DD202529A5 - PROCESS FOR THE PREPARATION OF 4-HYDROXYACETESSIGSAEUREALKYLESTER - Google Patents

Abstract

1. Alkylesters of 4-hydroxy-acetoacetic acid.

Description

Λ ΜΛ Π fs ^ Λ /

Drive to2 production of

4-Hydroxyacetessigsäurealkylester

Field of application of the invention

The invention relates to the novel compounds 4-Hydroxyacetessigsäurealkylester, in particular 4-Hydroxyacetessigsäuremethylester, and 4-Hydroxyacetessigsäureäthylester, which can be used, inter alia, for the preparation of tetronic acid.

Explanation of the essence of de Bafindung

The new compounds can be prepared starting from 4-Halogenacetessigsäuealkylester via the 4-Benzyloxyacetessigsäurealkylester by hydrogenolysis.

A preferred procedure is the fact that 4-halo acetoacetic ester with an alkali salt of the benzyl alcohol at temperatures of from 0 to 4O ⁰ C in an organic solvent, preferably dimethyl sulfoxide or tetrahydrofuran is reacted, and the thus obtained 4-hydrogenolys.iert Benzyloxyacetessigsäurealkylester.

As 4-Halogenacetessigester .können the bromine and Chloderivate be used. Preferably, one starts from 4-Chloracetessigsäurealkylester, in particular from the methyl and ethyl esters.

As alkali metal salts of benzyl alcohol, the potassium or sodium salts can be used. Preferably, the sodium salt is used. This is preferably made of sodium hydride and

Benzyl alcohol prepared in an organic solvent. The reaction temperature is suitably 0 to 40 ^° C.

By hydrogenolysis is meant the cleavage of a compound by hydrogen. This reaction is conveniently carried out in the present case under a pressure of 1 to 8 atm. Preferably, the hydrotreating is carried out in the presence of a hydrogenation catalyst, such as noble metal, e.g. Platinum, ruthenium, rhodium or Raney nickel, cobalt and others more. To increase the reacting surface, these catalysts are conveniently supported, e.g. Pumice, coal, silica gel, clay and more, applied.

Embodiments Example 1

7.56 g of 80% sodium hydride was removed by washing three times with 30 ml of petroleum ether (b.p. 40 to 60 ⁰ C) of white oil and added to 160 ml of tetrahydrofuran. With stirring, 14.28 g of benzyl alcohol were then added so that a reaction temperature of 40 ⁰ C was maintained. After completion of hydrogen evolution a Lö was for 1 hour Sung of 19, 7 4 g (95.5% = 0.1145 ig Mpl) was added dropwise ethyl 4-chloroacetoacetate in 80 ml of tetrahydrofuran, with a temperature of 40 ⁰ C prevailed. After stirring for 15 hours, the temperature assuming room temperature, half of the tetrahydrofuran was evaporated on a vacuum rotary evaporator and the still flowable residue in a thin stream into a mixture of 14.3 g of conc. HCl was poured into 150 g of ice water, the pH was adjusted to 5 after the end of the addition. Now it was extracted 4 times with ether

and after washing and drying the ether evaporated on a vacuum rotary evaporator. The residue was distilled. This gave 22.52 g (83.2%) of 4-Benzyloxyacetessigsäureä.tiiyjL ester (Kp _n . 126 ⁰ C). ,

U, 4

21.24 g of this ester, dissolved in ethyl acetate (100 ml), placed in a 200 ml steel autoclave, equipped with magnetic stirrer, and hydrogenolyzed in the presence of 1.05 g of Pd 5% on carbon with hydrogen at a pressure of 5 atm , After completion of the reaction, which was about 2 hours, and after a 2-hour post-reaction time, the catalyst was filtered off and the filtrate was evaporated at 35 ° C on a vacuum rotary evaporator. The residue was dried under high vacuum. This resulted in 13.4 g of 4-Hydroxyacetessigsäureäth ^! Ester in the form of a slightly yellowish oil.

Elemental analysis (C _c H _nn O, MW 146,14) 0X04

gef. C 49.7%. + 0.1. H 7.1% + 0.1 theor. C 49.3% H 6.9%

IR (thin film)

Gangs at 3480 (vs), 2950 (m) -, 1745 (vs), 1725 (vs), 1325 (m) /

1030 (m) cm " ¹ NMR (10% in CDCl-,)

<5 = 1.30 (t, 3H) S = 3.52 (s, 2H) S = 4.27 (q) T

> (4H) S = 4,10 (s) J

OH at S = 3.2-3.7 ppm MS: M ⁺ 164, M / e 115, 101, 88

7ΑΠ 7 QO ~ ^ ~

Example 2

22.68 g of 80% sodium hydride were washed with petroleum ether as in Example 1 and added to 460 ml of tetrahydrofuran. With stirring, 42.84 g of benzyl alcohol were added dropwise at 20 to 32 ° C within 45 minutes. After the ^ -developung has stopped, 54.2 g (97.5% strength = 0 ₇ 35 mol) of 4-Chloracetessigsäuremethylester were added dropwise in 45 minutes at 20 to 30 ⁰ C. The light brown suspension was then stirred for 4 hours at about 20 ⁰ C and then concentrated to a solution of 92.9 g. Hydrochloric acid poured into 400 ml of water. The light brown mixture was extracted with 3 portions of ether to 150 ml, the extracts combined and washed twice with 100 ml of saturated NaCl solution. The ether phase was over Na ₂ SO. dried, filtered and evaporated in a rotary evaporator at 30 to 40 ⁰ C. The residue was distilled to give 45.1 g (58.1%) of 4-benzyloxyacetessigsäuremethy! Ester (bp 1 mm = 126 to 129 ° C).

IR (thin film)

Bands at 1752 (vs), 1730 (vs), 1325 (m), 1100 (m) cms " ¹ NMR (DMSO-d6)

8 = 7.32 (m, 5H)

S = 4.51 (s, 2H).

«5 = 4.25 (s, 2H)

5 = 3.62 (s, 3H)

<* = 3.60 (s, 2H)

22.22 g of this ester, dissolved in 100 ml of ethyl acetate, were introduced into a 200 ml steel autoclave, equipped with magnetic stirrer, and in the presence of 1.1 g of Pd 5% on carbon with water.

^ / ^ f ^ i ^ o ^ - ff -

4 4 U / ^ 4 <j

hydrogenolysed at a pressure of 5 bar- After the reaction, the catalyst was filtered off and the filtrate was evaporated in a rotary evaporator at 30 to 35 ° C. The light brown residue was further dried for one hour in a high vacuum. The product was 13.3 g of methyl 4-hydroxyacetate in the form of a yellow liquid. , , IR (thin film) bands at 3460 (m), 1750 (Vs), 1730 (vs), 1440 (m), 1330 (m),

1270Cm), 1060 (m) cms " ¹ NMR (DMSO-d6) S = 5.00 (broad, 1 + H) ^ = 4.10 (s, 2H) S = 3.60 (s, 3H) S = 3.54 (s, 2H>

Claims (2)

240792 3 6 Sfrfindungsanspruch A process for preparing alkyl 4-hydroxyacetacetates, which comprises converting a 4-haloacetacetic acid alkyl ester into the 4-benzyloxyacetacetic acid alkyl ester and hydrogenolyzing the latter. 2 * Process according to item 1, characterized in that the hydrogenolysis is carried out under pressure and in the presence of hydrogenation catalysts.