Resolving agents, for alcohols

Resolving agent for alcohols, amines and amino acids. Cryst. (Et20). Mp 67-68°. [aj f +32.2° (CHCI3). -yform [35963-20-3]... 

Resolution of compounds containing functional groups that are not acidic or basic requires a reversible functional group interconversion involving a chiral resolving agent. For example, the reaction of a racemic alcohol with a chiral carboxylic acid results in a mixture of diastereomeric esters that can be separated. After separation, hydrolysis of the ester regenerates the desired alcohol. To resolve a racemic ketone or aldehyde, a reaction with a chiral diol or a chiral amine could be employed to form diastereomeric acetals or imines, respectively. 

Other rosin derivatives expand the range of rosin markets. For example, the alcohol derivatives are used in plastic heat stabilizers, ethoxylated amines are used in corrosion prevention and specialty cleaning, and polyols are used for polyurethane foams. Amines (dehydroabietylamine) are used as antimicrobials (fungicides, bactericides, and algicides), as cationic ore flotation agents, and in the laboratory as a resolving agent for racemic mixtures. 

Both enantiomers of mandelic acid are commercially available and these are suitable resolving agents for a variety of functional groups, and often used to isolate chiral alcohols. A sequential use of (R)- and (5)-mandelic acid allowed resolution of racemic amino alcohols (Eq. 3.3) [22]. Subsequent extraction gave 90% recovery of the amino alcohols with 99% ee or better. Mandelic acid was recovered in 93% yield. 

Whereas the chiral TEMPO analog 87 was used to resolve racemic secondary alcohols, the D-fructose-derived ketone 88 [137] proved useful for oxidative resolution of racemic diols (Table 10.13) [138, 139], Persulfate in the form of Oxone, Curox, etc., served as the final oxidizing agent, and the dioxirane generated from the ketone 88 is the chiral active species. Because of the relatively low conversions (except for unsubstituted dihydrobenzoin) at which the ee stated were achieved, the method currently seems to be of less practical value. Furthermore, typically 3 equiv. ketone 88 had to be employed [138, 139]. 

Rate of complex formation between chiral alcohols and DBTA monohydrate in hexane suspension is quite slow (see Figure 1) and numerous separation steps are necessarry for isolation of the alcohol isomers (filtration of the diastereoisomeric complex then concentration of the solution, decomposition of the complex, separation of the resolving agent and the enantiomer, distillation of the product). To avoid these problems, alternative methods have been developed for complex forming resolution of secondary alcohols. In a very first example of solid phase one pot resolution [40] the number of separation steps was decreased radically. Another novel method [41] let us to increase the rate of complex forming reaction in melt. Finally, first examples of the application of supercritical fluids for enantiomer separation from a mixture of diastereoisomeric complexes and free enantiomers [42, 43] are discussed in this subchapter. 

One of the most commonly used class of derivatization agents for diasteromer formation are isothiocyanates and isocyanates. Enantiomers of /3-blockers, amphetamine, epinephrine, methamphetamine, and mexiletine have been resolved after derivatization with these agents. Isothiocyanates produce thiourea derivatives upon reaction with primary and secondary amines. Thiourea derivatives also provide a strong UV absorbance for the detection of enantiomers lacking a strong UV chromophore. Isocyanates produce ureas when reacted with amines. The physical properties of these ureas are similar to thiourea derivatives. Isocyanates will also react with alcohols to yield carbamates. 

Frankland and Price 17 were the first to attempt the resolution of alcohols (and acids) by fractional crystallization of their solid esters. The isomeric solid esters formed from Z-s-butylcarbinol and di-dibenzoyl-glyceric acid failed to separate on crystallization the corresponding di-alcohol-i-acid ester was liquid. Marckwald and McKenzie 18-19 effected partial resolutions of dl-mandelic acid and related acids with 1-menthol and d-bomeol, and of di-2-octanol with d-tartaric acid, but did not develop a satisfactory method for resolving alcohols. Later investigators, however, have employed the following resolving agents in several more or less successful resolutions of certain alcohols (a) i-menthyl isocyanate, (6) d-camphoric acid, (c) d- or i-mandelic acid, (d) d- or... 

Miscellaneous Applications. Only one attempt to use (R)-pantolactone as an enantioselective protonating agent for enolates has been reported. A series of structurally diverse chiral alcohols afforded modest ee s with (R)-pantolactone affording the largest ee noted for the series. The complexities of attempting a proto-nation of this sort in the presence of base and under exchanging conditions are discussed. Finally, the lactone has been used to resolve chiral acids by crystallization and chromatographic techniques applied to the (R)-pantolactone-derived esters. - ... 

Problem 20.9 Alcohols are the class of compounds most commonly resolved (Sec. 7.9), despite the fact that they are not acidic enough or basic enough to form (stable) salts. Outline all steps in a procedure for the resolution of sec-butyl alcohol, using as resolving agent the base (-)-B. 

Chromatography of radiochemically homogeneous terpenoids has been reviewed useful gas-chromatographic techniques reported include the use of polyphenyl ether in g.c.-m.s. of 23 monoterpenoid hydrocarbons,the use of 3,4,5-trimethoxybenzylhydrazine for pre-column removal of aldehydes and ketones, and the resolution of some bicyclic alcohols and ketones by co-injection with a volatile chiral resolving agent. 

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