Patent GB-777794-A (GB)
Title: New 1:3-dioxolane derivatives and process for their preparation
IPC: C07D317/28
Filed: 1955-09-09
Abstract: The invention comprises 1 : 3-dioxolane derivatives of the formula <FORM:0777794/IV(b)/1> and their salts of general formula <FORM:0777794/IV(b)/2> in which R and R5 each represent hydrogen, a hydroxyl group or an alkoxy group containing from 1 to 10 carbon atoms; R1 is hydrogen or a straight or branched alkyl radical containing from 1 to 4 carbon atoms; R2 and R3, which may be the same or different, are hydrogen, a straight or branched chain alkyl radical containing from 1-4 carbon atoms, a hydroxyalkyl, cycloalkyl or aralkyl group; or together with the nitrogen atom form a four-, five- or six-membered saturated heterocyclic ring which may contain other hetero atoms; R4 is hydrogen, a straight or branched alkyl group containing from 1 to 4 carbon atoms, or a cycloalkyl or aralkyl radical; and X is an anion derived from an organic or inorganic acid, preferably halogen or an alkyl sulphate anion.  The compounds are prepared (a) by reacting a 2 - aryl - 2 - halogenomethyl - 1 : 3 - dioxolane with an amine NHR2R3 (preferably present in excess, e.g. 2-5 mols.), at an elevated temperature, preferably between 100 DEG and 200 DEG  C., and if required subsequently forming salts by treatment with HX or R4X; (b) by condensing an amino ketone of formula <FORM:0777794/IV(b)/3> or an acid addition salt thereof with a glycol, CH2OH.CHR1OH, or the corresponding 1 : 2-epoxide, preferably using an acid catalyst, e.g. HCl, H2SO4, SnCl4, acetic acid or its anhydride, or p-toluene sulphonic acid.  Method (a) may be effected in the presence or absence of a solvent such as ethanol, butanol, benzene, or xylene, and an acid binding agent, e.g. potassium carbonate or calcium oxide; method (b) is preferably carried out in a solvent such as benzene, xylene and ligroin, the water which is liberated when using the glycols being eliminated by azeotropic distillation.  In examples: (1) 2-phenyl - 2 - bromomethyl - 1 : 3 - dioxolane in ethanolic methylamine is autoclaved, the ethanol evaporated, the residue ether extracted and 2 - phenyl - 2 - methylaminomethyl - 1 : 3 - dioxolane hydrochloride precipitated with ethereal HCl; similarly, (2) to (23), are prepared 1 : 3-dioxolanes of formula I wherein R is hydrogen, p-methoxy, p-ethoxy, p-butoxy, o-butoxy, p-isoamyloxy, or p-n-octyloxy; R5 is hydrogen; R1 is hydrogen or methyl, R2 and R3 are respectively methyl and b -hydroxyethyl, n-butyl and b -hydroxyethyl, benzyl and b -hydroxyethyl, or both ethyl, or together with the nitrogen atom are morpholino-, or piperidino-; also salts of these compounds with HCl, MeI, Me2SO4 and EtBr; (24) p-butoxy-o -(N-methyl-N-cyclohexyl) amino-acetophenone hydrochloride in benzene is refluxed with ethylene glycol and p-toluene sulphonic acid, the benzene extracted with water and the aqueous solution basified, precipitating 2-p-butoxyphenyl - 2 - (N - methyl - N - cyclohexylamino) methyl-1 : 3-dioxolane as an oil purified by distillation; (25) p-butoxy-o -morpholino-acetophenone hydrochloride in chloroform is treated with ethylene oxide and stannic chloride in an autoclave, the mixture evaporated yielding 2-(p - butoxyphenyl) - 2 - morpholinomethyl - 1 : 3-dioxolane hydrochloride; (26) p-butoxy-o -morpholinomethyl-acetophenone methobromide is refluxed with ethylene glycol and phosphoric acid to give 2-(p-butoxyphenyl)-2-morpholinomethyl-1 : 3-dioxolane methobromide.  Further lists of reactant halomethyl-1 : 3-dioxolanes, amines, salt-forming acids, and quaternizing agents are given. Starting materials.  2-Aryl-2-halogenomethyl-1,3-dioxolanes are prepared by condensing an o  - halogeno - acetophenone with a glycol, CH2OH.CHR1OH, or the corresponding epoxide.  A detailed list of these starting materials in which the halogen is bromine or iodine and the aryl group is substituted by methoxy, ethoxy, hydroxy, decyloxy, 31-ethyl-21-pentyloxy-, 21-methyl - 11 - pentyloxy, and 31,31 - dimethyl-11-butyloxy groups is provided.