Research Article Zirconyl (IV) Nitrate as Efficient and ...downloads.hindawi.com/journals/jchem/2013/108318.pdf · and most Lewis acids immediately react with water rather thansubstrates[

Hindawi Publishing CorporationJournal of ChemistryVolume 2013 Article ID 108318 7 pageshttpdxdoiorg1011552013108318

Research ArticleZirconyl (IV) Nitrate as Efficient and Reusable Solid Lewis AcidCatalyst for the Synthesis of Benzimidazole Derivatives

Pratapsinha B Gorepatil Yogesh D Mane and Vilas S Ingle

Department of Chemistry Research Centre S C S College Omerga Osmanabad 413 606 India

Correspondence should be addressed to Pratapsinha B Gorepatil gorepatilpratap1986gmailcomand Vilas S Ingle inglevilas71yahooin

Received 27 April 2013 Accepted 24 May 2013

Academic Editor Stojan Stavber

Copyright copy 2013 Pratapsinha B Gorepatil et alThis is an open access article distributed under the Creative CommonsAttributionLicense which permits unrestricted use distribution and reproduction in anymedium provided the originalwork is properly cited

The present paper introduces a simple and efficient method for the synthesis of substituted benzimidazoles by heterocyclization ofdifferent o-phenylenediamines and substituted aromatic carboxylic acidaldehyde in the presence of zirconyl nitrate as catalyst inethanol under reflux which produced excellent yield of corresponding benzimidazoles in a short reaction time with reusability ofcatalyst

1 Introduction

Heteroaromatic compounds have awestruck significant at-tention in the design of biologically active molecules andadvanced organic materials [1 2] Because of their pharma-ceutical and biological significance nitrogen-containing het-erocyclic compounds have attracted considerable attention asan important class of organic molecules In the continuationof our search for efficient synthetic methodologies for bio-logically important heterocyclic compounds benzimidazoleshave been chosen as target molecules benzimidazole deriva-tives have several medicinal uses such as antivirals antican-cer antihypertensive antihistamines antiparasitics and anti-ulcer [3ndash8]

Diverse synthetic efforts for benzimidazoles have beenreported with the most common method being the hetero-cyclization of o-phenylenediamine and carboxylic acids [910] aldehydes [11 12] alcohols [13] and nitriles [14 15] whichusually require strong acid high temperature and sometimesphotoirradiation conditions preciousmetal salts [16] molec-ular oxygen [17 18] or 23-dichloro-56-dicyano-14-benzo-quinone as oxidant [19] Recently a variety of catalysts suchas homogeneous Lewis acids [20] pyridinium-p-toluenes-ulfonate [20] ultrasonic [21] I

2KIK

2CO3H2O [22] ionic

liquids [23] (bromodimethyl) sulfonium bromide [24] andpolyaniline-sulfate [25] and a tandem oxidation process [26]have been used for the synthesis of benzimidazole derivatives

Lewis acid catalyst has attracted considerable attention inheterogeneous catalysis [27] Although various kinds of Lewisacids have been developed most of them are used only understrictly anhydrous conditions in excess and with hazardousorganic solvents which are not environment friendly Thepresence of even a small amount of water stops the reactionsand most Lewis acids immediately react with water ratherthan substrates [28]

In this context in the present study we report here theuse of zirconyl nitrate as eco-friendly water-soluble Lewisacid catalyst for the synthesis of substituted benzimidazoleIn recent years Zr(IV) compounds have gained special atten-tion as catalysts in organic synthesis and some of these arestable in aqueous media [29ndash31] In the continuation of ourinterest in synthesis of nitrogen-containing heterocyclic com-pounds [32] herein wefoundedthe application of ZrO(NO

3)2

as a Lewis acid catalyst for the synthesis of substituted ben-zimidazoles viathe condensation reaction between o-phe-nylenediamine and aldehyde carboxylic acid derivatives(Scheme 1)

2 Experimental Section

All chemicals and reagents were purchased from commer-cial suppliers and used without further purification Col-umn chromatography was carried out with silica gel (200ndash300mesh) eluting with ethyl acetate and petroleum ether

2 Journal of Chemistry

ZrO(NO3)2 ZrO(NO3)2

COOHRR

HN

NR CHO

NH2

NH2

R

HN

N Reflux 2ndash5 h Reflux 2ndash4 h78ndash96 74ndash98

Scheme 1 Zirconyl nitrate-catalyzed synthesis of substituted benzimidazoles

Thin layer chromatographywas carried out usingMerck silicagel GF254 plates All products were characterized by NMR1HNMR spectra were recorded at 400MHz and 13CNMRspectra were recorded at 100MHz withCDCl3 orDMSO-119889

6

as solvent Chemical shifts are reported in parts per million(ppm) downfield from TMS with the solvent resonance asthe internal standard Coupling constants (J) are reported inHz and refer to apparent peak multiplications HRMS wasrecorded on an ESI source

3 A General Procedure for Synthesis ofSubstituted Benzimidazoles

05 (weight) of zirconyl nitrate was added to a solution ofaldehydecarboxylic acid (1mmol) and o-phenylenediamine(1mmol) in ethanol (10mL)The reactionmixture was stirredunder reflux for 2ndash6 h The progress of reaction was moni-tored by TLC After the completion of the reaction the reac-tionmixture was cooled to room temperature 20mL of etha-nol was added and resulting solution was filtered to removethe catalystThe solvent was removed under reduced pressureby distillation and residue was purified by column chroma-tography on silica gel using n-hexane-ethyl acetate or ethylacetate-petroleum ether as an elutingagent The structures ofthe benzimidazolewere characterized by 1HNMR 13CNMRFTIR and HRMS and were mostly known compounds

Note Excellent yield was obtained when 1 (weight) of zirco-nyl nitrate was used with carboxylic acids

Characterization of selected compounds is as follows

31 2-Methyl-1H-benzimidazole (Table 2 Entry 1) Solid mp178ndash180∘C (lit34mp 175-176∘C) IR (KBr) 3860 3735 36012815 2310 1700 1513 735 cmminus1 1HNMR (DMSO-d

6 400

MHz) 120575 982 (s 1H) 73 (d J = 80Hz 2H) 759 (d 2H) 270(s 3H) 13CNMR (DMSO-d

6 100MHz) 120575 15135 13860

12221 11448 1490 MS (EImz) 132 [M+]

32 2-Phenyl-1H-benzimidazole (Table 2 Entry 2) Solid mp300ndash302∘C (lit35mp 301ndash303∘C) IR (KBr) 3566 2360 17481716 1698 1683 1652 1616 cmminus1 1HNMR (DMSO-d

6 400

MHz) 120575 1292 (s 1H) 819 (d J = 80Hz 2H) 761ndash755 (m4H) 752ndash748 (m 1H) 723ndash719 (m 2H) 13CNMR (DMSO-d6 100MHz) 120575 1517 1443 1355 1307 1303 1294 1269

1230 1221 1194 1118 MS (EImz) 194[M+]

33 2-(4-Nitrophenyl)-1H-benzimidazole (Table 2 Entry 3)Solid mp 324ndash326∘C (lit35mp 326ndash327∘C) IR (KBr) 3740

3644 3058 1766 1691 1658 1649 1597 1563 1536 14931415 722 695 cmminus1 1HNMR (DMSO-d

6 400MHz) 120575 1330

(s 1H) 842 (s 4H) 774 (s 1H) 760 (s 1H) 728 (s 2H)13CNMR (DMSO-d

6 100MHz) 120575 1627 1578 1494 1482

1365 1278 1274 1247 1233 1198 1124 MS (EI mz) 239[M+]

34 5-Methyl-2-phenyl-1H-benzimidazole (Table 2 Entry 7)Solid mp 245ndash247∘C (lit36mp 243-244∘C) IR (KBr) 31091511 1463 1354 1176 739 701 657 cmminus1 1HNMR (CDCl

3

400MHz) 120575 854 (s 1H) 812ndash811 (m 2H) 753 (d J = 55Hz1H) 740 (m 2H) 728 (s 2H) 708 (d J = 55Hz 1H) 245 (s3H) 13CNMR (DMSO 100MHz) 120575 1513 1318 1308 13011296 1294 1292 1268 1266 1264 1240 218 MS (EImz)208 [M+]

35 2-(p-Tolyl)-1H-benzimidazole (Table 2 Entry 16) Solidmp 264ndash266∘C (lit35mp 263ndash265∘C) 1HNMR (DMSO-d

6

400MHz) 120575 1283 (s 1H) 808 (d J = 78Hz 2H) 759 (s2H) 737 (d J = 78Hz 2H) 721ndash719 (m 2H) 239 (s 3H)13CNMR (DMSO-d

6 100MHz) 120575 1519 1443 1400 1354

1300 1279 1269 1228 1220 1192 1117 214 MS (EI mz)208 [M+]

36 2-(4-Methoxyphenyl)-1H-benzimidazole (Table 2 Entry6) Solid mp 235ndash237∘C (lit35 mp 234-235∘C) 1HNMR(DMSO-d

6 400MHz) 120575 744 (d J = 72Hz 1H) 725ndash719 (m

2H) 709 (d J = 88Hz 2H) 695 (d J = 84Hz 2H) 685 (dJ = 88Hz 2H) 383 (s 3H) 13CNMR (DMSO-d

6 100MHz)

120575 1608 1536 1432 1363 1293 1279 1225 1194 1147 11461115 558 MS (EImz) 224 [M+]

37 5-Nitro-2-(4-methylphenyl)-1H-benzimidazole (Table 2Entry 12) Solid mp 288∘C (lit mp 290ndash292∘C) IR (KBr)3858 3747 3672 3059 2349 1805 1691 1649 1641 1597 14931135 1025 722 695 cmminus1 1HNMR (DMSO-d

6 400MHz) 120575

1350 (s 1H) 810 (d J = 77Hz 2H) 795 (d J = 89Hz 1H)739 (d J = 78Hz 2H) 673 (s 1H) 661 (d J = 89Hz 1H)239 (s 3H) 13CNMR (DMSO-d

6 100MHz) 120575 1562 1361

1302 1291 1274 1268 1192 1186 1151 1128 1121 215 MS(EImz) 254 [M+]

38 2-(4-Chlorophenyl)-1H-benzimidazole (Table 2 Entries 4and 15) Solid mp 294ndash296∘C (lit35mp 290ndash292∘C) IR(KBr) 3606 3001 2818 2310 1700 1513 735 cmminus1 1HNMR(DMSO-d

6 400MHz) 120575 1300 (s 1H) 820 (d J = 84Hz 2H)

Journal of Chemistry 3

Table 1 Optimization of reaction conditionsa for synthesis of substituted benzimidazoles from benzaldehydebenzoic acid with o-phenylenediamine

SolventCatalyst

+

OHC

HOOC

HN

N

NH2

NH2

Entry Solvents Catalyst conc(weight )

Yieldb ()reaction time (h)Benzaldehyde Benzoic acid

1 Ethanol No catalyst 276 45142 Ethanol 03 583 6563 Ethanol 05 962 9034 Ethanol 1 9425 9435 Dioxane 05 823 75456 EtOAc 05 8535 7857 DCM 1 704 806aReflux the reaction mixture bIsolated yield

HN

N

R

R

R

O R

OH

OHHO

minusH2O

H

H

N

N

H

HO

N

NH2NH2

NH2

+

Zr(IV)

Zr(IV)

Scheme 2 Possible mechanism for the Zr(IV)-catalyzed synthesis of benzimidazoles form carboxylic acids

764 (d J = 84Hz 4H) 724ndash721 (m 2H) 13CNMR (DMSO-d6 100MHz) 120575 1506 1443 1350 1348 1295 1286 1282

1229 1225 1194 1119 MS (EImz) 228 [M+]

39 5-Methyl-2-(4-nitrophenyl)-1H-benzimidazole (Table 2Entries 9 and 18) Solid mp 278ndash280∘C (lit mp 280ndash282∘C)1HNMR (DMSO-d

6 400MHz) 120575 839 (s 5H) 754 (d J =

80Hz 1H) 743 (s 1H) 709 (d J = 83Hz 1H) 244 (s 3H)13CNMR (DMSO-d

6 100MHz) 120575 1590 1536 1432 1363

1310 1293 1279 1194 1147 1146 1115 311 MS (EI mz)254 [M+]

310 2-(3-Methylphenyl)-1H-benzimidazole (Table 2 Entries 5and 19) Solid mp 285ndash287∘C (lit mp 286ndash288∘C) 1HNMR(DMSO-d

6 400MHz) 120575 1288 (s 1H) 803 (s 1H) 798 (d J

= 78Hz 1H) 760 (s 2H) 744 (t J = 76Hz 1H) 731 (d J =76Hz 1H) 723ndash719 (m 2H) 242 (s 3H) 13CNMR (DMSO-d6 100MHz)120575 1562 1431 1414 1361 1301 1274 1268 1267

1183 1128 215 MS (EImz) 208 [M+]

4 Results and Discussion

We examined the cyclocondensation of o-phenylenediaminewith different substituted aromatic carboxylic acidaldehydesusing zirconyl nitrateZr(IV) as a Lewis acid catalyst for thesynthesis of substituted benzimidazoles While establishing anew synthetic route solvent and catalyst play an importantrole in organic synthesis We studied the effect of solventand molecular percent weight of catalyst on the synthesis ofbenzimidazoles using ZrO(NO

3)2 Among various solvents


Table 2 Synthesis of substituted benzimidazoles by ZrO(NO3)2-catalyzed reaction between aromatic aldehydes and carboxylic acids witho-phenylenediamines

Entry Amine Reactant Product Yield()

Time(h)

1

NH2

NH2

OHC CH3

HN

N

CH3

85 39

2

NH2

NH2

OHC

HN

N

96 2

3

NH2

NH2

OHC NO2

HN

N

NO2

98 32

4

NH2

NH2

OHC Cl

HN

N

Cl 97 31

5

NH2

NH2

OHC

CH3

HN

N

CH3

94 35

6

NH2

NH2

OHC OCH3

HN

N

OCH3

78 43

7

NH2

NH2H

3C

OHC

HN

NH3C

86 35

8

NH2

NH2

H3C

OHC Cl

HN

N

Cl

H3C

94 23

9

NH2

NH2H

3C

OHC NO2

HN

N

NO2

H3C

95 25

10

H3C

NH2

NH2

OHC

CH3

HN

N

CH3

H3C

78 35


Table 2 Continued


Time(h)

11

NH2

NH2O

2N

OHC Cl

HN

N

Cl

O2N

92 3

12

NH2

NH2O

2N

OHC CH3

HN

NO2N

CH3 76 45

13

NH2

NH2

HOOC

HN

N

96 3

14

NH2

NH2

HOOC NO2

HN

N

NO2

97 25

15

NH2

NH2

HOOC Cl

HN

N

Cl 95 35

16

NH2

NH2

HOOC CH3

HN

N

CH3

80 45

17

NH2

NH2H

3C

HOOC CH3

HN

N

CH3

H3C

82 38

18

H3C

NH2

NH2

HOOC NO2

HN

N

NO2

H3C

96 27

19

H3C

NH2

NH2

HOOC

CH3

HN

N

CH3

H3C

78 4

20

NH2

NH2

O2N

HOOC

HN

NO2N

82 41

21

O2N

NH2

NH2

HOOC Cl

HN

N

Cl

O2N

85 31


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield

Table 3 Catalyst reusability study for the reaction of benzaldehyde with o-phenylenediaminea

HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2

Entry Yield b () Catalyst recovery ()1 96 972 93 943 90 924 88 91aReaction condition benzaldehyde (1mmol) o-phenylenediamine (1mmol) ZrO(NO3)2 (05 wt) ethanol reflux bIsolated yield

dichloromethane dioxane ethyl acetate and ethanol wereused and their results are shown in Table 1

Initially the reaction between o-phenylenediamine (1mmol) and benzaldehyde (1mmol) was selected for the syn-thesis of benzimidazoles as amodel reaction for optimizationIt was found that ethanol gave the highest yield (96) whenusing 05 zirconyl nitrate for 2 h compared to other solventsand different molecular percent weight of catalyst used in thereaction (Table 1 entry 3)

In the continuation of our scheme to search for betteralternative route by using the same catalyst we also carriedout the reaction between substituted benzoic acids with o-phenylenediamine To optimize this reactionwe used benzoicacid (1mmol) as a model it also produced good yield of 2-phenyl-1H-benzimidazole in ethanol but excellent yield wasobtainedwhen 1of zirconyl nitratewas usedwith carboxylicacid (Table 1 entry 4) As per a possible mechanism thereaction proceeds via the activation of carboxylic acid byZr(IV) which is shown in Scheme 2

After the optimization of the reaction condition we ex-tended the study with different o-phenylenediamine againstdifferent aromatic and aliphatic aldehydes aromatic carbox-ylic acids In general most of the reactions proceeded verysmoothly to give corresponding substituted benzimidazolesin moderate to excellent yields and the results are summa-rized in Table 2 (entries 1ndash22)

Then we examined the general applicability of this syn-thetic route by using a variety of substituted benzaldehydesand carboxylic acids for the study of electronic factors It isclearly seen from the Table 2 that the electron-deficient ana-logues give good yield in a short reaction time as comparedto electron-rich ones Another advantage of the presentmeth-odology is the reusability of the catalyst After the completion

of the reaction the catalyst is removed by the simple filtrationand it is treated with dichloromethane The catalyst is driedat 80∘C for 2 h and can be reused for another reaction Therecycled catalyst is used for four consecutive reactions with-out any appreciable change in its catalytic activity the resultsare shown in Table 3

5 Conclusion

In conclusion a facile methodology for synthesis of substi-tuted benzimidazoles in good to excellent yield is providedby zirconyl-nitrate-catalyzed condensation reaction of sub-stituted o-phenylenediamines and aldehydecarboxylic acidThe zirconyl-nitrate-catalyzed system reduced the reactiontime and increased the yieldsThe environmental compatibil-ity excellent reusability of the catalyst and ease for isolationof product are among the other added advantages that madethis approach a good alternative way for the synthesis ofbenzimidazole derivatives

Acknowledgment

Pratapsinha B Gorepatil is thankful to the CSIR New Delhifor Junior Research Fellowship (JRF)

References

[1] M S M Ahmed K Kobayashi and A Mori ldquoOne-pot con-struction of pyrazoles and isoxazoles with palladium-catalyzedfour-component couplingrdquo Organic Letters vol 7 no 20 pp4487ndash4489 2005

[2] M Kidwai R Poddar S Diwaniyan and R C Kuhad ldquoLaccasefrom basidiomycetous fungus catalyzes the synthesis of substi-tuted 5-deaza-10-oxaflavins via a domino reactionrdquo AdvancedSynthesis and Catalysis vol 351 no 4 pp 589ndash595 2009


[3] D A Horton G T Bourne and M L Smythe ldquoThe combina-torial synthesis of bicyclic privileged structures or privilegedsubstructuresrdquo Chemical Reviews vol 103 no 3 pp 893ndash9302003

[4] M Alamgir D S Black and N Kumar ldquoSynthesis reactivityand biological activity of benzimidazolesrdquoTopics in HeterocyclicChemistry vol 9 pp 87ndash118 2007

[5] JMWoynarowskiMMcHugh R D Sigmund andT A Beer-man ldquoModulation of topoisomerase II catalytic activity byDNAminor groove binding agents distamycin Hoechst 33258 and410158406-diamidine-2-phenylindolerdquo Molecular Pharmacology vol35 no 2 pp 177ndash182 1989

[6] A Y Chen C Yu B Gatto and L F Liu ldquoDNA minor groove-binding ligands a different class of mammalian DNA topoi-somerase I inhibitorsrdquo Proceedings of the National Academy ofSciences of the United States of America vol 90 no 17 pp 8131ndash8135 1993

[7] J S Kim B Gatto C Yu A Liu L F Liu and E J LaVoie ldquoSub-stituted 251015840-Bi-1H-benzimidazoles topoisoraerase I inhibitionand cytotoxicityrdquo Journal of Medicinal Chemistry vol 39 no 4pp 992ndash998 1996

[8] T Roth M L Morningstar P L Boyer S H Hughes R WBuckheit Jr and C J Michejda ldquoSynthesis and biological activ-ity of novel nonnucleoside inhibitors ofHIV-1 reverse transcrip-tase 2-aryl-substituted benzimidazolesrdquo Journal of MedicinalChemistry vol 40 no 26 pp 4199ndash4207 1997

[9] P N Preston ldquoSynthesis reactions and spectroscopic proper-ties of benzimidazolesrdquo Chemical Reviews vol 74 no 3 pp279ndash314 1974

[10] K Bahrami M M Khodaei and I Kavianinia ldquoA simple andefficient one-pot synthesis of 2-substituted benzimidazolesrdquoSynthesis no 4 pp 547ndash550 2007

[11] P L Beaulieu B Hache and E von Moos ldquoA practical oxonemdashmediated high-throughput solution-phase synthesis of ben-zimidazoles from 12-phenylenediamines and aldehydes and itsapplication to preparative scale synthesisrdquo Synthesis no 11 pp1683ndash1692 2003

[12] Y Shiraishi Y Sugano S Tanaka and T Hirai ldquoOne-pot syn-thesis of benzimidazoles by simultaneous photocatalytic andcatalytic reactions on PtTiO

2nanoparticlesrdquo Angewandte

ChemiemdashInternational Edition vol 49 no 9 pp 1656ndash16602010

[13] J Sluiter and J Christoffers ldquoSynthesis of 1-methylbenzimida-zoles from carbonitrilesrdquo Synlett no 1 pp 63ndash66 2009

[14] D W Hein R J Alheim and J J Leavitt ldquoThe use of polyphos-phoric acid in the synthesis of 2-aryl- and 2-alkyl-substitutedbenzimidazoles benzoxazoles and benzothiazolesrdquo Journal ofthe American Chemical Society vol 79 no 2 pp 427ndash429 1957

[15] R Trivedi S K De and R A Gibbs ldquoA convenient one-potsynthesis of 2-substituted benzimidazolesrdquo Journal of MolecularCatalysis A vol 245 no 1-2 pp 8ndash11 2006

[16] Y-X Chen L-F QianW Zhang and B Han ldquoEfficient aerobicoxidative synthesis of 2-substituted benzoxazoles benzothia-zoles and benzimidazoles catalyzed by 4-methoxy-TEMPOrdquoAngewandte ChemiemdashInternational Edition vol 47 no 48 pp9330ndash9333 2008

[17] G A Molander and K Ajayi ldquoOxidative condensations to formbenzimidazole-substituted potassium organotrifluoroboratesrdquoOrganic Letters vol 14 p 4242 2012

[18] M R Grimmett Imidazole and Benzimidazole Synthesis Aca-demic Press London UK 1997

[19] M Curini F Epifano F Montanari O Rosati and S TacconeldquoYtterbium triflate promoted synthesis of benzimidazole deriv-ativesrdquo Synlett no 10 pp 1832ndash1834 2004

[20] K R Hornberger G M Adjabeng H D Dickson and R GDavis-Ward ldquoA mild one-pot synthesis of disubstituted ben-zimidazoles from 2-nitroanilinesrdquo Tetrahedron Letters vol 47no 30 pp 5359ndash5361 2006

[21] VMirkhani MMoghadam S Tangestaninejad andH KargarldquoRapid and efficient synthesis of 2-imidazolines and bis-imid-azolines under ultrasonic irradiationrdquo Tetrahedron Letters vol47 no 13 pp 2129ndash2132 2006

[22] P Gogoi and D Konwar ldquoAn efficient and one-pot synthesisof imidazolines and benzimidazoles via anaerobic oxidation ofcarbon-nitrogen bonds in waterrdquo Tetrahedron Letters vol 47no 1 pp 79ndash82 2006

[23] R N Nadaf S A Siddiqui T Daniel R J Lahoti and K VSrinivasan ldquoRoom temperature ionic liquid promoted regios-elective synthesis of 2-aryl benzimidazoles benzoxazoles andbenzthiazoles under ambient conditionsrdquo Journal of MolecularCatalysis A vol 214 no 1 pp 155ndash160 2004

[24] B Das H Holla and Y Srinivas ldquoEfficient (bromodimethyl)sulfonium bromidemediated synthesis of benzimidazolesrdquo Tet-rahedron Letters vol 48 no 1 pp 61ndash64 2007

[25] U Srinivas C Srinivas P Narender V J Rao and S Palaniap-pan ldquoPolyaniline-sulfate salt as an efficient and reusable cat-alyst for the synthesis of 15-benzodiazepines and 2-phenyl ben-zimidazolesrdquo Catalysis Communications vol 8 no 1 pp 107ndash110 2007

[26] C D Wilfred and R J K Taylor ldquoPreparation of 2-substitutedbenzimidazoles and related heterocycles directly from activatedalcohols using TOPmethodologyrdquo Synlett no 9 pp 1628ndash16302004

[27] A Corma and H Garcıa ldquoLewis acids from conventional ho-mogeneous to green homogeneous and heterogeneous cataly-sisrdquo Chemical Reviews vol 103 no 11 pp 4307ndash4365 2003

[28] S Kobayashi and KManabe ldquoDevelopment of novel Lewis acidcatalysts for selective organic reactions in aqueous mediardquo Ac-counts of Chemical Research vol 35 no 4 pp 209ndash217 2002

[29] H Firouzabadi and M Jafarpour ldquoSome applications of zirco-nium(IV) tetrachloride (ZrCl

4) and zirconium(IV) oxydichlo-

ride octahydrate (ZrOCl2sdot8H2O) as catalysts or reagents in or-

ganic synthesisrdquo Journal of the Iranian Chemical Society vol 5no 2 pp 159ndash183 2008

[30] F K Behbahani P Ziaei Z Fakhroueian and N Doragi ldquoAnefficient synthesis of 2-arylbenzimidazoles from o-phenyl-enediamines and arylaldehydes catalyzed by FeCeO

2-ZrO2na-

no fine particlesrdquo Monatshefte fur Chemie vol 142 no 9 pp901ndash906 2011

[31] R V Shingalapur and K M Hosamani ldquoAn efficient and eco-friendly tungstate promoted zirconia (WO

119909ZrO2) solid acid

catalyst for the synthesis of 2-aryl benzimidazolesrdquo CatalysisLetters vol 137 no 1-2 pp 63ndash68 2010

[32] P B Gorepatil Y D Mane V S Surywanshi V S Shinde andV S Ingle ldquoOne pot synthesis of antimicrobial active new2-benzimidazolesulfonamide derivatives from 2-mercaptoben-zimidazolerdquo Journal Current Chemical and Pharmaceutical Sci-ences vol 2 no 4 p 367 2012

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ZrO(NO3)2 ZrO(NO3)2

COOHRR

HN

NR CHO

NH2

NH2

R

HN

N Reflux 2ndash5 h Reflux 2ndash4 h78ndash96 74ndash98

Scheme 1 Zirconyl nitrate-catalyzed synthesis of substituted benzimidazoles

Thin layer chromatographywas carried out usingMerck silicagel GF254 plates All products were characterized by NMR1HNMR spectra were recorded at 400MHz and 13CNMRspectra were recorded at 100MHz withCDCl3 orDMSO-119889

6

as solvent Chemical shifts are reported in parts per million(ppm) downfield from TMS with the solvent resonance asthe internal standard Coupling constants (J) are reported inHz and refer to apparent peak multiplications HRMS wasrecorded on an ESI source

3 A General Procedure for Synthesis ofSubstituted Benzimidazoles

05 (weight) of zirconyl nitrate was added to a solution ofaldehydecarboxylic acid (1mmol) and o-phenylenediamine(1mmol) in ethanol (10mL)The reactionmixture was stirredunder reflux for 2ndash6 h The progress of reaction was moni-tored by TLC After the completion of the reaction the reac-tionmixture was cooled to room temperature 20mL of etha-nol was added and resulting solution was filtered to removethe catalystThe solvent was removed under reduced pressureby distillation and residue was purified by column chroma-tography on silica gel using n-hexane-ethyl acetate or ethylacetate-petroleum ether as an elutingagent The structures ofthe benzimidazolewere characterized by 1HNMR 13CNMRFTIR and HRMS and were mostly known compounds

Note Excellent yield was obtained when 1 (weight) of zirco-nyl nitrate was used with carboxylic acids

Characterization of selected compounds is as follows

31 2-Methyl-1H-benzimidazole (Table 2 Entry 1) Solid mp178ndash180∘C (lit34mp 175-176∘C) IR (KBr) 3860 3735 36012815 2310 1700 1513 735 cmminus1 1HNMR (DMSO-d

6 400

MHz) 120575 982 (s 1H) 73 (d J = 80Hz 2H) 759 (d 2H) 270(s 3H) 13CNMR (DMSO-d

6 100MHz) 120575 15135 13860

12221 11448 1490 MS (EImz) 132 [M+]

32 2-Phenyl-1H-benzimidazole (Table 2 Entry 2) Solid mp300ndash302∘C (lit35mp 301ndash303∘C) IR (KBr) 3566 2360 17481716 1698 1683 1652 1616 cmminus1 1HNMR (DMSO-d

6 400

MHz) 120575 1292 (s 1H) 819 (d J = 80Hz 2H) 761ndash755 (m4H) 752ndash748 (m 1H) 723ndash719 (m 2H) 13CNMR (DMSO-d6 100MHz) 120575 1517 1443 1355 1307 1303 1294 1269

1230 1221 1194 1118 MS (EImz) 194[M+]

33 2-(4-Nitrophenyl)-1H-benzimidazole (Table 2 Entry 3)Solid mp 324ndash326∘C (lit35mp 326ndash327∘C) IR (KBr) 3740

3644 3058 1766 1691 1658 1649 1597 1563 1536 14931415 722 695 cmminus1 1HNMR (DMSO-d

6 400MHz) 120575 1330

(s 1H) 842 (s 4H) 774 (s 1H) 760 (s 1H) 728 (s 2H)13CNMR (DMSO-d

6 100MHz) 120575 1627 1578 1494 1482

1365 1278 1274 1247 1233 1198 1124 MS (EI mz) 239[M+]

34 5-Methyl-2-phenyl-1H-benzimidazole (Table 2 Entry 7)Solid mp 245ndash247∘C (lit36mp 243-244∘C) IR (KBr) 31091511 1463 1354 1176 739 701 657 cmminus1 1HNMR (CDCl

3

400MHz) 120575 854 (s 1H) 812ndash811 (m 2H) 753 (d J = 55Hz1H) 740 (m 2H) 728 (s 2H) 708 (d J = 55Hz 1H) 245 (s3H) 13CNMR (DMSO 100MHz) 120575 1513 1318 1308 13011296 1294 1292 1268 1266 1264 1240 218 MS (EImz)208 [M+]

35 2-(p-Tolyl)-1H-benzimidazole (Table 2 Entry 16) Solidmp 264ndash266∘C (lit35mp 263ndash265∘C) 1HNMR (DMSO-d

6

400MHz) 120575 1283 (s 1H) 808 (d J = 78Hz 2H) 759 (s2H) 737 (d J = 78Hz 2H) 721ndash719 (m 2H) 239 (s 3H)13CNMR (DMSO-d

6 100MHz) 120575 1519 1443 1400 1354

1300 1279 1269 1228 1220 1192 1117 214 MS (EI mz)208 [M+]

36 2-(4-Methoxyphenyl)-1H-benzimidazole (Table 2 Entry6) Solid mp 235ndash237∘C (lit35 mp 234-235∘C) 1HNMR(DMSO-d

6 400MHz) 120575 744 (d J = 72Hz 1H) 725ndash719 (m

2H) 709 (d J = 88Hz 2H) 695 (d J = 84Hz 2H) 685 (dJ = 88Hz 2H) 383 (s 3H) 13CNMR (DMSO-d

6 100MHz)

120575 1608 1536 1432 1363 1293 1279 1225 1194 1147 11461115 558 MS (EImz) 224 [M+]

37 5-Nitro-2-(4-methylphenyl)-1H-benzimidazole (Table 2Entry 12) Solid mp 288∘C (lit mp 290ndash292∘C) IR (KBr)3858 3747 3672 3059 2349 1805 1691 1649 1641 1597 14931135 1025 722 695 cmminus1 1HNMR (DMSO-d

6 400MHz) 120575

1350 (s 1H) 810 (d J = 77Hz 2H) 795 (d J = 89Hz 1H)739 (d J = 78Hz 2H) 673 (s 1H) 661 (d J = 89Hz 1H)239 (s 3H) 13CNMR (DMSO-d

6 100MHz) 120575 1562 1361

1302 1291 1274 1268 1192 1186 1151 1128 1121 215 MS(EImz) 254 [M+]

38 2-(4-Chlorophenyl)-1H-benzimidazole (Table 2 Entries 4and 15) Solid mp 294ndash296∘C (lit35mp 290ndash292∘C) IR(KBr) 3606 3001 2818 2310 1700 1513 735 cmminus1 1HNMR(DMSO-d

6 400MHz) 120575 1300 (s 1H) 820 (d J = 84Hz 2H)



SolventCatalyst

+

OHC

HOOC

HN

N

NH2

NH2




HN

N

R

R

R

O R

OH

OHHO

minusH2O

H

H

N

N

H

HO

N

NH2NH2

NH2

+

Zr(IV)

Zr(IV)



1229 1225 1194 1119 MS (EImz) 228 [M+]


6 400MHz) 120575 839 (s 5H) 754 (d J =


6 100MHz) 120575 1590 1536 1432 1363

1310 1293 1279 1194 1147 1146 1115 311 MS (EI mz)254 [M+]


6 400MHz) 120575 1288 (s 1H) 803 (s 1H) 798 (d J


1183 1128 215 MS (EImz) 208 [M+]







Time(h)

1

NH2

NH2

OHC CH3

HN

N

CH3

85 39

2

NH2

NH2

OHC

HN

N

96 2

3

NH2

NH2

OHC NO2

HN

N

NO2

98 32

4

NH2

NH2

OHC Cl

HN

N

Cl 97 31

5

NH2

NH2

OHC

CH3

HN

N

CH3

94 35

6

NH2

NH2

OHC OCH3

HN

N

OCH3

78 43

7

NH2

NH2H

3C

OHC

HN

NH3C

86 35

8

NH2

NH2

H3C

OHC Cl

HN

N

Cl

H3C

94 23

9

NH2

NH2H

3C

OHC NO2

HN

N

NO2

H3C

95 25

10

H3C

NH2

NH2

OHC

CH3

HN

N

CH3

H3C

78 35


Table 2 Continued


Time(h)

11

NH2

NH2O

2N

OHC Cl

HN

N

Cl

O2N

92 3

12

NH2

NH2O

2N

OHC CH3

HN

NO2N

CH3 76 45

13

NH2

NH2

HOOC

HN

N

96 3

14

NH2

NH2

HOOC NO2

HN

N

NO2

97 25

15

NH2

NH2

HOOC Cl

HN

N

Cl 95 35

16

NH2

NH2

HOOC CH3

HN

N

CH3

80 45

17

NH2

NH2H

3C

HOOC CH3

HN

N

CH3

H3C

82 38

18

H3C

NH2

NH2

HOOC NO2

HN

N

NO2

H3C

96 27

19

H3C

NH2

NH2

HOOC

CH3

HN

N

CH3

H3C

78 4

20

NH2

NH2

O2N

HOOC

HN

NO2N

82 41

21

O2N

NH2

NH2

HOOC Cl

HN

N

Cl

O2N

85 31


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield


HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2








5 Conclusion


Acknowledgment


References





































2-ZrO2na-















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



SolventCatalyst

+

OHC

HOOC

HN

N

NH2

NH2




HN

N

R

R

R

O R

OH

OHHO

minusH2O

H

H

N

N

H

HO

N

NH2NH2

NH2

+

Zr(IV)

Zr(IV)



1229 1225 1194 1119 MS (EImz) 228 [M+]


6 400MHz) 120575 839 (s 5H) 754 (d J =


6 100MHz) 120575 1590 1536 1432 1363

1310 1293 1279 1194 1147 1146 1115 311 MS (EI mz)254 [M+]


6 400MHz) 120575 1288 (s 1H) 803 (s 1H) 798 (d J


1183 1128 215 MS (EImz) 208 [M+]







Time(h)

1

NH2

NH2

OHC CH3

HN

N

CH3

85 39

2

NH2

NH2

OHC

HN

N

96 2

3

NH2

NH2

OHC NO2

HN

N

NO2

98 32

4

NH2

NH2

OHC Cl

HN

N

Cl 97 31

5

NH2

NH2

OHC

CH3

HN

N

CH3

94 35

6

NH2

NH2

OHC OCH3

HN

N

OCH3

78 43

7

NH2

NH2H

3C

OHC

HN

NH3C

86 35

8

NH2

NH2

H3C

OHC Cl

HN

N

Cl

H3C

94 23

9

NH2

NH2H

3C

OHC NO2

HN

N

NO2

H3C

95 25

10

H3C

NH2

NH2

OHC

CH3

HN

N

CH3

H3C

78 35


Table 2 Continued


Time(h)

11

NH2

NH2O

2N

OHC Cl

HN

N

Cl

O2N

92 3

12

NH2

NH2O

2N

OHC CH3

HN

NO2N

CH3 76 45

13

NH2

NH2

HOOC

HN

N

96 3

14

NH2

NH2

HOOC NO2

HN

N

NO2

97 25

15

NH2

NH2

HOOC Cl

HN

N

Cl 95 35

16

NH2

NH2

HOOC CH3

HN

N

CH3

80 45

17

NH2

NH2H

3C

HOOC CH3

HN

N

CH3

H3C

82 38

18

H3C

NH2

NH2

HOOC NO2

HN

N

NO2

H3C

96 27

19

H3C

NH2

NH2

HOOC

CH3

HN

N

CH3

H3C

78 4

20

NH2

NH2

O2N

HOOC

HN

NO2N

82 41

21

O2N

NH2

NH2

HOOC Cl

HN

N

Cl

O2N

85 31


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield


HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2








5 Conclusion


Acknowledgment


References





































2-ZrO2na-















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of




Time(h)

1

NH2

NH2

OHC CH3

HN

N

CH3

85 39

2

NH2

NH2

OHC

HN

N

96 2

3

NH2

NH2

OHC NO2

HN

N

NO2

98 32

4

NH2

NH2

OHC Cl

HN

N

Cl 97 31

5

NH2

NH2

OHC

CH3

HN

N

CH3

94 35

6

NH2

NH2

OHC OCH3

HN

N

OCH3

78 43

7

NH2

NH2H

3C

OHC

HN

NH3C

86 35

8

NH2

NH2

H3C

OHC Cl

HN

N

Cl

H3C

94 23

9

NH2

NH2H

3C

OHC NO2

HN

N

NO2

H3C

95 25

10

H3C

NH2

NH2

OHC

CH3

HN

N

CH3

H3C

78 35


Table 2 Continued


Time(h)

11

NH2

NH2O

2N

OHC Cl

HN

N

Cl

O2N

92 3

12

NH2

NH2O

2N

OHC CH3

HN

NO2N

CH3 76 45

13

NH2

NH2

HOOC

HN

N

96 3

14

NH2

NH2

HOOC NO2

HN

N

NO2

97 25

15

NH2

NH2

HOOC Cl

HN

N

Cl 95 35

16

NH2

NH2

HOOC CH3

HN

N

CH3

80 45

17

NH2

NH2H

3C

HOOC CH3

HN

N

CH3

H3C

82 38

18

H3C

NH2

NH2

HOOC NO2

HN

N

NO2

H3C

96 27

19

H3C

NH2

NH2

HOOC

CH3

HN

N

CH3

H3C

78 4

20

NH2

NH2

O2N

HOOC

HN

NO2N

82 41

21

O2N

NH2

NH2

HOOC Cl

HN

N

Cl

O2N

85 31


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield


HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2








5 Conclusion


Acknowledgment


References





































2-ZrO2na-















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table 2 Continued


Time(h)

11

NH2

NH2O

2N

OHC Cl

HN

N

Cl

O2N

92 3

12

NH2

NH2O

2N

OHC CH3

HN

NO2N

CH3 76 45

13

NH2

NH2

HOOC

HN

N

96 3

14

NH2

NH2

HOOC NO2

HN

N

NO2

97 25

15

NH2

NH2

HOOC Cl

HN

N

Cl 95 35

16

NH2

NH2

HOOC CH3

HN

N

CH3

80 45

17

NH2

NH2H

3C

HOOC CH3

HN

N

CH3

H3C

82 38

18

H3C

NH2

NH2

HOOC NO2

HN

N

NO2

H3C

96 27

19

H3C

NH2

NH2

HOOC

CH3

HN

N

CH3

H3C

78 4

20

NH2

NH2

O2N

HOOC

HN

NO2N

82 41

21

O2N

NH2

NH2

HOOC Cl

HN

N

Cl

O2N

85 31


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield


HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2








5 Conclusion


Acknowledgment


References





































2-ZrO2na-















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of


Table 2 Continued


Time(h)

22

NH2

NH2

O2N

HOOC NO2

HN

NO2N

NO2 87 4

aIsolated yield


HN

NEthanol

OHCZrO(NO

3)2

NH2

NH2








5 Conclusion


Acknowledgment


References





































2-ZrO2na-















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy



Journal of


Quantum Chemistry






CatalystsJournal of



































2-ZrO2na-















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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