Tertiary alcohols Grignard reactions

Thus hydroxide ion leads to saponification (p. 231) another alkoxide ion leads to transesterification (p. 231) and carbanions give keto compounds or tertiary alcohols (Grignard reaction). 

Conversion of Esters into Alcohols Grignard Reaction Esters and lactones react with 2 equivalents of a Grignard reagent to yield a tertiary alcohol in which two of the substituents are identical (Section 17.5). The reaction occurs by the usual nucleophilic substitution mechanism to give an intermediate ketone, which reacts further with the Grignard reagent to yield a tertiary alcohol. 

The abundance of fatty acids in triacylglycerols (TAG) can be determined by conversion of the acyl groups into tertiary alcohols on reaction with an alkyl Grignard reagent, followed by chromatographic separation. The method was found to be of advantage over saponification and conversion to a methyl ester, especially in the determination of short-chain fatty acids, which suffer losses by volatilization. ... 

Friedel-Crafts acylation is one of the most important methods of preparing ketones in which the carbonyl group is attached to an aromatic ring. Once formed, these ketones may be converted into secondary alcohols by reduction, into tertiary alcohols by reaction with Grignard reagents, and into many other important classes of compounds, as we shall see. 

Esters react with two equivalents of a Grignard reagent to give tertiary alcohols. The reaction proceeds by irreversible nucleophilic attack of the Grignard reagent on the ester carbonyl group. The initial product, a ketone, reacts further in the usual way to give the tertiary alcohol. 

The type of alcohol produced depends on the carbonyl compound. Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.1, formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. Analogous reactions take place with organolithium reagents. 

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 Formaldehyde reaction... 

Reaction of Grignard reagents with es ters (Section 14 10) Tertiary alcohols in which two of the substituents on the hy droxyl carbon are the same may be pre pared by the reaction of an ester with two equivalents of a Grignard reagent... 

Barbier reported (1) in 1899 that a mixture of methyl iodide, a methyl ketone, and magnesium metal in diethyl ether produced a tertiary alcohol. Detailed studies by his student Victor Grignard are documented in his now classical doctoral thesis, presented in 1901. Grignard estabUshed (2) that the reaction observed by Barbier could be separated into three distinct steps Grignard reagent formation, Grignard reaction, and hydrolysis. 

The reaction of Grignard reagents with the keto group of 5a-cholestan-3-one (7) was first described in 1937/ In a later study, Barton obtained the two epimeric tertiary alcohols (8) and (9), in a ratio of 40 60 by exposing (7) to the action of methyl Grignard reagent. 

The various Grignard reagents react with a variety of aldehydes and ketones to yield primary alcohols (yield, 27 6%), secondary alcohols (yield, 13 1-71 1%), and tertiary alcohols (yield, 24 9-81 7%) Products of the reactions with acetone are given in Table 4... 

An interesting appetite suppressant very distantly related to hexahydroamphetamines is somanta-dine (24). The reported synthesis starts with conversion of 1-adamantanecarboxylic acid (20) via the usual steps to the ester, reduction to the alcohol, transformation to the bromide (21), conversion of the latter to a Grignard reagent with magnesium metal, and transformation to tertiary alcohol 22 by reaction with acetone. Displacement to the fomiamide (23) and hydrolysis to the tertiary amine (24) completes the preparation of somantadine [6]. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Reaction of Acid Chlorides with Organometallic Reagents Grignard reagents react with acid chlorides to yield tertiary alcohols in which two of the substituents are the same. 

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