2-Bromoethyl esters, alkylation

The inter- vs. intramolecular alkylation of 2-bromoethyl ester a anions (99) cannot be explained on simple terms. 

Further application of the in-situ generation of chiral quaternary ammonium fluorides from the corresponding hydrogen sulfates has also been shown in the facile preparation of optically active esters via the alkylative kinetic resolution of secondary alkyl halides. For example, simple stirring of the mixture of 3-phenylpropionic acid, l-(l-bromoethyl)naphthalene, (S,S)-6b (X = HS04 2 mol%) and KF-2H20 (5 equiv.)... 

Use of Ci-bromoethyl methyl ketone as alkylating agent for malonic ester gives a 74% yield of ethyl a-carbethoxy-y0-methyllevulinate. The second a-hydrogen atom may be replaced by a methyl group in 76% yield. The keto acids, /3-methyllevulinic acid (40%) and a,/8-dimethyllevulinic acid (83%), are then obtained by decarboxylation of the dibasic acids at 140° and 120°, respectively. ... 

Alkyl halides are even less reactive than acyl halides, as indicated by the compilation of reaction rates of thiolate anions with various types of alkyl halides (282). Nevertheless, potentially useful affinity labels have been synthesized with alkyl halide substituents and have been shown to specifically inactivate several enzymes, albeit slowly the low reactivity of the alkyl halides may minimize nonspecific reaction. Adenosine 5 -(2-bromoethyl)phosphate has been characterized and reported to inactivate NAD -dependent isocitrate dehydrogenase (283). The 2 - and 3 -(2-bromoethyl)-AMP labels have also been synthesized, and model reactions of the bromoethyl-AMPs with cysteine, lysine, histidine, and tyrosine have been studied (284). More recently, esters of adenosine 5 -monophosphate have been prepared with ethyl, propyl, or hexyl moieties and bromo or chloro substituents at the w position (285). Yeast alcohol dehydrogenase exhibited enhanced inactivation by the hexyl derivative, but inactivation rates of other dehydrogenases were unremarkable. Two iodopropyl derivatives of cAMP have been described, namely, 1, A -(3-iodopropyleno)adenosine 3, 5 -cyclic monophosphate and 3 -0-(2-iodo-3-hydroxypropyl)adenosine 3, 5 -cyclic monophosphate the latter inactivates cAMP phosphodiesterase from human platelets, with a pseudo-first-order rate constant of 0.147 hr" (286). 

Alkyl benzenesulfonates 686 20-30% sodium hydroxide solution is added dropwise, with vigorous shaking, to benzenesulfonyl chloride (1 part) and the alcohol (1 part), until the alkaline reaction is permanent after considerable shaking and the oil that separates is completely free from chlorine. Benzene and water are added, the two layers are separated, the organic layer is washed and dried, and the solvent and alcohol are removed in a vacuum by means of a water-bath at 30-40° (not higher). This process has afforded the allyl (explosive decomposition on distillation), 2-chloroethyl, b.p. 184°/9mm, 2-bromoethyl, b.p. 185-187°/ 16 mm, and 2-chloro-l-(chloromethyl)ethyl ester, b.p. 200-205°/20 mm, m.p. 50° (from benzene). 

A large number of substituted alkyl halides, for instance, chloro ethers,266 chloro sulfides,267 and halo carboxylic esters,268 provide syntheses of phosphonic esters containing also other functional groups. A-(2-Bromoethyl)-phthalimide leads, after hydrolysis, to / -amino phosphonic esters.269... 

Related reactions in the oxygen series were first observed only recently as complications in Michaelis-Arbuzov reactions. The 2-halo-alkyl phosphate and phosphonate esters which occur as intermediates in the Michaelis-Arbuzov reaction of certain cyclic phosphites and phos-phonites (cf. Section II-A-1) undergo an internal alkyl exchange reaction (eq. 4) (176). Although reaction of 8-bromoethyl acetate with triethyl phosphite is said to furnish the expected product, diethyl fi-acetoxyethylphosphonate, in 28% yield (220), reaction of this same alkyl halide with dimethyl phenylphosphonite (129) gave the expected methyl phenyl(/9-acetoxyethyl)phosphinate in not greater than 5% yield (eq. 6). Instead, the major products were d-acetoxyethyl phenyl-(methyl)phosphinate (60%) (12) and a mixture of ethylene bi [phenyl-(methyl)phosphinate], [CH20P(0)(Me)Ph]2, (13) and an, ester of... 

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