Synthesis of tetra- and pentaazaheterocyclic systems and benzimidazo[1,2-c]quinazoline derivatives

Article abstract of DOI:10.1134/S1070428014020195

Starting with 5-carboxy-4-hydroxy-2-phenylpyrimidine and 4-hydroxy-6-methyl(hydroxy)-2-phenylpyrimidinyl-5-propanoic acids derivatives of two heterocyclic systems, benzimidazopyrido- and pyrimidopyrimidine, were synthesized. Synthesis of new S-substituted

Full text of DOI:10.1134/S1070428014020195

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 2, pp. 257−262. © Pleiades Publishing, Ltd., 2014.
Original English Text © A.A. Arutyunyan, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 2, pp. 264−269.
Synthesis of Tetra- and Pentaazaheterocyclic Systems
and Benzimidazo[1,2-с]quinazoline Derivatives
A. A. Arutyunyan
R&D Center of Organic and Pharmaceutical Chemistry, National Academy of Sciences of Armenia,
Mndzhoyan Institute of Fine Organic Chemistry, Yerevan, 0014 Armenia
e-mail: harutyunyan.arthur@yahoo.com
Received April 17, 2013
Abstract—Starting with 5-carboxy-4-hydroxy-2-phenylpyrimidine and 4-hydroxy-6-methyl(hydroxy)-
2-phenylpyrimidinyl-5-propanoic acids derivatives of two heterocyclic systems, benzimidazopyrido- and
pyrimidopyrimidine, were synthesized. Synthesis of new S-substituted benzimidazo[1,2-c]quinazolines was also
carried out.
DOI: 10.1134/S1070428014020195
Heterofused benzimidazoles are an extensively studied
class of polyazaheterocyclic compounds whose numerous
specimens find growing application in the technology,
biology, and medicine [1, 2]. For instance, nearly a cen-
tury after the first synthesis of the heterocyclic system of
benzimidazo[1,2-c]quinazoline [3] among its derivatives
compounds were found possessing a high cytotoxicity
with respect to tumor cells in vitro [4, 5]. These properties
are ascribed to the capability of the fused benzimidazoles
possessing a planar structure to intercalate between the
neighbor DNA bases thus impeding the replication and
transcription processes [2, 4].
adducts of ethyl acetoacetate or malonic ester and ethyl
acrylate or methyl methacrylate in the medium of anhy-
drous ethanol in the presence of sodium ethylate .
The reaction of propanoic acids Iа–Ig with
о-phenylenediamine in polyphosphoric acid (PPA)
takes different routes depending on the substituent in the
position 2 of the pyrimidine ring. In the case of 2-phenyl-
substituted pyrimidine-5-propanoic acids Iа, Ib [8] and
Ic [6] the condensation affords 2-phenyl derivatives
of the heterocyclic system 5,6-dihydrobenzо[4',5']-
imidazo[1',2':1,6]-pyrido[2,3-d]pyrimidine IIа–IIc [6]
(Scheme 1).
In the presence of the electron-acceptor phenyl group
in the position 2 the reaction proceeds apparently through
two stages: the primarily formed benzimidazole deriva-
tive under the reaction conditions undergoes further a
cyclization into compounds IIа–IIc; the replacement of
the methyl group in the position 6 of the pyrimidine ring
for the hydroxy group (acid Iа) does not prevent this
reaction course.
Considering this and in continuation of research
directed to finding new biologically active pyrimidine
and azaheterocycles derivatives [6, 7] we synthesized
new pyrimidin-5-ylbenzimidazoles and also tetracyclic
compounds, derivatives of tetra- and pentaazaheterocyclic
systems of benzо[4',5']imidazo[2',1',6,1]pyrido[2,3-d]-
pyrimidine and benzо[4,5]imidazo[1,2-c]pyrimido[5,4-e]
pyrimidine (pyrimidine isoster of benzimidazo[1,2-c]-
quinazoline), and also new S-benzyl-derivatives of
benzimidazo[1,2-c]quinazoline and its dimers.
However in the case of acids Id–Ig containing donor
substituents (R3 = Me, NH2, OH, SH) the condensation
proceeds only till the formation of benzimidazole deriva-
tives IIIа–IIId.
As initial compounds for the synthesis of pyrimidi-
nylbenzimidazoles and of derivatives of the heterocyclic
system 5,6-dihydrobenzо[4',5']imidazo-[2',1',6,1]-
pyrido[2,3-d]pyrimidine we used the corresponding
substituted pyrimidinyl-5-propanoic acids Iа–Ig obtained
from appropriate amidines, guanidine, or thiourea with
The methyl group in the position 6 of compound IIIа
reacted cleanly with 4-nitrobenzaldehyde in the presence
of ZnCl2 along Claisen condensation type giving a single
reaction product, styrylpyrimidine IV.
257

ARUTYUNYAN
258
Scheme 1.
OH
N
Ph
N
N
N
3
R = Ph
NH
2
N
H
N
N
R2
NH
R2
2
O
N
O
Ph
N
O
R1
R1
OH
IIa_IIc
HN
R3
R2
R1
PPA
HN
Ia_Ig
N
HN
R4
N
Me
IIIa_IIId
I, R3 = Ph: R1 = OH, R2 = Me (а); R1 = Mе, R2 = Н (b); R1 = R2 = Me (c); R1 = Me, R2 = H, R3 = Me (d), NH2 (e), OH (f),
SH (g); II, R1= OH, R2 = Me (а); R1 = Me, R2 = H (b); R1 = R2 = Me (c); III, R4 = Me (а), NH2 (b), OH (c), SH (d).
In order to prepare probable biologically ac-
tive benzimidazo[1,2-c]quinazolines we subjected
benzimidazo[1,2-c]quinazoline-2-thiol (X) [3] to al-
kylation with appropriate benzyl chlorides, 2-amino-
4-methyl-6-chloropyrimidine, and xylene dihalides in
the presence of NaOH to obtain new S-alkyl derivatives
of this system XIа–XIf and isomeric dimers XIg, XIh
(Scheme 3).
NO
2
O
N
HN
N
HN
Me
O
IIIa
ZnCl
2
EXPERIMENTAL
NO2
IV
IR spectra were recorded on a spectrophotometer
Nicolet Avatar 330 from mulls in mineral oil, 1Н NMR
spectra were registered on a spectrometer Varian Mer-
cury-300 at operating frequency 300 MHz, internal
reference TMS. TLC was carried out on Silufol UV-254
plates, development in iodine vapor.
The synthesis of derivatives of a new heterocyclic
system of benzо[4,5]imidazo[1,2-c]pyrimido[5,4-e]-
pyrimidine we performed on the basis of the classic ap-
proach developed at the preparation of benzimidazo[1,2-
c]quinazoline derivatives from anthranilic acid and
о-phenylenediamine [3].
3-(4-Hydroxy-6-oxo-2-phenyl-1,6-dihydropyrim-
idin-5-yl)-2-methylpropanoic acid (Iа). To a solution
of 2.3 g (0.1 mol) of sodium in 640 g (4 mol) of malonic
ester was added 100 g (1 mol) of methyl methacrylate,
the mixture was heated at reflux for 24 h at 70–80°С.
The reaction mixture was neutralized with 10% HCl, the
precipitated oily substance was separated, washed with
water, dried with Na2SO4, and distilled in a vacuum col-
lecting the fraction boiling at 200–210°С (110 mm Hg),
yield 60%. 26.0 g (0.1 mol) of compound obtained was
added to slurry of 15.7 g (0.1 mol) of benzamidine hy-
drochloride in a solution of 4.6 g (0.2 mol) of sodium in
250 mL of anhydrous ethanol, the reaction mixture was
The initial pyrimidine-5-carboxylic acid V [9] was
chlorinated with POCl3 and the obtained 4-chloro deriva-
tive VI was treated with ammonia in ethanol. 4-Amino-
pyrimidine VII was heated with o-phenylenediamine in
PPA to get the key benzimidazole derivative VIII whose
reaction with CS2 in the presence of KOH afforded thione
IX with a medium yield (34%). The variation of reaction
conditions, solvents, and the application of tetrabutylam-
monium bromide did not result in the enhanced yield of
compound IX, the composition of the other probable
reaction products was not studied (Scheme 2).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

SYNTHESIS OF TETRA- AND PENTAAZAHETEROCYCLIC SYSTEMS
259
Scheme 2.
O
O
O
O
POCl3
HN
Ph
OH
N
OH
N
OH
NH3
EtOH
N
Ph
N
Cl
Ph
N
NH2
N
V
VII
VI
NH2
,
CS KOH
2
N
_
H O dioxane
N
N
2
N
H
NH2
NH2
PPA
N
Ph
N
N
H
S
Ph
N
VIII
IX
Scheme 3.
Cl
N
N
N
N
N
N
N
RX
H N
2
Me
N
S
N
N
_
_
NaOH H O
NaOH H O
2
N
2
SR
N
SH
Me
N
NH2
XIa_XIe
X
XIf
Cl
N
N
S
Br
Br
N
N
N
Cl
XX
N
S
S
N
N
N
_
_
NaOH H O
NaOH H O
2
2
N
S
N
N
XIg
XIh
R = 2'-ClC6H4CH2 (а), 4-MeO-3-NO2C6H3CH2 (b), 2,4-Me2C6H3CH2 (c), 2,4,6-Me3C6H2CH2 (d), 4-F-C6H4CH2 (e).
refluxed for 5 h, the solvent was evaporated to dryness.
To the residue a solution was added of 4 g (0.1 mol) of
NaOH in 100 mL of water, the mixture was boiled at re-
flux for 4 h and acidified with HCl to pH 3. The precipitate
was filtered off and dried. Yield 70%, mp >320°С with
decomp. (DMF), Rf 0.55 (ethanol–dichloroethane, 1 : 10).
IR spectrum, ν, cm–1: 1706, 1660 (CO), 1618 (C=N).
1H NMR spectrum (DMSO), δ, ppm : 1.09 d (3Н, CH3,
J 6.8 Hz), 2.65–2.78 m (3Н, СНСН2), 7.37–7.51 m (3Н)
and 8.12–8.16 m (2Нarom), 11.58 br (3Н, NH, OH and
COOH). Found, %: N 10.52. C14H14N2O4. Calculated,
%: N 10.21.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

ARUTYUNYAN
260
General procedure of pyrimidin-5-ylpropanoic
2.87 m (2Н, СН2), 7.07–7.13 m, 7.35–7.53 m (2H each,
С6Н4), 10.54 s and 10.94 s (1H each, 2CONH), 12.17 br
(1Н, NH). Found, %: N 20.47. C14H14N4O2. Calculated,
%: N 20.73.
acids condensation with о-phenylenediamine. A mix-
ture of 1.08 g (0.01 mol) of о-phenylenediamine and
0.01 mol of acid Iа–Ig with 10 g of PPA was heated for
3 h at 210–220°С, after cooling it was treated with excess
NH4OH, filtered, the precipitate was dried.
5-[2-(1Н-Benzо[d]imidazo-2-yl)ethyl]-6-methyl-2-
thioxo-2,3,4-dihydropyrimidin-4(1Н)-one (IIId) was
obtained from acid Ig [10]. Yield 82%, mp 325–327 °С
(ethanol), Rf 0.78 (ethanol–dichloroethane, 1 : 10). IR
spectrum, ν, cm–1: 3440 (NH), 1660–1575 (CO, C=N,
(RS)-6-Methyl-2-phenyl-5,6-dihydrobenzо[4',5']-
imidazo[1',2':1,6]pyrido[2,3-d]pyrimidin-4-ol (IIа).
Yield 72%, yellow powder, mp >340°С (DMF), Rf 0.64
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
1
NH–C=S). H NMR spectrum (DMSO–CCl4, 1 : 3), δ,
ppm: 1.96 s (3Н, СН3), 2.73–2.82 m (2Н, СН2), 2.89–
2.97 m (2Н, СН2), 7.01–7.07 m (2Н) and 7.36–7.43 m
(2Н, С6Н4), 11.84 br, 11.92 br, and 12.03 br (all 1H each,
3NH). Found, %: N 19.30. C14H14N4OS. Calculated, %:
N 19.57.
1
1643 (СО), 1611 (C=N). H NMR spectrum (DMSO–
CCl4, 1 : 3), δ, ppm: 1.57 d (3Н, CH3, J 6.8 Hz), 2.52 d.d
(1H, CH2, 1J 16.4, 2J 11.2 Hz), 3.16 d.d (1H, CH2, 1J 16.4,
2J 6.6 Hz), 3.32 m (1H, CH), 7.25 m, 7.30 m, 7.62 m,
8.45 m (1H each, C6H4), 7.53–7.65 m, 8.28 m (3Н and
2H, C6H5), 12.95 br (1H, ОH). Found, %: N 17.25.
C20H16N4O. Calculated, %: N 17.06.
5-[2-(1Н-Benzо[d]imidazo-2-yl)ethyl]-2-methyl-4-
[(Е)-2-(4-nitrophenyl)-1-ethenyl]pyrimidin-4(3H)-one
(IV). A mixture of 2.68 g (0.01 mol) of pyrimidine IIIа,
1.51 g (0.01 mol) of 4-nitrobenzaldehyde, and 1.36 g
(0.01 mol) of ZnCl2 was melted at heating on Wood’s
metal bath at 150–160°С for 2 h, on cooling the melt
was treated with water and recrystallized from DMF.
Yield 65%, mp 297–298 °С, Rf 0.54 (ethanol – dichlo-
roethane, 1 : 10). IR spectrum, ν, cm–1: 3623 (OH),
3364 (NH), 1648 (CO), 1600 (C=N). 1H NMR spectrum
(DMSO–CCl4, 1 : 3), δ, ppm: 2.13 s (3Н, СН3), 2.93 t,
3.09 t (2H each, СН2СН2, J 7.5 Hz), 7.06 d (1Н, =CH,
J 16.1 Hz), 7.13–7.19 m, 7.48–7.64 m (2H each, С6Н4),
7.87 m, 8.27 m (2H each, С6Н4NO2), 7.89 d (1Н, =CH,
J 16.1 Hz), 12.52 br (2Н, NH, OH). Found, %: N 17.34.
C22H19N5O3. Calculated, %: N 17.45.
4-Methyl- and (RS)-4,6-dimethyl-2-phenyl-5,6-
dihydrobenzо[4',5']imidazo[1',2':1,6]pyrido[2,3-d]-
pyrimidines (IIb, IIc) were obtained from acid Ib [8]
and Ic [6] and о-phenylenediamine by procedure [6].
5-[2-(1Н-Benzо[d]imidazo-2-yl)ethyl]-2,6-dimeth-
yl-pyrimidin-4(3H)-one (IIIa) was obtained from acid
Id [8]. Yield 75%, mp 306–307°С (DMF), Rf 0.67
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
1
3350 (NH), 1652 (СО), 1610 (C=N). H NMR spec-
trum (DMSO–CCl4, 1 : 3), δ, ppm: 2.07 s, 2.30 s (3Н
each, СН3), 2.82–2.96 m (4Н, СН2СН2), 7.07–7.13 m,
7.42–7.48 m (2H each, С6Н4), 12.20 br, 12.24 br (1Н
each, ОН and NH). Found, %: N 20.62. C15H16N4O.
Calculated, %: N 20.88.
2-Phenyl-4-chloropyrimidine-5-carboxylic acid
(VI). A mixture of 2.16 g (0.01 mol) of acid V and
5.0 mL of POCl3 was boiled for 2 h, excess POCl3 was
distilled off, the oily residue was poured on 50 g of ice.
After 1 h the precipitate was filtered off, washed with cold
water, and dried. Yield 87%, mp 114–115°С (dioxane),
Rf 0.80 (ethyl acetate–octane, 1 : 2). 1H NMR spectrum
5-[2-(1Н-Benzо[d]imidazo-2-yl)ethyl]-2-amino-6-
methylpyrimidin-4(3H)-one (IIIb) was obtained from
acid Ie [10]. Yield 68%, mp 223–225°С (ethanol), Rf 0.69
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
3340, 3180 (NH2, NH), 1656 (СО), 1608 (C=N). 1H NMR
spectrum (DMSO–CCl4, 1 : 3), δ, ppm: 2.04 s (3Н, СН3),
2.76–2.83 m (2Н, СН2), 2.88–2.95 m (2Н, СН2), 6.24 br
(2Н, NH2), 7.00–7.05 m (2Н) and 7.36–7.42 m (2Н,
С6Н4), 11.07 br.s and 11.86 br.s (1H each, 2NH). Found,
%: N 26.30. C14H15N5O. Calculated, %: N 26.01.
(DMSO–CCl4, 1 : 3), δ, ppm: 7.49–7.56 m (2Нarom
,
,
Н3',5'), 7.58–7.64 m (1Нarom, Н4'), 8.24–8.29 m (2Нarom
Н2',6'), 8.78 s (1Н, N=CH), 13.73 br (1Н, ОH). Found, %:
N 11.70. C11H7ClN2O2. Calculated, %: N 11.94.
5-[2-(1Н-Benzо[d]imidazo-2-yl)ethyl]-6-methyl-
pyrimidine-2,4(1H,3H)dione (IIIc) was obtained
from acid If [11]. Yield 63%, ppm 200–202°С, Rf 0.49
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
3400 (NH), 1651 (СО), 1572 (C=N). 1H NMR spectrum
(DMSO), δ, ppm: 1.87 s (3Н, СН3), 2.69 m (2Н, СН2),
4-Amino-2-phenylpyrimidine-5-carboxylic acid
(VII). A solution of 2.35 g (0.01 mol) of 4-chloro-
pyrimidine VI in 50 mL of saturated ammonia solution
in ethanol was heated for 4 h in a pressure reactor at
120–130°С. After evaporation and treatment with 30 mL
of water the separated precipitate was filtered off and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

SYNTHESIS OF TETRA- AND PENTAAZAHETEROCYCLIC SYSTEMS
261
dried. Yield 82%, mp 273–274°С (dimethyl cellosolve),
Rf 0.59 (ethanol–dichloroethane, 1 : 10). IR spectrum, ν,
cm–1: 3484, 3309, 3170 (NH2), 1683 (CO), 1620 (C=N).
1H NMR spectrum (DMSO–CCl4, 1 : 3), δ, ppm: 7.07 br,
7.68 br, 7.91 br (1H each, NH2 and СООН), 7.36–7.43 m
(3Нarom, Н3'–5'), 8.33–8.40 m (2Нarom, Н2',6'), 8.78 s (1Н,
N=CH). Found, %: N 19.81. C11H9N3O2. Calculated,
%: N 19.53.
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
1615 (C=N). H NMR spectrum (DMSO), δ, ppm:
4.94 s (2Н, СН2), 7.23–7.32 m (2Н), 7.38–7.63 m (4Н),
7.73–7.81 m (2Н), 7.86–7.90 m (2Н), 8.39 br.d (1Н,
J 8.2 Hz), 8.56 d.d (1Нarom, J 8.0, 1.4 Hz). Found, %:
N 11.42. C21H14ClN3S. Calculated, %: N 11.18
1
6-(4-Methoxy-3-nitrobenzylsulfanyl)benzо[4,5]-
imidazo[1,2-c]quinazoline (XIb) was obtained from
4-methoxy-3-nitrobenzyl chloride. Yield 82%, mp 253–
255°С (DMF), Rf 0.54 (ethanol–dichloroethane, 1 : 10).
5-(1Н-Benzо[d]imidazo-2-yl)-2-phenylpyrimidin-
4-amine (VIII). A mixture of 2.15 g (0.01 mol) of acid
VII, 1.19 g (0.011 mol) of о-phenylenediamine, and
10.0 g of PPA was heated for 2 h on Wood’s metal bath at
220–230°С, cooled to room temperature, neutralized with
NH4OH, the separated precipitate was filtered off and dried.
Yield 85%, mp > 330°С (dioxane), Rf 0.68 (ethanol–di-
chloroethane, 1 : 10). IR spectrum, ν, cm–1: 3379, 3268
1
IR spectrum, ν, cm–1: 1621 (C=N). H NMR spectrum
(DMSO–CCl4, 1 : 3), δ, ppm: 3.93 s (3Н, OСН3), 4.82 s
(2Н, СН2), 7.21d (1Нarom, Н6,С6Н3, J 8.7 Hz), 7.42 d.d.d
(1Н, С6Н4, J 8.2, 7.2 and 1.5 Hz), 7.51 d.d.d (1Н, С6Н4,
J 8.0, 7.2, 1.2 Hz), 7.60 d.d.d (1Н, С6Н4, J 7.9, 7.2,
1.2 Hz), 7.77 d.d.d (1Н, С6Н4, J 8.7, 7.2 and 1.7 Hz), 7.83-
7.90 m (2Нarom), 7.85 d,d (1Н, Н5', С6Н3, J 8.7, 2.3 Hz),
8.15 d (1Н, Н3', С6Н3, J 2.3 Hz), 8.40 br.d (1Н, С6Н4,
J 8.2 Hz), 8.56 d.d (1Н, С6Н4 , J 8.0, 1.7 Hz). Found, %:
N 13.45. C22H16N4 O3S. Calculated, %: N 13.10.
1
(NH2, NH), 1625 (C=N). H NMR spectrum (DMSO–
CCl4, 1 : 3), δ, ppm: 7.12–7.22 m (2Н), 7.39–7.55 m (4Н),
7.59–7.66 m (1Н) and 8.40–8.46 m (2Нarom), 9.05 s (1Н,
N=CH), 9.28 br (2Н, NH2), 12.76 br.s (1Н, NH). Found,
%: N 24.58. C17H13N5. Calculated, %: N 24.37.
6-(2,4-Dimethylbenzylsulfanyl)benzо[4,5]
imidazo[1,2-c]quinazoline (XIc) was obtained from
2,4-dimethylbenzyl chloride. Yield 74%, mp 155–156°С
(ethanol), Rf 0.61 (ethanol–dichloroethane, 1 : 10). IR
3-Phenylbenzо[4,5]imidazo[1,2-c]pyrimido[5,4-
e]-pyrimidine-6(5H)-thione (IX). A mixture of 1.44 g
(5 mmol) of amine VIII, 1.4 g (25 mmol) of KОН, and
0.76 g (0.6 mL, 10 mmol) of CS2 in a mixture of 5' mL
of water and 35' mL of dioxane was boiled at reflux for
24 h, then the solvent was evaporated to dryness, 50' mL
of water was added, the mixture was heated to boiling,
the solution was filtered to remove tarry impurities and
it was acidified with HCl to рН 5. After standing in the
cold the separated precipitate was filtered off and dried.
Yield 0.56 g (34%), mp >340°С (ethyl cellosolve),
Rf 0.61 (ethanol–dichloroethane, 1 : 10). IR spectrum,
ν, cm–1: 1596 (NH–C=S). 1H NMR spectrum (DMSO–
CCl4, 1 : 3), δ, ppm: 7.11–7.18 m, 7.58–7.65 m (2H each,
С6Н4), 7.47–7.56 m, 8.28–8.34 m (3Н and 2Н, С6Н5),
9.14 br.s (1Н, =CH), 12.54 br (1Н, NH). Found, %: N
21.40. C18H11N5S. Calculated, %: N 21.26.
1
spectrum, ν, cm–1: 1620 (C=N). H NMR spectrum
(DMSO), δ, ppm: 2.31 s (3Н, СН3), 2.48 s (3Н, СН3),
4.80 s (2Н, СН2), 6.96 d.d (1Н, Н5', С6Н3, J 7.9, 1.9 Hz),
7.01 d (1Н, Н3', С6Н3, J 1.9 Hz), 7.35–7.41 m (2Н, С6Н4),
7.50 d.d.d (1Н, С6Н4, J 8.1, 7.3. 1.0 Hz), 7.60 d.d.d (1Н,
С6Н4, J 7.9, 7.1, 1.3 Hz), 7.76 d.d.d (1Н, С6Н4, J 8.2, 7.1,
1.5 Hz), 7.83–7.90 m (2Н, С6Н4), 8.38 br.d (1Н, С6Н4,
J 8.3 Hz), 8.57 d.d (1Н, С6Н4, J 7.9, 1.5 Hz). Found, %:
N 11.08. C23H19N3S. Calculated, %: N 11.37.
6-(2,4,6-Trimethylbenzylsulfanyl)benzо[4,5]
imidazo[1,2-c]quinazoline (XId) was obtained from
2,4,6-trimethylbenzyl chloride. Yield 67%, mp 186–
187°С (ethanol), Rf 0.76 (ethanol–dichloroethane, 1 : 10).
1
IR spectrum, ν, cm–1: 1621 (C=N). H NMR spectrum
Benzimidazo[1,2-c]quinazolines XIа–XIi. General
procedure. To a solution of 2.51 g (0.01 mol) of com-
pound X in 50 mL of 0.2 N NaOH was added 0.011 mol
of substituted benzyl chlorides, chloropyrimidine, or
0.005 mol of corresponding xylene dihalides, and the
slurry was heated at reflux for 24 h on a water bath. The
precipitate was filtered off, washed with water, and dried.
(DMSO– CCl4, 1 : 3), δ, ppm: 2.29 s (3Н, СН3), 2.46 s
(6Н, СН3), 4.81 s (2Н, СН2), 6.87 s (2Н, С6Н2), 7.35
d.d.d (1Н, С6Н4, J 8.3, 7.3, 1.2 Hz), 7.49 d.d.d (1Н,
С6Н4, J 8.0, 7.1, 1.0 Hz), 7.60 d.d.d (1Н, С6Н4, J 8.0,
7.0, 1.2 Hz), 7.75 d.d.d (1Н, С6Н4, J 8.1, 7.1, 1.5 Hz),
7.84 d.d (1Н, С6Н4, J 8.0, 1.0 Hz), 7.89 br.d (1Н, С6Н4,
J 8.1 Hz), 8.35 br.d (1Н, С6Н4, J 8.3 Hz), 8.59 d.d (1Н,
С6Н4, J 8.0, 1.4 Hz). Found, %: N 11.17. C24H21N3S.
Calculated, %: N 10.96.
6-(2-Chlorobenzylsulfanyl)benzо[4,5]imidazo[1,2-
c]quinazoline (XIа) was obtained from 2-chlorobenzyl
chloride. Yield 79%, mp 205–207°С (dioxane), Rf 0.59
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014

ARUTYUNYAN
262
6-(4-Fluorobenzylsulfanyl)benzо[4,5]imidazo[1,2-
1,4-Bis{(benzо[4,5]imidazo[1,2-c]quinazolin-6-
ylsulfanyl)methyl}benzene (XIh). Yield 52%, mp
290–292°С (DMF), Rf 0.62 (ethanol–dichloroethane,
1 : 10). IR spectrum, ν, cm–1: 1620 (C=N). 1H NMR spec-
trum (DMSO), δ, ppm: 4.84 s (4Н, СН2), 7.37–7.67 m
(6Нarom), 7.62 s (4Н, С6Н4), 7.79–7.96 m (6Нarom),
8.41 br.d (2Нarom, J 8.2 Hz), 8.51 br.d (2Нarom, J 7.7 Hz).
Found, %: N 13.65. C36H24 N6S2. Calculated, %: N 13.90.
c]quinazoline (XIe) was obtained from 4-fluorobenzyl
chloride. Yield 80%, mp 160–161°С (ethanol), Rf 0.50
(ethanol–dichloroethane, 1 : 10). IR spectrum, ν, cm–1:
1618 (C=N). 1H NMR spectrum (DMSO), δ, ppm: 4.82 s
(2Н, СН2), 7.04 m (2Н, Н3',5', С6Н4F), 7.41 d.d.d (1Н,
С6Н4, J 8.3, 7.2, 1.4 Hz), 7.51 d.d.d (1Н, С6Н4, J 8.0,
7.3, 1.2 Hz), 7.57–7.63 m (3Н, Н2',6', С6Н4F and С6Н4),
7.76 d.d.d (1Н, С6Н4, J 8.2, 7.1, 1.6 Hz), 7.83–7.90 m
(2Н, С6Н4), 8.40 br.d (1Н, С6Н4, J 8.3 Hz), 8.57 d.d (1Н,
С6Н4, J 8.0, 1.2 Hz). Found, %: N 11.52. C21H14 FN3S.
Calculated, %: N 11.69.
REFERENCES
1. Rohini, R., Shanker, K., Reddy, P.M., Ho, Y.P., and Ravin-
der, V., Eur. J. Med. Chem., 2009, vol. 44, p. 3330.
2. Lyakhova, E.A., Guseva, Yu.A., Lyakhov, S.A., and An-
dronati, S.A., Zh. Org. Farm. Khim., 2010, vol. 8, no. 30,
p. 3.
3. Von Niementowski, S., Ber., 1899, vol. 32, p. 1456.
4. Brana, M.F., Castellano, J.M., Keilhauer, G., Machuca,A.,
Martin, Y., Redondo, C., Schlick, E., and Wlker, N., Anti-
Cancer, Drug, Des., 1994, vol. 9, p. 527; Chem. Abstr.,
1995, vol. 122, 204569q.
5. Brana, M.F., De, Vega, M.J.P., Perron, D., Conlon, D.,
Bousquet, P.F., and Robinson, S.P., J. Heterocycl. Chem.,
1997, 34, (3), 807.
6. Arutyunyan,A.A., Khim. Zh. Armenii., 2012, vol. 65, no. 2,
p. 257.
7. Arutyunyan,A.A., Khim. Zh. Armenii., 2012, vol. 65, no. 3,
p. 317.
8. Hullar, T.L. and French, W.C., J.Med.Chem., 1969, vol. 12,
no. 3, p. 424.
9. Ruhemann, S., Ber., 1897, vol. 30, p. 821.
10. Baker, B.R. andAlmaula, P.I., J. Heterocycl. Chem., 1964,
vol. 1, no. 5, p. 263.
4-(Benzо[4,5]imidazo[1,2-c]quinazolin-6-
ylsulfanyl)-6-methylpyrimidin-2-amine (XIf) was
obtained from 2-amino-6-methyl-4-chloropyrimidine.
Yield 85%, mp 305–307°С (Н2О), Rf 0.74 (ethanol–di-
chloroethane, 1 : 10). IR spectrum, ν, cm–1: 3416, 3309
(NH2), 1628 (C=N). 1H NMR spectrum (DMSO), δ, ppm:
2.24 s (3Н, СН3), 6.38 s (1Н, Н5', pyrimidine), 6.54 br.s
(2Н, NH2), 7.34–7.40 m (2Н), 7.47 d.d.d (1Н, J 8.0, 7.3,
1.2 Hz), 7.56–7.64 m (2Н), 7.80 br.d (1Н, J 7.9 Hz),
8.41 br.d (1Н, J 8.0 Hz), 9.49 br.d (1Н, С6Н4, J 8.2 Hz).
Found, %: N 23.63. C19H14 N6S. Calculated, %: N 23.45.
1,2-Bis{(benzо[4,5]imidazo[1,2-c]quinazolin-6-
ylsulfanyl)methyl}benzene (XIg). Yield 52%, mp
288–290°С (DMF), Rf 0.60 (ethanol– dichloroethane, 1 :
10). IR spectrum, ν, cm–1: 1620 (C=N). 1H NMR spectrum
(DMSO), δ, ppm: 5.18 s (4Н, СН2), 7.21 d.d.d (2Нarom
J 8.4, 7.2, 1.2 Hz), 7.36–7.58 m (10Нarom), 7.69–7.74 m
(2Нarom), 7.84 br.d (2Нarom, J 8.1 Hz), 8.23 br.d (2Нarom
,
,
11. Ge, X. and Roux, B., J. Phys. Chem. B, 2010, vol. 114,
no. 29, p. 9525.
J 8.4 Hz), 8.27 d.d (2Нarom, J 7.5, 1.8 Hz). Found, %:
N 13.72. C36H24 N6S2. Calculated, %: N 13.90.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 2 2014