Nitriles, formation

Nitrile Process. Fatty nitriles are readily prepared via batch, Hquid-phase, or continuous gas-phase processes from fatty acids and ammonia. Nitrile formation is carried out at an elevated temperature (usually >250° C) with catalyst. An ammonia soap which initially forms, readily dehydrates at temperatures above 150°C to form an amide. In the presence of catalyst, zinc (ZnO) for batch and bauxite for continuous processes, and temperatures >250° C, dehydration of the amide occurs to produce nitrile. Removal of water drives the reaction to completion. 

Direct ammonolysis involving dehydratioa catalysts is geaerahy ma at higher temperatures (300—500°C) and at about the same pressure as reductive ammonolysis. Many catalysts are active, including aluminas, siUca, titanium dioxide [13463-67-7], and aluminum phosphate [7784-30-7] (41—43). Yields are acceptable (>80%), and coking and nitrile formation are negligible. However, Htfle control is possible over the composition of the mixture of primary and secondary amines that can be obtained. 

Diastereoselective amino nitrile formation from the following ulose may, however, be attributed to thermodynamic control. Flash chromatography of the product provides only one ri bo-derivative28. 

This contrary stereochemistry in the Bucherer - Bergs reaction of camphor has been attributed to steric hindrance of e.w-attack of the cyanide ion on the intermediate imine. Normally, equatorial approach of the cyanide ion is preferred, giving the axial (t>Mr/o)-amino nitrile by kinetic control. This isomer is trapped under Bucherer-Bergs conditions via urea and hydan-toin formation. In the Strecker reaction, thermodynamic control of the amino nitrile formation leads to an excess of the more stable compound with an equatorial (e.w)-amino and an axial (endo)-cyano (or carboxylic) function13-17. 

Oxidation of primary amines at a nickel oxide results in the formation of a nitrile. Formation of the nickel oxide electrode was discussed on p, 270. The rate determining stage ss the reaction between electrochemically formed nickel(ni) ox-... 

Reductive ring closure of l-(2-nitrobenzyl)-2-pyrrole carbaldehyde 200 results in pyrrolo[2,l-c][l,4]benzodiazepine 201 (Scheme 42 (1999BMCL1737)). On the other hand, oxo derivative 203 can be synthesized starting from aldehyde 200 through a nitrile formation/cyclizations multistep sequence. The alternate synthetic strategy included reduction of the intermediate acid (R = H) or ester (R = Et) 205 followed by CDI or thermal cyclization (1992JHC1005). 

The Beckmann fragmentation with nitrile formation is the main side reaction and may be predominant. This side reaction is more important when R and/or R can form a relatively stable carbocation (equations 68 and 69). 

When zeolites were placed in the reactor, benzaldehyde again completely disappeared, but benzonitrile was formed. Its yield depended slightly on the reaction temperature. In contrast to the reaction of chlorobenzene and ammonia, the yield of benzonitrile depended only slightly on the kind of metal cations, as seen in Table II. This suggests that the rate-determining step of the nitrile formation does not involve metal cations. The reaction mechanism is postulated as follows ... 

The last aspect to be discussed is the pathway of nitrile formation from arylnickel complexes 1 as suggested by IR evidence. The first band (A in Table IX) which is immediately formed on the reaction of NaCN and 1 has a frequency between 2120 and 2130 cm 1. 

Neighboring group participation, 191 Nitrile (formation), 274 Nitrilium ion, 294-297 Nitrobenzisoxazole carboxylic acid, 299... 

Surprisingly, detailed analysis of several NMR spectra of isolated and purified compounds and a crystal structure analysis revealed the formation of 2-amino-4-cyano-amides. This reaction is the first case in which the oxygen for the newly formed amide bond emerges not from the solvent (H2O) but rather from the amide bond of a reactant. Also noteworthy is the concomitant nitrile formation from the primary amide, which does not normally occur under such mild conditions. Typical examples and their yields are given in Scheme 3.9. 

Under acidic reaction conditions the formation of isonitriles can compete efficiently with nitrile formation (Scheme 4.87) [377]. Particularly effective reagents for the formation of isonitriles are mixtures of Me3SiCN with Lewis acids such as Zn(II), Pd(II), or Sn(II) salts. Aluminum-derived Lewis acids with Me3SiCN, on the other hand, mediate the conversion of epoxides into nitriles [378, 379]. 

An ab initio study of the. S N2 and E2 mechanisms has been performed for the reaction between the cyanide ion and ethyl chloride in dimethyl sulfoxide solution.5 Theoretical calculations have predicted a free energy barrier for nitrile formation of 24.1 kcal mol-1, close to the experimental value of 22.6 kcal mol-1 (Scheme 3). It has also been predicted that the isonitrile formation is less favorable by 4.7 kcal mol-1, while the elimination mechanism is less favorable by more than 10 kcal mol-1. These results indicated that isonitrile formation and bimolecular elimination are not significant side-reactions for primary alkyl chloride reactions. 

Thus, hydrogen peroxide has found application in the implementation of the well-known organic reactions in the gas phase—dehydrogenation, epoxidation, hydrogenolysis, nitrile formation from /V-alkylbcnzcne, nitrogen fixation, etc. 

To explore further the structural requirements for this unexpected nitrile formation (51 — 52) the reaction of the 1-methyl derivative 56 with sodium azide was examined. In this case the diazido derivative 57 was obtained instead of the nitrile 58. In a control experiment the nitrile 58 was also prepared by methylation of 52 with trimethyl phosphate in the presence of potassium carbonate. 58 reacted in analogy to 52 with sodium azide to furnish the tetrazole 59. Attempted decomposition of the geminal diazide 57 in refluxing DMF failed to give the tetrazole 59 (which is very surprising in view of the easy conversion of 38 to 39) [90LA505],... 

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