Acetoacetic ester bromination

If the reaction between the enol and the electrophile proceeds extremely fast, the enol tautomer of a carbonyl or carboxyl compound might be consumed completely. The generation of enol becomes the rate-determining step. This situation occurs with the enol titration of ace-toacetic ester, (Figure 12.4). In this process, bromine is added to an equilibrium mixture of the ketone form (B) and the enol form (iso-B) of an acetoacetic ester. Bromine functionalizes the enol form via the intermediacy of the carboxonium ion E to form the bromoacetic ester D. The trick of conducting the enol titration is to capture the enol portion of a known amount of acetoacetic ester by adding exactly the equivalent amount of bromine. From the values for... 

Reaction XLVII. Condensation of an Ester with itself by the action of Iodine on its Sodio-derivative. (B., 23, R., 141 A., 201, 144 266, 88.) When iodine, usually in ethereal solution, acts on the sodio-derivatives of esters, such as malonic or acetoacetic esters, the metal is eliminated, and higher dibasic esters are obtained. As will be seen, the reaction is especially useful for preparing cyclo-paraffins by acting with iodine (or bromine) upon disodio-methylene- and disodio-ethylene-, etc., di-malonic esters. 

The proper amount of bromine can be determined by a series of identical parallel experiments. Iron(III) chloride is added as an indicator to the equilibrium mixtures consisting of the ketone and the enol form of the acetoacetic ester and various amounts of bromine are added. If too much bromine has been added, the reaction mixture turns brown. If too little bromine has been added, the reaction mixture remians yellow, as the added iron(III) chloride reacts with the enol iso-B extremely fast, hut reversibly to form the yellow octahedral complex C. This way the enol tautomer is made visible. Only if the proper amount of bromine has been identified does the reaction mixture turn colorless—only for a few seconds, of course, until by HBr catalysis enough of the enol form (iso-B) has been regenerated from the ketone form (B) of the acetoacetic ester and complexed to give the yellow C. 

As a synthetic route, this organoborane synthesis parallels the aoetoaoetic ester and malonic ester syntheses. An acetone unit is furnished by acetoacetic ester or, here, by bromoacetone an acetic add unit is furnished by malonic ester or, here, by bromoacetic ester. In these syntheses, bromine plays the same part that the —COOEt group did by increasing the acidity of certain a-hydrogens, it determines where in the molecule reaction will take place it is easily lost from the molecule when its job is done. Unlike the loss of —COOEt, the departure of —Br is an integral part of the alkylation process. 

Acetic add, frons-cyclohexanediaminetetra-metal complexes, 554 Acetic add, ethylenediaminetetra-in analysis, 522 masking, 558 metal complexes, 554 Acetic acid, iminodi-metal complexes, 554 Acetic acid, nitrilotri-metal complexes titrimetry, 554 Acetoacetic add ethyl ester bromination, 419 Acetone, acetyl-deprotonation metal complexes, 419 metal complexes reactions, 422 Acetone, selenoyl-liquid-liquid extraction, 544 Acetone, thenoyltrifluoro-liquid-liquid extraction, 544 Acetone, trifluorothenoyl-in analysis, 523 Acetonitrile electrochemistry in, 493 exchange reactions, 286 metal complexes hydrolysis, 428 Acetylacetone complexes, 22 liquid-liquid extraction, 543 Acetylacetone, hexafiuorothio-metal complexes gas chromatography, 560 Acetylactone, trifluorothio-metal complexes gas chromatography, 560 Acetylation metal complexes, 421 Acetylenedicarboxylic add dimethyl ester cycloaddition reactions, 458 Acid alizarin black SN metallochromic indicator, 556 Actinoids... 

K. H. Meyer and collaborators developed the use of bromine in determining the amount of enol-form, and then separated the two forms in ordinary acetoacetic ester by vacuum distillation in a silica flask. 

Acetoacetic ester, sec-butyl amine, phosgene, bromine... 

The reaction was extended to the synthesis of cyclopentane derivatives by moving the leaving group to position 4 of the acetoacetate ester (Scheme 25.3a) [5c,d]. Bromine was selected as leaving group since the 4-chloro derivative afforded only the Michael addition. More recently the reaction was extended to non-stabilized alkyl halides (Scheme 25.3b) [5e]. Somewhat surprisingly no O- or N-alkylation by-products were observed despite the fact that 12 cannot be stabilized by the formation of vinyl haUdes by enolization, such as in 2-haloethyl-malonates (9) (Scheme 25.3a). 

The patent describes the formation of complex metal chelates by treatment of the ketoester simultaneously with an alcohol and a metal to effect trans-esterification and chelate formation by distilling out the by-product ethanol [1], This process was being applied to produce the zinc chelate of 2-tris(bromomethyl)ethyl acetoacetate, and when 80% of the ethanol had been distilled out (and the internal temperature had increased considerably), a violent decomposition occurred [2], This presumably involved interaction of a bromine substituent with excess zinc to form a Grignard-type reagent, and subsequent exothermic reaction of this with one or more of the bromo or ester functions present. 

C2]-Squalene, 80, has been produced71 in the reaction sequence shown in equation 31 which involves alkylation of 3-13C-ethyl acetoacetate with geranyl bromide, followed by hydrolysis, decarboxylation and treatment with triethyl phosphonoacetate and then reduction of the ester 82 with LiAlHr, bromination with CBr4/PPh3 and coupling the farnesyl bromide with Cul/Li-pyrrolidine. Epoxidation of 80 has been effected by... 

Bromination of Beta Keto Esters. The work of K. A. Pedersen on the bromination of beta keto esters in the presence of copper(II) and other divalent metal ions provides several examples of reactions proceeding via complexes (29), The complexes provide an alternative and much more rapid route for the bromination reaction. These reactions are accelerated by bases which take up a proton from the beta keto esters. For such substrates, e.g. ethyl acetoacetate, the general expression for the pseudo first order rate constant in the presence of copper has the form ... 

Another reaction in which the cleavage of a carbon-hydrogen bond is important is the bromination of ketones. In the bromination of ethyl acetoacetate and 2-carboethoxycyclopentanone, it was shown that multivalent cations are catalysts. In the latter reaction, cupric, nickelous, lanthanum, zinc, plumbous, manganous, cadmium, magnesium, and calcium ions were effective (45). One can interpret the effect of the metal ion in terms of its catalysis of the proton transfer from the ester to a base, whether the reaction is carried out in dilute hydrochloric acid solution (acid-catalyzed bromination) or in acetate buffer (base-catalyzed bromination). 

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. 

However, when ethyl acetoacetate was treated with diethylaminosulfur trifluoride, an entirely unexpected difluoro compound, C6H8F202, was obtained. The compound was an ester, and decolorized a solution of bromine in carbon tetrachloride. What is the structure of the product ... 

Methyl acetoacetate was condensed with diketene under basic conditions to give the resorcinyl ester 92 in 45% yield. Formation of the monomethyl ether followed by benzylic bromination afforded a 51% yield of 93. The remaining... 

The bromination of j8-keto esters is quite similar to that of /3-diketones. Ethyl acetoacetate was found to undergo electrophilic substitution at the... 

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