JPH0570427A - Production of disulfides - Google Patents

Abstract

PURPOSE:To obtain disulfides containing nitrogen atom and useful as an intermediate for fine chemicals such as pharmaceuticals having radioprotective action in one step and high yield from an inexpensive sulfur source on an industrial scale at a low cost. CONSTITUTION:The objective disulfides of formula RSSR (a part of which are new substances), e.g. new substance of formula I (m is 3-1,000) expected to be useful as a heat-resistant resin, a metal sequestering agent, etc., are produced by heating a Bunte salt of formula RSSO3M (R is N-containing organic substituent; M is alkali metal) in water and/or a water-soluble organic solvent in acidic state. The above Bunte salt is preferably the one produced by heating a nitrogen-containing halogen compound, especially the compound of formula II to IV (R1 to R5 are H or 1-8C alkyl; R1 and R2 may be 1-8C alkenyl, 2-8C acyl, 1-8C hydroxyalkyl, etc.; Alk is group having 1-4C alkylene as main chain; X is Cl or Br; Py is 2-, 3- or 4-pyridyl) and sodium thiosulfate in water and/or a water-soluble organic solvent.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing disulfides.

[0002]

2. Description of the Related Art A great number of disulfide-containing disulfide compounds are known,
It is an important synthetic intermediate for fine chemicals. Cystamine, which has a simple structure, is useful as a drug having an action of protecting radiation damage or an intermediate thereof, and is also an important starting material for pantethine as a drug. The amino acid cystine is also well known as a disulfide compound.

As a method for synthesizing disulfides, generally known is a method comprising two steps of synthesizing corresponding thiols and further oxidizing them. For example, as a method of obtaining cystamine, a method of oxidizing cysteamine obtained from ethyleneimine and hydrogen sulfide with hydrogen peroxide is generally used (JP-A-55-127360).
No. 57-62251, No. 59-108761,
59-110667, 60-8292, 61
-10961). In addition, other disulfides are generally similarly synthesized by oxidation of corresponding thiols.

On the other hand, an attempt to directly obtain a disulfide from a corresponding halide has been industrially advantageous from the viewpoint of shortening the process and reducing the cost, and has been made for many years, but it is still unsuccessful. I haven't arrived. For example, in the method of reacting halogenated hydrocarbons with sodium disulfide to lead to disulfides all at once, the resulting disulfides contain monosulfides and polysulfides as impurities, and these must be removed, which lengthens the process. Not industrial.

As another method, there is known a method in which a halogenated hydrocarbon and sodium thiosulfate are reacted to form a corresponding Bunte salt, and the Bunte salt is taken out as a solid and thermally decomposed at a high temperature (Chem. . Ber., 7, 646 (187
Four)). RX + Na ₂ S ₂ O ₃ → RSSO ₃ Na (Bunte salt) However, in this method, the yield of disulfide required is low, and the water-soluble Bunte salt is once taken out from the reaction solution and dried, and the obtained solid is decomposed by heating. This is a problem in industrial practice because it requires the operation to do so.

Another method is to use Bunte salt with iodine or 1
A method of adding 0 mol% of thiourea and heating under acidic conditions is known (J. Chem. Soc., 2172 (1962)). Although disulfide is directly obtained by this method, thiourea only acts as a catalyst and remains in the reaction system as it is. Therefore, it is necessary to separate thiourea and disulfide after the reaction. Furthermore, iodine is an expensive raw material and causes cost increase, so it cannot be said to be industrially advantageous. From this, the development of an advantageous method for easily obtaining disulfides in a short process is expected in the art,
No satisfactory method has been found yet.

[0007]

There have been many studies to obtain cystamine in one step, but in JP-A-57-62251, when the intermediate Bunte salt is treated with hydrochloric acid. It is described that cysteamine (thiol) is generated and cystamine (disulfide) is generated only when the Bunte salt is treated with hydrogen peroxide. In addition, there is an example that a thiol can be obtained by decomposing Bunte salt containing a nitrogen atom in the molecule under acidic condition with hydrochloric acid (Pharmaceutical Journal, 77 , 73).
0 (1957)). Thus, acid decomposition of Bunte's salt has been famous since ancient times as a means for synthesizing thiols, and it is generally believed so. However, as a result of repeated studies on the method for obtaining disulfides in one step without passing through a thiol in order to solve the above problems, the present inventors have found that the Bunte salt is acidic in water and / or a water-soluble organic solvent. under,
It is preferably within a range not exceeding pH 4, more preferably p
Surprisingly, it was found that the corresponding disulfides can be obtained in one step only by heating at H2 or lower, and the present invention was accomplished.

That is, the gist of the present invention is to formula (1) RSSO ₃ M (1) containing a nitrogen atom in the molecule (wherein R represents an organic substituent containing a nitrogen atom, and M represents an alkali metal). The Bunte salt represented by the formula (4) is heated in water and / or a water-soluble organic solvent under acidic condition, and is represented by the general formula (2) RSSR (2) (wherein R has the same definition as described above). The present invention relates to a method for producing disulfides represented by

The reaction formula is as follows.

[Chemical 1]

In the present specification, R is exemplified by an organic substituent containing a nitrogen atom, for example, an alkylaminoalkyl group, a trialkylammoniumalkyl group, a pyridylalkyl group and the like. M represents an alkali metal such as sodium or potassium.

As a method for obtaining a Bunte salt, there is known a method of reacting a halogenated hydrocarbon or a compound in which the halogen is converted to a sulfuric acid ester of alcohol with sodium thiosulfate as described above. The method for preparing the Bunte salt used in the method of the present invention is not particularly limited, but the availability of raw materials, cost problems,
Considering the ease of product separation and the like, the method of obtaining from a halogenated hydrocarbon and sodium thiosulfate is advantageously used. In particular, a nitrogen-containing halogen compound containing nitrogen in the molecule is reacted with sodium thiosulfate to form a corresponding Bunte salt, and the reaction system is heated under acidic conditions as described above, so that disulfides can be obtained in one step in good yield. can get.

That is, the Bunte salt which can be used in the present invention comprises a nitrogen-containing halogen compound represented by the following general formulas (3), (4) and (5) and sodium thiosulfate, which are water-soluble and / or water-soluble. The thing obtained by heating in an organic solvent is illustrated as a suitable thing. Here, as the nitrogen-containing halogen compound, a compound represented by R ₁ R ₂ N-Alk-X or a salt thereof (3) Quaternary ammonium salt represented by R ₃ R ₄ R ₅ N ⁺ -Alk-X (4) a pyridine derivative or a salt thereof Py-CH ₂ -X (5) can be exemplified.

Here, R ₁ and R ₂ are each a hydrogen atom,
A straight-chain or branched alkyl group having 1 to 8 carbon atoms, 2 to 2 carbon atoms
8 alkenyl group, 2 to 8 carbon acyl group, 1 carbon atom
8 represents a hydroxyalkyl group. Examples of the alkyl group having 1 to 8 carbon atoms include methyl group, ethyl group, propyl group, hexyl group and octyl group. Examples of the alkenyl group having 2 to 8 carbon atoms include allyl group, butenyl group and hexenyl group. Examples of the acyl group having 2 to 8 carbon atoms include acetyl group, propionyl group and hexanoyl group. Examples of the hydroxyalkyl group having 1 to 8 carbon atoms include the above alkyl groups substituted with a hydroxyl group. R ₁ and R ₂ may form a heterocycle with the nitrogen atom to which they are attached, and examples of such a heterocycle include pyrrolidine, piperidine, pyrrole and morpholine.

As Alk, a methylene group, an ethylene group,
Examples thereof include straight-chain or branched alkylene groups having a main chain of 1 to 4 carbon atoms such as trimethylene group and tetramethylene group. Examples of the linear or branched alkyl group having 1 to 8 carbon atoms represented by R ₃ , R ₄ and R ₅ are the same as those described above for R ₁ and R ₂ .

Specific examples of the nitrogen-containing halogen compound include:
Dimethylaminomethyl chloride, 2-aminoethyl chloride, 2-aminoethyl bromide, 3-aminopropyl chloride, 2- (methylamino) ethyl chloride, 2-
(Dimethylamino) ethyl chloride, 3- (dimethylamino) propyl chloride, 4-dimethylaminobutyl chloride, 2- (dimethylamino) -1-methylethyl chloride, 2- (diethylamino) ethyl chloride, 2-
(Dipropylamino) ethyl chloride, 2- (dioctylamino) ethyl chloride, 2- (ethyloctylamino) ethyl chloride, 2- (1-pyrrolidinyl) ethyl chloride, 2- (1-piperidino) ethyl chloride, 2
-(4-morpholino) ethyl chloride, 2- (1-piperazino) ethyl chloride, 2- (1-pyrrolyl) ethyl chloride, (2-chloroethyl) trimethylammonium chloride, (2-chloroethyl) triethylammonium chloride, (2 -Chloroethyl) dimethylethylammonium, 2-pyridylmethyl chloride, 3-pyridylmethyl chloride, 4-pyridylmethyl chloride, (2-acetamino) ethyl chloride, bis (2-hydroxymethyl) aminoethyl chloride and the like. The length of the substitutable alkyl group is not particularly limited, but it can be sufficiently used up to about C ₁₈ , and the alkyl group may be branched or aralkyl group. Furthermore, in addition to the compounds represented by the above general formulas (3), (4) and (5), a nitrogen-containing halogen compound represented by the general formula (6) can also be used in the present invention. An amine compound represented by H _(3-n) N (CH ₂ CH ₂ X) _n (6) (wherein n represents 2 or 3, X represents a chlorine atom or a bromine atom) or a salt thereof. .. Specific examples thereof include bis (2-chloroethyl) amine and tris (2-chloroethyl) amine.

The nitrogen atom in the nitrogen-containing halogen compound is 1
It may be any of secondary, secondary, tertiary or quaternary, and may be a nitrogen atom contained in the heterocycle. In the case of a quaternary nitrogen atom, a counter anion exists around the nitrogen atom, but the type of counter anion is not particularly limited.

The Bunte salt used in the present invention is obtained by heating such a nitrogen-containing halogen compound and sodium thiosulfate in water and / or a water-soluble organic solvent. As the water-soluble organic solvent used here, usually it is industrially advantageous to use only water, but when the reaction substrate is difficult to dissolve in water, alcohols, ethers, etc. are used for the purpose of improving the reactivity. It is often effective to add to the reaction system a solvent that is miscible with water and does not itself participate in the reaction. Examples of alcohols include methanol, ethanol, propanol, butanol, ethylene glycol and the like, and examples of ethers include dioxane, dimethyl cellosolve, diethyl cellosolve, diethylene glycol dimethyl ether and the like. The heating conditions differ depending on the kind of the nitrogen-containing halogen compound, but are usually preferably 60 ° C. to the reflux temperature for 0.5 to 10 hours.

The positional relationship between the nitrogen atom and the sulfur atom in the Bunte salt used in the present invention is not particularly limited, but a straight chain or a branched chain having 1 to 4 carbon atoms as the nitrogen atom and the sulfur atom is a main chain. It is particularly effective for the disulfide synthesis of the present invention if it is linked via an alkylene group. That is, in the general formulas (3) and (4), Alk is a methylene group,
Examples thereof include alkylene groups such as ethylene group, trimethylene group and tetramethylene group. Further, there is no particular problem even if the carbon atom directly bonded to the sulfur atom has a substituent. For example, 2-amino-1-methylethyl group, 2-
Amino-1,1-dimethylethyl group and the like.

When the compound represented by the general formula (6) is used as the nitrogen-containing halogen compound in the present invention, the Bunte salt may be, for example, NH (CH ₂ CH ₂ SSO).
Multivalent Bunte salts such as ₃ Na) ₂ and N (CH ₂ CH ₂ SSO ₃ Na) ₃ are obtained. Among these, NH (CH ₂ CH ₂
When SSO ₃ Na) ₂ is used as a raw material, the following compounds can be synthesized depending on the reaction conditions.

[Chemical 2] ^{_{Here, (SCH 2 CH 2 N +}} H 2 Cl - CH 2 CH 2
The compound S) _m is a novel compound and is expected to be used as a heat resistant resin and a metal scavenger.

Further, in the Bunte salt used in the present invention, a part of carbon atoms in the main chain may form a ring with a nitrogen atom. Examples thereof include 2-pyridylmethyl group, 3-pyridylmethyl group, 4-pyridylmethyl group, 2
-Pyrrolylmethyl group, 3-pyrrolylmethyl group, 2-indolylmethyl group, 3-indolylmethyl group, 2-piperidylmethyl group, 3-piperidylmethyl group, 4-piperidylmethyl group, 2-pyrrolidinylmethyl group, 3 -Pyrrolidinylmethyl group and the like. As the counter cation of the Bunte salt shown above, sodium, potassium and the like are used, and sodium is economically advantageous.

In the present invention, the reaction solvent used in the reaction for obtaining the disulfides from the Bunte salt may be water and / or a water-soluble organic solvent, as in the case of the Bunte salt forming reaction. Usually, it is industrially advantageous to use only water, but when the reaction substrate is difficult to dissolve in water, it is mixed with water such as alcohols and ethers for the purpose of improving the reactivity and the reaction itself is carried out. In many cases, it is effective to add a solvent not involved in the reaction to the reaction system. Examples of alcohols include methanol, ethanol, propanol, butanol, ethylene glycol and the like, and examples of ethers include dioxane, dimethyl cellosolve, diethyl cellosolve, diethylene glycol dimethyl ether and the like.

The reaction for obtaining the disulfides from the Bunte salt in the present invention is carried out by heating under acidic conditions, and the acid used here is preferably a mineral acid.
Mineral acid is added to the solution containing Bunte salt to acidify the reaction system and heated. Hydrochloric acid, sulfuric acid, etc. are generally used as the mineral acid, but other mineral acids are not a problem. A mineral acid / Bunte salt is usually added to the above solution in an equivalent ratio of 0.2 to 3.0 and heated. The pH of the reaction solution after addition of the mineral acid is preferably in a range not exceeding 4, particularly preferably 2 or less. If a large amount of the mineral acid is added, disulfide is generated immediately, but the mineral acid is added more than necessary, which is uneconomical. On the contrary, if the amount is small, it takes time to form the disulfide, which is not preferable. The mineral acid may be added all at once or in portions. The temperature of the reaction solution at the time of addition is 20 ° C to reflux temperature, and after the mineral acid is added, it is usually 60 ° C to reflux temperature for 10 minutes to 5
When heated for a long time, disulfide can be obtained in good yield. When the heating temperature is lower than this range, it takes a long reaction time, which is not preferable. In addition to mineral acids, organic acids such as acetic acid can be used in the present invention, but they are not advantageous because the reaction yield is slightly deteriorated and the organic acids are mixed in the product disulfide. The disulfide can be isolated from the obtained reaction solution by a usual method, for example, by making the reaction solution alkaline and liberating the nitrogen-containing disulfide, and extracting with an organic solvent. If the solvent is immiscible with water, it can be used as an extraction solvent. Depending on the product, there are some that are made alkaline only and separated from water.

Generally, a thiol having an amino group at the 2-position, such as cysteamine, is said to be oxidized relatively quickly by oxygen to give cystamine (J. Am. Chem. So.
c., 67, 1845 (1945)). However, in reality, this speed is not as fast as expected. It is said in the above-mentioned document that a thiol having an amino group at the 2-position is easily oxidized by oxygen, but there is no such description regarding a thiol having an amino group at the 3-position and 4-position. In reality, in order to obtain cystamine, it is oxidized with hydrogen peroxide (Japanese Patent Laid-Open No. 55-12).
No. 7360, No. 57-62251, No. 59-1087.
No. 61, No. 59-110667, No. 60-8292.
No. 61-10961). Even if the reaction of the present invention is carried out in a nitrogen atmosphere, disulfide can be obtained in good yield, and since the corresponding thiol is not detected even after the aging of the reaction, the reaction of the present invention is performed once the thiol is in the system. It is thought that this is not the mechanism by which it is oxidized to form disulfide.

[0024]

EXAMPLES The present invention will be specifically described below with reference to examples. Example 1 2-aminoethyl chloride hydrochloride 11.6 g (0.10
0 mol), sodium thiosulfate pentahydrate 24.9 g
(0.100 mol) and 50 g of water were charged into the reactor 10
Bunte salt was prepared by heating at 0 ° C. for 2 hours. This reaction proceeded almost quantitatively. 36% hydrochloric acid was added to this reaction solution for 10.
2 g (0.100 mol) was added. PH at this time is 1
It was below. The solution was heated to 100 ° C. for another 30 minutes. When analyzed at this point, all the starting 2-aminoethyl chloride had disappeared, and 10.2 g (0.045 mol) of bis (2-aminoethyl) disulfide hydrochloride had been formed. After the reaction solution was cooled to room temperature, caustic soda solution was added to make the reaction solution alkaline, and ethyl acetate 20
Extraction was performed 5 times at 0 g. When the ethyl acetate layers were combined and blown with hydrogen chloride gas, bis (2-aminoethyl) disulfide hydrochloride was precipitated. Bis (2-aminoethyl) disulfide hydrochloride was obtained after filtration and drying.
6 g (0.043 mol) were obtained with a yield of 86%.

Example 2 3- (Dimethylamino) propyl chloride hydrochloride 15.
8 g (0.100 mol), 24.8 g (0.100 mol) of sodium thiosulfate pentahydrate and 50 g of water were charged into a reactor and heated at 100 ° C. for 2 hours to carry out a reaction in the same manner as in Example 1. .. Thereafter, 10.1 g (0.100 mol) of 36% hydrochloric acid was added to this reaction solution. The pH at this time was 1 or less. The solution was heated for an additional hour. The reaction solution was cooled to room temperature, made alkaline with caustic soda, and extracted twice with 200 g of ethyl acetate. Hydrogen chloride gas was bubbled through the obtained ethyl acetate solution to precipitate the product as a hydrochloride. The precipitate was filtered and dried to give bis (3- (dimethylamino) propyl) disulfide hydrochloride 12.
4 g (0.040 mol) was obtained with a yield of 80%.

Example 3 3-Aminopropyl chloride hydrochloride was used instead of 3- (dimethylamino) propyl chloride hydrochloride as the reaction substrate.
0 g (0.100 mol) and 200 ethyl acetate for extraction
The reaction was performed in the same manner as in Example 2 except that g was used 3 times, and bis (3-aminopropyl) disulfide hydrochloride was 9.9.
g (0.039 mol), yield 78%.

Example 4 Same as Example 2 except that the reaction substrate was changed to 3- (dimethylamino) propyl chloride hydrochloride to 2- (dimethylamino) ethyl chloride hydrochloride 14.4 g (0.100 mol). To react with bis (2- (dimethylamino)
11.5 g (0.041) of ethyl) disulfide hydrochloride
Mol), and the yield was 82%.

Example 5 The same as Example 2 except that 17.2 g (0.100 mol) of 4- (dimethylamino) butyl chloride hydrochloride was used in place of 3- (dimethylamino) propyl chloride hydrochloride as the reaction substrate. To react with bis (2- (dimethylamino)
Butyl) disulfide hydrochloride is 13.5 g (0.040
Mol), and the yield was 80%.

Example 6 Dimethylaminomethyl chloride hydrochloride 1 was used instead of 3- (dimethylamino) propyl chloride hydrochloride as the reaction substrate.
The reaction was performed in the same manner as in Example 2 except that 3.0 g (0.100 mol) was added, and bis (dimethylaminomethyl) disulfide hydrochloride was 9.0 g (0.036 mol) in a yield of 72.
Obtained in%.

Example 7 Example 2 was repeated except that 2- (1-piperidino) ethyl chloride hydrochloride was replaced with 18.4 g (0.100 mol) as the reaction substrate instead of 3- (dimethylamino) propyl chloride hydrochloride. In the same manner, 13.5 g (0.037 mol) of bis (2- (1-piperidino) ethyl) disulfide hydrochloride was obtained with a yield of 74%.

Example 8 Example 3 was repeated except that the reaction substrate was changed to 3- (dimethylamino) propyl chloride hydrochloride to 2- (dimethylamino) -1-methylethyl chloride hydrochloride 15.8 g (0.100 mol). The same procedure as in Example 2 was repeated except that bis (2- (dimethylamino) -1-methylethyl) disulfide hydrochloride was converted to 1
2.7 g (0.041 mol) was obtained with a yield of 82%.

Example 9 2-Pyridylmethyl chloride hydrochloride in place of 3- (dimethylamino) propyl chloride hydrochloride as the reaction substrate 16.
The same procedure as in Example 2 was carried out except that the amount of bis (2-pyridylmethyl) disulfide hydrochloride was 12.6 g (0.039 mol) with a yield of 78%.

Example 10 (2-Chloroethyl) trimethylammonium chloride 1
5.8 g (0.100 mol), sodium thiosulfate 2
4.8 g and 50 g of water were charged into the reactor and heated at 100 ° C. for 2 hours. 10.1 g (0.1%) of 36% hydrochloric acid was added to the reaction solution.
00 mol) was added. The pH at this time was 1 or less.
The solution was heated for an additional hour. The product was extracted from the reaction solution with 100 g of butanol three times. Butanol layer 1
After being combined and concentrated to dryness, 11.4 g (0.037 mol) of 2,2′-dithiobisethylene-1,1′-bis (trimethylammonium dichloride) was obtained in a yield of 74%.

Example 11 17.8 g of bis (2-chloroethyl) amine hydrochloride
(0.100 mol), sodium thiosulfate 49.6 g
Charge (0.200 mol) and 50 g of water to the reactor 10
Heated at 0 ° C. for 2 hours. 36% hydrochloric acid was added to the reaction solution at 20.3
g (0.200 mol) was added. The pH at this time was 1 or less. The solution was heated for an additional hour. A precipitate was formed during the heating, and thus was collected by filtration. The product obtained is the corresponding polymer of disulfide hydrochloride (SCH ₂ CH
Was _{CH 2 CH 2 S) m 16.8g} (0.098 mole as a ^{_{monomer) - 2 N + H 2 Cl}} . According to the molecular weight measurement by gel permeation chromatography, it had a distribution centered on 37,000. Elemental analysis (as C ₄ H ₁₀ NClS ₂ ) Analytical value C 27.70, H 5.98, N 8.41, S 37.08, Cl 20.55
Calculated value C 27.98, H 5.87, N 8.16, S 37.34, Cl 20.65
% Melting point 187 ° C. (change in crystal structure) 223.2-226.1 ° C. (decomposition) ¹ H-NMR δ (DMSO-d ₆ ) 3.56 (broad singlet) IR cm ⁻¹ (KBr) 3450, 2960, 2750 , 2450,1640,1580,1470,1430,1140,630

[0035]

Industrial Applicability When a compound having a nitrogen atom and a halogen atom in the molecule is reacted with sodium thiosulfate to form a Bunte salt and then the reaction solution is acidified as it is, the corresponding disulfide is produced at a high yield. Conventionally, a method for obtaining a disulfide is a two-step reaction in which a thiol is first obtained and then the thiol is oxidized to form a disulfide. Therefore, the method of the present invention is superior as a method for obtaining a disulfide from a substrate containing a halogen atom at once. ing. Furthermore, since the sulfur source of disulfide is derived from inexpensive sodium thiosulfate, it is excellent from an industrial viewpoint.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Mikio Yamamoto 1 of 346 Miyanishi, Harima-cho, Kako-gun, Hyogo Prefecture Sumitomo Seika Co., Ltd. 1 Sumitomo Seika Co., Ltd. (72) Inventor Satoshi Oe 1 Sumitomo Seika Co., Ltd. at 346 Miyanishi, Harima-cho, Kako-gun, Hyogo Prefecture

Claims (7)

[Claims] 1. Bunte represented by the general formula (1) RSSO ₃ M (1) (wherein R is an organic substituent containing a nitrogen atom and M is an alkali metal) containing a nitrogen atom in the molecule. A disulfide represented by the general formula (2) RSSR (2) (wherein R has the same definition as described above), characterized in that the salt is heated in water and / or a water-soluble organic solvent under acidic conditions. Manufacturing method. 2. The method according to claim 1, wherein the Bunte salt is obtained by heating a nitrogen-containing halogen compound and sodium thiosulfate in water and / or a water-soluble organic solvent. 3. A nitrogen-containing halogen compound represented by the general formula (3) R ₁ R ₂ N-Alk-X (3) (wherein R ₁ and R ₂ are each a hydrogen atom and a carbon number of 1 to 8).
Is a linear or branched alkyl group, a C2-8 alkenyl group, a C2-8 acyl group, or a C1-8 hydroxyalkyl group. R ₁ and R ₂ may form a heterocycle together with the nitrogen atom to which they are bound. Alk
Is a linear or branched alkylene group having 1 to 4 carbon atoms as the main chain, and X is a chlorine atom or a bromine atom. The production method according to claim 2, which is a compound represented by the formula (4) or a salt thereof. 4. A nitrogen-containing halogen compound represented by the general formula (4) R ₃ R ₄ R ₅ N ⁺ -Alk-X (4) (wherein R ₃ , R ₄ and R ₅ are the same or different and each is hydrogen). The production method according to claim 2, wherein the quaternary ammonium salt is represented by an atom and a linear or branched alkyl group having 1 to 8 carbon atoms, and Alk and X have the same definition as above. 5. The nitrogen-containing halogen compound is represented by the general formula (5) Py—CH ₂ —X (5) (wherein Py represents a 2-, 3-, or 4-pyridyl group. The production method according to claim 2, which is a pyridine derivative represented by the same definition) or a salt thereof. 6. The nitrogen-containing halogen compound is represented by the general formula (6) H _(3-n) N (CH ₂ CH ₂ X) _n (6) (wherein, n represents 2 or 3, and X is the same as above. The method according to claim 2, which is an amine compound represented by the definition) or a salt thereof. 7. A general formula _{(7) (SCH 2 CH 2} N + H 2 Cl - CH 2 CH 2 S) m (7) ( wherein, m represents a 3 to 1000.) Nitrogen-containing represented by Compound.