Patent GB-726876-A (GB)
Title: Improvements in or relating to method of preparing substituted benz [cd] indolines and the substituted benz [cd] indolines resulting from said method
IPC: C07D209/90
Filed: 1953-07-07
Abstract: The invention comprises benz (cd) indolines of formula <FORM:0726876/IV (b)/1> wherein R represents an aliphatic acyl or monocyclic aroyl radical and R1 represents a formyl, cyano, acyl, formylsemicarbazone, carboxyalkyl or carbalkoxyalkyl radical. The compounds are prepared by dehydrogenating a compound of formula <FORM:0726876/IV (b)/2> where R2 corresponds to R1 except that R2 is an oxime (-CH=NOH) radical when R1 is cyano.  Dehydrogenation is preferably carried out with a palladium on carbon catalyst and in presence of a solvent comprising ethylene glycol monoethylether, toluene, xylene or paracymene.  Preferred compounds for dehydrogenation are N-benzoyl-5-formyl-1,2,2a,3-tetrahydrobenz (cd) indole and the oxime and semicarbazone thereof; N-acetyl-5-formyl-1,2,2a,3-tetrahydrobenz (cd) indole semicarbazone; N-benzoyl - 5 - carboxymethyl - 1,2,2a,3 - tetrahydrobenz (cd) indole; N-benzoyl-5-carbomethoxymethyl - 1,2,2a,3 - tetrahydrobenz (cd) indole; N - benzoyl - 5 - carbethoxymethyl - 1,2,2a,3 - tetrahydrobenz (cd) indole; and N - benzoyl - 5 - acetyl - 1,2,2a,3 - tetrahydrobenz (cd) indole. The examples describe the preparation of N - benzoyl - 5 - (formyl-, acetyl-, cyano-, carboxymethyl-, carbomethoxymethyl-, and carbethoxymethyl-) benz (cd) indolines and the semicarbazones of N-acetyl-, N-benzoyl-, N-butyryl-, N-toluoyl-, N-propionyl-, and N-cyclopentanecarboxyl-5-formylbenz (cd) indolines. In preparing intermediate compounds indole-3-propionic acid is hydrogenated (e.g. with hydrogen using a nickel catalyst) and reacted with an acyl halide to form an N-acyl (e.g. acetyl) - indoline - 3 - propionic acid which is treated with thionyl chloride to give the corresponding acid chloride (e.g. N-acetyl- and N-benzoyl - indoline - 3 - propionyl chlorides) and then cyclized with aluminium chloride to produce an N-acyl (e.g. acetyl- and benzoyl-)-5-keto - 1,2,2a,3,4,5 - hexahydrobenz (cd) indole; this latter compound is then reacted with (1) a chloroacetic acid ester in a Darzen's type reaction to produce a glycidic ester (e.g. ethyl-b -5 - (N - benzoyl - 1,2,2a,3,4,5 - hexahydrobenz (cd) indolyl)-glycidate) which is hydrolysed to the sodium salt of the glycidic acid, reaction of which with pyridine hydrobromide perbromide and subsequent treatment of the resulting bromoaldehyde with semicarbazide yields an N-acyl (e.g. acetyl- and benzoyl-) - 5 - formyl - 1,2,2a,3 - tetrahydrobenz (cd) indole semicarbazone from which an N-acyl (e.g. benzoyl-)-5-formyl - 1,2,2a,3 - tetrahydrobenz (cd) indole may be obtained by distillation with pyruvic acid, this latter product is converted to the corresponding oxime (e.g. N - benzoyl - 5 - formyl - 1,2,2a,3 - tetrahydrobenz (cd) indole oxime) by treatment with hydroxylamine hydrochloride; (2) an a -haloalkyl cyanide (e.g. a -chloropropionitrile, a -chlorobutyronitrile and a -chlorocapronitrile) in a Darzen's reaction to produce a glycidonitrile compound (e.g. a -methyl-b -5-(N-benzoyl - 1,2,2a,3,4,5 - hexahydrobenz (cd) indolyl)-glycidonitrile) which is treated with hydrogen chloride to give, for example, N-benzoyl-5 - acetyl - 5 - chloro - 1,2,2a,3,4,5 - hexahydrobenz (cd) indolecyanohydrin which yields on heating with collidine N-benzoyl-5-acetyl-1,2,2a,3-tetrahydrobenz (cd) indole; (3) an alkyl haloacetate (e.g. methyl and ethyl bromoacetate) and activated zinc to produce, for example, N-benzoyl - 5 - hydroxy - 5 - carbomethoxymethyl (and carbethoxymethyl) - 1,2,2a,3,4,5 - hexahydrobenz (cd) indole which on warming with formic acid yield corresponding N-benzoyl-5-carbomethoxymethyl (and carbethoxymethyl) - 1,2,2a,3 - tetrahydrobenz (cd) indole, subsequent hydrolysis of these with alcoholic sodium hydroxide giving N - benzoyl - 5 - carboxymethyl - 1,2,2a,3 - tetrahydrobenz (cd) indole.  The Specification also outlines the preparation of lysergic and norlysergic acids using benz (cd) indolines as starting materials.