Reagent, Grignard

Grignard reagents are widely used in organic chemistry. They are prepared by the interaction of magnesium with an organic halide in ethers. Grignard reagents 

Molecular structure of Grignard reagent (C2H5 )MgBr-2(C2 H5)20. 

In a Grignard compound the carbon atom bonded to the electropositive Mg atom carries a partial negative charge. Consequently a Grignard reagent is an extremely strong base, with its carbanion-like alkyl or aryl portion acting as a nucleophile. 

Molecular model of a complex of methyl-magnesium chloride, a Grignard reagent, in which two molecules of tetrahydrofuran, THF, are bound to magnesium. The model is based on the crystal structure. 

The polarity of the carbon-magnesium bond is opposite that of the carbon—halogen bond of haloalkanes. Because the carbon atom in a Grignard reagent has a partial negative charge, it resembles a carb-anion, and it reacts with electrophilic centers such as the carbonyl carbon atom of aldehydes, ketones, and esters. We will discuss this chemistry extensively in later chapters. 

Devise a synthesis of CHjCH,GHDGHj starting from 1-butene and heavy water (D O). 

Reaction of a Grignard reagent, RMgBr, with D O will yield R—D. The necessary Grignard reagent is obtained from the corresponding bromoalkane, RBr. 

The required 2-bromobutane can be prepared from 1-butene by adding HBr. This reaction occurs according to Markovnikovs rule, and a hydrogen atom adds to the less substituted carbon atom of the double bond. 

Careful evaporation of solvent from solutions of Grignard reagents leaves colourless solids or viscous liquids. It is diflBcult to remove all traces of ether below 100°C. Prolonged pumping to constant weight at 90-120°/10 mm leads to dismutation of RMgX to [R2Mg] and MgX (R = Me, Et X = Cl, Br). Careful crystallization, however, has yielded materials suitable for X-ray analysis. Some 

When dissolved in ethers, Grignard reagents have the composition RMgX. . On addition of dioxan, magnesium halide is precipitated as the dioxan complex MgX2 2 dioxan, leaving R Mg in solution. An equimolar mixture of R2Mg and 

MgX dissolved in an ether is identical to a Grignard solution, provided that sufficient time is allowed for equilibration. The rate of attainment of equilibrium falls X = Cl Br I R = primary secondary tertiary. This evidence points to the existence of an equilibrium, called the Schlenk equilibrium. 

This is consistent with the ready isotopic exchange which is observed when radioactive MgBr or MgBr is added to solutions of Et Mg or of EtMgBr. In ether RMgX predominates, whereas in THE there is a distribution close to random (Table 3.5). The difference between the two solvents arises from the greater degree of solvation by THE, especially of MgX.  

Solutions of Grignard reagents in ether conduct electricity, but the molar 

A convenient method for generating carbon nucleophiles is to combine an organic halide, RX, with magnesium metal. This yields RMgX, a Grignard reagent . 

What effect does the solvent have on the structure, charges and reactivity of Grignards Compare geometries, atomic charges and electrostatic potential maps of the diethyl ether complex to that of methylmagnesium chloride itself. How does solvent-magnesium bond formation affect the reactivity of the methyl group Explain. 

Electrostatic potential map for methylmagnesium chloride-diethyl ether complex shows negatively-charged regions (in red) and positively-charged regions (in blue). 

LUMO for equatorial methylcyclohexanone reveals likely site of nucleophilic attack. 

LUMO map for equatorial methylcyclohexanone shows (in blue) where the LUMO is most-heavily concentrated. 

Review Comprehensive Organic Synthesis, Eds. B. M. Trost and I. Fleming, Pergamon, Oxford (1991), Vol 3, Part 1.6, p 241 

For transition metal-catalyzed cross-coupling reactions of Grignard reagents, see the appropriate transition metal. 

---

CH3)2N]3P0. M.p. 4°C, b.p. 232"C, dielectric constant 30 at 25 C. Can be prepared from dimethylamine and phosphorus oxychloride. Used as an aprotic solvent, similar to liquid ammonia in solvent power but easier to handle. Solvent for organolithium compounds, Grignard reagents and the metals lithium, sodium and potassium (the latter metals give blue solutions). 

Methods of producing B —C bonds include hydroboration, nucleophilic displacement at a boron atom in BX., (X = halogens or B(0R>3) by e.g. a Grignard reagent, and a psewiio-Friedel-Crafts reaction with an aromatic hydrocarbon, BX3, and AICI3. 

Diethyl ether is a mobile, colourless liquid having b.p. 35° and dy 0720. It has a characteristic odour, and a burning taste. It is used chiefly as a solvent, and was formerly widely used as an anaesthetic owing to its chemical non-reactivity, it is very seldom used actually as a reagent, except in the preparation of Grignard reagents (p. 280) where probably its chemical properties reinforce its solvent action. 

Pure Ether. Pure ether (entirely free in particular from water) is frequently required in the laboratory, and especially for the preparation and use of Grignard reagents. It is best prepared in quantity for classes by adding an ample quantity of granular calcium chloride to a Winchester bottle of technical ether, and allowing the mixture to stand for at least 24 hours, preferably with occasional shaking. The greater part of the water and... 

Bromobenzene is a colourless liquid of b.p. 156°, and d, 1 50 it has a faint agreeable odour. The bromine atom, being directly joined to the benzene ring, is very inert, and the only common reactions in which it is split off from the ring are the Fittig reaction (p. 288) and the Grignard reagent (pp. 280-284). 

For the preparation of the Grignard reagent, the following factors should be noted ... 

No attempt is made to isolate the Grignard reagent from its ethereal solution before use. The reagent (usually also in ethereal solution) is added to the solution of the Grignard reagent, and when the reaction is complete the product is hydrolysed. 

Water, alcohols and hydroxy compounds generally, and also primary and secondary amines, give the hydrocarbon corresponding to the Grignard reagent,... 

Note that ethylene oxide reacts with the Grignard reagent to gi e a 2-substi tuted ethanol e.g. with methyl magnesium iodide ... 

Esters (a) and acid chlorides (6) readily react with Grignard reagents to give ketones, which immediately react with a second equivalent of the reagent as in (5) to give tertiary alcohols as before. 

Nitriles also react w ith Grignard reagents to give ketones, which arise from the hydrolysing action of the dilute sulphuric acid on the intermediate addition product. Acid amides beha e similarly. 

Since Grignard reagents can easily be obtained from aryl halides, they are of special value in the s nthesis of many aromatic compounds, particularly as, for reasons already stated (pp. 270, 276), aromatic compounds cannot generally be prepared by means of ethyl acetoacetate and ethyl malonate. 

The Reformatsky Reaction consists of the interaction of an ester of an a-halogeno-acid with an aldehyde, a ketone or another ester in the presence of zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is heated with zinc, the latter undoubtedly first combines with the ethyl bromoacetate to form a Grignard-like reagent (reaction A), which then adds on to the benzaldehyde Just as a Grignard reagent would do (reaction B). The complex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate (reaction C). Note that reaction A could not satisfactorily be carried out using... 

This preparation illustrates the preparation of a liquid hydrocarbon from a Grignard reagent. The Grignard reagent from n-hexyl bromide may be decomposed either with dilute sulphuric acid or with solid ammonium chloride the latter gives a somewhat better 3neld. 

A general method for the synthesis of l -alkenes is provided by the action of a Grignard reagent upon allyl bromide, for example ... 

---