PROCESS FOR THE PREPARATION OF THE ESTERS OF AN ALKYLTARTRONIC ACID

Abstract: The invention concerns a process for the preparation of the esters of an alkyltartronic acid by direct oxidation, with O₂ or the like, at 30-200°C, of the corresponding alkyl-malonic esters, in the presence of a catalytic system, comprising a salt of a transition metal, selected from Mn, Fe, Co and Cu, and an alkali-metal salt of an aliphatic carboxylic acid, optionally in the presence of a polar solvent.

Description: It is known to prepare the esters of alkyltartronic acids having formula (I): wherein R is an alkyl or cycloalkyl group and wherein R′ and R″, the same or different from each other, are organic groups inert towards the reaction medium, by oxidation of the corresponding alkyl-malonic esters having formula (II): using, as an oxidizing agent, 98% HNO₃ (see US-A-3,997,593). It is also known to alkylate mesoxalic esters with a Cd-dialkyl compound or with trialkylphosphites (Arbuzov reaction). According to other methods such esters are prepared by hydrolysis of meta-bromo-malonic acid with baryta and subsequent esterification with an alcohol, or by acidic alcoholysis of alpha-cyanolactic acid (pyruvic cyanohydrin) or of 2-acetoxy-2-methyl-malononitrile (1-acetoxy-1, 1-dicyano-ethane). Finally, according to a recent method which is described in EP-A-166 348, said esters are prepared by hydroxylating methacrylic acid to alpha-methyl-glyceric acid with H₂O₂ and in the presence of H₂WO₄, and by subsequent oxidation to methyl-tartronic acid, using HNO₃ or O₂ in the presence of either Pd or Pt, followed by an esterification with a suitable alcohol. It has now been found that it is possible to obtain the alkyl-tartronic esters of formula (I) by direct oxidation of the alkyl-malonic esters of formula (II) without any toxic or dangerous oxidizing agent such as, e.g., HNO₃, and without any use of noble metals, using extremely simple procedures. In its broadest aspect, the present invention provides a process for the preparation of esters of alkyl-tartronic acids having formula (I) by direct oxidation of the corresponding alkyl-malonic esters of formula (II) which is characterized in that the oxidation is carried out at 30-200°C with oxygen, air or other O₂-containing gases, in the presence of a catalytic system comprising: a) an inorganic salt (preferably selected from halides, carbonates and bicarbonates) or an organic salt of a transition metal selected from manganese, iron, cobalt and copper; b) an alkali-metal salt of an aliphatic carboxylic acid, in amounts up to 60 moles per mole of transition metal; optionally in the presence of a polar solvent having a dipolar moment equal to or higher than 1.68 Debye units. The groups R′ and R″ of formula (I) and (II) can be, e.g. alkyl groups containing from 1 to 6 carbon atoms, cycloalkyl, aryl, arylalkyl or alkylaryl groups. The reaction can be performed under atmospheric pressure, with an oxygen (or air) flow rate of about 2 m³/h per m³ of reaction volume, or under a pressure ranging from 1 to 50 bar. Salt (a) preferably is selected from the salts of aliphatic mono-carboxylic acids, preferably containing 1 to 22 carbon atoms, and among these the acetates are particularly preferred. Particularly advantageous is the use of a cobalt salt in combination with a manganese salt in a molar ratio from 1:9 to 9:1 (expressed in terms of metal). Generally, amounts from 0.03 to 0.003 moles of transition metal per mole of alkyl-malonic ester can be used. Preferably, the alkali-metal salt (b) is selected from sodium and potassium acetates and preferably is used in amounts from 10 to 20 moles per mole of transition metal. The polar solvent, in which also the catalyst should be soluble, preferably is selected from aliphatic carboxylic acids containing up to 5 carbon atoms, optionally in admixture with water. Best results were obtained by using acetic acid. The reaction temperature should generally be from 30° to 200°C, depending on the composition of the reaction mixture and on the predetermined reaction rate. The addition of up to 50% by weight, preferably at least 10% by weight, of an alcohol having from 2 to 6 carbon atoms (e.g. tert.-butanol) satisfactorily inhibits the cleavage of the alkyl-malonic ester used as the starting material, thus promoting the recovery of the unreacted material. At the end of the reaction, the alkyl-tartronic ester can be stripped from the reaction mixture by substantially usual techniques such as, e.g., distillation. It is also possible to recover the catalyst from the reaction mixture and to recycle said catalyst to the oxidation reactor. The process according to the invention, contrary to the processes used until now, allows to obtain alkyl-tartronic esters of formula (I) with good yields, avoiding the use of noble metals and of either toxic or dangerous oxidizing agents, with a good control of the course of the reaction, and in a very simple manner which is very suitable for exploitation on an industrial scale. The esters having formula (I) are particularly useful when R is CH₃ and when R′ = R″ are alkyl groups having from 1 to 4 carbon atoms. In this case they can be used, in fact, as intermediates for the preparation of amino acids, of barbituric derivatives and of oxazolidinyl derivatives having a pesticidal or analgesic effect. In particular, the diethyl ester of methyltartronic acid is an intermediate for the preparation of a fungicide known under the trade name "SERINAL"®. Some Examples are now given for illustrative purposes, but are by no way limitative of the scope of the present invention. EXAMPLE 1 A glass reactor equipped with stirrer, reflux condenser and temperature control system was charged with Through the mixture 7 dm³/h of oxygen were bubbled while keeping the reaction mixture at 130°C by means of an external oil bath. Five hours later, at the end of the reaction, the solvents were removed under vacuum and the residue was distilled under reduced pressure. A fraction was obtained which contained 2.4 g of diethyl methylmalonate and 2.4 g of diethyl methyltartronate, corresponding to a 52% conversion and a 84% selectivity to diethyl methyltartronate and thus a yield of 43.9%. EXAMPLE 2 The reactor of Example 1 was charged with: Then the procedure of Example 1 was followed. After the destillation there were obtained: 2.45 g of diethyl methyltartronate; 0.72 g of diethyl methylmalonate; and 0.4 g of residue; corresponding to 85.6% conversion, a 52.4% selectivity and a 45% yield. EXAMPLE 3 Repeating the procedure of Examples 1 and 2, the reactor was charged with: After the distillation there were obtained: 2.7 g of diethyl methyltartronate; 0.27 g of diethyl methylmalonate; and 0.7 g of residue; corresponding to a 94.6% conversion, a 52.3% selectivity and a 49.5% yield.

Claims: 1. A process for the preparation of esters of alkyltartronic acids having formula (I): wherein R is an alkyl or cycloalkyl group and wherein R′ and R", the same or different from each other, are organic groups inert towards the reaction medium; by direct oxidation of the corresponding alkyl-malonic esters having formula (II): characterized in that the oxidation is carried out at 30 to 200°C with oxygen, air or other O₂-containing gases in the presence of a catalytic system comprising: a) an inorganic or organic salt of a transition metal selected from manganese, iron, cobalt and copper; b) an alkali-metal salt of an aliphatic carboxylic acid, in amounts up to 60 moles per mole of transition metal; optionally in the presence of a polar solvent having a dipolar moment equal to or higher than 1.68 Debye units. 2. A process according to claim 1, wherein also an aliphatic alcohol having from 2 to 6 carbon atoms is present in amounts of up to 50% by weight with respect to the alkyl-malonic ester to be oxidized. 3. A process according to one or both of claims 1 and 2, wherein the substituents R′ and R″ are selected from alkyl groups containing from 1 to 6 carbon atoms, cycloalkyl, aryl, arylalkyl and alkylaryl groups. 4. A process according to one or more of claims 1 to 3, wherein the salts of said transition metals are salts of aliphatic mono-carboxylic acids, e.g. selected from Mn, Fe, Co and Cu acetates. 5. A process according to one or more of claims 1 to 4, wherein a cobalt salt is used in combination with a manganese salt in a molar ratio, expressed in terms of metal, from 1:9 to 9:1. 6. A process according to one or more of claims 1 to 5, wherein an amount from 0.03 to 0.003 moles of transition metal per mole of alkyl-malonic ester is used. 7. A process according to one or more of claims 1 to 6, wherein from 10 to 20 moles of alkali-metal salt per mole of transition metal are used. 8. A process according to one or more of claims 1 to 7, wherein the alkali-metal salt is selected from sodium acetate and potassium acetate. 9. A process according to one or more of claims 1 to 8, wherein the solvent is selected from aliphatic carboxylic acids containing up to 5 carbon atoms, e.g., acetic acid, optionally in admixture with H₂O. 10. A process according to one or more of claims 1 to 9, wherein an aliphatic alcohol containing from 2 to 6 carbon atoms, e.g., tert.-butanol, is added to the reaction mixture.

Inventors: COMETTI, GIUSEPPE, PAGANI, ANSELMO, SANTI, ROBERTO
Applicants: CONSIGLIO NAZIONALE DELLE RICERCHE, ISTITUTO GUIDO DONEGANI S.P.A.
Application year: 1987
Main classification: C07C69
IPC codes: C07B61, C07C69, C07C67, B01J31