Mechanisms cyanohydrin formation

Benzaldehyde cyanohydrin formation shown below may involve rate-determining attack by either H+ or CN-. A p value of +2.3 was found for the rate of formation of cyanohydrins from a series of substituted benzaldehydes. Which step is rate determining Based on the fact that cyanohydrin formation does not occur in basic solution, write a complete mechanism for the process. 

The mechanism of cyanohydrin formation involves the usual two steps of nucleophilic addition nucleophilic attack followed by protonation as shown in Mechanism 21.3. 

Each of these reactions is straight out of the textbook and each is a simple addition to the carbonyl group. The first is cyanohydrin formation and you need to draw out the aldehyde group to make a good job of the mechanism. 

The ElcB mechanism is rare in practice when the elimination reaction would result in a carbon/carbon double bond. When a carbon/oxygen double bond is to be formed then it is far more common. For example, the ElcB mechanism is found in the reverse of the cyanohydrin formation reaction. You will recall that the forward reaction involves the addition of a cyanide anion to a carbonyl group. Write down the pathway for the reverse reaction, i.e. the elimination reaction. 

Cyanohydrin Formation. The rate-determining step in the formation of cyanohydrins is the addition of cyanide ion to the carbonyl group. The mechanism of the reaction can be illustrated by the following equations ... 

It has been reported that histidine containing cyclic dipeptides catalyse the formation of optically active cyanohydrins. By this means a number of aromatic, aliphatic as well as heteroaromatic aldehydes and ketones could be converted into the corresponding enantiomerically enriched cyanohydrins [77 - 87]. Interestingly, cyanohydrin formation using this class of catalysts is suppressed by small amounts of benzoic acid. This finding suggests that the mechanism of the... 

The structures of HNLs from several plant species have been elucidated, giving insight into the respective mechanisms of cyanohydrin formation. The origin of these enzymes and thus the mechanisms of their action differ widely. The (S)-HNL from Hevea brasiliensis has a catalytic triad in its active center, which effects deprotonation of HCN and site-selective attack of CN to the substrate, which is fixed in the active site. In contrast, the HNL from Prunus amygdalus is a flavo-en-zyme. However, the role of the flavin group in the catalytic cycle is unclear. The present hypothesis states that the enzyme seems to act via electrostatic change of... 

FIGURE 17.7 The mechanism of cyanohydrin formation from an aldehyde or a ketone. Cyanide ion is a catalyst it is consumed in the first step, and regenerated in the second. 

Mechanism 17.3 describing cyanohydrin formation is analogous to the mechanism of base-catalyzed hydration. The nucleophile (cyanide ion) bonds to the carbonyl carbon in the first step of the reaction, followed by proton transfer to the carbonyl oxygen in the second step. 

Cyanohydrin formation is reversible in base. Using sodium hydroxide as the base, use curved arrows to show the elimination of HCN from the cyanohydrin product in the presence of sodium hydroxide in step 2 in Mechanism 17.3. 

PROBLEM The cyanohydrin formation used in the example is reversible. Draw a mechanism for the reverse reaction. 

The Wohl deffvdation, an alternative to the Ruff d radation, is nearly the reverse of the Kiliani-Fischer synthesis. The aldose carbonyl group is converted to the oxime, which is dehydrated by acetic anhydride to the nitrile (a cyanohydrin). Cyanohydrin formation is reversible, and a basic hydrolysis allows the cyanohydrin to lose HCN. Using the following sequence of reagents, give equations for the individual reactions in the Wohl degradation of D-arabiiK>se to D-erythrose. Mechanisms are not required. 

FIGURE 5.4 Mechanism for cyanohydrin formation (Ref. [21]). The model for this reaction involved two reaction dimensions, C—C bond formation and geometry change. 

Cyanohydrins form fastest under conditions where cyanide anions are present to act as the nucleophile. Use of potassium cyanide, or any base that can generate cyanide anions from HCN, increases the reaction rate as compared to the use of HCN alone. The addition of hydrogen cyanide itself to a carbonyl group is slow because the weak acidity of HCN (pA 9) provides only a small concentration of the nucleophilic cyanide anion. The following is a mechanism for formation of a cyanohydrin. 

Benzaldehyde cyanohydrin (mandelonitrile) provides an interesting example of a chemical defense mechanism in the biological world. This substance is synthesized by millipedes (Apheloria corrugata) and stored in special glands. When a millipede is threatened, the cyanohydrin is released from the storage gland and undergoes enzyme-catalyzed reversal of cyanohydrin formation to produce HCN, which is then... 

This process occurs via a nucleophilic acyl addition. A mechanism for cyanohydrin formation was discussed in Section 20.10. Building on Kiliani s observation, Emil Fischer (the same Fischer who gave us Fischer projections) then devised a multistep method for converting a cyano group to an aldehyde. 

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