Alkylanilines

Physical Properties, (i) Aromatic. Colourless when freshly prepared, but usually brown. MonomethylaniUne, CgHjNHCH, b.p. 193°, and monoethylaniline, CgHjNHCjHj, b.p. 206 , diphenylamine,(C6H5)2NH, m.p. 54 , are all insoluble in water, the two alkylanilines having well-marked basic properties, diphenylamine being feebly basic and insoluble in dilute mineral acids. 

Retrosynthetic path b in Scheme 3.1 corresponds to reversal of the electrophilic and nucleophilic components with respect to the Madelung synthesis and identifies o-acyl-iV-alkylanilines as potential indole precursors. The known examples require an aryl or EW group on the iV-alkyl substituent and these substituents are presumably required to facilitate deprotonation in the condensation. The preparation of these starting materials usually involves iV-alkyla-tion of an o-acylaniline. Table 3.3 gives some examples of this synthesis. 

Another version of the o-aminobenzyl anion synthon is obtained by dilithi-ation of A-f-Boc-protected o-alkylanilines. These intermediates are C-acylated by DMF or A"-methoxy-At-melhyl carboxamides, leading to either 3- or 2,3-disubstituted indoles. In this procedure dehydration is not spontaneous but occurs on brief exposure of the cyelization product to acid[4]. Use of CO as the electrophile generates oxindoles. 

Mixtures of /V-alkylanilines can usually be separated by fractional distillation. Mixtures of the methyl or ethyl derivatives have also reportedly been separated by converting the V/-ethyl or the /V-methyl derivative to the nonvolatile salt with -toluenesulfonic acid (12) or phthaUc anhydride (13), followed by distillation. 

V-Alkylaniline and /V,/V-di alkyl aniline hydrochlorides can be rearranged to C-alkyl anilines by heating the salts to 200—300°C. In this reaction, known as the Hofmann-Martius rearrangement, the alkyl group preferentially migrates to the para position. If this position is occupied, the ortho position is alkylated. 

Thermal or Lewis acid catalyzed rearrangement of N alkylanilines to o (p-) akylated anilines... 

The intramolecular cyclization of A -acylated-o-alkylanilines in the presence of a strong base at elevated temperatures is known as the Madelung indole synthesis. ... 

Houlihan et al. have described the successful indolization of iV-acylated-o-alkylanilines by employing -BuLi/LDA as bases at lower temperature. ... 

The modification of the Madelung indole synthesis achieved by introduction of an electron withdrawing group (EWG) at the benzylic carbon atom of the N-acylated-o-alkylanilines has been quite successful. Orlemans et al. reported that indoles were isolated in decent yields when the amides were treated with t-BuOK in THF for a period of 10 minutes at room temperature. ... 

The mechanism of oxidation (16 —> 17) is not well understood. Both tetrahydroquinoline (19) and A-alkylaniline (20) have been isolated from reaction... 

Therefore in this section we will focus first on the reactions of arenediazonium ions with secondary amines such as A-alkylanilines and dialkylamines. Reactions with primary amines will be discussed later in this section. Most diarylamines do not undergo Af-azo coupling to a significant extent, as they are weaker nucleophiles. 

Condensation, of oxalyl chloride, with di- -alkylanilines, 41, 3 with dimethylaniline, 41, 1 of 1,1,3,3-tetraethoxypropane with thiourea to give 2-mercaptopy-rimidine, 43, 68... 

Various l-alkyl-4-(benzotriazol-l-yl)-l,2,3,4-tetrahydroquinolines have been prepared by condensation of V-alkylaniline with two equivalents of an aldehyde and one equivalent of benzotriazole <95JOC(60)7631>. Quinolones 66 were simply prepared in good yield by heating a mixture of the appropriate vinylogous amide 65 and NaHCOj in the presence of a catalytic amount of palladium(II) acetate and triphenylphosphine in DMF under a carbon monoxide atmosphere <96CC2253>. 

Notes on the preparation of secondary alkylarylamines. The preparation of -propyl-, ijopropyl- and -butyl-anilines can be conveniently carried out by heating the alkyl bromide with an excess (2-5-4mols) of aniline for 6-12 hours. The tendency for the alkyl halide to yield the corresponding tertiary amine is thus repressed and the product consists almost entirely of the secondary amine and the excess of primary amine combined with the hydrogen bromide liberated in the reaction. The separation of the primary and secondary amines is easily accomplished by the addition of an excess of per cent, zinc chloride solution aniline and its homologues form sparingly soluble additive compounds of the type B ZnCl whereas the alkylanilines do not react with sine chloride in the presence of water. The excess of primary amine can be readily recovered by decomposing the zincichloride with sodium hydroxide solution followed by steam distillation or solvent extraction. The yield of secondary amine is about 70 per cent, of the theoretical. 

R. Bacskai and A. H. Schroeder. Alkylaniline/formaldehyde cooligomers as corrosion inhibitors. Patent US 4778654,1988. 

With aromatic amines there is the possibility of attack on either nitrogen or carbon, and, by contrast with phenols, attack is found to take place largely on nitrogen, with primary and secondary (i.e. N-alkylanilines) amines, to yield diazo-amino compounds (33) ... 

With most primary amines this is virtually the sole product, but with secondary amines (i.e. N-alkylanilines) some coupling may also take place on a carbon atom of the nucleus, while with tertiary amines (i.e. N,N-dialkylanilines) only the product coupled on carbon (34) is... 

Harmata and co-workers introduced a procedure for the reductive desulfurization of selected 2,1-benzothiazines with sodium amalgam, leading to the formation of the 2-alkylanilines in high yields <94S142>. This method is regioselective and general. As an example, alkylation of 187 followed by treatment with Na/Hg resulted in the formation of the aniline 188 in 68% overall yield (Scheme 50). 

Thoma A process for alkylating aniline with methanol or ethanol, to produce mixtures of mono- and di-alkylanilines. Operated in hot, concentrated phosphoric acid in a vertical tubular reactor. The proportions of secondary and tertiary amines can be partly controlled by controlling the ratios of the reactants the products are separated by fractional distillation. Invented in 1954 by M. Thoma in Germany. 

The first term represents the temperature dependence of the film density, being directly related to the thermal expansion coefficient of the film, and also indirectly related to that of the substrate. Generally, the thermal expansion coefficient of the organic substance is much larger than that of the inorganic substance like glass. In the case of the alternate LB film of fatty acid/alkylamine or fatty acid/alkylaniline, the pyroelectric coefficient p decreased as the thermal coefficient of the substrate increased [18]. 

The method gives better yields, utilizes more readily available starting materials, and is much less laborious than the hydrolysis of N-methyl-N-alkylarenesulfonamides and -nitroso-N, N-di-alkylanilines, or the lithium aluminum hydride reduction of alkyl isocyanates. Compared to the closely related procedure of Lucier, Harris, and Korosec,12 in which the N-benzylidenealkyl-amine is treated with dialkyl sulfate at atmospheric pressure, the present procedure tends to give higher yields and purer products, but it is less convenient because of the need for a pressure vessel. 

In an interesting catalysed conversion of trichloroethene by secondary amines into aminoacetamides, the initial steps are thought to involve the p-elimination of HC1 to produce dichloroethyne (Scheme 9.1), which reacts with the secondary amine under the wet conditions to produce the amide [35] the reaction does not work with N-alkylanilines. Such a mechanism is realistic, as it is well known [36] that trichloroethene is converted into the inflammable and explosive dichloroethyne by bases, and quaternary ammonium salts catalyse the formation of the alkyne when trichloroethene is reacted with oxiranes [37]. Chloroethynes have also been obtained by the catalysed reaction of terminal ethynes with carbon tetrachloride under basic conditions [38]. 

Aqueous NaOH (50%, 10 ml) is added to the trifluoroacetanilide (10 mmol), TEBA-C1 (2.45 g, 10 mmol), and the haloalkane (12.5 mmol) in PhMe (20 ml) and the mixture is stirred at room temperature until TLC analysis indicates complete consumption of the anilide. Aqueous NH4C1 (sat. soln., 20 ml) is added and the aqueous phase is separated and extracted with EtOAc (3 x 20 ml). The combined organic solutions are dried (MgS04) and evaporated to yield the /V-alkylaniline. 

Hofmann rearrangement org chem A chemical rearrangement of the hydrohalides of N-alkylanilines upon heating to give aminoalkyl benzenes. haf man. res ran)-mont ... 

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