Acetyl-o-toluidine

Boil a mixture of 10 g. (10 ml.) of o-toluidine and 38 g. (35 ml.) of acetic anhydride in a 75 or 100 ml. Claisen flask fitted with a reflux condenser (Fig. Ill, 28, 1, but with trap replaced by a calcium chloride or cotton wool guard tube) for 1 hour. Arrange the flask for distillation under reduced pressure (compare Fig. II, 20, 1) and distil acetic acid and the excess of acetic anhydride pass over first, followed by the diacetyl derivative at 152-153°/20 mm, some mono-acetyl-o-toluidine (1-2 g.) remains in the flask. The yield of diacetyl-o-toluidine is 14-15 g, it is a colourless, somewhat unstable hquid, which slowly sohdifies to yield crystals, m.p. 18°, To prepare the (mono-) acetyl-o-toluidine, warm a mixture of 5 g. 

Acetyl-o-toluidine Acetyl-m-tolnidine Acetyl-p-toluidine... 

To prepare the (mono-) acetyl-o-toluidine, warm a mixture of 5 g. 

The method of preparation adopted is substantially that of Buchka,- as this is the only one of practical value. w-Nitro-toluene has been obtained by a similar process from 5-nitro-2-aminotoluene (obtained by nitration of acetyl-o-toluidine), but this compound is not commercially available, and gives a poor product unless carefully purified. 

AcEIYLKETENE, 21, 64 Acetylsalicylyl chloride, 23, 66 Acetylsalicylyl peroxide, 23, 66 Acetyl-o-toluidine, 22, 94 substituted, conversion to indoles, 22, 95... 

Methylindole has been prepared, in very small yields, by distilling acetyl-o-toluidine with zinc dust,1 and in better yields by heating the toluidide with sodium ethoxide or with barium oxide in a current of hydrogen at 360-3800.2 The method described here has been used for the synthesis of substances related to physostigmine 3 and is a modification of Verley s procedure.4... 

Acetyl-o-toluidine, m.p. 110-111°, obtained from the Eastman Kodak Company, was used. After the reactants are introduced into the flask, they should be mixed thoroughly with a long spatula. 

An interesting case of intramolecular azo coupling to an activated methyl group is the well-known synthesis of indazoles 72 starting from o-toluenediazonium salts 69 or from N-nitroso-N-acetyl-o-toluidine 67 . Recently the reaction mechanism (32) was elucidated When the reaction is run in the presence of D O or... 

When groups such as hydroxyl or amino that are sensitive to oxidation are present as well as an alkyl group, then oxidation of the latter is seldom a smooth reaction. Amino groups can be acetylated, so that, for example, p-(acetylamino)benzoic acid is obtained from A-acetyl-p-toluidine by permanganate 404 anthranilic acid can be derived similarly from A-acetyl-o-toluidine. In such cases it is best to keep the reaction mixture neutral by adding magnesium sulfate. 

Two of these reactions are, in the most general terms, examples of intramolecular aldol condensations. Path A, which includes the Madelung method and its variants, uses o-substituted anilides as starting materials. Path B reverses the electrophilic and nucleophilic components for C2—C3 bond formation. Among the classic indole syntheses corresponding to the first pattern is the Madelung synthesis, exemplified by the preparation of 2-methylindole from iV-acetyl-o-toluidine (Equation (16)) <550SC597>. 

Deacetylase activity towards A -hydroxy-acetylaminofluorene (OH-AAF) was indicated to be absent in digestive gland microsomes of M. galloprovincialis (Kurelec and Krca 1987), but present in M. edulis towards AAF and N-acetyl-O toluidine (see Sect. 7.2.2). 

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