Silica sulfuric acid as a mild and efficient reagent for the synthesis of 1,4-Diazepine and 1,5-Benzodiazepine derivatives

Article abstract of DOI:10.5012/jkcs.2011.55.4.638

The synthesis of biologically active 1H-1,4-diazepines 4a-d and 3H-1,5-benzodiazepines 5a-d in good yields, from the heterocyclization reaction of 2-(4-methylthio benzenesulfonyl)-1,3-dimethyl/1-methyl-3-phenyl/1,3-diphenyl/ 1-methyl-3- ethoxy propane-1,3

Full text of DOI:10.5012/jkcs.2011.55.4.638

Journal of the Korean Chemical Society
2011, Vol. 55, No. 4
Printed in the Republic of Korea
DOI 10.5012/jkcs.2011.55.4.638
Silica Sulfuric Acid를 이용한 효율적인 1,4-diazepine and 1,5-benzodiazepine
유도체의 합성
†
Y. C. Joshi , Shalini Saingar, Kavita, P. Joshi , and Rajesh Kumar
‡
*
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
†
S. S. Jain Subodh P. G. College, Jaipur, Rajasthan, India
‡
Defence Laboratory, Jodhpur 342011, India
(접수 2010. 12. 12; 수정 2011. 2. 9; 게재확정 2011. 3. 16)
Silica Sulfuric Acid as a Mild and Efficient Reagent for the Synthesis of
1,4-Diazepine and 1,5-Benzodiazepine Derivatives
†
Y. C. Joshi , Shalini Saingar, Kavita, P. Joshi , and Rajesh Kumar
‡
*
Department of Chemistry, University of Rajasthan, Jaipur 302004, India
†
S. S. Jain Subodh P. G. College, Jaipur, Rajasthan, India
‡
*
Defence Laboratory, Jodhpur 342011, India. E-mail: rnunia@yahoo.com
(Received December 12, 2010; Revised February 9, 2011; Accepted March 16, 2011)
요
약. Silica sulfuric acid (SSA)를 이용하여 ethylenediamine (EDA)과 o-phenylenediamine (o-PDA)을 2-(4-methylthio benzene-
sulfonyl)-1,3-dimethyl/1-methyl-3-phenyl/1,3-diphenyl/1-methyl-3-ethoxypropane-1,3-dione 3a-d과의 헤테로고리화 반응을 통하
여 좋은 생리활성을 나타내는1H-1,4-diazepines 4a-d과 3H-1,5-benzodiazepines 5a-d을 좋은 수율로 합성하였다. 이 반응에
서 β-diketones/β-ketoesters 3a-d는 4-methylthiobenzenesulfonyl chloride 1과 다양한 β-diketones/β-ketoesters 2a-d과의 축합반
응으로 합성하였으며, 합성한4a-d와 5a-d 화합물들에 대해서 fantimicrobial, antifungal 및anthelmintic 활성을 측정하였다.
주제어: 3H-1,5-Benzodiazepines, 1H-1,4-Diazepines, Ethylenediamine, o-Phenylenediamine, Silica sulfuric acid
ABSTRACT. The synthesis of biologically active 1H-1,4-diazepines 4a-d and 3H-1,5-benzodiazepines 5a-d in good yields,
from the heterocyclization reaction of 2-(4-methylthio benzenesulfonyl)-1,3-dimethyl/1-methyl-3-phenyl/1,3-diphenyl/1-methyl-3-
ethoxy propane-1,3-dione 3a-d with ethylenediamine (EDA) and o-phenylenediamine (o-PDA), respectively, in the presence
of silica sulfuric acid (SSA) is described. The novel β-diketones/β-ketoesters 3a-d were synthesized by the condensation reac-
tion of 4-methylthiobenzenesulfonyl chloride 1 with various β-diketones/β-ketoesters 2a-d. All structures of the newly synthesized
compounds were elucidated by elemental analysis and spectral studies. The compounds 4a-d and 5a-d have been screened
for antimicrobial, antifungal and anthelmintic activity.
Keywords: 3H-1,5-Benzodiazepines, 1H-1,4-Diazepines, Ethylenediamine, o-Phenylenediamine, Silica sulfuric acid
11 12
enoyl-ACP reductase, FabI, antidepressive as well as
INTRODUCTION
13
anti-inflammatory agents. Other than their biologicalimpor-
Heterocyclic compounds have recently attracted atten-
tion as an important class of organic chemistry in the field
tance, benzodiazepines derivatives are also commercially
14
used as dyes for acrylic fibers.
1
of drugs and pharmaceuticals. A large number of hetero-
There are various methods for the synthesis of diaz-
epines and benzodiazepines by the condensation of o-phe-
nylenediamines with α,β-unsaturated carbonyl compounds,
cyclic compounds derived from β-diketones have been
2
reported as active entities. β-Diketones are important pre-
15
β-haloketones, or ketones in the presenceof acid. A vari-
cursors for the synthesis of pharmacologically active
heterocyclic compounds as 1,4-diazepines and 1,5-ben-
zodiazepines. These compounds are widely used as
ety of reagents, such as BF3-etherate, NaBH4, polyphos-
phoric acid, or SiO2, MgO/POCl3, Yb(OTf)3, Sc(OTf)3,
Al2O3/P2O5, (bromodimethyl) sulfonium bromide or under
microwave irradiation are utilized for condensation reac-
3
anticonvulsant, anti-HIV, CNS activity, anti-ulcer, anti-
4
5
6
7
proliferative, antitumor agents, antianxiety, and HDM2
8
9
10
antagonists. These were also inhibitor of the bacterial
16
tions. However, these methods are associated with sev-
-638-

Silica Sulfuric Acid를 이용한 효율적인 1,4-diazepine and 1,5-benzodiazepine 유도체의 합성
639
eral drawbacks such as harsh reaction conditions, complex
and tedious experimental procedures and low yields. In
recent years the use of organic-inorganic hybrid immo-
bilized solid support reagents have received great interest.
Such reagents not only simplify the purification process
but also provide help in preventing the release of reaction
ketoesters 2a-d in the presence of sodium methoxide yielded
corresponding substituted β-diketones/β-ketoesters 3a-d
(Scheme 1). All newly synthesized compounds were char-
acterized by elemental analysis and spectral studies
(experimental section). When compounds 3a-d were treated
with ethylenediamine in the presence of SSA underwent
dehydrative annulation to afford novel substituted 1H-
1,4-diazepines 4a-d. Further 3a-d were treated with o-
phenylenediamine on similar reaction conditions, to obtain
3H-1,5-benzodiazepines 5a-d (Scheme 2). SSA was pre-
17
residues into the environment. Furthermore, from the
synthetic point of view, these reagents significantly reduce
reaction time and make the workup easier. Recently, silica
and sulfuric acid in dichloromethane have been reported
18
22
for the oxathioacetalyzation of carbonyl compounds.
pared by reported method.
The efficiency of silica sulfuric acid (SSA), under oper-
ationally simple conditions, has prompted us to explore
the possibility of using this reagent for the synthesis of
1H-1,4-diazepine and 3H-1,5-benzodiazepines from the
reaction of β-diketones/β-ketoesters with ethylenediamine
(EDA) and o-phenylenediamine (o-PDA), respectively.
In continuation of our ongoing research program to
Antimicrobial, antifungal and anthelmintic activities
of compounds 4a-d and 5a-d
The newly synthesized diazepines 4a-d and benzodi-
azepines 5a-d were evaluated for the antibacterial activity
against Staphylococcus aureus, Klebsiella pneumoniae
and antifungal activity against Aspergillus niger, Candia
23
albicans by the cup-plate method. Ciprofloxin and ciclo-
develop new reagents and synthetic procedure for the syn-
19-21
thesis of novel heterocyclic compounds,
we report
piroxolamine were used as standards for comparison of
antibacterial and antifungal activities, respectively. The
results indicate that these compounds were active against
all the four organisms. The anthelmintic activity was car-
ried out on earth worms Pherituma posthuma, by a technique
here a new convenient method for the synthesis of 2-(4-
methylthiobenzenesulfonyl) containing 1H-1,4-diazepines
and 3H-1,5-benzodiazepines due to their importance in
medicinal chemistry. To achieve this target, we had syn-
thesized β-diketones/β-ketoesters 3a-d which were con-
densed with EDA and o-PDA in the presence of SSA, to
obtain the corresponding substituted 1H-1,4-diazepines 4a-d
and 3H-1,5-benzodiazepines 5a-d, respectively, in high
yields.
24
as described by Bagavant et al. with slight modification.
Piperazine citrate was used as standard drug. The values
of antimicrobial and anthelmintic activity are terms of
mean SEM of results done in triplicate, reported in
Table 1. The compounds 4a-c and 5a-c exhibited antimi-
crobial as well as antifungal activities, but 4d and 5d
showed significant anthelmintic activity due to presence
of more electronnegative groups.
RESULTS AND DISCUSSION
Thioanisole was sulfonated with chlorosulfonic acid, to
obtain 4-(methylthio)benzenesulfonyl chloride 1. This com-
pound 1, on condensation with various β-diketones/β-
From these results it is apparent that attempts to intro-
duce functionality methyl/phenyl at position 5 and 7 resulted
in significantly increased antibacterial and antifungal
Scheme 1.
2011, Vol. 55, No. 4

640
Y. C. Joshi, Shalini Saingar, Kavita, P. Joshi, and Rajesh Kumar
Scheme 2.
Table 1. Antimicrobial, antifungal and anthelmintic activities of compounds 4a-d and 5a-d
a
a
a
Antibacterial activity zone of inhibition in mm Antifungal activity zone of inhibition in mm Anthelmintic activity in min.
Compd.
S. aureus
21 0.57
19 0.48
21 0.65
15 0.75
22 0.57
20 0.48
21 0.65
16 0.75
K. pneumoniae
20 0.65
19 0.57
18 0.85
16 0.54
21 0.65
20 0.57
18 0.85
17 0.54
A. niger
19 0.58
18 0.54
20 0.57
17 0.55
19 0.58
18 0.54
20 0.57
16 0.55
C. albicans
21 0.58
19 0.57
20 0.54
16 0.48
21 0.58
19 0.57
20 0.54
16 0.48
Paralysis
92 0.65
93 0.69
91 0.57
101 0.85
92 0.65
93 0.69
92 0.57
98 0.85
Death
4a
4b
4c
4d
5a
5b
5c
5d
103 0.48
110 0.57
111 0.54
121 0.48
99 0.48
103 0.57
104 0.54
115 0.48
Ciprofloxin
24 0.57
26 0.24
--
22 0.44
--
--
24 0.74
--
--
--
--
--
Ciclopirox-olamine
Piperazine citrate
--
--
--
--
100 0.57
125 0.57
a
Values are in terms of Mean SEM of results done in triplicate.
activities due to its electron donating character but steric
hindrance also played a major important role. The diaz-
epine-5-one and benzodiazepine-2-one showed more anthel-
mintic activity than others due to more electronegativity
of oxygen. This result implies that the presence of elec-
tron withdrawing groups at position 5 in diazepines and
position 2 of benzodiazepines can increase anthelmintic
activity.
CONCLUSION
In conclusion, this new method for the synthesis of 1H-
1,4-diazepines and 3H-1,5-benzodiazepines using silica
sulfuric acid (SSA) offers significant improvement over
existing method. Also, this simple and reproducible method
affords various 1H-1,4-diazepines and 3H-1,5-benzodi-
azepines with short reaction times, high yields and with-
Journal of the Korean Chemical Society

Silica Sulfuric Acid를 이용한 효율적인 1,4-diazepine and 1,5-benzodiazepine 유도체의 합성
641
out the formation of undesirable by products. Among the
synthesized compounds evaluated (4a-d and 5a-d), com-
pound 4a-c, 5a-c exhibited antimicrobial as well as anti-
fungal activities in comparison the standard drug but
compounds 4d and 5d showed significant anthelmintic
activity. More extensive study is needed to confirm the
preliminaryresults and mode of action studies are required to
be able to optimize the effectiveness of this series of com-
pounds 4a-d and 5a-d.
zene:ethanol:ammonia) upper layer using as a mobile phase.
The yield and spectral data were reported in experimental
section.
2-[(4-Methylthio)benzenesulfonyl]-1,3-dimethylpro-
o
pane-1,3-dione (3a). 2.23 g (78%), mp 145 C; Anal.
Calcd. C12H14O4S2: C, 50.33; H, 4.93; S, 22.39. Found: C,
50.35; H, 4.90; S, 22.40. IR (KBr): 3025 (Ar-H), 2915 (C-
H), 1700 (C=O), 1290, 1415 (S-CH3), 1345, 1140 (-SO2)
-1 1
cm ; H NMR (CDCl3): δ 1.58 (s, 6H, CH3), 2.46 (s, 3H,
S-CH3), 6.07 (s, 1H, -CH=), 7.40 (dd, J = 7.46 , 6.89 Hz,
13
2H, Ar-H), 7.55 (dd, J = 7.45, 6.89 Hz, 2H, Ar-H);
C
EXPERIMENTAL
NMR (CDCl3): δ 18.9, 19.3, 106.2, 127.6, 129.0, 136.9,
+
198.4; MS (m/z): 287 (M+H ).
Instrumentation
All the melting points were determined in open capil-
lary tubes and are uncorrected. The purity of the newly
synthesized compounds was checked by TLC on alumin-
ium oxide 60 F254 plates (Merck) and spots were visual-
ized by exposing the dry plates in iodine vapor. The IR
spectra were recorded on a Nicolet-Magna-FT-IR-550 spec-
2-[(4-Methylthio)benzenesulfonyl]-1-methyl-3-phe-
o
nylpropane-1,3-dione (3b). 2.56 g (74%), mp 145 C;
Anal. Calcd. C15H16O4S2: C, 58.60; H, 4.63; S, 18.41.
Found: C, 58.57; H, 4.62; S, 18.40. IR (KBr): 3030 (Ar-
H), 2919 (C-H), 1715 (C=O), 1295, 1410 (S-CH3), 1345,
-1 1
1140 (-SO2) cm ; H NMR (CDCl3): δ 1.58 (s, 3H, CH3),
1
13
trometer in using KBr pellets. H NMR and C NMR
spectra were run on model DRX 300 at 300.13 MHz and
75 MHz, respectively, in CDCl3 and mass spectra on a
LCMS instrument. The elemental analysis (C, H, N) of
compounds was performed on Carlo Erba-1108 element
analyzer. Their results were found to be in good agree-
ment with the calculated values.
2.45 (s, 3H, S-CH3), 6.08 (s, 1H, -CH=), 7.40-7.86(m,10H,
13
Ar-H); C NMR (CDCl3): δ 18.9, 19.2, 101.2, 125.7, 127.6,
128.4, 128.6, 129.0, 132.9, 136.9, 137.5, 198.4; MS (m/z):
+
349 (M+H ).
2-[(4-methylthio)benzenesulfonyl]-1,3-diphenylpro-
o
pane-1,3-dione (3c). 3.54 g (82%), mp 155 C; Anal.
Calcd. C22H18O4S2: C, 64.37; H, 4.42; S, 15.62. Found: C,
64.35; H, 4.40; S, 15.63. IR (KBr): 3020 (Ar-H), 2915 (C-
H), 1710 (C=O), 1300, 1420 (S-CH3), 1345, 1140 (-SO2)
General procedure for the preparation of 2-[(4-
methylthio)benzenesulfonyl]-1,3-dimethyl/1-methyl-
3-phenyl/1,3-diphenyl/1-methyl-3-ethoxypropane-1,3-
dione (3a-d)
-1 1
cm ; H NMR (CDCl3): δ 2.46 (s, 3H, S-CH3), 6.10 (s,
13
1H, -CH=), 7.65-7.80 (m, 14H, Ar-H); C NMR (CDCl3): δ
19.8, 101.2, 125.7, 127.6, 128.4, 128.6, 129.0, 132.9, 136.9,
+
137.5, 198.4; MS (m/z): 411 (M+H ).
Sodium methoxide (0.54 g, 10.0 mmol) and β-diketones
(10.0 mmol) were placed in a dried round bottom flask
2-[(4-Methylthio)benzenesulfonyl]-1-methyl-3-ethox-
o
and stirred for 1 h on a magnetic stirrer at 50 C, after which
o
ypropane-1,3-dione (3d). 2.42 g (73%), mp 105 C;
a creamy mass was obtained. The 4-(methylthio)benze-
nesulfonyl chloride 1 (2.22 g, 10.0 mmol) was taken in dry
toluene and added drop by drop in above said reaction
Anal. Calcd. C13H16O5S2: C, 49.35; H, 5.10; S, 20.27.
Found: C, 49.36; H, 5.13; S, 20.25. IR (KBr): 3030 (Ar-
H), 2915(C-H), 1720 (C=O), 1297, 1415 (S-CH3), 1350,
o
mass. The reaction mixture was refluxed for 7 h at 100 C
-1 1
1145 (-SO2), 1210, 1240 (C-O-C) cm ; H NMR (CDCl3):
with stirring. The progress of the reaction was monitored
by TLC. After completion of the reaction, the mixture was
cooled and toluene was removed under reduced pressure.
The reaction mixture was extracted using chloroform and
washed with water. The chloroform layer was dried using
anhydrous sodium sulfate and distilled to yield the solid
compound. The product was purified by column chroma-
tography over silica gel using pet ether: ethyl acetate (1:2)
as an eluent. It was purified by recrystallization from abso-
lute ethanol. Purity of the compound was checked by TLC
on aluminum oxide 60 F254 plates (Merck) in a 7:2:1 (ben-
δ 1.30 (t, J = 7.25 Hz, 3H, CH3CH2-), 2.08 (s, 3H, CH3),
4.12 (q, J = 7.26 Hz, 2H, O-CH2CH3), 2.45 (s, 3H, S-
CH3), 6.15 (s, 1H, -CH=), 7.40 (dd, 2H, J = 7.46 , 6.89 Hz,
13
Ar-H), 7.55 (dd, J = 7.25, 7.09 Hz, 2H, Ar-H); C NMR
(CDCl3): δ 14.7, 18.9, 19.3, 59.5, 106.2, 127.6, 129.0,
+
136.9, 198.4; MS (m/z): 317 (M+H ).
General procedure for the preparation of 1H-1,4-diaz-
epine 4a-d and 3H-1,5-benzodiazepine 5a-d derivatives
An equimolar ratio of β-diketones/β-ketoesters (10
mmol) 3a-d, and EDA/o-PDA (10.0 mmol) in ethyl ace-
2011, Vol. 55, No. 4

642
Y. C. Joshi, Shalini Saingar, Kavita, P. Joshi, and Rajesh Kumar
tate (50 mL) in the presence of silica sulfuric acid (10.0
2.46 (s, 3H, S-CH3), 2.95-3.10 (m, 4H, N-CH2-CH2-N),
4.09 (s, 1H, -CH=), 7.45 (dd, J = 7.46, 6.89 Hz, 2H, Ar-H),
7.60 (dd, J = 7.46, 6.89 Hz, 2H, Ar-H), 8.30 (br s, 1H, NH);
o
mmol) was stirred 50 C for 2 h. The progress of reaction
was monitored by TLC using 7:2:1 (benzene:ethanol:
ammonia) upper layer as mobile phase. Upon completion
of reaction, the mixture was extracted with ethyl acetate (2
× 25 mL) and the solvent was removed. The crude prod-
uct was washed with dry ether and recrystallized from pet
ether:ethyl acetate (1:1). The product was purified by col-
umn chromatography over silica gel using pet ether:ethyl
acetate (40: 60) as an eluent.
13
C NMR (CDCl3): δ 13.7, 18.9, 43.8, 50.9, 64.9, 126.7,
+
127.6, 134.5, 140.6, 164.6, 170.8; MS (m/z): 313 (M+H ).
3-[(4-Methylthio)benzenesulfonyl]-2,4-dimethyl-3H-
o
1,5-benzodiazepine (5a). 2.49 g (70%), mp 165 C; Anal.
Calcd. C14H18N2O2S2: C, 60.31; H, 5.06; N, 7.81. Found:
C, 60.30; H, 5.07; N, 7.80. IR (KBr): 3050 (Ar-H), 2895
(C-H), 1580 (C=N), 1290, 1415 (S-CH3), 1345, 1140 (-
-1 1
SO2) cm ; H NMR (CDCl3): δ 1.60 (s, 6H, CH3), 2.45 (s,
6-[(4-Methylthio)benzenesulfonyl]-5,7-dimethyl-2,3-
dihydro-1H-1,4-diazepine (4a). 2.35 g (76%), mp 160
3H, S-CH3), 6.07 (s, 1H, -CH=), 7.65-7.80 (m, 8H, Ar-H);
o
13
C; Anal. Calcd. C14H18N2O2S2: C, 54.17; H, 5.84; N,
C NMR (CDCl3): δ 12.7, 18.9, 70.3, 114.5, 123.7, 127.9,
+
128.4, 134.3, 140.6, 142.5, 164.7; MS (m/z): 358 (M+H ).
9.02. Found: C, 54.15; H, 5.85; N, 9.03. IR (KBr): 3050
(Ar-H), 2895(C-H), 1580 (C=N), 1290, 1415 (S-CH3),
3-[(4-Methylthio)benzenesulfonyl]-2-methyl-4-phe-
-1
1
o
nyl-3H-1,5-benzodiazepine (5b). 2.64 g (63%), mp 185 C;
1345, 1140 (-SO2) cm ; H NMR (CDCl3): δ 2.07 (s, 6H,
CH3), 2.46 (s, 3H, S-CH3), 3.10 (t, J = 6.98 Hz, 4H, N-
CH2-CH2-N), 6.05 (s, 1H, -CH=), 7.43 (dd, J = 7.46, 6.89
Anal. Calcd. C23H20N2O2S2: C, 65.69; H, 4.79; N, 6.66.
Found: C, 65.70; H, 4.80; N, 6.65. IR (KBr): 3030 (Ar-H),
2919 (C-H), 1583 (C=N), 1295, 1413 (S-CH3), 1345, 1140 (-
13
Hz, 2H, Ar-H), 7.59 (dd, J = 7.46 , 6.89 Hz, 2H, Ar-H); C
-1 1
SO2) cm ; H NMR (CDCl3): δ 1.70 (s, 3H, CH3), 2.47 (s,
NMR (CDCl3): δ 12.7, 18.9, 48.5, 70.3, 114.5, 125.7,
127.6, 127.9, 128.4, 134.3, 140.5, 164.7; MS (m/z): 311
3H, S-CH3), 6.10 (s, 1H, -CH=), 7.65-7.80 (m, 13H, Ar-
+
(M+H ).
13
H); C NMR (CDCl3): δ15.3, 18.7, 70.8, 114.6, 125.7, 126.5,
6-[(4-Methylthio)benzenesulfonyl]-5-methyl-7-phenyl-
127.6, 127.9, 128.4, 130.7, 133.8, 140.5, 142.7, 164.9; MS
+
(m/z): 421 (M+H ).
2,3-dihydro-1H-1,4-diazepine (4b). 2.39 g (69%), mp
o
145 C; Anal. Calcd. C19H20N2O2S2: C, 61.26; H, 5.41; N,
3-[(4-Methylthio)benzenesulfonyl]-2,4-diphenyl-3H-
o
1,5-benzodiazepine (5c). 3.47 g (72%), mp 175 C; Anal.
7.52. Found: C, 61.28; H, 5.40; N, 7.50. IR (KBr): 3030
(Ar-H), 2919 (C-H), 1580 (C=N), 1295, 1410 (S-CH3),
Calcd. C28H22N2O2S2: C, 69.68; H, 4.59; N, 5.80. Found:
C, 69.67; H, 4.60; N, 5.83. IR (KBr): 3035 (Ar-H), 2915
(C-H), 1585 (C=N), 1295, 1410 (S-CH3), 1345, 1140 (-SO2)
-1
1
1350, 1145 (-SO2) cm ; H NMR (CDCl3): δ 2.10 (s, 3H,
CH3), 2.50 (s, 3H, S-CH3), 3.10 (t, J = 6.90 Hz, 4H, N-CH2-
CH2-N), 6.10 (s, 1H, -CH=), 7.45-7.88 (m, 10H, Ar-H);
-1 1
cm ; H NMR (CDCl3): δ 2.46 (s, 3H, S-CH3), 6.09 (s, 1H,
13
13
-CH=), 7.65-7.80 (m, 18H, Ar-H); C NMR (CDCl3): δ
C NMR (CDCl3): δ 15.3, 18.9, 47.9, 48.5, 70.3, 114.5,
125.7, 126.5, 127.6, 127.9, 128.7, 130.7, 135.3, 140.9,
18.9, 72.3, 114.5, 125.7, 126.9, 128.3, 129.4, 130.5, 134.5,
+
164.8; MS (m/z): 378 (M+H ).
+
142.4, 145.5, 146.9, 164.7; MS (m/z): 483 (M+H ).
6-[(4-Methylthio)benzenesulfonyl]-5,7-diphenyl-2,3-
3-[(4-Methylthio)benzenesulfonyl]-1,3-dihydro-4-
o
dihydro-1H-1,4-diazepine (4c). 5.36 g (83%), mp 175 C;
methyl-3H-1,5-benzodiazepine-2-one (5d). 2.30 g (68%),
o
mp 170 C; Anal. Calcd for C17H16N2O3S2: C, 56.65; H,
Anal. Calcd. C24H22N2O2S2: C, 66.35; H, 5.10; N, 6.45.
Found: C, 66.33; H, 5.08; N, 6.47. IR (KBr): 3030 (Ar-H),
2920 (C-H), 1585 (C=N), 1295, 1410 (S-CH3), 1345, 1140
4.47; N, 7.77. Found: C, 56.63; H, 4.45; N, 7.80. IR (KBr):
3420 (N-H), 3025 (Ar-H), 2920 (C-H), 1745 (C=O), 1625
-1 1
(-SO2) cm ; H NMR (CDCl3): δ 2.45 (s, 3H, S-CH3), 3.15
-1 1
(C=N), 1300, 1415 (S-CH3), 1350, 1145 (-SO2) cm ; H
NMR(CDCl3): δ 1.75 (s, 3H, CH3), 2.50 (s, 3H, S-CH3),
3.95 (s, 1H, -CH=), 7.65-7.80 (m, 8H, Ar-H), 8.30 (br s,
(t, J = 7.05 Hz, 4H, N-CH2-CH2-N), 6.09 (s, 1H, -CH=),
13
7.65-7.80 (m, 14H, Ar-H); C NMR (CDCl3): δ 18.9, 47.9,
+
72.3, 114.5, 125.7-137.9, 164.7; MS (m/z): 435 (M+H ).
13
1H, NH); C NMR (CDCl3): δ 13.7, 18.9, 64.9, 121.7, 125.4,
6-[(4-Methylthio)benzenesulfonyl]-7-methyl-2,3,4,6-
126.6, 127.6, 134.3, 134.7, 140.9, 164.6, 168.2; MS (m/z):
+
361 (M+H ).
tetrahydro-1H-1,4-diazepine-5-one (4d). 2.46 g (78%),
o
mp 140 C; Anal. Calcd. C13H16N2O3S2: C, 49.98; H,
5.16; N, 8.97. Found: C, 50.00; H, 5.15; N, 8.95. IR (KBr):
3350 (N-H), 3030 (Ar-H), 2915 (C-H), 1740 (C=O), 1630
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-1 1
(C=N), 1295, 1410 (S-CH3), 1345, 1140 (-SO2) cm ; H
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Journal of the Korean Chemical Society

Silica Sulfuric Acid를 이용한 효율적인 1,4-diazepine and 1,5-benzodiazepine 유도체의 합성
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2011, Vol. 55, No. 4