Grignard reagent with acids

Synthesis of ketones by reaction of Grignard reagents with acid chlorides bearing substituents susceptible to side reactions (COOCHj, Cl) is possible if.the reaction is conducted at —70° in T1IF.2... 

Ultraviolet spectral data have been reported for a few organocopper compounds 36, 77, 253, 303). Methyl(triphenylphosphine)copper complexes were decomposed by UV light 310). The reaction of Grignard reagents with acid chlorides in the presence of copper(I) chloride, in which free radicals are supposedly formed via organocopper compounds, was also promoted by UV light 103). 

Fig. 4. Ionic and radical mechanisms in the syntheses of hindered ketones from the copper-catalyzed reaction of Grignard reagents with acid chlorides.

Acetylenic ketones can be prepared in moderate yield by the reaction of acetylenic Grignard reagents with acid chlorides or anhydrides [Eq. (41) 75-78]. Alkynyl magnesium chloride reacts with acetic anhydride to give acetylenic ketones in good yield (see Table 4, entry 17). 

Section 19.11 Carboxylic acids can be prepared by the reaction of Grignard reagents with carbon dioxide. 

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]. 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

TABLE 8. Formation of sulphoxides, R2S=0, from the reaction of Grignard reagents with sulphurous acid derivatives, SOX2... 

Few racemic alkyl p-tolyl sulphoxides were prepared in rather low yields (16—40%) by the reaction of Grignard reagents with mixed anhydrides 108, 109 and compound HO formed in situ from p-toluenesulphinic acid and 3-phthalimidoxy-l,2-benzoisothiazole 1, 1-dioxide167 (equation 59). The mixed anhydrides 109 or 110 when reacted with cyclopen-tene and cyclohexene enamines 111 gave the corresponding a-ketocycloalkyl sulphoxides 112 in low yields (10-41%) along with small amounts of several by-products such as disulphides and thiosulphonates167 (equation 60). 

Oxidation, of Grignard reagents with peresters, 41, 91 43, 55 of 2-hydroxy-3-methylbenzoic acid to 2-hydroxyisophthalic acid by-lead dioxide, 40, 48 of indene, 41, S3... 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

Aldehydes can be obtained by reaction of Grignard reagents with triethyl orthoformate. The addition step is preceded by elimination of one of the alkoxy groups to generate an electrophilic oxonium ion. The elimination is promoted by the magnesium ion acting as a Lewis acid.93 The acetals formed by the addition are stable to the reaction conditions, but are hydrolyzed to aldehydes by aqueous acid. 

Phosphorylthiophenes such as thiophenephosphonic acid diesters can be synthesized by reaction of thienyllithium or Grignard reagents with phosphoryl electrophiles [40],... 

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 reaction of a Grignard reagent with C02 can be used to prepare a carboxylic acid. 

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