New general synthesis of benzo[4,5]imidazo[1,2-a]pyrimidine and benzo[4,5]imidazo[2,1-b]quinazoline derivatives

Article abstract of DOI:10.1134/S1070428016070150

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5

Full text of DOI:10.1134/S1070428016070150

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 7, pp. 1012–1017. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © A.A. Harutyunyan, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 7, pp. 1018–1023.
New General Synthesis of Benzo[4,5]imidazo[1,2-a]pyrimidine
and Benzo[4,5]imidazo[2,1-b]quinazoline Derivatives
A. A. Harutyunyan
Mndzhoyan Institute of Fine Organic Chemistry, Scientific Technological Center of Organic and Pharmaceutical Chemistry,
National Academy of Sciences of Armenia, pr. Azatutyan 26, Yerevan, 0014 Armenia
e-mail: harutyunyan.arthur@yahoo.com
Received December 11, 2015
Abstract—The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-
6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under
solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-
quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first
example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline
and is likely to follow ANRORC mechanism.
DOI: 10.1134/S1070428016070150
In recent years, an increased interest has been ob-
served in the synthesis and properties of fused nitrogen
heterocycles based on pyrimidine, quinazoline, and
benzimidazole, in particular benzo[4,5]imidazo[1,2-a]-
pyrimidine (1) and benzo[4,5]imidazo[2,1-b]quinazo-
line (2) derivatives, many of which exhibit a broad
spectrum of biological activity [1–4].
All known synthetic approaches to benzo[4,5]-
imidazo[1,2-a]pyrimidine derivatives are based on
the condensation of benzimidazol-2-amine (3a) as
1,3-N,N-binucleophile with various 1,3-bielectrophiles
and their synthetic equivalents [2, 3, 5], while benzo-
[4,5]imidazo[2,1-b]quinazoline derivatives are ob-
tained by condensation of 2-substituted benzimidaz-
oles 3a–3d with anthranilic or 2-chloro or 2-bromo-
benzoic acid, as well as by thermal rearrangement of
substituted indazole or by reaction of isatoic anhydride
with benzene-1,2-diamine [6]. Thus, all so-far-known
methods for the synthesis of heterocyclic systems 1
and 2 involve mainly closure of pyrimidine or quinazo-
line ring on benzimidazole derivatives, whereas an al-
ternative approach implying fusion of benzimidazole
to already existing pyrimidine or quinazoline ring has
not been reported.
As an implementation of the latter approach, the
present article describes a new general method for the
synthesis of derivatives of heterocyclic systems 1 and
2 according to a cascade mechanism. The condensation
of substituted ethyl acetoacetates 4a and 4b with thio-
urea in anhydrous ethanol in the presence of sodium
ethoxide gave 2-thioxopyrimidines 5b and 5d which,
as well as previously described analogs 5a and 5c,
were alkylated with propyl bromide and butyl bromide
to obtain key 2-(alkylsulfanyl)pyrimidines 6a–6d.
2-Propylsulfanyl derivatives 6a and 6b reacted with
benzene-1,2-diamine (7) at 175–185°C without a sol-
vent to give targeted benzo[4,5]imidazo[1,2-a]pyrimi-
dines 8a and 8b. Under analogous conditions, 5-aryl-
methyl-substituted compounds 6c and 6d gave rise to
mixtures of products, from which bis-pyrimidines 9a
and 9b were isolated in poor yield by crystallization
from DMF (Scheme 1).
N
N
N
N
N
N
1
2
H
N
These unexpected results may be rationalized in
terms of the ANRORC mechanism including several
fast consecutive reactions: double nucleophilic attack
on C2 in 6a and 6b by the vicinal amino groups of
benzene-1,2-diamine with elimination of propane-1-
R
N
3a–3d
R = H2N (a), Cl (b), MeS (c), HOSO2 (d).
1012

NEW GENERAL SYNTHESIS OF BENZO[4,5]IMIDAZO[1,2-a]PYRIMIDINE
1013
Scheme 1.
O
O
N
O
O
R
R
S
EtONa, EtOH
AlkBr, NaOH
HN
HN
+
EtO
Me
H2N
NH2
S
R
N
H
Me
AlkS
Me
R
4a, 4b
5a–5d
6a–6d
Me
O
N
O
MeI, DMF
NH2
NH2
N
Me
Me
6a, 6b
N
N
N
H
N
7
Me
10
175–185°C
8a, 8b
O
O
NH
HN
6c, 6d
R
NH HN
R
N
N
Me
Me
9a, 9b
4, R = 2,4-Me2C6H3 CH2 (a), CH2=C(Me)CH2 (b); 5, R = Me (a), CH2=C(Me)CH2 (b), PhCH2 (c), 2,4-Me2C6H3CH2 (d); 6, Alk = Pr,
R = Me (a), PhCH2 (c), 2,4-Me2C6H3CH2 (d); Alk = Bu, R = CH2=C(Me)CH2 (b); 8, R = Me (a), CH2=C(Me)CH2 (b);
9, R = PhCH2 (a), 2,4-Me2C6H3CH2 (b).
Scheme 2.
O
R
H2N
H
Me
O
O
N
NH
R
R
HN
HN
H
N
7
N
6a, 6b
8a, 8b
C
–AlkSH
–NH3
HN
N
Me
N
H
Me
NH
O
R
NH2
N
N
NH
Me
H2N
A
B
H
D
thiol and 1,3-proton migration (assumed intermediates
A and B), selective opening of the pyrimidine ring at
the C2–N3 bond, and final recyclization via nucleo-
philic substitution of the amino group in intermediate
butenamide by the NH group of the benzimidazole
fragment (assumed intermediate C) with elimination of
ammonia (Scheme 2).
is double (cf. structure F). On the other hand, both
N1,N3-prototropy (tautomer H) and amide–imidic acid
tautomerism (tautomer G) are possible for assumed
intermediate D with reduced contribution of the
HNC(NH)=NC=O structure (Scheme 3).
The alkylation of 2,3-dimethyl-substituted benzo-
[4,5]imidazo[1,2-a]pyrimidine 8a with methyl iodide
in DMF in the presence of potassium carbonate
regioselectively afforded 2,3,10-trimethyl derivative
10 (Scheme 1). The structure of 10 was confirmed by
the 2D NOESY spectrum which revealed NOE be-
The formation of only one isomer, 4-oxo derivative
8a or 8b, is likely to be favored by the higher strength
of the exocyclic C2–N bond in intermediate C which
may exist mainly as tautomer E where the above bond
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HARUTYUNYAN
1014
Scheme 3.
HO
O
NH2
Me
NH2
Me
R
R
H
N
N
C
N
N
N
H
N
H
F
E
Me
Me
NH2
O
NH2
OH
R
R
H
N
N
D
N
N
N
H
N
H
H
G
tween the 10-CH3 and 9-H protons. The lack of NOE
between the 10-CH3 and 2-CH3 protons also indicated
methylation at the 10-position.
sulfanyl)pyrimidines and -quinazolines. The proposed
method avoids the use of benzimidazol-2-amine which
is obtained from highly toxic starting materials.
Likewise, the alkylation of 2-thioxoquinazolines
11a and 11b with propyl bromide in water in the pres-
ence of NaOH gave 2-(propylsulfanyl)quinazolines
12a and 12b. Quinazoline 12c (R = R′ = H) was
described previously [7]. Compounds 12a–12c reacted
with diamine 7 at 175–185°C under solvent-free con-
ditions, yielding benzo[4,5]imidazo[2,1-b]quinazoline
derivatives 13a and 13b. The formation of 13a from
both 3-(3-methylphenyl)quinazoline 12a and 3-unsub-
stituted analog 12c confirmed selective cleavage of the
C2–N3 bond in the quinazoline ring system during the
reaction (Scheme 4).
EXPERIMENTAL
The IR spectra were recorded on a Nicolet Avatar
330 spectrometer from samples dispersed in mineral
oil. The H and 13C NMR spectra were measured on
1
a Varian Mercury-300 VX instrument at 300.8 and
75.46 MHz, respectively, using tetramethylsilane as
internal standard. Analytical thin-layer chromatog-
raphy was performed on Silufol UV-254 plates using
ethanol–dichloroethane (1:10) as eluent; spots were
visualized by treatment with iodine vapor.
2-Sulfanylidenepyrimidines 5b and 5d (general
procedure). Sodium metal, 2.3 g (0.1 mol), was dis-
solved in 100 mL of anhydrous ethanol, 13.0 g
(0.1 mol) of ethyl acetoacetate and 15.5 g (0.1 mol) of
2-(chloromethyl)-1,3-dimethylbenzene were added,
and the mixture was refluxed for 6 h. Excess ethanol
was distilled off, the residue was treated with 100 mL
of benzene, the benzene extract was washed with
water, dried, and evaporated, and the residue (ester 4a,
24 g, 97%) was used in the next step without ad-
ditional purification. Thiourea, 0.76 g (0.01 mol), and
The structure of the isolated compounds was
proved by spectral data and elemental analyses.
1
Signals in the H and 13C NMR spectra were assigned
using double resonance, DEPT, HMQC, and NOESY
techniques.
Thus, a new environmentally benign, economic,
and experimentally convenient method has been
developed for the synthesis of benzo[4,5]imidazo-
[1,2-a]pyrimidine and benzo[4,5]imidazo[2,1-b]quin-
azoline derivatives from readily accessible 2-(alkyl-
Scheme 4.
O
O
O
N
R
S
R'
R
S
R'
R'
7, 175–185°C
PrBr, NaOH
N
N
N
Pr
N
N
H
N
H
11a, 11b
12a, 12b
13a, 13b
11, 12, R = 3-MeC6H4, R′ = H (a); R = Me, R′ = I (b); 13, R = H (a), I (b).
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NEW GENERAL SYNTHESIS OF BENZO[4,5]IMIDAZO[1,2-a]PYRIMIDINE
1015
ester 4a or 4b [8], 0.01 mol, were added to a solution
of 0.46 g (0.02 mol) of sodium metal in 50 mL of
anhydrous ethanol, and the mixture was refluxed for
7 h. The solvent was distilled off, the residue was
dissolved in 50 mL of water, the solution was acidified
with acetic acid to pH 6, the mixture was kept for 8–
10 h in the cold, and the precipitate was filtered off
and dried.
4.53 m and 4.65–4.68 m (1H each, =CH2), 12.25 br.s
(1H, NH). 13C NMR spectrum (DMSO-d6–CCl4, 1:3),
δC, ppm: 13.2 (CH3CH2), 20.9 (CH3), 21.2 (CH2), 22.2
(CH3), 28.9 (CH2), 30.7 (CH2), 32.1 (CH2), 109.5
(=CH2), 116.2, 142.0, 157.2, 159.8, 162.4. Found, %:
N 11.10. C13H20N2OS. Calculated, %: N 11.10.
5-Benzyl-4-methyl-2-(propylsulfanyl)pyrimidin-
4(3H)-one (6c). Yield 79%, powder, mp 148–150°C
(from 60% EtOH), Rf 0.67. IR spectrum, ν, cm–1: 1653
6-Methyl-5-(2-methylprop-2-en-1-yl)-2-sulfanyli-
dene-2,3-dihydropyrimidin-4(1H)-one (5b) was syn-
thesized from ester 4b. Yield 1.0 g (51%), mp 226–
228°C (from EtOAc), Rf 0.28. IR spectrum, ν, cm–1:
3064 (N–H), 1648 (C=O), 1590 (C=C, C=N). Found,
%: N 14.39. C9H12N2OS. Calculated, %: N 14.27.
1
(C=O), 1573 (C=C, C=N). H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 1.03 t (3H, CH3CH2,
J = 7.4 Hz), 1.71 q.t (2H, CH3CH2, J = 7.4, 7.1 Hz),
2.19 s (3H, 4-CH3), 3.06 t (2H, SCH2, J = 7.1 Hz),
3.73 s (2H, CH2C6H5), 7.06–7.22 m (5H, C6H5),
12.38 br.s (1H, NH). 13C NMR spectrum (DMSO-d6–
CCl4, 1:3), δC, ppm: 12.9 (CH3), 21.3 (CH2), 22.0
(CH3), 30.0 (CH2), 31.2 (CH2), 125.2 (Cp), 127.6 (Co,
Cm), 139.5 (Ci). Found, %: N 10.18. C15H18N2OS.
Calculated, %: N 10.21.
5-[(2,4-Dimethylphenyl)methyl]-6-methyl-2-sul-
fanylidene-2,3-dihydropyrimidin-4(1H)-one (5d)
was synthesized from ester 4a. Yield 1.2 g (46%),
mp 307–308°C (from 60% AcOH), Rf 0.41. IR spec-
trum, ν, cm–1: 3060 (N–H), 1676 (C=O), 1620 (C=C,
C=N). Found, %: N 10.80. C14H16N2OS. Calculated,
%: N 10.76.
5-[(2,4-Dimethylphenyl)methyl]-4-methyl-
2-(propylsulfanyl)pyrimidin-4(3H)-one (6d). Yield
63%, powder, mp 175–177°C (from 60% EtOH),
Rf 0.62. IR spectrum, ν, cm–1: 1654 (C=O), 1553
5-Substituted 2-(alkylsulfanyl)pyrimidinones
6a–6d (general procedure). Propyl or butyl bromide,
0.011 mol, was added to a solution of 0.01 mol of
pyrimidinone 5a [9], 5b, 5c [10], or 5d and 0.4 g
(0.01 mol) of sodium hydroxide in 50 mL of water.
The mixture was heated for 15 h under reflux and left
overnight, and the precipitate was filtered off, washed
with water, and dried.
1
(C=C, C=N). H NMR spectrum (DMSO-d6–CCl4,
1:3), δ, ppm: 1.05 t (3H, CH3CH2, J = 7.3 Hz),
1.74 sext (2H, CH3CH2, J = 7.3 Hz), 2.09 s (3H, CH3),
2.25 s (3H, CH3), 2.32 s (3H, CH3), 3.09 t (2H, SCH2,
J = 7.3 Hz), 3.61 s (2H, CH2C6H3), 6.64 d (1H, 6′-H,
J = 7.7 Hz), 6.78 d.d (1H, 5′-H, J = 7.7, 1.7 Hz), 6.90 d
(1H, 3′-H, J = 1.7 Hz), 12.37 br.s (1H, NH). 13C NMR
spectrum (DMSO-d6–CCl4, 1:3), δC, ppm: 13.0
(CH3CH2), 19.1 (CH3), 20.3 (CH3), 21.2 (CH2), 22.0
(CH3), 26.8 (CH2), 31.3 (SCH2), 38.9, 39.2, 117.0,
125.8 (CH), 126.0 (CH), 130.1 (CH), 133.7, 133.9,
135.0, 157.4 br, 160.0, 162.5. Found, %: N 9.40.
C17H22N2OS. Calculated, %: N 9.26.
5,6-Dimethyl-2-(propylsulfanyl)pyrimidin-
4(3H)-one (6a). Yield 79%, finely crystalline powder,
mp 139–141°C (from EtOH), Rf 0.65. IR spectrum, ν,
1
cm–1: 1665 (C=O), 1620 (C=C, C=N). H NMR spec-
trum (DMSO-d6–CCl4, 1:3), δ, ppm: 1.02 t (3H,
CH2CH3, J = 7.3 Hz), 1.70 q.t (2H, CH2CH3, J = 7.3,
7.1 Hz), 1.89 s (3H, CH3), 2.19 s (3H, CH3), 3.05 t
(2H, SCH2, J = 7.1 Hz), 12.17 br.s (1H, NH).
13C NMR spectrum (DMSO-d6–CCl4, 1:3), δC, ppm:
10.1 (CH3), 12.9 (CH3), 21.1 (CH3), 22.0 (CH2), 31.2
(CH2), 114.3, 156.3, 158.2, 162.6. Found, %: N 14.33.
C9H14N2OS. Calculated, %: N 14.13.
2-Methyl-3-R-pyrimido[1,2-a]benzimidazol-
4(10H)-ones 8a–8d (general procedure). A mixture of
0.01 mol of compound 6a–6d and 1.19 g (0.011 mol)
of benzene-1,2-diamine was heated for 6 h at 175–
185°C on a Wood’s metal bath. After cooling, the melt
was treated with 20 mL of ethanol, the mixture was
kept for 2 h at 0°C, and the precipitate was filtered off
and recrystallized.
2-(Butylsulfanyl)-4-methyl-5-(2-methylprop-
2-en-1-yl)pyrimidin-4(3H)-one (6b). Yield 76%,
powder, mp 92–93°C (from 80% EtOH), Rf 0.57.
IR spectrum, ν, cm–1: 1638 (C=O), 1570 (C=C, C=N).
1H NMR spectrum (DMSO-d6–CCl4, 1:3), δ, ppm:
0.96 t (3H, CH3CH2, J = 7.3 Hz), 1.39–1.51 m (2H,
CH3CH2), 1.61–1.71 m (2H, CH3CH2CH2), 1.73 br.s
(3H, CH3C=CH2), 2.15 s (3H, 4-CH3), 3.07 br.s (2H,
CH2CCH3), 3.08 t (2H, SCH2, J = 7.2 Hz), 4.50–
2,3-Dimethylpyrimido[1,2-a]benzimidazol-
4(10H)-one (8a) was synthesized from 6a. Yield
1.46 g (69%), powder, mp 331–332°C (from
60% AcOH), Rf 0.73; published data [11]: mp 330°C.
IR spectrum, ν, cm–1: 1682 (C=O), 1643 (C=C, C=N).
1H NMR spectrum (DMSO-d6), δ, ppm: 2.02 s (3H,
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HARUTYUNYAN
1016
CH3), 2.33 s (3H, CH3), 7.26 d.d.d (1H, Harom, J = 7.9,
7.3, 1.2 Hz), 7.41 d.d.d (1H, Harom, J = 8.0, 7.3,
1.2 Hz), 7.49 br.d (1H, Harom, J = 7.9 Hz), 8.40 br.d
(1H, Harom, J = 8.0 Hz), 12.49 br.s (1H, NH). Found,
%: N 19.76. C12H11N3O. Calculated, %: N 19.71.
and dried. Yield 0.87 g (77%), mp 235–237°C (from
DMF), Rf 0.61. IR spectrum, ν, cm–1: 1670 (C=O),
1
1610 (C=C, C=N). H NMR spectrum (DMSO-d6–
CCl4, 1:3), δ, ppm: 2.05 s (3H, CH3), 2.35 s (3H,
CH3), 3.72 s (3H, NCH3), 7.34 d.d.d (1H, 7-H, J = 8.1,
7.4, 1.2 Hz), 7.52 d.d.d (1H, 8-H, J = 8.1, 7.4, 1.0 Hz),
7.63 d.d (1H, 9-H, J = 8.1, 1.2 Hz), 8.47 d.d (1H, 6-H,
J = 8.1, 1.0 Hz). 13C NMR spectrum (DMSO-d6–CCl4,
1:3), δC, ppm: 10.6 (CH3), 22.5 (CH3), 28.0 (CH3),
106.6, 109.4 (CH), 115.3 (CH), 121.7 (CH), 124.7,
125.8 (CH), 131.6, 146.2, 159.3, 159.5. Found, %:
N 18.65. C13H13N3O. Calculated, %: N 18.49.
2-Methyl-3-(2-methylprop-2-en-1-yl)pyrimido-
[1,2-a]benzimidazol-4(10H)-one (8b) was synthe-
sized from 6b. Yield 1.8 g (72%), powder, mp 292–
294°C (from 60% AcOH), Rf 0.43. IR spectrum, ν,
1
cm–1: 1668 (C=O), 1653, 1620 (C=C, C=N). H NMR
spectrum (DMSO-d6–CCl4, 1:3), δ, ppm: 1.74 br.s
(3H, CH3C=CH2), 2.29 s (3H, 2-CH3), 3.24 br.s (2H,
CH2C=), 4.55–4.58 m and 4.70–4.73 m (1H each,
=CH2), 7.27 d.d.d (1H, 8-H, J = 7.9, 7.3, 1.2 Hz),
7.42 d.d.d (1H, 7-H, J = 8.0, 7.3, 1.2 Hz), 7.51 d.d.d
(1H, 9-H, J = 7.9, 1.2, 1.2 Hz), 8.39 d.d.d (1H, 6-H,
J = 8.0, 1.2, 1.2 Hz), 12.60 br.s (1H, NH). 13C NMR
spectrum (DMSO-d6–CCl4, 1:3), δC, ppm: 19.7 (CH3),
22.4 (CH3), 32.2 (CH2), 106.7, 109.7 (=CH2), 113.42
br, 115.0 (CH), 121.0 (CH), 125.4 (CH), 126.9, 143.1,
146.8, 159.4. Found, %: N 16.72. C15H15N3O. Calcu-
lated, %: N 16.59.
3-(3-Methylphenyl)-2-(propylsulfanyl)quinazo-
lin-4(3H)-one (12a) was synthesized by alkylation of
quinazolinone 11a [12] as described above for 6a–6d.
Yield 2.44 g (79%), powder, mp 91–93°C (from
EtOAc–hexane), Rf 0.47. IR spectrum, ν, cm–1: 1695
1
(C=O), 1610 (C=C, C=N). H NMR spectrum
(DMSO-d6–CCl4, 1:3), δ, ppm: 1.03 t (3H, CH3CH2,
J = 7.3 Hz), 1.72 sext (2H, CH3CH2, J = 7.3 Hz),
2.46 s (3H, CH3), 3.04–3.18 m (2H, SCH2), 7.05–
7.09 m (2H, C6H4CH3), 7.31–7.35 m (1H, C6H4CH3),
7.38 d.d.d (1H, 6-H, J = 7.9, 7.1, 1.2 Hz), 7.39–7.45 m
(1H, C6H4CH3), 7.54 d.d (1H, 8-H, J = 8.2, 1.2 Hz),
7.72 d.d.d (1H, 7-H, J = 8.2, 7.1, 1.6 Hz), 8.09 d.d
(1H, 5-H, J = 7.9, 1.6 Hz). 13C NMR spectrum
(DMSO-d6–CCl4, 1:3), δC, ppm: 13.0 (CH3), 20.7
(CH3), 21.5 (CH2), 33.5 (SCH2), 119.4, 124.9 (CH),
125.6 (CH), 125.8 (CH), 126.4 (CH), 128.6 (CH),
129.2 (CH), 129.8 (CH), 133.7 (CH), 135.5, 138.4,
147.1, 156.8, 160.2. Found, %: N 8.85. C18H18N2OS.
Calculated, %: N 9.02.
2,2′-(Benzene-1,2-diyldiimino)bis[5-benzyl-
6-methylpyrimidin-4(3H)-one] (9a) was synthesized
from 6c. Yield 1.31 g (26%), mp 350–352°C (from
DMF), Rf 0.59. IR spectrum, ν, cm–1: 3460, 3375
1
(N–H), 1647 (C=O), 1615 (C=C, C=N). H NMR
spectrum (DMSO-d6–CCl4, 1:3), δ, ppm: 2.08 s (6H,
CH3), 3.70 s (4H, CH2), 7.04–7.12 m (4H, Harom),
7.14–7.23 m (8H, Harom), 7.70–7.79 m (2H, Harom),
7.89 sh.s (2H, NH), 10.99 br.s (2H, NH). Found, %:
N 16.47. C30H28N6O2. Calculated, %: N 16.66.
6-Iodo-3-methyl-2-(propylsulfanyl)quinazolin-
4(3H)-one (12b) was synthesized in a similar way
from quinazolinone 11b [13]. Yield 63%, powder,
mp 107–108°C (from EtOAc–hexane), Rf 0.64.
IR spectrum, ν, cm–1: 1665 (C=O), 1595 (C=C, C=N).
1H NMR spectrum (DMSO-d6–CCl4, 1:3), δ, ppm:
1.09 t (3H, CH3CH2, J = 7.4 Hz), 1.80 q.t (2H,
CH3CH2, J = 7.4, 7.2 Hz), 3.24 t (2H, SCH2, J =
7.2 Hz), 3.53 s (3H, NCH3), 7.24 d (1H, 8-H, J =
8.6 Hz), 7.92 d.d (1H, 7-H, J = 8.6, 2.1 Hz), 8.36 d
(1H, 5-H, J = 2.1 Hz). 13C NMR spectrum (DMSO-d6–
CCl4, 1:3), δC, ppm: 13.0 (CH3), 21.5 (CH2), 29.6
(CH3), 33.2 (CH2), 88.5, 120.3, 127.5 (CH), 134.8
(CH), 141.9 (CH), 146.0, 157.5, 158.9. Found, %:
N 8.29. C11H12IN2OS. Calculated, %: N 8.07.
2,2′-(Benzene-1,2-diyldiimino)bis{5-[(2,4-di-
methylphenyl)methyl]-6-methylpyrimidin-4(3H)-
one} (9b) was synthesized from 6d. Yield 2.4 g (43%),
mp 326–328°C (from DMF), Rf 0.37. IR spectrum, ν,
cm–1: 3342, 3312 (N–H), 1689 (C=O), 1609 (C=C,
1
C=N). H NMR spectrum (DMSO-d6–CCl4, 1:3), δ,
ppm: 1.94 s (6H, CH3), 2.20 s (6H, CH3), 2.28 s (6H,
CH3), 3.57 s (4H, CH2), 6.68 d (2H, 5′-H, J = 7.8 Hz),
6.83 d.d (2H, 6′-H, J = 7.8, 1.8 Hz), 6.95 d (2H, 3′-H,
J = 1.8 Hz), 7.10–7.19 m and 7.70–7.80 m (2H each,
C6H4), 8.08 br.s (2H, NH), 11.16 br.s (2H, NH). Found,
%: N 14.69. C34H36N6O2. Calculated, %: N 14.99.
2,3,10-Trimethylpyrimido[1,2-a]benzimidazol-
4(10H)-one (10). A mixture of 1.1 g (5 mmol) of 8a,
0.69 g (5 mmol) of K2CO3, and 0.71 g (5 mmol) of
methyl iodide in 7 mL of DMF was left overnight at
room temperature. The mixture was then heated for 1 h
on a boiling water bath, poured into 30 mL of water,
and kept in the cold. The white solid was filtered off
Compounds 13a and 13b were synthesized accord-
ing to the procedure described above for 8a and 8b.
Benzimidazo[2,1-b]quinazolin-12(6H)-one (13a)
was synthesized from 12a (yield 69%) or 12c (yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016

NEW GENERAL SYNTHESIS OF BENZO[4,5]IMIDAZO[1,2-a]PYRIMIDINE
1017
3. Nowicka, A., Liszkiewicz, H., Nawrocka, W.P.,
Wietrzyk, J., Kempinska, K., and Drys, A., Cent. Eur.
J. Chem., 2014, vol. 12, p. 1047.
86%). Powder, mp >380°C (from DMF), Rf 0.69;
published data [14]: mp 395–400°C. IR spectrum, ν,
1
cm–1: 1691 (C=O), 1657, 1610 (C=C, C=N). H NMR
4. Tardy, S., Orsato, A., Mologni, L., Bisson, W.H.,
Donadoni, C., Gambacorti-Passerini, C., Scapozza, L.,
Gueyrard, D., and Goekjian, P.G., Bioorg. Med. Chem.,
2014, vol. 22, p. 1303.
spectrum (DMSO-d6–CCl4, 1:3), δ, ppm: 7.19–7.28 m
(2H, Harom), 7.35 t.d (1H, Harom, J = 7.6, 1.2 Hz),
7.42 br.d (1H, Harom, J = 7.9 Hz), 7.50 br.d (1H, Harom
,
J = 8.3 Hz), 7.67 t.d (1H, Harom, J = 8.3, 1.6 Hz),
8.25 d.d (1H, Harom, J = 8.0, 1.6 Hz), 8.44 br.d (1H,
Harom, J = 7.8 Hz), 12.36 br.s (1H, NH).
5. Sirko, S.M., Gorobets, N.Yu., Musatov, V.I., and
Desenko, S.M., Molecules, 2009, vol. 14, p. 5223.
6. Carpenter, R.D., Lam, K.S., and Kurth, M.J., J. Org.
Chem., 2007, vol. 72, p. 284.
7. Murav’eva, K.M., Arkhangel’skaya, T.V., Shchuki-
na, M.N., Zykova, T.N., and Pershin, G.N., Khimiya
Geterotsiklicheskikh Soedinenii (Chemistry of Hetero-
cyclic Compounds), Giller, S.A., Ed., Riga: Zinatne,
1967, vol. 1, p. 411; Chem. Abstr., 1969, vol. 70,
no. 96748u.
2-Iodobenzimidazo[2,1-b]quinazolin-12(6H)-one
(13b) was synthesized from 12b. Yield 77%, powder,
mp >340°C (from 60% AcOH), Rf 0.63. IR spectrum,
ν, cm–1: 1692 (C=O), 1664, 1608 (C=C, C=N).
1H NMR spectrum (DMSO-d6–CCl4, 1:3), δ, ppm:
7.23 d.d.d (1H, 8-H, J = 7.9, 6.6, 2.0 Hz), 7.30 d (1H,
4-H, J = 8.7 Hz), 7.34–7.42 m (2H, 7-H, 9-H), 7.88 d.d
(1H, 3-H, J = 8.7, 2.1 Hz), 8.45 br.d (1H, 10-H, J =
8.0 Hz), 8.52 d (1H, 1-H, J = 2.1 Hz), 12.47 br.s (1H,
NH). 13C NMR spectrum (DMSO-d6–CCl4, 1:3), δC,
ppm: 83.7, 111.4, 115.1, 117.2, 120.7, 125.0, 125.3,
126.5, 134.8, 141.6, 146.9, 146.9, 157.1. Found, %:
N 11.30. C14H8IN3O. Calculated, %: N 11.64.
8. Makisumi, Y., Chem. Pharm. Bull., 1964, vol. 12,
p. 789.
9. Chi, Y.F. and Kao, Y.S., J. Am. Chem. Soc., 1936,
vol. 58, p. 769.
10. Wheeler, H.L. and McFarland, D.F., Am. Chem. J.,
1909, vol. 42, p. 101.
11. De Cat, A. and Van Dormael, A., Bull. Soc. Chim. Belg.,
1950, vol. 59, p. 573.
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14. Bird, C.W., Tetrahedron, 1965, vol. 21, p. 2179.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 7 2016