Ethyl 2-butyl-3- oxobutanoate (70%)
The Robinson annulation is a three-step process involving a Michael addition followed by an internal aldol condensation and a dehydration. Under appropriate experimental conditions, it is possible to stop the reaction after every step and to isolate the three products separately. This feature is particularly attractive in the frame of an organic chemistry course. It allows students to confirm experimentally the validity of the stepwise mechanism and to obtain a more thorough understanding of the whole process. It also permits them to synthesize a rich set of related molecules that can be compared and characterized through various analytical techniques. Thus, a stoichiometric mixture of chalcone and ethyl acetoacetate was reacted in ethanol. Depending on the quantity of barium hydroxide monohydrate used as catalyst, the reaction time, and the temperature, three different products were obtained. Their full IR, 1H, 13C, COSY, NOESY, and HETCOR NMR spectra are supplied. Examination of the spectroscopic data helps uncover many challenging structural analysis problems. Among them, the diastereoselective formation of chiral centers during the annulation process, the distinction between axial and equatorial substituents on a cyclohexane ring, and the possibility of a keto–enol tautomerism are extensively discussed.
Ethyl acetoacetate 1-Phenyl-1,4-pentanedione
Most of the reactions of ester enolates described so far have centered on stabilized enolates derived from 1,3-dicarbonyl compounds such as diethyl malonate and ethyl acetoacetate. Although the synthetic value of these and related stabilized enolates is clear, chemists have long been interested in extending the usefulness of nonstabilized enolates derived from simple esters. Consider the deprotonation of an ester as represented by the acid–base reaction
PROBLEM 21.13Ethyl acetoacetate behaves similarly to diethyl malonate in its reactivity toward , -unsaturated carbonyl compounds. Give the structure of the product of the following reaction sequence:
Synthesis of Ethyl Acetoacetate - YouTube
PROBLEM 21.9Cyclopentyl methyl ketone has been prepared from 1,4-dibromobutane and ethyl acetoacetate. Outline the steps in this synthesis by writing a series of equations showing starting materials, reagents, and isolated intermediates.
Ethyl acetoacetate is found in coffee and coffee products
Under the conditions of the classical acetoacetic ester route to methyl ketones [see, e.g.: Org. Synth. Coll., 1, 248, 351 (1941)], varying amounts of O-alkylation occur. Regioselective C-alkylation can be obtained by phase-transfer procedures: J. Org. Chem., 39, 3271 (1974). For improved alkylation using TBAB, see: Org. Prep. Proced. Int., 26, 469 (1994).
Ethyl acetoacetate is a flavouring agent
It’s reasonable to ask why one would prepare a ketone by way of a keto ester (ethyl acetoacetate, for example) rather than by direct alkylation of the enolate of a ketone. One reason is that the monoalkylation of ketones via their enolates is a difficult reaction to carry out in good yield. (Remember, however, that acylationof ketone enolates as described in Section 21.4 is achieved readily.) Asecond reason is that the delocalized enolates of -keto esters, being far less basic than ketone enolates, give a higher substitution–elimination ratio when they react with alkyl halides. This can be quite important in those syntheses in which the alkyl halide is expensive or difficult to obtain.
Acetoacetic Ester Synthesis - University of Calgary
Biginelli reported the synthesis of functionalized 3,4-dihydropyrimidin-2(1)-ones (DHPMs) via three-component condensation reaction of an aromatic aldehyde, urea, and ethyl acetoacetate.
Ethyl acetoacetate | Sigma-Aldrich
Anions of -keto esters are said to be synthetically equivalentto the enolates of ketones. The anion of ethyl acetoacetate is synthetically equivalent to the enolate of acetone, for example. The use of synthetically equivalent groups is a common tactic in synthetic organic chemistry. One of the skills that characterize the most creative practitioners of organic synthesis is an ability to recognize situations in which otherwise difficult transformations can be achieved through the use of synthetically equivalent reagents.