Nucleophilic addition reactions with hydrogen nucleophiles

The addition reactions we have met so far have involved electrophilic addition across the C = C bond in alkene molecules (see page 209). Aldehydes and ketones both undergo addition reactions with hydrogen cyanide, HCN. In this case, addition of HCN takes place across the C=0 bond. However, the attack is by a nucleophile, not an electrophile. We can show this using the nucleophilic addition reaction of propanal with HCN. The HCN is generated in situ (in the reaction vessel) by the reaction of sodium cyanide, NaCN, and dilute sulfuric acid. 

The a-hydrogens of nitroalkanes are appreciably acidic due to resonance stabilization of the anion [CH3NO2, 10.2 CH3CH2NO2, 8.5]. The anions derived from nitroalkanes give typical nucleophilic addition reactions with aldehydes (the Henry-Nef tandem reaction). Note that the nitro group can be changed directly to a carbonyl group via the Nef reaction (acidic conditions). Under basic conditions, salts of secondary nitro compounds are converted into ketones by the pyridine-HMPA complex of molybdenum (VI) peroxide. Nitronates from primary nitro compounds yield carboxylic acids since the initially formed aldehyde is rapidly oxidized under the reaction conditions. 

When an unsymmetrical alkene undergoes an addition reaction with a compound E-Nu, the electrophile (E) will add to the carbon with the greater number of hydrogens, and the nucleophile (Nu) will add to the carbon with the fewer number of hydrogen substituents. 

In contrast, the reaction of an aldehyde or a ketone with a carbon or hydrogen nucleophile forms a stable tetrahedral compound because the newly formed sp carbon is not bonded to a second electronegative atom. Thus, aldehydes and ketones undergo nucleophilic addition reactions with carbon and hydrogen nucleophiles, whereas they undergo nucleophilic addition-elimination reactions with nitrogen nucleophiles. 

DFP is stable and in the absence of moisture can be stored for considerable periods without decomposition. Hydrolysis in neutral aqueous solution occurs slowly. The reaction is catalyzed by both acid and base. At pH>7, hydrolysis is proportional to the hydroxide ion concentration and at high pH is extremely rapid. The product is always diisopropyl phosphoric acid (equation 38), except under more forcing conditions which eventually produce phosphate (and propan-2-ol). The hydrolysis is strongly catalyzed by the addition of a-effect nucleophiles such as hypochlorite, peroxide, hydroxylamine, hydroxamic acid and their substituted derivatives . Under basic conditions, such nucleophiles (HOX) are present as the anion and are responsible for the rapid initial displacement of fluoride ion from DFP to give intermediate 36 shown in equation 39. Displacement of OX by hydroxide ion regenerates the catalytic OX anion. The reaction with hydrogen... 

FIGURE 17.11 For carboxylic acids, the fastest reaction with a nucleophile is removal of the acidic hydroxyl hydrogen to give the carboxylate anion. The anion that results is resistant to addition reactions with a second nucleophile, which would introduce a second negative charge. 

When formulating a mechanism for the reaction of alkynes with hydrogen halides we could propose a process analogous to that of electrophilic addition to alkenes m which the first step is formation of a carbocation and is rate determining The second step according to such a mechanism would be nucleophilic capture of the carbocation by a halide ion... 

In addition to having typical A -oxide reactions, quinazoline 3-oxide also shows the same reactivity as quinazoline toward nucleophilic reagents, but the reaction goes a step further by eliminating water as shown in reaction 2d. Oxidation with hydrogen peroxide... 

This fact gives enough reason to suppose that the reaction of hydrogen sulfide addition to nitrile groups starts with the attack of the nucleophilic mercapto anion... 

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