STUDIES ON THE MAJOR PHOTOLYTTC PRODUCT 0F ENDRIN Thesis for the Degree of M. S. MICHIGAN STATE UNIVERSTTY WENDEL LAURENCE BURTON 1968 a " ”—7- m~f LIBRARY 1 THESIS Michigan sum 3 University I. ABSTRACT STUDIES ON THE MAJOR PHOTOLYTIG PRODUCT OF ENDRIN by Wendel L. Burton The persistence, toxicity, and use of the chlorinated hydrocarbon insecticide endrin (A) has brought major concern not only to researchers but also to the public. The objective of the research described here Ias to determine to that degree endrin is reactive to irradiation particularly in the range of natural sunlight and atmospheric surface conditions and to study the nature of its photolytie products. Indeed, endrin (A) sas found to be converted cleanly in yields up to 80 per cent to an entirely nee compound by irradiation at 2537A in cyclohexanc. The equivalent of dichloroaeetylcne sas eliminated from endrin to yield 3,3,4,5R-tctrachlcro-tetracyclo[5.2.1.02'5.0‘.9] decan-a-one (B), a ring system not previously reported. Compound (B) was found to be highly resistant to the usual oxidation and reduction procedures, and to be insoluble in the common organic solvents used in chloro- insecticide analysis. Simple toxicity tests showed (B) to be three times as toxic to mice and five times as toxic to flies relative to endrin. However (B) did react quite specifically and cleanly in over 90 per cent yields through ring closure and homoenolization to Wendel L. Burton 2,3,4,4-tetrachloro-pentacyclo[5.5.0.02'6.05'1905'q decanol (O). The chemistry of (0) proved interesting as it underwent cleanly and in excellent yields replacement of the hydroxy group by a chlorine by reaction with either thionyl chloride or phosphorus pcntachloride to give l,2,3,4,d-pentachloro-pcntacyclo[5.3.0.02’6.05’1°. 05'9] dccane (D). Reduction.sith lithium.metal, tertiary butyl alcohol in tetrahydrofuran of (D) gave a known compound pentacyclo[5.3.0.02’6.03'9.05“q&decane (E) established by direct comparison Iith.an authentic sample. Nuclear magnetic resonance spectroscopy proved to be the most singularly important tool in the structure determination of photolytie products of endrin, although infrared, ultraviolet, and mass spectroscopy, and gas, thin layer, and column chromatography were also utilised. It might be concluded that the photolytic product (3) may well be the real species causing the persisteney and toxicity instead of its parent (A), especially in vice of the fact that photolysis at 5600A (shich is the ultraviolet radiation in sunlight at earths surface) yielded results essentially similar to those obtained at the shorter savelength.25371. Wendel L. Burton hf . 2537A T’ \ Cil l \C) C' H (B) strong base (I HO : $0912 Cl C (I Cl Cl Cl C' ' (D) L, (c) T t-BuOH (E) STUDIES ON THE MAJOR PHOTOLYTIC PRODUCT 0F ENDRINA By Wendel Laurence Burton A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE Department of Chemistry 1968 36‘» C) I" ./ f?“ f»- :9) AMOWLEDGMENT Sincere thanks should be extended to Professors 3.1). Schuets and Id. Zabik shose friendship and insight have encompassed more than Just chemistry. 11 TABLE OF CONTENTS Page ACKNOWLEDGMENTS................ ii LIST OF FIGURES . . . . . . . . . . . . . . . . v LISTOFTABLES................ vi BACKGROUND.................. 1 RESULTS AND DISCUSSION . . . . . . . . . . . . 6 MPERmENTAL................. 18 Photolysis . . . . . . . . . . . . . . . . l9 Preparations . . . . . . . . . . . . . . . 22 ,e-Tgfgaehlcro-Pentacyclo[5.3.0.02'6 ecanol . . . . . . . . . . . 22 5, 4 fiiaPcnta hlorc-Pentacyelolb.5.0. “5 Decsne . . . . . . . . . 24 Pcntacyclc[5.3.0.02 5 .03v 9 .05 alDecane . 25 Pentacyclo[5.5.0.02”6.03’10.05’ 9]Dscan.ol 27 attempted Preparations . . . . . . . . . . 29 Dehalogenation of Photoproduct IV . . . 29 Tosyl Hydrazonc Formation of Photoproduct 30 Hydrazonc Formation of Photoproduct IV . 30 Wolff-Kischner Reduction of Photoproduct IV . . . . . . . . . . . . . . . . . . . 31 Olemmensen Reduction of Photoproduct IV 32 Thic Ketal Reduction of Photoproduct IV 53 iii TABLE OF CONTENTS (CONTINUED) Page Baeycr Yilliger Oxidation of Photoproduct I I O O O O O O O O O O O O O O O O O O 3‘ Photolysis of Compound 11, 1,9,10,1g,ll, SEQ-lz-H chloro Pentacyclo[7.2.l. ’5. 0 9 007’ Dodeoan-S-Oi’le e e e e e e e c 55 BIBLIOGRAPHY O O O O O O O O O O O O O O O O O 44 1' LIST OF FIGURES Figure Page I. The Infrared Spectrum of 3, 3, 4 fi- Tetrachloro-Tetracyclo[5. 2.1.02 5 O 4'9]D°can-8-One 1!! K31. e e o o e e e 57 II. The Infrared Spectrum of 2, 3 ,424 Tetrachgog -Pcntacyclo[§.3. 0.0 fDecanol in.KBr . . . . . . 38 Ila. The Infrared Spectrum of 2 ,3 ,42d- Tgtf8°h£°£ -Pentacyelo[3.3.0.0 O fDecanol in Garbontetra- chlor1&. O O O O O O O O O O O O O O 59 III. Them hfrared Spectrum of 1, 2 ,324 4- Paniaohijog -Pcntacyclo [5. 3. 0.0 .5, inecane Concentrate in garbangotraehlorid. e s c e e e e e e 40 IV. The Infrgrgd Spgctgug of Pcntacyelc 5. .0.0 v Decane Super- imposed on a Known.Authentic Sample 1n Km 0 O O O O O O O O O O O O C O 41 V. The Infrared0 apistrum9 f Pcntacyclc [5.3. e ’6 DecanOl in m 42 LIST OF TABLES Table Page I. Nuclear Magnetic Resonance Data . . . . 43 71 BACKGROUND The fate and persistence of organic pesticides has been given considerable attention recently. The side spread application of pesticides has preceded their in depth studies of the potential long range effects as health hasards to man and his environment. Studies have been made on the half lifes, residue levels, drift, runoff, and toxicities of the various pesticides. However, the chemical nature, especially under field conditions, of the pesticides and their potential photolytic decomposition products is still unknown. The need and importance for such.research is dramatic shen one considers the unexplored risks of the present applications of organic pesticides to our environment. For example, last year over 800 million pounds were applied in the United States alone and this level increases 35 million pounds a yesr.(l) A major portion of these pesticides belong to a group knosn as the chlorinated hydrocarbon insecticides. This group of insecticides recently has been getting greater publicity because of the events like the Gclorado River fish hill and the fire ant fiasco. 'The chlorinated hydrocarbon insecticides are applied yearly in the united States on the 150 million pound scale. They have developed and hold this market because of their broad spectrum and low cost. It is because of this broad spectrum and its supposed ability to remain active for long periods of time that has stimulated research interest in these materials here at Michigan State University. A widely used member of the chlorinated hydrocarbon insecticides is cndrin. Interest in cndrin ll,2,3,4,10, lO-hexachloro-6,7 cpoxy-l,4,4a,5,d,7,8,8a octahydro-l, dggggg,g§gg-5,8 dimethanonaphthalcne), I, has arisen from tee reasons. The first is its side use as an effective broad spectrum and los cost pesticide. The second is its unique stereoehemistry shich alloss it to underge a variety of reactions from simple addition to complex transannular rearrangements.(2-8) Bndrin’s major use has been in protecting the cotton plants from bollsorms, cabbage loppers, and numerous other pests.(9) It also is supposed to be highly toxic and stable for long periods of time under field conditions. For example, in comparison to DDT endrin is fifteen times as toxic to mammals, thirty times as poisonous to fishflO), 300 times as toxic to some birds, and has been found to kill at least fifty per cent of the shrimp in as los concentration as one half part per billion.lll) This toxicity level, combined with data like the residues found in vegetables treated sith insecticides (2,420-d,370 parts per billion DDT in spinach)(la), or the runoff of surface actors on sprayed fields (0.36 parts per billion in furrow cater from cotton field sprayed sith.0.d lbs/acre or roughly eoo ppb/acre) (9), or that of the endrin spray applied ten feet above the ground in three mile per hour mind the ten micron sise drifted one mile shereas the tso micron size sas found as far as tsenty one miles asayllZ) gives one some indication of its potential hasard to human environment. Half life studies have indicated that cndrin is one of the more persistent insecticides with a half life of over seven years in the field. While cndrin is moderately persistent, it does however disappear through some avenue other than the general routes like runoff, leaching, and translocation. A reasonable avenue for its removal is by photochemical reactions and chemical rearrangements into other chemical compounds as a result of irradiation by sunlight, most probably in the range belos 36001. Roburn (13) reported 4 qualitfartively that endrin was-partially converted to see compounds by irradiation of the deposited solid at 85375. Rosen and Sutherland (14) isolated the previously reported (6) ketone 11 and aldehyde III in Ci 0‘ H \ CI Cl Cl CI (II) (III) thirty seven and nine per cent yield respectfully follosing irradiation of endrin at 2537A using hexane: acetone as the extracting solvent. Compounds II and III sere found to be nontoxic to the housefly and mosquito at concentrations 0.24 pg/fly and 96 ppb, respectfully. Yields of thirty seven and nine per cent does not explain shat is the fate to even one half of the endrin applied. A better initial approach.sould be to study the photolysis of cndrin.in solution. more exacting conditions can be attained in solution versus solid irradiation; and since the usual application of endrin is in the form of a tsenty per cent active ingredients in a hydrocarbon solvent, tso such inert solvents were 5 chooses: hexane and cyclohexnns. Therefere, photolysis experiments were carried out in these laboratories to ascertain whether endrin does undergo photochemical rearrangements in solution. RESULTS AND DISCUSSION Endrin, indeed, underwent photochemical reaction in solution. In varying the percent of endrin from 0.3 to 8.9 percent by weight (or 0.0065 to 0.1000 molar) the rate of disappearance of cndrin was found to be nearly complete sithin eight hours. At concentrations greater than one per cent, precipitation occurred during the photoreaction, probably due to the insolubility of some of the photolytie products. After an initial photolytie lag phase of one hour, precipitation commenced and continued until, at the end of the second hour of photolysis the reaction had to be stopped due to the density of the product‘s). Up to an 80%ryicld of a pure shite crystalline material sas recovered from such photolysis reactions. Simple toxicity tests (19) chose! this major photolytie product, IV, to be three times as toxic to mice and five times as toxic to flies relative to I, cndrin. compound IV became of immediate interest for several reasons. (1.)The initial product IV sas found to be insoluble in most of the common organic solvents used for the detection of organo-chloride pesticides. For example, no change was noticed in Iv by refluxing it in ethanol, benzene, carbon tetrachloride, chloroform, petroleum hydrocarbons, ether or dimethyl sulfoxide. It was soluble only in methylene chloride. However, shen IV was ground to a very fine powder it became readily soluble in hot absolute ethanol and chloroform. (2.)IV's retention time, using two types of columns and different temperatures on the gas chromatograph, sas nearly identical to its parent compound I, and could not be distinguished from the latter. Either material or a mixture of the tso gave only a single peak Iith.a proportional increase of area as one increased the concentration. (5.)Its infrared absorption spectrunnas nearly superimposible on that of compound II above 1550Kt All three reasons lead to the same conclusion. The most widely used methods today for the detection of pesticides and their residues could have been missing the identification of IV. Also IV might be the persistent and toxic residue that is now attributed to cndrin. The problem, therefore, ass to identify compound IV and ascertain if its chemical properties Justified the above possibilities. IV's physical data was encouraging in this direction. The melting point sas not sharp but rather indefinite, melting from Zia-218° with some prior softening and close to the reported 220°! for its parent compound I. The infrared spectra showed a strong absorption at 1745K‘ and no absorption at leOK’shieh could be attributed to a carbonyl in a five membered ring with no alpha K. Kaysers or reciprocal centimeters methylene groups. a medium intensity absorption at 1465K can be ascribed to a methylene group. The soak lines at 2960K and 2890K could be ascribed to the carbon-hydrogen stretching frequency of a five membercd ring and a tertiary carbon hydrogen stretching respect- fully by extending the near superimposibility of its infrared to the known compound II. Multiple bonding frequencies were absent from the spectrum which can also confirmed by the lack of absorption in its visible and ultraviolet Spectrums. Finally absorption frequencies below 1400K more too numerous and strong to be of much value in assigning the presence of functional groups. The elemental analysis of IV established that the equivalent of dichloroacetylene had been eliminated during the photodecomposition of cndrin. Calculated for 610H80140: 65 48.00: E, 2.82; c1, 49.59 and found c, 42.09, 41.95; H, 2.79, 2.88; 01, 49.64, 49.55. Mall spectra and vapor phase osmometry placed the molecular weight at 286 g/molc. Nuclear magnetic resonance (nmr) spectrometry revealed at least four chemically distinct types of protons based on the observed chemical shifts. The first type was attributed to the protons of a methylene group at ten 8.2. This group shosed a solvent effect with increasing dielectric constant of the solvent. In carbon tetrachloride («-8.2) the methylene group appeared as a singlet. In methylene chloride (c=9.l) there appeared an AB type quartet with area integration of 1:5:5:l, J: 7.2 cps, and m7: 7.4 cps. In dimethylform- amide (e=36.7), the AB type quartet had an integration of l:l.6:l.6:l withna§=ld.6 cps. The second distinct type of proton was attributed to a tertiary hydrogen. It appeared as a broad symmetrical multiplet at tau 7.2. The third type of proton was also attributed to tertiary hydrogens. Total integration assigned four protons to this region of tau 6.7-6.9. The coupling in this region did not allow satisfactory resolution to assign J and at values from the spectrum. The fourth type of proton was attributed to a hydrogen bonded to the same carbon as a chlorine with a chlorine atom located on one of the adjacent carbon atoms. It appeared as a sharp singlet at tau 5.4. Spin decoupling techniques failed to alter the spectra. From the physical data alone a number of possible working models were constructed to serve as a guide to develop experimental procedures to distinguish between the models and to finally arrive at a known structure or system for IV. The hydrocarbon portion of endrin was assumed to be left intact as supported by the nmr data and the three known thermolysis derivatives of cndrin. The positioning of the carbonyl on either side where the epoxide could 10 open was not important so long as a new carbon-carbon bond was formed on the other side to meet the condition of no alpha methylene groups to the carbonyl. This new carbon bond at carbon three would necessarily be endo to the norbornyl system identical to the supposedly unreacted linkages at carbons five and six. Using the adage that five membcred rings were preferred as photolytie products, two such models could be suggested, (IVa and IVb). (IVa) Models with four membcred rings were also possibil- ities. (IVc, IVd, and IVe). Three membcred rings were unlikely as indicated by the lack of characteristic absorptions in both the infrared and nmr spectras. 11 a C\ H \ \s a! ‘ U ‘0 U o H ‘ \‘0 Ci U c C\ u c‘ (IVc) (IVd) (IVc) The most apparent difference between the models was that IVa and IVc should be capable of olefin formation whereas IVb,d,e should not. Such olefin formation could be easily detected by a very sharp characteristic band at 1600K for a mono- or dihalo- ethylene in the infrared. Application of Attcnburrow's dehalogcnation procedure to IV resulted in only starting material being recovered.ll5) Dehydrohalogcnation using alcoholic potassium hydroxide also failed to produce any olefin; however, reaction did occur and a new product was formed which exhibited a hydroxyl band in the infrared spectrum. Since the ring systems for the models have not been reported in the literature, chemical studies were begun to attempt to convert IV into a known compound. Initial efforts were directed at the carbonyl group. However it was quickly discovered that IV was quite unreactive. Attempts to prepare the tosyl hydrasone and hydrazone 12 derivatives were fruitless. Likewise IV was unreactive to normal oxidation and reduction procedures. Carbonyl reducing procedures involving the Huang-Minlon modification of the Wolff-Kischner, the 01cmmensen, and the Thio-ketal reductions were unsuccessful. With the Clemmensen reduction 80% of the starting material, Iv, was recovered. Using the thio ketal reaction, 99% of the starting material IV was recovered. Even drastic conditions utilising phosphorus pentachloride at high temperatures in a sealed tube failed. Also the Baeyer Villiger and Haller Bauer oxidations did not give any expected products. A quantitative amount of starting material was recovered from the Baeyer Villiger oxidation. Compound IV, under the Heller Bauer conditions did give a nice clean reaction to V. Elemental analysis showed V to be an isomer of IV. The infrared spectrum compared favorably with the spectra of the product obtained from IV following its reaction with alcoholic potassium hydroxide. The carbonyl band had been replaced be a hydroxyl band. The nmr had lost the singlet at ten 5.4 and did not show any absorptions characteristic of a secondary alcohol. This observation lead to the conclusion that a ring closure had very probably occurred by base-catalyzed homoenolization. Ring closures of this type are not unknown. For example, one of the more familar cases was the direct formation of the hexachloro birdcage alcohol, VI, as reported by 13 linstein.(16) Returning to the models, only IVb and IVc could easily undergo such a homoenolization. IVc though should have been ruled out for not undergoing dehalogenation. Therefore, V could be assigned the structure 8,3,4,4-tetrachloro-pentaoyclo[5.5.0.02'6.03’10. 05 ' 9] decanol. . PK) \ Cr- If structures V and VI were dechlorinated, then the resulting products would have the relationship of the hydroxyl group to the methylencs shown below. *4d l4C) L4c | u . I I I ' I k—---«\ \\ ~\\ ‘\ \\\ ’1’ \I H Him, \ I (v11) (v111fi42EF4b 14 Compound VIII has been prepared by Winstein; the tar methylene protons from the hydroxyl showed an AB type quartet with chemical shift values of tau 8.52 and 8.22 with JAB==10.5 cps, whereas the near methylene HcHd signal appeared as a singlet at tau 8.28 super- impesed on one member or the HaHb quartet.fld) The reasoning extended to this was that Ed was probably deshielded by the hydroxyl. Returning to the models, if IVc actually underwent homoenolization followed by dehalogcnation, the resulting compound would have the same hydrocarbon ring structure as compound V, except that the hydroxyl would be in the 0-10 position and the predicted splitting of the two methylenes groups would become identical which disagrees with the nmr evidence. Further if in IVc one were to exchange the sin chlorine of the geminal dichloro group with a hydrogen (which.would give a further down field shift to that proton than recorded), the predicted final product after ring closure and dehalogenation would again give identical methylene absorptions. Similarly, it in structure IVd the geminal chlorine was replaced with hydrogen to allow homoenolization, the result would be the same as above, contradicting the analogous evidence. Compound 711 was not originally prepared by the dechlorination of 1. However it did arise from the lithium metal, t-butyl alcohol reduction of IV. 15 Reduction of IV was originally carried out to obtain its hydrocarbon skeleton. However in the isolated reaction product only two methylene groups appeared in the nmr instead of the expected three, indicating that some- thing had to be amiss. Elemental analysis confirmed this suspicion by reporting two less hydrogens in the product than expected (expected 610Hi40 and found CID 31301 Subsequent work lead to the realization of the possibility of homcenolozation occurring since lithium metal is a Lewis base. In: studies revealed the expected results. In.thc methylene region of absorption there appeared an AB type quartet with chemical shift values of tau 8.53 and 8.81 with.JAB;=lO.5 cps plus a singlet Head at tau 8.29 superimposed on one member of the Han} quartet. Further, the bridgehead proton signals which were reported as a broad peak at tau 7.57 (8H) and a complex multiplet at tau 7.87 (1H) in VIII were found in VII as a broad peak at tau 7.59 (GB) and a complex multiplet at tau 7.92 (13) plus the remaining proton as a singlet at tau 6.89 (1H). The carbon ring system in V and VII is known. Dilling had prepared the ends and exo hydroxyl derivatives. (17) From here he used phosphorus pentachloride to substitute a chlorine for the hydroxyl, reporting that thionyl chloride was completely unreactive.!la) Dechlorination of the chlorine derivative using the 16 common lithium metal, t-butyl alcohol in tetrahydrofuran procedure afforded the hydrocarbon Ix, pentacyclo[5.3.0. 6' 6 03’ 9. 05 816.908.110. 7 (IX) Hmr showed a quartet at tau 8.79 and 8.36 with J==10.7 cps, with relative areas indicative of a methylene group containing nonequivalent atoms. The tertiary protons were evident at tau 7.48 and 7.28 with (5.8K to 2.43) respectfully. The final proof of the structure, then was to get to II from V. Reactions were carried out with phosphorus pentachloride using Dilling's procedure and also with thionyl chloride. After four days, on work up both reactions were found to be clean and nearly quantitative to give.X, 1,2,5,4,d-pentachlcro-pentacyclo [5.3.0.02-5.o?21°.o5'9] decane. Dehalogenation of X.gave the known hydrocarbon IX. Therefore the major photolytic product of endrin can be assigned the structure IVb, 3,3,4,5R-tetrachloro-tetra cyclo[5.2.l.oz’6.o4'9]decan-B-one. Its chemical nature 17 being unreactive to normal oxidation and reduction procedures could justify the reported persistence and toxicity. Its physical properties could help obscure or make difficult its proper identification. Photolysis of endrin was also conducted at 3600A(l9) and yielded results essentially similar to those obtained at the shorter wavelength (2537A). This observation is of great importance as it demonstrates that photolytic rearrangements will occur under normal field conditions as the ultraviolet energy reaching the earths surface has wavelengths above 8863A. Therefore, application of endrin could lead to IV's subsequent build up in soils, plants, and animals and may even begin to approach toxic levels. Consequently, this as of yet unexplored potential health hazard may exist to man. EXPERIMENTAL All melting points are uncorrected and were determined on a Hoover capillary melting point apparatus. Infrared spectra were determined with a Perkin Elmer model 337 grating infrared spectrophotometer, in either carbon tetrachloride solutions or as potassium bromide pellets. Ultraviolet and visible spectra were determined with a Beckman model D.U. and D.B. instruments. Gas chromatography was conducted in a Beckman model 60.4 using a 6' by 1/8" id. quartz tube packed with 5%~Dow ll in 60/80 Chromosorb Q using helium gas as the carrier for electron capture detection and nitrogen gas as the carrier for flame ionization detection. A silanised 2§% SE-SO column was temporarily used in conjunction with the other column. Nuclear magnetic resonance spectra were determined with a Varian 1-60 high.resolution spectruweter and Jeolcc c eo-n instrument using tetra— methyl silane as an internal standard. ‘Mass spectrometric spectra were determined with a Consolidated Engineering Model 21-1030 machine. 18 PHOTOLYSIS Photolysis of endrin was carried out under varying conditions of both concentration of endrin in appropriate solvents and output energy (2537A) of the various medium pressure mercury arc lamps. Endrin was obtained from the commercial Endrin Emulsible Concentrate (20% endrin in 75% petroleum hydrocarbons) by evaporation of the solvent and numerous recrystallizations of the residue from absolute ethanol using activated charcoal until no variation in the melting point of the purified endrin occurred. Gas chromatography of this material at 220° gave a single peak and the nmr spectra showed no interfering impurities. The hexane and cyclohexane solvents used in the photolysis were classified as nanograde-distilled in glass, from the Burdick and Jackson Laboratories. The irradiation for the most part was carried out in a clear fused quarts immersion well using a Hanovia type L, 2537A, 450 watt laboratory photo- chemical lamp, although a 250 watt lamp was also utilised. It should be noted that no attempt was made to exclude other irradiation wavelengths emitted by the above lamps. A Bayonet Southern New England photochemical reactor (2557A) gave identical results. Varying concentrations of endrin, from 1.200 to 58.09 g., were dissolved in 500 ml. of cyclo- hexane. Photolysis was carried out at approximately 21° using a magnetically stirred system. 19 20 Nitrogen gas was bubbled through the reaction system on various trials, collecting any volatile acids in a standardised sodium hydroxide solution. No change in results was noticeable using nitrogen gas, thus it played no apparent role in the photolysis reaction (0.70 mole of acid per initial mole of endrin was evolved during the reaction). The extent of the reaction was followed by both gas chromatography and infrared spectrometry and showed a minimum of 90%lconversion of endrin in eight hours. A coloration change in the reaction medium from a clear solution to dark orange-brown.along with the evolution of a pugnent odor accompanied the reaction. Hexane solutions gave essentially the same results as those obtained with cyclohexane except the solubility of endrin in hexane is less. Precipitation of the white crystalline product, IV, occurred one hour after initiation of light exposure and the reaction was stopped after two hours of reaction time. The product was recovered by filtration. The reaction was then continued until precipitation was no longer apparent. The recovered product was washed with cyclohexane and dried. This photolytic product IV’was found to be insoluble in the common organic solvents used in the detection of the organo-chloride pesticides. After thorough grinding to a powder, it could be recry- stallized and chromatographed to yield a fine whdte 21 crystalline material, melting at 215-2ie°. Its infrared spectrum is shown in Figure I. and its nmr spectrum is summarized in Table I. Compound IV was assigned the structure 3,3,4,BR-tetrachloro-tetracyclo[5.2.1.02'5.04’§] decan-B-one. Analysig: Calc'd. for 010H80140: c, 42.00; H, 2.82; 01, 49.59; and found 0, 42.09, 41.93; H, 2.79, 2.88: 61, 49.64, 49.55. CI #4 (IVb) PREPARATIONS Preparation of 2,3,4,4-tetrachloro-pentacyclo[5.5.0.02’6. 03’10.05’9]decanol PK) ciOHBCl40 M.W. 286 CI C1 (V) This compound was prepared under the experimental conditions generally used for the Heller Bauer oxidation. A mixture of 4.00 g. (0.014 moles) of the photo product IV and 1.28 g. (0.035 moles) of sodamide in 150 ml. of nanograde benzene was heated under reflux. After seven hours, the reaction mixture was cooled by immersion in an ice bath and 250 ml. of ice water were slowly added to the rapidly stirred mixture. The organic layer was separated. The aqueous layer was extracted three times with 100 ml. portions of methylene chloride containing a little chloroform, dried over magnesium sulfate, and the solvents were removed under reduced pressure to obtain a White crystalline product. This was dissolved in hot carbon tetrachloride, filtered hot, and cooled in an ice bath to yield 2.60 g. (0.0091 moles) nice white crystals. 0n removal of the remaining solvent 22 23 an additional 0.90 g. (0.0052 moles) was recovered to bring the total per cent theoretical yield to 83%. Final purification of the product was afforded by chromatography using neutral alumina and eluting with ten per cent methanol-carbon tetrachloride. compound V'was also prepared under dehydrohalogen- ation conditions.(20) A mixture of 2.00 g. (0.0070 moles) photoproduct I? and 1.25 g. (0.022 moles) potassium:hydroxide were refluxed in 60 ml. of absolute ethanol. During the seventeen hour reflux.time, the reaction solution underwent coloration changes from colorless to yellow to cherry red. The solution was then poured into 200 ml. of ice water, filtered, and extracted three times with 100 ml. portions of ether. The combined other extracts.were saturated with sodium chloride solution, separated, and dried over magnesium sulfate. It was then filtered and the ether was removed by distillation under reduced pressure at room temperature to yield 2.0 g. (0.0070 moles) of crude product. This was recrystallized from 95% ethanol to obtain 1.60 3. (0.0055 moles) product in two crystalline forms: the major portion in the form of needles and the other in the form of clusters. These were purified by chromatography using 55 3. Fisher alumina with carbon tetrachloride- methanol as the elutant, followed by a final recrystallisation from ethanolawatcr to obtain 1.55 3. (0.0054 moles), 75% theoretical yield of the pure 24 product melting from 204-207°d. The infrared spectrum is shown on figure 11, and its nmr spectrum is summarised in Table I. dnalzs; : Calc'd. for 010H3014O: 0, 42.00; H, 2.82; 61, 49.59; and found 0, 41.93, 41.96; H, 2.76, 2.84: 31, 49.65, 49.54. Preparation of 1,2,3,4,4-pentachloro-pentacyclo[5.3.0. 610H7015 M.W. 304 Cl Cl C] (I) a 0.50 3. (0.0019 moles) quantity of compound 1 plus 0.70 ml. (0.0022 moles) thionyl chloride were refluxed in 20 ml. of spectrograde carbon tetrachloride. After a refluxing period of one hundred hours, the solvent was removed by distillation under reduced pressure to obtain a yellow oily product, which on being set aside for two weeks crystallised. The crude product precipitated from solutions as an oil on initial recrystallisation attempts. Hewever, by setting the dissolved material aside in an ice bath, it did eventually crystallize from solution as a 25 solid. Gas chromatographic analysis showed a clean reaction had occurred yielding 95%rproduct and 1% of the starting material. The reaction was repeated up to the points of removal of the reaction solvent. At this sancture an infrared spectrum, Figure III, and an nmr spectrum, as summarised in Table I, showed removal of the starting material was complete. The product was then used directly for the next step of the synthesis. Preparation of pentacyelo[5.3.0.02’6.03'9.05'8]decane 010312 mm. 132 (IX) Compound IX was prepared by the dehalogenation of compound X. To approximately 0.70 3. (0.0025 moles) of essentially pure, as described above, X in 70 ml of anhydrous tetrahydrofuran, was slowly added 0.70 g. (0.100 moles) of finely cut lithium metal under a nitrogen gas atmosphere at 0°. 0n the addition of 5.4 g. (0.046 moles) of tntiary butyl alcohol to the reaction solution, the solution turned a bluish grey. The reaction mixture was allowed to gradually warm to 26 room temperature during the thirty six:hour reaction period. The mixture was then poured directly into 200 ml. of ice water, saturated with.sodium chloride, and extracted with three 85 ml. portions of ether. The combined other extracts were washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and distilled under reduced pressure to obtain a camphor like smelling oily product. Sublimation of this material at 1000 at atmospheric pressure following the suggested procedure of Dilling(l7) gave a small yield of a clear liquid. nmr studies were inconclusive as the sample was not pure. The product was set aside in carbon tetrachloride solution in at closed container for a month, during which time a*white sticky material apparently sublimed to the eontainer's tsp. Thin.layer chromatography of the sticky material using plates of silica gel F254 in methanol and in one to one ratio solution of chloroform and acetonitrile gave identical RF values with that of a known sample of compound Ixfi 0.54 and 0.62 respectfully. The total remaining sample, 0.0012 g. (approximately one per cent theoretical yield) gave an infrared spectrum comparing rather favorably'with that of a known sample of compound II as shown in Figure 17. * The author would like to extend his appreciation to Dr. Wendell L. Dilling of the Britten Research Laboratory of the Dow Ohemica§ Company for sending a sample of pentacyclolb.5.0.0 .5, o9.04v9]decane. 27 Preparation of pentacyclo[5.5.0.02'5.03'10.05’9]decanol (3103130 M. W. 148 H O (VII) To a mixture of 2.00 g. (0.0070 moles) of the photoproduct I? and a minimum of two grams or better than four times the molar ratio per mole chlorine of finely cut lithium metal was stirred under a nitrogen atmosphere in 50 ml. of anhydrous tetrahydrofuran. 0n the addition of 10 ml. of tntiary butyl alcohol to the mixture, a smooth exothermic reaction was initiated. This was controlled by immersion in an ice bath. The following day, the unreacted pieces of lithium metal were removed. The reactiontmixture was poured into water, extracted with four 60 m1. portions of methylene chloride, dried over magnesium sulfate, and filtered. The solvent was removed by distillation under reduced pressure to obtain 0.750 g. (0.0051 moles) 73% of the theoretical yield. Product purification involved two chromatographic elutions through loclm neutral activated grade one alumina and, finally, sublimation at water aspirator pressure to obtain a white crystalline product with a 28 camphor like small. The product melted at 18451860, but the majority of it sublimed prior to melting. Infrared spectra of the pure product is shown on Figure V, and its nmr spectra is summarised in Table I. Analysigx Galc'd. for 8102120: 0, 81.08; H, 8.11; 01, 0.00; and found 0, 82.08; H, 8.32; 01, 0.00. ATTEMPTED PREPARATIONS Attempted Dehalogenation Reaction of Photoproduct IV dttenburrow's procedure (15) was carried out to examine the possibility of olefin formation from the photolytic product. A 1.72 g. (0.0060 moles) quantity of the photcproduct IV, 1.6 g. of anhydrous sodium acetate, 10 ml. of methylene chloride, 20 ml. of acetic acid, and 5.0 g. (0.077 moles) of sine dust was stirred at 50:.8° for three fourths of an hour. The reaction mixture was filtered hot and the sine residue was washed with 5 m1. of methylene chloride, 5 ml. of acetic acid, and finally with 5 m1. of methylene chloride. The volume of the filtrate and washings was reduced to one half of its original volume on the steam bath employing a filtered dry air stream ever the surface. Water was added to the concentrated filtrate to the point of developing clouding. Cooling this solution induced crystallization of the product. This was collected by filtration and‘was vacuum dried to obtain 1.50 g. (0.0045 moles) of a pure white crystalline material. The infrared spectra of this solid showed no olefin formation had occurred and it compared favorably 'with the spectra of the starting material, even though its melting point was l40-200‘. 50 Attempted Tosyl Hydrasone Formation of Photoproduct IV A 1.00 g. (0.0055 moles) quantity of the photoproduct IV and 0.65 g. (0.0055 moles) of tosyl hydrasine were refluxed in 100 ml. of methanol. After a twenty hour reaction period, a small quantity of para toluene sulfonic acid was added as a catalyst. Following an additional thirty four hours of refluxing, one half of the original methanol was removed under reduced pressure to obtain an initial 0.57 g. of a white crystalline material. 0n cooling the concentrated reaction solution, an additional 0.59 g. of product were obtained. These had a melting point of 215.5-217.5° and 212.0-217.0°, respectfully. Mixed melting points of each of the product fractions with starting material were 215.0- 217.5°. Attempted Hydrasone Formation of Photoproduet I? A 1.00 g. (0.0055 moles) quantity of the photo- product I? and 0.20 3. (0.0040 moles) of hydrasine hydrate were refluxed in 250 m1. of nanograde bensene. Following a forty eight hour reflux period, the benzene was removed by distillation under reduced pressure to obtain 1.01 g. of a material melting at 212-214o. Gas chromatographic analysis of this material at 190° was 31 found to be identical with the starting material. Attempted Wolff-Kisehner Reduction of Photoproduct IV Application of the Huang-Minion modification of the Welff-Kischner reduction (21) to the photoproduct IV failed to yield any of the desired products. A 0.500 5. (0.0018 moles) quantity of the photoproduct 1?, 0.540 3. (0.0061 moles) of potassium hydroxide, 0.24 ml. of 100% hydrazine hydrate, and 10.0 ml. of ethylene glycol were heated at 180° for an hour. During this initial hour of heating, the solution began to take on a brown coloration. The reaction temperature slowly rose to 182° during the three and one half hours of refluxing. The reaction mixture was cooled, then acidified with 2.5 ml. (0.090 moles) of hydrochloric acid. The acidic solution was extracted three times with.methylene chloride and once with hexane. The combined solvents were removed by heating on a steam bath to obtain a dark syrup which dissolved in absolute ethanol and reprecipitated on the addition of petroleum ether. 0n neutralization of the water layer, a fine black precipitate formed and was recovered by filtration. Infrared speetras of both products showed a strong hydroxyl absorption as well as the presence of a carbonyl band. When the photoproduct was found to be unstable 32 in a basic media due to homoenolization, the merit of the Wolff-Kischner method as a reduction procedure failed. Attempted Glemmensen Reduction of Phot0product IV when the photoproduct IV was found to be stable in acidic solutions, it was first reacted under the elemmensen reduction procedure using the mild conditions with methanol as the reaction solvent.(22) When the recovered material was found to be starting material, more rigorous reaction conditions were used. (25) Zinc amalgam was freshly prepared by adding 0.5 ml. of concentrated hydrochloric acid (57%) to 6.7 g. of granular zinc and then quickly adding 4 ml. of water followed by 0.50 g. of mercuric chloride. After stirring the slurry for five minutes, the mixture was decanted and added to the reaction flask containing 2.05 g. (0.0070 moles) of the photoproduct IV, 25 ml. of concentrated hydrochloric acid, 15 ml. of water, and 60 ml. of glacial acetic acid. After the first hour of reflux, 15 ml. of concentrated hydrochloric acid was added followed by the addition of 5 ml. acid after the third hour. The reaction was stopped after a total of twenty four hours under reflux, diluted with 200 ml. of cold water, filtered, neutralized to pH 6, saturated with 53 sodium chloride, extracted four times with methylene chloride and chloroform. The combined extracts were dried over magnesium sulfate, filtered, and the solvents were removed by distillation under reduced pressure. 0n the addition of acetone a precipitate formed which remained insoluble on the addition of 95% ethanol and methylene chloride. This material was submitted to column chromatography and was.eluted through 70 g. Woelm activation grade one alumina. This gave no real separation of the four products shown to be present by gas chromatographic analysis at 220°. Chloroform and methylene chloride were used as the elutants. Infrared analysis of the chromatographic fractions indicated that some carbonyl reduction had occurred but in very low yield. Further, the major carbon hydrogen stretchdng frequencies were above 5000K indicating possible decomposition. Since the object was the conversion of the photoproduct IV into a known structure, the practicality of using this experimental route became undesircable and further work with the Clemmcnson reduction was discontinued. Attempted Thio Ketal Reduction of Photoproduct IV The smooth, reliable thio ketal, rainyynickel reduction for difficulty reducible ketones was next 34 considered. To a 1.4 ml. (0.0167 moles) quantity of freshly distilled ethane dithiol, 1.00 g. (0.0035 moles) of the photoproduct IV, 10 m1. of methylene chloride was slowly added until the solution became homogeneous, after which 1.4 ml. of freshly distilled boron trifluor- ide ethcrate was stirred into the reaction mixture at room temperature. During the reaction period of an hour f37 and half, the solution underwent coloration changes from colorless to a very light clear tan orange. The reaction solution was extracted with four 20 ml. portions of ether and once with 25 ml. of methylene chloride. The L} combined extracts were washed with 5% sodium hydroxide solution, twice with.watcr, and finally with a saturated sodium chloride solution. Removal of the solvents yielded 0.99 g. of material whose infrared spectrum was identical to the spectrum of the starting material. Attempted Bacycr Villiger Oxidation of Photoproduct Iv To a stirred solution of 0.500 g. (0.0018 moles) of the photoproduct IV and 11 ml. of methylene chloride (dried over magnesium sulfate) cooled to 0°, was added 0.40 g. of 40% peracetie acid in acetic acid followed by two ml. of glacial acetic acid. After five minutes, the reaction flask was removed from the ice bath and set aside for a week at room temperature. 35 The reaction mixture was then neutralized to pH 8 with a saturated solution of sodium bicarbonate; and 10 m1. of methylene chloride was added to the neutralized solution. The organic layer was separated and washed with 50 ml. water. The aqueous portion was extracted twice with 50 ml. portions of ether. The combined organic portions were dried over magnesium sulfate, filtered, and the solvent was removed under reduced pressure to obtain 0.50 3. (0.0018 moles) of a white crystalline material melting from 813.0-216.5°. A mixed melting point of this material with photoproduct Iv melted at 211.5-215.7°. Photolysis of Compound II, 1 ,9,10,10,ll, exo-lB-hexa- chloropentacyclo h.2.1.02’6.04’8.07'IQdodeean-5-one 0H 9 (II) compound II was readily prepared using Soloway's procedure (4) to determine whether II might be a possible route in the formation of IV from I. A 1.45 g. (0.0038 36 moles) quantity of II was ground to a fine powder in order to be dissolved in an equivalent amount of cyclohexane that was used in the photolysis of I. However compound II's solubility in cyclohexane was considerably less than compound I and it only partially dissolved (perhaps 85%) in 1250 ml. of the solvent. After twenty six hours of irradiation at 2557A, the clear colorless reaction solution.was concentrated under reduced pressure (bp. solvent 25°) to 50 ml. total volume. Gas chromatographic analysis of the remaining solution strongly suggests that compound II is not a significant intermediate tn the photosynthesis of compound IV from compound I. 37 9mm cw enclmlsmomm Hm“: .oqmo.H.N.MHoaohomnpoenouoanomapmeimquamam Ho ssnpooum.monmsmuH one .Hoaswfirm So 000 00m OOOH OONH OomH OOON 00mm Doom 00mm 000; a. _ _ _ _ _ a _ _ _ a; 0». 0m. om. ON. 0H. sourqsosqv 38 .oa.m .o.m HI . .cmm an Hoodoomma. o O. OeMemH .0HO>O$#C$&IO.HOH£OM.HP QEIJAJAM «N .HO Evommm 50.9”th 0mm. eHH mgmfih So 000 com OOOH OONH oomH OOON 00mm 000m comm .000: _ _ _ _ l _ A llILHI 1 sousqmosqv 39 .11. . . Eva'f '7 033283353st 5.” H0580 memo .oaam .0605.m.mflOdocmompsomioaogomsglz«Janum mo 55$on momma m a 9&3 .83me HIEU 000 00w 000a 00NH 00mH 000N 00mm 000m 00mm 000: a _ _ _ _ _ a 8... 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Ammv a oéuwe $3 a 06 #80 N e e e e QONOOHHH. , , $3 8 a mm a A as m a 3 a a m a #80 a 9a a as as 88 a . aaoméaue A m8 m as m m e e e :5 as o 33 s cm a :5 a mm a. $3 a as $5 88 H» mm mm” A 05 a 8.x. mi .5 3;. m N A 0 Mom A a :80 up as 8 me a .mmootmu H. smootoaucd EH a am an a fierm. encasement Em En E a t A V e A V A as a a; as Q 0 R. Q 0 nu EV . a} as a at? as 5 an. m a a a m a a. a. News a ) E0 a 35 and a , can a .3 as a 3.3 and a mg as a can as B ma m a. m s m. . . s . m w A 0 n T: cum 0 05 mo 0. $3 a has :3 .88 HH mmowtonb : .m s H . a 0 H8 A a a o Q8 3 as a fin S; H cocoons meant: seasons 8333a . bonanza inmate mm... to. at. 1. 2. 3. 5. 6. 7. 8. 9. 10. 11. 18. 13. 14. 15. 16. BIBLIOGRAPHY L.E. Mitchell in ”Organic Pesticides in the Environment”, R.F. Gould, Ed., American Chemical Society Publications, Washington D.C., 1966, pp 1-21. R.C. Cookson and E. Crundwell, Chem. Ind. (London), 1004 (1958). 2.0. Cookson and E. Crundwell, Chem. Ind. (London), 705 (1959). 3,3. Soloway, J. Am. Chem. Soc.,'§§, 5577 (1960). 6.". Bird, 3.0. Cookson, and E. Crundwcll, J. Chem. doc., 4809 (1961). D.D. Phillips, 0. Pollard and 3.3. Solcway, J. Agr. Food Chem.,‘;g, 217 (1952). L. DeVries and S. Winstcin, J. Am. Chem. Soc., 82, 5565 (1960). P. Bruck, S. Winstein, and D. Thomson, Chem. Ind. (London) , 590 (1960) . B.I. Sparr, et. a1. in 'Organic Pesticides in the Environment“, op. cit., pp 146-162.. 1. West, ibid., p 44. 0.8.‘Myers #45, (1958). 6.3. VanMiddelcm in "Organic Pesticides in the Environment", op. cit., pp 228-249. J. Roburn, Chem. Eng. News, 1555 (1965). Penna. Dept. of Health Research Report J.D. Rosen and D.J. Sutherland, Bull. Environ. Contamin. Toxicol.,.;, 155 (1966). J. Attenburrow, J. Chem. 300., 4547 (1961). P. Carter, R. Howe, and S. Winstein, J. Am. Chem. 3000. .81. 914 (1966). 44 17. 18. 19. 20. 21. 22. 25. 45 ".3. Billing and C.E. Reineke, Tetrahedron Lett., _2_1, 2547 (1967). W.L. Dilling et. a1., Tetrahedron,.§§, 1211 (1967). private communication, M.J. Zabik. 0. Grummitt, A. Buck, and A. Jenkins, J. Am. Chem. Soo., _§_s_, 155 (1945). D. Todd in "Organic Reactions", V01. BL Jehn Wiley and Sons Inc., New York, p 578. J.H. Brewster, J. Am. Chem. Soc.,.1§, 6564 (1954). E.L. martin in "Organic Reactions", Vol. I, op. cit., p 155. ARIES TAT NIVERSITY LI III M)! fulfill)" )l 306] 398 930 WCIIWIITIII 3 12