Patent GB-819771-A (GB)
Title: A process for the manufacture of ketones
IPC: C07C45/29
Filed: 1957-08-14
Abstract: Open chain or cyclic unsaturated ketones structurally related to alpha- or beta-ionone are prepared by condensing an aldehyde of the general formula <FORM:0819771/IV (b)/1> with an organic metallic compound of the general formula Hc3-Me, wherein Hc1 and Hc2 each stands for a hydrocarbon radical containing 1-3 carbon atoms, Hc3 stands for a hydrocarbon radical containing 1-6 carbon atoms and Me represents the lithium atom or the chloro-, bromo- or iodo-magnesium group, the sum total of carbon atoms in Hc3 and the optional methyl and Hc1 and Hc2 groups present being from 2 to 8, hydrolysing the condensation product and oxidizing the resulting unsaturated alcohol having the general formula <FORM:0819771/IV (b)/2> to the corresponding open chain unsaturated ketone and if desired cyclising this ketone by treatment with an acidic agent.  The groups Hc1 and Hc2 may be alkyl, alkenyl or alkinyl groups and Hc3 may be one of these groups or a cyclo aliphatic group or the phenyl group.  The condensation step may be effected in an inert solvent and the subsequent hydrolysis is suitably carried out in dilute hydrochloric acid and ice or in a cold dilute ammonium chloride solution.  The oxidation may be achieved using manganese dioxide, a compound containing hexavalent chromium, such as chromic acid or tertiary butyl chromate, or a combination of a metal alkoxide or phenoxide, such as aluminium isopropoxide or phenoxide, and a carbonyl compound such as acetone or cyclohexanone; an aqueous or non-aqueous solvent may be present.  Cyclisation of the open chain unsaturated ketones may be effected with phosphoric acid or, as described in Specification 666,993, with BF3 to form mainly a -ionone type ketones or with concentrated sulphuric acid to form mainly b -ionone type ketones.  The open chain and cyclic ketones are odour-imparting compounds.  In examples: (1) methyl magnesium iodide is reacted with 2,5,9-trimethyl-decatrien-(2,4,8-al-(1) in ether and the product decomposed with cold aqueous NH4Cl yielding 3,6,10-trimethyl - undecatrien - (3,5,9) - ol - (2) which is oxidized with aluminium isopropoxide and acetone in benzene and the resulting 3,6,10-trimethyl - undecatrien - (3,5,9) - one - (2) is cyclized with H3PO4 in benzene to 4-[21,61,61-trimethyl - cyclohexen - (21) - yl - (11)] - 3-methyl - buten - (3) - one - (2); (2) the undecatrien-one of (1) is cyclized with H2SO4 in acetic acid to give the isomeric cyclohexen-(11)-yl-(11)-buten-one; (3) ethyl magnesium iodide is used in place of the methyl compound in (1) yielding in similar manner 4,7,11-trimethyldodecatrien-(4,6,10)-ol-(3) which is oxidized to the corresponding ketone with MnO2 and this ketone is cyclized with phosphoric acid to 5-[21,61,61 - trimethyl - cyclohexen - (21) - yl - (11)]-4 - methylpenten - (4) - one - (3) (4) isopropyl magnesium bromide is similarly employed to give 2,4,7,11 - tetramethyl - dodecatrien-(4,6,10) - one - (3) which on cyclizing with H3PO4 is converted into 5-[21,61,61-trimethylcyclohexen - (21) - yl - (11)] - 2,4 - dimethylpenten - (4) - one - (3); (5) 2,5,9 - trimethyldecatrien - (2,4,8) - al - (1) is reacted with phenyl-lithium in ether and the product decomposed as in (1) yielding 2,5,9-trimethyl-1-phenyl-decatrien-(2,4,8)-ol-(1) which is then oxidized with MnO2 to the corresponding ketone which is cyclized to 3-[21,61,61-trimethyl-cyclohexen - (21 - yl - (11)] - 2 - methyl - 1 - phenylpropen - (2) - one - (1); (6) 2,5,8,9 - tetramethyl - decatrien - (2,4,8) - al - (1) is reacted with ethyl magnesium bromide as in (1) yielding in turn 4,7,10,11 - tetramethyl - dodecatrien-(4,6,10) - ol - (3), the corresponding ketone and 5 - [21,51,61,61 - tetramethyl - cyclohexen - (21)-yl - (11)] - 4 - methyl - penten - (4) - one - (3).  Aldehydes of the above general formula are prepared by acetalizing an aldehyde of the general formula <FORM:0819771/IV (b)/3> with an orthoformic ester, e.g. ethyl orthoformate, in the presence of a small amount of toluene sulphonic acid or phosphoric acid, condensing the resulting acetal with an enol ether of the general formula [Hc1 or H]-CH = CH-O-alkyl, Hc1 and Hc2 being as defined above, such as ethyl propenyl ether, in the presence of an acid catalyst, e.g. ZnCl2, and heating the product with acetic acid.  The detailed preparations are given of 2,5,9-trimethyl-decatrien-2,4,8-al-(1) from 3,7-dimethyl-octadien-(2,6)-al(1) and of 2,5,8,9 - tetramethyl - decatrien - (2,4,8) - al - (1) from 3,6,7 - trimethyl - octadien - (2,6) - al - (1), itself obtained by reacting 3,6,7-trimethyloctadien-(1,6)-ol-(3) with PBr3 and reacting the resulting 1 - bromo - 3,6,7 - trimethyl - octadien-(2,6) with 2-nitro-propane in aqueous isopropanolic KOH.