D -Mandelic acid

D(-) mandelic acid Thionyl chloride Monotrimethyl sllyl acetamide... 

Chiral dienes or chiral dienophiles or chiral Lewis acid catalysts may be involved in cycloaddition reactions. When any two of these are combined double asymmetric induction operates111. Thus the chiral diene 223 and the optically active dienophile 224 (from D-mandelic acid) gave 225 in high de values, whereas the same diene and the enantiomeric dienophile 226 (from L-mandelic acid) — a mismatched pair—formed the diastereomeric cycloadduct 227 in only 4% de (equation 121)112. 

Sertraline is an antidepressant that is sold as a single enantiomer and prepared commercially through a resolution of a racemate. The starting material for the resolution step is the hydrochloride salt of racemic sertraline (13.22) (Scheme 13.3). The hydrochloride salts are first neutralized through the addition of NaOH to form the racemic free amine (13.23). The amine is then reacted with 1.0 equivalents of d-(— )-mandelic acid (13.24) in ethanol to form diastereomeric salts. The solution of the salts in ethanol is allowed to stand at room temperature, and a solid consisting of predominantly diastereomer 13.25 precipitates. Filtration of the solid followed by recrystallization from ethanol affords essentially... 

To 21.6 kg (17.8 I) of 98% formic acid was added 1.14 kg (7.5 mols) of D-(-)-mandelic acid and the reaction mixture was heated for 4 hours at 70°C with stirring. The excess formic acid was evaporated off in vacuo and the residual syrup was dissolved in 6 I of benzene. The solution was washed twice with 6 I portions of water and was dried over magnesium sulfate. The drying agent was filtered and washed with 1.5 I of benzene, the washes being added to the filtrate. The dried filtrate was evaporated in vacuo to obtain the D-(-)-mandelic acid formate ether as a syrup. The product can be crystallized from cyclohexane to yield material melting at about 55°C to 58°C. 

LXIII). Only LXI would permit this relationship, in that the anomeric configuration of LXII would be related to d-( — )-mandelic acid. 

Independent synthesis of the crystalline amide LXVII established its identity and its configurational relationship to L-(+)-mandelic acid. The latter acid was converted to ethyl L-(+)-mandelate (LXVIII), and the ether linkage introduced by reaction with ethyl bromoacetate in the presence of silver carbonate, under conditions such that Walden inversion was impossible. The resulting ethyl D-(+)-2-phenyldiglycolate (LXVI), was subjected to ammonolysis, giving a crystalline product, m. p. 174-174.5°, [a]26D 106.2°. This showed no mixed melting point depression and an identical infrared absorption spectrum with the sample of LXVII obtained from /3-D-xylopyranosylbenzene. The enantiomorphic l-(—)-2-phenyldiglycolamide was also prepared by identical synthetic steps from d-( —)-mandelic acid. 

In contrast to benzyl alcohol, a-substituted benzyl alcohols, benzyl ethers, and aryl ketones may be successfully hydrogenated over rhodium and rhodium-platinum catalysts to give the corresponding saturated products in high yields, as shown in eqs. 11.38-11.41. In the hydrogenations shown in eqs. 11.38 and 11.39, no racemization took place D-mandelic acid afforded D-hexahydromandelic acid in 94% yield and meso- and dl-2,3-dicyclohexyl-2,3-butanediol were obtained in 93 and 94% yields, respectively, by hydrogenation of the corresponding diphenyl compounds. 

The racemic aminoalcohol 207 has been resolved into both enantiomeric forms with (D)-(-)-mandelic acid. Liberation of the amines, following by quaternization with methyl iodide, treatment with silver oxide, and heating in water gave the optically active oxiranes 208 and 209. 

The hetero-Diels-Alder reaction with inverse electron demand is an attractive route for the synthesis of 3.4-dihydro-2//-pyrans. Enone 7, esterified with D-mandelic acid as chiral auxiliary, adds to ethyl vinyl ether (8) to give a 2 1 mixture of 9 and 10 [d.r. (2S,4S) (2RAR) 67 33]1. The enone 11 requires high pressure to add to the much less reactive enol ether 12, yielding a 2 3 mixture of 13 and 14 [d.r. (2S, 3S,45 )/(21 ,37 ,4/ ) 40 60]8. The introduction of the additional stereogenic center in the enone 15 leads to a substantially improved diastereofacial selectivity, and adducts 16 and 17 are obtained as a 1 10 mixture [d.r. (2S.4S) (2RAR) 9 91]9. 

A16. Armstrong, M. D., McMillan, A., and Shaw, K. N. F., 3-Methoxy-4-hydroxy-D-mandelic acid, a urinary metabolite of norepinephrine. Biochim. et Biophus. Acta 26, 422 (1957). 

Form, prulaurasin. Slightly bitter needles from ethyl acetate + ether, mp 123-125". [a]D —54 (water). Soluble in water, alcohol practically insol in etheT. On hydrolysis yields d(-mandelic acid. 

---