Bromobenzene, reaction with potassium

Bromoacetyl fluoride, 46, 6 Bromobenzene, reaction with potassium f-butoxide, 46, 89... 

Bromobenzene is converted into t-butyl phenyl ether by reaction with potassium t-butoxide in DMSO at 25° for 15 hrs. (86% yield) the reaction is much slower in t-butanol."... 

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. 

Large isotope effects were found by Roberts and co-workers (1956) for bromobenzene-2-d in the reaction with potassium amide in ammonia = 5-5) and for the reactions of chloro- and bromo-benzene-2-d with lithium diethylamide in ether = 5-7 and 5 6 respec-... 

A similar substitution reaction occurs with other strong bases. Treatment of bromobenzene with potassium amide (KNH2) in liquid Nhh solvent, for instance, gives aniline. Curiously, though, when bromobenzene labeled with radioactive 14C at the Cl position is used, the substitution product has equal amounts of the label at both Cl and C2, implying the presence of a symmetrical reaction intermediate in which Cl and C2 are equivalent. 

Reaction of potassium phenoxide with p-nitro-bromobenzene in the presence of 18-crown-6 [3] anddibenzo-18-crown-6 111] at 100°C ... 

In addition, aryl chlorides, bromides, and iodides can be converted to arene-amines ArNH2 by the conjugate bases of amines. In fact, the reaction of potassium amide with bromobenzene is extremely rapid, even at temperatures as low as —33°, with liquid ammonia as solvent ... 

The 2- and 4-picolyl anions are phenylated or mesitylated on reaction with chlorobenzene, phenyltri-methylammonium ion and 2-bromomesitylene under stimulation by light or potassium metal. The mechanism of reaction with bromobenzene and iodobenzene is not certain, with die aryne mechanism almost certainly intruding, and with iodobenzene some diarylation of the picolinyl anion results. The reaction of the 2-picolyl anion with 2-bromomesitylene, where an aryne process is impossible, is shown in equation (44). Similar reactions take place between the 4-picolyl anion and 2- or 4-bromopyridine or 2-chloro-quinoline.134... 

The optional site selective metallation of fluorotoluenes158 with the superbasic mixture of butyllithium and potassium fert-butoxide has been applied to the synthesis of the anti-inflammatory and analgesic drug Flurbiprofen.171 3-Fluorotoluene is selectively metallated in the 4-position with LIC-KOR in THF at — 75 °C to afford, after reaction with fluorodimethoxyborane and hydrolysis, the corresponding boronic acid in 78% yield. A palladium-catalyzed coupling with bromobenzene gives the 2-fluoro-4-methylbiphenyl in 84% yield. This four-step sequence can also be contracted to a one-pot procedure with an overall yield of 79%. A double metallation with the superbasic mixture lithium diisopropylamide/potassium tert-butoxide (LIDA-KOR)172 173 is then required to produce flurbiprofen. 

Evidence supporting the bcnzyne mechanism has been obtained by studying the reaction between bromob izene and the strong base potassium amideCKNHj) in liquid NHn solvent. When bromobenzene labeled with radioactive at the Cl position is us, the substitution product has the label scrambled between Cl and 02. The reaction must therefore proceed through a symmetrical intermediate in which Cl and C2 are equivalent— a requiremer.r that only benzyne can meet. 

Thus, the regioselectivity of the Heck reactions with unsymmetrical aikenes can favorably be manipulated by appropriate variations of the catalyst cocktail [123] for example, the best conditions for the couphng of bromobenzene with t-butyl acrylate in the presence of Pd[(o-Tol)3P]2Cl2 (Tol, tolyl) were found to be with potassium carbonate in ethanol at 80 °C. This is unusual for this kind of catalyst system. The active catalyst is actually believed to be nanodispersed palladium metal generated by reduction of the catalyst precursor by ethanol under basic conditions (Table 8.5). 

Several optimization studies have been carried out under these phosphine-free conditions. The reaction of bromobenzene and styrene was studied using Pd(OAc)2 as the catalyst, and potassium phosphate and (V,(V-dimethylacetamide (DMA) were found to be the best base and solvent. Under these conditions, the Pd content can be reduced to as low as 0.025 mol %.142 The reaction of substituted bromobenzenes with methyl a-acetamidoacrylate has also been studied carefully, since the products are potential precursors of modified amino acids. Good results were obtained using either N, (V-diisopropylethylamine or NaOAc as the base. 

In a loosely stoppered 1-1. round-bottomed flask are placed 37.5 g. (48 ml.) of <-butyl alcohol, 150 ml. of dimethyl sulfoxide (Note 1), and a Teflon -coated magnetic stirring bar. The solution is heated in an oil bath which is placed on a combination magnetic stirrer-hotplate. When the temperature of the mixture reaches 125-130°, 75 g. (0.67 mole) of alcohol-free potassium -butoxide (Notes 2 and 3) is added, the stopper is replaced loosely, and the mixture is stirred. When all the potassium /-butoxide is in solution, the stopper is removed, 25 g. (0.159 mole, 17 ml.) of bromobenzene is added in one portion to the hot solution, and an air condenser fitted with a dr dng tube is rapidly placed on the flask. The solution immediately turns dark brown, and an extremely vigorous, exothermic reaction occurs. After 1 minute the reaction mixture is poured into 500 ml. of water. The aqueous solution is saturated with sodium chloride and extracted with four 200-ml. portions of ether (Note 4). The ether extract is washed with three 100-ml. portions of water and dried over anhydrous potassium carbonate. The ether is distilled at atmospheric pressure on a steam bath to leave 17-18 g. of crude phenyl /-butyl ether (Note 5). The brown oil is distilled to yield 10-11 g. (42-46%) of pure phenyl /-butyl ether, b.p. 45-46° (2 mm.), m.p. —17 to —16°, 1.4860-1.4890 (Note 6).-... 

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. 

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