Patent GB-675779-A (GB)
Title: A process for the manufacture of substituted phosphorus oxyacids
IPC: C07F9/09
Filed: 1949-12-08
Abstract: A process for the partial de-esterification of organic orthophosphoric tri-esters of the general formula <FORM:0675779/IV (b)/1> in which X is an organic residue derived from the organic compound X.OH, where OH is a phenolic or alcoholic hydroxy group, R3 and R4 are the same or different and each is an alkyl or aromatic group, to produce the corresponding di-esters, wherein the tri-ester is treated in a polar or substantially polar solvent with a salt of the general formula [R.S-]vM, wherein R is -CN, CS.O Alkyl or -CS.NR3R2 (where R1 and R2 each represent hydrogen or an alkyl or aralkyl group or together with the N atom to which they are attached, form a piperidino or morpholino group) or any carbon containing group which renders the compound RSH acidic, M is a metallic cation, preferably of the alkali metal or alkaline earth series or a non-metallic cation such as ammonium or substituted ammonium derived from strong amines, and v is the valency of the cation M. Groups which may be removed include straight or branched chain alkyl groups and phenylmethyl, naphthylmethyl, pyridylmethyl, quinolylmethyl or pyrimidylmethyl groups.  The solvents are neutral or substantially neutral solvents capable of ionizing the reagents used in the partial de-esterification.  The carbon-containing group which renders the compound RSH acidic is one yielding a mercaptol capable of forming a stable salt with the cation M.  "Strong amines" are those having a dissociation constant greater than 1 X 10-7, e.g. cyclohexylamine, benzylamine, morpholine, b -phenyl-ethylamine and piperidine. Thiocyanates are the preferred de-esterifying reagents.  Where the groups R3 and R4 are different, aromatically-substituted groups are removed preferentially to alkyl groups.  A mixture of products may result when R3 and R4 are different aromatic groups.  In examples, di-(p-nitrobenzyl) phosphoric acid is prepared by reacting tri-(p-nitrobenzyl) phosphate with (1) potassium thiocyanate; (2) ammonium thiocyanate; (3) potassium ethyl xanthate, and as its morpholine, cyclohexyl amine benzylamine and piperidine salts from the tri-ester; and (4) morpholinium thiocyanate; (5) cyclohexyl ammonium thiocyanate; (6) benzyl-ammonium thiocyanate; and (16) piperidinium-N-piperidinodithioformate.  In an analagous manner are prepared: (7) the cyclohexylamine salt of and (10) the benzylamine salt of benzyl 2-hydroxycyclohexyl phosphoric acid; (8) the cyclohexylamine salt of p-bromobenzyl 2-hydroxycyclohexyl phosphoric acid; (9) the cyclohexylamine salt of p-nitrobenzyl 2-hydroxy-cyclohexyl phosphoric acid; (11) sym.-di-potassium dibenzyl hexoestrol diphosphate (from hexoestrol diphosphate tetrabenzyl ester); (12) sym.-di-potassium dibenzyl stilboestrol diphosphate and (13) the barium salt (from stilboestrol diphosphate tetrabenzyl ester); (14) sym.-di-cyclohexylamine salt of dibenzyl stilboestrol diphosphoric acid; (15) barium diethyl phosphate; (17) 4-methyl-morpholine salt of di-(p-nitrobenzyl) phosphoric acid; (18), (19) and (20) the cyclohexyl amine, benzylamine and lithium salts of dibenzyl phosphoric acid; (21) the cyclohexylamine salt of benzyl phenyl phosphoric acid (from dibenzyl phenyl phosphate); (22), (23), (24) the cyclohexylamine salt of diphenyl phosphoric acid (from diphenyl, ethyl, propyl, or isopropyl phosphates; (25) morpholine salt of diphenyl phosphoric acid; (26) the cyclohexylamine salt of b -(2 : 3 : 4 : 6-tetra-acetyl-D-glycosyl) benzyl phosphoric acid (from the corresponding dibenzyl phosphate).  In (1) and (2) the by-products p-nitrobenzyl thiocyanate, and in (3) S-p-nitrobenzyl ethyl xanthate are isolated from the reaction mixture.  Reagents employed include lithium and 4-methyl morpholinium thiocyanates. Other solvents mentioned are 2-ethoxyethanol, methyl ethyl ketone and n-propanol.  The process may also be applied to orthophosphoric acid triesters derived from glucose-6-phosphate, vitamin E phosphate, 2-methyl-naphthohydroquinone phosphate, oestrone-3-phosphate and testosterone-17-phosphate.