Patent GB-788680-A (GB)
Title: A process for the manufacture of unsaturated aliphatic ketones and the conversion thereof into unsaturated cyclic ketones
IPC: C11B9/00
Filed: 1955-10-05
Abstract: Unsaturated aliphatic ketones of formula <FORM:0788680/IV (b)/1> wherein at least three of the substituents R are hydrogen and the fourth is hydrogen or methyl and R1 is an alkyl, alkenyl or alkynyl radical of 1-3 carbon atoms, are prepared by alkylating, alkenylating or alkynylating an acetoacetate of formula <FORM:0788680/IV (b)/2> wherein the R substituents are as defined above, so as to substitute at the activated methylene group a radical containing 1-3 carbon atoms and heating the substituted acetoacetate so as to eliminate therefrom the elements of carbon dioxide and cause a rearrangement. The ketones of formula (1) obtained as products may be cyclized by treatment with acidic agents to give cyclohexenyl-substituted unsaturated ketones.  Specified starting materials, i.e. compounds of formula (2), are the acetoacetates of the following acetylenic carbinols: 1-ethinyl-1:5-dimethyl-hexen- or -hepten-(4)-ol-(1) and 1-ethinyl-1:4:5- or -1:3:5- or -1:2:5-trimethyl-hexen-(4)-ol-(1). The acetoacetates may be prepared by condensing the carbinols with diketene as disclosed in Specification 733,884.  The alkylation, alkenylation or alkynylation of the acetoacetate is preferably carried out by reacting an excess of an alkali metal salt of the acetoacetate with an appropriate agent, e.g. a p-toluene sulphonic acid alkyl ester, dialkyl sulphate or preferably an alkyl, alkenyl, or alkynyl halide.  The substituted acetoacetates are next heated, preferably to 170-190 DEG  C.  A preferred method is to heat the substituted acetoacetates in an inert solvent such as decahydronaphthalene, methyl - heptanone or methyl-heptenone, in the presence of a carboxylic acid catalyst at 175-190 DEG  C.  Specified carboxylic acid catalysts are acetic, propionic, acrylic, benzoic, p-hydroxy-benzoic, salicylic, isonicotinic and, preferably, nicotinic acids.  The stronger carboxylic acids such as chloroacetic, formic and oxalic are not used as they tend to cause cyclisation.  The ketones of formula (1) may be cyclized to give compounds containing a cyclohexenyl radical and having an a  or b -ionone structure, by heating with acidic agents such as syrupy phosphoric acid, boron trifluoride or concentrated sulphuric acid, the structure of the final product depending upon the acidic agent employed.  (The suffix (SC) used below indicates that the semi-carbazone of the compound was prepared.)  In examples: (1) the sodium salt of 1-ethinyl-1 : 5-dimethylhexen-(4)-yl acetoacetate was reacted with methyl bromide to give 1-ethinyl-1 : 5-dimethylhexen-(4)-yl a -methyl-acetoacetate, which was heated to give 3 : 6 : 10-trimethyl-undecatrien-(3 : 5 : 9)-one-(2) (SC), which was cyclized with sulphuric acid to give 4-[21 : 61 : 61-trimethyl cyclohexen - (11) - yl] - 3 - methyl - buten - (3) - one-(2) (SC) or with boron trifluoride to give 4 - [21 : 61 : 61 - trimethyl - cyclohexen - (21) - yl] - 3 - methyl - buten - (3) - one - (2) (SC) and by a similar procedure of methylation, pyrolysis and cyclization with boron trifluoride 1-ethinyl-1 : 5-dimethyl-hepten-(4)-yl acetoacetate gave 4-[21 : 61 - dimethyl - 61 - ethyl - cyclohexen - (21) - yl] - 3 - methyl - buten - (3) - one - (2) (SC), 1 - ethinyl - 1 : 4 : 5 - trimethyl - hexen - (4) - yl acetoacetate gave 4-[21 : 51 : 61 : 61-tetramethylcyclohexen - (21) - yl] - 3 - methyl - buten - (3) - one-(2) (SC) and 1-ethinyl-1 : 2 : 5-trimethylhexen-(4)-yl acetoacetate gave 4-[21 : 31 : 61 : 61-tetramethyl - cyclohexen - (21) - yl] - 3 - methyl - buten - (3) - one - (2) (SC); (2) the sodium salt of 1 - ethinyl - 1 : 5 - dimethyl - hexen - (4) - yl acetoacetate was reacted with allyl bromide to give 1 - ethinyl - 1 : 5 - dimethyl - hexen - (4) - yl a -allyl-acetoacetate, which was heated to give 3 - allyl - 6 : 10 - dimethyl - undecatrien-(3 : 5 : 9)-one-(2) (SC), which was cyclized with phosphoric acid to give 4-[21 : 61 : 61-trimethylcyclohexen - (21) - yl] - 3 - allyl - buten - (3) - one - (2) (SC) and by a similar procedure 1-ethinyl-1 : 5-dimethyl-hepten-(4)-yl acetoacetate gave 4 - [21 : 61 - dimethyl - 61 - ethyl - cyclohexen - (21) - yl] - 3 - allyl - buten - (3) - one - (2) (SC), 1 - ethinyl - 1 : 4 : 5 - trimethyl - hexen - (4) - yl acetoacetate gave 4-[21 : 51 : 61 : 61-tetramethylcyclohexen - (21) - yl] - 3 - allyl - buten - (3) - one - (2) (SC) and 1 - ethinyl - 1 : 3 : 5 - trimethyl-hexen-(4)-yl acetoacetate gave 4-[21 : 41 : 61 : 61 - tetramethyl - cyclohexen - (21) - yl] - 3 - allyl - buten - (3) - one - 2 (SC); (3) the sodium salt of 1-ethinyl-1 : 4 : 5-trimethyl-hexen - (4) - yl acetoacetate was reacted with methyl bromide to give 1-ethinyl-1 : 4 : 5-trimethyl - hexen - (4) - yl a  - methyl - acetoacetate, which was heated to give 3 : 6 : 9 : 10-tetramethyl - undecatrien - (3 : 5 : 9) - one - (2) (SC), which was cyclized with sulphuric acid to give 4 - [21 : 51 : 61 : 61 - tetramethyl - cyclohexen - (11) - yl] - 3 - methyl - buten - (3) - one - (2) or with boron trifluoride or phosphoric acid to give 4-[21 : 51 : 61 : 61-tetramethyl-cyclohexen-(21) - yl] - 3 - methyl - buten - (3) - one - (2); (4) 3 - allyl - 6 : 10 - dimethyl - undecatrien - (3 : 5 : 9)-one-(2) produced as in (2) was partially hydrogenated to give 3-propyl-6 : 10-dimethylundecatrien-(3 : 5 : 9)-one-(2) which was cyclized with sulphuric acid to give 4-[21 : 61 : 61-trimethyl - cyclohexen - (11) - yl] - 3 - propyl - buten-(3)-one-(2) (SC) or with phosphoric acid to give 4-[21 : 61 : 61-trimethyl-cyclohexen-(21)-yl]-3-propyl-buten-(3) -one-(2) (SC) and by a similar procedure (i.e. allylation, pyrolysis, partial hydrogenation and cyclization with phosphoric acid) 1-ethinyl-1 : 4 : 5-trimethylhexen-(4)-yl acetoacetate gave 4-[21 : 5 : 61 : 61-tetramethyl - cyclohexen - (21) - yl] - 3 - propyl - buten - (3) - one - (2) (SC); (5) the sodium salt of 1 - ethinyl - 1 : 5 - dimethyl - hexen - (4) - yl acetoacetate was reacted with propargyl bromide to give 1-ethinyl-1 : 5-dimethyl-hexen-(4)-yl a -propargyl-acetoacetate, which was heated to give 3-propargyl-6 : 10-dimethyl-undecatrien-(3 : 5 : 9) - one - (2) (SC), which was cyclized with phosphoric acid to give 4-[21 : 61 : 61-tri methyl - cyclohexen - (21 - yl] - 3 - propargyl - buten(3)-one-(2) which may be partially hydrogenated to give the product of (2).  Tables are given showing the properties of a number of compounds of formula (1) and a -ionone derivatives obtained therefrom.  1 - Ethinyl - 1 : 5 - dimethyl - hepten - (4) - ol - (1) was prepared by chlorinating 3-methylpenten-(1)-ol-(3), condensing the resulting 1-chloro - 3 - methyl - pentene - (2) with ethyl acetoacetate, saponifying the resulting 3-carboethoxy - 6 - methyl - octen - (5) - one - (2), eliminating the elements of carbon dioxide from the resulting 3-carboxy-6-methyl-octen-(5)-one-(2) and condensing the 6-methyl-octen-(5)-one-(2) so obtained with acetylene in liquid ammonia.  Specification 741,047 also is referred to.