O-halo-aniline

Intramolecular Heck reaction of o-halo-aniline with pendant olefin to prepare indole. 

The didehydroazepine (1) or benzazirine intermediates that are generated by the photolysis of phenyl azide have also been intercepted by the naked anions that are produced from various potassium salts when they are used in the presence of crown ethers Potassium acetate and hydroxide both gave the azepinone (2) while potassium halides gave only the o-halo-anilines. 

Mori-Ban reaction refers to a synthesis of indole derivatives by an intramolecular Heck reaction of o-halo-aniline with pendant olefin catalyzed by a low-valent metal complex Pd and Ni. The preferred ortho-haXogcn is bromine or iodine (chlorine has very low reactivity under this case). More often, the o-iodo-iV-allylaniline is more reactive than corresponding o-bromo-and o-chloro-substrate. Also, it has been found that the catalyst can be deactivated under the reaction. Therefore, a periodic provision of fresh catalyst normally gives higher overall yields than that using the same total amount of catalyst with one addition. In the past three decades, the Mori-Ban reaction has been improved and applied to variety of organic synthesis. 

Professor Buchwald has also developed Angew. Chem. Int. Ed. 2007, 46, 7236) a protocol for the Pd-mediated a-arylation of aldehydes. This procedure converted an o-halo aniline 29 to the indole 31. In a C-H activation-based approach, Mark Lautens of the University of Toronto demonstrated Organic Lett. 2007, 9, 5255) that Pd-catalyzed condensation of 32 with the aniline 33 led to the indole 34. 

Rctrosynthetic path a corresponds to Pd-catalysed exo-trig cyclization of o-halo-JV-allylanilines. Path b involves the endo-trig cyclization of o-halo-JV-vinyl anilines. Path c is a structurally similar cyclization which can be effected photochemically in the absence of an o-substituent. Retrosynthetic path d involves intramolecular Friedel-Crafts oxyalkylation followed by aromatiz-ation. 

Halogen-Metal Interconversions with Halo-geneted Anilines. A highly explosive compound which appears to be p-N,N-Trilithioani-line is formed as a by-product in the reaction of BuLi and p-Br-aniline but not o-Br-aniline (Ref 1). More recently this reaction was repeated but no by-product is mentioned (Ref... 

Aniline, JV-alkyl-o-allyl-indole synthesis from, 4, 321 Aniline, N-allyl-indole synthesis from, 4, 326 Aniline, AT-allyl-o-bromo-indole synthesis from, 4, 327 Aniline, N-allyl-o-iodo-indole synthesis from, 4, 327 Aniline, o-bromo-in indole synthesis, 4, 340 Aniline, o-halo-cyclization, 4, 340 Aniline, m-nitro-in indole synthesis, 4, 338 Aniline black, 3, 197 Anilines... 

The preparation of benzothiazoline-2-thiones from o-halo or w-halo anilines and carbon disulfide in basic medium is discussed at greater lenght in Section IV.4. 

In this connection it is perhaps worthwhile to reconsider the synthesis of benzothiazoline-2-thiones. These substances can, as already mentioned, be made from o-nitrochlorobenzene with sodium hydrogen sulfide and carbon disulfide (method C). Starting from 0- or w-halo anilines, benzothiazoline-2-thiones are also obtainable with carbon disulfide in strong alkali (55). The intermediate in this reaction is an aryne (CXXXIII). 

Heck cyclization reactions of o-halo-A-(2-alkenyl)anilines have proven useful for the development of type Ic approaches to indoles. Recent applications include the preparation of a... 

For the retrosynthesis of indole (see Fig. 5.8), two routes (I/II) are proposed, as for pyrrole (see p 94). Route I suggests o-aminobenzyl ketone 1 or 6>-alkyl-A -acylaniline 2 as starting material on the basis of operations a - c. Their retroanalysis (d,e) in turn leads to 2-alkylaniline 5 and carboxylic acid derivative 6. Construction of the indole system should thus occur by N- or C-acylation of 5 (utilizing the o-nitrotoluene derivative 4) followed by cyclodehydration of 1/2. The alternative route n, based on retrosynthetic analysis g-i, leads to aniline via the a-(A -phenylamino)ketones 3 and to a-halo ketones 7 as possible precursors for the indole synthesis. 

Heating arylamines with carbon dioxide at 200°C (8500 atm) gives good yields of 3-aryl derivatives of 2,4-dihydroxyquinazoline (see 5e). The method is unsatisfactory when riitro, halo, and phenolic anilines and o- or jS-naphthylamines are used. 

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