JPH06321904A - Production of thionicotic acid and isothionicotic acid - Google Patents

Abstract

PURPOSE:To provide a method for readily producing large amounts of thionicotic acid and isothionicotic acid. CONSTITUTION:This method for producing thionicotic acid and isothionicotic acid comprises chlorinating nicotic acid or isonicotic acid with thionyl chloride in an inert solvent having a boiling point of >=100 deg.C, distilling off the unreacted thionyl chloride and subsequently blowing hydrogen sulfide through the residue. Since the chlorination reaction and the hydrogen sulfide reaction are performed in a dispersion state, the uniform progress of the reaction, the easy control of the reaction and the easy treatment of the reaction product after the reaction are achieved.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a process for producing thionicotinic acid and isothionicotinic acid, which are useful as organic synthetic intermediates.

[0002]

2. Description of the Related Art As a synthetic literature for thionicotinic acid, J
aroslaw, boehn et al. (Rocznik
i Chem. Vo128 501 (1954)) is currently the most practical one, but this is because nicotinyl chloride crystals obtained by heating nicotinic acid in thionyl chloride and then distilling off excess thionyl chloride are dissolved in a large amount of pyridine. A method of obtaining thionicotinic acid through hydrogen sulfide gas.

However, synthesizing a large amount of thionicotinic acid by this method is difficult in terms of handling nicotinyl chloride and requires a large amount of pyridine, which is difficult in terms of environment and cost.

Further, in this method, since a large amount of pyridine hydrochloride is produced together with thionicotinic acid, operations such as filtration and washing are difficult.

Further, no practical synthetic literature could be found for isothionicotinic acid.

[0006]

DISCLOSURE OF THE INVENTION The object of the present invention is to eliminate the above-mentioned drawbacks of the conventional method, to facilitate the handling of nicotinyl chloride, to reduce the amount of pyridine used, and to simplify the filtration and washing operation after the synthesis. The purpose of the present invention is to provide an economical method for mass-producing thionicotinic acid or isothionicotinic acid.

[0007]

According to the present invention, the reaction of nicotinic acid or isonicotinic acid with thionyl chloride has a boiling point of 10
By carrying out in an inert solvent having a high boiling point of 0 ° C. or higher, nicotinyl chloride can be transferred to the next step in the form of a slurry in which the solvent is dispersed.

Further, the amount of pyridine used can be reduced by adding pyridine as it is after distilling thionyl chloride and blowing in hydrogen sulfide.

Furthermore, by adding methanol directly to the slurry after blowing hydrogen sulfide and extracting pyridine hydrochloride, the amount of cake in filtration and washing in the next step is greatly reduced, and the operation can be facilitated. It was

The reaction of the present invention is a chlorination of nicotinic acid or isothionicotinic acid with thionyl chloride (first step).
And the reaction of the chloride and hydrogen sulfide obtained thereby (second step).

Although nicotinic acid will be described in detail below, it is possible to carry out isonicotinic acid under exactly the same conditions.

First, the chlorination step is carried out by dispersing nicotinic acid in a high boiling point solvent and adding thionyl chloride.

The high boiling point solvent must have a boiling point of 100 ° C. or higher, preferably 120 ° C. or higher, and must not react with thionyl chloride.

When the boiling point is low, when the excess thionyl chloride is distilled off, the thionyl chloride is not completely distilled off, and when the reaction with hydrogen sulfide gas occurs, sulfur is produced as a byproduct and nicotinic acid is produced, and the yield of Degradation occurs and purity also declines.

Examples of such a high boiling point solvent include aliphatic or aromatic hydrocarbons such as octane, decane, decalin, tetralin, toluene, xylene, ethylbenzene, solvent naphtha, etc., monochlorobenzene, dichlorobenzene, tetrachloroethylene, etc. Ether compounds such as halogenated hydrocarbons, diethylene glycol diethyl ether, and ethylene glycol dibutyl ether can be used, but hydrocarbons, particularly xylene, are preferable in terms of cost, stability, solubility in methanol, and the like.

Of course, the reaction can also be carried out by adding nicotinic acid to a mixed system of thionyl chloride and a high boiling point solvent, but there is a risk that a toxic gas such as sulfur dioxide is generated at one time, and nicotinic acid is gradually added. Need to add.

The amount of the high boiling point solvent used is preferably 1 to 8 times by weight that of nicotinic acid, and the amount of thionyl chloride is preferably about 1.01 to 2.0 mol per mol of nicotinic acid.

Next, excess thionyl chloride is distilled off from the reaction solution thus obtained. At this time, if the boiling point of the solvent is 100 ° C. or less, the solvent is distilled out together with thionyl chloride, and the viscosity of the reaction system is increased. It increases and stirring becomes difficult, and the next reaction does not proceed smoothly.

Further, if the distillation of thionyl chloride is incomplete, the purity and the yield are lowered. Therefore, the residual thionyl chloride is distilled off until the amount thereof becomes less than 10 mol% of the charged nicotinic acid, preferably less than 3 mol%. It is desirable to do.

Since the reaction liquid thus obtained has nicotinyl chloride dispersed in a high boiling point solvent, hydrogen sulfide gas can be easily blown in the next step.

The hydrogen sulfide gas is blown in by adding pyridine to the dispersion system of nicotinyl chloride obtained by the above reaction.

The amount of pyridine is preferably 1 to 5 mol per 1 mol of nicotinic acid charged, and the amount of the high boiling point solvent is 3 to 15 times the weight of nicotinic acid charged because the viscosity of the system increases during the reaction. Is desirable.

It is desirable to blow the hydrogen sulfide gas at 50 ° C. or lower, and since this reaction is an exothermic reaction, it is necessary to blow it while cooling.

The amount of hydrogen sulfide to be blown in may be 1.0 to 2.0 mol per 1 mol of charged nicotinic acid, and the yield will not increase even if it is added more.

The reaction solution thus obtained is a viscous slurry in which thionicotinic acid and pyridine hydrochloride are dispersed in a solvent. Therefore, filtration is performed as it is, and then washing with a solvent such as methanol or water is carried out. Although thionicotinic acid can be obtained by removing pyridine hydrochloride, a large amount of pyridine hydrochloride must be used to treat a large amount of cake, and the cake absorbs moisture in the air to become hard. Due to its nature, it is difficult to handle.

When methanol is added to this dispersion system, the hydrochloride of pyridine is dissolved in methanol and phase-separated. By filtering this, the amount of cake can be reduced and the workability can be greatly improved.

The amount of methanol added at this time is 1.3 to 5 times the weight of the charged nicotinic acid. If the amount is too large, the yield will decrease, and if it is too small, the pyridine hydrochloride will not be sufficiently removed.

The purified thionicotinic acid can be obtained by recrystallizing the cake thus obtained in water or methanol.

[0029]

By using a high boiling point solvent in this way, the chlorination and hydrogen sulfide blowing reactions can be carried out in the dispersion liquid, so that the reaction progresses uniformly and is easy to control. Since it is possible to shift to the hydrogen blowing reaction, workability is greatly improved.

By adding methanol after blowing hydrogen sulfide, the amount of cake in the subsequent filtration and washing steps can be greatly reduced.

The present invention will be described in detail with reference to the following examples, but the examples are merely examples, and the present invention is not limited thereto.

[0032]

【Example】

Example 1 A 1500-liter glass-lined reaction vessel was charged with 228 kg of xylene and 105 kg of nicotinic acid, and 150 kg of thionyl chloride was added dropwise at 60 ° C. over 3 hours.

After refluxing for 3 hours, the water pump was depressurized at 85 ° C. for 6 hours.
0 liters of thionyl chloride (containing a small amount of xylene) was distilled off, 390 kg of xylene and 170 kg of pyridine were added, and the mixture was cooled to 7 ° C.
It was blown in over 0 hours.

The resulting viscous slurry was degassed, 180 kg of methanol was added, and the mixture was well stirred for 2 hours and then centrifugally filtered to give a crude thionicotinic acid cake 180 k.
g (wet product) was obtained.

This cake was recrystallized from 750 liters of water, washed with methanol and dried to give 63.4k of thionicotinic acid having a liquid chromatography purity of 99.0%.
g was obtained.

Example 2 When xylene was changed to toluene under the same conditions as in Example 1 to carry out the synthesis, 58 kg of thionicotinic acid obtained was obtained.
(Purity 97.3 percent).

Comparative Example Further, when benzene was used as the solvent, distilling thionyl chloride was carried out until stirring became impossible, but the obtained product contained impure nicotinic acid in an amount of 10% or more. It was something.

Example 3 200 ml of xylene, 100 g of isonicotinic acid and 15 thionyl chloride were placed in a 500 ml flask.
When 0 g was charged and the temperature was gradually raised, vigorous gas generation occurred on the way.

After aging this solution at 80 ° C. for 3 hours, it was heated to 21 kP.
Thionyl chloride was distilled off in (a), hydrogen sulfide gas (50 g) was blown into this, and the cake was washed with methanol and isopropyl ether after filtration and recrystallized with water to obtain 71 g of red-orange isothinicotinic acid.

[0040]

As described above, according to the method of the present invention, since the chlorination reaction and the reaction with hydrogen sulfide are carried out in a dispersed state, the reaction proceeds uniformly and the reaction can be easily controlled. Also, isothionicotinic acid can be easily mass-produced without using a large amount of pyridine.

Claims (3)

[Claims] 1. A method of producing thionicotinic acid by reacting nicotinyl chloride obtained by reacting thionyl chloride with nicotinic acid with hydrogen sulfide to carry out the chlorination reaction and the reaction with hydrogen sulfide in an inert solvent having a boiling point of 100 ° C. or higher. A method for producing thionicotinic acid, characterized in that 2. The method for producing thionicotinic acid according to claim 1, wherein methanol is directly added to the slurry containing a precipitate formed by blowing hydrogen sulfide to dissolve and remove pyridine hydrochloride. 3. A method for producing isothionicotinic acid, characterized in that isonicotinic acid is used in place of the nicotinic acid of claim 1.