Novel cyclopropanecarboxylate
United States Patent 1 1 Okuno et al.  
 [ Apr. 8, 1975 1 NOVEL CYCLOPROPANECARBOXYLATE [75] Inventors: Yoshitoshi Okuno, Toyonaka;  
 Nobushige ltaya, lkeda Toshio Mizutani, Toyonaka, all of Japan [73] Assignee: Sumotomo Chemical Company,  
 Limited, Osaka. Japan 221 Filed: May 29,1973  
  2] Appl. No.: 364,271  
 [30] Foreign Application Priority Data Primary Examiner-Robert Gerstl Attorney, Agent, or Firm-Stevens, Davis, Miller &amp; Mosher [57] ABSTRACT A compound of the formula,  
 CH3 cu-0004a TC i CH5 I C-R CH; CIO I wherein R is hydrogen or methyl group, which is harmless to warm-blooded animals, useful as an active ingredient of insecticides, particularly in the form of fumigant, and prepared by reacting a compound of the formula,  
 with a compound of the formula,  
 CH5 CH- coon C CH5 C-R wherein R has the same meanings as defined above. or a reactive thereof.  
 3 Claims, No Drawings 1 NOVEL CYCLOPROPANECARBOXYLATE This invention relates to novel cyclopropanecarboxylic acid esters, to a process for preparing the said esters. and to insecticidal composition containing the said es-. ters.  
  More particularly, the present invention pertains to cyclopropanecarboxylic acid esters represented by the formula (1),  
 wherein R is hydrogen atom or methyl group.  
 Specific examples of the cyclopropanecarboxylate that the present compounds of the formula (I) have far more excellent insecticidal activities when used in the form not only of oil sprays, emulsifiable concentrate and aerosols, but particularly, of fumigant.  
  Therefore, an object of the present invention is to provide novel carboxylic acid esters excellent in insecticidal activity.  
  Another object is to provide a process for preparing novel carboxylic acid esters excellent in insecticidal activity.  
  Further object is to provide insecticidal compositions containing novel carboxylic acid esters as active ingredients.  
  The insecticidal effects of the ester compound obtained by reacting 2-propargyl-3-methyl-4-hydroxy-2- cyclopentene-l-on (alcohol moiety of the present ester) represented by the formula (ll),  
  HO-CH \CCH2-CECH (II) (l) are in Table 1. CH2 O Table l I l l igg Name l Formula CH3 2-propar-55yl-FJ- l methyL-Z-cyelo- H C so penten lon4-yl CH C COO-CH C-CH C CZ 1 2&#39;,2&#39;,&#39;5&#39;-1;ri- 1 methyl--cyc1o- CH C l propane carboxy- &#39;CH CH O late l 2prope.r; l?j-- Q methyl &#39;1-eyelol pencene-l-on-A-5,&#39;l CH7, CH COO-CH C-CHy C LI-I 2 l I 2 CH; C l .611 6-611 Various insecticides of the cyclopropanecarboxylic acid ester type. such as pyrethrin or allethrin, have with chrysanthemic acid have been reported by Gersdorff and Piquett [(Gersdorff, Piquett; J. Econ.  
 heretofore been known and widely been used for the Entomol 54, 1250 (l96l )1.  
 control of sanitary injurious insects and agricultural and horticultural injurious insects because of their such excellent insecticidal properties that they are not only high in insecticidal activity but also low in toxicity to mammals and quick in knock-down effect on injurious insects.  
  Recently, it is the most important problem to control mosquitoes carrying encephalitis, filariasis or other infection diseases, among domestic injurious insects. As  
 the most suitable insecticide such fumigants as mos- According to the report, the effect of this chrysanthemic acid ester to house flies was only 64 percent of that of the composition containing allethrin in the turn table method of oil sprays. The present inventors attempted the modification of the homologs of this chrysanthemic acid esters and examined the insecticidal effects of the present esters. As the result. the present inventors have found that the present esters of the formula (l) have more excellent knock down effect and killing effect than that of allethrin, and moreover vapor pressure of present compounds was higher than that of allethrin. Therefore, present inventors have found that the present compounds exhibit far more excellent insecticidal effects in particular when used as fumigant.  
  2,2,3-Trimethylcyclopropanecarboxylic acid and 2,- 2,3,3-tetramethylcyclopropanecarboxylic acid (the acid moiety of the present ester) can be prepared by the method of Matsui and Kitahara [described in Agr.  
 Biol. Chem. 31, 1143 (1967)], and these acids can be synthesized more easily and at lower costs. As the result. the present esters of the formula (1) can be also obtained at far lower costs and have more excellent practicity than that of known insecticides of pyrethroid type.  
  The present esters of the formula (I) are novel compounds and can be obtained by reacting 2-propargyl-3- methyl-4-hydroxy-2-cyclopentene-l-on with cyclopropanecarboxylic acid or reactive derivative thereof represented by the formula (lll).  
  CH-COOH (III) (II-R CH5 wherein R is the same meanings as defined above, if necessary, in the presence of auxiliary agent.  
  Embodiments of the above mentioned reactive derivative include acid halide and acid anhydride.  
  In accordance with the process of the present invention, in case a carboxylic acid of the formula (111) is used, the reaction is carried out under dehydration conditions. That is, the acid is reacted at room temperature or at an elevated temperature with cyclopentenone of the formula (ll) in a suitable inert solvent in the presence of a dehydrating agent such as dicyclohexyl carbodiimide, whereby a desired ester can be obtained in a high yield.  
  In case an acid halide is used as a reactive derivative of the carboxylic acid of the general formula (lll), the reaction can be sufficiently accomplished at room temperature by reacting the acid halide with a cyclopentenolone of the formula ([1), using as a hydrogen halide-removing reagent such as organic tertiary base as pyridine. triethylamine or the like. The acid halide used in this case may be any of the halides within the scope of the present invention, but is ordinarily an acid chloride. In the reaction, the use ofa solvent is desirable for smooth progress of the reaction. and such an inert solvent as benzene, toluene or petroleum benzine is ordinarily used. The acid halide of the formula (lll) which is used in the present invention may be prepared easily according to the ordinary procedure comprising halogenating the carboxylic acid with thienyl halide, phosphorous polyhalide or the like.  
  In case an acid anhydride is used as a reactive derivative of the carboxylic acid of the formula (lll), no auxiliary agent is particularly required. and the object can be accomplished by reacting the acid anhydride with a cyclopentenone of the formula (ll). In this case, the el- Example I A solution of 5,3 g of 2-propargyl-3-methyl-4- hydroxy-2-cyclopentene-l-on and 4.2 g of pyridine in ml of dry benzene was cooled with ice, and a solution of 5.3 g of 2,2,3-trimethylcyclopropanecarbonyl chloride in 15 ml of dry benzene was added dropwise thereto. The resulting reaction mixture was sealed and left overnight. After the reaction mixture was poured into ice water, the organic layer was separated and washed with 5 percent (by weight) aqueous hydrochloric acid solution, 5 percent (by weight) aqueous sodium carbonate solution and an aqueous solution saturated with sodium chloride, and then dried over anhydrous magnesium sulfate. Benzene was evaporated to obtain 9.] g of yellowish oil. Distillation under a reduced pressure gave 7.9 g of a yellowish oil of 2- evation of temperature is preferable for acceleration of propargyl-3-methyl-2-cyclopentenel -on-4-yl-2 &#39;,2 &#39;,3 trimethylcyclopropanecarboxylate (n,, 1.4988).  
 Elementary Analysis C &#34;/1 H 71 Found 73.91 7( 7.74 &#39;/1 Calculated 73.82 71 7.74  
 EXAMPLE 2 EXAMPLE 3 To a solution of 5.3 g of 2-propargyl-3-methyl-4- hydroxy-2-cyclopentene-l-on and 4.5 g of 2,2,3- trimethylcyclopropanecarbonxylic acid dissolved in ml of methylenechloride, 7.9 g of dicyclohexycarbodiimide was added thereto. The resulting reaction mixture was stirred at room temperature for 24 hours and heated for 3 hours to complete the reaction. After cooling, the deposited dicyclohexylurea was separated and then the similar manner as in the operational procedure of the Example 1 is effected to obtain 7.6 g of the same ester compound of Example 1.  
 EXAMPLE 4 A solution of 5.3 g of 2-propargyl-3-methyl-4- hydroxy-Z-cyclopentene-l-on and 4.2 g of pyridine in 25 ml of dry benzene was cooled with ice, and a solution of 5.9 g of 2,2,3,3-tetramethylcyclopropanecarbonyl chloride in 15 ml of dry benzene. The resulting reaction mixture was sealed and left overnight. After the reaction mixture was poured into ice water, the organic layer was separated and washed with 5 percent (by weight) aqueous hydrochloric acid solution, 5 percent (by weight) aqueous sodium carbonate solution and an aqueous solution saturated with sodium chloride and then dried over anhydrous magnesium sulfate. Benzene was evaporated to obtain 9.6 g of yellowish oil. Distillation under a reduced pressure gave 8.5 g of a yellowish oil of 2-propargyl-3-methyl-Z-cyclopentene-l-on-4-yl- 3,3-tetramethylcyclopropanecarboxylate (n,,--&#34;:  
 Elementary Analysis To a solution of 5.3 g of 2-propargyl-3-methyl-4- hydroxy-Z-cyclopentene-l-on and 5.9 g of 22.33- tetramethylcyclopropanecarboxylic acid in 100 ml of methylenechloride. 7.9 g of dicyclohexycarbodiimide was added thereto and the resulting mixture was left overnight. After the deposited dicyclohexyl urea was filtered, the similar operation procedure described in Example 4 gave 8.3 g of the same ester compound of Example 4.  
  In order to make it clear whether the present compounds are superior or not in insecticidal effect to not only the commercially available allethrin but the corresponding chrysanthemic acid ester. comparisons in effectiveness are shown below with reference to Experimental Examples.  
 Experimental Examples cyclopropanecarboxylic acid ester or corresponding tetramethyl cyclopropanecarboxylic acid ester. were prepared according to the ordinarly procedure.  
  Into a (70 cm) glass chamber were liberated about 20 adults of Northern house mosquitoes. l g of each of the mosquito coils obtained above was ignited at both ends placed at the center of the bottom of the chamber. After ignition of the mosquito coil. the number of knocked down mosquitoes was counted with lapse of time for 24 minuts to calculate a knock down ratio at each time. At the same time, a 50 percent knock down time (KT-, was calculated.  
  At every time after 24 minuts. knocked down mosquitoes were taken out. removed. fed and allowed to stand for one day in the room for observation. and the numbers of alive and dead mosquitoes were observed to calculate the ratio of killed insects.  
 The results obtained were as set forth in Table I. As is clear from the above-mentioned Experimental Examples. the present compounds exhibit not only more quick knock down effect than that of allethrine widely used as fumigant. but also excellent killing effect. And the present compounds have more excellent effect than that of the corresponding chrysanthemic acid esters.  
  The present compounds of the formula (I) which is an active ingredient of the present invention. may not only be used singly but may be incorporated with suitable amounts of phenol or bisphenol derivatives such as BHT or the like, or arylamines such&#39;as phenyl-anaphthylamine, phenyl-B-naphthylamine or condensation product of phenetidine with acetone, whereby compositions which have been more stabilized in insecticidal effects can be obtained. Further. the composi- Table 1 Test compound 0.3 7 mosquito coil 0.6 mosquito coil 31% Km Formula I {T5 Killing ratio KT 0 Killirm ratio (min. sec) a) (min. see) ,i  
  l 1 Present compound (1) CH ,ca-cooam C]3-CH -CECH 4&#39;42&#34; 96 2&#39;50&#34; 100 C i 011 ea CH C Present; compound 3\ f&#39; Z m CH2 C 3&#39;12&#34; 100 2&#39;00&#34; 100 CH C-CH-COO C 3/ ca \C-CHZ-CECH 72 95 CH3 (EH I l CH en e CH -;C-CH-COO c r l 4 Allethrin CH f CHZCH CH2 1o&#39;4a&#34; 31 7&#39;36&#34; 77 CH CH C 0 C CH3 tions may be increased in insecticidal activity by incorporation of synergists for pyrethroid type insecticides such as N-(2-ethyl-hexyl)-bicyclo[2,2,l}hepta-5ene- 2,3-dicarboxyimide (hereinafter referred to as MGK- 264). octachlorodipropyl ether [hereinafter referred to as S-42l&#34;], oz-l2-(2-butoxyethoxy)ethoxy]-4,5- methylene-dioxy-2-propyl toluene (hereinafter referred to as piperonylbutoxide&#34;). 4-(3,4- methylendioxyphenyl)-5-methyl-l,3-dioxane (hereinafter referred to as Sufroxane&#34;). and the known syncrgists.  
 Furthermore. the present compounds can display wider insecticidal activities when used in combination of 2 or more, and can be enhanced in insecticidal effect when used in admixture with other physiologically active materials, e.g. pyrethrin. allethrin, d-transallethrin. N-(chrysanthemoxymethyl)-3,4,5.6-tetrahydrophthalimide. dimethylmaleimidomethyl chrysanthemate. 5-benzyl-3-furylmethyl chrysanthemate, 5-propargylfurfuryl chrysanthemate, 5-propargyl-2-methyl-3- furylmethyl chrysanthemate, 3-phenoxybenzyl chrysanthemate. and optical isomers thereof or derivatives such as corresponding tetraor tri-methylcyclopropane carboxylic acid esters of the above mentioned chrysanthemic acid esters, other insecticides of pyrethroid type, other insecticides such as BHC, Diazinone. phenitrothion. DDVP and the like. In preparing the insecticidal compositions of the present invention, the present compounds may be formulated into oil sprays. emulsifiable concentrates, dusts. aerosols. wettable powders, granules, mosquito coils and other heating or non-heating fumigants according to the procedures thoroughly known to those skilled in the art, using diluting adjuvants for general insecticides like in the case of the conventional pyrethroides. Alternatively. they may be formulated into death-inducing powder or solid preparations incorporated with baits or other substances attractive for injurious insects.  
  Procedures for the preparation of the present compositions and biological effects thereof are illustrated below with reference to the blending examples and test examples, but it is needless to say that the scope of the present invention is not limited to the examples.  
 Blending Example 1 Each 0.3 g of the present compounds (1) or (2) is dissolved in 5 ml of methanol and the each mixture is sufficiently mixed with 60 g of pyrethrum marc, g of Tabu powder and 9.7 g of wood flour. The each mixture is sufficiently kneaded with 100 ml of water, and then shaped and dried to obtain 100 g of a mosquito coil.  
  If necessary, the mosquito coil may be colored by addition of 5 percent of a dye such as Malachite Green or the like, or may be incorporated with a phenol or phydroxybenzoic acid ester.  
 Blending Example 2 To 0.25 g of the present compound 0.1 g of each allethrin, d-trans allethrin, dimethylmaleimidomethyl chrysanthemate, dimethylmaleimidomethyl-2,2,3,3- tetramethylcycopropanecarboxylate or S-propargylfulfuryl chrysanthemate is added, and the each mixture is dissolved in 5 ml of methanol.  
  These mixtures are operated by the same manner as described in the Blending Example 1 to obtain each combined mosquito coil.  
 Blending Example 3 Each 0.2 g of the present compound (I) or (2) and each 0.5 g of 5-421 are dissolved in chloroform. This each solution is uniformly absorbed on the surface of an asbestos piece of 2.5 cm X 1.5 cm in area and 0.3 cm in thickness. Onto the asbestos surface is pasted another asbestos piece identical in size therewith to obtain respective insecticidal fibrous fumigant compositions for use on an electrically heated plate. As the fibrous carrier, there may be used, in addition to asbestos. a pulp sheet or the like material which is identical in effectiveness therewith.  
 Blending Example 4 A mixture comprising 0.2 g of the present compound (2) and 0.05 g of DDVP is dissolved in chloroform. This solution is treated in the same manner as in Blending Example 3 to obtain the respective insecticidal fibrous fumigant composition for use on an electrically heated plate.  
 Blending Example 5 To 0.2 g of the present compound (2) 0.1 g of each 5-benzyl-3-furylmethyl chrysanthemate. 5-benzyl-3- furylmethyl-2&#39;,2&#39;,3&#39;-trimethylcyclopropanecarboxylate or 3-phenoxybenzyl-2&#39;,2&#39;,3&#39;,3&#39;-tetramethylcyclopropanecarboxylate is added, and in addition to these mixture each 0.6 g of BHT is added thereto and the each resulting mixture is dissolved in 5 ml of methanol. 60 G of pyrethrum marc, 30 g of Tabu powder and 9.] g of wood flour are added to each mixture and mixed sufficiently. These mixture are operated by the same manner as described in the Blending Example 1 to obtain each combined mosquito coil.  
 Blending Example 6 A mixture comprising 0.1 part by weight of the present compound (2) and 0.5 part by weight of piperonyl butoxide was dissolved in deorderized kerosene to make the total amount 100 parts, whereby oil spray obtained.  
 Blending Example 7 A mixture comprising 20 parts by weight of the pres-- ent compound (2), 10 parts by weight of Sorpol SM- 200 (registered trade mark of Toho Chemical Co.) and parts by weight of xylene was thoroughly stirred to obtain emulsifiable concentrate.  
 Blending Example 8 A mixture comprising 0.4 part by weight of the present compound (I), 2 parts by weight of p.pdichlorodiphenyl trichloroethane, 6 parts by weight of xylene and 6.6 parts by weight of deorderized kerosene was mixed and packed in the aerosol container.  
  After attaching a valve portion to the container, parts by weight of a propellant (i.e., fleon, vinyl chloride monomer. liquefied petroleum gas and the like) was introduced under pressure through said valve portion into the container to obtain an aerosol.  
  9 Blending Example 9 0.3 Part by weight of the present compound l was dissolved in deorderized kerosene to make the total amount l parts. whereby oil spray was obtained.  
 Blending Example A mixture comprising 0.4 part by weight of the present compound (2). 0.3 part by weight of 0.0-dimethyl- 0-( 3-methyl-4-nitrophenyl )thiophosphate. 6 parts by weight of xylene and 8.3 parts by weight of deorderized kerosene was mixed and treated in the same manner as in Blending Example 8 to obtain an aerosol.  
 Blending Example l l A mixture comprising 5 parts by weight of the present compound (2). 5 parts by weight of Toyolignin CT (registered trade mark of Toyo Spinning Co.) and 90 parts by weight of GSM clay (registered trade mark of Zieglite Mining Co.) was thoroughly stirred in a mortar. Subsequently. the mixture was kneaded l0 percent by weight. based on the amount of said mixture. of water and granulated by means of a granulator. followed by air-drying. to obtain granule.  
 Blending Example 12 A mixture comprising parts by weight of the present compound&#39; I 1.5 parts by weight of Sorpol 5029-0 (registered trade mark of Toho Chemical Co.) and 3.5 parts by weight of lignin was mixed and 70 parts by weight of diatomaceous earth were added thereto. The resulting mixture was thoroughly stirred in a mortar to obtain wettable powder.  
 Blending Example 13 To a solution of 1 part by weight of the present compound (2) in 20 parts by weight of acetone was added 99 parts by weight of 300 mesh diatomaceous earth. The resulting mixture was thoroughly stirred in a mortar. and then the acetone was vaporized to obtain dust.  
  Insecticidal effects of the thus obtained compositions of the present invention are as set forth in the examples shown below.  
 Example 6 lnto a (70 cm) grass chamber were liberated about 50 adults of Northern house mosquitoes. 0.2 Grams of each of the mosquito coils obtained according to Examples l. 2 and 5 was ignited at both ends placed at the center of the bottom of the chamber. The smoke inside the chamber was stirred by means of a small motor fan (blade diameter 13 cm). As the result. every mosquito coil could knock down more than 90 percent of the mosquito adults within 20 minutes and could kill more than 80 percent of the insects on the next day.  
 Example 7 .10 EXAMPLE 8 Into a cm) glass chamber were liberated about 50 adults of Northern house mosquitoes. Each of the insecticidal fibrous fumigant compositions obtained according to Examples 3 and 4 was put on an electric heating means. which was then placed at the center of the bottom of the chamber. Subsequently. an electric current was applied to the heating means. and the interior of the chamber was stirred by means of a small motor fan (blade diameter 13 cm As the result. every composition could kill more than 90 percent of the mosquito adults within 20 minutes. and could kill more than percent of the insects on the next day.  
 EXAMPLE 9 According to the campbells turn table method [disclosed in Soap &amp; Sanitary Chemicals. Vol. l4. No. 6. page 119 (1938)]. 5 ml of the each oil sprays obtained in Blending Example 9 was sprayed using 0.3 percent oil spray. 0.l5 percent oil spray diluted with deoderized kerosene&#39;and 0.075 percent oil diluted with deoderized kerosene. Adults of house flies (a group of about l00 flies) were exposed to the settling mist for 10 minutes. Thereafter. the flies were taken out. fed and allowed to stand in a constant temperature room at 27C. and the numbers of alive and dead were observed after 24 hours to calculate the ratio of killed insects.  
  Insecticidal effect of oil spray obtained in the above Blending Example 9 to the house fly adults was measured by the LC (50 percent lethal concentration). The results obtained were as set forth in Table 2.  
 Table 2 Insecticidal composition LG.&#34; 7!) (oil spray) 1 Present compound l 0.047 2 Allethrin 0.095 3 Pyrethrin 0.052  
 EXAMPLE 10 About 20 adults of house flies were liberated in a (70 cm)&#34; glass chamber. and 0.7 ml of each of the oil sprays obtained in Blending Example 9 was sprayed intothe chamber under a pressure of 20 pounds/in by use of a glass-made atomizer.  
  Thereafter. the numbers of knocked down house flies was counted to calculate the KTso (5.0 percent knock down time) of each compound. The results obtained About 20 adults of Northern house mosquitoes were liberated in a (70 cm) glass chamber. and 0.7 ml of each of the diluted oil sprays. obtained in Blending Example 9. with deoderized kerosene to contain 0.l percent by weight of active ingredient was sprayed into the chamber under a pressure of 20 pounds/in by use of a glass-made atomizer. Thereafter, the numbers of knocked down Northern house mosquitoes were counted to calculate the KT (50 percent knock down time). The results obtained were as set forth in Table Table Knock down ratio (02) Insecticidal composition After l0 min. After 1 day Present compound (2) I00 100&#39; EXAMPLE 13 About adults of house flies were liberated in a (70 cm) glass chamber. the aerosol obtained in Blending Example 8 and 10 was sprayed one second, and the knocked down flies were observed after 15 minutes. The only knocked down flies were collected, removed tothe new observation cage, fed and the numbers of alive and dead were observed after one day. The results obtained were set forth in Table 6.  
 Table 6 Knock down ratio (&#39;7() After 15 minutes Insecticidal Ratio of killed composition insects (71) After 1 day 1 Aerosol of Blending 86 Example 8 2 Aerosol of Blending Example 10 EXAMPLE [4 Into a 300 milliliter-glass beaker containing 200 ml of each solution of emulsiflable concentrate obtained in Blending Example 7 and of wettable powder obtained in Blending Example 12, prepared to the tested concentration with water, about 30 full-grown larvae of Northern house mosquitoes were liberated in the case. The numbers of alive and dead were observed after one day to calculate the LC (50 percent lethal concentration). The results obtained were set forth in Table 7.  
 Table 7 Insecticidal composition LC (p.p.m.l  
 Emulsifiable concentrate of Blending 0.02 Example 7 wettable powder of Blending Example 0.0) II Wettable powder of Allethrin 0.10  
 EXAMPLE l5 Into a 14 liter-polyethylene backet containing 10 liters of water was charged 400 mg. of granule obtained in Blending Example 1 1. After 1 day, fullgrown larvae of Northern house mosquitoes were liberated in the water. and then the alive and dead of the larvae were observed. As the result, more than 90 percent of the larvae could be killed within 24 hours.  
 EXAMPLE l6 Onto the bottom of a grass Petri dish of 14 cm. in diameter and 7 cm in height was uniformly dusted by 2 g/in&#34; of the dust obtained in Blending Example 13. and the dish was coated on the inner wall with butter. leaving at the lower part an uncoated portion of about I cm in width. Subsequently. a group of 10 German cockroach adults were liberated in the dish and contacted with the dust for 30 minutes. As the result, percent of the cockroaches were knocked down. and I00 percent of the knocked down cockroaches could be killed on the third day after the contact.  
 What is claimed is:  
  l. A cyclopropanecarboxylic acid ester of the formula (I).  
 wherein R is hydrogen or methyl group.  
 2. A compound of the formula,  
 l H CH ,c-cooea C-CH uf-ECH 2- CH5 CH 0 l CH5 3. A compound of the formula,