JPS609027B2 - Method for producing 2-mercapto pyridine N oxide zinc salt - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides an improvement in producing 2-mercapto pyridine N-oxide zinc salt by alkali decomposition of S-2-pyridylisothiuronium N-oxide hydrohalide. It is related to the method used.

That is, after alkali decomposition of S-2-pyridylisothiuronium N-oxide hydrohalide, the pH of the reaction mixture is adjusted to 6.0 or less and reacted with zinc salt or its aqueous solution. The present invention relates to a method for producing a characteristic 2-mercapto pyridine N oxide zinc salt. 2-Mercapto pyridine N oxide zinc salt has bactericidal and antifouling properties and is useful as a compounding agent for medicated shampoos and the like, and its production method has conventionally been generally carried out as follows.

For example, S-2-pyridylisothiuronium N oxide hydrohalide is decomposed with an aqueous solution of sodium carbonate to form the sodium salt of 2-mercapto pyridine N oxide, and an aqueous hydrochloric acid solution is added thereto to adjust the pH of the mixture. is adjusted to 2.3 or less, the liberated 2-mercapto pyridine N oxide is separated in the form of crystals, and then 2-mercapto pyridine N oxide is mixed with an aqueous solution of an alkali such as sodium hydroxide in an equimolar amount. Add
The alkaline salt of 2-mercapto pyridine N oxide is again converted into an aqueous solution and a stoichiometric amount of zinc salt, such as zinc chloride, is added to produce a zinc salt of 2-mercapto pyridine N oxide. The reaction formula for this method is as follows. Equation (1) Equation (2) Equation (3) Equation (4) The problem with this method is that in the reaction equation {1',
- The process of obtaining mercapto pyridine N oxide generally has a low yield.

For example, in Pharmaceutical Journal 81-614, 2.8 equivalents of potassium carbonate was added to S-2-pyridylysothiuronium N-oxide hydrochloride, and the mixture was reacted at room temperature for 2 days to acidify with hydrochloric acid, resulting in a yield of 65%. 2-mercapto pyridine N.
I'm getting oxide. Nuri. am. Chem. Soc.
．． 72 4362 ('50), a yield of 78% was obtained by adding 3.6 equivalents of sodium carbonate and reacting at room temperature. Furthermore, J. Chem. S ratio. In 1960 2941, only 49% yield was obtained using 3.1 equivalents of sodium carbonate. On the other hand, in US Pat. No. 2,745,826, a yield of 84.8% was obtained using the same process. Another problem is that the method for obtaining the zinc salt from the free 2-mercapto pyridine N oxide obtained by the reaction formula '2} is carried out by the formulas {3} and '4', and the yield is not very good. is not recognized, but the sodium salt of 2-mercapto pyridine N oxide obtained by formula '1} can be expressed as formula '
2) It is necessary to carry out a complicated process of recovering the free form, returning it to the sodium salt using formula '31, and reacting it with the zinc salt. The necessity of going through such a process is that it is preferable to react with an excess amount of alkali used in formula '1} rather than the theoretical amount. When sodium salt is directly reacted with zinc salt, an insoluble inorganic salt is generated due to the reaction between excess alkali and zinc salt, which is mixed into the 2-mercapto pyridine N oxide zinc salt of the product. It was speculated that this was due to the occurrence of inconvenient phenomena such as Based on this knowledge, the present inventors obtained 2- with low intermediate yield by using only the combination of formula '1' and formula side from SM2-pyridylisoturonium N-oxide hydrohalide. A study was conducted on an improved and efficient method for producing 2-mercapto pyridine N oxide zinc salt, which does not include the step of separating mercapto pyridine N oxide and does not include the above-mentioned insoluble inorganic salts. In addition, the present invention has been completed. The present invention involves alkaline decomposition of S-2-pyridylisothiuronium N-oxide hydrohalide, adjusting the pH of the reaction mixture to 6.0 or less, and reacting it with zinc salt or its aqueous solution. This is a method for producing 2-mercapto pyridine N oxide zinc sea.

The S-2-pyridylisothiuronium N● oxide hydrohalide used in the present invention is 2-halogen/
It is easily obtained by reacting pyridine N oxide with thiourea in an alcoholic solvent.

As typical examples, 2-chloropyridine N-oxide and 2-prompyridine N-oxide are used.
S-pyridylisothiuronium N derived from this
- It is preferable to use oxide hydrohalide. ZS
- Potassium hydroxide, sodium hydroxide, soda carbonate, potassium carbonate, potassium hydrogen carbonate, sodium hydrogen carbonate, etc. are used as the alkali used to decompose the 2-pyridylisothiuronium N-oxide hydrohalide. However, there is no need to limit this to Z. The amount of alkali used is preferably 2.0 or more equivalents of alkali per mole of S-2-pyridylisothiuronium N-oxide hydrohalide, and if it is less than 2, decomposition may be insufficient. However, there is no point in using a large overboard, and the disadvantage is that it increases the consumption when adjusting the boat.

For alkaline decomposition, an aqueous alkali solution may be added to an aqueous solution of S-2-pyridylisothiuronium N-oxide hydrohalic acid, or the other may be added in solid form to an aqueous solution of one of them. . The concentration in the aqueous solution sometimes need not be limited, preferably S-2-pyridylisothiuronium N-oxide hydrohalide 1
Preferably, the amount is 2000 molar or less per mole. A temperature of room temperature is sufficient for decomposition, and a reaction time of 3 hours at room temperature is sufficient. The reaction mixture after alkaline decomposition is a homogeneous solution, and the pH of this solution is usually over 6.0.

Dilute hydrochloric acid is added to this to adjust the pH to 6.0 or less. The pH range of the reaction system at this time is 6.0 or less, but p
If H is 5.0 or less, some free 2-mercapto pyridine N oxide will be liberated, so it is best to carry out the process preferably in the range of 50 or more and 6.0. Even if an aqueous solution of zinc salt is added under the condition of 5.0 or less, zinc salt of 2-mercapto pyridine N oxide will be produced, but the yield will be lower and the stability of the obtained product will be lower. If exposed to sunlight, it may change over time and turn yellow.

For example, pHI. If you add zinc salt after adjusting to 4, it will be 2
The yield of merkabuto-pyridine-N-oxide zinc salt decreased to 92.0%, and the surface of the resulting product gradually changed. Spot 6. In cases where the zinc salt is excessively high, a considerable amount of insoluble inorganic salt is generated upon addition of the zinc salt, which is mixed into the 2-mercapto pyridine N oxide zinc salt and impairs the solubility of the product. After adjusting the pH, it is reacted with a zinc salt or an aqueous solution thereof to obtain a 2-mercaptopyridine zinc salt. As the zinc salt, zinc chloride, zinc sulfate, etc. are preferably used, but there is no particular limitation thereto. Although the zinc salt may be added as a solid, it is usually preferable to use it as an approximately 20% aqueous solution after removing insoluble matter. The amount of zinc used should be 1/2 times the amount of S-2-pyridylisothiuronium N-oxide hydrohalide used, or a slight excess of this, and a large excess should be used. do not have to.

After adding the zinc salt, it is slowly stirred for about 3 minutes, and the produced 2-mercapto pyridine N oxide zinc salt is separated in an oven, washed with water, and dried to produce a product.

The effects of the present invention will be shown below using Examples and Comparative Examples.

Example 1 4.1 hours of purified S-2-pyridylisothiuronium N-oxide hydrochloride was dissolved in 40M water, 2.7 hours of potassium carbonate was dissolved therein, and the mixture was reacted at room temperature for 3 hours. The pH of the mixture was measured to be 6.6.

After adding dilute hydrochloric acid dropwise to adjust the pH to 6.0,
When a small amount of a 15% zinc chloride aqueous solution is added dropwise, a white precipitate is immediately formed. This is filtered through a G3 glass filter, thoroughly washed with water, and then vacuum dried until it reaches a constant weight. The yield was 95.4% of the theoretical yield. The melting point of the obtained product was 257q0, and KBr infrared analysis was consistent with that of the standard product. When dissolved in DMF at 500° C., a colorless and transparent homogeneous solution was obtained. Comparative Example 1 The reaction was carried out under the same conditions as in Example 1, but without adjusting the pH.
Immediately, 15 parts of a 20% zinc chloride aqueous solution was added and treated in the same manner, resulting in a yield of 96.2% of the theoretical amount.

When this product was dissolved in DM for 5,000 times, it became cloudy, suggesting the presence of insoluble inorganic substances. Examples 2 to 4 and Comparative Examples 2 and 3 Purified S-2-pyridylysothiuronium.
N. Oxa. Dissolve 20.5 parts of hydroxide hydrochloride in 200 parts of water, add 16.0 parts of sodium hydroxide, and mix at room temperature.
After reacting for some time, the pH was measured and found to be 13.
6 was shown.

Divide this into 5 equal parts, add dilute hydrochloric acid to each part until the pH reaches the value shown in the table below, add 15 parts of a 20% zinc chloride aqueous solution to each part, let it react for 30 minutes, and wash it with water in a furnace using a ○3 glass filter. Vacuum dried. Kawa: This product turns yellow during storage.

X2 2-Mercapto Pyrisone N Oxide Zinc Sea 0.259 was dissolved at MF50'' and the progress of the dissolution was observed.

Claims (1)

[Claims] 1. After alkali decomposition of S-2-pyridylisothiuronium N-oxide hydrohalide, the pH of the reaction mixture is adjusted to 6.0 or less, and the reaction mixture is reacted with a zinc salt or an aqueous solution thereof. Method for producing 2-mercapto pyridine N oxide zinc salt.