Heterocyclization of Aromatic Amino Acids: Novel Syntheses and Antibacterial Activity of Fused, Non-fused, and Spiro Polyheterocyclic Derivatives

Article abstract of DOI:10.1134/S1070428020060159

Abstract: Commercially available p-aminobenzoic acidwas used as a precursor for the synthesis of novel fused, non-fused, and spiropolyheterocyclic derivatives bearing indene, imidazole, pyrazole, and/ortriazine nucleus via addition to simple and accessibl

Full text of DOI:10.1134/S1070428020060159

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2020, Vol. 56, No. 6, pp. 1062–1069. © Pleiades Publishing, Ltd., 2020.
Heterocyclization of Aromatic Amino Acids: Novel Syntheses
and Antibacterial Activity of Fused, Non-fused,
and Spiro Polyheterocyclic Derivatives
E. O. Hameda,*, M. G. Assya, and M. M. Galahomb
a Department of Chemistry, Faculty of Science, Zagazig University, Zagazig, 44519 Egypt
b Department of Chemistry, Faculty of Science, Jazan University, Jazan, 45142 Saudi Arabia
*e-mail: dremanomar54@gmail.com
Received December 26, 2019; revised March 18, 2020; accepted March 29, 2020
Abstract—Commercially available p-aminobenzoic acid was used as a precursor for the synthesis of novel
fused, non-fused, and spiro polyheterocyclic derivatives bearing indene, imidazole, pyrazole, and/or triazine
nucleus via addition to simple and accessible reagents such as ninhydrin, o-phenylenediamine, and carbon
disulfide. The experimental procedures were straightforward and simple, the products were isolated in 15–86%
yields, and. their structure was confirmed by spectroscopic data. The synthesized compounds were evaluated for
their antibacterial activity against some Gram-positive and Gram-negative bacteria.
Keywords: amino acid, imidazole, spiro compounds, indenopyrrole, thiazole, antibacterial activity
DOI: 10.1134/S1070428020060159
INTRODUCTION
[18], antimalarial [19], antibacterial [20], antiprolif-
erative [21], and CRF1 receptor antagonistic [22]
activities. This invigorated our enthusiasm for the syn-
thesis of novel polyheterocyclic derivatives in conti-
nuation of our past work [23].
In recent years, indeno-fused heterocycles have
attracted considerable attention because of their thera-
peutic and synthetic importance and broad spectrum of
biological activity [13]. Like indenopyrrole derivative
(Fig. 1) [4], many spiroheterocyclic systems have
shown good biological activities [5, 6]. Thiazoles have
been used in improvement of drugs for the treatment of
allergies [7], hypertension [8], inflammation [9],
schizophrenia [10], bacterial [11] and HIV infections
[12], as hypnotics [13], and more recently for the treat-
ment of pain [14]. 1,2,4-Triazines possess a broad
spectrum of biological properties, including antifungal
[15], anti-HIV [16], antitumor [17], neuroprotective
Aromatic amino acids are precursors for reactive
intermediates that are utilized for further heterocyciza-
tion resulting in organic systems of potential biological
activity. Ninhydrin also bears suitable functionalities
for further cyclization [24–27]. The present article
reports the synthesis of non-fused and fused poly-
heterocyclic systems containing indene, imidazole,
pyrazole, and/or triazine rings from amino acid and
simple and available laboratory reagents [23, 28, 29].
RESULTS AND DISCUSSION
COOH
The condensation of ninhydrin (1) with enaminone
2, followed by intramolecular addition of the enamino
carbon atom to the carbonyl group produced pyrrolo-
indene 3 (Scheme 1). The structure assigned for 3 was
established from analytical and spectral data. The IR
spectrum of 3 showed a characteristic peak around
3380 cm–1 due to OH group and a broad band around
OH
N
COOEt
O
OH
COOEt
Fig. 1. An example of biologically active indenopyrrole
1
derivative.
1691 cm–1 for C=O function. The H NMR spectrum
1062

HETEROCYCLIZATION OF AROMATIC AMINO ACIDS
1063
Scheme 1.
COOH
O
O
COOH
OH
OH
EtOH, reflux, 2 h
OH
+
O
HN
75%
N
Me
EtO
Me
O
OH
COOEt
1
2
3
O
H
N
HO
OH
N
NH2
NH2
N
Me
COOH
4
N
OH
N
N
H
O
HO
Me
COOEt
5
Scheme 2.
Cl
O
HO
N
OH
COOH
COOH
O
O
EtOH, reflux, 2 h
15%
7
1
+
Cl
N
H
O
O
6
HO
N
OH
COOH
O
8
showed a downfield carboxylic proton signal at
δ 13.22 ppm, aromatic multiplet at δ 7.35–7.98 ppm,
and two OH signals at δ 6.56 and 5.86 ppm; signals
from the ester ethyl and methyl protons were also
present. The 13C NMR spectrum of 3 showed three
downfield signals at δC 198.57, 167.33, and 165.63 ppm
for the three carbonyl carbons. The condensation of 3
with o-phenylenediamine selectively involved the ester
group to furnish compound 4, whereas the carboxy
group remained intact (no alternative product 5 was
detected; Scheme 1). The structure of 4 was supported
by the presence of carboxylic proton signal and the
absence of ethoxy protons; the NH signal of the imid-
azole ring was located at a low field. The 13C NMR
spectrum of 4 contained two downfield signals at
δC 189.71 and 167.21 ppm for two carbonyl carbons.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 6 2020

HAMED et al.
1064
Chloroacetamide 6 underwent oxazine cyclization
of compound 9 displayed one carbonyl carbon signal at
δC 189.77 ppm due to its symmetric structure.
with compound 1 via alkylation followed by addition
of the imino group to carbonyl carbon affording
indenooxazine 8, but no cycloaddition product 7 was
detected (Scheme 2). The IR spectrum of 8 displayed
peaks at 3401 (broadened) and 1685 cm–1 for OH and
C=O groups, respectively. The 1H NMR spectrum of 8
contained downfield signals at δ 12.76 and 10.41 ppm
for COOH and OH, and three carbonyl carbon signals
were observed in its 13C NMR spectrum at δC 189.71,
167.3, and 165.59 ppm.
Coupling of ethyl acetoacetate with the diazonium
salt derived from p-aminobenzoic acid (2) resulted in
hydrazone 10. The 1,3-bielectophilic system of 10
underwent pyrazole cyclization with hydrazine to give
3-hydroxypyrazole 11. Acid-catalyzed condensation of
11 with 2 equiv of o-phenylenediamine yielded spiro
compound 13 while no reaction at the carboxy group to
form 12 was observed (Scheme 4). The structure of 13
was supported by the presence of D2O exchangable
signals of COOH and four NH groups at δ 13.30, 8.09,
8.07, 4.37, and 3.49 ppm. The carbonyl carbon signal
of 13 was located at δC 167.21 ppm in the 13C NMR
spectrum.
p-Aminobenzoic acid reacted with ninhydrin
through elimination of two water molecules, and the
subsequent acid-catalyzed intermolecular cyclocon-
densation with o-phenylenediamine afforded 2-imino-
indandione 9 (Scheme 3). Compound 9 showed stretch-
ing frequencies at 3435, 1727 and 1603 cm–1 due to
NH, C=O and C=N groups, respectively. The 1H NMR
spectrum of 9 lacked signals for COOH and OH groups
but contained a downfield D2O-exchangeable signal at
δ 7.71 ppm for imidazole NH. The 13C NMR spectrum
Treatment of potassium dithiocarbamate 14 with
chloroacetic acid resulted in alkylation of the sulfur
atom, and subsequent intramolecular nucleophilic at-
tack of the nitrogen atom on the electrophilic carbonyl
carbon with elimination of water afforded dihydro-
Scheme 3.
O
N
(1) 4-H2NC6H4COOH, AcOH, reflux, 2 h
(2) o-(H2N)2C6H4, AcOH, reflux, 6 h
N
1
39%
O
HN
9
Scheme 4.
COOH
COOH
COOH
O
(1) NaNO2/HCl
(2) MeC(O)CH2C(O)OEt
Me
N2H4·H2O
N
O
N
Me
N
H
N
H
N
N
EtO
OH
NH2
10
11
Me
N
N
N
NH2
N
H
N
H
N
2
OH
NH2
AcOH, reflux, 6 h
12
COOH
Me
N
N
H
N
NH
HN
70%
HN
13
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 6 2020

HETEROCYCLIZATION OF AROMATIC AMINO ACIDS
1065
Scheme 5.
COOH
COOH
S
COOH
ClCH2COOH
H2O, reflux, 3 h
S
CS2, KOH, EtOH, 20 h
N
40%
S
KS
N
H
OH
NH2
14
15
NH2
NH2
2
N
NH
N
EtOH, reflux, 6 h
N
N
80%
HO
16
Scheme 6.
COOH
S
N2H4·H2O
14
H2N
N
H
N
H
17
NH2
NH2
N
O
2
COOH
O
Me
COOH
N
H
O
pyridine, reflux, 5 h
EtOH, reflux, 6 h
Me
Me
N
N
40%
30%
H
N
N
N
N
H
S
N
H HN
18
19
C(O)Cl
COOH
S
N
(20)
O
O
N
pyridine, reflux, 5 h
HN
30%
O
O
21
thiazole 15 (Scheme 5). Compound 15 showed stretch-
NH and C=N, respectively. The OH and NH protons of
16 resonated in the H NMR spectrum at δ 6.98 and
6.97 ppm (D2O exchangeable).
1
ing frequencies at 3311, 1671, and 1605 cm–1 for OH,
1
C=O, and C=S groups, respectively. The H NMR
spectrum of 15 displayed downfield signals at
δ 12.8 and 10.22 ppm for COOH and OH protons. The
reaction of 15 with 2 equiv of o-penylenediamine
involved both condensation at the carboxy group and
recyclization of the dihydrothiazole ring to furnish
imidazobenzimidazole derivative 16. Compound 16
displayed IR frequencies at 3441 and 1608 cm–1 for
Treatment of compound 14 with hydrazine hydrate
gave thiosemicarbazide 17 which reacted with pyruvic
acid to produce 1,2,4-triazine 18 (Scheme 6) which
displayed IR bands at 3437 (OH), 1673 (C=O), 1600
1
(C=O), and 1292 cm–1 (C=S). The H NMR spectrum
of 18 showed two downfield signals at δ 12.65 and
10.20 ppm for COOH and NH protons. The reaction of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 6 2020

HAMED et al.
1066
18 with 2 equiv of o-phenylenediamine involved both
the thione and carboxylic acid functionality, leading to
spiro triazine derivative 19. Compound 19 showed
peaks at 3434, 1692, and 1610 cm–1 for NH, C=O, and
C=N stretchings, respectively, in the IR spectrum. Four
was performed on Silica gel 60 F254 plates (Merck)
with detection by UV light. The products were purified
by crystallization. The IR spectra (KBr disc) were
recorded on a Pye Unicam Sp-3-300 or a Shimadzu
FTIR 8101 PC infrared spectrophotometer. The 1H and
13C NMR spectra were recorded at a Varian Mercury
VX-300 spectrometer at 300 and 75.4 MHz, respec-
tively, using DMSO-d6 as a solvent and TMS as an in-
ternal standard. The analytical data and in vitro anti-
microbial activities were obtained from the Micro-
analysis Center at the Cairo University, Giza, Egypt.
1
NH protons of 19 resonated in the H NMR spectrum
of 19 at δ 8.62, 8.33, 8.03, 6.85 ppm (D2O exchange-
able), and the C=O signal was located at δC 167.21 ppm
in the 13C NMR spectrum.
2-Oxochromene-3-carbonyl chloride (20) reacted
with thiosemicarbazide 17 via hydrazinolysis followed
by intramolecular cyclodehydration to form triazole
derivative 21 (Scheme 6). The OH, NH, C=O, and C=S
groups of 21 gave rise to IR absorption bands at 3457,
3309, 1698, 1246 cm–1 respectively. The COOH and
NH proton signals of 21 were observed at δ 12.39 and
Compounds 2, 6, 10, 11 and 17 were prepared by
the procedures described in the literature [23, 28, 29].
4-[3-(Ethoxycarbonyl)-3a,8b-dihydroxy-2-
methyl-4-oxo-3a,4-dihydroindeno[1,2-b]pyrrol-
1(8bH)-yl]benzoic acid (3). A mixture of ninhydrin
(1, 4.0 mmol) and compound (2, 4.0 mmol) in 10 mL
of ethanol was refluxed for 2 h. The mixture was
cooled and poured into ice-cold water, and the product
was filtered off, washed with water, dried, and recrys-
tallized from ethanol. Yield 1.26 g (75%), pink crystals,
mp 160–164°C. IR spectrum, ν, cm–1: 3654 (OH), 3380
(OH), 3257 (OH), 1691 (C=O), 1593 (C=O), 1526
1
10.86 ppm, respectively, in the H NMR spectrum.
The 13C NMR spectrum showed signals at δC 167.31,
163.03, 160.55 ppm due to C=S and two C=O groups,
respectively.
Compounds 8, 9, 13, 16 and 19 were investigated in
vitro for antibacterial activity against Gram-positive
(Bacillus subtilis, Staphylococcus aureus) and Gram-
negative bacteria (Escherichia coli, Pseudomonas
aeruginosa) utilizing the disc diffusion method [30] at
a concentration of 1 mg/mL. DMSO was used as
solvent, and ciprofloxacin was used as standard anti-
bacterial agent. The results are given in Table 1 (zone
of inhibition of bacterial growth). Compounds 8, 16,
and 19 showed a high antibacterial activity and, while
compounds 9 and 13 were moderately active against
the tested bacteria.
1
(C=O). H NMR spectrum, δ, ppm: 13.22 s (1H,
COOH), 7.35–7.98 m (8H, Harom), 6.56 s (1H, OH),
5.86 s (1H, OH), 4.02 q (2H, CH2, J = 4.5 Hz), 2.01 s
(3H, CH3), 1.01 t (3H, CH3, J = 4.1 Hz). 13C NMR
spectrum, δC, ppm: 198.57, 167.33, 165.63 (C=O);
158.91, 130.65, 125.27, 123.68 (C6H4); 147.67, 135.44,
135.25, 130.34, 130.28, 130.23, 98.82, 84.76 (indene);
141.18, 96.01 (pyrrole); 58.74, 14.99 (CH2CH3); 14.83
(CH3). Found, %: C 64.41; H 4.60; N 3.35. C22H19NO7.
Calculated, %: C 64.54; H 4.68; N 3.42.
EXPERIMENTAL
4-[3-(1H-benzimidazol-2-yl)-3a,8b-dihydroxy-2-
methyl-4-oxo-3a,4-dihydroindeno[1,2-b]pyrrol-
1(8bH)-yl]benzoic acid (4). A mixture of compound 3
(1.0 mmol) and o-phenylene diamine (1.0 mmol) in
10 mL of ethanol was refluxed for 6 h. The mixture
The melting points were measured using an Electro-
thermal IA 9100 apparatus with open capillary tubes
and are uncorrected. All experiments were carried out
using dry solvents. Thin-layer chromatography (TLC)
Table 1. In vitro antibacterial activity of compounds 8, 9, 13, 16, and 19 ( inhibition zone diameter, mm/mg sample)
Staphylococcus
aureus
Pseudomonas
aeruginosa
Compound no.
Bacillus subtilis
Escherichia coli
8
22
13
11
21
20
–
24
14
12
22
21
–
23
15
10
23
23
–
28
12
11
21
20
–
9
13
16
19
Control (DMSO)
Ciprofloxacin (reference drug)
19
22
28
24
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 6 2020

HETEROCYCLIZATION OF AROMATIC AMINO ACIDS
1067
was cooled and poured into ice-cold water, and the
product was filtered off, washed with water, dried, and
recrystallized from ethanol. Yield 0.23 g (86%), black
powder, mp 178–180°C. IR spectrum, ν, cm–1: 3758
(OH), 3429 (OH, NH), 3058 (OH), 1685 (C=O), 1605
4-{2-[5′-Methyl-1,3-dihydrospiro[benzimidazole-
2,3′-pyrazol]-4′(2′H)-ylidene]hydrazinyl}benzoic
acid (13). A mixture of compound 11 (1.0 mmol) and
o-phenylenediamine (1.0 mmol) in 10 mL of acetic
acid was refluxed for 6 h. The mixture was cooled and
poured into ice-cold water, and the product was filtered
off, washed with water, dried, and recrystallized from
acetic acid. Yield 0.03 g (70%), yellow crystals,
mp 288–290°C. IR spectrum, ν, cm–1: 3767 (OH), 3435
(NH), 1671 (C=O), 1606 (C=N). 1H NMR spectrum, δ,
ppm: 13.30 s (1H, COOH, D2O exchangeable), 8.09 s
(1H, NH, D2O exchangeable), 8.07 s (1H, NH, D2O
exchangeable), 7.25–7.42 m (8H, Harom), 4.37 s (1H,
NH, D2O exchangeable), 3.49 s (1H, NH, D2O ex-
changeable), 1.24 s (3H, CH3). 13C NMR spectrum,
δC, ppm: 167.21 (C=O); 147.45, 61.07 (pyrazole);
145.50, 130.21, 127.04, 115.69 (C6H4); 131.46, 126.03,
115.76 (imidazole); 14.66 (CH3). Found, %: C 60.63;
H 4.69; N 24.91. C17H16N6O2. Calculated, %: C 60.71;
H 4.79; N 24.99.
1
(C=O), 1548 (C=N). H NMR spectrum, δ, ppm:
12.43 s (1H, COOH), 8.65 s (1H, NH), 7.81–8.10 m
(12H, Harom), 7.11 s (1H, OH), 3.46 s (1H, OH), 1.22 s
(3H, CH3). 13C NMR spectrum, δC, ppm: 189.71
(C=O), 167.21 (C=O); 156.85, 131.39, 124.64, 120.51
(C6H4); 150.19, 133.21, 132.87, 137.38, 129.79,
122.70, 121.42, 117.84 (indene); 142.55, 118.92 (pyr-
role); 142.26, 141.36, 137.02, 130.79 (imidazole);
14.66 (CH3). Found, %: C 68.69; H 4.14; N 9.18.
C26H19N3O5. Calculated, %: C 68.87; H 4.22; N 9.27.
4-[4a,9b-Dihydroxy-3,5-dioxo-2,3,4a,5-tetra-
hydroindeno[1,2-b][1,4]oxazin-4(9bH)-yl]benzoic
acid (8). A mixture of ninhydrin (1, 7.0 mmol) and
compound 6 (7.0 mmol) in 10 mL of ethanol was
refluxed for 2 h. The mixture was cooled and poured
into ice-cold water, and the product was filtered off,
washed with water, dried, and recrystallized from
ethanol. Yield 0.5 g (15%), pink crystals, mp 218–
222°C. IR spectrum, ν, cm–1: 3401 (OH), 3278 (OH),
4-[4-Hydroxy-2-sulfanylidene-1,3-thiazol-3(2H)-
yl]benzoic acid (15). Carbon disulfide (14.0 mmol)
was added dropwise to an ice-cold solution of KOH
(14.0 mmol) in 20 mL of absolute ethanol containing
p-aminobenzoic acid (14.0 mmol). The mixture was
stirred at room temperature for 20 h, chloroacetic acid
(14.0 mmol) and 5 mL of water were added to the
resulting suspension of potassium salt 14, and the
mixture was refluxed for ~3 h. It was then diluted with
50 mL of water and acidified with aqueous HCl, and
the precipitate was filtered off, washed with water,
dried, and recrystallized from ethanol. Yield 0.7 g
(40%), yellow crystals, mp 248–252°C. IR spectrum, ν,
cm–1: 3438 (OH), 3311 (OH), 1671 (C=O), 1605
1
3206 (OH), 1685 (C=O), 1603 (C=O). H NMR spec-
trum, δ, ppm: 12.76 s (1H, COOH), 10.41 s (1H, OH),
7.66–7.89 m (8H, Harom), 4.26 s (1H, OH), 3.32 s (2H,
CH2). 13C NMR spectrum, δC, ppm: 189.71 (C=O),
167.30 (C=O), 165.59 (C=O); 150.28, 141.18, 135.44,
135.25, 130.65, 130.23, 123.68, 113.03 (indene);
142.93, 130.34, 130.28, 125.27 (C6H4); 44.05 (OCH2).
Found, %: C 60.76; H 3.58; N 3.86. C18H13NO7. Cal-
culated, %: C 60.85; H 3.69; N 3.94.
1
2-{[4-(1H-benzimidazol-2-yl)phenyl]imino}-1H-
indene-1,3(2H)-dione (9). A mixture of ninhydrin
(1, 1.5 mmol) and 4-aminobenzoic acid (1.5 mmol) in
10 mL of acetic acid was refluxed for 2 h. o-Phenylene-
diamine (1.5 mmol) was then added, and the mixture
was refluxed for 6 h, cooled, and poured into ice-cold
water. The product was filtered off, washed with water,
dried, and recrystallized from acetic acid. Yield 0.19 g
(39%), green crystals, mp 210–212°C. IR spectrum, ν,
(C=S). H NMR spectrum, δ, ppm: 12.80 s (1H,
COOH), 10.22 s (1H, OH), 7.63–7.84 m (4H, Harom),
3.34 s (1H, =CH). Found, %: C 47.34; H 2.71; N 5.45.
C10H7NO3S2. Calculated, %: C 47.42; H 2.79; N 5.53.
1-[4-(1H-Benzimidazol-2-yl)phenyl]-1H-imidazo-
[1,2-a]benzimidazol-2-ol (16). A mixture of compound
15 (1.0 mmol) and o-phenylenediamine (2.0 mmol) in
10 mL of ethanol was refluxed for 6 h. The mixture
was cooled and poured into ice-cold water, and the
product was filtered off, washed with water, dried, and
recrystallized from ethanol. Yield 0.65 g (80%), green
crystals, mp 182–184°C. IR spectrum, ν, cm–1: 3441
1
cm–1: 3435 (NH), 1727 (C=O), 1603 (C=N). H NMR
spectrum, δ, ppm: 7.72–8.06 m (12H, Harom), 7.71 s
(1H, NH, D2O-exchangeable). 13C NMR spectrum, δC,
ppm: 189.77 (2C, C=O); 156.92, 141.42, 132.91,
131.43 (imidazole); 150.28, 137.42, 137.10, 129.83
(C6H4); 142.60, 142.30, 133.24, 130.83 (indene).
Found, %: C 75.09; H 3.65; N 11.87. C22H13N3O2.
Calculated, %: C 75.20; H 3.73; N 11.96.
1
(NH), 2910 (OH), 1608 (C=N). H NMR spectrum, δ,
ppm: 7.00–7.79 m (12H, Harom), 6.98 s (1H, OH, D2O
exchangeable), 6.97 s (1H, NH, D2O exchangeable),
4.17 s (1H, =CH). Found, %: C 71.23; H 4.06; N 19.11.
C22H15N5O. Calculated, %: C 72.32; H 4.14; N 19.17.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 6 2020

HAMED et al.
1068
4-[6-Methyl-5-oxo-3-sulfanylidene-2,3-dihydro-
CONFLICT OF INTEREST
The authors declare the absence of conflict of interest.
SUPPLEMENTARY MATERIALS
1,2,4-triazin-4(5H)-yl]benzoic acid (18). A mixture of
compound 17 (4.0 mmol) and pyruvic acid (4.0 mmol)
in 20 mL of pyridine was refluxed for 5 h. The reaction
mixture was cooled and poured into ice-cold water.
The formed product was filtered off, washed with
water, dried and recrystallized from ethylacetate. Yield
0.44 g (40%), yellow powder, mp 260–264°C. IR spec-
trum, ν, cm–1: 3437 (OH), 3306 (NH), 1673 (C=O),
Supplementary materials are available for this article at
https://doi.org/10.1134/S1070428020060159 and are acces-
sible for authorized users.
1
1600 (C=O), 1292 (C=S). H NMR spectrum, δ, ppm:
REFERENCES
12.65 s (1H, COOH), 10.20 s (1H, NH), 7.26–8.30 m
(4H, ArH’s), 1.95 s (3H, CH3). Found, %: C 50.12;
H 3.37; N 15.89. C11H9N3O3S. Calculated, %: C 50.18;
H 3.45; N 15.96.
1. Maheswari, S.U., Balamurugan, K., Perumal, S., and
Yogeeswari, P., Bioorg. Med. Chem. Lett., 2010, vol. 20,
p. 7278.
4′-[4-(1H-benzoimidazol-2-yl)phenyl]-6′-methyl-
1,3-dihydro-2′H-spiro[benzoimidazole-2,3′-[1,2,4]-
triazin]-5′(4′H)-one (19). A mixture of compound 18
(1.0 mmol) and o-phenylenediamine (2.0 mmol) in
10 mL of ethanol was refluxed for 6 h. The mixture
was cooled and poured into ice-cold water, and the
product was filtered off, washed with water, dried, and
recrystallized from ethanol. Yield 0.24 g (30%), green
crystals, mp 282–285°C. IR spectrum, ν, cm–1: 3434
(NH), 1692 (C=O), 1610 (C=N). 1H NMR spectrum, δ,
ppm: 8.62 s (1H, NH, D2O exchangeable), 8.33 s (1H,
NH, D2O exchangeable), 8.03 s (1H, NH, D2O ex-
changeable), 6.86–7.81 m (12H, Harom), 6.85 s (1H,
NH, D2O exchangeable), 1.06 s (3H, CH3). 13C NMR
spectrum, δC, ppm: 167.21 (C=O); 165.82, 131.39,
123.92, 118.92 (imidazole); 139.33, 129.19 (triazine);
131.28, 124.64, 122.66, 121.42 (C6H4); 126.59, 120.51,
117.84 (spiro imidazole); 14.77 (CH3). Found, %:
C 67.38; H 4.55; N 23.88. C23H19N7O. Calculated, %:
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