Reformatsky Reaction in Water:  Evidence for a Radical Chain Process

Abstract

The Reformatsky reaction of 2-bromo esters and carbonyl compounds in the presence of zinc can be carried out in concentrated aqueous salt solutions without any cosolvent. The reaction of bromoacetates is greatly enhanced by catalytic amounts of benzoyl peroxide or peracids and gives satisfactory yields with aromatic aldehydes. Preparative yields comparable to those of the traditional procedure are obtained with ethyl 2-bromoisobutyrate. This ester needs no catalyst and reacts even with saturated aldehydes and aromatic ketones, although in low yields. A radical chain mechanism, initiated by electron abstraction from the organometallic Reformatsky reagent, is proposed. Two nonchain pathways, involving radicals directly produced on the metal surface, may compete, especially in the case of secondary and tertiary halides.

A novel electrosynthesis cell with a compressed graphite powder cathode and minimal organic solvent content: Application to the Reformatsky reaction

“…The presence of fluorine in the ortho position had no effect on the reaction yield when compared with benzaldehyde as substrate (Table 3, entries 1 and 2), whereas the presence of electron donating groups gave rise to slight reductions in yield (Table 3, entries 3 and 4) in keeping with the nucleophilic character of the intermediate. Table 4 presents the yields of coupling products formed by the electrochemical reaction of ethyl bromoacetate, ethyl 2-bromopropionate and 1 with 2 in comparison with those obtained previously in the aqueous Reformatsky reaction promoted by zinc [30]. All procedures show the same trend, namely, a decrease in product yield from tertiary to secondary to primary bromoester, and the values are numerically somewhat similar.…”

“…As already discussed in a previous publication [30], the order of reactivity is best explained in terms of radical intermediates derived from the bromoesters by dissociative electron transfer adding to the carbonyl bond. The resulting alkoxy radical would then be reduced by a second electron and protonated to give 3 [40].…”

“…In 1997, Bieber et al [30] described a novel, three-phase, zincpromoted Reformatsky reaction for the preparation of a large number of aromatic and aliphatic aldehydes and primary, secondary and tertiary ␣-halo-esters. The reaction was efficiently catalyzed by dibenzoyl peroxide (BzO) 2 , suggesting the participation of a radical mechanism, and the system, which consisted of a heterogeneous mixture of concentrated aqueous salt solution, organic reagents and zinc powder, had to be stirred vigorously throughout the procedure.…”

Reductive coupling reaction of benzyl, allyl and alkyl halides in aqueous medium promoted by zinc

“…In contrast to the aqueous Reformatsky reaction, 18 the presence of a radical initiator (benzoyl peroxide) and/or radical scavenger (galvinoxyl) produced no significant effects, although these results by themselves can not exclude either a radical mechanism or an S N 2 reaction.…”

Radical intermediates in the Zn-promoted Barbier-type alkylation of diphenyl diselenide in aqueous medium

“…1 The metal-promoted one-pot addition of allylic, 2 benzylic 3 and propargylic halides 4 to carbonyl compounds has shown comparable or even better results than traditional methods using Li or Mg reagents under anhydrous conditions. Saturated halides 5 and a-haloesters 6 have also been reacted successfully. On the other hand, different electrophilic substrates such as carboxylic esters and anhydrides, 7 nitriles, 8 oximes, 9 imines, 10 and iminium ions 11 have shown interesting reactivities.…”