Preparation of methyl ketones

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

Use of DMF as a solvent for the oxidation of l-o1efins has been reported by Clement and Selwitz. The method requires only a catalytic amount of PdCl2 and gives satisfactory yields under mild conditions. A small amount of olefin migration product is the only noticeable contaminant in the cases reported. The procedure can be applied satisfactorily to various 1-olefins with other functional groups. This useful synthetic method for the preparation of methyl ketones has been applied extensively in the syntheses of natural products such as steroids,macrolides, dihydrojasmone, and muscone. " A comprehensive review article on the palladium-catalyzed oxidation of olefins has... 

Fig. 6.49. Preparation of methyl ketones by (1) chemoselective acylation of a sulfinyl-stabilized "carbanion," (2) reduction (mechanism analogous to Figure 17.48).

Alkylation of the enolate anion derived from ethyl acetoacetate followed by removal of the ester group is known as the acetoacetic ester synthesis and is an excellent method for the preparation of methyl ketones. The product of an acetoacetic ester synthesis is the same as the product that would be produced by the addition of the same... 

Methoxybenzenetellurinic anhydride served as catalyst for the preparation of methyl ketones from terminal acetylenic compounds4. 

The a-hydrogens of enol ethers may be deprotonated with tert-BuLi Alkylation of the resultant vinyl anions followed by acidic hydrolysis provides an efficient route for the preparation of methyl ketones. 

Acetoacetic ester synthesis preparation of methyl ketones (Section 19.19). 

A new vitamin A synthesis has been described featuring an efficient dehydration step without double bond migration Olefins can be obtained from glycols with complete control of the position as well as the stereochemistry of the double bond. Together with Irans-hydroxylations this reaction constitutes a general and unambiguous method for the interconversion of ci5- and trans-olefins Monoperoxysuccinic acid has recently been recommended for the conversion of olefins into trans-glycols Also a convenient preparation of methyl ketones from terminal olefins has been reported... 

Coupling with Organometallic Reagents. Coupling of organometallic reagents with AcCl is a valuable method for preparation of methyl ketones. Generally a catalyst (either a Lewis acid or transition metal salt) is required. 

A related synthesis of apratoxin began with the preparation of methyl ketone 119, which was then condensed with (R)-55 to obtain hydrazone 120 (Scheme 7.20). ACC hydrazone 120 was then subjected to the a,a-bisalkylation sequence using methyl iodide followed by allyl bromide, which proceeded in excellent overall yield and with excellent stereoselectivity dr > 99 1). At this stage, attempts to remove the auxiliary under standard conditions were unsuccessful. However, it was established that the hydrolysis was effective following deprotection of the a -hydroxyl. The derived ketone 123 then underwent a series of transformations, ultimately leading to the first asymmetric total synthesis of apratoxin D 124. 

Thus if R = n-propyl (ethyl n-propylacetoacetate), methyl n-butyl ketone is produced. The preparation of this ketone is described in Section 111,152 under Ethyl Aceioacetate. 

For the preparation of methyl n butyl ketone and methyl n amyl ketone by another method, see Section 111,152. 

Cool the mixture and decant the solution from the sodium bromide wash the salt with two 20 ml. portions of absolute alcohol and add the washings to the main solution. Distil off the alcohol, which contains the slight excess of n-propyl bromide used in the condensation, through a short fractionating column from a water bath. The residue A) of crude ethyl n-propylacetoacetate may be used directly in the preparation of methyl n-butyl ketone. If the fairly pure ester is required, distil the crude product under diminished pressure and collect the fraction boihng at 109-113727 mm. (183 g.) (R). 

If cyclic ketones are monosubstituted in the a-position, their rates of reaction decrease as compared to the rate for the parent ketone (9,41). More highly substituted ketones (e.g., diisobutyl ketone, diisopropyl ketone) can be caused to react using newer preparative techniques (39,43,44, see Section VII). Monosubstituted acetones often can give selfcondensation products, but the recent literature (13,39,43) contains reports of the successful formation of the enamines of methyl ketones. 

If used for the preparation of methyl benzyl ketone (p. 54) the product should not be dried. 

The study of alkynylation of methyl ketones using a terminal alkyne, ZnMe2, and a salen derivative 196 as a chirality inductor provided a new method for the preparation of ct-hydroxyacetylenes (197, Scheme 112).292... 

Uses Manufacture of flotation agents, esters (perfumes and flavors), dyestuffs, wetting agents ingredient in industrial cleaners and paint removers preparation of methyl ethyl ketone solvent in lacquers in hydraulic brake fluids organic synthesis. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

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