Patent GB-574432-A (GB)
Title: Improvements in and relating to the preparation of 7-dehydrosterols
IPC: C07J75/00
Filed: 1943-12-06
Abstract: Sterols of the type illustrated by the general formula:-<PICT:0574432/IV/1> wherein R represents a saturated open-chain hydrocarbon residue and in which the hydroxyl group may be esterified, are converted, at least in part, to the corresponding 7-dehydro derivatives by reacting the sterol esterified with a carboxylic acid, carrying in its acyloxy residue no other reactive groups, with an N-halogenated acid amide or imide, dehydrohalogenating the product by treatment with a tertiary amine liquid at the reaction temperature and bearing no reactive group other than the tertiary amine group and, if desired, removing the ester group by hydrolysis.  On irradiation with ultra-violet light, the products may lead to compounds having vitamin D activity. Specified halogenating reagents are N-bromosuccinimide, N-bromophthalimide, unsubstituted N-chloro- or bromo-amides of fatty acids containing not more than six carbon atoms, N-chloro- or bromo-acetanilides having on the para-position, and optionally on either or both of the ortho-positions, inert substituents preventing migration of the N-halogen into the p- and/or p-position. Halogenation is advantageously effected in a relatively low-boiling inert solvent, e.g. a light petroleum fraction, especially of boiling range 60-80 DEG  C., ether, ethyl acetate or carbon tetrachloride, advantageously with agitation and dehydrohalogenation is advantageously performed with agitation, using a fairly large excess of the tertiary amine at or near its boiling point. Purification of the products may be effected by chromatographic treatment of derivative esters, e.g. the 3 : 5-dinitrobenzoates, followed by subsequent hydrolysis and, if desired, re-esterification.  In examples: (1) N-bromosuccinimide is heated for 8 hours under reflux with cholesteryl acetate in ether and the product is heated for 15 minutes under reflux in diethyl aniline, whereupon the esters is hydrolysed with sodium ethoxide in ether; (2) cholesteryl benzoate- and (3) cholesteryl 3 : 5-dinitrobenzoate are heated for 30 and 15 minutes respectively, under reflux with N-bromosuccinimide in carbon tetrachloride and the products are further treated as in (1); (4) cholesteryl acetate is heated for 5 hours under reflux with N-bromosuccinimide in ether and the product is further treated as in (1); (5) crude b -sitosterol acetate is heated for 4 hours under reflux with N-bromosuccinimide in ether and the product is further treated as in (1); (6) cholesteryl acetate is heated for 15 minutes under reflux with N-bromosuccinimide in ethyl acetate and the product is further treated as in (1); (7) the diethylaniline in (1) is replaced by dimethylaniline; (8) cholesteryl acetate is heated for 6 hours under reflux with N-bromophthalimide in ether and the product is further treated as in (1); (9) cholesteryl acetate is brominated as in (1) and the product is heated for 30 minutes in diethylaniline on the water-bath at 95-100 DEG  C.; (10) cholesteryl acetate is heated under reflux with N-bromosuccinimide in 60-80 DEG  C. petroleum on a water-bath with stirring until the solid is substantially free from active bromine, whereupon the solution is filtered, the filtrate is added to diethylaniline, the petroleum is removed under reduced pressure and the residual solution is heated at 95-100 DEG  C. for 3 hours and diluted with light petroleum, washed and the solid obtained on removal of the petroleum is hydrolysed with alcoholic potash; (11) an excess of N-bromosuccinimide is used in (10) to obtain a product richer in 7 - dehydrocholesterol; (12) cholesteryl n-butyrate is heated for 15 minutes under reflux with N-bromosuccinimide in 60-80 DEG  C. petroleium and the product is further treated as in (10); (13), (14) and (15) cholesteryl acetate is heated under reflux with N-bromosuccinimide in 60-80 DEG  C. petroleum, the product is treated with (13) N-ethyl-piperidine, (14) N : N-diethylcyclohexylamine, (15) N : N-di-propylaniline prior to removing the petrol and heating at 95-100 DEG  C.; (16) cholesteryl acetate is heated for 6 hours under reflux with N-bromoacetamide in ether and the product is heated for 10 minutes under reflux in diethylaniline and further treated as in (1); (17) cholesteryl acetate is heated for 48 hours under reflux with N : o : p - trichloroacetanilide in ether and the product is further treated as in (15).