CS275926B6 - New epoxymethylene-1,4-butanedioic acid derivatives - Google Patents

Abstract

Epoxymethylene-1,4-butanedioic acid derivatives of the general formula I, where R represents phenyl, phenyl mono, di, or tri substituted independently by a chlorine, bromine, fluorine atom, a methoxy, nitro, methyl, ethyl, carbethoxy 2-propyl group, or a combination thereof. They are prepared by epoxidation of imides of general formula II with peroxyacids, preferably in the presence of buffering agents. Substances are used as intermediates for other biologically active derivatives.

Description

The invention relates to novel epoxymethylene-1,4-butanedioic acid derivatives (epoxyitaconic acid) and to a process for their preparation. 2-Methylenebutanedioic acid has been described e.g. Moritsu H-, et al .: Eur. J. Appl. Microbiol. Biotechnol 1Θ, 358 (1980) as a product of Aspergilus terreus. Some of its derivatives, such as mono- and diesters or imides, are described e.g. European patent specification no. 34556 or Belgian patent no. 613,136, where a fungicidal effect and stimulation of plant growth is declared for these substances.

The present invention relates to novel epoxymethyl-1,4-butanedioic acid derivatives of the general formula I

/ 1, where R | is phenyl, mono di or tri, substituted independently with chlorine, bromine, fluorine, methoxy, nitro, methyl, ethyl, carboxy 2-propyl or a combination thereof, and a process for their preparation.

The compounds of the formula I are prepared according to the invention by reacting methylene butanedioic acid imides of the formula II

with an epoxy reagent selected from the group of peroxyacids such as peroxytrifluoroacetic acid, peracetic acid, peroxyformic acid, metachloroperoxybenzoic acid, peroxyphthalic acid, hydrogen peroxide, in an inert organic solvent such as chlorinated hydrogen chloride especially dichloromethane, chloroform, dichloroacetate, tetrahydrofuran, acetonitrile. If hydrogen peroxide is used, water-miscible solvents such as acetone, ethanol, diosane, acetonitrile are preferably used. The reaction may be carried out in the presence of buffering agents such as sodium or potassium carbonate, sodium hydrogen phosphate. The compounds of the formula I are used as intermediates for the preparation of biologically active substances. The details of the individual preparation methods are given in the following examples, without being limited thereto.

Example ·

5- (3-chlorophenyl) -1-oxa-5-azaspiro- (2,4) heptane-4,6-dione (30%) of 30% hydrogen peroxide is shaken with 40 ml of ether. The ether layer was separated and concentrated by evaporation. To the residue was added 40 ml of dichloromethane, the solution was cooled to 0 to 5 ° C, and then 2.8 ml of trifluoroacetic anhydride was obtained. The solution is stirred further

CS 275926 66 hours. The reaction mixture is added to a solution of 1.6 g (0.0068 mol) of itaconic acid 3-chlorophenylimide in 50 ml of trichloromethane. After refluxing for 40 hours, it is concentrated on an evaporator and 20 ml of ethanol are added to the residue. The precipitated substance is filtered off. 1.6 g of 5- (3-chlorophenyl) -1-5-azaspiro- (2,4) heptane-4,6-dione are obtained, m.p. 146-148 ° C.

Example 2-8

The following derivatives were prepared analogously to Example 1 and are in Table 1.

Example

mp / ° C / ¹ H NMR ppm

2 3 3-NO ₂ -Ph 3-Cl-Ph 173 to 176 146 to 148 3.02,3.29,3.20,7,86,8.29 3.06,3.33,3.28,3.36,7.34-7.58 4 4-C1 114 to 116 3.05,3.33,3.27,3.36,7.43,7.58 5 2-C1 114 to 116 3.13,3.34,3.31,3.39,7.42-7,60 6 3-Cl, 4-F-Ph 148 to 150 3.06,3.33,3.29,3.36,7.43-7,65 7 Ph 137 to 139 3.06,3.31,3.25,3.36,7.25-7.59 8 2,4,6-Clj-Ph 152 to 155 3.03,3.31,3.24,3.39,7.32-7.51

Ph = phenyl

Example 9

5- (3-chlorophenyl) -1-oxa-5-azaspiro (2,4) heptane-4,6-dione

A mixture of 1.6 g (0.0068 mol) of itaconic acid 3-chlorophenylimide and 1.2 g of 3-chloroperoxybenzoic acid is refluxed for 48 hours in 50 ml of dichloromethane, working up as in Example 1 to give 1.6 g of 5- (3 -chlorophenyl) -1-oxa-5-azaspiro (2,4) hepta-4,6-dione with m.p. 146-148 ° C.

Claims (3)

PATENTS Novel epoxymethylene-1,4-butanedioic acid derivatives of the general formula I wherein R is phenyl, phenyl mono, dialeno trisubstituted independently with chlorine, bromine, fluorine, methoxy, nitro, methyl, ethyl, carbotoxy-2-propyl, or a combination thereof. 2. A process for the preparation of derivatives according to item 1, characterized in that the 2-methylenebutanedioic acid imide of formula II / 11, is reacted with an epoxidizing agent selected from the group of peroxyacids such as peroxytrifluoroacetic acid, peracetic acid, peroxyformic acid, metachloroperoxybenzoic acid, peroxyphthalic acid, or hydrogen peroxide. 3. The process according to item 2, characterized in that the epoxidation is carried out in a buffering medium.