Reactions with bromoanilines

A combination of organometallic procedures has been used in the design of a simple, efficient synthesis of 2-alkylindoles from o-bromoanilines.76 The arylamines are converted in reactions with 73-allylnickel dimers77 into 2-allylarylamines (36, Scheme 48) which can be cyclized in a separate step... 

Palladium complexes have been used for the electroreductive cycliza-tion of Ai-alkenyl-2-bromoanilines to the corresponding indoline derivatives (Scheme 69) [101]. The postulated carban-ion intermediate undergoes a reaction with the electrophiles (H+, CO2). 

A recent procedure which utilizes the pivaloyl derivative of o-bromoaniline as one of the fragments is also a type llac approach. The compound is converted to its dilithio derivative at -78 °C. Reaction with a-halo ketones then affords indole hydrates by N-alkylation and reaction of the o-lithiated position with the carbonyl group dehydration subsequently yields indoles (equation 108) (81TL1475). The (V-trifluoroacetyl and N-t-butoxycarbonyl derivatives of o-bromoaniline exhibit similar reactivity. 

Protection of the amino group by acetylation, as in acetanilide, therefore usually permits monosubstitution reactions with appropriate electrophilic reagents to proceed smoothly. Thus with bromine, p-bromoacetanilide is the main product the small quantity of the ortho isomer simultaneously formed can be easily eliminated by recrystallisation (Expt 6.67) hydrolysis of p-bromoacetanilide gives p-bromoaniline. Nitration leads similarly to p-nitroacetanilide which can be hydrolysed to p-nitroaniline (Expt 6.68). 

As a side product in these reactions a novel bridged steroid alkaloid 230 is formed, presumable by an intermediate hydride shift in 227 from the benzylic position to the iminium ion to give a secondary amine, which then attacks the formed cationic benzylic position. This reaction becomes the main reaction with aniline, p-bromoaniline or nitroaniline in the presence of BF3 -OEt2 if a derivative of 224 is used containing a propyl instead of a propenyl side chain [61]. 

Show the products from reaction of / -bromoaniline with the following reagents ... 

Similarly, reaction with, V-acetyI-2-bromoaniline gives quinolones after retro-Diels-Alder cleavage13. With 2-bromophenol and norbornadiene under similar conditions, a competitive pathway results in simple hydrocarboxylation without cleavage of the C-Br bond13. The reaction of 2-iodophenol with ethynylbenzene leads to an alkylidenebenzofuranone,3. 

The reaction of PI with 4-iodoaniline in the presence of lmol% Pd(PPhs)4 provided 2-(4-aminophenyl)pyridine (8a) with similar results (89% isolated yield, Table 3.37, entry 6). 3-lodoaniline and 2-iodoaniline were also coupled with PI under the same conditions (Table 3.37, condition C), affording the aminophenyl pyridines (8d and 8e) in 64% and 74% isolated yields, respectively (Table 3.37, entries 7 and 8). Another successful coupling reaction (Table 3.37, entry 9) was achieved from a sterically hindered 3-methyl-2-pyridylzinc bromide (P2), resulting in 68% isolated yield with the formation of 8f. Unfortunately, no satisfactory coupling reaction occurred with 4-bromoaniline using the Pd(0) catalyst (Table 3.37, entry 10). With the results obtained from the coupling reactions with haloaromatic amines, it can be concluded that the Pd(0)-catalyzed reaction of 2-pyridylzinc bromides works effectively with iodoaromatic amines and also the relatively more reactive bromoaromatic amines. 

The reaction with some of the less-reactive aryl bromides bearing electron-donor substituents, such as o-bromoaniline or 5-bromo-2-aminopyridine, is better carried out in aqueous DMF with high content of water, in the presence of an inorganic base such as K2CO3 and palladium catalyst with (0-MeC6H4)3P ligands ... 

The use of various a-amino acids such as 309b, c, 311, 312a-d instead of pipecolinic acid 309a in the reaction with 2-bromoaniline 308a in the presence of copper(I) iodide made it possible to synthesize various annulated (in the cases of 309b, c), spiro (in the cases of 311), and 3-substimted (in the cases of 312a-d) quinoxalines 313, 314, 315, and 316 (Scheme 2.56) (Tanimori et al. 2009). 

Unlike the reaction with 2-iodoaniline that was completed in 8 h, the reaction with 2-bromoaniline (in the presence of Cul, base, and L-proIine in DMSO) took 16 h to reach completion and produce the product in a 78 % yield (Table 3.10,... 

Table 3.10 Scope of reaction with different 2//-isoindole-l-carbaldehydes and 2-bromoanilines...

Bromodiphenyl. Diazotise 43 g. of p-bromoaniline (Section IV,49) in the presence of 40 ml. of concentrated hydrochloric acid and 22 -5 ml. of water (see Section IV,61) with a concentrated solution of sodium nitrite. Mix the filtered diazonium solution with 500 ml. of cold benzene, stir vigorously and add a solution of 30 g. of sodium hydroxide in 150 ml. of water dropwise (during 30-45 minutes) whilst maintaining the temperature at 5-10°. Complete the reaction as for 2-chlorodiphenyl. The 5rield of 4-bromodiphenyl, b.p. 170-175°/8 mm., m.p. 90° (from ethanol) is 25 g. 

No practical type B syntheses of quinoxalines are commonly in use, largely because of the fact that type A syntheses are more facile however, some phenazine syntheses of this type are known, particularly those described in the older chemical literature. Hillemann (38CB42) has effected dimerization of 0-bromoaniline by heating its solution in nitrobenzene with K2CO3 and copper powder. The reaction is believed to proceed through the intermediacy of 5,10-dihydrophenazine, but the latter has not been isolated (Scheme 68). 

The following reductions have been carried out at 80° with the use of an excess of 2-propanol as the reaction medium (see Note 3) carbon tetrachloride to methane (47%), 1-bromonaph-thalene to naphthalene (90%), /3-bromostyrene to styrene (72%), jfi-bromoaniline to aniline (61%), p-bromophenol to phenol (66%), and monochloroacetone to acetone (30%). 

A few additional Pd-catalyzed schemes have been employed for Ilac type cyclization chemistry. Palladium-phenanthroline complexes were used by the Ragaini group to prepare indoles via the intermolecular cyclization of nitroarenes and alkynes in the presence of carbon monoxide <06JOC3748>. Jia and Zhu employed Pd-catalysis for the annulation of o-haloanilines with aldehydes <06JOC7826>. A one-pot Ugi/Heck reaction was employed in the preparation of polysubstituted indoles from a four-component reaction system of acrylic aldehydes, bromoanilines, acids, and isocyanides <06TL4683>. 

Kuroda and Suzuki used reaction of 267a with 2-bromoaniline leading to anilide 312 as the first step of their sequence in the preparation of 1H-imidazo[4,5-c]quinolin-4(5//)-ones (Scheme 77) (91TL6915). Reaction of 267a with amines usually does not require any catalyst and/or base, but in this case use of sodium hydride was reported. The anilide 312 was sequentially alkylated, first with methyl iodide in ethanol with potassium hydroxide at room temperature and then with different alkyl iodides in acetone at reflux to provide intermediate 313. This compound was then cyclized via palladium catalyzed reaction leading to product 314. This reaction provides a new entry to l//-imidazo[4,5-c]quinolin-4(5//)-ones that are of current interest as antiasthmatic agents. 

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