JPH05294931A - Production of new intermediate and 2-chloro-5-@(3754/24)aminomethyl)pyridine - Google Patents

Abstract

PURPOSE:To obtain 2-chloro-5-(aminomethyl)pyridine useful as an intermediate for medicines and agricultural chemicals such as insecticide from a raw material safe in terms of handling through a new inbermediate under a safe and mild condition by easy handling in high yield. CONSTITUTION:(a) A compound of formula I having no irritation to eyes and skin is reacted with an aryl (or alkyl)sulfonyl chloride in water and a slightly water-soluble organic solvent in the presence of a quaternary ammonium salt and a caustic alkali (acid eliminator) to give a partially new compound of formula II (R is R' or alkyl; R' is phenyl which may contain substituent group; a new compound when R is R'). (b) Then, the compound is reacted with hexamethylenetetramine in water or an organic solvent to give a new substance of formula III. (c). Further the substance is hydrolyzed with a mineral acid in the presence of a lower alcohol in a water solvent and formaldehyde occurring as a by-product in the reaction is removed as a formal with a lower alcohol out of the reaction system to industrially and advantageously give the objective compound of formula IV.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION

[Chemical 9] The present invention relates to a novel method for producing 2-chloro-5- (aminomethyl) pyridine, and the compound (IV) is an extremely useful compound as an intermediate for medicines and agricultural chemicals.

2. Description of the Related Art Conventionally, the formula

[Chemical 10] Regarding the method for producing 2-chloro-5- (aminomethyl) pyridine in (2), a method using 2-chloro-5- (chloromethyl) pyridine as a starting material is known. , Japanese Patent Application 1-33
6232, Japanese Patent Application No. 1-333623, Japanese Patent Application 2-6
No. 8472, and all of them relate to a method of obtaining a desired product by reacting 2-chloro-5- (chloromethyl) pyridine with phthalimide or hexamethylenetetramine and then hydrolyzing it. However, 2-chloro-5- (chloromethyl) pyridine, which is the starting material for these production methods, is highly irritating to eyes and skin and has problems in handling.

[0003]

The present invention provides a safe, industrially easy and inexpensive compound (I) without using 2-chloro-5- (chloromethyl) pyridine, which is highly irritating.
V) is to be established.

[0004]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems, and as a result, a formula that is safe in handling has been obtained.

[Chemical 11] Starting from 2-chloro-5- (hydroxymethyl) pyridine as a starting material, the compound of the general formula

[Chemical 12] (In the formula, R represents a phenyl group which may be substituted or an alkyl group), and the reactivity of the obtained sulfonic acid ester with hexamethylenetetramine is 2 -Chloro-5- (chloromethyl) pyridine is far superior to that of the general formula in that it reacts easily and in high yield under milder reaction conditions.

[Chemical 13] The hexamethylenetetraammonium salt of can be produced, and the hexamethylenetetraammonium salt obtained can be easily hydrolyzed by acid hydrolysis in the presence of a lower alcohol.

[Chemical 14] It was found that 2-chloro-5- (aminomethyl) pyridine can be obtained, and the present invention was completed.

Next, the present invention will be described more specifically.
The reaction scheme of the present invention is as follows.

[Chemical 15] (In the formula, R has the same meaning as described above. R ″ represents a lower alkyl group.) Examples of the substituent of the phenyl group include an alkyl group such as methyl, ethyl, propyl and hexyl. .. R is preferably an optionally substituted phenyl group.

In the step (a), the compound (I) is added to a mixed solution of a poorly water-soluble organic solvent and an aqueous solution of caustic alkali.
Was added and well stirred, and then a quaternary ammonium salt was added as a catalyst, and then a solution of arylsulfonyl chloride or alkylsulfonyl chloride or a poorly water-soluble organic solvent thereof was added dropwise while cooling with stirring, and 0 to 30 ° C. It is possible to obtain a solution of the poorly water-soluble organic solvent of the compound (II) very easily and in a high yield by thoroughly stirring at.
According to the method of the present invention, the compound (II) can be obtained without adding a quaternary ammonium salt to the reaction system. However, the addition of the quaternary ammonium salt allows the reaction to proceed more rapidly and to give the desired product with a high yield. Can be obtained. As the quaternary ammonium salt, a commercially available aliphatic quaternary ammonium salt such as tetraethylammonium chloride, tetrabutylammonium chloride, triethylbenzylammonium chloride, tributylbenzylammonium chloride or the above quaternary ammonium bromide can be used. The use of 0.1 to 2 mol% with respect to the compound (I) can sufficiently achieve the purpose. As the caustic alkali, caustic soda or caustic potash can be used, and 1 to 1 equivalent of compound (I) can be used.
Use 1.5 equivalents. As a poorly water-soluble organic solvent,
Examples of the compound obtained after the reaction include aromatic solvents such as benzene, toluene and xylene, chlorine solvents such as methylene chloride, chloroform, ethylene dichloride and chlorobenzene, and ketone solvents such as methyl isobutyl ketone. It is sufficiently possible to directly use the solution of these organic solvents containing II) in the step (b) of the present invention. The amount of these organic solvents used depends on the type of organic solvent and the type of compound (II), and it is generally convenient to use a sufficient amount to dissolve compound (II), but use an amount less than that. However, the purpose can be fully achieved. Examples of the aryl or alkyl sulfonyl chloride include benzene sulfonyl chloride, P-toluene sulfonyl chloride, O-toluene sulfonyl chloride, methane sulfonyl chloride and the like, and 1 to 1 equivalent of the compound (I) is used.
~ 1.1 equivalents should be used.

The compound (I obtained by the method of the present invention
I) can be generally obtained by separating the reaction solution and distilling or recrystallizing the solvent from the obtained organic layer.
When a solvent inert to hexamethylenetetramine used in step (b) is used, it is not necessary to isolate the compound (II), and the compound (II) obtained by separating after the reaction is used. The solution of the poorly water-soluble organic solvent contained can be directly subjected to the step (b) without drying, which is very advantageous industrially.

In the step (b), the compound (II) and hexamethylenetetramine are reacted in water or an organic solvent with stirring to obtain the compound (III) in a high yield. Hexamethylenetetramine is a compound (I
The purpose can be sufficiently achieved by using 1 to 1.2 equivalents relative to 1 equivalent of I). The solvent used in the reaction is water or an organic solvent such as methanol, ethanol, propanol, a lower alcohol solvent such as isopropanol, benzene,
Aromatic solvents such as toluene and xylene, nitrile solvents such as acetonitrile, ketone solvents such as methyl ethyl ketone and methyl isobutyl ketone, and chlorine solvents such as chloroform and chlorobenzene can be used. The reaction temperature ranges from 20 ° C. to the boiling point of the solvent used, but the optimum reaction temperature varies depending on the type of compound (II) or the type of solvent used. After completion of the reaction, when water or a lower alcohol solvent is used as the reaction solvent, the reaction solution may be directly subjected to the step (c), and when a solvent other than water or a lower alcohol solvent is used, the compound (I
Since II) is precipitated, the compound (III) can be easily obtained by a usual operation such as filtration and washing. When a poorly water-soluble organic solvent is used as the reaction solvent, water or a dilute mineral acid aqueous solution is added to the slurry solution after the reaction to give the compound (I
II) may be extracted and the obtained aqueous layer may be subjected to the step (c).

As the mineral acid used in the acid hydrolysis in the step (c), hydrochloric acid or sulfuric acid can be mentioned.
From 3.0 to 5.0 equivalents may be used per equivalent of II). Examples of the lower alcohol used in the reaction include methanol, ethanol, propanol, isopropanol, etc., but industrially inexpensive methanol is preferable, and 12.0 to 3 per 1 equivalent of the compound (III).
6.0 equivalents should be used. The reaction is carried out from room temperature under reflux, and after the reaction is completed, the formal produced by the formaldehyde by-produced by the hydrolysis of the compound (III) and the lower alcohol added to the reaction system is distilled off from the reaction system. Formaldehyde, which is a by-product of hydrolysis, can be easily removed. When the compound (IV) is taken out in the presence of formaldehyde, the reaction between the compound (IV) and formaldehyde occurs, and the purity and the yield of the obtained compound (IV) are significantly reduced. After distilling off the formal, the aqueous solution containing the obtained mineral salt of the compound (IV) is made alkaline with caustic alkali, extracted with a poorly water-soluble solvent such as chloroform, and then subjected to usual treatments such as concentration. As a result, the compound (IV) can be obtained.

[0010]

EXAMPLES The following examples illustrate the invention and are not intended to limit it in any way. Example 1 2-chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester

[Chemical 16] 2-chloro-5- (hydroxymethyl) pyridine 201.
1 of 0 g (1.40 mol) dissolved in 1 l of chloroform
672.0 g (1.68 mol) of 0% NaOH aqueous solution and 50%
Triethylbenzylammonium chloride 12.7 g (0.
028 mol) was added and the mixture was cooled to 15 ° C., and while maintaining the same temperature with stirring, 285.7 g of P-toluenesulfonyl chloride
A solution prepared by dissolving (1.50 mol) in 750 ml of chloroform was added dropwise over 1 hour and then stirred at the same temperature for 3 hours.
After the reaction, the chloroform layer obtained by liquid separation was concentrated under reduced pressure, 500 ml of toluene was added to the obtained crystals to wash, then cooled to 5 ° C., filtered, and washed twice with 100 ml of cold toluene. It was dried to obtain 352.3 g of the target white crystal.
mp 92-93 ° C. Yield 84.5% ¹ H-NMR spectrum (CDCl ₃ ) δ _ppm ; 2.46
(3H, s) 5.06 (2H, s) 7.29 to 8.25
(3H, m, aromatic) 7.33 to 7.79 (4H, q,
aromatic)

Example 2 2-Chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester

[Chemical 17] 2-chloro-5- (hydroxymethyl) pyridine 29.6
g (purity 97.0%, 0.2 mol) to chloroform 60 ml, 1
96.0 g (0.24 mol) of 0% NaOH aqueous solution and 0.46 g (0.04%) of 50% triethylbenzylammonium chloride.
(01 mol) was added and the mixture was cooled to 15 ° C. with stirring. While maintaining the same temperature with stirring, P-toluenesulfonyl chloride 40.
A solution prepared by dissolving 04 g (0.21 mol) in 60 ml of chloroform was added dropwise over 0.5 hour, and then the mixture was reacted at the same temperature for 5 hours, and the reaction was almost completed. After the reaction, the chloroform layer obtained by liquid separation was analyzed by high performance liquid chromatography, and as a result, it was found that the target product contained 57.5 g (0.193 mol). Yield 96.5%

Example 3 2-Chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester

[Chemical 18] 2-chloro-5- (hydroxymethyl) pyridine 29.6
g (purity 97.0%, 0.2 mol) to toluene 60 ml, 10%
Aqueous NaOH solution 96.0 g (0.24 mol) and 50% tributylbenzylammonium chloride 0.31 g (0.000%)
5 mol) was added and the mixture was cooled to 15 ° C. with stirring, and P-toluenesulfonyl chloride (4.0%) was added while keeping the same temperature with stirring.
1 g of a solution of 4 g (0.21 mol) dissolved in 60 ml of toluene
When the mixture was dropped over a period of time and then reacted at the same temperature for 3.5 hours, the reaction was almost completed. After the reaction, toluene 120
ml was added and the mixture was heated to 45 ° C to dissolve the precipitated target substance slurry and then liquid separation was performed. The obtained toluene layer was analyzed by high performance liquid chromatography. As a result, the target substance was found to be 58.8.
It was found to contain g (0.197 mol). Yield 98.5
%

Example 4 2-Chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester

[Chemical 19] 2-chloro-5- (hydroxymethyl) pyridine 28.7
60 ml of methyl isobutyl ketone to 10 g of g (0.2 mol)
Aqueous NaOH solution 96.0 g (0.24 mol) and 50% triethylbenzylammonium chloride 0.92 g (0.002)
mol) and cooled to 15 ° C with stirring, while maintaining the same temperature with stirring, P-toluenesulfonyl chloride 40.04
A solution prepared by dissolving g (0.21 mol) in 60 ml of methyl isobutyl ketone was added dropwise over 1 hour, and then the mixture was reacted at the same temperature for 8 hours, and the reaction was almost completed. After the reaction, 120 ml of methyl isobutyl ketone was added and heated to 45 ° C., the precipitated target slurry was dissolved and then separated, and the obtained methyl isobutyl ketone layer was analyzed by high performance liquid chromatography. 57.9 g (0.194 g)
(mol) was found. Yield 97.3%

Example 5 2-Chloro-5-pyridylmethylhexamethylenetetraammonium P-toluenesulfonate

[Chemical 20] 2-chloro-5- (hydroxymethyl) pyridine P-
Toluenesulfonic acid ester (29.8 g, 0.1 mol) was dissolved in chloroform (150 ml), hexamethylenetetramine (15.4 g, 0.11 mol) was added, and the mixture was refluxed for 7 hours with stirring until the raw material disappeared. After the reaction, the reaction mixture was cooled to room temperature, and the precipitated crystal was filtered, washed with chloroform and dried to obtain 43.8 g of the target white crystal. mp157-8 ° C. Yield 10
0% ¹ H-NMR spectrum (DMSO-d ₆ ) δ _ppm ; 2.
86 (3H, s) 4.12 (2H, s) 4.40 to 4.5
9 (6H, q) 5.08 (6H, s) 7.12 to 7.14
(4H, q, aromatic) 7.64 to 8.52 (3H, m,
aromatic)

Example 6 2-Chloro-5- (aminomethyl) pyridine

[Chemical 21] 2-chloro-5-pyridylmethylhexamethylenetetraammonium P-toluenesulfonate 43.8 g (0.
30 ml of water, 36.5 g (0.35 mol) of 35% hydrochloric acid and 76.8 g (2.4 mol) of methanol were added to 1 mol) and stirred for 1.5
Reflux for hours. After completion of the reaction, dimethylformal produced as a by-product and excess methanol were slowly distilled off until the internal temperature reached 100 ° C. Then add 20 ml of water, 50
After cooling to ℃, add 50 ml of chloroform, cool to room temperature, and, with stirring, 72.0 g (0.
(45 mol) was added to make the mixture alkaline and the layers were separated. The aqueous layer was extracted well with chloroform, combined with the preceding chloroform layer, dried over magnesium sulfate and concentrated, and a pale yellow oil (crystallized on cooling. Mp 25-26 ° C) 13.
90 g (0.0975 mol) were obtained. Yield 97.5% ¹ H-NMR spectrum (CDCl ₃ ) δ _ppm ; 1.49
(2H, s, broad) 3.90 (2H, s) 7.29 to 8.3
4 (3H, m, aromatic)

Example 7 2-Chloro-5- (aminomethyl) pyridine

[Chemical formula 22] 2-chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester 29.
8g (0.1mol) and hexamethylenetetramine 15.4g
(0.11 mol) was added, and the mixture was reacted at 30 ° C. for 1 hour while stirring. After the reaction was completed, 40 ml of water and 35% hydrochloric acid were added to the reaction solution.
6.5 g (0.35 mol) was added, the mixture was refluxed for 1.5 hours, and then dimethylformal by-produced in the reaction and excess methanol were slowly distilled off until the internal temperature reached 100 ° C. After that, it was cooled to 50 ° C., 50 ml of chloroform was added and further cooled to room temperature, and then 72.0 g of 25% NaOH aqueous solution was added.
(0.45 mol) was added to make the mixture alkaline and the layers were separated. The aqueous layer was further extracted well with chloroform, and the extract was combined with the preceding chloroform layer and analyzed by high performance liquid chromatography. As a result, it was found that the desired product was contained in an amount of 14.14 g (0.0992 mol). Yield 99.2%

Example 8 2-Chloro-5- (aminomethyl) pyridine

[Chemical formula 23] 2-chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester 29.8 g (0.1
mol) and hexamethylenetetramine 15.4g (0.11mo
l) was added, and the mixture was reacted at 40 ° C. for 6 hours with stirring. After completion of the reaction, 100 ml of methanol and 35% hydrochloric acid were added to the reaction solution
6.5 g (0.35 mol) was added, the mixture was refluxed for 1.5 hours, and then dimethylformal by-produced in the reaction and excess methanol were slowly distilled off until the internal temperature reached 100 ° C. Then, the same operation as in Example 7 was carried out to obtain a chloroform solution containing the desired product, and the product was analyzed by high performance liquid chromatography. As a result, it was found that the desired product contained 13.35 g (0.0936 mol). .. Yield 93.6%

Example 9 2-Chloro-5- (aminomethyl) pyridine

[Chemical formula 24] 2-chloro-5- (hydroxymethyl) pyridine 29.6
A chloroform solution containing 2-chloro-5- (hydroxymethyl) pyridine P-toluenesulfonic acid ester obtained in the same manner as in Example 2 from g (purity 97.0%, 0.2 mol) was added to hexamethylenetetramine 30 0.8 g (0.22
(mol) was suspended in 180 ml of chloroform, and the mixture was reacted at 50 ° C. for 5 hours while stirring. Then, after cooling to room temperature, 60 ml of water and 73.0 g (0.7 mol) of 35% hydrochloric acid were added to dissolve and extract the precipitated crystals, and the layers were separated. 200 ml of methanol was added to the obtained aqueous layer and the mixture was refluxed for 1.5 hours with stirring, and then dimethylformal produced as a by-product of the reaction and excess methanol were slowly distilled off until the internal temperature reached 100 ° C. Then, cool to 50 ° C, add 20 ml of water and 100 ml of chloroform and further cool to room temperature, then 25%
An aqueous NaOH solution (144.0 g, 0.9 mol) was added to make the mixture alkaline, and the layers were separated. The aqueous layer was extracted well with chloroform, and the extract was combined with the chloroform layer and concentrated to obtain 26.5 g of the target oil. As a result of analysis by high performance liquid chromatography, the purity was 98.0%. 2-chloro-5
-Yield 91.2% based on (hydroxymethyl) pyridine

Example 10 2-Chloro-5- (aminomethyl) pyridine

[Chemical 25] 2-chloro-5- (hydroxymethyl) pyridine P-
Toluenesulfonic acid ester 29.8g (0.1mol) and hexamethylenetetramine 15.4g (0.11mol) were added to methyl isobutyl ketone (saturated with water) 150ml and reacted at 40 ° C for 3 hours with stirring. Let After the reaction, the mixture was cooled to room temperature, 30 ml of water and 36.5 g of 35% hydrochloric acid (0.35 mo)
l) was added, the precipitated crystals were dissolved and extracted, and the layers were separated. The obtained aqueous layer was further washed with 30 ml of toluene and then separated, and 100 ml of methanol was added to the aqueous layer and refluxed for 1.5 hours. Then, dimethylformal produced as a by-product of the reaction and excess methanol had an internal temperature of 100 ° C. It slowly distilled off until it reached.
After that, cool to 50 ° C, 20 ml of water and 50 of chloroform.
After adding ml, the mixture was further cooled to room temperature, and then 72.0 g (0.45 mol) of 25% NaOH aqueous solution was added to make the mixture alkaline, and the layers were separated. The aqueous layer was further extracted with chloroform, combined with the preceding chloroform layer, and analyzed by high performance liquid chromatography. As a result, it was found that the desired product was contained in an amount of 13.8 g. Yield 96.5%

Example 11 2-Chloro-5- (aminomethyl) pyridine

[Chemical formula 26] 2-chloro-5- (hydroxymethyl) pyridine P-
Toluenesulfonic acid ester (29.8 g, 0.1 mol) and hexamethylenetetramine (15.4 g, 0.11 mol) were added to 150 ml of toluene, and the mixture was reacted at 60 ° C. for 6 hours with stirring. After the reaction, the mixture was cooled to room temperature, 30 ml of water and 35% hydrochloric acid 36.
5 g (0.35 mol) was added, and the precipitated crystals were dissolved and extracted for liquid separation. 100 ml of methanol was added to the obtained aqueous layer and the mixture was refluxed for 1.5 hours. Then, dimethylformal by-produced in the reaction and excess methanol were slowly distilled off until the internal temperature reached 100 ° C. After that, cool to 50 ℃ and water 20ml
After adding 50 ml of chloroform and further cooling to room temperature, 72.0 g (0.45 mol) of 25% NaOH aqueous solution was added to make the mixture alkaline and the layers were separated. The aqueous layer was further extracted well with chloroform, combined with the previous chloroform layer and concentrated,
14.3 g of the target oil was obtained. As a result of analysis by high performance liquid chromatography, the purity was 97.2%. Yield 9
7.5%

Reference Example 1 2-chloro-5- (hydroxymethyl) pyridine methanesulfonic acid ester

[Chemical 27] 2-chloro-5- (hydroxymethyl) pyridine 14.4
Chloroform 100 ml, 25% caustic aqueous solution 19.2 g (0.12 mol) and 50% benzyltriethylammonium chloride aqueous solution 0.34 g (0.75 mmol) were added to g (0.1 mol), and the mixture was cooled to 5 ° C. with stirring. While maintaining the temperature, 12.6 g (0.11 mol) of methanesulfonyl chloride was added dropwise over 30 minutes, and the mixture was further stirred at the same temperature for 2 hours. To the resulting reaction solution was added 29 ml of water, the mixture was stirred and then separated, and the chloroform layer was dried over magnesium sulfate and then concentrated. The obtained residue was recrystallized from toluene to obtain 18.13 g (0.1
0818 mol) was obtained. Yield 81.8% ¹ H-NMR spectrum (CDCl ₃ ) δ _ppm ; 3.04
(S, 3H), 5.24 (s, 2H), 7.40 (d, 1
H, J = 7.9 Hz), 7.75 (dd, 1H, J = 2.5,
7.9Hz), 8.44 (d, 1H, J = 2.5Hz)

Example 12 2-Chloro-5-pyridylmethylhexamethylenetetraammonium methanesulfonate

[Chemical 28] 2-chloro-5- (hydroxymethyl) pyridine methanesulfonic acid ester 22.2 g (0.1 mol) was dissolved in water-saturated 1,2-dichloroethane 150 ml, and hexamethylenetetramine 15.4 g (0.11 mol). ) Was added, and the mixture was reacted under stirring at 50 ° C. for 5 hours until the raw material was consumed. After the reaction, the reaction mixture was cooled to room temperature, and the precipitated crystals were filtered to give 1,2-
The crystals were washed with dichloroethane and dried to give 36.0 g of the desired product, white crystals. mp 142-3 ° C. Yield 99.6% ¹ H-NMR spectrum (D ₂ O) δ _ppm ; 2.85
(S, 3H), 4.29 (s, 2H), 4.56 to 4.80
(M, 12H), 7.74 (d, 1H, J = 8.4Hz),
8.05 (dd, 1H, J = 2.5, 8.4Hz), 8.55
(D, 1H, J = 2.5Hz)

Example 13 2-Chloro-5- (aminomethyl) pyridine

[Chemical 29] 2-chloro-5- (hydroxymethyl) pyridine 29.6
g (purity 97.0%, 0.2 mol), 200 ml of 1,2-dichloroethane and 25.2 g of methanesulfonyl chloride (0.22)
mol) was added and the mixture was cooled to 10 ° C., and while maintaining the same temperature with stirring, 24.3 g (0.24 mol) of triethylamine was added to 30
The mixture was added dropwise over a period of 20 minutes and the reaction was continued for 20 minutes. After the reaction
67 ml of water was added to dissolve the precipitated triethylamine hydrochloride, and the mixture was separated, containing 1,2-chloro-5- (hydroxymethyl) pyridine methanesulfonate.
A dichloroethane solution was obtained. Then add 1,2 to this solution
After diluting with 100 ml of dichloroethane, 30.8 g (0.22 mol) of hexamethylenetetramine was added, and the mixture was reacted at 50 ° C. for 5 hours with stirring. After reaction, cool to room temperature,
Water (60 ml) and 35% hydrochloric acid (93.9 g, 0.9 mol) were added, and the precipitated crystals were extracted by dissolution and extraction. 200 ml of methanol was added to the obtained aqueous layer, and the mixture was refluxed for 1 hour and a half with stirring, and then dimethylformal produced by the reaction and excess methanol were slowly distilled off until the internal temperature reached 100 ° C.
After that, it is cooled to 50 ° C., 30 ml of water and 100 of chloroform.
ml was added, the mixture was further cooled to room temperature, and 90.0 g (1.10 mol) of 49% aqueous caustic soda solution was added to make the mixture alkaline, followed by liquid separation. The aqueous layer was extracted well with chloroform, and the extract was combined with the previous chloroform layer and concentrated to obtain 27.0 g of the target oil. As a result of analysis by high performance liquid chromatography,
The purity was 97.6%. Yield 92.5%

[0024]

INDUSTRIAL APPLICABILITY The process for producing the compound (IV) according to the present invention is easier than the conventional process by using the compound (I), which is not irritating to eyes and skin, as a starting material and under safe and mild reaction conditions. This is an industrially advantageous production method, since the desired product can be obtained in a high yield by the reaction operation. Compound (IV) obtained by the production method of the present invention is, for example, WO 91 /
The synthetic method shown in 04965 can be used for producing the insecticide shown in the publication.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Takashi Okabe 950 Fujisawa, Nakago-mura, Nakakubiki-gun, Niigata Prefecture Nihongi Plant, Soda Co., Ltd.

Claims (4)

[Claims] 1. A compound represented by the general formula (III): (In the formula, R represents an optionally substituted phenyl group or an alkyl group.), A hexamethylene tetraammonium salt is hydrolyzed with a mineral acid in a water solvent in the presence of a lower alcohol, and a by-product is produced in the reaction. Formaldehyde with lower alcohol is removed by distilling it out of the reaction system. A method for producing 2-chloro-5- (aminomethyl) pyridine represented by: 2. Formula (IV): In the method for producing 2-chloro-5- (aminomethyl) pyridine represented by: 1) a compound represented by the formula: 2-chloro-5- (hydroxymethyl) pyridine of
A general formula in which caustic alkali is used as a deoxidizing agent in the presence of a quaternary ammonium salt in water and a poorly water-soluble organic solvent to react with arylsulfonyl chloride or alkylsulfonyl chloride A step of producing a sulfonic acid ester represented by the formula (wherein R has the same meaning as described above), 2) a general formula for reacting the compound (II) with hexamethylenetetramine in water or an organic solvent. [Chemical 6] (Wherein R has the same meaning as described above), the step of producing a hexamethylenetetraammonium salt, 3) the compound (III) is treated with a mineral acid in a water solvent in the presence of a lower alcohol. A step for producing the compound (IV), which comprises hydrolyzing and removing formaldehyde by-produced in the reaction as a formal with a lower alcohol by distilling it out of the reaction system. The above-mentioned compound comprising three steps (IV)
Manufacturing method. 3. A compound represented by the general formula (III): (In the formula, R has the same meaning as described above). 4. A compound represented by the general formula (II ′): (In the formula, R ′ represents an optionally substituted phenyl group).