Methyl retinoate

There have been many reports on the use of this method for the syntheses of vitamin A, methyl retinoic acid methyl ester, related derivatives, and polyenes300-310. 

Retinol Derivatives. Aryl sulphones have been used in two new syntheses in the vitamin A series. Reaction of /8-cyclocitryl phenyl sulphone (102) with the bromo-compound (103) gives the intermediate sulphone (104), which on base-catalysed elimination affords methyl retinoate (98). Alternatively retinol (99) has been prepared in high yield by condensation of the C15 bromide (105) with the C5 hydroxy-sulphone (106), followed by elimination of sulphinic acid. The syntheses... 

This reaction is a key step in a route to methyl retinoate (1). ... 

Q108R all-tram-Retinoic acid all-tram-Retinal Methyl retinoate all-/rans-Retinol... 

Photoisomerization of tranj-13-demethylretinal (115) gave a mixture of C-7, C-9, C-11, and C-13 stereoisomers which were separated by h.p.I.c. and identified by 400 MHz n.m.r. The photochemistry of (115) and of 14-methylretinal (116) in polar and non-polar solvents has been examined. Conditions for the photoisomerization of methyl retinoate (117) to various ci5-isomers have been studied.Photoisomerization studies of the all-tran -isomers of 3,4-dehydroretinal (118), 10-fluororetinal (119), and 14-fluororetinal (120) suggest Zwitterion intermediates, e.g. (121), the stability of which is influenced by the fluorine substituent or the extra double bond. Conditions have been optimized for reduction of the retinal-hydroquinone complex to retinol by aluminium isopropylate. The electrodimerization of retinal in the presence of electron donors has been studied. ... 

The C15 + C5 route is effective for preparing the sterically hindered (7Z)-isomer of methyl retinoate (19) (Scheme 6) [7]. Upon irradiation under selective sensitization (benzanthrone as sensitizer), the (all-E)-C2o-sulphone 20, which has been prepared by the Julia method, is converted into the (7Z)-isomer. Exposure of this isomer to methanolic KOH furnishes methyl (7Z)-retinoate [(7Z)-/9] together with a minor amount of the (7Z,9Z)-isomer. Analogously, the (7Z, 13Z)-retinoate is accessible starting from the (13Z)-C2o-sulphone. This strategy, starting from the Ci -sulphone 7, is also useful for preparing 13-substituted retinoates [8]. 

Disulphonyl compounds also serve as precursors for methyl retinoate (79). Coupling of the Cio-sulphones 25 and 26 gives the Cio-disulphonyl compound 27 (Scheme 8) [10]. 

Base-promoted desulphonylation of this compound provides methyl retinoate (19) (aIl- 13Z=5 l). The Cio-sulphone 28 also works as a coupling partner of 25 (Scheme 9) [11]. The Cio-disulphone 29 thus obtained is converted into 30 by successive oxidation, Pummerer reaction, NaBH4-reduction, Jones oxidation and methylation with diazomethane. Treatment of 30 with NaOMe in MeOH furnishes methyl retinoate (18) (all- 13Z=6 4). 

This new reaction provides a simple route to methyl retinoate (19) (Scheme 14) [15]. 

Reaction between the lithiate of cyclogeranyl sulphone (25) and the aldehyde ester 43, followed by tetrahydropyranylation of the hydroxy group of the coupling product, furnishes 44. Treatment of 44 with ten equivalents of f-BuOK in refluxing f-BuOH leads to methyl retinoate (19) (all- 13Z= 1 1). The versatility of the double elimination method is highlighted by a novel synthesis of vitamin A acetate (JO) (Scheme 15) [17,18]. 

Methyl retinoate (43) was hydrogenated at the double bond in a cathodic reduction reaction under kinetic control to give (93) (Terem and Utley, 1979). 

The direct oxidation of methyl retinoate (43) with manganese(IV) oxide to give methyl 4-oxoretinoate (317) has been described (Rao eta/., 1972 Henbest, 1957 Barua and Ghosh, 1972 Sokolova et al., 1980). In this manner, retinoids... 

Didehydro compounds have been prepared from derivatives of the natural retinoids (2) and (3) (Henbest et aL, 1955) and from methyl retinoate (43). 

Bromination of methyl retinoate (43) with A -bromosuccinimide (NBS), followed by elimination of hydrogen bromide gave the 3,4-didehydro ester (72), which was reduced with lithium aluminum hydride to give (289). 

Oxidation of methyl retinoate (43) with manganese(IV) oxide gave the 4-keto ester (317), which was converted to the acid (188), and to the 4-hydroxy ester (318). The latter compound has also been employed as an intermediate in the synthesis of 3,4-didehydro compounds (Henbest, 1957 Rao et aL, 1972 Barua and Ghosh, 1972). 

Wolf et al, (1954, 1957). The key intermediate retinoic-14-acid (preparation described in Section II,A,l,a,i) purified by crystallization was esterified with diazomethane. The ester was reduced with lithium aluminum hydride at low temperature to furnish the labeled retinol. Garbers (1956) isolated three isomers of retinoic-14-acid (see Section II,A,l,a,i) and reduced each to its corresponding retinol, thereby obtaining M-trans-, 3-cis-, and 9-c/5-retinol-14- C. Retinol labeled with carbon-14 in position 10 was obtained by Bu Lock et al. (1973) by direct reduction of purified methyl retinoate-lO- C. Labeling in positions 6, 7, and 15 has been reported (Mayer and Isler, 1971). 

Fig. 5. Chromatogram of an isomerate resulting from irradiation for 56 h of methyl aW-tranS retinoate in (A) dimethyl sulfoxide and (B) heptane. Column, Partisil lO-ODS-2 (10 xm) mobile phase, methanohwater (85 15) flow rate, 0.7 ml/min peak (0) 13-m-(photocyclized) methyl retinoate peak (1)9,11,13-tri-cw-methyl retinoate peak (2) 11,13-di-cw-methyl retinoate peak (2A) 7,13-di-cis-methyl retinoate peak (3) 13-cw-methyl retinoate peak (4) 9,13-di-d5-methyl retinoate peak (5) 11-cw-methyl retinoate peak (6) 9-c -methyl retinoate peak (6A) 7-c/5-methyl retinoate peak (7) all-tra/i5-methyl retinoate. (Reprinted with permission from Halley and Nelson, 1979.)...

E7 Retinoic acid methyl ester [339-16-2] Methyl retinoate... 

Retinol and retinyl esters tend to dehydrate under the conditions of electron-impact ionization mass spectroscopy, so that the most prominent ion is that of anhydroretmol (m/z 268) instead of retinol (m/z 286), with small but detectable amounts of the parent ion (20). Methyl retinoate and the trimethylsilyl derivative of retinol usually give prominent molecular ions by electron-impact ionization. Chemical ionization usually gives an identifiable adduct to the molecular ion, thus providing useful information on molecular weight. 

Preparation of Methyl Retinoate from Retinoic Acid and Diazomethane... 

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