DD291086A5 - 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 a * or its esters of the general formula I with a Orthokohlensaeureester in an inert organic solvent or without solvents under Erwaermen over 130C to a * of the general formula II. Among the compounds of general formula II are fungicidal or plant growth regulatory substances. Formulas I, II {* * * Orthokohlensaeureester}

Description

For this 1 page formulas

Field of application of the invention

The invention relates to a process for the preparation of i-alkyl-I ^ Atotrahydro ^ -dioxo-quinazolin-S-yl-alkansäuroestern of the general formula II. The invention is for the agriculture, horticulture and forestry of interest, where orfindungsgemäß prepared compounds 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 phyto-effectors, fungicides, acaricides, insecticides or herbicides are known (Süße, S.Johne, Z. Chem., 21, 431 (1981)).

Of the compounds of the general formula II, some representatives are known. Thus, 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazolin-3-yl-pentanoic acid ethyl ester and -hoxansäureethylester (II: η = 0, R = CH ₃ , R ³ = CjH ₆ , X = (CH ₂ I ₄ or (CH] Is) 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, Yl Krylova, VKAntonov, MMShemyakin, Tetrahedron Lett 28,2701119671; AMShkrob.YIKrylova.VKAntonov.MMShemyaki ^ Zh.Obshch.Khim.ae, 2030 [19681, Chem. Abstr.

70.47397V (19I39J).

The 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-chmazolin-3-yl-acetic acid ethyl ester and the corresponding 1-ethyl compound (II: η = 0, R = CH ₃ or C ₂ H ₆ , X = CHj, R ³ = C ₂ H ₆ ) were obtained from 1-methyl- or 1-ethyl-quinazoline-2,4-dione after salt formation by reaction with ethyl chloroacetate. This method is not generally applicable (AR El N. Ossmann,

A.N. Osman, A.A. E.Helby, Bull. Pharm. Asiut Univ. 9 (1), 105 (1986), Chem. Abstr. 107, 168619k (1987)).

The corresponding 1-methyl-propanoic acid ethyl ester (II: η = 0, R = CH ₃ , X = CH ₂ CH ₂ , R ³ = C ₂ H ₅ ) was followed over several stages by reaction of N-methyl-anthranilic acid with potassium cyanate from cyanothylation and alcoholysis

Lespagnol, J.L. Bernier, Ch. Lespagnol, J. Cazin, M.Cazin, Eur. J. Med. Chem. Chim. Ther. 9,263 (1974), Chem. Abstr. 82, 16784 (19751).

As a by-product in a very low yield of 1,2,3, '4-Tetrahydro-1-methyl ^ -dioxo-quinazolin-S-yiessigsäureethylester (II: n = 0, R = CH ₃ , X = CH ₂ , R ³ = C ₂ H ₆ ) (M.Suess, S.Johne, Monatsh. Chem. 118, 71 (1987)).

Object of the invention

The aim of the invention is to provide biologically active 1-alkyl-1 ^, SAtetrahydro ^ -dioxo-quinazolin-S-yl-alkansSureester the practice in the desired variety, in sufficient quantity and using more environmentally friendly and less hazardous agents available.

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 N- (2-aminobenzoyl) -aminoalkanoic acid or its ester of general formula I is reacted with an orthocarbonic acid ester in an inert organic solvent or without solvent, with heating to give an i-alkylsafetrahydro-dioxo-chinaiolin-S yl-alkanoic acid ester of the general formula II implemented.

In general formulas I and II, R and R ³ (same or different) are alkyl, R ^{1 is} H or alkyl, X is alkylene

(straight-chain IC ₁ -C ₁₀ I or branched, optionally substituted), R ^{1 is} alkyl, alkoxy, halogen, CF), NO ₁ , CN or Dlalkylaminound and η is from 0 to 4, where In the cases η - 2,3 or 4 the R ^{1 are the} same or different.

Ubwjuciienderweise takes place a cyclization of the compounds of the old Fürmol I to an intermediate compound,

which converts under the angegbbenen reaction conditions into a compound of general formula II.

Suitable solvents for the orfindungsgomäßo method are preferably absolute solvent, such as DMF, DMSO or an alkyl ethylene glycol acetate. The reaction of the compounds of the general formula I with a Orthokohlonsäureester is at temperatures above

13O ⁰ C performed. In general, the reaction mixture is heated to reflux. Of advantage is the removal of low-boiling products from dom reaction mixtures z. B. by distillation, and continue the reaction under reflux.

The Orthokohlensäureestor is used in excess and / or itself as a solvent. The compounds of general formula I are from isatoic anhydrides and aliphatic amino acids or their esters

readily available (M.Suess, S.Johne, HeIv. Chim. Acta 68, 892 (1985)) and can be used as crude products, but with careful consideration

Remaining water to be used. The inventive method is generally applicable and is easy to handle, inexpensive and, im Compared to the known processes, environmentally friendly and less hazardous starting materials, the commercial Products are or can be prepared by known Verfahron. It provides the compounds of general formula M

in the desired variety and in sufficient quantities.

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

pest growth regulatory activity.

The invention will be explained below by way of Ausführungsbeispiole. embodiments example 1

2.08 g of 2-amino-hippuric acid-1-methyl ester (I: η = O, R ² = CH ₃ , X = CHj) are refluxed with 4.08 g of tetramethyl orthocarbonate for 4 hours. The excess of orthocarbonic acid ester is distilled off in vacuo and the residue is separated by column chromatography (Kieselgel 60, elution with chloroform, to which increasing amounts of methanol are added) and recrystallized. R | = 0.6 (benzene / Acoton = 20: 7), m.p .: 135-137 ⁰ C, yield 1.50 g of 1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazoline 3-yl-acetic acid methyl ester (II: η = 0, R = R ³ = CH ₃ , X = CHj).

Example 2

1,94g2-Amino-hippuric acid (1: η = 0, R ² = H, X = CH ₂ ) are heated with 4.08 g of tetramethyl orthocarbonate for 1 hour in a Dostillationsapparatur (bath temperature 130 ° C) and then refluxed for 3 hours. Further as in Example I. Yield: 1.60 g of 1S-SAT-tetrahydro-i-mothyl-adioxo-quinazolin-S-yl-acetic acid methyl ester residue: η = 0, R = R a = CH ₃ , X = CH ₂ ).

Example 3

2.08 g of N- (2-amino-benzoyl) aminopropane acid (I: η "= 0, R ² = H, X = CH ₂ CH ₂ ) and 4.5 g of orthocarbonic acid tetramethoxyl are dissolved in 20 ml of methyl ethylene glycol acetate for 1 hour at 140-150 ° C., then distilling off the low-boiling products and refluxing the reaction mixture for 2 hours. Further as in Example 1. R ₁ = 0.5 (benzene / acetone = 20: 7), mp: 90-94 ° C (amorphous), yield: 500mg of Sd ^ .S ^ -Tetrahydro-i-methyl ^ Adioxo-quinazolin-3-yl) -propanoic acid methyl ester (II: η = 0, R = R ³ = CH ₃ , X = CHjCH ₂ ).

Example 4

1.63 g of 2H-3,1-benzoxazine-2,4 (1H) -dione are added with stirring to a solution of 1.7 g of 4-Aminobuttersäuremethylosterhydrochlorid and 1.1 g of triethylamine in 50ml abs. Given methanol. The mixture is stirred at 30-50 ° C. until the CO 2 evolution has ended (2-3 hours), evaporated to dryness in vacuo and taken up with chloroform, filtered and the filtrate again evaporated to dryness reacted, for example R 1 | = 0.5 (benzene / acetone = 20: 7)., m.p .: 64-66 ⁰ C, yield: 1,15gan4- (1,2,3,4-tetrahydro-1-methyl- 2,4-dioxo-quinazolin-3-yl) -butanoic acid methyl ester (II: η = 0, R = R ³ = CH ₃ , X = CHjCH ₂ CHj).

Example 5

1.63 g of 2 H-3,1-benzoxazine-2,4 (1H) -dione are added with stirring to 70 mmol of an aqueous solution of 1.1 g of 4-amino-butyric acid and 1.1 g of triethylamine and at 30-50 ⁰ C stirred until completion of CO ₂ evolution (2 hours). The reaction solution is concentrated in vacuo and the residue is reacted with 4.1 g of tetramethyl cristocarbonate. Yield:

1.10 g of methyl 4- (1,2,3,4-tetrahydro-1-methyl-2,4-dioxo-quinazolin-3-yl) butanoate (II: η = O, R = R ³ = CH ₃ , X = CH ₂ CH ₂ CH ₂ )

JS <t 636

(R ¹ ) _n

-C00R3

Claims (3)

1. Method for the production of i alkanoic acid esters of the general formula II, characterized in that an N- (2-AminobenzoyD-aminoalkansäure or esters thereof of the general formula I with a Orthokohlensäureester in an inert organic solvent or without solvent under egg heating to an i-alkyl-i ^^^ tetrahydro ^^ - dioxo-quinazolin-S-yl-alkanoic acid of the general formula II, where in the general formulas I and II R and R ³ (identical or different) are alkyl, R ^{2 is} H or alkyl, X is alkylene ( straight-chain (C ₁ -C ₁₀ ) or branched, optionally substituted), R ^{1 is} alkyl, alkoxy, halogen, CF ₃ , NO ₂ , CN or dialkylamino and η is 0 to 4, where in the cases η = 2,3 or 4 the R ^{1 are the} same or different. 2. The method according to claim 1, characterized in that one uses the Orthokohlensäuretetraalkylester in excess and operates at temperatures above 130 ⁰ C. Process according to claims 1 and 2, characterized in that the compounds of general formula I are used as crude products.