Aspects of the Chemistry of DDT FRANCIS A. GUNTHER University of California Citrus Experiment Station, Riverside, California
M
UCH to the discomfiture of the chemist, DDT has become the popularized symbol for dichlorodiphenyltrichloroethane, and is understood to designate a white, odorless, crystalline material, the crude form of which is 71 years old. Unfortunately, dichlorodiphenyltrichloroethane must be regarded as a loose portmanteau word and a misnomer, for it may signify any one of 27 different compounds ( I ) , only a few of which are rigidly isomeric. As commonly used, however, the letters DDT actually refer to 2,2-bis-(9-chloropheny1)l,l,l-trichloroethane, I.
Zeidler duly published the above facts, indicating his compound to be "2,2-bis-(2-chloropheny1)-l,l,ltrichloroethane" because of the uncertainty regarding the exact placements of the two chlorine atoms in the aromatic nuclei. The deduction of the remainder of the assignment of structure was based upon the work of Fischer (6).who had previously synthesized 2,2-ditolyll,l,l-trichloroethane and degraded i t to the known para-substituted benzophenone derivative by way of the ethylenic intermediate. Zeidler further stated that his compound readily lost hydrogen chloride upon refluxing with alcoholic potash. About 1925, the J. R. Geigy Company of Basel, Switzerland, a firm devoted to the manufacture of dyestuffs and of dyestuff intermediates, began a study of the chemistry of the toxicology of rotenone and of the pyrethrins, two excellent insecticidal materials. This septuagenerian has been termed the penicillin Their methodical study enabled them to determine that of insecticides, and i t may indeed be regarded as one of these toxicants apparently acted by virtue of a toxic the outstanding accompaniments of the present war (2). nucleus which was carried to a site of action within the To it has been ascribed fantastic prowess as an insect insect integument via lipoid-soluble portions of the exterminator. Sufficient of this prowess is true to molecule. This verification of an old concept enabled warrant the present report as an attempt to rectify Paul Miiller (7), of the Geigy Company, to modify one some of the prevailing misinformation concerning its of the Geigymothproofingagents, p,pl-dichlorodiphenylchemistry and to discuss briefly certain developments sulfone, into a lipoid-soluble material capable of funcconcerning,its chemical behavior as an insecticide. A tioning as a contact insecticide. Miiller performed this discussion of the entomological and pharmacological transformation by substituting for the sulfone groupaspects of the story of DDT is beyond the scope of this ing a portion of the excellent lipoid solvent trichlororeport; excellent reviews in these two fields may be ethane, namely =C-CCL. The result, of course, was DDT, recrudesced after 70 years.' found elsewhere (3 and 4). In 1939 first reports of this outstanding new insectiIn 1874, Othmar Zeidler (5), a graduate student in a laboratory in Strasbourg, synthesized a number of cide reached the United States from Switzerland, where organic compounds as a very minor part of his doctorate it had been used successfully to subdue an infestation of research. In one experiment, by treating one part of the Colorado potato beetle. This insect is not particuchloral with two parts of chlorobenzene in the presence larly difficult to control, however, and American of sulfuric acid, he readily obtained a pasty mass of entomologists exhibited very little interest. Addiwhite pellets, in poor yield. These pellets, upon tional, more spectacular reports of this new insecticide crystallization from alcohol, yielded a small quantity ' For the complete story underlying this series of investigations of fine white needles, m. p. 105'C., with a fruity odor. which resulted in DDT, see LXUGER,P.,H. MARTIN,AND P. This condensation product is now known as DDT. Miir.L&~, Heh. Chin. Acla, 27, 892 (1944).
appeared, then began to pyramid, and American ento- from the oleum by settling, then by water and alkaline washings. 3. Vacuum distillation and recovery of chlorobenzene solmologists seized upon DDT with a firm grasp. Pro- vent, followed by air stripping of the residual chlorobenzene duction in the United States now exceeds .2,000,000 from the DDT. pounds per month, all under allocation control. 4. Cooling and solidification of the DDT, followed by pulThough DDT had become such an important com- verizing, blending with extenders, and final packaging. modity, its structure was never unequivocally proved The over-all yield in this process, based upon DDT of but was tacitly assumed upon bases of analogy until setting point 8S°C., is 95 per cent. very recently. Grummitt and coworkers ( 8 ) , in 1945, An unconfirmed newspaper report (11) suggests that established the structure of DDT (the principal isomer zinc chloride may be a better condensing agent than obtained by Zeidler's procedure) by dehydrochlorina- sulfuric acid in this process; preliminary work indicated tion to 2,2-his-(9-chloropheny1)-1,l-dichloroethylene that the zinc chloride treatment yielded a much cleaner (loosely called "DDD"), 11, with alcoholic product in better yield. Technical DDT, of setting point 88°C. as obtained in the Brothman continuous process, possesses the following approximate composition:
.................................... ...........................................
potassium hydroxide; the $-placements of the aromatic. chlorine atoms in the latter compound were proved by its oxidative degradation to the known 4,4'-dichlorobenzophenone. In another detailed report the writer (9) discusses the complete historical background for this apparent oversight of proof of structure, and shows that the procedure employed by Grummitt, et el.,has been the standard one for proofs of structure of nearly all the known compounds of the type RKH-CXs, wherein R is a substituted phenyl and X is a halogen (usually chlorine or bromine). In general, the dehydrohalogenation step proceeds smoothly and qnantitatively, whereas the ease of oxidation of the resulting ethylenic derivative varies tremendously. As reported by Grummitt, et al. (8) and corroborated by the writer (9), attempted oxidation of DDT itself under the same conditions as above indicated practically no attack by the reagents. In the usual commercial process for the manufacture of crude DDT, the basic procedure of Zeidler (5) is employed. This process consists of bringing together two mols of chlorobenzene and one mol of chloral hydrate, or free chloral, in the presence of excess concentrated sulfuric acid as the condensing agent. The reaction may be brought about a t room temperature, over a period of several hours, but the resulting yield is low. In the laboratory, increasing the temperature to about 6OoC. results in a better product in a somewhat better yield, although the theoretical yield cannot be attained by this method because of the very strong main competing reaction, namely, sulfonation of the chlorobenzene. Reaction conditions must he adjusted to minimize sulfonation and to favor c~ndensation.~ In actual commercial practice, the Brothman continuous process (10) for the production of DDT is utilized. This process consists of the following individual stages :
P,D'-lromer (DDT) 70% o.#'-lromer 18% 0.0'-Isomer ........................................... 6% '.Oily by-product" (unidentified)........................ 2% Uoideotified solids.................................... 2%
volatile material.. ....................................
Ash..................................................
1%
1%
A material of higher setting point would contain a greater percentage of actual DDT. The o,$'-isomer, mentioned above, is also loosely known as the "ortho-" or "oily" isomer. As will be discussed in detail later, this isomer does not dehydrochlorinate, under the influence of alkali, in as straightforward a manner as does DDT. Instead of releasing 1.0 mol of halogen acid per mol of parent compound, i t releases 1.1 mols of halogen acid. This type of behavior is not unknown for ortho-substituted halogencontaining compounds of this general structure. The o,p'-isomer is reported to melt around 40°C. (12). Even less information is available concerning the chemistry of the o,ol-isomer and the other commonly occurring contaminants in technical DDT. Ordinary technical DDT, which varies in color from off-shade white to deep gray, and which possesses a fruit-like odor, may be partially purified with ease by recrystallization from excess ethanol or isopropanol. One or two recrystallizations will usually yield a crystalline material of m. p. 105'C. In order to secure a very pure product, however, it is usually necessary to decolorize the material a t least once with charcoal, followed by four or five recrystallizations. Very pure DDT, obtained in this manner, occurs as tiny, glistening, white needles, with no odor, and melts sharply a t 108-9°C. (con.). It apparently will sublime very slowly, even a t atmospheric pressure (12,30). Schechter and Haller (13) reported that a "nitrated derivative from $,$I-DDT" exhibited an absorption maximum at 600 mp with a minimum a t 443 mp, and they used these values in a proposed colorimetric method (discussed on p. 2130) for the quantitative estimation of DDT. The same type derivatives of p,$'DDD (see above) exhibited maxima and minima, re1. Reaction of chloral and chlorobenzene with oleum to form spectively, of 598 mp and 442 mp. The o,$'-DDT DDT, its isomers and polymers. 2. Sewration and neutralization of the dissolved DDT derivatiGe exhibited two maxima, namely, 590 mp and 511 mp, and two minima, namely, 558 mp and 426 mp. For laboratory methods of preparation see THISJOURNAL, 22, Work in this laboratory (14) has shown that pure $ , P I 122 and 170 (1945) (Editor).
DDT itself exhibits a pronounced maximum absorption a t 236 mp with two weak peaks near 221 mp and 265 mfi; three minimal values appear a t 218 mp, 226 mp, and 263 mp. These values were determined in 95 per cent ethyl alcohol; in cyclohexane, each of the values was shifted upward by approximately 3 mp. In both solvents p,p'-DDD exhibited maxima near 246 mp, with no definite minimal values discernible. The complete absorption data for DDT and certain of its derivatives will be presented in detail elsewhere. An elementary, but very important, property of any new compound such as DDT is its solubility in a great many different solvents. For practicable reasons, solubility a t room temperature is of prime importance. Incorporation of DDT into liquid sprays, for example, obviously requires a knowledge of relative solubilities only a t that temperature a t which the spray mixture will be stored and used. Consequently, there is available very little information regarding the solubility of DDT a t temperatures other than room temperature. Only a few solubility curves have been determined (15); these apply to a narrow temperature range, and are reproduced in Figure 1. From this figure it appears that the solubility of DDT in 95 per cent ethyl alcohol is low. Actually, however, above 50% the curve slopes very sharply upward, and a t 7S°C. a given weight of alcohol will dissolve approximately an equal weight of DDT. This fact is mentioned because of the widespread acceptance
of alcohol as one of the best recrystallizing solvents for DDT. Campbell and West (16) report the solubilities, in grams per 100 grams of solvent a t "ordinary temperatures," of DDT in the following solvents:
.....................
Benzene 106 99.5 pereenteth>l alcohol.. .... n-butyl almhol.. ............. 8 Kerosene (vnporiring).,. ...... tert-butyl alcohol.. ........... 4 liquid paraffin.. ............. Chlomform.. 96 Orchard and $pray oil.. ....... Cycloberanol. ............... 8 Petroleum ether (40-60'C.I.. Cydahexanone ............... I00 Petroleumether(100-18O'C.) 45 Tetmehloroethane Ether ....................... Ethyl acetate.. .............. 68 Tetralin.. ................... Toluene .....................
................
.. ...
............
4 11 4 5 6 10 56 52 48
It will be noticed that some of these values do not quite agree with those values in Figure 1, assuming "ordinary temperatures" to mean about 25°C. In addition to the above list, the following solubilities may be mentioned, in grams per 100 milliliters of solvent, temperature again unspecified (17): Dimdhylphthalatc ................................... Freon (12) ........................................... Pveloi1#2 ........................................... Indeloa Keroreo Kerosene (purified). .................................. Serameoil ........................................... Triton ............................................... Tungoil ............................................. Xylene ..................................... z . . . . . . . .
31 2
10 29 5 8
2-4 10 20 10-14 56
DDT, of course, is insoluble in water, in dilute mineral acids, and in dilute alkalies, including aqueous ammonia solutions. Some of the pioneer work with DDT indicated that it was a remarkably stable compound, but actually such is not the case. As mentioned previously, i t is very sensitive to alkaline materials. Furthermore, the pure compound also dehydrohalogenates upon heating slightly above its melting point. The technical grade, which contains appreciable quantities of the heatsensitive o$'-isomer, may begin to cleave hydrogen chloride as low as 50°C. A temperature of 80°C. results in a 90 per cent loss of insecticidal efficacywithin 24 hours (18). Interestingly enough, the heat-induced decomposition of DDT appears to be autocatalytic, with the liberated hydrogen chloride initiating further decomposition. In the absence of excessive temperatures, the primary decomposition product, DDD, is comparatively more stable than the parent compound. Fleck and Haller (19) have reported that anhydrous ferric and aluminum chlorides, iron, iron oxides, and certain mineral materials, such as fuller's earth, were found to act catalytically to eliminate hydrogen chloride from DDT and certain of its analogs, yielding the corresponding ethylenic derivatives. Solvents such as stearic acid, n-octadecyl alcohol, and petroleum fractions (b. p. over 100°C.) inhibited the reaction. Contrary to the early reports, under summer field conditions in southern California where leaf temperatures may exceed 125'F. and fruit temperatures may 10 20 30 40 50 exceed 135OF. (ZO),DDT was found to lose its residual Temperature, T. FIGURE 1.-SOLUBIL~Y OFPURE DDT INVARIOUS SOLVENTS: effect very quickly (21). Usually two weeks were more 1. ACETONE; 2. BENZENE;'3. CARBONTETRACHLORIDE; 4, than sufficient to eliminate toxic effects completely. ~ H L O P . ~ F O R M5,6DIoxAN;~f6,fi ;~ ETHER; 7, ETHANOL (95 PER Similar experiments performed under winter condiCENT);-8, PETROLEUM ETHER(30-60°C.); 9. PYRIDINE.
i
tions, however, indicated little, if any, loss of toxicity over periods of several months. These results, and similar reports filtering in from other investigators, suggest that ultraviolet energy, between 2875 and 3100 A. U.,3may be another catalyst for the dehydrohalogenation of DDT, although Garman and Townsend (23) report that sun-lamp irradiation does not destroy the effectiveness of DDT as a dust. Furthermore, since it is possible to deprive DDT of all its toxicity under these field conditions, and since DDD is about half as toxic as DDT against certain insects (24), it is here postulated that the following reaction chain may accompany the field decomposition of DDT in the absence of accepted dehydrohalogenators : U.V.
light
I
11
It is a matter of coincidence that this series of reactions is the same as that used to confirm the structure of DDT (8 and 9). As has been shown (25) previously, the benzophenone derivative, 111, is functionally capable of undergoing several other sunlight-induced degradations and rearrangements. Although t h i s benzophenone derivative itself possesses no toxic propkties as an insecticide (24), certain of the theoretically possible further degradation intermediates possess considerable theoretical toxicological significance. This matter is being investigated thoroughly, and will be reported in detail elsewhere. From the above results i t may be implied that the user of DDT as an insecticide should: (a) avoid strongly alkaline diluents or strongly alkaline detergents; ( b ) avoid contamination of his material with active salts of iron, aluminum, and other hydrogen carriers; (c) not expect too much from DDT under extreme summer conditions; and (d) keep all DDTcontaining preparations stored in a cool place. Certain of the preceding data have been obtained by means of bio-assay only, whereas others have been confirmed with chemical estimations, also. To date, there are four methods extant for the chemical assay of DDT and of DDT residues on treated materials. These methods are sufficiently different to offer considerable choice to the prospective user as regards range and sensitivity desired. The author's method (26) consists of stripping the treated object with benzene, evaporating most of the
-
a Approximate minimal values for summer and winter sunlight, respectively, in southern California (22).
solvent, and then quantitatively dehydrohalogenatiug the residual DDT with alcoholic potash, thus liberating one molecule of chloride ion per molecule of parent DDT. This chloride ion is then titrated quantitatively. Unfortunately, as mentioned previously, the o,p'isomer interferes with this method sufficiently to require a blank for all batches of technical DDT employed by the experimenter. On the other hand, the method will not respond to any chloride-containing organic compound that is not functionally capable of dehydrohalogenation under the recommended conditions. The influence of fats, waxes, and other saponifiable substances in the fruit or leaf strip, and which would conceivably interfere with a standard silver titration of chloride ion, may be minimized by treatment of the saponified (digested) mixture with barium chloride solution, followed by a quantitative filtration, before the titration. Approximately 2 milligrams of DDT per sample is the minimum quantity that can be determined accurately with this method. Hall, Schechter, and Fleck (27) have employed a modification of the Winter (28) method for the determination of DDT in emulsions and other materials. This method involves volatilizing the sample to be analyzed, burning it in a flame of ordinary illuminating gas, and absorbing the chlorine-containing combustion products in an alkaline solution of sodium arsenite. The resulting solution is then titrated for chloride ion. A correction factor, due to a consistent low error of 6 per cent chlorine is necessary, and special apparatus is required. The major disadvantage of this method, of course, is its nonspecificity for DDT or related compounds; any organic halogen-containing material would respond. Details as to range and sensitivity were not presented. Schechter and Haller (13) have described in a preliminary manner a sensitive colorimetric test for DDT and related compounds based on nitration to polynitro derivatives, 6 t h the production of intense colors upon treatment of the nitration products with sodium methylate. The derivatives of p,pl-DDT and p,plDDD give transient blue colors, while the derivative of o,pl-DDT gives a transient violet-red color. This method appears to be very sensitive, and i t is especially noteworthy because i t appears capable of determining both the total and the relative amounts of p,p'-DDT and o,pl-DDT in mixtures of the two. A number of interferences have been found, sonie of which-would be expected to occur or be used with DDT. The obvious manipulative disadvantages of this method are that it requires extremely careful technique, that completely anhydrous conditions must be maintained throughout the complicated procedure, and that a skilled, trained operator is required to prepare the necessary reagents. A theoretical drawback is found in the fact that without the use of a spectrophotometer, this method will not distinguish between p,pf-DDT and p,pl-DDD, for in this method their absorption maxima and minima are practically identical. Bailes and Payne (29) have recently proposed a
method involving the use of the Friedel-Crafts reaction upon DDT. Their procedure results in a reaction product with a stable orange color. Too little is known about this method a t present to discuss its possibilities, although it looks promising. It is rapid, simple, and extremely sensitive, but the matter of interference by the other isomers will require further attention. From the foregoing review it may be seen that actually very little precise information concerning the chemical behavior of DDT is available. There is a great need for a systematic investigation of the chemical phenomena attendant upon the proved decomposition of DDT upon exposure to the elements and to possible adjuvants in insecticidal compositions; the inhibition of this decomposition must be studied in detail; and, finally, the mechanism of its toxicological action should be investigated, for it is not likely that the mere liberation of hydrogen chloride at the site of action would account for its amazing eficiency. LITERATURE CITED
( 1 ) ANONYMOUS,Monsanto Magazine, XXIII, 23 (1944). J . G., Sat. Ewe.Post,217,86 (January 6 , 1945). ( 2 ) SIMMONS, ( 3 ) ANNAND,P.N.. J.Econ. Entomol.,37,125 (1944). J . X., et al., Chenr. Eag. New, 22, 1503 (1944); ( 4 ) DRA~ZE, ANONYMOUS, ibid., 2025; STENERSON, H. W., ibid., 2179; WO~DWARD, G., et al., J . Pharmecol. and Exptl. Therepeuticr, 82, 152 (1944). ( 5 ) ZEIDLER.0.. Ber., 7 , 1181 (1874). 0.. ibid., 1191. ( 6 ) FISCHER, (7) M ~ L L E R P.,, U . S. Pat. 2,329,074. et ad., J . A m . Chem. SOL..67. 155 (1945). ( 8 ) Gnunrmrr. 0..
( 9 ) GUNTHER, F. A,, Oid., I n Press. (10) ANONYMOUS, Chem. & Met. E~ng.,51, 112 (1944). Fresm Bee (March 31, 1944). (11) ANONYMOUS, J. J.. Personal communication. (12) JACOBS, (13) SCHECHIER, M . S . . AND H. L. HALLER, J . A m . C k m . Soc., 66, 2129 (1944). (14) GUNTHER, F. A., Unpublished data. Manuscript on file a t the University of California Citrus Experiment Station.
-...-.-.-- .
(15) GUNTHER, F . A., J . A m . Chem. Soc., 67, 189 (1945). (16) CAMPBELL G. A., AND P. F. WEST,Chem. Trade J . and Chem. Eng., 115, 195 (1944). (17) ANONYMOUS, U. S. Navy Manual, "Navmed," 292, 2 ilcldd)
(20) (21)
TARELL, F. M., Callf. Citrograph, 28,287 (1943). LINDGREN, D. L., Unpublished data on file a t the University
of California Citrus Experiment Station, Riverside. (22) M., "Artificial Sunli~ht."D. Van Nostrand Com. . LUCKIESH. pany, Inc., New York, 1930,p. 34'. P., AND J. F. TOWNSEND, Conn. State Entomologist. (23) GARMAN, Bull. 481 (1944). 0.280. , CARMAN, G. E., AND F. A. GUNTHER, Unpublished data on file at the University of California Citrus Experiment Station, Riverside. MONTAGNE. P., Rec. de tram. chim., 21, 6 (1902); ibid., 24, 105 (1905). GuNTaER, F. A., University of California Citrus Experiment Station 4 P. mimeo. (June, 1944). Also Ind. Eng. Chcm.. A n d . Ed., In Press. HALL,S. A., M. S. SCHECHTER. A N D E. E. FLECK, U.S. D.A. Bull. ET-211, (November. 1944). WINTER,P. K., Ind. Eng. Chcm., Anal. Ed., 15, 571 (1943). BAILES,E. L.. AND M . G. PAYNE, Unpublished manuscript on file at the Colorado Agricultural Experiment Station. Fort Collins. FLECK, E. E., J. Econ. Entonol., 37, 853 (1945). ~~
~
,..
~~
