Acetoacetic acid ester derivatives for the manufacture of .alpha

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters

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260408, 2604109R, 131276, 426538, 512 8, 568346, 568379, 568380, C07C 69716

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048929662

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BRIEF SUMMARY
The invention is concerned with a novel process for the manufacture of .alpha.-hydroxycarbonyl compounds, especially those of the formula ##STR3## wherein R.sup.1 signifies C.sub.1-5 -alkyl, especially methyl, ethyl, propyl or isopropyl, and the radicals R.sup.2 each independently represent hydrogen or C.sub.1-5 -alkyl, especially hydrogen or methyl, ethyl, propyl or isopropyl.
The process in accordance with the invention is characterized in that a compound of the general formula ##STR4## wherein R stands for C.sub.1-4 -alkoxy, chlorine, bromine or C.sub.1-4 -alkanoyloxy, e.g. acetoxy, propionyloxy, butyryloxy, R.sup.1 and R.sup.2 have the above significance and R.sup.3 represents C.sub.1-4 -alkyl, is hydrolyzed and subjected to an aldol condensation.
In this alkaline hydrolysis the ester bonds which are present in II (R in II=C.sub.1-4 -alkanoyloxy and the group --COOR.sup.3) are cleaved. The aldol condensation yields the compound I.
Where R=chlorine or bromine, only the group --COOR.sup.3 is initially cleaved hydrolytically and, after the aldol condensation has been carried out, the halogen residue R must also be hydrolyzed alkalinically.
As the aldol condensation is preferably carried out alkalinically, where R=C.sub.1-4 -alkoxy the compound ##STR5## wherein R.degree. stands for C.sub.1-4 -alkyl and R.sup.1 and R.sup.2 have the above significance, which is initially formed in this manner must, of course, thereupon be subjected to an acidic ether cleavage.
Tautomerism is possible where R.sup.1 .noteq.R.sup.2 .noteq.H. Formula I is accordingly intended to embrace both tautomeric forms and their mixtures.
The convenient parameters for the process in accordance with the invention, i.e. the conversion in accordance with the invention of II into I, are indicated in the following Reaction Scheme and Table I relating thereto.
Moreover, this Scheme and Table I contain the convenient parameters for the process for the preparation of the compounds II.
In this Scheme:
The novel compounds II are obtained by alkylating a compound of the formula ##STR6##
wherein R, R.sup.2 and R.sup.3 have the above significance, conveniently by means of halocarbonyl compounds in accordance with the Reaction Scheme.
In a particular embodiment in the case of R.sup.2 .dbd.C.sub.1-5 -alkyl (R.sup.2 in the .alpha.-position to the ester group) a corresponding compound III is not used, but the compound of formula II is alkylated prior to its hydrolysis and the aldol condensation which are conveniently carried out without separating the alkylated product. ##STR7##
Table I provides information concerning convenient methods and reagents as well as convenient and preferred reaction parameters for the individual process steps.


TABLE 1 __________________________________________________________________________ Type of Step reaction Reagent T Literature __________________________________________________________________________ a 1 Hydrolysis (1) Metal hydroxides, metal carbon- 20-100.degree. C. H.O. House, Modern Synthetic a 3 alkaline ates, metal bicarbonates Reactions, 2nd ed. W. A. (ester cleav- in aqueous solution Benjamin Inc. Menl. Park, age) California, 1972, 511 seq., concomitant 629 seq. aldol conden- sation a 11 Enol-ether Strong acids e.g. H.sub.2 SO.sub.4, Reflux H.O. House loc, cit. 504 cleavage (1) HCl, H.sub.3 PO.sub.4 temper- aqueous solution; ature HI, HBr/CH.sub.3 COOH a 2 Hydrolysis (1) Alkaline conditions: 20-100.degree. C. Metal hydroxides, e.g. alkali metal hydroxides, alkaline earth metal hydroxides, preferably in aqueous solution. aqueous ammonia solution a 22 Hydrolysis (1) Weakly basic: 20-100.degree. C. H.O. House, loc. cit., alkaline Metal carbonates, metal bi- 511 seq., 629 seq. (ester cleav- carbonates age) in aqueous solution concomitant aldol conden- ation b 1 Substitution Alkali alcoholate in excess: prefer- EP-PS 76,378 (alkoxylation) aprotic solvent, e.g. ably CH-PS 562,191 acetonitrile, prop

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