Nitrile partial hydrolysis

Amides without any A-alkyl groups (RCONH2) can also be prepared by partial hydration of a nitrile (RC N). Addition of one equivalent of water across the nitrile triple bond results in an enol-like intermediate that tautomer-izes to give a carbonyl. This mechanism is analogous to the hydration of an alkyne to give a ketone product. Since amides can also be hydrolyzed to give carboxylic acids, the nitrile partial hydrolysis reaction conditions are kept relatively mild when the amide product is desired. 

Pyridazinecarboxamides are prepared from the corresponding esters or acid chlorides with ammonia or amines or by partial hydrolysis of cyanopyridazines. Pyridazinecarboxamides with a variety of substituents are easily dehydrated to nitriles with phosphorus oxychloride and are converted into the corresponding acids by acid or alkaline hydrolysis. They undergo Hofmann degradation to give the corresponding amines, while in the case of two ortho carboxamide groups pyrimidopyridazines are formed. 

The cyano group is at the carboxylic acid oxidation level, so nitriles are potential precursors of primary amides. Partial hydrolysis is sometimes possible.146... 

Partial hydrolysis of nitrile gives amides. Conventionally, such reactions occur under strongly basic or acidic conditions.42 A broad range of amides are accessed in excellent yields by hydration of the corresponding nitriles in water and in the presence of the supported ruthenium catalyst Ru(0H)x/A1203 (Eq. 9.19).43 The conversion of acrylonitrile into acrylamide has been achieved in a quantitative yield with better than 99% selectivity. The catalyst was reused without loss of catalytic activity and selectivity. This conversion has important industrial applications. 

In addition to transacylation reactions and the heating of ammonium carboxylates (Section 16.3), unsubstituted amides may be prepared by careful partial hydrolysis of nitriles ... 

Cyclizative condensations based on aldol-type reactions which conform to the llbd pattern have also been developed. Condensation of bis(alkoxycarbonylmethyl)amines or bis(cyanomethyl)amines with benzil affords 3,4-diarylpyrrole-2,5-dicarboxylic add esters or nitriles. These reactions frequently lead to partial hydrolysis of at least one of the alkoxycarbonyl substituents and if the 3,4-diarylpyrrole is the ultimate objective, work-up involving complete hydrolytic decarboxylation is appropriate (equation 119) (6lLA(639)l02, 65JOC859). 

Nicotinamide is prepared by partial hydrolysis of the nitrile, or by animation of nicotinic acid chloride or its esters, Some of the compounds mentioned in the foregoing aie shown below. 

The survey in Figure 7.1 has already shown that nucleophiles can add to nitriles and thus produce carboxylic acid derivatives. Water as a nucleophile either undergoes clean addition to nitriles, and thus produces primary amides (corresponding to a partial hydrolysis of the nitrile ), or it continues with hydrolyzing the amides in situ to give carboxylic acid or carb-oxylate, which would amount to a total hydrolysis of the nitrile ... 

Fig. 7.8. Partial hydrolysis of a nitrile to a primary carboxylic acid amide under acidic conditions initiating the two-step total hydrolysis of acetone cyanohydrin (B). Grey background overall reaction above the grey area competing reactions with inappropriate choice of pH below the grey area mechanistic details.

Synthesis of Amides Amides are the least reactive acid derivatives, and they can be made from any of the others. In the laboratory, amides are commonly synthesized by the reaction of an acid chloride (or anhydride) with an amine. The most common industrial synthesis involves heating an acid with an amine (at high temperatures, in the absence of oxygen) to drive off water and promote condensation. This simple industrial technique rarely works well in the laboratory, but it may succeed with the use of a coupling reagent (Section 24-11). Esters react with amines and ammonia to give amides, and the partial hydrolysis of nitriles also gives amides. 

The preparation of y-phenoxybutyric acid (61%) by acid hydrolysis of the phenoxycyanide is a typical example of the formation of an ether acid by this method. Nine alkoxypropionic acids, ROCH CHjCOjH, have been made in 4S> 86% yields by acid hydrolysis of the alkoxy nitriles. Basic hydrolysis gives readily polymerizable material propably because of partial decomposition of the alkoxy nitrile into the alcohol and acrylonitrile. ... 

From 94, several compounds were generated such as the 3-thioalkyl compounds 96 (40-67%) by reaction with alkyl bromides. Intermediate 94 was also treated with HCl, iodine, 1,3-dibromopropane or with ethyl chlorocar-bonate affording the mercaptane 97 (68%), the disulfide 98 (45%, n = 0), compound 99 (37%, = 3) and the thiocarbonate 100 (67%), respectively. By a partial hydrolysis of the nitrile group with H2SO4 at reflux, carboxamides lOla-b (92%) were prepared from 96. The same reagents 96 can be transformed into methyl esters 102 (Scheme 26). 

Partial hydrolysis of nitrile 71 gave the amide 106 which was treated with triethyloxonium tetrafluoroborate (Meerwein s reagent) to give the imino ether salt 107 (Scheme 15). This salt was... 

Benzonitrile acts in a similar way to form benzoic acid but requires sulfuric acid in the reacting mixture. Nicotinic acid amide (nicotinamide) has been prepared by the mild hydrolysis of 3-cyanopyridine, and acrylamide by the partial hydrolysis of acrylonitrile. Acrylonitrile may also be hydrolyzed to acrylic acid with mineral acids or with alkalies. Polyacrylonitrile is partially converted to the amide by nitric acid, and the nitrile oups of a number of polymers and copolymers have been hydrolyzed to amide and carboxylic acid groups to produce water-soluble polyelectrolytes. Isooyanides are stable toward alkalies but hydrolyze in the presence of acids to form an acid and an amine ... 

Stoy and co-workers (2) reported an approach that used alternative materials and involved the partial hydrolysis of poly(acrylonitrile) to form a complex structure that was presumed to involve sequences of unhydrolyzed poly(acrylonitrile) interspersed with acrylamide and acrylic acid sequences that resulted from hydrolyzed nitrile groups. Crystallites of unhydrolyzed poly(acrylonitrile) provided the physical cross-link domains within a matrix of the water-swellable portions of the structure. The tensile properties for such materials were considerably enhanced in comparison to the conventional covalently cross-linked hydrogels, and the absence of cross-links allowed processing under certain conditions. 

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