Methyl hypobromite

Because the presence of methanol markedly facilitates the bromination of phenols, we decided that the active species is probably methyl hypobromite produced by the reaction of these tribromides with methanol as shown below (Fig. 5) (ref. 7). 

A very high degree of asymmetric induction was observed in the addition of hypobromous acid and methyl hypobromite to the optically active styryl sulfoxide (R)-311 (323). The ratio of diastereomeric 3-hydroxy sulfoxides 324 formed in the first reaction was... 

A phosgene-free synthesis of alkylisocyanates makes use of the indirect electrochemical oxidation in the alpha-position to nitrogen of formamides. Bromide in methanol solution acts as the redox catalyst, which, presumably, is oxidized to the methyl hypobromite [9] ... 

Reaction of phenols with BTMABr3 or TBABr3 in a methanol/methylene chloride solvent mixture results in a step-by-step bromination. The degree of bromination depends solely on the molar ratio of reagent to substrate (equation 64)522. With the first mole of reagent / -bromophenol is obtained, followed by 2,4- dibromophenol and, finally, 2,4,6-tribromophenol. The role of methanol in these systems is apparently the in situ formation of methyl hypobromite. The same selectivity is, however, found in chloroform523. 

Methylenetiiphenylphosphorane, 307 Methylenomycin A, 183 Methylenomycin B, 184 N-Mcthylephedrine, 308 N-Methyl-i//-ephedrine, 421 Methyl fluorosulfonale, 302, 307 (+)-(S)-4-Methyl-3-heptanone, 17 Methyl 3-hydroxybutyrate, 406 Methyl hydroxymethoxyacetate, 19, 20 Methyl hypobromite, 501 Methyl iodide, 308-309 5-Methylisoxazole, 309 3-Methyl-5(4/0-isoxazolone, 309 Methyl jasmonate, 92, 358 Methylketene methyl trimethylsilyl acetal, 310... 

Phosphoryl chloride-Pyridine dehydration of alcohols [1, 878-879, at end]. Although thebaine (1) can be considered as the methyl enol ether of codeinone (2), no direct synthesis has been achieved. Rapoport123 has recently carried out a convenient indirect synthesis of (1) from Ae-dihydrothebaine (3). Addition of methyl hypobromite (generated from NBA in methanol) gave (4) in 62% yield, and this... 

Methyl hypobromite, 330 Methyl iodide, 274, 370 c/j-l-Methyl-2-isobutoxycyclopropane, 134... 

In the absence of sodium methoxide only traces of the a-bromo acetal are obtained. Hamaoka and Brown suggest that the reaction involves methyl hypobromite. 

Recently, Rapoport et al. described a new synthesis of oripavine and thebaine, a practical synthesis of codeine from dihydrothebainone, and the conversion of thebaine to codeine (yield 85% from thebaine) (497, 498). The transformation of thebaine into codeine with sulfonyl hydrazine and later with methyl hypobromite was reported by Krausz (yield 70%) (499) (Scheme 16). 

Methyl-2-hexyne, 178 Methylhydrazine, 281 Methyl hypobromite, 72 2-Methylimidazole, 357 2-Methyl-2-imidazoline, 357 1-Melhylindenes, 468 Methyl iodide, 384... 

The closing sequence comes from Kenner C. Rice and comprises seven stages. [103] Acetalisation of the keto-function and elimination of methanol with p-toluenesulfonic acid in chloroform is followed by addition of methyl hypobromite. Ehmination of HBr and hydrolysis of the ketal leads to the unsaturated ketone, which is reduced stereoselectively with sodium borohydride to produce (-)-codeine. This generates the fifth stereogenic centre. The methyl ether is finally cleaved with boron tribromide. 

In search of a route from codeinone (17) to thebaine (the corresponding dienol ether) it was found that attempted ketalization of (17) under the usual conditions (trimethyl orthoformate) led to the methoxy enol ether (18). On the other hand, treatment of (17) with methyl hypobromite gave the bromo-ketal (19), which could be dehydrobrominated to (20) [66]. 

Certain electrophilic species such as CI2, Brg, and BrNg can add to olefins by ionic or molecule-induced radical mechanisms depending on the conditions. Under radical-inhibiting conditions, methyl hypobromite adds to hex-l-ene to yield primarily (348), but (349) is obtained under radical-stimulating conditions. Acetyl hypobromite added to hex-l-ene exclusively... 

Since adding Br to the solution would have the affect of reducing the concentration of the methyl h3q>obromite (by Le Chateher s Principle) the observed reduction in the rate of the reaction upon addition of bromide ions can be explained by this one-step mechanism. However, Bartlett reported that there was no such rate di-minishment as a result of the addition of hydrogen ions, which should — in parallel with bromide ions — also diminish the methyl hypobromite concentration by Le Chatelier s principle. This means that the species involved in the rate-determining step of the reaction must be one whose concentration is diminished by the presence of bromide ions, but not by the presence of hydrogen ions. 

Bartlett and Tarbell, 1936] P. Bartlett and S. Tarbell. The Mechanism of Addition Reactions A Kinetic Study of the Addition of Methyl Hypobromite to Stilbene, Journal of the American Chemical. Society 58 466-474, 1936. 

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