Methylanilines

The principle of this method has been explained above. The reaction is best carried out in a wide-necked 250 ml. conical flask for which a cork having the usual two delivery-tubes for steam-distillation is available when the Strictly termed iV-methylaniline. t. Strictly termed iV,i -dimcthyliiniline. 

Meanwhile, filter the original cold reaction product at the pump, and wash the sulphonyl-methylaniline on the filter first with 10% sodium hydroxide solution (to ensure complete removal of the sulphonyl-aniline) and then with water drain thoroughly. Recrystallise from ethanol toluene-/)-sulphonyl-methylaniline, C H5N(CH3)S02C4H4CH3, is thus obtained as colourless crystals, m.p. 95° yield, 7-5 g. 

Green coloration. Catechol (colour rapidly darkens). [Aniline (pale green), o-toluidine (pale green initially), mono-methylaniline, and diphenylamine, each in dil. HCl.]... 

Secondary and tertiary amines are not generally prepared in the laboratory. On the technical scale methylaniline is prepared by heating a mixture of aniline hydrochloride (55 parts) and methyl alcohol (16 parts) at 120° in an autoclave. For dimethylaniline, aniline and methyl alcohol are mixed in the proportion of 80 78, 8 parts of concentrated sulphuric acid are added and the mixture heated in an autoclave at 230-235° and a pressure of 25-30 atmospheres. Ethyl- and diethyl-anihne are prepared similarly. One method of isolating pure methyl- or ethyl-aniline from the commercial product consists in converting it into the Y-nitroso derivative with nitrous acid, followed by reduction of the nitroso compound with tin and hydrochloric acid ... 

Reduction of A-nitrosomethylaniline. Into a 1 litre round-bottomed flask, fitted with a reflux condenser, place 39 g. of A-nitroso-methylaniline and 75 g. of granulated tin. Add 150 ml. of concentrated hydrochloric acid in portions of 25 ml. (compare Section IV.34) do not add the second portion until the vigorous action produced by the previous portion has subsided, etc. Heat the reaction mixture on a water bath for 45 minutes, and allow to cool. Add cautiously a solution of 135 g. of sodium hydroxide in 175 ml. of water, and steam distil (see Fig. II, 40, 1) collect about 500 ml. of distillate. Saturate the solution with salt, separate the organic layer, extract the aqueous layer with 50 ml. of ether and combine the extract with the organic layer. Dry with anhydrous potassium carbonate, remove the ether on a water bath (compare Fig. II, 13, 4), and distil the residual liquid using an air bath (Fig. II, 5, 3). Collect the pure methylaniline at 193-194° as a colourless liquid. The yield is 23 g. 

Methylaniline Ethylaniline n-Propylaniline n-Butylaniline Benzylaniline 2 -MethyIbenzylamine N-Ethylbenzylamine 2 -Methyl o-toluidine N-Methyl m-toluidine 2 -MethyI p-toluidine N-Ethyl o-toIuidine N-Ethyl m-toIuidine 2S -Ethyl p-toluidine 2 -MethyI a-naphthylamine N-Methyl p-naphthylamine N-Phenyl- a-naphthylamine 2 -Phenyl-P-naphthylamine... 

A solution of At-(tcrt-butoxycarbonyl)-6-methoxy-2-methylaniline (11.9 g, 50 mmol) was cooled to — 40°C and s-BuLi (96 ml of 1.3 M in cyclohexane. 125mmol) was added. The mixture was stirred at —45°C to —55°Cfor 30min and then allowed to warm slowly to — 15"C over 60 min. The yellow solution was recooled to —45 C and DMF (5.8 ml, 75 mmol) was added. After 5 min the reaction mixture was diluted with water (250 ml) and the product was extracted with EtOAc (2 x 150 ml). The extract was washed with w ater (200ml) and then concentrated in vacuo. The residue was dissolved in THF (100 ml) and 12 N HCl (2 ml) was added. The solution was stirred for 5 min at room temperature and then diluted with ether (250 ml). The solution was washed with water (250 ml), sat. aq. NaHCOj (250 ml), and brine (250 ml), dried (Na2S04) and evaporated. The product was purified by chromatography using 2% EtOAc in hexane for elution. The yield (9.3 g) was 75%. 

Methoxy-4-methyl-3-methylthio I Methyl methylthioacetate, SO2CI2 2 2-Methoxy-5-methylaniline 3 l,8-W.s-(Dimethylammo)naphthalene 81, [14]... 

Methoxy-4,7-hi.s-(methoxymethyl)-6-niethyl- 3-mcthylthio 1 CI2, Ethyl methylthioacetate 2 4-Methoxy-2,5-6/.s-(methoxvmethyl)-3-methylaniline 3 EtjN 4 Xylene, 120 C 74. [17]... 

Reaction takes place on nitrogen when the electrophilic center is an sp carbon, particularly if it is charged. Thus Mannich reaction yields the N-substituted compound (71 and 72) (Scheme 34) (54. 157-159). The same reaction is reported with piperidine, o-toluidine. and methylaniline (158). 

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