Synthesis and in vitro antimicrobial activity of 3-aryl-4-s-benzyl-6- phenylimino-2-hepta-O-acetyl-β-D-lactosylimino-2,3-dihydro-1,3, 5-thiadiazine (hydrochloride)

Article abstract of DOI:10.1080/00397911.2011.592625

The present work includes synthesis of several 3-aryl-4-S-benzyl-6- phenylimino-2-hepta-O-acetyl-β-D-lactosylimino-2,3-dihydro-1,3, 5-thiadiazines (hydrochloride) by the interaction of N-hepta-O-acetyl-β-D- lactosyl isocyanodichloride and 1-aryl-5-phenyl-

Full text of DOI:10.1080/00397911.2011.592625

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Synthesis and in Vitro Antimicrobial
Activity of 3-Aryl-4-S-benzyl-6-
phenylimino-2-hepta-O-acetyl-β-
D-lactosylimino-2,3-dihydro-1,3,5-
thiadiazine (Hydrochloride)
Sharayu M. Thorat a & Shirish P. Deshmukh a
a P. G. Department of Chemistry, Shri Shivaji College, Akola, India
Accepted author version posted online: 09 Feb 2012. Version of
record first published: 05 Sep 2012
To cite this article: Sharayu M. Thorat & Shirish P. Deshmukh (2013): Synthesis and in Vitro
Antimicrobial Activity of 3-Aryl-4-S-benzyl-6-phenylimino-2-hepta-O-acetyl-β-D-lactosylimino-2,3-
dihydro-1,3,5-thiadiazine (Hydrochloride), Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 43:1, 105-109
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Synthetic Communications1, 43: 105–109, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.592625
SYNTHESIS AND IN VITRO ANTIMICROBIAL ACTIVITY
OF 3-ARYL-4-S-BENZYL-6-PHENYLIMINO-2-HEPTA-
O-ACETYL-b-D-LACTOSYLIMINO-2,3-
DIHYDRO-1,3,5-THIADIAZINE (HYDROCHLORIDE)
Sharayu M. Thorat and Shirish P. Deshmukh
P. G. Department of Chemistry, Shri Shivaji College, Akola, India
GRAPHICAL ABSTRACT
Abstract The present work includes synthesis of several 3-aryl-4-S-benzyl-6-phenylimino-2-
hepta-O-acetyl-b-D-lactosylimino-2,3-dihydro-1,3,5-thiadiazines (hydrochloride) by the
interaction of N-hepta-O-acetyl-b-D-lactosyl isocyanodichloride and 1-aryl-5-phenyl-
2-S-benzyl-2,4-isodithiobiurets. All these products have been characterized through the
usual chemical transformations and infrared, 1H NMR, and mass spectral analysis. The
compounds were also screened for their antimicrobial activities.
Keywords Isodithiobiurets; lactosyl isocyanodichloride; thiadiazines
INTRODUCTION
Nitrogen-containing heterocycles with sulfur atoms are widely utilized
compounds in both pharmaceutical and agricultural fields. Azoles, triazoles, substi-
tuted thiazoles, and thiadiazoles have been known to possess wide spectra of
activities such as anti-HIV,[1] antimicrobial,[2,3] and selective PDE7 inhibitory[4]
Received March 26, 2011.
Address correspondence to Shirish P. Deshmukh, P. G. Department of Chemistry, Shri Shivaji
College, Akola 444 001, M.S., India. E-mail: sharayu_deshmukh@rediffmail.com
105

106
S. M. THORAT AND S. P. DESHMUKH
activities in the pharmaceutical industry. Similar studies have been reported on the
synthesis of N- and S-linked heterocycles attached to different carbohydrate tem-
plates.[5–7] To expand these views and application profiles, efforts have been
developed for the synthesis of a new class of N-lactosylated 1,3,5 thiadiazine (hydro-
chlorides). These were synthesized by the reaction of N-hepta-O-acetyl-b-D-lactosyl
isocyanodichloride with 1-aryl-5-phenyl-2-S-benzyl-2-4-isodithiobiurets.
N-Hepta-O-acetyl-b-D-lactosyl isocyanodichloride[8] (1) was prepared by the
extension of an earlier method by passing excess gaseous chlorine into a chlorofor-
mic solution of hepta-O-acetyl-b-D-lactosyl isothiocyanate. The required 1-aryl-5-
phenyl-2-S-benzyl-2-4-isodithiobiurets (2) were prepared by the interaction of
1-aryl-2-S-benzyl isothiocarbamides and phenyl isothiocyanate in benzene medium.
RESULTS AND DISCUSSION
3-Aryl-4-S-benzyl-6-phenylimino-2-hepta-O-acetyl-b-D-lactosylimino-2,3-dihydro-
1,3,5 thiadiazine (hydrochlorides) (3a–g, Scheme 1) were prepared by the condensation
of N-hepta-O-acetyl-b-D-lactosyl isocyanodichloride (1) with 1-aryl-5-phenyl-2-S-
benzyl-2,4-isodithiobiurets (2a–g) in chloroform. After condensation, the solvent
was distilled off to obtain a sticky residue, which when triturated with petroleum ether
(60–80 ꢀC) afforded a pale yellow solid (3a–g). The product was found to be nondesul-
furizable when boiled with alkaline plumbite solution. Infrared (IR) spectrum of the
product shows characteristic absorption of lactose unit in the ranges of 900–910,
1000–1100, and 1200–1300 cmꢁ1. Mass spectrum showed the characteristic of lactose
unit.[9]
All the compounds have been screened for both antibacterial and antifungal
activity using cup plate agar diffusion method.[10] The compounds were taken at a
concentration of 10 mgmLꢁ1 using dimethylsulfoxide (DMSO) as solvent. Cotrima-
zine was used as a standard for antibacterial activity, and griseofulvine was used
as standard for antifungal activity. The compounds were screened for antibacterial
Scheme 1. Ac ¼ COCH3. R ¼ (a) phenyl, (b) o-Cl-phenyl, (c) m-Cl-phenyl, (d) p-Cl-phenyl, (e) o-tolyl, (f)
m-tolyl, and (g) p-tolyl.

SYNTHESIS OF THIADIAZINES
107
Table 1. Antimicrobial activities of compounds
Antimicrobiala
Antifungala
Compounds
E. coli S. aureus S. typhi P. vulraris Pseudomonas A. niger F. riazoctomia
3a
3b
09
08
09
08
09
10
09
15
—
10
18
16
16
13
14
15
20
—
—
09
10
09
11
12
12
18
—
11
10
11
10
11
12
12
17
—
—
—
—
—
—
—
—
17
—
15
11
11
13
12
12
12
—
18
13
14
14
18
11
15
18
—
22
3c
3d
3e
3f
3g
Co-trimazine
Griseofulvin
aIncluding the well diameter of 5 mm.
Note: Zone of inhibition in mm.
activity against Escherichia coli, Staphylococcus aureus, Salmonella typhi, Proteus
vulgaris, and Pseudomonas in nutrient agar medium and for antifungal activity
against Aspergillus niger and Fusarium riazoctomia in potato dextrose agar medium.
The zone of inhibition observed around the cups after respective incubation was
measured, and the results are presented in Table 1.
It has been observed that the compounds 3a, 3b, 3c, and 3f showed moderate
activity against S. aureus, P. vulgaris, and S. typhi while the other compounds were
resistant against Pseudomonas. All the compounds exhibited the most significant
activity against A. niger and F. riazoctomia.
EXPERIMENTAL
All the chemicals were research grade. Melting points are uncorrected. All the
products were crystallized from ethanol before recording the physical data. Optical
rotations were measured at 28 ꢀC. IR spectra[11] were recorded in the range 4000–
1
450 cmꢁ1. H NMR spectra[12] were obtained at 300 MHz for solutions in CDCl3
(reference to tetramethylsilane). The fast atom bombardment (FAB) mass spectra[13]
were recorded on a Jeol SX-102=Da-600 mass spectrometer = data system using
˚
argon=xenon (6 kv, 10 mA) as the FAB gas. The accelerating voltage was 10 kV,
and the spectra were recorded at room temperature. m-Nitrobenzyl alcohol (NBA)
was used as the matrix unless specified otherwise. Thin-layer chromatography (TLC)
was conducted on E. Merck TLC aluminium sheet silica gel 60 F254 using CHCl3–
ethyl acetate as the mobile phase.
Preparation of 3-Phenyl-4-S-benzyl-6-phenylimino-2-hepta-O-acetyl-
b-D-lactosylimino-2,3-dihydro-1,3,5-thiadiazine (Hydrochloride) (3a)
A solution of N-hepta-O-acetyl-b-D-lactosyl isocyanodichloride (1) (0.0025 M,
1.78 g in 5 ml CHCl3) was added to a solution of 1,5-diphenyl-2-S-benzyl-2,4-
isodithiobiurets (2a) (0.0025 M, 0.94 g in 20 ml CHCl3), and the reaction mixture
was gently refluxed for 3 h. The evolution of hydrogen chloride was noticed. The

108
S. M. THORAT AND S. P. DESHMUKH
solvent chloroform was distilled off, and the resultant syrupy mass was triturated
several times with petroleum ether (60–80 ꢀC) to afford a pale yellow solid (3a).
The product was purified by chloroform–ether and recrystallized by ethanol–water,
mp 119–122 ꢀC (2.46 g, 93.60%). On extending the reaction of N-hepta-O-acetyl-b-
D-lactosyl isocyanodichloride with 1-aryl-5-phenyl-2-S-benzyl 2,4-isodithiobiurets,
several 3-aryl-4-S-benzyl-6-phenylimino-2-hepta-O-acetyl-b-D-lactosylimino-2,3-
dihydro-1,3,5-thiadiazine (hydrochlorides) have been isolated.
Analytical and Spectral Data of Prepared Compounds
28
Compound 3a. Mp 119–122 ꢀC; yield 93.60% [a]D þ 20 (c, 1.013 in CHCl3);
=
=
Rf 0.70; IR (KBr): n 2958.41 (C-H aliphatic), 1750.0 (C O), 1568.2 (C N), 1371.3
(C–N), 1227.7 (C – O), 757.1 (C-S), characteristic of lactose at 1050.6 and 904.4 cmꢁ1
1H NMR (ppm) d 7.74–7.27 (15H, m, Ar – H), d 5.36–3.77 (16H, m, lactosyl protons,
S-CH2), 2.18–1.97 ppm (21H, m, acetyl protons). Mass spectrum (m=z) 1056 (Mþ),
979, 933, 620, 560, 331, 169, 109. Anal. calcd. for C48H52O17N4S2 ꢂ HCl: C, 54.54;
H, 5.01; N, 5.30; S, 6.06% (found: C, 54.49; H, 4.94; N, 5.26; S, 6.17%).
28
Compound 3b. Mp 140 ꢀC (d); yield 97.30% [a]D þ 22 (c, 1.013 in CHCl3);
Rf 0.81. Anal. calcd. for C48H51O17N4S2Cl ꢂ HCl: C, 52.84; H, 4.77; N, 5.13; S, 5.87%
(found: C, 52.78; H, 4.73; N, 5.08; S, 5.94%).
Compound 3c. Mp 128–130 ꢀC; yield 92.81% [a]D28–60 (c, 1.013 in CHCl3);
=
=
Rf 0.69. IR (KBr): n 2958.7 (C-H aliphatic), 1750.6 (C O), 1571.6 (C N), 1370.6
(C – N), 1226.5 (C – O), 770.9 (C-S), characteristic of lactose at 1051.0 and
902.9 cmꢁ1. 1H NMR (ppm) d 7.77–7.20 (14H, m, Ar – H), d 5.40–3.79 (16H, m, lac-
tosyl protons, S-CH2), 2.21–1.85 (21H, m, acetyl protons). Mass spectrum (m=z) 1090
(Mþ), 967, 620, 560, 413, 331, 169, 109. Anal. calcd. for C48H51O17N4S2Cl ꢂ
HCl: C, 52.84; H, 4.77; N, 5.13; S, 5.87% (found: C, 52.76; H, 4.70; N, 5.09; S, 5.80%).
28
Compound 3d. Mp 115–117 ꢀC; yield 85.51% [a]D þ 10 (c, 1.013 in CHCl3);
Rf 0.72. Anal. calcd. for C48H51O17N4S2Cl ꢂ HCl: C, 52.84; H, 4.77; N, 5.13; S, 5.87%
(found: C, 52.77; H, 4.72; N, 5.08; S, 5.84%).
28
Compound 3e. Mp 113–115 ꢀC; yield 97.63% [a]D þ 110 (c, 1.013 in
=
CHCl3); Rf 0.74. IR (KBr): n 2939.3 (C-H aliphatic), 1747.3 (C O), 1564.8
=
(C N), 1371.2 (C – N), 1230.2 (C – O), 764.6 (C-S), 699.4 characteristic of lactose
.
at 1049.4 and 906.1 cmꢁ1 1H NMR (ppm) d 7.78–7.14 (14H, m, Ar – H), d
5.39–3.58 (14H, m, lactosyl protons, S-CH2), 2.46–1.84 (21H, m, acetyl protons),
1.25 (3H, s, Ar-CH3). Mass spectrum (m=z) 1070 (Mþ), 979, 870, 620, 560, 331,
169, 109. Anal. calcd. for C49H54O17N4S2 ꢂ HCl: C, 54.95; H, 5.14; N, 5.23; S,
5.98% (found: C, 54.90; H, 5.12; N, 5.19; S, 6.06%).
28
Compound 3f. Mp 118–120 ꢀC; yield 86.36% [a]D þ 90 (c, 1.013 in CHCl3);
Rf 0.68. Anal. calcd. for C49H54O17N4S2 ꢂ HCl: C, 54.95; H, 5.14; N, 5.23; S, 5.98%
(Found: C, 54.88; H, 5.09; N, 5.17; S, 6.08%).
28
Compound 3g. Mp 122–125 ꢀC; yield 90.38% [a]D þ 40 (c, 1.013 in CHCl3);
Rf 0.77. Anal. calcd. for C49H54O17N4S2 ꢂ HCl: C, 54.95; H, 5.14; N, 5.23; S, 5.98%
(found: C, 54.88; H, 5.07; N, 5.19; S, 6.10%).

SYNTHESIS OF THIADIAZINES
109
ACKNOWLEDGMENTS
The authors acknowledge SAIF, CDRI, Lucknow, for providing the spectral
data. They are also thankful to the principal, S. G. Bhadange, for encouragement
and the necessary facilities.
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