Patent GB-1187642-A (GB)
Title: Keto-Hydroxy-Alkenes and-Alkanes and Derivatives thereof
IPC: B23B39/16
Filed: 1967-05-15
Abstract: 1,187,642. Keto - hydroxy - alkenes and alkanes; derivatives thereof. F. HOFFMANN - LA ROCHE & CO. A.G. 15 May, 1967 [13 May, 1966; 23 Dec., 1966], No. 12652/68. Divided out of 1,187,641. Heading C2C. The invention comprises compounds of the formula where Y is hydrogen, a C 1-6  alkyl group, a 3- oxo-butyl group or a butyl group (where R 5  is hydrogen or C 1-8  alkyl, R<SP>4</SP> is hydrogen, R<SP>3</SP> is -O-R<SP>6</SP> or R<SP>3</SP> and R<SP>4</SP> together are -O-A-O-, where R<SP>6</SP> is hydrogen or a C 1-8  alkyl or C 1-8  oxyhydrocarbyl group and A is a C 1-8  alkylene group), B is a C 1-8  alkyl or C 1-8  acyl group and R<SP>9</SP> is the #-chloroethyl, #- hydroxyethyl, #-(C 1-8  alkoxy) ethyl, #-(C 1-8  hydrocarbyl)-aminoethyl or #-(di-C 1-8 -hydrocarbyl) aminoethyl group, and the isomers of such compounds in which B is absent and R<SP>9</SP> is an aminoethyl group having the Formula IX where R<SP>10</SP> is a C 1-8  hydrocarbylamino or di-(C 1-8  hydrocarbyl) amino group, and the acid addition salts of those compounds containing an amino group. The compounds are prepared by (a) reacting a compound of the Formula II with a vinyl magnesium halide to give a diol of the Formula III and selectively oxidizing the 3-hydroxy group therein with manganese dioxide to give the alkenone of the formula which may, if desired, be converted to the 7- ester or ether by conventional esterification or etherification methods, or (b) reacting a cyclic ketone of the formula with thionyl chloride in the presence of ZnCl 2  to give the acid chloride reacting the acid chloride with a cadmium compound (Y-CH 2 ) 2 Cd to give the chloroketone reacting this ketone in the form of its ketal with magnesium, reacting the resulting Grignard reagent with acrolein, hydrolysing the complex so obtained to the hydroxy ketone and reducing the keto group therein with LiAlH 4  to obtain the diol of the above Formula III which can, if desired, be etherified or esterified. The compounds in which R<SP>9</SP> is present are obtained by reacting the alkenones with HCl, water, a C 1-8  alkanol or a mono- or di-C 1-8  hydrocarbylamine. The cyclic-isomeric forms of the amino compounds of the Formula IX are obtained in an equilibrium mixture with the acyclic isomers. The cyclic isomer is more stable than acyclic form to which it is converted under acidic conditions. Those amino compounds obtained by addition of an optically active amine to an alkenone can be resolved by salt formation into the optically pure isomers. By using an optically active isomer of the starting compound II in process (a) above, or by effecting a chemical resolution of suitable intermediate, optically active isomers of the novel compounds can be obtained. A number of examples in which the intermediate compounds described above are isolated are provided. Particularly preferred products are 7-hydroxy-1- nonen - 3 - one and 7 - (S) - hydroxy - 1 - dodecen-3-one. The tetrahydropyran-2-ols of the Formula II can be obtained by reduction, e.g. with LiAIH 4  or diisobutyl aluminium hydride, of the corresponding 5-hydroxy-5-valerolactones which, in turn, can be prepared from the appropriate 5-hydroxy-carboxylic acids.