Ionic liquid-mediated facile synthesis and antimicrobial study of thiazolo [2,3-b]benzo[h]quinazolines and thiazino[2,3-b] benzo-[h]quinazolines

Article abstract of DOI:10.1080/10426507.2011.647145

8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene- 1(2H)-one with thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H- benzo[h]thiazolo[2,3-b] quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro- benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with 1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl- 6,7,9,10-tetrahydro-5 H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo [h][1,3]thiazino[2,3-b] quinazoline respectively. Arylidene derivatives have been obtained by two routes. The structures of the cyclized compounds have been established on the basis of elemental analysis and spectroscopic data. The synthesized compounds were screened for antimicrobial activity. Some of the compounds showed promising antimicrobial activities. Copyright

Full text of DOI:10.1080/10426507.2011.647145

This article was downloaded by: [The University of British Columbia]
On: 13 June 2013, At: 20:38
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the
Related Elements
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/gpss20
Ionic Liquid-Mediated Facile Synthesis
and Antimicrobial Study of Thiazolo
[2,3-b]Benzo[h]Quinazolines and
Thiazino[2,3-b] Benzo-[h]Quinazolines
Richa Gupta a & Ram Pal Chaudhary a
a Department of Chemistry, Sant Longowal Institute of Engineering
and Technology, Longowal (Sangrur), Punjab, India
Accepted author version posted online: 04 Jan 2012.Published
online: 05 Apr 2012.
To cite this article: Richa Gupta & Ram Pal Chaudhary (2012): Ionic Liquid-Mediated Facile Synthesis
and Antimicrobial Study of Thiazolo [2,3-b]Benzo[h]Quinazolines and Thiazino[2,3-b] Benzo-
[h]Quinazolines, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:6, 735-742
To link to this article: http://dx.doi.org/10.1080/10426507.2011.647145
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Phosphorus, Sulfur, and Silicon, 187:735–742, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.647145
IONIC LIQUID-MEDIATED FACILE SYNTHESIS
AND ANTIMICROBIAL STUDY OF THIAZOLO
[2,3-b]BENZO[h]QUINAZOLINES AND THIAZINO[2,3-b]
BENZO-[h]QUINAZOLINES
Richa Gupta and Ram Pal Chaudhary
Department of Chemistry, Sant Longowal Institute of Engineering and Technology,
Longowal (Sangrur), Punjab, India
GRAPHICAL ABSTRACT
( )n
S
( )n
S
S
O
N
N
NH
N
N
HN
3
H
H
A
H
A
ClCH2(CH2)nCO2H
Ionic liquid
A
BrCH2(CH2)nCH2Br
CH3O
Ph
Ph
Ph
CH3O
CH3O
4; n=0
9; n=1
5; n=0
10; n=1
Abstract 8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione, obtained
by the condensation of 2-benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one with
thiourea, on reaction with chloroacetic acid and 3-chloropropanoic acid in the presence of
the ionic liquid N-methylpyridinium tosylate furnishes 3-methoxy-7-phenyl-7,10-dihydro-5H-
benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-one and 3-methoxy-7-phenyl-5,6,10,11-tetrahydro-
benzo[h][1,3]thiazino[2,3-b]quinazoline-9(7H)-one. Further, condensation of the thione with
1,2-dibromoethane and 1,3-dibromopropane yields 3-methoxy-7-phenyl-6,7,9,10-tetrahydro-5
H-benzo[h]thiazolo[2,3-b]quinazoline and 3-methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo
[h][1,3]thiazino[2,3-b]quinazoline respectively. Arylidene derivatives have been obtained by
two routes. The structures of the cyclized compounds have been established on the basis of
elemental analysis and spectroscopic data. The synthesized compounds were screened for
antimicrobial activity. Some of the compounds showed promising antimicrobial activities.
Keywords Ionic liquid; 4-thiazolidinone; antimicrobial activity; arylidene derivatives
INTRODUCTION
Thiazolidinone, with a carbonyl group at position 2, 4,1 or 5 have been subjected
to extensive study in the recent past. Among them 4-thiazolidinone is the most important
Received 23 October 2011; accepted 28 November 2011.
One of the authors, R. Gupta, is thankful to the authorities of Sant Longowal Institute of Engineering
and Technology, Longowal, for providing financial assistance. The facilities provided by SLIET authorities are
gratefully acknowledged.
Address correspondence to Ram Pal Chaudhary, Department of Chemistry, Sant Longowal Institute of
Engineering and Technology, Longowal (Sangrur), Punjab-148106, India. E-mail: rpchaudhary65@gmail.com
735

736
R. GUPTA AND R. P. CHAUDHARY
scaffold known to be associated with several biological activities such as antibacterial,2
antiprotozoal,3 antifungal,4 anticonvulsant,5 anticancer,6 antituberculosis,7 antiparasitic,8
anti-inflammatory,9 herbicidal agents,10 etc. 4-Thiazolidinones have also been reported as
novel inhibitors of the bacterial enzyme Mur B which is a precursor during the biosynthesis
of peptidologycan11 and also non-nucleoside inhibitors of HIV-RT12 and HIV-1 integrase
inhibitors.13
In the present paper, a convenient synthesis of thiazolo[2,3-b]benzo[h]quinazoline
and thiazino[2,3-b]benzo[h]quinazoline using the ionic liquid N-methylpyridinium tosylate
as well as the conventional method is reported. Ionic liquids are a class of organic salts
with high selectivity that have attracted much attention from the scientific community
in recent years. As a class of potentially greener solvents, Ionic liquids exhibit many
unique physicochemical properties, such as negligible volatility and non-flammability under
ambient conditions, large liquid range, high thermal stability, wide electrochemical window,
and strong ability to dissolve many chemicals.14 Therefore, Ionic liquid mediated synthesis
to furnish thiazoloquinazoline and thiazinoquinazoline systems in good yield is described.
RESULTS AND DISCUSSION
2-Benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one 2, obtained by the re-
action of 6-methoxy-1-tetralone and benzaldehyde, when condensed with thiourea gave
compound 3. The unsymmetrical thione 3 on reaction with chloroacetic acid followed by
cyclization of the intermediate in situ was likely to give compound 4 or 7 or both depending
on the mode of cyclization. However, the thione 3 when treated with chloroacetic acid
in the presence of anhydrous sodium acetate and absolute ethanol (conventional method)
afforded a single product [TLC (thin layer chromatography)] 4 or 7 with 58% yield. The
condensation of thione 3 with chloroacetic acid in the presence of the ionic liquid N-
methylpyridinium tosylate at 100–110 ◦C for 3–4 h furnished a single product (TLC) with
72% yield. The appearance of a band at 1728 cm−1 (C O) in the IR spectrum as well as
a molecular ion peak at m/z 363 (100%) and the fragment ions [M CH2CO]+ at m/z 321
(4%), [M SCH2CO]+ at m/z 289 (19%), and [M SCH2CHO]+, at m/z 288 (10%) in the
mass spectrum of the TLC-pure product suggested the formation of thiazolidinone 4 or 7.
A peak at δ 170 in the 13C NMR spectrum assigned to the carbonyl group of the tertiary
amide supports the cyclized product 4 or 7. The appearance of two multiplets at δ 2.03 and
δ 2.79 in the 1H NMR spectrum have been assigned to the tetrahydronaphthalene ring of 4
or 7. A double doublet at δ 3.62 assignable to the SCH2 group confirms the formation of
the thiazolidinone ring. The IR and MS data were of little help in deciding in favor of either
structure 4 or 7. However, the structure 4 was finally assigned to this cyclization product in
preference to the structure 7 on the basis of 1H NMR spectroscopic data.
The reaction of compound 3 with 1,2-dibromoethane gave a product which was
purified by column chromatography and characterized by its molecular ion peak at m/z 349
(25%) and [M – SCH2CH2]+ at m/z 289 (3.5%) as a compound which could exhibit either
structure 5 or 8. In either structure (5 or 8), the singlet at δ 4.86 in its 1H NMR spectrum
integrating for one proton was assignable to HA. The comparison of chemical shifts of HA
of thione 3 at δ 5.25 and of 5 or 8 at δ 4.86 favors structure 5 and rules out structure 8 as
HA should appear more downfield in 8 due to the de-shielding effect of the imine group
on HA. If the structure 7 is correct for the cyclization product obtained from thione 3 and
chloroacetic acid, the HA should resonate in the same region as that of 5. On the other

ILMF SYNTHESIS AND ANTIMICROBIAL STUDY
737
hand, if the structure 4 is correct, HA would be de-shielded by the thiazolidinone ring and
consequently HA would resonate downfield in comparison with HA in 5. The appearance of
a downfield singlet at δ 5.52 for HA in structure 4 or 7 as compared to a singlet at δ 4.86 for
HA in structure 5 supported the structure 4 and ruled out the structure 7 from which such a
downfield shift is not expected. The de-shielding effect is due to the magnetic anisotropy
of the C O group with a minor contribution from the rest of the ring.
Although the comparison of the chemical shifts of HA in the structures 4 and 5 is on
a better footing because both structures 4 and 5 are tetracyclic compounds, yet the same
conclusion is derived by comparing the chemical shifts of HA of the thione 3 with that
of the cyclization product 4. The HA proton in thione 3 resonates at δ 5.25 whereas the
downfield signal at δ 5.52 (s, 1H, HA) in the cyclized product supports the structure 4 in
preference to structure 7. Further support to structure 4 is provided by the appearance of
HA at δ 5.62 in the arylidene derivatives 6a and 6b due to the extended conjugation with
the carbonyl group. This downfield shift due to extended conjugation of carbonyl group is
possible only in case of the proposed structure 4 and not in 7. Therefore, the structure 7 has
been rejected.
Arylidenethiazolidinones (6) were prepared by two routes. In the first approach, the
thiazolidinone 4 was condensed with aldehydes to give the arylidenethiazolidinones 6a–b
while in the second approach, compound 6a was obtained directly by heating compound 3
with chloroacetic acid and p-methylbenzaldehyde. The structures of 6a–b were established
1
by IR and H NMR spectroscopy. The parent thiazolidinone 4 exhibited an absorption
band at 1728 cm−1 (C O), but the unsaturation at the 2-position being conjugated with
the carbonyl group at the 3-position as in the arylidenethiazolidinones 6a–b expectedly
produced a bathochromic shift15: the carbonyl absorption band appeared at 1697 and
1690 cm−1 in structure 6a–b respectively.
The reaction of the thione 3 with 3-chloropropanoic acid with both methods, i.e.,
conventional as well as ionic liquid mediated method yielded a TLC pure single product.
The appearance of an IR band at 1682 cm−1 (C O) and MS peaks of [M + 1]+ at m/z
377 (100%), [M–C6H5]+ at m/z 300 (26%), and [M SCH2CH2CO]+ at m/z 279 (4%)
1
supports the cyclized structure 9 or 11. A singlet at δ 6.07 in the H NMR spectrum due
to HA corroborated the structure 9 for the final product in analogy with structure 4 and
ruled out structure 11. Structure 10 was similarly assigned to the product obtained from the
reaction of thione 3 with 1,3-dibromopropane on the basis of spectroscopic data that ruled
out structure 12.
The ionic liquid N-methylpyridinium tosylate was synthesized by the literature
method. The optimum amount of ionic liquid and reaction temperature were established
after trying different reaction conditions and comparing the obtained yields of the product.
The recovery of the ionic liquid was also attempted and found that it can be reused for two
more cycles.
Antimicrobial Studies
The antimicrobial activity was assayed by use of the disc diffusion method16 by
measuring the zone of inhibition in mm. All compounds were screened in vitro for their
antimicrobial activity against a variety of bacterial strains, such as S. aureus and C. diph-
theriae (gram positive bacteria), P. aeruginosa and E. coli (gram negative bacteria), and
fungi like A. niger, C. albicans, and A. fumigatus at 40 µg/mL concentrations. The standard
drug Ampicillin trihydrate was used for comparison purposes. Compounds 4 and 9 showed

738
R. GUPTA AND R. P. CHAUDHARY
Table 1 Antibacterial activity studies of compounds 4–6 and 9–10
Zone of inhibition (in mm)
Gram positive
Gram negative
Entry
Compound
S. aureus
C. diphtheriae
P. aeruginosa
E. coli
1.
2.
3.
4.
5.
6.
4
5
6a
6b
9
10
18
14
12
13
17
12
26
00
16
12
14
14
18
10
28
00
18
13
13
14
16
10
24
00
19
14
11
14
16
12
21
00
Ampicillin trihydrate
DMSO
maximum activity in terms of the zone of inhibition against gram positive bacteria, while the
compounds 5, 6a, 6b, and 10 showed moderate activity. Compounds 4 and 9 again showed
maximum activity against gram negative bacteria. The other compounds showed moderate
activity (Table 1). The cyclized compounds were also screened for their antifungal activity
and the results are reported in Table 2.
EXPERIMENTAL SECTION
Melting points were determined in a sulfuric acid bath and are uncorrected. TLC was
performed on silica gel G plates using pet ether/ethyl acetate (4:1) as irrigant and iodine
vapors as visualizing agent. IR spectra were recorded on an ABB FTIR spectrometer and
1
the results are reported in cm−1. H NMR (400 MHz) and 13C NMR (100 MHz) were
recorded in CDCl3 on a Bruker Advance II 400 NMR spectrometer using tetramethylsilane
(TMS) as internal standard (δ in ppm, J in Hz). Mass spectra were recorded on a TOF
MS ES+ 1.23e5 and 3.21e4 instrument. Elemental analyses were performed on a Carlo
Erba-1108 elemental analyzer.
N-Methylpyridinium tosylate. Pyridine (1.1 mol) was added to methyl 4-
◦
toluenesulfonate (1.0 mol) at 0–10 C. After completion of the addition, the reaction
mixture was stirred at room temperature for 1 h. The solid N-methylpyridinium tosylate
Table 2 Antifungal activity studies of compounds 4–6 and 9–10
Zone of inhibition (in mm)
Entry
Compound
A. niger
C. albicans
A. fumigatus
1.
2.
3.
4.
5.
6.
4
5
6a
6b
9
10
19
12
12
13
18
14
25
00
18
14
11
12
16
15
23
00
18
14
14
14
17
16
21
00
Ampicillin trihydrate
DMSO

ILMF SYNTHESIS AND ANTIMICROBIAL STUDY
739
was filtered off, washed with ethyl acetate to remove unreacted reactants and dried. The
physical parameters of the ionic liquid are in good agreement with those reported in the
literature.17
2-Benzylidene-6-methoxy-3,4-dihydronapthalene-1(2H)-one (2). A mixture of 6-
methoxy-1-tetralone 1 (8.8 g, 0.05 mol) and benzaldehyde (5.3 g, 0.05 mol) in aqueous
NaOH (2.0 g in 40 mL water) was heated under reflux for 5 h. The reaction mixture
was cooled to room temperature and neutralized with dil. HCl. The solid so obtained was
filtered, washed with petroleum ether, and finally crystallized from ethanol to give brown
shining crystals. Yield 85%; mp 100–102 ◦C. IR: 1667 (C O). 1H NMR: δ 2.92 (t, 2H, J
= 6.1, CH2); 3.13 (t, 2H, J = 6.6, CH2); 3.83 (s, 3H, OCH3); 6.93–8.11 (m, 8H, C6H5);
7.82 (s, 1H, CH). C18H16O2 (264.32), calcd. C, 81.79; H, 6.10; found, C, 81.96; H, 6.14.
8-Methoxy-4-phenyl-3,4,5,6-tetrahydrobenzo[h]quinazoline-2(1H)-thione (3).
Compound 2 (5.28 g, 0.02 mol) and thiourea (1.52 g, 0.02 mol) in ethanolic potash (2.0 g
KOH in 75 mL ethanol) was heated under reflux for 5 h and kept overnight. The volume
was reduced to half, and the concentrate poured into ice-cold water. The solid thus obtained
was filtered, washed well with water and finally crystallized from DMF to give 3.
Compound 3 was also obtained directly from 6-methoxy-1-tetralone 1 (8.8 g, 0.05
mol), benzaldehyde (5.3 g, 0.05 mol), and thiourea (3.8 g, 0.05 mol) in alc. KOH by
refluxing for 4 h. The solid obtained was filtered, washed well with water, and finally
crystallized from DMF to give a white solid. Yield 75%; mp 248–250 ◦C. IR: 3202 (NH);
1304 (C=S). 1H NMR: δ 2.12 (t, 2H, J = 7.7, CH2); 2.76 (t, 2H, J = 7.2, CH2); 3.82 (s,
3H, OCH3); 5.25 (s, 1H, HA); 6.77–8.16 (m, 8H, C6H5). C19H18N2OS (322.43), calcd. C,
70.78; H, 5.63; N, 8.69; S, 9.95; found, C, 70.58; H, 5.44; N, 8.58; S, 9.82.
Conventional Procedure for the Synthesis of Compound 4
A mixture of compound 3 (3.22 g, 0.01 mol), chloroacetic acid (0.94 g, 0.01 mol),
anhydrous sodium acetate (0.82 g, 0.01 mol), acetic acid (10 mL), and acetic anhydride
(2 mL) was heated under reflux for 8 h. The reaction mixture was cooled to room temperature
and then poured into water to afford a light brown solid. Crystallization from glacial acetic
acid gave 4 with 58% yield.
Solvent Free Synthesis of Compound 4
An equimolar mixture of compound 3 (0.005 mol) and chloroacetic acid (0.47 g, 0.005
mol) in pre-molten ionic liquid (2.0 g) was stirred at 100–110 ◦C for 3–4 h. The progress of
the reaction was monitored by TLC. After completion of the reaction the reaction mixture
was poured into ice-cold water. The solid was filtered off, dried, and crystallized from ethyl
acetate to give compound 4 with 72% yield.
3-Methoxy-7-phenyl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-b]quinazoline-9(6H)-
one (4). Brown needles, mp 225–227 ◦C. IR: 1728 (C O), 1643 (C C), 1597 (C N). 1H
NMR: δ 2.03–2.20 (m, 2H, CH2); 2.67–2.79 (m, 2H, CH2); 3.67 (dd, 2H, SCH2); 3.77 (s,
3H, OCH3); 5.52 (s, 1H, HA); 6.83–7.95 (m, 8H, C6H5). 13C NMR: δ 24, 27 (CH2CH2),
31 (SCH2), 55.3 (OCH3), 114.07, 115, 123–135 (Ar–C), 159.93 (C–OCH3), 170 (C O).
MS m/z (%): 363 [M + 1]+ (100), 321 [M CH2CO]+ (4), 289 [M SCH2CO]+ (19), 288
[M SCH2CHO]+ (10). C21H18N2O2S (362.33), calcd. C, 69.61; H, 5.01; N, 7.73; S, 8.85;
found, C, 69.36; H, 4.88; N, 7.67; S, 8.78.

740
R. GUPTA AND R. P. CHAUDHARY
3-Methoxy-7-phenyl-6,7,9,10-tetrahydro-5H-benzo[h]thiazolo[2,3-b]-quinazo
line (5). A mixture of thione 3 (3.22 g, 0.01 mol), 1,2-dibromoethane (1.88 g, 0.01 mol) in
DMF (10 mL), and anhydrous ethanol (20 mL) was refluxed for 2 h. The reaction mixture
was cooled and neutralized with sodium carbonate. The crude solid thus separated, was
purified by column chromatography to give a light yellow solid. Yield 60%; mp 220–222
◦C. IR: 1674 (C C), 1574 (C N). 1H NMR: δ 2.5–2.6 (m, 2H, CH2); 2.64–2.69 (m, 2H,
CH2); 2.73–2.79 (m, 2H, CH2); 2.85–2.95 (m, 2H, CH2); 3.71 (s, 3H, OCH3); 4.86 (s, 1H,
HA); 6.6–6.71 (m, 2H, C6H5); 7.22–7.53 (m, 4H, C6H5); 8.8 (s, 1H, C6H5); 9.2 (s, 1H,
C6H5). MS: m/z (%): 349 [M + 1]+ (25), 272 [M–C6H5]+ (95), 289 [M – SCH2CH2]+
(3.5). C21H20N2OS (348.47), calcd. C, 72.38; H, 5.78; N, 8.04; S, 9.20; found, C, 72.57;
H, 5.84; N, 7.96; S, 9.06.
(E)-3-Methoxy-10-(4-methylbenzylidene)-7-phenyl-7,10-dihydro-5H-benzo[h]
thiazolo[2,3-b]quinazoline-9(6H)-one (6a). (1) A mixture of thiazolidinone 4 (0.362
g, 0.001 mol), p-methylbenzaldehyde (0.14 g, 0.001 mol), anhydrous sodium acetate
(0.82 g, 0.01 mol), and acetic acid (10 ml) was heated under reflux for 2 h. The reaction
mixture was cooled to room temperature and poured into water. The solid thus obtained
was filtered and washed well with water and finally crystallized from acetic acid to give
◦
an orange colored solid. Yield 86.2%; mp 195–197 C. IR: 1697 (C O), 1636 (C C),
1
1597 (C N). H NMR: 1.97–2.02 (m, 1H, CH2); 2.12–2.15 (m, 1H, CH2); 2.31 (s, 3H,
CH3); 2.59–2.76 (m, 2H, CH2); 3.74 (s, 3H, OCH3); 5.62 (s, 1H, HA); 6.60 (d, 1H,
J = 2.5, C6H5); 6.74 (dd, 1H, C6H5); 7.17–7.32 m, (9H, C6H5); 7.56 (s, 1H, HB); 7.82 (d,
1H, J = 8.5, C6H5). C29H24N2O2S (465.59), calcd. C, 74.81; H, 5.20; N, 6.02; S, 6.89;
found, C, 75.14; H, 5.24; N, 6.18; S, 6.99.
(2) A mixture of thione 3 (0.322 g, 0.001 mol), chloroacetic acid (0.09 g, 0.001 mol),
and p-methylbenzaldehyde (0.14 g, 0.001 mol) and anhydrous sodium acetate (0.082 g;
0.001 mol) in acetic acid (10 mL) and acetic anhydride (2 mL) was refluxed for 2 h. A
similar work up as in (1) gave compound 6a, mp 195–197 ◦C that remained undepressed
when mixed with the compound obtained by method (1), yield 70%.
(E)-3-Methoxy-10-(4-methoxybenzylidene)-7-phenyl-7,10-dihydro-5H-benzo[h]-
thiazoline-9(6H)-one (6b). was prepared as 6a by the method (1). Orange colored shining
◦
1
solid. Yield 81.3%; mp 140–142 C. IR: 1690 (C O), 1589 (C C), 1504 (C N). H
NMR: δ 2.01 (m, 1H, CH2); 2.15–2.17 (m, 1H, CH2); 2.61–2.72 (m, 2H, CH2), 3.74 (s,
3H, OCH3); 3.78 (s, 3H, OCH3); 5.62 (s, 1H, HA); 6.60 (d, 1H, J = 2.5, C6H5); 6.74 (dd,
1H, C6H5), 6.89 (d, 2H, J = 2.0, C6H5); 7.35–7.39 (m, 4H, C6H5); 7.55 (s, 1H, HB); 7.83
(d, 1H, J = 8.5, C6H5); 7.18–7.28 (m, 3H, C6H5). C29H24N2O3S (480.59), calcd. C, 72.48;
H, 5.03; N, 5.83; S, 6.67; found, C, 72.68; H, 4.81; N, 5.72; S, 6.78.
3-Methoxy-7-phenyl-5,6,10,11-tetrahydro-benzo[h][1,3]thiazino[2,3-b]-quinazo
line-9(7H)-one (9). was obtained as white solid from compound 3 and 3-chloropropanoic
acid following the procedure of compound 4 by the conventional (yield 52%) and the
◦
solvent free method (yield 68%). Mp 190–192 C. IR: 1682 (C O), 1643 (C C), 1605
1
(C N). H NMR: δ 2.09–2.23 (m, 2H, CH2); 2.66–2.68 (m, 3H, CH2CH2); 2.91–3.05
(m, 3H, SCH2, CH2); 3.73 (s, 3H, OCH3); 6.07 (s, 1H, HA); 6.59 (d, 1H, J = 2.5, C6H5);
6.69 (dd, 1H, C6H5); 7.18–7.26 (m, 3H, C6H5); 7.34 (dd, 2H, C6H5); 7.71 (d, 1H, J =
8.4, C6H5). 13C NMR: δ 21.80, 25.17, 27.97 (3 CH2), 36.13 (SCH2), 55.28 (CN), 56.13
(OCH3), 111.13, 113.63, 115.21, 124.42, 127.99, 128.50, 128.89, 137.02, 139.87 (Ph–C),
159.24 (C–OCH3), 168.72 (C O). MS: m/z (%): 377 [M]+ (100), 300 [M–C6H5]+ (25.5),
279 [M SCH2CH2CO]+ (4). C22H20N2O2S (377.33), calcd. C, 70.03; H, 5.34; N, 7.42;
S, 8.50; found, C, 70.32; H, 5.24; N, 7.54; S, 8.62.

ILMF SYNTHESIS AND ANTIMICROBIAL STUDY
741
S
S
O
N
N
N
N
H
H
A
A
Ph
Ph
CH3O
(Possible isomer of 5)
CH3O
(Possible isomer of 4)
7
8
S
S
S
O
NH
HN
3
N
N
N
N
H
H
A
H
A
BrCH2CH2Br
A
ClCH2CO2H
Ionic liquid
Ph
Ph
Ph
CH3O
CH3O
CH3O
5
4
ClCH2CO2H,
ArCHO
PhCHO
ArCHO
gl.HOAc
H2NCSNH2
alc.KOH
H2NCSNH2
alc.KOH
CHB-Ar
O
S
O
O
CHPh
PhCHO
NaOH
N
N
H
A
Ph
CH3O
CH3O
2
1
CH3O
(a) Ar= p-MeC6H4
6
(b) Ar= p-MeOC6H4
Scheme 1
3-Methoxy-7-phenyl-5,6,7,9,10,11-hexahydrobenzo[h][1,3]thiazino[2,3-b]-quinaz
oline (10). was obtained from compound 3 and 1,3-dibromopropane following the
procedure of compound 5 as cream colored solid. Yield 65.4%; mp 150–152◦C. IR: 1643
(C C), 1574 (C N). 1H NMR: δ 2.09–2.23 (m, 2H, CH2); 2.66–2.68 (m, 3H, CH2CH2);
S
S
N
N
O
N
N
H
H
A
A
Ph
Ph
CH3O
(Possible isomer of 10)
CH3O
(Possible isomer of 9)
12
11
S
S
O
N
N
N
N
H
H
A
ClCH2CH2CO2H
Ionic liquid
A
BrCH2CH2CH2Br
3
Ph
Ph
CH3O
CH3O
9
10
Scheme 2

742
R. GUPTA AND R. P. CHAUDHARY
2.74–2.82 (m, 2H, CH2); 2.91–3.05 (m, 3H, SCH2, CH2); 3.78 (s, 3H, OCH3); 4.92 (s,
1H, HA); 6.57 (d, 1H, J = 2.5, C6H5); 6.60 (dd, 1H, C6H5); 7.10–7.19 (m, 3H, C6H5);
7.30 (dd, 2H, C6H5); 7.69 (d, 1H, J = 8.4, C6H5). MS: m/z (%): 363 [M + 1]+ (23.5), 285
[M–C6H5]+ (34), 288 [M SCH2CH2CO]+ (3). C22H22N2OS (362.49), calcd. C, 72.90;
H, 6.12; N, 7.73; S, 8.85; found, C, 72.84; H, 5.91; N, 7.62; S, 8.96.
REFERENCES
1. Horton, D. A.; Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893-930.
2. Kucukguzel, G.; Kocatepe, A.; DeClercq, E.; Sahin, F.; Gulluce, M. Eur. J. Med. Chem. 2006,
41, 353-359.
3. Tenorio, R. P.; Carvalho, C. S.; Pessanha, C. S.; de Lima, J. G.; de Faria, A. R.; Alves, A. J.; de
Melo, E. J. T.; Goes, A. J. S. Bioorg. Med. Chem. Lett. 2005, 15, 2575-2578.
4. Fahmy, H. T. Y. Boll. Chim. Farmaco. 2001, 140, 422-27.
5. Ragab, F. A.; Eid, N. M.; El-Tawab, H. A. Pharmazie 1997, 52, 926-929.
6. Gududuru, V.; Hurh, E.; Dalton, J. T.; Miller, D. D. J. Med. Chem. 2005, 48, 2584-2588.
7. Kachhadia, V. V.; Patel, M. R.; Joshi, H. S. J. Serb. Chem. Soc. 2005, 70, 153-161.
8. Mahran, M. A.; El-Nassry, S. M.; Allam, S. R.; El-Zawawy, L. A. Pharmazie 2003, 58, 527-530.
9. El-Ansary, A. K.; Omar, A. H. Bull. Fac. Pharm. (Cairo Univ.) 2001, 39, 17-25; Chem. Abstr.
2002, 136, 216712.
10. Suzuki, M.; Morita, K.; Yukioka, H.; Miki, N.; Mizutani, A. J. Pestic. Sci. 2003, 28, 37-43.
11. Rawal, R. K.; Prabhakar, Y. S.; Katti, S. B.; DeClercq, E. Bioorg. Med. 2005, 13, 6771-6776.
12. Dayam, R.; Sanchez, T.; Clement, O.; Shoemaker, R.; Sei, S.; Neamati, N. J. Med. Chem. 2005,
48, 111-120.
13. Unangst, P. C.; Connor, D. T.; Cetenko, W. A.; Sorenson, R. J.; Sircar, J. D.; Wright, C. D.;
Schrier, D. J.; Dyer, R. D. Bioorg. Med. Chem. Lett. 1993, 3, 1729-1734.
14. Murugesan, S.; Linhardt, R. J. Curr. Org. Synth. 2005, 2, 437-451.
15. Randall, H. M.; Fowler, R. G.; Fuson, N.; Dangl, J. R. Infrared Determination of Organic
Structures; Van Nostrand: New York, 1949.
16. Arthington-Skaggs, B. A.; Motley, M.; Warnock, D. W.; Morrison, C. J. J. Clin. Microbiol. 2000,
38, 2254-2260.
17. Kroutil, J.; Budesinsky, M. Carbohydr. Res. 2007, 342, 147-153.