Nitriles, addition reactions hydrolysis

A few 6- and 8-cyanopurines have been prepared and undergo characteristic nitrile addition reactions rather readily. Thus, alkaline hydrolysis produces carboxamides, then carboxylic acids, alcoholysis leads to imidates, ammonolysis to amidines, hydrazinolysis to amidhydrazines, hydroxylamine to amidoximes, and hydrogen sulfide to thioamides. Acid hydrolysis tends to give the decarboxylated acid derivative. Reduction either by sodium-ethanol or, preferably, by catalytic hydrogenation affords aminoalkylpurines and addition of Grignard reagents produces, in the first place, acylpurines. As with aldehydes, most of the compounds examined have been relatively non-polar derivatives. Table 28 lists some reactions and relevant literature. 

Nitriles are similar in some respects to carboxylic acids and are prepared either by SN2 reaction of an alkyl halide with cyanide ion or by dehydration of an amide. Nitriles undergo nucleophilic addition to the polar C=N bond in the same way that carbonyl compounds do. The most important reactions of nitriles are their hydrolysis to carboxylic acids, reduction to primary amines, and reaction with organometallic reagents to yield ketones. 

Mixing trichlorosilane, acetonitrile and diphenylsulphoxide, carried out at 10°C, detonated. This accident was put down to the exothermic addition reaction of the silicon-hydrogen bond on the carbon-nitrogen triple bond of nitrile. Other interpretations are possible for instance, the effect of traces of hydrogen chloride formed by the hydrolysis of chlorosilane on acetonitrile. 

Exercise 24-11 Nitriles of the type RCH2CN undergo a self-addition reaction analogous to the aldol addition in the presence of strong bases such as lithium amide. Hydrolysis of the initial reaction product with dilute acid yields a cyanoketone, O CN... 

You met nitrile hydrolysis and addition reactions, for example, in Chapter 12. 

Hydrolysis. Alcohols a dioxolanes, respectively, on t Michael reactions. Th< acceptors is promoted by CeC without solvent. A preparatki from organocerium derivative Li/Ce exchange. (The san a,a-difluoro-p-ketophosphoni Nitrile aldol reactions. CeClj-THjO. Addition of a ch... 

Examples include high-pressure hydrolysis of a nitrile paraffin autoxidation homogeneous aldehyde hydrogenation olefin hydroformylation to alcohol with paraffin by-product formation, aldehyde condensation to heavy ends, and olefin isomerization cyclo-addition reactions and hydrogen-halide reactions. 

During hydrolysis, water acts simultaneously as solvent, reactant and catalyst via self-dissociation. Often the addition of a further catalyst, usually acids or bases, is necessary to avoid undesirable side reactions. Hydrolysis reactions which have been investigated include the hydrolysis of amines [14-16], amides [17], nitriles... 

Other reactions of carbohydrates include those of alcohols, carboxylic acids, and their derivatives. Alkylation of carbohydrate hydroxyl groups leads to ethers. Acylation of their hydroxyl groups produces esters. Alkylation and acylation reactions are sometimes used to protect carbohydrate hydroxyl groups from reaction while a transformation occurs elsewhere. Hydrolysis reactions are involved in converting ester and lactone derivatives of carbohydrates back to their polyhydroxy form. Enolization of aldehydes and ketones leads to epimerization and interconversion of aldoses and ketoses. Addition reactions of aldehydes and ketones are useful, too, such as the addition of ammonia derivatives in osazone formation, and of cyanide in the Kiliani-Fischer synthesis. Hydrolysis of nitriles from the Kiliani-Fischer synthesis leads to carboxylic acids. 

Halonitriles in Barbier Reactions. Barbier reactions with halonitriles will lead to cyclic ketones after hydrolysis of the primary nitrile addition product [82] ... 

Addition reactions to the nitrile group and hydrolysis of nitriles to the corresponding carboxylic acids may, to a certain extent. 

Another method for converting a haloalkane into a carboxylic add with an additional carbon atom is through the preparation and hydrolysis of a nitrile, RC=N. Recall (Section 6-2) that cyanide ion, C=N , is a good nucleophile and may be nsed to synthesize nitriles through Sn2 reactions. Hydrolysis of the nitrile in hot acid or base furnishes the corresponding carboxylic acid (and ammonia or ammonium ion). 

In landmark studies involving the determination of the relative configuration of carbohydrates, Emil Fischer reported in 1889 that the homologation of D-(-t-)-mannose (1) with cyanide gave a single diastereomeric adduct (Equation 1) [34]. Following hydrolysis of the nitrile, heptonic acid 2 was isolated in 87 % yield. This is perhaps the earliest example of acyclic substrate control in diastereoselective carbonyl addition reactions. 

The addition of active methylene compounds (ethyl malonate, ethyl aoeto-acetate, ethyl plienylacetate, nltromethane, acrylonitrile, etc.) to the aP-double bond of a conjugated unsaturated ketone, ester or nitrile In the presence of a basic catalyst (sodium ethoxide, piperidine, diethylamiiie, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields trlcarballylic acid ... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Acid-catalyzed hydrolysis of a nitrile to give a carboxylic acid occurs by initial protonation of the nitrogen atom, followed by nucleophilic addition of water. Review the mechanism of base-catalyzed nitrile hydrolysis in Section 20.7, and then write all the steps involved in the acicl-catalyzed reaction, using curved arrows to represent electron flow in each step. 

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