Synthesis of 2-Tert-butylimino-3-hepta-O-benzoyl-β-D-lactosylimino-4- S-benzyl-6-arylimino-2,3-dihydro-1,3,5-thiadiazines

Article abstract of DOI:10.1080/00397911.2013.815214

A new series of synthesis of 2-tert-butylimino-3-hepta-O-benzoyl-β-D- lactosylimino-4-S-benzyl-6-arylimino-2,3-dihydro-1,3,5-thiadiazines (hydrochloride) were synthesized by the interaction of 1-aryl-5-hepta-O-benzoyl- β-D-lactosyl-2-S-benzyl-2,4-isodithiobiurets with tert-butyl isocyanodichloride. The identities of these newly synthesized N-lactosides have been established on the basis of usual chemical transformations and infrared, ¹H NMR, and mass spectral analysis.

Full text of DOI:10.1080/00397911.2013.815214

This article was downloaded by: [Case Western Reserve University]
On: 20 October 2014, At: 11:10
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
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of 2-Tert-butylimino-3-
hepta-O-benzoyl-β-D-lactosylimino-4-S-
benzyl-6-arylimino-2,3-dihydro-1,3,5-
thiadiazines
Kavita Manoj Heda a & Shirish Panjabrao Deshmukh a
a P. G. Department of Chemistry , Shri Shivaji College , Akola , India
Published online: 27 Dec 2013.
To cite this article: Kavita Manoj Heda & Shirish Panjabrao Deshmukh (2014) Synthesis of 2-
Tert-butylimino-3-hepta-O-benzoyl-β-D-lactosylimino-4-S-benzyl-6-arylimino-2,3-dihydro-1,3,5-
thiadiazines, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 44:4, 488-492, DOI: 10.1080/00397911.2013.815214
To link to this article: http://dx.doi.org/10.1080/00397911.2013.815214
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
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. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 44: 488–492, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.815214
SYNTHESIS OF 2-TERT-BUTYLIMINO-3-HEPTA-O-
BENZOYL-b-D-LACTOSYLIMINO-4-S-BENZYL-
6-ARYLIMINO-2,3-DIHYDRO-1,3,5-THIADIAZINES
Kavita Manoj Heda and Shirish Panjabrao Deshmukh
P. G. Department of Chemistry, Shri Shivaji College, Akola, India
GRAPHICAL ABSTRACT
Abstract
A new series of synthesis of 2-tert-butylimino-3-hepta-O-benzoyl-b-D-
lactosylimino-4-S-benzyl-6-arylimino-2,3-dihydro-1,3,5-thiadiazines (hydrochloride) were
synthesized by the interaction of 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,4-
isodithiobiurets with tert-butyl isocyanodichloride. The identities of these newly synthesized
N-lactosides have been established on the basis of usual chemical transformations and
infrared, 1H NMR, and mass spectral analysis.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords -2,4-isodithiobiurets; tert-butyl isocyanodichloride; -1,3,5-thiadiazines
Received March 11, 2013.
Address correspondence to Kavita Manoj Heda, P. G. Department of Chemistry, Shri Shivaji
College, Shivaji Park, Akola 444001, India. E-mail: kavitaheda25@gmail.com
488

SYNTHESIS OF 1,3,5-THIADIAZINES
489
INTRODUCTION
Thiadiazines and their derivatives are important biologically active precursors
in the field of medicinal chemistry. Thiazine, thiazole, and thiadiazines have been
explored to the maximum extent owing to their pharmacological activities and uses,
such as development of new fungicides against rice blast disease, Magnaporthe
grisea.[1] Some amino derivatives of thiadiazines show antiviral, anesthetic,
cardiovascular, and hypometabolic activities.[2,3] Some 1,3,5-thiadiazines are found
to possess antifungal, anti-inflammatory, and analgesic activities.[4] A variety of
1,3,5-thiadiazines and 1,3,5-triazines have been prepared by the interaction of
phenyl isocyanodichloride and several thioamido group containing compounds.[5–8]
The chemistry of organo-sulfur system[9,10] prompted us to extend our work
into a series of lactosyl-1,3,5-thiadiazines hydrochlorides. Herein we synthesize
several N-lactosylated-1,3,5-thiadiazines hydrochlorides by the interaction of tert-
butyl isocyanodichloride with 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,
4-isodithiobiurets. The required 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-
2,4-isodithiobiurets were obtained by the reaction of 1-aryl-S-benzyl isothiocarba-
mides with hepta-O-benzoyl-b-D-lactosylisothiocyanate.
RESULTS AND DISCUSSION
A solution of 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,4-isodithio-
biuret (Ia) was added to a solution of tert-butyl isocyanodichloride and the reaction
mixture was refluxed for 3 h. A brisk reaction with evolution of hydrogenchloridegas
was noticed. Afterward, the solvent was distilled off to obtain a sticky residue. This
residue was triturated with petroleum ether (60–80 ꢀC) to afford a pale yellow solid
(IIIa). The product was purified by chloroform–petroleum ether.
The specific rotation was measured in chloroform. In spectral analysis[11–13] IR
spectra of product showed characteristic absorption of the lactose unit in the ranges
1
of 900–910 and 1000–1100 cmꢁ1. H NMR spectra of product distinctly displayed
signals due to aromatic protons and lactose ring protons. The mass spectra of
product were also evaluated.
When the interaction of 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,
4-isodithiobiurets (Ib–l) was extended to tert-butyl isocyanodichloride, the
resepective products of 2-tert-butylimino-3-hepta-O-benzoyl-b-D-lactosylimino-
4-S-benzyl-6-arylimino-2,3-dihydro-1,3,5-thiadiazines (IIIb–l) were isolated.
EXPERIMENTAL
All chemicals were research grade. Melting points were taken in open capillary
tubes and are uncorrected. Infrared (IR) spectra were recorded in Nujol, KBr on a
1
FT-IR Perkin-Elmer RXI (4000–450 cmꢁ1) spectrophotometer. H NMR measure-
ment were performed on a Bruker DRX-300 (300 MHz FT NMR) NMR spec-
trometer in CDCl3 solution with tetramethylsilane (TMS) as an internal reference.
The mass spectra were recorded on a Make-Waters Model-QToF Micro Source-ESI
mass spectrometer. Optical rotation [a]D31 was measured on a Equip-Tronics Digital
Polarimeter EQ-800 at 31 ꢀC in CHCl3. Thin layer chromatography (TLC) was per-
formed on silica gel G for TLC (Merck) and spots were visualized by iodine vapor.

490
K. M. HEDA AND S. P. DESHMUKH
Starting Materials
1-Aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,4-isodithiobiurets
(ia–l). 1-Aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2, 4-isodithiobiurets have
been prepared by the interaction of hepta-O-benzoyl-b-D-lactosylisothiocyanate and
1-aryl-2-S-benzyl isothiocarbamides. Hepta-O-benzoyl-b-D-lactosylisothiocyanate
was added to a benzene solution of 1-phenyl-2-S-benzyl isothiocarbamide. The
reaction mixture was then refluxed over a boiling water bath for 6 h. After heating, sol-
vent benzene was distilled off and the sticky mass was obtained as residue. This residue
was triturated several times with petroleum ether, and a white product separated out.
It was crystallized from ethanol (Ia, Scheme 1). Compound Ia: White powder, yield:
75%, mp 140 ꢀC, [a]29D þ 120 ꢀ (c, 0.15, CHCl3), Rf 0.68 (CCl4–EtOAc, 3:2). Anal.
calcd. for C76H63O17N3S2; C, 67.40; H, 4.65; N, 3.10; S, 4.73. Found: C, 67.36; H,
4.61; N, 3.14; S, 4.70.
Tert-butyl-isocyanodichloride (II). Through a chloroformic solution of tert-
butyl isothiocyanate, pure and dry chlorine gas (generated from 15 g KMnO4 and
35 ml conc. HCl) was bubbled, maintaining the temperature of the system below
10 ꢀC. After the addition of excess of chlorine was completed, the yellow reaction
mixture was diluted with 10–15 ml dry petroleum ether (60–80 ꢀC). The solvent
was then removed by distillation under vacuum. The whole operation was repeated
several times with petroleum ether. A pale yellow liquid (II) was obtained (Scheme 2).
General Procedure for Synthesis of 2-Tert-butylimino-3-hepta-O-
benzoyl-b-D-lactosylimino-4-S-benzyl-6-phenylimino-2,3-
dihydro-1,3,5-thiadiazines (IIIa)
A solution of tert-butyl isocyanodichloride (0.001 M, 0.15 g in 15 ml CHCl3)
was added to a solution of 1-phenyl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-
2,4-isodithiobiurets (0.001 M, 1.35 g 15 ml CHCl3) (Ia) and the reaction mixture
was refluxed for 4 h. A brisk reaction with evolution of hydrogenchloride gas was
noticed. Afterward, the solvent was distilled off to obtain a sticky residue. This resi-
due was triturated with petroleum ether (60–80 ꢀC) to afford a pale yellow solid
(IIIa). The product was purified by chloroform–petroleum ether (Scheme 3).
On the basis of elemental analysis and IR, 1H NMR, and mass spectral studies,
the product with mp 145 ꢀC was assigned the structure 2-tert-butylimino-3-hepta-O-
benzoyl-b-D-lactosylimino-4-S-benzyl-6-phenylimino-2,3-dihydro-1,3,5-thiadiazine
(hydrochloride) (IIIa). Compound IIIa: Pale yellow powder, yield: 85%, mp 145 ꢀC,
Scheme 1. Synthesis of 1-aryl-5-hepta-O-benzoyl-b-D-lactosyl-2-S-benzyl-2,4-isodithiobiurets.

SYNTHESIS OF 1,3,5-THIADIAZINES
491
Scheme 2. Synthesis of N-tert-butyl isocyanodichloride.
Scheme 3. OBz ¼ Benzoyl; R ¼ (a) Phenyl, (b) o-Cl-phenyl, (c) m-Cl-phenyl, (d) p-Cl-phenyl, (e) o-tolyl,
(f) p-tolyl, (g) o-hydroxy-phenyl, (h) m-hydroxy-phenyl, (i) p-hydroxy-phenyl, (j) o-methoxy phenyl,
(k) m-methoxy-phenyl, (l) p-methoxy-phenyl.
[a]29Dꢁ50.36ꢀ (c, 0.11, CHCl3), Rf 0.65 (pet. ether–EtOAc, 7:3) IR (KBr): t 3062,
1
2976, 1730, 1600, 1492, 1315, 1267, 1026, 935, 709, cmꢁ1; H NMR (d in ppm,
CDCl3) d8.04–7.21 (45H, m, 7C6H5CO, 2C6H5), 6.43–3.72 (16H, m, lactose ring pro-
tons, S-CH2), d2.17–1.25 (9H, 3CH3); mass(m/z): 1494 (Mþ þ 1), 1456(Mþ-HCl),
1410 (Mþ-C5H9N), 1356 (Mþ-C8H9O2), 1053 (HBLþ), 579 (TBGþ), 353 (TBGþ-
C14H10O3), 335 (TBGþ-C14H12O4), 231(C13H11O4), 136 (C6H5CH2COOH), 105
(C6H5CO). C81H70O17N4S2 2HCl: C, 64.49; H, 4.64; N, 3.71; S, 4.24%. Found: C,
64.45; H, 4.62; N, 3.68; S, 4.20%
ACKNOWLEDGMENTS
Authors thank the Sophisticated Analytical Instrumentation Facility, Panjab
University, Chandigarh, for providing spectral data. They are also thankful to
S. G. Bhadange for encouragement and necessary facilities.

492
K. M. HEDA AND S. P. DESHMUKH
REFERENCES
1. Vicentine, C. B.; Forlani, G.; Manfrini, M.; Romagrioli, C.; Mares, D. J. Agric. Food
Chem. 2002, 50, 4839.
2. Farghaly, A. R.; Decterqi, E.; Ei-Kashef, H. Arkivoc 2006, 10, 137.
3. Chupakhin, O. N.; Sidorova, L. P.; Tarakhty, E. A.; Novikova, A. P.; Perova, N. M.;
Vinogradov, V. A.; Vanginkel, M. F. U. S. Patent 2001, 131B, 63.
4. Mathew, V.; Keshavayya, J.; Vaidaya, V. P.; Giles, D. G. Eur. J. Med. Chem. 2007, 42(6),
623–840.
5. Berad, B. N.; Deshmukh, S. P.; Paranjpe, M. G. J. Ind. Chem. Soc. 1984, 61, 883–884.
6. Dhonde, M. G.; Deshmukh, S. P. J. Carbohydr. Chem. 2004, 23(5), 305–311.
7. Heda, K. M.; Deshmukh, S. P. Rasayan J. Chem. 2012, 5(1), 24–27.
8. Pathe, P. P.; Ambekar, M. W.; Paranjpe, M. G. Indian J. Chem. 1981, 20B, 824.
9. Rees, C. W. J. Heterocycl. Chem. 1996, 33, 1419.
10. Clarke, D.; Emayan, K.; Rees, C. W. J. Chem. Soc., Perkin Trans. 1998, 1, 77.
11. Silverstein, R. M.; Webster, F. X. Spectrometric identification of organic compounds,
6th ed., John Wiley and Sons, New York, 2004.
12. Colthup, N. B.; Daly, L. H.; Wibereley, S. E. Introduction to Infrared and Raman
Spectroscopy; Academic Press: New York, 1964.
13. Williams, D. H.; Fleming, L. Spectroscopic Methods in Organic Chemistry, 4th ed., Tata:
McGraw-Hill, 1988.