4-Methyl-3-aminobenzophenone,

Methoxyphenylurea, 31,10,13 Methyl -acetylbenzoate, 32, 81 Methyl acrylate, 30, 65 32, 86 y-Methylallophanate, 32, 62 Methylamine, 30, 60 4 -Methyl-2-aminobenzophenone, 32,12 N-Methylaniline, 30, 62 31,110 N-Methylarylamines, preparation by reductive alkylation, 30, 59, 60 Methylation, of e-caprolactam, 31, 72 of quinacetophenone, with dimethyl sulfate, 31, 91 with methyl iodide, 31, 90 2-Methyl-3,l,4-benzoxaz-4-one, 32, 12 N-Methyl-a-bromo-n-butyranilide, 30, 63... 

Methyl-2-aminobenzophenone can be prepared similarly by substituting toluene for benzene. The yield of crude material, m.p. 85-88°, is 70%. On recrystallization from 95% ethanol, using 5 ml. per g., there is obtained, in two crops, a 70% recovery of 4/-methyl-2-aminobenzophenone, m.p. 92-93°. Because of the higher temperature required in the steam distillation (cf. Note 5), the sulfonamide is obtained in a form difficult to purify. As a result the crude aminoketone usually contains 1-2 g. of aluminum oxide. 

A solution of 2-aminobenzophenone (98 g, 0.50 mol) and methyl 2-(methyl-thio)propanoate (74 g, 0,50 mol) in CH Clj (21) was cooled to —70 C and 95% 7-butyl hypochlorite (56 g, 0.5 mol) was added dropwise at such a rate that the temperature did not rise above — 65 C. One hour after the addition was complete, EtjN was added and the mixture was allowed to come to room temperature. The solution w as mixed with 3 N HCl (800 ml) and stirred for 1 h. The organic layer was separated, dried (Na2S04 ) and filtered. The solution was evaporated in vacuo and the residue triturated with ether. Filtration gave the 3-(methylthio)oxindole intermediate (92 g) in 62% yield. 

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

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... 

Amide reduction with lithium aluminum hydride, 39, 19 Amine oxide formation, 39, 40 Amine oxide pyrolysis, 39, 41, 42 -Aminoacetanilide, 39, 1 Amino adds, synthesis of, 30, 7 2-Amino-4-anilino-6-(chloro-METHYl) -S-TRIAZINE, 38, 1 -Aminobenzaldehyde, 31, 6 hydrazone, 31, 7 oxime, 31, 7 phenylhydrazone, 31, 7 > -Aminobenzoic add, 36, 95 2-Aminobenzophenone, 32, 8 c-Aminocaproic acid, 32, 13 6-Aminocaproic acid hydrochloride,... 

Reaction of anthranilonitrile or methyl anthranilate with 3-hydroxy-2-butanone followed by malononitrile gave the pyrrolo [1,2-a] quinazoline 16 (79AP552). Both of the diazine and azole rings of pyrroloquinazolines were also simultaneously formed by cyclization of the anilide 17 derived from 3-chloropropionic acid and 2-aminobenzophenone with potassium cyanide to afford the pyrrolo [1,2-a] quinazoline 18 (68JHC185 71USP3595861). 

The availability of o-benzoylbenzenesulfonyl chlorides, prepared by diazotization of o-aminobenzophenones followed by reaction with sulfur dioxide in the presence of cuprous ions, can be exploited in the reaction with hydrazine or methylhydrazine to give 1,2,3-benzothiadiazine 14. Product 14 (R1 = Me) can also be obtained by methylationof 14(R = H) with methyl iodide and sodium hydroxide. The reduced form 15 results from catalytic hydrogenation of 14 (R = H, R2 = H)(68JHC453). Hydra-zobenzene reacts with 2-chlorosulfonylbenzoyl chloride in the presence of triethylamine to give diphenyl derivative 16 (79MI1). 3,1,2-Benzothia-... 

The 1,4-benzodiazepinones, exemplified by diazepam (53), undergo hydrolysis in acid and base to yield the corresponding o-aminobenzophenones (54). However, unusual byproducts were observed when diazepam (53) or 2-((V-methyl)amino-5-chlorobenzophenone (54) was hydrolysed in aqueous methanolic hydrochloric acid, and now a mechanism involving a nitrene has been proposed to account for the... 

Figure 4 Separation of chromatographic test mix showing generic method diversity. Separation conditions are identical to those reported in Figure 2B. Peaks 1 -5 are uracil, l-hydroxy-7-azabenzotriazole, methoxybenzenesulfonamide, methyl-3-amino-2-thio-phenecarboxylate, and 4-aminobenzophenone, respectively.

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