Mandelic acid, 2,5-dimethyl

Mandelic acid, 20, 62 23, 48 Mandelic acid, 2,5-dimethyl-, 25, 33 Mannich reaction, 23, 30... 

The pyridine subcycle unit has been introduced into a wide range of 18-crown-6 derivatives. For example, reaction of 2,6-pyridinedicarbonyl chloride with the dimethyl substituted tetraethylene glycol (SS)-84, derived from (S)-lactic acid, afforded (126) the chiral macrocyclic polyether diester (5S)-184. A similar preparative approach (127) gave (SS)-185, where the source of the chirality is (5)-mandelic acid. 

Many other groups may be present in the alcohol or phenol during alkylation. Dimethyl sulfate and chlorohydrins give chloro ethers. Halo ethers are also prepared by the action of this reagent on halogenated phenols, e.g., w-bromoanisole (91%)- Phenolic aldehydes are converted in excellent yields to alkoxy aldehydes with dimethyl sulfate or alkyl p-toluenesulfonates. The conversion of a phenolic ketone to an alkoxy ketone is illustrated by the preparation of p-methoxypropiophenone (88%). Phenolic acids, esters, and cyanides, and nitrophenols respond favorably to this method for methylation. The sodium salt of mandelic acid, C H, CHOHCOOH, is methylated with dimethyl sulfate to furnish, after acidification, a-methoxyphenylacetic acid (42%). ... 

Biphenyl-bridged bis-Cp titanocene dichloride and dimethyl complexes have been synthesized, and the kinetic resolution of the racemic final mixture of the products has been carried out. A mixture of diastereomers is obtained by treatment of the dimethyl compound with O-acetyl-mandelic acid, while enantiomerically pure products result in the reaction of the dichloro derivative with (i )-binaphthol and 1 equiv. of LiBun (Scheme 661).1050... 

Examples.—Ks examples of this there may be taken dimethyl tartrate and mandelic acid, the freezing-point curves of which are given in Figs. 55 and 56. As can be seen, the curve for the racemic... 

Active dimethyl tartrate melts at 43 3° racemic dimethyl tartrate at 89-4°. Active mandelic acid melts at 132 8 the racemic acid at n8 0°. In the one case, therefore, the racemic compound has a higher, in the other a lower, melting-point than the active forms. 

O-Methylation of mandelic acid leads to the enantiomers of a-methoxy-M-phcnylacetic acid (10), which are also commercially available. This methylation without noticeable racemiza-tion was achieved with diazomethane, using aluminum tris(tert-butanoate) as catalyst8. Alternatively, dimethyl sulfate/ sodium hydroxide has been used15, as described in detail for the racemic compound10. The acids have been used for the construction of quite sophisticated chiral auxiliaries, e.g., a rhodium cyclopentadienyl complex (Section 7.2.2.), and for chiral dienes applied in both normal and inverse Diels-Alder reactions (Section D.1.6.1.1.1.). Chiral dienes, e.g., 1, for normal Diels -Alder reactions were prepared by pyrolysis (460 C) of a tricyclic precursor cstcrified with (S)-O-methylmandeloyl chloride or with the free acid and dicyclohexylcarbodiimide/4-dimethylaminopyridine11 -13. 

Mandelic acid derivatives are useful resolving agents. While (/ )-( +)-phenethyl alcohol (77) is commercially available, it is relatively expensive. As shown in Scheme 16, (5)-l can be converted readily into multigram quantities of 77. Reduction of 1 with borane-dimethyl sulfide provides the diol 76, which is selectively tosylated at the primary hydroxy position and then detosylated with lithium aluminum hydride to provide 77 in 48% overall isolated yield (Scheme 16). The low yield is a result of the problematic tosylation step, in which ditosylation is unavoidable. 

The Pd-catalyzed reaction of allylic carbonates with the lithio derivatives of diox-olanone prepared by the treatment of mandelic acid with acetone dimethyl acetal gives the desired a-allylation products in good yields. Upon treatment with HCl in ethanol the corresponding a-hydroxy ethyl esters can be obtained " (Scheme 11). 

Diethyl dl-1 -aminobenzylphosphonate has been prepared by a Mannich reaction of diethyl phosphite, benzaldehyde, and ammonia, resolved as its D-mandelate salt, and hydrolysed to give (+)-l-aminobenzylphosphonic acid.27 While the tetraethyl-diamide (33) reacts with benzaldehyde to give the expected phosphonic diamide (34), the corresponding tetramethyl-diamide reacts, with migration of the dimethyl-amino-group, to give (35).28... 

Figure 2. NMR Spectra (60 MHz)15c of 3,3-dimethyl-2-butanol esters of four different nonracemic enantiomeric mixtures of carboxylic acids. Excess of the (R,R)- or (5,5 )-diasLereomers mandelate 22% atrolactate 18% MTPA 7.5% 0-methylmandelate 12.8%.

Pollock and Jermany (1968), using the asymmetric alcohols, butan-2-ol, 3-methylbutan-2-ol and 3,3-dimethyl butan-2-ol as the esterification reagents for each of a number of acids including lactic, glyceric, malic, mandelic and tartaric acids, demonstrated the separation of the resulting diastereoisomers after acetylation on a Carbowax 20M column. Their study, however, was directed principally at resolving various racemic carbohydrate diastereoisomers by conversion to aldonic acids prior to derivatization and gas chromatography. 

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