Patent GB-760214-A (GB)
Title: Improvements in or relating to the preparation of phenol-formaldehyde condensation products and polyoxy-alkylene ethers derived therefrom
Inventor: CORNFORTH JOHN WARCUP
IPC: C08G8/28
Filed: 1951-05-30
Abstract: A water-soluble chemo-therapeutic agent active against tuberculosis is obtained by reacting an alkylene oxide with a condensation product of formaldehyde and a phenol substituted in the para-position by an alkyl group containing 4-8 carbon atoms, said condensation product consisting predominantly of condensation products containing 4-6 phenolic nuclei and being substantially free from condensation products containing less than 4 phenolic nuclei.  In examples in which the p-octyl phenol used is para-alpha-alpha-gamma-gamma-tetramethyl-butyl phenol: (1) 1 mol. of p-octyl phenol was heated under reflux with 0.925 mol. of aqueous formaldehyde in presence of oxalic acid and "Teepol" (Registered Trade Mark) (i.e. a long chain alkyl sodium sulphonate) and finally in presence of toluene; after neutralization the resin was heated under vacuum at 245-250 DEG  C. Lighter molecules were removed from the resin by distillation under high vacuum and the residue was dissolved in toluene and heated in an autoclave with ethylene oxide; (2) 4 mols. of p-octyl phenol were heated under reflux with 1 mol. of aqueous formaldehyde in presence of oxalic acid and later in presence of toluene; after distilling off excess p-octyl phenol the residue was 2,21-dihydroxy-5,51 di-tertiaryoctyl diphenyl methane ("twin" resin); 4 mols. of "twin" resin and 1 mol. of formaldehyde were heated under reflux in presence of oxalic acid and "Teepol" and finally in presence of toluene and the product distilled under high vacuum to produce a residue which was reacted with ethylene oxide as in Example (1); (3) similar to Example (2), except that toluene was used from the beginning of the refluxing; (4) "Twin resin" (3.0 mol.) was dissolved in glacial acetic acid, aqueous formaldehyde (1.0 mol.) added and dry hydrogen chloride passed in.  The solution was extracted with toluene which was later removed by distillation and after removal of the "twin" resin by distillation in high vacuum the residue was treated with ethylene oxide as in Example (1); (5) the residue of Example (4) was dissolved in toluene and heated in a molecular still to yield a condensate which was dissolved in ether and the ether evaporated.  The residue was principally two molecules of "twin" resin linked by a methylene group (i.e. "quad" resin). After removal of "twin" resin from the crude "quad" resin the latter was purified by distribution between two solvents (viz. ligroin and aqueous ethanol).  The purified "quad" resin was reacted with ethylene oxide as in Example (1); (6) o-o1-dihydroxymethyl-p-tertiary octyl phenol obtained by condensing p-tertiary octyl phenol with aqueous formaldehyde in alkaline medium was condensed with excess "twin" resin, using trichloracetic acid as solvent and catalyst and the resulting resin distilled to yield a fraction consisting mainly of "quin" resin.  The product was then condensed with ethylene oxide; (7) p-tertiary butyl phenol (1.0 mol.) was condensed with aqueous formaldehyde (1.0 mol.) in presence of oxalic acid and finally toluene.  After removing the toluene the product was freed from lighter molecules and was then condensed with ethylene oxide.ALSO:A solution for injection against tuberculosis comprises (1) a neutral aqueous solution of a Chemo-therapeutic agent which is a reaction product of an alkylene oxide with a condensation product of formaldehyde and a phenol substituted in the paraposition by an alkyl group containing 4-8 carbon atoms (see Group IV(a)) diluted with (2) physio logical saline.