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United States Patent - O?ice 3,021,358 Patented Feb. 13, 1962 2 1 We are now aware (though this was not known to us 3,021,358 at the outset of our research) that 2,2,2-tri?uoro-l,1-bis . INSECTICIDAL BIS-HALOPHENYL DI-FLUORO ' (p-halophenyl)~ethanes, ethanols and ethyl acetates have ALIPHATIC COMPOUNDS been disclosed as synergists for DDT (see Tahori in Jour nal of Economic Entomology, 1955, vol. 48, pp. 63 8-642, and Kaluszyner et al. in American Chemical Society Jour Joseph Bornstein, Brighton, Mass., Murray S. Blum, Baton Rouge, La., and John J. Pratt, Jr., Wayland, Mass., assignors to the United States of America as nal, 1955, vol. 77, pp..4164-4168); however, we have found surprisingly that our 2,2-di?uoro compounds have unexpectedly more powerful synergistic insecticidal action No. 751,579, now Patent No. 2,990,321, dated June 27, 1961. Divided and th'm application Jan. 29, 1960, 10 in combination with DDT than the results obtained by the Ser. No. 9,154 . foregoing workers with 2,2,2-tri?uoro compounds would 6 Claims. (Cl. 260-488) have permitted to expect. (Granted under Title 35, US. Code (1952), sec. 266) We will now proceed to illustrate the practice of our represented by the Secretary of the Army No Drawing. Original application July 28, 1958, Ser. inventionby means of several examples, but wish to have The invention described herein, if patented, may be manufactured and used by or for the Government for 15 it understood that we do not intend to limit the practice of our invention to the particular methods therein set governmental purposes, without the payment to us of any forth, inasmuch as our novel compounds can be made by royalty thereon. other syntheses and may ’be combined with DDT in any This application is a division of our co-pending appli desired proportion, as may be most effective under the cation Serial Number 751,579, ?led July 5, 1958; now 20 circumstances of a particular application. Patent No. 2,990,321 dated June 27, 1961. This invention relates to insecticides and more particu EXAMPLE 1 larly to new bis-(halophenyl)-?uoroaliphatic‘ compounds 2,2-di?uoro-1,I-bis-(p-chlorophenyl) -ethanol Freshly puri?ed ethyl di?uoroacetate (20.0 g., 0.16 having insecticidal properties. Compounds of this invention have the general struc 25 mole), diluted with an equal volume of ether, was added ture: with stirring in the course of 1 hr. to the ice-cold Grig H FCF nard reagent prepared from 10.7 g. (0.44 g.-atom) of magnesium turnings and 81 g. (0.44 mole) of l-bromo 4-chlorobenzene in 100 ml. of ether. Stirring and cooling 30 in the ice-bath were maintainedfor 2 hours after comple wherein Hal and Hal’ are halogen atoms of an atomic tion of the addition of the ester. The reaction mixture, after standing at room temperature overnight, was treated, while stirring and cooling, with saturated ammonium weight not above 80 -(i.e., ?uorine, chlorine and bro mine), and wherein Y is hydrogen, hydroxyl or acetoxyl. Compounds falling under this general formula are 2,2-di 35 chloride, prepared by shaking 40 g. of the salt with ‘100 ml. of water. The yellow suspension was ?ltered with ?uoro-1,1-bis-(p-halophenyl) —ethanes, 2,2-di?uoro-1,1-bis suction through a sintered-glass funnel, the ?lter cake was washed with ether, and the combined ethereal extract washed twice with water before being dried over sodium ?uoro-1,1-bis-(p-halophenyl)-ethanes, which analogs have 40 sulfate. Evaporation of the ether yielded a dark orange oil which was diluted-with an equal volume of methanol the general formula: and refrigerated at —35° for 2 days in order to allow the (p~halophenyl)-ethanols, and 2,2-di?uoro-l,l-bis-(p-halo phenyD-ethyl acetates. Also within the purview of our invention are dehydro?uoro ethene analogs of 2,2-di ' HG F traces of biphenyl to crystallize. Filtration of the mix ture followed by steam distillation of the ?ltrate (2 l. of distillate was collected and discarded) gave a product 45 which was essentially free of starting material and de rived products. The oily residue was dissolved inether The foregoing compounds may be prepared by a Grig and dried over sodium sulfate. Removal of the solvent nard type reaction, as will be more fully explained here and distillation of the residue afforded a 53% yield of after. ' Tests have shown that among the foregoing compounds 50 2,2-di?uoro-1,1-bis-(p-chlorophenyl)-ethanol, a liquid QAQ the 2,2-di?uoro-1,l-bis-(p-halophenyl)-ethanols are highly potent insecticides, and are surprisingly and strikingly ef fective as synergists for DDT; these effects are particu larly striking when the halogen atoms on the respective having a RP. of 130—136° C. at 0.20 mm.; index of re fraction nD2° 1.5780. With concentration H2804 it gave a cherry-red color. Analysis (c,,H,,c1,F,0)= phenyl groups are either chlorine or bromine. However, 55 Calculated the other compounds herein disclosed are likewise valu able weapons in the arsenal of economic entomology, in- ' 0. - 55. 47 Found 55. 63 H a. 33 3. 47 asmuch as experience has shown that succeeding genera C1 23. 40 2a. 94 tions of insects quickly acquire immunity to a given type of insecticide through the breeding of resistant strains. It 60 Upon prolonged standing, t-hick prisms formed, having a is therefore important to have alternate insecticides and MP. of 54.5-56.0° C. 1 . insecticidal. synergists on hand to combat insects which The m-chlorophenyl and o-chlorophenyl analogs are have thus acquired immunity against a previously very ef produced by substituting the same amounts of l-bromo- . fective insecticide. ' 3 4 3-chlorobenzene or l-bromo-Z-chlorobenzene in lieu of the l-bromo-4-chlor0benzene of the above example. ‘ ethyl acetate was obtained in liquid form from the 2,2-di ?uoro-1,l-bis-(p-?uorophenyl)-ethanol of Example 3; it EXAMPLE 2 . resisted attempts to induce crystallization and isolated as a very viscous oil at 80° C. and 0.1 mm. pressure; index ' ' 2.2-di?uom-L1-bis-(p-bwmophenyb-erhanol s of refraction up” 1.5158. Analysis (cmHnFpg: Example 1 was repeated, but a stoichiometrically equiv alent amount ( 104 grams; 0.44 mole) of 1,4-dibromo- ‘ benzene was used in lieu of l-bromo-4-chlorobenzene. Calculated A 40% yield of 2,2-di?uoro-l,1-bis-(p~bromophenyl)0-ethanol was obtained as a liquid which had a boiling point 10 H of 153-164‘ C. at 0.17 mm.; index of refraction nun-5 01.53 3- 87, 1.6039._ With concentrated H1804 it gave a red color. Analys“ (CII‘HMBHF'O): 2,2-di?uor0-1,I-bis-(p-halophenyl)ethane 15 8.0-10.0 grams of 2,2 - di?uoro - 1,1 - bis - (p - chloro phenyD-ethanol (Ex. 1) were heated under re?ux for ten days with a mixture of 33 g. of red phosphorus, 1.27 g. 43;‘; of iodine, so ml. of glacial acetic acid, and 1.0 ml. of 40.6 water. The cooled reaction mixture was ?ltered with , 20 suction directly into a separator";l1funnel containing 300 . .‘ . . ml. of 2.5% sodium bisul?te. Upon prolonged ‘magma’ thick m‘ formed’ hams 0‘ 545-56. ' ate with intermittent shaking and was then extracted with ether. The ether extract was dried over sodium sulfate _ 25 after being washed with water. > 2.2-dr?uoro-1.I-bir-(p~?wrophmI)-¢thmwl In Removal of the ether and distillation of the residue in vacuo yielded an oil Example 1 was repeated, but a stoichiomd?cany equiw _ alem amount (0 44 mole) of Lb e only suspension was neutralized‘ by adding portions of solid sodium bicarbon EXAMPLE 3 - 61.8 3-9 EXAMPLE 5 ‘ Calculated a Found . which spontaneously crystallized. The crude crystals I “one were recrystallized by means of a methanol-water solvent, and a 90% yield of 2,2-di?uom-1,l-bis-(p-chlorophenyl) was used in lieu of 1-bromo-4-chlorobenzene. A 43% . yield . . . a M.P. of 37.5-38.5’ C. and of 2,2-d1?uoro-l,l-bis-(p-?uorophenyl)-ethanol was 30 ethane crystals having a - a obtained in liquid form having a 13.1’. of 99-100‘ 0. at 251°‘. “(é-:11; C91,“; 9'“ mm 1mm” was waned‘ 0.05 mm.; index of refraction "1,“ 1.5276. with concentrated H,S04 it gave a red orange color. Analysis (C14H1oF4o)= Y” 1 1° ’ = ' ' 35 Calculated 58. 56 3. 51 24. 69 4° Folmd 58. 3. 24. 2,2-di?uoro-l,l-bis-(p- bromophenyl) - ethane crystals were obtained in a 89% yield from the 2,2-di?uoro-1,l EXAMPLE 4 bis-(p-bromophenyD-ethanol of Example 2 in the same 2,2-di?uoro-1,1-bis-(p-halophenyl)-ethyl acetate vent for recrystallization. M.P. 42.0-42.8‘ C. Analysis way as the chloro analog; methanol was used as the sol in. 2,2-di?uoro-1,l-bis-(p-chl0rophenyl)-ethan°1 of 4*‘ (cnHmBrsFm ExamPle 1 was permitted to stand at room temperature for several hours with a mixture of acetic acid and tri- “1mm ?uoro acetic anhydride, in accordance with the procedures generally set forth by Tedder in Chem. Revs. 55, 787 50 g(1955). The resulting product was extracted with petroBr__. leum ether solvent and recrystallized. A 82% yield of 2,2-di?uoro-l,1-bis-(p-chlorophenyl)-ethyl acetate crys Calculated Found . Fmmd ‘g-g 4:20 4214s 4215 tained in the form of a viscous oil from the 2,2-di?uoro 55 1,1-bis-(p-?uorophenyD-ethanol of Example 3 in a 90% yield. It resisted attempts to crystallize; its B.P. is 79 80' C. at 1.5 mm. pressure; index of refraction up“ _1.5179. Analysis (CuHmF?r 55.01 3.60 55.8 as so Calculated 2,2-di?uoro-1,1 - bis - (p - bromophenyl) - ethyl acetate 66. 14 3. 97 crystals having a M.P. of 80-805‘ C. were obtained in the same manner in an 86% yield from the 2,2-di?uoro 1,1-bis-(p-hmmophenyD-ethanol of Example 2. Analysis 65 I (CHHuBQFaOaP Found 66.6 4.0 EXAMPLE 6 Dehydro?uoridatian products-(C??alhQCHF Z-?u Calculated Found 70 oro-I ,1 -bis-(p-halophenyl) when: 3.8 grams of 2,2-di?uoro-l,l-bis-(p-bromophenyl)-eth ane (Ex. 5) were dehydro?uorinated (removal of 1 mole of hydrogen ?uoride) by heating under re?ux for 2.5 hours with 60 ml. of 2% ethanolic potassium hydroxide. ' The solvent was removed under reduced pressure and the An 89% yield of 2,2-di?uoro-l,l-bis-(p-?uorophenyl)- 75 residue extracted with several portions of ether. The 3,021,353 6 action of our compounds in combination with DDT, combined ethereal extract was washed with water and dried over magnesium sulfate. Removal of the'ether ‘ when applied to a DDT-resistant strain of adult female house?ies in the same manner. The ‘ratio of ?uoro com a?orded a colorless oil which was distilled at diminished pressure. Upon recrystallization with methanol there was obtained an 85% yield of 2-?uoro-1,1-bis-(p-bromo ' phenyl)-ethene crystals having a M.P. of 84.2-85.2° C. 5 pounds to DDT was one part of ?uoro compound to 5 parts of DDT. TABLE I Analysis (CHI-1.13511‘): LD» Calculated Fotmd 10 C 47. 20 DDT-Sus- 47. 0 H 2. 55 2. 4 Br 44. 86 44. 7 oentible Flies, Fluoro Com- pound Crystals of Z-?uoro-1,1-bis-(chlorophenyl)-ethene were 15 Alone obtained in the same manner from 2,2-di?uoro-1,1-bis (p-chlorophenyl)-ethane of Example 5, in an 85% yield; M.P. 78.0-79.5° C. Analysis (Cal-1.01m): ll‘ound 20 pound, 5 Parts DDT 2,2-Di?uoro-1,l-bis-(n-chlorophenyD-ethane ____ __ 2. 2 0.96 2,2,Drtluoro-1,1-bis-(p-chlorophenyl)-ethanol..___ .2,2-D1?uoro-1,l-bis-(p-chlorophenyl)ethyl ace 3. 8 0. 62 tate_ Calculated DDT-Re sistant Flies, 1 Part Fluoro Com 9. 4 1. 6 2-Fluoro-1,1-bls-(n-chlorophen l)-ethene _______ _- 22 11.5 2,2~Ditluoro-l,1-bis-(p-bromop enyl)-ethane_____ 2. 1 0.96 4. 9 0. 56 2,2-Di?uoro-1,1-bis-(p-bromphenyD-ethanol ____ __ 2,2¢Dl?uoro-1,1-bis-(p-bromophenyD-ethyl ace 62. 3. 26. fate 35 83 9. 7 1. 7 2-Fluoro-1,l-bis-(p-bromopheuyl)-ethene _______ -. 2,2-Dl?uor0-1,1-b1s-(p-?uorophenyD-ethane ____ .. 21) 5. 1 7. 1 70 25 2,2-Di?uoro-l,l-bis-(p-fluorophenyD-ethanoL.___ 2,2-Di?uoro-1,1-bis-(p-?uorophenyD-ethyl ace 7. 2 2. 8 35 8. 5 Liquid Z-?uoro-1,1-bis-(p-?uorophenyl)—ethene was ob tained from 2,2-di?uoro-L1-bis-(p-?uorophenyD-ethane tate. ' 2-Fluoro-1,1-bis-(n-?uorophenyD-ethene _______ __ 18 28 Control: DDT alone __________________________ __ 0.35 1 150 - in a 93% yield; B.P. 81—82° C. at 1 mm. pressure, in 1 (No ?uoro compound, 6 parts DDT.) den of refraction uni“ 1.5481. Analysis (CHI-19B): Calculated ‘ Folmd C 71. 79 71.9 H 3. 87 4. 0 In a further control experiment with the DDT-re sistant strain of ?ies, a mixture of 1 part of 1,1-bis (p-chlorophenyl)-ethanol (DMC, a known DDT syner gist) and 5 parts of DDT was found to have an LD5° of 3.9, which is less potent thanmost of our new com pounds. It appears from the foregoing test results that the com pounds of the present invention are e?ective as insecti cides, even when applied alone to insects which have not house?ies. - 40 yet bred immunity to DDT, even though the quantity of The ?rst column of test results indicates the lethal our ?uoro compounds to achieve the desired insect mor The following table (Table I) shows the biological results obtained by testing the foregoing compounds on effect of our compounds, applied alone to ordinary DDT susceptible adult female house?ies which were t1'eated tality is larger than a corresponding quantity of DDT. to the thorax (1 microliter of the solutions were applied However, as pointed out, the principal utility of our com pounds is in the ?eld of DDT synergists where, as shown in the foregoing table, a most surprising reduction of, in each instance). quantity of synergistic mixture (as compared with the topically by applying acetone solutions of the compounds Mortality data were taken 24 hours after treatment quantity of DDT alone) results in e?ective kills of DDT of the ?ies. One hundred and sixty ?ies were used in resistant insect strains; (the effectiveness of the compo each test-4 replicates of 20 ?ies each duplicated from sitions being in inverse’ratio to their numerical LD5° 2 di?erent ?y populations. The quantity of test com 50 ratings.) This is borne out by a control computation. pound required to kill 50% of the test ?ies (LD-SO) on the synergistic effect on a number of the above 2,2 was determined by plotting on a logarithmic scale per di?uoro compounds, as compared with the synergistic cent mortality versus dose of test compound. effect with DDT of the corresponding 2,2,2-tri?uoro com The second column of test results shows the synergistic pounds reported by Tahori, supra. TABLE II 1 Part 1 Part 2,2-Di Compound 1 Part 2,2,2-tri2.2.2411 Fluoro Fluoro Com pound Compound Fluoro to 5 Parts DDT to 1 Part DDT to 10 Parts DDT 2,2 - Di?uoro - 1,1 - bis - (p-chloro- 171 2,2,2-Tri?uoro - 1,1 -bis - (p-ehloro- 14 0 2,2 - Di?uoro - 1.1 - bis -(p-chloro- 194 2,2,2 - Tri?uoro -1,1-'bis -(p-chloro- 25 15 15 11 phenyD-ethane. phenyD-ethanol. 2,2 - Di?uoro -1,1 - bis -(p~chloro- 71 2,2,2-Tri?uoro41J-bis-(p-chloro- 125 2,2,2 - tri?uoro -1,1 - bis -(p-bromophenyD-ethane. 2,2.2- Tri?uoro - 1,1 ~bis-(p-bromo- phenyll-ethyl acetate. 2,2 ‘ Di?uoro -l,1 - bis - (p-bromophenyD-ethane. 2,2 - Di?uoro - 1,1 - bis- (p-bromo- phenvD-ethanol. phenyD-ethane. phenyll-ethanol. phenyll-ethyl acetate. 169 phenyD-ethanol. 10 0 , 16 12 2,2 - Di?uoro -1,1 - bis - (p-bromo- 71 2,2,2- Tri?uoro -1,1 -bis- (p-bromo- 14 1O 2,2 - Di?uoro -1,1 - bis -(p-?uoro- 42 2,2,2-Tri?uoro -1.1-bls -(p-?uoro- 10 10 phenyll-ethyl acetate. phenyD-ethanol. phenyD-ethyl acetate. phenyD-ethanol. 3,021,358 7 _ 8 In the foregoing table, Tahori’s de?nition of syner gistic activity was used in lieu of an LDm rating, namely be clear that several modi?cations and changes thereof may be made without departing from the spirit of our the factor by which it is possible to reduce the amount of DDT and still obtain the same mortaility; for exam invention or from the scope of the subjoined claims. We thus desire to claim our invention as broadly as the prior 5 art and the essential features of our invention will permit, pie, with 2,2,2-vtri?uoro-Ll-bise(p-chlorophenyl)-ethanol and to this end have appended the following claims. We claim: 1. An insecticidal compound having the formula: (bis-(p-chlorophenyl)-tri?uoromethyl-carbinol) could be reduced 15 times (1:15). Thus a high numerical rating ‘ in Table 11 indicates a high degree of synergism. It should be noted in this connection that the tests reported H FCF by Tahori, supra, were conducted on a DDT-resistant strain of Palestinian house?ies (“T” strain) which ap pear, by reason of Tahori’s comparison ofv that strain with at “Berkeley” strain, to have less immunity to DDT a] than the DDT-resistant house?ies on which our tests were conducted. weight not above 80 and wherein Y is a member of the group consisting of hydrogen, hydroxyl and acetoxyl. 2. The insecticidal compound 2,2-di?uoro-l,l-bis-(p~ chlorophenyl)-ethane. with DDT, such as carbon black, talc, pyrophyllite, hy 20 _ ‘ 3. The insecticidal compound 2,2-di?uoro-l,l-bis-(p chlorophenyl)-ethanol. 4._ The insecticidal compound 2,2-di?uoro-1,1-bis-(p drocarbon solvent, alcohol, or aqueous emulsion. The term DDT, as used in the speci?cation and claims, denotes dichlorodiphenyltrichloroethane (pure or tech chlorophenyD-ethyl acetate. 5. The insecticidal compound 2,2-di?uoro-1,1-bis-(p nical grade). It will thus be seen that we have provided a series of 25 new insecticidal compounds which are particularly e?ec tive as DDT synergists; they may be arranged as to the bromophenyD-ethan‘ol. 6. An insecticidal compound being a member of the group consisting of 2,2-di?uoro-1,l-bis-(p-chlorophenyl) degree of synergistic ef?ciency in the following general order: 30 2,2-di?uoro-l,l-bis-(p-halophenyl)-ethyl acetates 2-tluoro-l,1-bis.(p-halophenyl) -ethenes Bromine and chlorine are generally superior to ?uorine 35 as synergistically e?cient substituents in the phenyl groups of the above—named compounds; while the para position I 15 wherein Hal and Hal’ are halogen atoms having an atomic For economic reasons it is advisable to apply our new insecticides, when used as the sole active ingredient or in synergistic combination with DDT, by the use of a proper solid or liquid diluent, e.g., of the type customarily used 2,2-di?uoro-l,l-bis- (p-halophenyD-ethanols 2,2-di?uoro-l,1-bis- (p-halophenyD-ethanes l l ethane, 2,2-di?uoro-l,l-bis-(p-chlorophenyl)-ethanol, 2, ZI-di?uoro-1,1-bis-(p-bromophenyl)-ethane, 2,2-di?uoro l,l-bis-(p-bromophenyl)-ethanol, 2,2-di?uoro-1,1-bis-(p ?uorophenyl)-ethane,_ and 2,2-di?uoro-1,l-bis-(p-?uoro phenyD-ethanql. References Cited in the ?le of this patent UNITED STATES PATENTS 2,729,681 Wilson et al. __________ ..- Ian. 3, 1956 is generally preferred, the meta and ortho positions are 2,776,988 Craig et a1. __________ .. Jan. 8, 1957 not excluded from the purview of our invention. OTHER REFERENCES Having thus described our invention and several modes 40 by which the same may be carried into practice, it will “Nature,” vol. 176, Aug. 6, 1955, p. 266 and 267.