P-Nitroacetophenone

Ketones such as p-nitroacetophenone 1877 are reduced by dimethylchlorosilane Me2HSiCl 882/In(OH)3, in high yields, to chloro compounds such as 1878 [90] (Scheme 12.26). 

The photoreduction of aromatic nitro compounds to the amino compounds can be carried out on the surface of semiconductor particles such as titanium oxide1 with H-atom donors (equation 1). At a shorter duration of the photoinduced reduction of p-nitroacetophenone, the hydroxylamine intermediate can be obtained in about 30% yield. The reaction mechanism proposed is based on the photoexcitation of TiC>2 to generate an electron and a positive hole (equations 2 and 3). Aliphatic nitro compounds such as 12-nitrododecanoic acid can be reduced to 12-amino dodecanoic acid in 90% yield by this method. 

A variety of aliphatic and aromatic ketones have been investigated (cyclohexanone, cyclopentanone, acetophenone, p-nitroacetophenone) and they all usually lead to 2-R -3-R"-5-nitropyridine in moderate to good yields. Better yields were recorded when enamines of the respective ketones were used. With aldehydes the yields are in general lower than with ketones. 

The CCH of p-nitroacetophenone (5) (Scheme 2) was inefficient and unselective giving p-aminoacetophenone (6) in about 20% yield together with some 10-12% of unindentified compounds (30% mass balance). Attempts to recover more material were unsuccessful. The ECH at a RCu cathode in an alkaline (0.28 M KOH, pH 13.5) MeOH-HzO (1.5% of H2O) solution was reported to give exclusively p-amino-acetophenone (6) (79% yield of isolated product) (3,8). 

Table 15.5 Calculation of the Near-Surface Total Specific Light Absorption Rate A of p-Nitroacetophenone (PNAP) at 40°N Latitude at Noon on a Clear Midsummer Day...

When an N(l)-H is avalable as in free-base systems, deprotonation at N( 1) speeds up the hydrolysis (Steenken and Jagannadham 1985). For example, the corresponding p-nitroacetophenone Ura adduct decays with 2.4 x 10s s-1 when deprotonated at N(l). The N(l)-alkylated pyrimidines also hydrolyze, but slower (e.g., k = 4.5 x 103 s-1 in the case of uridylic acid) when deprotonated at N(3). In neutral solution, the rate of hydrolysis must be considerably slower, possibly that slow that other reactions may compete. 

The oxidation of DNA radicals by hypoxic sensitizers, normally nitro compounds, has found considerable interest in the context of attempts to improve irradiation regimes in the radiotherapy of solid tumors (Chap. 12.11). Concomitantly, model studies have been undertaken in order to shed some light on potential mechanism of their reactions. p-Nitroacetophenone (PNAP) has often been used as a convenient model sensitizer. 

Hissung A, von Sonntag C (1979) The reaction of solvated electrons with cytosine, 5-methylcytosine and 2 -deoxycytidine in aqueous solution. The reaction of the electron adduct intermediates with water, p-nitroacetophenone and oxygen. A pulse spectroscopic and pulse conductometric study. Int J Radiat Biol 35 449-458... 

Skvortzov VG, Myasnik MN, Sokolov VA, Morozov II (1981) Action spectrum for photoreactivation of Escherichia coli Bs.i after y-irradiation. Photochem Photobiol 33 187-190 Smith GJ (1979) The triplet-state charge-transfer reaction between p-nitroacetophenone and gu-anosine monophosphate. A possible mechanism for electron-affinic radiosensitization. Int J Radiat Biol 35 265-271... 

The method is especially valuable for the preparation of certain substituted acetophenones, namely, o- and p-nitroacetophenone and o-chloro-acetophenone. Methods involving Grignard, Friedel-Crafts, or nitration reactions are apparently not applicable for the preparation of these nitro compounds, and the Friedel-Crafts reaction is not applicable to the preparation of o-chloroacetophenone. Although the acetoacetic ester synthesis has been used for the preparation of these and other substituted acetophenones, it may be complicated by O-acylation and also by cleavage at either acyl group (cf. method 212). 

Problem 19.3 Would it be feasible to make p-nitroacetophenone via the reaction between di(p-nitrophenyl)cadmium, (p-02NC6H4)2Cd, and acetyl chloride ... 

---