Patent GB-1112681-A (GB)
Title: N-aminoalkyl-benzothiazacycloalkanones and- cycloalkanes
Inventor: MORREN HENRI
IPC: C07D337/08
Filed: 1965-09-15
Abstract: Novel compounds of formula <FORM:1112681/C2/1> wherein A represents hydrogen, halogen, alkyl, alkoxy, acyl, haloalkyl or cyano, D and E taken separately each represent a hydrogen atom, or taken together represent an oxygen atom, R and R1 are hydrogen atoms, or alkyl or alkenyl radicals containing up to 5 carbon atoms, or together with the nitrogen atom to which they are attached represent a heterocyclic ring which may be substituted and/or contain other hetero atoms, Y is a straight or branched alkylene chain which may contain up to 5 carbon atoms, and n is 3 or 4, and wherein one of the hydrogen atoms in the (CH2)n group can be replaced by an alkyl radical containing up to 5 carbon atoms, and the addition salts thereof with organic and inorganic acids, are prepared (1) when D and E together represent an oxygen atom, (a) by condensing an alkali metal derivative of a benzothiazacycloalkanone with an aminoalkyl halide of formula Hal-Y-NRR1 where Hal is a halogen atom, or (b) by reacting the alkali metal derivative of a benzothiazacycloalkanone with an a ,o -chlorobromoalkane of formula Br-Y-Cl and reacting the resulting N -(o -chloroalkyl) derivative with an amine R-NH-R1, and (2) when D and E both represent hydrogen atoms, (a) by reducing the carbonyl group of the corresponding benzothiazacycloalkanone with lithium aluminium hydride, (b) by condensing a benzothiazacycloalkane with an aminoalkyl halide of formula Hal-Y-N-RR1, (c) by condensing a benzothiazacycloalkane with an a ,o -chlorobromoalkane of formula Br-Y-Cl, in the presence of an acid acceptor, and condensing the resulting N -(o -chloroalkyl) derivative with an amine R-NH-R1, (d) when R is a hydrogen atom and R1 is other than hydrogen, by reacting a benzothiazacycloalkane N-substituted by a -Y-NR1R11 group in which R11 represents a methyl radical with ethyl chloroformate and subjecting the resultant carbethoxylated derivative to alkaline or acid hydrolysis, (e) when R is a hydrogen atom and R1 is a methyl radical by reacting an aminoalkylbenzothiazacycloalkane with ethyl chloroformate and subjecting the carbethoxylated derivative to reduction with lithium aluminium hydride, or (f) when R and R1 are hydrogen and Y is an ethylene radical, by reacting a benzothiazacycloalkane with chloroacetonitrile, and reducing the cyanomethyl derivative obtained with lithium aluminium hydride.  The intermediate benzothiazacycloalkanones may be obtained by subjecting the corresponding benzothiacycloalkanones to Schmidt reaction using acetic acid, sulphuric acid and sodium azide.  The benzothiazacycloalkanes can be obtained by reducing the corresponding benzothiazacycloalkanones with lithium aluminium hydride.  The 3,4-dihydro-(2H)-1-benzothiepin -5-ones may be made by treating a phenylthiobutyryl chloride, prepared from the corresponding acid, with aluminium chloride and carbon disulphide. The phenylthiobutyric acid is prepared either by the hydrolysis of ethyl phenylthiobutyrate obtained by condensing thiophenol with ethyl 4-chlorobutyrate or by hydrolysis of phenylthiobutyronitrile obtained by condensing thiophenol with 4-chlorobutyronitrile.