Nitriles, preparation

The simplest method of nitrile preparation is the Sj 2 reaction of CN with a primary or secondary alkyl halide, as discussed in Section 20.5. Another method for preparing nitriles is by dehydration of a primary amide, RCONH2. Thionyl chloride is often used for the reaction, although other dehydrating agents such as POCI3 also work. 

Fatty nitriles, preparation, 2 524-525 Fatty odor, 3 228t... 

NUCLEOPHILIC AROMATIC SUBSTITUTION OF ARYL FLUORIDES BY SECONDARY NITRILES PREPARATION OF 2-(2-METHOXYPHENYL)-2-METHYLPROPIONITRILE... 

Addition of organometallic reagent to nitrile preparation of ketones... 

Hydrolysis of nitriles preparation of primary amides and carboxylic acids... 

Reduction of amides, azides and nitriles Preparation of amines... 

The solution of the nitrile prepared as in Preparation 61 from 100 gms. (1 mol.) of ethylene dibromide and 75 gms. (excess) of potassium cyanide, after filtration from the separated potassium bromide, is evaporated on a... 

The details of this preparation are practically the same as those given for p-tolu-nitrile (Preparation 82). A cuprous-potassium cyanide solution, prepared as therein described, is warmed to about 70°, and added in small portions to a solution of benzene-diazonium chloride prepared from 18-6 gms. (1 mol.) of aniline as described in Preparation 379. When the addition is complete, the liquid is warmed on a water bath for 15 minutes and distilled in steam the distillate is extracted with ether. The ethereal solution is washed repeatedly with dilute caustic soda and with dilute sulphuric acid, dried over anhydrous potassium carbonate, filtered, and the oil which remains on driving off the ether fractionated. Owing to the evolution of cyanogen and hydrocyanic acid, this preparation must be carried out in a good fume cupboard. 

Aromatic ketones arylations, 10, 140 asymmetric hydrogenation, 10, 50 G—H bond alkylation, 10, 214 dialkylzinc additions, 9, 114-115 Aromatic ligands mercuration, 2, 430 in mercury 7t-complexes, 2, 449 /13-77-Aromatic nitriles, preparation, 6, 265 Aromatic nucleophilic substitution reactions, arene chromium tricarbonyls, 5, 234... 

A few examples will show the importance of these reactions in synthetic organic chemistry. If X is an alkoxide ion, equation (1) describes the Williamson ether synthesis (2). If X is a cyanide ion, (1) describes a standard nitrile preparation (3). If X is an aromatic nucleus, and the departure of the leaving group is facilitated by A1C13, then (1) describes the Friedel-Crafts alkylation (4). With X as the cyanate ion, (1) describes the preparation of isocyanates (5) and if it is ammonia, (1) describes a common method of preparation of amines (6). In addition, nucleophilic transmethylation is a very... 

Tlie nitrile, prepared as above, is next digested with the calculated amount of sodium malonic ethyl ester, on the water-bath, till no alkaline reaction is obtained. After removal of the alcohol aud sodium chloride, the cyano-propyl-malonic ethyl ester is fractionally distilled nnder reduced pressure. B.p. 170°—175° at 40 mm. 

Another method employing nitriles for the synthesis of enamides starts from amino nitriles prepared by Strecker synthesis641. An aminonitrile has been acylated to form the acylaminonitrile, and pyrolysis of the latter under reduced pressure over quartz at 450-650 °C yielded the enamide in approximately 95% yield (equation 45). 

The simplest method of nitrile preparation is S, -2 reaction of CN withs primary alkyl halide, as discus in Section 20.6. Hus method is Itocled by the usual Sx2 steric oonstrauiu to the synthesis of u-umidiKiUitRl nitriles. RCKjCN. 

Unsaturated nitriles prepared by the dehydration of amides include 1-cyano-1-alkynes, e.g. 1-cyano-l-heptyne (85%), and 1-cyano-l-alkenes, e.g. /3-isopropylacrylonitrile (80%). Some dehydrating agents such as phosphorus pentachloride may lead to the formation of halogen-containing products phosphorus pentoxide is preferred in these cases. In a comparison of methods for preparing olefinic nitriles, it has been shown that... 

Acid amide-triphenylphosphine dihalide adducts (4) have found wide application in organic synthesis. - Synthetic equivalents are adducts (5) from acid amides and triphenylphosphine/CCU, which are prepared in situ from the educts. - With these reagents the following transformations have been performed dehydration of amides or aldoximes to nitriles, preparation of isonitriles from secondary form-amides, preparation of imidoyl halides from amides or acylhydrazines and preparation of ketene imines from amides. Using polymer-supported triphenylphosphine the work-up procedure is much easier to achieve. Triphenylphosphine can be replaced by tris(dialkylamino)phosphines. - Instead of CCI4 hexa-chloroethane, hexabromoethane or l,l,2,2-tetrabromo-l,2-dichloroethane can be used " the adducts thus formed are assumed to be more effective than those from the triphenylphosphine/CCU system. 

Amide —> nitrile. Preparation of malononitrile.° The sodium chloride gives a... 

Although initially prepared and evaluated as a racemate, the NMDA antagonist activity was likely to reside primarily in a single enantiomer. The stereoselective nature of the NDMA receptor is well established, albeit not completely understood. Consequently, several attempts have been undertaken to develop synthetic protocols that would allow preparation of optically active compounds. Early reports of preparation of optically active co-amino-o-carboxyalkylphosphonic acids describe the preparation of (.S )-A P-3 from an optically active amino nitrile prepared by reaction of diethyl 1-formylphosphonate with hydrogen cyanide and (5)-(-)-a-methylbenzylamine. Acid hydrolysis, enrichment of the diastereomers by fractional recrystaUization, and debenzylation lead to the isolation of (.S )-A P-3 in 86% enantiomeric excess. " Recently reported procedures, which use chemoenzymatic processes, offer a more convenient and mild approach for the production of optically pure aminophosphonic acids. Enzymatic hydrolysis of amides using penicillinacylase (EC... 

The Wohl method for shortening the carbon chain of the sugars utilizes the acetylated nitrile prepared by the above procedure and is described in more detail elsewhere (Chapter II). 

Rogic, M.M., J.F. Van Peppen, K.P. Klein et al. 1974. New facile method for conversion of oximes to nitriles. Preparation and acid-catalyzed transformation of aldehyde oxime ortho esters. J Org Chem 39 3424—3426. 

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