{"id":1606,"date":"2015-03-26T07:05:30","date_gmt":"2015-03-26T07:05:30","guid":{"rendered":"http:\/\/biomedpharmajournal.org\/?p=1606"},"modified":"2020-04-26T06:47:26","modified_gmt":"2020-04-26T06:47:26","slug":"synthesis-spectral-evaluation-and-potential-antimicrobial-screening-of-some-substituted-thiosemicarbazides-and-substituted-thiosemicarbazones-under-microwave-irradiation-and-classical-heating","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol3no2\/synthesis-spectral-evaluation-and-potential-antimicrobial-screening-of-some-substituted-thiosemicarbazides-and-substituted-thiosemicarbazones-under-microwave-irradiation-and-classical-heating\/","title":{"rendered":"Synthesis, Spectral Evaluation and Potential Antimicrobial Screening of some Substituted Thiosemicarbazides and Substituted Thiosemicarbazones Under Microwave Irradiation and Classical Heating"},"content":{"rendered":"

Introduction<\/strong><\/p>\n

The chemistry and pharmacology of thio-semicarbazide, thiosemicarbazone have been of great interest to medicinal chemists for their wide range of biological activity1<\/sup>, Thiosemicarbazide and their derivatives are simple sulphur containing compound and possessing N-C-S group. In the recent year\u2019s chemistry of thiosemi-carbazides and thiosemicarbazones have received much attention due to their use as intermediates for the synthesis of some heterocyclic systems.<\/p>\n

Thiosemicarbazide and it\u2019s derivatives have been reported to possess anti-bacterial2<\/sup>, anti-tubercular3<\/sup>, antifungal4<\/sup>, hypotensive5<\/sup>, herbicidal and growth regulating6<\/sup>, hypoglyceamic7<\/sup> activity.<\/p>\n

Thiosemicarbazone is a important class of heterocyclic chemistry and have shown unique spectrum as analytical, structural and biological activities. Substituted thiosemicarbazones have been found to possess antiviral8<\/sup>, antitumor9<\/sup>, anti-bacterial10<\/sup>, anti-tubercular11<\/sup> activity .<\/p>\n

Microwave assisted reactions attracted substantial attention in recent years, because of the simplicity in operation, milder reaction condi-tions, increasing reaction rates and formation of cleaner products. In particular microwave assisted \u201cGreen Chemistry\u201d reactions12<\/sup> have gained more popularity as they compared to conventional heating method. The present study is devoted to synthesize some substituted thiosemicarbazide & thiosemicarbazone derivatives by the both technique. In this context in continuation of our previous work13<\/sup>, IR, 1<\/sup>H NMR characterization and their antibacterial screening of some synthesized compounds have been reported. By various workers several substituted thiosemicarbazides & thiosemicarbazones have also been prepared in our laboratory14-18<\/sup>.<\/p>\n

Experimental<\/strong><\/p>\n

Material and Methods<\/strong><\/p>\n

All the chemicals required for the present study were obtained from Sigma-Aldrich Com-pany Germany. Melting points were determined by open capillary tube method and using electro thermal apparatus were uncorrected. TLC was run on silica-gel-coated AI Plates using 10% (benzene\/methanol). The IR spectra of the compounds were recorded on Perkin-Elmer spectrum RX-1 FT-IR spectrophotometer by using Kbr pellet technique and 1<\/sup>H-NMR of the synthesized compounds was recorded on Advanced Bruker DRX-300 spectrometer, DMSO was used as solvents, chemical shifts are given in (ppm) and protons signals are indicated as: s = singlet, d = doublet, t = triplet, m = multiplet. The physical and analytical properties of compounds are furnished in the Table-1 and spectral analysis are in the Table-2, antibacterial screening are recorded in the Table-3. The microwave irradia-tions for the synthesis of compounds were carried out in an IFB domestic microwave oven.<\/p>\n

Synthesis of N(R)-phenyl malonamic acid hydrazide (a1<\/sub>-j1<\/sub>)<\/strong><\/p>\n

To the substituted aniline (0.025 mole), freshly distilled diethyl malonate (0.05 mole) was added with few drops of catalyst DMF, refluxed the reaction mixture for 45-minutes, add (20 ml) of ethanol to it, concentrated the reaction mixture over the boiling water-bath, add ethyl alcohol (20ml) with hydrazine hydrate 99%, the obtained solid part was purified by recrystallization from absolute ethanol.<\/p>\n\n\n\n
\"Table<\/td>\nTable 1<\/strong><\/p>\n

 <\/p>\n

Click here to View Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

General method A (heating) for the synthesis of substituted <\/strong>thiosemicarbazide (2a-2j)<\/strong><\/p>\n

The substituted phenyl anilic acid hydrazide\u00a0<\/strong>(a1<\/sub>-j1<\/sub>; 0.001 mole), stirred solution of 4-fluoro phenyl isothiocyanate (0.001mole) in 20 ml of ethanol , the reaction mixture was refluxed for 3-hours, cooling, filtered, obtained solid part was recrystallized from ethyl alcohol 99%.<\/p>\n

General method B (microwave irradiation) for the synthesis of substituted <\/strong>thiosemicarbazide<\/strong> (2a-2j)\u00a0<\/strong><\/p>\n

To the (a1<\/sub>-j1<\/sub>; 0.001mole) and stirred solution of substituted phenyl isothiocyanate ( RI<\/sup><\/strong> ; 0.001 mole), in (15 ml) absolute ethanol, were irradiated in microwave oven for 2-5 minutes. The obtained solid part was purified by recrystallization from hot absolute ethanol.<\/p>\n\n\n\n
\"Table<\/td>\nTable 2<\/strong><\/p>\n

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Click here to View Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

General method C (heating) for the synthesis of substituted thiosemicarbazone (3a-3f,4a- 4f)<\/strong><\/p>\n

\u00a0<\/strong>A mixture of (2a,2b; 0.001 mole), substituted aldehydes and ketone (0.001 mole)in (20 ml) of absolute ethanol with few drops of glacial acetic acid, reaction mixture was refluxed for 3-hours, the solid part was obtained during refluxing period, cooling, filtered, it was purified by recrystallization from absolute ethanol.<\/p>\n

General method D (microwave irradiation) for the synthesis of substituted <\/strong>thiosemicarbazone<\/strong> (3a-3f, 4a- 4f)<\/strong><\/p>\n

To the substituted thiosemicarbazide (2a, 2b; 0.001 mole) and stirred solution of substituted aldehydes and ketone in (15 ml) of absolute ethanol with 4 – 5 drops of glacial acetic \u00a0acid as a<\/p>\n

catalyst, reaction mixture was irradiated in microwave oven for 2-5 minutes, the obtained solid was purified by recrystallization from hot ethanol 99%.<\/p>\n

Table 3: Antibacterial activity data of <\/strong>synthesized compounds<\/strong><\/p>\n\n\n\n
\"Table<\/td>\nTable 3:<\/strong><\/p>\n

 <\/p>\n

Click here to View Table<\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

 <\/p>\n

Key to Symbols: Resistance = R; Slightly active = + (inhibition zone 6-9 mm); Moderately active = ++ (inhibition zone 9-12 mm); Highly active = +++ (inhibition zone > 12 mm); (-) = inactive (Less than 6 mm).<\/p>\n

Antibacterial Activity<\/strong><\/p>\n

The newly synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus and Escherichia coli bacterial strains by the\u00a0 filter paper disc diffusion method19-20<\/sup> was followed by using special Hi-Media sterile disc code 067. Control experiment was carried out using Streptomycin as a known standard antibacteria drug for comparison with the results at a concentration of 25 \u03bcg\/ml. Screening was carried out in DMF solution. The bacteria were subcultured on nutrient agar medium and petridishes were incubated at 37O<\/sup>C for 24hrs. The results of the activity are given in Table-3.<\/p>\n

Results and Discussion<\/strong><\/p>\n

The IR spectra (in Kbr) of synthesized compounds have been recorded in the frequency region 4000-500 cm-1<\/sup> and 1<\/sup>H NMR Spectral data are recorded in the Table-2.<\/p>\n

The IR spectra of the of substituted thiosemi-carbazide (2a) showed absorption frequencies (in cm-1<\/sup>) at 3441.9 (-NH), 3022.0(-CH), 1671.8 (CO NH), 1518.5 (C=O), 1429.3(-CH2 <\/sub>group), 1334.5 (C=S),1216.2(N-N), 671.0(mono substitution ring) .These infrared spectral analysis results Indicated the absorption spectrum was in agreement with the assigned structure of compound 2a, (2b,2d,2e) and other compounds 2c, 2f-2j. The IR spectra of compound (3e) and (4d) in Kbr showed absorption frequencies in (cm-1<\/sup>) at 3426.2 and 3445.5(-NH), 3022.2 and 3022.0(-CH), 2358.9 and 2358.0 (CH=C), 1676.4 and 1672.0(CONH), 1520.9 and 1518.4(C=O), 1338.1 and 1336.6 (C=S), 1216.5 and 1216.6(N-N), 671.9 and 671.9 (mono substitution ring). These results indicated the absorption spectrum was in agreement with the assigned structure of compound 3e, 4d and other compounds 3a-3d, 3f, 4a-4c, 4e-4f.<\/p>\n

The 1<\/sup>H NMR spectra of compound 2a showed singlet at 3.358(CH2<\/sub>),7.170(NH),9.8 58(CONH), 10.264(C=S) and 1<\/sup>H NMR spectra of compound 2b showed doublet at : 3.3 36(-CH2<\/sub>), singlet at \u00a07.171(-NH), 9.860(-CONH), 10.332(-C=S). These results are confirming the structure of compounds 2a, 2b and other newly synthesized compounds.<\/p>\n

The results of antimicrobial screening indicates the title compounds showed moderate to strong activity against these two micro organisms.<\/p>\n

Acknowledgements<\/strong><\/p>\n

The author thanks to Head, Central Drug\u00a0\u00a0\u00a0 Research Institute (CDRI), Lucknow for spectral data (IR, 1<\/sup>H-NMR) and Head, Department of Botany, Raja Balwant Singh College, Agra for valuable support in antimicrobial activity.<\/p>\n

Referenc<\/strong><\/p>\n

    \n
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  3. Y.Aoki (Inst. Infectious Diseases, Tokyo) Japan, J.Bacterial, <\/em>9: 433-38(1986).<\/li>\n
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  9. H.G.Petering, H.H.Buskirk and G.E.Under wood., Cancer Res.,<\/em> 64: 367(1963).<\/li>\n
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  11. R.Behnisch, F.Mietzsch and H.Schimdt, Amer .Rev.Tuberc.,<\/em> 61: 1-7(1950).<\/li>\n
  12. A.V.Rao, A.Naqvi, Mohd. Shahnawaz, Daya S.Seth and P.E.Joseph, BioMed.& Pharm.J., <\/em>2(1): 185-188(2009).<\/li>\n
  13. Alok K.Pareek, P.E.Joseph and Daya S.Seth, Orient.J.Chem.,<\/em> 26(1): 207-210(2010).<\/li>\n
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  15. Mamta Agrawal, Ibid,<\/em> Agra Univ., Agra(1980).<\/li>\n
  16. Arun Kumar, Ibid,<\/em> Agra Univ., Agra(1981).<\/li>\n
  17. S.Bhatnager, Ph.D.Thesis,<\/em> Agra Univ., Agra (1990).<\/li>\n
  18. A.Chaudhary, G.Saxena, Shah.N.Khan, A. Naqvi and Daya S.Seth, Orient.J.Chem.,<\/em> 23 (3): 1089-1092(2007).<\/li>\n
  19. R.Cruickshank, J.P.Duguid, B.P.Marion and R.H.A, Medicinal Microbiology, 12th<\/sup> Edn.,<\/em> 2: 196-202(1975).<\/li>\n
  20. L.J.Bradshow Ed., A Text book of Microbio-logy, <\/em>W.P.Sounders Co., Philadelphia, New York (1979).<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

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