Patent GB-812267-A (GB)
Title: The manufacture of carotenoids
Filed: 1956-12-28
Abstract: The invention comprises the 11, 12; 111, 121-dicis form of betacarotene and its 3,4; 31, 41-bisdehydro-derivative and the 4,41-disubstituted derivatives of the 11,12; 111,121-dicis form of betacarotene in which each substituent is a hydroxy or acyloxy group, 11,12; 111,121-dicis - zeaxanthine, and 1,18 - disubstituted-3,7,12,16 - tetramethyl - octadecaheptaene - (1,3,7,9,11,15,17) - diyne - (5,13) in which each of the substituents in the 1- and 18-positions 2,6,6 - trimethyl - cyclohexadien - (1,3) - yl radical or the 2,6,6-trimethyl-cyclohexen-(1)-yl radical which contains in the 4-position a hydroxy or acyloxy group, and a process for the preparation of carotenoids by bilaterally condensing 3,8 - dimethyl - decatriene - (3,5,7)-diyne - (1,9) with a 4-substituted 2-methyl-buten-(2)-al-(1), the 4-substituent being the 2,6,6 - trimethyl - cyclohexadiene - (1,3) - yl radical or a 2,6,6-trimethyl-cyclohexen-(1)-yl or a 2,6,6 - trimethyl - cyclohexylidene radical which may contain in the 4-position a hydroxy or acyloxy group, in an alkali metal or Grignard reaction, hydrolysing the metal containing compound so formed, eliminating the elements of 2 molecules of water from the resulting 1,18-disbustituted - 3,7,12,16 - tetramethyl - 4,15-dihydroxy - octadecapentaene - (2,7,9,11,16)-diyne - (5,13), hydrolysing any 41 - acyloxy groups in the product if desired, catalytically hydrogenating the triple bonds in the resulting 1,18 - disubstituted - 3,7,12,16 - tetramethyl-octadecaheptaene - (1,3,7,9,11,15,17) - diyne - (5,13) to double bonds and, if desired, isomerizing the resulting di-cis carotenoid to the corresponding all-trans carotenoid.  The dimetal-containing compound formed may be the dilithium, disodium or di-(halogeno-magnesium) derivative.  The bilateral condensation may be carried out in an inert solvent, e.g. diethyl ether or benzene, or in liquid ammonia.  The removal of 2 molecules of water may be carried out directly, or the diol may be esterified, e.g. by acetylation or by treatment with aqueous or anhydrous hydrohalic acid, and two molecules of an acid eliminated.  The elimination of acid or water may be carried out with phosphorus oxychloride in pyridine, or in the case of dihalide esters, the dihalide may be treated with water or a basic compound.  The hydrogenation step may be carried out in suspension, for example, in petroleum ether or toluene, preferably using a lead-inhibited palladium catalyst in the presence of quinoline. The isomerization step is preferably carried out by healing the di-cis carotenoid in petroleum ether.  In the examples: (1) betacarotene is prepared by removing the elements of 2 molecules of water from 1,18 - di - [21,61,61 - trimethyl - cyclohexen - (11) - yl - (11)] - 3,7,12,16 - tetramethyl - 4,15 - dihydroxy - octadecapentaene-(2,7,9,11,16) - diyne - (5,13) using hydrobromic acid as the reactant, to form 11,12; 111,121-bisdehydro - betacarotene, hydrogenating this compound to form 11,12; 11,12-di-cis-betacarotene, and isomerizing the di-cis compound to betacarotene; (2) by a similar series of steps as in (1), 3,4; 31,41-bisdehydro-betacarotene is prepared, the intermediates being 3,4; 31,41; 11,12; 111,121 - tetradehydro - betacarotene, and 3,4; 31,41 - bisdehydro - 11,12; 111,121 - di-cis-beta-carotene; and (3) by a similar series of steps as in (1), all-trans-zeaxanthine is prepared, the intermediates being 3,31-diacetoxy-11,12; 111,121 - bisdehydro - betacarotene and the corresponding 3,31-dihydroxy compound, and 11,12; 111,121-di-cis-zeaxanthine. Specifications 775,060, 789,693, 797,200, 802,136, 812,268 and 812,269 are referred to.