DD269382A1 - PROCESS FOR THE PREPARATION OF 3-AMINO-4-HYDROXY-CHINOL-2-ONEN - Google Patents

Abstract

The invention relates to a process for the preparation of 3-amino-4-hydroxy-quinol-2-ones. The title compounds, which may be used as intermediates, are made available by a one step process according to the invention by treating 2-oxo-3- (1-pyridinium) -1,2-dihydroquinoline-4-olates with 40-80% aqueous hydrazine hydrate solution become.

Description

Process for the preparation of 3-amino-4-hydroxy-quinol-2-ones

Field of application of the invention

The invention relates to a process for the preparation of 3-amino-4-hydroxy-quinol-2-ones. These compounds can be used as intermediates for pharmaceuticals.

Characteristic of the known technical solutions

It is known that 3-amino-4-hydroxy-quinol-2-ones can be prepared according to Chenu Pharm. Bull. 2 (1977) 2602 from isatoic anhydrides and isocyanacetic acid esters in 2 stages. However, this method requires as a component the hard to represent Isccyanessigester. Ring N-substituted products also require a prior, specific N-alkylation of the corresponding isatoic anhydrides. Further, in J · Heterocycle Uhem. 1981. "1061 describes a process for the preparation of 4-alkyl, - aryl and unsubstituted 3-aminoquinol-2-ones based on the treatment of 2-oxo-i, 2-dihydroquinol-3-yl-pyridinium salts with aniline based. But this does not produce 3-amino-4-hydroxy-quinol-2-ones.

Object of the invention

The aim of the invention is to produce 3-amino-4-hydroxy-quinol-2-ones in a simple manner.

Explanation of the nature of the invention

The object of the invention is to produce 3-amino-4-hydroxy-ohinol-2-ones by a new, cheap and variable-substituent process.

According to the invention the object is achieved daduroh that 3-amino · 4-hydroxy-ohinol -? - one of the general formula I ₁

be prepared by 2-0χο · -3- (1-pyridinium) -1,2-dihydroquinoline-4-olates of general formula II,

II

with 40-80% In addition, the unreacted hydrazine hydrate can be recovered in large part again. In formulas I and II, R is a hydrogen or halogen atom, an alkyl, alkoxy or hydrazinhydrate solution

Amino, R is a hydrogen atom, an alkyl or alkoxy group, R 1 is a hydrogen or halogen atom and R 1 is a hydrogen atom, an alkyl or aralkyl group. The process discloses both known and novel 3-amino compounds which have not previously been described The advantage of the process is that it avoids the use of the expensive isocyanoacetic acid ester. In addition, it allows a relatively simple variation of the substituents, in particular on the ring nitrogen. The pyridinium quinolates 2 required are obtained by a process which, for other examples, is described in US Pat. No. 3,774,216 (1971), Chem. Abstr. 75 (1971) 5734, is obtained in a simple manner from o-chloroacetaminobenzoic acid esters and pyridine.

hältlich. Halogenated and amino-substituted starting materials in the quinoline nucleus can be prepared by customary aromatic substitution on the corresponding unsubstituted pyridinequinolates 2 . Au Chinolinstickstcff substituted starting materials are available from both N-Alkylanthranilsäureestern as well as by customary Ghinolone N-alkylation of corresponding Pyridiniumchinolaten 2 .

embodiments

Example 1 3-Amino-4-hydroxy-quinol-2-one

20 mmol of 2-oxo-3- (1-pyridinium) -1,2-dihydroquinoline-4-olate are heated to boiling for 4 hours in 40 ml of 50% aqueous hydrazine hydrate. After cooling, the mixture is diluted with 20 ml of water (30 ml of water / hydrazine can be distilled off beforehand for recovery), neutralized with glacial acetic acid and, after completion of the crystallization, suctioned off. It is washed with water and recrystallized from ethanol. Yield 86 % » Melting point above 36O ⁰ O (See Chem. Pharm. BiUl. 25 (1977) 2602).

(Condensation product with benzaldehyde: mp 246-250 ⁰ C, recrystallized as ethanol).

Example 2

3-amino-4-hydroxy-6,7-dimethoxy-quinol-2-one

10 mmol of 6,7-dimethoxy-2-oxo-3- (1-pyridinium) - !, 2-dihydroquinino-4-olate are boiled in 40 ml of 50% aqueous hydrazine hydrate for 20 to 22 hours, so that a clear solution arises. After cooling, it is diluted with 15 ml of water (30 ml of water / hydrazine can be distilled off beforehand), neutralized with glacial acetic acid and, after crystallization has ended, the reaction product is filtered off with suction, washed with water and recrystallized from ethyl acetate / ethanol. Yield 78 % Melting point: from 36O ⁰ G decomposition. (Condensation product with benzaldehyde: mp 275-280 ⁰ C, from dimethylformamide / water recryst ^ llisiert).

249382

Example 3 3-Amino-6-bromo-4-hydroxy-ohinol-2-one

20 mmol of 6-bromo-2-oxo-3- (1 -pyridinium) -i ^ -dihydroquinoline ^ -olat are heated for 14 to 16 hours in 60 ml of 50% aqueous hydrazine hydrate to boiling · After cooling, the reaction solution with Diluted 15 ml of water (to recover 40-45 ml V / ass er / hydrazine previously be distilled off), and adjusted by the dropwise addition of bisessig a pH of 7-8 · The precipitate is filtered off with suction, washed with water and to Purification dissolved in dimethylformamide · The still warm solution is mixed with the same amount of ethanol. Cooling crystallizes the reaction product. Yield 63 % melting point above 36 ° C.

Example 4 3-Amino-6-chloro-4-hydroxy-quinol-2-one

10 mmol of 6-chloro-2-oxo-3- (1-pyridinium) -1,2-dihydroquinoline-4-olate are heated to boiling in 10 ml of dimethylformamide and 50 ml of 50% aqueous hydrazine hydrate for 12 hrs. Distilled 40 ml of water / hydrazine, diluted with 15 ml of water, filtered and adjusted by dropwise addition of glacial acetic acid a pH of 7-8. After 2 hours, the reaction product is filtered off with suction, washed with water and recrystallized from ethanol. Yield 83 % _t melting point: decomposition from 35O ⁰ (cf. Synthesis 1976, 8O5). (Condensation product with acetic anhydride: melting point 332-335 ⁰ G, from., Glacial acetic acid recrystallized).

Example 5

3-amino-6,8-d-dichloro-4-hydroxy-quinol-2-one

10 mmol of 6,8-dichloro-2-oxo-3 ~ (1-pyridinium) -1,2-dihydroquinoline-4-olate are heated to boiling point in 10 ml of dimethylformamide and 50 ml of 80% aqueous hydrazine hydrate for 36 hours. Ulan distils off 35 ml of hydrazine hydrate, adds 20 ml of water and adjusted with glacial acetic acid a pH of 7-8. After 3 hours, the reaction product is filtered off, washed with water

and recrystallized from dimethylformamide. Yield 71%, Schnelzpunkt: from ⁰ C 3IO sublimation, from 350 ⁰ G decomposition.

Example 6 3-Amino-1-benzyl-4-hydroxy-ohinol-2-one

10 mmol of 1-benzyl-2-oxo-3- (1-pyridinium) -ohinolin-4-olate are heated to boiling in 30 ml of 50% aqueous hydrazine hydrate for 8 hrs. After cooling, the reaction solution is neutralized with glacial acetic acid, the precipitate is filtered off, washed with water and recrystallized from ethanol. Yield 67 % · Melting point 247-250 ⁰ O.

Example 7

3-Ano-4-hydroxy-1-methyl-quinol-2-one

10 mmol of 1-methyl-2-oxo-3- (1-pyidinium) -quinoline-4-olate are dissolved in about 30 ml 50proz. aqueous hydrazine hydrate solution for 6 hrs. Boiled. After Eckalten is diluted with 10 ml of water (previously 20 ml of water / hydrazine can be distilled off), adjusted with glacial acetic acid to pH 7-8 and the precipitate sucked off. Yield 62%, melting point: 322-27 Z. (ethanol) (see Chera Pharm. Bull. 25 (1977) 2602). (Condensation product with acetic acid anhydride: mp 207-209 ⁰ C, recrystallized from ethanol).

Example 8 1-Allyl-3-smino-4-hydroxy-quinol-2-one

0.01 mmol of 1-allyl-2-oxo-3- (1-pyridinium) -1,2-dihydro-quinoline-4-olate are dissolved in 35 ml 85proz. aqueous hydrazine hydrate heated to boiling for 4.5 hrs. Finally, 25 ml are distilled off, the solution diluted with 20 ml V / aaser and adjusted with glacial acetic acid to pH = 7-8. After 12 hrs. Is filtered off, washed with water and recrystallized from acetonitrile. Yield 87%, melting point 176-179 ⁰ C.

Example 9 3,6-Diamino-4-hydroxy-ohinol-2-one dihydrochloride

10 mmol of 6-acetylamino-2-oxo-3- (i-pyridinium) -1,2-dihydroquinoline-4-olate are boiled for 7 hours in 5 ml of dimethylformamide and 30 ml of 80% aqueous hydrazine hydrate distilled off and 30 ml of 4N methanolisohe hydrochloric acid added · After 12 hrs · the precipitate is filtered off and washed with a little methanol «yield 65%, mp 170-180 ° 0 · condensation product with acetic anhydride: 365-370 ⁰ O (from dimethylformamide) · das The same product is obtained when 6-nitro-2-oxo-3- (1-pyridinium) -1,2-dihydroohinoline-4-olate is heated to boiling in the same manner for 35 hours.

Claims (1)

2 <93 82 claim Process for the preparation of 3-amino-4-hydroxy-ohinol-2-ones of the formula I, Wherein R is a hydrogen or halogen atom, an alkyl, alkoxy or amino group, R is a hydrogen atom, an alkyl or alkoxy group, B? is a hydrogen or halogen atom and R 1 is a hydrogen atom, an alkyl or aralkyl group, characterized in that 2-oxo-3-P-pyridinium) -1,3-dihydroquinoline-A-olates of the formula II, II in which R to R ^{4 have} the abovementioned meaning, are reacted with hydrazine hydrate as 40-80% by weight aqueous solution in the boiling point.