JPH01287058A - Production of 2-alkyl-3-acyloxy-1,4-naphthoquinone - Google Patents

Abstract

PURPOSE:To obtain a compound useful as an agricultural chemical in high purity and yield from an inexpensive raw material by deaminating a 2-(1- alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone, hydrogenating, oxidizing and acyloxylating the resultant product. CONSTITUTION:A 2-(1-alkylaminoalkyl)-3-hydroxy-1, 4-naphthoquinone is ther- mally decomposed and deaminated in the presence of an acid. The resultant product is then hydrogenated at 20-100 deg.C using a hydrogenation catalyst (e.g. Pd-C) to provide a 2-alkyl-1,3,4-trihydroxynaphthalene, which is subsequently oxidized with an oxidizing agent (e.g. air) at 20-100 deg.C to afford a 2-alkyl-3- hydroxy-1,4-naphthoquinone. The resultant compound is then acyloxylated in the presence of a base (e.g. p-toluenesulfonic acid) using an acid anhydride or halide to provide the aimed substance.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a method for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone.

2-Alkyl-3-acyloxy-1,4-naphthoquinone is known as a compound having insecticidal activity against mites, aphids, etc.
No. 0, No. 52-48648, etc.), its intermediate 2-(l-alkenyl)-3-hydroxy-1,
2-Alkyl-3 of 4-naphthoquinone and its hydride
-Hydroxy-1,4-naphthoquinone is also useful as medical straw, veterinary medicine, and pesticides.

[Prior art 1 Conventionally known 2-alkyl-3-acyloxy-1,
Methods for producing 4-naphthoquinone include (1) a method using 4-phenylacetoacetate as a starting material (US Pat. No. 2,553,647);

■ Method using α-naphthol as a starting material (Unexamined Japanese Patent Publication No. 52
-48648, U.S. Patent 411047:1), ■
2. A method using 3-dichloro-1,4-naphthoquinone as a starting material 1 and an organometallic compound as a reaction reagent (
(U.S. Pat. No. 4,507,741) and (1) A method in which 2-acyloxy-1,4-naphthoquinone is used as a raw material and an alkyl group is added thereto (Pestic).

Sci,, 17, 511-516 f1986N
etc.

In addition, as a method for producing 2-alkyl-3-hydroxy-1,4-naphthoquinone, which is a compound before acyloxylation of the compound, (1) 2-hydroxy-1,4-naphthoquinone is treated with an alkyl radical generated from diacyl peroxide. Method for adding (J, Amer, CheIl-Sac,
70. 3174+19481) and 2-(l
-Alkenyl)-3~Hydroxy-1,4-naphthoquinone hydrogenation and oxidation method (J, Amer, Che
Il.

Soc, 58.1163-116N1936N are known.

[Problems to be Solved by the Invention] Although 2-alkyl-3-acyloxy-1,4-naphthoquinone has been known to exhibit high performance as an insecticide, particularly as an acaricide, there is currently no problem with it. It has not been commercialized to date. The reason for this is that it is difficult to synthesize this compound, and it has not been possible to find an industrial and simple manufacturing method that can produce it at a cost commensurate with its use.

In other words, among the various manufacturing methods mentioned above, methods ① and ③ require long steps and complicated operations, making them unsuitable as industrial manufacturing methods; Manufacturing costs are too high because the materials are expensive. ■
Methods (1) and (2) have poor yields and are not industrially operated. Therefore, both of these methods are industrially simple and inexpensive methods for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone. It's hard to say.

The object of the present invention is to overcome the above-mentioned drawbacks and to produce an inexpensive 2-alkyl-3-acyloxy-1,4-
The object of the present invention is to provide a method for industrially producing naphthoquinone and its intermediates.

[Means for Solving the Problems j] The present inventors previously reacted 2-hydroxy-1,4-naphthoquinone with an aliphatic aldehyde and a primary amine in an inert organic solvent to obtain 2-( We have developed a method for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone, which is suitable as a raw material for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone. The present invention was achieved by discovering that intermediates in the manufacturing process are also useful.

That is, the present invention subjects 2-+1-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone to a deamination step to obtain 2-11-alkenyl)-3-hydroxy-1,4-naphthoquinone. Bond, 2-alkyl-! , 3,4-trihydroxynaphthalene, and then this 2-alkyl-1,3,4-1-
Rehydroxynaphthalene was subjected to an oxidation step to obtain 2
- A method for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone, which is characterized by subjecting alkyl-3-hydroxy-1,4-naphthoquinone to an acyloxylation step, and does not use expensive raw materials. , 2-alkyl-3-acyloxy-1,4 can be produced industrially easily, with high yield, and at low cost.
- Naphthoquinone can be produced.

[Detailed Description of the Invention] 凰■1 The 2-(l-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone used as the starting material of the present invention is a non-2-hydroxy-1,4-naphthoquinone. Obtained by reaction with aliphatic aldehydes and primary amines in active organic solvents.

The aldehyde used is a saturated aliphatic aldehyde having 5 to 20 carbon atoms, preferably 8 to 14 carbon atoms, and having at least one hydrogen at the α position, and from a practical standpoint, a straight chain aliphatic aldehyde is usually used. However, the alkyl group may be branched, cyclically alkylated, or have an inert substituent.

Examples of such saturated aliphatic aldehydes include valeraldehyde and isovaleraldehyde.

Piparaldehyde, capronaldehyde, heptylaldehyde, caprylaldehyde, pelargonaldehyde, capricaldehyde, undecylaldehyde, dodecylaldehyde (lauric aldehyde), tridecylaldehyde, myristicaldehyde, pentadecylaldehyde, margaric aldehyde, stearyl aldehyde, etc. Can be mentioned.

The amount of the aldehyde used is based on the raw material 2-hydroxy-1,
Generally more than an equimolar amount of 4-naphthoquinone, usually 1
．． The amount is 0 to 2.0 times by mole, preferably 1.1 to 1.4 times by mole. If it is less than 1 times by mole, the yield will decrease, and if it is too much, it is not economical.

The amines used in this reaction are limited to primary amines. The amine may be gaseous or liquid, and
Examples of the primary amine, which may be an aqueous solution, include alkylamines such as monomethylamine, ethylamine, n-propylamine, i-propylamine, n-butylamine, and cyclobutylamine, or cycloalkylamines such as cyclohexylamine.

The amount of the primary amine to be used is generally 0.8 to 1.5 moles, preferably 0.9 to 1.1 moles, and more preferably equimolar to 2-hydroxy-1,4 naphthoquinone. It's double. Whether the amount of amine used is large or small, the yield of the target compound decreases.

Examples of inert organic solvents used in this reaction include alcohols (e.g. methanol, ethanol, propatool), cellosolves (e.g. methyl cellosolve), ethers (e.g. dioxane, T)IF), diols (e.g. ethylene glycol, propylene glycol). , ketones (e.g. MIBK), fatty acid esters (e.g. ethyl acetate, butyl acetate), aromatic hydrocarbons (e.g. benzene, toluene, xylene), halogenated hydrocarbons (e.g. trichloroethane, tetrachloroethane), etc. When a substance is easily isolated as a crystal, alcohol bases such as methanol and ethanol are usually convenient.

As for the conditions for this reaction, it is desirable that the reaction temperature is 35°C or lower, preferably 1 to 30°C, particularly preferably 20 to 25°C, and the reaction time is 1 to 5 hours.

The thus obtained 2-(l-alkylaminoalkyl)
-3-Hydroxy-1,4-naphthoquinone does not necessarily need to be isolated, and can be directly subjected to the deamination step as a raw material for the present invention.

Deamination step The raw material 2-(l-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone in the present invention is deaminated to form 2-(l-alkenyl)
The deamination reaction in the present invention capable of obtaining -3-hydroxy-1,4-naphthoquinone is preferably carried out by thermal decomposition in the presence of an acid.

The acid used in the above thermal decomposition reaction may be any acid that can react with the amino group of 2-(l-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone to form a quaternary ammonium salt. Examples include hydrohalic acid such as hydrochloric acid, hydrobromic acid, and hydroiodic acid, or sulfuric acid.

The amount of the above acid to be used is generally at least equimolar to 2-(l-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone, preferably 1.0 to 1.5 times by mole. If the amount used is small, side reactions will occur and the yield will decrease. In addition, if the amount is too large, the reaction will be slow.

As the solvent used in the reaction, the same inert solvent used for producing the raw materials can be used.

The reaction conditions include a reaction temperature of 75°C or higher, preferably 90°C or higher.
The reaction may be carried out at 140° C. at normal pressure, under elevated pressure or under autogenous pressure, and a reaction time of 0.5 to 10 hours is sufficient.

The obtained 2-(1-alkenyl)-3-hydroxy-1
゜4-Naphthoquinone is used in I#fiL for pharmaceuticals, veterinary drugs, a
Although it can be used as a medicine, in the present invention, when it is subjected to the next hydrogenation step, it can be used as it is in the hydrogenation step without being isolated from one reaction solution.

A hydrogenation catalyst is usually used in this hydrogenation process. As a hydrogenation catalyst, palladium carbon catalyst (Pd-C
), platinum catalyst, rhodium carbon catalyst fRh-C1,
Examples include common metal catalysts such as Raney nickel.

The reaction conditions include a reaction temperature of 20 to 100°C, preferably 3°C.
0 to 70°C, and the reaction time varies depending on the type of catalyst and other conditions such as pressure and temperature, but is usually about t-io time. Hydrogen may be supplied either continuously or batchwise under normal pressure or increased pressure.

1 Chemical Engineering 1 In this oxidation step, the reaction solution containing 2-alkyl-1,3,4-trihydroxynaphthalene obtained in the previous step is used after removing the hydrogenation catalyst. -1,3,4-)lyhydroxynaphthalene may be isolated and used. As the solvent in this case, an inert solvent used in the production of raw materials can be used, as in the past.

Air is usually used as the oxidizing agent, but nitrogen may be added to adjust the oxygen concentration for operational reasons.If necessary, peroxides such as hydrogen peroxide or Oxidizing agents such as iron chloride may also be used.

The reaction conditions are 1 reaction temperature of 20 to 100°C, preferably 3
The reaction time varies depending on the amount of oxygen supplied and the efficiency of the reactor, and the end point of the oxidation reaction is preferably determined while observing the amount of oxygen absorbed.

The reaction solution after the oxidation reaction can be used as it is in the next acyloxylation step, but in order to separate by-products, 2-alkyl-3-hydroxy-
Preferably, the 1,4-naphthoquinone is isolated.

Isolation involves condensing the reaction solution in the oxidation step to obtain 2-alkyl-3
-Crystallize hydroxy-1,4-naphthoquinone 1
This can be carried out by evaporating the reaction solution to dryness and washing the obtained solid with a solvent such as alcohol.

The isolated 2-alkyl-3-hydroxy-1,4-naphthoquinone itself is useful in medicine, veterinary medicine, agricultural chemicals, and the like.

For acyloxyhiea siloxylation, use the reaction solution obtained in the previous step as it is, preferably a solution of the 2-alkyl-3-hydroxy-1,4-naphthoquinone isolated in the previous step dissolved in an inert solvent, Generally, using an aliphatic carboxylic anhydride or aliphatic carboxylic acid halide having 2 to 6 carbon atoms in the presence of an acid such as para-toluenesulfonic acid, methanesulfonic acid, or sulfuric acid or a base such as pyridine, piperidine, or triethylamine,
Usual acyloxylation methods (e.g. JP-A-52-4864)
It can be carried out according to the method described in Specification No. 8).

Examples of the aliphatic carboxylic anhydride of the acyloxylating agent include acetic anhydride, propionic anhydride, butyric anhydride, and examples of the aliphatic carboxylic acid halide include acetic acid chloride,
Examples include propionic acid chloride and butyric acid chloride.

The conditions for the acyloxylation reaction are generally 80 to 150°C when an acid anhydride and an acid are used, and 60°C when an acid anhydride or acid halide and a base are used.
The following steps are usually carried out at a temperature of 10 to 50'C.

The production of the 2-alkyl-3-acyloxy-1,4-naphthoquinone of the present invention is generally carried out as follows.

A predetermined amount of 2-hydroxy-1,4-naphthoquinone was added to a predetermined amount of an inert organic solvent, an amine such as a 40 t methylamine aqueous solution was added, and the mixture was heated to a predetermined temperature.

A predetermined amount of aliphatic aldehyde such as n-dodecylaldehyde is added dropwise, and the mixture is stirred for a predetermined period of time to react.

A predetermined amount of acid such as sulfuric acid is added to the obtained reaction solution containing 2-(l-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone, and the temperature in the system is raised to a predetermined temperature. 2-(1-alkenyl)-3- by deamination reaction
Hydroxy-1,4-naphthoquinone is produced.

The obtained 2-(l-alkenyl)-3-hydroxy-1
The reaction solution containing 4-naphthoquinone is cooled to near room temperature, a hydrogenation catalyst such as Pd-C is added, and the system is replaced with hydrogen, then heated to a predetermined temperature and hydrogenated by passing a hydrogen stream.

The catalyst was filtered from the resulting reaction solution, and 2-alkyl-1,
The filtrate containing 3,4-trihydroxynaphthalene is oxidized at a predetermined temperature by passing air diluted with nitrogen, the oxidation reaction solution is cooled, the crystals that crystallize are filtered, and the resulting crystals are washed to obtain 2- The alkyl-3-hydroxy-1,4-naphthoquinone is isolated. By concentrating and cooling the filtrate, further crystals can be crystallized.

This isolated 2-alkyl-3-hydroxy-1,4
- Add naphthoquinone to a solvent such as 0-xylene.

Furthermore, acetic anhydride or the like as an acyloxylating agent and para-toluenesulfonic acid or the like as an acid are added, and the mixture is heated to 100° C. or higher and reacted for a predetermined period of time.

The reaction solution was cooled, acid components and water-soluble components were extracted with an aqueous alkali solution, and the organic layer containing the product was washed and evaporated to dryness to obtain the target product, 2-alkyl-3-acyloxy-1,4-
Obtain naphthoquinone.

Alternatively, if necessary, concentrate the organic layer containing the product,
By cooling, filtering and drying the precipitated crystals, 2
-Alkyl-3-acyloxy-1,4-naphthoquinones can also be obtained.

The method of the present invention basically consists of four steps, but before proceeding to the acyloxylation step, 2-alkyl-3-hydroxy-1°4-naphthoquinone is isolated from the reaction solution obtained in the oxidation step. That is advantageous. Through this isolation, impurities are easily removed, there is no need to isolate intermediates between other steps, and the target product, 2-alkyl-3-acyloxy-1,4-naphthoquinone, is obtained with high purity. This is because it is possible.

[Example 1] Hereinafter, the present invention will be explained in detail with reference to Examples. In the examples, 1% represents weight % unless otherwise specified.

After adding 2.00 g of 50% hydrated Pd-C as a hydrogenation catalyst and replacing the inside of the reaction system with hydrogen, the system temperature was raised to 55°C and hydrogenation was performed under a hydrogen stream for 5 hours. . After the hydrogenation was completed, the atmosphere in the system was replaced with nitrogen, and the catalyst was filtered off.

The hydrogenation reaction filtrate from which the catalyst was filtered was kept at 50 to 55°C,
800 m12 of air diluted with nitrogen to an oxygen concentration of 10%
It was blown into the reaction solution after 7 minutes, and the reaction was continued for 6 hours with stirring.

After the reaction was completed, the reaction solution was cooled to 8° C. to precipitate crystals. Separate the crystallized crystals by filtration and use cold methanol for 60 hours! 2-dodecyl-3-hydroxy-1,4-
43.0 g of naphthoquinone was obtained.

Add 400 wβ of 0-xylene to a four-bottle flask, and while stirring, 41.0 g of 2-dodecyl-3-hydroxy-1,4-naphthoquinone obtained in the previous step (11
9.7 mmol), acetic anhydride 37.0 g (362,
4 mmol) and para-toluenesulfonic acid 1.03 g
(5,4 mmol Example 1 Put ethyl cellosolve 550-β into a 1β four-loaf flask, and add 2-hydroxy-1,4-naphthoquinone 38.0 g f218 mmol) while stirring gently with a stirrer. When the mixture became sufficiently homogeneous, 17.40 g (224 mmol) of a 40% aqueous methylamine solution was added. The temperature of the liquid in the flask was maintained at 22°C in a water bath, and a mixture of 48.00 g (260 mmol) of 1-dodecylaldehyde and ethyl cellosolve 5012 was added dropwise using a dropping funnel over 30 minutes, followed by a 2-hour reaction. I let it happen.

Oboro 79/Step 24.00 g (233 mmol) of 95% sulfuric acid was added to this reaction solution, and the temperature in the reaction system was raised to 120°C.
Thereafter, deamination reaction by thermal decomposition was carried out for 15 minutes.

The above deamination reaction solution was cooled to 30°C, water was added to it, the temperature was raised to 120°C over 40 minutes, and at that temperature
．． The reaction was allowed to proceed for 5 hours.

After the reaction was completed, the reaction solution was cooled to 30° C., the acid component and the water-soluble component were extracted with 250μ of a 15% aqueous sodium carbonate solution, and the organic layer was further washed with 250μ+ff of water. This organic layer was evaporated to dryness, and the resulting crystals were dried to form crystals of 2-dodecyl-3-acetoxy-1,4-naphthoquinone.
6.45 g (120, δ mmol) was obtained.

2-(l-methylaminododecyl)-3-hydroxy-
2-Hydroxy- used in the production of 1,4-naphthoquinone
The yield based on 1,4-naphthoquinone was 56.7 mol%. In addition, the raw material 2-(l-methylaminododecyl)
The yield based on -3-hydroxy-1,4-naphthoquinone was 61.0 mol%.

Example 2 Butyl acetate 200 meetings! Among them, 2-hydroxy-1,4-
7.35 g (42.2 mmol) naphthoquinone,
40% methylamine aqueous solution 3.28g (42,3
mmol) and n-dodecylaldehyde 9.33g
(50.7 mmol) was reacted for 2 hours at room temperature.

When the obtained reaction solution was analyzed by high performance liquid chromatography, 15.50 g (41.8 mmol) of 2-(l-methylaminododecyl)-3-hydroxy-
It was confirmed that it contained 1,4-naphthoquinone.

1. Main Resistance Unit I 4.70 g (45.5 mm IJ-11-L) of the above reaction solution N951 sulfur M was gradually added to form a uniform solution of sulfate at about 50°C. Next, the temperature was raised to 120°C, and deamination reaction by thermal decomposition was carried out for 1 hour.

Step 1 Step I The reaction solution containing 2-dodecenyl-3-hydroxy-1,4-naphthoquinone obtained in the deamination step was cooled to 30°C, and 0.50 g of 501-containing Pd-(:catalyst) was added. After the addition, hydrogenation was performed at 50° C. for 3 hours under a hydrogen stream.

After completion of hydrogenation, the inside of the reaction system was replaced with nitrogen, the catalyst was filtered out,
A filtrate containing 2-dodecyl-1,3,4-trihydroxynaphthalene was obtained.

i±Step 1 The filtrate from the previous step was kept at 50°C and reacted for 4 hours while blowing in nitrogen diluted air with an oxygen concentration of In% at 400 mff/min. Thereafter, the reaction solution was cooled to 10° C., and the crystals that had crystallized were separated by filtration. The obtained crystals were washed with cold methanol,
After drying, 9.23 g (f27.0 mmol) of 2-dodecyl-3-hydroxy-1,4-naphthoquinone crystals were obtained.

The filtrate from which the crystals were filtered off was concentrated to 60 mI2, cooled, and the precipitated crystals were filtered off, washed, and dried to give 1.62 g of 2-dodecyl-3-hydroxy-1,4-naphthoquinone crystals ( 4.7 mmol) was obtained.

2-dodecyl-3-hydroxy-1 obtained in the acyloxie pre-step,
4.67 gf (13.6 mmol) of 4-naphthoquinone crystals were added to 50 g of 0-xylene, and 3.5 g of acetic anhydride was added.
0.00 g (29.4 mmol) and 0.40 g of para-toluenesulfonic acid were added and reacted at 120° C. for 4 hours.

The reaction solution was cooled to 30° C., the acid component and the water-soluble component were extracted with 30×2 of a 10% aqueous sodium carbonate solution, and the organic layer was further washed with 3011I2 of water. This solution was evaporated to dryness to give 5.26 g (13,3
mmol) was obtained.

2-(l-methylaminododecyl)-3-hydroxy=
2-Hydroxy- used in the production of 1.4-naphthoquinone
The yield based on 1,4-naphthoquinone was 73.5 mol%. In addition, the raw material 2-(l-methylaminododecyl)
The yield based on -1,4-naphthoquine was 74.2 mol%.

[Effect of the invention 1 2-alkyl-3-acyloxy-1,4- according to the present invention
The method for producing naphthoquinone uses 211alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone as its raw material, so it does not require expensive raw materials such as organometallic compounds, it uses inexpensive raw materials, and it is simple. , and can produce high-purity products at high yields.
Unlike conventional methods, this method is extremely useful as an industrial manufacturing method.

In particular, in the method of the present invention, by selecting the solvent used in the step, intermediates can be isolated and appropriately purified in intermediate steps, and impurities can be easily separated.

Claims (3)

[Claims] (1) 2-(1-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone is subjected to a deamination step to produce 2-(1-alkenyl)-3-hydroxy-1,4-
After forming naphthoquinone, it is subjected to a hydrogenation step to obtain 2-alkyl-1,3,4-trihydroxynaphthalene, and then this 2-alkyl-1,3,4-trihydroxynaphthalene is subjected to an oxidation step to obtain 2-alkyl-3-
A method for producing 2-alkyl-3-acyloxy-1,4-naphthoquinone, which comprises subjecting hydroxy-1,4-naphthoquinone to an acyloxylation step. (2) The method according to claim 1, wherein the 2-alkyl-3-hydroxy-1,4-naphthoquinone produced in the oxidation step is isolated from the reaction solution and subjected to the acyloxylation step. (3) 2-(1-alkylaminoalkyl)-3-hydroxy-1,4-naphthoquinone is 2-hydroxy-1
, 4-naphthoquinone and an aliphatic aldehyde having at least one hydrogen at the α-position in an inert organic solvent in the presence of a primary amine, according to claim 1. the method of.