Cyanohydrin ester, hydrolysis

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

The use of sodium amalgam originates with E. Fischer. The method was a cornerstone of his aldose homologation (cyanohydrin formation, hydrolysis, lactone formation and reduction) which was so important to the development of carbohydrate chemistry. Although the yields obtained by Fischer were moderate ca. 20-50%), more recent work by Sperber et al. has resulted in significant improvements. In particular, they discovered that control of the pH of the reaction mixture was very important. At pH 3-3.5, yields in the range 52-82% were obtained with a variety of aldonolactones. As an example, the preparation of arabinose is shown in equation (4). If the pH was allowed to rise, yields were lower due to overreduction. Methyl esters of aldonic acids could also be used as substrates. 

Lipases have been used to effect the enantioselective esterification of cyanohydrins or the enantioselective hydrolysis of cyanohydrin esters. This works for aldehyde cyanohydrins. Selective (S)-cyanohydrin esterification is effected by the enzyme from Pseudomonas sp. [11], There is also an example of selective (R)-cyanohydrin esterification by Candida cylindracea lipase [12]. Effenberger has shown the feasibility of this approach in principle to produce a number of enantiopure cyanohydrins derived from aldehydes. In situ derivatization with racemization as shown in Fig. 7 is possible, resulting in theoretically 100% yield of the desired enantiomer [13]. Ketone cyanohydrins, which are tertiary alcohols, do not easily undergo this reaction. 

Esterase or lipase as catalyst. Application of hydrolytic enzymes is realized in three different systems enzymatic hydrolysis or transesterification of racemic cyanohydrin esters (see Figure 14.7-4.) as well as enzymatic acylation of racemic cyanohy-... 

The 11-deoxyprostaglandins, a group not found in nature, have been synthesised by workers at the Ayerst Laboratories [115, 148-151]. 11-Deoxy-PGFy (LXXI) has been prepared starting from the enone (LXXII), obtained by the action of sulphuric acid on the monobromo derivative of the condensation product of ethyl 2-cyclopentanone carboxylate and (o-bromoethylheptanoate [115, 148, 149]. Reaction of (LXXII) with acetone cyanohydrin, hydrolysis of the ester-nitrile to the dicarboxylic acid and reaction with methanol and />-toluenesulphonic acid gave the mono ester (LXXIII) of which the acid chloride was converted with heptyne and aluminium chloride into the chlorovinylketone (LXXIV). The sequence was then completed by replacement of chloro with methoxyl, ester hydrolysis and borohydride reduction to the unsaturated ketone (LXXV) followed by borohydride reduction of the side chain carbonyl group. 

Scheme 2.70 Hydrolysis of cyanohydrin esters using microbial lipases...

In the context of these studies, the same group has demonstrated that the synthesis of cyanohydrin esters via DKR was highly dependent on the carrier of the enzyme. The carrier influenced the amount of water available in the reaction mixture, suppressing or enhancing the undesired hydrolysis of the acyl donor and the final product. Indeed, the DKR proved to be prone to residual water. However, when the hpase was immobilised on cehte as a carrier, the celite absorbed the water and suppressed the water-induced side reactions. Thereby, the enantioselectivity and the reaction times (3 10 days without cehte) for this DKR were improved, enabling a nearly enantiospecific and high-yielding synthesis of mandelonitrile acetate (Scheme 3.28). 

Effenberger F, Gutterer B, Ziegler T, Eckhardt E, Aichholz R. Enzyme-catalyzed reactions. 7. Enantioselective esterification of racemic cyanohydrins and enantioselective hydrolysis or transesterification of cyanohydrin esters by lipases. Liebigs Ann. Chem. 1991 47-54. 

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

Hydroxy-20-cyanohydrins can be oxidized to 3-ketones in good yield with chromic acid, and the osmate ester of the unsaturated nitrile is also stable to this oxidant. " After hydrolysis of the osmate ester, the new 17-hydroxy-20-cyanohydrin which is presumably formed cannot be isolated, but loses hydrogen cyanide during the hydrolysis, and only the 17a-hydroxy-20-ketone is obtained. 

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

Hydrolysis of cyanohydrins 6-16 Reaction between aldehydes, ammonia. and carboxylic acids or esters 6-50 Addition of cyanide and ammonium ions to aldehydes or ketones, followed by hydrolysis (Strecker)... 

Preparation. The general preparation of u-hydroxy acids is by the hydrolysis of an a-halo acid or by Ihe acid hydrolysis of the cyanohydrins of an aldehyde or a ketone. 0-Hydroxy acids may be made by catalytic reduction of 0-keut esters followed by hydrolysis. 0-Hydroxy acids can also he prepared by ihe ReformaCsky reaction y-Hydroxy acids are seldom obtained in the free slate because of ihe case wilh which they form... 

While the addition-oxidation and the addition-protonation procedures are successful with ester enol-ates as well as more reactive carbon nucleophiles, the addition-acylation procedure requires more reactive anions and the addition of a polar aptotic solvent (HMPA has been used) to disfavor reversal of anion addition. Under these conditions, cyano-stabilized anions and ester enolates fail (simple alkylation of the carbanion) but cyanohydrin acetal anions are successful. The addition of the cyanohydrin acetal anion (71) to [(l,4-dimethoxynaphthalene)Cr(CO)3] occurs by kinetic control at C-P in THF-HMPA and leads to the a,p-diacetyl derivative (72) after methyl iodide addition, and hydrolysis of the cyanohydrin acetal (equation 50).84,124-126... 

Not surprisingly, active M11O2 is able to oxidize unsaturated cyanohydrins, resulting in the generation of acyl cyanides. Interestingly, both the formation of the cyanohydrins by reaction of aldehydes with cyanide, and the hydrolysis of acyl cyanides with MeOH, resulting in the formation of methyl esters, can be carried out in situ with the MnC>2 oxidation. Thus, Corey et al. proved68 that aldehydes can be directly transformed into methyl esters by treatment with NaCN and active MnC>2 in a mixture of acetic acid and methanol. This represents a useful protocol for the oxidation of unsaturated aldehydes to esters. 

Pyrethroids are commercially important insecticides that usually contain a cyclopropyl unit that is m-substituted and a cyanohydrin derivative. They are usually sold as a mixture of isomers. However, asymmetric routes have been developed, especially because these compounds are related to chrysanthemic esters (Chapter 12).251 The pyrethroids can be resolved through salt formation or by enzymatic hydrolysis.252... 

This article describes our results on lipase-catalyzed enantio-selective hydrolysis of carboxylic acid esters of two industrially important alcohols related to synthetic pyrethroids in two-liquid phase systems. The two alcohols are 4-hydroxy-3-methyl-2-(2 -propynyl)-2-cyclopentenone (HMPC) and the cyanohydrin, a-cyano-3-phenoxybenzy1 alcohol (CPBA). The configurations, and 2y are given for the liberated stereoisomers of the two alcohols in our lipase-catalyzed reactions. 

Methyl methacrylate (MMA) is one of the most important monomers [80-82]. It forms the basis of acrylic plastics and of polymer dispersion paints. The traditional production is by the formation of acetone cyanohydrin, elimination of water and hydrolysis of the nitrile group, followed by the ester formation. In the carbon-carbon bond forming reaction large amounts of excess HCN and ammonium bisulfate are left as waste. Although these problems have been addressed there is still much room for improvement. In particular the number of reaction steps should be reduced and, in order to achieve this, cyanide should be avoided. The building block to replace it is CO. 

Lactic acid is produced chemically from acetaldehyde, by hydrocyanation, followed by acid hydrolysis of the cyanohydrin (Fig. 8.6 a). The cmde lactic acid is purified via esterification with methanol, distillation of the ester and hydrolysis with recycling of the methanol [34]. Major drawbacks are the production of an equivalent of ammonium sulfate and the cumbersome purification procedure that is required to obtain food-grade lactic acid. 

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