O-Nitrotoluene derivatives

Bis(2,4,6-trinitrophenyl)methane when treated with NaAc in acetic acid produced (580) as a thermostable explosive (80MIP41600). The conversion of o-nitrotoluene into 2,1-benzisoxazole was effected by mercury(II) oxide catalysis. A mercury containing intermediate was isolated and was demonstrated to be converted into 2,1-benzisoxazole (67AHC(8)277). The treatment of o-nitrotoluene derivative (581) with sulfuric acid gave (582) in 35% yield (72MI41607). 

The Batcho-Leimgruber indole synthesis involves the condensation of o-nitrotoluene derivatives 1 with formamide acetals 2, followed by reduction of the trans-p-dimethylamino-2-nitrostyrene 3 which results to furnish indole derivatives represented by... 

The Reissert procedure involves base-catalyzed condensation of an o-nitrotoluene derivative 1 with an ethyl oxalate (2) which is followed by reductive cyclization to an indole-2-carboxylic acid derivative 4, as illustrated below . ... 

In 1897, Reissert reported the synthesis of a variety of substituted indoles from o-nitrotoluene derivatives. Condensation of o-nitrotoluene (5) with diethyl oxalate (2) in the presense of sodium ethoxide afforded ethyl o-nitrophenylpyruvate (6). After hydrolysis of the ester, the free acid, o-nitrophenylpyruvic acid (7), was reduced with zinc in acetic acid to the intermediate, o-aminophenylpyruvic acid (8), which underwent cyclization with loss of water under the conditions of reduction to furnish the indole-2-carboxylic acid (9). When the indole-2-carboxylic acid (9) was heated above its melting point, carbon dioxide was evolved with concomitant formation of the indole (10). 

The most extensively used photoremovable protecting groups are based on o-nitrotoluene derivatives, which, on exposure to light, undergo intramolecular H-atom abstraction to form photoenols (Scheme 9), followed by the elimination of their protected or caged substrate. ... 

The mechanism of photoenolization of o-nitrotoluene derivatives, studied extensively in the past, is different from the photoenolization of o-alky arylketones. ... 

The mechanism of photorelease from o-nitrotoluene derivatives is different from and more complicated than the release mechanism of the photoenols from o-alkyl arylketones (Scheme 12). The photorelease mechanism from o-nitrotoluene derivatives is strongly affected by the reaction medium and its pH value. 

Wirz and coworkers also studied photorelease from o-nitrotoluene derivative 89 (Scheme 46). The authors proposed a mechanism of photorelease from these compounds that is similar to that proposed for 83. The authors demonstrated that the reaction medium, including solvent, pH, and buffer concentration, affects the rate of release (Scheme 45). For example, in methanol (pH up to 8), the rate of release from... 

Indole synthesis.3 A general indole synthesis involves reaction of an o-nitrotoluene derivative with dimethylformamide dimethyl acetal in refluxing DMF with removal of the methanol to form a nitro N,N-dimethyl enamine. Reduction of the nitro group is accompanied by spontaneous cyclization to an indole. Catalytic hydrogenation is generally preferred for this step. 

As can be seen in Table I, variation of the substituent has a profound effect on the rate of reaction of the o-nitrotoluene derivative with dimethyl-formamide acetals, but has little effect on the yields, which are often almost quantitative. As can be predicted, electron withdrawing groups accelerate the reaction. To shorten the somewhat lengthy reaction times which are often... 

For the retrosynthesis of indole (see Fig. 5.8), two routes (I/II) are proposed, as for pyrrole (see p 94). Route I suggests o-aminobenzyl ketone 1 or 6>-alkyl-A -acylaniline 2 as starting material on the basis of operations a - c. Their retroanalysis (d,e) in turn leads to 2-alkylaniline 5 and carboxylic acid derivative 6. Construction of the indole system should thus occur by N- or C-acylation of 5 (utilizing the o-nitrotoluene derivative 4) followed by cyclodehydration of 1/2. The alternative route n, based on retrosynthetic analysis g-i, leads to aniline via the a-(A -phenylamino)ketones 3 and to a-halo ketones 7 as possible precursors for the indole synthesis. 

Condensation of o-nitrotoluene derivatives with formamide aeetals, followed by reduetion of die tr[Pg.28]

A general indole synthesis involves reaction of an o-nitrotoluene derivative with DMF dimethyl acetal in refluxing DMF (eq 12). - The initially formed o-nitroaryl-substituted ( )-MiV-dimethylenamine is submitted to catalytic hydrogenation to give the indole by spontaneous cyclization. According to a variation of this methodology, 2-arylindoles are readily available by reaction of o-nitrotoluene with DMF diethyl acetal and o-halobenzoyl chloride. This reaction proceeds via benzoylation of the respective enamine. 

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