Ortho- benzonitrile

As a further example of these eflFects, benzonitrile with its strongly activating cyano group, shows the greatest selectivity for para over meta for trans isomers. The situation is complicated by the observation of two normal and one somewhat abnormal cis isomers (Figure 2). The normal isomers are attributable to meta and para species the unusual one is ortho. When the reaction is carried out with p-tolunitrile, only the cis-ortho isomer is observed. A space-filling molecular model of cis-ortho-benzonitrile can be constructed, but it is not possible to build a model of the trans-ortho isomer. 

Recently, it was shown that the attack of CN on [FeCp(C6H5Cl)]+ PFortho-position. In the intermediate cyclohexadienyl complex, the CN group migrates to the ipso-carbon, whereas Cl is displaced. The monosubstituted benzonitrile complex is subjected to a second ortho-CN- attack but hydride is not removed spontaneously to give back an arene complex (Scheme XIX). Removal of the hydride is achieved by oxidation using DDQ (2,3-dichloro-... 

A dipolarophile bearing an ionic group and an associated counterion provides enhanced selectivity as has been recently demonstrated by Raposo and Wilcox [14]. Cycloaddition of benzonitrile 4 and the uncharged amine 5 a (a chiral phenylmaleimide derivative) in THE or chloroform provides a mixture of cycloadducts 6-9a in 1 4 4 4 diastereomeric ratio (i.e., 8 5 in favor of the methyl face approach of the dipolarophile. The ortho-substituents of the... 

Scheme 11.11 gives some representative preparative reactions based on these methods. Entry 1 is an example of the classical procedure. Entry 2 uses crown-ether catalysis. These reactions were conducted in the aromatic reactant as the solvent. In the study cited for Entry 2, it was found that substituted aromatic reactants such as toluene, anisole, and benzonitrile tended to give more ortho substitution product than expected on a statistical basis.180 The nature of this directive effect does not seem to have been studied extensively. Entries 3 and 4 involve in situ decomposition of A-nitrosoamides. Entry 5 is a case of in situ nitrosation. 

In addition to coordination by heteroatoms, the 7r-bond of cyano group also participates the activation of C-H bonds (Equation (14)).14 The ruthenium-catalyzed alkylation of benzonitriles with triethylvinylsilane proceeds at the ortho-position predominantly. 

CI.AISI. N RF.ARRANGEMENT Benzyl-amine. Bis(benzonitrile)d ichlorupalla-dium(ll). Trimethyl 3-(methoxy)ortho-propionate. 

Similar rearrangements are observed with the nitrogen analogues l7). N, N-dimethylaniline isomerizes to ortho- and para-N-methyltoluidines and is partly fragmented to N-methylaniline, benzonitrile and methyleneaniline. When N-methylaniline is the starting material, the main products are toluidines and aniline. 

Ortho photocycloaddition was first reported in a U.S. patent [1] dated September 3, 1957. Irradiation of benzonitrile in the presence of various alkenes resulted in the formation of derivatives of l-cyanobicyclo[4.2.0]octa-2,4-diene. The first ortho photocycloaddition to benzene was reported in 1959 by Angus and Bryce-Smith [2], who discovered that benzene and maleic anhydride react to form a stable adduct at 60°C under the influence of ultraviolet radiation. This 1 2 adduct was formed from one molecule of benzene and two molecules of maleic anhydride. Two years later, Bryce-Smith and Lodge [3] found that acetylenes could also be photoadded to benzene. The isolated products were cyclooctatetraenes, formed by ring opening of the primarily formed bicyclo[4.2.0]octa-2,4,7-trienes. Since those early years, hundreds of examples of ortho photocycloadditions of alkenes to the benzene ring and many mechanistic investigations have been reported and they will be discussed in this chapter. 

Atkinson et al. [73] have described the photochemical addition of 3-hexyne and 5-decyne to benzonitrile. The products were 2,3-diethylcyclooctatetraene-l-carbonitrile and 2,3-n-butylcyclooctatetraene-l-carbonitrile, respectively. The ortho addition apparently takes place at positions 1 and 2 of benzonitrile. Subsequent ring opening of the initial bicyclo[4.2.0]octa-2,4,7-trienes leads to the 1,2,3-trisubstituted cyclooctatetraenes. 

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. 

The first examples of ortho cycloaddition can be found in a U.S. patent of Ayer and Buchi [1], Benzonitrile and 2-methylbut-2-ene are reported to yield 7,8,8-trimethylbicyclo[4.2.0]octa-2,4-diene-l-carbonitrile upon irradiation under nitrogen with a mercury resonance arc. Similar reactions, all leading to derivatives of bicyclo[4.2.0]octa-2,4-diene-l-carbonitrile occurred when benzonitrile was irradiated in the presence of 2,4,4-trimethylpent-l-ene, ethyl vinyl ether, vinyl acetate, methyl vinyl ketone, and methyl acrylate. The addend pairs para-tolunitrile/oct-l-ene, ort/m-dicyanobenzene/2-methylbut-2-ene, para-dicyanobenzene/but-l-ene, 2,3-dimethylbenzonitrile/propene, and 3,4,5-trimethylbenzonitrile/ethene likewise produced ortho photocycloadducts. 

In one of the earliest reports on ortho photocycloaddition, in which the reaction of benzonitrile with 2-methylbut-2-ene is described, a diradical (triplet) intermediate was proposed [73], The structure of the product corresponds to the most stable of the four possible diradical intermediates. When benzophenone was added as a sensitizer in an attempt to increase the yield of the photoadduct, only 0.05% of ortho adduct was isolated along with 54% of an oxetane formed by the addition of benzophenone to 2-methylbut-2-ene. In the absence of benzophenone, the ortho adduct was isolated in 63% yield. It is, however, thermally as well as photochemically unstable and reverts to starting materials, supposedly also via a biradical. The authors propose that benzophenone catalyzes bond cleavage of the adduct more efficiently than ortho addition and this would account for the low yield of photoadduct in the presence of benzophenone. From these experiments, no conclusion about the identity of the reactive excited state can be drawn. 

In spite of these deviations, the ionization potential rule still has considerable predictive value, although it may be a little too restricted to cover all the addends [116,184], A slight modification of the rule was introduced by Gilbert et al. [12] who proposed that it might be more meaningful to relate the relative effi-ciences of the meta and ortho photocycloaddition with the difference in ionization potential only within a series of structurally very similar alkenes. It was also recognized that ionization potentials relate to properties of the ground state of the reactants rather than of the excited state [185], Nevertheless, the IP rule retains its predictive value in a series in which various arenes are irradiated in the presence of the same alkene [133], Ethyl vinyl ether and benzonitrile (IP = 10.02 eV) yield... 

A correlation between free enthalpy of electron transfer and mode of the photoreaction was also constructed for addition of alkenes to benzonitrile. Four areas could be differentiated Full electron transfer, leading to substitution, is only observed if AG < 0 eV cycloaddition to the cyano group occurs if 0 < AG < 0.4 eV. All olefins for which AG > 0.4 eV preferentially undergo cycloaddition to the aromatic ring, ortho cycloaddition if AG < 1.7 eV and meta cycloaddition if AG > 1.7 eV. 

The ortho cycloaddition is thermally forbidden in a suprafacial-suprafacial manner and the photochemical reaction is forbidden with S benzene and ground-state alkene. On the basis of these considerations, it could be understood that the ortho addition had only been observed with systems where the alkene is the lowest excited singlet species (as with maleimides [37,74,75] or where either the alkene or the arene has marked acceptor properties (the only examples known at that time were benzene-acrylonitrile [127] and benzonitrile + a mono-olefin [1,73], Benzene-acrylonitrile and benzonitrile-olefin systems do not display charge-transfer absorption, but charge transfer could well follow excitation. Bryce-Smith further stated that irradiation of benzene in the presence of simple mono-olefins normally provides B2u (Si) benzene as the lowest excited singlet species, which leads to meta rather than ortho addition, but the latter process might, in principle, be able to occur under conditions where a Biu (S2) state of benzene is populated. 

One of the secondary reactions that ortho adducts from alkenes and benzene or benzene derivatives may undergo is formation of a tetraene, by complete ring opening. The process was first described by Atkinson et al. [73] in their report on the ortho photocycloaddition of benzonitrile to 2-methylbut-2-ene (Scheme 49). They did not detect the tetraenes among the irradiation products, but found it when they pyrolyzed or photolyzed the ortho adduct. Pyrolysis at 128°C gave 53% alkene, 6% benzonitrile, and 41% tetraene photolysis caused almost complete reconversion (90%) to arene and alkene, whereas formation of tetraene occurred to the extent of 8-10%. Most likely a mixture of cis and trans isomers of 2-methyl-... 

Scheme 49 Ortho photocycloaddition of benzonitrile and 2-methylbut-2-ene and secondary reactions of the adduct.

Ring opening of ortho adducts may also have occurred in the experiments reported by Perrins and Simons [192], who irradiated benzene, toluene, and anisole in the presence of dichloroethenes (all isomers), trichloroethene, and tetrachloroethene. The products were chlorine-substituted linear tetraenes, but no ortho adducts were found. An analogous reaction occurred with benzonitrile and 2-methylbut-2-ene, but, in contrast to the results reported by Atkinson et al. [73], the ortho adduct was not detected. 

Answer The meta substitution pattern of Xll-g looms as the major difficulty in this-synthesis. The ethoxy group is an ortho iara director while the cyano function is a meta director. It appears that an easy approach to take would be to nitrate benzonitrile, reduce the -NO, group to the amine, diazotizc, and treat the diazonium salt with ethanol. However, jl is not feasible to reduce the -NO, group of meta-nitrobenzonitrilc without also reducing the -CN group. 

Nitrilases are largely very sensitive to steric hindrances by the substituent or heteroatom at the ortho-position, 2-substituted benzonitriles or 2-cyanopyridine being rarely hydrolyzed at acceptable rates. 

In benzonitrile, G3H5CN, the dipole moment is also noticeably greater than in methylcyanide, CH3CN, since the nitrogen atom may be negative not only with respect to the adjacent carbon atom, but also to the ortho and para carbon atoms in the ring ... 

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