HU199422B - Process for producing 8-hydroxyquinoline - Google Patents

Abstract

8-hydroxy-quinoline is prepd. from o-nitro and o-quinol phenols and acrolein in acid medium. O-nitro-phenol is hydrogenated in aq. and/or 1-6C alkanol contg. medium at 20-120 deg. C in the presence of 0.001-0.01 pts. wt. (based on o-nitro-phenol) of palladium catalyst. Prior to, or following hydrogenation at least equimolar amts. of hydrogen-halides (based on o-amino-phenol) are added. In this partic. case, 1-6C alkanols are removed and acrolein is added to the mixt. contg. o-amino-phenol. Opt. further amts. of o-nitro-phenol and hydrogen-halide are added. 8-hydroxy-quinoline is prepd. by known means.

Description

The present invention relates to an improved process for the preparation of 8-hydroxyquinoline. 8-Hydroxyquinoline is a valuable intermediate for the production of pharmaceuticals such as iodochlorooxyquinoline and pesticides such as copper 8-hydroxyquinolate.

8-Hydroxyquinoline is disclosed in U.S. Pat. According to the process described in Austrian Patent No. 6,018,128, SkraupS is synthesized by reacting o-aminophenol with o-nitrophenol and acrolein in a hydrochloric acid medium, and separating the product formed in a 50-80% yield by steam distillation.

One of the starting materials, o-aminophenol, is a volatile compound which, upon standing in the air, is rapidly transformed into colored polymeric products. These impurities and their reaction products with acrolein are also present in the final product and can only be separated from it by complex purification operations (e.g., distillation at very low pressure, high temperature). These purification operations significantly increase the cost and energy requirement of the process and reduce the yield of the end product. It is also a disadvantage that the contaminated end product is separated from the reaction mixture by steam distillation, since about 100 parts by weight of water vapor are needed to separate 1 part by weight of the final product.

It is also known (French Patent No. 1,354,430) that o-aminophenol can be prepared from o-nitrophenol by catalytic hydrogenation. According to the cited patent, hydrogenation is carried out in an aqueous alkaline solution in the presence of palladium on charcoal. With this reaction, o-aminophenol can be produced in only 70-80% yield and is formed in a state which is heavily contaminated due to the aforementioned decomposition processes and is not suitable for further direct reaction. Repeated treatment of the resulting o-aminophenol with sodium dithionite is required in order to obtain a reactant grade material.

It is an object of the present invention to provide a process for preventing the decomposition of o-aminophenol and the direct further reaction of o-aminophenol to produce highly pure 8-hydroxyquinoline.

Surprisingly, our experiments have shown that when hydrogenation of o-nitrophenol is carried out in an aqueous and / or alcoholic medium instead of the previously used aqueous alkaline solution, the reaction mixture is at least equimolar to the o-aminophenol formed before or immediately after hydrogenation. hydrogen halide is added, it is safe to eliminate the decomposition reactions of o-aminophenol, and the o-aminophenol formed can be further reacted with o-nitrophenol and acrolein without isolation. This discovery is extremely surprising, since it was expected that under the conditions used, side reactions would occur, such as the formation of alkyl halides and the alkylation of o-aminophenol.

The present invention relates to a process for the preparation of 8-hydroxyquinoline by catalytic hydrogenation of o-nitrophenol palladium in the presence of a catalyst followed by reaction of the resulting o-aminophenol with o-nitrophenol and acrolein in an acidic medium and formation of 8-hydroxy According to the invention, the hydrogenation of o-nitrophenol is carried out in an aqueous and / or C 1 -C 6 alkanolic medium, at least equimolar to the o-aminophenol, before or after the hydrogenation. an amount of hydrogen halide is added, and if a C 1-6 alkanol is used, the alkanol is removed from the reaction mixture.

As the aliphatic alkanol having from 1 to 6 carbon atoms in the process of the invention, for example, methanol, ethanol, n- or i-propanol or butanols or mixtures thereof may be used. The use of methanol is preferred because it can be easily removed from the reaction mixture after hydrogenation. If the reaction medium for the hydrogenation of the o-nitrophenol is a C 1 -C 6 alkanol, the alkanol must be removed from the reaction mixture after the hydrogenation, otherwise 8-hydroxyquinoline will not be obtained at all or in very low yields. This experience also confirms that the co-presence of alkanol and acid leads to side reactions, so it is extremely surprising to find that these side reactions do not occur during hydrogenation and after the hydrogenation after hydrogenation.

The hydrogen halide may be added to the reaction mixture either before or after hydrogenation. If water is used as the reaction medium, the hydrogen halide is preferably added before the hydrogenation begins, and if the reaction medium is a C 1-6 alkanol, the hydrogen halide is preferably added after the hydrogenation has taken place but before the alkanol is removed.

It is possible to convert only part of the added o-nitrophenol, preferably 60-70%, to the o-aminophenol in the hydrogenation step. Unreduced o-nitrophenol serves as a reagent in the next step.

If necessary, the hydrogenation may be carried out at atmospheric pressure.

The invention is illustrated in detail by the following non-limiting Examples.

Example 1

Dissolve 20.8 g of o-nitrophenol in 60 g of methanol, add 0.05 g of 10% w / w pall-2HU 199422 Β Cd / C and mix in a gas-liquid contact apparatus at 70 to 90 ° C. hydrogen at a temperature of 0.4-0.5 MPa. The catalyst was filtered off under a nitrogen atmosphere and the filtrate was combined with a little excess concentrated aqueous hydrochloric acid. Methanol was distilled off from the mixture, and 33.2 g of concentrated aqueous hydrochloric acid solution, 9.2 g of acetic acid were added and the mixture was heated to 100-110 ° C for 2 hours.

A solution of 10.4 g of o-nitrophenol and 13.7 g of acrolein is added dropwise. After stirring for 1 hour, the reaction mixture was cooled, filtration aids (e.g., perlite) were added, and the excess hydrochloric acid was neutralized with aqueous ammonium hydroxide solution. The resulting impurities are filtered off and the 8-hydroxyquinoline is precipitated from the filtrate by further alkalization. PH of the aqueous suspension with concentrated sulfuric acid

The solution was adjusted to 2, the solution was clarified with hot charcoal, filtered, and after cooling, the pure 8-hydroxyquinoline was precipitated by basification.

By this method, 8-hydroxyquinoline is obtained in a yield of 70%, which is greater than 95% pure by HPLC.

If, after hydrogenation, the methanol is not completely removed, but the reaction mixture contains 5% by weight of methanol, the reaction mixture is worked up to give midpse 8-hydroxyquinoline in 10% yield.

Example 2

20.8 g of o-nitrophenol are hydrogenated in 60 g of n-butanol in the presence of 0.05 g of 10% palladium on charcoal at 90 ° C and 0.5 MPa. The catalyst is filtered off hot, an aqueous solution of hydrochloric acid equivalent to o-aminophenol is added to the filtrate, and the butanol is distilled off under reduced pressure. The resulting non-alcoholic residue was further reacted as described in Example 1 to give a purity of greater than 95% in 70% yield.

8-hydroxyquinoline.

Example 3

20.8 g of o-nitrophenol are hydrogenated in the presence of 300 ml of water and 5 g of palladium catalyst at 80 ° C and 0.5 MPa.

After hydrogenation, 0.2 mol / L hydrochloric acid was added as a concentrated aqueous solution, the catalyst was filtered off and most of the water was evaporated. To the resulting suspension was added 33.2 g of concentrated aqueous hydrochloric acid and 9.2 g of acetic acid. Hereinafter referred to as

Example 1 was followed. The reaction mixture was worked up to give a purity greater than 95% in 60% yield

8-hydroxyquinoline.

Example 4

20.8 g of o-nitrophenol are dissolved in 60 g of methanol and the solution is hydrogenated as in Example 1. After filtration of the catalyst, the filtrate was mixed with a 5% (w / w) 48% aqueous hydrobromic acid solution. Methanol was distilled off, to the residue were added 40 g of 48% aqueous hydrogen 20-bromide solution and 10 g of acetic acid, and 10.4 g of o-nitrophenol and 13.7 g of acrolein at 100-110 ° C for 2 hours. solution. After a further half hour at 100-110 ° C, the reaction mixture was cooled and neutralized to pH 7 with aqueous sodium hydroxide solution. The pH of the mixture was then adjusted to 2 with concentrated sulfuric acid, the solution clarified hot by the addition of perl and clarifying charcoal, and after cooling, precipitated with aqueous alkaline solution.

3q of 8-hydroxyquinoline. The product was found to be 97% pure by HPLC. 8-Hydroxyquinoline was obtained in 75% yield.

Claims (1)

Process for the preparation of 8-hydroxyquinoline in the presence of o-nitrophenol palladium catalyst Catalytic hydrogenation of the 40 finished, and then the resulting p-amino-phenol, p-nitrophenol, and reacting the resulting 8-hydroxyquinoline from the reaction mixture alkaline precipitation in an acid medium with acrolein, wherein signal ₄₅ with plate to the p-nitro-phenol hydrogenation in an aqueous and / or C 1 -C 6 alkanolic medium, before or after hydrogenation, at least equimolar hydrogen halide relative to o-aminophenol is added to the reaction mixture and, if C 1 -C 6 alkanol is used, the alkanol is removed from the reaction mixture. .