Cyanohydrins formation from carbonyl compounds

It will destabilise the carbonyl compound a lot, and have very little effect on the product it will therefore push the equilibrium over to the cyanohydrin side. Consider cyanohydrin formation from ... 

Table 3. Equilibrium Constants for Formation of Cyanohydrins from Hydrogen Cyanide Plus Carbonyl Compounds ...

Production of cyanohydrins is accompHshed through the base-cataly2ed combination of hydrogen cyanide and the carbonyl compound in a solvent, usually the cyanohydrin itself (17). The reaction is carried out at high dilution of the feeds, at 10—15°C, and pH 6.5—7.5. The product is continuously removed from the reaction 2one, cooled to push the equilibrium toward cyanohydrin formation, and then stabili2ed with mineral acid. Purification is usually effected by distillation. 

The formation of hydantoin (2) from carbonyl compound 1 with potassium cyanide and ammonium carbonate or from cyanohydrin 3 and ammonium carbonate is referred to as... 

Attack by eCN is slow (rate-limiting), while proton transfer from HCN or a protic solvent, e.g. HzO, is rapid. The effect of the structure of the carbonyl compound on the position of equilibrium in cyanohydrin formation has already been referred to (p. 206) it is a preparative proposition with aldehydes, and with simple aliphatic and cyclic ketones, but is poor for ArCOR, and does not take place at all with ArCOAr. With ArCHO the benzoin reaction (p. 231) may compete with cyanohydrin formation with C=C—C=0, 1,4-addition may compete (cf. p. 200). 

Formation of hydantoins from carbonyl compounds with potassium cyanide (KCN) and ammonium carbonate [(NH4)2C03] or from cyanohydrins and ammonium carbonate. It belongs to the category of multiple component reaction (MCR). 

Cyanation of carbonyl compounds has one of the richest histories of any transformation in the field of asymmetric catalysis, and intensive research efforts have continued unabated since the editorial deadline for the first edition of Comprehensive Asymmetric Catalysis in 1998. This chapter will summarize all efforts in this area from 1998 to date, highlighting the most important catalytic systems from a synthetic and/or mechanistic standpoint. Significant advances in both the cyanation of aldehydes (formation of secondary cyanohydrins Section 28.2.1) and the cyanation of ketones (formation of tertiary cyanohydrins Section 28.2.2) will be addressed [1,2]. 

Cyanohydrin derivatives have also been widely used as acyl anion synthons. They are prepared from carbonyl compounds by addition of hydrogen cyanide. A very useful variant is to use trimethylsilyl cyanide with an aldehyde to produce a trimethylsilyloxy cyanide. The cyano group acidifies the a position (pKA 25) and the a proton can be removed by a strong base. Alkylation of the anion and unmasking of the hydroxy group cause elimination of cyanide and re-formation of the carbonyl group. 

Fig. 9.9. Formation of cyanohydrin or a-aminonitrile from a carbonyl compound, ammonium chloride and sodium cyanide a matter of reaction time. The formation of the cyanohydrin proceeds fast and reversibly, that of a-aminonitrile slowly and irreversibly.

Cyanohydrin formation. The transfer of a cyano group from acetone cyanohydrin to other carbonyl compounds is rapidly accomplished with the alkoxide catalyst. 

D-Glucose orthoesters of complex alcohols can be easily obtained with the help of silver salicylate Alcohols and amines can be conveniently prepared from olefins by ozonization-reduction and ozoni-zation-reductive amination respectively without isolation of intermediates Inverted amines can be obtained from optically-active alcohols through stereospecific formation of N-alkylphthalimides 3-Methoxy-l-phenyl-l-propyne has been used as starting material for the synthesis of a,/ -unsatd. carbonyl compounds through allenic di-carbanions a-Ketocarboxylic acids can be easily prepared from cyanohydrins through a Ritter reaction... 

Most of the elementary reactions in the classic MCRs are equilibrium processes. Therefore, thermodynamic factors can significantly impact the reaction pathways in addition to the reaction kinetics. A classic example is the Strecker synthesis of a-amino nitrile 9 from aldehydes, amines, and cyanide (Scheme 15.5). The key step in this reaction is the nucleophilic addition of cyanide to the in situ formed iminium. However, condensation of a carbonyl compound with an amine leading to iminium is an equilibrium process, especially under aqueous conditions. Therefore, the desired addition reaction is in competition with direct addition of cyanide to the aldehyde, leading to cyanohydrin 10. However, since the formation of both 9 and 10 were reversible, only the more stable adduct 9 was produced at the expense of cyanohydrin 10 under thermodynamically controlled conditions. 

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