Patent GB-690119-A (GB)
Title: Improvements in or relating to the manufacture of heterocyclic compounds
Inventor: MAMALIS PATRICK
IPC: C07H19/052
Filed: 1950-07-13
Abstract: Benziminazole glycosides of the formula <FORM:0690119/IV (b)/1> where R and R1 are hydrogen, methyl or ethyl and R2 is a residue of the formula <FORM:0690119/IV (b)/2> n being 2 and R3 being -CH2OH or -CHOH-CH2OH or else n being 3 and R3 being -H or -CH2OH, are prepared by reacting the R,R1,R2-substituted o-phenylene diamine with an alkyl orthoformate to give the isoformanilide and ring-closing the latter with acid, e.g. hydrochloric or picric.  The first step is preferably carried out by refluxing with ethyl orthoformate in an inert solvent, e.g. alcohol, ethyl acetate or benzene.  The hydroxyl groups may be protected by acetylation before the reaction and the final product then deacetylated.  Alternatively the terminal hydroxyl group may be converted into the trityl, benzyl, toluenesulphonyl or diphenylphosphoryl derivative; some or all of the remaining hydroxyl groups may then be protected by way of the acetyl, isopropylidene or benzylidene derivatives.  In the examples: (1) o-nitraniline tetracetyl-d-glucoside is catalytically reduced to the diamine derivative and reacted with ethyl orthoformate to give N-ethoxymethylene-o-phenylene diamine N1-tetracetylglucoside; ring-closure yields benziminazole - d - tetracetylglucoside (picrate described), hydrolysed to the hydrochloride of benziminazole-1b -d-glucopyranoxide; the free base is formed by passage of the hydrochloride through a basic ion-exchange resin; (2) o-nitraniline is condensed with d-xylose to give the xyloside and converted into o-nitraniline-triacetylxyloside; treatment as above gives benziminazole-triacetylxyloside (via picrate) and benziminazole-1b -d-xylopyranoside (via hydrochloride); (3) 3-nitro-p-toluidine condensed with d-xylose gives a mixture of isomeric xylosides; these are acetylated and converted as above into 5-methylbenziminazole - triacetyl - xyloside (via picrate) and 5-methylbenziminazole - 1 - d - xylopyranoside; (4) 3-nitro-p-toluidine similarly gives a mixture of glucosides separated after acetylation and reduced to the diamine derivative; treatment as above gives 5-methylbenziminazole-tetracetylglucoside (via picrate) and 5-methylbenziminazole - 1 - d - glucopyranoside; (5) 5 - nitro - o - xylidine is condensed with glucose, acetylated, separated into isomers and reduced; treatment as above gives 5 : 6-dimethylbenziminazole - tetracetylglucoside and 5 : 6 - dimethylbenziminazole - 1b  - d - glucopyranoside; (6) there are similarly prepared 5 - nitro - o - xylidine - triacetylarabinoside (2 isomers), 5 : 6 - dimethylbenziminazoletriacetylarabinoside (via picrate) and 5 : 6-dimethylbenziminazole - 1a  - l - arabopyranoside (forms picrate); (7) 5 : 6-dimethylbenziminazole - 1b  - d - ribopyranoside is similarly prepared (as hydrochloride).  According to the Provisional Specification R and R1 are hydrogen or an alkyl grouping of molecular weight not exceeding 43 and R2 is a sugar residue of the formula -CHOH-(CHOH)n-CH2OH, n being not greater than 4; R2 may be in the furano, pyrano or open chain form of the sugar, and may be derived from a pentose or hexose.  Reference has been directed by the Comptroller to Specification 682,960.