O-Nitrobenzyl

Dicbloronitrobenzene o-Nitrobenzyl chloride m-Nitrobenzyl chloride p-Nitrobenzyl chloride o-Nitrobenzyl bromide m-Nitrobenzyl bromide p-Nitrobenzyl bromide o-Nitrobenzyl iodide m-Nitrobenzyl iodide p-Nitrobenzyl iodide o-Nitrobenzyl cyanide... 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

A variation of the Madelung cyclization involves installing a functional group at the o-methyl group which can facilitate cyclization. For example, a triphenylphosphonio substituent converts the reaction into an intramolecular Wittig condensation. The required phosphonium salts can be prepared by starting with o-nitrobenzyl chloride or bromide[9]. The method has been applied to preparation of 2-alkyl and 2-arylindoles as well as to several 2-alkenylindoles. Tabic 3.2 provides examples. 

Photolytic cleavage reactions (e.g., of o-nitrobenzyl, phenacyl, nitrophenylsul-fenyl derivatives) take place in high yield on irradiation of the protected compound for a few hours at 254-350 nm. For example, the o-nitrobenzyl group, used to protect alcohols, amines, and carboxylic acids,has been removed by irradiation. Protective groups that have been removed by photolysis are described at the appropriate places in this book in addition, the reader may wish to consult five review articles. 

The o-nitrobenzyl and p-nitrobenzyl ethers can b prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also prepared from an alcohol and p-nitrobenzyl alcohol (trifluoroacetic anhydride, 2,6-lutidine, CH2CI2, 67% yield). In addition, the o-nitrobenzyl ether can be cleaved by irradiation (320 nm, 10 min, quant, yield of carbohydrate " 280 nm, 95% yield of nucleotide ). The p-nitrobenzyl ether has been cleaved by electrolytic reduction (—1.1 V, DMF, R4N X, 60% yield) and by reduction with Na2S204 (pH 8-9, 80-95% yield). These ethers can also be cleaved oxidatively (DDQ or electrolysis) after reduction to the aniline derivative. ... 

The nitrobenzyl caibonates were prepared to protect a secondary hydroxyl group in a thienamycin precursor. The o-nitrobenzyl carbonate was prepared from the chloroformate (DMAP, CH2CI2, 0° - 20°, 3 h) and cleaved by irradiation, pH 7. The p-nitrobenzyl carbonate was prepared from the chloroformate (—78°, n-BuLi, THE, 85% yield) and cleaved by hydrogenolysis (H2/Pd-C, dioxane, H2O, EtOH, K2HP04). It is also cleaved by electrolytic reduction. ... 

The o-nitrobenzyl ester, used in this example to protect penicillin precursors, can be cleaved by irradiation (H20/dioxane, pH 7). Reductive cleavage of benzyl or p-nitrobenzyl esters occurred in lower yields. 

The American authors suggested (X) or (XI), already considered by Spath and Nikawitz for vasicine, and support for a formula of type (XI) was provided by Spath, Kuffner and Platzer, who, by condensing o-nitrobenzyl chloride with methyl y-aminobutyrate to o-nitrobenzyl-pyrrolidone (XII), reduction of this to the amino-compound (XII NOa —> NHj) and ring-closure in presence of phosphoryl chloride obtained the base d -pegene (XIII), m.p. 99-100°, identical with the product formed by the reduction of deoxychloropeganine. The same substance... 

The o nitrobenzyl and /7 nitrobenzyl ethers can be prepared and cleaved by many of the methods described for benzyl ethers. The p-nitrobenzyl ether is also... 

H. Sajiki, H. Kuno, and K. Hirota, Tetrahedron Lett., 38, 399 (1997). o-Nitrobenzyl Ether o-N02-QH4CH20Ar (Chart 4)... 

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