Patent GB-800649-A (GB)
Title: Improvements in or relating to cyclohexenone derivatives
IPC: C07D295/116
Filed: 1957-01-28
Abstract: The invention comprises compounds of formula: <FORM:0800649/IV (b)/1> wherein R1 and R2 are alkyl groups having not more than four carbon atoms, or together with the nitrogen atom to which they are attached complete a heterocyclic ring system and R is hydrogen or a methyl group.  The preparation of compounds of formula I may be schematically illustrated as follows: <FORM:0800649/IV (b)/2> <FORM:0800649/IV (b)/3> <FORM:0800649/IV (b)/4> <FORM:0800649/IV (b)/5> <FORM:0800649/IV (b)/6> In these formul  R1 is an alkyl group of 2-6 carbon atoms, X is a halogen atom, R11 is an alkyl group and M is an alkali metal.  Compound II may be converted to compound III by refluxing it in benzene with the alcohol, preferably isobutyl or isoamyl alcohol, in the presence of para-toluene sulphonic acid and with continuous removal of water.  In the conversion of compound III to compound IV by the Reformatsky reaction the ester X-CH2-COOR11 is preferably ethyl or isobutyl bromacetate.  The conversion of compound IV to compound V and thence into compound I is preferably carried out by saponification of compound IV to the corresponding alkali metal salt followed by the condensation with formaldehyde and the amine, while maintaining the reaction mixture neutral by the addition of a mineral acid.  Preferred amines: <FORM:0800649/IV (b)/7> are pyrrolidine and morpholine.  The compounds of formula I may also be prepared by reacting an amine: <FORM:0800649/IV (b)/8> with a 3-ethenyl-cyclohex-2-ene-1-one of formula: <FORM:0800649/IV (b)/9> The compounds of formula VII may be prepared by reacting a compound of formula III with lithium acetylide to give a 3-ethynylcyclohex-2-ene-1-one and partially hydrogenating to obtain the 3-ethenyl compound, or by treating a compound of formula III with a vinylmagnesium halide and hydrolysing the product with sulphuric acid.  The preparation of the compounds of formula I by the latter method may be carried out by boiling the amine and the dienone under reflux preferably under a current of inert gas and in the presence of an antioxidant (e.g. hydroquinone).  The dienones of formula VII may also be prepared from the products of formula I by exhaustive methylation.  In examples: (1) 2-methyl-3-isobutoxy - cyclohex - 2 - ene - 1 - one is converted by means of the Reformatsky reaction using ethyl bromacetate, to the ethyl ester of 2-methyl - cyclohex - 2 - ene - 1 - one - 3 - acetic acid from which the corresponding semicarbazone, phenyl hydrazone and 2 : 4-dinitrophenylhydrazone are prepared; the ethyl and isobutyl esters of cyclohex-2-ene-1-one-3-acetic and the semicarbazone of the ethyl ester are prepared similarly; (2) the ethyl ester of 2-methyl - cyclohex - 2 - ene - 1 - one - 3 - acetic acid is reacted with potassium hydroxide and then with morpholine or pyrrolidine as described above to give 2-methyl-3-(21-morpholino - or pyrrolidino - ethyl) - cyclohex - 2 - ene-1 - one; (3) 2 - methyl - 3 - ethenyl - cyclohex-2 - ene - 1 - one is reacted with morpholine, pyrrolidine or diethylamine to give 2-methyl-3-(21 - pyrrolidino - or morpholino - or diethylamino - ethyl) - cyclohex - 2 - ene - 1 - one and the corresponding semicarbazones, 2 : 4-dinitrophenyl hydrazones and methiodides are also prepared.