JP3077268B2 - Novel clathrate compound and its production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a novel clathrate compound and, more particularly, to tetrakis (hydroxyphenylethanes as host compounds and 5-chloro-2-methyl-
The present invention relates to a novel inclusion compound having 4-isothiazolin-3-one as a guest compound. The inclusion compound of the present invention is effective as a bactericide, but is water-soluble and has strong skin irritation.
-Chloro-2-methyl-4-isothiazolin-3-one is solidified by inclusion, and the irritation to the skin is reduced, so that it can be widely used as a disinfectant that is easy to handle.

[0002]

2. Description of the Related Art In a water circulation system such as a cooling water system or a pulp and paper making system of various factory facilities, slimes of various fungi, algae, animals and plants, etc. adhere and cause various obstacles. For example, in a cooling water system, slimes of zooglia-like bacteria, algae, filamentous fungi, etc. adhere, causing a decrease in thermal efficiency, deterioration of water flow, and induction of corrosion of metal materials and the like. In the paper pulp papermaking system, bacteria,
Slime such as filamentous fungi and yeast is mainly generated in the papermaking process, and this is mixed into and adhered to the pulp slurry, causing deterioration in the quality of the product and failure in the production process such as paper breakage.

Further, seawater algae, bacteria, marine mussels, sea squirts and other organisms adhere to the intakes of cooling water systems and the inner walls of cooling pipes, such as thermal power plants and steelworks, which use seawater. These adhering organisms are separated by a water flow or the like, and also cause obstacles such as clogging of a tube or a strainer of a heat exchanger, which causes a deterioration in the function of the entire water passage system.

[0004] Conventionally, in order to prevent such an obstacle due to slime or the like, it is common to use a slime control agent (antibacterial agent) because it is simple and inexpensive to handle. Examples of widely used antibacterial agents include water-soluble antibacterial agents of isothiazoline compounds. Among them, 5-chloro-2-methyl-4-isothiazolin-3-one (hereinafter, abbreviated as “CMI”) is particularly excellent in antibacterial activity, and is used for cooling water systems, paper pulp, swimming pools and the like. Widely used as various slime control agents for water systems, antibacterial agents, algicides, and fungicides.

[0005] The CMI generally involves 1) halogenating beta thioketoamide in an inert organic ester solvent such as acetate. 2) Beta-substituted thiocyanoacrylamide is treated with an acid to obtain isothiazolone, which is then halogenated. (Special Publication 46-2
Regarding the method of synthesizing CMI, it is not possible to obtain only CMI by using any one of the above-mentioned methods 1) and 2), and the antibacterial activity is about 1/10 that of CMI as an auxiliary component. 2-methyl-4-isothiazolin-3-one (hereinafter, “MI”)
Can be obtained. In addition, it is difficult to selectively remove only CMI from the reaction product mixture by the conventional technique, and it is unavoidable that MI having poor antibacterial activity is required.
The fact is that they are used in a state of being mixed.

[0006] On the other hand, although CMI has excellent antibacterial activity, it is extremely irritating to the skin, and its handling requires great care. In addition, when used in water, it loses its activity by reacting with organic substances (amines, reducing substances, etc.) in the water, so that it has been difficult to maintain the antibacterial activity for a long time. In recent years, attempts have been made to selectively include this CMI, and bisphenol compounds and compounds having a chemical structure similar thereto have been proposed as host compounds. (JP-A-1-190602, JP-A-62
No. 22701, JP-A-61-53201).

[0007]

Problems to be Solved by the Invention The host compounds described in the above cited references are excellent in the inclusion ability of CMI, and these inclusion compounds have greatly reduced skin irritation and are easy to handle. Has become. However, in the clathrate compounds using these host compounds, the
Was too fast to be released into the water system, and could not be applied to systems requiring sustainability, such as sterilization of circulation toilets for trains and the like. An object of the present invention is to provide a novel clathrate compound which selectively clathrates CMI and has a relatively low release rate of CMI in an aqueous system.

[0008]

Means for Solving the Problems The present inventors have made intensive studies to achieve the above object, and as a result, certain tetrakis (hydroxyphenyl) ethanes are extremely excellent as host compounds that selectively include CMI. And found that the release rate of CMI from these clathrates in an aqueous system was much higher than that of known clathrates, and completed the present invention. The present invention provides the following general formula [1]
An inclusion compound characterized by using tetrakis (hydroxyphenyl) ethane represented by the following formula as a host compound and 5-chloro-2-methyl-4-isothiazolin-3-one represented by the chemical formula [2] as a guest compound. is there.

[0009]

Embedded image

[0010]

Embedded image Hereinafter, the present invention will be described in detail.

(Host compound) As specific examples of the compound represented by the general formula [1] used in the present invention, 1,1,1
Examples thereof include 2,2-tetrakis (p-hydroxyphenyl) ethane (hereinafter abbreviated as "TEP-DF"), 1,1,2,2-tetrakis (m-hydroxyphenyl) ethane, and the like. Among them, TEP-DF is particularly preferably used because the obtained clathrate is solid at room temperature and easy to handle.

[0012]

Embedded image (Guest compound) The CMI represented by the chemical formula [2] used in the present invention is a water-soluble sterilizer containing MI which is a commercially available auxiliary component at the time of synthesis, and magnesium chloride, magnesium nitrate and the like as a stabilizer. Agent (trade name: Caisson WT, manufactured by Rohm & Haas).

[0013]

Embedded image

(Clathrate compound) The clathrate compound of the present invention is usually prepared by adding a water-soluble bactericide containing CMI as a main component to a slurry in which the host compound is suspended in water.
By reacting at 0 ° C with stirring for 15 to 180 minutes, C
MI is included in the host compound. The inclusion amount of CMI is
Although it depends on the type of the host compound, the reaction temperature and the reaction time, it is 1.2 to 2.0 mol per 1 mol of the host compound.
In the above reaction, MI present as a secondary component in the water-soluble bactericide is also included, but its inclusion amount is MI / CMI.
(Molar ratio) is 7% or less. In particular, in the case of TEP-DF, the MI / CMI (molar ratio) is as small as 1%, which is suitable as a host compound.

(Method of using clathrate compound) The clathrate compound re-releases the clathrated CMI in an aqueous system, and exhibits an effect as a fungicide. Therefore, various methods for adding a conventionally known water treatment agent such as a disinfectant to the treated water system can be adopted. For example, (1) a method of continuously or intermittently adding a liquid or powdery clathrate compound to a treated water system, (2) a molded product of a clathrate compound solid at room temperature, for example, tablets, granules, etc. Method of filling column and passing treated water, (3)
A method of putting the clathrate compound in a water-insoluble and water-permeable bag, a container such as a cartridge, and immersing or floating in treated water,
(4) It is possible to adopt a method of directly or mixing with paint, resin, etc., and applying or attaching to the surface of equipment such as equipment and piping that is in contact with the treated water.

[0016]

The present invention is characterized in that CMI is used as a guest compound and tetrakis (hydroxyphenyl) ethanes are selected as a host compound, as described in detail above. Conditions for this type of host compound are as follows: (1) A phenyl group for including a guest molecule is included in the molecular structure. (2) In order to release water-soluble CMI in an aqueous system, the host compound must be sparingly soluble in water. (3) The rate of re-release of CMI in the water system is constant. (4) at a low price, it is low in toxicity.

Although the above tetrakis (hydroxyphenyl) ethane was selected as a host compound satisfying these conditions, the re-release rate of CMI from these clathrates was lower than that of a conventionally known similar clathrate. It is not clear why it is slow . On the other hand, when CMI is included, its toxicity and skin irritation are reduced because it depends on the toxicity and skin irritation of the host compound, and it also reacts with other substances during use to have antibacterial activity. Is also prevented from decreasing.

[0018]

The present invention will be described below in more detail with reference to examples and comparative examples. However, the scope of the present invention is not limited at all by these examples. (1) Production of clathrate compounds

Example 1 TEP-DF (produced by Asahi Organic Materials Industry) in 10 ml of water 1.1
After adding 355 g (2.85 mmol) and dispersing while stirring at 25 ° C. for 30 minutes, 20 g of Caisson WT (manufactured by Rohm & Haas) (11.4 mmol as CMI) was added.
l) was gradually added dropwise, and reacted while stirring at 25 ° C. for 3 hours. Next, the precipitate was suction-filtered, and the residue was vacuum-dried at room temperature to obtain a pale yellow powder sample A-1.

Example 2 1.1355 g of TEP-DF was added to 10 ml of water, and the mixture was stirred and dispersed at 50 ° C. for 20 minutes. 20 g of Caisson WT was gradually added dropwise thereto, and the mixture was reacted at 50 ° C. with stirring for 30 minutes. Then, after cooling this solution to room temperature, the precipitate was filtered by suction, and the residue was vacuum-dried at room temperature to obtain a pale yellow powder sample A-
2 was obtained.

Example 3 1.1355 g (2.85 mmol) of TEP-DF in 5 ml of methanol
And stirred while warming until the TEP-DF is completely dissolved. After the solution was cooled to 25 ° C., 20 g of Caisson WT was gradually added dropwise, and reacted at 25 ° C. for 1 hour. Next, the precipitate was filtered by suction, and the filtrate was vacuum-dried at room temperature to obtain a pale yellow crystal sample A-3.

Example 4 1.1355 g (2.85 mmol) of TEP-DF in 5 ml of methanol
And stirred while warming until the TEP-DF is completely dissolved. While maintaining this solution at 40 ° C., 20 g of caisson WT was gradually added dropwise, and the mixture was reacted at 40 ° C. for 15 minutes. Then, after cooling the solution to room temperature, the precipitate was filtered by suction, and the residue was dried in vacuo to obtain a pale yellow crystal sample A-
4 was obtained.

Comparative Example 1 0.827 g (2.85 g) of β-dinaphthol in 17 ml of methanol
mmol) and 5.04 g of Caisson WT (0.368 g, 2.86 mmol as CMI) was added thereto and stirred.
A dark black precipitate was deposited. The precipitate is filtered by suction,
The residue was dried under vacuum to obtain Comparative Sample C-1. Note): The analysis values of the water-soluble bactericide (Caisson WT) used in Examples 1 to 4 and Comparative Example 1 are as follows. CMI: 10.1 wt% MI: 3.8 wt% The balance: magnesium chloride + magnesium nitrate + water

The production conditions, clathrates of CMI and MI, and guest re-use of the clathrate samples A-1 to A-4 and the clathrate C-1 for comparison of the present invention obtained as described above. The release temperatures are shown in Table 1.

[0025]

[Table 1] For each clathrate compound sample, IR spectrum, N
MR spectrum, X-ray diffraction, DTA, HPLC and TL
Analysis by C confirmed the formation of the clathrate, and the X-ray microanalyzer confirmed that magnesium chloride and magnesium nitrate were not included.

As a CMI release test, each of the obtained sample A-3, comparative sample C-1 and CMI alone was put into a cellulose dialysis membrane so as to have a CMI equivalent of 10 mg, and this was mixed with pure water. The sample was immersed in 1 l, and the CMI release amount after a certain period of time was measured while stirring at a stirring speed of 100 rpm using a dissolution tester, and the change with time was examined. The results are shown in Table 2, and the release curve is shown in FIG.

[0027]

[Table 2]

Further, the clathrate compound sample A obtained in the present invention
3, IR spectra of the CMI isolated from the host compound TEP-DF and the guest water-soluble germicide (Caisson WT) are shown in FIGS. 1, 2 and 3, respectively, and the X-ray diffraction patterns are shown in FIGS. And FIG.

[0029]

As described above, the clathrate of the present invention is a novel clathrate containing CMI, which is effective as a fungicide, as a guest and tetrakis (hydroxyphenyl) ethanes as a host. The clathrate has the following characteristics. (1) Toxicity and skin irritation can be reduced by including CMI having high toxicity and skin irritation as a host with tetrakis (hydroxyphenyl) ethanes having lower toxicity. (2) Since it is solid at normal temperature, tableting is also possible and handling is extremely easy. (3) In the water system, the CMI of the active ingredient is re-released at an appropriate speed, so that it is effective as a disinfectant for recirculating toilets for trains, which is replaced every 2-3 days. (4) Since the host compound protects the CMI of the active ingredient, it is possible to prevent the CMI from reacting with other substances and reducing the antibacterial activity. Therefore, the present invention provides a novel clathrate compound which is effective as a bactericide having a moderate sustained release property and is easy to handle, and a method for producing the same. Particularly, the utility value in the field of water treatment is extremely large. .

[0030]

[Brief description of the drawings]

FIG. 1 shows an IR spectrum of clathrate compound sample A-3.

FIG. 2 shows an IR spectrum of a host compound TEP-DF.

FIG. 3 shows an IR spectrum of CMI isolated from a guest compound water-soluble fungicide (Caisson WT).

FIG. 4 shows an X-ray diffraction diagram of clathrate compound sample A-3.

FIG. 5 shows an X-ray diffraction diagram of TEP-DF.

FIG. 6 shows an X-ray diffraction pattern of CMI isolated from a guest compound water-soluble fungicide (Caisson WT).

FIG. 7 shows the obtained sample A-3, comparative sample C-1 and CM
It is the figure which showed the release curve obtained by performing the release test about I alone and measuring the release amount. (Below)

──────────────────────────────────────────────────続 き Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07D 275/02-275/03 C07C 39/15 A01N 43/80 CA (STN) REGISTRY (STN) WPI (DIALOG) )

Claims (2)

(57) [Claims] 1. A compound comprising tetrakis (hydroxyphenyl) ethane represented by the following general formula [1] as a host compound and 5-chloro-2-methyl-4-isothiazolin-3-one represented by a chemical formula [2] as a guest compound. An inclusion compound characterized by the following. Embedded image Embedded image (2) tetrakis (hydroxyphenyl) ethane and 5-chloro-2-methyl-4-isothiazoline-3-
2. The method for producing an inclusion compound according to claim 1, wherein the reaction is performed by turning on.