research article regioselective synthesis of some...

Research ArticleRegioselective Synthesis of Some Pyrazole Scaffolds Attached toBenzothiazole and Benzimidazole Moieties

Nabila A Kheder12 Yahia N Mabkhot3 Fawzia R Zahian2 and Sara S Mohamed2

1 Department of Chemistry Faculty of Science Cairo University Giza 12613 Egypt2 Department of Pharmaceutical Chemistry Faculty of Pharmacy King Khalid University Abha 61441 Saudi Arabia3 Department of Chemistry College of Science King Saud University PO Box 2455 Riyadh 11451 Saudi Arabia

Correspondence should be addressed toNabilaAKheder nabila abdelshafyyahoocomandYahiaNMabkhot yahiaksuedusa

Received 7 January 2014 Accepted 5 February 2014 Published 10 March 2014

Academic Editor Nihal Onul

Copyright copy 2014 Nabila A Kheder et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Condensation of 2-(benzothiazol-2-yl)acetonitrile (1) or 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile (2) with thiophene-2-carbaldehyde afforded the corresponding acrylonitrile derivatives 3 or 4 respectively The 13-dipolar cycloaddition reaction ofthe acrylonitrile 3 or 4 with nitrile-imine 6 gave novel pyrazole derivatives pendant to benzothiazole and benzimidazole Thepyrazoline derivative 7 was converted into the corresponding pyrazole derivative 11 via thermal elimination of hydrogen cyanideupon heating in sodium ethoxide solution The structures of the synthesized products were confirmed by IR 1H NMR and massspectral techniques

1 Introduction

Benzothiazole derivatives have been reported to possessdiverse biological properties [1 2] Benzimidazole is aninteresting heterocyclic ring system because it is presentin naturally occurring cyanocobalamin and several knowncommercialized drugs such as mebendazole astemizoleand emedastine difumarate Moreover they have shownanthelmintic [3] and antimicrobial activities [4ndash6] Alsomany benzimidazole derivatives are used as inhibitors ofHIV-1 that causes AIDS [7ndash9] as well as anticancer agents[10] In addition pyrazoline derivatives have been foundantifungal [11] antidepressant [12ndash15] anticonvulsant [1415] anti-inflammatory [16] antibacterial [17] and antitumor[18] properties Also thiophene derivatives are importantheterocycles found in several biologically active and naturalcompounds [19ndash21] For example 2-amino-3-aroylthiophenederivatives are reported as agonist allosteric enhancers atthe A1 adenosine receptor [22 23] In view of the above-mentioned findings and in continuation of our previouswork aimed at the synthesis of a variety of heterocyclic ringsystems for biological and pharmacological evaluation [24ndash29] we report here an efficient method for the synthesis

of some pyrazole derivatives attached to benzothiazole andbenzimidazole moieties

2 Experimental Section

21 Materials and Methods All melting points were mea-sured on a Gallenkamp melting point apparatus (Weiss-Gallenkamp London UK) The infrared spectra wererecorded in potassium bromide disks on a Pye Unicam SP3300 and Shimadzu FT-IR 8101 PC infrared spectrophotome-ters (Pye Unicam Ltd Cambridge England and ShimadzuTokyo Japan resp) The NMR spectra were recorded on aVarian Mercury VX-300 NMR spectrometer (Varian PaloAlto CA USA) 1H spectra were run at 300MHz in deuter-ated chloroform (CDCl

3) or dimethyl sulphoxide (DMSO-

d6) Chemical shifts were related to that of the solvent

Mass spectra were recorded on a Shimadzu GCMS-QP1000 EX mass spectrometer (Shimadzu) at 70 eV The start-ing materials 2-(benzothiazol-2-yl)acetonitrile (1) [30] 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile (2) [31 32] and1198731015840-phenylbenzohydrazonoyl chloride 5 [33] were prepared

according to the reported literature procedures

Hindawi Publishing CorporationJournal of ChemistryVolume 2014 Article ID 581721 5 pageshttpdxdoiorg1011552014581721

2 Journal of Chemistry

22 Synthesis

221Synthesis of 2-(Benzothiazol-2-yl)-3-(thiophen-2-yl)acry-lonitrile (3) and 2-(1-Methyl-1H-benzimidazol-2-yl)-3-(thiophen-2-yl)acrylonitrile (4)

General Procedure To a mixture of acetonitrile 1 or 2(10mmol) and the thiophene 2-carbaldehyde (10mmol) inethanol (10mL) piperidine (02mL) was added and themix-ture was refluxed for 30minThe formed coloured crystallineproducts were collected by filtration washed with ethanoland dried Recrystallization from the appropriate solvent gave3 or 4 respectively

(1) 2-(Benzothiazol-2-yl)-3-(thiophen-2-yl)acrylonitrile (3)Yield (70) mp 156ndash7∘C IR (KBr) ] 2211 (CequivN) 3055(aromatic CH) cmminus1 1H NMR [DMSO-d6] 120575 734ndash760(m 3H) 804ndash818 (m 4H) 868 (s 1H) MS mz () 268(M+ 1000) 242 (781) 134 (96) 83 (114) Anal Calcd forC14H8N2S2 C 6266 H 300 N 1044 Found C 6275 H

312 N 1035

(2) 2-(1-Methyl-1H-benzimidazol-2-yl)-3-(thiophen-2-yl)acry-lonitrile (4) Yield (75) mp 100∘C (methanol) IR (KBr)] 1609 (C=N) 2207 (CequivN) 2956 (aliphatic CH) 3087(aromatic CH) cmminus1 1H NMR [DMSO-d6] 120575 40 (s 3HCH3) 725ndash736 (m 3H) 763ndash770 (m 2H) 795 (d 1H) 808

(d 1H) 847 (s 1H) MS mz () 267 (596) 265 (M+ 1000)131 (2395) 83 (447) Anal Calcd for C

15H11N3S C 6790 H

418 N 1584 Found C 6782 H 425 N 1577

222 Synthesis of 5-Cyanopyrazole Derivatives 7 and 9

General Procedure Equimolar quantities of the appropriateacrylonitrile 3 or 4 (5mmol) and 1198731015840-phenylbenzohydra-zonoyl chloride 5 (5mmol) were dissolved in dry benzene(20mL) To the resulting solution triethylamine (05mL5mmol) was added and the reaction mixture was stirred for12 h and then the solvent was distilled under reduced pres-sure The oil residue was triturated with MeOH and the solidproduct was collected by filtration washed with methanoland recrystallized from the suitable solvent to afford thecorresponding pyrazole derivatives 7 and 9 respectively

(1) 5-(Benzothiazol-2-yl)-13-diphenyl-4-(thiophen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (7) Yield (56) mp190ndash1∘C IR (KBr) ] 1600 (C=N) cmminus1 1H NMR [CDCl

3]

120575 568 (s 1H Pyrazole-H) 702ndash819 (m 17H ArH) MSmz () 465 (21) 464 (81) 463 (M+ 144) Anal Calcd forC27H18N4S2 C 7010 H 392 N 1211 Found C 7005 H

385 N 1217

(2) 5-(1-Methyl-1H-benzimidazol-2-yl)-13-diphenyl-4-(thio-phen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (9) Yield(45) mp 176ndash7∘C (ethanol) IR (KBr) ] 1600 (C=N) cmminus1

1H NMR [CDCl3] 120575 371 (s 3H CH

3) 566 (s 1H Pyrazole-

H) 695ndash796 (m 17H ArH) For C28H21N5S Calcd C 7318

H 461 N 1524 Found C 7309 H 466 N 1518

(3) Synthesis of 2-(13-diphenyl-4-(thiophen-2-yl)-1H-pyrazol-5-yl)benzothiazole (11) A mixture of 5-cyanopyrazole 7(138 g 3mmol) and sodiumethoxide (prepared from sodiummetal (007 g 3mmol) in EtOH (15mL)) was heated underreflux for 1 h and then left to cool The precipitated solid wascollected by filtration washed with water and recrystallizedfrom ethanol to give compound 11 in 75 yield mp 178ndash9∘C(ethanol) IR (KBr) ] 1600 (C=N) cmminus1 1H NMR [CDCl

3] 120575

704ndash799 (m ArH) MSmz () 438 (16) 437 (81) 436 (M+254) 352 (13) 134 (28) 83 (16) 77 (1000) For C

26H17N3S2

Calcd C 7170 H 393 N 965 Found C 7179 H 398 N960

3 Results and Discussion

The key starting materials 2-(benzothiazol-2-yl)acetonitrile(1) [30] and 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile(2) [31 32] are characterized by the presence of an activemethylene aswell as nitrile functionwhichmakes them activeso they can be used as a precursors for the synthesis ofbiologically and chemically active compounds In the presentwork the synthetic potential of the acrylonitriles 3 and 4 hasbeen explored

The usual method for the synthesis of acrylonitrile 3 or4 employs condensation of 2-(benzothiazol-2-yl)acetonitrile(1) or 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile (2)with thiophene-2-carbaldehyde in refluxing ethanol contain-ing a catalytic amount of piperidine (Scheme 1) The ana-lytical and spectroscopic data were consistent with the finalproducts 3 and 4 (see Section 2)

Treatment of compound 3 with nitrile imine 6 (gen-erated in situ from 1198731015840-phenylbenzohydrazonoyl chloride 5[33] by the action of triethylamine in benzene) affordedonly one cycloadduct as deduced from TLC and 1HNMR analysis of the crude reaction product (Scheme 2)The structure of the isolated cycloadduct was assignedas 5-(benzothiazol-2-yl)-13-diphenyl-4-(thiophen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (7) based on its ele-mental analysis and its spectroscopic data The distinctionbetween the two possible regioisomeric cycloadducts 7 and8 (Figure 1) was made on the basis of the IR and 1H NMRspectra of the isolated product

The structure of the product 7 was in agreement with itselemental analysis and spectroscopic data Although com-pound 7 bears a nitrile function its IR spectrum did notafford nitrile absorption band similar to the case of aliphaticnitriles activated by a nitrogen or oxygen atom in the 120572-position [34 35] This similarity of the absence of the nitrileabsorption in the IR spectrum excludes the possibility of theother regioisomer 8 for the isolated product This is becausecompound of type 8 is expected to exhibit strong nitrileabsorption in their IR spectra [36]

Journal of Chemistry 3

N

X CN

SN

X CN

S+

1 2 3 4

CHOndashH

2O

1 3 X = S2 4 X = NMe

Scheme 1

N

X CN

N

X

NN Ph

PhN

X

N NPh

Ph

5

Cl

NN

NN

PhPh

PhPh

H

HH

NCNCS

S

S

TEA

+

+

3 4 6

8 107 9

3 7 8 X = S4 9 10 X = NMe

ndashHCl

minus

Scheme 2

Versus

N

SNC

8

S

NNPh Ph

N

S

NN

7

S

Ph Ph

NC

Figure 1 The two possible regioisomeric cycloadducts 7 and 8


N

S

N N7

PhPh

Ph

PhN

S

N N

11

EtONaNC

H

S

S

ndashHCN

Scheme 3

In analogous manner the nitrile imine 6 added regiose-lectively to the carbon-carbon double bond of 2-(1-methyl-1H-benzimidazol-2-yl)-3-(thiophen-2-yl)acrylonitrile (4) inbenzene at room temperature to afford 5-(1-methyl-1H-benzoimidazol-2-yl)-13-diphenyl-4-(thiophen-2-yl)-45-di-hydro-1H-pyrazole-5-carbonitrile (9) (Scheme 2) The struc-ture of the latter product was assigned on the basis of itselemental analysis and spectral data For example its IRspectrum revealed no nitrile absorption band Moreoverstructure 9 was confirmed by 1H NMR spectrum whichrevealed a sharp singlet signal at 120575 566 assignable to theproton at C-4 of the pyrazoline ring This chemical shiftis very similar to those reported for the C-4 proton of45-dihydro-1H-pyrazole derivatives [37]

When compound 7 was heated in ethanolic sodiumethoxide solution it afforded the pyrazole derivative 11 inhigh yield (Scheme 3) The structure of the product was con-firmedby 1HNMRspectra which revealed the disappearanceof the proton signal at C-4

4 Conclusion

We have successfully synthesized some pyrazole deriva-tives attached to benzothiazole and benzimidazole moietiesof biological and pharmacological interest via 13-dipolarcycloaddition reaction

Conflict of Interests

The authors declare that there is no conflict of interests

Acknowledgment

The authors extend their appreciation to the Deanship ofScientific Research at King Saud University for funding thework through the Research Group Project no RGP-VPP-007

References

[1] A Rana N Siddiqui and S A Khan ldquoBenzothiazoles a newprofile of biological activitiesrdquo Indian Journal of PharmaceuticalSciences vol 69 no 1 pp 10ndash17 2007

[2] G Wells T D Bradshaw P Diana et al ldquoAntitumourbenzothiazolesmdashpart 10 the synthesis and antitumour activityof benzothiazole substituted quinol derivativesrdquo Bioorganic andMedicinal Chemistry Letters vol 10 no 5 pp 513ndash515 2000

[3] Q A McKellar and E W Scott ldquoThe benzimidazoleanthelmintic agentsmdasha reviewrdquo Journal of Veterinary Pharma-cology andTherapeutics vol 13 no 3 pp 223ndash247 1990

[4] H Goker M Tuncbilek S Suzen C Kus and N Altan-lar ldquoSynthesis and antimicrobial activity of some new 2-phenyl-N-substituted carboxamido-1H-benzimidazole deriva-tivesrdquo Archiv der Pharmazie vol 334 no 5 pp 148ndash152 2001

[5] G Ayhan-Kilcigil and N Altanlar ldquoSynthesis and antimicrobialactivities of some new benzimidazole derivativesrdquo Farmaco vol58 no 12 pp 1345ndash1350 2003

[6] O O Guven T ErdoganHGoker and S Yildiz ldquoSynthesis andantimicrobial activity of some novel phenyl and benzimidazolesubstituted benzyl ethersrdquo Bioorganic and Medicinal ChemistryLetters vol 17 no 8 pp 2233ndash2236 2007

[7] A Chimirri S Grasso P Monforte et al ldquoSynthesis and bio-logical activity of novel 1H3H-thiazolo[34-a]benzimidazolesnon-nucleoside human immunodeficiency virus type 1 reversetranscriptase inhibitorsrdquo Antiviral Chemistry and Chemother-apy vol 10 no 4 pp 211ndash217 1999

[8] T M Evans J M Gardiner N Mahmood and M SmisldquoStructure-activity relationships of anti-HIV-1 N-alkoxy- andN-allyloxy-benzimidazolesrdquo Bioorganic and Medicinal Chem-istry Letters vol 7 no 4 pp 409ndash412 1997

[9] T Roth M L Morningstar P L Boyer S H Hughes RW Buckheit Jr and C J Michejda ldquoSynthesis and biologicalactivity of novel nonnucleoside inhibitors of HIV-1 reversetranscriptase 2-Aryl-substituted benzimidazolesrdquo Journal ofMedicinal Chemistry vol 40 no 26 pp 4199ndash4207 1997

[10] K-J Soderlind B Gorodetsky A K Singh N R Bachur G GMiller and J W Lown ldquoBis-benzimidazole anticancer agentstargeting human tumour helicasesrdquo Anti-Cancer Drug Designvol 14 no 1 pp 19ndash36 1999

[11] S S Korgaokar P H Patil M J Shah and H H ParekhldquoStudies on pyrazolines preparation and antimicrobial activityof 3-31015840(P-chlorophenylsulphonamidophenyl)-5 aryl-1Hacetylpyrazolinesrdquo Indian Journal of Pharmaceutical Sciences vol 58no 6 pp 222ndash225 1996

[12] E Palaska M Aytemir I T Uzbay and D Erol ldquoSynthesis andantidepressant activities of some 35-diphenyl-2-pyrazolinesrdquoEuropean Journal ofMedicinal Chemistry vol 36 no 6 pp 539ndash543 2001

[13] Y Rajendra Prasad A Lakshmana Rao L Prasoona KMurali and P Ravi Kumar ldquoSynthesis and antidepressant activ-ity of some 135-triphenyl-2-pyrazolines and 3-(210158401015840-hydroxynaphthalen-110158401015840-yl)-15-diphenyl-2-pyrazolinesrdquo Bioorganic andMedicinal Chemistry Letters vol 15 no 22 pp 5030ndash5034 2005

[14] Z Ozdemir H B Kandilci B Gumusel U Calis and A ABilgin ldquoSynthesis and studies on antidepressant and anticon-vulsant activities of some 3-(2-furyl)-pyrazoline derivativesrdquo


European Journal ofMedicinal Chemistry vol 42 no 3 pp 373ndash379 2007

[15] O Ruhoglu Z Ozdemir U Calis B Gumusel and A A BilginldquoSynthesis of and pharmacological studies on the antidepressantand anticonvulsant activities of some 135-trisubstituted pyra-zolinesrdquo Arzneimittel-ForschungDrug Research vol 55 no 8pp 431ndash436 2005

[16] R H Udupi A S Kushnoor and A R Bhat ldquoSynthesis andbiological evaluation of certain pyrazoline derivatives of 2-[6-methoxy naphthyl]-propionic acid (naproxen)rdquo Indian Journalof Heterocyclic Chemistry vol 8 no 1 pp 63ndash66 1998

[17] S Kini and A Gandhi ldquoNovel 2-pyrazoline derivatives aspotential antibacterial and antifungal agentsrdquo Indian Journal ofPharmaceutical Sciences vol 70 no 1 pp 105ndash108 2008

[18] P J Jainey and I K Bhat ldquoAntitumor analgesic and anti-inflammatory activities of synthesized pyrazolinesrdquo Journal ofYoung Pharmacists vol 4 no 2 pp 82ndash87 2012

[19] C Heyde I Zug and H Hartmann ldquoA simple route toNN-dialkyl derivatives of 2-amino-5-thiophenecarboxylatesrdquoEuropean Journal of Organic Chemistry vol 2000 no 19 pp3273ndash3278 2000

[20] A Noack and H Hartmann ldquoSynthesis and characterisationof NN-disubstituted 2-amino-5-acylthiophenes and 2-amino-5-acylthiazolesrdquoTetrahedron vol 58 no 11 pp 2137ndash2146 2002

[21] T S Jagodzinski ldquoThioamides as useful synthons in the synthe-sis of heterocyclesrdquoChemical Reviews vol 103 no 1 pp 197ndash2272003

[22] C E Tranberg A Zickgraf B N Giunta et al ldquo2-Amino-3-aroyl-45-alkylthiophenes agonist allosteric enhancers athuman a1 adenosine receptorsrdquo Journal of Medicinal Chemistryvol 45 no 2 pp 382ndash389 2002

[23] A P Kourounakis P A M van der Klein and A P IjzermanldquoElucidation of structure-activity relationships of 2-amino-3- benzoylthiophenes study of their allosteric enhancing vsantagonistic activity on adenosine A1 receptorsrdquoDrug Develop-ment Research vol 49 no 4 pp 227ndash237 2000

[24] N A Kheder S M Riyadh and A M Asiry ldquoAzoles and bis-azoles synthesis and biological evaluation as antimicrobial andanti-cancer agentsrdquo Chemical and Pharmaceutical Bulletin vol61 no 5 pp 504ndash510 2013

[25] S M Riyadh N A Kheder and A M Asiry ldquoSynthesisanticancer and antimicrobial activities of some new antipyrine-based heterocyclesrdquo Chemical Monthly vol 144 no 10 pp1559ndash1567 2013

[26] N A Kheder and Y N Mabkhot ldquoSynthesis and antimicrobialstudies of some novel bis-[134]thiadiazole and bis-thiazolependant to thieno[23-b]thiophene moietyrdquo International Jour-nal of Molecular Sciences vol 13 no 3 pp 3661ndash3670 2012

[27] Y N Mabkhot N A Kheder and A M Farag ldquoSynthesis andantimicrobial evaluation of some new tetrahydropyrimidinederivativesrdquo Heterocycles vol 83 no 3 pp 609ndash617 2011

[28] N A Kheder ldquoSynthesis of some novel bis(pyrazole)bis(pyridine) and bis(pyrazolo[51-c]-124-triazine derivativesrdquoHeterocycles vol 78 no 7 pp 1815ndash1822 2009

[29] N A Kheder ldquoConvenient synthesis of novel bis(hydrazone)and bis(indole) derivativesrdquoHeterocycles vol 78 no 5 pp 1281ndash1288 2009

[30] K Saito S Kambe Y Nakano A Sakurai and H MidorikawaldquoSynthetic studies using 120572120573-unsaturated nitriles a convenientpreparation of 13-benzothiazole derivativesrdquo Synthesis vol 3pp 210ndash212 1983

[31] R A B Copeland andA RDay ldquoThepreparation and reactionsof 2-benzimidazolecarboxylic acid and 2-benzimidazoleaceticacidrdquo Journal of the American Chemical Society vol 65 no 6pp 1072ndash1075 1943

[32] WOzegowski andDKrebs ldquoAmino acid antagonists IVExper-iments for the preparation of [I-methyl-5-bis-(p-chlorathyl)aminobenzimidazolyl-(2)]-acetic acidrdquo Journal fur PraktischeChemieChemiker-Zeitung vol 29 p 18 1965

[33] P Wolkoff ldquoA new method of preparing hydrazonyl halidesrdquoCanadian Journal of Chemistry vol 53 no 9 pp 1333ndash13351975

[34] G Butt J Cilmi P M Hoobin and R D Topsom ldquoThetransmission of resonance effects through a methylene group-spectroscopic studies on some 120572-substituted-acetonitriles andp-toluonitrilesrdquo Spectrochimica Acta A vol 36 no 6 pp 521ndash524 1980

[35] J P Jesson and H W Thompson ldquoVibrational band intensitiesof the CequivN group in aliphatic nitrilesrdquo Spectrochimica Acta vol13 no 3 pp 217ndash222 1958

[36] B HThomas andW J Orville-Thomas ldquoInfrared intensities ofV(CequivN) bandsrdquo Journal of Molecular Structure vol 7 no 1-2pp 123ndash135 1971

[37] A KMansourMM Eid andN S AMKhalil ldquoSynthesis andreactions of some new heterocyclic carbohydrazides and relatedcompounds as potential anticancer agentsrdquoMolecules vol 8 no10 pp 744ndash755 2003

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


Advances in

Physical Chemistry

Hindawi Publishing Corporationhttpwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2014

Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

SpectroscopyInternational Journal of


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy

Analytical ChemistryInternational Journal of


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Organic Chemistry International

ElectrochemistryInternational Journal of



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22 Synthesis

221Synthesis of 2-(Benzothiazol-2-yl)-3-(thiophen-2-yl)acry-lonitrile (3) and 2-(1-Methyl-1H-benzimidazol-2-yl)-3-(thiophen-2-yl)acrylonitrile (4)

General Procedure To a mixture of acetonitrile 1 or 2(10mmol) and the thiophene 2-carbaldehyde (10mmol) inethanol (10mL) piperidine (02mL) was added and themix-ture was refluxed for 30minThe formed coloured crystallineproducts were collected by filtration washed with ethanoland dried Recrystallization from the appropriate solvent gave3 or 4 respectively

(1) 2-(Benzothiazol-2-yl)-3-(thiophen-2-yl)acrylonitrile (3)Yield (70) mp 156ndash7∘C IR (KBr) ] 2211 (CequivN) 3055(aromatic CH) cmminus1 1H NMR [DMSO-d6] 120575 734ndash760(m 3H) 804ndash818 (m 4H) 868 (s 1H) MS mz () 268(M+ 1000) 242 (781) 134 (96) 83 (114) Anal Calcd forC14H8N2S2 C 6266 H 300 N 1044 Found C 6275 H

312 N 1035

(2) 2-(1-Methyl-1H-benzimidazol-2-yl)-3-(thiophen-2-yl)acry-lonitrile (4) Yield (75) mp 100∘C (methanol) IR (KBr)] 1609 (C=N) 2207 (CequivN) 2956 (aliphatic CH) 3087(aromatic CH) cmminus1 1H NMR [DMSO-d6] 120575 40 (s 3HCH3) 725ndash736 (m 3H) 763ndash770 (m 2H) 795 (d 1H) 808

(d 1H) 847 (s 1H) MS mz () 267 (596) 265 (M+ 1000)131 (2395) 83 (447) Anal Calcd for C

15H11N3S C 6790 H

418 N 1584 Found C 6782 H 425 N 1577

222 Synthesis of 5-Cyanopyrazole Derivatives 7 and 9

General Procedure Equimolar quantities of the appropriateacrylonitrile 3 or 4 (5mmol) and 1198731015840-phenylbenzohydra-zonoyl chloride 5 (5mmol) were dissolved in dry benzene(20mL) To the resulting solution triethylamine (05mL5mmol) was added and the reaction mixture was stirred for12 h and then the solvent was distilled under reduced pres-sure The oil residue was triturated with MeOH and the solidproduct was collected by filtration washed with methanoland recrystallized from the suitable solvent to afford thecorresponding pyrazole derivatives 7 and 9 respectively

(1) 5-(Benzothiazol-2-yl)-13-diphenyl-4-(thiophen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (7) Yield (56) mp190ndash1∘C IR (KBr) ] 1600 (C=N) cmminus1 1H NMR [CDCl

3]

120575 568 (s 1H Pyrazole-H) 702ndash819 (m 17H ArH) MSmz () 465 (21) 464 (81) 463 (M+ 144) Anal Calcd forC27H18N4S2 C 7010 H 392 N 1211 Found C 7005 H

385 N 1217

(2) 5-(1-Methyl-1H-benzimidazol-2-yl)-13-diphenyl-4-(thio-phen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (9) Yield(45) mp 176ndash7∘C (ethanol) IR (KBr) ] 1600 (C=N) cmminus1

1H NMR [CDCl3] 120575 371 (s 3H CH

3) 566 (s 1H Pyrazole-

H) 695ndash796 (m 17H ArH) For C28H21N5S Calcd C 7318

H 461 N 1524 Found C 7309 H 466 N 1518

(3) Synthesis of 2-(13-diphenyl-4-(thiophen-2-yl)-1H-pyrazol-5-yl)benzothiazole (11) A mixture of 5-cyanopyrazole 7(138 g 3mmol) and sodiumethoxide (prepared from sodiummetal (007 g 3mmol) in EtOH (15mL)) was heated underreflux for 1 h and then left to cool The precipitated solid wascollected by filtration washed with water and recrystallizedfrom ethanol to give compound 11 in 75 yield mp 178ndash9∘C(ethanol) IR (KBr) ] 1600 (C=N) cmminus1 1H NMR [CDCl

3] 120575

704ndash799 (m ArH) MSmz () 438 (16) 437 (81) 436 (M+254) 352 (13) 134 (28) 83 (16) 77 (1000) For C

26H17N3S2

Calcd C 7170 H 393 N 965 Found C 7179 H 398 N960

3 Results and Discussion

The key starting materials 2-(benzothiazol-2-yl)acetonitrile(1) [30] and 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile(2) [31 32] are characterized by the presence of an activemethylene aswell as nitrile functionwhichmakes them activeso they can be used as a precursors for the synthesis ofbiologically and chemically active compounds In the presentwork the synthetic potential of the acrylonitriles 3 and 4 hasbeen explored

The usual method for the synthesis of acrylonitrile 3 or4 employs condensation of 2-(benzothiazol-2-yl)acetonitrile(1) or 2-(1-methyl-1H-benzimidazol-2-yl)acetonitrile (2)with thiophene-2-carbaldehyde in refluxing ethanol contain-ing a catalytic amount of piperidine (Scheme 1) The ana-lytical and spectroscopic data were consistent with the finalproducts 3 and 4 (see Section 2)

Treatment of compound 3 with nitrile imine 6 (gen-erated in situ from 1198731015840-phenylbenzohydrazonoyl chloride 5[33] by the action of triethylamine in benzene) affordedonly one cycloadduct as deduced from TLC and 1HNMR analysis of the crude reaction product (Scheme 2)The structure of the isolated cycloadduct was assignedas 5-(benzothiazol-2-yl)-13-diphenyl-4-(thiophen-2-yl)-45-dihydro-1H-pyrazole-5-carbonitrile (7) based on its ele-mental analysis and its spectroscopic data The distinctionbetween the two possible regioisomeric cycloadducts 7 and8 (Figure 1) was made on the basis of the IR and 1H NMRspectra of the isolated product

The structure of the product 7 was in agreement with itselemental analysis and spectroscopic data Although com-pound 7 bears a nitrile function its IR spectrum did notafford nitrile absorption band similar to the case of aliphaticnitriles activated by a nitrogen or oxygen atom in the 120572-position [34 35] This similarity of the absence of the nitrileabsorption in the IR spectrum excludes the possibility of theother regioisomer 8 for the isolated product This is becausecompound of type 8 is expected to exhibit strong nitrileabsorption in their IR spectra [36]


N

X CN

SN

X CN

S+

1 2 3 4

CHOndashH

2O

1 3 X = S2 4 X = NMe

Scheme 1

N

X CN

N

X

NN Ph

PhN

X

N NPh

Ph

5

Cl

NN

NN

PhPh

PhPh

H

HH

NCNCS

S

S

TEA

+

+

3 4 6

8 107 9

3 7 8 X = S4 9 10 X = NMe

ndashHCl

minus

Scheme 2

Versus

N

SNC

8

S

NNPh Ph

N

S

NN

7

S

Ph Ph

NC



N

S

N N7

PhPh

Ph

PhN

S

N N

11

EtONaNC

H

S

S

ndashHCN

Scheme 3



4 Conclusion




Acknowledgment


References

















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

X CN

SN

X CN

S+

1 2 3 4

CHOndashH

2O

1 3 X = S2 4 X = NMe

Scheme 1

N

X CN

N

X

NN Ph

PhN

X

N NPh

Ph

5

Cl

NN

NN

PhPh

PhPh

H

HH

NCNCS

S

S

TEA

+

+

3 4 6

8 107 9

3 7 8 X = S4 9 10 X = NMe

ndashHCl

minus

Scheme 2

Versus

N

SNC

8

S

NNPh Ph

N

S

NN

7

S

Ph Ph

NC



N

S

N N7

PhPh

Ph

PhN

S

N N

11

EtONaNC

H

S

S

ndashHCN

Scheme 3



4 Conclusion




Acknowledgment


References

















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


N

S

N N7

PhPh

Ph

PhN

S

N N

11

EtONaNC

H

S

S

ndashHCN

Scheme 3



4 Conclusion




Acknowledgment


References

















































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



































Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of

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