Halogenated Benzonitriles

Because only one stable electroactive product arises from the reduction of /7-chlorobenzonitrile, the interpretation of the cyclic voltammetric behavior is relatively straightforward. The fact that electron attachment to halogen-containing compounds frequently results in the cleavage of the carbon-halogen bond immediately suggests benzonitrile as a possible product. The similarity between the cyclic voltammetric behavior of benzonitrile and that of the p-chlorobenzo-nitrile reduction product supports this prediction (see Fig. 21.1). 

The phenolic derivatives indicated in Figure 8.1 are also bound to the same binding niche on PS II as the triazines (Oettmeier, 1992). However, they have a somewhat different inhibition pattern than the classical family of PS II herbicides (e.g., triazines and ureas) and, therefore, were regarded as a separate family with a somewhat different mode of action (Van Rensen et al., 1978 Trebst and Draber, 1986). It is now clear that they just orient somewhat differently in the same binding niche, as discussed below. Although the phenolics are photosynthesis inhibitors, dinoseb and the halogenated benzonitriles also inhibit respiration. 

Some good inhibitors of the Hill reaction, however, do not contain the carbonyl oxygen-nitrogen moiety. Examples are the dinitroanilines, diphenylethers, 2,4-dinitrophenols, halogenated benzonitriles, and pyridinols. Hence, the postulates proposed are not all inclusive. Three of these herbicides are phenols. Under physiological pH s, the molecules can be expected to be ionized, and it may be the ionized form of the molecule that binds to the receptor. 

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>. 

Nucleophilic substitution of aryl halogen atoms requires significant energy input. Thus, in the Dow process for the synthesis of phenol from chlorobenzene, the chlorine atom is only successfully hydrolysed by aqueous sodium hydroxide at 300 °C under pressure. Displacement by ammonia is achieved at 200 °C over copper(I) oxide and conversion to benzonitrile occurs using copper(I) cyanide in boiling dimethylfor-mamide, HCONMe. ... 

The amine group in primary amines can be replaced by halogen by warming the benzoyl derivative with phosphorus pentachloride or phosphorus pentabromide. Oftentimes, the separation of the halide from the benzonitrile, which is also formed, is troublesome. The process has been applied mostly to high-moIecuIar-weight amines obtained by the Hofmann degradation of acid amides or by reduction of nitriles." Diamines lead to dihalogen derivatives." If N-benzoyl piperidines are treated, substituted pentamethylene halides are formed. An example is the synthesis of pentamethylene bromide by the action of phosphorus pentabromide on N-benzoyl piperidine (72%). ... 

In the nitrobenzonitriles, such resonant structures will be mutually suppressed and consequently no large deviations from the additivity rule occur, such as exist when the two groups are of opposite charge so that the resonance is augmented by additional valence bond structures. The dipole moment of />-nitrobenzonitrile is zero, of o-nitrobenzonitrile, 6 19, D and m-nitro-benzonitrile, 3-78, D. Similar behaviour is observed with the di-substituted halogen derivatives of benzene and with the phenylenediamines. 

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 quality of the crystals also depends on the nature and purity of the solvent.29,30 Acetonitrile (MeCN), tetrachloroethylene (TCE), CH2CI2, benzonitrile, nitromethane, nitrobenzene, THF, and chlorobenzene are the more commonly used solvents. The addition of 10% v/v of ethanol or methanol is sometimes made either for solubility purposes or crystal growth amelioration. The solvents should be distilled before use. Halogen containing solvents are further passed over basic alumina in order to eliminate traces of acid. Solid starting compounds are either recrystallized or sublimed. Inert conditions are maintained during electrocrystal growth. 

The course of the reaction between halogenoboranes and the aminoben-zonitriles depends upon the position of the NH2 group.169 With the 3- and 4-amino-derivatives the products are the corresponding amine-boranes and compounds obtained by loss of hydrogen halide, (25) and (26). With the 2-amino-benzonitrile, however, the nitrile group is inserted into a B-halogen... 

In all cases (Tables 16, 17), DMSO is the best solvent, concerning both kinetics and yields of the halogen exchange, but its sensitivity to bases and its poor thermal stability do not favour its use in practice. For other solvents, the scale of efficiency is somewhat dependent on the substrate (and may be, as a consequence, on the temperature). For instance, sulfolane is better than NMP in the case of 3,4-dichloronitrobenzene and the reverse is true for 2,4-dichloronitrobenzene. Reactions are very slow in benzonitrile which, in practice, is devoted to Halex reactions on very stable substrates, like polychlorobenzenes, at temperatures above 300°C. N,N-dimethylethyleneurea (DMEU) and N,N-dimethylpropyleneurea (DMPU), claimed to replace advantageously the carcinogenic HMPT, are not suited to aromatic halogen-exchange. 

Fig. 35.5. Soil degradation (DT50) of (a) benzonitriles (8-10) and (b) BPUs (33, 34) - the effect of halogen substituents, (c) Relative orientations of the 2,6-dichloro- and 2,6-difluoro-benzoyl moieties in 33 and 34, respectively.

Electrochemistry can also be used to induce aromatic nucleophilic substitutions by setting up the electrode potential at the level, which is appropriate to reduce an aromatic substrate. When this electrochemical process is carried out in the presence of a nucleophilic reagent, the or reactions take place. Indeed, halogenated derivatives of benzophenone, benzonitrile, and naphthalene undergo nucleophilic displacement reactions with thiolates, which are able to occur catalytically [76, 77]. The reaction mechanism involves the formation of the anion radical at the electrode and its further decomposition into a neutral radical, which reacts with a nucleophile, thus yielding the anion-radical of the substitution product. In case of the catalytic reaction, oxidation of the anion-radical species may occur by electron transfer with the substrate and/or the electrode (Scheme 17). 

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