Patent GB-796757-A (GB)
Title: The synthesis of carotenoids
IPC: C07C29/42
Filed: 1956-07-20
Abstract: The invention comprises 3,7,12,16-tetramethyl - 8,11 - dihydroxy - octadecahexaene-2,4,6,12,14,16-yne-9's which contain as a substituent in the 1-position the radical 2,6,6-trimethyl - cyclohexylidene- or 2,6,6,-trimethylcyclohexen-2-ylidene and in the 18-position the radical 2,6,6-trimethyl-cyclohexen-1-yl or 2,6,6-trimethyl - cyclohexadien - 1,3 - yl or 2,6,6 - trimethyl - cyclohexylidene, 3,7,12,16 - tetramethyl - 8 - 11 - dihydroxy - octadecahexaen-2,4,6,12,14,16-yne-9's which contain as a substituent in the 1-position the radical 2,6-dimethyl-heptaen-5-ylidene and in the 18-position the radical 2,6,6-trimethyl-cyclohexen-1-yl or 2,6,6 - trimethyl - cyclohexadien - 1,3 or 2,6,6-trimethyl-cyclohexylidene-, and a process for the manufacture of C40-(acetylenic diols) and the conversion of the same into carotenoids, which comprises bilaterally condensing acetylene in an organo-metallic reaction with an aldehyde of the general formula <FORM:0796757/IV (b)/1> in which n stands for 1 or 2 according to whether the valency of R is 2 or 1 and R stands for a 2,6,6-trimethyl-hex[en]yl or -hex[en]ylidene radical, either in a single stage by reacting 2 mols. of the C19-aldehyde with an acetylenedi(magnesium halide) in an inert solvent and hydrolysing the product or in two stages by reacting one mol. of the C19-aldehyde with an alkali-metal or an alkaline-earth-metal acetylide in liquid ammonia and condensing the product after hydrolysis, if desired) with one mol. of the same or different C19-aldehyde in a Grignard condensation, and, where the carotenoids are desired, treating the resulting C40-(acetylenic diol) with excess lithium aluminium hydride.  Suitable alkyl halides for the Grignard reaction are ethyl, butyl, and hexyl bromides or chlorides.  Examples describe the preparation of b -C40-(acetylenic diol), bisdehydro-b -C40-(acetylenic diol), iso-b -C40-acetylenic diol and bisretrodehydro-C40-(acetylenic diol) and the conversion thereof into 7,71-dihydro-b -carotene, 3,4,31,41-bisdehydro - 7,71 - dihydro - b - carotene, asymmetric isocarotene, and 4,41-dehydro-b -carotene respectively.  Starting compounds.  8-R-2,6-Dimethyl-octatrien - 2,4,6 - al - 1 is obtained by condensing 4 - R - 2 - methyl - buten - 2 - al - 1 with the diethyl acetal of 2-methyl-2-hydroxy-butin-3-al-1 in a Grignard reaction, reducing the condensation product with LiAlH4 to obtain a b -C19-aldehyde diethyl acetal which is hydrolysed.  The diethyl acetal of 2-methyl-2-hydroxybutin-3-al-1 is prepared from 1,1-diethoxypropanone-2 and lithium acetylide. Retrodehydro-C14-aldehyde is obtained by treating b -C14-aldehyde with N-bromo-succinimide and subsequent heating of the product with quinoline. Dehydro-b -C14-aldehyde is obtained by treating retrodehydro-C14-aldehyde with isopropanol acetate and hydrolysing the product.  Iso-C14-aldehyde is obtained by condensing 2,6,6 - trimethyl - cyclohexanone - 1 with ethoxy-acetylene, hydrogenating, hydrolizing, acetalizing and condensing the acetal so formed with a propenyl ether, and treating the product with acid. Pseudo-C14-aldehyde is obtained from pseudo-ionone and chloro-acetic acid ethyl ester by a glycidic ester synthesis and subsequent alkali treatment of the resulting glycidic ester.