Synthesis of benzonitriles

Earlier work in this laboratory showed that chromium oxide supported on alumina is a good catalyst for the conversion of olefins (ref. 1) as well as paraffins (ref. 2) to nitriles with high selectivities, by reaction of NO with the hydrocarbons (nitroxidation). Recent work (ref. 3) reported preliminary results of the nitroxidation of paraxylene as an extension of the use of C Oj-Al Oj to the catalytic synthesis of aromatic nitriles. It should be mentioned that only few data are available in the literature related to the nitroxidation of aromatic hydrocarbons. Teichner et al (ref. 4 ) reported interesting results of selective synthesis of benzonitrile by nitroxidation of toluene on NiO-AlgO catalysts. Improvements of the catalytic activity and selectivity in this reaction were reached by use of C Og-Al. which also exhibits striking properties in the synthesis of paratolunitrile by contact of NO with paraxylene (ref. 3). 

A similar beneficial effect of 1,1-diphenylethylene on the yields of arylation products was later observed in the synthesis of benzonitrile derivatives by reaction of diaryliodonium salts with potassium cyanide and in the reaction of diaryliodonium salts with the sodium salt of nitroalkanes. 7 In the latter case, the reaction was therefore considered to result from intermediate inner-sphere radicals. Some years later. Barton et al. showed that 1,1-diphenylethylene acts as an efficient inhibitor of the radical chain process in the reaction of enolates with diaryliodonium salts. They concluded that the arylation products arose from a non-radical process. 

MILLER-SNYDER Aryl Cyanide Synthesis Synthesis of benzonitriles from aldehydes via oxime ethers in the presence of p-nitrobenzonitrile. Formation of p-cyanophenol fron p-nitrobenzaldoxime and p-nitrobenzonitrile (used as a sometimes recyclable chain carrier) (see 1st edition). 

Other catalysts, used in types of reactions not listed above, vary with the specific reaction involved. A few examples are cited. For the reaction involving the removal of hydrogen from NHa and CH4 to produce HCN, noble-metal catalysts are used. For the synthesis of benzonitrile from toluene and NHs by splitting out hydrogen, molybdenum trioxide is used. 2-Methyl-5-ethylpyridine is produced by reacting methylvinyl ether and NHs at elevated temperatures and pressures over a titanium phosphate or manganese phosphate catalyst supported on calcined silica. ... 

Synthesis of Benzonitriles. Arylthallium(III) salts with copper(I) cyanide or copper(II) cyanide afford fair to excellent yields of benzonitriles when heated at reflux in pyridine solvent (eq 24). The use of acetonitrile as solvent gives lower product yields. 

Feng Q, Song Q (2014) Copper-catalyzed decarboxylative C=N triple bond ftmtiation direct synthesis of benzonitriles from phenylacetic acids under O2 atmosphere. Adv Synth Catal 356(8) 1697-1702... 

Xu J-H, Jiang Q, Guo C-C (2013) Phenyliodonium diacetate mediated direct synthesis of benzonitriles from styrenes through oxidative cleavage of C=C bonds. J Oig Chem 78 (23) 11881-11886... 

An unusual final example of a synthesis from pyridines involves the 4-lithiotetra-chloropyridine (128), which with two moles of benzonitrile gave the trichlorodiphenyl-pyrido[3,4- f]pyrimidine (130) via the intermediate (129) (72JCS(P1)2190). The 2-lithio analogue gave the corresponding [3,2-c] derivative. 

In considering an appropriate starting material for the synthesis of taranabant the commercial availability of a number of 3-substituted benzonitriles was evaluated, however, with the exception of the previously employed 3-bromobenzonitrile, cost effective options from recognized large-scale suppliers were limited (Figure 9.2). 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

The synthesis of phthalimidines by dicobalt octacarbonyl-catalyzed carbonylation of Schiff bases was first described by Pritchard78 and the scope of the reaction was evaluated by Murahashi et a/.79 Later Rosenthal et al.80-83 subjected a variety of related compounds to carbonylation, and also achieved a phthalimidine synthesis directly from benzonitrile under the conditions of the oxo process.84 An example illustrating the formation of a phthalimidine is shown in Scheme 49 a comprehensive review of the scope and mechanism of reactions of this type is available.85... 

Hynninen and coworkers <99JCS(PT1)2403> used a similar approach to prepare phytochlorin-C6o diad 38 (Scheme 11). The protocol employed the pyrolysis of the natural chlorophyll a molecule 35, followed by transesterification and demetallation to furnish derivative 36. Subsequent oxidation of 36 with OsCU and NaI04 has allowed the synthesis of the formyl derivative 37, which was further used as precursor of the azomethinic ylide intermediate in the 1,3-DC reaction with Cm leading to the formation of diad 38. Photochemical studies revealed that this diad underwent a fast intramolecular photoinduced electron transfer in polar solvents such a benzonitrile <99JACS9378>. 

Two unique type Had syntheses of pyrroles that were reported both involved cyclopropane fragmentations. The first allowed for a synthesis of 2-arylpyrroles <06SL2339>. In the event, treatment of stannylcyclopropane 25 with -BuLi followed by benzonitrile produced 2-phenylpyrrole 26 via tin-lithium exchange, addition to the nitrile, ring fragmentation of ketimine intermediate, intramolecular condensation, and loss of dibenzylamine. 

Kobayashi and co-workers have also reported an alternate synthesis of 1,4-disubstituted isoquinolines and a new synthesis of 1,3,4-dihydroisoquinoline derivatives <06BCJ 1126 06S2934>. The 1,4-disubstituted isoquinolines 121 are synthesized in good yields by reacting a variety of organolithiums 122 with different benzonitriles 123. In addition, a variety of lithium dialkylamides 124 were also reacted with different benzonitriles 123 to form 1 -amino-4-substituted isoquinolines 121 in moderate yields. 

For more than a century, stoichiometric methods were presumed in the preparation of benzonitriles in laboratory and industry. These particularly include the Rosenmund-von Braun reaction of aryl halides, the diazotization of anilines and subsequent Sandmeyer reaction, and the ammoxidation. Because of (over)stoichiometric amounts of metal waste, lack of functional group tolerance, and harsh reaction conditions, these methods do not meet the criteria of modern sustainable synthesis. 

The Pd-catalyzed reaction of simple arenes and nitriles provides a useful synthesis of aromatic ketones.120 The reaction of toluene and benzonitrile in the presence of Pd(OAc)2 as a catalyst in DMSO and TFA gives diarylketones (Equation (92)). The presence of DMSO is essential in this reaction. 

Synthesis of the oxadiazolopyrimidone 358 was accomplished by reaction of the amide 357 with phosphorus pentoxide and methylsulfonic acid in low yield <1994PHA880>. Also, its benzologue 360 could only be obtained in very modest yield <2004TL8741> in the case, reaction of the benzonitrile derivative 359 with acetylhydrazine resulted in formation of the bicyclic product 360. 

N-Sulfinylaniline, the procedure for the preparation of which is described in Part A, is a versatile intermediate in the synthesis of heterocyclic compounds. Benzohydroxamoyl chloride, the method for the preparation of which is given in Part B, is the precursor of the highly reactive benzonitrile oxide, the diverse dipolar addition reactions of which have been thoroughly investigated. A wide array of heterocyclic compounds can be prepared starting with benzonitrile oxide. ... 

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