DD276479A1 - PROCESS FOR THE PREPARATION OF BENZO / B / FUR-2-YLCHINOXALINES - Google Patents

Abstract

The invention relates to a novel process for preparing benzo & b! Fur-2-ylquinoxalines (formula I), which have hitherto been difficult to access, and which can be used as intermediates for the preparation of biologically active preparations, in particular of algicides and herbicides. The synthesis is carried out by cyclization of substiutierten Phenoxymethylchinoxalinen the general formula II by the action of strong bases.

Description

Field of application of the invention

The invention relates to a process for the preparation of Benzolblfur-2-ylquinoxalines, which are useful as intermediates for the preparation of biologically active preparations, in particular of algicides and herbicidal agents.

Characteristic of the known technical solutions

Benzo [b] fur-2-yl quinoxalines have been found to be biologically active and have previously been prepared by oxidation, bromination or isonitrosation of 2-acyl-benzo [b] furans and cycloaddition of the reaction products with o-1-phenylenediamine DD -PS 258 165A1 worn 13.7.88). Although this process provides the 3-unsubstituted quinoxalines having good results. However, it has the disadvantage that the 3-methyl-substituted quinoxalines (formula I) are poorly accessible, since the 2-propionyl-benzo [b] furans required as starting materials are in some cases more difficult to prepare than the 2-acetylbenzenes used in the lesser case. bonzo | b] furans. If the 2-propionyl-benzo | b) furano were to be obtained according to the same synthesis protocol as the 2-acetylbenzo | b | furane, the 1-halo-butan-2-one is required, but only in the case of the halogenation of butanone low Mengo arises next to the main product incurred as 3-halo-butan-2-one. Therefore, 2-propionylbenzo | b] furan has not been synthesized in the dioxygen fashion, but as a result of multistep syntheses using organosilicon or organometallic reagents (A.ch. (11) 17 [1942] 335, Tetrahedron 40 (1984 ] 621). In the known, disadvantageous process, at first the benzofuran and then the fhinoxa'in ring closure are carried out.

Object of the invention

The aim of the invention is to find a new process for the preparation of such 8enzo b] fur-2-ylch! Noxalinen, which are currently difficult to access. The new process should be superior to those known hitherto and make it easier to prepare the previously poorly accessible 2- (benzo (b) fur-2-yl) -3-methylquinoxalines (formula I).

Explanation of the essence of the invention

The object of the invention is to find a novel process for the preparation of Benzofb | fur-2-ylquinoxalines, which are methyl-substituted in the 3-position of quinoxaline, since such compounds have biological activity, but are so far poorly accessible. In contrast to the previous process, a starting material with a prefabricated quinoxaline system should be used, in which the benzofuran ring closure is carried out in the synthesis process.

Features of the invention

According to the invention the object is achieved in that the readily available from 2- (bromomethyl) -3-methyl-quinoxartn and aromatic o-hydroxy-carbonyl compounds Phenoxvmethylchinoxaline (eg DD-PS 258226A1 of 13.7.1988) of the general formula II, in R and R 'independently of one another can be H, alkyl, aryl, alkoxy or hydroxyalkyl, in the melt or in solution, preference being given to using commercial or absolute ethanol as solvent, by the action of strong bases, preferably alkali metal hydroxide or alkali metal ethanolate at least equimolar amount at temperatures from 0 ° C to 250 ⁰ C, preferably at the boiling temperature of the solvent, cyclized, wherein de 2- (benzo [b] fur-2-ylj-3-methyl-quinoxalines of the general formula I, in R 'is H, OH, alkyl or aryl and R' has the same meaning as in the eingosotzten phenoxymethylquinoxaline arise.As it can be seen from Examples 2 and 3 i it, the process may advantageously also Runaway are led, df> 3 the phenoxymethylquinoxaline to be cyclized is not isolated as a substance, but after its formation from the above-mentioned starting materials in dissolved form as a component of the reaction mixture is mixed with the base causing the Cyclisiorung.

CH ₃ OC

CH ₂ -O

R /

Ausfuhrungebeispiel ·

BeUpIeM:

2- (benzo | b) fur-2-yl) -3-mothylchinoxalin

27.8 TI. 2- (3-Methyl-quinoxalin-2-ylmethoxybenzaldehyde are dissolved in 220 μl of ethanol and dissolved with the 6 TI solution.

Kelium hydroxide in 100 TI. Ethanol added. It is refluxed for 3 hours and allowed to cool. The ausgiifallene product

is filtered off with suction, washed neutral with water and recrystallized from ethanol.

Yield 92% of theory, melting point 142-143.5 ° C.

Belelplel 2:

? - (Denzo | b) fur-2-yl) -3-methyl-quinoxaline

The solution of β Ti. Potassium hydroxide In 100 TI. Ethanol is initially charged with 13.4 TI. Salicylaldehyde and then with the solution of

23.7 TI. 2- {bromomethyl) -3-methylquinoxaline in 400 TI. Ethanol added. Boil for 1 hour under reflux, again adding β TI.

Add potassium hydroxide and reflux for a further 3 hours. The reaction mixture is filtered hot. The severed Salt is boiled with ethanol. The combined ethanolic solutions are allowed to cool. The crystallized product

is filtered off with suction, washed neutral with water and recrystallized from ethanol.

Yield 82%.

Example 3:

2-methyl-3- (3-methyl-benzolb] fur-2-yl) chinoxt \ lin

To a from 2.5Tl. Sodium and 120Tl. absolute ethanol prepared alkanolate solution is added with stirring first 15.6Tl.

2-Hydroxy-acetophenone and then a solution of 23.7 TI. 2- (bromomethyl) -3-methyl-quinoxal! In 320 TI. absolute ethanol and boiled for 2 hours under reflux. Since the reaction mixture is again 2.5 TI. Sodium, dissolved in 30 TI. absolute

Ethanol, added and boiled under reflux for a further 4 hours. It is concentrated in vacuo, filtered off with suction and washed thoroughly Water and recrystallized sus ethanol. Yield 74% of theory, melting point 117-118 ° C.

BeUpIeU:

2-Methyl-3- (5-methyl-3-phenyl-benzo [b) fur-2-yl) quinoxaline

The solution of 36.8 TI. 5-methyl-2- (3-methyl-quinoxalin-2-ylmethoxy) benzophenone and 7 TI. Potassium hydroxide in 700 TI. ethanol

is refluxed for 3 hours and then concentrated in vacuo. The product is filtered off with suction, washed with water neutral and recrystallised from ethanol.

Yield 85% of theory, melting temperature 143-144.5 ⁰ C.

Example: 2- (6-Methoxy-3-phenyl-benzo [blur-2-yl) -3-methyl-quinoxaline

a) Analogously to Example 2 with 25 TI. 2-hydroxy-4-methoxy-benzophenone; The combined ethanolic solutions are concentrated in vacuo and placed in the refrigerator for crystallization;

Yield 63% of theory, melting temperature 115-117 ⁰ C.

b) Analogously to Example 4 with 38.4 TI. 4-Methoxy-2- (3-methyl-2-oxyn-2-ylmethoxy) benzophenone, yield 73% of theory.

Example β:

2- (3-hydroxy-benzo [b) fur-2-yl) -3-methyl-quinoxaline

The methanolic solution of 2- (3-methyl-quinoxalin-2-ylmethoxy) benzoic acid methyl ester is mixed with the equimolar amount Sodium methoxide added and boiled under reflux for 3 hours. By Am with acetic acid falls the desired Product, which is filtered off and recrystallized from pyridine. Yield 51% of theory, melting point 222-224 ° C.

Claims (6)

1. A process for the preparation of 3onzo _l b] fur-2-ylquinoxalines, characterized in that substituted phenoxymethyl quinoxalines are cyclized by the action of strong bases to benzo (b) fur-2-yl quinoxalines. 2. The method according to item 1, characterized in that the substituted Phenoxymethylchinoxaüne correspond to the general formula II, in which R and R 'independently of one another can mean H, alkyl, aryl, alkoxy or Aioxy. 3. The method according to item 1, characterized in that alkali metal hydroxide or Alkalialkanolat, preferably NaOH, KOH or C ₂ H ₅ ONa, can be used as strong bases and are added in mindostens equimolar amount. 4. The method according to item 1, characterized in that in the cyclization reaction benzo [b] fur-2-ylchinoxaline arise, which correspond to the general formula I, in which R = H, OH, alkyl or aryl and R 'has the same meaning as in the phenoxymethylquinoxaline used (see point 2.I). 5. The method according to item 1, characterized in that the cyclization reaction in the melt or in solution, preferably commercially or absolute ethanol is used as a solvent, at temperatures of ^{0 0} C to 250 ⁰ C, preferably at the boiling temperature of the solvent carried out becomes. 6. The method according to item 1-5, characterized in that the Phenoxymethylchinoxalin to be cyclized is not isolated as a substance, but after its formation from, for example, 2- (bromomethyl) -3-methyl-quinoxaline and aromatic o-hydroxy-carbonyl - compounds in dissolved form as part of the de? Reaction mixture is added to the cyclization causing base.