Patent GB-593480-A (GB)
Title: Process for the manufacture of phosphorus compounds
IPC: C07F9/12
Filed: 1944-12-22
Abstract: Dibenzyl ortho-phosphoric acid esters and amides are prepared by reacting organic compounds containing a hydroxyl or primary or secondary amino group attached to a carbon atom with a solution of a dibenzyl chloro- or bromo-phosphonate in an inert organic solvent. When a hydroxy compound is used, the reaction is preferably carried out in the presence of a tertiary organic base whilst when a phenolic compound is used it is advantageously reacted in the form of its alkali metal salt.  In general, anhydrous conditions are preferred. The resulting esters or amides of dibenzyl phosphoric acid are converted to the corresponding free phosphoric acid derivatives or salts thereof by removing the benzyl groups by catalytic hydrogenation preferably in the presence of sufficient of an inorganic or organic base, especially a tertiary nitrogen base, to neutralize the acidic groups liberated.  In examples: (1) dibenzyl anilino phosphonate is prepared by adding excess of aniline to a carbon tetrachloride solution of dibenzyl chloro phosphonate, the mixture being allowed to stand overnight at room temperature and then filtered, washed with dilute hydrochloric acid, dried and the solvent distilled off; (2) dibenzyl ethyl phosphate is prepared similarly using a mixture of absolute ethyl alcohol and pyridine in place of the aniline; the dibenzyl ethyl phosphate is dissolved in methanol, catalytically hydrogenated in the presence of a palladium charcoal catalyst and the resulting ethyl dihydrogen phosphate isolated as the barium salt; (3) monoacetone glucose-6-phosphate dibenzyl ester is prepared by reacting together dibenzyl chlorophosphonate and monoacetone glucose in pyridine; the resulting dibenzyl ester is catalytically hydrogenated in ethanol solution in the presence of dimethylcyclohexylamine using a platinum oxide catalyst so yielding monoacetone glucose-6-phosphate, isolated as the barium salt, which on hydrolysis is converted to glucose-6-phosphate; (4) dibenzyl phenyl phosphate is prepared by reacting anhydrous sodium phenate with dibenzyl chlorophosphonate in carbon tetrachloride and is hydrogenated as in (2) to give phenyl dihydrogen phosphate; (5) di-benzyl p-sulphonamido phenyl amino-phosphonate is prepared by reacting dibenzyl chlorophosphonate with p-aminobenzene sulphonamide in a pyridineether solution; (6) dibenzyl ester of 3 : 4-dimethyl ribitylaminobenzene-51-phosphate is prepared by reacting a pyridine solution of 3 : 4 - dimethylribitylaminobenzene with dibenzyl chlorophosphonate in pyridine and is catalytically hydrogenated in ethanol as in (2) yielding 3 : 4-dimethylribitylaminobenzene-51-phosphate which is isolated as its sodium salt and treated with barium chloride forming the barium salt; (7) tetrabenzyl-2-methyl-1 : 4-naphthohydroquinone diphosphate is prepared by reacting dibenzyl chlorophosphonate in carbon tetrachloride with the anhydrous sodium salt of 2 - methyl - 1 : 4 - naphthohydroquinone (prepared by reacting 2-methyl-1 : 4-naphthohydroquinone with sodium methylate) in an inert atmosphere, the ester being catalytically hydrogenated as in (6) to form 2-methyl-1 : 4-naphthohydroquinone phosphate, isolated as the barium salt; (8) hexoestrol diphosphate tetrabenzyl ester is prepared by reacting the anhydrous disodium salt of hexoestrol with dibenzyl chlorophosphonate and is catalytically hydrogenated as in (6) to hexoestrol diphosphate; (9) dibenzyl tetra-acetyl glucose-6-phosphate is prepared by reacting d-glucose and dibenzyl chlorophosphonate in pyridine-carbon tetrachloride solution and adding acetic anhydride; tetra-acetyl-glucose-6-phosphate is prepared therefrom by hydrogenation in presence of Raney nickel and isolated as the barium salt; the barium salt is converted to the free acid which is then converted into its brucine salt.  The dibenzyl chlorophosphonate solutions employed above are prepared by mixing carbon tetrachloride, chloroform or benzene solutions of chlorine and dibenzyl phosphite at -5 DEG  to -10 DEG  C.; the bromo compound is prepared likewise; they are converted to dibenzyl amino phosphonate by reaction with ammonia. Dibenzyl phosphite may be prepared by reacting benzyl alcohol with phosphorus trichloride in benzene in the presence of dimethylaniline; it may also be prepared together with some tri-benzyl phosphite by adding phosphorus trichloride to benzyl alcohol in pyridine-dry ether. Specifications 527,499, 534,150 and 547,764 are referred to.