Cyanide quaternary

Benzyltrimethyl-ammonium cyanide Quaternary ammonium halides... 

Ethyldiisopropylamine hydrobromide Pyridine — Me2NCHF2,3HF H2NOH, HCl Chlorides Methiodides Benzyltrimethyl-ammonium cyanide Quaternary ammonium halides... 

Hydrochlorides, Hydrobromides, Hydriodides Diisopropylamine hydrofluoride Dimethylamine Di-butylamine Prime thy lamine Tri-ethylamine Pyridine -y Quinoline hydrochloride Ethyldiisopropylamine hydrobromide Pyridine hydrobromide (CH2).NCHF2, SHF H2NOHy HCl Chlorides Methiodides Benzy Itrimethy l-ammonium cyanide Quaternary ammonium halides (CH2)4N-F-y... 

Sodium cyanide does not dissolve m butyl bromide The two reactants contact each other only at the surface of the solid sodium cyanide and the rate of reaction under these con ditions IS too slow to be of synthetic value Dissolving the sodium cyanide m water is of little help because butyl bromide is not soluble m water and reaction can occur only at the interface between the two phases Adding a small amount of benzyltrimethyl ammonium chlonde however causes pentanemtnle to form rapidly even at room temper ature The quaternary ammonium salt is acting as a catalyst it increases the reaction rate How7... 

Reactions of the Side Chain. Benzyl chloride is hydrolyzed slowly by boiling water and more rapidly at elevated temperature and pressure in the presence of alkaHes (11). Reaction with aqueous sodium cyanide, preferably in the presence of a quaternary ammonium chloride, produces phenylacetonitrile [140-29-4] in high yield (12). The presence of a lower molecular-weight alcohol gives faster rates and higher yields. In the presence of suitable catalysts benzyl chloride reacts with carbon monoxide to produce phenylacetic acid [103-82-2] (13—15). With different catalyst systems in the presence of calcium hydroxide, double carbonylation to phenylpymvic acid [156-06-9] occurs (16). Benzyl esters are formed by heating benzyl chloride with the sodium salts of acids benzyl ethers by reaction with sodium alkoxides. The ease of ether formation is improved by the use of phase-transfer catalysts (17) (see Catalysis, phase-thansfer). 

Nearly all uses and appHcations of benzyl chloride are related to reactions of the active haUde substituent. More than two-thirds of benzyl chloride produced is used in the manufacture of benzyl butyl-phthalate, a plasticizer used extensively in vinyl flooring and other flexible poly(vinyl chloride) uses such as food packaging. Other significant uses are the manufacture of benzyl alcohol [100-51-6] and of benzyl chloride-derived quaternary ammonium compounds, each of which consumes more than 10% of the benzyl chloride produced. Smaller volume uses include the manufacture of benzyl cyanide [140-29-4], benzyl esters such as benzyl acetate [140-11-4], butyrate, cinnamate, and saUcylate, benzylamine [100-46-9], and benzyl dimethyl amine [103-83-8], and -benzylphenol [101-53-1]. In the dye industry benzyl chloride is used as an intermediate in the manufacture of triphenylmethane dyes (qv). First generation derivatives of benzyl chloride are processed further to pharmaceutical, perfume, and flavor products. 

Monoammonium phosphate Diammonium phosphate Nitric oxide Actylonitrile Caprolactam Monomethylamine Dimetliylamine Hexametliylenetetramine Trimetliylamine Monoethanolamine Dietlianolamine Trietlianolamine Hydrogen Cyanide Fatty nitrogen compounds (nitriles, amines, quaternary ammonimn compounds)... 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

These major routes to quinoxalmecarbonitriles have been covered already by primary synthesis (Chapter 1), by cyanalysis of halogenoquinoxalines (Section 3.2.5), by deoxidative cyanation of quinoxaline N-oxides (Section 4.6.2.2), by cyanolysis of nitroquinoxalines (Section 6.1.2.2), from primary quinoxalina-mines by a Sandmeyer-type reaction (Section 6.3.2.3), from quaternary ammonio-quinoxalines with cyanide ion (Section 6.3.2.4), and by dehydration of quinoxalinecarboxamides (Section 7.4.2). Those remaining preparative routes that have been used recently are illustrated in the following examples. 

For example, Mannich reaction of N-methylpyrrole affords the corresponding dimethylaminomethyl derivative (2) and treatment with methyl iodide affords the quaternary salt (3). Displacement of the quaternary amine by means of cyanide leads to the substituted... 

The wide latitude of structural variation consistent with bioactivity in this series is illustrated by the observation that antiinflammatory activity is maintained even when the second aromatic group is attached directly to the pyrrole nitrogen rather than to the heterocyclic ring via a carbonyl group as in the previous case. Condensation of p-chloroaniline with hexane-2,5-dione (or its dimethoxy-tetrahydrofuran equivalent) affords pyrrole 7. The acetic acid side chain is then elaborated as above. Thus, Mannich reaction leads to the dimethylaminomethyl derivative 8, which is in turn methylated (9) the quaternary nitrogen replaced by cyanide to afford 10. Hydrolysis of the nitrile then gives clopirac (11). 

The asymmetric synthesis achieved when the base is an optically active one is proof that the base is present in a transition state with the carbonyl and not just an agent for removal of protons from hydrogen cyanide. It has further been shown that asymmetric synthesis is still achieved even if the only optically active molecules present are quaternary ammonium compounds, i.e., positive ions without any protons to donate. This probably means that the important thing is to have some positive ion near the carbonyl oxygen, an actual covalent... 

These two phase reactions summarized in Scheme 1 are strongly promoted by catalytic amounts of the quaternary onium salts which will transfer between aqueous and organic phases, as shown in Scheme 2 for the substitution of halides with cyanides. The effect was termed by Starks... 

Ammonium cyanide, 8 194 Ammonium derivatives, quaternary, 24 45 Ammonium dichromate, 6 538 manufacture, 6 541 Ammonium dichromate(VI), physical properties, 6 528t... 

Probably the most important group of phase transfer reactions, and certainly the commonest, are those in which an anion is transferred from the aqueous phase into the organic solvent, where nucleophilic substitution occurs. These would once have been performed in a dipolar aprotic solvent such as DMF. A good example is the reaction between an alkyl halide (such as 1-chlorooctane), and aqueous sodium cyanide, shown in Scheme 5.5. Without PTC, the biphasic mixture can be stirred and heated together for 2 weeks and the only observable reaction will be hydrolysis of the cyanide group. Addition of a catalytic amount of a quaternary onium salt, or a crown ether, however, will lead to the quantitative conversion to the nitrile within 2 h. 

The hydration number (the number of water molecules intimately associated with the salt) of the quaternary ammonium salt is very dependent upon the anion. The change in the order of reactivity is thus believed to be due to the hydration of the anion the highly hydrated chloride and cyanide ions are less reactive than expected, and the poorly hydrated iodide fares better under phase transfer conditions than in homogeneous reactions. Methanol may specifically solvate the anions via hydrogen bonding, and this effect is responsible for the low reactivity of more polar nucleophiles in that solvent. 

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],... 

In a sequential continuous process, alcohols are converted initially into the corresponding chloroalkanes, which are flushed without isolation into an aqueous mixture of sodium cyanide and the quaternary ammonium catalyst to produce nitriles [17]. 

Other classic examples illustrating the use of quaternary salts as phase transfer catalysts were published by Makosza(2), and by Brandstrom(3). Subsequent development of crown ethers(4-7) and crvptands(7-8) as phase transfer catalysts gave PTC an entirely new dimension since now the inorganic reagent, as sodium cyanide in the above equation, need no longer be dissolved in water but can be used... 

In an extension of this work, the reuse of the polymeric catalyst was addressed and several new PE-poly(alkene) glycol copolymers were prepared [68]. Commercially available oxidized polyethylene (CO2H terminated, both high and low molecular weight) was converted to the acid chloride and reacted with Jeffamine D or Jeffamine EDR, and subsequently converted to the tributylammonium bromide salt with butyl bromide. These new quaternary salts were shown to catalyze the nucleophihc substitution of 1,6-dibromohexane with sodium cyanide or sodium iodide. While none of the polymeric quaternary salts catalyzed the reaction as well as tetrabutylammonium bromide, the temperature-dependent solubility of the polymers allowed removal of the polymer by simple filtration. 

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