DD291085A5 - PROCESS FOR PREPARING 1,2,3,4-TETRAHYDRO-1-METHYL-2,4-DIOXO-CHINAZOLIN-3-YL-ALKANSAEUREESTERS - Google Patents

Abstract

The invention relates to a process for the preparation of the invention. A salt or its ester is reacted with diazomethane in solution or suspension in an organic solvent to give a general formula II. Among the compounds of the general formula II are fungicidally or plant growth-regulatory active substances. {* * * Diazomethane}

Description

For this 1 page formulas

Field of application of the invention

The invention relates to a process for the preparation of 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazyclin-3-yl-alkanoic acid, of general formula II. The invention is suitable for agricultural, garden and forestry of interest, where compounds prepared according to 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 effects as phytooffektoron, fungicides, acaricides, insecticides or Herbicides are known (M.Suess, S.Johne, Z. Chem. 21,431 [19811]. Of the compounds of the general formula II, some representatives are already known. Thus, 1,2,3,4-tetrahydro-1-methyl

Ethyl 2,4-dioxo-quinazolin-3-yl-pentanoate and ethylhexanoate (II: η = O, R ³ = C ₂ H ₆ , X = [CH ₂ W or (CH ₂ I ₅ ) in low yields and in a mixture in addition to pyrido (2, 1b) quinazolin-10-ones are obtained from 1-methyl-isatoic anhydrides and corresponding carbethoxylactam (AM Shkrob, YI Krylova, VK Antonov, MM Shemyakin, Tetrahedron Lett 28,2701119671; Zh Obshch. Khim. 2030 (19681, Chem. Abstr. 70, 47, 397v (1969)).

The 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazolin-3-yl-acetic acid ethyl ester (II: η = 0, X = CH ₂ , R ³ = C ₂ H ₆ ) was from

1-methyl-quinazoline-2,4-dione obtained after salt formation by reaction with ethyl chloroacetate. This method is not generally applicable (A. R. El N. Ossmann, A. N. Osman, A. A. E-Helby, Bull. Pharm., Asiut Univ., 9 (11, 105 (1986), Chem. Abstr.

107,168 619 K (19871).

Deri ^ .SATetrahydro-i-methyl ^ Adioxo-quinazolin-S-yl-propanesMethylesterlll: η = 0, X = CH ₂ CH ₂₁ R '= C ₂ H ₆ ) was about

several stages by reaction of N-methyl-anthranilic acid with potassium cyanate, followed by a cyanoethylation and

Alcoholysis, presented (A. Lespagnol, J. L.Bernier, Ch. Lespagnol, J. Cazin, M. Cazin, Eur. J. Med. Chem. Chim. Ther. 9,263

(19741, Chem. Abstr. 82,16784, η (19751).

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

ethyl acetate: η = 0, X = CH ₂₁ R ³ = C ₂ H ₆ ) (M.Suess, S.Johne, Monatsh. Chem. 113, 71 (19871).

Object of the invention

The aim of the invention is to provide biologically active I ^ .S ^ -Tetrahydro-i-methyl ^ -dioxo-quinazolin-S-yl-alkansa'ureester the practice in the desired variety and in sufficient quantities cost-effective.

Explanation of the essence of the invention

The object of the invention is to develop a simple, generally applicable process for the preparation of compounds of general formula II, which is characterized by technically easy to handle and cost-effective starting materials.

According to the invention an I ^ .S ^ -Tetrahydro ^ -dioxo-quinazolin-S-yl-alkanoic acid or its esters of general formula I with diazomethane in solution or suspension in an inert organic solvent to a 1,2,3,4-tetrahydro -i-methyl-2,4-dioxo-quinazolin-3-yl-alkanoic acid ester of the general formula II reacted, wherein in the case of R ² = H always the methyl ester of compounds of general formula II (R ³ = CH ³ ) is obtained.

In Ίβη general formulas Lundllstehen R * is H or alkyl, R ^{1 is} alkyl (In the case of R ² = H, R ³ = methyl, in the case R ² = alkyl

R ¹ -R ¹ I ₁ X for alkylene (straight-chain [Ci-Ci ₀ ) or branched, optionally substituted), R 'is alkyl, alkoxy, halogen, CF ₃ , NO ₂ ,

CN or · N (alkyl) ₂ and η is O to 4, where in the precipitate η = ₂ , 3 or 4 the R 'are identical or different. Surprisingly, a Mothylierung takes place on the N-atom without its additional activation and in the case of R ² = H, a simultaneous quantitative formation of Mbthylesters in only t inem Raaktionsschritt.

The solvents used for the ancestor according to the invention are aliphatic and aromatic hydrocarbons, alkanoic acid esters, alcohols, Fth'.r, acotone, acetonitrile, DMF and OMSO.

In the case of the acids of the compounds of the general formula I (R ² = H), at least two equivalents are used

Diazomethane. It is advantageous to use diazomethane in excess and to work in the presence of a Lewis acid, preferably boron trifluoride etherate.

The process of the invention is generally applicable and is based on easily manageable and cost-effective starting materials which are commercial products or can be prepared by known processes. In only one reaction step, the compounds of general formula II are inexpensive in the desired variety and in sufficient quantities.

The compounds of the general formula II are biologically active, but they are those which have a fungicidal or plant growth regulatory activity.

The invention will be explained below by Ausführungsbeisplolo.

Ausführungsbelsplele

example 1

220 mg of 1,2,3,4-tetrahydro-2,4-dioxo-quinazolin-3-yl-o-sacetic acid (1: η = O, R ² = H, X = CH ₂ ) are dissolved in 5 ml of abs. Toluene and 20 ml of abs , Dissolved methanol and treated with a solution of diazomethane in toluene in portions with stirring until no more nitrogen evolution is observed and a slight yellowing dor solution occurred. It is evaporated to dryness in vacuo, the residue is purified by column chromatography (silica gel 60, elution with chloroform, to which increasing amounts of methanol are added) and recrystallized from methanol / water. Rf = 0.6 (Bonzen / acetone = 20: 7), mp: 135-137 ° C, yield: 80mg of (! ^, S ^ -Tetrahydro-i-methyl ^^ - dioxo-quinazolin-S-yD -acetic acid methyl ester dl: η = 0, R = CHj, X = CH ₂ ).

Example 2

To a mixture of 262 mg of 4- (1,2,3,4-tetrahydro-2,4-dioxo-quinazolin-3-yl) -butanoic acid methyl ester (I: η = O, R ² = CH ₃ , X = CH ₂ CH ₂ CH ₂ ; and 142 mg of boron trifluoride etherate (as ethereal solution) in 20 ml of dioxane is added in portions a solution of dichloromethane in dioxane until no evolution of nitrogen is observed stirred and evaporated to dryness in vacuo, water is added and the mixture is extracted with chloroform The chloroform extracts are evaporated in vacuo and purified as in Example 1, R ₍ = 0.5 (benzene / acetone = 20: 7), m.p. 64-66 ° C, yield: 125 mg of 4- (1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazoliii-3-yl) -butsenate (II: η = 0, R ³ = CH ₃ , X = CH ₂ CH ₂ CH ₂ ).

Claims (4)

1. A process for the preparation of i ^^ - tetrahydro-i-methyl ^ Adioxo-quinazolin-S-ylalkansäureestern the general formula II, characterized in that a 1,2,3,4-tetrahydro ^^ - dioxo-quinazoline S-yl-alkanoic acid or its esters general formula I with diazomethane in solution or suspension in an inert organic solvent to an I ^ .S ^ -Tetrahydro-i-methyl ^^ - dioxo-quinazolin-S-yl-alkanoic acid ester of the general formula In the general formulas' and II, R ^{2 is} H or alkyl, R ^{3 is} alkyl (in the case of R ² = H, R ³ = methyl, in the case of R ² = alkyl, R ³ = R ² ), X for alkylene (straight-chain [C, -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, wherein 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 uses diazomethane in excess. 3. The method according to claim 1 and 2, characterized in that one carries out the reaction in the presence of a Lewis acid. 4. The method according to claim 3, characterized in that one uses as Lewis acid boron trifluoride etherate.