Diversified synthesis of novel quinoline and dibenzo thiazepine derivatives using known active intermediates

Article abstract of DOI:10.14233/ajchem.2013.14818

The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15) and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported compounds were structural characterized by elemental analysis and spectral studies such as 1H, ¹³C NMR and MS.

Full text of DOI:10.14233/ajchem.2013.14818

Asian Journal of Chemistry; Vol. 25, No. 14 (2013), 7959-7966
http://dx.doi.org/10.14233/ajchem.2013.14818
Diversified Synthesis of Novel Quinoline and Dibenzo
Thiazepine Derivatives Using Known Active Intermediates
*
L.N. SHARADA , G.S. SATYANARAYANA REDDY, B. SAMMAIAH and D. SUMALATHA
Department of Chemistry, Osmania University, Hyderabad-500 007, Inida
*Corresponding author: Fax: +91 40 27095171; Tel: +91 40 27152892; E-mail: dr.sharadaln@gmail.com
(Received: 12 November 2012; Accepted: 29 July 2013)
AJC-13850
The novel drug development to control resisting infections in conventional drug therapy is a need of today. Few antiulcer relative derivatives
developed by approaching convergent synthesis. The derivatives synthesized successfully are dibenzo thiazepine-pyridine (SLN11-SLN15)
and benzimidazole-hydroquinoline based derivatives (SLN16-SLN20). It involved the coupling through microwave, sonication and
conventional techniques at final step. The efficient technology identified as sonication technique basically time and yield. The reported
compounds were structural characterized by elemental analysis and spectral studies such as 1H, 13C NMR and MS.
Key Words: Sonication, Benzimidazole, Dibenzo thiazepine, Antiulcerative.
Pantoprazole (c) suppresses the final step in gastric acid
production by forming a covalent bond to two sites of the (H+,
K+)-ATPase enzyme system at the secretary surface of the
gastric parietal cell6,7. Rabeprazole (d) is also demonstrated
efficacy in healing and symptom relief of gastric and duodenal
ulcers8-10. Ilaprazole (e) is a proton pump inhibitor (PPI) used
in the treatment of dyspepsia, peptic ulcer disease (PUD) and
duodenal ulcer11. Tenatoprazole is an extended plasma half-
life which makes it more effective in the treatment of nocturnal
acid breakthrough than esomeprazole12.
INTRODUCTION
For therapeutic purposes, a drug substance with well-
known chemical structure is used for developing more efficient
drugs. The basic idea to prepare more analogues compounds
that related drug candidates with efficient technologies. Organic
molecules owe their biological activity to a variety of structural
features. Sometimes a set of activities is associated with the
structural backbone of a molecule.
The antiulcer drugs, omeprazole (a), is a proton pump
inhibitor (PPIs) and inhibits the action of hydrogen/potassium
adenosine triphosphatase (H+/K+ATPase) in parietal cells1-5.
Lansoprazole (b) is an antiulcer agent and proton pump
inhibitor4,5. The structures of some antiulcer drugs available
in market are given in Fig. 1.
The art has endeavoured to synthesize a variety of
piperzine derivatives.Among the piperzine derivatives available
as antiulcer drugs, 1-[2-(orthochloro-chlorobenzydryloxy)
ethyl]-4-(ortho-methylbenzyl)piperzine well known13,14. The
H
N
H
N
O
O
O
O
O
H
N
F
O
O O
O
S
S
CF3
S
N
N
F
N
N
N
N
Omeprazole (a)
Lansoprazole (b)
Pantoprazole (c)
H
H
O
O
H
N
O
N
N
O
O
N
O
O
N
S
S
S
N
O
N
N
N
N
N
Ilaprazole (e)
Rebepraprazole (d)
Tenatoprazole (f)
Fig. 1. Several antiulcer drugs in the market

7960 Sharada et al.
Asian J. Chem.
selection of well-known skeleton, strategic synthetic approach,
technologies applied for reactions. The maximum antiulcerative
drugs are prazoles. The prazoles skeleton considered for deve-
lopment of novel moieties into literature. The idea to incorporate
the piperzine with pyridine derivatives of prazoles considered
to design new skeleton (a) and benzimidazoles of different
prazoles with hydroquinoline derivative.
The microwave mediated organic reactions15 take place
more rapidly, safely and in an environmentally friendly
manner, with high yields. Very little solvent and even the use
of water as a solvent is a big advantage of microwave chemistry.
Recently, microwave16 and ultrasonication17 assisted synthesis
in organic chemistry is quickly growing. Many organic reac-
tions proceed much faster with higher yields under microwave
irradiation compared to conventional heating. It has long been
known that molecules undergo excitation with electromagnetic
radiation is a technique for microwave synthesis18. Simulta-
neously, sonication reactions enhances the reaction rates up
to a million times, believed to be due small cavities (100 µ)
which implode, creating tremendous heat and pressure, shock
waves and particular accelerations.
R1
O
R2
R3
N
NH
N
N
N
NH
R1
R4
S
O
N
S
(a)
(b)
Fig. 2. Designed skeletons
EXPERIMENTAL
All the reactions routinely monitored by thin-layer
chromatography (TLC) using Merck silica gel 60 F254 coated
aluminium plates using several solvent systems of different
polarity. The following mobile phases were employed ethyl
acetate/hexane, ethylacetate/dichloromethane, methanol/
dichloromethane and methanol-ethyl acetate with different
percentage combinations. The column chromatography by
using all vensil columns are used for purification of compounds
used (60-120 mesh) silica-gel. The melting points were deter-
mined in open capillaries on a Thermonick melting point
A strategy of convergent synthesis, that aims to improve
the efficiency of multi-step chemical synthesis, most often in
organic synthesis. In linear synthesis the overall yield quickly
drops with each reaction step. Here in, the synthesis of two
tile derivatives and coupled considered easy and found excellent
literature for easy synthesis of both ends approached convergent
than linear.
The reliable technology useful for reaching target is very
important to reach target very simple and cost effective. The
second technology is the way of reaction conditions are using,
for getting lesser reaction timings and high yield. The N-alky-
lation step differentiated via microwave, sonication and
conventional method.
1
apparatus and found uncorrected. H NMR (400 MHz) and
13C NMR (100 MHz) recorded on CDCl3 and DMSO-d6 solution
in a 5 mm tube on Varian 400 MHz Unity Inova using TMS
NH
N
N
(SM1)
S
R1
N
C-N
N
N
N
(Tile-1)
COUPLING
via
Micro-Wave (or)
Ultra - Sonication
(or) Conventional
S
R1
Cl
(SM2)
N
(Target)
(Tile-2)
Scheme-I: Retro of the skeleton (a) based on convergent methodology
H
N
O
O
Br
(SM1)
O
(Tile-1)
NH
C-S
R1
NH
COUPLING
via
Micro-Wave (or)
Ultra - Sonication
(or) Conventional
H
N
O
N
S
R1
SH
(SM2)
(Target)
N
(Tile-2)
Scheme-II: Retro of the skeleton (b) based on convergent methodology

Vol. 25, No. 14 (2013)
Diversified Synthesis of Novel Quinoline and Dibenzo Thiazepine Derivatives 7961
internal reference standard (chemical shifts in δ). Mass spectra
were recorded onAgilent 6310 Ion Trap and Shimadzu LCMS
(e/z and relative intensity). Microwave reactions are carried
out in SEM Discovery (sixty). Ultra sonication reactions per-
formed in Sonirex sonicator.
7.21-7.32 (m, 4H), 7.39 (d, J = 6.2Hz, 1H), 7.49 (d, J = 6.2Hz,
1H), 8.31(d, J = 6Hz, 1H) ). 13C NMR (100 MHz, CDCl3): δ
(ppm) 10.61, 29.41, 53.13, 58.74, 62.85, 64.87, 68.96, 105.51,
121.94, 122.63, 122.71, 125.3127.96, 128.18, 129.02, 130.06,
132.05, 132.12, 134.16, 139.84, 147.40, 149.02, 156.49,
160.80, 163.27; MS (e/z): 499 (M+). Anal. calcd. (%) for
C26H25F3N4OS: C, 62.64; H, 5.05; F, 11.43; N, 11.24; O, 3.21;
S, 6.43. Found (%): C, 62.64; H, 5.05; F, 11.43; N, 11.24; O,
3.21; S, 6.43.
General procedure for preparation of diazathiazapine-
pyridine derivatives (SLN11-SLN15) and benzimidazole-
hydroquinoline derivatives (SLN16 - SLN20)
SLN14: 1H NMR (400 MHz, CDCl3): δ 2.31 (s, 3H), 2.42-
2.81 (m, 4H), 3.21-3.49 (m, 4H), 3.65 (s, 2H), 3.72 (s, 3H),
6.76 (d, J = 6Hz, 2H), 7.14 (t, 1H), 7.21-7.32 (m, 4H), 7.39
(d, J = 6.2Hz, 1H), 7.49 (d, J = 6.2Hz,1H), 8.23(d, J = 6Hz,
Conventional method (A): To a mixture of (Int-1 or Int-
2), (Int-3 to Int-12) and potassium carbonate in anhydrous
DMF at room temperature. The reaction mixture was stirred
at 40 ºC for 5-6 h. The reaction mixture was diluted with water
and extracted product into ethyl acetate. The resultant crude
product purified through silica-gel (60-120 mesh) column
chromatography to afford yield (calcd. 35-52 %) (SLN11-
SLN20).
13
1H) ). C NMR (100 MHz, CDCl3): δ (ppm) 59.84, 53.13,
58.74, 62.84, 62.85, 64.87, 68.96, 105.53, 121.95, 122.64,
122.72, 125.82, 127.96, 128.18, 129.12, 130.08, 132.07,
132.15, 134.19, 139.88, 147.48, 149.08, 156.51, 160.83,
163.31; MS (e/z): 431 (M+).Anal. calcd. (%) for C25H26N4OS:
C, 69.74; H, 6.09; N, 13.01; O, 3.72; S, 7.45. Found (%): C,
69.83; H, 6.17; N, 13.05; O, 3.83; S, 7.53.
Micro-wave method (B): To a mixture of (Int-1 or Int-
2), (Int-3 to Int-12) and potassium carbonate in anhydrous
DMF at room temperature in a micro tube. The reaction
mixture was stirred at 80 ºC for 0.5 h, 100-200 watts. The
reaction mixture was diluted with water and extracted product
into ethyl acetate. The resultant crude product purified through
silica-gel (60-120 mesh) column chromatography to afford
yield (calcd. 35-50 %) (SLN11-SLN20).
1
SLN15: H NMR (400 MHz, CDCl3): δ 2.50-2.57 (m,
4H), 3.46-3.68 (m, 4H), 3.85 (s, 2H), 3.87 (s, 3H), 388 (s,
3H), 6.67 (d, J = 5.6 Hz, 1H), 6.84-6.88 (m, 2H), 7.04-7.07
(m, 2H), 7.34-7.38 (m, 2H), 7.38 (d, J = 1.6 Hz, 1H), 7.49 (d,
13
J = 2Hz, 1H), 8.29 (d, J = 6Hz, 1H). C NMR (100 MHz,
Sonication method (C): To a mixture of (Int-1 or Int-2),
(Int-3 to Int-12) and potassium carbonate in anhydrous DMF
at room temperature. The reaction mixture was sonicated at
40 ºC for 0.5 h. The reaction mixture was diluted with water
and extracted product into ethyl acetate. The resultant crude
product purified through silica-gel (60-120 mesh) column
chromatography to afford yield (calcd. 45-70 %) (SLN11-
SLN20).
CDCl3): δ (ppm) 10.55, 53.13, 55.33, 62.80, 104.74, 121.94,
122.66, 125.34, 127.99, 128.18, 129.05, 130.66, 132.08,
132.14, 134.19, 139.90, 147.47, 149.02, 156.48, 160.83,
163.98; MS (e/z): 447 (M+).Anal. calcd. (%) for C25H26N4O2S:
C, 67.24; H, 5.87; N, 12.55; O, 7.17; S, 7.18. Found (%): C,
67.28; H, 5.94; N, 12.62; O, 7.25; S, 7.243.
1
SLN16: H NMR (400 MHz, CDCl3): δ 1.62-1.84 (m,
4H), 2.53 (t, 2H), 2.75 (t, 2H), 3.22 (t, 2H), 3.64 (t, 2H), 6.25
(t, 1H), 6.35 (t, 1H), 6.75 (m, 2H), 6.89 (d, J = 8.4Hz,1H),
7.00 (s, 1H), 7.42 (d, J = 8.8Hz, 1H), 8.29 (s, 1H), 9.61(s,
1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 24.38, 26.35,
28.05, 30.94, 31.00, 32.57, 67.24, 102.19, 109.14, 111.45,
115.66, 128.59, 138.07, 149.63, 156.12, 158.37, 172.94; MS
(e/z): 368 (M+). Anal. calcd. (%) for C20H21N3O2S: C, 65.37;
H, 5.76; N, 11.44; O, 8.71; S, 8.73. Found (%): C, 65.42; H,
5.81; N, 11.47; O, 8.75; S, 8.75.
1
SLN11: H NMR (400 MHz, CDCl3): δ 2.21 (s, 3H),
2.31(s, 3H), 2.49-2.55 (m, 4H), 3.44-3.65 (m, 4H), 3.65 (s,
2H), 3.72 (s, 3H), 6.69 (t, 1H), 7.01-7.18 (m, 3H), 7.34-7.38
(m, 2H), 7.39 (d, J = 1.6 Hz, 1H), 7.49 (d, J = 2Hz, 1H), 8.20
(s, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 11.04, 13.27,
59.84, 62.84, 122.66, 125.14, 125.31, 126.23, 127.97, 128.21,
129.04, 130.70, 132.06, 132.02, 132.12, 134.11, 139.81,
148.58, 148.98, 155.91, 160.84, 164.078; MS (e/z): 445 (M+).
Anal. calcd. (%) for C26H28N4OS: C, 70.24; H, 6.35; N, 12.60;
O, 3.60; S, 7.21. Found (%): C, 70.31; H, 6.42; N, 12.69; O,
3.69; S, 7.29.
SLN12: 1H NMR (400 MHz, CDCl3): δ 2.02-2.07 (m,
2H), 2.25 (s, 3H), 2.39-2.61 (m, 4H), 3.01-3.32 (m, 4H), 3.33
(s, 3H), 3.52 (t, 2H), 3.68 (s, 2H), 4.06 (t, 2H), 6.60 (d, J =
6Hz, 2H), 7.10 (d, J = 6.2Hz, 2H), 7.13 (t, 1H), 7.19-7.32 (m,
2H), 7.39 (d, J = 6.2Hz, 1H), 7.49 (d, J = 6.2Hz,1H), 8.26 (d,
J = 6Hz, 1H) ). 13C NMR (100 MHz, CDCl3): δ (ppm) 10.60,
29.39, 53.12, 58.72, 62.84, 64.86, 68.94, 105.49, 121.92,
122.63, 125.3127.96, 128.18, 129.02, 130.06, 132.05, 132.12,
134.16, 139.84, 147.40, 149.02, 156.49, 160.80, 163.27; MS
(e/z): 489 (M+). Anal. calcd. (%) for C28H32N4O2S: C, 68.82;
H, 6.60; N, 11.47; O, 6.55; S, 6.56. Found (%): C, 68.89; H,
6.69; N, 11.54; O, 6.64; S, 6.64.
1
SLN17: H NMR (400 MHz, CDCl3): δ 1.84-1.85 (m,
4H), 2.61 (brs, 2H), 2.82 (brs, 2H), 2.83 (brs, 2H), 3.31 (brs,
2H), 6.25-6.27 (brm, 2H), 6.41 (brs, 2H), 6.95 (brs, 2H), 7.32
(brs, 2H), 9.77(brs, 1H). 13C NMR (100 MHz, CDCl3): δ (ppm)
24.31, 26.31, 28.05, 30.97, 32.28, 67.28, 102.33, 109.14,
113.97, 115.04, 115.78, 116.55, 119.12, 128.64, 137.99,
146.69, 152.33, 158.37, 173.18; MS (e/z): 434 (M+). Anal.
calcd. (%) for C21H21F2N3O3S: C, 58.19; H, 4.88; F, 8.77; N,
9.69; O, 11.07; S, 7.40. Found (%): C, 58.23; H, 4.93; F, 8.82;
N, 9.73; O, 11.13; S, 7.52.
1
SLN18: H NMR (400 MHz, CDCl3): δ 1.84-1.89 (m,
4H), 2.62 (t, 2H), 2.84 (t, 2H), 3.32 (t, 2H), 3.82 (t, 2H), 3.91(s,
3H), 6.27 (s, 1H), 6.37 (s, 1H), 6.44 (m, 1H), 6.57 (d, J = 8.4
Hz, 1H), 6.75 (d, J = 8.4 Hz,1H), 6.96 (d, J = 8.4Hz,1H), 7.72
(d, J = 8.8Hz, 1H), 9.35 (s, 1H). 13C NMR (100 MHz, CDCl3):
δ (ppm) 24.43, 26.24, 28.05, 30.94, 31.00, 32.12, 53.96, 67.37,
102.40, 105.04, 109.08, 115.759, 128.577, 138.07, 158.42,
160.94, 172.76; MS (e/z): 398 (M+). Anal. calcd. (%) for
SLN13: 1H NMR (400 MHz, CDCl3): δ 2.30 (s, 3H), 2.40-
2.80 (m, 4H), 3.20-3.49 (m, 4H), 4.35 (m, 2H) 6.60 (d, J =
6Hz, 2H), 6.84 (t, 1H), 7.12 (d, J = 6.2Hz, 1H), 7.14 (t, 1H),

7962 Sharada et al.
Asian J. Chem.
O
O
O2N
Cl
O2N
H2N
(a)
(c)
(b)
HN
SH
S
S
S
1
2
3
4
5
NH
Cl
O
N
H
N
N
.HCl
(f)
N
(e)
(d)
S
S
S
Int-1
6
7
Reaction & Conditions: (a) NaOH, DMSO, 80oC (b) Ra Ni, MeOH, H2, 80PSI (c) Phenyl chloroformate, Na2CO3, THF, H2O
(d) PPA, 100oC (e) POCl3, N,N'-dimethyl aniline, DCM (f) Piperzine, Toluene/THF, triehtylamine.
Scheme-III: Synthesis of 11-pyrazolyldibenzo[b,f][1,4]thiazepine (Int-1)
C20H22N4O3S C21H23N3O3S: C, 63.45; H, 5.83; N, 10.57; O,
12.08; S, 8.07. Found (%): C, 63.51; H, 5.92; N, 10.63; O,
12.15; S, 8.15.
at 105 ºC. The final coupling was carried out in presence of
triethylamine in toluene/THF to afford Int-1 according to
Scheme-III.
1
SLN19: H NMR (400 MHz, CDCl3): δ 1.60-1.85 (m,
The reported procedure incorporated during the synthesis
of 7-(4-bromobutoxy)-3,4-dihydroquinolin-2(1H)-one (Int-
2)19. Simple acylation carried out on 3-amino phenol using
NaHCO3 in acetonitrile at 0 ºC to afford 10. The cyclisation of
10 done with AlCl3 in dichloromethane to afford 11. Finally,
11 were coupled with 1,4-dibromo butane using K2CO3 in
DMF at 60 ºC for 12 h to afford Int-2 according to Scheme-IV.
4H), 2.57 (t, 2H), 2.79 (t, 2H), 3.24 (t, 2H), 3.66 (t, 2H), 3.71(s,
3H), 6.29 (s, 1H), 6.37 (d, 1H), 6.77 (d, J = 8.4Hz,1H), 6.91
(d, J = 8.4Hz,1H), 7.01 (s, 1H), 7.43 (d, J = 8.8Hz, 1H), 9.61(s,
1H). 13C NMR (100 MHz, CDCl3): δ (ppm) 24.38, 26.35,
3
28.05, 30.94, 31.00, 32.57, 55.82, 67.24, 102.19, 109.14,
111.45, 115.66, 128.59, 138.07, 149.63, 156.12, 158.37,
172.94; MS (e/z): 399 (M+).Anal. calcd. (%) for C20H22N4O3S:
C, 60.28; H, 5.56; N, 14.06; O, 12.05; S, 8.05. Found (%): C,
60.35; H, 5.65; N, 14.12; O, 12.14; S, 8.11.
O
O
(a)
(b)
Cl
Cl
HO
HO
NH
HO
N
H
Cl
2
1
9
10
8
SLN20: H NMR (400 MHz, CDCl3): δ 1.84-1.88 (m,
4H), 2.60 (brs, 2H), 2.83 (brs, 2H), 2.85 (brs, 2H), 3.33 (brs,
2H), 6.02 (brs, 2H), 6.25-6.27 (brm, 2H), 6.41 (brs, 2H), 6.71
(brs, 2H) 6.95 (brs, 2H), 7.32 (brs, 1H), 9.77(brs, 1H). 13C
NMR (100 MHz, CDCl3): δ (ppm) 24.28, 26.29, 28.00, 30.92,
32.23, 67.24, 102.31, 208.19, 109.10, 113.90, 115.02, 115.71,
116.51, 117. 21, 119.10, 128.58, 137.96, 146.67, 152.36,
158.39, 173.19; MS (e/z): 433 (M+). Anal. calcd. (%) for
C24H24N4O2S: C, 66.64; H, 5.59; N, 12.95; O, 7.40; S, 7.41.
Found (%): C, 66.64; H, 5.59; N, 12.95; O, 7.40; S, 7.41.
(c)
Br
O
N
H
O
N
H
O
11
Int-2
Reagents & Conditions: (a) NaHCO3 (b) AlCl3 (c) 1,4-dibromo butane
Scheme-IV: Synthesis of 7-(4-bromobutoxy)-3,4-dihydroquinolin-2(1H)-
one (Int-2)
The traditional approach for the synthesis of Int-3 - Int-7
as shown in Scheme-V20. The conversion of nitro compounds
9 and 14 to corresponding chloro 10 and 15 using POCl3 as a
chlorinating reagent. The further conversation of choro com-
pounds 10 and 15 into 11, 16, 17, 22 and 27 using appropriate
alcohols, the methylation of compound 25 using DMS to
afford methylated compound 26. The further conversion of
compounds, 11, 16, 17, 22 and 27 to acetate using acetic
anhydride to afford compounds, 12, 17, 20, 23 and 28. All
these compounds hydrolyzed using NaOH to afford 13, 18,
21, 24 and 29. Finally, alcohol of 13, 18, 21, 24 and 29 con-
verted to chloro using SOCl2 to afford Int-3 to Int-7 according
RESULTS AND DISCUSSION
In continuation of our research interest was to synthesize
a series of novel (SLN11-SLN20) relevant to antiulcer related
drug skeleton candidates prepared. The main focus in this paper
described the synthesis and rest of the activity studies is under
progress.
In the synthesis of Int-1, was followed the some earlier
reported work18. The coupling of 1 and 2 using NaOH in
DMSO at 80 ºC. The reduction of compound 3 with Ra Ni, H2
in methanol into 4. The carbamate 5 was prepared by protection
of amine 4 using phenyl chloroformate and Na2CO3. The
cyclisation of carbamate 5 into compound 6 was carried out
in presence of PPA at 80-90 ºC. The imino chloride was
prepared by treating 6 with POCl3 and N,N'-dimethyl aniline
to Scheme-V21,22
.
The earlier reported paper used for the synthesis of Int-
823. Herein, the required 2-mercapto benzimidazole (Int-8) was
prepared by refluxing o-phenylenediamine (33), CS2 and

Vol. 25, No. 14 (2013)
Diversified Synthesis of Novel Quinoline and Dibenzo Thiazepine Derivatives 7963
NO2
(a)
N
Cl
N
O
N
O
O
O
(b)
(d)
(e)
(c)
Cl
O
O
OH
N
N
.HCl
N
.HCl
O
O
O
11
O
13
Int-3
12
9
10
O
O
O
O
O
O
O
(b)
(c)
(d)
(e)
OH
O
Cl
N
N
.HCl
N
N
.HCl
Int-4
O
16
O
17
18
NO2
Cl
N
O
CF3
O
CF3
O
CF3
O
O
CF3
(b)
(b)
(b)
(a)
(c)
(c)
(e)
(d)
OH
N
Cl
N
N
.HCl
N
N
.HCl
O
O
O
O
21
Int-5
20
14
19
15
O
O
O
O
(e)
(d)
O
Cl
OH
N
N
.HCl
N
N
.HCl
O
O
Int-6
23
24
22
Cl
O
Cl
O
O
O
O
O
O
O
O
O
(f)
(c)
(e)
(d)
OH
Cl
O
N
N
O
N
N
.HCl
N
.HCl
N
O
O
O
Int-7
25
26
Reagents & Conditions: (a) POCl3, reflux for 3-4h (b) appropriate alchohols and NaOH (c)acetic anhydride,
27
28
29
acetic acid, MeOH, Toluene (d) NaOH, MeOH, MDC (e) SOCl2 (f) DMS
Scheme-V: Synthesis of 2-chloromethyl-4-methoxy-3,5,-dimethyl-pyridine. HCl (Int-3), 2-chloromethyl-3-methyl-4-(3-
methyoxypropoxy) pyridine. HCl (Int-4), 2-chloromethyl-3-methyl-4-(2,2,2-trifluoromethoxy)pyridine. HCl (Int-5), 2-
Chloromethyl-3-methyl-4-methoxy pyridine. HCl (Int-6) and 2-chloromethyl-3,4-dimethoxypyridine.HCl (Int-7)
NaOH and further salt freed by using acetic acid according
Scheme-VI.
nitro compound 41 using HNO3, H2SO4. Then deprotected 41
into 42 using NaOH, MeOH. The nitro group reduced using
tin, HCl and further cyclized using KOH, CS2 to afford Int 10
according to Scheme-VIII.
In this process, fluorination of 4-hydroxyacetanilide (34)
yielded the intermediate N-[4-(difluoromethoxy)phenyl]-
acetamide 35. Subsequent reactions like nitration followed by
hydrolysis, reduction and cyclization of intermediate 35 gave
the title compound, 2-mercapto-5-difluoromethoxy-1H-
benzimidazole Int-9 according Scheme-VII24.
The coupling of 44 with sodium methoxide in methanol
and further reduction and cyclisation leads Int-11 according
to Scheme-IX25.
The reaction of 2-mercapto-5-nitrobenzimidazole 47 with
iron and concentrated HCl in refluxing ethanol and water gives
monoamine 48, which on condensation with 2,5-dimethoxy-
tetrahydrofuran 49 in acetic acid yields 2-mercapto-5-(1-
pyrrolyl)benzimidazole Int-12 according to Scheme-X26.
The novel targets (SLN11-SLN20) were synthesized by
simple coupling using different technologies (microwave,
ultra-sonication and normal conventional method). Basically,
we observed ultra-sonication condition looking better compa-
ratively with other techniques used based on yield according
to Table-1.
The important intermediate for omeprazole, 2-mercapto-
5-methoxy benzimidazole (Int 10)23 was prepared from anisidine
(39), acetyl protection leads 40. The Int 40, converted into
NH2
NaOH
N
CS2
SH
N
H
Int-8
NH2
33
Scheme-VI: Synthesis of 2-mercapto benzimidazole

7964 Sharada et al.
Asian J. Chem.
O
F
OH
O
F
(c)
O
O
(a)
(b)
O
F
F
N
H
N
H
N
H
NO2
36
34
35
H
N
O
F
O
F
F
O
(e)
(d)
SH
F
F
F
H2N
N
H2N
NO2
NH2
38
Int-9
37
Reagents & conditions:
(a) PEG-600, difluoromethylenchloride, 50-550C, 70-74h (b)HNO3, H2SO4, 20-250C, 2h.(c)CH3OH, Reflux,
3h. (d) Raney-Nickel, hydrazine hydrate, reflux, 4h. (e)CS2, reflux, 4h.
Scheme-VII: Synthesis of 6-(difluromethoxy)-1H-benzo[d]imidazole-2-thiol (Int-9)
O
O
O
O
(a)
(b)
O
(c)
N
H
H2N
N
H
39
NO2
40
41
H
N
O
O
O
(e)
(d)
SH
H2N
N
H2N
NO2
NH2
Int-10
42
43
Reagents & Conditions: (a) acetic anhydride, acetic acid (b) HNO3, H2SO4 (c) NaOH, MeOH (d) Sn, HCl (e)
CS2, KOH, EtOH
Scheme-VIII: Synthesis of 6-methoxy-1H-benzo[d]imidazole-2-thiol (Int-10)
NO2
NH2
NO2
NH2
N
(b)
(a)
HS
N
H
S
Cl
N
k+
N
O
O
N
4465
4454
S
O
46
47
Int-11
Reagents & Conditions: (a) NaOMe, MeOH (b) Ra-Ni, H2, EtOH
Scheme-IX: Synthesis of 5-methoxy-3H-imidazo[4,5-b]pyridine-2-thiol (Int-11)of 5-methoxy-3H-imidazo[4,5-b]pyridine-2-thiol (Int-11)
OCH3
O
H3CO
O2N
H2N
N
N
N
(a)
N
(b)
50
49
SH
SH
SH
N
H
N
H
N
H
(Int-12)
48
47
49
48
Reagents & Conditions: (a) Fe, Con.HCl, EtOH, H2O (b) AcOH
Scheme-X: Synthesis of 5-(1H-pyrrol-l-yl)-1H-benzo[d]imidazole-2-thiol (Int-12)

Vol. 25, No. 14 (2013)
Diversified Synthesis of Novel Quinoline and Dibenzo Thiazepine Derivatives 7965
TABLE-1
RESULTS OF TARGETS (SLN11-SLN20)
Conventional method
yield (%)
Microwave method
yield (%)
Sonication method
yield (%)
Entry-1
Int-1
Entry-2
Int-3
Product
O
N
N
N
N
52
50
49
42
50
49
49
39
70
65
55
49
S
SLN-11
O
N
N
N
N
Int-1
Int-1
Int-1
Int-4
Int-5
Int-6
O
S
SLN-12
O
N
N
CF3
N
N
S
SLN-13
O
N
N
N
N
S
SLN-14
O
N
S
N
N
O
Int-1
Int-2
Int-2
Int-7
Int-8
Int-9
50
49
39
49
45
41
55
55
47
N
SLN-15
O
HN
H
N
O
N
S
SLN-16
F
F
O
HN
H
N
O
O
N
S
SLN-17
SLN-18
SLN-19
O
O
HN
H
N
O
O
O
N
N
S
Int-2
Int-2
Int-10
Int-11
Int-12
46
35
41
43
35
39
52
45
48
HN
H
N
N
O
S
N
HN
H
N
O
O
N
S
Int-2
SLN-20
Conclusion
nique is good for getting good yield and time. In almost all
reactions happened more spots in microwave reaction may be
due to microwave other bonds also dislocated and afford low
yield. The same conventional reaction yield shown less and
taking long time.The explosive reactions, like azide and Mitsunobu
reactions, etc. are not useful for bulk scale.
The quinoline and dibenzo thiazepine derivatives were
(SLN11-SLN20) successfully synthesized by using literature
procedure. The derivatives developed based on drug candidates,
prepared skeleton. Simple convergent methodology worked
for getting good yields overall. The final, C-N and C-S coupling
approached three techniques, In this regard, sonication tech-

7966 Sharada et al.
ACKNOWLEDGEMENTS
Asian J. Chem.
11. Belgium Patent No. 549,420.
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The authors acknowledged the Osmania University for
providing the research facility and the direct contributions for
the staff of Department of Chemistry and Analytical team.
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Compounds, US patent 3,238,209, March (1966).
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