ2,4ꢀdione 1 (0.02 mol), triethyl
orthoformate (0.06 mol), and morpholine (0.06 mol) was
refluxed for 2 h. On cooling to 80 °C, EtOH (15 mL) was added
and the resulting suspension was refluxed for 3—5 min. The
precipitate was filtered off, washed with EtOH, and dried
at 80—100 °C.
5ꢀBenzoylꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀmorpholinoethenyl)pyrimiꢀ
dineꢀ2,4(1H,3H)ꢀdione (2a). Yield 4.12 g (58%), yellow crystals,
m.p. 154—156 °C (EtOH). Found (%): C, 63.88; H, 5.83.
C19H21N3O4. Calculated (%): C, 64.21; H, 5.96. 1H NMR
(CDCl3), δ: 2.91 (t, 4 H, N(CH2)2, J = 4.9 Hz); 3.35 (s, 3 H,
N(3)Me); 3.41 (s, 3 H, N(1)Me); 3.45 (t, 4 H, O(CH2)2,
J = 4.9 Hz); 4.51 (d, 1 H, C(6)CH, J = 12.95 Hz); 6.45 (d, 1 H,
C(6)CHCH, J = 12.95 Hz); 7.36 (t, 2 H, mꢀHPh, J = 7.07 Hz); 7.48
(t, 1 H, pꢀHPh, J = 7.27 Hz); 7.79 (d, 2 H, oꢀHPh, J = 6.95 Hz).
IR, ν/cm–1: 1605, 1660, 1695 (C=O).
5ꢀ(4ꢀBromobenzoyl)ꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀmorpholinoethenyl)ꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdione (2b). Yield 7.82 g (90%), yellow
crystals, m.p. 236—238 °C (EtOH). Found (%): C, 52.29;
H, 4.77; Br, 18.01. C19H20BrN3O4. Calculated (%): C, 52.55;
H, 4.64; Br, 18.40. 1H NMR (CDCl3), δ: 2.96 (t, 4 H, N(CH2)2,
J = 5.0 Hz); 3.34 (s, 3 H, N(3)Me); 3.41 (s, 3 H, N(1)Me);
3.51 (t, 4 H, O(CH2)2, J = 5.0 Hz); 4.54 (d, 1 H, C(6)CH,
J = 13.11 Hz); 6.44 (d, 1 H, C(6)CHCH, J = 13.11 Hz); 7.52
(d, 2 H, oꢀHAr, J = 8.48 Hz); 7.67 (d, 2 H, mꢀHAr, J = 8.48 Hz).
IR, ν/cm–1: 1620, 1670, 1705 (C=O).
5ꢀ(4ꢀMethoxybenzoyl)ꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀmorpholinoꢀ
ethenyl)pyrimidineꢀ2,4(1H,3H)ꢀdione (2c). Yield 5.93 g (77%),
yellow crystals, m.p. 172—176 °C (EtOH). Found (%): C, 62.65;
H, 5.80. C20H23N3O5. Calculated (%): C, 62.33; H, 6.02.
1H NMR (CDCl3), δ: 2.91 (t, 4 H, N(CH2)2, J = 4.9 Hz); 3.31
(s, 3 H, N(3)Me); 3.39 (s, 3 H, N(1)Me); 3.44 (t, 4 H, O(CH2)2,
J = 4.9 Hz); 3.80 (s, 3 H, OMe); 4.54 (d, 1 H, C(6)CH,
J = 13.14 Hz); 6.48 (d, 1 H, C(6)CHCH, J = 12.80 Hz); 6.84
(d, 2 H, mꢀHAr, J = 8.76 Hz); 7.78 (d, 2 H, oꢀHAr, J = 8.76 Hz).
IR, ν/cm–1: 1605, 1655, 1680 (C=O).
(%): C, 40.25; H, 2.70; Br + Cl, 25.77. 1H NMR (CDCl3
+
CF3COOH), δ: 3.49 (s, 3 H, N(3)Me); 3.86 (s, 3 H, N(1)Me);
7.63 (d, 2 H, mꢀHAr, J = 8.49 Hz); 7.76 (d, 2 H, oꢀHAr, J = 8.49 Hz);
7.84 (d, 1 H, C(8)H, J = 5.40 Hz); 8.95 (d, 1 H, C(7)H, J = 5.40 Hz).
IR, ν/cm–1: 1075, 1100 (Cl—O); 1630, 1690 (C=O).
5ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀ
pyrano[4,3ꢀd]pyrimidinium perchlorate (3c). Yield 2.59 g (65%),
colorless crystals, m.p. 196—198 °C (AcOEt). Found (%):
C, 48.42; H, 3.63; Cl, 8.60. C16H15ClN2O8. Calculated (%):
C, 48.19; H, 3.79; Cl, 8.89. 1H NMR (CDCl3 + CF3COOH), δ:
3.52 (s, 3 H, N(3)Me); 3.85 (s, 3 H, N(1)Me); 4.00 (s, 3 H,
OMe); 7.11 (d, 2 H, mꢀHAr, J = 8.42 Hz); 7.71 (br.s, 1 H, C(8)H);
7.88 (d, 2 H, oꢀHAr, J = 8.68 Hz); 8.84 (br.s, 1 H, C(7)H).
IR, ν/cm–1: 1095 (Cl—O); 1620, 1690 (C=O).
6ꢀ(2ꢀArylethenyl)ꢀ5ꢀbenzoylꢀ1,3ꢀdimethylpyrimidineꢀ
2,4(1H,3H)ꢀdiones 4 (general procedure). A solution of ketone
1a (0.02 mol), an aromatic aldehyde (0.03 mol), and piperidine
(0.01 mol) in EtOH (20 mL) was refluxed for 15 h. On cooling,
the precipitate that formed was filtered off, washed with EtOH,
and dried at 80—100 °C.
5ꢀBenzoylꢀ1,3ꢀdimethylꢀ6ꢀ(2ꢀphenylethenyl)pyrimidineꢀ
2,4(1H,3H)ꢀdione (4a). Yield 4.98 g (72%), yellow crystals,
m.p. 149—151 °C (EtOH). Found (%): C, 72.49; H, 5.05.
C21H18N2O3. Calculated (%): C, 72.82; H, 5.24. 1H NMR
(CDCl3), δ: 3.38 (s, 3 H, N(3)Me); 3.46 (s, 3 H, N(1)Me); 6.51
(d, 1 H, C(6)CH, J = 16.43 Hz); 6.81 (d, 1 H, C(6)CHCH,
J = 16.12 Hz); 7.14—7.22 (m, 2 H, oꢀHAr´); 7.23—7.29 (m, 3 H,
mꢀHAr´, pꢀHAr´); 7.38 (t, 2 H, mꢀHPh, J = 7.43 Hz); 7.50 (t, 1 H,
pꢀHPh, J = 7.43 Hz); 7.82 (d, 2 H, oꢀHPh, J = 6.95 Hz).
IR, ν/cm–1: 1630, 1655, 1700 (C=O).
5ꢀBenzoylꢀ6ꢀ[2ꢀ(4ꢀbromophenyl)ethenyl]ꢀ1,3ꢀdimethylpyriꢀ
midineꢀ2,4(1H,3H)ꢀdione (4b). Yield 5.95 g (70%), yellow
crystals, m.p. 195—198 °C (EtOH). Found (%): C, 59.08;
H, 4.30; Br, 18.52. C21H17BrN2O3. Calculated (%): C, 59.31;
H, 4.03; Br, 18.79. 1H NMR (CDCl3), δ: 3.37 (s, 3 H, N(3)Me);
3.45 (s, 3 H, N(1)Me); 6.49 (d, 1 H, C(6)CH, J = 16.2 Hz);
6.74 (d, 1 H, C(6)CHCH, J = 16.2 Hz); 7.03 (d, 2 H, oꢀHAr´
,
J = 8.48 Hz); 7.33—7.41 (m, 4 H, mꢀHAr´, mꢀHPh); 7.49 (t, 1 H,
pꢀHPh, J = 7.33 Hz); 7.79 (d, 2 H, oꢀHPh, J = 7.33 Hz). IR,
ν/cm–1: 1635, 1655, 1700 (C=O).
5ꢀBenzoylꢀ6ꢀ[2ꢀ(4ꢀmethoxyphenyl)ethenyl]ꢀ1,3ꢀdimethylꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdione (4c). Yield 5.86 g (78%), yellow
crystals, m.p. 178—181 °C (EtOH). Found (%): C, 70.47; H,
5.25. C22H20N2O4. Calculated (%): C, 70.20; H, 5.36. 1H NMR
(CDCl3), δ: 3.37 (s, 3 H, N(3)Me); 3.45 (s, 3 H, N(1)Me);
3.74 (s, 3 H, OMe); 6.35 (d, 1 H, C(6)CH, J = 16.11 Hz);
6.75 (d + d, 3 H, C(6)CHCH, mꢀHAr´, JCH—CH = 16.2 Hz,
5ꢀArylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀpyranoꢀ
[4,3ꢀd]pyrimidinium perchlorates 3 (general procedure). 70%
Perchloric acid (0.06 mol) was added dropwise to a stirred
suspension of enamine 2 (0.01 mol) in HC(OEt)3 (30 mL). The
resulting solution was refluxed for 5 min, cooled, and diluted
with AcOEt (30 mL). The precipitate that formed was filtered
off, washed with AcOEt, and dried at 80—100 °C.
JAr´ = 9.16 Hz); 7.12 (d, 2 H, oꢀHAr´, J = 8.47 Hz); 7.36 (t, 2 H,
1,3ꢀDimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,2H,3H,4Hꢀpyranoꢀ
[4,3ꢀd]pyrimidinium perchlorate (3a). Yield 3.21 g (87%),
colorless crystals, m.p. 153—155 °C (AcOEt). Found (%):
C, 48.64; H, 3.41; Cl, 9.42. C15H13ClN2O7. Calculated (%):
C, 48.86; H, 3.55; Cl, 9.61. 1H NMR (CDCl3 + CF3COOH), δ:
3.49 (s, 3 H, N(3)Me); 3.87 (s, 3 H, N(1)Me); 7.60 (t, 2 H,
mꢀHPh, J = 7.7 Hz); 7.76—7.79 (d + t, 3 H, oꢀHPh, pꢀHPh); 7.83
(d, 1 H, C(8)H, J = 5.34 Hz); 8.96 (d, 1 H, C(7)H, J = 5.34 Hz).
IR, ν/cm–1: 1090 br (Cl—O); 1630, 1695 (C=O).
mꢀHPh, J = 7.27 Hz); 7.48 (t, 1 H, pꢀHPh, J = 7.27 Hz); 7.80 (d,
2 H, oꢀHPh, J = 6.95 Hz). IR, ν/cm–1: 1640, 1660, 1700 (C=O).
7ꢀArylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,2H,3H,4Hꢀ
pyrano[4,3ꢀd]pyrimidinium bromides 5 (general procedure).
A solution of Br2 (0.01 mol) in CHCl3 (10 mL) was added
dropwise at 50—60 °C to a stirred solution of compound 4
(0.01 mol) in CHCl3 (30 mL). The reaction mixture was refluxed
for 30 min. The yellow precipitate that formed was filtered off,
washed with CHCl3 and AcOEt, and dried at 80—100 °C.

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Kostrub et al.
1,3ꢀDimethylꢀ2,4ꢀdioxoꢀ5,7ꢀdiphenylꢀ1H,2H,3H,4Hꢀpyranoꢀ
[4,3ꢀd]pyrimidinium bromide (5a). Yield 3.83 g (90%), yellow
crystals, m.p. 248—251 °C (CHCl3). Found (%): C, 59.12;
H, 3.88; Br, 18.59. C21H17BrN2O3. Calculated (%): C, 59.31;
H, 4.03; Br, 18.79. 1H NMR (CDCl3 + CF3COOH), δ: 3.52
(s, 3 H, N(3)Me); 4.01 (s, 3 H, N(1)Me); 7.63—7.72 (m, 4 H,
mꢀHPh, mꢀHPh´); 7.79—7.90 (m, 4 H, oꢀHPh, pꢀHPh, pꢀHPh´);
8.12 (s, 1 H, C(8)H); 8.19 (d, 2 H, oꢀHPh´, J = 7.53 Hz). IR,
ν/cm–1: 1620, 1695 (C=O).
7.29 (d, 2 H, oꢀHAr, J = 8.79 Hz); 7.97 (d, 1 H, C(8)H, J = 7.54
Hz); 8.91 (d, 1 H, C(7)H, J = 7.54 Hz). IR, ν/cm–1: 1090 br
(Cl—O); 1625, 1675 (C=O); 3260, 3325 (NH2).
8ꢀArylꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimido[5,4ꢀd][1,2]ꢀ
diazepineꢀ2,4(3H,9H)ꢀdione hydrobromides 7 (general procedure).
Hydrazine hydrate (2.2 mmol) was added to a stirred suspension
of pyrano[4,3ꢀd]pyrimidinium salt 5 (2 mmol) in AcOH (10 mL).
The resulting orange solution was refluxed for 1 min. On cooling,
the precipitate that formed was filtered off, washed with AcOH,
and dried at 80—100 °C.
7ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ
1H,2H,3H,4Hꢀpyrano[4,3ꢀd]pyrimidinium bromide (5b). Yield
4.03 g (80%), yellow crystals, m.p. 273—277 °C (CHCl3). Found (%):
C, 50.35; H, 3.47; Br, 32.14. C21H16Br2N2O3. Calculated (%):
1,3ꢀDimethylꢀ5,8ꢀdiphenylꢀ1Hꢀpyrimido[5,4ꢀd][1,2]ꢀ
diazepineꢀ2,4(3H,9H)ꢀdione hydrobromide (7a). Yield 648 mg
(74%), colorless crystals, m.p. 242—245 °C (AcOH). Found (%):
C, 57.17; H, 4.16; Br, 17.84. C21H19BrN4O2. Calculated (%):
1
C, 50.03; H, 3.20; Br, 31.70. H NMR (CDCl3 + CF3COOH),
1
δ: 3.52 (s, 3 H, N(3)Me); 4.00 (s, 3 H, N(1)Me); 7.68 (t, 2 H,
C, 57.41; H, 4.36; Br, 18.19. H NMR (DMSOꢀd6), δ: 2.91 (d,
mꢀHPh, J = 7.70 Hz); 7.80—7.88 (m, 5 H, oꢀHPh, pꢀHPh
,
1 H, C(9)H, J = 14.13 Hz); 3.03 (s, 3 H, N(3)Me); 3.50 (s, 3 H,
N(1)Me); 4.73 (d, 1 H, C(9)H, J = 14.13 Hz); 4.95—5.50 (br.s,
H+ + H2O); 7.34—7.41 (m, 3 H, mꢀHPh, pꢀHPh); 7.44—7.51
(m, 3 H, mꢀHPh´, pꢀHPh´); 7.61—7.66 (m, 2 H, oꢀHPh);
7.93—8.02 (m, 2 H, oꢀHPh´). IR, ν/cm–1: 1665, 1705 (C=O),
3380 br (NH).
8ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimidoꢀ
[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdione hydrobromide (7b).
Yield 652 mg (63%), colorless crystals, m.p. 281—286 °C (AcOH).
Found (%): C, 48.35; H, 3.38; Br, 30.56. C21H18Br2N4O2.
Calculated (%): C, 48.67; H, 3.50; Br, 30.84. 1H NMR (DMSOꢀd6),
δ: 2.91 (d, 1 H, C(9)H, J = 14.13 Hz); 3.02 (s, 3 H, N(3)Me);
3.51 (s, 3 H, N(1)Me); 4.38—4.53 (br.s, H+ + H2O); 4.69 (d,
1 H, C(9)H, J = 14.13 Hz); 7.33—7.42 (m, 3 H, mꢀHPh, pꢀHPh);
mꢀHAr´); 8.05 (d, 2 H, oꢀHPh, J = 8.48 Hz); 8.13 (s, 1 H,
C(8)H). IR, ν/cm–1: 1615, 1685 (C=O).
7ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ
1H,2H,3H,4Hꢀpyrano[4,3ꢀd]pyrimidinium bromide (5c). Yield
3.78 g (83%), yellow crystals, m.p. 227—229 °C (CHCl3). Found (%):
C, 58.28; H, 4.10; Br, 17.73. C22H19BrN2O4. Calculated (%):
1
C, 58.04; H, 4.21; Br, 17.55. H NMR (CDCl3 + CF3COOH),
δ: 3.51 (s, 3 H, N(3)Me); 3.96—4.01 (both s, 6 H, N(1)Me, OMe);
7.18 (d, 2 H, mꢀHAr´, J = 8.84 Hz); 7.66 (t, 2 H, mꢀHPh, J = 7.59 Hz);
7.78—7.87 (m, 3 H, oꢀHPh, pꢀHPh); 7.95 (s, 1 H, C(8)H); 8.21
(d, 2 H, oꢀHAr´, J = 8.85 Hz). IR, ν/cm–1: 1605, 1680 (C=O).
6ꢀAminoꢀ5ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,2H,3H,4Hꢀ
pyrido[4,3ꢀd]pyrimidinium perchlorates 6 (general procedure).
Hydrazine hydrate (0.55 mmol) was added to a stirred suspenꢀ
sion of pyrano[4,3ꢀd]pyrimidinium salt 3 (0.5 mmol) in AcOH
(2 mL). The resulting bright red solution was refluxed for 5 min.
On cooling, the precipitate that formed was filtered off, washed
with AcOH, and dried at 80—100 °C.
6ꢀAminoꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,2H,3H,4Hꢀ
pyrido[4,3ꢀd]pyrimidinium perchlorate (6a). Yield 151 mg (79%),
colorless crystals, m.p. 234—236 °C (AcOH). Found (%):
C, 47.22; H, 3.76; Cl, 8.91. C15H15ClN4O6. Calculated (%):
C, 47.07; H, 3.95; Cl, 9.26. 1H NMR (DMSOꢀd6), δ: 3.11 (s,
3 H, N(3)Me); 3.60 (s, 3 H, N(1)Me); 7.15 (br.s, 2 H, NH2);
7.60—7.71 (m, 4 H, oꢀHPh, mꢀHAr´); 7.92 (d, 2 H, oꢀHAr´
,
J = 8.47 Hz). IR, ν/cm–1: 1670, 1710 (C=O), 3380 br (NH).
8ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimidoꢀ
[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdione hydrobromide (7c).
Yield 748 mg (80%), colorless crystals, m.p. 259—261 °C (AcOH).
Found (%): C, 56.43; H, 4.32; Br, 17.37. C22H21BrN4O3.
Calculated (%): C, 56.30; H, 4.51; Br, 17.02. 1H NMR (DMSOꢀd6),
δ: 2.89 (d, 1 H, C(9)H, J = 14.22 Hz); 3.06 (s, 3 H, N(3)Me);
3.56 (s, 3 H, N(1)Me); 3.83 (s, 3 H, OMe); 4.50—5.05 (br.s + d,
H+ + H2O, C(9)H, J = 13.90 Hz); 7.05 (d, 2 H, mꢀHAr´
,
J = 8.85 Hz); 7.38—7.44 (m, 3 H, mꢀHPh, pꢀHPh); 7.63—7.69
7.30—7.36 (m, 2 H, mꢀHPh); 7.50—7.56 (m, 3 H, oꢀHPh
,
(m, 2 H, oꢀHPh); 7.98 (d, 2 H, oꢀHAr´, J = 8.84 Hz). IR, ν/cm–1
:
pꢀHPh); 8.01 (d, 1 H, C(8)H, J = 7.54 Hz); 8.94 (d, 1 H, C(7)H,
J = 7.54 Hz). IR, ν/cm–1: 1070, 1090 (Cl—O); 1615, 1670
(C=O); 3245, 3350 (NH2).
1660, 1705 (C=O), 3375 br (NH).
8ꢀArylꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimido[5,4ꢀd][1,2]ꢀ
diazepineꢀ2,4(3H,9H)ꢀdiones 8 (general procedure). Diazepine
bromide 7 (200 mg) was treated with a mixture of water (10 mL)
and CHCl3 (10 mL). The chloroform layer was separated and
evaporated to dryness. The product was dried at 80—100 °C.
1,3ꢀDimethylꢀ5,8ꢀdiphenylꢀ1Hꢀpyrimido[5,4ꢀd][1,2]ꢀ
diazepineꢀ2,4(3H,9H)ꢀdione (8a). Yield 146 mg (90%), colorless
crystals, m.p. 255—258 °C (CHCl3). Found (%): C, 70.04;
H, 5.17. C21H18N4O2. Calculated (%): C, 70.38; H, 5.06. 1H
NMR (CDCl3), δ: 3.02 (d, 1 H, C(9)H, J = 13.50 Hz); 3.26 (s,
3 H, N(3)Me); 3.62 (s, 3 H, N(1)Me); 4.41 (d, 1 H, C(9)H,
6ꢀAminoꢀ5ꢀ(4ꢀbromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium perchlorate (6b). Yield
196 mg (85%), colorless crystals, m.p. 320—324 °C (AcOH).
Found (%): C, 38.86; H, 3.05; Br + Cl, 24.65. C15H14BrClN4O6.
Calculated (%): C, 39.03; H, 3.06; Br + Cl, 24.99. 1H NMR
(DMSOꢀd6), δ: 3.18 (s, 3 H, N(3)Me); 3.66 (s, 3 H, N(1)Me);
7.19 (s, 2 H, NH2); 7.31 (d, 2 H, mꢀHAr, J = 8.4 Hz); 7.69 (d,
2 H, oꢀHAr, J = 8.4 Hz); 8.03 (d, 1 H, C(8)H, J = 7.5 Hz); 8.94
(d, 1 H, C(7)H, J = 7.5 Hz). IR, ν/cm–1: 1100 br (Cl—O);
1630, 1685 (C=O); 3255, 3340 (NH2).
J = 13.19 Hz); 7.39—7.50 (m, 6 H, mꢀHPh, pꢀHPh, mꢀHPh´
,
6ꢀAminoꢀ5ꢀ(4ꢀmethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium perchlorate (6c). Yield
148 mg (72%), colorless crystals, m.p. 300—303 °C (AcOH).
Found (%): C, 46.28; H, 4.03; Cl, 8.37. C16H17ClN4O7. Calcuꢀ
lated (%): C, 46.56; H, 4.15; Cl, 8.59. 1H NMR (DMSOꢀd6), δ:
3.12 (s, 3 H, N(3)Me); 3.59 (s, 3 H, N(1)Me); 3.82 (s, 3 H,
OMe); 7.09 (d, 2 H, mꢀHAr, J = 8.79 Hz); 7.17 (br.s, 2 H, NH2);
pꢀHPh´); 7.67—7.72 (m, 2 H, oꢀHPh); 7.83—7.90 (m, 2 H,
oꢀHPh´). IR, ν/cm–1: 1645, 1700 (C=O).
8ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimidoꢀ
[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdione (8b). Yield 128 mg
(76%), colorless crystals, m.p. 283—287 °C (CHCl3). Found (%):
C, 57.85; H, 4.07; Br, 17.93. C21H17BrN4O2. Calculated (%):
C, 57.68; H, 3.92; Br, 18.27. 1H NMR (CDCl3), δ: 3.00 (d,

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 8, August, 2008
1759
1 H, C(9)H, J = 13.50 Hz); 3.26 (s, 3 H, N(3)Me); 3.60 (s, 3 H,
N(1)Me); 4.33 (d, 1 H, C(9)H, J = 13.50 Hz); 7.39—7.45 (m,
3 H, mꢀHPh, pꢀHPh); 7.59 (d, 2 H, mꢀHAr´, J = 8.79 Hz);
7.66—7.70 (m, 2 H, oꢀHPh); 7.73 (d, 2 H, oꢀHAr´, J = 8.80 Hz).
IR, ν/cm–1: 1650, 1705 (C=O).
8ꢀ(4ꢀMethoxyphenyl)ꢀ1,3ꢀdimethylꢀ5ꢀphenylꢀ1Hꢀpyrimidoꢀ
[5,4ꢀd][1,2]diazepineꢀ2,4(3H,9H)ꢀdione (8c). Yield 149 mg
(90%), colorless crystals, m.p. 266—268 °C (CHCl3). Found (%):
C, 67.74; H, 5.12. C22H20N4O3. Calculated (%): C, 68.03; H,
5.19. 1H NMR (CDCl3), δ: 2.97 (d, 1 H, C(9)H, J = 13.19 Hz);
3.26 (s, 3 H, N(3)Me); 3.61 (s, 3 H, N(1)Me); 3.85 (s, 3 H,
OMe); 4.38 (d, 1 H, C(9)H, J = 13.50 Hz); 6.96 (d, 2 H,
mꢀHAr´, J = 9.1 Hz); 7.38—7.43 (m, 3 H, mꢀHPh, pꢀHPh);
7.66—7.71 (m, 2 H, oꢀHPh); 7.82 (d, 2 H, oꢀHAr´, J = 9.1 Hz).
IR, ν/cm–1: 1650, 1700 (C=O).
6ꢀAminoꢀ7ꢀarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium bromides 9 (general
procedure). Method A. Hydrazine hydrate (1.5 mmol) was added
to a stirred suspension of pyrano[4,3ꢀd]pyrimidinium salt 5
(0.5 mmol) in AcOH (2 mL). The reaction mixture was refluxed
for 30 min, the original orange solution turning pale yellow. The
solution was cooled and diluted with Et2O (2 mL). The precipiꢀ
tate that formed was filtered off, washed with Et2O and AcOH,
and dried at 80—100 °C.
C, 56.58; H, 4.42; Br, 16.67. C22H21BrN4O3. Calculated (%):
C, 56.30; H, 4.51; Br, 17.03. H NMR (DMSOꢀd6), δ: 3.15 (s,
3 H, N(3)Me); 3.70 (s, 3 H, N(1)Me); 3.88 (s, 3 H, OMe); 6.39
(s, 2 H, NH2); 7.19 (d, 2 H, mꢀHAr´, J = 8.66 Hz); 7.47—7.53
(m, 2 H, mꢀHPh); 7.54—7.60 (m, 3 H, oꢀHPh, pꢀHPh); 7.92 (d,
3 H, C(8)H, oꢀHAr´, J = 7.93 Hz). IR, ν/cm–1: 1600, 1690
(C=O); 3250, 3285 (NH2).
1
References
1. E. B. Tsupak, M. A. Shevchenko, V. V. Kostrub, Yu. N.
Tkachenko, Izv. Akad. Nauk, Ser. Khim., 2007, 2251 [Russ.
Chem. Bull., Int. Ed., 2007, 56, 2330].
2. A. T. Balaban, A. Dinculescu, G. N. Dorofeenko, G. W.
Fischer, A. V. Koblik, V. V. Mezheritskii, W. Schroth,
Pyrylium Salts: Synthesis, Reactions and Physical Properties,
Adv. Heterocycl. Chem., Suppl. 2, Academic Press, New York,
1982, 434 pp.
3. E. V. Kuznetsov, I. V. Shcherbakova, A. T. Balaban, Adv.
Heterocycl. Chem., 1990, 50, 157.
4. G. N. Dorofeenko, E. I. Sadekova, V. M. Goncharova, Khim.
Geterotsikl. Soedin., 1970, 1308 [Chem. Heterocycl. Compd.,
1970, 1218 (Engl. Transl.)].
5. J. Korösi, T. Lang, Chem. Ber., 1974, 107, 3883.
Method B. Hydrazine hydrate (0.55 mmol) was added to a
stirred suspension of diazepine bromide 7 (0.5 mmol) in AcOH
(2 mL). The reaction mixture was refluxed for 30 min, the original
orange solution turning pale yellow. The solution was cooled
and diluted with Et2O (2 mL). The precipitate that formed was
filtered off, washed with Et2O and AcOH, and dried at 80—100 °C.
6ꢀAminoꢀ1, 3ꢀdimethylꢀ2, 4ꢀdioxoꢀ5, 7ꢀdiphenylꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (9a). Yield
178 mg (81%) (method A) or 158 mg (72%) (method B), colorꢀ
less crystals, m.p. 192—195 °C (AcOH). Found (%): C, 57.20;
H, 4.21; Br, 17.98. C21H19BrN4O2. Calculated (%): C, 57.41;
H, 4.36; Br, 18.19. 1H NMR (DMSOꢀd6), δ: 3.12 (s, 3 H,
N(3)Me); 3.66 (s, 3 H, N(1)Me); 6.34 (s, 2 H, NH2); 7.44—7.65
(m, 8 H, 4 mꢀHPh + 2 pꢀHPh + 2 oꢀHPh); 7.84—7.90 (m, 2 H,
2 oꢀHPh); 7.96 (s, 1 H, C(8)H). IR, ν/cm–1: 1610, 1660 (C=O);
3250, 3350 (NH2).
6ꢀAminoꢀ7ꢀ(4ꢀbromophenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ
1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (9b). Yield
194 mg (75%) (method A) or 181 mg (70%) (method B), colorꢀ
less crystals, m.p. 272—275 °C (AcOH). Found (%): C, 48.36;
H, 3.35; Br, 31.09. C21H18Br2N4O2. Calculated (%): C, 48.67;
H, 3.50; Br, 30.84. 1H NMR (DMSOꢀd6), δ: 3.12 (s, 3 H,
N(3)Me); 3.65 (s, 3 H, N(1)Me); 6.32 (s, 2 H, NH2); 7.41—7.46
(m, 2 H, mꢀHPh); 7.51—7.58 (m, 3 H, oꢀHPh + pꢀHPh); 7.82
(d + d, 4 H, oꢀHAr´, mꢀHAr´, J = 9.1 Hz); 7.99 (s, 1 H, C(8)H).
IR, ν/cm–1: 1610, 1670 (C=O); 3300, 3330 (NH2).
6. S. L. Bogza, S. Yu. Suikov, N. M. Bogdan, V. I. Dulenko, K.
I. Kobrakov, Khim. Geterotsikl. Soedin., 2004, 1507 [Chem.
Heterocycl. Compd., 2004, 40, 1300 (Engl. Transl.)].
7. S. L. Bogza, S. Yu. Suikov, N. M. Bogdan, Yu. A. Nikolyukin,
V. I. Dulenko, Khim. Geterotsikl. Soedin., 2004, 1645 [Chem.
Heterocycl. Compd., 2004, 40, 1421 (Engl. Transl.)].
8. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A. Montꢀ
gomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J.
M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O.
Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B.
Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma, D. K.
Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J.
Cioslowski, J. V. Ortiz, A. G. Baboul, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L.
Martin, D. J. Fox, T. Keith, M. A. AlꢀLaham, C. Y. Peng, A.
Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson,
W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Headꢀ
Gordon, E. S. Replogle, J. A. Pople, Gaussian 98, Revision
A.9, Gaussian, Inc., Pittsburgh PA (USA), 1998.
9. E. B. Tsupak, M. A. Shevchenko, A. F. Pozharskii, Yu. N.
Tkachenko, Khim. Geterotsikl. Soedin., 2003, 1096 [Chem.
Heterocycl. Compd., 2003, 39, 953 (Engl. Transl.)].
6ꢀAminoꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
5ꢀphenylꢀ1H,2H,3H,4Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (9c).
Yield 173 mg (74%) (method A) or 185 mg (79%) (method B),
colorless crystals, m.p. 207—208 °C (AcOH). Found (%):
Received January 10, 2008