JP3077243B2 - Inclusion compound and method for producing the same - 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 hydroxybenzophenones as host compounds and 5-chloro-2-methyl-4-isothiazolin-3-one as guest compounds. Related to inclusion compounds.

The inclusion compound of the present invention, which is effective as a bactericide, includes 5-chloro-2-methyl-4-isothiazolin-3-one, which is water-soluble and has strong skin irritation, and solidifies it. Since it has reduced skin irritation, it can be widely used as an easy-to-handle bactericide.

[0003]

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, slime of zooglue-like bacteria, algae, filamentous fungi and the like adheres, causing a decrease in heat efficiency, deterioration of water flow, induction of corrosion of metal materials and the like. In the paper pulp papermaking system, slimes such as bacteria, fungi and yeast are mainly generated in the papermaking process, which are mixed into the pulp slurry and cause problems in the production process such as deterioration of product quality and paper breakage. . In addition, seawater algae, bacteria, mussels, sea squirts, and other organisms adhere to the intakes and cooling pipe inner walls of cooling water systems such as thermal power plants and steelworks that use seawater, causing a decline in their functions. In addition, these attached organisms are separated by a water flow or the like, and also cause obstacles such as clogging of a portion of a heat exchanger tube or a strainer, 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, a slime control agent (antibacterial agent) has been used.
Is generally used because it is easy to handle and inexpensive. 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 can be used in various water systems such as cooling water systems, paper pulp, and swimming pools. Widely used as slime control agents, antibacterial agents, algicides, and fungicides.

The CMI generally (1) halogenates beta-thioketoamide in an inert organic ester solvent such as acetate. (2) The beta-substituted thiocyanoacrylamide is treated with an acid to obtain isothiazolone, which is further halogenated. (See Japanese Patent Publication No. 46-21240).

As a method for synthesizing CMI, the above (1) and
Regardless of the synthesis method of (2), only CMI cannot be selectively obtained, and the antibacterial activity is C as a secondary component.
2-methyl-4-isothiazoline which is about 1/10 of MI
Only a mixture of 3-one (hereinafter abbreviated as "MI") is obtained. Moreover, it is difficult to selectively remove only CMI from the reaction product mixture by the conventional technique, and in fact, MI is used in a state in which MI having inferior antibacterial activity is inevitably mixed.

On the other hand, although CMI has excellent antibacterial activity, it is extremely irritating to the skin, and its handling requires great care. 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 period of time.

In recent years, attempts have been made to selectively encapsulate 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-1-190602). 1962
22701, JP-A-61-53201, etc.).

[0009]

Problems to be Solved by the Invention The host compounds described in the above cited references and the like are excellent in the inclusion ability of CMI, and those inclusion compounds have greatly reduced skin irritation and are easy to handle. It has become.

However, in the clathrate compounds using these host compounds, the release rate of CMI into the aqueous system at the time of use is too slow, and sterilization of systems that require immediate action, for example, circulating toilets for trains and the like, is required. Etc. could not be applied.

An object of the present invention is to provide a novel clathrate compound which selectively clathrates CMI and has a high release rate of CMI in an aqueous system.

[0012]

Means for Solving the Problems The present inventors have made intensive studies to achieve the above object, and as a result, hydroxybenzophenones are extremely excellent as host compounds that selectively include CMI, The present inventors have found that the release rate of CMI in an aqueous system from an inclusion compound is extremely faster than that of a known inclusion compound, and thus completed the present invention.

The present invention provides a compound represented by the following general formula (I):

Embedded image (Wherein at least two of R ^{1 to} R ⁴ represent a hydroxyl group, and the remainder represents a hydrogen atom and / or a lower alkoxy group), and a hydroxybenzophenone represented by the following chemical formula (I)

Embedded image 5-chloro-2-methyl-4-isothiazoline-
An inclusion compound characterized in that 3-one is a guest compound. Hereinafter, the present invention will be described in detail.

(Host compound) As specific examples of the host compound represented by the general formula (I), 2,4-dihydroxybenzophenone (hereinafter, referred to as "2,4-DHB"), 4,
4'-dihydroxybenzophenone (hereinafter referred to as "4,4'-DH
B ". ), 2,2'-dihydroxybenzophenone
(Hereinafter referred to as "2,2'-DHB"), 2,2'-dihydroxy-4-methoxybenzophenone (hereinafter referred to as "2,2'-DHM").
B ". ), 2,2′4,4-tetrahydroxybenzophenone (hereinafter referred to as “THB”). Among them, 2,4-DHB, 4,4'-DHB and THB are preferable because the obtained inclusion compound is a solid at room temperature and easy to handle. Particularly, 2,4-DHB is a selective inclusion property of CMI. It is preferable because it is excellent.

(Guest Compound) The CMI represented by the chemical formula (II) is a water-soluble bactericidal agent containing MI, which is a commercially available auxiliary component during synthesis, and magnesium chloride, magnesium nitrate, and the like as a stabilizer. Agent (Caisson WT, manufactured by Rohm and Haas).

(Clathrate compound) The clathrate compound is prepared by adding the water-soluble bactericide containing CMI as a main component to a slurry in which the host compound is suspended in water, at a temperature of room temperature to 50 ° C.
CMI is included in the host compound by stirring for 30 minutes to 180 minutes. The amount of inclusion of CMI varies depending on the type of the host compound, the reaction temperature and the reaction time, but is 0.1 to 0.5 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.
MI / CMI (molar ratio) is 0.15 or less. In particular, 2,4-
In the case of DHB, MI / CMI (molar ratio) is as small as 0.05, which is suitable as a host compound.

(Method of Using Inclusion Compound) The inclusion compound re-releases the CMI included in an aqueous system, and exhibits an effect as a bactericide. 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 which is solid at ordinary temperature, for example, tablets, granules, etc. (3) Put the clathrate compound in a container such as a water-insoluble and water-permeable bag or cartridge and immerse or float it in the treated water, (4) Directly Alternatively, it is possible to adopt a method in which the material is mixed with a paint, a resin, or the like, and is applied or adhered to a surface of equipment such as equipment and piping that is in contact with treated water.

[0018]

The present invention is characterized in that CMI is used as a guest compound and hydroxybenzophenones are selected as a host compound as described in detail above. Conditions for this type of host compound include: (1) a phenyl group in the molecular structure for maintaining the rigidity of the molecule. (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 at a certain level. (4) Low price and low toxicity. It is. As a host compound satisfying these conditions,
Although the hydroxybenzophenones were selected, it is not clear why the rate of re-release of CMI from these clathrates is higher than similar clathrates previously known.

On the other hand, inclusion of CMI reduces the toxicity and skin irritation of the host compound due to the toxicity and skin irritation of the host compound, and also reacts with other substances during use. Therefore, the antibacterial activity is prevented from being reduced.

(Examples) The present invention will be described in more detail with reference to Examples and Comparative Examples. However, the scope of the present invention is not limited by the following examples.

(1) Production of clathrate compounds (samples: A-1 to A-9, and comparative sample: C-1) 2,4-DHB, 4,4'-DHB, 2,4
5.7 mmol each of 2'-DHB, 2,2'-DHMB and THB
Was dispersed and suspended in 10 ml of water. Among them, a water-soluble disinfectant containing CMI as a main component (trade names: Caisson WT, ROHM
10 g (equivalent to 5.7 mmol as CMI) was added, and the mixture was stirred and reacted at a temperature of 25 to 50 ° C for 30 minutes to 3 hours. After the reaction solution was cooled to room temperature, it was filtered or separated with a membrane filter, and dried at room temperature under vacuum to obtain samples A-1 to A-9. For comparison, CMI was included under the same conditions as in the above sample, except that 2,2′-methylenebis (4-chlorophenol) was used as a host compound, to prepare a comparative sample: C-1.

The analytical values of the used water-soluble germicides are shown below. CMI: 10.1 wt% MI: 3.8 wt% The balance: magnesium chloride + magnesium nitrate + water

The obtained sample and the comparative sample were subjected to IR, X
As a result of analysis by line diffraction, DTA, HPLC, and TLC, the behavior was different from those of both starting materials, and thus the formation of an inclusion body was confirmed. Further, it was confirmed by an X-ray microanalyzer that magnesium chloride and magnesium nitrate were not contained. Table 1 shows the production conditions of each sample and the comparative sample, the amounts of inclusion of CMI and MI, and the melting points of the samples solid at room temperature. Sample (A-1),
The IR spectra of CMI isolated from 2,4-DHB and the water-soluble fungicide are shown in FIGS. 1, 2 and 3, respectively.
The X-ray spectrum is shown in FIG.

[0024]

[Table 1]

[0025]

FIG.

[0026]

FIG. 2

[0027]

FIG. 3

(2) CMI release test The sample (A-1) obtained in the above item (1) and the comparative sample (C
-1) and CMI alone are converted to CMI by 10
mg into a cellulose dialysis membrane, and add
Liter and agitating speed 100 rpm using a dissolution tester
Measure the amount of CMI released after a certain time while stirring with
The change with time was examined. The measurement results are shown in Table 2, and the release curve is shown in FIG.

[0029]

[Table 2] In the table, test number 2-1 is an example, and test numbers 2-2 and 2-3 are comparative examples.

As is evident from Table 2, CMI alone releases CMI 30 minutes after the dialysis membrane bag is immersed. On the contrary, in the comparative sample (C-1), about 50 hours elapse after 7 hours.
In contrast, the sample (A-1) has a release rate of about 90% in about 3 hours, indicating a moderate sustained release.

[0031]

As described above, the clathrate compound of the present invention is a novel clathrate compound using CMI, which is effective as a fungicide, as a guest and dihydroxybenzophenones as a host.

The clathrate compound of the present invention has the following effects: (1) Toxicity and skin irritation are reduced by inclusion of CMI having high toxicity and skin irritation with dihydroxybenzophenones having lower toxicity as a host. (2) Particularly, those which are solid at room temperature can be tableted and are extremely easy to handle. (3) Since CMI of the active ingredient is re-released at an appropriate rate in an aqueous system, it is effective as a fungicide having both immediate effect and sustained release. (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.

The present invention provides a novel clathrate compound which is effective as a bactericide having both immediate action and sustained release properties and is easy to handle, and a method for producing the same. The significance in the field of water treatment is extremely large.

[Brief description of the drawings]

FIG. 1 is an infrared absorption spectrum of a sample (A-1, clathrate) by a KBr method.

FIG. 2 is an infrared absorption spectrum of 2,4-DHB (host compound) by a KBr method.

FIG. 3 is an infrared absorption spectrum of a CMI (guest compound) by the KBr method.

FIG. 4 is an X-ray diffraction diagram of Sample A-1 (inclusion compound), 2,4-DHB (host compound), and CMI (guest compound). In the figure, (a) shows the case of sample A-1, (b) shows the case of 2,4-DHB, and (c) shows the case of CMI.

FIG. 5 shows sample A-1 (inclusion compound) and comparative sample C-
Re-release curve of CMI from 1. In the figure, (a) shows sample A-1.
(B) shows the comparison sample C-1 and (c) shows the case of CMI alone.

Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) C07D 275/02-275/03 C07C 49/83-49/84 A01N 43/80 CA (STN) REGISTRY (STN) WPI ( DIALOG)

Claims (2)

(57) [Claims] 1. A compound represented by the following general formula (I): (Wherein at least two of R ^{1 to} R ⁴ represent a hydroxyl group, and the remainder represents a hydrogen atom and / or a lower alkoxy group), and a hydroxybenzophenone represented by the following chemical formula (II): A clathrate compound comprising 5-chloro-2-methyl-4-isothiazolin-3-one represented by the formula: 2. A suspension of a hydroxybenzophenone represented by the general formula (I) in 5-chloro-2-methyl-4
2. A process for producing an inclusion compound according to claim 1, wherein a water-soluble bactericide containing isothiazolone is added.