Patent GB-633874-A (GB)
Title: Improvements in and relating to isoquinoline derivatives
IPC: C07D217/10
Filed: 1947-04-19
Abstract: 1 - Dicarbalkoxymethylene - 2 - alkyl - 1 : 2-dihydroisoquinolines of the formula <FORM:0633874/IV (b)/1> wherein R, R1 and R2 are alkyl or substituted alkyl groups, are prepared by condensing the corresponding 1 - alkylmercaptoisoquinoline alkyl quaternary salts with a malonic ester of formula <FORM:0633874/IV (b)/2> The condensation may be effected in presence of a diluent such as an alcohol and an acid-binding agent such as a trialkylamine. 1-Dicarbethoxymethylene - 2 - methyl - 1 : 2 - dihydroisoquinoline is prepared by heating together 2 - methyl - 1 - thioisoquinolone and methyl p-toluenesulphonate, adding diethyl malonate, ethyl alcohol and triethylamine, and refluxing. 1 - Dicarbethoxymethylene - 2 - ethyl - 1 : 2 - di - hydroisoquinoline, 1 - dicarbethoxymethylene-2-n-propyl - 1 : 2 - dihydroisoquinoline, 1 - dicarbethoxymethylene - 2 - n - butyl - 1 : 2 - dihydroisoquinoline, 1 - dicarbethoxymethylene - 2 - benzyl-1 : 2 - dihydroisoquinoline, 1 - dicarbethoxymethylene - 2 - allyl - 1 : 2 - dihydroisoquinoline, 1 - carbethoxymethylene - 2 - b  - hydroxethyl - 1 : 2-dihydroisoquinoline, 1 - dicarbmethoxymethylene-2 - methyl - 1 : 2 - dihydroisoquinoline, 1 - dicarbpropoxymethylene-2-methyl-1 : 2-dihydroisoquinoline and 1-dicarbisobutyroxymethylene-2-methyl - 1 : 2 - dihydroisoquinoline are similarly prepared. 2-Methyl-1-thiosoquinoline is prepared by refluxing together 2-methyl-1-isoquinolone and phosphorus pentasulphide in pyridine. 2-Ethyl-1-thioisoquinolone, 2-n-propyl-1-thioisoquinolone, 2 - isobutyl - 1 - thioisoquinolone, 2 - allyl - 1 - thioisoquinoline, 2 - b  - hydroxyethyl - 1 - thioisoquinolone and 2-benzyl-1-thioisoquinolone are similarly prepared. 2-Methyl-1-isoquinolone is prepared by heating together isoquinoline with methyl p-toluenesulphonate, and adding a cold aqueous solution of the quaternary salt so produced to a cold aqueous solution of potassium hydroxide and potassium ferricyanide. 2-Ethyl-1-isoquinolone, 2-n-propyl-1-isoquinolone, 2-n-butyl-2-isoquinolone, 2 - allyl - 1 - isoquinolone, 2 - b  - hydroxyethyl - 1 - isoquinolone and 2 - benzyl - 1 - isoquinolone are similarly prepared.  1-Methylisoquinoline methiodide is prepared by heating 1-dicarbethoxymethylene-2-methyl-1 : 2 - dihydroisoquinoline with concentrated hydrochloric acid, and treating the hot ethanol solution of the methochloride obtained with a hot ethanol solution of NaI.  1-Methylisoquinoline ethiodide is prepared by heating together 2-ethyl-1-thioisoquinolone and ethyl p-toluenesulphonate, adding diethyl malonate, ethyl alcohol, and triethylamine and refluxing, heating the 1-dicarbethoxymethylene-2-ethyl-1 : 2-dihydroisoquinoline so produced with concentrated hydrochloric acid, and adding to a hot ethyl alcohol solution of the 1-methylisoquinoline ethochloride so produced an ethyl alcohol solution of sodium iodide. 1-Methylisoquinoline n - propiodide, 1 - methylisoquinoline n - butiodide, 1 - methylisoquinoline b  - hydroxyethiodide and 1-methylisoquinoline benziodide are similarly produced. Specification 633,873, [Group IV (c)], is referred to.