4-Nitrophenylacetyl chloride

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. 

By a modified Bischler-Napieralsky reaction, 6 -nitrophenylaceto-jS-3 4-methylenedioxyphenylethylamide, resulting from the condensation of -3 4-methylenedioxyphenylethylamine with 2-nitrophenylacetyl chloride, was converted into 6 nitro-l-benzyl-6 7-methylenedioxy-3 4-dihydroisoquinoline. The methiodide of the latter was reduced with zinc and hydrochloric acid to 6 -amino-l-benzyl-2-methyl-6 7-methylenedioxy-1 2 3 4-tetrahydro/soquinoline dihydrochloride, which by the Pschorr ring-closure reaction, produced dZ-roemerine (IV, p. 317), m.p. 85-7°. By treatment in succession with d- and Z-tartaric acids, the dZ-base was resolved into Z- and tZ-forms. Synthetic Z-roemerine is dimorphic, m.p. 85-7° and 102°, and has [aju — 79-9° (EtOH), these constants being in good agreement with those of the natural base. 

Note o-Nitrophenylacetyl Chloride, 02N.CgH4.CH2C0Cl, is also likely to expld under similar conditions (Ref 4)... 

Methyl-2-nitrobenzoyl chloride, 2913 2-Nitrobenzoyl chloride, 2653 2-Nitrophenylacetyl chloride, 2914... 

Methoxy-2-nitrophenylacetyl chloride was never isolated from the reaction mixture. It is known5 6 that 2-nitrophenylacetyl chloride is a potentially explosive material, but it is not documented that the 5-methoxy derivative is also hazardous. 5-Methoxy-2-nitrophenylacetyl chloride was also prepared as described by Rosenmund and his co-workers,7 and was used in the crude form. 

There are several procedures by which o-nitrobenzyl ketones can be obtained. Enolates and enamines can be acylated with o-nitrophenylacetyl chloride. For example, the enamine intermediates from the Leimgruber-Batcho procedure can be acylated prior to reduction to give 2-substituted indoles (Scheme 16) <74JHC291>. Acylation followed by alkylation at the benzylic position leads to 2,3-disubstituted indoles (Scheme 17) <91G499>. 

The acylation of enolates of ethyl acetoacetate (Scheme 18) <76CB3282> and Meldrum s acid (Scheme 19) <90JCS(Pl)673> by o-nitrophenylacetyl chloride leads to indole precursors. 

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