Reaction of 2,3-tetramethylen-3,4-dihydroquinazol-4-one and its derivatives with aromatic aldehydes and furfurol

Article abstract of DOI:10.1007/s10600-009-9334-x

α-Aryliden-6H(nitro)- and 6,8-dibromo-2,3-tetramethylen-3,4- dihydroquinazol-4-ones were synthesized by condensation of 6H(nitro)- and 6,8-dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-ones with aromatic aldehydes, furfurol, and of α-formyl-2,3-tetramethylen-3,4- dihydroquinazol-4-one with benzaldehyde and 4-nitrobenzaldehyde in glacial acetic acid.

Full text of DOI:10.1007/s10600-009-9334-x

Chemistry of Natural Compounds, Vol. 45, No. 3, 2009
REACTION OF 2,3-TETRAMETHYLEN-3,4-DIHYDROQUINAZOL-4-ONE
AND ITS DERIVATIVES WITH AROMATIC ALDEHYDES AND FURFUROL
A. Sh. Abdurazakov, B. Zh. Elmuradov,*
Zh. E. Turdibaev, and Kh. M. Shakhidoyatov
UDC 547.944/945
+547.856
α-Aryliden-6H(nitro)- and 6,8-dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-ones were synthesized by
condensation of 6H(nitro)- and 6,8-dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-ones with aromatic
aldehydes, furfurol, and of α-formyl-2,3-tetramethylen-3,4-dihydroquinazol-4-one with benzaldehyde and
4-nitrobenzaldehyde in glacial acetic acid.
Key words: alkaloids, 6H(nitro)-, 6,8-dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-ones, aromatic aldehydes,
condensation.
2,3-Tetramethylen-3,4-dihydroquinazol-4-one (alkaloid 6,7,8,9-tetrahydropyrido[2,1-b]quinazolin-11-one from
Mackinlaya subulata Philipson, 1, R = R = H) and its derivatives are interesting from a theoretical and practical point of view
1
[1-4].
We have previously studied the condensation of 2,3-trimethylen-3,4-dihydroquinazol-4-one (deoxyvacisinone) and
its 6-bromo(nitro) derivatives with various aliphatic, aromatic, and heterocyclic aldehydes. It was found that the corresponding
α-aryliden- or α-hydroxyarylmethyl derivatives could be formed depending on the conditions and duration of the reaction and
the nature of the substituents in the quinazolone and aldehyde ring [5-11].
We studied the condensation of 1-3 with benzaldehyde; 4-hydroxy-, -dimethylamino-, -nitro-, and 3,4-dimethoxy-
benzaldehydes; 2-bromoisovanillin, 5-bromovanillins, and furfurol in order to find biologically active compounds and to
determine the reactivity of 1 and its 6-nitro- (2) and 6,8-dibromo (3) derivatives in reactions with aromatic and heterocyclic
aldehdyes in addition to the influence of the size of the cycloalkane ring and substituents on the course of the reactions. The
reaction proceeded according to the scheme below and gave α-aryliden(furfuryliden)-2,3-tetramethylen-3,4-dihydroquinazol-
4-ones (4-25).
O
O
O
N
5
5
3
N
R
R
R
N
11
11
N
7
R
R
R
9
2
3
7
3'
5'
1'
N
N
1
O
1
R
CH
R
4
R
CH
5'
1
1
1'
R
1
13
13
R
5
6
1 - 3
11, 19, 25
4 - 10, 12 - 18, 20 - 24
1: R = R = H; 2: R = NO , R = H; 3: R = R = Br; 4 - 10: R = R = H; 12 - 18: R = NO , R = H
1
2
1
1
1
2
2
1
20 - 24: R = R = Br; 11: R = R = H; 19: R = NO , R = H; 25: R = R = Br; 4, 12, 20: R = R = R = R = R = H
1
1
2
1
1
3
4
5
6
5, 13, 21: R = R = R = R = H, R = OH; 6, 14, 22: R = R = R = R = H, R = N(CH )
2
3
5
6
4
2
3
5
6
4
3 2
3
7, 15, 23: R = R = R = R = H, R = NO 8, 16, 24: R = R = R = H, R = R = OCH
2
3
5
6
4
2;
2
5
6
3
4
9, 17: R = R = H, R = Br, R = OH, R = OCH 10, 18: R = R = H, R = OCH , R = OH, R = Br
5
6
2
3
4
3;
2
6
3
3
4
5
S. Yu. Yunusov Institute of the Chemistry of Plant Substances, Academy of Sciences of the Republic of Uzbekistan,
Tashkent, fax: (99871) 120 64 75, e-mail: burkhon@rambler.ru. Translated from Khimiya Prirodnykh Soedinenii, No. 3,
pp. 342-347, May-June 2009. Original article submitted December 25, 2008.
©
402
0009-3130/09/4503-0402 2009 Springer Science+Business Media, Inc.

The reactions were carried out in glacial acetic acid under reflux for 3-5 h [12, 13].
Reactions of 1-3 with carbonyl compounds (aldehydes, acid chlorides, disubstituted formamides in the presence of
inorganic acid chlorides) have not been reported. Furthermore, although 2,3-trimethylen-3,4-dihydroquinazol-4-one underwent
acylation, 2,3-tetramethylen-3,4-dihydroquinazol-4-one reacted difficultly with acylating agents [14]. These compounds behaved
similarly in formylation reactions [3, 15].
Our research showed that reactions of 6H(nitro)- and 6,8-dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-ones
(1-3) with aromatic aldehydes occurred exclusively at the α-C atom. Performing the reaction with 1:2 ratios of (1-3):aromatic
aldehyde and with prolonged (10-12 h) heating in glacial acetic acid did not affect the β-, γ-, and δ-C atoms, i.e.,
6H(nitro)-, 6,8-dibromo-, β(γ,δ)-aryliden-; or bisaryliden- derivatives were not observed. Therefore, it seemed interesting to
study the condensation of an α-substituted derivative of 2,3-tetramethylen-3,4-dihydroquinazol-4-one, in particular, α-formyl-
2,3-tetramethylen-3,4-dihydroquinazol-4-one (26) with benzaldehyde and 4-nitrobenzaldehyde. It was expected that the
α-formyl-(β,γ,δ)- (more probably β-)-aryliden-substituted quinazol-4-ones would form:
O
N
O
N
N
ArCHO
N
CH
R
1
H
C O
4, 7
26
4: R = H; 7: R = NO
2
Ar = C H , C H -NO -4
1
1
6
5
6
4
2
The reactions of 26 with benzaldehyde and p-nitrobenzaldehyde were carried out in glacial acetic acid under reflux
for 5 h. The formyl group in 26 had no electron-acceptor affect on the methylene groups in the β-, γ-, or δ-positions. The
corresponding α-benzyliden(4′-nitrobenzyliden)-2,3-tetramethylen-3,4-dihydroquinazol-4-ones (4 and 7) were formed. The
structures of the α-arylidene derivatives 4 and 7 that were prepared by this method were proved using mass and PMR spectra.
Thus, we observed anomalous behavior of α-formyl-2,3-tetramethylen-3,4-dihydroquinazol-4-one (26) in reactions with
carbonyl compounds that consisted of exchange of the formyl group by an aromatic aldehyde. Such behavior of 26 could be
explained by cleavage of the formyl group in acetic acid to form 1, which reacted with the aromatic aldehydes to form the
corresponding α-arylidene derivatives 4 and 7.
The structures of the synthesized compounds 4-25 were confirmed by IR, PMR, and mass spectra. Their IR spectra
−1
had stretching vibrations ν
at 1650-1717 cm ; ν
, 1591-1618; ν
, 1531-1590; ν
for 12-19, 1495-1516.
C=O
C=N
C–N
C–NO2
Mass spectra of the synthesized compounds showed principal fragmentation according to the following scheme
(using 16 as an example):
189 - 191
121
O
O N
2
N
N
231
OMe
OMe
46
C
H
163
256
16
362
243 - 245
PMR spectra showed methylene protons in the β-position had chemical shifts (CS) at 2.65-2.75 ppm (2H, triplet); in
the γ-position, 1.84-1.87 (2H, multiplet); in the δ-position, 3.84-3.96 (2H, triplet); methyl protons of N(CH ) of 6 and 14,
3 2
3.066-3.1 (6H, singlet); of OCH for 8-10 and 16-18, 3.38-3.62 (3H, singlet); aromatic protons, 6.31-8.85 ppm. The appearance
3
of the β- and δ-methylene protons as triplets and the γ-methylene protons as multiplets and the lack of protons on the
α-C atom at 2.8-3.0 ppm confirmed that the condensation occurred at the α-C atom.
403

Bactericidal properties of 4-25 were studied toward various Gram-positive and Gram-negative strains Staphylococcus
T50a, Klebsiella pneumoniae T3a, S. aureus T48a, Acinetobacter sp. T16, Enterococcus hormaechei T2, Escherichia coli
T60a, Enterococcus hormaechei T10, Proteus rettgerri T33a, B. cereus T80, Citrobacter freundii T1a, Enterococcus feaecalis
T23a, Pseudomonas aureginosa T31a, Proteus agglomerans T26, A. faecalis T3, Micrococcus luteus T52a, Pseudomonas
aureginosa T145, S. saprophyticus T415, Klebsiella oxitoca T4a, and A. haumanii T15a at concentrations of 0.01%, 0.1 and
1%. The results showed that they had low bactericidal activity.
EXPERIMENTAL
Mass spectra were recorded in an MS-30 (Kratos) instrument; IR spectra in mineral oil, on an IR-Fourier System
2000 spectrometer; PMR spectra in TFA, TFA+CD COOD, and CDCl solutions, on a Unity 400+ instrument (operating
3
3
frequency 400 MHz, TMS internal standard, δ scale). The purity of products and course of reactions were monitored using
TLC on Silufol UV-254 plates and solvent systems benzene:MeOH (3:1, system A; 5:1, system B) and CHCl :MeOH (15:1,
3
system C; 20:1, system D).
2,3-Tetramethylen-3,4-dihydroquinazol-4-one (1) was prepared by the literature method [16].
6-Nitro-2,3-tetramethylen-3,4-dihydroquinazol-4-one (2) was synthesized by a modified method [3].
2,3-Tetramethylen-3,4-dihydroquinazol-4-one (10 g, 0.05 mol) was dissolved with vigorous stirring in cold (0-2°C)
3
conc. H SO (95.72%, ρ = 1.835 g/cm , 20 mL), treated dropwise with a nitrating mixture consisting of nitric (7.5 mL,
2
4
3
3
59.69%, ρ = 1.365 g/cm ) and sulfuric (7.5 mL, ρ = 1.835 g/cm ) acids, stirred at room temperature for 2 h, and poured onto
ice. The resulting precipitate was filtered off, washed with water until neutral, and dried. Recrystallization from MeOH
produced 2 (9.5 g, 79%), mp 183-184°C, in agreement with the literature [3].
6,8-Dibromo-2,3-tetramethylen-3,4-dihydroquinazol-4-one (3) was synthesized by the literature method [17].
α-Oxymethyliden-2,3-tetramethylen-3,4-dihydroquinazol-4-one (26) was prepared by the literature method [3].
α-Benzyliden-2,3-tetramethylen-3,4-dihydroquinazol-4-one (4). Method A. Compound 1 (1.0 g, 5 mmol) was
3
dissolved in glacial acetic acid (10 mL), treated with benzaldehyde (0.53 mL, 0.56 g, 5.3 mmol, ρ = 1.0498 g/cm ), and
refluxed for 3-5 h. Solvent was distilled off. The solid was recrystallized from aqueous DMF to afford 4 (1.05 g, 73%).
C H N O, mp 146-147°C, R 0.83 (system C).
19 16
2
f
Method B. Compound 26 (0.456 g, 2 mmol) was dissolved in glacial acetic acid (5 mL), treated with benzaldehyde
3
(0.21 mL, 0.22 g, 2.1 mmol, ρ = 1.0498 g/cm ), and refluxed for 5 h. Solvent was distilled off. The solid was recrystallized
from aqueous DMF to afford 4 (0.37 g, 64%). C H N O, mp 146-147°C, R 0.83 (system C).
19 16
2
f
A mixed melting point with an authentic sample did not show depression.
PMR spectrum (δ, ppm, J/Hz): 8.01 (1H, dd, J = 8.0, 1.0, H-5), 7.65 (1H, ddd, J = 8.0, 7,7, 1.0, H-7), 7.53 (1H, s,
H-13), 7.42 (1H, d, J = 7.7, H-8), 7.40 (1H, t, J = 8.0, H-6), 7.11-7.17 (5H, m, H-2′,3′,4′,5′,6′), 3.93 (2H, t, J = 5.6, H-12), 2.75
(2H, td, J = 6.6, 1.8, H-10), 1.85 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1717 (ν
), 1605 (ν
), 1531 (ν
).
C–N
C=O
C=N
α-(4′-Hydroxybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (5) was synthesized analogously as
above from 1 (1.0 g, 5 mmol) and 4-hydroxybenzaldehyde (0.7 g, 5.3 mmol) to afford 5 (0.97 g, 64%). C H N O , mp 246-
19 16
2 2
247°C (alcohol), R 0.61 (system C).
f
PMR spectrum (δ, ppm, J/Hz): 8.0 (1H, dd, J = 8.0, 1,2, H-5), 7.63 (1H, td, J = 8.6, 1.2, H-7), 7.47 (1H, s, H-13), 7.35-
7.40 (2H, m, H-6,8), 7.18 (2H, d, J = 8.6, H-2′,6′), 6.68 (2H, d, J = 8.6, H-3′,5′), 3.92 (2H, t, J = 5.4, H-12), 2.72 (2H, t, J = 6.8,
H-10), 1.85 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1684 (ν
), 1606 (ν
), 1532 (ν
).
C–N
C=O
C=N
α-(4′-Dimethylaminobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (6) was synthesized analogously
as above from 1 (1.0 g, 5 mmol) and 4-dimethylaminobenzaldehyde (0.79 g, 5.3 mmol) to afford 6 (1.01 g, 61%). C H N O,
21 21
3
mp 174-175°C (alcohol), R 0.91 (system D).
f
PMR spectrum (δ, ppm, J/Hz): 8.03 (1H, br.d, J = 7.8, H-5), 7.66 (1H, br.t, J = 8.1, H-7), 7.57 (1H, s, H-13), 7.46 (1H,
d, J = 8.1, H-8), 7.42 (1H, t, J = 7.8, H-6), 7.36-7.39 (4H, m, H-2′,3′,5′,6′), 3.94 (2H, t, J = 5.7, H-12), 3.07 [6H, s, N(CH ) ],
3 2
2.68 (2H, t, J = 6.9, H-10), 1.86 (2H, m, H-11).
404

−1
IR spectrum (ν, cm ): 1662 (ν
), 1599 (ν
), 1535 (ν
).
C–N
C=O
C=N
α-(4′-Nitrobenzylidene)-2,3-tetramethylen-3,4-dihdyroquinazol-4-one (7). Method A. The reaction was carried
out analogously as above from 1 (1.0 g, 5 mmol) and 4-nitrobenzaldehyde (0.8 g, 5.3 mmol) to afford 7 (1.36 g, 82%).
C H N O , mp 226-227°C (EtOAc), R 0.91 (system C).
19 15
3
3
f
Method B. Compound 26 (0.456 g, 2 mmol) was dissolved in glacial acetic acid (5 mL), treated with
4-nitrobenzaldehyde (0.306 g, 2.1 mmol), and refluxed for 5 h. The resulting crystals were filtered off, washed thoroughly
with water, and dried. Recrystallization from EtOAc afforded 7 (0.526 g, 72%). C H N O , mp 226-227°C (EtOAc),
19 15
3 3
R 0.91 (system C).
f
A mixed melting point with an authentic sample did not show depression.
PMR spectrum (δ, ppm, J/Hz): 8.03 (1H, d, J = 7.7, H-5), 7.98 (2H, d, J = 8.9, H-3′,5′), 7.67 (1H, t, J = 8.4, H-7), 7.61
(1H, s, H-13), 7.44 (1H, d, J = 8.4, H-8), 7.42 (1H, t, J = 7.4, H-6), 7.34 (2H, d, J = 8.9, H-2′,6′), 3.95 (2H, t, J = 5.7, H-12), 2.71
(2H, td, J = 1.5, 6.6, H-10), 1.87 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1717 (ν
), 1607 (ν
), 1541 (ν
), 1509 (ν
).
C=O
C=N
C–N
C–NO2
α-(3′,4′-Dimethoxybenzylidene)-2,3-tetramethylen-3,4-dihdyroquinazol-4-one (8) was synthesized analogously
as above from 1 (0.5 g, 2.5 mmol) and 3,4-dimethoxybenzaldehyde (0.415 g, 2.5 mmol) to afford 8 (0.61 g, 70%). C H N O ,
21 20
2 3
mp 156-157°C (MeOH), R 0.85 (system A).
f
PMR spectrum (δ, ppm, J/Hz): 8.0 (1H, d, J = 7.0, H-5), 7.63 (1H, t, J = 8.4, H-7), 7.46 (1H, s, H-13), 7.36-7.41 (2H,
m, H-6,8), 6.96 (1H, dd, J = 8.4, 1.7, H-6′), 6.81 (1H, d, J = 1.7, H-2′), 6.71 (1H, d, J = 8.4, H-5′), 3.92 (2H, t, J = 5.6, H-12),
3.58 [6H, d, 2(OCH )], 2.75 (2H, t, J = 5.2, H-10), 1.86 (2H, m, H-11).
3
−1
IR spectrum (ν, cm ): 1672 (ν
), 1609 (ν
), 1539 (ν
).
C=O
C=N
C–N
α-(2′-Bromo-3′-hydroxy-4′-methoxybenzylidene)-2,3-tetramethylen-3,4-dihdyroquinazol-4-one (9) was
synthesized from 1 (0.5 g, 2.5 mmol) and 2-bromoisovanillin (0.58 g, 2.5 mmol) to afford 9 (0.55 g, 54%). C H N O Br,
20 17
2 3
mp 178-180°C (benzene), R 0.41 (system B).
f
PMR spectrum (δ, ppm, J/Hz): 8.02 (1H, dd, J = 8.1, 1.2, H-5), 7.64 (2H, td, J = 8.4, 1.2, H-7,8), 7.45 (1H, d, J = 8.1,
H-6), 7.4 (2H, dd, J = 7.8, H-5′,6′), 6.91 (1H, s, H-13), 3.94 (2H, t, J = 5.4, H-12), 3.55 (3H, s, OCH ), 2.62 (2H, t, J = 6.0,
3
H-10), 1.85 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 3183 (ν
), 1669 (ν
), 1594 (ν
), 1564 (ν
).
C–N
O–H
C=O
C=N
α-(3′-Methoxy-4′-hydroxy-5′-bromobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (10) was
synthesized analogously as above from 1 (0.34 g, 1.7 mmol) and 5-bromovanillin (0.4 g, 1.7 mmol) to afford 10 (0.46 g, 66%).
C H N O Br, mp 202-204°C (aq. DMF), R 0.76 (system B).
20 17
2
3
f
PMR spectrum (δ, ppm, J/Hz): 8.0 (1H, dd, J = 7.3, 1.0, H-5), 7.63 (1H, td, J = 7.3, 1.4, H-7), 7.37-7.41 (3H, m,
H-6,8,13), 7.05 (1H, d, J = 1.7, H-6′), 6.70 (1H, d, J = 1.7, H-2′), 3.92 (2H, t, J = 5.6, H-12), 3.56 (3H, s, OCH ), 2.73 (2H, t,
3
J = 5.6, H-10), 1.86 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 3183 (ν
), 1650 (ν
), 1594 (ν
), 1545 (ν
).
C–N
O–H
C=O
C=N
α-(Furfurylidene-1′)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (11) was synthesized analogously as above
3
from 1 (0.5 g, 2.5 mmol) and furfurol (0.22 mL, 0.24 g, 2.65 mmol, ρ = 1.1598 g/cm ) to afford 11 (0.56 g, 80%). C H N O ,
17 14
2 2
mp 136-138°C (aq. alcohol), R 0.76 (system B).
f
PMR spectrum (δ, ppm, J/Hz): 7.98 (1H, dd, J = 8.1, 1.2, H-5), 7.61 (1H, td, J = 7.2, 1.2, H-7), 7.32-7.39 (4H, m,
H-6,8,13,5′), 6.71 (1H, d, J = 3.9, H-3′), 6.30 (1H, dd, J = 3.9, H-4′), 3.94 (2H, m, H-12), 2.79 (2H, td, J = 6.6, 1.8, H-10), 1.83
(2H, m, H-11).
−1
IR spectrum (ν, cm ): 1715 (ν
), 1608 (ν
), 1550 (ν
).
C–N
C=O
C=N
6-Nitro-α-benzyliden-2,3-tetramethylen-3,4-dihydroquinazol-4-one (12). A mixture of 2 (0.5 g, 2.0 mmol) was
3
dissolved in glacial acetic acid (5 mL), treated with benzaldehyde (0.23 mL, 0.24 g, 2.3 mmol, ρ = 1.0498 g/cm ), and refluxed
for 5 h. Solvent was distilled off. The solid was recrystallized from benzene to afford 12 (0.54 g, 80%). C H N O , mp 200-
19 15
3 3
202°C, R 0.86 (system A).
f
PMR spectrum (δ, ppm, J/Hz): 8.83 (1H, d, J = 2.4, H-5), 8.38 (1H, dd, J = 8.9, 2.4, H-7), 7.65 (1H, d, J = 8.9, H-8),
7.63 (1H, s, H-13), 7.13-7.19 (5H, m, H-2′,3′,4′,5′,6′), 3.93 (2H, t, J = 5.4, H-12), 2.76 (2H, t, J = 5.9, H-10), 1.86 (2H, m,
H-11).
405

−1
IR spectrum (ν, cm ): 1653 (ν
), 1604 (ν
), 1560 (ν
), 1505 (ν
).
C=O
C=N
C–N
NO2
6-Nitro-α-(4′-hydroxybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (13) was synthesized
analogously as above from 2 (0.5 g, 2.0 mmol) and 4-hydroxybenzaldehyde (0.28 g, 2.3 mmol) to afford 13 (0.53 g, 75%).
C H N O , mp 262-264°C (aq. DMF), R 0.73 (system A).
19 15
3
4
f
PMR spectrum (δ, ppm, J/Hz): 8.82 (1H, d, J = 2.6, H-5), 8.37 (1H, dd, J = 8.8, 2.6, H-7), 7.60 (1H, d, J = 8.8, H-8),
7.57 (1H, s, H-13), 7.22 (2H, d, J = 8.8, H-2′,6′), 6.7 (2H, d, J = 8.8, H-3′,5′), 3.92 (2H, t, J = 5.6, H-12), 2.73 (2H, t, J = 5.6,
H-10), 1.86 (2H, m, H-11).
+
+
+
Mass spectrum (m/z, Irel, %): 349 (15.4) [M] , 348 (46) [M - 1] , 332 (3.5) [M - OH] , 318 (100), 317 (57.3), 303
+
(4.8) [M - NO ] , 302 (42.6), 243 (7), 122 (2.5), 76 (4.8).
2
−1
IR spectrum (ν, cm ): 1653 (ν
), 1604 (ν
), 1560 (ν
), 1505 (ν
).
C=O
C=N
C–N
NO2
6-Nitro-α-(4′-dimethylaminobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (14) was synthesized
analogously as above from 2 (0.5 g, 2.0 mmol) and 4-dimethylaminobenzaldehyde (0.34 g, 2.3 mmol) to afford 14 (0.55 g,
72%). C H N O , mp 242-243°C (aq. DMF), R 0.87 (system A).
21 20
4
3
f
PMR spectrum (δ, ppm, J/Hz): 8.85 (1H, br.s, H-5), 8.40 (1H, d , J = 8.8, H-7), 7.69 (1H, d, J = 8.8, H-8), 7.68 (1H,
s, H-13), 7.42 (2H, d, J = 8.8, H-2′,6′), 7.38 (2H, d, J = 8.8, H-3′,5′), 3.94 (2H, t, J = 5.5, H-12), 3.07 [6H, s, N(CH ) ], 2.7 (2H,
3 2
t, J = 6.6, H-10), 1.87 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1674 (ν
), 1614 (ν
), 1580 (ν
), 1505 (ν
).
C=O
C=N
C–N
NO2
6-Nitro-α-(4′-nitrobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (15) was synthesized analogously
as above from 2 (0.5 g, 2.0 mmol) and 4-nitrobenzaldehyde (0.34 g, 2.3 mmol) to afford 15 (0.67 g, 87%). C H N O ,
19 14
4 5
mp 243-244°C (aq. DMF), R 0.88 (system A).
f
PMR spectrum (δ, ppm, J/Hz): 8.84 (1H, d, J = 2.4, H-5), 8.4 (1H, dd, J = 8.9, 2.4, H-7), 7.99 (2H, d, J = 8.6, H-3′,5′),
7.70 (1H, d, J = 8.9, H-8), 7.69 (1H, s, H-13), 7.35 (2H, d, J = 8.6, H-2′,6′), 3.95 (2H, t, J = 5.4, H-12), 2.73 (2H, t, J = 6.6,
H-10), 1.88 (2H, m, H-11).
+
+
Mass spectrum (m/z, Irel, %): 378 (100) [M] , 332 (14) [M - NO ] , 331 (73), 317 (73), 302 (16.8), 286 (14)
2
+
[M - (NO ) ] , 243 (5.6), 164 (2.8), 151 (2.8), 143 (4.2), 120 (4.2), 77 (12.6).
2 2
−1
IR spectrum (ν, cm ): 1681 (ν
), 1614 (ν
), 1588 (ν
), 1512 (ν
).
C=O
C=N
C–N
NO2
6-Nitro-α-(3′,4′-dimethoxybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (16) was synthesized
analogously as above from 2 (0.5 g, 2.0 mmol) and 3,4-dimethoxybenzaldehyde (0.332 g, 2.0 mmol) to afford 16 (0.62 g,
77%). C H N O , mp 230-231°C (aq. DMF), R 0.86 (system A).
21 19
3
5
f
PMR spectrum (δ, ppm, J/Hz): 8.83 (1H, d, J = 2.6, H-5), 8.38 (1H, dd, J = 9.1, 2.6, H-7), 7.62 (1H, d, J = 9.1, H-8),
7.58 (1H, s, H-13), 7.01 (1H, dd, J = 8.8, 1.9, H-6′), 6.84 (1H, d, J = 1.9, H-2′), 6.73 (1H, d, J = 8.8, H-5′), 3.92 (2H, t, J = 5.6,
H-12), 3.58 [6H, d, (OCH ) ], 2.77 (2H, t, J = 5.9, H-10), 1.88 (2H, m, H-11).
3 2
+
+
+
Mass spectrum (m/z, Irel, %): 393 (12.6) [M] , 363 (93) [M - OCH ] , 362 (100), 348 (28) [M - NO ] , 332 (12.6),
3
2
317 (4.2), 244 (2), 231 (3.5), 219 (4.2), 191 (4.2), 165 (2.8), 151 (1.7), 149 (23), 145 (3.5), 130 (5), 121 (4.2), 101 (5.6),
76 (12).
−1
IR spectrum (ν, cm ): 1673 (ν
), 1610 (ν
), 1578 (ν
), 1506 (ν
).
C=O
C=N
C–N
NO2
6-Nitro-α-(2′-bromo-3′-hydroxy-4′-methxoybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (17) was
synthesized from 2 (0.4 g, 1.6 mmol) and 2-bromoisovanillin (0.39 g, 1.7 mmol) to afford 17 (0.45 g, 60%). C H N O Br,
20 16
3 5
mp 248-250°C (aq. DMF), R 0.63 (system B).
f
PMR spectrum (δ, ppm, J/Hz): 8.84 (1H, d, J = 2.6, H-5), 8.38 (1H, dd, J = 8.8, 2.6, H-7), 7.77 (1H, s, H-13), 7.65
(1H, d, J = 8.8, H-8), 6.82 (1H, d, J = 8.5, H-6′), 6.65 (1H, d, J = 8.5, H-5′), 3.93 (2H, t, J = 5.6, H-12), 3.61 (3H, s, OCH ), 2.64
3
(2H, t, J = 6.2, H-10), 1.85 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 3464 (ν
), 1689 (ν
), 1614 (ν
), 1583 (ν
), 1506 (ν
).
O–H
C=O
C=N
C–N
NO2
6-Nitro-α-(3′-methoxy-4′-hydroxy-5′-bromobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (18) was
synthesized analogously as above from 2 (0.4 g, 1.6 mmol) and 5-bromovanillin (0.39 g, 1.7 mmol) to afford 18 (0.55 g, 74%).
C H N O Br, mp 278-280°C (aq. DMF), R 0.47 (system B).
20 16
3
5
f
PMR spectrum (δ, ppm, J/Hz): 8.83 (1H, d, J = 2.6, H-5), 8.38 (1H, dd, J = 9.1, 2.6, H-7), 7.63 (1H, d, J = 9.1, H-8),
7.49 (1H, s, H-13), 7.10 (1H, d, J = 1.6, H-6′), 6.72 (1H, d, J = 1.6, H-2′), 3.93 (2H, t, J = 5.2, H-12), 3.58 (3H, s, OCH ), 2.75
3
(2H, t, J = 5.9, H-10), 1.88 (2H, m, H-11).
406

−1
IR spectrum (ν, cm ): 3422 (ν
), 1659 (ν
), 1618 (ν
), 1570 (ν
), 1495 (ν
).
O–H
C=O
C=N
C–N
NO2
6-Nitro-α-(furfuryliden-1′)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (19) was synthesized analogously as
3
above from 2 (0.3 g, 1.2 mmol) and furfurol (0.11 mL, 0.12 g, 1.3 mmol, ρ = 1.1598 g/cm ) to afford 19 (0.37 g, 93%).
C H N O , mp 236-238°C (benzene), R 0.87 (system A).
17 13
3
4
f
PMR spectrum (δ, ppm, J/Hz): 8.81 (1H, d, J = 2.3, H-5), 8.36 (1H, dd, J = 9.0, 2.3, H-7), 7.58 (1H, d, J = 9.0, H-8),
7.46 (1H, d, J = 1.6, H-3′), 7.45 (1H, s, H-13), 6.81 (1H, d, J = 3.7, H-5′), 6.34 (1H, dd, J = 3.7, 1.6, H-4′), 3.94 (2H, m, H-12),
2.8 (2H, t, J = 6.4, H-10), 1.85 (2H, m, H-11).
6,8-Dibromo-α-benzyliden-2,3-tetramethylen-3,4-dihydroquinazol-4-one (20). Amixture of 3 (0.4 g, 1.12 mmol)
3
was dissolved in glacial acetic acid (5 mL), treated with benzaldehyde (0.16 mL, 0.168 g, 1.66 mmol, ρ = 1.0498 g/cm ), and
refluxed for 6 h. Solvent was distilled off. The solid was recrystallized from cyclohexane to afford 20 (0.36 g, 72%).
C H N OBr , mp 168-170°C, R 0.89 (system B).
19 14
2
2
f
PMR spectrum (δ, ppm, J/Hz): 8.1 (1H, d, J = 2.0, H-5), 8.0 (1H, d, J = 2.0, H-7), 7.13-7.19 (3H, m, H-2′,6′,13),
6.93-6.96 (3H, m, H-3′,4′,5′), 3.9 (2H, t, J = 5.7, H-12), 2.74 (2H, t, J = 1.7, H-10), 1.82 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1681 (ν
), 1572 (ν
), 1543 (ν
).
C=O
C=N
C–N
6,8-Dibromo-α-(4′-hydroxybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (21) was synthesized
analogously as above from 3 (0.2 g, 0.56 mmol) and 4-hydroxybenzaldehyde (0.087 g, 0.72 mmol) to afford 21 (0.164 g,
64%). C H N O Br , mp 288-289°C (aq. DMF), R 0.72 (system A).
19 14
2
2
2
f
PMR spectrum (δ, ppm, J/Hz): 8.08 (1H, d, J = 2.0, H-5), 7.94 (1H, d, J = 2.0, H-7), 7.48 (1H, s, H-13), 7.22 (2H, d,
J = 8.4, H-2′,6′), 6.69 (2H, d, J = 8.4, H-3′,5′), 3.89 (2H, t, J = 5.6, H-12), 2.72 (2H, t, J = 6.6, H-10), 1.85 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 3070 (ν ), 1656 (ν
), 1580 (ν
), 1542 (ν
).
OH
C=O
C=N
C–N
6,8-Dibromo-α-(4′-dimethylaminobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (22) was synthe-
sized analogously as above from 3 (0.4 g, 1.12 mmol) and 4-dimethylaminobenzaldehyde (0.21 g, 1.44 mmol) to afford 22
(0.37 g, 68%). C H N OBr , mp 215-216°C (benzene), R 0.89 (system B).
21 19
3
2
f
PMR spectrum (δ, ppm, J/Hz): 8.12 (1H, d, J = 2.0, H-5), 7.97 (1H, d, J = 2.0, H-7), 7.58 (1H, s, H-13), 7.41 (2H, d,
J = 9.0, H-2′,6′), 7.38 (2H, d, J = 9.0, H-3′,5′), 3.91 (2H, t, J = 5.7, H-12), 3.06 [6H, s, N(CH ) ], 2.69 (2H, t, J = 5.7, H-10),
3 2
1.86 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1664 (ν
), 1601 (ν
), 1542 (ν
), 1515 (ν
).
C=O
C=N
C–N
NO2
6,8-Dibromo-α-(4′-nitrobenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (23) was synthesized analo-
gously as above from 3 (0.4 g, 1.12 mmol) and 4-nitrobenzaldehyde (0.22 g, 1.5 mmol) to afford 23 (0.45 g, 82%).
C H N O Br , mp 270-271°C (aq. DMF), R 0.86 (system B).
19 13
3
3
2
f
PMR spectrum (δ, ppm, J/Hz): 8.12 (1H, d, J = 2.0, H-5), 8.0 (2H, d, J = 9.0, H-3′,5′), 7.97 (1H, d, J = 2.0, H-7), 7.62
(1H, s, H-13), 7.36 (2H, d, J = 9.0, H-2′,6′), 3.92 (2H, t, J = 5.7, H-12), 2.72 (2H, td, J = 6.7, 1.7, H-10), 1.87 (2H, m, H-11).
IR spectrum (ν, cm-1): 1666 (ν ), 1584 (ν ), 1547 (ν ), 1508 (ν ).
C=O
C=N
C–N
NO2
6,8-Dibromo-α-(3′,4′-dimethoxybenzylidene)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (24) was synthesized
analogously as above from 3 (0.2 g, 0.56 mmol) and 3,4-dimethoxybenzaldehyde (0.12 g, 0.72 mmol) to afford 24 (0.19 g,
68%). C H N O Br , mp 192-193°C (benzene), R 0.85 (system B).
21 18
2
3
2
f
PMR spectrum (δ, ppm, J/Hz): 8.09 (1H, d, J = 2.0, H-5), 7.94 (1H, d, J = 2.02, H-7), 7.48 (1H, s, H-13), 7.0 (1H, dd,
J = 8.4, 2.0, H-6′), 6.84 (1H, d, J = 2.0, H-2′), 6.73 (1H, d, J = 8.4, H-5′), 3.89 (2H, t, J = 5.7, H-12), 3.58 [6H, d, (OCH ) ],
3 2
2.75 (2H, t, J = 6.7, H-10), 1.86 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1668 (ν
), 1585 (ν
), 1549 (ν
).
C–N
C=O
C=N
6,8-Dibromo-α-(furfuryliden-1′)-2,3-tetramethylen-3,4-dihydroquinazol-4-one (25) was synthesized analogously
3
as above from 3 (0.3 g, 0.84 mmol) and furfurol (0.1 mL, 0.115 g, 1.2 mmol, ρ = 1.1598 g/cm ) to afford 25 (0.265 g, 73%).
C H N O Br , mp 224-226°C (benzene), R 0.86 (system B).
17 12
2
2
2
f
PMR spectrum (δ, ppm, J/Hz): 8.26 (1H, d, J = 2.3, H-5), 8.12 (1H, t, J = 4.0, 2.0, H-13), 8.02 (1H, d, J = 2.3, H-7),
7.53 (1H, d, J = 1.8, H-5′), 6.65 (1H, d, J = 3.3, H-3′), 6.49 (1H, dd, J = 3.3, 1.8, H-4′), 4.09 (2H, m, H-12), 3.0 (2H, td, J = 6.6,
2.0, H-10), 2.0 (2H, m, H-11).
−1
IR spectrum (ν, cm ): 1672 (ν
), 1572 (ν
), 1554 (ν
).
C–N
C=O
C=N
407

ACKNOWLEDGMENT
The work was supported financially by Basic Research of TsNT RU (Project No. FA-FZ-T047). We thank Candidate
of Chemical Sciences V. I. Vinogradova for supplying the substituted vanillins.
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