Synthetic Organic Compounds as Potential Insecticides L. E. SMITH, Bureau of Entomology and Plant Quarantine, U. S. Department of Agriculture, Washington, D. C.
T
HE synthesis and testing of organic compounds as insecticides has been an important activity of the United States Department of qgriculture since 1932. During this time about two thousand materials have been prepared and tested against a great variety of insects. When tests in the laboratory indicate that a compound has insecticidal properties, more extensive tests, including field tests, are made to evaluate the compound in the natural environment of the insect. Observations are recorded as to the effect of is sent the compound upon the foliage Of Plants, and to the Bureau of Agricultural Chemistry and Engineering for pharmacological testing, since the object of all this work is to develop new insecticides that are less hazardous to man than the present widely used arsenical and fluorine compounds. p-Pyridyl-a-piperidine (Neonicotine) was found by Smith, Richardson, and Shepard (11) to be the toxic ingredient of the reaction product of sodium and pyridine; because of its resemblence to nicotine it was called “neonicotine”. Subsequently Russian chemists found i t present in the optically active form in a weed belonging to the sugar beet family (Chenopodiaceae), and was called “anabasine” by them from the name of the plant Anabasis aphylla L. Anabasine is an excellent contact insecticide, being four or five times as toxic as nicotine against certain aphids; but when tested as a stomach poison it did not give promising results (6).
believed that, when proper methods of application have been worked out, phenothiazine may replace lead arsenate for the control of this insect, in some areas a t least. I n addition, i t also has fungicidal and anthelmintic properties.
Xanthone, Laboratory insecticidal tests indicated that xanthone was toxic to the mosquito larva, the codling moth larva, the diamondback moth, the southern army worm, and It has recently been made available in quantity and has been tested against codling moth larvae and other insectsunder field conditions. Further experimentation to determine the proper modes of application,its compatibility with fungicides, etc.,are necessary before any recommendations can be made for its use for the control of any insect pest. Phenazine (27) was found to be toxic to the clothes moth, the southern beet webworm, the Hawaiian beet webworm, the rice weevil, termites, and the larva of the codling moth. When tested against codling moth larvae under orchard conditions, however, this compound burned foliage severely. Experiments are under way in which various materials are being added to the spray mixture to eliminate this burning action. Dimethylacridan (8) was found to be toxic to the crossstriped cabbage worm, the diamondback moth, mosquito larvae, termites, the Colorado potato beetle, and the first instars of the southern army worm, the cabbage webworm, and the cabbage looper. It was also fairly toxic to the Hawaiian beet webworm. The compound was not injurious to bean and collard foliage. W i l e it is commercially available, dimethylacridan has not been tested extensively under field conditions.
Phenothiazine was first prepared as a possible insecticide in 1934 (ZOO). Laboratory tests indicated that the compound not only was more toxic than rotenone to mosquito larvae (S), but was fully as effective as lead arsenate in controlling codling moth larvae (24). It has also been found to be toxic to the tent caterpillar, the Mexican bean beetle, the grape-berry moth, the European corn borer, the screwworm,
1,4-Diphenyl Semicarbazide is toxic to the European corn borer, the southern army worm, the southern beet webworm, the Hawaiian beet webworm, the greenhouse leaf
This paper calls attention to some of the synthetic organic compounds that have been tested by the Bureau of Entomology and Plant Quarantine and found to possess sufficient insecticidal value to warrant more extensive trial. All the compounds have been prepared in sufficient quantity for more extensive laboratory testing, but their practical use has not been demonstrated, in most cases because insufficient amounts of the materials were available.
and several other insects of economic importance ( l a ) . I n common with other organic insecticides, phenothiazine is specific in its insecticidal action. For example, when tested against insect pests of cotton, the mortality was very low. Phenothiazine is available in large quantities at reasonable cost and has been tested under field conditions for several years, especially for the control of codling moth larvae. It is
tier, the yellow woolly bear, the melon worm, the pepper weevil, the bean leaf roller, and codling moth larvae. Although not available commercially, this compound is easily prepared in the laboratory; because of the promise it has shown as a potential insecticide, it has been prepared in considerable quantity and this year is being tested in small-scale field experiments against several species of insects. 499
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I N D U S T R I A L A N D E N G I N E E R I N G CHEMISTRY
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Phenoxathiin (Phenothioxin) Insecticidal tests have shown this compound ( I S ) to be effective when tested against the cabbage aphid, termites, the American cockroach, codling moth larvae (immediately after application), mosquito larvae, the Hawaiian beet webworm, the southern beet webworm, the diamondback moth, the screwworm, the housefly, and the rice weevil. Tests are being conducted under field conditions to determine its practical use, especially against the screwworm. p-Aminoacetanilide ($2) is toxic under laboratory conditions to the melon worm, the imported cabbage worm, the southern beet webworm, the Hawaiian beet webworm, the southern army worm, termites, the Mexican bean beetle, the diamondback moth, the bean leaf roller, the cross-striped cabbage worm, and the cabbage looper. Field tests are under way to determine its practicality. The compound is available from commercial sources a t a reasonable cost. Ortho-, Meta-, and Para-Iodonitrobenzenes. While these three isomers (14) differ in their toxicity to the various species of insects available for test purposes, some of them have been found to be effective when tested against the Hawaiian beet webworm, the grape-berry moth (both as a larvicide and ovicide), the diamondback moth, the tobacco hornworm, the codling moth, the first instar of the southern army worm, termites, and the rice weevil. They have been tested only in a limited way under field conditions, and the results are inconclusive.
a,@-Dibromoethylbenzene(Styrene Dibromide) , when tested in the laboratory (9),was found t o be effective against the southern beet webworm, the Hawaiian beet webworm, termites, the cabbage aphid, the greenhouse leaf tier, the diamondback moth, the cross-striped cabbage worm, the southern army worm, and the banded cucumber beetle. Phthalonitrile (IO), which i6 available commercially, is toxic to codling moth larvae, the screwworm, the southern army worm, the imported cabbage worm, the melon worm, the Hawaiian beet webworm, the southern beet webworm, the cowpea weevil, the rice weevil, and termites. Phthalonitrile is being tried rather extensively in small-field tests for the control of several species of insects.
N-Nitrosodiphenylamine was found in laboratory tests (6) to be toxic to the southern beet webworm, the Colorado potato beetle, termites, mosquito larvae, and tobacco hornworm larvae. It proved to be fairly toxic to the Hawaiian beet webworm, the cross-striped cabbage worm, the melon worm, and the American cockroach. Pentaerythrityl Bromide was effective when tested against the southern beet webworm, the Hawaiian beet webworm, the melon worm, termites, the cabbage looper, the southern army worm, and the cross-striped cabbage worm (7). Ortho-, Meta-, and Paranitrophenyl Iodochlorides (19) are easily prepared by treating the three isomeric iodonitrobenzenes with chlorine. They vary in their effectiveness against any particular insect, but one or more of the isomers was found to be toxic to the carpet beetle, the clothes moth, the rice weevil, the cabbage aphid, the greenhouse leaf tier, the Colorado potato beetle, the yellow woolly bear, the southern army worm, the diamondback moth, the Hawaiian beet webworm, the southern beet webworm, the melon worm, and the tobacco hornworm.
Iodosobenzene and Its Mononitro Derivatives (18) were toxic to the screwworm, the tobacco hornworm, the
European corn borer, the carpet beetle, the clothes moth, the rice weevil, the American cockroach, the Colorado potato beetle, the yellow woolly bear, the southern army worm, the
Vol. 34, No. 4
diamondback moth, the greenhouse leaf tier, the southern beet webworm, the Hawaiian beet webworm, and the melon worm, when tested under laboratory conditions.
Iodoxybenzene and Its Mononitro Derivatives (17) were found in laboratory tests to be toxic to the tobacco hornworm, the first instar of the southern army worm, the cross-striped cabbage worm, and the imported cabbage worm, and fairly toxic to the Hawaiian beet webworm, and the southern beet webworm.
4,6-Dinitro-o-cresol Methyl Ether has been known as an insecticide for many years. However, it burns foliage severely. When the phenolic hydroxyl was methylated, the resulting ether not only had insecticidal properties but also was only slightly injurious to bean foliage and noninjurious t o smartweed. This compound (16) proved to be toxic to the Mexican bean beetle and codling moth larvae, and fairly toxic to the tobacco hornworm. 4,6-Dinitro-o-cresol Acetate (16) was also found to be less injurious to foliage than was the free phenol and to be toxic to insects. While toxic to the tobacco hornworm, it caused severe foliage burning in all tests. While as toxic as lead arsenate t o the Japanese beetle, it produced severe wilting on smartweed foliage. On bean and apple foliage only slight injury was observed. The compound was toxic to termites, the southern beet webworm, the American cockroach, the Mexican bean beetle, the rice weevil, the Hawaiian beet webworm, the melon worm, the European corn borer, and codling moth larvae. Azo Compounds. A number of compounds of this class have been prepared and tested (26). They were found to be toxic to mosquito larvae (4). Fluorene and Its Derivatives. Fluorene is known to possess insecticidal properties. The substitution of various groups into the fluorene nucleus has in many cases increased the insecticidal action of the parent compound. For example, 2-chlorofluorene ( 3 ) proved to be toxic to the rice weevil, the melon worm, mosquito larvae, the diamondback moth, the Colorado potato beetle, the American cockroach, the European corn borer, and termites. The compound was fairly toxic to the southern army worm, the southern beet webworm, and the Hawaiian beet webworm. Field tests indicate that this material gives excellent control of the European corn borer. Other fluorene derivatives as insecticides are covered by a patent (23). Hydrazobenzene (26) was found to be toxic to the southern army worm, the cross-striped cabbage worm, the melon worm, and codling moth larvae. Halogenated Acetanilides (81) are very toxic to several species of insects, but the toxicity varies considerably, depending on the halogen involved, its position in the benzene ring, and the test insect. For example, orthochloroacetanilide is fairly toxic to the clothes moth, the meta derivative is very toxic to this pest, but the para compound is ineffective. One or move of the compounds in this class are toxic t o termites, the clothes moth, the southern army worm, the Colorado potato beetle, the cross-striped cabbage worm, the melon worm, the European corn borer, the greenhouse leaf tier, the Hawaiian beet webworm, the diamondback moth, and the yellow woolly bear. Semicarbazones. A number of members of this class of compounds are toxic to insects. For example, acetone semicarbazone is toxic to the southern beet webworm, the Hawaiian beet webworm, the melon worm, the greenhouse leaf tier, and the diamondback moth, and fairly effective against the imported cabbage worm.
April, 1942
INDUSTRIAL AND ENGINEERING CHEMISTRY
N-Substituted Amides have shown considerable promise as insecticides. 2-Furan acrylamide ( I ) , for example, has been found to be toxic to screwworm larvae, the southern beet webworm, the melon worm, the imported cabbage worm, and the southern army worm. Literature Cited (1) Bowen, C. V., U. S. Patent 2,224,243 (1940). (2) Campbell, F. L., Sullivan, W. N., Smith, L. E., and Hailer, H. L. J., J. Econ. Entomol., 27, 1176-85 (1934). (3) Claborn, H. V., and Smith, L. E., U. S. Patent 2,175,109 (1939). (4) Fink, D. E., and Vivian, D. L., J . Econ. Entomol., 29,804 (1936). (5) Freeman, A. F., U. S. Patent 2,155,010 (1939). (6) . . Roark. R. C.. U. S. Bur. Entomol. and Plant Quarantine, Mimeogra& E-537 (1941). (7) Rose, W. G., and Haller, H. L. J., U. 9. Patent 2,140,481 (1938). (8) Schaffer, P. S., and Haller, H. L. J., Ibid., 2,099,826 (1937). (9) Schechter, M. S.. and Haller, H. L. J., Ibid., 2,189,570 (1940).
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Smith, C. R., Richardson, C. H., and Shepard, H. H., J. Econ. Entom~l.,23, 863-7 (1930). Smith, L. E., U. 8. Bur. Entomol. and Plant Quarantine, Mimeograph E-399 (1937). Smith, L. E., U. S. Patent 2,049,725 (1936). Ibid., 2,100,493 (1937). Ibid., 2,115,046 (1938). Ibid., 2,127,090 (1938). Ibid., 2,191,299 (1940). Ibid., 2,191,300 (1940). Ibid., 2,191,301 (1940). Ibid., 2,217,566 (1940). Ibid., 2,226,672 (1940). Ibid., 2,239,832 (1941). Smith, L. E., and Claborn, H. V., Ibid., 2,197,249 (1940). Smith, L. E., Munger, F., and Siegler, E. H., J . Econ. Entomol., 28, 727-8 (1935). Vivian, D. L., U. S. Patent 2,173,386 (1939). Vivian, D. L., and Haller, H. L. J., Ibid., 2,094,831, 2,095,93941, 2,096,414 (1937) ; 2,110,896-7, 2,111,879 (1938). Ibid., 2,110,614 (1938).
Derivatives of Dithiocarbamic Acid as Pesticides . . W. H. TISDALE AND A. L. FLENNER E. I. du Pont de Nemours & Company, Inc., Wilmington, Del.
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NVESTIGATIONS by the du Pont Company in 1931 showed some of the derivatives of dithiocarbamic acid,
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dN-i-" to have insecticidal and fungicidal value. Some of the alkyl derivatives, including the methyl and ethyl derivatives, appeared to be most promising. The thiuram sulfides, R R \ / N-C-S-C-N
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and the metal dithiocarbamates, R
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were of special interest. More extensive investigations since that time have developed further valuable information on the efficiency of these products as insecticides and fungicides, and have shown some of them to be toxic to mites and highly toxic to the protozoan causing cecal coccidiosis of poultry. A marked degree of specificity is shown by members of this group of organic sulfur compounds on the different kinds of pests. Substitution of one or both alkyl groups by aryl groups has been shown to lower the fungicidal efficiency. Some of those with only alkyl groups are sufficiently outstanding in effectiveness for certain specific purposes to justify some optimism with regard to their practical use. As is true with many sulfur compounds, the thiuram sulfides have shown a tendency to cause dermatitis on a low percentage of humans. The derivatives tested have proved to be unusually free from injury to plant life.
Fungicidal Efficiency Laboratory evaluations with the thiuram sulfides and thiocarbamates indicated that there was a wide range of difference in the toxic action of different members of these groups under the conditions of the experiments. Water and nutrient agar media were employed. Sodium dimethyl dithiocarbamate was the most effective of these chemicals when applied in water to the spores of Ustilago hordei (covered smut of barley). A dilution of this chemical (1 to 30,000) in water was highly effective in killing spores of the fungus. Tetramethylthiuram monosulfide was effective in twice the foregoing concentration. The 'derivatives of a lower degree of water solubility proved less effective in these tests. These compounds were less effective against Fomes annosus and Aspergillus niger when incorporated in nutrient media which were inoculated with mycelium of these fungi. The metal derivatives showed a low degree of effectiveness in such laboratory tests. Solubility and possibly stability may have contributed to the results, the more soluble and less stable compounds showing higher efficiency. Experiments on Tricophyton sp. and other fungus infections of the skin showed tetramethylthiuram monosulfide, tetraethylthiuram monosulfide, and sodium dimethyl dithiocarbamate to be effective in low concentrations. The first of the three was used on a large number of cases in a concentration of 0.8 per cent in alcohol solution and resulted in slightly over 90 per cent cures. Approximately 2 per cent of these cases developed'a dermatitis, in most cases slight, which was attributed to the treatment. Field investigations in the control of fungus diseases of plants have developed some interesting results which tend to emphasize the specific action of these compounds. Tetramethylthiuram disulfide has proved to be highly effective for the control of tulip fire, Botrytis tulipae, in Europe. It is effective for the control of apple scab, Venturia inaequalis. Harrington (4)reported this compound to be effective for the control of turf diseases.
