Bromobenzene butoxide

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

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).-... 

Exercise 14-22 Bromobenzene "reacts rapidly with potassium fert-butoxide in (CH3)2SO (methylsulfinylmethane, dimethyl sulfoxide, DMSO) to give fert-butyl phenyl ether ... 

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. 

Any nucleophile basic enough to remove the ortho proton can carry out this reaction. Known examples include oxyanions, amide anions (R2N"), and carbanions. The rather basic alkoxide t-butoxide will do the reaction on bromobenzene if the potassium salt is used in the dipolar aprotic solvent DMSO to maximize reactivity. 

Catalysts generated from A-heterocyclic carbenes 23-25 (Figure 7) have been shown to efficiently catalyze the coupling of aryl and heteroaryl halides with indoles. Reactions conducted with the terf-butoxide base, which is typically used for the C—N coupling, did not occur, but reactions with NaOH as base occurred to high conversion85. Although 4-bromotoluene and bromobenzene reacted with numerous substituted indoles under these conditions, electron-rich and orf/zo-substituted aryl bromides reacted slowly and in low or moderate yields. 

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."... 

A 4-mL vial was charged with bromobenzene (63 mg, 0.40 mmol), Pdtdbaii (11.5 mg, 0.0200 mmol), Ph5FcP-(Z-Bu)2 (14.2 mg, 0.0200 mmol), and sodium zcrt-butoxide (47 mg, 0.48 mmol). Anhydrous toluene (2 mL) was added, and the vial was sealed with a cap containing a PILE septum and removed from the dry box. The reaction mixture was stirred at room temperature for 23 h. The reaction solution was then adsorbed onto silica gel, and the product was isolated by eluting with EtOAc/hexanes (0 to 10% gradient) to give the ether (58 mg, 97%). 

The group also reported DME in the presence of potassium tert-butoxide to be an efhcient source of carbon monoxide and dimethyl-amine in palladium-catalyzed aminocarbonylation (Heck carbonylation Scheme 25.2D). The addition of excess amines to the reaction mixture provided good yields of the corresponding aryl amides. The reaction proceeded smoothly with bromobenzene and more electron-rich aryl bromides, but not with electron-deficient aryl bromides. 

Bromobenzene allowed to react 2 hrs. at 35-40 with diethylamine in tetrahydro-furan containing NaNHg-Na-t r -butoxide mixture prepared from NaNHg and r -butanol -> diethylaniline. Y ca. 100%. - The above base mixture is highly reactive. F. e. and reactions s. P. Caubere and B. Loubinoux, Bl. 1968, 3857 1969, mi. 

Bromobenzene added in one portion at 125-130° to a soln. of K-ferf-butoxide in ferf-butanol-dimethyl sulfoxide whereupon a vigorous exothermic reaction occurs, and after 1 min. poured into water phenyl ferf-butyl ether. Y 42-46%. — This is another example showing the activating effect of dimethyl sulfoxide on base-catalyzed reactions (s. a. Synth. Meth. 17, 106). M. R. V. Sahyun and D. J. Gram, Org. Synth. A5, 89 (1965). 

---