Alkylation 3-diketones

Tellurium Tetrachloride and Cs-Diketones Alkylated in the Methylene Group.1... 

Diketones. Alkyl benzyl ketones (1) are oxidized by PCC in combination with pyridine to 1,2-diketones (2) in 80-85% yield. This oxidation fails with dialkyl ketones. 

Cation Exchange Extractants. This class of extractants includes phenols, branched alkyl carboxylic acids, alkyl phosphoric acids, diketones, and alkyl-aryl sulfonic acids. The last group listed, sulfonic acids, are analogous to sulfonic-acid cation exchange resins and have very little selectivity. Diketones, alkyl phosphoric acids and carboxylic acids can provide both cation exchange functions and coordination functions. This feature has made bis(2-ethylhexyl)phosphoric acid one of the most versatile and powerful extractants of this type. (5) The nation below illustrates simple cation exchange extraction. 

Replacing ligand hydrogen with fluorine generally increases volatility, for instance, in j5-diketone alkyl groups. 

The volatile metal or semimetal compounds used as precursors in ALE can be selected from a wide range of compounds including metal chlorides, P-diketonates, alkyls, alkoxides, and metallocenes etc. [16,17]. The precursor can be liquid, solid, or gas at room temperature and must be stable enough to withstand heating. It should also be free of impurities that volatilize below or at the temperatures used in the processing. Often moisture is the most serious impurity, and the compound should be dried before use. Any solvent coordinated to metal compounds such as P-diketonates needs to be removed. 

The synthesis will therefore normally produce a 2,4-substituted pyrrole, with in addition an ester group or an acyl group at the 3-position, if a keto ster or a diketone respectively has been employed, and an ester group or an alkyl (aryl) group at the 5-position, according to the nature of the amino-ketone. 

Dibromopropene was used in an efficient thermodynamically controlled alkylation. Hydrolysis of the vinyl bromide yielded a 1,4-diketone (S.C. Welch, 1979). 

The carbonylation of aryl iodides in the presence of alkyl iodides and Zn Cu couple affords aryl alkyl ketones via the formation of alkylzinc species from alkyl iodides followed by transmetallation and reductive elimination[380]. The Pd-catalyzed carbonylation of the diaryliodonium salts 516 under mild conditions in the presence of Zn affords ketones 517 via phenylzinc. The a-diketone 518 is formed as a byproduct[381],... 

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 basic metal salts and soaps tend to be less cosdy than the alkyl tin stabilizers for example, in the United States, the market price in 1993 for calcium stearate was about 1.30— 1.60, zinc stearate was 1.70— 2.00, and barium stearate was 2.40— 2.80/kg. Not all of the coadditives are necessary in every PVC compound. Typically, commercial mixed metal stabilizers contain most of the necessary coadditives and usually an epoxy compound and a phosphite are the only additional products that may be added by the processor. The requited costabilizers, however, significantly add to the stabilization costs. Typical phosphites, used in most flexible PVC formulations, are sold for 4.00— 7.50/kg. Typical antioxidants are bisphenol A, selling at 2.00/kg Nnonylphenol at 1.25/kg and BHT at 3.50/kg, respectively. Pricing for ESO is about 2.00— 2.50/kg. Polyols, such as pentaerythritol, used with the barium—cadmium systems, sells at 2.00, whereas the derivative dipentaerythritol costs over three times as much. The P-diketones and specialized dihydropyridines, which are powerful costabilizers for calcium—zinc and barium—zinc systems, are very cosdy. These additives are 10.00 and 20.00/kg, respectively, contributing significantly to the overall stabilizer costs. Hydrotalcites are sold for about 5.00— 7.00/kg. 

Carbon is alkylated ia the form of enolates or as carbanions. The enolates are ambident ia activity and can react at an oxygen or a carbon. For example, refluxing equimolar amounts of dimethyl sulfate and ethyl acetoacetate with potassium carbonate gives a 36% yield of the 0-methylation product, ie, ethyl 3-methoxy-2-butenoate, and 30% of the C-methylation product, ie, ethyl 2-methyl-3-oxobutanoate (26). Generally, only one alkyl group of the sulfate reacts with beta-diketones, beta-ketoesters, or malonates (27). Factors affecting the 0 C alkylation ratio have been extensively studied (28). Reaction ia the presence of soHd Al O results mosdy ia C-alkylation of ethyl acetoacetate (29). 

Monooximes of a-diketones have found applicability in the synthesis of 2-aminopyrazine 1-oxides by condensation with a-aminonitriles, and this reaction was used by White and coworkers in an approach to the synthesis of Cypridina etioluciferamine (Scheme 66 R = 3-indoloyl) (73T3761). In this instance, the use of TiCU as a catalyst was essential, since the carbonyl group in 3-acylindoles is normally deactivated and the required amine/carbonyl condensation is impractically slow. Under normal circumstances the carbonyl group in simple alkyl-substituted monoximes of a-diketones is the more reactive site and the reaction is rapid, requiring no catalysis (69LA(726)loo). 

The 2-alkyl group of 2-alkylisoxazolium salts is also susceptible to a -deprotonation. For example, treatment of 3,5-distyrylisoxazolium salt (199) with potassium methoxide followed by acid hydrolysis gave the natural /3-diketone curcumine (77H(7)24l). 

Alkyl-5-arylisoxazoles (303) were prepared by the regiospecific reaction of appropriate 1,3-diketones (302) (R = alkyl or perfluoroalkyl) with hydroxylamine hydrochloride in pyridine (79MI41601). 

The reaction of appropriate 1,3-diketones (302) with hydroxylamine hydrochloride in pyridine (79MI41601) has been reported to result in a regiospecific synthesis of 3-alkyl-5-arylisoxazoles, as has the reaction of an a -bromoenone (307) with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate (81H(16)145). Regiospecific syntheses of 5-alkyl-3-phenylisoxazoles also result from the reaction of an a-bromoenone (307) with hydroxylamine in the presence of sodium ethoxide (81H(16)145). 3-Aryl-5-methylisoxazoles were prepared from phosphonium salts (304) and hydroxylamine (80CB2852). 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

The initially formed ]5-dicarbonyl compounds are subject to further photo-transformations. One example is provided in the case of epoxy ketone (88), where the resulting /5-diketone (89) undergoes partly a-cleavage and acyl-alkyl... 

Perfluoroalkylcopper reagents react with thiocyanates to give perfluoro-alkyl-substituted sulfides in low yields [230] and with benzoylformyl chloride to give the oi-diketone in 49% yield [231] However, other a-ketoacyl halides were prepared in less than 5% yield [231]... 

Polyfluorinated a-diketones react with 1,2-diainino compounds, such as ortlio-phenylenediamine, to give 2,3-substituted quinoxalmes [103] Furthermore, the carboxyl function of trifluoropyruvates offers an additional electrophilic center. Cyclic products are obtained with binucleophiles [13, 104] With aliphatic or aromatic 1,2-diamines, six-memhered heterocycles are formed Anilines and phenols undergo C-alkylation with trifluoropyruvates in the ortho position followed by ring closure to form y-lactams and y-lactones [11, 13, 52, 53, 54] (equation 23). 

OL Alkylation of aldehydes and ketones (Section 18.15) Alkylation of simple aldehydes and ketones via their enolates is difficult. p-Diketones can be converted quantitatively to their enolate anions, which react efficiently with primary alkyl halides. 

Even 5,5-dimethyl-3-cyclohexylaminocyclohex-2-en-l-one (52), the mono-Schiff s base derived from the 1,3-diketone which is stable in the enamino ketone form (7) and theoretically could alkylate on nitrogen, gave the O-alkylated product (53) (23). 

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