SYNTHESIS OF ALCOHOLS USING GRIGNARD REAGENTS

Grignard reagents, alkyl magnesium halides (R - Mg - X), react with aldehydes and ketones. 

If a primary alcohol is desired, the reaction should be initiated with formaldehyde. By this way, an alcohol, containing at least two carbons, is produced. 

If a secondary alcohol is desired, Grignard reagents should be reacted with an aldehyde other than formaldehyde. 

If a tertiary alcohol is desired the Grignard reagent should be reacted with a 

Give the required reactants needed to produce the following compounds using Grignard reagents and write down the chemical equations. 

Grignard reagents add to carbonyl compounds to give primary, secondary, and tertiary alcohols. A primary alcohol is synthesized by reacting the Grignard reagent, R —MgX, with formaldehyde. 

Reacting a Grignard reagent with an aldehyde gives a secondary alcohol. 

The main synthetic application of Grignard reagents is their reaction with carbonyl-containing compounds to produce alcohols. Carbon-carbon bond formation is rapid and exothermic when a Grignard reagent reacts with an aldehyde or ketone. 

TABLE 14.2 Reactions of Crignard Reagents with Aldehydes and Ketones 

Reaction with formaldehyde Grignard reagents react with formaldehyde (H2C=0) to give primary alcohols having one more carbon than the Grignard reagent. 

Reaction with aldehydes Grignard reagents react with aldehydes (R CH=0) to give secondary alcohols. 

Reaction with ketones Grignard reagents react 0 

PROBLEM 14.4 Butyllithium is commercially available and is frequently used by organic chemists as a strong base. Show how you could use butyllithium to prepare solutions containing 

SAMPLE SOLUTION When butyllithium is used as a base, it abstracts a proton, in this case a proton attached to nitrogen. The source of lithium diethylamide must be diethylamine. 

Although diethylamine Is not specifically listed in Table 14.2, its strength as an acid (/Ca 10 ) is, as might be expected, similar to that of ammonia. 

Deuterium Is the mass 2 Isotope of hydrogen. Deuterium oxide (D2O) Is sometimes called heavy water.  

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Synthesis of alcohols using organolithium reagents (Section 14.7) Organolithium reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to produce alcohols. 

Synthesis of Alcohols Using Grignard and Organolithium Reagents... 

Acetic formic anhydride has been prepared by the reaction of formic acid with acetic anhydride2 3 and ketene,4,5 and of acetyl chloride with sodium formate.6 The present procedure is essentially that of Muramatsu.6 It is simpler than others previously described and gives better yields. It is easily adapted to the preparation of large quantities, usually with an increase in yield. Acetic formic anhydride is a useful intermediate for the formyl-ation of amines,3,7 amino acids,8,9 and alcohols,2,10 for the synthesis of aldehydes from Grignard reagents,11 and for the preparation of formyl fluoride.12... 

In the addition reactions of aldehydes and ketones, a tetrahedral product forms because of attack of a nucleophile at the carbonyl carbon atom. Examples include the formation of hemiacetals with alcohols, and the synthesis of alcohols using the Grignard reagent. 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

The reaction of esters with Grignard reagents and with lithium aluminum hydride, both useful in the synthesis of alcohols, were described earlier. They are reviewed in Table... 

A-7. Synthesis of the following alcohol is possible by three schemes using Grignard reagents. Give the reagents necessary to carry out each of them. 

The coupling of propargyl alcohols with Grignard reagents in the presence of HMPT and Cul provides a useful synthesis of allenes in yields of 60-95%. 

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