Ketones, methyl self-condensation

MIBK is a flammable, water-white Hquid that boils at 116°C. It is sparingly soluble in water, but is miscible with common organic solvents. It forms an a2eotrope with water as shown in Table 2. Condensation of MIBK with another methyl ketone can produce ketones containing 9—15 carbons. For example, condensation with acetone produces diisobutyl ketone, and self-condensation of two MIBK molecules produces 2,6,8-trimethyl-4-nonanone [123-17-1]. Condensation with 2-ethylhexanal gives 1-tetradecanol (7-ethyl-2-methyl-4-undecanol), avaluable surfactant intermediate (58). 

The poor yield in this conjugate addition is due primarily to the numerous competing reactions the ketone enolatecan self-condense (aldol), can condense with the ketone of MVK (aldol), or can deprotonate the methyl of MVK to generate a new nucleophile. The complex mixture of products makes this route practically useless, (continued on next page) ... 

In practice this reaction is difficult to carry out with simple aldehydes and ketones because aldol condensation competes with alkylation Furthermore it is not always possi ble to limit the reaction to the introduction of a single alkyl group The most successful alkylation procedures use p diketones as starting materials Because they are relatively acidic p diketones can be converted quantitatively to their enolate ions by weak bases and do not self condense Ideally the alkyl halide should be a methyl or primary alkyl halide... 

The Friedlander reaction is quite versatile. The primary limitation on the o-aminobenzaldehyde component is preparation of the starting material as one might expect, these compounds are prone to self-condensation. Both electron rich and electron poor o-aminobenzocarbonyl compounds undergo the Friedlander reaction. When ketone partner 2 has only one available reactive methyl or methylene or is symmetrical, only one product is obtained. Even when two products can be formed, it is possible to choose reaction conditions such that only one product is isolated vide infra). The reaction can be promoted by acid catalysis, sometimes with improved results. 

Synthesis of pyrazole 3 by the Medicinal Chemistry route was straightforward from N-Boc isonipecotic acid (45), so we utilized the route after some optimizations, as summarized in Table 2.4. The key 1,3-diketone intermediate 48 was prepared from 45 without issues. A minor problem in the original route was the exothermic nature of the Claisen condensation between methyl ketone 47 and methyl phenylacetate. Slow addition of l.lequiv of methyl phenylacetate to a mixture of 47, 0.2equiv of MeOH, and 2.5equiv of NaH in THF at room temperature solved this exothermic issue and reduced the amount of self-condensation of... 

Reaction of 2-aminobenzophenone with acetyl acetone in the presence of Bi(OTf)3 (5 mol%) results in the formation of 3-acetyl-2-methyl-4-phenylquinoline [117]. Various 1,3-diketones, acyclic ketones and cyclic ketone undergo the condensation with 2-aminoaryl ketones. The scope and generality of this process is illustrated with respect to various 2-aminoaryl ketones and a wide array of a-methylene ketones, and the results are summarized in Table 6. This method is free from side reactions such as the self-condensation of ketones, which is normally observed under basic conditions. Unlike reported methods, the present protocol does not require high temperature or drastic conditions to produce quinoline derivatives. 

There are a series of communications about the formation of dihydroazines by direct reaction of urea-like compounds with synthetic precursors of unsaturated carbonyls—ketones, containing an activated methyl or methylene group. The reaction products formed in this case are usually identical to the heterocycles obtained in reactions of the same binuclephiles with a,(3-unsatu-rated ketones. For example, interaction of 2 equiv of acetophenone 103 with urea under acidic catalysis yielded 6-methyl-4,6-diphenyl-2-oxi- 1,6-dihydro-pyrimidine 106 and two products of the self-condensation of acetophenone— dipnone 104 and 1,3,5-triphenylbenzene 105 [100] (Scheme 3.32). When urea was absent from the reaction mixture or substituted with 1,3-dimethylurea, the only isolated product was dipnon 104. In addition, ketone 104 and urea in a multicomponent reaction form the same pyrimidine derivative 106. All these facts suggest mechanism for the heterocyclization shown in Scheme 3.32. 

A standard method for enamine synthesis from aldehydes or ketones is to heat the carbonyl compound and the secondary amine in benzene or toluene and remove the water formed by azeotropic distillation. This method cannot, however, be used the preparation of enamines from methyl ketones which undergo self-condensation under these conditions. A procedure which overcomes these difficulties has been given by White and Weingarten [31]. The method employs anhydrous titanium tetrachloride as water scavenger. In the original procedure by White and Weingarten, titanium tetrachloride is added dropwise to a cooled... 

If the electron-withdrawing group is such that self-condensation does not occur then the anion can be generated in the normal manner. Thus, the anion 349 of cyclopropyl phenyl sulfone (348) can be readily prepared by treatment of the parent compound with n-butyllithium at 0°C in THF. The anion has been shown to condense in excellent yield with aldehydes, ketones, methyl iodide and allyl and benzyl bromides to yield 350. The... 

A standard method for enamines synthesis from carbonyl compounds is to heat the parent aldehyde or ketone and a secondary amine in benzene or toluene and to remove the eliminated water by azeotropic distillation. However, this method fails with methyl ketone substrates which are prone to self-condensation imder these conditions. These difficulties could be overcome by a procedure using anhydrous titanium tetrachloride as water scavenger.[6] In the original procedure, titanium tetrachloride was added dropwise to a cold solution of the ketone and the amine, followed by prolonged stirring at room temperature. It was later found that the reaction time could be considerably shortened by a modified procedure, in which the... 

Although dihydropyrans (48) are formed from MVK and enamines at low tempera-tures S in refluxing benzene the pyrrolidine enamine of isobutyraldehyde gives tricyclic ketone 51 (R = Me) via the intermediacy of the cross-conjugated dienamine 49 " and of 50 (Scheme 27). A similar product to 50 but without the geminal methyl groups was obtained by self-condensation of cyclohex-2-enone in the presence of pyrrolidinium perchlorate ... 

With somea-bromoketones, self-condensation to a furane overshadows alkylation. Thus a-bromocycloheptanone (5) at a concentration of only 0.016 M reacts chiefly to give the a-methyl ketone (6,43%), but in a more concentrated solution (0.28 M) gives the furane (7, 58%). 

A proposed mechanism for the self-condensation reaction of n-butanal over a solid base catalyst is shown in Fig. 5. This mechanism is consistent with the inability of wo-butane to carry out a self-condensation as wo-butane is unable to form a carbanion species on the catalyst surface in this way. Although the reaction of n-butanone has high selectivity towards the formation of terminal aldol products (>85%), the formation of trimers limits the overall selectivity. Higher selectivties should be achieved if the reactant ketone was branched on the internal carbon adjacent to the carbonyl group (i.e. 3-methyl butanone). According to the mechanism shown in Fig. 5 this would prevent the formation of trimers. 

Hydrated lime is used as an alkaline catalyst to promote the self-condensation of acetone to form diacetone alcohol (4-hydroxy-4-methyl-2-pentanone) [31.26]. Diacetone alcohol is used as a solvent for natural and synthetic resins. It is also used as an intermediate in the produetion of mesityl oxide, methyl isobutyl ketone and hexylene glycol. 

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