Patent GB-771116-A (GB)
Title: Improvements in the manufacture of organic compounds containing nitrogen, arsenic, sulphur or selenium
IPC: C07D295/027
Filed: 1953-10-07
Abstract: a -Substituted heterocyclic compounds of the general formula <FORM:0771116/IV(b)/1> (wherein R represents hydrogen or an alkyl, aryl, aralkyl or heterocyclic radical, R1 represents an alkyl, carbalkoxy-substituted alkyl, aryl, aralkyl or heterocyclic radical, n is a whole number greater than 2, and A represents S, Se, AsH or NH) are prepared by reacting an organometallic compound of the general formula R1MX (wherein M represents magnesium or zinc and X halogen) with an aldehyde or ketone of the general formula R-CO-(CH2)n-X to produce a compound of the general formula <FORM:0771116/IV(b)/2> and reacting this, or the alcohol of the general formula <FORM:0771116/IV(b)/3> obtained therefrom by hydrolysis, with a compound of the general formula (X1)2A (wherein X1 represents hydrogen, or a monovalent metal when A is S, Se or AsH). When the alcohol is intermediately produced, the reaction thereof with the compound (X1)2A (wherein A is NH, S or AsH) may take place in two stages with the intermediate formation of an aminoalcohol, monothioglycol or hydroxyalkylarsine which is then cyclized by heating.  In a further modification, when n is 3 or 4, the alcohol is first heated with caustic alkali solution to form an a -substituted tetrahydrofuran or tetrahydropyran, and this is then reacted, preferably with heating, with the compound (X1)2A.  In examples: (1) g -chlorobutyraldehyde is reacted with phenyl magnesium bromide in ether, the product is hydrolysed to 1-phenyl-4-chloro-butanol-1 which with caustic potash yields a -phenyltetrahydrofuran, and this is heated with ammonia under pressure to form a -phenyl-pyrrolidine; (2) 1-phenyl-4-chlorbutanol-1 is prepared as in (1) and treated with gaseous ammonia in the cold, and the resulting 1-phenyl - 4 - aminobutanol - 1 is converted to a -phenylpyrrolidine by heating; (3) hydrogen sulphide similarly yields C6H5.CHOH.(CH2)3.SH and thence a -phenylthiophan; (4) the initial condensation product of (1) is directly reacted with gaseous ammonia; and (5) with hydrogen sulphide; (6) 5-chloropentanone-2 is reacted with dimethyl bromosuccinate and zinc foil in benzene and the product with gaseous ammonia to produce a  - methyl - a  - (a 1 : b 1 - dicarbo-methoxyethyl)-pyrrolidine; (7)-(9) the ammonia in (6) is replaced by hydrogen sulphide, hydrogen selenide and arsine, yielding the corresponding -S-, -Se- and -AsH- compounds; (10) the phenyl magnesium bromide in (2) is replaced by ethyl magnesium bromide to produce successively 1-ethyl-4-chloro- and 4-amino-butanol-1 and a -ethylpyrrolidine; (11) d -chlorovaleraldehyde similarly yields 1-ethyl- 5 - chloro - and 5 - amino - pentanol - 1 and a -ethylpiperidine; (12) d -chlorovaleraldehyde is reacted with phenyl magnesium bromide in ether, the product is hydrolysed and the resulting 1 - phenyl - 5 - chloropentanol - 1 heated with caustic potash solution to form a -phenyl-tetrahydropyran, which on heating with gaseous ammonia under pressure yields a -phenyl-piperidine; (13) 1-phenyl-5-chloropentanol-1 is treated with arsine to form C6H5.CHOH. (CH2)4.AsH2 which is converted by heating into a compound of the formula <FORM:0771116/IV(b)/4> (14) the phenyl magnesium bromide in (12) is replaced by b -pyridyl magnesium bromide.