CS240772B1 - Method of 7-hydroxyquinoline derivatives production - Google Patents

Description

The invention relates to a process for the production of quinoline hydroxy derivatives which are used as intermediates in the manufacture of dyes or pharmaceutical compositions.

Some hydroxy derivatives of quinoline have been previously described in the literature. Thus were prepared from 3-acetylacetone hydroxyanilu farm is considerably ^Pr I ^{p / J} - / - 3-hydroxy ^{phenyl when} n ^amino- / bu ^t YRO enonuдо7ádёn ^{f r} M 'chloride or by acidification with conc. sulfuric acid. [Bulow, Issler, Chem. Ber 36, 4016 (1904); Bulow Chem.Ber. 35, 2452 (1903). 2,4 Dimethyl-7-hydroxyquinoline. was prepared by reacting the aminosalicylic amide with acetylacetone for 100 hours and resulting in 7-hydroxy-2,4-dimethylquinoline-8-carbonic acid, which was then decarboxylated (Sci). ^: Papers Inst. Phys. Chem. Res. (Tokyo) £ 6, No 1, 101 (1962); CA. 58, '4515 f.

2-Methyl-4-phenyl-7-hydroxyquinoline was prepared by Kazutoschi Yamada by reacting the ammonium or alkylammonium salt of 6-aminosalicylic acid with benzoylacetone in the same manner (Nippon, Kagaku Zaashhi 82, 1368 (1961)). CA 59, 3892 (ab). Said processes start from hardly available intermediates and the reaction processes result in low yields.

This invention relates to the production of the 7-hydroxyquinoline of the formula I which is technologically feasible and based on the availability ^NYC h between ^p roducts. Progress is oíÉipnově _ ^ ^p and ^p ožadované roduk ^those formed in good quality and high yield.

A process for the preparation of a compound of formula (I) wherein R = -phenyl, -methyl, comprises treating m-aminophenol with a compound of formula (II), RCOCH2COCH3, wherein R is as defined above,

2,240,772 preferably in the presence of an inert organic solvent such as tetrachlorethylene, carbon tetrachloride and dichlorobenzene miscible with dehydrating agents such as sulfuric acid, phosphorus pentoxide, aluminum chloride and zinc chloride, to which it is inert. Under these conditions, an exothermic reaction occurs to produce the desired product. After cooling, the reaction product is dissolved in water and the free base precipitated by dilute sodium hydroxide which can be recrystallized from an aliphatic alcohol such as methanol to increase purity.

The preparation process is illustrated by the following examples.

Example 1

Preparation of 2,4-dimethyl-7-hydroxyquinoline.

In a two-necked flask equipped with a stirrer and a reflux condenser, 0.2 mol of 3-eminophenol and 0.2 mol of acetylacetone were mixed. 0.4 moles of horse were added slowly with vigorous stirring. I ^ SO ^. The reaction proceeds strongly exothermically, excluding the salt of 2,4-dimethyl-7-hydroxyquinoline. To eliminate the free base, the crude product is dissolved in a small amount of water and adjusted to pH with a slightly alkaline solution with sodium hydroxide solution. The precipitated base was recrystallized from a small amount of methanol.

The precipitated product melts at 217.5-218 ^e C.

Example 2 Preparation of 2-methyl-4-phenyl-7-hydroxyquinoline.

In a two-necked flask equipped with a stirrer and reflux condenser, 0.2 mole of m-aminophenol and 0.2 mole of benzoyleoetone in carbon tetrachloride were mixed. With vigorous stirring, 0.4 mol of conc. sulfuric acid. The course of the reaction is exothermic and a crystalline product precipitates. The solvent is distilled off under vacuum. The free base is liberated in dilute sodium hydroxide. The product was recrystallized from methanol.

The product precipitated as orange needles of m.p. 262. C.

Example 3

Preparation of 2-methyl-4-phenyl-7-hydroxyquinoline.

- 3 240 772

In a two-necked flask equipped with a stirrer and a reflux condenser ₇ 0.2 were mixed. mole of 3-aminophenol and 0.2 mole of benzoylacetone and dichlorobenzene. For. 0.4 ml of aluminum chloride was added slowly with vigorous stirring. The reaction proceeds, exothermically, and a crystalline product precipitates. · After removing the solvent, liberation of the base with sodium hydroxide and recrystallisation from methanol, ^the ZIS ^AJ crystals with t-t.'263 ° C ·

Example 4

Preparation of 2-methyl-4-phenyl-7-hydroxyquinoline.

In a two-necked flask OPA ^{é é} en ^tr m and ^I C ^h em ^dl and zpětoým c ^h tuner amíseny were 0.2 mol of 3-aminophenol and 0.2 mole · benzoylacetone in tetrachlorethylene. 0.4 mol of zinc chloride was added slowly with vigorous stirring. The reaction proceeds exothermically and a crystalline product precipitates. After removal of solvent, liberation of the base with sodium hydroxide and recrystallisation from methanol are obtained ^{by the y} r S ^{t ly} with mp 263 "C.

Example 5

Preparation of 2-methyl-4-phenyl-7-hydroxyquinoline.

The reaction proceeds as in Example 4 except that benzoylacetone is dissolved in dichlorobenzene and 0.4 moles of phosphorus pentoxide is used as the dehydrating agent.

Claims (2)

A process for the preparation of 7-hydroxyquinoline derivatives of the general formula I, wherein R <phenylphenethyl, characterized in that m-aminophenol is treated with a compound of the general formula II RCOCH2COCH3, where R is as defined above, in the presence of a dehydrating agent such as Sulfur, phosphorus pentoxide, aluminum chloride and zinc chloride and alkali metal hydroxide release the base. 2. The process according to claim 1, wherein the reaction is carried out in an environment of an organic solvent miscible with dehydrating agents to which it is inert, such as tetrachlorethylene, carbon tetrachloride and dichlorobenzene.