DD291082A5 - PROCESS FOR PREPARING 1-ALKYL-1,2,3,4-TETRAHYDRO-2,4-DIOXO-CHINAZOLIN-3-YL-ALKANSAEURE ESTERS - Google Patents

Abstract

The invention relates to a process for the preparation of * according to the invention is a * in an inert high-boiling organic solvent or without solvent under Erwaermen about 200C to a * of the general formula II implemented. Among the compounds of general formula II are fungicidal or plant growth regulatory substances. Formula II {* *}

Description

For this 1 page formulas

Field of application of the invention

The invention relates to a process for the preparation of 1-alkyl-1,2,3,4-tetrahydro-2,4-dioxo-quinazolin-3-yl-alkanoic acid esters of the general formula II. The invention relates to agricultural, garden and forestry of interest, where compounds produced by the invention z. B. can be used as fungicides or plant growth regulators.

Characteristic of the known state of the art A large number of quinazolines with potential action as phytoeffectors, fungicides, acaricides, insecticides or Herbicides are known (M.Suess, S.Johne, Z. Chem. 21, 431 [1981]). Of the compounds of the general formula II, some representatives are already known. Thus, 1,2,3,4-tetrahydro-i-methyl

Ethyl 2,4-dioxo-quinazolin-3-yl-pentanoate and ethylhexanoate [II: η = O, R-CH ₃ , R ² = C ₂ H ₆ , X = (CH ₂ J ₄ or (CH ₂ Ie) in low yields and in a mixture in addition to pyrido (2,1-b] quinazolin-10-ones obtained from 1-methyl-isatoic anhydrides and the corresponding Carbethoxylactam (AMShkrob, YIKiylova, VK Antonov, MMShemyakin, Tetrahedron Lett.

28,2701 (1967); Zh. Obshch. Khim. 38, 2030 (1968), Chem. Abstr. 70, 47, 397 (1969)).

The I ^ .S ^ -Tetrahydro-i-methyl ^ Adioxo-quinazolin-S-yl-acetic acid ethyl ester and the corresponding 1-ethyl compound

{I = 0, R = CH ₃ or C ₂ H ₆ , X = CH ₂₁ R ² = C ₂ H _e ) were prepared from 1-methyl or ₂ -methyl-1-methylphenyl. 1-ethyl-quinazoline-2,4-dione after salt formation by

Reaction with chloroacetic acid ethyl ester. This method is not generally applicable (A.R. El N. Ossmann, A. N. Osman, A. A. E. Helby, Bull. Pharm. Asiut Univ. 9 (1), 105 (1986); Chem. Abstr. 107, 1668, 619k [1987]). The 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazolin-3-yl-propanoic acid ethyl ester (II: η = 0, R = CH ₃ , X = CH ₂ CH ₂ , R ² = C ₂ H ₆ )

was prepared in several stages by reaction of N-methyl-anthranilic acid with potassium cyanate, followed by canethylation and alcoholysis (A. Lespagnol, JL Bernier, Ch. Lespagnol, J. Cazin, M. Cazin, Eur. J. Med. Chem Chim. Ther. 9,263 [1974], Chem. Abstr. 82, 16, 784 (197)].

As a by-product in very low yield of the I ^ .S ^ -Tetrahydro-i-methyl ^ -dioxo-quinazolin-S-yl-

ethyl acetate (II: η = 0, R = CH ₃ , X = CH ₂ , R ² = C ₂ H ₆ ) (M.Susso, S.Johne, Monatsh. Chem. 118,71 [1987]).

Object of the invention

The aim of the invention is to provide biologically active 1-alkyl-1,2,3,4-tetrahydro-2,4-dioxo-quinazolin-3-yl-alkanoic acid esters in practice in sufficient quantity and under more environmentally friendly and safer conditions ,

Explanation of the essence of the invention The object of the invention is a simple process for the preparation of compounds of the general formula II

to develop, which is characterized by technically easy to handle starting materials.

According to the invention, a 2-alkoxy-3,4-dihydro-4-oxo-quinazolin-3-yl-alkanoic acid ester of the general formula I in a

reacted inert, high-boiling, organic solvents or solvents with heating to give a 1-alkyl-1,2,3,4-tetrahydro-2,4-dtoxo-quinazolin-3-yl-alkanoic acid ester of the general formula II.

In the general formulas I and II, R and R ² (identical or different) are alkyl, X is alkylene [straight-chain (C ₁ -C ₁₀ ) or

Prefixed, optionally substituted], R ^{1 is} alkyl, alkoxy, halogen, CF ₃ , NO ₂ , CN or N (alkyl) ₂ and η is 0 to 4, wherein in the

Cases η = 2,3 or 4, the R ^{1 are the} same or different. Surprisingly, a migration of the radical R under the given conditions without further aids to Nitrogen in 1-Stelhng instead. Suitable solvents for the process according to the invention are polyethylene glycols, HMPT, biphenyl or diphenyl ether. The reaction of the compounds of general formula I erfoigt at temperatures from 200 ⁰ C, preferably from 25O ⁰ C to

300 ⁴ C. It is advantageous to carry out the reaction under protective gas, for example nitrogen or argon.

The process according to the invention is generally applicable and starts from easy-to-handle starting materials which are suitable for use in industry

known processes can be carried out, in comparison to the known processes, under environmentally friendlier and safer conditions and provides the compounds of general formula II in sufficient quantities.

The compounds of general formula II are biologically active. Among them are those that have a fungicidal or

show plant growth-regulatory activity.

The invention will be explained below by embodiments. Ausführungsbelsplele example 1

100MP _l 3,4-dihydro-2-methoxy-4-oxo-chlnazolln-3-yl) acetate (I: η = 0, R = R ² = CH _3, X = CHj) In the metal bath at 250 ° C melted to 270 ⁰ C10 minutes under nitrogen. After cooling, the mixture is separated by preparative layer chromatography (silica gel PF, Merck). R ₁ = 0.6 (benzene / acetone = 20: 7), m.p .: 135-137 ⁰ C, yield: 20mg au (i ^^ - ^ TetrahydroO-methyl--dloxo chinaiolin-S-yll-essigsäu emethylester ( II: η = 0, R = R ² = CH ₃ , X = CH ₁ ).

Example 2

100mg of 4- (3,4-dihydro-2-methoxy-4-oxo-quinazoline-3-yl) -butan ^r äuremethylester (I: η = 0, R = R ² = CH _3, X = CH ₂ CH ₂ CH ₂ ) are in 5ml abs. Triethylene glycol (freshly distilled) in a metal bath at 270-280 ⁰ C for 10 minutes. The resulting reaction mixture is poured into 50 ml of water, extracted several times with chloroform and the chloroform extracts were concentrated. The residue is separated by preparative layer chromatography (silica gel PF, Merck). Rf = 0.5 (benzene / acetone = 20: 7), mp: 64-66 ° C, yield: 30 mg of 4- (1,2,3,4-tetrahydro-1-methyl-2,4-dioxo -quinazolin-3-yl) -butanoic acid methyl ester (II: η = 0, R = R ² = CH ₃ , X = CH ₂ CH ₂ CH ₂ ).

Example 3

100 mg (3,4-dihydro-2-methoxy-4-oxo-quinazolin-3-yl) -acetic acid ethyl ester (1: n = 0, R = .R ² = CH ₃ , X = CH ₂ ) are dissolved in 5 ml of diphenyl ether 10 Minutes under argon heated. It is then separated by column chromatography (Kieselgel 60, Merck, elution with chloroform to which increasing amounts of methanol are added). R ₍ = 0.6 (benzene / acetone = 20: 7), mp: 135-137'C, Yield: ISmgand ^ .S ^ -Tetrahydro-i-methyl -dioxo-quinazolin-S-yD-acetic acid methyl ester dl: η = 0, R = R ² = CH ₃ , X = CH ₂ ).

JSt ΰ

(R ¹ ) _n

NX COOR ²

OR

N-X-C00R2

Claims (4)

1. Method for the production of i alkansäureestem the general formula II, characterized in that mar, a 2-alkoxy-3,4-dihydro-4-oxo-quinazolin-3-yl-alkanoic acid ester of the general formula I in an inert high-boiling organic solvent or without solvent with heating to an i-alkyl-I ^^ Atetrahydro ^^ - dioxo-quinazolin-S-yl-alkanoic acid ester of the general formula II, wherein in the general formulas I and Il R and R ² (same or different) for alkyl, X for alkylene [straight-chain (C ₁ -C 10) or branched, optionally substituted], R ^{1 is} alkyl, alkoxy, halogen, CF ₃ , NO ₂ , CN or N (alkyl) ₂ and η is 0 to 4, where in the cases η = 2,3 or 4, the R ^{1 are the} same or different, stand. 2. The method according to claim 1, characterized in that one works at temperatures above 200 ⁰ C. 3. The method according to claim 2, characterized in that one works at temperatures of 250-300 ⁰ C. 4. The method according to any one of claims 1 to 3, characterized in that one carries out the reaction under protective gas.