Patent GB-417785-A (GB)
Title: Improvements in or relating to the manufacture of antibacterial and germicidal compounds
Filed: 1933-01-07
Abstract: Monochlorinated hydroxydiphenylmethane compounds are manufactured by condensing a reactive a -arylalkyl derivative with a phenol or a homologue thereof or the corresponding phenolate, one of said compounds having a single chlorine atom substituted in the nucleus and the other being free from halogen.  When using the free phenol, the reaction is advantageously effected in the presence of a condensing agent, e.g. zinc or other heavy metals, anhydrous zinc chloride, aluminium chloride, ferric chloride or the chlorides of other heavy metals or mineral acids such as sulphuric acid.  In the production of alkyl- or polyalkylhydroxydiphenylmethanes the phenolic body used may have one or more alkyl radicles substituted in the nucleus.  The products are antibacterial and germicidal compounds. In examples: (1) phenol is condensed with p-chlorobenzyl chloride in the presence of zinc chloride to produce 4<1>-chloro-4-hydroxydiphenylmethane; (2) p-chlorophenol and benzyl chloride similarly yield 5-chloro-2-hydroxydiphenylmethane; 3-chloro-4-hydroxydiphenylmethane may be obtained by a similar method; similar compounds may be obtained by reacting a monochlorine substituted alkali metal phenate, e.g. sodium p-chlorophenate, with benzyl chloride in a non-dissociating solvent, e.g. toluene; (3) the sodium compound of p-chloro-o-cresol is treated with benzyl chloride in toluene to produce 5-chloro-3-methyl-2-hydroxydiphenylmethane; (4) the sodium p  compound of p-chloro-m-cresol is condensed with benzylchloride, the product being probably a mixture of 4- and 6-methyl-5-chloro-2-hydroxydiphenylmethanes; (5) sodium o-cresolate and p-chlorobenzyl chloride similarly yield 4<1>-chloro-3-methyl-2-hydroxydiphenylmethane; by condensing p-chlorobenzyl chloride with o-cresol in the presence of a heavy metal chloride there is obtained 4<1>-chloro-3-methyl-4 hydroxydiphenylmethane; corresponding ethyl, propyl, isopropyl, butyl and higher alkyl compounds may be prepared by using the corresponding alkyl substituted phenols, whilst changes in the position of the alkyl groups may be effected by employing the m- or p-substituted alkyl phenols; (6) 4-chloro-sym.-m-xylenol is converted into an alkali metal compound, e.g. by the action of sodium in toluene, and the product is reacted with benzyl chloride to produce 5 - chloro - 4 : 6 - dimethyl - 2 - hydroxydiphenylmethane, which may also be obtained by condensing 4-chloro-sym.-m-xylenol with benzyl chloride in the presence of a condensing agent; monochloro-derivatives of other polyalkylphenols, e.g. diethylphenol, dipropylphenol, thymol or carvacrol may be similarly employed, e.g. by condensing the sodium compound of chlorothymol with benzyl chloride there is obtained 5-chloro-6-methyl-3-isopropyl-2-hydroxydiphenylmethane; the chlorine may be substituted in the other nucleus, e.g. by condensing p-chlorobenzyl chloride with the sodium compound of sym.--m--xylenol there is obtained 4<1>-chloro-4 : 6-dimethyl-2-hydroxydiphenylmethane; the xylenol may be replaced by other polyalkylphenols, e.g. diethylphenol, dipropylphenol, thymol or carvacrol, and the p-chlorobenzyl chloride by the m-compound. Specification 332,960, [Class 2 (iii)], is referred to.  The Specification as open to inspection under Sect. 91 comprises in general the manufacture of substituted diphenylalkyl compounds (including those in which alkyl groups are attached to the carbon atom connecting the nuclei) by condensing an arylalkyl halide body with a phenolic body, a halogen being introduced into the nucleus of one or both of said bodies either before or after the condensation, and the obtaining of antibacterial and germicidal action by the application of aqueous solutions of the products. In additional examples: (1) the following compounds are obtainable by methods similar to that of (2) above : 3-bromo-4-hydroxydiphenylmethane; 5-bromo-2-hydroxydiphenylmethane; 3 : 4<1> - dichloro-4-hydroxydiphenylmethane; 3 - chloro - 4<1> - bromo - 4 - hydroxydiphenylmethane; halogens including iodine may be substituted in either nucleus of the products; (2) the product of (3) above may be prepared by condensing sodium o-cresolate with benzyl chloride and chlorinating the product; (3) chlorine or other halogen may be substituted in either nucleus of the products of (3), (4) and (5) above; (4) the product of (6) above may be prepared by condensing the sodium compound of sym.-m-xylenol with benzylchloride and chlorinating the product; bromo- or iodoxylenols may be employed in the process of (6) above to produce the corresponding halogenated compounds; (5) 4<1>-bromo-4 : 6-dimethyl-2-hydroxydiphenylmethane may be prepared from p-bromobenzyl chloride and the sodium compound of sym.-m-xylenol.  This subject-matter does not appear in the Specification as accepted.