Acetyl toluidine

Cyclization of acetyl -toluidine occurs with sodium amide at 250° to give 2-methyl indole (83%). The formyl derivative of toluidine requites the presence of potassium ions for condensation to indole (7S>%). Potassium alkoxide or a mixture of sodium alkoxide and potassium acetate is effective. 

On the other hand, A-[ C]acetylation procedures have found wide application for substances needed either for in vitro studies (for carbon-14 labeling of proteins see next section) or as valuable synthetic intermediates. In the latter case, 3-substituted 7V-[1- C]-acetylated toluidine M served as a key intermediate for the synthesis of [2- C]mepindolol... 

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... 

Acetyl-AT-methyl-o tolnidine Acetyl-AT-raethyl-m-toluidine. Acetyl-AT-methyl-p-toluldine. Acetyl-AT-methyl-a-naphthylam Ine Acety l- /-raethy 1- -naphthy lamlne... 

If pure isomers are required, the ortho and meta compounds can be prepared by indirect methods. o-Nitrotoluene can be obtained by treating 2,4-dinitrotoluene with ammonium sulfide followed by diazotization and boiling with ethanol. / -Nitrotoluene can be prepared from -toluidine by acetylation, nitration deacetylation, diazotization, and boiling with ethanol. A fairly pure -nitrotoluene, which has been isolated from the isomeric mixture, can be purified further by repeated crystallization. 

Important analogs of aniline include the toluidines, xyUdines, anisidines, phenetidines, and its chloro-, nitro-. A/-acetyl. A/-alkyl. A/-aryl. A/-acyl, and sulfonic acid derivatives. 

The preparation of 3-alkyl quinolines by traditional Skraup/Doebner-von Miller reaction typically results in very low yields. When ethylacrolein (9) is condensed with m-toluidine (8) under typical Skraup/Doebner-von Miller conditions, the yield of 10 is only 25%, compared to 65% with di-acetyl acetal 11. 

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

Acetyl-AT-metbyl-o toluidine. Acetyl-AT-metbyl-m-toluidine. Acetyl-AT-methyl-p-toluidine. Acetyl-A7-methyl-a-napbthylamine Acety 1-AT-metbyl- P-naphthy lamine... 

Although practically important in other cases, the replacement of an NH2-group by hydrogen via the diazo-compound naturally has none in the example here given. Thus m-nitrotoluene (and from it m-toluidine) is obtained from p-toluidine by nitration of the acetylated base and replacement of the NH2-group (after elimination of the acetyl) by H, as shown above. 

The method of preparation adopted is substantially that of Buchka,3 as this is the only one of practical value. fw-Nitro-toluene has been obtained by a similar process from s-nitro-2-aminotoluene 4 (obtained by nitration of acetyl-0-toluidine), but this compound is not commercially available, and gives a poor product unless carefully purified. 

Co-exposures 4,4 -Methylene bis (2-methylaniline) (2B) Magenta (2B) Safranine T or/ oNitrotoluene (3) 2,5-Diaminotoluene (3) Aniline (3) ori/io-Amino-azotoluene (2B) Multiple ejqjosures including 4-chloro-o/t/io-toluidine and 4-chloroacetyl-or/Zio-toluidine A/ Acetyl-or//io-toluidine 6-Chloro-or//io-toluidine 4-Chloro-or//io-toluidine (2A) Aniline (3) Hydroquinone (3) Toluene (3) Carbon disulfide Sulfur Benzothiazole 4-Aminobiphenyl (contaminant) (1) 2-Mercaptobenzothiazole (Ward et al, 1996) (Proprietary chemical) Aniline (3) 2-Mercaptobenzothiazole Phenyl-p-naphthylamine (3)... 

I Acetyl-Af-methyl-m-toluidine. Acetyl-Af-methyl-p-toluidine. Acetyl-Af-methyl-a-naphthylamine. Acetyl-Af-methyl-P-naphthylamine. ... 

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

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