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					                                                        International Journal of Advances in Science and Technology,
                                                                                                   Vol. 1, No. 5, 2010


Synthesis of Novel 2-Phynel-1H-Indole-5-Sulphadimidine
                               Dharmendra Kumar, Gajendra Singh, C. P. Singh*

                      Research Lab, Chemistry Division, Sahu Jain College, Najibabad, 246763, India

                                           Email Id- cpsingh.sahu@gmail.com
                                               Phone. No. +919411952228


                                                  Abstract


  Novel 2-phenyl-1H-indole-5-sulphadimidine has been synthesized by the interaction of sulphadimidine and
phenacyl halide. The newly synthesized compound was screened for anti-tubercular activity.


Keywords: Synthesis, Anti-tubercular activity, sulphadimidine, Indole, 2-phenyl-1H-indole-5-sulphadimidine.

1. Introduction

The indole nucleus are important substructures found in numerous natural or synthetic alkaloids [1,2]. The diversity
of the structure encountered, as well as their biological and pharmaceutical relevance, have motivated research
aimed at development of new economical, efficient and selective synthetic, particularly for the synthesis of
substituted indole rings [4,5]. A large number of indoles and their derivatives are reported to possess a broad
spectrum of biological activities [5-15]. Thus, these were found to be useful especially in the treatment of fungal and
bacterial diseases. Indoles and their derivatives exhibited anti-inflammatory [5,6], antitumor [7], antibacterial [6,8],
antiamoebic [9], antifungal [10,13], anti-HIV [11], and anticancer [12] activities. These properties of indole and
their derivatives prompted us to synthesize this novel compound.

2. Methodology


2.1 Material
The sulphadimidine, α-halo acyl benzene, and reference compound were purchased from Aldrich Chemicals.
Ethanol, glacial acetic acid and all other reagents were purchased from S. D. Fine Chem. TLC was performed on
pre-coated plastic sheets of silica gel G/UV-254 of 0.2 mm thickness (Macherey-Nagel, Germany).

 2.2 General
 Melting points of the 2-phenyl-1H-indole-5-sulphadimidine was determined using an open-ended capillary tube
 method and are uncorrected. The purity of the synthesized compound was checked by TLC. A FT-IR spectrum was
 recorded on a Perkin-Elmer 1605 series FT-IR in a KBr disc. 1H NMR spectra were recorded at 300 MHz on a
 Bruker FT-NMR spectrophotometer using TMS as internal standard.

2.3 Preparation of 2-phenyl-1H-indole-5-sulphadimidine
A mixture sulphadimidine and phenacyl halide in 2:1 ratio was dissolved in glacial acetic acid and refluxed on water
bath for half an hour, the phenacylsulphadimidine underwent rapid cyclization to form 2-phenyl-1H-indole-5-
sulphadimidine and a trace of sulpadimidinium halide. On cooling, a crystalline solid compound was obtained and it




December Issue                                     Page 100 of 108                                    ISSN 2229 5216
                                                            International Journal of Advances in Science and Technology,
                                                                                                       Vol. 1, No. 5, 2010



 was recrystallization from ethyl alcohol as shining crystals (Fig.1). On analysis, it was found to be 2-phenyl-1H-
indole-5-sulphadimidine.

2.3.1 2-phenyl-1H-indole-5-sulphadimidine

A light yellow crystalline powder, mp 224-226 oC, Yield 86.22%, molecular formula C20H18N4O2S, anal. Calcd for
C20H18N4O2S (378.45): C, 63.47; H, 4.79; N, 14.81; O, 8.46; S, 8.47. Found: C, 63.53; H, 4.74; N, 14.78; O, 8.44; S,
8.52. UV (λmax) 277.6, IR (KBr) νmax in cm−1 3283 (−SO2NH), 770 (C−C), 1265 (C−N), 1555 (C=C or aromatics
ring), 3033 (aromatics C−H), 3340 (N−H), 1HNMR (CDCl3) δ in ppm, 5.9 (b, 1H, NH, indole ring), 7.65-6.85 (m,
9H, Ar−H), 10 (1H, SO2NH), 6.45 (s, 1H, indole ring), 2.35 (t, 6H CH3).



3. Results and Discussion


The synthesized 2-phynel-1H-Indole-5-Sulphadimidine was screened for anti-tubercular activity [14] against
Mycobacterium tuberculosis H37Rv using employing REMA (Resazurin microtitre assay) method [15]. Anti-
tubercular screening: 2-phenyl-1H-indole-5-sulphadimidine was tested at concentration 1.25, 2.5, 3.75, 5.0, 6.25,
7.5, 8.75 and 10.0 μg/ml. The antituberculosis tests indicated that the title compound showed the highest inhibition
(42%) against Mycobacterium tuberculosis H37Rv at a concentration of 6.25 μg/ml.


4. Conclusion


We have presented a synthesis of novel 2-phynel-1H-Indole-5-Sulphadimidine for the anti-tubercular activity. It
may be considered promising for the development of new antituberculosis agent.



Acknowledgments

The authors express their sincere thank to the principal, Sahu Jain College, Najibabad, for providing lab facilities
and also thank to CDRI (CSIR) Lucknow, IIT Roorkee for Providing IR, NMR spectral data and pharmacological
data.




References

    1.   R. J. Sundberg, Indoles, Academic Press, London, 1996.
    2.   J. A. Joule, in: E. J. Thomas (Ed.), Science of synthesis, 10, Thieme, Stuttgart, p.361, 2001.
    3.   R. J. Sundberg, in: A. R. Katritzky, C. W. Rees (Eds.), Comprehesive Heterocyclic Chemistry, 4, Pergamon, Oxford, p.
         314, 1984
    4.   J. Tois, R. Franzen, A. Koskinen, Tetrahedron 59, 5395, 2003.




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                                                            International Journal of Advances in Science and Technology,
                                                                                                       Vol. 1, No. 5, 2010




    5.    N. Singh, S. K. Bhati, A. Kumar, Thiazolyl/oxazolyl formazanyl indoles as potent anti-inflammatory agents, European
          Journal of Medicinal Chemistry 43, 2597-2609, 2008.
    6.    D. Kumar, N. Kumar, S. Kumar, T. Singh, C. P. Singh, Synthesis of Pharmacologically active 2-phenyl
          sulpha/substituted indoles, International Journal of Engineering Science and Technology 2, 2553-2557, 2010.
    7.    T. Owa, T. Okauchi, K. Yoshimatsu, N. H. Sugi, Y. Ozawa, T. Nagasu, N. Koyanagi, T. Okabe, K. Kitoh, H. Yoshino,
          A focused compound library of nobel N-(7-Indolyl)benzenesulfonamides for the Discovery of potent cell cycle
          inhibitors, Bioorganic & Medicinal Chemistry Letters 10, 1223-1226, 2000.
    8.    R. K. Tiwari, D. Singh, J. Singh, V. Yadav, A. K. Pathak, R. Dabur, A. K. Chhillar, R. Singh, G. L. Sharma, R.
          Chandra, A. K. Verma, Synthesis and antibacterial activity of substituted 1,2,3,4-tetrahydropyrazino [1,2-a] indoles,
          Bioorganic & Medicinal Chemistry Letters 16, 413-416, 2006.
    9.    K. Husain, A. R. Bhat, A. Azam, New Pd(II) Complexes of the synthesized 1-N-substituted thiosemicarbazones of 3-
          indole carboxaldehyde: Characterization and antiamoebic assessment against E. histolytica, European Jouranal of
          Medicinal Chemistry 43, 2016-2028, 2008.
    10. A. Dandia, B. Rani, M. Saha, I. J. Gupta, Microwave induced synthesis of 2-substituted phenyl-3-(3-alkyl/aryl-5,6-
          dihydro-S-triazolo) [2,4-B] [1,3,4] thiadiazo 6-yl indoles and 2-phenyl-3 [2,substituted benzothiazole] derivatives and
          their fungicidal activity, Phosphorus, Sulphur, and Silicon 130, 217-227, 1997.
    11. P. Selvam, M. Chandramohan, E. D. Clercq, M. Witvrouw, C. Pannecouque, Synthesis and anti-HIV activity of 4-
          [(1,2-dihydro-2-oxo-3H-indol-3-ylidene)     amino]-N(4,6-dimethyl-2-pyrimidinyl)-benzene      sulfonamide     and   its
          derivatives, European Journal of Pharmaceutical Sciences, 14 , 313-316, 2001.
    12. G. Laconde, N. Pommery, P. Depreux, P. Berthelot, J. P. H. Nichart, New Analogues of the Anticancer E7070:
          Synthesis and Pharmacology, Journal of Enzyme Inhibition and Medicinal Chemistry, 18, 89–94, 2003.
    13. U. K. Singhl, S. N. Pandeya, A. Singh1, B. K. Srivastava, M. Pandey, Synthesis and Antimicrobial Activity of Schiff’s
          and N-Mannich Bases of Isatin and Its Derivatives with 4-Amino-N-Carbamimidoyl Benzene Sulfonamide,
          International Journal of Pharmaceutical Sciences and Drug Research 2, 151-154, 2010
    14. A. Naqvi, M. Shahnawaaz, A. V. Rao, D. S. Seth, N. K. Sharma, Synthesis of novel 3-hydrazino-3-oxo-N-(4-
          sulfamoylphenyl)-propanamide, Molbank M586, 2009.
    15. N. Solak, S. Rollas, Synthesis and antituberculosis activity of 2-(aryl/alkylamino)-5-(4-aminophenyl)-1,3,4-thiadiazoles
          and their Schiff bases, ARKIVOC 12, 173-181, 2006




Figures

The diagram depicts the Synthesis of 2-phenyl-1H-indole-5-sulphadimidine.




December Issue                                         Page 102 of 108                                        ISSN 2229 5216
                                              International Journal of Advances in Science and Technology,
                                                                                         Vol. 1, No. 5, 2010




                     O
                                                                                   N
                     C       CH 2Br + 2NH2                               SO2NH
                                                                                   N


                                                                  HBr
                                                                  H 2O




                                                  N           N




                                                      SO2NH


                     N
                 N           HN                       NH
                               O
                                 2S                           CH 2

                                                              C
                                                      N


                                   Cyclization                    C12H13N 4O2 Br




                             N

                         N            HN              O
                                              S
                                       O
                                                                         N

                                                                         H




December Issue                             Page 103 of 108                                 ISSN 2229 5216
                                                           International Journal of Advances in Science and Technology,
                                                                                                      Vol. 1, No. 5, 2010

                                  Fig.1. Synthesis of 2-phenyl-1H-indole-5-sulphadimidine.



                                                Mr. Dharmendra Kumar completed his Master Degree in Organic Chemistry
                                                from Sahu Jain College, Najibabad affiliated by M. J. P. Rohilkhand University
                                                Bareilly, Bareilly (UP) in 2006. He is currently doing his research programme
                                                in the area of Pharmacology. He has published various research papers in
                                                international, national and conferences in the area of Bio-Fuels, Coordination
                                                Chemistry and Pharmacology.




                                                Mr. Gajendra Singh completed his Master degree in Organic Chemistry from
                                                Sahu Jain College, Najibabad affiliated by M. J. P. Rohilkhand University
                                                Bareilly, Bareilly (UP) in 2007. He is currently doing his research in the area
                                                of Pharmacology.




                                                Dr. C. P. Singh completed his Master Degree in Organic Chemistry from Sahu
                                                Jain College, Najibabad affiliated by Agra University Agra and Ph.D. in
                                                Organic Chemistry from M.J.P. Rohilkhand University Bareilly, Bareilly (UP)
                                                in area of Pharmacology. Duration the Ph.D. and after the Ph.D. Degree he has
                                                awarded various research position like as JRF, SRF, PDF, Pool Officer, CSIR
                                                New Delhi. He obtained also FICS and FIC degree.. Now He is working as an
                                                Associate Professor, Deptt. of chemistry, in the Sahu Jain College, Najibabad
                                                (Bijnor), Uttar Pradesh.




 Dr. C. P. Singh has published more than 50 research papers in the Nation and International Journal in area of Bio-Fuels and
Pharmacology. He has presented more than 50 papers in national and international Conferences. He has received various awards
and honours like as “Life Time Achievement award 2006 from Health and Educational Development Association, New Delhi,”
“National Integration Award 1993, New Delhi”, “Vice Chancellor, Agra University Agra hounoured me on securing Ist Position
in P.G. Class in 1976”. He has completed two research projects, one was “Studies on Multicidal Biologically Active Heterocyclic
Compounds” CSIR New Delhi and one another were “Studies on Potential Antitumor agent” UGC New Delhi. 14 research
scholars (Ph.D students) also completed his research work in his supervision.




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