Process for transesterifying &agr;-Ketocarboxylic esters

Details Process for transesterifying &agr;-Ketocarboxylic esters Process for transesterifying &agr;-Ketocarboxylic esters

1999-08-06

2001-04-24

Geist, Gary (Department: 1623)

Organic compounds -- part of the class 532-570 series

Organic compounds

Carboxylic acid esters

C051S302000, C051S295000, C556S054000, C556S056000

Reexamination Certificate

active

06222063

ABSTRACT:

&agr;-Ketocarboxylic esters, such as ethyl pyruvate (PAEE), are used in a multiplicity of areas, for instance as intermediates for agricultural and pharmaceutical active compounds, as solvents etc. However, preparation processes employed hitherto have proved unsuitable from the economic and technical aspect for the most varied reasons. Thus, for example, preparing PAEE similarly to methyl pyruvate (PAME) by ozonolysis and subsequent reduction starting from ethyl methacrylate in ethanol instead of methyl methacrylate in methanol has considerable disadvantages. Firstly, ethyl methacrylate is considerably more expensive than methyl methacrylate, secondly, the by-product formaldehyde is not completely acetalated with ethanol as solvent, as a result of which an interfering residual content of formaldehyde remains for the further work-up, thirdly, because of the heavier formaldehyde diethylacetal formed, during the work-up more by-product must be burned and, fourthly, the ketal cleavage in the case of PAEE diethylketal proceeds with much more difficulty than with PAME dimethylketal.
According to J. Liebigs Ann. Chem., 564, 34 (1949), PAEE is prepared in only 53% yield by esterifying pyruvic acid with absolute ethanol and benzene and subsequently drying the ternary azeotrope ethanol/benzene/water over K
2
CO
3
.
Possibilities have already been investigated of preparing PAEE by transesterifying PAME.
This preparation path, however, has failed to date on the versatile reactivity of the molecule owing to the &agr;-ketocarboxylic acid structural element. Thus, during the transesterification in a basic medium, because of a rapid condensation of the carbonyl group with the adjacent activated methyl or methylene group, unwanted by-products occur, while in an acidic medium, ketals and water are formed, the water in turn leading to unwanted hydrolysis of the ester. Under approximately neutral conditions, acceptable conversion rates are not achieved.
Unexpectedly, it has now been found that, by using special metal catalysts and anhydrous conditions in the reaction medium, transesterification of &agr;-ketocarboxylic esters is possible in good yield and without side reactions.
The present invention therefore relates to a process for transesterifying &agr;-ketocarboxylic esters using an alcohol, which comprises carrying out the transesterification in an anhydrous alcohol as reaction medium in the presence of tin catalysts, titanium catalysts, zirconium catalysts or lithium catalysts or of acetylacetonates as catalysts.
According to the invention, all &agr;-ketocarboxylic esters having the structural element of the formula I
can be transesterified.
R
1
and R
2
here are a saturated or unsaturated, branched, unbranched or cyclic C
1
-C
30
alkyl radical or an aromatic or heteroaromatic radical, where these radicals can have substituents such as C
1
-C
10
alkoxy, substituted amino, carbonyl, derivatized carboxyl and underivatized carboxyl, ester, halogen, hydroxyl, nitro substituents, and other nitrogen functions, boron compounds, phosphorus compounds, sulfur compounds or silicon compounds, it being necessary to take care that non-neutrally-reacting functional groups are substantially neutralized either intramolecularly or by acidic or basic additions or solvents, in order to prevent condensation reactions or acid-catalyzed ketalization. Preferably, R
1
and R
2
are a C
1
-C
4
alkyl radical such as methyl, ethyl, propyl or isopropyl or a benzyl radical. Particular preference is given to the methyl radical.
The process according to the invention is preferably used for transesterifying methyl pyruvate (PAME). The preferred transesterification product is ethyl pyruvate (PAEE).
Transesterification is performed in an anhydrous reaction medium. The reaction medium which is used here is an alcohol R
3
—OH, where R
3
is the radical which is exchanged for R
1
. R
3
is therefore defined as R
1
and R
2
, where R
1
and R
3
are not identical. Preferably, R
3
is therefore a branched or unbranched C
2
-C
6
alkyl radical or a benzyl radical. Preferably, therefore, PAME is reacted in anhydrous ethanol to form PAEE by the process according to the invention.
In addition to the alcohol used, a further anhydrous solvent, such as unsubstituted and substituted alkanes, such as hexane, heptane, etc., alkenes, alkynes, alcohols, substituted amines, amides, aromatics, esters, ethers, halogen compounds, heteroaromatics, lactones, ketones, other nitrogen-containing compounds, such as nitroalkanes, silicon compounds, such as silicone oils, sulfur compounds, such as sulfoxides, can be used, it again being necessary to take care that non-neutrally-reacting functional groups are substantially neutralized either intramolecularly or by acidic or basic additions respectively to the alcohol component or ester component, in order to prevent condensation reactions or acid-catalyzed ketalization.
The transesterification takes place according to the invention in the presence of special metal catalysts. Suitable catalysts are selected from the group consisting of the tin catalysts dialkyltin dicarboxylates, such as dibutyltin dicarboxylates, in particular dibutyltin diacetate, dibutyltin dilaurate, dibutyltin diisooctoate, dibutyltin maleate and mixed dibutyltin dicarboxylates, in particular with relatively long-chain fatty esters, dioctyltin dicarboxylates, in particular dioctyltin dilaurate, trialkyltin alkoxides, such as tributyltin oxide, monoalkyltin compounds, such as monobutyltin dihydroxychloride and monobutyltin dioxide, tin salts such as tin acetate, tin oxalate and tin chloride, tin oxides, such as SnO, selected from the group consisting of titanium catalysts, monomeric and polymeric titanates and titanium chelates such as tetraisopropylorthotitanate, tetrapropylorthotitanate, tetraethylorthotitanate, tetrabutylorthotitanate, tetraisobutylorthotitanate, 2-ethylhexyltitanate, stearyltitanate, cresyltitanate, titaniumacetylacetonate, triethanolaminetitanate, octylene glycol titanate, isostearyltitanate, diethyl citrate titanate selected from the group consisting of the zirconium catalysts, zirconates and zirconium chelates such as tetrapropylzirconate, tetraisopropylzirconate, tetra-butylzirconate, triethanolaminezirconate, diethyl-citrate zirconate, zirconium(IV) acetylacetonate, and lithium catalysts such as lithium salts, lithium alkoxides, and aluminum(III) acetylacetonate, chromium(III) acetylacetonate, iron(III) acetylacetonate, cobalt(II) acetylacetonate, nickel(II) acetylacetonate and zinc(II) acetylacetonate.
Preference is given to dibutyltin diacetate, mixed dibutyltin dicarboxylates with relatively long-chain fatty esters, dioctyltin dilaurate, monobutyltin dihydroxychloride, monobutyltin dioxide, tin acetate, tin oxalate, tin chloride, tetraisopropylorthotitanate, tetrapropylorthotitanate, tetraethylorthotitanate, tetrabutylorthotitanate, tetrapropylzirconate, and also lithium salts and alkoxides and abovementioned acetylacetonates. Particular preference is given to dibutyltin diacetate, tetraisopropylorthotitanate, tetraethylorthotitanate.
The amount of catalyst used is from 0.0001 to 20% by weight, preferably from 0.005 to 5% by weight, and particularly preferably from 0.02 to 1% by weight. The reaction mixture is preferably heated to the boiling point of the reaction mixture, so that the reaction temperature is between 20° C. and 200° C., depending on the reactants. The transesterification can in addition be carried out at atmospheric pressure, but also at reduced pressure or overpressure from 0.001 to 200 bar. The alcohol eliminated in the transesterification is preferably continuously distilled off. Preferably, the reaction is carried out using a distillation tower having a high separation efficiency.
The catalyst, after transesterification is complete, is separated off in good yield by washing with water, hydrolyzing the catalyst and filtering the precipitated metal oxide, or preferably by distilling off the product from the catalyst, preferably on a thin-film or short-path evaporator.
By means of th

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