Aniline from methylaniline

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 ... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

In another investigation81,185, the rates of formation of para-nitroso-N-methyl-aniline from N-nitroso-N-methylaniline in hydrochloric acid solution at 31 °C were measured by noting the appearance of the absorption at 340 mn due to the protonated from of the para-nitroso-N-methylaniline. A typical run is shown in Fig. 3. The decreasing absorption at about 260 m/i represents the disappearance... 

Let us now compare the pA, values (in AN) of the cation-radicals derived from aniline, N-methylaniline, and A-phenylaniline 5.5, 4.2, and 1.8, respectively (Jonsson et al. 1996). An N-methyl substitnent produces only a marginal effect on the pA, valne of the aniline cation-radical. At the same time, the effect of the A-phenyl snbstitnent in aniline is considerable. The phenyl group (electron-withdrawing) effect on the aniline cation-radical acidylation is self-obvious. 

If either the o- or -position is occupied, only one isomer is obtained transformation to the mefo-position does not occur. This is a standard method of preparation of acyl-amino-ketones, or by a further hydrolysis of amino-ketones. The tendency, illustrated in this reaction, of groups to wander from the amino group to the nucleus, is also shown in previous reactions and in the preparation of aminoazobenzene from diazoamino-benzene (Preparation 456), of sulphanilic acid from aniline sulphate (Preparation 292), of o- and p-chloroacetanilides from acetochloranilide (Preparation 328), of o- and p-toluidine from methylaniline hydrochloride, and of 1 2 4-aminodimethylbenzene (2 4-xylidine) from dimethylaniline hydrochloride. 

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. 

Li et al. [87,88] found that aniline will process the photopolymerization of AN either in N,N-dimethylformamide (DMF) solution or in bulk with a fair rate of polymerization only next to DMT. From UV spectra it is proved that aniline will form a CTC with AN. Using 313-nm radiation that CTC is excited to an exciplex and polymerization proceeds. N-methylaniline will polymerize AN similarly. The following mechanism was proposed ... 

Pure samples are best prepd by the methylation of acetanilide or benzanilide to the N-methyl compds followed by acid hyd. It has been prepd commercially by the action of methyl ale on aniline in an autoclave under press and by the action of methyl amine on halobenzenes. For a summary of prepns see Refs 6 9. It may be separated from aniline and dime thy laniline by treatment of the mixt with benzenesulfonyl chloride. Dimethylamline fails to react and is extd out with dil acid. Aniline forms benzenesulfonanilide which is acidic and is removed by washing with dil base, leaving the N-methylbenzenesulfonanilide. Purified N-methylaniline is obtd by acid hyd (Ref 8). N-Methylaniline is used as an additive to raise the octane no of motor fuels (Ref 6), as a dyestuff intermediate (Ref 3), in the prepn of Tetryl (see below), and in the prepn of Methylcentralite (Encycl, Vol 2, C137-R)... 

The formation of 151 from the phosphonate 171 could be proved only by indirect means. Electron-rich aromatic compounds such as N,N-diethylaniline and N,N,N, N -tetraethyl-m-phenylenediamine U0 1I9> and N-methylaniline 120> are phosphorylated in the para- and in the ortho- plus para-positions by 151. Furthermore, 151 also adds to the nitrogen lone pair of aniline to form the corresponding phosphor-amidate. Considerable competition between nucleophiles of various strengths for the monomeric methyl metaphosphate 151 — e.g. aromatic substitution of N,N-diethylaniline and reaction with methanol or aromatic substitution and reaction with the nitrogen lone pair in N-methylaniline — again underline its extraordinary non-selectivity. 

The product is free from secondary aniline product on the basis of infrared and n.m.r. proton analysis. If equimolar amounts of aniline and phosphate are employed, the product is obtained in a higher yield (12.3 g., 65%), but it contains a trace of w-trifluoromethyl-N-methylaniline as detected by infrared analysis. This secondary aniline is readily removed by heating the product to reflux with 1 ml. of acetic anhydride followed by... 

N-methylation of aniline is an interesting reaction from the products selectivity point of view, especially N-methylaniline (NMA), due to the presence of chemically equivalent protons attached to the nitrogen atom. The high nucleophilicity of the amine nitrogen results in the formation of mixture of N-methyl and N, N-dimethylated products. Ko et al [90]... 

Ackermann and Althammer reported an efficient synthesis of murrayafoline A (7) starting from the easily accessible 2-methoxy-4-methylaniline (598) (see Scheme 5.33) (898). This methodology involves a Pd(0)-catalyzed domino N-H/C-H bond activation to afford the carbazole framework directly. Thus, in a one-pot operation, 2-chloro-bromobenzene (1573) and the aniline 598 were directly transformed into murrayafoline A (7) in 74% yield by reacting with a catalytic amount of Pd(ll) acetate in the presence of K3PO4, PCys, and N-methylpyrrolidone (NMP). This reaction also proceeds with 1,2-dichlorobenzene, albeit in 72% yield (898) (Scheme 6.4). 

In broad outline the scheme of methylaniline formation from aniline and methanol may be presented as follows ... 

Refs l)Beil 12, [401,402] 2)W.G Macmillan T.H.Reade, JCS 1929, 2866 Dinitrobromomethylaniline, C7HgN304Br mw 276.06 N 15.22%. Three N-methyl derive, (02N)2CgH2Br.NH.CH3, are described in the lieerature 2,4-Dinit.ro-5-bromo-N-methylaniline, yel crysts(from ale), mp l49-l50° 2,4-Dinitro-6 -bromo-N-methylaniline, yel crysts(from AcOH), mp 147° and 2,6-Dinitro-4-bromo-N-metbylaniline, om ndls or yel crysts(from ale or petr eth), mp 104-6°(Ref 1). Two aminotoluene or methylaniline derivs, (OzN)2C6H(Br)NH2.CH3, are described in the literature 4,6-Dinitro-3-bromo-2-methyl-aniline, yel crysts, mp 200°-, and 3,5-Dinitro-2 -bromo-4-methylaniline, It yel ndls or prisms (from ale), mp 170-4°(Ref 2). Other props methods of prepn are given in the Refs Refs l)Beil 12, 761 [417, 418] 2)Beil 12, (397, 445) [540]... 

The nitration of aniline in the presence of a large amount of strong sulfuric acid results wholly in the formation of m-nitro-aniline, but the similar nitration of dimethylaniline gives principally a mixture of the ortho- and para-derivatives. Mono-methylaniline stands between aniline and dimethylaniline in respect to the orienting effect of its amino group it yields a considerable amount of the m-nitro- compound—and dimethylaniline is preferred for the preparation of tetryl. Commercial dimethylaniline contains a certain amount of monomethylaniline, from which it is extremely difficult to free it, and this in the manufacture of tetryl is converted in part into 2,3,4,6-tetranitro-phenylmethylnitramine, or m-nitrotetryl, pale yellow, almost white, crystals from benzene, m.p. 146-147.087... 

The nitro group in the 3-position is readily removed by hydrolysis. Since monomethyl-aniline, on nitration in strong sulfuric acid furnishes some m-nitromonomethylaniline, crude Tetryl made from dime thylaniline contg mono-methylaniline will contain m-Nitrotetryl as an impurity (Ref 2)... 

N-Methylaniline adds to cyclopropanone to give the expected carbinol amine in quantitative yield. 5-90> On the other hand, a mixture of addition products may be isolated from the reaction of cyclopropanone 5>90> or cyclopropanone ethyl hemiketal4) with aniline (Scheme 18). At — 78°C, the carbinol amine 104 (66%) and the dimeric species 105 (33%) were obtained when the reactants were present in stoichiometric amounts. With excess aniline, 104 was produced almost quantitatively. However, at 25 °C, both 104 and the dianilino product 106 were obtained. These products could be interconverted by the addition of aniline or cyclopropanone, respectively. At 125 °C, o-propionylaminopropiophenone (107) was formed, possibly by further reaction of the carbinol amine with cyclopropanone as shown. 4>... 

Alkoxy derivatives of biphenyl can be obtained either from alkoxy-anilines or by coupling with alkoxybenzenes. From diazotized p-bromo-aniline and anisole a 20% yield of 4-bromo-2 -methoxybiphenyl and a 7% yield of 4-bromo-4 -methoxybiphenyl are obtained. In connection with their studies on Cannabis Indica, Ghosh, Pascall, and Todd u prepared the highly substituted biphenyl compound, 2-cyano-5-methyl-2, 5 -dimethoxy-4 -n-amylbiphenyl (VII), in 27% yield from the nitrosoacetyl derivative of 2-cyano-5-methylaniline and 2,5-dimethoxy-n-amylben-zene. 

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