Patent GB-802136-A (GB)
Title: Synthesis of carotenoids and novel substances usable therein
Filed: 1956-08-29
Abstract: The invention comprises 1,18-disubstituted-3,7,12,16 - tetramethyl - octadecaheptaene - 2,4,7,9,11,14,16 - diol - 6,13's and the corresponding octadecahexaene - 2,4,7,11,14,16 - yne-9-diol-6,13's, wherein each of the said substituents is 2,6,6-trimethyl-cyclohexylidene (which may contain a hydroxy or acyloxy group as a substituent in the 4-position) or 2,6,6-trimethyl-cyclohexen-1-yl (which may contain a hydroxy or acyloxy group as substituent in the 4-position) or 2,6,6-trimethyl-cyclohexadiene-1,3-yl or 2,6,6 - trimethyl - hexen - 5 - ylidene and the corresponding 6,13-diacyloxy compounds, and the preparation thereof which comprises bilaterally condensing in the presence of an acidic condensing agent a 3,8-dimethyl-2,9-dialkoxydecapentaene-1,3,5,7,9 or the correspondingly substituted decatetraene-1,3,7,9-yne-5 with a 1,1 - dialkoxy - 2 - methyl - 4 - substituted - butene-2 in which the substituent is a 2,6,6-trimethyl-cyclohexylidene (which may contain an oxo or hydroxy or acyloxy as a substituent in the 4-position) or 2,6,6-trimethyl-cyclohexen-1-yl (which may contain a hydroxy or acyloxy group as a substituent in the 4-position) or a 2,6,6-trimethyl-cyclohexadien-1,3-yl or 2,6,6-trimethylhexen-5-ylidene, hydrolysing the resulting 1,18-disubstituted - 3,7,12,16 - tetramethyl - 4,6,6,13, 13,15 - hexaalkoxy - octadecapentaene - 2,7,9,11, 16 or the correspondingly substituted octadecatetraene-2,7,11,16-yne-9 in the presence of an acid, reducing 1,18 - disubstituted - 3,7,12,16 - tetramethyl - octadecaheptaene - 2,4,7,9,11,14, 16-dione-6,13 or the correspondingly substituted octadecahexaene - 2,4,7,11,14,16 - yne - 9 - dione-6,13 thus obtained to give the corresponding 6,13-diol and if required acylating said diol.  The condensation may be effected in an inert solvent between 15-50 DEG  C.  As condensing agents there may be used boron trifluoride etherate, zinc chloride, titanium tetrachloride, ferric chloride or tin tetrachloride.  Hydrolysis of the condensation product is carried out in the presence of water-soluble organic or inorganic acids, e.g. p-toluene-sulphonic acid, acetic acid, propionic acid, oxalic acid, sulphuric acid and phosphoric acid, or in the presence of water-soluble metal salts having an acid reaction, e.g. zinc chloride or sodium bisulphate. The dione may be reduced by means of sodium- or lithium-boron hydride or sodium- or lithium aluminium hydride or using aluminium alcoholate.  In the final step, water or acid is split off with aqueous or water-free hydrohalic acids and the carotenoids thus obtained.  Examples describe the preparation of 1,18-di-[21,61,61-trimethyl-cyclo hexen - 11 - yl] - 3,7,12,16 - tetramethyl - octadecahexaene - 2,4,7,11,14,16 - yne - 9 - diol - 6,13, the corresponding octadecaheptaene - 2,4,7,9,11,14,16, 1,18 - di - [21,61,61 - trimethyl - 41 - hydroxy - cyclohexylidene] - 3,7,12,16 - tetramethyl - octadecahexaene - 2,4,7,11,14,16 - yne-9-diol-6,13, the corresponding acetylated compound, 1,18 - di - [21,61,61 - trimethyl - 41 - hydroxy - cyclohexen - 11 - yl] - 3,7,12,16 - tetramethyl - octadecahexaene - 2,4,7,11,14,16 - yne - 9-diol-6,13, and 1,18-di-[21,61,61-trimethyl-cyclohexadien - 11,31 - yl] - 3,7,12,16 - tetramethyl - octadecahexaene - 2,4,7,11,14,16 - yne - 9 - diol - 6,13.  Starting compounds: 2,6,6-trimethyl-cyclohexen-1-one-4 is treated with peracetic acid to obtain 2,6,6-trimethyl-cyclohexen-2-ol-1-one-4 (1); (1) with chromic anhydride gives 2,6,6-trimethyl - cyclohexene - 2 - dione - 1,4 (2); (2) with zinc dust and acetic acid gives 2,6,6-trimethyl - cyclohexane - dione - 1,4 (3); (3) with ethylene glycol gives 2,6,6-trimethyl-4-ethylenedioxy - cyclohexanone - 1 (4); (4) with 1 - methoxy - 2 - methyl - butyn - 3- ol - 2 gives 4 - (21,61,61 - trimethyl - 41 - ethylenedioxy - 11 - hydroxy - cyclohexyl) - 2 - methyl - 1 - methoxybutyn - 3 - ol - 2 (5); (5) with L.AlH4 gives the corresponding buten-3(6); (6) with formic acid gives 4 - (21,61,61 - trimethyl - 41 - oxo - cyclohexylidene) - 2 - methyl - buten - 2 - al - 1 (7); (7) is acetalized to give 4-(21,61,61-trimethyl-41-oxo - cyclohexylidene) - 2 - methyl - 1,1 - diethoxy - butene - 2 (8); (8) with LiAlH4 gives 4 - (21,61,61 - trimethyl - 41 - hydroxy - cyclohexylidene) - 2 - methyl - 1,1 - diethoxy - butene-2(9); (9) with acetic anhydride gives 4-(21,61, 61-trimethyl - 41 - acetoxy - cyclohexylidene) - 2 - methyl - 1,1 - diethoxy - butene - 2 (10); (10) with glacial acetic acid and sodium acetate gives 4 - (21,61,61 - trimethyl - 41 - acetoxy - cyclohexylidene) - 2 - methyl - buten - 2 - al - 1 (11); (11) with isopropenyl acetate gives 4-(21,61, 61 - trimethyl - 41 - acetoxy - cyclohexen-11 - yl) - 2 - methyl - 1 - acetoxy - butadien - 1,3 (12); (12) with NaHCO3 gives 4-(21,61,61-trimethyl - 41 - hydroxy - cyclohexen - 11 - yl) - 2 - methyl - buten - 2 - al - 1 (13); (12) is acetalized to give 1,1-diethoxy-4-(21,61,61-trimethyl-41 - acetoxy - cyclohexen - 11 - yl) - 2 - methyl - 2-butene (14); (14) with NaHCO3 gives 1,1-diethoxy - 4 - (21,61,61 - trimethyl - 41 - hydroxy - cyclohexen - 11 - yl) - 2 - methyl - butene - 2. b -chloro-vinyl ethyl ether is reacted with 2,6,6-trimethyl-cyclohexanone to obtain (2,6,6-trimethyl-cyclohexylidene)-acetaldehyde which is acetalized to obtain (2,6,6-trimethyl-cyclohexylidene)-acetaldehyde diethyl acetal, which is condensed with ethyl propenyl ether to give 4 - (21,61,61 - trimethyl - cyclohexylidene) - 2 - methyl - 1,1,3 - triethoxy - butane, which with sodium acetate and acetic acid gives 4-(21,61, 61-trimethyl - cyclohexylidene) - 2 - methyl - buten-2-al-1. 2,7-Dimethyl-octadiene-2,6-yne-4-dial-1,8 is treated with methyl magnesium bromide to obtain 3,8 - dimethyl - 2,9 - dihydroxydecadiene - 3,7 - yne - 5, which is oxidized with MnO2 to obtain 3,8-dimethyl-2,9-dioxo-decadiene - 3,7 - yne - 5, which is acetalised to obtain 3,8 - dimethyl - 2,2,9,9 - tetraethoxy - decadiene - 3,7 - yne - 5 which with phosphorus oxychloride gives 3,8-dimethyl-2,9-diethoxy - decatetraene - 1,3,7,9 - yne - 5. Specifications 802,137 and 802,138 are referred to.