International Journal of Application or Innovation in Engineering & Management (IJAIEM)

Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com Volume 3, Issue 1, January 2014 ISSN 2319 - 4847

Synthesis, antimicrobial and antifungal study of 2,4-substituted-1,5-substitutedbenzothiazepine

Swati.V. Gaikwad* ,DrA.B.Bhakea, DrS. E. Bhandarkarb
*research student,Department of Applied Chemistry, DBACER ,Nagpur11
a

AssociateProfessor,Department of Applied Chemistry,YeshwantraoChavan C.O.E., Nagpur33

b

Associate Professor, Department of Chemistry, G.V.I.S.H., Amravati

ABSTRACT
Synthesis of 2,4-substituted-1,5-substituted- benzothiazepine was first carried out by the acetylation of substituted napthol in presence of glacial acetic acid and zinc chloride. The 1-(1-hydroxy-naphthalene-2-yl)ethanone obtained is then heated with aromatic aldehyde using ethanol as a solvent and 40% KOH which on condensation gave 1-(substituted-1-hydroxynaphthalen -2yl)-3-aryl-prop-2-en-1-one.This compound on microwave irradiation in presence of substituted aminobenzothiol and zinc acetate gave 2,4-substituted-1,5-substituted- benzothiazepine .The synthesized compounds are characterized by elemental analysis, 1H NMR, IR Spectroscopy. Newly synthesized compound shows an excellent antimicrobial and antifungal activities.

Keywords: Synthesis, benzothiazepine,elementalanalysis,antimicrobial

INTRODUCTION
Benzothiazepines are seven membered heterocyclic compounds.Benzothiazepines have received a considerable attention nowadays because of its versatile biological activities like anticonvulsant [1],CNS depressant [2,3,4] ,anticancer[5],antifungal[6] and antimicrobial activities[7,8].As disease poses a major threat to human beings and scientists are fighting to find solutions in the form of various medications, benzothiazepine finds its importance in bioinorganic and medicinal chemistry in designing new therapeutic agents with improved pharmacological properties.[9,10].Present work deals with the synthesis of 2,4-substituted-1,5-substituted- benzothiazepine and their characterization by spectral analysis ( IR, 1H NMR ). EXPERIMENTAL All the melting points were taken in silicon oil bath with open capillary tubes and are uncorrected. IR spectra were recorded on a Nicolet-Impact 400 FT-IR spectrometer 1 H NMR spectra were recorded on a Brucker AC300 FNMR spectrometer(300 MHz), using TMS as an internal standard. Microanalysis of nitrogen was obtained by Kjeldahals Method. Thin Layer Chromatography on silica gel-G, was used to check the purity of the compounds. Procedure for the synthesis of 2-acetyl-substituted-1-naphthol: In hot glacial acetic acid, fused ZnCl2 was added and refluxed till dissolved, then powdered substituted 1-naphthol was added and the mixture was refluxed for about 8 hours then cooled & poured in acidulated water. The solid obtained was filtered, washed, dried and recrystallized from rectified spirit to obtain compound (2a). Synthesis of 1-(substituted-1-hydroxynaphthalen -2-yl)-3-aryl-prop-2-en-1-one (3a): 2-acetyl-substituted-1-naphthol and aromatic aldehydes were added in ethanol solvent. To this mixture KOH (10%) solution was added dropwise with constant stirring. The reaction mixture was kept overnight. Then the mixture was poured over crushed ice & little HCl. The product was filtered and recrystallized from ethanol to obtain the compounds (3a). Synthesis of 2,4-substituted-1,5-substituted- benzothiazepine (1-25): 1-(substituted-1-hydroxynaphthalen -2-yl)-3-aryl-prop-2-en-1-one and substituted 2-aminobenzenethiol was heated in presence of catalyst zinc acetate to obtain a compound 2,4-substituted-1,5-substituted- benzothiazepine.The physical data of newly synthesized compounds is given in Table.I Table I - Physical and analytical characterization data of newly synthesized compounds

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International Journal of Application or Innovation in Engineering & Management (IJAIEM)

Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com Volume 3, Issue 1, January 2014 ISSN 2319 - 4847
Melt ing Poin 0 t C 75 85 76 73 71 80 91 88 65 72 90 88 92 70 69 88 Melt ing Poin 0 t C 95 71 80 91 88 65 72

Compound R1 2a 3a 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Compound R1 15 16 18 19 20 21 22 R Br Cl C6H5 OCH3 Br Cl C6H5 R2 OCH3 OCH3 OCH3 OCH3 OCH3 OCH3 OCH3 --H H H H OH OH OH OH OCH3 OCH3 OCH3 OCH3 H H R R2

% Nitrogen % Yield 85 75 68 64 69 50 72 55 56 61 80 65 67 85 75 80 Found 4.66 5.45 4.52 5.38 4.25 5.25 4.35 5.89 4.26 4.99 4.19 4.88 4.26 4.85 Calculated 4.78 5.67 4.74 5.57 4.52 5.30 4.49 6.01 4.32 5.04 4.29 4.96 4.32 5.04 0.65 0.64 0.56 0.64 0.59 0.56 0.57 0.69 0.58 0.56 0.54 0.53 0.58 0.62 R.F. Value 0.63 0.52 0.65 0.56 0.54 0.53 0.64 R.F. Value

-C6H5 C6H5 OCH3 Br Cl C6H5 OCH3 Br Cl C6H5 OCH3 Br Cl C6H5 OCH3

-H H H H H H H H H H H H H OCH3 OCH3

% Yield 55 69 50 72 55 56 61

% Nitrogen Found 4.20 4.72 4.08 5.00 4.02 4.65 3.86 Calculated 4.29 4.96 4.12 5.04 4.09 4.69 3.95

H H OH OH OH OH OCH3

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International Journal of Application or Innovation in Engineering & Management (IJAIEM)

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OCH3 OCH3 OCH3

23 24 25

OCH3 OCH3 OCH3

OCH3 Br Cl

90 70 69

80 85 75

4.75 3.90 4.45

4.79 3.93 4.48

0.56 0.58 0.55

SPECTRAL INTERPRETATION IR (KBr) : 1650 (C=O), 3350 (-OH) , 3131(-NH) NMR (CDCl3 + DMSO-d6) : 2.35 (s,3H,CH3), 6.88- 7.11 (m, 11H, Ar-H), 9.83 (s,1H,-OH) , 3.86(s,3H, OCH3) SCHEME

OH OH O ZnCl2 CH3 R1
R1

O CH3

HO

(2a)
O

naphthalen-1-ol

acetic acid R2 SH OH NH2 10%KOH R O

R S HO N H R2

R1

R1

(3a)

(1-25)

R1 = H, OH, OCH3; R = aryl, CH3, Br,Cl; R2 = H, OCH3

ANTIMICROBIAL STUDIES All abovebenzothiazepine derivatives have been studied for their antimicrobial activity against Escherichia coli, Proteus mirabilis, Staphylococcus aureas, Pseudomonas aeruginosa,. The culture of each species was incubated at 370C and the zone of inhibition was measured after 24 hr. Most of these compounds were found active.

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International Journal of Application or Innovation in Engineering & Management (IJAIEM)

Web Site: www.ijaiem.org Email: editor@ijaiem.org, editorijaiem@gmail.com Volume 3, Issue 1, January 2014 ISSN 2319 - 4847
ACKNOWLEDGEMENT The authors are thankful to Principal, YeshwantraoChavan C.O.E., Nagpur33 for providing necessary laboratory facilities. REFERENCES 1. Sarro J G De, Chimirri A, Sarro A De ,5H[1,2,4]Oxadiazolo[5,4d][1,5]benzothiazepins as anticonvulsant agents in DBA/2 A. R. Trivedi, D. K. Dodiya, N. R. Ravat, V. H. Shah, Arkivoc XI (2008) 131 2. Basawaraj R., Naubade K., Sangapure S.S, Synthesis of some Benzodiazepins and benzothiazepins bearing benzofuran moiety as a possible CNS depressants. Ind.J.Hetr.Chem,17,2008;217220 3. Nikalje AG, Pattan SR , Synthesis of 1,5benzothiazepins as a potential CNS and CVS agents.Int.J.Chem.Sci,2007;5(1),290296 4. MasafumiHagiwara,Satomi AdachiAkahane and TakuNagao,High Affinity Binding of DTZ323, a novel derivative of Diltiazem. Ind. J.Pharmacology, 1997; 281( 1) :173179 5. Sharma KA., Singh G., Yadav AK. , Prakash L. Improved method for synthesis of new 1,5benzothiazepins derivative as analogue of anticancer drugs. Molecules, 1997; 2(2):130135 6. DandiaAnshu, Singha R. ,Khaturia S. Efficient microwave enhanced solvent free synthesis of potent antifungal agents:Fluorinatedbenzothiazepin fused lactom derivative. Cheminform,2007;38(36):236239 7. Giuliano G., Luana P., Valeria A. Synthesis of new 1,4benzothiazepins tricyclic derivative with structural analogue with TIBO and their screening for antiHIV activity. Eur. Journal of Medicinal Chemistry,1999; 34, (9) , 701709 8. Nikalje AG, Mane RA, Ingle DB , Synthesis of new 1,5benzothiazepins as potent antimicrobial agents,Ind. J.Het.Chem,2006;15(3),309310 9. K. L. Ameta, Nitu S. Rathore and Bireshkumar , Synthesis and in vitro anti-breast cancer activity of some novel 1,5-benzothiazepine derivatives, J. Serb. Chem. Soc. 77 (6) 725731 (2012) 10. DeepikaVyawahare, MangeshGhodke and Anna PratimaNikalje, green synthesis and pharmacological screening of novel 1,5benzothiazepines as CNS agents. International Journal of Pharmacy and Pharmaceutical Sciences Vol 2, Issue 2, 2010

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