EnvironmentallybenignSynthesisandBiologicalActivityofBenzo[d]Thiazol-2-yl)Phenyl)-N-(5-aryl-1H-1,2,3-Triazol-1-yl)Methanamines
1MahatmaGandhiUniversity,Anneparthy,Nalgonda-508254(Telangana)India
2SreenidhiInstituteofScienceandTechnology(Autonomous),Ghatkesar,Hyderabad-501301(Telangana)India.
*CorrespondingAuthorE-mail:mandalajyothi@yahoo.co.in
ABSTRACT:
InthispresentcommunicationwereportsynthesisofBenzo[d]thiazol-2-yl)phenyl)-N-(5-aryl-1H-1,2,3-triazol-1-yl)methanaminesbymicrowaveirradiationingoodyieldsandlessreactiontime.AlltitlecompoundswerecharacterizedbyIR,NMRandMassspectralanalyses.Theantibacterialactivityofthecompoundswasalsoinvestigated.HighestactivitywasseenagainstStaph.aureusfollowedbyBacillussubtilis.
KEYWORDS:Synthesis,methanamines,microwaveassisted,antibacterialactivity.
INTRODUCTION:
Heterocyclicbearingabenzothiazoleringresiduearereportedtoshowanticancer,antiinflammatory,analgesic,muscle-relaxant,sedative,antitubercular,diuretic,antimicrobial,anticonvulsant,antiallergic,antimalerial,antiviral,antioxidant,CNSdepressant,andplantgrowthregulatoryactivityetc.Benzothiazolepossessderivativesanextendedconjugatedsystemandlongerfluorescencelifetimeforms.2
Tuberculosis (TB) is the leading infectious cause of death in the world today, with ∼3 million deceasing every year. An increase in the global burden of TB with the worldwide mortality rate of 23% is a major concern in the socioeconomic and health sectors.3-7 Recently, certain triazole-based compounds were reported to possess antimicrobial activities.8-10 It is believed that aryl-azolyl-ethane moiety, present in many azole antifungal drugs, serves as pharmacophore in compounds having Mycobacterium killing activity.11,12
Scheme
Ar=2-methylphenyl,4-methoxyphenyl,3-methoxyphenyl,4-chlorophenyl,phenyl
EXPERIMENTAL:
AlltheChemicalandreagentsusedwerepurchasedfromAldrich.Allthesolventswereofanalyticalgrade.Thin-layerchromatography(TLC)wascheckedbyMerckALsilicagel60F254platesandvisualizedunderUVlight.1HNMRspectrawererecordedinCDCl3andDMSO-d6withaVarianMercuryplus400MHzinstrument.Allthechemicalshiftswerereportedinδ(ppm)usingTMSasaninternalstandard.The1HNMRchemicalshiftsandcouplingconstantsweredeterminedassumingfirst-orderbehaviour.Multiplicityisindicatedbyoneormoreofthefollowing:s(singlet),d(doublet),t(triplet),q(quartet),m(multiplet),br(broad);thelistofcouplingconstants(J)correspondstotheorderofmultiplicityassignment.MassspectrawererecordedonaShimadzuLCMS-QP1000massspectrometer.Allthereactionswereperformedunderinertatmosphere.
1-((Benzo[d]thiazol-2-yl)methyl)-2-arylhydrazines(3a-e):
1-((benzo[d]thiazol-2-yl)methyl)hydrazine(2)(0.001mmole)andaldehyde(0.001mmole)andafewdropsofpyridinearemadeaspasteandirradiatedundermicrowavefor2-3min.Itwasthencooled,concentratedandpouredontocrushediceandfiltered.Thesolidthusobtainedwaspurifiedbyrecrystallizationfrommethanol.
1-((Benzo[d]thiazol-2-yl)methyl)-2-(2-methylbenzylidene)hydrazine(3a):
1HNMR(DMSO-d6):d=2.23(s,3H),4.71(s,2H),6.75(d,2H),7.15(d,2H),7.12(d,1H),7.33(m,3H),7.55(s,1H),9.44(brs,1H).
Mass:m/z281.9(M+H).
1-((Benzo[d]thiazol-2-yl)methyl)-2-(4-methoxybenzylidene)hydrazine(3b):
1HNMR(DMSO-d6):d=3.77(s,3H),4.76(s,2H),7.21(d,2H),7.31(d,2H),7.40-7.46(m,4H),7.55(s,1H),9.12(brs,1H).
Mass:m/z298.4(M+H).
1-((Benzo[d]thiazol-2-yl)methyl)-2-(3-methoxybenzylidene)hydrazine(3c):
1HNMR(DMSO-d6):d=3.71(s,3H),4.85(s,2H),7.01(d,2H),7.21(d,2H),7.24-7.35(m,4H),7.62(s,1H),9.31(brs,1H).
Mass:m/z297.8(M+H).
1-((Benzo[d]thiazol-2-yl)methyl)-2-(4-chlorobenzylidene)hydrazine(3d):
1HNMR(DMSO-d6):d=4.78(s,2H),7.03(d,2H),7.12(d,2H),7.21-7.25(m,4H),7.56(s,1H),9.19(brs,1H).
Mass:m/z302.9(M+H).
1-((Benzo[d]thiazol-2-yl)methyl)-2-benzylidenehydrazine(3e):
1HNMR(DMSO-d6):d=4.88(s,2H),6.85-7.10(m,5H),7.19-7.29(m,4H),7.62(s,1H),9.31(brs,1H).
Mass:m/z267.8(M+H).
Benzo[d]thiazol-2-yl)-N-(5-aryl-1H-1,2,3-triazol-1-yl)methanamines:
Toasolutionof1-((benzo[d]thiazol-2-yl)methyl)-2-(4-methylbenzylidene)hydrazine(3a)(0.001mmole)inDMSO,diazomethane(0.001mmole)wasaddedandiraadiatedundermicrowavefor2-3min.Thereactionmixturewascooledandpouredintocrushedice,andthenfiltered.Thesolidobtainedwaspurifiedbyrecrystalization.
Benzo[d]thiazol-2-yl)-N-(5-(2-methylphenyl)-1H-1,2,3-triazol-1-yl)methanamine:
1HNMR(DMSO-d6):d=2.35(s,3H),4.83(s,2H),7.05(d,2H),7.11(m,2H),7.29(d,2H),7.50(d,2H),7.61(s,1H),9.18(brs,1H).
Mass:m/z398.1(M+H).
Benzo[d]thiazol-2-yl)-N-(5-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methanamine:
1HNMR(DMSO-d6):d=3.78(s,3H),4.88(s,2H),7.107.21(m,4H),7.29(d,2H),7.39(d,2H),7.59(s,1H),9.30(brs,1H).
Mass:m/z414.3(M+H).
Benzo[d]thiazol-2-yl)-N-(5-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methanamine:
1HNMR(DMSO-d6):d=3.85(s,3H),4.84(s,2H),7.107.22(m,4H),7.31(d,2H),7.41(d,2H),7.59(s,1H),9.28(brs,1H).
Mass:m/z414.3(M+H).
Benzo[d]thiazol-2-yl)-N-(5-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)methanamine:
1HNMR(DMSO-d6):d=4.81(s,2H),7.10(d,2H),7.12(d,2H),7.22(d,2H),7.38(d,2H),7.58(s,1H),9.39(brs,1H).
Mass:m/z418.1(M+H).
Benzo[d]thiazol-2-yl)-N-(5-(4-chlorophenyl)-1H-1,2,3-triazol-1-yl)methanamine:
1HNMR(DMSO-d6):d=4.78(s,2H),7.02-7.22(m,5H),7.29(d,2H),7.41(d,2H),7.60(s,1H),9.28(brs,1H).
Mass:m/z383.8(M+H).
RESULTSANDDISCUSSION:
2-(Chloromethyl)benzo[d]thiazolereactswithhydrazinetoform 1-((benzo[d]thiazol-2-yl)methyl)hydrazine(2),whichoncondensationwitharomaticaldehydesconvertsinto1-((4-(benzo[d]thiazol-2-yl)phenyl)methyl)-2-arylidenehydrazines(3a-f).Compounds3a-fonreactionwiththioglycolicacidanddiazomethaneleadtoform(4-(benzo[d]thiazol-2-yl)phenyl)-N-(5-aryl-1H-1,2,3-triazol-1-yl)methanaminesrespectively(4a-f).Compound4cwasmostactiveagainstbothgroupsofmicroorganisms(Table1)comparedtoallothercompounds.Compound4e&4fweretheleasteffectivewhencomparedtoallthetestedbacterialstrains.HighestactivitywasseenagainstStaph.aureusfollowedbyBacillussubtilis.
Table1:Antibacterialactivityof(4-(benzo[d]thiazol-2-yl)phenyl)-N-(5-aryl-1H-1,2,3-triazol-1-yl)methanamines(4a-f).
|
NameoftheOrganism |
4a (50µg/50µl) |
4b (50µg/50µl) |
4c (50µg/50µl) |
4d(50µg/50µl) |
4e (50µg/50µl) |
4f (50µg/50µl) |
Ampicillin (25µg/50µl) |
|
Escherichiacoli |
3.6 |
6.4 |
6.8 |
6.2 |
3.6 |
4.2 |
10.0 |
|
Bacillussubtilis |
7.0 |
3.8 |
7.4 |
7.0 |
4.2 |
3.8 |
10.2 |
|
Klebsiellapneumoniae |
5.2 |
6.8 |
6.6 |
5.2 |
3.4 |
5.2 |
11.2 |
|
Staphylococcusaureus |
3.6 |
3.4 |
8.4 |
6.5 |
5.4 |
6.0 |
11.0 |
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Receivedon03.03.2018Modifiedon05.04.2018
Acceptedon16.04.2018İAJRCAllrightreserved