4-nitrobenzophenone

The following description is taken from U.S. Patent 3,116,203. A stirred solution of 75 g of 2-amino.2 -nitrobenzophenone in 700 ml of hot concentrated hydrochloric acid was cooled to 0°C and a solution of 21.5 g of sodium nitrite in 50 ml of water was added in the course of 3 hours. The temperature of the suspension was kept at 2° to 7°C during the addition. The resulting clear solution was poured into a stirred solution of 37 g of cuprous chloride in 350 ml of hydrochloric acid 1 1. The solid which had formed after a few minutes was filtered off, washed with water and recrystallized from ethanol. Crystals of 2-chloro-2 -nitrobenzophenone melting at 76° to 79°C were obtained. 

A solution of 20 g of 2-chloro-2. nitrobenzophenone in 450 ml of ethanol was hydrogenated at normal pressure and room temperature with Raney nickel. After uptake of about 6 liters of hydrogen the catalyst was filtered off, and the alcohol then removed in vacuo. The residue was distilled in a bulb tube at 0.4 mm and a bath temperature of 150° to 165°C giving a yellow oil. The oil was dissolved in alcohol, and on addition of water, needles of 2.amino.2. chlorobenzophenone melting at 58° to 60°C were obtained. 

C7H4CINO4 99-60-5) see Ethacridine 2-chloro-2 -nitrobenzophenone (C HjClNO, 2894-44-2) see Clonazepam... 

The above procedure is essentially that of Ullmann and Bleier.2 2-Aminobenzophenone has also been prepared by reduction of 2-nitrobenzophenone,3 by the Hofmann reaction of the amide of o-benzoylbenzoic acid with sodium hypobromite,4 by the action of an excess of benzoyl chloride on aniline at 220°,6 and by hydrolysis of the acetyl derivative which is obtained by the action of phenylmagnesium bromide on 2-methyl-3,l,4-benzoxaz-4-one (from anthranilic acid and acetic anhydride).6 Various methods for the preparation of 2-aminobenzophenones have been summarized critically by Simpson, Atkinson, Schofield, and Stephenson.7... 

Nitrobenzophenone, 32, 12 o-Nitrobenzoyl chloride, 30, 70 o-Nitrochlorobenzene, 32, 24 9-Nitro-10-chloro-9,10-dihydroanthra-... 

Condensation of 3-chloro-3-methylbutyne with 2,6-dimethoxy-7-hydroxy-2-nitrobenzophenone ... 

Amino-2 -nitrobenzophenone Bromoacetyl bromide Sulfuric acid... 

From SAR studies, introduction of an amino group at the ortho position of the B-ring was expected to maintain the quasi cis conformation to obtain more potent anti-tubulin agents and also increase water solubility by potential salt formation. A variety of 2-aminobenzophenone derivatives was then synthesized via Grignard reaction of (3,4,5-trimethoxyphenyl)magnesium bromide with several commercially available or synthesized substituted 2-nitrobenzaldehydes, followed by oxidation of the obtained benzhydrol derivatives with PDC to 2-nitrobenzophenones, which were in turn reduced to the corresponding aminobenzophenones with Fe/AcOH (Scheme 19). 

A totally different approach to acridones involves formation of the bond adjacent to the hetero-atom during cyclisation. Thus, 2,4,6-trihydro3y-2 -nitrobenzophenone yields 1,3-diliydroxyacridone after prior reduction (I.H. Bowen, P. Gutpa and J.R. Lewis, Chem. Comm., 1970, 1625). In a similar approach, the cyclisation of 2 -amino-2-methoxybenzophenones and related compounds occurs on treatment with sodium hydride in dimethylsulphoxide, providing a route to acridone alkaloids (J.H. Adams et dl. j. chem. Soc. Perkin I, 1977, 2173). 

Lewis and his co-workers have reported three interrelated syntheses of acronycine 208 (81T209). In one synthesis, 2,6-dimethoxy-4-hydroxy-2 -nitrobenzophenone 250, obtained as a minor product from Friedel-Crafts acylation of 3,5-dimethoxyphenol with 2-nitrobenzoylchloride, was treated with 3-chloro-3-methylbut-l-yne under basic conditions. The resultant nitro compound 251 was reduced to the amine 252 with zinc. Upon reaction with sodium hydride in DMSO, this amine provided a mixture of de-N-methylisoacronycine 253 and de-N-methylacronycine 210. T>e-N-methylacronycine 210 was converted to acronycine 208 by methylation with methyl iodide (Scheme 42). 

Force-field calculations have shown that when there is a spacer between the two phenyl rings, such as in (2-nitrophenyl) phenyl thioether and 2-nitrobenzophenone, the distances between the nitrene nitrogen and the ortho carbon, where cyclization should occur in the hypothetical imido clusters, are much longer than in compound This explains why these substrates afforded the corresponding amines, with only trace amounts of the desired six-membered heterocycles being observable, when subjected to reaction conditions the same as those used for Eq. (12). ... 

Formation of the a bond has been achieved by irradiation of acetyl esters of 2,2 -dinitrodiphenyl-carbinols in protic solvents, such as Pr OH, to give dibenzo[c/][l,2]diazepin-l 1-one 5-oxides <9IMI 904-05>. The corresponding dibenzo[c/][l,2]diazepin-l l-ones, 2,2 -dinitrobenzophenones, 2-amino-2 -nitrobenzophenones and iV-hydroxyacridones are also formed in varying amounts the reaction becomes more complex in aprotic solvents. 

When methanol is added the yield of (28) is lowered and the neutral fraction of the product contains 5-benzoyl-2-methoxybenzonitrile (29). Although no intermediate such as 5-benzoyl-2-nitrobenzophenone was isolated, its formation and... 

Obtained by partial demethylation of 2,4,6-trimethoxy-2 -nitrobenzophenone with boron tribromide in methylene chloride at 0° for 10 min and at r.t. overnight (97%) [1122]. 

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