Benzonitrile derivatives

Condensation of 2-azido benzonitrile derivatives 703 with ethyl aeetonediearboxylate in presenee of NaOEt gave the triazoloquinoline derivatives 705 presumably through the intermediate 704 (90S654). Reaetion of 703 with dibenzyl ketone gave the triazole 706 aeeompanied by 707 whieh upon treatment with NaH in THF afforded 706 (97S773) (Seheme 122). 

It is noted that the reaction of aryl diazonium salts with CuCN to give benzonitrile derivatives is also called the Sandmeyer reaction. It is usually conducted in neutral solution to avoid liberation of HCN. 

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. 

An easy access to the title compounds has been found by Shukorov et al. <1994IZV908, 1995IZV2035>. These authors reported that reaction of benzonitrile derivatives with thiosemicarbazide and ethyl acetoacetate in the presence of polyphosphoric acid gives rise to the cyclized products 367 in good to excellent yields. 

In 2003, Balalaie and co-workers published a new paper in the area of imidazole synthesis39. In the above examples reported by Westman, ammonium acetate and primary amines act as the nitrogen source for the imidazole ring. In the Baladie novel one-pot three-component method, ammonium acetate was replaced by benzonitrile derivatives. Thus, benzil, primary amines and benzonitrile derivatives underwent a condensation reaction on acidic silica gel as the solid support, Scheme 5.23. The reaction mixtures were irradiated for 8 min in a domestic oven under solvent-free conditions to give the products in 58-92% yield. 

A number of studies have also been made of the hydrolysis of nitriles in the coordination sphere of cobalt(III). Pinnell et al.3 4 found that benzonitrile and 3- and 4-cyanophenol coordinated to pentaamminecobalt(III) are hydrolyzed in basic solution to the corresponding N-bonded carboxamide (equation 22). The reaction is first order in hydroxide ion and first order in the complex with koH= 18.8M 1s 1 at 25.6 °C for the benzonitrile derivative. As fc0H for the base hydrolysis of benzonitrile is 8.2 x 10-6 M-1 s at 25.6 °C, the rate acceleration is ca. 2.3 x 106-fold. The product of hydrolysis is converted to [(NH3)5CoNH2COPh]3+ in acidic solution and the pJC of the protonated complex is 1.65 at 25 °C. Similar effects have been observed with aliphatic nitriles.315 Thus, base hydrolysis of acetonitrile to acetamide is promoted by a factor of 2 x 106 on coordination to [Co(NH3)5]3+. 

The regioselective functionalization of nitrobenzene and benzonitrile derivatives has been performed via nucleophilic aromatic substitution of hydrogen by phosphorus-stabilized carbanions.41 Lithium phosphazenes have been found to be the most suitable nucleophiles for the substitution of hydrogen in nitrobenzene. This method represents a convenient alternative to the vicarious nucleophilic substitution for the synthesis of benzylic phosphorus derivatives using phosphorus-stabilized anions that do not bear a leaving group at the carbanionic centre. 

For synthetic purposes a number of sodium JV,JV -bis(trimethylsilyl)benz-amidinates 2 have been synthesized in an analogous manner by addition of NaN(SiMe3)2 to p-substituted benzonitrile derivatives [30, 33] ... 

Isatin-3-oximes are also decomposed to benzonitrile derivatives under Vilsmeier-... 

Butoxy-benzonitrile derivatives prepared by Birkinshaw (4), (III), were effective as nitric oxide synthase inhibitors and used in the treatment of smooth muscle relaxation disorders and in the regulation of blood pressure and blood flow. 

The reaction of amines with 1,2-diketo substrates led to a variety of substituted imidazole derivatives. Treatment of various substituted anilines 88 with glyoxals 89 gave the imine intermediate 90, which was then cyclized to the 1-arylimidazoles 91 with paraformaldehyde and ammonium chloride under acidic conditions <0382661>. A one-pot, three-component condensation of benzil 92, benzonitrile derivatives and primary amines on the surface of silica gel under solvent-free conditions and microwave irradiation provided tetrasubstituted imidazoles 93<03TL1709>. 

Intramolecular cyclisation following halogen-metal exchange in the benzonitrile derivatives 25 provides a route to xanthones and thioxanthones. Incorporation of a second aryl halide function into the benzonitrile substrate allows an anionic cascade ring-closing sequence and the formation of pentacyclic xanthene derivatives 26 <03JOC4091>. 

Tetrasubstituted imidazoles (xxviii) were also obtained in high yields by a one-pot, three-component condensation of benzyl, benzonitrile derivatives and 1° amines on the surface of silica gel under solvent free microwave condition [2]. 

RU-58841 Aventis Benzonitrile derivative Non-steroidal topical antiandrogen Acne, alopecia... 

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. 

There are a number of organic acids that interfere with plant metabolism. Dicamba (3,6-dichloro-2-methoxybenzoic acid) and tricamba are herbicides which interfere with protein synthesis, while picloram (4-amino-3,5,6-trichloro-2-pyriidinecarboxylic acid) interacts with nucleic acid synthesis in susceptible plants. Dicamba is primarily eliminated in the urine due to its hydrophilic properties. Some benzonitrile derivatives are also employed as herbicides, including dichlobenil (2,6-dichlorobenzonitrile), bromoxynil (3,5-dibromo-4-hydroxybenzonitrile), and ioxynil. Linuron (N -(3,4-dichlorophenyl)-N-methoxy-N-methylurea) is a phenyl urea while trifluralin (a,a,a-trifhiro-2,6-dinitro-N,N-dipropyl-p-toluidine) is a dinitroaniline. The major concern with the substituted ureas is induction of hepatic microsomal enzymes which could modulate the disposition of simultaneously exposed chemicals metabolized by the same enzymes. Finally, one of the most common herbicides presently in use is glyphosphate, or Roundup , a phospho-... 

Treatment of diazonium salts with cuprous, Cu(I), salts generates aryl halides. When 398 reacts with CuCl (cuprous chloride) or CuBr (cuprous bromide), the products are chlorobenzene or bromobenzene via what is probably a radical reaction.29l jhis conversion is known as the Sandmeyer reaction. 2 The use of copper powder rather than cuprous salts for this transformation is often called the Gattermann reaction. 93,292b,c Aryl iodides are also produced from diazonium salts by reaction with potassium iodide (KI) but the actual reactive species may be l3-.294,295 Treatment of aniline derivative 403 with sodium nitrite and HCl followed by treatment with KI, for example, gave a 89% yield of 404.Aryl nitriles are generated under Sandmeyer conditions using cuprous cyanide (CuCN), as in the conversion of 405 to benzonitrile derivative 407 via diazonium chloride, 406. 

Polarographic investigations of a number of substituted nitro- and m-dinitrobenzonitriles in DMF solution revealed stable radical anion formation at the first polarographic wave by a reversible 1 -electron transfer. A cyano group at the 5-position of nitrobenzene and 1,3-dinitrobenzene proved to exert an important influence on the half-wave potentials of these benzonitrile derivatives and on the spin densities of the radical anions which were formed. The latter effect was confirmed by ESR measurements. 

Tetrasubstituted imidazoles have been prepared in high yield by one-pot three-component condensation of benzil, benzonitrile derivatives, and primary amines adsorbed on silica gel without solvent (Scheme 10.87) [169]. Under irradiation conditions yields range from 58 to 92% (8 min). 

The same study also showed that adding para-substituted benzonitrile derivatives furnished the corresponding 2H-l,2-azaphosphole complexes, whereby their amounts significantly depended on the electronic effects of the para-substituent whereby electron-donating groups such as methoxy favored and electron-withdrawing groups such as trifluoromethyl disfavored the formation of the 2H-l,2-azaphosphole complexes [29]. These observations created the idea of... 

Ruthenium phthalocyanine 49 (R = -H, M = Ru(II)) monolayers were obtained by self-assembly on pyridyl-functionalized SiOa or AI2O3 substrates by coordination between Ru and the pyridino group to obtain 63 [155]. The pyridino-functionalized metal oxides were dipped into a solution containing the more soluble benzonitrile derivative of the phthalocyanine RuPc(NC-C6H5)2, and ligand exchange reactions led to 63. Strategies have been described to immobilize a second layer of a Ru-phthalocyanine or a Co tetraphenyl-porphyrin. 

Balalaie et al. (2003) reported a one-pot, three-component condensation of benzil, benzonitrile derivatives, and primary amines on the surface of silica gel with acidic character under microwave irradiation as a new and efficient method to produce 1,2,4,5-tetrasubstituted imidazoles (Scheme 6.14). This methodology offers several advantages, such as solvent-free conditions, the use of substances without any modi-hcation or activation, high yields, shorter reaction times, and reusability of solid catalysts, and it is environmentally benign compared to the existing methodologies. 

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