Indian Journal of Chemistry Vol. 41B, October 2002, pp. 2136-2144

Syntheses and structural elucidation of novel benzimidazolium dichromates obtained from simple benzimidazoles and chromium (VI) reagents

K Ramaiah, P K Dubey*, J Ramanatham & C Ravi Kumar Department of Chemistry, College of Engineering, J.N.T.University, Kukatpally, Hyderabad SOO 072, India

and

J S Grossert, T S Cameron & s V Sareda Department of Chemistry, Dalhousie University, Halifax , Nova Scotia, Canada B3H 413

Received 4 July 2000; accepted (revised) 15 No vember 2001

Benzimidazole and its simple 2-substituted derivatives react with chromium (VI) reagents such as CrO), K2Cr20 7, K2Cr04 or pyridinium dichromate in aq. acet ic ac id at RT to yield eautifully coloured, yellow to yellowish-orange prod­ucts. Spectral and analy tical data have been used to characterize the products. Structures for these producls as benzimida­zolium dichromate have been ass igned on the basis of single crystal X-ray analyses.

Benzimidazoles are an important group of hetero­cyclic compounds possessing a wide spectrum of biological activities I. Among benzirnidazoles, the 2-substituted derivatives have been found to be most potent, notable examples I being thiabendazole, cambendazole, albendazole etc. During the course of our studies2 on benzimidazoles, we needed a sample of 2-acetylbenzimidazole. It was consider d desirable to prepare the latter from 2-ethylbenzimidazole by oxidation with a suitable oxidizing agent such as a chromium (VI) reagent. Results of this study form the subject matter of this paper.

Results and Discussion

a-Phenylenediamine 1 was condensed with pro­panoic acid under Phillips' conditions3 to yield the known 2-ethylbenzimidazole (2a, i.e. 2, R=Et). It was presumed that oxidation of 2a using a suitable oxidizing agent such as a chromium (VI) compound4 would yield 2-acetylbenzimidazole 3 (Scheme I). Accordingly, 2a was treated with Cr03 in aqueous acetic acid at RT in the hope of getting 3. However, the reaction gave an orange-yellow crystalline product 4a, m.p. 155-57° C, which was different from both the staIting material 2a and the expected 3 (m.p. and TLC). A sample of 3 was, however, obtained, for comparison purposes, from 2-(a-hydroxyethyl)benzimidazole 5 by oxidation with ac id dichromate using a reported procedure2

.5

. Com­pound 5 itself was obtained from 1 by condensation with lactic acid under Phillips' conditions3.

The IR spectrum of 4a recorded as KBr pellet showed a strong broad band at around 3000 cm· l

. This was also the case with the IR spectrum of 2a recorded in KBr phase. However, the IR spectrum of 2a as a dil ute solution in CHCI3 showed a medium intensity sharp band at 3300 cm·1 in addition to the broad strong band at around 3000 cm· l

. The former absorp­tion is assignable to free -NH- and the latter to the bonded - NH- stretching vibrations. This behaviour is typical of compounds containing an imidazole6

- H­or a benzimidazole7 -NH- grouping. The spectra of 2a and 4a, in KBr phase, were very similar in the func­tional group region but there were discernible differ­ences in the fingerprint and bending regions. Unfortu­nately, the spectrum of 4a could not be recorded in solution phase since the compound was insoluble in most of the common solvents like CCI.j, CHCb, sym.CHCI 2- CHCI2, CCI3- CCI3 etc.

The UV spectra of 2a and 4a, each recorded in MeOH, showed identical peaks (Am•lx I = 242.9 nm, Amax 2 = 272.9 nm and Amax 3 = 279.0 nm) but for an extra longer wavelength band at 358.0 nm in the spec­trum of 4a .

The IH NMR spectrum of 4a in DMSO-ch / TMS showed signal s at 8 1.40 (br s, 3H, -CH3), 2.98 and 3.05 (br d, 2H, -CH2), 5.97 (br s, 2H, 2 x -NH­proton), 6.9-8.2 (complex broad peaks, 4H, ary l pro­tons) and that 2a in DMSO-d6 / TMS showed signals

RAMAIAH el al.: SYNTHESES OF NOVEL BENZIMIDAZOLIUM DICHROMATES 2137

+ Cr(VI) / H

RT

HOOC-RI.{

:;:N~CI

2 2 4

+ Cr(VI) / H

(XNH2

'.& NH2 ~HOOC-CH(OH)-CH3

1 4N HCI / .6. H + o=N Cr(VI) / H

, }-CH(OH)-CH3---~·-.& N RT

RT

5 3

Scheme I

Table I-Preparation or 4 rrom 2

2 Type or Yield (%) Recrystall isat ion m.p. % Chromium Oxidizing agent (Molar) solvent °C Calcd for Found by Found by

lIsed 4 obtained AAS analyses Volumetri c analyses

CrO}. 64.89 GI.AcOH or H2O 155-57 (dec) 19.67 (4a) 18.372 19.79

2a K2Cr04. 63.46 -do- -do- -do- -do- -do-

(2. R=C2Hs) K2Cr20 7. 65.96 -do- -do- -do- -do- -do-(Py Hh Cr20 7 6 1.46 -do- -do- -do- -do- -do-

CrO). 68.73 GI.AcOH or H2O 150-52 (dec) 22 .03 (4b) 22.302 22.15

2b K2CrO •. 64.45 -do- -do- -do- -do- -do-

(2. R=H ) K2Cr20 7. 69.86 -do- -do- -do- -do- -do-(PyH)2Cr20 7 63.56 -do- -do- -do- -do- -do-

CrO). 55.46 GI.AcOH or H2O 148-50 (dec) 20.80 (4c) 19.956 20.76

2c K2Cr04. 53.26 -do- -do- -do- -do- -do-

(2. R=CH) K2Cr20 7. 52.26 -do- -do- -do- -do- -do-(PyH h Cr20 7 54.46 -do- -do- -do- -do- -do-

CrO). 43. 16 GI.AcOH or H2O 140-43 (dec) 18.7 1 (4d) 17.968 18.68 2e1 K2Cr04. 4 1.26 -do- -do- -do- -do- -do-

(2. R=n - K2Cr20 7. 40.36 -do- -do- -do- -do- -do-C3H7) (PyH h Cr20 7 41.56 -do- -do- -do- -do- -do-

2138 INDIAN J. CHEM., SEC B, OCTOBER 2002

C4

C5

C8 ~C9

OIA

C9A

C4A

Figure 1

at 8 1.30 (t, 3H, -CH3), 2.82 (q, 2H, -CH2), 7.05-7.50 (complex m, 4H, aryl protons) andl2.10 (br s, IH, -NH-). This indicated that 4a has the same structural features of 2a but for one/two extra protons. How­ever, the spectrum of 4a showed severe line broaden­ing which may be due to the presence of a paramag­netic species - in all likelihood - chromium, in one of its oxidation states.

The mass spectrum of 4a, as electron-impact GC -MS, showed the molecular ion peak at M+· = 146 which was also the molecular ion peak in the spectrum of 2a indicating the latter to be the only thermal degradation product of the former - as

expected for a chromium derivative having any C-Cr covalent bonds.

of 2a , not

Direct heating of 4a in a gravimetric silica crucible, over Bunsen fl ame, gave a non-volatile residue equivalent to 30% of the weight of the starting mate­rial. Volumetric estimation of 4a, based on a known procedures, using K2Cr207 as primary standard, fer­rous ammonium sulfate as link solu tion and diphenyl­amine as internal indicator, showed the chromium content to be 19.79%. Atomic Absorption Spectro­scopic analysis of 4a using a chromium reference standard showed the amount of chromium to be 18.372%. This data indicated 4a to be a I : 1 or 2:2

Crystal data: r C 1RH22NiCrz07)

1 Mr=SI0.39 Monoclinic p2/n a=7 .1 66(4)oA b = IS.OO4-{2) 0 A

c = 9.909 ( I) °A ex = 90° ~ = 98.60 (2)0

RAMAIAH el al.: SYNTHESES OF NOVEL BENZIMIDAZOLIUM DICHROMATES 2139

MoKex radi ati on

A = 0.7 107 °A Cell parameters from 20 renec­tions 8 = 10.00 - 16.S00

~ = I.OS mm·1

T = 293 K Needle

O.SO x 0.20 x 0.20 mm

2 (4a)

Data Collection: Rigak u AFCSR diffractome- 1100 observed renections ter w-28 scans [ 1>3a (I) 1 Absorption correc tion: R int = 0 .024

None 8max = 2S.00 1683 measured rcnections h = 0 -> 10 IS46 independent re nections k = 0 -> 2 1

1= -14 -> 14 3 standard renect ions frequency: 120 min; Inte nsity variation: I .S %

Y= 90° Yell ow V = IOS9 (9) A3

Z=2 Dx = I.S99 Mg m·)

Refinement:

Refi nement on F Max . & Min . peak in Final Difr. Map: 0.38, -0.33 e ° A·)

R = 0.037 Atom ic Scattei·ing factors from In­ternati onal Tables for X-ray crystal­lography ( 1974, Vol. IV, Table 2.2B)

WR = 0.043

S = 2.37

11 00 reneet ions

ISS parameters

W = [ a2 (Fo) + ( 0.0 I Fo/ 2)2rl

Max. shi ft Error < 0.0 I

Crystall ographic data for 4a (Figure 1)

derivative in composition considering the benzimida­zole : Chromium content.

Treatment of 4a with aq. NaOH (5 %) at RT for less than 5 min . gave back almost quanti tatively 2a. Further, it was found that 4a cou ld also be prepared readil y from 2a by react ing it independently with K2Cr20 7, K2CrO~ or pyrid inium dichromate in aq. Acetic ac id at RT. These results indicate that a common species obtainable in situ fro m all these

chromium-containing reagents (namely CrO), K2Cr20 7, K2Cr04 or pyridinium dichromate) i.e. H2CrO~ or H2Cr20 7 is in volved in the format ion of 4a from 2a.

Since all the above data did not lead us to a clear­cut picture regarding its structure, 4a was subjected to single crystal X-ray analysis. The latter, shown in Figure 1, indicated 4a to be 2-ethylbenzimidazolium dichromate.

2140 INDIAN 1. CHEM., SEC B, OCTOBER 2002

07C!' ,

05

C6 04 C13

C14 C3

N4

C4 03

Crystal data: [ CI4HI4N4(Cr207) 1

Mr = 454.28 Triclinic p - I a = 10.068 (3) °A b = 11.749 (2) °A

c = 8.306 (2) °A

a = 10 1.44 (2)° ~ = 11 2.72 (2)0

y = 77.95 (2)0 V = 880.8 (8) A3

Z=2 Ox = 1.71 3 Mg m'3

Refinement:

Figure 2

H O=N -2

I ~ +:>-H Cr20 7

H

(4b)

MoKa radiation

t..=0.71070A Cell parameters from 20 reflections

0= 10.00 - 16.50° ~ = 1.25 mm'l

T = 293 K

Needle

0.35 x 0.20 x 0.15 mm

Yellow

2

Data Collection: Rigaku AFC5R dif­fractometer w-20 scans Absorption correct ion:

None 3279 measured reflec­tions 3085 independent re­flections

2 120 observed reflections

[ 1>3(J (I) ] R int = 0.039

Om<lx = 25 .00 h=0 -> 14

k = 0 -> 17

1=-12->12 3 standard reflect ions frequency: 120 min; In tensity variation: 0. 1 %

Refinement on F Max . & Min. peak in Final Difr. Map: 0.38, -0.32 eO A,3

wR = 0 .039 S = 2,06

R = 0.033 Atom ic Scattering factors from In­ternational Tables for X-ray crysta l­lography ( 1974, Vol. IV, Table 2.2B)

2 120 reflections 245 parameters W = [ (J2 (Fo) + ( 0.0 I Fo /2)2,, 1 Max. shirt Error < 0.0 I

Crystallographi c data for 4b (Figure 2)

RAMAIAH el al.: SYNTHESES OF NOVEL BENZIMIDAZOLIUM DICHROMATES 2141

The above reactions of 2a with different chromium reagents have been extended to the parent benzimida­zole (2b, i.e. 2, R=H), 2-methylbenzimidazole (2c, i.e. 2, R=Me) and 2-n-propylbenzimidazole (2d, i.e. 2, R=n-C3H7). The products obtained in each case have been characteri zed by their melting points and chro­mium contents (Table I). Further, the structures of each of these products as benzimidazolium dichro­mates 4 have been confirmed by their X-ray analyses shown in Figures 2, 3 and 4 respectively. It has been observed that crystals of 4a, 4c and 4d are monoclinic while those of 4b are tri cli nic in character.

C3

C4 ~ , ~N2

C5~~ C7

C6

02

Experimental Section

Melting points are uncorrected and were deter­mined in open capillaries using sulfuric acid bath. TLC analyses were done on glass plates coated with silica gel-G and spotting was done using iodine or UV lamp. a-Phenylenediamine was obtained from com­mercial suppliers and was used as such. Chromium reagents such as K2Cr20 7, K2Cr04 and pyridiniu ll1 dichromate, with the exception of Cr03 were of AR grade.

01 05A

02A

C4A

C5A

Figure 3

2142

Crystal data : I CI6H IRN4(Cr20 7) I

Mr = 482.33 Monoc linic

p21/e a = 8.463 (2) °A b = 16.662 (2) °A

e = 7.569 (2) °A

ex = 90 ° ~ = 11 2.94 (1)0

Y= 90 ° V = 982.9 (7) A.l

Z=2 D, = 1.630 Mg m-.l

Crystallography

INDI AN J. CHEM., SEC B, OCTOBER 2002

H

CC}-CH, H

(4c) 2

Data Collection: MoKex radiation Ri gaku AFC5 R

diffr:lc tometer 1022 observed rcflections

A. = 0.7107 0 A w-28 scans Cell parameters from 20 reflections Absorption correction:

8 = 10.00 - 16.500 None f..l = 1.12 mn,- I 1935 measured refl ec-

tions T = 293 K 1796 independent re-

fkctions Plate

r 1>3a (I) I R int = 0.035

81lla, = 25.00 h = 0 -> I I

k = 0 -> 23

1= -12-> 12 0.50 x 0.30 x 0.10 mm 3 standard reflections frequcncy:

120 min ;

Yellow

Refinement: Refi nement on F

R = 0.04 1

wR = 0.042

S = 2.40

1022 refl ections

146 paramctcrs

W = I a2 (Fo) + (0.01 Fo/2lrl

Max. shift Error < 0.05

Intcnsi ty variat ion : 0.3 %

Max. & Min. peak in Fi nal Di fr. Map: 0.28, -0.3 1 eO A-.l

Atomic Scattering factors from In­ternational Tables for X-ray crystal­

lography (1974, Vol. IV, Table 2.2 B)

Crys tallographic data for 4c (Figure 3)

The X-ray crystal structure analyses of the com­pounds 4a-d have been performed with a RIGAKU AFC5R diffractometer (graphite monochromator). Structures were solved by direct method and refined by full-matrix least- squares techniques in the anisot­ropic approxi mation on F, except structure 4d, where all atoms of cations were refined isotropically (crystal was a very weak scaterer). H atoms were not located

in Fourier difference maps and were set geometrically and included in the final refinement with fixed posi­tional and thermal parameters. Col lect ions for Lorentz and polari zation effects but not for absorbtion was app lied. All the calcul ations were carried out with Texasan programme package (Tex:1san, 1989).

Preparation of 4 (General procedure). To a solu­tion of the benzimidazole ( 10 mM) in aq. acetic ac id (5%, vlv , 10 mL) was added at RT a solution of the

RAMAIAH el al.: SYNTHESES OF NOVEL BENZIMIDAZOLIUM D1C HROMATES

coo

C"

Crystal data: [ C20H2s N4(Cr207) 1

Mr = 538.44 Monoclinic p211 I a = 7.864 (8) °A b = 18.65 (I) °A

c = 16.1 61 (7) °A

a = 90 0

~ = 96.80 (6)IJ

y = 90 ° V = 2354 (6) A3

Z = 4 Ox = 1.51 9 Mg m-3

Refinement:

o.

Cll

Figure 4

19:tc~-c~-cJ C"O;'

2

MoKa rad iation

A=0.7 1070A Cell parameters from 20 reflections

8 = 10.00 - 16.50° 11 = 0.95 mm· 1

T = 293 K

Plate

0 .30 x 0.30 x 0.05 mm

Ycllow

( 4d ) Data Collection: Ri gaku AFC5R dif­fractometer (j)-28 scans Absorption correction:

None Decay correction: done 3696 measured reflec­tions 3402 independent re­fl ect ions

84 1 observed reflections

[ 1>3cr (I) 1 R int = 0.069

8m, x = 25.00 h = 0 -> II

k = 0 -> 26

I = -23 -> 23 3 standard reflections frequency: 120 min; Intensity variation: 35.0 %

Refi nement on F Max. & Min. peak in Final Diff. Map: 0.45, -0.27eoA-3

wR = 0 .056 S = 2.49

R = 0.059 Atomic Scattering factors from International Tables for X-ray crystallography ( 1974, Vol. IV , Table 2.2B)

Crystallographic data for 4d (Figure 4)

84 1 reflec ti ons 179 parameters W = [cr2 (Fo) + (0.01 Fo I 2)2]"1 Max . shift Error < 0.0 I

2143

2144 INDIAN J. CHEM., SEC B, OCTOBER 2002

chromium reagent (Cr03, K2Cr20 7, K2Cr0 4 or pyridinium dichromate) ( 10 mM) in ag. acetic acid (5%. v/v, 10 mL) and the mixture was stirred for 15min. The separated product was filtered, washed with water and dri ed. The dried product was recrystal­lized from a suitable solvent (Table J).

Acknowledgement

The authors are thankful to the authorities of J N T Uni versity, Hyderabad and Dalhousie Un iversity , Hal ifax, for laboratory and instrumentation facilities respectively. They are highly indebted to UGC, New Delhi , India and NSERC, Ottawa, Canada, fo r finan­cial support of the work done.

References I (a) Bell::.illlida::.ole (llId cOllgell eric Iricyclic cOlllpoullds, edited

by P N Pres ton (Wiley Intersc ience, New York), 1980, Part 2, Chap. 10, 53 1. (b) Preston P N, Chelll Rev, 74, 1974,279. (c) Grimmett M R. in K T Pott s (Ed), COlllp rehellsive helero­cyclic chelllislry, A R Katri tzky & C W Rees (General Eds) (Pergaon Press, Oxrord), 1984, Vol. 5, Chap. 4.08, 457 .

(d) Horman n K, IlIlidazole alld ils denvarives (The chelllislr), of ilelerocyclic call/pounds, A Wei sberger, series Editor) (Wiley Intersc ience, New York), 1953, Part I, 247 .

2 Ramaiah K, Dubey P K, Ramanathalll J & Grossert J S, J Indian Chelll Soc, 76, 1999, 140 .

3 Phillips M A, J Chelll Soc, 1930, 1409. 4 (a) ChrollliulII oxidalions in organic chem ist ry, edited by G

Cainelli & G Card illo, (React ivity and Structure Concepts in Organic Chemistry Seri es) (Springer-erlag, Berlin ), 1984. Vol 19, Chap IV , 161. (b) Cornrorth R H, Cornforth J W & Popjak G, Telrahedroll, 18, 1962, 135 I. (c) Coates W M & Corri gan J R, Chelll IlId, 44, 1969, 1594. (d) Fieser L F & Fieser M, ReagelltJ fur organic synthesis, Vol 3 (W iley Interscience, New York), 1972,239.

5 (a) Matrick H, Ph. D. thesis, Uni versi ty of Pennsy lvania , USA, 1960,93. (b) Merck & Co, Netherlands Patent , ,413,8 16,31 May 1965: Chelll Abstr 63. 1965, P 16357h. (c) Cheesc man G W H, J. Chelll. Suc, 1964,4645. (d) Zellner H, Zellner G, Kopple F & Dirn berger J, Mil Gelll , 98, 1967, 643.

6 Rabiger D J & Jou lli e M M, J Org Gelll. 29, 1964,476. 7 Morgan K J , J Chelll Soc, 1961 ,2343. 8 Bassett J, Jerrery G H, Mendham J & Denney R C, (Eds) ,

Vogels Text Book of QuallIitaLive Illorgallic Analvsis (ELBS Long man , London), Fourth Edn, 1978, 360.