Alcohols from Carbonyl Compounds Grignard Reaction

5 Alcohols from Carbonyl Compounds Grignard Reaction 

The reaction of Grignard reagents with carbonyl compounds has no direct counterpart in biological chemistry because organomagnesium compounds are 

As examples of their addition to carbonyl compounds, Grignard reagents react with formaldehyde, H2C=0, to give primary alcohols, with aldehydes to give secondary alcohols, and with ketones to give tertiary alcohols. 

Esters react with Grignard reagents to yield tertiary alcohols in which two of the substituents bonded to the hydroxyl-bearing carbon have come from the Grignard reagent, just as UAIH4 reduction of an ester adds two hydrogens. 

Carboxylic acids don t give addition products with Grignard reagents because the acidic carboxyl hydrogen reacts with the basic Grignard reagent to yield a hydrocarbon and the magnesium salt of the acid. 

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I Alcohols from Carbonyl Compounds Grignard Reaction 635... 

Reduction of the carbonyl function in acetophenones using sodium in ethanol also produces an alcohol. More complex aromatic alcohols may be prepared from carbonyl compounds by reaction with Grignard reagents followed by hydrolysis (see Chapter 10). 

Alcohols may be prepared (1) by hydration of alkenes (1) in presence of an acid and (11) by hydroboratlon-oxidatlon reaction (2) from carbonyl compounds by (1) catalytic reduction and (11) the action of Grignard reagents. Phenols may be prepared by (1) substitution of (1) halogen atom In haloarenes and (11) sulphonic acid group In aiyl sulphonic acids, by -OH group (2) by hydrolysis of diazonium salts and (3) industrially from cumene. 

Alcohols from Reaction of Carbonyl Compounds with Grignard Reagents 613... 

One way to create a carbon-carbon bond is to react a Grignard reagent with a carbonyl compound. The result of this reaction is an alcohol derived from an aldehyde. Formaldehyde gives a primary alcohol, but any other aldehyde gives a secondary alcohol. Ketones and esters both react to form tertiary alcohols. 

Enolization is an acid-base reaction (2-24) in which a proton is transferred from the a carbon to the Grignard reagent. The carbonyl compound is converted to its enolate ion form, which, on hydrolysis, gives the original ketone or aldehyde. Enolization is important not only for hindered ketones but also for those that have a relatively high percentage of enol form, e.g., p-keto esters, etc. In reduction, the carbonyl compound is reduced to an alcohol (6-25)... 

All of these syntheses involve a Grignard reaction at some step. Both the carbonyl compound and the Grignard reagent must be prepared from alcohols. 

Another isohypsic transformation of special significance involves elimination of H-X elements from allylic derivatives to form 1,3-dienes. Besides being extremely important compounds as monomers, 1,3-dienes occupy a unique position in synthetic practice as components in the Diels-Alder reaction. One of the common routes of synthesis of 1,3-dienes also employs a vinyl Grignard addition to carbonyl compounds as the initial step (Scheme 2.55). Allylic alcohols thus formed can easily undergo 1,2-elimination (in some cases it is preferable first to transform the alcohols into their respective acetates). 

In 1912 Victor Grignard received the Nobel prize in chemistry for his work on the reaction that bears his name, a carbon-carbon bond-forming reaction by which almost any alcohol may be formed from appropriate alkyl halides and carbonyl compounds. The Grignard reagent is easily formed by reaction of an alkyl halide, in particular a bromide, with magnesium metal in anhydrous ether. Although the reaction can be written and thought of as simply... 

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