Hetaryl-1,5 Benzodiazepines—Part I: Synthesis of 3-pyrimidinyl- and Imidazolyl-1,5-benzodiazepines

Article abstract of DOI:10.1002/jhet.2573

Nucleophilic substitution of 3-bromo-4-phenyl-1H-[1,5]benzodiazepin-2-one (1) with thiourea or guanidine in presence of potassium carbonate afforded 1,5-benzodiazepin-3-ylimidothiocarbamate 2 or 1,5-benzodiazepin-3-ylguanidine 3, respectively. Pyrimidylthiobenzodiazepines 5, 6, 7, 8, 9, 10, 11, 12, 13 were obtained via the reaction of compound 2 with malononitrile dimer, diethyl malonate, methylenemalononitriles, or a mixture of an aldehyde and β-keto esters or acetylacetone, catalyzed using ceric ammonium nitrate. Reaction of compound 2 or 3 with α-halo esters, nitriles, and/or ketones afforded imidazoles 14, 15, 16, 17, 18, 19, 20, respectively.

Full text of DOI:10.1002/jhet.2573

Month 2016
Hetaryl-1,5 Benzodiazepines—Part I: Synthesis of 3-pyrimidinyl- and
Imidazolyl-1,5-benzodiazepines
*
Ahmed Khodairy, Eman A. Ahmed, and Hossam Abdel Ghany
aChemistry Department, Faculty of Science, Sohag University, Sohag, Egypt
*
E-mail: khodairy@yahoo.com
Received July 5, 2015
DOI 10.1002/jhet.2573
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
Nucleophilic substitution of 3-bromo-4-phenyl-1H-[1,5]benzodiazepin-2-one (1) with thiourea or guani-
dine in presence of potassium carbonate afforded 1,5-benzodiazepin-3-ylimidothiocarbamate 2 or 1,5-
benzodiazepin-3-ylguanidine 3, respectively. Pyrimidylthiobenzodiazepines 5–13 were obtained via the
reaction of compound 2 with malononitrile dimer, diethyl malonate, methylenemalononitriles, or a mixture
of an aldehyde and β-keto esters or acetylacetone, catalyzed using ceric ammonium nitrate. Reaction of
compound 2 or 3 with α-halo esters, nitriles, and/or ketones afforded imidazoles 14–20, respectively.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
groups at ῡ 3300, 3210, and 3197cmꢀ1. 1H-NMR spectrum
of compound 2 showed three new singlet signals at δ 8.95,
4.80, and 3.60ppm, corresponding to N–H, NH2 (deuterium
exchangeable protons), and C–H groups, respectively.
Pyrimidines are reported to possess pharmacological
activities, such as antineoplastic and anticancer agents [1],
analgesic, anti-pyretic [2], anti-HIV [3], and anti-tubercular
[4], and are used as antibiotics [5]. On the other hand, imid-
azoles possess significant medicinal applications, such as
antibacterial and anti-inflammatory activities [6], antifungal
activity [7], antiparasitic activity [8], antiviral activity [9],
and antidepressant activity [10]. In view of the previous
applications, and in continuation of our interest in synthesis
of some fused and spiro-1,5-benzodiazepinones [11–17],
we aimed to use 2-oxo-4-phenyl-2,3-dihydro-1H-1,5-
benzodiazepin-3-ylimidothiocarbamate (2) and 1-(2-
oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-yl)
guanidine (3) as building blocks for the synthesis of
some new family of 3-pyrimidinyl- and imidazolyl-
1,5-benzodiazepines with the hope to possess better
antimicrobial activity.
Treatment of compound 2 with 2-aminoprop-1-ene-
1,1,3-tricarbo-nitrile (malononitrile dimer), in presence of
sodium ethoxide, furnished malononitrile derivative 5 in
80% yield. This product was formed through nucleophilic
addition of the NH2 group (compound 2) to the cyano group
and another nucleophilic addition of the NH2 (reagent) to
the C¼NH group, followed by elimination of ammonia
molecule. Its IR spectrum showed appearance of cyano
stretching bands at ῡ 2201cmꢀ1 beside N–H and NH2
groups at ῡ 3412, 3300, and 3248cmꢀ1. 1H-NMR spectrum
of the product revealed the presence of two singlet signals at
δ 8.20 and 4.90, belonging to Hpyrimidine and amino protons
besides a wide range of multiplet peaks, at δ 8.00–7.10, ow-
ing to aromatic protons and NH. Compound 2 was sub-
jected to react with diethyl malonate using sodium
ethoxide as a catalyst, to afford thiobarbituric acid deriva-
tive 6, in 70% yield (Scheme 2). Its IR spectrum represented
a new stretching vibration at ῡ 1700 and 3250cmꢀ1 owing to
C¼O and NH groups of pyrimidine ring. 1H-NMR spectrum
of compound 6 revealed the presence of new singlet signal,
at δ 3.80, attributed to CH2 group (Scheme 2). Treating com-
pound 2 with both of benzylidenemalononitrile and
ethoxymethylenemalononitrile, in presence of triethylamine,
yielded 4-aminopyrimidine-5-carbonitrile derivatives 7 and
8 (Scheme 2). Their IR spectra showed new absorption band
RESULTS AND DISCUSSION
2-Oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-
ylimidothiocarbamate (2) and 1-(2-oxo-4-phenyl-2,3-
dihydro-1H-1,5-benzodiazepin-3-yl)guanidine (3) were
obtained along with 4-phenyl-1H-1,5-benzodiazepin-2
(3H)-one (4) [12] via treatment of 3-bromo-4-phenyl-
1H-[1,5]-benzodiazepin-2(3H)-one (1) [12] with thiourea
or guanidine in presence of potassium carbonate (Scheme 1).
The structure of both compounds 2 and 3 was established on
the basis of their spectral and analytical data. Their IR spectra
displayed absorption bands corresponding to NH and NH2
corresponding to CN groups at ῡ 2210 and 2189cmꢀ1
,
respectively, while their 1H-NMR spectra showed new sig-
nals corresponding to NH2 groups at δ 5.50 and 4.90ppm,
and CH pyrimidine at δ 6.10.
© 2016 Wiley Periodicals, Inc.

A. Khodairy, E. A. Ahmed, and H. Abdel Ghany
Vol 000
Scheme 1
Scheme 2
new signals corresponding to ester group at δ 1.00–1.20 as
triplet and 4.00–4.20 as quartet; δ 5.90 owing to Hpyrimidine
and δ 2.39 owing to CH3; and also, an increase in aromatic
signals including NH group, appeared at δ 7.00–8.00.
Moreover, when compounds 2 and 3 were allowed to react
with active halo-compounds, namely, ethyl bromoacetate,
bromomalononitrile, chloroacetonitrile, or phenacyl bromide,
in presence of triethylamine in boiling ethanol, they gave
3-[(imidazol-2-yl)thio(amino)benzodiazepinones] 14–20, in
55–90% yields (Scheme 5).
The expected imidazoles had been proved via alkylation
reaction followed by a nucleophilic addition of the amino
group at cyano group to form compounds 16–18 or at
carbonyl group with elimination of ethanol molecule to
form compound 14 or water molecule to form com-
pounds 19 and 20. IR spectra of the compounds 14–20
showed appearance of new absorption bands corre-
sponding to cyano and carbonyl groups at ῡ 2193 and
1730 cmꢀ1 in imidazole moiety, respectively. The struc-
ture of these new compounds received good elucidation
The reaction of compound 2 with aromatic alde-
hydes (namely, benzaldehyde, p-chlorobenzaldehyde,
or p-anisaldehyde) along with β-keto ester or β-diketone com-
pounds (namely, ethyl acetoacetate, ethyl benzoylacetate,
and/or acetylacetone), in presence of ceric ammonium nitrate,
afforded dihydropyrimidine derivatives 9–13 (Scheme 3). The
reaction mechanism may proceed via a single electron transfer
[18] with formation of a β-keto radical, which in turn adds to
the imine intermediate and follows (Scheme 4). IR spectra
of compounds 9–13 showed new absorption bands corre-
sponding to NH groups at ῡ 3394 and 3230cmꢀ1, and ῡC¼O
1
thorough their H-NMR spectral data and correct elemen-
tal analyses of C, H, and N elements in which calcd./found
results are within 0.4%.
CONCLUSION
The reaction of 2-oxo-4-phenyl-2,3-dihydro-1H-1,5-
benzodiazepin-3-yl imidothiocarbamate 2 and 1-(2-oxo-4-
phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-yl)guanidine
3 with nitriles, a mixture of an aldehyde and β-keto esters
or acetylacetone, and/or α-halo ketones or nitriles yielded
new interesting pyrimidine and imidazole derivatives
of ester group at 1716cmꢀ1 and ῡC¼O 1670 and 1660cmꢀ1
,
1
respectively. H-NMR spectrum of compound 8a showed
Scheme 3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Hetaryl-1,5 Benzodiazepines—Part I: Synthesis of 3-pyrimidinyl- and Imidazolyl-
1,5-benzodiazepines
Scheme 4
Scheme 5
attached to benzodiazepine moiety. These new compounds
are of promising biological applications.
and potassium carbonate (3g) in dry acetone (50mL) was
refluxed for 1h. The reaction mixture was left to cool to
room temperature and poured onto crushed ice. The
separated solid was filtered, washed with cold water, and
dried. This crude solid material was boiled in chloroform
(54mL) for 10min and filtered off. The insoluble solid
was washed thoroughly several times with hot chloroform
(~50mL) and crystallized from dioxane to give
compounds 2 and 3. The collected chloroform filtrate was
concentrated and left to stand at room temperature
overnight to give crystalline of 4-phenyl-1H-[1,5]
benzodiazepin-2(3H)-one (4) [12].
EXPERIMENTAL
All melting points were determined on a MEL-TEMP
II (LABORATORY DEVICES, Dubuque, NJ) and are
uncorrected. IR spectra were obtained on a Nicolet
710 FT-IR spectrometer (ThermoFisher, Waltham City,
MA). 1H-NMR spectra, at 400 MHz, and 13C-NMR
spectra, at 100 MHz, were recorded on a Bruker Avance
III-400MHz instrument, using DMSO-d6 as a solvent
(Bruker, Zurich, Switzerland). Elemental microanalyses
were performed on a Perkin-Elmer CHN-2400 elemen-
tal analyzer (PerkinElmer, Waltham, MA). All com-
pounds were checked their purity on thin-layer
chromatography plates.
2-Oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-
ylimidothiocarbamate (2). Yield (40%), mp 220–222°C.
IR (KBr), ῡ (cmꢀ1): 3331, 3250, 3190, 3157 (NH, NH2),
1
1686 (C¼O), 763 (C–S–C). H-NMR (DMSO-d6), δ: 8.80
(s, 1H, N–Hbenzodiazepine), 7.81 (s, 1H, N–H disappeared on
addition of D2O), 7.69–6.58 (m, 9H, Harom), 4.74 (s, 2H,
NH2 disappeared on addition of D2O), 2.60 (s, 1H, CH).
Anal. Calcd for C16H14N4OS (310.37): C, 61.92%; H,
4.55%; N, 18.05%; S, 10.33%. Found: C, 61.61%; H,
4.21%; N, 18.23%; S, 10.54%.
Reaction of compound 1 with thiourea and/or guanidine
HCl. General procedure. A mixture of 3-bromobenzo
diazepinone
1
(3.15g, 10mmol), thiourea (0.76g,
10mmol) or guanidine hydrochloride (0.95g, 10mmol),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

A. Khodairy, E. A. Ahmed, and H. Abdel Ghany
Vol 000
1-(2-Oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-yl)
guanidine (3). Yield (90%), mp 181–183°C. IR (KBr), ῡ
(cmꢀ1): 3430, 3350, 3200, 3183 (N–H, NH2), 1697
(C¼O). 1H-NMR (DMSO-d6), δ: 8.00 (s, 1H, N–H),
7.50–6.60 (m, 9H, Harom), 5.10 (brs, 4H, 2NH2), 2.70 (s,
1H, C–H). Anal. Calcd for C16H15N5O (293.32): C,
65.52%; H, 5.15%; N, 23.88%. Found: C, 65.69%; H,
5.34%; N, 23.60%.
C28H18N6OS (462.52): C, 67.52%; H, 3.92%; N,
18.17%; S, 6.93%. Found: C, 67.70%; H, 3.75%; N,
18.30%; S, 6.60%.
4-Amino-2-[(2-oxo-4-phenyl-2,3-dihydro-1H-1,5-benzo
diazepin-3-yl)thio]pyrimidine-5-carbonitrile (8).
Yield
(70%), mp 159–161°C. IR (KBr), ῡ (cmꢀ1): 3390,
3223 (NH2), 3176 (N–H), 2189 (C≡N), 1690 (C¼O).
1H-NMR (DMSO-d6), δ: 8.10 (s, 1H, N–Hbenzodiazepine),
7.80–7.00 (m, 9H, Harom), 6.10 (s, 1H, Hpyrimidine),
4.90 (s, 2H, NH2), 2.60 (s, 1H, C–H). Anal. Calcd for
C20H14N6OS (366.42): C, 62.16%; H, 3.65%; N,
21.75%; S, 8.30%. Found: C, 62.21%; H, 3.80%; N,
21.54%; S, 8.60%.
Reaction of compound 2 with malononitrile dimer and/or
diethyl malonate.
General procedure.
A mixture of
compound 2 (0.63 g, 2 mmol) and malononitrile dimer
(0.26 g, 2 mmol) and/or diethyl malonate (0.32g,
2 mmol), in ethanol (25 mL), was treated with sodium
ethoxide [sodium metal (0.23 g, 10 mmol) was dissolved
in absolute ethanol (5 mL)]. The reaction mixture was
refluxed on water bath, for 2 h, left to cool to room
temperature, and poured into ice-cold dilute hydrochloric
acid solution (100 mL, 3%). The resulting solid product
was filtered, washed with water, and crystallized from
dioxane.
{6-Amino-2-[(2-oxo-4-phenyl-2,3-dihydro-1H-1,5-benzo
diazepin-3-yl)thio]pyrimidin-4(3H)-ylidene}malononitrile (5).
Yield (69%), mp 266–268°C. IR (KBr), ῡ (cmꢀ1): 3412,
3300, 3248, 3180 (N–H, NH2), 2201 (C≡N), 1665 (C¼O).
1H-NMR (DMSO-d6), δ: 8.70 (s, 1H, N–H), 8.20 (s, 1H,
Hpyrimidine), 8.00–7.30 (m, 10H, Harom +N–H), 4.90 (s, 2H,
NH2), 2.60 (s, 1H, CH). Anal. Calcd for C22H15N7OS
(425.46): C, 62.10%; H, 3.55%; N, 23.04%; S, 7.54%.
Found: C, 62.24%; H, 3.68%; N, 23.25%; S, 7.71%.
2-[(2-Oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-3-
yl)thio]-pyrimidine-4,6-(1H,5H)-dione (6). Yield (70%), mp
172–173°C. IR (KBr), ῡ (cmꢀ1): 3250, 3100 (2N–H),
1700, 1683 (C¼O), 1665 (C¼Obenzodiazepine). 1H-NMR
(DMSO-d6), δ: 8.50 (s, 1H, N–Hbenzodiazepine), 7.80–7.10
(m, 10H, Harom +N–H), 3.80 (s, 2H, CH2), 2.60 (s, 1H,
CH). 13C-NMR δ: 182, 166, 163, 160, 143, 137, 132,
132, 131, 130, 129, 127, 126, 125, 122, 55, 41. Anal.
Calcd for C19H14N4O3S (378.40): C, 60.31%; H, 3.73%;
N, 14.81%; S, 8.47%. Found: C, 60.51%; H, 3.90%; N,
14.70%; S, 8.61%.
Ceric ammonium nitrate-catalyzed reaction of compound 2
with some aldehydes/active methylene compounds. General
procedure.
To a mixture of compound 2 (3.15g,
10mmol), 10mmol of the appropriate aldehyde [namely,
benzaldehyde (1mL), p-chlorobenzaldehyde (1.42 g), or
p-methoxybenzaldehde (1.34mL)] and appropriate β-
ketonic compound [namely, ethyl acetoacetate (1.30 mL),
ethyl benzoylacetate (1.62 mL), or acetylacetone (1 mL)],
in ethanol (20 mL), ceric ammonium nitrate (0.03 g) was
added. Then the mixture was heated under reflux for
20min. On completion of the reaction (thin-layer
chromatography checked), the reaction mixture was
diluted with cold water, and the resulting solid was
filtered, dried, and crystallized from ethanol to give
compounds 9–13.
Ethyl (3-[(4-phenyl-6-methyl-1,6-dihydropyrimidin-2-yl)thio]-
4-phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one)carboxylates
(9). Yield (85%), mp 232–234°C. IR (KBr), ῡ (cmꢀ1):
3300, 3170 (2N–H), 1730 (C¼Oester), 1688
(C¼Obenzodiazepine). 1H-NMR (DMSO-d6), δ: 8.20
(s, 1H, N–Hbenzodiazepine), 8.00–7.00 (m, 15H, Harom
+ NH), 6.00 (br, 1H, Hpyrimidine), 3.95–3.80 (q, 2H,
CH2), 2.40 (s, 1H, Hbenzodiazepine), 2.23 (s, 3H, CH3),
1.32–1.00 (t, 3H, CH3). 13C-NMR (100 MHz,
DMSO-d6), δ: 170, 166, 164, 163, 160, 139, 138, 137,
136.9, 130.6, 130.7, 130.4, 130.2, 130, 129, 128, 127,
125, 121, 117, 63, 57, 51, 24, 13. Anal. Calcd for
C29H26N4O3S (510.60): C, 68.21%; H, 5.13%; N,
10.97%; S, 6.28%. Found: C, 68.04%; H, 5.28%; N,
10.75%; S, 6.43%.
Reaction of compound 2 with methylenemalononitriles.
General procedure. A mixture of compound 2 (1.26g,
4 mmol), benzylidenemalononitrile (0.71 g, 4 mmol), or
ethoxymethylenemalononitrile (0.48 g, 4 mmol) and
triethylamine (0.4 mL) in methanol (30 mL) was refluxed
for 4 h. The separated product after evaporation was
crystallized from dioxane.
Ethyl (3-[(4-p-chlorophenyl-6-methyl-1,6-dihydropy-rim
idin-2-yl)thio]-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-
one)carboxylates (10).
Yield (80%), mp 240–242°C. IR
(KBr), ῡ (cmꢀ1): 3356, 3198 (2N–H), 1716 (C¼Oester),
1
1678 (C¼Obenzodiazepine). H-NMR (DMSO-d6), δ: 8.00 (s,
4-Amino-2-[(2-oxo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-
1H, N–Hbenzodiazepine), 7.90–7.00 (m, 14H, Harom +N–H),
5.90 (s, 1H, C–H), 4.20–4.00 (q, 2H, CH2), 2.39 (s, 3H,
CH3), 2.22 (s, 1H, Hbenzodiazepine), 1.42–1.00 (t, 3H, CH3).
Anal. Calcd for C29H25ClN4O3S (545.06): C, 63.90%; H,
4.62%; N, 10.28%; S, 5.88%; Cl, 6.50%. Found: C,
63.64%; H, 4.40%; N, 10.10%; S, 5.63%; Cl, 6.70%.
3-yl)thio]-3-phenylpyrimidine-5-carbonitrile (7).
Yield
(60%), mp 201–202°C. IR (KBr), ῡ (cmꢀ1): 3342,
3218, 3180 (N–H, NH2), 2210 (C≡N), 1676 (C¼O).
1H-NMR (DMSO-d6), δ: 8.30 (s, 1H, N–
Hbenzodiazepine), 8.10–7.30 (m, 14H, Harom), 5.50–5.30
(br, 2H, NH2), 2.60 (s, 1H, CH). Anal. Calcd for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Hetaryl-1,5 Benzodiazepines—Part I: Synthesis of 3-pyrimidinyl- and Imidazolyl-
1,5-benzodiazepines
Ethyl (3-[(4-methoxyphenyl-6-methyl-1,6-dihydropyrimidin-
(m, 10H, Harom + N–H), 6.00 (s, 2H, NH2), 3.05 (s, 2H,
CH2), 2.60 (s, 1H, CH). Anal. Calcd for C18H16N6O
(332.35): C, 65.05%; H, 4.85%; N, 25.29%. Found: C,
65.30%; H, 4.91%; N, 25.49%.
2-yl)thio]-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one)
carboxylates (11). Yield (70%), mp 252–254°C. IR (KBr), ῡ
(cmꢀ1): 3295, 3190 (2N–H), 1720 (C¼Oester), 1680
1
(C¼Obenzodiazepine). H-NMR (DMSO-d6), δ: 8.20 (s, 1H,
5-Amino-2-[(2-oxo-4-phenyl-2,3-dihydro-1H-1,5-ben
zodiazepin-3-yl)thio]-4H-imidazole-4-carbonitrile (16). Yield
(70%), mp 174–176°C. IR (KBr), ῡ (cmꢀ1): 3372, 3200
NHbenzodiazepine), 8.00–7.20 (m, 14H, Harom +N–H), 6.10 (s,
1H, C–H), 4.40–4.02 (q, 2H, CH2), 3.78 (s, 3H, OCH3),
2.39 (s, 3H, CH3), 2.22 (s, 1H, C–H), 1.33–1.00 (t, 3H,
CH3). Elemental Anal. Calcd for C30H28N4O4S (540.63): C,
66.65%; H, 5.22%; N, 10.36%; S, 5.93%. Found: C,
66.30%; H, 5.37%; N, 10.12%; S, 5.71%.
1
(NH2), 3188 (N–H), 2193 (C≡N), 1664 (C¼O). H-NMR
(DMSO-d6), δ: 8.20 (s, 1H, NHbenzodiazepine), 7.80–7.10
(m, 10H, Harom +NH), 5.00 (s, 2H, NH2), 2.70 (s, 1H,
C–H). Anal. Calcd for C19H14N6OS (374.41): C, 60.95%;
H, 3.77%; N, 22.45%; S, 8.56%. Found: C, 60.60%; H,
3.58%; N, 22.70%; S, 8.80%.
Ethyl (3-[(4,6-diphenyl-1,6-dihydropyrimidin-2-yl)thio]-4-
phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one)carboxylate
(12). Yield (66%), mp 270–272°C. IR (KBr), ῡ (cmꢀ1):
3230, 3190 (2N–H), 1729 (C¼O), 1682 (C¼O benzodiazepine).
1H-NMR (DMSO-d6), δ: 8.30 (s, 1H, N–Hbenzodiazepine),
8.10–7.20 (m, 19H, Harom +NH), 5.50 (s, 1H, CHpyrimidine),
4.20–3.90 (q, 2H, CH2), 2.34 (s, 1H, CHbenzodiazepine),
1.40–1.10 (t, 3H, CH3). Anal. Calcd for C34H28N4O3S
(572.67): C, 71.31%; H, 4.97%; N, 9.78%; S, 5.60%.
Found: C, 71.04%; H, 4.68%; N, 9.55%; S, 5.72%
3-[(5-Amino-4H-imidazol-2-yl)thio]-4-phenyl-1,3-dihydro-
2H-1,5-benzodiazepin-2-one (17).
Yield (60%), mp
210–212°C. IR (KBr), ῡ (cmꢀ1): 3452 (OH), 3200, 3150
1
(3N–H), 1730 (C¼O), 1674 (C¼O). H-NMR (DMSO-
d6), δ: 8.10 (s, 1H, N–Hbenzodiazepine), 7.60–6.90 (m, 10H,
H
arom + N–H), 2.90 (s, 1H, CH). Anal. Calcd for
C18H14N4O2S (350.39): C, 61.70%; H, 4.03%; N,
15.99%; S, 9.15%. Found: C, 61.50%; H, 4.18%; N,
15.80%; S, 9.30%.
{3-[(4-Phenyl-3-acetyl-6-methyl-1,6-dihydropyrimidin-2-
yl)thio]-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepin-2-one}
(13). Yield (90%), mp 236–237°C. IR (KBr), ῡ (cmꢀ1):
3-[(5-Amino-4H-imidazol-2-yl)amino]-4-phenyl-1,3-dihydro-
x2H-1,5-benzodiazepin-2-one (18).
Yield (55%), mp
1
143–145°C. IR (KBr), ῡ (cmꢀ1): 3270 (2NH), 3200, 3150
3294, 3190 (2N–H), 1670 (C¼Obenzodiazepine). H-NMR
1
(DMSO-d6), δ: 8.30 (s, 1H, N–Hbenzodiazepine), 7.90–710
(m, 15H, Harom + N–H), 5.95 (s, 1H, C–H), 2.60 (s, 3H,
COCH3), 2.40 (s, 3H, CH3), 2.30 (s, 1H, CHbenzodiazepine).
Anal. Calcd for C28H24N4O2S (480.58): C, 69.98%; H,
5.03%; N, 11.66%; S, 6.67%. Found: C, 69.70%; H,
5.19%; N, 11.76%; S, 6.47%.
(NH2), 1700 (C¼O), 1684 (C¼O). H-NMR (DMSO-d6),
δ: 8.10 (s, 1H, N–Hbenzodiazepine), 7.90–7.00 (m, 12H,
H
arom +2N–H), 6.60–6.40 (br, 1H, N–H), 2.65 (s, 1H,
CH). Anal. Calcd for C18H15N5O2 (333.34): C, 64.86%;
H, 4.54%; N, 21.01%. Found: C, 64.61%; H, 4.32%; N,
21.24%.
3-[(5-Phenyl-4H-imidazol-2-yl)thio]-4-phenyl-1,3-dihydro-
Reaction of compounds 2 and 3 with some Α-halo esters,
nitriles, and/or ketones. General procedure. To a mixture
of 4mmol of compound 2 (1.26g) or 3 (1.24 g), the
appropriate halocompound [chloroacetonitrile (0.45mL),
bromomalo-nonitrile (0.58g), ethyl chloroacetate (0.49mL),
or phenacyl bromide (0.937g)] and triethylamine (0.4mL)
in ethanol (20mL) was refluxed for 2h. The precipitated
product after cooling was collected, dried, and
recrystallized from dioxane.
3-[(5-Oxo-4,5-dihydro-1H-imidazol-2-yl)thio]-4-phenyl-1,3-
dihydro-2H-1,5-benzodiazepin-2-one (14). Yield (60%), mp
186–187°C. IR (KBr), ῡ (cmꢀ1): 3360, 3313 (NH2), 3171
(N–H), 1672 (C¼O). 1H-NMR (DMSO-d6), δ: 8.80
(s, 1H, NHbenzodiazepine), 7.56–7.00 (m, 9H, Harom), 6.00
(s, 2H, NH2), 3.20 (s, 2H, CH2), 2.60 (s, 1H, CH). Anal.
Calcd for C18H15N5OS (349.40): C, 61.87%; H, 4.33%; N,
20.04%; S, 9.18%. Found: C, 61.44%; H, 4.64%; N,
21.24%; S, 9.34%.
2H-1,5-benzodiazepin-2-one (19).
Yield (80%), mp
201–203°C. IR (KBr), ῡ (cmꢀ1): 3181 (2N–H), 1682
(C¼O). 1H-NMR (DMSO-d6), δ: 8.60 (s, 1H,
N–Hbenzodiazepine), 7.90–7.00 (m, 16H, Harom +NH), 2.65
(s, 1H, C–H). Anal. Calcd for C24H18N4OS (410.49): C,
70.22%; H, 4.42%; N, 13.65%; S, 7.81%. Found: C,
70.46%; H, 4.47%; N, 13.90%; S, 7.70%.
3-[(5-Phenyl-4H-imidazol-2-yl)amino]-4-phenyl-1,3-dihydro-2H-
1,5-benzodiazepin-2-one (20). Yield (70%), mp 177–179°C.
IR (KBr),
ῡ
(cmꢀ1): 3211, 3181 (3N–H), 1690
(C¼O). 1H-NMR (DMSO-d6), δ: 8.60 (s, 1H,
N–Hbenzodiazepine), 7.90–7.00 (m, 17H, Harom +2N–H),
2.50 (s, 1H, C–H). Anal. Calcd for C24H19N5O (393.44):
C, 73.27%; H, 4.87%; N, 17.80%. Found: C, 73.32%; H,
4.67%; N, 17.62%.
REFERENCES AND NOTES
3-[(5-Oxo-4,5-dihydro-1H-imidazol-2-yl)amino]-4-phenyl-
1,3-dihydro-2H-1,5-benzodiazepin-2-one (15). Yield (90%),
mp 159–161°C. IR (KBr), ῡ (cmꢀ1): 3301, 3211, 3171
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DMSO-d6), δ: 8.80 (s, 1H, N–Hbenzodiazepine), 7.56–7.00
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