PREPARATION OF KETONES

Q The nucleophile attacks the electrophilic carbon of the cyano group. 

This intermediate is too weak an electrophile to react with the Grignard reagent. It is stable in the solution until acid is added during the workup. 

Mechanism of the reaction of a Grignard reagent with a nitrile to produce a ketone. 

Suggest methods to accomplish the following transformations. More than one step may be necessary in some cases. 

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Related Methods Section 48 (Aldehydes from Alcohols and Thiols). 

1 % Cu(II) 2-ethyl hexanoate 18% allyl ethyl ether, MeCN 

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Related Methods Aldehydes from Alcohols and Phenols (Section 48) 

SECTION 170 Ketones from Alkyls, Methylenes, and Aryls 

SECTION 174 Ketones from Ethers, Epoxides, and Thloethers 

Kgneko, Y. Kumagawa, T., Izawa, T. Sakata, K.J Yamakawa, K. 

Related Methods Ketones from Ketones (Section 177) Aldehydes from halides (Section 55) 

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The main use of organocadmium compounds is for the preparation of ketones and keto-esters, and their special merit lies in the fact that they react vigorously with acid chlorides of all types but add sluggishly or not at all to multiple bonds (compare addition of Grignard reagents to carbonyl groups). Some t3rpical syntheses are ... 

Section 20 20 Nitriles are useful starting materials for the preparation of ketones by reaction with Grignard reagents... 

Acetoacetic ester synthesis (Section 21 6) A synthetic method for the preparation of ketones in which alkylation of the enolate of ethyl acetoacetate... 

Ketones are an important class of industrial chemicals that have found widespread use as solvents and chemical intermediates. Acetone (qv) is the simplest and most important ketone and finds ubiquitous use as a solvent. Higher members of the aUphatic methyl ketone series (eg, methyl ethyl ketone, methyl isobutyl ketone, and methyl amyl ketone) are also industrially significant solvents. Cyclohexanone is the most important cycHc ketone and is primarily used in the manufacture of y-caprolactam for nylon-6 (see Cyclohexanoland cyclohexanone). Other ketones find appHcation in fields as diverse as fragrance formulation and metals extraction. Although the industrially important ketones are reviewed herein, the laboratory preparation of ketones is covered elsewhere (1). 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

Dialkylcadmium reagents are often useful alternatives to the more reactive Gngnard reagents in the preparation of ketones from acyl halides However, bis(trifluotomethyl)cadmium glyme is decomposed by acyl halides and does not give trifluoromethyl ketones [, 124] Nevertheless, this reaction can be used as a low-temperature source of difluorocarbene [S, 124] (equation 102)... 

Ethyl acetoacetate (acetoacetic ester), available by the Claisen condensation of ethyl acetate, has properties that make it a useful starting material for the preparation of ketones. These properties are... 

This reaction sequence is called the acetoacetic ester synthesis. It is a standard procedure for the preparation of ketones from alkyl halides, as the conversion of 1-bromobutane to 2-heptanone illustrates. 

Iodine in functionalization of C 19 meth> 1 group of 3d acetoxy 20/3 hydroxy 5 pregnene 46, 58 Iron powder in preparation of ketones from carboxylic acids, 47, 75 Isobutene, 45, 49... 

The reaction has been extended to the preparation of ketones treatment of a... 

For a list of preparations of ketones by the reaction of organometallic compounds with carboxylic esters, salts, anhydyrides, or amides, with references, see Ref. 568, pp. 685, 693. 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

V-Methyl-A-methoxyamides are also useful starting materials for preparation of ketones Again, the reaction depends upon the stability of the tetrahedral intermediate against elimination and a second addition step. In this case chelation with the IV-methoxy substituent is responsible. 

The most common application of organocadmium compounds has been in the preparation of ketones by reaction with acyl chlorides. A major disadvantage of the use of organocadmium reagents is the toxicity and environmental problems associated with use of cadmium, and this has limited the recent use of organocadmium reagents. 

The preparation of ketones proceeds conveniently by reaction of imidazolides with organomagnesium reagents, as shown in Table 14-6 for several examples of purely aromatic, aromatic-aliphatic, and purely aliphatic ketones. The yields are very satisfactory even for purely aliphatic ketones, since in this case, too, alcohol formation is completely suppressed.t851,t861... 

Another method for the preparation of ketones is the reaction of imidazolides, ben-zimidazolides, or benzotriazolides with organoaluminum compounds [94]... 

This is a general method for the preparation of higher aliphatic ketones, it has been found suitable for the preparation of ketones from fatty acids containing 12 to 20 carbon atoms. 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

Scheme 14.37. Preparation of ketones by the titanocene(ll)-promoted reaction of thioacetals with nitriles.

Too-fast addition of acyl halides during preparation of ketones may lead to explosive reactions. 

Thioacetals and thioketals have significant synthetic potential for use in organic chemistry but are often neglected because of their unpleasant odor. A polymeric reagent for the preparation of ketones via 1,3-dithianes has been reported using... 

The in situ generation of an afkyllithium reagent, from an alkyl chloride 13 and lithium in the presence of a catalytic amonnt of naphthalene (10%), and its reaction with carboxylic acids 14 allowed a general preparation of ketones 15 in a one-pot procednre (Scheme 6) °. 

Addition of organometallic reagent to nitrile preparation of ketones... 

Oxidative cleavage of syn-diols preparation of ketones and aldehydes or carboxylic acids... 

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