Benzonitrile, addition reactions

The relatively high aromaticity of the parent 1,2,5-thiadiazole renders it good thermal stability (stable up to 220 °C) despite this, 3,4-diphenyl-l,2,5-thiadiazole 8 suffers slow photochemical degradation to give benzonitrile and sulfur. The low basicity of 1,2,5-thiadiazole indicates a relatively high electron density in the Jt-orbital and corresponding low electron density of the nitrogen lone pairs. Addition reactions such as Walkylation do not occur readily. A-Oxidation is... 

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. ... 

It is not always easy to ascertain if the addition reaction proceeds via the triplet excited state of the arene. Benzene and its simple derivatives such as anisole and benzonitrile have high triplet energies (benzene, 84 kcal/mol 1 anisole, 81 kcal/mol" benzonitrile, 77 kcal/mol-1) which makes sensitization impracticable. Results of quenching experiments are sometimes difficult to interpret, as has become evident from the work of Cantrell. He found [109] that the formation of adducts from benzonitrile and 2,3-dimethylbut-2-ene, vinyl acetate, and 2-methoxypropene in solutions 0.5 M in cri-l,3-pentadiene occurs at a rate only approximately one-fourth that in the absence of added quencher. Five years later, the author reported [110] that m-l,3-pentadicnc itself adds slowly to benzonitrile to give ortho adducts. When a correction was made for the reaction of benzonitrile with the quencher, it became apparent that little, if any, triplet quenching had occurred. 

Tretyakov and Filimonov (219) describe a coordinative interaction between benzonitrile and aprotic sites on magnesium oxide, and Zecchina et al. (256) came to the same conclusion for the adsorption of propionitrile, benzonitrile, and acrylonitrile on a chromia-silica catalyst. Chapman and Hair (257) observed an additional chemical transformation of benzonitrile on alumina-containing surfaces, which they describe as an oxidation. Knozinger and Krietenbrink (255) have shown that acetonitrile is hydrolyzed on alumina by basic OH- ions, even at temperatures below 100°C. This reaction may be described as shown in Scheme 2. The surface acetamide (V) is subsequently transformed into a surface acetate at higher temperatures. Additional reactions on alumina are a dissociative adsorption and polymerizations (255) analogous to those observed for hydrogen cyanide by Low and Ramamurthy (258), and a dissociative adsorption. Thus, acetonitrile must certainly be refused as a probe molecule and specific poison. 

Some examples of the lower reactivity of acetylenic Grignard reagents are the 1,2-addition reactions involving benzonitrile [29], and nucleophilic substitution reactions with halogen compounds that are limited to those highly reactive compounds, such as... 

The most convenient synthetic approach to 2,4-diaminotriazines utilizes the addition reactions of nitrile compounds with dicyandiamide (also called cyanoguanidine). The reaction is catalyzed by base. Benzonitrile, resulting from the reaction of benzaldehyde with 12/aq. NH3 in situ, was treated with dicyandiamide 169 to afford 2,6-diamino-4-phenyl-... 

Azetines.—1-Azetines are an uncommon group of compounds, a recent synthesis has been described and a simple member of the group, 2-phenyl-1-azetine, has been reported to undergo ready decomposition. The photochemical addition of benzonitrile to 2,3-dimethylbut-2-ene has been previously reported and the azabutadiene (168) was obtained 2-phenyl-3,3,4,4-tetramethyl-l-azetine (167) was proposed as an intermediate a- and jS-naphthonitriles were reported to undergo an addition reaction but not to the nitrile, and the tricyclic adducts (169) and (170) were obtained instead. Yang and co-workers have re-examined this reaction, and from 1-naphthonitrile they obtained azetine (171) whereas benzonitrile gave (167). 

Now add the diazonium solution to the potassium cupro-cyanide in small quantities at a time so that the temperature of the mixture remains between 60° and 70° shake the mixture vigorously after each addition of the diazo solution. Then fit a reflux air- or water-condenser to the flask, and heat the latter on a boiling water-bath for 15 minutes to complete the reaction. Finally steam-distil the solution until no more oily benzonitrile passes over (usually until about 600 ml. of distillate have been collected). 

Conventional synthetic schemes to produce 1,6-disubstituted products, e.g. reaction of a - with d -synthons, are largely unsuccessful. An exception is the following reaction, which provides a useful alternative when Michael type additions fail, e. g., at angular or other tertiary carbon atoms. In such cases the addition of allylsilanes catalyzed by titanium tetrachloride, the Sakurai reaction, is most appropriate (A. Hosomi, 1977). Isomerization of the double bond with bis(benzonitrile-N)dichloropalladium gives the y-double bond in excellent yield. Subsequent ozonolysis provides a pathway to 1,4-dicarbonyl compounds. Thus 1,6-, 1,5- and 1,4-difunctional compounds are accessible by this reaction. 

Aryl, heteroaryl, and alkenyl cyanides are prepared by the reaction of halides[656-658] or triflates[659,660] with KCN or LiCN in DMF, HMPA, and THF. Addition of crown ethers[661] and alumina[662] promotes efficient aryl and alkenyl cyanation. lodobenzene is converted into benzonitrile (794) by the reaction of trimethylsiiyl cyanide in EtiN as a solvent. No reaction takes place with aryl bromides and chlorides[663]. The reaction was employed in an estradiol synthesis. The 3-hydroxy group in 796 was derived from the iodide 795 by converting it into a cyano group[664]. 

Isoxazole-3-carbaldehyde has been obtained as a minor product from the reaction of acetylene with a mixture of nitric oxide and nitrogen dioxide (61JOC2976). Although 3-aryl-4-formylisoxazoles have been synthesized in good yields from the reaction of benzonitrile Af-oxides with 3-(dimethylamino)-2-propen-l-one (71S433), the parent member of the series, isoxazole-4-carbaldehyde, has never been reported. It may possibly be obtained by the addition of fulminic acid to 3-(dimethylamino)-2-propen-l-one. 

The addition of benzonitrile oxide to acrylic acid gave only the 4-carboxylic acid (441) (59MI41601), while addition to cis- and trans-cinnamic esters gave cis and trans diastereomeric pairs of 4-carboxylic acids (442) (Scheme 100) (59MI41600). Arbisono repeated the experiment and, when methyl c/s-cinnamate was used, in addition to the 4-carboxylic acid some 5-carboxylic acid (442) was isolated (66MI41600). The reaction of vinyl bromides with benzonitrile oxide yielded only an isoxazole and not a bromoisoxazoline (Scheme 101) (78JCR(S)192). 

The addition of benzonitrile oxide to cyclooctatetraene produced a monoadduct which was induced to undergo valence tautomerism to produce a tricycloisoxazoline (Scheme 104). A similar reaction with tropone gave a minimum of eight adducts from which two monoadducts were isolated (Scheme 104) (70T5113). 

A variety of 1-azirines are available (40-90%) from the thermally induced extrusion (>100 °C) of triphenylphosphine oxide from oxazaphospholines (388) (or their acyclic betaine equivalents), which are accessible through 1,3-dipolar cycloaddition of nitrile oxides (389) to alkylidenephosphoranes (390) (66AG(E)1039). Frequently, the isomeric ketenimines (391) are isolated as by-products. The presence of electron withdrawing functionality in either or both of the addition components can influence the course of the reaction. For example, addition of benzonitrile oxide to the phosphorane ester (390 = C02Et) at... 

Because of resonance stabilization of the anion, a tet-nazolyl moiety is often employed successfully as a bioisosteric replacement for a carboxy group. An example in this subclass is provided by azosemide (27). Benzonitrile analogue is prepared by phosphorus oxychloride dehydration of the corresponding benzamide. Next, a nucleophilic aromatic displacement reaction of the fluorine atom leads to The synthesis concludes with the 1,3-dipolar addition of azide to the nitrile liinction to produce the diuretic azosemi de (27). ... 

In a similar reaction, dimethyl 3-oxa-2,4-octanoquadricyclane-l,5-dicarboxylate gives the 6-hydroxyfulvene in 45% yield in addition to oxepin (15%) when bis(benzonitrile)dichloropal-ladium is used as catalyst.132 In the presence of silver(I) perchlorate the yield of 6-hydroxyful-vene reaches 85% whereas the thermal isomerization gives exclusively the oxepin (95% yield). 

Many of the early workers who studied the thermal decomposition reactions of diazocarbonyl compounds found that the addition of copper metal or copper salts allowed the reaction to be achieved at a lower temperature,<63AG(E)565, 64CB2628, 73JOU431> although no detailed study of this catalytic effect was undertaken. Alonso and Jano studied the copper-salt reaction of ethyl diazopyruvate 26 with acetonitrile and benzonitrile. The... 

In the reaction of benzonitrile oxide (1,3-dipolar addition) with AyV -thiocarbonyldi-1,2,4-triazole the cyclic addition product has been isolated in 87% yield -170- ... 

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