The Preparation of Some Reductively Dechlorinated Analogues of Dieldrin, Endosulfan and Isobenzan
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J. Pesticide Sci. 5, 565-574 (1980) The Preparation of Some Reductively Dechlorinated Analogues of Dieldrin, Endosulfan and Isobenzan Gerald T. BROOKS Agricultural Research Council, Unit of Invertebrate Chemistry and Physiology, University of Sussex, Brighton BN1 9RQ (Received May 21, 1980) A combination of photochemical and reductive dechlorination techniques is used to prepare analogues of dieldrin, endosulfan (a- and (3-series) and isobenzan in which the chlorine atoms at Cl and C4 (bridge-end) of the 1, 2, 3, 4, 7, 7-hexachlorobicyclo[2. 2. 1. ]hept-2-ene system are retained whilst those at C2,C3 (ethylenic) and C7 (methano-bridge) are variously replaced by hydrogen atoms. The identification of chlorine substitution patterns by nmr is discussed in relation to available information on known compounds. This is part of an investigation to determine whether there is any consistent relationship between different groups of cyclo- diene insecticides in regard to the effect of reductive dechlorination on their toxicities to insects. environmentally more degradable cyclodiene INTRODUCTION insecticides, without serious loss of the acute In the last two decades, concern for the toxicity necessary for insecticidal efficiency. possible deleterious consequences of environ- The preparation of some reductively de- mental contamination by chlorinated insecti- chlorinated analogues of dieldrin, endosulf an cides resulted in extensive exploration of the (a-andl-isomers) and Isobenzan is now terminal residues produced from them by reported, as part of an investigation to deter- oxidative, reductive and photochemical reac- mine whether there is any consistent relation- tions in the biotic environment. 1-4) Reactions ship between different groups of cyclodiene that result in the replacement of chlorine insecticides in regard to the effect of system- atoms in the parent molecules by hydrogen atic chlorine replacement on their toxicities to are of special interest, since in principle, they insects. should afford molecules which are more amen- MATERIALS AND METHODS able to further biological degradation. How- ever, reductive dechlorination does not neces- 1. Physical Measurements sarily result in lower toxicity. For example, Nmr spectra were recorded on. JEOL PS 100 early structure-activity studies showed that or FX90Q (Fourier transform) 'spectrometers reductive replacement of the ethylenic chlorine using solutions in deuterochloroform with atoms in dieldrin resulted in up to four-fold tetramethylsilane as internal standard (q= increases in toxicity to certain species of 0.00). Nmr spectra are compared in Tables insects. 5-7) Furthermore, the methano-bridge 1-4 for convenient comparison. Mass spectral chlorine anti-to the double bond in aldrin molecular weights were measured by direct derivatives was found to be more significant insertion at 70 eV on a Varian CH5 double- for toxicity than the syn-chlorine.7) This focussing mass spectrometer equipped with limited information suggested the possibility8) a Varian SS 100 data system. that the selective replacement of appropriate chlorine atoms by hydrogen might afford 566 日本 農 薬学 会 誌 第5巻 第4号 昭 和55年11月 Journal of Pesticide Science 5 (4), November 1980 567 568 日本 農 薬 学 会 誌 第5巻 第4号 昭 和55年11月 2. Ultra-Violet Light Sources Co. Analar solvents were used for chromato- Photolytic experiments were conducted with graphy. Authentic specimens (see Table 1 and either a low pressure Camag Universal UV section 4. 1) of syn- and anti-dechlorodieldrin lamp type TL-900 (chromatolite) using the (3 and 4, respectively, Table 1) were provided 254 nm tube without filter (designated UVL by Dr. J. D. McKinney, monodechlorodieldrin below) or a Hanovia Lamps Ltd (Slough, UK) (1) by Dr. W. Klein and bis-dechlorodieldrin, U. V. S. 500 unit with a medium pressure (2) by Shell Research Ltd, who also provided mercury arc tube type 509/10 (designated photodieldrin and isobenzan. Purified a- and UVM below), emitting wavelengths down to /3 endosulf an were the gift of Farbwerke-Hoe- 185 nm. Unless otherwise stated, irradiations chst, A. G. Melting points are not corrected. were carried out in spectroscopic grade hexane 4.1 Preparation of dieldrin analogues in quartz spectrophotometer cells (1 or 2 cm 1,8, 9, 11,11-pentachloro-4, 5-exo-epoxy-2, 3- light path; 3. 5 ml or 8 ml capacity, respec- 7,6-endo-2, 1-7, 8-exo-tetracyclo [6. 2. 1. 13, 6 02,7] tively) sited about 2. 5 cm from the chromato- dodec-9-ene (1; Table l)* and the derived 1,8, lite tube held vertically or on a water-cooled 11,11-tetrachloro-compound (2) were prepared metal block about 7. 5 cm from the Hanovia by a method10' here adapted for exploration of arc held horizontally. reaction conditions on a 1-50 mg scale. Dieldrin (50 mg) was irradiated (UVL) as in 2 (2 cm 3. Chromatography cells) for 3 hr, when tlc (solvent A) and glc The progress of photolyses and other reac- analysis indicated complete conversion into tions was followed by sampling and analysis photolyses products. The combined semi- on a Perkin Elmer Fl 7 gas chromatograph solid residue from several runs on this scale, fitted with an electron-capture detector and cleaned up by boiling with a little light petro- a glass column (1m; 3mm i. d) containing leum+diethylether (1+1, by volume), gave 2. 5% SE 30 on 80-100 mesh Chromosorb W, nearly colourless compound 1 (66%) mp 164- carrier gas nitrogen (50 ml/min), injector and 1650C, after recrystallization from light petro- detector temperatures 2000C, oven tempera- leum (lit. 10): 150-1530C). This was further ture 1750C (glc), and by thin-layer chromato- irradiated (UVM) in batches of 30 mg (2 cm graphy (tlc) on Merck Silicagel 60 F254 chrom- cells) until chromatographic analysis indicated atoplates (0.2 mm gel thickness on aluminium complete conversion into compound 2. After foil, Anderman and Co. UK) developed with initial clean-up as before, the combined product hexane+diethyl ether (3+1 or 3+2, by volume; (50% yield) was passed in light petroleum solvent A and B respectively) or hexane+ace- through a short column of basic aluminium tone (4+1, by volume ; solvent C). For spot oxide (grade II-III) then recrystallized from detection, plates were sprayed with Mitchell's a little ethanol+water (4+1, by volume) to silver nitrate reagent9) then irradiated (UVM), give compound 2, mp 194-1950C, identical with repeated spraying if necessary, until the with a specimen provided by Shell Research spots appeared. Cleanup of crude reaction Ltd. mixtures was effected on short columns of When irradiated (UVL) in hexane+acetone Merck aluminium oxide 90 (Brockmann grade (99+1, by volume) for 2 hr, compound 2 gave II, III or IV, as indicated) with appropriate the photoisomer 5, 6,6, 7-tetrachloro-1 1,12-exo- mixtures of diethyl ether+light petroleum as epoxy-pentacyclo [6.4.0.0210.0, 7 05,s] dodecane eluting solvent. Light petroleum refers to the (2A), mp 131-131. 50C (lit. 10):127-1280C), M+ 40-600C boiling fraction unless otherwise stated. 310, nmr (CDC13): 8 3.45, 3.27 (dd, 3. 5, 1. 75 Hz, 1H; dd, 3.5, 1.75Hz, 1H; epoxide ring protons), 4. Chemicals 2.85-2. 36 (m, 7H), 1.88 (d, 11.8 Hz, 1H; endo- 2, 2'-Azobis (2-methylpropionitrile) (azobis- H4). isobutyronitrile, AIBN; Aldrich Chemical Co.) 1,8, 9, 10,anti-11-pentachloro-4, 5-exo-epoxy- and tri-n-butyl tin hydride (Lancaster Syn- 2, 3-7, 6-endo-2, 1-7, 8-exo-tetracyclo [6.2. 1.13, 6 thesis Ltd. U. K.) were reagent grade, cyano- cobalamin (Vitamin B12) from Sigma Chemical * von Baeyer/IUPAC nomenclature3, 35) Journal of Pesticide Science 5 (4), November 1980 569 02,7]dodec-9-ene(3) and its 1,8, 9, 10,syn-11- A): Compound 2 ( 78 mg, 0. 25 mmole ) pentachloro-isomer (4). was heated under reflux for 1 hr in benzene Dieldrin (478 mg, 1.25 mmole) was heated (0. 5 ml) containing tri-n-butyl tin hydride under reflux in benzene (2.5 ml) containing (0.25 mmole) and AIBN (0. 5 mg). The reac- tri-n-butyl tin hydride (1.25 mmole) and tion product, isolated as in the preparation of AIBN (2.5mg) for 1 hr, the solution evaporat- compound 3, gave the anti-trichloro-derivative ed to about 1 ml and the crystalline deposit 7 (42 mg, 60%), mp 164-1650C13'M+ 276. The washed with light petroleum, then cold diethyl corresponding syn-11-trichloro-isomer 8, iso- ether. Recrystallization from ethanol gave lated from the mother liquors by preparative compound 3 (170 mg, 39%) mp 196-1970C tic as for compound 4, had mp 137-1380C, (lit.11): 192-1950C), M+344, free from the 11- M+ 276 (3C1). Photolysis (UVL, 1 cm cell) of syn-pentachloro-isomer (4), which was separat- compound 7 (6 mg) in acetone (2 ml) for 2 hr ed from compound 3 in the reaction residues gave the cage photoisomer 7A, mp 141-1420C, by preparative tic on Merck silica gel 60F254 M+ 276, nmr (CDC13): 8 3. 45, 3.25 (d, 2.6 Hz, chromatoplates (0.25mm gel thickness on l H, d, 2. 6 Hz, 1 H ; epoxide ring protons). glass) developed with solvent C (section 3), or See Table 2. by column chromatography on basic aluminium B) : The reductive dechlorination of com- oxide (grade II-III), using light petroleum- pound 2 with sodium borohydride in the increasing proportions of diethyl ether for presence of nickel chloride or cobalt nitrat&' selective elution of the isomers. Compound gave unsatisfactory results but cyanocobalamin 4 had mp 140-1410C (lit. 12): 139-1410C), M+ gave a good conversion into compound 7. To 344.