Patent GB-563171-A (GB)
Title: Manufacture of pyridine-3-acetic acid esters and quaternary compounds thereof
IPC: C07D213/55
Filed: 1942-08-11
Abstract: Esters of pyridine-3-acetic acid are prepared by acting on pyridine 3-acetic acid or certain of its derivatives with an alcohol. Derivatives of the acid which may be used include the nitrile, amide, anhydride, halides and salts.  Alcohols mentioned include saturated or unsaturated aliphatic, aliphatic - aromatic, or isocyclic alcohols, such as methanol, ethanol, propanol, isopropanol, amyl alcohol, benzyl alcohol, phenol, cyclohexanol, furyl carbinol and basic substituted alcohols such as diethylaminoethanol.  Instead of the alcohols themselves, certain of their derivatives may be used, such as alcoholates, esters and ethers including alkyl halides, dialkyl sulphates, and diazoalkenes such as diazomethane.  The esterification preferably takes place in the presence of a solvent which may either be an excess of the alcohol used in the esterification or an inert solvent such as benzene.  Condensing agents such as hydrochloric, or sulphuric acid, phosphorus oxychloride, phosgene, an alkali or an alkaline earth carbonate, an alkali acetate, an alkaline earth halide, or a tertiary base such as pyridine.  The quaternary derivatives of esters of pyridine-3-acetic acid may be either obtained from the esters by reaction with an alkyl halide, an alkylene halide, an aralkyl halide, a dialkyl sulphate or an aryl sulphonic acid ester, or the quaternary compound of the pyridine-3-acetic acid may be used as starting material.  The operations of esterification and conversion into a quaternary compound may be performed in one operation.  In examples: (1) a methanol solution of pyridine-3-acetic acid is boiled under reflux in the presence of hydrogen chloride.  The solvent is removed and the product treated with sodium carbonate.  Instead of the free acid, the acid amide may be used as starting material.  To convert the pyridine-3-acetic acid methyl ester so prepared into its quaternary compound, it is boiled with methyl iodide under reflux to form pyridine-3-acetic acid methyl ester methiodide.  Treatment of this compound with silver chloride forms the corresponding methochloride. Treatment of the methyl ester with dimethyl sulphate yields the dimethylsulphonate.  Instead of dimethyl sulphate there may be used p-toluene sulphonic acid methyl ester. (2) As in example (1) using ethanol instead of methanol.  (3) As in example (1) using as the esterifying alcohol isopropanol.  (4) As in example (1) using isobutyl alcohol.  (5) Pyridine-3-acetic acid is converted into its acid chloride with thionyl chloride and this compound esterified with n - propanol.  (6) Pyridine-3-acetic acid methyl ester is treated with allyl alcohol in the presence of a small amount of sulphuric acid to form the pyridine-3-acetic acid allyl ester.  (7) The dry sodium salt of pyridine-3-acetic acid is boiled with chlorethyldiethylamine to form pyridine-3-acetic acid diethylaminoethanol.  (8) Pyridine-3-acetic acid is heated with excess of methyl iodide under reflux to form pyridine-3-acetic acid methyl ester methiodide.  The Specification as open to inspection under Sect. 91 includes also the application of the process of the invention to aromatic and heterocyclic alcohols.  This matter is not included in the Specification as accepted.