NOKXIN ('i.BRINK. \ N U I.; I R L F C J L K K R ~
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[COSTRIRUTIOS FROM THE KRSBARCH ~ A B V K A T O R I E SOR J f E R C K
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1'01. ;I" ]
Vitamin BIZ. X. 5,6-Dimethylbenzimidazole,a Degradation Product of Vitamin B,, NORMA4N(>. BRINK AND
KARLFOLIiERS
Acid hydrolysis of vitamin BIZyielded a basic in aqueous alkali was described by Bamberger product which was identified by degradation and and Berl6, and was used by Windaus and Knoop5 by synthesis as ,5,6-diiiiethylbeiizirnida%(~le ( 1'1.' ,is a diagnostic test for imidazoles. Cl'hen the This observation was recently confirmed bv reaction was applied to the degradation product irotn vitamin JJ12, a crystalline product melting others2 who based their identificatioii of dimethylbenzimidazole oil sp~ctrophotortietric.e \ i- a t 262--%3 was obtained. I t was identical with dence. It is the purpose of the present r o n ~ - &t sytithetic sdinple of the new 4,5-dibenzainidoiriunication to describe the details of lhe isolation i ,~-dixnetliylberizene(11) prepared by benzoylation oi 4,Xiamino- 1,2-dimethylbenzene. The and identification of the degradation product. hydrochloric degradation product was consequently assigned h solution of vitamin BIZ in ti acid was heated a t 150 for tviwity hours. Con- the .i.ti-dimethylbeiizimirlazolestructure (I). tinuous chloroform extraction of an alkaline SIi ,rqueous solution of the products of hydrolysis CII3/\ ' i C6H,COC1 CHiq"COC6Hb qavc an extract whose content was further puri'CH ---d T;:iOIT CtI {,J'SHCOC~R~ fied by removal of ail ether-insoluble fraction. L'he ethc~=solubletnnterial vas heated in :~ C I I O v Lit about 140*, yidding a ;Jal-ti,dlJ- c ~ ~ ~ t a l l i n e 1 iI sublimate. From this stthliniatr, the pure deg'The structure of tlie degradation product was radation product was obtai-ird by cryst''111'i7a- confirmed by the synthesis of j,(i-diiiiethylbenzimition. The rompound is hasic. to litmus paper, dazole froiii 1,3-didrnino-l,%ditnethylbenzene and and melts a t 205-206". It is optically inactive. formic acid. l'he synthetic compound melted Elementary analyses, n potentiometric titration and a molecular weight determination indicated a t 204--20~5*,and caused no depression of the melting point when mixed with the degradation prodthat the compound is a monoacidic base with the uct. The absorption spectra of the natural and formula CqHloNz. A crystalline picrate which synthetic products were identical within the melts a t 273-27;j3 was prepared. X K u h w limits of experimental error. Koth determination gavr 1.1 tnolcs of acetic The yield of 3,(i-dimethylbenzimidazole from cicid per mole of cornpound, indicating more than vitaniin u12 was consistently dbout 70(2, of one one C-niethyl group in the ticy-ati,i tiori proriiict. molar equivalent. The stability of the product In 955% ethanol snlutio~iin the prvsency O I 0.01 is such that there is no reason to believe that 1' hytirochioric acid, thv abwrption spectrum more than m e mole of ~,A-dimethylbenzimiddzole .howe$ maxima a t 27 13 A. (Ehf 7.700 ;itit1 I X100). \T'hrn the solutioti was made This is 111 agreement with other observations2 alkaline by addition oi a small c'x that vitamin Biz contains only one such moiety hyctroxide, m a x i p were observe in its molecule. ( E M 3900), 277.7 "1.(En5 IlOOOj, 231 I t is reasonable to assume that in vitamin Biz and 2880 A. ( E M 5700). The chariz:t~111 the the .?,A-dimethylbenziniidazole moiety is terminal absorption with pH is reversible. m d 14 liiiked to the remainder of the molecule The molecular formula of thc dcpadation through one of the nitrogen atoms of the imidazole protfuct and its properties indicated that it might ring O n this basis, a partial formula for vitamin he a substituted bcnzimida~ole. X perusual of B1, ti1a.i- ht. provisionalls represciltetl bv structure the literature revealed that the reported proper- 7 1 1 ties of 2,5-dimethylbenzimidazole3(m. 11. 203" 1 N-- C,1-.,H,,-g,~,1O,IPCO are quite similar to those of the compound obtained from vivamin R t z . Accordingly, the 2,.5dimethyl derivative was prepared. -Although it was not identical with the degradation product, .. the close resemblance of the ultraviolet absorptioii 111 spectra of the two compounds strengthened the Experimental propqsed benzimidazole formulation. The cleavag,. iif lwn [imidazole t o 1,2-tlibenz5,6-Dimethylbenzimidazole from Vitamin BI2.-A sample of vitamin BIZweighing 82 mg. was dissolved in 6 amitlobenzene by i.reatn:cnt .with b e n ~ o y chloride l )
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[ I ) Brink and Folkers, TIII? T n r a % 4 1 ,71, 2951 (1949) (2) Holliday and X'rtrom, J Phimn oitd Phormncol , 1, 734 (1948); BeaQen IIolliday, Johi.~o:i, R i l l s M a m a l i c . Pi%trow and Sturgeon, rbid , 1, Y57 (19401 71 Hohrecker, l3w 6. '%?I f 1 W 2
i d . of 6 A' hydrochloric acid and the resulting solution ..
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