Patent GB-735454-A (GB)
Title: Improvements in or relating to threo-aminodiols and intermediates therefor
IPC: C07D319/06
Filed: 1952-10-17
Abstract: The invention comprises threo-1 : 3-dioxane compounds of the general formula <FORM:0735454/IV (b)/1> (wherein R1 represents hydrogen or an alkyl1 group, R2 and R3 represent hydrogen atoms or alkyl, aryl, aralkyl, alicyclic or heterocyclic radicals or jointly form a ring with the 2-carbon atom of the dioxane ring, and X represents hydrogen or a carboxylic acyl residue), and their salts, and a process (in which they are intermediates) for preparing threo-2-acylaminopropanediols-1 : 3 of the general formula <FORM:0735454/IV (b)/2> by reacting a 5-halogeno-6-phenyl-2-R1,R2-1 : 3-dioxane with a basic substance R1-NH2, treating the resulting 5-amino compound with an acylating agent, and subjecting the product to acid hydrolysis.  The acylation step may be preceded by resolution by means of an optically active acid.  The hydrolysis may be effected with dilute inorganic or organic acids, or in some cases with alcoholic hydrochloric acid.  In examples (1) an ethanolic solution of 2 : 6-diphenyl-5-bromo-1 : 3-dioxane is saturated with ammonia and then heated in an autoclave to form the basic hydrobromide of threo-2 : 6-diphenyl-5-amino-1 : 3-dioxane, which is benzoylated with benzoyl chloride in pyridine and the product hydrolysed by heating with alcoholic hydrochloric acid to give dl-threo-1-phenyl-2-benzamidopropanediol - 1 : 3; (2) 2 : 2 - dimethyl - 5 - bromo - 6 - phenyl - 1 : 3 - dioxane yields the same final product by similar treatment, except that the solvent in the first step is methanol; (3) the alcoholic hydrochloric acid for the hydrolysis step in (2) is replaced by dilute acetic acid; (4) the starting material of (2) is autoclaved with ammonia in 80 per cent ethanol, the resulting amine is acetylated with acetic anhydride in pyridine and benzene, and the product is allowed to stand with aqueous alcoholic hydrochloric acid to produce dl-threo-1-phenyl - 2 - acetylaminopropanediol - 1 : 3; (5) threo - 2 : 2 - dimethyl - 5 - amino - 6 - phenyl-1 : 3 - dioxane is treated with dichloroacetyl chloride in pyridine and benzene, and the product is hydrolysed as in (3) to dl-threo-1-phenyl-2 - dichloroacetylaminopropanediol - 1 : 3; (6) 2 : 2 - dimethyl - 5 - bromo - 6 - phenyl - 1 : 3-dioxane is autoclaved with ethanolic methylamine, the resulting threo-2 : 2-dimethyl-5-methylamino - 6 - phenyl - 1 : 3 - dioxane is dichloroacetylated as in (5) or acetylated with acetyl chloride, and the product is hydrolysed as in (4) to dl-threo-2 : 2-dimethyl-5-dichloroacetyl - or - acetyl - methylaminopropanediol-1 : 3; the dichloroacetylchloride, pyridine and benzene in (5) are replaced by methyl dichloroacetate and methanol, and the hydrolysis is effected as in (4); (8) 2 : 2-pentamethylene-5-bromo - 6 - phenyl - 1 : 3 - dioxane is treated with ammonia as in (4) and the product is dichloroacetylated as in (5); (9) dl-threo-2 : 2-dimethyl - 5 - amino - 6 - phenyl - 1 : 3 - dioxane is resolved into its optically active forms by means of d-tartaric acid.  Specification 707,193 is referred to.  2 : 2 - Pentamethylene - 5 - bromo - 6 - phenyl-1 : 3 - dioxane is prepared by refluxing 1-phenyl - 2 - bromopropanediol - 1 : 3 with cyclohexanone and p-toluenesulphonic acid in benzene.