Selective esterification

Oxidation of polysaccharides is a far more attractive route to polycarboxylates, potentially cleaner and less cosdy than esterification. Selectivity at the 2,3-secondary hydroxyls and the 6-primary is possible. Total biodegradation with acceptable property balance has not yet been achieved. For the most part, oxidations have been with hypochlorite—periodate under alkaline conditions. In the 1990s, catalytic oxidation has appeared as a possibiUty, and chemical oxidations have also been developed that are specific for the 6-hydroxyl oxidation. 

Esterification. Selective acetylation of primary alcohols occurs with methyl orthoacetate as reagent and LaCL/SiOj as catalyst. 

Oxalic acid produced from syngas can be esteiified (eq. 20) and reduced with hydrogen to form ethylene glycol with recovery of the esterification alcohol (eq. 21). Hydrogenation requires a copper catalyst giving 100% conversion with selectivities to ethylene glycol of 95% (15). 

The methyl a-hydroxyisobutyrate produced is dehydrated to MMA and water in two stages. First, the methyl a-hydroxyisobutyrate is vaporized and passed over a modified zeoHte catalyst at ca 240°C. A second reactor containing phosphoric acid is operated at ca 150°C to promote esterification of any methacrylic acid (MAA) formed in the first reactor (74,75). Methanol is co-fed to improve selectivity in each stage. Conversions of methyl a-hydroxyisobutyrate are greater than 99%, with selectivities to MMA near 96%. The reactor effluent is extracted with water to remove methanol and yield cmde MMA. This process has not yet been used on a commercial scale. 

Several variations of the above process are practiced. In the Sumitomo-Nippon Shokubai process, the effluent from the first-stage reactor containing methacrolein and methacrylic acid is fed directiy to the second-stage oxidation without isolation or purification (125,126). In this process, overall yields are maximized by optimizing selectivity to methacrolein plus methacrylic acid in the first stage. Conversion of isobutjiene or tert-huty alcohol must be high because no recycling of material is possible. In another variation, Asahi Chemical has reported the oxidative esterification of methacrolein directiy to MMA in 80% yield without isolation of the intermediate MAA (127,128). 

Various techniques have been proposed for the recovery of pure succinic acid, including extraction (141—145), selective crystalliza tion (146—151), heating to dehydrate the acid and subsequent recovery of succinic anhydride by distillation (152), esterification foUowed by fractionation of the mixture of the esters (65—69), and separation as urea adduct (118,119). 

Resolution of racemic alcohols by acylation (Table 6) is as popular as that by hydrolysis. Because of the simplicity of reactions ia nonaqueous media, acylation routes are often preferred. As ia hydrolytic reactions, selectivity of esterification may depend on the stmcture of the acylatiag agent. Whereas Candida glindracea Upase-catalyzed acylation of racemic-cx-methylhenzyl alcohol [98-85-1] (59) with butyric acid has an enantiomeric value E of 20, acylation with dodecanoic acid increases the E value to 46 (16). Not only acids but also anhydrides are used as acylatiag agents. Pseudomonasfl. Upase (PFL), for example, catalyzed acylation of a-phenethanol [98-85-1] (59) with acetic anhydride ia 42% yield and 92% selectivity (74). 

The reaction conditions can be selected so as to be able to separate substances with the same or similar chromatographic properties (critical substance pairs) by exploiting their differing chemical behavior, thus, making it easier to identify them. Specific chemical derivatization allows, for example, the esterification of... 

It was of interest to determine whether glycosides of 6-deoxy-D-xylo-hex-5-enopyranose were susceptible to enzyme hydrolysis by / -glucosi-dase. Since aromatic glucosides are hydrolyzed by this enzyme at a much faster rate than aliphatic glycosides, phenyl 6-deoxy-/ -D-rt/Zo-hex-5-enopyranoside (18) was prepared (20). Phenyl / -D-glucopyranoside was converted to the 6-tosylate by selective esterification and then, by conventional procedures, transformed to phenyl 2,3,4-tri-0-acetyl-6-deoxy-... 

Schemes 15 and 16 summarize the syntheses of intermediates that represent rings A and D of vitamin Bi2 by the Eschenmoser group. Treatment of lactam/lactone 51, the precursor to B-ring intermediate 8 (whose synthesis has already been described, see Scheme 8), with potassium cyanide in methanol induces cleavage of the y-lac-tone ring and furnishes intermediate 76 after esterification of the newly formed acetic acid chain with diazomethane. Intermediate 76 is produced as a mixture of diastereomers, epimeric at the newly formed stereocenter, in a yield exceeding 95%. Selective conversion of the lactam carbonyl in 76 into the corresponding thiolactam...

Whereas treatment of ( )-29 with camphanic chloride achieves the selective esterification of the hindered C-9 hydroxyl group, the action of acetic anhydride on (+)- 29 results in the equally selective acetylation of the C-10 hydroxyl group It is not clear to what this discrepancy should be attributed, so we will not offer a rationalization here. This unexpected result is, however, most gratifying because TPAP-NMO oxidation27 of the remaining C-9 hydroxyl furnishes keto acetate 6 (88 % overall yield). You will note that the contiguous keto and acetate functions in 6 are both expressed in the natural product. 

The only other esterification method which rivals the present procedure in convenience, mildness of conditions, selectivity, and yield js the preparation of methyl esters wdth diazomethane [Methane, diazo-] 10 Esterification with trialkyloxonium salts, however, allows... 

Transesterification of fat triglycerides is the predominant method for manufacture of mixed fatty acid methyl esters, and direct esterification of fatty acids (FA) is practiced if very selective cuts of product, in general as an intermediate detergent range alcohol, are desired. Methyl cocoate is a mobile, oily liquid above 25 °C with a yellow tint and a characteristic fatty pungent odor. FAME sulfonation to FAMES is technically possible but been rarely applied up to now (1990) (Table 13). 

The primary OH group can be selectively blocked by the bulky triphenyl-methyl (trityl) moiety, followed by esterification at the secondary OH groups and removal of the protecting trityl group. Thus 2,3-di-O-acetyl cellulose has been obtained by this procedure. Moreover, regioselectively substituted mixed cellulose esters, acetate/propionate, were prepared by subsequent acy-... 

Hydrogenation of methyl salicylate gave mostly exs (25) implying that the last double bond to be reduced is often between the two functional groups. Selective esterification of diol (23) with p-bromobenzenesul-phonyIchloride (BsCl) gave (26) which cyclised in strong base. 

Clearly under such circumstances there is considerable scope for fine-tuning of selectivity if the relative amoxmts/ concentrations of the various species are taken into accoxmt. Analysis of another inportant clay—catalysed reaction (that of the esterification of acetic acid (2U)) also demonstrates how variation of the exchangeable... 

The ability of enzymes to achieve the selective esterification of one enantiomer of an alcohol over the other has been exploited by coupling this process with the in situ metal-catalysed racemisation of the unreactive enantiomer. Marr and co-workers have used the rhodium and iridium NHC complexes 44 and 45 to racemise the unreacted enantiomer of substrate 7 [17]. In combination with a lipase enzyme (Novozyme 435), excellent enantioselectivities were obtained in the acetylation of alcohol 7 to give the ester product 43 (Scheme 11.11). A related dynamic kinetic resolution has been reported by Corberdn and Peris [18]. hi their chemistry, the aldehyde 46 is readily racemised and the iridium NHC catalyst 35 catalyses the reversible reduction of aldehyde 46 to give an alcohol which is acylated by an enzyme to give the ester 47 in reasonable enantiomeric excess. 

Further work by the Ye group has shown that NHCs derived from pre-catalyst 215 can also promote the asymmetric dimerisation of alkylarylketenes 193 to generate alkylidene P-lactones 216 in good diastereo- and enantio-selectivity [83], The asymmetric [4+2] addition of enones and alkylarylketenes to generate 8-lactones 218 in high ee has also been accomplished [84], as has the asymmetric esterification of alkylarylketenes to give esters 217 using benzhydrol, which is assumed to proceed via a Lewis-base mediated mechanism (Scheme 12.46) [85]. 

---