O-Nitroacetanilide

Add 26 g. of flnely-powdered, dry acetanihde to 26 ml. of glacial acetic acid contained in a 500 ml. beaker introduce into the well-stirred mixture 92 g. (60 ml.) of concentrated sulphuric acid. The mixture becomes warm and a clear solution results. Surround the beaker with a freezing mixture of ice and salt, and stir the solution mechanically. Support a separatory funnel, containing a cold mixture of 16 5 g. (11 ml.) of concentrated nitric acid and 12-6 g. (7 ml.) of concentrated sulphuric add, over the beaker. When the temperature of the solution falls to 0-2°, run in the acid mixture gradually while the temperature is maintained below 10°. After all the mixed acid has been added, remove the beaker from the freezing mixture, and allow it to stand at room temperature for 1 hour. Pour the reaction mixture on to 260 g. of crushed ice (or into 500 ml. of cold water), whereby the crude nitroacetanihde is at once precipitated. Allow to stand for 15 minutes. Alter with suction on a Buchner funnel, wash it thoroughly with cold water until free from acids (test the wash water), and drain well. RecrystaUise the pale yellow product from alcohol or methylated spirit (see Section IV,12 for experimental details), filter at the pump, wash with a httle cold alcohol, and dry in the air upon filter paper. [The yellow o-nitroacetanilide remains in the filtrate.] The yield of p-nitroacetanilide, a colomless crystalline solid of m.p. 214°, is 20 g. 

Various nitrosoarenes have been utilized as benzofurazan precursors including o-azido derivatives generated from the o-chloro analogues <66JCS(B)1004>, and 1-amino-2-nitrosoarenes which can be oxidized with ferricyanide or hypochlorite. Treatment of o-nitrosophenols with hydroxylamine also affords the furazan, presumably via an oximation-dehydration pathway involving the tautomeric o-quinone monooxime. Other related approaches involve the reduction of o-dinitroarenes with borohydride, and the thermolysis of o-nitroanilines and o-nitroacetanilides. 

Cyclization of cr-aryl-o-nitroacetanilides 56 to quinoxaline A-oxides has been reported independently by three groups.66-68 Thus treatment with ethanolic sodium ethoxide of 56 (R=R =H R2=Ph), synthesized from o-nitroaniline and PhCH2COCl, gives l,2-dihydro-2-oxo-3-phenyl-quinoxaline 4-oxide (57 R=R =H, R =Ph). 

The mother-liquor contains two readily visible yellow components, which are p-nitroaniline (RF 0.24) and o-nitroaniline (RF 0.45), as well as both p- and o-nitroacetanilide. 

Khmer [2] found that acetanilide when nitrated also yields o- nitroacetanilide, from which o- nitroaniline may be obtained by hydrolysis. The nitration of acetanilide... 

The reduction of o-nitroacetanilide to 2-methylbenzimidazole06 07 and of 2-nitrophenylthiocyanate to 2-aminobenzothiazole08 have been reported, but when no other reducible groups are present the advantage of using electrolytic methods for the reduction is questionable. 

Methyl-o-nitroacetanilide [98] (20 g) is added to a solution of ethanol (200 ml) and ethanol saturated with ammonia at 0°C (100 ml). Hydrogen... 

Diacetyl-orthonitric acid reacts with acetic anhydride to form tetranitromethane, [C(N02)4 ot (N02)3C.0.N0] and with acetanilide to give mainly o-nitroacetanilide,... 

The reductions of o-nitroacetanilide [65, 66] to 2-methylbenzimidazole, acylated nitronaphthylamines to naphthimidazoles [54], 2-nitrophenylthiocyanate [65] to 2-amino-benzothiazole, and 2,2 -dicarboxy-6,6 -dinitrobiphenyl to 4,9-diaza-5,10-dioxo-4,5,9,10-tetrahydropyrene [67] have been reported. 

For the preparation of o-nitroaniline the method outlined above may be used. Nitration at a temperature of 40° is employed so as to increase the proportion of the o-nitroacetanilide to 25 per cent. Another variation is to treat aniline with excess of acetic anhydride and then with nitric acid. Acetanilide is first formed, which in the presence of acetic anhydride nitrates to give a larger proportion of the ortho isomer. The nitrating agent is assumed to be acetyl nitrate, CHaCOONOs. Finally, a number of indirect methods are... 

The following compounds o-nitroacetanilide and phenyl-(p-nitrophenyl) acetate lead to the elimination of radicals, such as (a) NOj (and also NHCOCH3 for acetanilide) directly from the initial negative molecular ion (b) NO, OH, (NO -f CH2CO) after molecular ion isomerization. Under collision conditions in the FFR, direct cleavages occur without isomerization of the molecular ion and lead to the formation of [M-NO2] , [M-O-Ph] and [M-PhCOO]" ions. 

For acetylcholinesterase, it is thought that the protonated imidazole of His acts as a general-acid to assist departure of aniline during hydrolysis of anilide substrates. Based on analysis of the isotope effect in light and heavy water, it was estimated that departure of o-nitroaniline during hydrolysis of o-nitroacetanilide is accompanied by a modest solvent isotope near 1.5, supporting the general-acid role of ImH+-His ° [19]. 

The nitration of acetanilide with mixed acid yields nitroacetanilides in which the ortho para ratio is less than 0.1. When the nitration medium is nitric acid, this ratio is 0.7, when acetyl nitrate in acetic anhydride is used, the product is almost entirely o-nitroacetanilide. No satisfactory explanation has been given for these results. The 40-50 per cent yield of m-nitro-aniline that results from the nitration of aniline in mixed acid or in nitric acid can be explained in the following manner. In the strong acids, nitric and sulfuric acid, aniline is largely ionized. 

H-Et see 5-Chloro-2-nitro-iV-ethylaniline. "S-Acetyl 5 - chloro - o - nitroacetanilide. 

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