Condensation, of acetoacetic ester, acid

Condensation of acetoacetic ester with a-bromocyclopentanone, followed by ring closure with cold sulfuric acid, gave 2-methyl-3-carboxy-4,5-trimethylenefuran in 41% yield53 ... 

Dehydroacetic acid (40, 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one) is obtained by self-condensation of acetoacetic ester in the presence of Na2C03 [15] ... 

By prolonged boiling of acetoacetic ester under a reflux condenser at ordinary pressures, condensation occurs, and dehydracetic acid is formed. The parent acid, a 8-hydroxy-acid, is unstable, and has not yet been isolated. 

In a stoppered bottle of 500 c.cs. capacity provided with a reflux condenser, 25 gms. (2 mols.) of acetoacetic ester are dissolved in 150 gms. of pure ether which has been dried over sodium, and to this solution 5 gms. (2 mols.) of fine sodium wire are added. After 2 hours, the bottle is shaken at intervals, being stoppered while so doing, till no further evolution of hydrogen takes place, and all the metal has been converted into sodio-acetoacetic ester. 20 gms. (excess) of finely powdered iodine are dissolved in pure anhydrous ether, and the solution added in small portions, and with constant shaking, to the solution of the sodio-acetoacetic ester. Sodium iodide is precipitated as soon as the colour of the iodine no longer vanishes at once, the solution is filtered, the ether evaporated off, and the diacetosuccinic ester allowed to solidify. It is then pressed on a porous tile, and recrystallised from warm 50% acetic acid. 

However, over Ni-kieselguhr in the absence of solvent or in ether and methylcyclo-hexane 32-33% of a diester, ethyl 3-(3 -hydroxybutyryloxy)butyrate (8), was produced along with 68-67% of ethyl 3-hydroxybutyrate and small quantities of dehydroacetic acid, and over copper-chromium oxide 16% of the diester and 7% of dehydroacetic acid were formed in the absence of solvent. It was suggested that the diester is formed through the hydrogenation of the intermediate 9, which results from 2 mol of acetoacetic ester with elimination of 1 mol of ethanol and that the condensation reaction is reversible (Scheme 5.6). Hence, the formation of the diester is depressed in the hydrogenation in ethanol.121 The reaction pathway in Scheme 5.6 has... 

Some examples of the addition of one carbonyl compound to another are the aldol condensation the formation of acetoacetic ester the condensation of benzaldehyde with one of the components of a mixture of an acid anhydride and a carboxylate salt the formation of mesityl oxide, phoroiie, and mesitylene from acetone and the condensations of aromatic aldehydes and ketones. Acids and bases are generally catalysts for these reactions. They have sufficient in common to warrant their being classed together as the aldol type of... 

A few drops of coned, sulfuric acid added to a mixture of ethyl acetoacetate and triethyl orthoformate, stored 24 hrs., and neutralized with a slight excess of quinoline ethyl j -ethoxy-cis-crotonate (Y 89%) dissolved in dry ether, added to a suspension of 2 moles LiNHg in anhydrous liq. NHg, stirring continued 10 min., a soln. of benzaldehyde in dry ether added, stirred 1 hr., NHg replaced by ether, refluxed 5 min., and ice-water added 3-ethoxy-5-phenyl-cis-2-frans-4-pentadienoic acid (Y 74%). — Excess LiNHg is used to prevent self-condensation of the ester. F. e. s. E. E. Smissman and A. N. Voldeng, J. Org. Ghem. 29, 3161 (1964). 

The so-called Michael condensation involves the additive condensation of aj8-unsaturated acids, their esters, or aj3-unsaturated ketones with the sodium derivative of ethyl malonate, acetoacetate, or cyanoacetate. To explain this and other addition reactions Michael published many papers setting out a negative-positive rule and a distribution principle . The first assumed, for example, that in propylene, CHa CHrCHg, the positive radical CH3 makes the adjacent carbon in CH more positive than that in CHg, so that hydrogen iodide H+I adds mainly to form CHg-CHI-CHg, but I+C1 adds to form mostly CHa CHChCHgl. With BrCl, in which both atoms are nearly equally positive, about equal amounts of CHs-CHCl-CHaBr and CHg-CHBr-CHgCl are formed. In longer chains there are spatial influences. 

This reaction consists of the condensation of two molecular equivalents of a 1,3 diketone (or a J3-keto-ester) with one equivalent of an aldehyde and one of ammonia. Thus the interaction of ethyl acetoacetate and acetaldehyde and ammonia affords the 1,4-dihy dro-pyridine derivative (1), which when boiled with dilute nitric acid readily undergoes dehydrogenation and aromatisation" to gb e the diethyl ester of collidine (or 2,4,6-trimethyl-pyridine-3,5 dicarboxylic acid (II)). For the initial condensation the solid aldehyde-ammonia can conveniently be used in place of the separate reagents. 

The formation of acyloins (a-hydroxyketones of the general formula RCH(OH)COR, where R is an aliphatic residue) proceeds best by reaction between finely-divided sodium (2 atoms) and esters of aliphatic acids (1 mol) in anhydrous ether or in anhydrous benzene with exclusion of oxygen salts of enediols are produced, which are converted by hydrolysis into acyloins. The yield of acetoin from ethyl acetate is low (ca. 23 per cent, in ether) owing to the accompanying acetoacetic ester condensation the latter reaction is favoured when the ester is used as the solvent. Ethyl propionate and ethyl ji-butyrate give yields of 52 per cent, of propionoin and 72 per cent, of butyroin respectively in ether. 

Methylsuccinic acid has been prepared by the pyrolysis of tartaric acid from 1,2-dibromopropane or allyl halides by the action of potassium cyanide followed by hydrolysis by reduction of itaconic, citraconic, and mesaconic acids by hydrolysis of ketovalerolactonecarboxylic acid by decarboxylation of 1,1,2-propane tricarboxylic acid by oxidation of /3-methylcyclo-hexanone by fusion of gamboge with alkali by hydrog. nation and condensation of sodium lactate over nickel oxide from acetoacetic ester by successive alkylation with a methyl halide and a monohaloacetic ester by hydrolysis of oi-methyl-o -oxalosuccinic ester or a-methyl-a -acetosuccinic ester by action of hot, concentrated potassium hydroxide upon methyl-succinaldehyde dioxime from the ammonium salt of a-methyl-butyric acid by oxidation with. hydrogen peroxide from /9-methyllevulinic acid by oxidation with dilute nitric acid or hypobromite from /J-methyladipic acid and from the decomposition products of glyceric acid and pyruvic acid. The method described above is a modification of that of Higginbotham and Lapworth. ... 

A modihed Hantzsch synthesis has been utilized for the preparation of 1,4-dihydropyridines (Scheme 66). Thus, condensation of formylfurazans 116 with an acetoacetic ester and aminocrotonic acid ester in isopropanol at reflux led to 1,4-dihydropyridine derivatives 117 in about 70% yield (92AE921). Both isomeric furoxan aldehydes reacted in a similar way. 

Sterically hindered derivatives of isoxazole carboxylic acids have yielded a goodly number of antibiotics. Chlorination of the oxime of the appropriately substituted benzaldehydes (15) leads to the intermediates, ( 16. Condensation of the chloro oximes with ethyl acetoacetate in base gives the esters (17) of the desired isoxazole carboxylic acids. Alternately, the esters... 

Pyrimidinopyrazines related to folic acid have been investigated in some detail for their antimeta-bolic and antineoplastic activities. A related compound, which lacks one nitrogen atom, has been described as an antiproliferative agent, indicating it too has an effect on cell replication. Aldol condensation of the benzaldehyde 99 with ethyl acetoacetate gives the cinnamate 100. This is then reduced catalytically to the acetoacetate 101. Reaction of that keto ester with 2,4,6- triami-nopyrimidine gives the product 102 which is subsequently chlorinated (103) and subjected to hydrogenolysls. There is thus formed piritrexim (104) [17]. 

Pyrido- and pyrimido[l, 4]diazepinones have been produced by condensing pyridinediamines and a pyrimidinediamine with esters of /i-oxo acids. Because of the unsymmetrical structures of the diamines the reactions may take two courses, as exemplified by the action of ethyl acetoacetate on pyridine-2,3-diamine.308... 

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