JPS6075402A - Fungicide - Google Patents

Abstract

PURPOSE:To provide a fungicide containing an ethynyl ketone as an active component, exhibiting remarkable fungicidal effect to microorganisms, especially yeasts, molds, etc., and useful as a fungicide for pharmaceuticals, cosmetics, textiles, paper products, leather, wood works, plastics, etc. CONSTITUTION:The objective fungicide contains 10-1,000ppm of an ethynyl ketone of formula (X<1>-X<3> are H, or one of X<1> and X<3> is H and the other forms a bond together with X<2>; X<4>-X<6> are H, or one of X<4> and X<6> is H and the other forms a bond together with X<5>; n is 0 or 1). The compound of formula exhibits remarkable fungicidal effect to the yeasts such as Saccharomyces, Candida, etc., and the fungi such as Aspergillus, Penicillium, Trichophyton, etc., and has excellent bacteriostatic effect to Gram-positive and Gram-negative bacteria. It is low-toxic to human body and is free from irritation to the skin.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a pesticide containing ethynyl ketone represented by the general formula (I) 1-CHs CHs CHa O as an active ingredient.

However, in the above general formula (1), Xl, X2 and
3 are all hydrogen atoms, or one of Xl and X3 is a hydrogen atom and the other forms a bond with X2, and x', x5 and X6 are all hydrogen atoms, or One of X4 and X6 is a hydrogen atom, and the other forms a bond with X5. n represents an integer of O or 1.

Since ancient times, in Japan, sake, miso, and soy sauce have been made by fully utilizing the unique characteristics and abilities of microorganisms, and the microbial industry has a long history. In recent years, the discovery and development of antibiotics has progressed rapidly, and this has led to the synthesis and production of amino acids by microorganisms, the production of proteins from petroleum, and the extraction of useful metals from ores using the action of microorganisms. The new role that microorganisms play in a variety of industries, such as pollution control technology and pollution control technology, is now becoming more and more highly regarded. However, on the other hand, the damage caused by the action of microorganisms can include diseases of animals and plants, spoilage and deterioration of food and feed, cosmetics, quasi-drugs, textile and paper products, leather products, wood products, paints, and plastic materials. , metals, electronic equipment, optical machinery, and other industries, causing great losses.

Traditionally, for the purpose of preventing damage caused by microorganisms, organic metal agents such as inorganic metal agents, organic mercury agents, and organic tin agents, aromatic phenol derivatives such as phenol, and their halogen-substituted products have been used. Although they have been mainly used, the toxicity of these compounds has recently become a problem, and the use of most of them has had to be discontinued. Therefore, a wide range of industries are searching for substances that prevent deterioration and corrosion caused by microorganisms, are non-hostile or have extremely low toxicity to the human body, are easy to handle, and have stable effects over a long period of time. has continued.

As a result of repeated research by the present inventors on the prevention of deterioration and corrosion caused by microorganisms from the above-mentioned viewpoint, we have found that ethynyl ketone represented by the general formula 3 (I) is effective against microorganisms, especially yeasts such as Satucharomyces and Candida, Aspergillus, Penicillium, etc.・1. Against mold such as Lycophyton.
They discovered that it has a remarkable bactericidal effect and completed the present invention.

Ethinyl ketone represented by the general formula (1) can also be used for Staphylococcus, Streptococcus, Streptococcus, Tetracoccus, Dilococcus, Monococcus, Bacillus, Aerococcus, Corynebacterium,
It has excellent bacteriostatic activity against Gram-positive bacteria such as Clostridium, Mycobacterium, Lactic Acid Bacteria, and Nocardia, and Gram-negative bacteria such as Salmonella, and has extremely low toxicity to the human body and is non-irritating to the skin. It also has the advantage of being free of blemishes.

Representative examples of ethynyl keto/ represented by general formula (I) are shown below.

4- (4) Length, length, etc. 4 5- The ethynyl ketone represented by the general formula (I) can be produced, for example, by the following method.

(n) (III) 11 oxide → (1) (wherein, Xl, Xl, X3, X4, X5, X6 and n
is as defined above, and X represents a halogen atom. ) That is, ethynyl alcohol represented by the general formula (III) is obtained by reacting the aldehyde represented by the general formula (■) with ethynylmagnesium halide. Examples of the aldehyde represented by the general formula ([) include citronellal and dihydrof-6-arnesal. Ethynylmagnesium halide is prepared by reacting an alkyl halide with metallic magnesium at a temperature of about -30°C to 50°C in an ethereal solvent such as tetrahydrofuran or diethyl ether under an inert gas atmosphere such as nitrogen or helium. It can be prepared by dropping an ether-based solvent solution of an alkylmagnesium halide that can be prepared into an ether-based solvent such as tetrahydrofuran saturated with acetylene under a stream of acetylene while maintaining the temperature at about -30°C to 50°C. can.

The aldehyde represented by the general formula ([) is added dropwise to this prepared solution at a temperature of about -30°C to 50°C, preferably about -10°C to 20°C, and the mixture is left at the same temperature or at room temperature for about 0.5 to
By stirring for 10 hours, a reaction mixture containing ethynyl alcohol represented by general formula (III') is obtained.

The amount of aldehyde represented by general formula (n) used is about 0.3 to 1 equivalent relative to ethynylmagnesium oxide. Separation and recovery of ethynyl alcohol from the reaction mixture can be carried out by a conventional method. For example, the reaction mixture is poured into a large amount of water, then extracted with a solvent such as diethyl ether, hexane, or benzene, and the extract is washed with water and dried.
By distilling off the solvent, ethynyl alcohol represented by general formula (III) is obtained.

This ethynyl alcohol can be subjected to the next oxidation reaction without being purified, but it is also possible to subject ethynyl alcohol that has been further purified by distillation or column chromatography to the oxidation reaction. Ethynyl ketone represented by general formula (1) is obtained by oxidizing ethynyl alcohol represented by general formula (■). This oxidation reaction can be carried out according to a conventional oxidation method, but it is convenient to carry out a known method of treating with a suitable oxidizing agent such as pyridinium chlorochromate or chromium sulfuric acid. The appropriate amount of the oxidizing agent to be used is about 1 to 2 equivalents based on ethynyl alcohol. This oxidation reaction is carried out by stirring at a temperature of about -30°C to 50°C, preferably at room temperature, for about 0.5 to 24 hours. Further, this reaction is preferably carried out in the presence of an 8-solvent, and an inert solvent such as methylene chloride or acetone is used as the solvent. After the reaction is complete, add diethyl ether, hexane,
After adding a solvent such as heptane and removing the solid matter by decantation, the solvent is distilled off and the remaining oil is subjected to, for example, column chromatography to obtain the ethynyl ketone represented by the general formula (1). I can do it.

The ethynyl ketone represented by the general formula (I) can be used as a disinfectant as it is or a mixture of two or more thereof, or one or more of the ethynyl ketones can be used with various dilution aids. It can also be used as a bactericidal agent by blending it with a solvent, surfactant, etc., and formulating it in the form of an emulsion, an aquarium, etc.

When using a bactericide containing ethynyl ketone represented by the general formula (1) of the present invention as an active ingredient, the bactericide may be used in pharmaceuticals, quasi-drugs, cosmetics, textiles, paper products, leather products, processed wood products, etc. Paints, plastic materials, metals, electronic equipment,
Depending on the shape of the product, such as an optical machine, it may be mixed, applied, or sprayed. In particular, when mixed with cosmetics such as medicated soaps, make-up soaps, lotions, lotions, and creams, they may be used to disinfect the skin or cause irritation to the skin, such as impetigo, hair rash from shaving, folliculitis, acne scars, skin irritation, and eczema. Effective in preventing diseases. Furthermore, by mixing the disinfectant of the present invention with a cleaning agent, etc., the cleaning action of the cleaning agent can be improved. The appropriate amount of the disinfectant of the present invention to be used is usually about 10 to 11,000 pp in terms of the amount of the active ingredient of ethynyl ketone represented by the general formula (I) contained in quasi-drugs, cosmetics, paints, etc., for example.

An example of the synthesis of ethynyl ketone represented by the general formula (1) is shown below, as well as test examples and examples to clarify the effect of the ethynyl ketone on microorganisms.

Synthesis Example 500 100 wrl of tetrahydrofuran was placed in a glass flask, and dry acetylene was dissolved therein dropwise. Then, while blowing in the acebon,
100 mg of a tetrahydrofuran solution containing 16.0 fQ of ethylmagnesium bromide was gradually added dropwise to prepare a tetrahydrofuran solution of ethynylmagnesium bromide. A solution of citronellal 15.4F dissolved in 50 yul of tetrahydrofuran was added to this prepared solution at a temperature of 1.
The mixture was added dropwise while maintaining the temperature at 0 to 15°C, and after addition of drop F, the mixture was further stirred at room temperature for 6 hours.

Pour the reaction mixture into 11 ml of water and add 600 ml of diethyl ether.
Extracted with /. The extract was added 3 times with 300 ml of water, for a total of 90
After washing with 0 ml of water, it was dried with anhydrous sulfuric acid (IJ). Ether was removed from this extract using an evaporator, and the remaining oil was distilled under reduced pressure to obtain fraction 9.02 with a boiling point of 132-b. This fraction was mixed with 200rue of methylene chloride containing 11.99% of pyridinium chlorochromate.
The solution was added dropwise to the solution at room temperature, and after the dropwise addition, the solution was stirred for 5 hours. After adding 300 d of diethyl ether to the reaction mixture and removing the dark brown solid by decantation,
Methylene chloride and ether were removed using an evaporator, and the remaining oil was subjected to silica gel column chromatography to obtain a pale yellow liquid 6.2y.

This liquid was subjected to the following M a s s spectrum and NM
The compound was identified as 5.9-dimethyldec-8-en-1-yn-3-one [compound (1)] in the R spectrum.

Mass area #mle: 178 [M] 11
63 (M-CHs)
The presence of on was confirmed.

NMR spectrum (500MHz) δCDα3・HM
S' 0.90 (d, 3H); 1.62 (s, 3H); 1.0
~1.4(m, 3H); 1,'l-2,6(m, 4H
); 1.55 (S, 3H) ; 3.25 (s
, IH); 5.05 (t, LH) Compounds (2) to (γ) were obtained by the same method. The mass spectra of each compound are as described above.

Test Example MIC (Minimum Inhibitory Concentration) (I-
Shown in Table 1.

Test method: Dilute the test bath solution with a concentration of 10 μg/wte in 10 steps, put 1 rue of each concentration into a Petri dish, add 9 rag of potato dextrose agar medium, and mix and dilute well before solidifying. , prepare a flat plate. On the other hand, a bacterial suspension of test bacteria cultured on a potato dextrose agar slant medium is prepared, a loopful of the suspension is applied onto a previously prepared plate, and cultured at 27°C for 72 hours. Then, determine the minimum concentration that inhibits the growth of the applied bacteria. The bacterial strains used in the test are shown below.

Strain 1 Candida albicans IFO1060
(Candida albicans IFO1060
)42 7 Svergillus niger M-63 (Asper
gillus niger M-63) 43 Penicillium tutatum IFO4640 (Penicill
tum notatum IFO4640) 44) Lycophiton mentagrophytes AHU 9244
(Trichophyton mentagrophy
tes A)lU9244) flat 5
Rubrum IFO5467 (Trichophyton
rubrum IFO5467) = 13 - Table 1 The numbers in the table indicate the concentration of the compound that inhibits bacterial growth by γ/1.
Indicated by

Example White ointment consisting of purified lanolin 101, brush beeswax 10f1, white petrolatum 802, and glycerin 10? A base was prepared by adding . Base 252 was prepared with compound (1) and undecylenic acid added at 10 γ/1, -]4-50 γ/V, and 100 γ/2, respectively, and a base 252 was added with potato dextrose slanted agar. Cultured Penicillium tutatum IFO4640 (Penicilli) for 3 days at 27°C using medium
um notatum IFO4640) (7) Spore suspension l tnl (approximately 106 to 107 spores/1n
1) was inoculated, stirred well, and then cultured at 27°C. After 1 day and 3 days of culture, a loopful of each base was taken and spread on a potato dextrose agar medium and cultured for 3 days, after which the growth state of the bacteria was examined.

The results are shown in Table 2. The symbols in the table have the following meanings.

+: Growth of bacteria is observed.

±: Slight bacterial growth is observed.

-: No bacterial growth is observed.

Table 2 15- 9-

Claims (1)

[Claims] General formula (wherein xl, x2 and X4
, X5 and X6 are both hydrogen atoms or λ
Either one of 4 and X6 is a hydrogen atom and the other is X
Together with 5, it forms a bond, and n represents an integer of 0 or 1. ) A disinfectant containing ethynyl ketone as an active ingredient.