JPH01106840A - Production of 2-(1-alkyenyl optionally having inert substituent group)-3-hydroxy-1,4-naphthoquinone - Google Patents

Abstract

PURPOSE:To industrially and advantageously obtain the titled compound useful as an agricultural chemical, etc., in high yield, by reacting 2-hydroxy-1,4- naphthoqinone with an aldehyde in the presence of an acid having an acidity stronger than that of lower fatty acids and weaker than that of hydrochloric acid in an inert organic solvent. CONSTITUTION:2-Hydroxy-1,4-naphthoquinone is reacted with a >=2C aldehyde having at least one H at the alpha-position in an inert organic solvent (preferably lower fatty acid) in the presence of an acid having about 0-4.8pKa, preferably about 0-3pKa within the range of stronger than that of the lower fatty acid and weaker than that of hydrochloric acid to industrially and advantageously afford the titled compound useful as a raw material for insecticides, medicines, veterinary drugs and agricultural chemicals in high purity and yield at a low cost with facilitated separation of the product without requiring special corrosion-resistant materials due to no use of extremely highly corrosive hydrochloric acid though a smaller amount of the aldehyde used than a conventional one is sufficient, etc.

Description

Detailed Description of the Invention "Industrial Application Field" The present invention is directed to the use of 2-(1-alkenyl which may have an inert substituent)-3-hydroxy-1,4- which has insecticidal activity as an agricultural chemical. Concerning a method for producing naphthoquinone.

"Prior Art" Generally 2-(1-alkenyl)-3-hydroxy-L4
- Naphthoquinone has traditionally been shown to have insecticidal activity [e.g., Pe5
ticide 5science vol. 17, 511-51
6 (1986)] and bactericidal activity [e.g., Pe5t
icide 5science vol. 17, 686-690
(1986)), it is also important as a raw material for 2-alkyl-3-hydroxy-1,4-naphthoquinone obtained by hydrogenating this compound. The 2-alkyl-3-hydroxy-1,4-naphthoquinones are known to be useful as pharmaceuticals, veterinary drugs, and agricultural chemicals.

As a conventional method for producing 2-(l-alkenyl)-3-hydroxy-14-naphthoquinone, (2) 2-hydroxy-1,4-naphthoquinone and several moles of aldehyde are mixed in an acetic acid solvent of about 1.7 Method for producing by dehydration condensation using twice the molar amount of hydrochloric acid as a catalyst CJ, Am, Chep
A, Soc, 58 pH63-1167 (193
6)] or method (J) using triethylamine instead of hydrochloric acid as a catalyst and dimethylformamide or acetonitrile as a solvent (J,
CheIl, Soc, Perkin Trans
I.

ρ659-664 (1986)) is only known.

"Problems to be Solved by the Invention" However, hydrochloric acid is an extremely corrosive acid, requires special equipment materials, and is not industrially practical. In addition, in all of these methods, the yield is about 30 to 40 mol χ
However, since a large excess of aldehyde is used, a large amount of aldehyde condensation products and other by-products are produced, and the method for isolating the target product is complicated. This cannot be said to be an advantageous method.

"Means for Solving the Problems" As a result of intensive research into ways to overcome the drawbacks of the conventional methods, the present inventors have developed an acid with an acidity that is higher than lower fatty acids such as acetic acid and weaker than hydrochloric acid. In the presence of 2-
The present invention was completed based on the discovery that a good yield and easy separation of the product can be obtained by reacting hydroxy-1,4-naphthoquinone with an aldehyde.

In the present invention, 2-hydroxy-1,4-naphthoquinone and an aldehyde having two or more carbon atoms and at least one hydrogen at the α-position are mixed in an inert organic solvent with an acidity equal to or higher than a lower fatty acid. 2-(1-alkenyl which may have an inert substituent)-3-hydroxy-1, characterized in that the reaction is carried out in the presence of an acid weaker than hydrochloric acid.
It consists in a method for producing 4-naphthoquinone.

The aldehyde used in the present invention may be an aldehyde having two or more carbon atoms and at least one hydrogen at the alpha position; - aliphatic saturated aldehyde for boat fishing; Straight-chain aliphatic aldehydes are used, although the alkyl groups may be branched or have inert substituents such as phenyl, benzyl, halogen, and the like.

The reaction between 2-hydroxy-1,4-naphthoquinone (A) and aldehyde (B) in the present invention is represented by the following reaction formula, and the corresponding "1" has the same number of carbon atoms as the aldehyde.
- an alkenyl group which may have an inert substituent, i.e. -1jl=cHR', R'' (where R1, R
2 is hydrogen or an alkyl group which may have an inert substituent. ) is introduced at the 2-position of the naphthoquinone skeleton to obtain 2-(1-alkenyl which may have an inert substituent)-3-hydroxy-1,4-naphthoquinone (C).

Major aldehydes include, for example, acetaldehyde,
Propionaldehyde, butyraldehyde, isobutyraldehyde, valeraldehyde, isovaleraldehyde, pivalaldehyde, capronaldehyde, heptylaldehyde, caprylicaldehyde, pelargonaldehyde, capricaldehyde, undecylaldehyde, dodecylaldehyde (lauric aldehyde), tridecylaldehyde, myristicin Examples include aldehydes, aliphatic saturated aldehydes such as pentadecyl aldehyde, margaric aldehyde, and stearyl aldehyde, and aldehydes with substituents such as phenylacetaldehyde and hydrocinnamaldehyde.

The amount of aldehyde used is the raw material 2-hydroxy-1,4
-Generally more than an equimolar amount of naphthoquinone, usually 1.
The amount is 0 to 4.0 times by mole, preferably 1.2 to 2.0 times by mole; if it is too little, the yield will decrease, and if it is too much, it is not economical.

The acid used as a so-called catalyst in the present invention is selected from the range of acids whose acidity is higher than lower fatty acids to acids whose acidity is weaker than hydrochloric acid, and may be an organic acid or an inorganic acid. Acids whose acidity is lower than that of lower fatty acids are not suitable because the reaction rate is slow.

Typically, the acidity is from about 0 to about 4.8, preferably from about 0 to about 3 pKa.

Examples of organic acids include lower fatty acids (pKa approximately 4.8) such as acetic acid, propionic acid, and butyric acid; chloroacetic acid, dichloroacetic acid, trichloroacetic acid, bromoacetic acid, fluoroacetic acid, difluoroacetic acid, trifluoroacetic acid, and 2-chloroacetic acid. Examples include α-halogenated lower fatty acids such as propionic acid (pKa of about 0 to about 3); divalent carboxylic acids such as oxalic acid and maleic acid (pKa of about 1 to 2). Examples of inorganic acids include phosphoric acid and polyphosphoric acid (pKa of about 2).

A lower fatty acid having a pKa of 3 or more can be used both as a solvent and as a catalyst in the present invention, and there is no particular limitation on the amount used. However, since the reaction rate of lower fatty acids alone is slow, industrially an acid with a pKa of 3 or less is usually added as a catalyst. The amount added varies depending on the type of acid, but is generally 0.1 to 3.0 per 2-hydroxy-1,4-naphthoquinone.
It is twice the mole amount, preferably 0.3 to 1.0 times the mole amount.

The solvent used in the present invention is preferably one that is inert to the reaction raw materials, products, and acids under the reaction conditions, and the most preferred are lower fatty acids such as acetic acid, propionic acid, and butyric acid. Other examples include aromatic hydrocarbon solvents such as benzene, toluene, and xylene, cellosolves such as ethyl cellosolve and butyl cellosolve, and ethers such as dioxane, but these solvents are used as a mixed solvent with lower fatty acids rather than used alone. It is preferable to do so.

The amount of this solvent used is generally determined by
, 4-naphthoquinone, usually 3 to 30 times, preferably 3.5 to 20 times by weight.

The reaction conditions in the present invention include a reaction temperature of 60 to 170°C.
, preferably at 100 to 150 DEG C. 1 Normal pressure to elevated pressure may be used, but usually reflux or autogenous pressure may be used, and a reaction time of about 1 to 10 hours is sufficient.

"action" The method of the invention is generally carried out as follows.

A predetermined amount of 2-hydroxy-1,4-naphthoquinone and an aldehyde are added to a predetermined amount of a solvent, a predetermined amount of an acid is further added as a catalyst, and the mixture is reacted with a stirrer at a predetermined temperature for 1 to 7 hours. The reaction mixture is cooled, the precipitated crystals are filtered, and the resulting filter cake is washed with alcohol or the like.
By drying, 2-(1-alkenyl optionally having an inert substituent)-3-hydroxy-1,4-naphthoquinone is obtained. If necessary, the product can be recovered from the filtrate. For example, it can be recovered by concentrating the filtrate, cooling it, and crystallizing it.

In the present invention, the action of the acid acts as a catalyst to promote the reaction, while the aldehyde has two 2-hydroxy-1,4-
It suppresses the formation of so-called dimers, which are condensed naphthoquinones, but when the acidity becomes strong, it has the effect of promoting condensation of the aldehyde itself.

"Effects of the Invention" The present invention does not use extremely corrosive hydrochloric acid as in the prior art and does not require special corrosion-resistant materials, so it is possible to use extremely low-cost industrial equipment. In addition, although the amount of aldehyde used is smaller than before,
It is an industrially extremely effective method that can produce 2-(1-alkenyl optionally having an inert substituent)-3-hydroxy-1,4-naphthoquinone with high purity and high yield. be.

Next, the present invention will be explained in detail with reference to Examples. However, in the Examples, "%" represents "% by weight" unless otherwise specified.

"Example" Example 1 2.02 g of 2-hydroxy-1,4-naphthoquinone was added to 50 g of propionic acid, and 3.7 g of n-cabrylaldehyde (2.02 g of 2-hydroxy-1,4-naphthoquinone was added to 50 g of propionic acid. 1 mole) and 2.0 g of oxalic acid trihydrate (2-
1.4 moles of hydroxy-1,4-naphthoquinone) was added as a catalyst, and the reaction was carried out under reflux (approximately 135'C) for 5 hours. The obtained reaction solution was cooled to about 5°C, the precipitated crystals were filtered, and the obtained filter cake was washed with methanol and dried to obtain 2-(1-decenyl)-3-hydroxy-1, 4-naphthoquinone 2.41
I got g.

Analysis of 2-(1-decenyl)-3-hydroxy-1,4-naphthoquinone in the filtrate and washing liquid by high performance liquid chromatography revealed that it was 0.35 g, and when this was combined with the crystals obtained as above, 2-(1-decenyl)
The yield of -3-hydroxy-1,4-naphthoquinone is 7
It was 6.8 mol χ.

Example 2 2-hydroxy-1,4-naphthoquinone 4.02 g was added to 1112100 g of vinegar, and 3.0 g of isovaleraldehyde (5 carbon atoms) (2-hydroxy-1,4
- 3.3 times the mole relative to naphthoquinone) and 4.02 g of oxalic acid dihydrate (1.4 times the mole relative to 2-hydroxy-1,4-naphthoquinone) were added as catalysts, and under reflux (approximately 120 °C) for 7 hours. The resulting reaction solution was cooled to about 5°C, the precipitated crystals were filtered, and the resulting filter cake was washed with methanol and dried to obtain 2-
1.89 g of (1-isopentenyl)-3-hydroxy-1,4-naphthoquinone was obtained.

2-(1-isopentenyl)-3 in the filtrate and wash solution
-Hydroxy-1,4-naphthoquinone was analyzed by high performance liquid chromatography and found to be 2.71 g, and when this was combined with the crystals obtained above, 2-(1-isopentenyl)-3-hydroxy-1 The yield of 4-naphthoquinone was 75.3 mol2.

Example 3 (1) When oxalic anhydride is used as a catalyst 4.01 g of 2-hydroxy-1,4-naphthoquinone is added to 100 g of propionic acid, and further 7.4 g of n-dodecylaldehyde is added.
g (1 for 2-hydroxy-1,4-naphthoquinone)
．． 7 moles) and 1.90 g of oxalic anhydride (1.4 moles relative to 2-hydroxy-1,4-naphthoquinone) were added as catalysts, and the reaction was carried out under reflux (approximately 135"C) for 4.0 hours. The resulting reaction solution was cooled to about 5°C, the precipitated crystals were filtered, and the resulting filter cake was washed with methanol and dried to obtain 2-(1-dodecenyl)-3.
-Hydroxy-1,4-naphthoquinone 5.04 g was obtained.

Analysis of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone in the filtrate and washing liquid using high performance liquid chromatography revealed that it was 0.82 g, and when this was combined with the crystals obtained as above, The yield of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone was 74.9 mol χ.

(2) When propionic acid is used as both a solvent and a catalyst without using oxalic acid as a catalyst In Example (1) above, except that oxalic acid was not used and the reaction time was 5.0 hours, this Example (1) ) to obtain 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone in a yield of 64.9 mol χ.

Example 4 2-Hydroxy-1,4-naphthoquinone2. Add Og to 50 g of propionic acid, and further add 3.6 g of n-dodecylaldehyde (1.7 times the mole of 2-hydroxy-1,4-naphthoquinone) and 1.13 g of phosphoric acid (2-hydroxy-1,4-naphthoquinone). 1.0 mole of the total amount) was added as a catalyst, and the reaction was carried out under reflux (approximately 135°C) for 4°0 hours. The resulting reaction solution was cooled to about 5°C, the precipitated crystals were filtered, and the resulting filter cake was washed with methanol and dried to obtain 2-(1-dodecenyl)-3.
2.63 g of -hydroxy-1,4-naphthoquinone was obtained.

Analysis of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone in the filtrate and washing liquid by high performance liquid chromatography revealed that it was 0.3 g, and when this was combined with the crystals obtained as above, The yield of 2-(l-dodecenyl)-3-hydroxy-1,4-naphthoquinone is
It was 74.8 mol χ.

Example 5 In Example 4, 1.6 g of polyphosphoric acid (
1.9 for 2-hydroxy-1,4-naphthoquinone
2-(1-dodecenyl)-3-hydroxy-1,4-
2.54 g of naphthoquinone was obtained.

Analysis of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone in the filtrate and washing solution using high performance liquid chromatography revealed that it was 0.34 g, and when this was combined with the crystals obtained as described above, The yield of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone was 73.5 mol χ.

Example 6 2-Hydroxy-1,4-naphthoquinone2. Add Og to a mixed solvent of 20 g of propionic acid and 20 g of ortho-xylene, and further add 3.6 g of n-dodecylaldehyde (1.7 times the mole of 2-hydroxy-1,4-naphthoquinone) and 1 mol of oxalic acid dihydrate. .0g (2-hydroxy-1゜4-
A 0.7 mole amount of naphthoquinone was added as a catalyst, and the mixture was reacted under reflux (approximately 135°C) for 6 hours. After the resulting reaction solution was cooled, it was directly analyzed by high-performance liquid chromatography, and it was found that it contained 2.77 g of 2-(1-dodecenyl)-3-hydroxy-1,4-naphthoquinone, and the yield was 70%. .2 mol2.

Example 7 2.0 g of 2-hydroxy-1,4-naphthoquinone was added to 50 g of propionic acid, and 2.0 g of dodecylaldehyde was added.
0 g (1.7 times the mole relative to 2-hydroxy-1,4-naphthoquinone) and 0.8 g of trichloroacetic acid (0.43 times the mole relative to 2-hydroxy-1,4-naphthoquinone) or trifluoroacetic acid 0.8 g (0.61 mole times relative to 2-hydroxy-1,4-naphthoquinone) were added as catalysts, and the mixture was heated under reflux (approximately 135°C).
The reaction was carried out for 6.0 or 5.5 hours, respectively. The resulting reaction solution was cooled to about 5°C, the precipitated crystals were filtered,
The obtained filter cake was washed with methanol and dried to obtain 2-(1-dodecenyl)-3-hydroxy-1.
, 2.41 g or 2.5 g of 4-naphthoquinone, respectively.
Obtained in 2g.

2-(1-dodecenyl)-3- in the filtrate and washing solution
Hydroxy-1,4-naphthoquinone was analyzed by high-performance liquid chromatography and found to be 0.31 g or 0.
．． 33g, and when this is combined with the crystals obtained as described above, 2-(1-dodecenyl)-3-hydroxy-
The yields of 1,4-naphthoquinone were 69.5 mol χ and 72.8 mol χ, respectively.

Comparative Example 1 2.5 g of 2-hydroxy-1,4-naphthoquinone (
14°4 mmol) was added to acetic acid 5011, and further 5.4 g of dodecylaldehyde (2-hydroxy-1,4
-2.03 moles relative to naphthoquinone) and concentrated hydrochloric acid 7.
5 g (1.4 times the mole of 2-hydroxy-1,4-naphthoquinone) was added as a catalyst, and the mixture was reacted at 85°C for 2 hours. The resulting reaction solution was cooled to about 5°C.
Since crystals do not crystallize, after putting it in 300ml of water,
Extracted with 200ml of benzene. This organic layer was added twice with 150 ml of lχ aqueous sodium carbonate solution, and then with 150 ml of water.
2-(1-dodecenyl)-3-hydroxy-1,
1.97 g of 4-naphthoquinone was obtained. The yield is 40.2
The mole was χ.

Claims (4)

[Claims] (1) 2-Hydroxy-1,4-naphthoquinone and an aldehyde having 2 or more carbon atoms and at least one hydrogen at the α-position are mixed with hydrochloric acid in an inert organic solvent at an acidity of lower fatty acid or higher. 2-(1-Alkenyl optionally having an inert substituent)-3-hydroxy-1,4-, characterized in that the reaction is carried out in the presence of an acid in the weaker range.
Method for producing naphthoquinone. (2) The method according to claim 1, wherein the inert solvent is a lower fatty acid. (3) The method according to claim 1, wherein the acidity of the acid is in the range of about 0 to about 4.8 in terms of pKa. (4) The method according to claim 1, wherein the acidity of the acid is about 0 to about 3 in pKa.