JPS5943934B2 - Separation and purification method for monochlorinated side chains of naphthalene derivatives - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for separating and purifying side chain monochlorinated products of naphthalene derivatives useful as intermediates in the production of pharmaceuticals, agricultural chemicals, etc. More specifically, the present invention relates to a method for separating and purifying side chain monochlorinated products of naphthalene derivatives, which are useful as intermediates in the production of pharmaceuticals, agricultural chemicals, etc. The present invention relates to a method for separating and purifying only monochlorinated side chains of naphthalene derivatives from chlorinated side chains of derivatives with high yield and high purity.

Naphthalene compliance @11 Lead monochloride is the corresponding naphthalene U? νノ? Ri,! How old is it? Although it is produced by chemical treatment,
At this time, as by-products, di- and trichlorinated products of the naphthalene derivative side chain and nuclear chlorinated products having boiling points similar to those of the monochlorinated product of the naphthalene derivative side chain are produced.

Conventionally, separation and purification of monochlorinated side chains of naphthalene derivatives from crude chlorinated side chains of naphthalene derivatives containing these by-products has been carried out by distillation or rectification.

However, separation and purification using distillation or rectification is extremely difficult due to the small boiling point difference between the side chain monochlorinated product of the naphthalene derivative and the above-mentioned by-product, and these methods cannot completely separate and purify the product. Since this is not easy, the side chain monochlorinated naphthalene derivatives obtained had low purity and low yield.

For example, in the crude side chain chlorinated product of 2-methylnaphthalene, 2-chloromethylnaphthalene (side chain monochlorinated product, boiling point 168-169°C/20m7nHg) and 1-
Chloro-2-methylnaphthalene (nuclear chloride, boiling point 16
It is impossible to separate and purify 2-chloromethylnaphthalene by distillation and rectification because its boiling point is almost the same as that of 2-chloromethylnaphthalene (8° C./21 mmHg). The present inventors aimed to produce high-purity monochlorinated side chains of naphthalene derivatives by chlorinating the side chains of naphthalene derivatives. As a result of various studies on methods for separating and purifying monochlorinated products, we found that if a chlorinated side chain of a crude naphthalene derivative is reacted with an aliphatic secondary amine, only the monochlorinated product of the side chain of the naphthalene derivative reacts, resulting in a tertiary product. Amine derivatives can be generated and separated from naphthalene derivative side chain chlorinated by-products such as naphthalene derivative side chain di- and trichlorinated products and chlorinated products, and then separated into tertiary amine derivatives of naphthalene derivative side chain monochlorinated products. The present invention was completed based on the discovery that monochlorinated side chains of naphthalene derivatives can be obtained in high yield by reacting acid chlorides.

That is, the present invention is based on the general formula A-CH3 (1) (wherein A represents [''[~='', and Y represents a hydrogen atom or a halogen atom].

) is produced by chlorinating the side chain of a naphthalene derivative represented by the general formula (wherein A has the same meaning as above).

) In a method for separating and purifying a side chain monochlorinated product of a naphthalene derivative represented by the general formula R and w are the same or different lower alkyl groups.

) is reacted with an aliphatic secondary amine represented by the general formula (
In the formula R. R' and A have the same meanings as above.

) The tertiary amine derivative represented by the general formula () obtained in the first step is combined with the tertiary amine derivative represented by the general formula (where B is a lower alkoxy group or zo indicates a phenyl group represented by -.

z represents a halogen atom, lower alkyl group, lower alkoxy group, nitro group or cyano group, n represents 011, 2 or 3, and when n is 2 or 3, even if Z is a different group from each other, good.

) is reacted with the acid chloride represented by the above general formula ().
Separating and purifying the naphthalene derivative side chain monochlorinated product represented by the above general formula () from the crude naphthalene derivative side chain chlorinated product, which is characterized by a second step of separating the naphthalene derivative side chain monochlorinated product represented by It's a method.

The present invention is illustrated as follows.

The first step of the present invention is to react a chlorinated side chain of a crude naphthalene derivative with an aliphatic secondary amine represented by the general formula () in a solvent-free or organic solvent to obtain a tertiary amine represented by the general formula (). An amine derivative is obtained, and then an acid is added to obtain an acid salt of a tertiary amine derivative, and an aqueous layer containing this and a chlorinated side chain of a naphthalene derivative such as di- and trichlorinated products and nuclear chlorinated products of the naphthalene derivative side chain are separated. After separating the organic layer containing living organisms and neutralizing the resulting aqueous layer with an alkaline aqueous solution, extraction is performed with a water-insoluble organic solvent, and then the solvent is distilled off to form a compound represented by the general formula (). It consists of isolating a tertiary amine derivative.

The crude naphthalene derivative side chain chlorinated product used in the method of the present invention is a naphthalene derivative represented by general formula (1),
For example, side chain chlorination of naphthalene, methylnaphthalene, chloro-methylnaphthalene, or promomethylnaphthalene, etc. In addition to side chain monochlorinated products, side chain di- and totrichlorinated products and side chain chlorinated products such as nuclear chlorinated products are used. Contains chlorinated by-products. Further, aliphatic secondary amines represented by the general formula () used in the method of the present invention include, for example, dimethylamine, diethylamine, dipropylamine, dibutylamine, ethylmethylamine, ethylpropylamine, butylmethylamine, butylethylamine, These include butylpropylamine and methylpropylamine.

The amount of aliphatic secondary amine to be used is 1 mol or more per 1 mol of the monochlorinated side chain of the naphthalene derivative contained in the chlorinated side chain of the crude naphthalene derivative, and no problem will occur in the reaction no matter what amount is used. but preferably 1.0 to 1.1
It is appropriate to use moles.

The reaction between the side chain chlorinated product of the crude naphthalene derivative and the aliphatic secondary amine is carried out by mixing the two and stirring with or without heating, in the absence of a solvent or in an organic solvent.

Although the reaction proceeds satisfactorily even in the absence of a solvent, it is usually preferable to carry out the reaction in a water-insoluble organic solvent. Examples of water-insoluble organic solvents include aromatic hydrocarbons such as benzene and toluene-xylene, halogen-substituted aromatic hydrocarbons such as chlorobenzene and chlorotoluene, aliphatic hydrocarbons such as n-hexane and cyclohexane, and chloroforhedichloromethane. Examples include halogen-substituted aliphatic hydrocarbons such as dichloroethane, dichloropropane, tricrene, and carbon tetrachloride, and ethers such as diethyl ether and diisopropyl ether. The reaction temperature is -20°C to 150°C, preferably 0°C to
80°C is suitable.

The reaction time is suitably 1 hour to 8 hours, preferably 2 hours to 5 hours.

In this reaction between the chlorinated side chain of the crude naphthalene derivative and the aliphatic secondary amine, only the monochlorinated side chain of the chlorinated side chain of the crude naphthalene derivative reacts with the aliphatic secondary amine, resulting in the general formula (). producing a tertiary amine derivative represented by
Naphthalene derivative side chain chlorination by-products such as side chain di- and trichlorides and nuclear chlorides do not react.

After the reaction is completed, the generated tertiary amine derivative is separated by adding an acid to the resulting reaction mixture to make it acidic and separate the mixture.

Tertiary amine derivatives are dissolved in the aqueous layer as acid salts, and side chain chlorinated by-products of naphthalene derivatives, such as di- and trichlorinated naphthalene derivatives and nuclear chlorides, are dissolved in the organic layer. By separating the layers, the tertiary amine derivative and the side chain chlorinated by-product of the naphthalene derivative can be easily separated. Examples of acids used here include mineral acids such as hydrochloric acid, sulfuric acid, and nitric acid, and organic acids such as formic acid, acetic acid, and propionic acid, and these are preferably used in the form of an aqueous solution.

The amount of acid used is suitably 1 mol or more, preferably 1.05 to 1.15 mol, per 1 mol of aliphatic secondary amine. The aqueous layer obtained by separation is neutralized by adding an alkaline aqueous solution, and then a water-insoluble organic solvent is added to perform solvent extraction.
The tertiary amine derivative represented by the general formula () can then be isolated by distilling off the organic solvent from the obtained organic solvent solution.

The alkaline aqueous solution used here is potassium hydroxide,
Examples include aqueous solutions of sodium hydroxide, calcium hydroxide, potassium carbonate, sodium carbonate, and the like. In addition, water-insoluble organic solvents used here include benzene, toluene,
Aromatic hydrocarbons such as xylene, halogen-substituted aromatic hydrocarbons such as chlorobenzene and chlorotoluene, aliphatic hydrocarbons such as n-hexane and cyclohexane, and chloroform, dichloromethane, dichloroethane, dichloropropane, trichlene, and carbon tetrachloride. and ethers such as diethyl ether and diisopropyl ether.

The second step of the present invention is produced by reacting the tertiary amine derivative represented by the general formula () obtained in the first step with the acid chloride represented by the general formula (V) in a solvent-free or organic solvent. The method consists of isolating a side chain monochlorinated naphthalene derivative represented by the general formula ().

The acid chloride represented by the general formula () used in the method of the present invention includes a general formula group.

) chloroformic acid ester, or general formula (In the formula, Bi is phenyl represented by D. Z and n have the same meanings as above.

) is an aromatic acid chloride represented by Here, as the chloroformic acid ester represented by the general formula (V-), R/
' has a lower alkyl group such as a methyl group, an ethyl group, a propyl group, or a butyl group.

In addition, in the aromatic acid chloride represented by the general formula (V-), Z is a halogen atom such as fluorine, chlorine, bromine, or iodine, a lower alkyl group such as methyl group, ethyl group, propyl group, or butyl group, or methoxy groups, lower alkoxy groups such as ethoxy groups, propoxy groups and butoxy groups, nitro groups or cyano groups, and when n is O, 1, 2 or 3 and n is 2 or 3, they are different from each other. It may also be a group. When a chloroformic acid ester represented by the general formula (-T) is used as the acid chloride represented by the general formula (V), a tertiary amine represented by the general formula () is prepared in an organic solvent without a catalyst or in the presence of a catalyst. The derivative and chloroformic acid ester are reacted to form a naphthalene derivative side chain monochlorinated product represented by the general formula () and a carbamate ester represented by the general formula () (B=B″0-
) is obtained, an acid is added to this to hydrolyze the carbamate ester into an aliphatic secondary amine represented by the general formula (), alcohol and carbon dioxide gas, and then by conventional operations such as distillation. The desired naphthalene derivative side chain monochlorinated product can be separated and purified. The reaction between the tertiary amine derivative and the chloroformic acid ester is carried out by mixing the two in an organic solvent without a catalyst or in the presence of an acid catalyst, and stirring the mixture with or without heating.

The amount of chloroformic acid ester to be used is preferably 1 mole per mole of the tertiary amine derivative, but even if it is used in excess of 1 mole, there will be no problem with the reaction. Examples of organic solvents include aromatic hydrocarbons such as benzene, toluene, and xylene, halogen-substituted aromatic hydrocarbons such as chlorobenzene and chlorotoluene, aliphatic hydrocarbons such as n-hexane and cyclohexane, and chloroform, dichloromethane, dichloroethane, and dichloromethane. Chloropropane, trichlene, carbon tetrachloride, etc.
-Rogge 7-substituted aliphatic hydrocarbons, ethers such as diethyl ether, diisopropyl ether, etc. The reaction temperature is -3°C to 150°C, preferably 0°C to 120°C.
°C is appropriate.

Although the reaction proceeds satisfactorily without a catalyst, the reaction can be accelerated and the reaction time can be shortened by using an acid catalyst or a zinc catalyst. As acid catalysts, mineral acids such as hydrochloric acid, sulfuric acid, phosphoric acid, or formic acid,
Organic acids such as acetic acid and propionic acid are suitable, and the amount of this acid catalyst used is 0.00 per mole of tertiary amine derivative.
01 mole to 0.5 mole, preferably 0.001 mole to 0.01 mole.
2 moles is suitable. In addition, zinc chloride,
Zinc compounds such as zinc bromide, zinc oxide, zinc sulfide, zinc hydroxide, zinc carbonate, zinc sulfate, zinc nitrate, zinc phosphate, zinc acetate, zinc benbrozoate, etc. are suitable, and the amount used is tertiary. A suitable amount is 0.02 mol to 0.1 mol, preferably 0.04 to 0.06 mol, per mol of the amine derivative. Carbamate ester (B-R
Hydrolysis of 1'O-) is carried out by adding an aqueous mineral acid solution such as hydrochloric acid, sulfuric acid, or nitric acid, or formic acid, acetic acid, or propionic acid to a reaction mixture containing a monochlorinated side chain of the naphthalene derivative represented by the general formula () and a carbamate ester. The reaction is carried out at 0°C to 100°C, preferably 2°C to 80°C.

Carbon dioxide gas is generated with the start of the hydrolysis reaction. After the hydrolysis reaction is completed, the reaction system contains an organic layer containing a monochlorinated side chain of a naphthalene derivative, an alcohol produced by hydrolysis of a carbamate ester, and water containing a mineral acid or an organic acid salt of an aliphatic secondary amine. By separating the two layers and separating both layers, the side chain monochlorinated product of the naphthalene derivative can be separated together with the organic solvent, and then the desired naphthalene can be separated by conventional operations such as distillation. Derivative side chain monochlorinated products can be easily separated and purified with good yield. On the other hand, the remaining aqueous layer is neutralized, and the aliphatic secondary amine produced by hydrolysis can be isolated by performing operations such as extraction and distillation. In addition, when using an aromatic acid chloride represented by the general formula (V-) as the acid chloride represented by the general formula (V), the general formula A tertiary amine derivative represented by () is reacted with an aromatic chloride to obtain a reaction mixture containing a naphthalene derivative side chain monochlorinated product represented by general formula () and an acid amide represented by general formula (). The desired side chain monochlorinated naphthalene derivative can be separated and purified by operations such as distillation using conventional methods.

The reaction between the tertiary amine derivative and the aromatic acid chloride is carried out by mixing the two in the absence of a catalyst or in the presence of a catalyst in a solvent-free or organic solvent, and heating and stirring the mixture. The aromatic acid chloride may be used in an amount of 1 mole or more per mole of the tertiary amine derivative without any problem in the reaction, but preferably 1 mole is appropriate. The reaction is usually carried out without a solvent, but the reaction can be carried out in an organic solvent without any problem. Benzene as an organic solvent,
Examples include aromatic hydrocarbons such as toluene and xylene, and halogen-substituted aromatic hydrocarbons such as chlorobenzene, dichlorobenzene, chlorotoluene, and dichlorotoluene. The reaction temperature is 30°C to 300°C, preferably 70°C to
250°C is suitable.

Although the reaction proceeds satisfactorily without a catalyst, the use of a catalyst accelerates the reaction and significantly shortens the reaction time. Suitable catalysts include zinc compounds such as zinc chloride, zinc bromide, zinc oxide, zinc sulfide, zinc hydroxide, zinc carbonate, zinc sulfate, zinc nitrate, zinc phosphate, zinc acetate, and zinc benzoate. is 0.02 mol to 0.02 mol to 1 mol of tertiary amine derivative.
1 mol, preferably 0.04 mol to 0.06 mol, is suitable. The reaction mixture obtained by reacting a tertiary amine derivative with an aromatic acid chloride can be directly subjected to a conventional operation such as distillation to easily separate and purify the desired naphthalene derivative side chain monochlorinated product with good yield.

Further, the aromatic acid amide can be isolated from the residue obtained by separating and purifying the side chain monochlorinated product of the naphthalene derivative by a conventional operation such as high vacuum distillation. Next, the features and advantages of the method of the present invention will be explained.

The feature of the method of the present invention is to obtain monochlorinated naphthalene derivative side chains from crude naphthalene derivative side chain chlorinated products, including mono-, di- and tri-chlorinated products and nuclear chlorinated products obtained by side-chain chlorination of naphthalene derivatives. It can be easily separated and purified with high yield and high purity.
Advantages arise in the process of producing side chain monochlorinated naphthalene derivatives useful as intermediates in the production of agricultural chemicals, medicines, etc. Side chain monochlorinated naphthalene derivatives are produced by side chain chlorination of the corresponding naphthalene derivatives, and in this case, side chain di- and trichlorinated naphthalene derivatives having a boiling point similar to that of the side chain monochlorinated naphthalene derivatives are produced as by-products. and nuclear chlorides are produced.

Conventionally, separation and purification of monochlorinated side chains of naphthalene derivatives from crude chlorinated side chains of naphthalene derivatives containing these by-products has been carried out by distillation or rectification. However, separation and purification using distillation or rectification is extremely difficult due to the small boiling point difference between the side chain monochlorinated product of the naphthalene derivative and the above-mentioned by-product, and these methods cannot completely separate and purify the product. Since this is not easy, the side chain monochlorinated naphthalene derivatives obtained had low purity and low yield. However, if the method of the present invention is carried out here, the side chain monochlorinated product of the naphthalene derivative can be easily separated and purified from the above-mentioned by-products from the crude naphthalene derivative side chain chlorinated product obtained by side chain chlorination of the naphthalene derivative. purity,
This gives rise to the advantage of being obtained in high yields.

When carrying out the method of the present invention using a chloroformic acid ester represented by the general formula (V-1) as the acid chloride represented by the general formula (V), in addition to the naphthalene derivative side chain monochlorinated product, the general It has the advantage that the aliphatic secondary amine represented by the formula () can be recovered in high yield and can be reused, and when carried out using the aromatic acid chloride represented by the general formula (-), In addition to side chain monochlorinated products of naphthalene derivatives, this method has the advantage of being able to isolate and produce aromatic acid amides, which are useful as intermediates in the production of agricultural chemicals, medicines, etc., in high yields.

The present invention will be explained in more detail with reference to Examples below.

Example 1 (1) Crude 2-methylnaphthalene with a purity of 70.6% obtained by side chain chlorination of 2-methylnaphthalene in a 1,e four-bottle flask equipped with a thermometer, condenser, dropping load and stirrer.
250 tons of chloromethylnaphthalene and 300 tons of benzene
ml of diethylamine and 75.07 g of diethylamine under stirring.
(1.03 mol) was added dropwise, and the mixture was heated and reacted at 50'C for 4 hours.

Then, concentrated hydrochloric acid 1207 (1.1
5 mol) was added thereto and reacted for 30 minutes at room temperature.

After the reaction was completed, the obtained reaction solution was transferred to a 21-separation load and separated. The obtained aqueous layer was neutralized with 0% caustic soda aqueous solution, and ethyl ether was added to give N-N-diethyl-2
- Naphthylmethylamine is extracted, and the resulting ethyl ether extracted solution is concentrated and the ethyl ether is distilled off to remove N-N-diethyl-2-naphthylmethylamine 211.
I got 07. The resulting N-N-diethyl 2-naphthylmethylamine was analyzed by gas chromatography and found to have a purity of 99.9%, with a pure yield based on 2-chloromethylnaphthalene in the crude 2-chloromethylnaphthalene. The rate was 98.8%. (2) 1 similar to (1) above
1? The purity obtained in (1) above is 99.
9% N-N-diethyl-2-naphthylmethylamine 2
11.07 (0.988 mol) and benzene 200m
To this was added methyl chloroformate 1 at room temperature under stirring.

After adding 000 mol dropwise, the mixture was heated and reacted at 50° C. for 6 hours.

Next, 30% aqueous sulfuric acid solution 1207 was added to the obtained reaction solution at room temperature with stirring, and the mixture was heated and reacted at 50° C. until the generation of carbon dioxide gas was completed for hydrolysis. After the hydrolysis reaction is completed,
After the reaction solution was cooled to room temperature, it was transferred to an 11-minute liquid load and separated.

The obtained organic layer was washed twice with 100 ml of water, then dried over anhydrous sodium sulfate, and then benzene was distilled off under reduced pressure, and further vacuum distillation was performed to obtain a boiling point of 168-169°C/20°C.
m7!1 Hg of 2-chloromethylnaphthalene 133.7
I got y. Analysis of this by gas chromatography revealed that the purity was 99.7%, and the yield (recovery rate) based on P-chlorobenzyl chloride in the crude P-chlorobenzyl chloride was 75.5%. On the other hand, after the hydrolysis reaction, the aqueous layer obtained by separating the reaction solution was neutralized by adding a 10% aqueous solution of caustic soda, and then ethyl ether was added to extract diethylamine.

The ethyl ether extraction solution was washed twice with 100 ml of water,
Then, after drying over anhydrous sodium sulfate, ethyl ether was distilled off, and further distillation was performed to reduce the boiling point to 52-55°C/7.
Diethylamine 53.37 at 60 mmHg (recovery 71
．． 0%) was obtained. Example 2 N-N diethyl-2-naphthylmethylamine 211.07 (0.9
88 mol), 200 ml of benzene, and 17 ml of concentrated sulfuric acid were added dropwise to a mixed solution of 1.000 mol of methyl chloroformate at room temperature while stirring, and then heated and reacted at 50° C. for 4 hours.

After the reaction was completed, the same procedure as in Example 1 was carried out to obtain 136.57% of 2-chloromethylnaphthalene and 52.57% of diethylamine.
77 (recovery rate 70.2%) was obtained.

The resulting 2-chloromethylnaphthalene was analyzed by gas chromatography and found to have a purity of 99.8%.
The yield (recovery rate) based on 2-chloromethylnaphthalene in the crude 2-methylnaphthalene side chain monochlorinated product is 77.
．． It was 2%. Example 3 (1) In the same manner as in Example 1 and Example 2, crude 1-chloro-2-chloromethylnaphthalene containing 1.0 mol of 1-chloro-2-chloromethylnaphthalene and 1.0 mol of diethylamine were prepared. was reacted in 300 ml of chlorotol to obtain a tertiary amine derivative.

(2) Perform the same operation as in Example 1 and Example 2 to
The tertiary amine derivative obtained in step 1) and 1.0 mol of chloroformic acid ester are reacted in 200 ml of benzene by adding concentrated hydrochloric acid, and the resulting reaction solution is hydrolyzed to obtain the desired 1-chloro- 2-chloromethylnaphthalene was obtained.

The obtained results are shown in Tables 1 and 2.

In addition, the purity in (1) and (2) is the result of analysis by gas chromatography, and the pure yield is crude 1-chloro-2.
-Yield based on pure 1-chloro-2-chloromethylnaphthalene in chloromethylnaphthalene.

Example 4 (1) 211.0 t of N-N-diethyl-2-naphthylmethylamine was obtained from crude 2chloromethylnaphthalene and diethylamine in the same manner as in the method (1) of Example 1 above.

The purity was 99.9%, and the pure yield was 98.8%. (2) 500m1 equipped with the same equipment as in (1) above
N-N-diethyl-2-naphthylmethylamine 211,07 (0.98
8 mol) and 0.998 mol of O-toluic acid chloride were charged, heated under stirring, and reacted at 180°C to 200°C for 20 hours.

After the reaction is complete, the resulting reaction solution is distilled under reduced pressure to a boiling point of 168°C.
139.27 of 2-chloromethylnaphthalene was obtained at ˜169° C./20 mmHg.

Analysis of this by gas chromatography revealed that the purity was 99.8% and the yield (recovery rate) based on 2-chloromethylnaphthalene in crude 2-chloromethylnaphthalene was 78.7%. Example 5 (1) Crude 1-chloro-2-chloromethylnaphthalene (purity 70.4%) 3007 (purity 1-chloro-2-chloromethylnaphthalene content: 1 mol) in the same manner as in (1) of Example 3. ) and diethylamine 75.07 (1.03 mol) with a purity of 99.
245.87 of 8% N-N diethyl-1-chloro-2-naphthylmethylamine was obtained.

Pure yield 98.8% o (2) N-N obtained in (1) above
-diethyl-1-kuro-2-naphthylamine 245.
87 (0.988 mol) and zinc chloride 6.87 (0.988 mol).
A mixed solution of 0.05 mol) was heated with stirring to give a
Benzoic acid chloride 138.97 (
0.988 mol) was added dropwise to react. The reaction proceeds as the benzoyl chloride is added dropwise, and is completed at the end of the dropwise addition. After the reaction is complete, the resulting reaction solution is distilled under reduced pressure to a boiling point of 173.
192.6y of 1-chloro2-chloromethylnaphthalene with C/20 mmHg was obtained.

The resulting 1-chloro-2-chloro-methylnaphthalene was analyzed by gas chromatography and found to have a purity of 99.8.
% and the yield based on 1-chloro-2-methylnaphthalene in crude 1-chloro-2-chloro-methylnaphthalene (
The recovery rate) was 91.0%. Also, 1-chloro-2
The distillation residue of -chloromethylnaphthalene was further distilled under high vacuum to obtain N-N-diethylbenzoic acid amide with a boiling point of 100° C./1 mmHg in a yield of 90.5%.

Claims (1)

[Claims] 1 General formula A-CH_3......(I) (In the formula, A represents ▲a mathematical formula, a chemical formula, a table, etc.▼, and Y
represents a hydrogen atom or a halogen atom. ) The general formula A-CH_2Cl produced by side chain chlorination of the naphthalene derivative represented by (II) (wherein A has the same meaning as above) In the separation and purification method, [1] The crude naphthalene derivative side chain chlorinated product obtained by side chain chlorination of the naphthalene derivative represented by the above general formula (I) has the general formula ▲ mathematical formula, chemical formula, table, etc. ▼... ...(III) (in the formula R and R'
represent lower alkyl groups that are the same or different from each other. ) is reacted with the aliphatic secondary amine represented by the general formula ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼……(IV) (R in the formula
, R' and A have the same meanings as above. ) The first step of producing and isolating the tertiary amine derivative represented by [2] the tertiary amine derivative represented by the above general formula (IV) obtained in the first step and the general formula ▲ mathematical formula, chemical formula, There are tables, etc.▼......(V) (In the formula, B represents a lower alkoxy group or a phenyl group represented by ▲There are mathematical formulas, chemical formulas, tables, etc.▼.Z is a halogen atom, a lower alkyl group, a lower alkoxy group , represents a nitro group or a cyano group, n represents 0, 1, 2 or 3, and when n is 2 or 3, Z may be mutually different groups. and the above general formula (I
A second step of separating the monochlorinated side chain of the naphthalene derivative represented by I) from the chlorinated side chain of the crude naphthalene derivative represented by general formula (II) above. A method of separation and purification. 2 General formula A-CH_3……(I) (In the formula, A indicates ▲There are mathematical formulas, chemical formulas, tables, etc.▼,
Y represents a hydrogen atom or a halogen atom. ) The general formula A-CH_2Cl produced by side chain chlorination of the naphthalene derivative represented by (II) (wherein A has the same meaning as above) In the separation and purification method, [1] The crude naphthalene derivative side chain chlorinated product obtained by side chain chlorination of the naphthalene derivative represented by the above general formula (I) has the general formula ▲ mathematical formula, chemical formula, table, etc. ▼... ...(III) (in the formula R and R'
represent lower alkyl groups that are the same or different from each other. ) is reacted with the aliphatic secondary amine represented by the general formula ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼……(IV) (R in the formula
, R' and A have the same meanings as above. ) The first step of producing and isolating the tertiary amine derivative represented by formula (IV) [2] In the presence of an acid catalyst, the tertiary amine derivative represented by the general formula (IV) obtained in the first step and the general Formulas▲There are mathematical formulas, chemical formulas, tables, etc.▼……(V- I
) (in the formula, B' represents a lower alkoxy group) to react the acid chloride represented by the above general formula (I
A second step of separating the monochlorinated side chain of the naphthalene derivative represented by I) from the chlorinated side chain of the crude naphthalene derivative represented by general formula (II) above. A method of separation and purification. 3 General formula A-CH3……(I) (In the formula, A indicates ▲There are mathematical formulas, chemical formulas, tables, etc.▼,
Y represents a hydrogen atom or a halogen atom. ) The general formula A-CH_2Cl produced by side chain chlorination of the naphthalene derivative represented by (II) (wherein A has the same meaning as above) In the separation and purification method, [1] The crude naphthalene derivative side chain chlorinated product obtained by side chain chlorination of the naphthalene derivative represented by the above general formula (I) has the general formula ▲ mathematical formula, chemical formula, table, etc. ▼... ...(III) (in the formula R and R'
represent lower alkyl groups that are the same or different from each other. ) is reacted with the aliphatic secondary amine represented by the general formula ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼……(IV) (R in the formula
, R' and A have the same meanings as above. ) The first step of producing and isolating the tertiary amine derivative represented by formula (IV) [2] In the presence of a zinc catalyst, the tertiary amine derivative represented by the general formula (IV) obtained in the first step and the general Formulas▲There are mathematical formulas, chemical formulas, tables, etc.▼……(V-I
I) (In the formula, B″ represents a phenyl group represented by ▲There are mathematical formulas, chemical formulas, tables, etc.▼, Z represents a halogen atom, lower alkyl group, lower alkoxy group, nitro group, or cyano group, and n represents 0 , 1, 2 or 3, and when n is 2 or 3, Z may be a mutually different group.
The side chain monochlorinated product of the naphthalene derivative represented by the above general formula (II), which consists of a second step of separating the side chain monochlorinated product of the naphthalene derivative represented by I), consisting of the chlorinated product of the crude naphthalene derivative side chain. A method of separating and purifying.