Alkyl halides with magnesium

The synthesis of 18 exemplifies the Grignard method. The reagent is made1 from the alkyl halide with magnesium metal in dry ether and combined, without isolation, with the electrophile— all steps being carried out under strictly anhydrous conditions. 

When a Grignard reagent is formed by reaction of an alkyl halide with magnesium metal, the stereochemical configuration at the Q -carbon is randomized. Radical intermediates in the formation of the Grignard reagent (see Section 4.2) are held responsible. Very rarely, as in the formation of (17), is there incomplete racemization ... 

By using this competitive technique for the reaction of alkyl halides with magnesium, the plots of Eq. (5) exhibited a linear character as illustrated in Figure 2. The relative rates (/C1//C2) were independent of the concentration of alkyl halide or the type of magnesium used, the size, the purity, the surface area, and the quantity. 

The same authors again concerned themselves [8 Id] with the question of the existence of alkyl radical anions as discrete intermediates along the reaction coordinate and whether the reaction of alkyl halides with magnesium proceeds by pathway 1 or 2 (see Fig. 1). In contrast to the view of Volger et al. [80], who referred to pathway 2 as an electron-transfer process [Eq. (6)] as originally described, Whitesides et al. viewed pathway 2, if it has an existence, as a halogen abstraction [Eq. (7)]. 

The in situ synthesis of organoboranes via reaction of alkyl halides with magnesium in the presence of diborane can also be used to prepare coupled products (equations 20 and 21). Oxidation of the reaction mixture with alkaline silver nitrate leads to good yields of dimeric products. The reaction is successful for primary and secondary halides. A related reaction is the coupling of secondary alkyl halides in the presence of catalytic quantities of thallium salts. This procedure fails for primary alkyl halides and gives modest yields for secondary alkyl halides (equation 22). 

Grignard reagent in this article, will refer to the solution prepared by reaction of an alkyl halide with magnesium metal, without implication as to molecular species actually present... 

A Grignard reagent is an organomagnesium compound formed by the reaction of an alkyl halide with magnesium metal 1,2,3,4, 5, 6,7,8,12,26,33,41. 

Specifically in the reaction of cyclopentyl bromide (R Br) in EtgO it was established that (/) -d[R Bi]jdt is proportional not only to [R Br] and the surface area of magnesium, but also to the rate of stirring of the solution and inversely proportional to the viscosity and (i7) the activation energy is small, ca. 2—3 kcal mol. There appears to be an upper limit to the rate of reaction of alkyl halides with magnesium. For less reactive halides, e.g., MeaCCHaBr, the rates are also dependent on the dielectric constant. 

At ordinary temperatures, zinc forms an addition compound with an alkyl halide (cf magnesium) ... 

The reaction is carried out by first reacting the alkyl or aryl halide with magnesium shavings in an ether suspension and then treating with silicon tetrachloride (prepared by passing chlorine over heated silicon). With methyl chloride the following sequence of reactions occur ... 

Oddo reported that the organomagnesium derivatives of p3Trole, indole, skatole, and carbazole could be prepared in a single operation by mixing the parent heterocyclic compound with an alkyl halide and magnesium in anhydrous ether.The product formed was reported to be the same as that obtained by the more conventional procedure. However, this approach to the synthesis of the indole Grignard reagents does not seem to have been exploited in subsequent work. 

Grignard reagents are made by reacting alkyl or aryl halides with magnesium turnings . 

Many other kinds of orgonometallic compounds can be prepared in a manner similar to that of Grignard reagents. For example, nlkyllithium reagents, RU. can he prepared by the reaction of an alkyl halide with lithium metal. Alkyllithiuma are both nucleophiles and bases, and their chemistry is similar in many respects to that of the alkyl magnesium halides. 

Alkyl halides, as well as sulfonates, besides being useful for the preparation of derivatives as shown above, are widely utilized for the preparation of phosphorus derivatives such as R-PPhi Hal , precursors for the generation of Wittig reagents. Alkyl halides are also extremely important as intermediates in the preparation of the most valuable derivatives of oxidation level 0, the organometallic compounds. The required reduction step is usually carried out via direct reaction of the alkyl halides with an active metal such as lithium or magnesium. 

By treating magnesium alkyl halides with arsenic trihalides ... 

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