Pyrano[4,3-d]pyrimidinium salts Transformations of 5, 7-diaryl-1, 3-dimethyl-2, 4-dioxo-1/7, 3/7-pyrano[4, 3-d]pyrimidinium bromides under the action of phenylhydrazines and aromatic acid hydrazides

Article abstract of DOI:10.1007/s11172-009-0197-x

Reactions of 5, 7-diaryl-1, 3-dimethyl-2, 4-dioxo-15, 35-pyrano[4, 3-d]pyrimidinium bromides with phenylhydrazines and aromatic acid hydrazides have been studied. The reaction of the salts indicated with phenylhydrazine at ～20 °C results in the pyrylium r

Full text of DOI:10.1007/s11172-009-0197-x

Russian Chemical Bulletin, International Edition, Vol. 58, No. 7, pp. 1469—1475, July, 2009
1469
Pyrano[4,3ꢀd]pyrimidinium salts
4.* Transformations of 5,7ꢀdiarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀ
pyrano[4,3ꢀd]pyrimidinium bromides under the action of phenylhydrazines
and aromatic acid hydrazides
V. V. Kostrub,a E. B. Tsupak,a and A. F. Smol´yakovb
aDepartment of Chemistry, South Federal University,
7 ul. Zorge, 344090 RostovꢀonꢀDon, Russian Federation.
Fax: +7 (863) 297 5267. Eꢀmail: dastr@yandex.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: rengenhik@gmail.com
Reactions of 5,7ꢀdiarylꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrano[4,3ꢀd]pyrimidinium broꢀ
mides with phenylhydrazines and aromatic acid hydrazides have been studied. The reaction of
the salts indicated with phenylhydrazine at ~20 °C results in the pyrylium ring opening, whereas
elevated temperature leads to recyclization products, i.e., 1,3ꢀdimethylpyrido[4,3ꢀd]pyrimidineꢀ
2,4(1H,3H)ꢀdiones. The reactions of the starting bromides with mꢀcarboxyphenylhydrazine
and aromatic acid hydrazides lead to 6ꢀ(Rꢀamino)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrido[4,3ꢀd]ꢀ
pyrimidinium salts.
Key words: pyrano[4,3ꢀd]pyrimidinium salts, phenylhydrazine, hydrazone, Xꢀray diffracꢀ
tion analysis, pyrido[4,3ꢀd]pyrimidines, aromatic acid hydrazides, recyclization, pyrido[4,3ꢀd]ꢀ
pyrimidinium salts.
Earlier,2 we have reported that 5,7ꢀdiarylꢀ1,3ꢀdimethꢀ
ylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrano[4,3ꢀd]pyrimidinium bromꢀ
ides 1 upon a shortꢀtime heating with equimolar amount
of hydrazine undergo recyclization to 1Hꢀpyrimido[5,4ꢀd]ꢀ
[1,2]diazepineꢀ2,4(3H,9H)ꢀdione hydrobromides 2. At the
same time, compounds 1 and 2 upon treatment with exꢀ
cess hydrazine for 30 min are transformed to 6ꢀaminoꢀ
1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinꢀ
ium salts 3 (Scheme 1).
depends differently on the reaction conditions: the action
of equimolar amount of hydrazine results in recyclization
to Nꢀaminoisoquinoline derivatives, whereas excess nuꢀ
cleophile leads to the pyrylium ring expansion and formaꢀ
tion of benzoꢀ2,3ꢀdiazepines.3—5
The reactions of benzo[c]pyrylium salts with phenylꢀ
hydrazine and aromatic acid hydrazides under various
conditions furnish Nꢀ(Rꢀamino)isoquinolinium derivaꢀ
tives,6—8 benzoꢀ2,3ꢀdiazepines,8,9 or yield mixtures of both
products.5
Analogous transformations of benzo[c]pyrylium salts
are also described, however, structures of the products
In the present work, we study reactions of 5,7ꢀdiarylꢀ
1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀpyrano[4,3ꢀd]pyrimidinium
salts 1 with phenylhydrazines and aromatic acid hydrazides.
* For Part 3, see Ref. 1.
Scheme 1
i. 1 min; ii. 30 min.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1426—1432, July, 2009.
1066ꢀ5285/09/5807ꢀ1469 © 2009 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
Kostrub et al.
We found that the reaction of pyrimidopyrylium broꢀ
mides 1a—c with phenylhydrazine in glacial acetic acid at
~20 °C results in the formation of 1,3ꢀdimethylꢀ6ꢀ(2ꢀarylꢀ
2ꢀoxoethyl)ꢀ5ꢀ[phenyl(phenylhydrazono)methyl]pyrimiꢀ
dineꢀ2,4(1H,3H)ꢀdiones 4a—c (Scheme 2).
C(11A)
C(10A)
C(12A)
C(13A)
C(9A)
C(8A)
C(7A)
O(4A)
C(3NA)
N(3A)
C(6A)
N(2A)
N(4A)
C(19A)
C(4A)
C(5A)
N(1A)
C(18A)
C(17A)
Scheme 2
C(2A)
C(20A)
C(14A)
O(2A)
C(2S)
C(3S)
C(21A)
C(16A)
C(15A)
O(21A)
C(22A)
O(1S)
C(27A)
C(1NA)
C(26A)
C(25A)
C(23A)
C(24A)
Br(1A)
Fig. 1. Molecular structure of conformer A of compound 4b.
a weak intermolecular hydrogen bond with atom O(2B)
(the distance H(4NB)...O(2B) is 2.30(3) Å, the angle
N(4B)—H(4NB)—O(2B) is 156(4)°). The solvate moleꢀ
cule of alcohol, in turn, is involved into the formation of
hydrogen bond with the O atom of the uracil fragment
of molecule A (O(1S)—H(1OS)...O(2A), the distance
H(1OS)...O(2A) is 2.06(5) Å, the distance O(1S)...O(2A) is
2.867(4) Å, the angle O(1S)—H(1OS)—O(2A) is 156(4)°).
The intermolecular interactions Br(1A)...N(2A) [–x, 1 – y,
2 – z] (3.1250(2) Å) combine molecules A in dimers, which
are additionally stabilized by the stackingꢀinteraction beꢀ
tween the phenyl rings of the 4ꢀbromophenacyl substituꢀ
ent (the distance between atoms C(26A) and C(23A)
[–x, 1 – y, 2 – z] is 3.6918(4) Å). Despite the difference in
the nature and stability of the Hꢀbonds, the bond disꢀ
Ar = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
The structures of products 4a—c are established by
spectroscopic methods. The structure of compound 4b is
confirmed by Xꢀray diffraction analysis. The 1H NMR
spectra of products 4 exhibit the signals for the CH2 protons
in the form of two doublets in the region δ 4.00—4.29
with the spinꢀspin coupling constant of 17.89 Hz, which
do not disappear by deuteration and do not change on
heating. The singlet in the region δ 7.57—7.88 disapꢀ
pearing on deuteration was assigned by us to the proton of
the NH group. In the IR spectra, there are found bands in
the region 1646—1713 cm–1 related to the stretching vibraꢀ
tions of the C=O groups and the maximum at ~3290 cm–1
corresponding to the NH group. In the mass spectrum of
compound 4a, there is a molecular ion peak with m/z 452
[M]+, as well as peaks with m/z 375 [M – C6H5]+, 333
[M – C6H5COCH2]+.
According to the Xꢀray analysis data, compound 4b is
crystallized in the centerꢀsymmetric space group (Рꢀ1).
The crystal contains two crystallographically independent
molecules (A and B) and one solvate ethanol molecule.
Molecules A and B are two conformers differing in the
degree of turning of the substituent on the atom C(5) with
respect to the C(5)—C(7) bond (Figs 1 and 2). The differꢀ
ences observed lead to a change in the type of hydrogen
bonds. In molecule A, there is present intramolecular hyꢀ
drogen bond N(4A)—H(4NA)...O(21A) (the distance
H(4NA)...O(21A) is 2.25(4) Å, the distance N(4A)...O(21A)
is 2.980(4) Å, the angle N(4A)—H(4NA)—O(21A) is
141(3)°). In molecule B, the N(4B)—H(4NB) group forms
O(2B)
C(1NB)
C(2B)
C(23B)
C(3NB)
O(21B)
C(21B)
N(1B)
C(6B)
C(20B)
C(27B)
C(22B)
C(24B)
N(3B)
C(4B)
O(4B)
C(25B)
Br(1B)
C(26B)
C(5B)
C(7B)
C(13B)
C(8B)
C(12B)
C(11B)
N(4B)
N(2B)
C(9B)
C(14B)
C(15B)
C(10B)
C(19B)
C(16B)
C(17B)
C(18B)
Fig. 2. Molecular structure of conformer B of compound 4b.

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
1471
Scheme 3
Scheme 5
tances in the two independent molecules A and B are virꢀ
tually the same, and the uracil fragment geometry is close
to the geometry of 1,3ꢀdimethyluracil10 (Table 1).
The fact that the reaction under consideration leads to
hydrazones 4 definitely indicates a predominance of the
nucleophilic attack at position 5 rather than at position 7
of the pyrylium ring in the molecules of compound 1
(Scheme 3).
According to the literature data,11,12 the formation of
the pyrylium ring opening products upon the action of
Nꢀnucleophiles occurs extremely rare and so far has not been
known in the series of pyrano[4,3ꢀd]pyrimidinium salts.
We found that pyrimidopyrylium bromides 1a—c upon
heating with phenylhydrazine in glacial acetic acid for 2 h
are converted to 5,7ꢀdiarylꢀ1,3ꢀdimethylpyrido[4,3ꢀd]ꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdiones 5a—c (Scheme 4).
Ar = 4ꢀBrC6H4
Scheme 4
Table 1. Main bond distances (d) and bond angles (ω) in
independent molecules A and B of compound 4b
Parameter
Bond
A
B
d/Å
N(2)—C(7)
N(2)—N(4)
N(3)—C(3N)
N(4)—C(14)
C(4)—O(4)
C(4)—C(5)
C(5)—C(6)
C(5)—C(7)
C(6)—C(20)
C(7)—C(8)
C(20)—C(21)
C(21)—O(21)
1.290(4)
1.347(3)
1.470(4)
1.393(4)
1.217(3)
1.459(4)
1.352(4)
1.503(4)
1.514(4)
1.474(4)
1.527(4)
1.213(3)
1.283(4)
1.347(3)
1.478(4)
1.396(4)
1.226(4)
1.444(4)
1.355(4)
1.507(4)
1.498(4)
1.473(4)
1.525(4)
1.219(4)
Ar = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c)
The structures of products 5a—c were confirmed by alꢀ
ternative synthesis from salts 1a—c and ammonia in aqueous
ethanol according to the procedure described earlier.13
We suggested that hydrazones 4 obtained at ~20 °C are
intermediate compounds in the reaction leading to pyriꢀ
do[4,3ꢀd]pyrimidineꢀ2,4(1H,3H)ꢀdiones 5 upon heating
pyrimidopyrylium salts 1 with phenylhydrazine. In fact,
after heating hydrazone 4b for 2 h in acetic acid, pyriꢀ
do[4,3ꢀd]pyrimidineꢀ2,4(1H,3H)ꢀdione 5b was isolated in
48% yield (Scheme 5).
Angle
ω/deg
N(2)—C(7)—C(5)
N(2)—N(4)—C(14)
N(2)—C(7)—C(8)
C(4)—C(5)—C(7)
C(5)—C(6)—C(20)
C(6)—C(5)—C(7)
C(7)—N(2)—N(4)
122.5(3)
119.7(3)
117.5(3)
117.5(2)
121.4(3)
122.7(3)
119.6(2)
122.9(3)
120.6(3)
118.6(3)
116.1(3)
121.8(3)
122.8(3)
120.1(3)

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Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
Kostrub et al.
Scheme 6
R = Ph
Probably, upon elevation of temperature hydrazone 4
undergoes cyclization due to the intramolecular attack by
the hydrazone N atom on the C atom of the aroylmethyl
group at the adjacent position of the uracil ring, which
leads to the intermediate C. Further, the O atom of the
hydroxy group intramolecularly attacks the N atom of the
phenylamino group, as a result, the "aniline" fragment
migrates to the hydroxyl to form compound D, which
aromatizes to product 5 by elimination of phenylhydroxyꢀ
lamine (Scheme 6).
At the same time, the reactions of pyrimidopyrylium
bromides 1 with mꢀcarboxyphenylhydrazine and aroylꢀ
hydrazines in boiling acetic acid lead to Nꢀsubstituted deꢀ
rivatives of 6ꢀ(Rꢀamino)ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ1H,3Hꢀ
pyrido[4,3ꢀd]pyrimidinium 6a—c and 7a—c (Scheme 7).
The 1H NMR spectra of compounds 6a—c exhibit
signals for the protons of three aromatic substituents,
the singlet in the region δ 8.13—8.24 belonging to the
CH proton of the pyridinium ring, as well as the signals
for the NH proton at δ 10.11—10.16 and proton of
the carboxy group in the region δ 11.40—13.80, which
disappear on deuteration. The IR spectra of compounds
6a—c contain the bands in the region 1675—1700 cm–1
and at 3270—3275 cm–1 related to the stretching viꢀ
brations of the carbonyl groups and NH group, respecꢀ
tively. In the 1H NMR spectra of salts 7a—c, there
are also present the signals for the protons of three aroꢀ
matic substituents and the signal for the NH proton
of the aroylamide group at δ 12.05—13.87, disappearꢀ
ing on deuteration. In the IR spectra of compounds
7a—c, there are observed the bands in the region
1620—1690 cm–1 corresponding to the stretching vibraꢀ
tions of the carbonyl groups, and a broad absorption band
at 3406—3408 cm–1 related to the aroylamino group. The
mass spectra of compounds 6a, 7a, and 7b exhibit peaks
corresponding to the fragmentation with the cleavage of
the N—N bond.
Scheme 7
The formation of pyridopyrimidium bromides 6 and 7
proceeds apparently also through the formation of the inꢀ
termediate of the type C, which with participation of the
substituent at the exocyclic atom N undergoes another
transformations. For instance, the mꢀcarboxyphenyl group
promotes formation of poorly soluble pyridinium salts 6,
which immediately precipitates and does not undergo furꢀ
ther transformations (Scheme 8).
In the reaction of salts 1 with aromatic acid hydrazides
due to the involvement of the carbonyl O atom of the aroyl
group into the intramolecular hydrogen bond, the stabiliꢀ
zation of the type C intermediate does not follow the mechꢀ
anism given in Scheme 6, rather it is due to the eliminaꢀ
1, 6: Ar = Ph (a), 4ꢀBrC6H4 (b), 4ꢀMeOC6H4 (c);
6: R = 3ꢀCO2HC6H4;
7: Ar = Ph: R = PhCO (a), 4ꢀClC6H4CO (b), 4ꢀMeOC6H4CO (c)

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
1473
Scheme 8
1.75 kV). Bromides 1 were synthesized according to the proceꢀ
dures described earlier.2
6ꢀ(2ꢀArylꢀ2ꢀoxoethyl)ꢀ1,3ꢀdimethylꢀ5ꢀ[phenyl(phenylhydrꢀ
azono)methyl]pyrimidineꢀ2,4(1H,3H)ꢀdiones 4 (general proceꢀ
dure). A suspension of salt 1 (0.5 mmol), phenylhydrazine
(0.054 mL, 59.4 mg, 0.55 mmol), and triethylamine (0.077 mL,
55.6 mg, 0.55 mmol) in AcOH (2 mL) was stirred for 1 h at
~20 °C. The solvent was evaporated at ~20 °C (on a watch glass
or in a porcelain dish), the oil formed was recrystallized using
water. A precipitate was filtered off, washed with water and EtOH
and dried at 80—100 °C.
1,3ꢀDimethylꢀ6ꢀ(2ꢀoxoꢀ2ꢀphenylethyl)ꢀ5ꢀ[phenyl(phenylꢀ
hydrazono)methyl]pyrimidineꢀ2,4(1H,3H)ꢀdione (4a). The yield
was 160 mg (71%), pale yellow crystals, m.p. 145—148 °C (from
EtOH). Found (%): C, 71.54; H, 5.29. C27H24N4O3. Calculatꢀ
ed (%): C, 71.67; H, 5.35. 1H NMR (CDCl3), δ: 3.40, 3.44
(both s, 3 H each, N(1)Mе, N(3)Mе); 4.05 (d, 1 H, CH2,
J = 17.89 Hz); 4.29 (d, 1 H, CH2, J = 17.89 Hz); 6.80 (t, 1 H, Ar,
J = 7.19 Hz); 7.05 (d, 2 H, Ar, J = 7.37 Hz); 7.17 (t, 2 H, Ar,
J = 7.90 Hz); 7.26—7.39 (m, 5 H, Ar); 7.53 (t, 1 H, Ar, J = 7.37 Hz);
7.62 (dd, 2 H, Ar, Jo = 8.07 Hz, Jm = 1.40 Hz); 7.69—7.78 (m, 3 H,
Ar, NH). IR, ν/cm–1: 1646, 1695 (C=O); 3299 (NH). MS, m/z:
452 [M]+, 375 [M – C6H5]+, 333 [M – C6H5COCH2]+, 92
[C6H5NH]+, 77 [C6H5]+.
6ꢀ[2ꢀ(4ꢀBromophenyl)ꢀ2ꢀoxoethyl]ꢀ1,3ꢀdimethylꢀ5ꢀ[phenylꢀ
(phenylhydrazono)methyl]pyrimidineꢀ2,4(1H,3H)ꢀdione (4b). The
yield was 207 mg (78%), pale yellow crystals, m.p. 161—163 °C
(from EtOH). Found (%): C, 60.82; H, 4.47; Br, 15.19.
C27H23BrN4O3. Calculated (%): C, 61.03; H, 4.36; Br, 15.04.
1H NMR (CDCl3), δ: 3.40, 3.43 (both s, 3 H each, N(1)Mе,
N(3)Mе); 4.03 (d, 1 H, CH2, J = 17.89 Hz); 4.20 (d, 1 H, CH2,
J = 17.89 Hz); 6.80 (t, 1 H, Ar, J = 7.37 Hz); 7.01 (d, 1 H, Ar,
J = 7.71 Hz); 7.16 (t, 1 H, Ar, J = 7.89 Hz); 7.26—7.37 (m, 3 H,
Ar); 7.45 (d, 1 H, Ar, J = 8.41 Hz); 7.53 (d, 1 H, Ar, J = 8.77 Hz);
7.57—7.67 (m, 3 H, Ar, NH). IR, ν/cm–1: 1651, 1700 (C=O);
3289 (NH).
tion of the water molecule to form Nꢀaroylaminopyrimiꢀ
dopyridinium derivatives 7 (Scheme 9).
Scheme 9
1,3ꢀDimethylꢀ6ꢀ[2ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀoxoethyl]ꢀ5ꢀ[phenꢀ
yl(phenylhydrazono)methyl]pyrimidineꢀ2,4(1H,3H)ꢀdione (4c).
The yield was 190 mg (79%), colorless crystals, m.p. 178—180 °C
(from EtOH). Found (%): C, 69.86; H, 5.57. C28H26N4O4. Calꢀ
culated (%): C, 69.70; H, 5.43. 1H NMR (CDCl3), δ: 3.42, 3.46
(both s, 3 H each, N(1)Mе, N(3)Mе); 3.82 (s, 3 H, OMе); 4.00
(d, 1 H, CH2, J = 17.89 Hz); 4.27 (d, 1 H, CH2, J = 17.89 Hz);
6.77—6.87 (m, 3 H, Ar); 7.10 (dd, 2 H, Ar, Jo = 8.60 Hz,
Jm = 1.24 Hz); 7.20 (t, 2 H, Ar, J = 7.90 Hz); 7.29—7.41 (m, 3 H,
Ar); 7.66 (dd, 2 H, Ar, Jo = 8.24 Hz, Jm = 1.58 Hz); 7.73 (d, 2 H,
Ar, J = 8.77 Hz); 7.88 (s, 1 H, NH). IR, ν/cm–1: 1657, 1713
(C=O); 3291 (NH).
7ꢀArylꢀ1,3ꢀdimethylꢀ5ꢀphenylpyrido[4,3ꢀd]pyrimidineꢀ
2,4(1H,3H)ꢀdiones 5 (general procedure). A suspension of salt 1
(0.5 mmol) and phenylhydrazine (0.054 mL, 59.4 mg, 0.55 mmol)
in AcOH (2 mL) was refluxed for 1—2 h. The reaction progress
was monitored by TLC on Al2O3 (eluent, CHCl3). The reaction
solution was concentrated to dryness, a tar obtained was subjectꢀ
ed to chromatography on Al2O3 (eluent, CHCl3). The fracꢀ
tion, fluorescing blue under the UV light and being visualized
as dark violet spots after treatment with iodine, was collected.
The chloroform solution was concentrated, the forming redꢀ
dish orange tar was rubbed with diethyl ether, the ether
was decanted. The product was recrystallized from AcOH and
dried at 100 °C.
In conclusion, we have shown that the reactions of
bromides 1 with phenylhydrazine at room temperature
lead to noncyclic hydrazones, whereas heating salts 1 with
phenylhydrazines and aromatic acid hydrazides affords
products of various structure, which depends on the naꢀ
ture of nucleophile. Mechanisms for the transformations
observed have been suggested.
Experimental
IR spectra were recorded on a Specord IRꢀ71 and Varian
FTꢀIR 1000 spectrophotometers in Nujol. 1H NMR spectra were
recorded on a Bruker DPXꢀ250 spectrometer in CDCl3 or
DMSOꢀd6 with HMDS as an internal standard. Mass spectra
were obtained on a Kratos instrument with direct injection of the
sample in the source of irradiation (EI, 70 eV, directing voltage:

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Kostrub et al.
1,3ꢀDimethylꢀ5,7ꢀdiphenylpyrido[4,3ꢀd]pyrimidineꢀ
2,4(1H,3H)ꢀdione (5a). The yield was 82 mg (48%), colorless
crystals, m.p. 208—210 °C (from AcOH). Found (%): C, 73.68;
H, 5.06. C21H17N3O2. Calculated (%): C, 73.45; H, 4.99. 1H NMR
(CDCl3), δ: 3.38 (s, 3 H, N(3)Mе); 3.71 (s, 3 H, N(1)Mе);
7.41—7.54 (m, 9 H, Ar, C(8)H); 8.05—8.12 (m, 2 H, Ar). IR,
ν/cm–1: 1675, 1705 (C=O). MS, m/z: 343 [M]+, 328 [M – CH3]+,
103 [C6H5CN]+, 77 [C6H5]+.
decomp. temperature >176 °C (from AcOH). Found (%):
C, 59.32; H, 4.35; Br, 13.40. C29H25BrN4O5. Calculated (%):
C, 59.09; H, 4.28; Br, 13.56. 1H NMR (DMSOꢀd6), δ: 3.18 (s, 3 H,
N(3)Mе); 3.77, 3.78 (both s, 3 H each, N(1)Mе, OMe); 6.36
(dd, 1 H, Ar, Jo = 8.07 Hz, Jm = 1.76 Hz); 6.69 (s, 1 H, Ar); 6.93
(d, 1 H, Ar, J = 7.72 Hz); 6.99—7.16 (m + d, 4 H, Ar, H(3´),
H(5´), 7ꢀAr, J = 9.12 Hz); 7.22 (d, 1 H, Ar, J = 7.72 Hz); 7.40
(t, 1 H, Ar, J = 7.37 Hz); 7.56 (t, 1 H, Ar, J = 7.72 Hz); 7.75
(d, 1 H, Ar, J = 8.07 Hz); 7.81 (d, 2 H, H(2´), H(6´), 7ꢀAr, J =
= 8.77 Hz); 8.13 (s, 1 H, C(8)H); 10.15 (s, 1 H, NH); 11.40—13.80
(br.s, 1 H, CO2H). IR, ν/cm–1: 1690, 1700 (C=O); 3275 (NH).
6ꢀAroylaminoꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5,7ꢀdiphenylꢀ1H,3Hꢀ
pyrido[4,3ꢀd]pyrimidinium bromides 7 (general procedure). A susꢀ
pension of salt 1 (0.5 mmol) and aroylhydrazine (0.55 mmol) in
AcOH (2 mL) was refluxed for 0.5—2.0 h. The reaction progress
was monitored by TLC on Al2O3 (eluent, CHCl3). The mixture
was concentrated cold and rubbed with diethyl ether. The prodꢀ
uct was recrystallized from suitable solvent and dried at 100 °C.
6ꢀBenzoylaminoꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5,7ꢀdiphenylꢀ1H,3Hꢀ
pyrido[4,3ꢀd]pyrimidinium bromide (7a). The yield was 204 mg
(75%), colorless crystals, m.p. 208—211 °C (from AcOH).
Found (%): C, 62.01; H, 4.18; Br, 14.46. C28H23BrN4O3. Calꢀ
culated (%): C, 61.89; H, 4.27; Br, 14.70. 1H NMR (CDCl3), δ:
3.35 (s, 3 H, N(3)Mе); 3.80 (s, 3 H, N(1)Mе); 7.14—7.23 (m, 3 H,
Ar); 7.26—7.33 (m, 1 H, Ar); 7.34—7.47 (m, 7 H, Ar); 7.53—7.60
(m, 2 H, Ar); 8.02—8.12 (m, 2 H, Ar); 8.28 (d, 1 H, Ar, J = 7.75 Hz).
IR, ν/cm–1: 1620, 1687 (C=O); 3408 (NH). MS, m/z: 462
[M – Br – H]+, 385 [M – Br – H – C6H5]+, 343 [M – Br –
– C6H5NHCO]+, 119 [C6H5NCO]+, 77 [C6H5]+.
6ꢀ[(4ꢀChlorobenzoyl)amino]ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5,7ꢀ
diphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (7b). The
yield was 256 mg (89%), colorless crystals, m.p. 213—217 °C
(from AcOH). Found (%): C, 58.42; H, 3.95; Br + Cl, 19.63.
C28H22BrClN4O3. Calculated (%): C, 58.20; H, 3.84; Br + Cl,
19.97. 1H NMR (CDCl3), δ: 3.36 (s, 3 H, N(3)Mе); 3.80 (s, 3 H,
N(1)Mе); 7.10—7.22 (m, 3 H, Ar); 7.29 (dd, 1 H, Ar, Jo = 7.72 Hz,
Jm = 1.05 Hz); 7.35—7.50 (m, 6 H, Ar); 7.53—7.62 (m, 2 H, Ar);
7.99—8.11 (m, 2 H, Ar); 8.25 (d, 1 H, Ar, J = 7.72 Hz);
12.05—13.87 (br.s, 1 H, NH). IR, ν/cm–1: 1620, 1690 (C=O);
3406 (NH). MS, m/z: 497 [M]+, 343 [M – 4ꢀClC6H5NHCO]+,
153 [4ꢀClC6H5NCO]+.
7ꢀ(4ꢀBromophenyl)ꢀ1,3ꢀdimethylꢀ5ꢀphenylpyrido[4,3ꢀd]ꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdione (5b). The yield was 107 mg (51%),
colorless crystals, m.p. 274—278 °C (from AcOH). Found (%):
C, 59.80; H, 3.74; Br, 18.61. C21H16BrN3O2. Calculated (%):
C, 59.73; H, 3.82; Br, 18.92. 1H NMR (CDCl3), δ: 3.38 (s, 3 H,
N(3)Mе); 3.71 (s, 3 H, N(1)Mе); 7.41 (s, 1 H, C(8)H); 7.43—7.50
(m, 5 H, 5ꢀAr); 7.60 (d, 2 H, H(3´), H(5´), 7ꢀAr, J = 8.59 Hz);
7.98 (d, 2 H, H(2´), H(6´), 7ꢀAr, J = 8.77 Hz). IR, ν/cm–1
:
1665, 1700 (C=O).
1,3ꢀDimethylꢀ7ꢀ(4ꢀmethoxyphenyl)ꢀ5ꢀphenylpyrido[4,3ꢀd]ꢀ
pyrimidineꢀ2,4(1H,3H)ꢀdione (5c). The yield was 80 mg (43%),
colorless crystals, m.p. 236—239 °C (from AcOH). Found (%):
C, 70.61; H, 5.19. C22H19N3O3. Calculated (%): C, 70.76;
H, 5.13. 1H NMR (CDCl3), δ: 3.37 (s, 3 H, N(3)Mе); 3.69 (s, 3 H,
N(1)Mе); 3.85 (s, 3 H, OMе); 6.97 (d, 2 H, H(3´), H(5´), 7ꢀAr,
J = 9.12 Hz); 7.35 (s, 1 H, C(8)H); 7.41—7.53 (m, 5 H, 5ꢀAr);
8.07 (d, 2 H, H(2´), H(6´), 7ꢀAr, J = 8.77 Hz). IR, ν/cm–1
:
1660, 1690 (C=O).
7ꢀArylꢀ6ꢀ[(3ꢀcarboxyphenyl)amino]ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ
5ꢀphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium bromides 6 (general
procedure). A suspension of salt 1 (0.5 mmol) and 3ꢀcarboxypheꢀ
nylhydrazine (83.6 mg, 0.55 mmol) in AcOH (2 mL) was reꢀ
fluxed for 2 h. During the reflux, a colorless precipitate was
formed, which was filtered off, washed with AcOH and CHCl3
and dried at 100 °C.
6ꢀ[(3ꢀCarboxyphenyl)amino]ꢀ1,3ꢀdimethylꢀ2,4ꢀdioxoꢀ5,7ꢀ
diphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (6a). The
yield was 210 mg (75.5%), colorless crystals, decomp. temperaꢀ
ture >209 °C (from AcOH). Found (%): C, 60.33; H, 4.02; Br,
14.05. C28H23BrN4O4. Calculated (%): C, 60.12; H, 4.14; Br,
14.28. 1H NMR (DMSOꢀd6), δ: 3.16 (s, 3 H, N(3)Mе); 3.75 (s, 3 H,
N(1)Mе); 6.35 (dd, 1 H, Ar, Jo = 8.07 Hz, Jm = 1.41 Hz); 6.65
(t, 1 H, Ar, J = 1.76 Hz); 6.90—7.21 (m, 4 H, Ar); 7.32—7.57
(m, 5 H, Ar); 7.67—7.77 (m, 3 H, Ar); 8.17 (s, 1 H, C(8)H);
10.11 (s, 1 H, NH); 12.41—13.31 (br.s, 1 H, CO2H). IR,
ν/cm–1: 1675, 1700 (C=O); 3270 (NH). MS, m/z: 343 [M –
– 3ꢀCO2H—C6H4NH]+, 137 [3ꢀCO2H—C6H4NH]+, 81 [Br]+,
79 [Br]+, 77 [C6H5]+.
7ꢀ(4ꢀBromophenyl)ꢀ6ꢀ[(3ꢀcarboxyphenyl)amino]ꢀ1,3ꢀdiꢀ
methylꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium
bromide (6b). The yield was 254 mg (79.6%), colorless crystals,
decomp. temperature >193 °C (from AcOH). Found (%):
C, 52.86; H, 3.50; Br, 24.87. C28H22Br2N4O4. Calculated (%):
C, 52.69; H, 3.47; Br, 25.04. 1H NMR (DMSOꢀd6), δ: 3.19 (s, 3 H,
N(3)Mе); 3.77 (s, 3 H, N(1)Mе); 6.39 (dd, 1 H, Ar, Jo = 8.07 Hz,
Jm = 1.75 Hz); 6.69 (s, 1 H, Ar); 6.96 (d, 1 H, Ar, J = 7.72 Hz);
7.02—7.17 (m, 2 H, Ar); 7.24 (d, 1 H, Ar, J = 7.72 Hz); 7.40 (t, 1 H,
Ar, J = 7.37 Hz); 7.56 (t, 1 H, Ar, J = 7.54 Hz); 7.68—7.78 (m, 5 H,
Ar); 8.24 (s, 1 H, C(8)H); 10.16 (s, 1 H, NH); 11.75—13.49
(br.s, 1 H, CO2H). IR, ν/cm–1: 1680, 1700 (C=O); 3270 (NH).
6ꢀ[(3ꢀCarboxyphenyl)amino]ꢀ1,3ꢀdimethylꢀ7ꢀ(4ꢀmethoxyꢀ
phenyl)ꢀ2,4ꢀdioxoꢀ5ꢀphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium
bromide (6c). The yield was 161 mg (55%), colorless crystals,
1,3ꢀDimethylꢀ6ꢀ[(4ꢀmethoxybenzoyl)amino]ꢀ2,4ꢀdioxoꢀ5,7ꢀ
diphenylꢀ1H,3Hꢀpyrido[4,3ꢀd]pyrimidinium bromide (7c). For
purification, a suspension of the compound in benzene was three
times refluxed and filtered hot. The yield was 194 mg (68%),
colorless crystals, m.p. 212—216 °C (from benzene). Found (%):
C, 60.56; H, 4.31; Br, 14.08. C29H25BrN4O4. Calculated (%):
C, 60.74; H, 4.39; Br, 13.93. 1H NMR (CDCl3), δ: 3.39 (s, 3 H,
N(3)Mе); 3.74, 3.83 (both s, 3 H each, N(1)Mе, OMе); 6.71
(d, 2 H, H(3″), H(5″), 6ꢀAr, J = 9.12 Hz); 7.19 (d, 1 H, Ar,
J = 7.71 Hz); 7.32 (d, 1 H, Ar, J = 7.36 Hz); 7.41—7.52 (m, 6 H,
Ar); 7.56—7.66 (m, 2 H, Ar); 8.07—8.16 (m, 2 H, Ar); 8.31 (d, 1 H,
Ar, J = 8.06 Hz); 12.53—13.09 (br.s, 1 H, NH). IR, ν/cm–1
:
1620, 1687 (C=O); 3408 (NH).
Xꢀray diffraction study of compound 4b. Monocrystals of comꢀ
pound 4b were obtained by crystallization from EtOH. Crystals
4b (C28H26BrN4O3.50) are triclinic, M = 554.44, the space
group is Pꢀ1, at 120 K a = 11.6260(6) Å, b = 14.5900(7) Å,
c = 17.0219(9) Å, α = 66.601(1)°, β = 88.501(1)°, γ = 77.87(1)°,
V = 2585.6(2) Å3, Z = 4 (Z´ = 2), μ(MoꢀKα) = 1.63 mm–1
F(000) = 1140. Intensities of 23078 reflections were measured
,

Reactions of pyrano[4,3ꢀd]pyrimidinium salts
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 7, July, 2009
1475
on a Bruker SMART 1000 CCD diffractometer (λ(MoꢀKα) =
= 0.71072 Å, ωꢀscanning, 2θ < 52°), 10162 of independent reꢀ
flections (Rint = 0.0356) were used in further refinement. The
structure was solved by the direct method and refined by the
fullꢀmatrix leastꢀsquares method on F2 with anisotropic thermal
parameters for all the nonhydrogen atoms. Positions of the
hydrogen atoms of the amino groups in two independent molecules
A and B were localized from differential Fourierꢀsyntheses of
electron density and refined in isotropical approximation, whereꢀ
as on carbon atoms, they were calculated geometrically and reꢀ
fined using the riding model. The final values of nonconfidence
factors for 4b: wR2 = 0.1185, GOF = 1.030 for all the indepenꢀ
dent reflections (R1 = 0.044, calculated on F for 7573 observed
reflections with I > 2σ(I)). All the calculations were performed
using the SHELXTL PLUS 5.10 program package.
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Received August 15, 2008;
in revised form February 20, 2009