JPS5855472A - Purification of 2-mercaptothiazoline compound - Google Patents

Abstract

PURPOSE:To prepare the titled substance useful as an intermediate of agricultural and pharmaceutical raw material, in high purity, by treating crude 2- mercaptothiazoline compound containing alkali or alkaline earth metal compounds as impurities, with a halogenated aliphatic hydrocarbon. CONSTITUTION:Crude thiazoline compound containing impurities selected from MiS, MiHS, MiSO4, MiCO3 and MiX' (M is alkali or alkaline earth metal; X' is halogen atom; i is 1/2, 1 or 2) is treated with the compound of formulaI(m and l are integer of 1-4; n is integer of 1-10; X is Cl or Br) (e.g. 1- chlorobutane) to obtain 2-mercapto-thiazoline compound of formula II (R<1>-R<4> are H, lower alkyl, or hydroxy-substituted lower alkyl) in high purity. The above purification can be carried out easily, because the compound of formulaIis a solvent of the compound of formula II and nonsolvent of the inorganic salts existing as impurities. The amount of the solvent is 500-3,000pts. per 100pts. of the raw material.

Description

[Detailed Description of the Invention] The present invention tiM's S # M" Ha e M's
The present invention relates to a method for purifying crude 2-mercaptothiazolines containing 804-mercaptothiazoline salt as an impurity.

2-mercaptothiazoline S represented by the following formula (1)
t is the R number (in the formula, R1, ill, ill and R4 are water bulk atoms,
It represents a lower alkyl group or a lower alkyl group substituted with a human or ``oxy, which may be the same or different from each other.'' It is an industrially heavy *1 compound that has physiologically active effects and is used as an intermediate for agricultural and pharmaceutical raw materials.

Method (2) (2') of directly reacting monoethanol 1ytiA and carbon disulfide in the presence of an alkali hydroxide such as sodium hydroxide, potassium hydroxide, and potassium hydroxide (cartau hydroxide), (in the formula, R1, R'', (Ra and %A represent a hydrogen atom, a lower alkyl group, or a hydroxy-substituted lower alkyl group, and may be the same or different) Method of reacting with carbon disulfide in the presence of alkali oxide (3)
), (where %fimJ(*, Ra and R4 are the formula (2
) has the same meaning as in the case of ) -1, seven ethanolamines, chloroethyl, 2
4I! A method of reacting with carbon disulfide in the presence of an alkali hydroxide (4) m (5) a ((4), (5), where R1, R-rich, C, and Ba are represented by the formula (2) I (3) ) has the same meaning as in the case of Xrij
Synthesized by Oj, Br, I/%Ogen) etc.

The reaction of the above formula (2> e (3) * (s) is usually carried out at a temperature of 30 to SaC for 4 to 10 hours.

The produced 92-mercaptothiazolites precipitate as crystals, and the reaction system becomes a slurry.
After cooling to preferably 20° C. to 20° C. to extract a sufficient amount of 2-mercaptothiazolines, the mixture is subjected to over-separation. In addition, since the above-mentioned salt-free salts are also precipitated at this time, riNaH8 is added to the obtained crude 2-mercaptothiazoline crystals.
.

N C2S , N a 2S O4e N a C1e
It contains a large amount (approximately 10 to 70 salts) of inorganic salts such as N C2 COa, and cannot be used as is for other purposes.

For example, when producing aminoalkylthiols by hydrolyzing 2-mercaptothiazolines with hydrologonic acid, (i) If Na2S, NaH3, etc. are mixed, a large amount of H2S, a harmful gas, will be generated. (11) Aminoalkylthiols, which are the final products, are required to have a fairly high purity (at least 98% or higher), so a recrystallization operation is indispensable, but the contamination of the above salts greatly prevents this operation and is not sufficient. The inability to improve product purity, 01D and, most importantly, Na25
If even a small amount of salt such as O4 is present in the hydrolysis reaction system, a large amount of cystamines, which are by-products in the form of oxidized trimerization of aminoalkylthiols, will be produced, which will greatly reduce the yield and purity. This is because problems such as this may occur.

Therefore, the crude 2-mercaptothiazoline crystals must be purified to sufficiently remove the above-mentioned inorganic salts before being used for other purposes.

However, when recrystallization using water as the solvent, which is the most common purification procedure, is used, a large amount of water must be used to dissolve the 2-mercaptothiazoline crystals, as their solubility in water is extremely low. This inevitably leads to industrial disadvantages.

In view of this point, the inventors have made extensive studies and found that
The inventors have discovered that the above object can be achieved by treating crude 2-mercaptothiazolines with a specific organic solvent that dissolves only 2-mercaptothiazolines and does not substantially dissolve inorganic salts, and has completed the present invention. .

That is, in the present invention, as impurities, Mis, MiH8, MiSO4, Mi
At least one kind of inorganic salt selected from the group consisting of CO3゜MiX' (MVi alkali metal and alkaline earth metal, X' is F, (represents a halogen atom of 31, Br, I, and represents iVi+t1pz) A method for purifying crude 2-mercaptothiazolines containing as impurities, the crude 2-mercaptothiazolines having the general formula % () (where m゛ and β are 1 to 4, nViO to is an integer of 10, and X is represented by (representing a halogen atom of J or Br). A method for purifying 2-mercaptothiazolines, which is characterized by treatment with a halogenated aliphatic hydrocarbon.

The main points are as follows.

The present invention will be explained in detail below.

Crude 2-mercaptothiazolines, which are the object of the present invention, are produced using monoethanolamines and carbon disulfide as main raw materials, and are mainly produced by the above-mentioned (2), (
a) , (4) s It is a crude crystal obtained by reacting according to the formula (5) and separating the resulting slurry into solid and liquid, but it is not limited to this, and M4 S r M
'H8p M' SO4r M 'CjOa p
M1X' (M is an alkali metal and alkaline earth metal, x' is a halogen atom of F, Cρ, Br, I, 1
Ha+.

Products obtained by other methods may be used as long as they contain as an impurity at least one inorganic salt selected from the group consisting of 1.2). Such inorganic salts include Na2S*NaH8, Na25o,
, Na2Co3. aaan, K2S, K2So
, .

Kcn, cas, (ja%H8, caso, ,
caco3. Examples include Qa%aX. The content of this inorganic salt is usually about 10 to 70 inches. In addition, it may contain up to about 10% of organic by-products.

The 2-mercaptothiazolines of the present invention have the general formula (1
), such as 2-mercaptothiazoline, 4-methyl-2-mercaptothiazoline, 4
．． 4'-dimethyl-2-mercaptothiazoline, 4
．． 4'-bis(hydroxymethyl)-2-mercaptothiazoline, 5.5-dimethyl-2-mercaptothiazoline, 5-ethyl-2-mercaptothiazoline, 4,5
-dimethyl-2-mercaptothiazoline, 4,4.5
-Trimethyl-2-mercaptothiazoline, 4,4,5
゜5-tetramethyl-2-mercaptothiazoline, 4.
5-bis(hydroxymethyl)-2-mercaptothiazoline, 4-propyl-2-mercaptothiazoline, 4-
Ethyl-2-mercaptothiazoline, 5-propyl-2
-Mercaptothiazoline, 5-methyl-2-mercaptothiazoline, etc.

The processing solvent used in the present invention has the general formula (I) CmHnXl! (I) (In the formula, m and ft are integers of 1 to 4, n is an integer of 0 to 1o, and represents a halogen of xVi, cβ#Brj.) It is a halogenated aliphatic hydrocarbon.

Examples of such solvents include: 1-chlorobutane, 1-bromobutane, monochloromethane, monobromomethane, dichloromethane, dibromomethane, monochloroethane, monobromoethane, 1.2=dichloroethane, 1.2-dibromoethane, 1 .1-dichloroethane, 1,2-dichloropropane, 1,2-
dibromopropane, trichloromethane, tribromomethane, 1,1.1-trichloroethane, 1,1.2-)
Dichloroethane, 1,1,1,2-tetrachloroethane, 1,1,2-trichloropropane, L2+3-)'
J dichloropropane tetrachloromethane, 1,1-dichloroethene, 1,2-dichloroethene, 1,1.2-
) Lichloroethene, 1,1,2.2-f trichloromethane, 3-chloropropene-1, etc.

If the number of carbon atoms is 5 or more (for example, dichloropentane etc.), the solubility of the 2-mercaptothiazolines is low and it is not practical.

Aromatic halogens such as chlorobenzene, chlorobenzene, and chlorotoluene, and aromatic hydrocarbons such as benzene, toluene, and xylene have low solubility and are unsuitable as processing solvents.

The present invention deals with the treatment of crude 2-mercaptothiazolines containing inorganic salts such as Na2S as impurities using the above-mentioned specific halogenated aliphatic hydrocarbon solvent.
- The entire amount of the mercaptothiazoline component is dissolved and transferred to the solvent, and the inorganic salt that is substantially insoluble in the solvent is left as a residue to be separated from the 2-mercaptothiazolines, and then extracted from the extractant solution. Purified 2-mercaptothiazoline crystals are obtained by means such as crystallization or concentration to dryness.

The amount of solvent used may vary depending on the solvent used, the type of target 2-mercaptothiazoline, the treatment temperature, the number of treatment operations, the amount of inorganic salt, etc., but is usually 200 parts per 100 parts of crude 2-mercaptothiazoline. It may be selected as appropriate within the range of 5,000 parts, preferably from 500 to 3,000 parts.In this case, it is of course preferable to use a necessary and sufficient amount to dissolve the crude 2-)1 lucatothiazolines. .

It is desirable that the treatment temperature (dissolution temperature) be as high as possible in order to increase purification efficiency, but at temperatures exceeding the boiling point of the solvent used, dissolution must be performed under pressure, so in practice it is necessary to dissolve at or below the boiling point of the solvent. Preferably, the treatment is carried out.

In this way, the entire amount of the 2-mercaptothiazoline component is dissolved and transferred to the solvent, but the inorganic salts such as Na28 are not substantially dissolved and remain as crystals, forming a residue.
Separate the harvest by means such as filtration or centrifugation. The separation is preferably carried out under heat retention in some cases so that the dissolved 2-mercaptothiazolines do not precipitate.

Finally, purified 2-mercaptothiazolines are obtained by taking out the 2-mercaptothiazolines in the solvent as crystals. The means for obtaining these purified crystals is arbitrary, but usually purified 2-mercaptothiazolines with a sufficiently high purity can be obtained simply by evaporating the entire amount of the solvent under normal pressure or reduced pressure and then concentrating to dryness. . In addition, in some cases, if the solvent in which 2-mercaptothiazolines are dissolved contains some organic by-products (2-oxazolidones, 2-thiazolidones, etc., unreacted alkanolamines, etc.), the above-mentioned Purified 2-mercaptothiazolines can be purified by removing a part of the solvent by evaporation under normal pressure or reduced pressure, or by simply cooling to about 25 to 0°C, preferably about 20 to 5°C, without concentration to dryness. It is preferable to crystallize the organic by-product to ensure separation from the organic by-product.

The present invention will be explained below with reference to examples, but these are merely illustrative, and it is understood that the technical scope of the present invention as defined in Article 70 of the Patent Act is interpreted to be limited by these examples. Must not be.

In the following examples, 2-mercaptothiazolines were analyzed by the method of quantifying -8H groups using iodine.

The amount of inorganic salts in the crystals was determined by atomic absorption spectrometry from a sample treated at 600 to 700° C. by scorching heat, and the amount of organic by-products was determined by liquid chromatography and gas chromatography.

Example 1 According to formula (3), carbon disulfide was added dropwise at 45°C for 3 hours.
Reaction: 1 hour at 60°C, filtration separation: 80g of crude 2-mercaptothiazoline crystals having the following composition synthesized via sulfuric acid ester of monoethanolamine at 40°C, 2-mercaptothiazoline 73.0% Na
25o4 20.2% Organic by-products (2-thiazolidone, etc.) 0.44H206
, 4% was placed in a lρ4 tube flask equipped with a stirrer, condenser and thermometer, 125 g of 1,2-dichloroethane was added as a treatment solvent, heated to 60°C and stirred for 10 minutes, and the treated solution was quickly transferred to a separating funnel. Undissolved inorganic salts were separated from the lower part of the funnel along with some solvent, and the separated residue consisting mainly of inorganic salts was charged again into a 1fi4 Turow flask, 1,2-dichloroethane 125II was added, and the same operation was performed. The separated residue was separated by filtration, the separated crystals on the filter paper were washed with 60 g of 1,2-dichloroethane, the washing liquid was transferred together with the previously separated dichloroethane layer to a 1ρ eggplant-shaped flask, and the mixture was evaporated using a rotary evaporator.
It was concentrated to dryness under conditions of 0 mmHf and 80°C to obtain 58.3f of purified 2-mercaptothiazoline having the following composition.

2-Mercaptothiazoline 99.4% Na2SO
4trace Organic by-product 0.6 Polycrystal recovery rate Vi was 99.8%.

Example 2 From monoethanolamine via chloroethylamine hydrochloride, dropwise addition of 20% sodium hydroxide at 120°C at 4°C.
2-mercaptothiazoline crystal 301 having the following composition synthesized according to formula (5) under the reaction conditions of 15 minutes at 50°C, 2-mercaptothiazoline 57.1
%Nacn 35.7% Organic by-product trace H207, 2% Dichloromethane as solvent 2101F, 210F.

18.3 g of purified 2-mercaptothiazoline crystals having the following composition were obtained by carrying out the same operation as in Example 1, except that 60F and 5 portions were used and the treatment temperature was 30°C.

2-Mercaptothiazoline 99.4% NaC!
0.0ti organic by-product
The trace % crystal recovery rate was 99.0%.

Example 3 Dropwise addition of 20 sodium hydroxide according to formula (2) 43
℃ for 2 hours, reaction at 80℃ for 2 hours, filtration separation at 60℃.2 synthesized from monoethanolamine with the following composition.
-Crystals of mercaptothiazoline 309, 2-mercaptothiazoline 59, 3% organic by-products (2-thiazolidones) s, a% H206, 7% 1,2-dichloroethane as solvent 140f, 1
40f.

Inorganic salts were separated in the same manner as in Example 1 using 609 and 609. The obtained solvent layer was cooled to 5° C., and the precipitated crystals were separated and separated to dry to obtain purified 2-mercaptothiazoline 17. I got Of.

2-mercaptothiazoline 99.7% inorganic salt
Organic impurities: o, o: 0.3% The crystal recovery rate was 95.3%.

Example 4 An experiment similar to Example 1 was conducted except that the treatment solvent was changed. The results are shown in Table 1.

Comparative Example 1 80f of crude 2-mercaptothiazoline crystals obtained by the same synthesis method as in Example 1 were converted into 2-mercaptothiazoline 72·1g6N
a, 5o422.0% Organic by-products (2-thiazolidone, etc.) 0.54
The inorganic salt separation operation was carried out in the same manner as in Example 1 except that toluene was used as the H205°4 treatment solvent.

The purified 2-mercaptothiazoline obtained by concentrating the toluene layer to dryness was o.sg (recovery rate 0.014%).

Patent applicant: Mitsui Toatsu Chemical Co., Ltd.

Claims (1)

[Claims] (1) As impurities, Mis, Mi)Is, M
iSO,, MiC03゜MiX' (M is alkali metal and alkaline earth metal, X'ij F, Of, B
r, indicates a halogen atom of I; 'i; t +, 1
A method for purifying crude 2-mercaptothiazolines containing as an impurity at least one inorganic salt selected from the group consisting of ) amHnXノ σ
) (where m and ) are integers of 1 to 4, n is an integer of 0 to 10, and represents a halogen atom of xVici or Br) characterized by treatment with a halogenated aliphatic hydrocarbon. 2 - A method for purifying mercaptothiazolines.