CHLOROACETATE DERIVATIVES AND GERMICIDES

Abstract: A 2-nitroalkyl chloroacetate derivative having the for­ mula: wherein each of R¹ and R² is a hydrogen atom or a lower alkyl group.

Description: CHLOROACETATE DERIVATIVES AND GERMICIDES The present invention relates to a 2-nitroalkyl chloroacetate and a germicide containing it as an active ingredient. In recent years, intensive horticultural cultivation and cultivation of garden products have become popular. Accordingly, not only the efficiency in cultivation but also repeated cultivation on the same ground is required. In general, repeated cultivation of the same crop on the same ground tends to lead to a decrease in the harvest without application of agricultural chemicals, and in an extreme case, there will be substantially no harvest. It is believed that this is caused mainly by soil disease-germs. In order to avoid such an undesirable situation, it has been common to employ gaseous fumigating agents such as chloropicrin, methyl bromide or methyl isothiocyanate. However, such agents have some drawbacks. For instance, 1) they show strong phytotoxicity against crop plants, 2) they bring about an inconvenience in their application such that after their application to the soil surface to attain the desired effectiveness, it is necessary to plow the soil to prevent phytotoxicity, and 3) some of them are lachrymatory or skin-irritative, and some others are likely to induce mutation, thus bringing about a difficulty in the safety. Under the circumstances, it has been desired to develop an effective agent which has no phytotoxicity and which is convenient and safe in its use. The present inventors have conducted extensive studies to solve such problems, and have finally accomplished the present invention on the basis of a discovery that certain chloroacetate compounds have extremely effective germicidal activities. In a first aspect, the present invention provides a compound having the formula: EMI2.1 wherein each of R1 and RZ is a hydrogen atom or a lower alkyl group. In a second aspect, the present invention provides an germicide comprising an germicidally effective amount of the compound of the formula I and a carrier. Now, the present invention will be described in further detail with reference to the preferred embodiments. The compounds of the present invention are readily synthesized by the following methods. Namely, they can be synthesized almost quantitatively in a simple manner by such a method in which a 2-nitroalkyl alcohol and chloroacetic acid chloride or chloroacetic acid anhydride are reacted in the presence of a base, or a method in which a 2-nitroalkyl alcohol and chloroacetic acid are condensed by means of a dehydrating agent. The physical properties of representative compounds of the present invention are as shown in Table 1. Table 1 EMI4.1 <tb> Compound <SEP> Boiling <SEP> point <tb> <SEP> No. <SEP> ( C/mmHg) <SEP> <tb> No. <SEP> 1 <SEP> 53-55/0.1 <SEP> 40.5(t) <SEP> 60.9(t) <tb> <SEP> R1:H <SEP> 73.2(t) <SEP> 166.8(s) <tb> <SEP> R2 <SEP> H <tb> No. <SEP> 2 <SEP> 61-63/0.09 <SEP> 15.3(q) <SEP> 40.3(t) <SEP> 65.4(t) <tb> <SEP> R1:H <SEP> 80.5(d) <SEP> 166.4(s) <tb> <SEP> R2 <SEP> :CH3 <SEP> <tb> No. <SEP> 3 <SEP> 72-73/0.1 <SEP> 9.5(q) <SEP> 23.3(t) <SEP> 40.2(t) <tb> <SEP> R1:H <SEP> 64.5(t) <SEP> 87.0(d) <SEP> 166.6(s) <tb> <SEP> Rê:C2H5 <SEP> <tb> No. <SEP> 4 <SEP> 62-63/0.1 <SEP> 16.1(q) <SEP> 40.2(t) <SEP> 68.3(d) <tb> <SEP> R1 <SEP> :CH1 <SEP> <SEP> 77.4(t) <SEP> 165.8(s) <tb> <SEP> Rê:H <SEP> <tb> No. <SEP> 5 <SEP> 70-71/0.08 <SEP> 8.8(q) <SEP> 24.2(t) <SEP> 40.5(t) <tb> <SEP> R1 <SEP> vC2H5 <SEP> <SEP> 72.7(d) <SEP> 76.5(t) <SEP> 166.3(s) <tb> <SEP> R2:H <SEP> <tb> No. <SEP> 6 <SEP> 69-72/0.07 <SEP> 12.9(q) <SEP> 15.5(q) <SEP> 40.5(d) <tb> <SEP> R1 <SEP> :CH3 <SEP> 71.5(d) <SEP> 72.3(d) <tb> <SEP> R2:CH3 <SEP> 84.0(d) <SEP> 85.2(d) <SEP> 165.9(s) <tb> Compound No. 1: ClCH2COOCH2CH2NO2 Compound No. 2: ClCH2COOCH2CH(CH3)NO2 Compound No. 3: ClCH2COoCH2CH(C2H5)NO2 Compound No. 4: ClCH2COOCH(CH3)CH2NO2 Compound No. 5: ClCH2COOCH(C2H5)CH2NO2 Compound No. 6: ClCH2CoOCH(CH3)CH(CH3)N02 The compounds of the present invention are useful not only for the agricultural purposes, but also in many other fields such as medical or industrial fields wherein microorganisms are concerned. Further, they may be used in various optional formulations such as oil, emulsifiable concentrates, wettable powders, granules or dusts by mixing them with various carriers depending upon the particular purposes. Particularly useful are emulsifiable concentrates and granules. The carriers for this purpose may be liquid or solid, or a combination thereof. As solid carriers, there may be mentioned bentonite, talc, clay, diatomaceous earth, fuller's earth (Japanese acid clay) or dextrin. As liquid carriers, there may be mentioned inert solvents such as xylene, isophorone, kerosine or alcohols. For the preparation of formulations, surfactans or the like may be incorporated to provide emulsifiable or dispersible properties. Such formulations are readily obtainable by conventional methods for the preparation of agricultural chemicals which are commonly employed. The effective amount of the active ingredient is usually within a range of from 5 to 30% by weight in the case of granules, and within a range of from 5 to 95% by weight in the case of oil or emulsifiable concentrates. The compounds of the present invention may be used alone. However, in some cases, they may be used in a combination with other agricultural chemicals such as other germicides, insecticides or herbicides. Compounds of the present invention have no phytotoxicity, and they are simple in use and show little toxicity against human and animals and extremely high germicidal activities. The compounds of the present invention are effective against Gram positive bacteria, Gram negative bacteria, Ascomycetes, Basidomycetes, Phycomycetes, etc. Now, the effectiveness of the compounds of the present invention will be shown by Test Examples. Test Example 1 To a 20 ml of a meat extract-peptone agar culture medium, 100 pQ of a dimethylsulfoxide solution of a 2-nitroalkyl chloroacetate having a predetermined concentration was added, and the mixture was poured into a Petri dish to form a plate culture medium. Onto this culture medium, Bacillus subtilis and Salmonella typhimurium were applied in straight lines and cultured at 37 0C overnight, whereupon the concentration for the inhibition of the growth of the bacteria was determined. The evaluation of the effectiveness was made in accordance with the following ratings: Ratings Evaluation standards 4 Complete growth inhibition 3 More than 75% growth inhibition 2 50 - 75% growth inhibition 1 25 - 50% growth inhibition 0 No substantial growth inhibition The results are shown in Table 2. Table 2 EMI7.1 <tb> Bacteria <SEP> Bacillus <SEP> subtilis <SEP> | <SEP> Salmonella <tb> <SEP> t <SEP> typhimurium <tb> <SEP> Concentration <SEP> 1 <SEP> Concentration <SEP> (ppm) <SEP> Concentration <SEP> (ppm) <tb> compound <SEP> No. <SEP> ¯ <SEP> 1 <SEP> 12.5 <SEP> ¯ <SEP> 25 <SEP> 50 <SEP> 100 <SEP> i12.5 <SEP> 25 <SEP> 50 <SEP> 100 <tb> <SEP> No. <SEP> 1 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> No. <SEP> 2 <SEP> 0 <SEP> 1 <SEP> 4 <SEP> 4 <SEP> 0 <SEP> 3 <SEP> 4 <SEP> 4 <tb> <SEP> No. <SEP> 3 <SEP> 0 <SEP> 0 <SEP> 4 <SEP> 4 <SEP> 0 <SEP> 0 <SEP> 4 <SEP> 4 <tb> <SEP> No. <SEP> 4 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <tb> <SEP> No. <SEP> 5 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 0 <SEP> 2 <tb> <SEP> No. <SEP> 6 <SEP> 0 <SEP> 0 <SEP> 4 <SEP> 4 <SEP> 0 <SEP> 3 <SEP> 4 <SEP> 4 <tb> Test Example 2 To 20 ml of a potato-dextrose agar culture medium (PDA medium), 100.QDf a dimethylsulfoxide solution of a 2-nitroalkyl chloroacetate having a predetermined concentration was added at a temperature of from 40 to 42 0C, and the mixture was poured into a Petri dish to form a plate culture medium. Onto this culture medium, two disc specimens with a diameter of 4 mm of each of Fusarium solani, Rhizoctonia solani and Pythium aphanidermatum, which were preliminarily cultured on PDA culture media, were placed, and cultured at 25 0C for 5 days in the case of Fusarium solani, and 3 days in the cases of Rhizoctonia solani and Pythium aphanidermatum. Then, the diameter of each colony was measured, and the inhibition value was calculated as compared with the non-treated medium, and thus the effectiveness was evaluated. Colony diameter on Inhibition (1 = treated medium value (1 Colony diameter on non- ) x 100 trated medium The test was repeated twice for each concentration, and to the non-treated medium, only dimethylsulfoxide was added. The average values of the results are shown in Table 3. Table 3 EMI8.1 <tb> <SEP> Bacteria <SEP> Pythium <SEP> Fusarium <SEP> Rhizoctonia <tb> <SEP> aphanidermatum <SEP> solani <SEP> solani <tb> Concentration <SEP> 12.5 <SEP> 25 <SEP> 50 <SEP> Concentration <SEP> (E <SEP> (ppm) <tb> <SEP> 12.5 <SEP> 25 <SEP> 50 <SEP> 12.5 <SEP> 25 <SEP> 50 <SEP> 3.125 <SEP> 6.25 <SEP> 12.5 <tb> Compound <SEP> No. <tb> <SEP> No. <SEP> 1 <SEP> 16 <SEP> 50 <SEP> 92 <SEP> 20 <SEP> 100 <SEP> 100 <SEP> 16 <SEP> 77 <SEP> 100 <tb> <SEP> No. <SEP> 2 <SEP> 31 <SEP> 74 <SEP> 100 <SEP> 11 <SEP> 100 <SEP> 100 <SEP> 16 <SEP> 100 <SEP> 100 <tb> <SEP> No. <SEP> 3 <SEP> 41 <SEP> 71 <SEP> 93 <SEP> 9 <SEP> 18 <SEP> 59 <SEP> 9 <SEP> 29 <SEP> 87 <tb> <SEP> No. <SEP> 4 <SEP> 14 <SEP> 39 <SEP> 92 <SEP> 14 <SEP> 72 <SEP> 100 <SEP> 0 <SEP> 7 <SEP> 64 <tb> <SEP> No. <SEP> 5 <SEP> 21 <SEP> 64 <SEP> 94 <SEP> 16 <SEP> 41 <SEP> 100 <SEP> 6 <SEP> 23 <SEP> 40 <tb> <SEP> No. <SEP> 6 <SEP> 67 <SEP> 94 <SEP> 100 <SEP> 22 <SEP> 40 <SEP> 100 <SEP> 28 <SEP> 53 <SEP> 75 <tb> Test Example 3 Into a l/l0,000a pot, 1 kg of soil infested with Fusarium oxysporum raphani, was put, and one of the compounds of the present invention according to Example 1 given hereinafter and comparative agents i.e. Difolatan lN-(1,1,2,2-tetrachloroethylthio)-4-cyclohexene-1,2- dicarboxyimide] and chloropicrin, was mixed to the soil isnraypredetermined amount. The treated soil was left to stand in a glass chamber (20 - 300C) for a week. Further, in the case of chloropicrin, the soil was spread for degassing for 3 hours. Then, 15 seeds per pot of a Japanese radish (variety: Aokubimiyashige) were sown. Three weeks after the seeding, the presence or absence of the blackening of the stem portion was examined to determine the deseased rate. The test was repeated twice for each compound. The average values of the results are shown in Table 4. Table 4 EMI9.1 <tb> <SEP> Concentration <SEP> of <SEP> Diseased <tb> impound <SEP> the <SEP> active <SEP> rate <SEP> Phytotoxicity <tb> <SEP> No. <SEP> ingredient <SEP> (sum) <SEP> (%) <tb> <SEP> No. <SEP> 1 <SEP> 50 <SEP> 0 <SEP> Nil <tb> <SEP> 100 <SEP> 0 <SEP> Slight <SEP> growth <tb> <SEP> inhibition <tb> <SEP> No. <SEP> 2 <SEP> 50 <SEP> 16 <SEP> Nil <tb> <SEP> 100 <SEP> 0 <SEP> Nil <tb> <SEP> No. <SEP> 3 <SEP> 50 <SEP> 8 <SEP> Nil <tb> <SEP> 100 <SEP> 6 <SEP> Nil <tb> <SEP> No. <SEP> 4 <SEP> 50 <SEP> 6 <SEP> Nil <tb> <SEP> 100 <SEP> 0 <SEP> Slight <SEP> rolling <SEP> of <tb> <SEP> leaves <tb> <SEP> No. <SEP> 5 <SEP> 50 <SEP> 8 <SEP> Nil <tb> <SEP> 100 <SEP> 0 <SEP> Nil <tb> <SEP> No. <SEP> 6 <SEP> 50 <SEP> 16 <SEP> Nil <tb> <SEP> 100 <SEP> 0 <SEP> Nil <tb> (Comparative compounds) Diafolatan 50 17 Slight growth inhibition Chloropicrin 300 3 Nil Non-treatment - 88 Nil Test Example 4 At an agricultural field infested with Fusarium oxysporum f. Sp. raphani, an oil agent of 2-nitroethyl chloroacetate according to Example 5 given hereinafter, was applied to the soil surface at a rate of 40 liter per 10 ares, and immediately, the soil was plowed by a tractor. As a comparative agent, chloropicrin was applied by injection treatment at 30 cm intervals at a depth of 15 cm from the soil surface at a rate of 20 liter per 10 ares, and 7 days later, the soil was plowed for degassing. Ten days after the application of the germicide, seeds of a Japanese radish (variety: Aokubimiyashige) were sown at 30 cm intervals. One month later, thinning out was conducted, and 3 months later, roots were cut off to examine the presence or absence of the desease. The test was repeated 3 times each with a unit field area of 7.5 m2, and 40 radishes per unit field area were examined. The average values of the results are shown in Table 5. Table 5 Amount of the active Diseased Germicide ingredcient applied rate (kg/l0 a) Germicide of the 19.2 5.8% present invention Chloropicrin 32.3 6.7% Non-treatment - 81.7% As shown above, 2-nitroalkyl chloroacetates of the present invention show high germicidal activities against not only various filamentous fungi which give serious damages to crops, but also Gram positive bacteria and Gram negative bacteria which create various problems in various fields. Yet, they do not require cumbersome degassification as is required in the case of chloropicrin, and they show no substantial phytotoxicity to crop plants. Now, formulation examples of the present invention will be described. In these Examples, "parts" means "parts by weight". EXAMPLE 1: Granules 2-Nitroethyl chloroacetate 20 parts Granular terra abla 80 parts The active ingredient was impregnated in granular terra abla to obtain the granules of the present invention. EXAMPLE 2: Granules Bentonite 35 parts Diatomaceous earth 60 parts Nonarl 204 (trademark, 2 parts manufactured by Toho Kagaku K.K.) RapizolB-80 (trademark, 3 parts manufactured by Nippon oil and Fat Co., Ltd.) The above components were mixed and kneaded with water. The mixture was granulated in a wet system, and then dried. To 70 parts of the dried granular product, 30 parts of 2-nitropropyl chloroacetate was impregnated to obtain granules of the present invention. EXAMPLE 3: Etnulsion 2-Nitrobutyl chloroacetate 85 parts Xylene 12 parts Sorpol 900B (trademark, 3 parts manufactured by Toho Kagaku K.K.) The above components were mixed to obtain an emulsion of the present invention. EXAMPLE 4: Oil l-Methyl-2-nitroethyl chloroacetate 50 parts Xylene 50 parts The above components were mixed to obtain an oil of the present invention. EXAMPLE 5: Oil 2-Nitroethyl chloroacetate 40 parts 2-Chlorotoluene 60 parts The above components were mixed toobtain an oil of the present invention. EXAMPLE 6: Emulsifiable concentrate 2-Nitroethyl chloroacetate 50 parts Xylene 40 parts Toxanon 1006 (trademark, 10 parts manufactured by Sanyo Chemical Industries Co., Ltd.) The above componests were mixed to obtain an emulsion of the present invention.

Claims: CLAIMS: 1. A 2-nitroalkyl chloroacetate derivative having the formula: EMI14.1 wherein each of RÚ and Rê a hydrogen atom or a lower alkyl group. 2. The 2-nitroalkyl chloroacetate derivative according to Claim 1, wherein the lower alkyl group is a methyl group or an ethyl group. 3. 2-Nitroethyl chloroacetate according to Claim 1. 4. l-Methyl-2-nitroethyl chloroacetate according to Claim 1. 5. l-Ethyl-2-nitroethyl chloroacetate according to Claim 1. 6. 2-Nitropropyl chloroacetate according to Claim 1. 7. 2-Nitrobutyl chloroacetate according to Claim 1. 8. l-Methyl-2-nitropropyl chloroacetate according to Claim 1. 9. A germicide comprising a germicidally effective amount of a 2-nitroalkyl chloroacetate derivative as defined in Claim 1 and a carrier.

Inventors: KAWADA, HIROSHI, SHINDO, NOBORU
Applicants: HODOGAYA CHEMICAL CO., LTD.
Application year: 1985
Main classification: C07C79
IPC codes: C07C67, A01N37, C07C205, C07C201