SU1659407A1 - Method for obtaining sodium salts of 8-mercaptochinoline and its derivatives - Google Patents

Abstract

The invention relates to heterocyclic substances, in particular the preparation of sodium salts of 8-mercaptoquinoline derivatives, which are used as analytical reagents. The goal is to simplify and cheapen the process. The latter is carried out by reduction of 8-quinoline sulfonyl chloride or its derivatives with a mixture of sodium hypophosphite and concentrated hydrochloric acid, taken in a molar ratio of 1: (0.8-1.2), in a mixture of chloroform and water, taken in a volume ratio

Description

This invention relates to a process for the preparation of sodium salts of 8-mercaptoquinoline or its derivatives, which are used as analytical reagents.

The aim of the invention is to simplify and cheapen the process.

According to the proposed method, 8-quinoline sulfonyl chloride or its derivatives are reduced with a mixture of sodium hypophosphite and hydrochloric acid, taken in a molar ratio (NaHaP02 -H20): HCI 1: (0.8-1.2) in a mixture of chloroform and water, taken in a volume ratio of (2.2-1.5): 1 at boiling or boiling in water.

Example 1. - Method for preparing 8-mercaptoquinoline.

10 g of freshly distilled quinoline are slowly added dropwise to 50 ml of chlorosulfonic acid at room temperature. the reaction mixture is kept under reflux at 150-160 ° C for 4 hours. After cooling, the mixture is slowly poured out onto 0.5 kg of crushed ice with stirring.

The 8-quinoline sulfonyl chloride is filtered off, washed with cold water, transferred to a reaction flask, and with stirring, dissolved in 55 ml of chloroform for 5 minutes.

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A solution is prepared containing 19.5 g (0.185 mol) of sodium hypophosphite, 19 ml (0.23 mol) of concentrated hydrochloric acid, and 25 ml of distilled water. The solutions are mixed, 0.01 g of tetrabutylammonium bromide catalyst is added and heated under reflux on a boiling water bath for 2 hours. At the same time, the color of the aqueous phase gradually becomes yellow and then orange-red. The reaction mixture is cooled without separating the chloroform layer, the aqueous phase is neutralized with a saturated solution of sodium acetate (65 ml) to pH 4-6 and shaken for 1 minute to more completely extract 8-mercaptoquinoline with chloroform.

To convert the free 8-mercaptoquinoline to the sodium salt, a 5% solution of NaOH in ethanol (27-30 ml) was added to the resulting chloroform solution. The resulting yellow precipitate of the 8-mercaptoquinoline sodium salt is filtered off and dried in a vacuum oven. The output of 6.1 g (36% of the original quinoline).

Example 2. A method for producing 4,6-dimethyl-8-mercaptoquinoline.

While cooling in small portions, to 10 g (0.035 mol) of 4,6-dimethylquinoline is added to 50 ml of chlorosulfonic acid and heated under reflux for 3 hours at 150 ° C. After cooling, the reaction mixture is poured onto 500 g of crushed ice. The white precipitate of 4,6-dimethyl-8-quinoline sulfonyl chloride is washed with chilled water, transferred to a flask and dissolved in 30 ml of chloroform. 0.01 g of tetrabutylammonium chloride catalyst is added to the same flask. A solution containing 14 g (0.13 mol) of sodium hypophosphite, 13 ml (0.16 mol) of concentrated hydrochloric acid and 19 ml of water is added to the flask. The reaction flask was heated at reflux for 2 hours. The chloroform layer became intensely red. After cooling, the reaction mixture is neutralized with a saturated solution of sodium acetate to pH 4-6 (about 40 ml), shaken vigorously, about 20 ml of 5% ethanolic NaOH solution are added. A yellow precipitate of 4,6-dimethyl-8-mercaptoquinoline sodium is immediately precipitated, the precipitated salt is filtered and dried in a vacuum oven,

Yield 7.7 g (48% of the original 4,6-dimethylquinoline).

In a similar way, other methyl derivatives of 8-mercaptoquinoline obtained in Table 2 are obtained. one,

Example 3. A method for preparing 5-bromo-8-mercaptoquinoline.

To 50 g of chlorosulfonic acid at room temperature, 10 g (0.048 mol) of 5-bromoinrline was added in small portions and heated under reflux for 3 hours at 130-150 ° C. After cooling, the reaction mixture is slowly poured onto 250 g of crushed ice. The precipitate is filtered off, washed with water, transferred to a beaker, dissolved in 30-35 ml of chloroform, and the chloroform layer is separated from the aqueous suspension and non-dissolved chloroform

5-bromo-8-quinoline sulfonic acid. The chloroform solution is dried over anhydrous NaaS04 and evaporated. 9.2 g of 5-bromo-8-ch.nolinesulfonyl chloride are obtained.

19 g (0.19 mol) of sodium hypophosphite are dissolved in 30 ml of water, 20 ml (0.24 mol) of concentrated HCl, 9.2 g (0.03 mol) of 5-bromo-8-quinoline sulfonyl chloride are added and heated. The reaction mixture boils, becomes yellow, then red. Whole

5-bromo-8-quinoline sulfochloride is dissolved. Boil t another 15 min. During this time, the color of the reaction mixture changes to orange and a yellow precipitate of 5-bromo-8-mercaptoquinoline hydrochloride precipitates. TO

600 ml of water are added to the reaction mixture and alkalinized with a 20% solution of NaOH to pH 10. The precipitate is dissolved. The resulting solution of sodium salt of 5-bromo-mercaptoquinoline is filtered,

neutralized with glacial acetic acid to pH 4-6. A nearly colorless precipitate of 5-bromo-8-mercaptoquinoline is precipitated, which is filtered, washed with water, and dried in a vacuum oven. Yield 3.8 g (33%

to the original 5-bromoquinoline).

By neutralizing the ethanolic solution of 5-bromo-8-mercaptoquinoline with sodium hydroxide, the reagent sodium salt is obtained. Example 4. Analogously to example 1

Prepare a solution of 8-quinoline sulfonic chloride. A solution is prepared containing 19.5 g (0.184 mol) of sodium hypophosphite, 12 ml (0.15 mol) of concentrated hydrochloric acid and 25 ml of distilled water. The solutions are mixed, 0.01 g of tetrabutylammonium bromide catalyst is added and heated under reflux on a boiling water bath for 2 hours. At the same time, the color of the aqueous phase gradually becomes yellow and then orange-red. The reaction mixture is cooled without separating the chloroform layer, the aqueous phase is neutralized with a saturated solution of sodium acetate (65 ml) to a pH of 4-6 and dried for 1 minute.

for a more complete extraction of 8-mercaptoquinoline with chloroform.

To convert the free 8-mercaptoquinoline to the sodium salt, a 5% solution of NaOH in ethanol (27-30 ml) was added to the chloroform solution obtained. The resulting yellow precipitate of 8-mercaptoquinoline sodium salt is filtered and dried in vacuo. The yield of 8-mercaptoquinoline sodium salt relative to quinoline is 36%. The yield of the 8-mercaptoquinoline sodium salt relative to the sulfochloride is 60%.

Example 5. A solution of 4,6-dimethyl-8-quinoline sulfochloride is prepared analogously to example 2. 0.01 g of tetrabutylammonium chloride catalyst is added to this solution. A solution is prepared containing 14 g (0.13 mol) of sodium hypophosphite and 8.5 ml (0.11 mol) of concentrated hydrochloric acid and 19 ml of distilled water. The solutions are mixed. The reaction flask was heated under reflux for 2 hours. The chloroform layer became intensely red. After cooling, the reaction mixture is neutralized with a saturated solution of sodium acetate to pH 4-6 (about 40 ml), shaken vigorously, about 20 ml of 5% ethanolic NaOH solution are added. A yellow precipitate of 4,6-dimethyl-8-mercaptoquinoline sodium is precipitated. The precipitate formed is filtered and dried in a vacuum oven. The yield of 4,6-dimethyl-8-mercaptoquinoline sodium salt with respect to sulfochloride and quinoline is 80 and 48%, respectively.

Example 6. Analogously to Example 3, a solution of 5-bromo-8-quinoline sulphonic acid is prepared. The chloroform solution is dried over anhydrous N32S04 and evaporated. 9.2 g of 5-bromo-8-quinoline sulfonyl chloride are obtained.

19 g (0.18 mol) of sodium hypophosphite are dissolved in 30 ml of distilled water, 11.5 ml (0.14 mol) of concentrated hydrochloric acid, 9.3 g (0.03 mol) of 5-bromo-8- quinoline sulfonyl chloride and heated. The reaction mixture boils, becomes yellow, the stream red. The entire 5-bromo-8-quinoline sulfochloride is dissolved. Boil t another 15 min. During this time, the color of the reaction mixture changes to orange and a yellow precipitate of 5-bromo-8-mercaptoquinoline hydrochloride precipitates. Analogously to Example 3, 5-bromo-8-mercaptoquinoline is obtained from 5-bromo-8-mercaptoquinoline hydrochloride, the yield of which is relative to the sulfochloride and quinoline, respectively, 53 and 33%.

The catalyst has little effect on the yield of the product, so it is possible to carry out the reaction without a catalyst.

Example 7. Carrying out the synthesis without a catalyst.

10 g of freshly distilled quinoline are slowly added dropwise to 50 ml of chlorosulfonic acid at room temperature. The reaction mixture is incubated with

0 under reflux 4 hours at 150-160 ° C. After cooling, the mixture is poured onto 0.5 kg of ice with stirring. The precipitate of 8-quinolin sulfonyl chloride is filtered off, washed with ice water, transferred to

5 reaction flask and dissolved in 55 ml of chloroform.

A solution is prepared containing 19.5 g (0.185 mol) of sodium hypophosphite in 25 ml of water, and 19 ml (0.23 mol) of concentrated hydrochloric acid is added. The solutions are mixed and heated under reflux in a boiling water bath for 4 hours. At the same time, the color of the aqueous phase turns yellow and then changes to orange-red. The reaction mixture is cooled without separating the chloroform layer and neutralized with a saturated solution of sodium acetate (l / 65 ml) to pH 4-6. The reaction mixture was shaken for 1 minute to more fully extract 8-mercaptoquinoline with chloroform.

To convert the 8-mercaptoquinoline to the sodium salt, a 5% solution of NaOH in ethanol is added to the chloroform solution.

5 (l zo ml). The resulting yellow precipitate of the sodium salt is filtered and dried. 5.3 g of sodium salt of 8-mercaptoquinoline are obtained, which is 52% of the theoretical ratio

0 8-quinoline sulfonyl chloride and 31% relative to quinoline.

Found,%: S- 14.50. CgHeNSNa -2H20 Calculated,%: S 14.63.

5 5-Bromo-8-quinoline sulfochloride in a water-chloroform two-phase system at the boiling point of chloroform is reduced in low yield. Therefore, the restoration is carried out with more

0 high temperature in aqueous solution. Since a single phase interphase catalyst system is not required.

Example 8. The process of obtaining 5-bromo-8-mercaptoquinoline in

5 environment water - chloroform.

At room temperature, 10 g (0.048 mol) of 5-bromoquinoline is added in small portions to 50 ml of chlorosulfonic acid and heated under reflux for 3 hours at 130-150 ° C. After

cooling the reaction mixture is slowly poured onto 250 g of ice. The precipitate is filtered off, washed with cold water and dissolved in 35 ml of chloroform.

A solution of 19 g (0.18 mol) of sodium hypophosphite in 19 ml of water and 19 ml of concentrated hydrochloric acid is prepared. The solutions are mixed, 0.01 g of catalyst — tetrabutylammonium bromide is added and heated on a boiling water bath for 2 hours. After cooling, the reaction mixture is neutralized with a saturated solution of sodium acetate to pH 4-6. The chloroform layer is separated and evaporated. 0.2 g of 5-bromo-8-mercaptoquinoline is obtained (mp. 80 ° C), 2.8% with respect to 5-bromo-8-quinoline sulfonyl chloride and 1.7% with respect to 5-bromoquinoline. . Found,%; S 13.00.

CgHeNSBr

Calculated,%: S 13.35.

In tab. 2 shows the elemental analysis data and the UV spectra of the compounds obtained.

The use of sodium hypophosphite, hydrochloric acid in smaller quantities than in the ratio of NaH2P02 H20: HCI 1: 0.8, leads to a decrease in the yield of the target product.

The use of sodium hypophosphite and hydrochloric acid in larger quantities than in the ratio of NaHaPCte N20} 1: 1.2 does not increase the yield of the target product.

The reduction reaction of 8-quinol sulphonium chloride and its methyl derivatives proceeds in a water-chloroform two-phase system, where the aqueous phase is sodium hypophosphite solution with the addition of an appropriate amount of hydrochloric acid and sulfochloride solution in chloroform.

In aqueous solution, recovery of 8-quinoline sulfonyl chloride and its methyl derivatives does not occur due to the hydrolysis of 8-quinoline sulfonyl chloride to 8-quinoline-. sulfonic acids.

Chloroform is not miscible with water and it dissolves sulfochlorides well.

At room temperature, the reduction reaction does not proceed, and hydrolysis of 8-quinoline sulfonic chloride and the release of 8-quinoline sulfonic acid are observed, therefore

the reaction mixture is brought to a boil; chloroform is 61.2 ° C.

A catalyst can be used to accelerate the start of the reduction reaction.

- tetrabutylammonium methyl.

5-Bromo-8-quinoline sulfochloride is most resistant to hydrolysis and can be reduced in hydrochloric acid when heated. In a two-phase water system

-chloroform does not react as chloroform has a low boiling point.

In a known method, the target product contains tin impurity, which is unacceptable for the analytical reagent used to determine metals. Therefore, additional purification of the final product is carried out. When using the proposed method, the target product is not subjected to additional purification, and in three stages 8-mercaptoquinoline and its derivatives are obtained. This method uses cheaper reducing agents as compared to the known method.

The method can be used in the manufacture of analytical reagents.

Claims (2)

Claim 1. Investigation of the sodium salts of 8-mercaptoquinoline or its derivatives of formula G $ ka where Ri-H, CH3, R2-H, CH3B2, reduction of 8-quinoline sulfonic acid or its derivatives using hydrochloric acid and conversion of the obtained product into its sodium salt, characterized in that, in order to simplify and cheapen the process, the reduction of 8-quinoline sulfonic chloride or its derivatives are carried out with a mixture of sodium hypophosphite and concentrated hydrochloric acid, taken in a molar ratio of 1: (0.8-1.2) in a mixture of chloroform: water, taken in a volume ratio of (2.2-1.5): 1, at the boiling point of the reaction mass. 2. A method according to claim 1, characterized in that the reduction process is carried out in water. Table 1 8-Mercaptoquinoline, sodium salt 2-Methyl-8-mercapt oxy n oli n, sodium salt 4-Methyl-8-mercaptoquinoline, sodium salt 6-Methyl-8-mercaptoquinoline, sodium salt 7-Methyl-8-mer captoquinoline, sodium salt 4,6-Dimethyl-8mercaptoquinoline, sodium salt 2,7-Dimethyl-8-mercaptoquinoline, sodium salt 2,5-Dimethyl-8-mercaptoquinoline, sodium salt 2,4,6-Trimethyl8-mercaptoquinoline, sodium salt 5-Br ohm-8-mercaptotoquinoline, base 36 24 32 37 sixteen 40 46 26 33 Total formula Elemental analysis data Found, T. Sodium salt 9 merhaptoquinoline C HjNSNa 49.00 4,626.48 14.70 Natrieva sel m tyl-8-mercapon Juvenile C IIjMSNa 21IfO 51.64 5.285.95 I3, fl0 Sodium salt 4-methyl-8-mer aptohinolin S) 0 HaNSMa-2H 0 51.50 5.256.19 13.80 Sodium salt & -methyl-8-merMptohinolnias, 0 HeNSNa -2UjO 51.57 5.295.99 13.85 Sodium salt 7-met11l-8-nerkpptohnnolina Sodium salt, 6-dimethyl-8-ercaptochne pin Sodium salt of 2,7-dimethyl-8-yerkaptohnnol on 2,5-diketyl-8-cvhrhpt-to-quinoline sodium salt 2,4,6-trimethyl-8-mercaptoquinolate sodium salt 5-Bron-8-mer-haptohinolin from 1 .. 1c 49.30 4,606,3914,63 51.44 5.186.0113.75 51.44 5.186.0113.75 51.44 5.186.0113.75 51.44 5.186.0113.75 C, l NSNa-21l (051,305,096,1213,84 q ,,; y) SNa-211tO53,605,495,7313,15 With „H, UNStJa: 2No49,996,285,4012,29 C H NSNa-SHtO51, 305,705, So13,15 53.38 5.665.66 12.95 49, 80 6.075.28 12.09 53.38 5.665.66 12.95 c1tn "NSNa 2I4 ° 55.40 4.705.50 12.49 -55.16 4.625.36 12.27 vv NSNa 45.31 2.706 13.45 33.40 45.01 2.515.83 13.35 33.28 table 2 X 1c Spectral data R Hee Ai. 26022300 26222800 25818700 26323000 26323000 5.665.66 12.95 6, 075.28 12.09 5.665.66 12.95 26019500 26724400 26618800 25716500