JP4868197B2 - Method for vaporizing hinokitiol - Google Patents

Description

  Hinokitiol exhibits antibacterial properties at extremely low concentrations, has a broad antibacterial spectrum against general bacteria and fungi, and is known to be resistant to the generation of resistant bacteria. Moreover, hinokitiol (sometimes abbreviated as HT) has a sublimation property, and has the characteristic that the antibacterial property is exhibited in a non-contact manner.

  In recent years, it has been demonstrated that HT inhibits plant ethylene production, and HT has been used as a freshness-preserving agent for fruits and vegetables. In addition, physiological effects such as onion and potato germination inhibitory action, mite and termite control action, mosquito repellent action, allergic disease symptom relief action, etc. are found, and HT is vaporized as needed. There has been a strong demand for a method of maintaining the required spatial density. Hinokitiol has a sublimation property of the fine crystal powder of only 0.6 to 0.7% / day even in the summer open system, and it is required to use a large amount of HT for the use as described above. Problems are limiting their use.

  Although it is desirable to add hinokitiol directly to packaging materials such as films and papers for antibacterial or freshness preservation, exposure to high temperatures in the manufacturing process due to its sublimation properties eliminates most of the added HT. I will let you. Therefore, various ideas have been made in the past, but the actual situation is that no definitive result has been obtained. In addition, the packaging material to which the metal salt of HT is added may not be expected to have an effect other than the part that is in direct contact, and restrictions on use cannot be ignored.

  Hinokitiol tends to form complex salts with various metals, and the resulting complex salt is stable and can withstand high temperatures, but its antibacterial properties are not much different from that of free hinokitiol, so attempts have been made to add it to packaging materials. There is also a device to release HT from a complex salt of hinokitiol by reacting with other compounds, but since liberated hinokitiol is easily dissolved in both alkali and acid, it is very difficult to evaporate hinokitiol as a gas. It was difficult.

  On the other hand, trialkyltin and triaryltin bonded to the carboxyl group of polycarboxylic acid are known to hydrolyze in seawater and exhibit antifouling effects, and have been industrialized and already used as antifouling paints. Yes. The present inventor previously discovered a method for binding hinokitiol to polycarboxylic acid via a copper or zinc atom. A compound in which hinokitiol is bound to water-soluble polycarboxylic acid to a certain extent does not dissolve in water, but for a long time. It was confirmed that hinokitiol was released slowly by hydrolysis reaction when it was contacted with water (Japanese Patent Application No. 2002-33711).

  In order to develop a new means for evaporating hinokiol as a gas, the present invention has been intensively studied so far. In this research, a method for bonding hinokitiol to a polycarboxylic acid via a copper or zinc atom. The research was further advanced based on this method, and finally the present invention was completed.

That is, a powder obtained by bonding hinokitiol to zinc with polycarboxylic acid and adding an alkali metal salt of ethylenediaminetetraacetate, particularly its sodium salt, to the compound obtained in the kneading mixture is brought into contact with water, for example, water It was found that hinokitiol is liberated and vaporized at room temperature by adding or absorbing moisture under high humidity. As a result of further investigation, it was discovered that zinc of hinokitiol (Zn (HT) ₂ · 2H ₂ O) can vaporize HT by the same method, and the present invention was completed here.

That is, in the present invention, (i) a compound in which hinokitiol is bound to polycarboxylic acid via zinc and / or zinc salt of hinokitiol is added with ethylenediaminetetraacetic acid disodium salt (EDTA · 2Na) and ground and mixed.
(B) A method for vaporizing hinokitiol characterized in that, by absorbing moisture in the presence of water, for example, under high humidity, or by adding water, both are reacted to liberate hinokitiol.
It is related to.

In particular, the following new facts were found in the study of the present invention.
(A) The ground mixture with hinokitiol using ethylenediaminetetraacetic acid trisodium salt (EDTA.3Na) should not cause HT to be free-vaporized even if water is added. That is, especially as ethylenediaminetetraacetic acid sodium salt, HT can be successfully released only when mono- or disodium salt is used.
(B) The copper salt of hinokitiol should not react even if EDTA / sodium salt is ground and mixed and water is added. In addition, for compounds in which HT is bonded to polycarboxylic acid via copper, the hinokitiol produced when water is added under the storage of EDTA / sodium salt is captured as the copper salt of hinokitiol and does not vaporize HT. In other words, the behavior is completely different when using zinc and copper.

  As the polycarboxylic acid used in the present invention, particularly preferred are homopolymers of acrylic acid, methacrylic acid, and maleic anhydride, at least two types of these copolymers, or these and other monomers. The copolymer of can be illustrated. Preferred examples of other vinyl monomers at this time include ethylene, vinyl acetate, styrene and the like.

  In the present invention, a water-soluble polycarboxylic acid is used because it can easily come into contact with water and liberate HT.

In the present invention, the method of Japanese Patent Application No. 2002-33711 can be substantially applied to the method of producing a compound in which hinokitiol is bonded to the polycarboxylic acid via zinc. The typical method is exemplified as follows.
(A) Concentrate a preferably equimolar alcohol solution of zinc chloride and hinokitiol to remove hydrochloric acid as much as possible and cool to precipitate crystals of a compound consisting of one molecule of hinokitiol and one atom each of zinc and chlorine. ,
(B) Then in an alcohol solvent, preferably in the presence of tetramethylammonium hydroxide,
(C) A method in which a polycarboxylic acid and hinokitiol are bonded by reacting with a polymer compound having a carboxyl group.

  At this time, it is preferable that the alcohol in the alcohol solution of zinc chloride and hinokitiol is ethyl alcohol, and the amount of tetramethylammonium hydroxide used is equal to or less than the equimolar amount of the precipitated compound.

  As detailed means of this method, all means described in the above Japanese Patent Application No. 2002-33771 can be applied to the present invention.

The zinc salt of hinokitiol used in the present invention is preferably exemplified by Zn (HT) ₂ .2H ₂ O.

As the alkali metal salt of ethylenediaminetetraacetic acid used in the present invention , the sodium salt, particularly the disodium salt can be used. In this case, it is better to avoid using trisodium salt.

  In the present invention, when ethylenediaminetetraacetic acid sodium salt is added, not only a zinc compound of hinokitiol, that is, a compound bonded to polycarboxylic acid via zinc, but also a case of using a zinc salt of hinokitiol is included. The amount added is 0.1 to 10 mol or more, preferably 0.5 to 5 mol, particularly preferably 1.0 to 2.0 mol, based on the amount of zinc.

  Mix after grinding. This mixture is then brought into contact with water to vaporize hinokitiol. As a means for bringing the mixture into contact with water at this time, a means for absorbing moisture under high humidity or adding water can be mentioned as a preferred means.

  According to the present invention, hinokitiol can be easily evaporated and vaporized by simply contacting with water, and the range of utilization of hinokitiol becomes extremely wide.

The features of the present invention will be described with reference to examples and comparative examples of the present invention. However, the metal salt of hinokitiol used in these examples was synthesized in an alcohol solvent using hinokitiol and zinc chloride or copper chloride (hereinafter abbreviated as Zn (HT) ₂ , Cu (HT) ₂ ). In addition, for the synthesis of a compound in which hinokitiol is bonded to a water-soluble polycarboxylic acid through a metal atom, tetraacrylic acid (Jurimer AC-10LP, manufactured by Nippon Pure Chemical), hinokitiol metal salt, and metal salt compound are used. Methyl ammonium hydroxide {(CH ₃ ) ₄ NOH · 5H ₂ O} was used as a catalyst (Examples 1-2 and 12-13 of Japanese Patent Application No. 2002-33711. The products were PAA-Zn-HT, PAA- Abbreviated Cu-HT).

Clewat N (EDTA · 2Na · 2H ₂ O, manufactured by Teikoku Chemical Industry) is used as the disodium salt of ethylenediaminetetraacetic acid, and a reagent (EDTA · 3Na · nH ₂ O, n = 0.1) is used as the trisodium salt of ethylenediaminetetraacetic acid. Was used.

  A compound in which hinokitiol is bonded to polyacrylic acid via Zn, for example, PAA-Zn-HT (Lot No. 3, HT 19.03%, Zn 7.54%) contains a molar ratio of HT to Zn of about 1. In theory, it is theoretically considered that only about 11 —ZnHT groups are bonded to 100 acrylic acid units, and a considerable number of free carboxyl groups remain.

  It was found that this compound is insoluble in water, but it absorbs water and emits a hinokitiol odor when placed under high humidity.

Therefore, 266 mg (0.563 mmol) of Clewat N (EDTA2Na · 2H ₂ O) was added to 400 mg of PAA-Zn-HT (Lot No. 3), and the mixture was ground and mixed. Left for a week. To this, 20 ml of chloroform was added, followed by stirring and extraction for 1 hour, and 29.01 g of a chloroform solution was collected. The residue was extracted by stirring with 20 ml of ethanol, and the residue was dried under reduced pressure to give 390 mg of white powder.

  As a result of the analysis, the chloroform solution contains 52.2 mg (0.32 mmol) of HT, but hardly contains Zn, and the white powder contains 22.3 mg (0.34 mmol) of Zn, but the presence of HT is recognized. And was found to dissolve easily in water.

  Therefore, it is considered that PAA-Zn-HT insoluble in water and chloroform is hydrolyzed to liberate HT, and zinc equivalent to this is captured by EDTA · 2Na, and hinokitiol bound via Zn. Came to be convinced that liberating hinokitiol by adding water.

  244 mg of PAA-Zn-HT (Lot No. 3, HT 19.03%, Zn 7.54%, HT / Zn = 1.0 / 1.0 mol / mol) was ground and mixed with 127 mg (0.34 mmol) of Clewat N. Expand to a glass petri dish.

  This is held in a 2 l beaker with 50 ml of water at the bottom, sealed with a polyethylene film and left at room temperature. The water absorption increased almost linearly, and an increase of 166 mg was observed in 3 weeks.

  After 3 weeks, the petri dish contents were extracted by stirring with chloroform and separated into a chloroform solution and a white residue. When the contents of HT and Zn were measured, respectively, HT34.52 mg (recovery rate 93.7%), Zn0 .54 mg, and HT 3.8 mg and Zn 17.2 mg (recovery rate 93.7%) were detected in the white residue. That is, under this experimental condition, 93.7% of PAA-Zn-HT is hydrolyzed to liberate HT, and Zn is fixed to polyacrylic acid together with crewat N to form a water-soluble white residue. .

The zinc salt of hinokitiol is a very stable compound against water. For example, 907 mg of Zn (HT) ₂ · 2H ₂ O (Lot No. 11, moisture 10.47%, HT 73.32%, Zn 14.82%) is suspended in 20 ml of ion-exchanged water and left at room temperature for 1 week, followed by filtration. When washed with water and dried, the zinc salt of hinokitiol is recovered as it is. The yield was 870 mg (Zn content: 15.38%, recovery rate as Zn: 100.6%).

However, 103 mg (0.24 mmol) of Zn (HT) ₂ .2H ₂ O (Lot No. 11) was suspended in 5 ml of water together with 11.5 mg (0.30 mmol) of Clewat N and stirred vigorously for 15 minutes, followed by washing with filtered water. The white precipitate obtained by drying was a yield of 86 mg (Zn content 15.4%). In addition, 2.5 mg of Zn was detected in the dried product obtained by concentrating the filtrate with the filtrate. This is in complete agreement with the zinc content of 2.5 mg of 17 mg Zn (HT) ₂ .2H ₂ O dissolved in water with Clewat N.

  Therefore, it was convinced that the zinc salt of hinokitiol also gradually reacted with water to release hinokitiol in the presence of crewat N.

Add 198 mg of Clewat N (EDTA · 2Na · 2H ₂ O) to 222 mg of Zn (HT) ₂ · 2H ₂ O (Lot No. 11, moisture 10.47%, HT 73.32%, Zn 14.82%) and mix by grinding (Zn / EDTA · 2Na = 1.00 / 1.06 mol / mol).

  50 mg of water was added to this powder, sealed and allowed to stand at room temperature for 1 week, and then the soluble material was extracted with 10 ml of chloroform, washed with a small amount of chloroform, and 18.26 g of chloroform solution and 253 mg of insoluble residue were separated. As a result of analysis, it was found that the chloroform solution contained 0.45 mg Zn, HT 127.8 mg (recovery rate 78.6%), and the insoluble residue contained 25.7 mg Zn (recovery rate 78.1%).

Accordingly, Zn (HT) ₂ .2H ₂ O is hydrolyzed in the presence of EDTA.2Na.2H ₂ O to release hinokitiol.

_{Zn (HT) 2 · 2H 2} O (LotNo.12, H 2 O8.63%, HT76.38%, Zn15.56%) and (2.1 mmol as Zn) 903 mg, Kurewatto N (EDTA · 2Na · 2H ₂ O) 770 mg of (2.1 mmol) were mulled spread on petri dish. If this is left at room temperature for 3 weeks, the weight is only reduced by 13 mg and almost no change is observed. Then, this is made to absorb moisture using the same apparatus as Example 2, and this is then returned indoors and HT is vaporized. This operation is repeated on the schedule as shown in FIG. On the 25th day from the start, the contents were mixed and homogenized and subjected to analysis. The second and subsequent moisture absorptions were performed in the same day for 5 hours as shown in FIG. FIG. 1 shows the weight change before and after each moisture absorption.

  Since the hinokitiol content in the final residue of 1440 mg was 442 mg as a result of the analysis, it was found that the decrease in HT for 24 days was 227 mg, which was almost equal to the weight loss of 248 mg during the same period.

In addition, since the weight at the end of each vaporization step is almost linearly reduced, Zn (HT) ₂ · 2H ₂ O reacts with water in the presence of EDTA · 2Na · 2H ₂ O to release hinokitiol. This material is considered to vaporize and dissipate with water.

Incidentally, the vaporization rate is 247 mg / 16 days = 15.4 mg / day = 2.24% / day, and the sublimation rate of the hinokitiol fine crystal powder is 0.6 to 0.7% / day, which is three times or more.

That is, a powder obtained by grinding and mixing hinokitiol zinc salt with an equivalent amount or more of EDTA · 2Na · 2H ₂ O needs water by adding water or absorbing moisture as necessary, thereby necessitating the necessary space. It shows that it can be filled with hinokitiol vapor.

Comparative Example 1

PAA-Cu-HT (Lot No. 20, Cu 5.84%) HT 13.69%, Cu / HT1.1 / 1.0 mol / mol) 1100 mg and Crewat N (EDTA · 2Na · 2H ₂ O) 420 mg (1 .13 mmol) is triturated and mixed, 310 mg of water is added and sealed, left at room temperature for 1 week, and then 20 ml of chloroform is added and extracted with stirring for 1 hour. Further, 5 ml of chloroform was added and extracted in the same manner to obtain a total of 37.93 g of chloroform layer. The residue was dried under reduced pressure to obtain 1.51 g of a blue solid. As a result of analysis, the chloroform extract contained 28.45 mg (0.447 mmol) of Cu and 147.9 mg (0.907 mmol) of HT, and no hinokitiol was detected in the extraction residue, but 34.4 mg (0.54 mmol) of copper. ) Existed.

The total recoveries of Cu and HT in the extract and residue are 97.7% and 98.6%, respectively, and Cu / HT = 1.0 / 2.0 mol / mol contained in the chloroform extract. Therefore, in PAA-Cu-HT, 1/2 of Cu produced by hydrolysis is extracted into chloroform as Cu (HT) ₂ , and the remaining 1/2 of Cu is captured by EDTA in the extraction residue together with PAA. It is considered to exist.

Comparative Example 2

Powder obtained by grinding and mixing 390 mg (1.0 mmol) of Cu (HT) ₂ (mp 173.5 to 174.5 ° C.) and 409 mg (1.1 mmol) of Clewat N (EDTA · 2Na · 2H ₂ O) Does not increase the moisture absorption even when left under high humidity for 1 week. Therefore, 20 ml of water was added and left overnight, then washed with filtered water and dried to give 360 mg of blue crystals. This product was confirmed to be the original Cu (HT) ₂ as a result of IR spettle measurement at mp 174.5 to 175 ° C. (recovery rate 92.3%).

This fact indicates that Cu (HT) ₂ does not react with EDTA · 2Na · 2H ₂ O even in the presence of water, and the results of Comparative Example 1 are endorsed.

Comparative Example 3

Zn (HT) ₂ (moisture 10.47%, HT 73.32%, Zn 14.82% HT / Zn = 1.98 / 1.00 mol / mol) 600 mg (1.37 mmol) was added to EDTA · 3Na 490 mg (1. 37 mmol). 1090 mg of this is left at room temperature in a closed container (2 l capacity, 50 ml water held at the bottom). After 38 days, the content increased in water absorption, leaving 1690 mg of mud (water absorption 600 mg, water supply rate 55.0%).

A portion of 620 mg was weighed and extracted twice with 10 ml of water to separate 200 mg of water soluble material and 185 mg of water insoluble material. The water-soluble material does not show any color reaction of hinokitiol by FeCl _3, and all hinokitiol in the system is considered to be contained in the water-insoluble material. As a result of analysis, the water-insoluble matter contained HT 74.78% and Zn 15.01%, and the molar ratio of HT to Zn was 0.458 / 0.237 = 1.99 / 1.00 mol / mol. This indicates that Zn (HT) ₂ was recovered with a yield of 85%. Therefore, it is understood that the reaction does not occur even in the presence of Zn (HT) ₂ , EDTA · 3Na and water, and hydrolysis does not occur.

It is a graph which shows the schedule and weight change of vaporization of HT of Example 5.

Claims (2)

(I) A compound in which hinokitiol is bonded to polycarboxylic acid via zinc and / or zinc salt of hinokitiol is added with ethylenediaminetetraacetic acid disodium salt (EDTA · 2Na) and ground and mixed.
(B) A method for vaporizing hinokitiol, wherein the hinokitiol is liberated by bringing it into contact with water and allowing them to react. The vaporization method according to claim 1, wherein equimolar or more EDTA · 2Na is used with respect to the zinc content of the hinokitiol zinc compound.

Images