Alkylation, of ethyl acetoacetate

It may be pointed out that C-alkylation of ethyl acetoacetate is readily aooount for by the mesomeric nature of the carbanion (IV), as will be evident from the following ... 

Ethyl acetoacetate may also be subjected to double alkylation Show how you could prepare 3 methyl 2 butanone by double alkylation of ethyl acetoacetate ... 

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). 

The starting material in the example is obtained by alkylation of ethyl acetoacetate with allyl bromide. 

Cyclization of the two pendant alkyl side chains on barbiturates to form a spiran is consistent with sedative-hypnotic activity. The synthesis of this most complex barbiturate starts by alkylation of ethyl acetoacetate with 2-chloropentan-3-one to give 152. Hydrolysis and decarboxylation under acidic conditions gives the diketone, 153. This intermediate is then reduced to the diol (154), and that is converted to the dibromide (155) by means of hydrogen bromide. Double Internal alkylation of ethyl... 

A change in the pK of the molecule by elimination of the acidic enol function and inclusion of basic nitrogen leads to a marked change in biologic activity. That agent, chromonar (13) shows activity as a coronary vasodilator. Alkylation of ethyl acetoacetate with 2-chlorotriethylamine affords the substituted ketoester (10). Condensation with resorcinol in the presence of sulfuric acid affords directly the substituted coumarin (11). 

A biomimetic synthesis of (-)-xestospongin A (116), (+)-araguspongine B (129), and (+)-xestospongin C (130) was developed (Scheme 12) [43], starting from a Weiler s alkylation of ethyl acetoacetate (131) with 1-bromo-4-chlorobutane (132) to give the ethyl ester of 8-chloro-3-oxooctanoate... 

Preparation of the requisite side chain starts by alkylation of ethyl acetoacetate with 1,3-dibromopen-tane the initially formed bromoketone (shown as the enol 97) undergoes O-alkylation under the reaction conditions to give the dihydropyran 98. Reaction of that masked hydroxy ketone derivative with hydrogen... 

Note also that we can even make good use of the reverse Claisen reaction. Thus, alkylation of ethyl acetoacetate followed by suitable base treatment to effect a reverse Claisen reaction would also generate a substituted acid. Alcoholic base would... 

The synthesis of the module is provided in Scheme 10.5 (Kushner et al. 2007). Double alkylation of ethyl acetoacetate followed by guanidine condensation afforded alkenyl-pyrimidone intermediate 24 (Kushner et al. 2007). Isocyanate 25 was coupled to pyrimidone 24 to yield 26. Upon dimerization in DCM, RCM effectively cyclized the two UPy units (Mohr et al. 1997 Week et al. 1999). A one-pot reduction and deprotection through hydrogenation using Pearlman s catalyst gave diol module 27. Finally, capping 27 with 2-isocyanatoethyl methacrylate at both ends provided the UPy sacrificial cross-linker 28, which was thoroughly characterized by H- and C-NMR, Fourier transform IR (FTIR), and mass spectrometry. 

Polymer-supported reagent. HMPT supported on a polystyrene-type resin is a catalyst for SN2 reactions5-7 and for reduction of ketones by NaBIi4.7 It also has a marked effect on the alkylation of ethyl acetoacetate with diethyl sulfate. In the presence of solid HMPT the enolales undergo 60 70% O-alkylation. In the absence of HMPT, the lithium enolate does not react and the sodium and potassium enolates undergo C-alkylation (90-100%). There is some difference in the effect of solid and liquid I1MPT The solid HMPT increases the reactivity of the K. enolate more than the liquid form, whereas the reverse is true with the Li enolate.8... 

Alkylation of ethyl acetoacetate with 1,4-dibromobutane gives a product that can cyclize to a five-membered ring. 

Isopropyl anisole (171) was converted to bromide (172) by metalation, formylation and bromination. Alkylation with cyclopropyl ketoester produced (173) whose transformation to alcohol (174) was achieved by saponification, decarboxylation and reduction.. Its conversion to homoallylic bromide (175) was accomplished by the method of Julia et al. [56]. Alkylation of ethyl acetoacetate with bromide (175) furnished p-ketoester (176). It was subjected to cyclization with stannic chloride in dichloromethane. The resulting tricyclic alcohol provided the olefinic ester (177) by treatment with mesylchloride and triethylamine. Epoxidation followed by elimination led to the previously reported intermediate (146) whose conversion to triptolide (149) has already been described. 

The same base is used in the alkylation of ethyl acetoacetate with butyl bromide. 

The alkylation of ethyl acetoacetate with butyl bromide on p. 677 was done with the expressed intention of decarboxylating the product to give hexan-2-one. Here are the conditions for this decarboxylation the heating step drives off the CO2 by increasing the gearing on the entropy term (TAS ) of the activation energy (two molecules are made from one). 

A rapid Michael addition of secondary amines to a,P-nnsatnrated carbonyl compounds has been achieved in good to excellent yields to provide (64) in the presence of water under microwave irradiation. In the absence of water and nnder conventional method, the reaction does not proceed, or rather, takes place with a very low yield after a long reaction time (Moghaddam et al, 2000). Deng et al. (1994) performed the rapid alkylation of ethyl acetoacetate with a series of halides in a domestic microwave oven and reported the isolated yield of monoalkylated prodnct (65) varying from 59 to 82%. 

Deng, R., Wang, Y., and Jiang, Y. 1994. Solid-liquid phase transfer catalytic synthesis X The rapid alkylation of ethyl acetoacetate under microwave irradiation. Synthetic Communications, 24 111-15. 

The acetoacetic ester synthesis and direct enolate alkylation are two different methods that prepare similar ketones. 2-Butanone, for example, can be synthesized from acetone by direct enolate alkylation with CH3I (Method [1]), or by alkylation of ethyl acetoacetate followed by hydrolysis and decarboxylation (Method [2]). 

Robinson, R. Extension of the theory of addition to conjugated unsaturated systems. II. The C-alkylation of certain derivatives of (i-aminocrotonic acid and the mechanism of the alkylation of ethyl acetoacetate and similar substances. J. Chem. Soc., Abstracts 1916,109, 1038-1046. 

Alkylation and acylation. A procedure for alkylation of ethyl acetoacetate with isopropanol specified that the gas be passed through a saturated solution of boric acid in coned, sulfuric acid and bubbled into a mixture of the reactants at 0-7°. ... 

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