Aniline from bromobenzene

Notice the symmetry in this mechanism. Benzyne is formed from an ortho carbanion and it gives an ortho carbanion when it reacts with nucleophiles. The whole mechanism from bromobenzene to aniline involves an elimination to give benzyne followed by an addition of the nucleophile to the triple bond of benzyne. In many ways, this mechanism is the reverse of the normal addition-elimination mechanism for nucleophilic aromatic substitution and it is sometimes called the elimination-addition mechanism, the elimination step... 

Salicyl-u-toluide has been prepared only by the action of phosphorus oxychloride upon a mixture of salicylic acid and o-toluidine. The useful methods of preparation of salicylanilide are by the interaction of salicylic acid and aniline in the presence of phosphorus trichloride, by heating phenyl salicylate and aniline, and from o-hydroxybenzamide and bromobenzene in the presence of small amounts of sodium acetate and metallic copper. A number of these and other anilides have been described. ... 

Similarly, benzene and hydrazoic acid in the presence of a mixture of fluorosulphonic and trifluoromethanesulphonic acid give aniline quantitatively. From toluene 100% of a mixture of o-, m- and p-toluidines is obtained and bromobenzene yields 42% o-bromoaniline and 47% p-bromoaniline, Butyl azide gives iV-butylarylamines under these conditions89. Photolysis of 1-aminoquinolinium perchlorate (76) in aromatic hydrocarbons (benzene, toluene, ethylbenzene or mesitylene) in the presence of 18-crown-6 affords arylamines, e.g. aniline and p-toluidine, by way of the nitrenium ion90 cf Reference 91. 

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). 

Dipheny[amine (7) is prepared industrially either by heating aniline with aniline hydrochloride at 140 °C under pressure, or by heating aniline with phenol at 260 °C in the presence of zinc chloride. The most convenient laboratory synthesis uses the Ullmann reaction (Scheme 8.9) (see Chapter 10), in which acetanilide is refluxed with bromobenzene in the presence of potassium carbonate and copper powder in nitrobenzene solvent. Triphenylamine is similarly prepared from diphenylamine and iodobenzene. 

Support for the proposed mechanism comes from the observation that the L-phenyl-aniline-Cu(II) complex reacted with bromobenzene in the presence of K2CO3 under N2 to yield the product in 43% yield after 48 h, despite low solubility of the complex in the solvent DMA. However, the same reaction carried out with Cul in air did not give the coupled product only the L-phenylalanine-Cu(II) complex was isolated. This result implies that the major species that forms the C—N bond is the L-phenylalanine-Cu(I) complex. 

Heating the diethanolamine or bis(2-chloroethyl)amine hydrochlorides with aniline derivatives gave 1-arylpiperazine derivatives. The 1-substituted piperazines were deuteromethylated. 1,4-Dithiocarbonyl piperazine was obtained from reaction of benzaldehyde with piperazine and sulfur. l,4-Diacetylpiperazine-2,5-dione were reacted with aldehydes to give the monoarylidene products and then 73. 4-Benzylpiperazine-2,5-dione was reacted with bromobenzene to give 74. Diels-Alder cycloaddition of pyrazinone with ethene gave 75 . ... 

Jy/ .-tribromobenzene has been prepared from 3,5-dibromo-aniline by the replacement of the amino group by bromine from bromoacetylene by the action of light by the decomposition of 2,4,6-tribromophenylhydrazine by the reduction of 2,4,6-tri-bromobenzene diazonium sulfate and as a by-product in the preparation of 2,4,6-tribromobenzonitrile. ... 

Treatment of diazonium salts with cuprous, Cu(I), salts generates aryl halides. When 398 reacts with CuCl (cuprous chloride) or CuBr (cuprous bromide), the products are chlorobenzene or bromobenzene via what is probably a radical reaction.29l jhis conversion is known as the Sandmeyer reaction. 2 The use of copper powder rather than cuprous salts for this transformation is often called the Gattermann reaction. 93,292b,c Aryl iodides are also produced from diazonium salts by reaction with potassium iodide (KI) but the actual reactive species may be l3-.294,295 Treatment of aniline derivative 403 with sodium nitrite and HCl followed by treatment with KI, for example, gave a 89% yield of 404.Aryl nitriles are generated under Sandmeyer conditions using cuprous cyanide (CuCN), as in the conversion of 405 to benzonitrile derivative 407 via diazonium chloride, 406. 

Piperidine or lithium piperidide and benzyne form N-phenylpiperidine, as expected, but the same product (40-50%) was also obtained unexpectedly from V-methylpiperidine, fluorobenzene, and phenyllithium before the formation of benzyne under these conditions was properly recognized. A series of N-alkylmorpholines gives secondary and tertiary aniline derivatives 213 and 214 when treated with bromobenzene and sodium amide. A route for formation of these products via the ylid 211 is outlined in Scheme 19, in which the formation of 211 is similar to that of 16 in Scheme 2 and the step 212 -+ 213 is similar to the decomposition of 33 in Scheme 5. The final... 

The synthesis of SFs-substituted phenothiazine was disclosed in a patent from Smith, Kline French Laboratories (63USP3107242). 3-SFs-Acetanilide (120), prepared by acetylation of d-SFs-aniline (39) with acetic anhydride, was first condensed with bromobenzene under basic conditions, in the presence of Cul and copper-bronze powder, and after add hydrolysis provided 3-SFs-diphenylamine (121). This product was then fused with sulfur in the presence of a catalytic amount of iodine to give 2-SFs-phenothiazine (122) in unreported yield (Scheme 34). 

Then, using radiolabeled ( C) bromobenzene (CeHsBr), it was shown that the aniline (aminobenzene, C6H5NH2) resulting from the reaction with sodium amide in liquid ammonia was a 1 1 mixture of ipso- and ortho-[ Ci]-anihnes (aminoben-zenes) (Equation 7.65). 

Figures Chromatograms on MIL-53(Al)-packed column (7-cm longx4.6-mm i.d.) for RP HPLC separation using CHjCN/HjO as mobile phase at l.OmLmin b (a) ethylbenzene and toluene (b) PAHs (c) thiourea (1), phenol (2), aniline (3), benzaldehyde (4), bromobenzene (5), naphthalene (6) (d) o-benzenediol, m-benzenediol, and p-benzenediol (e) aniline, N,N-dimethylaniline, and m-nitroaniline (f) xanthine, theophylline, and caffeine. Mobile phase composition (CHjCN/HjO, v/v) (a) 7 3 (b) 10 0 (c) 6 4 (d) 1 9 (e) 9 1 (f) 5 5. UV detection at 210 run (a, c), 256 run (b), 70 run (f), and 280 nm (d, e). (Reproduced from Ref 69 with permission of The Royal Society of Chemistry. DOI 10.1039/C2AN15925B.)...

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