Patent GB-789985-A (GB)
Title: Ethyl esters of thiolcarboxylic acids
Inventor: DRIVER GEORGE WILLIAM
Filed: 1954-10-29
Abstract: The invention comprises compounds of the formula R,COSEt, wherein R stands for an alkyl group of 3-10 carbon atoms, an aralkyl group, a heterocyclic radical or a cycloalkylene imine residue or for a group OR1 wherein R1 is an alkyl group of more than 2 carbon atoms which may optionally be substituted by EtSCOO groups or nitro groups, an aryl group which may optionally be substituted by alkoxy, aldehydo or EtSCOO groups or halogen atoms, or for a heterocyclic radical.  The compounds are prepared: (a) in the case where R stands for the group R1O, by interaction of a compound of the formula R11OH wherein R11 is an alkyl group of more than 2 carbon atoms, optionally substituted by hydroxy or nitro groups, or is a cycloalkyl group, or an aryl group optionally substituted by alkoxy, aldehydo or hydroxy groups or halogen atoms, or is a heterocyclic radical, with ethyl chlorothiolformate; (b) in the case where R is a cycloalkylene imine residue, by the reaction of a cycloalkylene imine with ethyl chlorothiolformate; and (c) in the case where R is an alkyl group of 3-10 carbon atoms or an aralkyl or heterocyclic radical, by reaction of an acid halide of the formula RCOX, wherein X is a halogen atom, with ethyl mercaptan.  The above reactions are preferably carried out in a solvent or diluent in the presence of an acidbinding agent.  The products are used in the treatment of tuberculosis.  Examples describe the preparation of compounds of the formula R1CO,COSEt wherein R1 is a cyclohexyl, n-butyl, tert.-butyl, phenyl, a -naphthyl, b -naphthyl, p-methoxyphenyl, 8-quinolyl, 2:4-dichlorophenyl, 2 - methoxy - 4 - aldehydrophenyl, and 3 - ethylthiocarbonyloxyphenyl radical; compounds of the formula R,COSEt wherein R is a n-pentyl, n-propyl, benzyl, piperidino and pyridyl-(4) radical and also tetrakis (ethylthiocarbonyloxymethyl) methane and tris (ethylthiocarbonyloxymethyl) nitromethane.  The Provisional Specification relates to compounds of the above general formula in which R is an alkyl group of 2-10 carbon atoms, an aralkyl or cycloalkyl group, or a substituted or unsubstituted heterocyclic radical, or wherein R1 is a substituted or unsubstituted hydrocarbon radical of more than 2 carbon atoms or heterocyclic radical.ALSO:Pharmaceutical compositions suitable for the treatment of tuberculosis comprise compounds of the formula RCOSEt (I) or R1OCOCEt (II), wherein R is an alkyl group of 3-10 carbon atoms, an aralkyl group, a heterocyclic radical or a cycloalkylene imine residue, and R1 is an alkyl group of more than 2 carbon atoms, which may optionally be substituted by EtSCOO groups or nitro groups, an aryl group, which may optionally be substituted by alkoxy, aldehydo or EtSCOO groups or halogen atoms, or is a heterocyclic radical, admixed with a pharmaceutical excipient.  The compounds may be used for example in pills, tablets, capsules or other pharmaceutical forms.  Examples describe compositions suitable for intramuscular administration comprising solutions in arachis oil of active compounds of the formula I wherein R is amyl, propyl and benzyl and compounds of the formula II wherein R1 is cyclohexyl, n-butyl, tert.-butyl, phenyl, a -naphthyl, b -naphthyl, p-methoxyphenyl, 8-quinolyl and 2 : 4-dichlorophenyl.  Other specified active compounds are tetrakis (ethylthiocarbonyloxymethyl) methane, tris-(ethylthiocarbonyloxymethyl) nitromethane, ethyl N-cyclopentamethylenethiolcarbamate, ethyl O-(2-methoxy-4-aldehydophenyl) thiolcarbonate, ethyl O-m-phenylene - bis - ethylthiolcarbonate and ethyl thiolisonicotinate.  The definition of the groups R and R1 in the Provisional Specification is somewhat wider.