Patent GB-753319-A (GB)
Title: High molecular, phosphorus-containing anti-enzymatic substances and the production thereof
IPC: C08G79/04
Filed: 1953-06-15
Abstract: Phosphorus-containing polymers having antienzymatic properties are prepared by condensing phosphorus oxychloride, thiophosphoryl chloride or phenoxyphosphoryl dichloride with one or more aromatic compounds containing three or more OH and/or NH groups in the aromatic nucleus or containing two of such groups either in different nuclei or in m- or p-position to ether other in the same nucleus, said compounds not being flavones, flavanones, or the corresponding chalcones or dihydrochalcones or glycosides thereof.  The condensation product is hydrolysed, e.g. with ice water to remove surplus acid chloride group and, if desired to reduce the molecular weight.  The products must contain free hydroxyl groups linked to phosphorus and have a molecular weight exceeding 2000 but not high enough to render them insoluble in water or aqueous alkali. Preferably a tertiary amine is used as hydrogen-halide binding agent in the condensation.  In multicuclear starting materials the nuclei may be linked by a bridge containing not more than two carbon atoms and not more than one O, N or S atom.  Suitable materials which may be linked to the phosphorus radicals are hydroquinone, resorcinol, m- or p-phenylenediamine, m- or p-aminophenol, m- or p-N-alkylaminophenol in which the alkyl groups may for example be methyl, butyl, dodecyl, octadecyl, or cycloalkyl The materials may also contain substituents such as alkyl, halogen, nitro, carboxyl, sulphonic acid, keto or acetyl groups.  Some suitable starting materials are p,p1-dihydroxy-diphenyldimethyl methane, phloroglucinol, pyrogallol, hydroxyhydroquinone, symmetrical aminoresorcinol, vicinal aminoresorcinol, orcinol, hydroquinone, resorcinol, phloroglucinaldehyde, phloracetophenone, gallic acid, gentiric acid, 1,2,5,8 tetrahydroxyanthraquinone, 2,4,41,6- tetrahydroxybenzonthenone, diphenylamine, triphenylamine, dinaphthylamine, phenylbenzylamine, 4,41-dihydroxy diphenyl ether, 4,41-diaminodiphenyl ether, ethylene glycol bis-4-hydroxy phenyl ether, 4,41-dihydroxydiphenyl-sulphide, p,p1 - methylanedi - thiodianilin, and 4 - hydroxybenzoic acid - 3,5 - dihydroxyphenyl ester.  Phosphorylation may be effected in solution in the halogen halide-binding agent or other solvent. The temperature is maintained low by cooling, by slow continuous addition of the phosphorylating agent or hydrogen halide-binding agent if desired with intervals between the additions.  The products are isolated by dialysis, by precipitation with acid or by cautious evaporation to dryness if desired together with a salting-out.  Many examples are given of the preparation of suitable compounds, the potency of the products as antihyaluronidose agents being determined in an explained manner and expressed.  In a typical example phloroglucinol is dissolved in anhydrous pyridine and cooled.  Phosphorus oxychloride in pyridine is added dropwise with cooling and shaping.  The mixture is left to stand in a cooling bath and when turbility commences is hydrolysed with crushed ice.  After evaporation in vacuo, oily poly-phloroglucinol phosphate is obtained.  Dissolved in water and treated with barium chloride and alkali this yields the barium salt of the polymer which is precipitated with ethanol and dried over P2O5.  The acid phosphate may be obtained by addition of sulphuric acid to an aqueous solution of the barium salt.  Specification 700,761, [Group IV (b)], is referred to.