FI64347C - FOERFARANDE FOER SYNTETISERING AV METYLGLYOXALACETALER - Google Patents

Description

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Patents and registration requirements Ansökan utlagd och utl.scriften pubffcerad (32) (33) (31) Claim claimed privilege — Begird prlorltet (71) Pfizer Inc., 235 East U2nd Street, New York, NY, USA (72) Shyara Kirti Gupta, Ledyard, Connecticut, USA (7b) Oy Kolster Ab (5I +) Method for the synthesis of methylglyoxal acetals -Forfarande för synthetizering av methylylyoxalacetaler

The invention relates to a process for the synthesis of methylglyoxal acetals of the formula ch3coch (OR) 2 in which R is alkyl having 1 to 4 carbon atoms from dihydroxyacetone (HO1 ^ C ^ CO.

The preparation of methylglyoxal acetals by reacting methylglyoxal with an alcohol in the presence of an acid catalyst is described in U.S. Patent 2,421,559. The starting material for this synthesis, methylglyoxal, is obtained by oxidizing acetone with selenium dioxide or by an acid catalytic modification of dihydroxyacetone (DE Patent 1,914,037; GB Patent 1,234,685 and U.S. Patent 3,607,943). Yet another process for preparing methylglyoxal acetals uses the reaction of acetone with an alcohol and a nitrosating agent in the presence of an acid catalyst (U.S. Patent 3,478,060).

U.S. Patent No. 2,421,559 discloses that the non-use of a water-immiscible organic solvent and the use of a monohydric alcohol as a solvent in itself results in the formation of large amounts of undesirable alkyl esters of C 1-4 alkoxypropionic acid and methylglyoxal dialkyl acetal dialkyl alkyl.

In the one-step process according to the invention, in which an excess of alkanol is preferably used, the formation of these undesirable products is surprisingly avoided. The products of the process according to the invention are particularly valuable in the synthesis of growth promoters, for example in the synthesis of quinoxaline di-N-oxide anti-bacteria.

The process of the invention for synthesizing methylglyoxal acetals from dihydroxyacetone is characterized in that the dihydroxyacetone is reacted at a temperature of about 50 to 150 ° C with at least an equivalent amount of an alkanol having 1 to 4 carbon atoms in the presence of a catalytic amount of a cation exchange resin than 1.

For the purposes of the present invention, the pH is defined as the negative logarithm of the base 10 of the equilibrium constant K at 25 ° C. Mineral acids can be used as catalysts, for example sulfuric acid. The acetal formed is then obtained by conventional extraction and distillation procedures. Water is a by-product of this reaction, but its continuous removal is not necessary. Impurities in the dihydroxyacetone starting material do not adversely affect the reaction. The reaction is generally shown as follows: (CH2OH) 2CO + 2 ROH -> CH3COCH (OR) 2 + 2H2O Θ

B

wherein R is alkyl of 1 to 4 carbon atoms.

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As will be readily apparent to those skilled in the art, the present invention is also useful when an alkanol having up to 10 carbon atoms is used as the reactant. Likewise, alkanols having a non-reactive group as a substituent are useful in the present invention.

The cation exchange resins used in the invention are based on strong acids as described above and are generally used in an amount of 1 to 10% by weight of dihydroxyacetone. Examples of resins suitable for use in this invention include sulfonated polystyrene and sulfonated styrene-divinylbenzene copolymer.

The reaction is usually carried out without a solvent. However, non-reactive solvents such as benzene, hexane or chloroform may be used.

The alkanol is used in at least an equivalent amount to dihydroxyacetone (2 moles to 1 mole), however, it is preferred to use an excess in the range of 2 moles to 200 moles, with a five-fold excess being particularly preferred (10 moles to 1 mole).

A surprising feature of the invention is that the alkanol can be used in excess while acting as both a reactant and a solvent in the reaction.

A wide temperature range is possible in the reaction; it is between about 50 and 150 ° C, but preferably between 60 and 120 ° C.

The reaction is carried out at either normal atmospheric pressure, a.i.i or overpressure.

Treatment of the resulting reaction mixture is usually carried out by distilling the reaction mixture or extracting it with a water-immiscible solvent such as methylene chloride after adding water to the reaction mixture.

The acetals obtained according to the invention have a purity of more than 98% and, surprisingly, do not contain impurities caused by undesirable by-products, such as 1,1,2,2-tetraalkoxypropane or alkyl C1-CY-dialkoxypropionate, as in the above-mentioned prior art. methods.

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The following examples illustrate the invention.

Example 1

dimethyl acetal

A mixture of 90 g of dihydroxyacetone, 270 ml of methanol and 9 g of sulfonated polystyrene cation exchange resin in acid form was heated at 65-70 ° C for 16 hours. The resin catalyst was removed by filtration, and the filtrate was diluted with water, followed by extraction with methylene chloride. Distillation of the methylene chloride extract gave dimethyl acetal, yield 82%, and purity 98%.

Example 2

The reaction of Example 1 was performed at 100 ° C in a pressure vessel for 4 hours. In this case, GLPC analysis of the reaction product using toluene as an internal standard showed a yield of 96%. The yield when isolated was 80% when the isolation was performed by extraction and distillation as in Example 1.

Example 3

Methylglyoxal-di-n-propylacetal- (1,1-di-n-propoxy-2-propanone

A mixture of 36 g of dihydroxyacetone, 200 ml of 1-propanol and 4 g of sulfonated polystyrene cation exchange resin was heated at 80-90 ° C for 5 hours. The catalyst resin was removed by filtration, and the reaction mixture was extracted and distilled as in Example 1 to give an isolated propyl acetal product.

Example 4

Methylglyoxal-di-n-butylacetal- (1,1-di-n-butoxy-2-propanone

A mixture of 30 g of dihydroxyacetone, 100 ml of 1-butanol and 2 g of sulfonated polystyrene cation exchange resin was heated at 90-110 ° C for 4 hours. The resin catalyst was removed by filtration, and the filtrate was extracted and distilled as in Example 1 to give a butyl acetal product.

The yields and characteristic values of the representative examples by this method are shown in Table I.

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Table I

Synthesis of 1,1-dialkoxy-2-propanones (H 2 C-CO-CH- (OR)

Yield% No. Substituent Analysis Isolated _kp. NMR δ (CDCl 3,> TMS) 2.2 (S, 3H) 1 CH 3 -96 82 82 ° (70 mm) 2.4 (S, 6H) and 4.43 (S, 1H) 1.23 (T, 6H) 2 C 2 H 5 99 99 92 82 ° (50 mm) 2.2 (S, 3H) 3.7 (M, 4H) and 4.53 (S, 1H) 0.91 (T, 6H) 1.57 ( M, 4H) 3 CH 3 CH 2 CH 2 9898.5 90 82 ° (14 mm) 2.15 (S, 3H) 3.55 (M, 4H) and 4.5 (S, 1H) CH 3 1.1 (doublet pair, 12H) 4 CH-98 85 59 ° (14 nm) 2.11 (S, 3H) CH 3 • 3.86 (M, 2H) and 4.55 (S, 14H) 0.92 (M) δ CH 3 CH 2 CH 2 CH 2 -95 90 92 ° (29 nm) 1.5 (M, total 14H) 2.15 (S, 3H) 3.61 (M, 4H) and 4.5 (S, 1H)

Claims (4)

6,64347 A process for the synthesis of methylglyoxal acetals of the formula CH 3 COCH (OR) wherein R is alkyl of 1 to 4 carbon atoms from dihydroxyacetone (HO 2 CO 2 CO 2), characterized in that the dihydroxyacetone is reacted at about 50 to 150 ° C for at least with an equivalent amount of an alkanol having 1 to 4 carbon atoms in the presence of a catalytic amount of a cation exchange resin formed from an acid having a pK value of less than 1. Process according to Claim 1, characterized in that the cation exchange resin is a sulphonated polystyrene or a sulphonated styrene-divinylbenzene copolymer. Process according to Claim 1, characterized in that the temperature is kept at about 60 to 120 ° C during the reaction. Process according to Claim 1, characterized in that the catalyst is used in an amount of 1 to 10% by weight of dihydroxyacetone. II