Grignard reaction with water

The reactions of Grignard reagents with water and alcohols are simply acid-base reactions => the Grignard reagent behaves as if it contained an carbanion. 

The Grignard reaction is often one of the first reactions encountered for the preparation of organometallic compounds. As such it provides a method for the conversion of an alkyl bromide to an alkane. From the example shown below it is seen that the overall oxidation level change from the organic reactants to the products is from 0 to —2, so a reduction has occurred. Magnesium is the reductant and is itself oxidized from 0 to +2 oxidation state. The actual reduction takes place in the first step of the process in which the C-Br bond is converted to a C-Mg-Br bond. The reaction with water is merely a hydrolysis that does not change the oxidation state of carbon. 

Reactions with Water-Sensitive Reagents such as Grignard Reagents, Lithium Alkyls, or Zinc Oiganyls [375] on Solid Phases... 

Organolithium and Grignard reagents are prepared from alkyl (or aryl) halides. The reactions are carried out under anhydrous conditions because reaction with water leads to the formation of alkanes. 

Once again, the RD side-reaction proceeds by the protonation of arylnickel (or palladium) intermediates with water or other protic sources (see Chapter 3). The reaction is related to the quenching of Grignard reagent with water or alcohols to furnish a parent hydrocarbon. 

The reaction of a Grignard reagent with water can be put to useful purpose. For example, if heavy water (D2O) is used, deuterium (an isotope of hydrogen) can be substituted for a halogen. 

The reaction of the Grignard reagent with water is the basis of the analytical method used in this experiment. 

Reaction of a Grignard reagent with water is an example of an acid-base reaction (Section 1.7.6)... 

Preparation of Isocyanates. Isocyanates are prepared by rearrang-ii azides in inert solvents such as ethers, chloroform, benzene and its homologs, malonic ester, mid ligroin. If the isocyanate is to be isolated, the solvent is removed by distillation, or, if the isocyanate is the lower boiling, it is distilled directly. In this operation, a safety shield is advisable to guard against a possible explosion of yet undecomposed azide. Isocyanates can be converted to sym-ureas by reaction with water, to urethans by reaction with alcohols, to os-ureas by reaction with amines, or to acylamines by reaction with anhydrous acids or acid anhydrides, or they can be hydrolyzed directly to amines. Acylamines can also be obtained. from isocyanates by reaction with Grignard re-... 

Synthesis of Vitamin D3 Core 248 Phosphine oxide 245 (1.1 equiv) was dissolved in anhydrous THF, cooled to —50°C, and treated with nBuLi (1.0 equiv) under argon. The mixture was then transferred via cannula to a solution of resin-bound ketone 244 (0.72 equiv) in anhydrous THF and reacted at —40°C to — 10°C for 3 hours to yield immobilized triene 246. Concomitant alkylation and cleavage from the polymer-support occurred via a copper-promoted Grignard reaction with 247 at room temperature for 3 hours. The crude protected product was then immediately treated with CSA in methanol and water at room temperature for 6 hours to afford vitamin D3 analog 248 in 47% yield (from 244). 

Now let s draw the forward scheme. Hydrolysis of acetonitrile gives acetic acid which is subsequently reduced to ethanol upon treatment with excess LAH, followed by water work-up. Upon treatment with PBrj, ethanol is converted to ethyl bromide which is then converted to ethyl magnesium bromide (a Grignard reagent). A Grignard reaction with acetaldehyde (produced by PCC oxidation of ethanol, as shown), followed by water work-up, produces the desired alcohol, 2-butanol. 

The alcohol can be made from a ketone, via a Grignard reaction (with methyl magnesium bromide, followed by water work-up). 

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