Nitriles phase-transfer catalysis

These reactions proceed more rapidly in polar aprotic solvents. In DMSO, for example, primary alkyl chlorides are converted to nitriles in 1 h or less at temperatures of 120°-140°C.36 Phase transfer catalysis by hexadecyltributylphosphonium bromide permits conversion of 1-chlorooctane to octyl cyanide in 95% yield in 2 h at 105° C.37... 

Nitriles have been synthesized by a variety of methods. The formation of nitriles by the alkylation of potassium cyanide using solid-liquid phase-transfer catalysis without added solvent is... 

Alkylation of nitriles. An example (equation I) of a general method for alkylation of active methylene groups by phase-transfer catalysis has been 4Ncribed in detail. ... 

The term phase transfer catalysis was coined by Starks to describe the mechanism of catalysis of reactions between water-soluble inorganic salts and water-insoluble organic substrates by lipophilic quaternary ammonium and phosphonium ions Ql). His investigations of nucleophilic displacement reactions, such as that of aqueous sodium cyanide with 1-chlorooctane, and the investigations of Makosza on reactions of aqueous sodium hydroxide with chloroform to generate dichlorocarbene, and with active ketones and nitriles to generate carbanions, pioneered the field in the mid-1960 s. It was nearly fifteen years before many such processes were adopted in industry. Starks now estimates there are about sixty phase transfer catalytic processes in use worldwide, mostly in pharmaceutical and fine chemical manufacturing (32V... 

A few pyrazolo-[3,4-e]-2H-pyrans were made 6 m the heterocyclization of l-phenylpyrazolidine-3,5-dione with active nitriles, under phase-transfer catalysis conditions (14JHC860). The natural chromone-fused 2H-pyran macakurzin C was obtained from phlorc ucinol in a multistep synthetic approach, a Claisen rearrangement-cyclization of propai loxychromone derivative being the key transformation to build the pyran core (14SL2794). 

The fundamental theory of phase transfer catalysis (PTC) has been reviewed extensively. Rather than attempt to find a mutual solvent for all of the reactive species, an appropriate catalyst is identified which modifies the solubility characteristics of one of the reactive species relative to the phase in which it is poorly solubilized. The literature on the use of PTC in the preparation of nitriles, halides, ether, and dihalocarbenes is extensive. Although PTC in the synthesis of C- and 0-alkylated organic compounds has been studied, the use of PTC in polymer synthesis or polymer modification is not as well studied. A general review of PTC in polymer synthesis was published by Mathias. FrecheE described the use of PTC in the modification of halogenated polymers such as poly(vinyl bromide), and Nishikubo and co-workers disclosed the reaction of poly(chloromethylstyrene) with nucleophiles under PTC conditions. Liotta and co-workers reported the 0-alkylation of bituminous coal with either 1-bromoheptane or 1-bromooctadecane. Poor 0-alkylation efficiencies were reported with alkali metal hydroxides but excellent reactivity and efficiencies were found with the use of quaternary ammonium hydroxides, especially tetrabutyl- and tetrahexylammonium hydroxides. These results are indeed noteworthy because coal is a mineral and is not thought of as a reactive and swellable polymer. Clearly if coal can be efficiently 0-alkylated under PTC conditions, then efficient 0-alkylation of cellulose ethers should also be possible. 

The application of both ultrasonification and phase-transfer catalysis to the lithium aluminium hydride reductions of amides and nitriles to amines has been documented. Such nitrile reductions... 

Stoichiometric amounts of tetraethylammonium cyanide react with aliphatic bromides in dichloromethane, acetonitrile or DMSO to give reasonable yields of the corresponding nitriles [13]. These reactions are clearly related to, but not actually examples of, phase transfer catalysis. It is interesting, however, that under these homogeneous conditions, tetraethylammonium cyanide reacts in acetonitrile with neopentyl bromide to give the corresponding nitrile (see Eq. 7.3). Bimolecular displacements on such sterically hindered substrates are usually quite difficult to effect. 

Similarly, new reagents have been reported for the dehydration of aldoximes to nitriles. Thus, sulphuryl chloride fluoride, triphenylphosphine under controlled potential electrolysis, and phosphorus tri-iodide effect this transformation under mild conditions. The latter reagent, like diphosphorus tetraiodide (c/. Vol. 4, p. 179), also effects the conversion of primary aliphatic nitro-compounds into nitriles, as does sodium hypochlorite under phase-transfer catalysis and... 

Alk-2-enenitriles also result from the dehydrobromination of y-hromo-P-oxo-nitriles, alk-3-enenitriles from the palladium-catalysed reductive cleavage of 2-acyloxy-3-ethylenenitriles, 2-dimethylamino-alk-2-enenitriles from the reaction between aldehydes and diethyl 1-dimethylamino-l-cyanomethane-phosphonate under phase-transfer catalysis, 2-ureido-alk-2-enenitriles via... 

The simplest C-C bond formation reaction is the nucleophilic displacement of a halide ion from a haloalkane by the cyanide ion. This was one of the first reactions for which the kinetics under phase-transfer catalysed conditions was investigated and patented [l-3] and is widely used [e.g. 4-12], The reaction has been the subject of a large number of patents and it is frequently used as a standard reaction for the assessment of the effectiveness of the catalyst. Although the majority of reactions are conducted under liquiddiquid two-phase conditions, it has also been conducted under solidrliquid two-phase conditions [13] but, as with many other reactions carried out under such conditions, a trace of water is necessary for optimum success. Triphase catalysis [14] and use of the preformed quaternary ammonium cyanide [e.g. 15] have also been applied to the conversion of haloalkanes into the corresponding nitriles. Polymer-bound chloroalkanes react with sodium cyanide and cyanoalkanes under phase-transfer catalytic conditions [16],... 

A full study of some 5n reactions of alkyl halides to give other halides, nitriles, ethers, etc. under triphase catalysis conditions i.e. organic and aqueous liquid phases with a heterogeneous phase-transfer catalyst) has appeared. 

Tertiary amines are also known to effect the phase transfer addition of cyanide ion to primary, allylic, and benzylic halides [9]. The reported effect of amine structure on catalytic efficiency closely parallels that reported by Hennis for ester formation in a two-phase system (see Sect. 1.7). Both the nitrogen of the amine and the carbon bearing halide of the alkyl bromide must be sterically accessible for the reaction to succeed. Thus, -hexylamine is effective in concert with -butyl bromide but the combinations of either 5-butyl bromide and -hexylamine or -butyl bromide and cyclohexylamine are not. Tertiary amines are generally more effective than secondary or primary amines. In addition, the yields of primary nitriles decrease dramatically with the size of the primary alkyl bromide from quantitative with n-butyl to only 6% with -decyl bromide when -hexylamine is used as phase transfer catalyst. On the other hand, tributylamine was equally useful as a catalyst for the quantitative conversion of either 1-bromohexane or 1-bromodecane to the corresponding nitriles [9]. In general, these observations accord with those of Hennis and coworkers indicating that this reaction is an example of in situ formation of and catalysis by quaternary ammonium salts [10]. 

Alkyl cyanides have been prepared by three major variations of the phase transfer method. These include the liquid-liquid phase transfer method (including catalysis by quats and amines), the crown catalyzed solid-liquid method and the tri-phase catalytic method. Each of these methods has been discussed with reference to the mechanism in the preceding section and it remains largely to exemplify these approaches. It should be noted, however, that numerous stoichiometric syntheses of aliphatic nitriles are available, including those involving dipolar aprotic solvents [12]. 

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