Water reaction with nitriles

Other acid-catalysed addition reactions include reaction with nitriles (Ritter reaction), formaldehyde (Prins reaction) and carbon monoxide and water (Koch reaction). These reactions are normally catalysed by concentrated sulphuric acid. Extensive isomerization occurs and may even lead to quaternary compounds of the type RC(CH3)XR where X is the new functional group introduced into the molecule. Homogeneous catalysts have been developed which give simpler products without extensive isomerization. 

A similar process leads from dimethylaniline to the three-component reaction with nitriles and water under photocatalysis upon visible light irradiation in the presence of titania or of phenothiazine derivatives. ... 

Hoesch synthesis A variation of the Gattermann synthesis of hydroxy-aldehydes, this reaction has been widely applied to the synthesis of anthocyanidins. It consists of the condensation of polyhydric phenols with nitriles by the action of hydrochloric acid (with or without ZnCl2 as a catalyst). This gives an iminehydrochloride which on hydrolysis with water gives the hydroxy-ketone. 

The zwitterion (6) can react with protic solvents to produce a variety of products. Reaction with water yields a transient hydroperoxy alcohol (10) that can dehydrate to a carboxyUc acid or spHt out H2O2 to form a carbonyl compound (aldehyde or ketone, R2CO). In alcohoHc media, the product is an isolable hydroperoxy ether (11) that can be hydrolyzed or reduced (with (CH O) or (CH2)2S) to a carbonyl compound. Reductive amination of (11) over Raney nickel produces amides and amines (64). Reaction of the zwitterion with a carboxyUc acid to form a hydroperoxy ester (12) is commercially important because it can be oxidized to other acids, RCOOH and R COOH. Reaction of zwitterion with HCN produces a-hydroxy nitriles that can be hydrolyzed to a-hydroxy carboxyUc acids. Carboxylates are obtained with H2O2/OH (65). The zwitterion can be reduced during the course of the reaction by tetracyanoethylene to produce its epoxide (66). 

Organic solutions of HOCl can be prepared in near quantitative yield (98—99%) by extraction of CU -containing aqueous solutions of HOCl with polar solvents such as ketones, nitriles, and esters (131). These organic solutions of HOCl have been used to prepare chlorohydrins (132) and are especially useful for preparation of water-insoluble chlorohydrins. Hypochlorous acid in methyl ethyl ketone has also been used to prepare Ca(OCl)2, by reaction with CaO or Ca(OH)2 (133), and hydrazine by reaction with NH3 (134). 

The nitrile may best be saponified with methyl alcoholic potash while heating to 190° to 200°C with application of pressure. After the methyl alcohol has evaporated the salt is introduced into water and by the addition of dilute mineral acid until the alkaline reaction to phenolphthalein has just disappeared, the amphoteric 1-methyl-4-phenyl-piperidine-4-carbOxylic acid is precipitated while hot in the form of a colorless, coarsely crystalline powder. When dried On the water bath the acid still contains 1 mol of crystal water which is lost only at a raised temperature. The acid melts at 299°C. Reaction with ethanol yields the ester melting at 30°C and subsequent reaction with HCI gives the hydrochloride melting at 187° to 188°C. 

Reaction of Nitriles with Organometallic Reagents Grignard reagents add to a nitrile to give an intermediate imine anion that is hydrolyzed by addition of water to yield a ketone. 

It has already been known that the reaction of primary amines with alkaline hypobromite gives nitriles, and the reaction of hydrazo compounds with bromine affords azo compounds. Recently, we also found that the reaction of primary amines and hydrazo compounds with BTMA Br3 in aq. sodium hydroxide or in water gave corresponding nitriles and azo compounds in satisfactory yields, respectively (Fig. 27) (ref. 35). 

The nitrile produced in the above reaction can be converted into the corresponding carboxylic acid by acid hydrolysis, l.e. reaction with water catalysed by hydrogen ions from the acid. 

In summary, (R)-phenylglycine amide 1 is an excellent chiral auxiliary in the asymmetric Strecker reaction with pivaldehyde or 3,4-dimethoxyphenylacetone. Nearly diastereomerically pure amino nitriles can be obtained via a crystallization-induced asymmetric transformation in water or water/methanol. This practical one-pot asymmetric Strecker synthesis of (R,S)-3 in water leads to the straightforward synthesis of (S)-tert-leucine 7. Because (S)-phenylglycine amide is also available, this can be used if the other enantiomer of a target molecule is required. More examples are currently under investigation to extend the scope of this procedure. ... 

The basic hydrolysis (reaction with water) of a nitrile (R-CN) followed by acidification yields a carboxylic acid. In general, an reaction (nucleophilic substitution) of an alkyl halide is used to generate the nitrile before hydrolysis. Figure 12-12 illustrates the formation of a carboxylic acid beginning with an alkyl halide. 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

A novel method for the convenient synthesis of alkenyl fluorides 15, as well as diflu-oromethyl-substituted alcohols 16 and amides 17, via electrophilic fluorination with one equivalent of F-Teda BF4 (6) of alkenyl boronic acids and trifluoroborates, has been reported.87 The alkenyl fluorides 15 are obtained as Z/E mixtures when the reaction is carried out with one equivalent of F-Teda BF4 in acetonitrile at room temperature. When the reaction is performed with two equivalents of F-Teda BF4 in water or a nitrile solvent the difluoromethyl-substituted alcohols 16 or amides 17, respectively, are obtained. 

In reactions with aliphatic azides gas evolution did not usually begin until approximately 5 min had elapsed from the time of initial addition. In contrast, immediate gas evolution was observed after the initial addition of azido nitriles and phenoxy azides to the nitrosonium salt. Total gas evolution was measured on the closed system by water displacement from a calibrated gas buret. Total gas evolution reflected the total amount of reacted azide and the different pathways for the production of gaseous products (nitrosative decomposition and Curtius rearrangement). The rate of production of gaseous products slowed markedly after the evolution of 40-60 mL (1-2 mmol of reacted azide) with the exception of nitrosative reactions wi th 4-azidobutanonitrilc and 5-azidopentanonitrile, gas evolution terminated when approximately 50 % of the azide had reacted. Gas evolution in the nitrosative reactions of aliphatic azides continued to completion as a result of protonic decomposition. Reactions were usually complete within 2 h. 

Cyclic imines are obtained in the related transformation of methylenecyclpropanes with nitriles mediated by triflic acid700 (Scheme 5.68). The reaction pathway suggested to interpret product formation is similar to that in Scheme 5.67. The reaction of intermediate 162 with water may give Ritter products (carboxamides) isolated in some cases. 

The reaction of 81 with KCN in the presence of tricaprylylmethylammonium chloride (aliquat 336) in 1 1 benzene-water gives the nitrile 82 (Scheme 15) <1996FES425>. 

The treatment of benzaldehyde with potassium hydroxide in acetonitrile results in the formation of the same product, i.e., cynnamyl nitrile (Sawyer Gibian 1979). Thus, in the presence of water or other proton sources, the 02 ion forms strong bases as well as oxygen and the peroxide anion. Therefore, many reactions that are ascribed to the superoxide ion are actually reactions with proton donors. These reactions produce effective oxidants (02 and HOO-) and strong bases (OH- or B-). 

Cu(II) or Fe(III) salts are applied as catalysts. In Scheme 8.30, the reaction of nitrile 41i with benzylamine gives an almost quantitative yield if FeCl3-7H20 is applied as the catalyst, which is, however, in contrast to the hexahydrate, not commercially available [98], Water is normally considered as an environmentally benign solvent. The authors curiously needed CFI2CI2 and other organic solvents for workup and purification of the product 67 (Scheme 8.30). 

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