Methyl ketones, preparation

The sodium salts of the hydrazones of 2-hydroxybenzaldehydes or of 2-hydroxyphenyl methyl ketones, prepared from the phenols and sodium methoxide in methanol, condensed... 

Terminal double bonds are selectively oxidized to methyl ketones. A typical procedure for the oxidation of 1-decene to 2-decanone in 65-73% yield with PdCli/CuCl is given in Organic SynthesisAlthough there are several known synthetic methods for methyl ketone preparation, the PdCh-catalyzed oxidation of terminal alkenes seems to be one of the best. In other words, terminal alkenes can be regarded as precursors of methyl ketones, or as masked methyl ketones based on this reaction. This re-... 

Good results are obtained by the oxidation of the commercially available cyclo-propyl methyl ketone with sodium hypobromite solution, and the preparation may be regarded as an excellent example of the oxidation of the —COCH, group to — OOH ... 

Several 1,4-dicarbonyl compounds are prepared based on this oxidation. Typically, the 1,4-diketone 10 or the 1,4-keto aldehyde 12 can be prepared by the allylation of a ketone[24] or aldehyde[61,62], followed by oxidation. The reaction is a good annulation method for cyclopentenones (11 and 13). Syntheses of pentalenene[78], laurenene[67], descarboxyquadrone[79], muscone (14 R = Me)[80]) and the coriolin intermediate 15[71] have been carried out by using allyl group as the masked methyl ketone (facing page). 

The haloform reaction is sometimes used for the preparation of carboxylic acids from methyl ketones... 

Cyclopentyl methyl ketone has been prepared from 1 4 dibro... 

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). 

Garyophyllene. (-)-CaryophyUene can be isolated from Indian turpentine and has been used to prepare a number of woody aroma products. The epoxides are produced by reaction with peracids. Acetylation of caryophyUene also gives a usehil methyl ketone (180) (Fig. 8). Acid-catalyzed rearrangement of caryophyUene in the presence of acetic acid gives a mixture of esters, which are related to caryolan-l-ol and clovan-2-ol (181). 

Cyanopyridazines add ammonia, primary and secondary amines and hydroxylamine to give amidines or amidoximes. Substituted amides, thioamides and carboximidates can be also prepared. With hydrazine, 3-pyridazinylcarbohydrazide imide is formed and addition of methylmagnesium iodide with subsequent hydrolysis of the imine affords the corresponding pyridazinyl methyl ketone. 

The type of synthesis in which the two-atom fragment supplies C-5 + C-6 is uncommon but useful in preparing pyrimidine- and 5,6,7,8-tetrahydroquinazoline-2,4-diamines. Thus, dicyandiamide (S78) with benzyl methyl ketone (S77) yields 6-methyl-5-phenylpyrimidine-2,4-diamine (S79), or with acetophenone it yields 6-phenylpyrimidine-2,4-diamine (62JOC2708). Likewise, with cyclohexanone it yields the tetrahydroquinazolinediamine (SSO) and by using N- substituted dicyandiamides, 2- and/or 4-alkylamino groups may be introduced (65JOC1837). 

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... 

This method may be used for the preparation of larger quantities, a batch twenty times this size giving a yield of 87 per cent. It may be used also for the preparation of other aromatic acids where suitable ketones are available. Methyl a-naphthyl ketone prepared by Caille s method is not suitable for the preparation of a-naphthoic acid as it contains at least 30 per cent of the methyl d-naphthyl ketone. 

Naphthoic acid has been prepared principally by the hydrolj sis of d-naphthonitriled the overall yields from (3-naph-thylamine, from sodinm-/3-naphthalene sulfonate, and from calcium d-naphthalene sulfonate being given as (approximately) 20 per cent, 21 per cent, and 50 per cent, respectively. The acid has been prepared also by the carbonation of the Grignard reagent from the less accessible /3-bromo derivative and. more recendy, from the readily available methyl ketone. ... 

The more important methods of preparation of diazomethane include those from nitrosomethylurea, nitrosomcthylurethane, N-nitroso-/3-methylaminoisobutyl methyl ketone, and 1-methyl-l-nitroso-3-nitroguanidine. ... 

Grignard additions to conjugated ketones preparation of la-methyl-17,20 20,21-bismethylenedioxypregna-4,6-diene-... 

Morpholine enamine of methyl isopropyl ketone prepared by this method was found to be a 3 7 mixture of di- and tetrasubstituted isomers (126 and 127). 

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. 

Enamines of several methyl ketones have been prepared and their isomer content estimated by NMR spectroscopy (13,39,43). The reaction of Ti[N(CH3)2l4 as the amine source and 3-methyl-2-butanone gave only 26 (Ri = Rj = CH3), which could be isomerized by prolonged heating to a 1 1 mixture ofthatenamine and enamine 27 (R, = Rj = CH3)(39). The reaction of morpholine and 3-methyl-2-butanone in benzene with a trace of acetic... 

Many aryhydrazones provide two or more isomers when subjected to the conditions of the Fischer indole cyclization. The product ratio and the direction of indolization can also be affected by different reaction conditions (i.e. catalysts and solvents), which is attributed, at least in part, to the relative stabilities of the two possible tautomeric ene-hydrazine intermediates. Generally, strongly acidic conditions favor formation of the least substituted ene-hydrazine, while cyclization carried out in weak acids favors the most substituted ene-hydrazine. Eaton s acid (10% P2O5 in MeSOsH) has been demonstrated to be an effective catalyst for the preparation of 3-unsubstituted indoles from methyl ketones under strongly acidic conditions. Many comprehensive reviews on this topic have appeared. ... 

The dehydrogenative condensation of unsaturated ketones with methyl ketones was used for preparing various series of 2,4,6-tri-arylpyrylium salts not only by Dilthey, but also by Wizinger and co-workers (for combinations of phenyl, p-anisyl, and p-dimethyl-aminophenyl substituents), by Amoros-Marin and Carlin (combinations of phenyl and p-chlorophenyl), by Le Fevre and Le Fevre (for combinations of pbenyl and m- or p-nitrophenyl), and by others. ... 

---