W-Nitroacetophenone

The reaction of o-diamines with w-nitroacetophenone in the presence of sodium dithionite furnishes 2-phenylquinoxalines, and reaction of o-phenylenediamine with p-N0..C,-.H4C0CH2X02 similarly gives 2- (4 -nitrophenyl) quinoxaline ... 

Although 550 suffices to dissolve the w-nitroacetophenone it is desirable to bring the alcoholic solution to a boil to avoid crystallization during filtration. 

Since the solubility curve is so flat in the vicinity of room temperature it is not necessary to cool very low before filtering. The difference between 20° and io° amounts to only 1 g per 100 cc. of solution. The solubility of w-nitroacetophenone in 96 per cent alcohol is as follows ... 

Mr. W. W. Hartman (Eastman Kodak Company) has stated that larger runs of w-nitroacetophenone than those described in the procedure can be carried out if the beaker is surrounded with carbon dioxide and solid carbon dioxide is added directly to the reaction mixture. 

We also have to beware of the limitations of each type of substitution process. We recall that Friedel— Crafts acylation does not occur when the ring contains a meta-directing group. For example, we can make w-nitroacetophenone by nitration of acetophenone, but not from Friedel—Crafts acylation of nitrobenzene. 

In this method the nitro group in the aliphatic nitro compound is usually present on a carbon atom, which is also activated by CO-functionality (aldehyde, ester, arylketone). A successful application of this method is the Borsche modification of the Friedlander synthesis, involving condensation of A-(3-amino-4-picolylidene)-p-toluidine (17) with w-nitroacetophenone (18) and leading to 3-nitro-2-phenyl-l,7-naphthyridine (19) (57JOC138). The preparation of (17) is, however, tedious and requires several steps the yield in the transformation of (17) to (19) is very low (10%). 

The catalyst used throughout this study was a 1% w/w palladium on graphite powder (S.A. 10 mV ) supplied by Johnson Matthey. 2-nitroacetophenone, 3-nitroacetophenone and 4-nitroacetophenone (all Aldrich >99 %) were used without further purification. No significant impurities were detected by GC. Gases (BOG, >99.99 %) were used as received. 

Dimethylamine hydrodiloride dissolved in aq. 40%-formaldehyde soln., after 0.5 hr. acetic anhydride added, warmed with shaking until a gently refluxing clear soln. results, o-nitroacetophenone added, and heated 0.5 hr. on a water bath -> o-nitro- -dimethylaminopropiophenone. Y 64.2%. - This procedure minimizes reaction of the product with the remaining formaldehyde. F. e. s. W. Back, Ardi. Pharm. 303, 491 (1970). 

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