Environ. Sci. Technol. 1993, 27, 1673-1680
Improved Syntheses and Complete Characterization of Some Poiychloronaphthalenes Pat Auger, Murugan Malalyandl, and Robert H. Wlghtman' Department of Chemistry, Centre for Environmental and Analytical Chemistry, Carleton University, Ottawa, Ontario, Canada K I S 586
Corlnne Benslmon Department of Chemistry, University of Ottawa, Ottawa, Ontario, Canada K I N 6N5
Davld T. Wllllams Environmental Health Centre, Health and Welfare Canada, Ottawa, Ontario, Canada K1A OL2
Improved methods of preparation are reported for the following isomerically pure polychloronaphthalenes: 1,2,3,4,5,6,7- and 1,2,3,4,5,6,8-heptachloro;1,2,3,4,5,6-, 2,3,4,5,6,7-,and 1,2,4,5,6,7-hexachloro;2,3,4,5,6-pentachloro; plus the mixture of 1,2,3,4,6,7- and 1,2,3,5,6,7hexachloro isomers. Sufficient quantities of these environmentally ubiquitous materials have been obtained so that for the first time complete physicochemical data are presented that unambiguously characterize these compounds. Also included is an X-ray crystallographic analysis of 2,3,4,5,6,7-hexachloronaphthalenewhich crystallized in the space group P212121 with cell dimensions: a = 11.2187 (13), b = 14.7768 (22), and c = 6.898 (3). The structure was determined by direct methods and was refined by a full-matrix least-squares calculation to give a final R value of 0.034 for 944 unique reflections with I/a(I) > 2.5. Introduction
The polychlorinated naphthalenes (PCNs) are a known and ubiquitous class of environmental pollutants whose detailed investigation to date has been greatly hindered by the lack of sufficient quantities of pure, well-characterized individual congeners, especially the pentachloro and higher isomers (1,2). Although there are a substantial number of publications alluding to some of these compounds, very little "characterizable" data are in fact available ( 3 , 4 ) . Octachloronaphthalene, 2, is by far the most cited of the polychlorinated naphthalenes (3, 4). Perhaps the simplest source of 2 is by repeated crystallization of commercially available Halowax 1051, which has the approximate composition of 85% octachloronaphthalene, 5-7% each of the two heptachloroisomers, and small amounh of other polychlorinated congeners. A variety of solvents have been suggested (5, 6 ) but 5-10 crystallizations appear to be necessary to achieve octachloronaphthalene>97 % purity because of the tenacious tendency of the heptachloro isomers to cocrystallize. Alternately, 2 can be prepared from naphthalene by perchlorination to a decachlorodihydronaphthalene,1, which pyrolytically (- 200 "C) eliminates chlorine to produce mainly octachloronaphthalene (7,8). The various octa-, hepta-, and hexachloro isomers can generally be differentiated by capillary GC (9)or reversephase (RP)-HPLC (10). A mass spectral analysis of
* To whom correspondence ahould be addressed. 0013-936X/93/0927-1673$04.0010
0 1993 American Chemical Society
octachloronaphthalene has been reported (5,19)as well as X-ray (11)and 13C NMR data (12). Scattered reports concerning chemical transformations of octachloronaphthalene have appeared. Most reports concern displacement reactions, usually of one of the a-chlorine atoms, by various nucleophiles, e.g., hydride (13, 14), alkoxide (131, or sulfur (15). The two heptachloro isomers are obtained by quite different routes. The 1,2,3,4,5,6,7-heptachloronaphthalene or 1H isomer, 3, is reported to be obtained by hydride reduction of octachloronaphthalene, e.g., lithium aluminum hydride (13) or sodium bis(2-methoxyethoxy)aluminum hydride (14). Multiple recrystallization and/or chromatographic methods are usually required to obtain >95% purity. The W isomer, 6, Le., 1,2,3,4,5,6,8heptachloronaphthalene, has apparently only been obtained by exhaustive recrystallization of commercial Halowax 1051 to remove most of the relatively insoluble octachloronaphthalene; final chromatographic purification seems necessary to obtain material of >95% purity ( 4 6 , 14). Each heptachloronaphthalene appears to have distinctive characteristics, i.e., melting point (4,6),lH NMR chemical shift (4, 13,14),and capillary GC (4) or HPLC (4,16)retention times. On the other hand, no substantially distinctive features are observable in the respective mass spectra (5, IO),IR (41, or UV (4). It is arguable whether any of this data represents a totally unambiguousstructure proof for these two isomers, and X-ray crystallographic data has not been reported. The few hexachloronaphthalenesthat are reported have been obtained by several general procedures: either (i) controlled "reductionslhydrodechlorinations" from octachloronaphthalene or (ii) by perchlorination of various functionalized naphthalenes and subsequent modification of functionality. Accordingly, a hexachloronaphthalene, purportedly the 1,2,3,5,6,7-isomer,4, has been obtained by LiAlH4 reduction of octachloronaphthalene (9, 10). Hexachlorination of 2-nitronaphthalene followed by reduction to 2-aminohexachloronaphthaleneand reductive diazotization apparently produced the 1,2,3,4,5,6-hexachloro isomer (19). Another report mentions that octachloronaphthalene when successively treated with sulfur and Raney nickel produces the 2,3,4,5,6,74somer, 11,(201,via a peri-bridged 1,8-dithiole derivative, 10 (15). Other reports describe the preparation of 14, or the 1,2,4,5,7,8isomer, from 1,5-or l,&dinitro- (or diamino-)naphthalenes via tetrachlorination and subsequent replacement of the nitrogen functionalities (9, 17,18). Envlron. Scl. Technoi., Vol. 27, No. 8, 1993 1673
In general, much of the usual physicochemical data and, consequently, structure proofs were absent in these publications. For some compounds, i.e., 9 and 11, no characterizing data are available (19,20). Structures of the various isomers were generally assumed from expected chlorination patterns, and the only analytical data reported are mass spectra (5, 9, 10,211 or microanalyses (13). In the earlier reports, purity was based on recrystallization and sharpness of mp (13);while in later reports, the small amounts of material obtained were shown by GC to be only -80% pure (18). Thus, the objectives of this investigation are to provide complete and unambiguous physicochemical characterization of these environmentally prevalent compounds plus the necessary details for their preparation and purification in high isomeric purity.
-
8MC C
NAPHTHALENE
Cl$@,,: c1
CI ICI CI w
cI
CI
2200
CI
CI CI
CI CI CI
/&
*IC CI
CI
CI
+I* CI
/ / C I
CI
CI CI
/ ' C I
CI
4
9
CI
i CI C1
HALowky,os,
Cryrlallizrtion L
+ HPLC
CI
CI
CI
6
Experimental Section
General Procedures. I3CNMR spectra were acquired from a Varian XL-200 or a Bruker AMX-400spectrometer, and 'H NMR spectra were obtained from either of these instruments or a Varian XL-300 instrument. All NMR spectra were taken in CDCl3, unless otherwise indicated, with 1%TMS. All values are recorded in ppm (6) with reference to TMS. Band shape is indicated by s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), or b (broad). Thin-layer chromatography (TLC) was performed on silica gel 6OF2~,0.2mm thickness on aluminum. Preparative-scale HPLC (prep RP-HPLC) separations were accomplished on a Waters Delta 3000 LC system using C18 RP prep cartridges (47 X 300 mm) and pure methanol. Injections of 30-60 mg of impure PCN in 3075 mL of methanol were routinely used. For analytical HPLC work, a Varian 9010 instrument was employed using a Varian 9050 UV/vis variable wavelength detector at 240 nm and a C18 RP column (25 cm X 4.6 mm with 5-pm packing) and a flow rate of 1.5 mL/min. Retention times in methanol (or acetonitrile) are in minutes. Capillary gas chromatography ( G O results were obtained with a 30 m X 0.25 mm i.d. column coated with DB-17 (thickness 0.25 pm). The followingstandard program was used; inject at 150°, hold 2 min, ramp at 10 "C/min to 280 "C, hold for 2 min, then ramp to 300 "C at 20 "Urnin with final hold after 2 min. Helium was employed as the carrier gas with linear velocity of 41 cm/s, and retention times are recorded in minutes. Samples were 10 ppm solutions in HPLC-grade dichloromethane or hexane. Various instruments were employed: Varian Vista 6000 with FID, Varian 3600 with ECD and a Varian Saturn I1 GC/MS system, i.e., series 3400 GC with ion trap detector. Melting points were obtained on a Buchi SMP-20 melting range apparatus and are recorded in degrees Celsius as are all temperatures. Mass spectra were obtained on a VG707E instrument at 70 eV under electron impact (EI) mode. Specific Results. The synthetic scheme for compounds 1-9 is shown in Figure 1. Preparation of Octachloronaphthalene, 2. ( A ) Decachloro-l ,kdihydronaphthalene, l. As previously described (7,22),a solution of naphthalene (2 g, 15.6 mmol) and SpClp (0.6 mL, 7.4 mmol) in fresh S02C12 (50 mL) was slowly added to a fluxing solution of anhydrous A1C13 (500 mg, 3.8 mmol) in S02C12(150 mL). The usual conditions and workup yielded a brown residue (6.81 g, 92%) which could be crystallized from CH2C12 to give yellow-colored crystals: mp, 206-208 "C dec., lit. 207-209 "C (7,22);lH 1674
Envlron. Scl. Technol., Vol. 27, No. 8, 1993
/
RONODMF
CI g Q
c1
I
E%
9
CI CI
e Figure 1. Synthesis scheme for 1-0.
NMR, no peaks; 13CNMR, 138.9,134.0,132.5,130.8,69.2; MS, identical with octachloronaphthalene; retention times, GC, same as octachloronaphthalene; HPLC, 8.78 (7.93). ( B ) Dechlorination of Decachloro-1,Cdihydronaphthalene, 1. (i) Decachlorodihydronaphthalene,1, (500 mg) was melted and heated at 220 "C for 15min. After cooling, the orangish-brown residue (381 mg) was composed of 80 % octachloronaphthalene plus other congeners as determined by capillary GC. (A "profile" similar to Halowax 1051.) (ii) Decachlorodihydronaphthalene (500 mg) was dissolved in hot methanol (100 mL), and to this solution was added Zn dust (500 mg). After refluxing and stirring for 4 h, the Zn was filtered off, and the hot filtrate was treated with H2O (200 mL) and cooled. The yellow precipitate was collected and dried (376 mg). Analysis by GC/MS of this crude product indicated the major components to be octachloro 25 % , the 1H-heptachlor0 50 % , and lower congeners 25 % . (iii) Decachlorodihydronaphthalene (500 mg) was dissolved in hot acetone (100 mL) and treated with sodium iodide (500 mg). After refluxing for 3 h, the reaction mixture was cooled to room temperature and diluted with H2O (200 mL), and the yellowish precipitate was filtered and dried (398mg). GC/ MS of this crude product indicated octachloro (-85961, 1H-heptachlor0 ( 10% ), and various hexachloro isomers (-5%). All of the above products were also checked by RP-HPLC to confirm that no unreacted decachlorodihydronaphthalene remained (24). Purification of Octachloronaphthalene, 2. Commercial Halowax 1051 was repeatedly (lox) crystallized from chloroformto produce white, needle-likecrystals. Isomeric purity by GC, -99%. mp, 197 OC, lit. 198 "C (5); 'H NMR, no peaks; 13C NMR, 135.3, 129.7, 129.0; MS, 408(39),406(93),404(58),403(100),402(54),400(53),334(53),
-
-
-
N
-
332(67), 330(34), 262(27), 260(22), 166(24);HRMS, calcd for ClOCls: 399.7512; found: 399.75137. Retention times: GC, 19.10; HPLC, 17.51(11.30). 1,2,3,4,5,6,8-Heptachloronaphthalene (the2 H Isomer), 6. Commercial Halowax 1051 (15.0 g) was suspended in boiling methanol (900 mL) for 10 min and then filtered while hot to give undissolved solid (13.4 g; fraction a). The hot filtrate was allowed to cool to room temperature and was refiltered, yielding a white solid (0.91 g; fraction b). This filtrate was cooled to -5 "C, and a third crop of solid was recovered (0.30 g; fraction c). The filtrate was evaporated to yield a solid residue (0.35 g; as fraction d). Fractions a-c were primarily octachloronaphthalene while fraction d was considerably enriched in the 2H isomer. Similar "fractionations" could be achieved from acetone or dichloromethane. Repeated crystallizations from a variety of solvents produced white crystals, but GC and HPLC showed such material always to contain some of the 1Hisomer (10-15 '5%) and some octachloronaphthalene (2-5%). Recrystallization, but no further enrichment, could be achieved from a variety of solvents, e.g., dichloromethane, hexane, diethyl ether, acetone. Final purification was achieved by preparative RP-HPLC to give the 2H isomer that was >98% pure by GC. mp, 108-110 "C, lit. 194 "C (4),no data (14);lH NMR, 7.79; I3C NMR, 135.5,135.3,134.5,132.5 (strong), 131.4,130.1,129.3,129.1, 128.7,127.9; MS, 372(54) 370(94), 368(100),366(43), 300(41), 298(63), 296(38), 228(29), 226(33), 156(33), 155(22), 149(22), 143(32); HRMS, calcd for CloHC17, 365.7901; found: 365.7926. Retention times: GC, 18.25; HPLC, 12.85(9.56). 1,2,3,4,5,6,7-Heptachloronaphthalene (the1HIsomer), 3. (A) Partially purified (>90 % ) octachloronaphthalene (2.0 g, 5.0 mmol) was dissolved in dry THF (75 mL) and treated with fresh LiAlH4 (0.11 g, 3 mmol). After 2 h of stirring a t room temperature, the reaction mixture was diluted with water (700 mL), acidified with HC1, and extracted with CHzClz (3 X 50 mL). After drying and removing the solvent, a white solid was obtained, 1.85 g (by GC, -75% "hepta"/25% "hexa"). Exhaustive recrystallization from ether or dichloromethane could produce material of 95 % purity but prep RP-HPLC was more effective at producing material of >98% isomeric purity. mp, 179-182 "C, lit. 175-180 "C (18),160-162 "C (13);lH NMR, 8.46; l3C NMR, 135.6, 134.9, 134.1, 132.5, 131.1, 130.1,129.7,129.1,127.1,125.2(strong); MS, 372(50),370(93),368(100), 366(44),300(30),298(46),296(29), 149(29); HRMS, calcd for CloHC17: 365.7901; found 365.78912. Retention times: GC, 17.86; HPLC, 14.83(12.25). (B)From 7-amino-1,2,3,4,5,6-hexachloronaphthalene, 8 (see below for preparation from 2-nitronaphthalene). This preparation is adapted from the Doyle modification (28)of the Sandmeyer displacement and is preferred over method A. To a mixture of aminohexachloronaphthalene,8 (0.35 g, 1.0 mmol), dissolved in dry acetonitrile (20 mL) and anhydrous CuClz (0.16 g, 1.3 mmol) with stirring and heating (65"C), was added slowly fresh isoamylnitrite (0.3 mL, 2.0 mmol) in acetonitrile (5 mL) over 10min. Heating was continued for 0.5 h and the workup was by dilution with HzO (200 mL), acidification with HC1, and extraction with CHzClz (3 X 50 mL). The combined organic phases were washed with dilute aqueous HC1 (1 X 50 mL) and water (1 X 50 mL), and after drying and removing the solvent, a crude, pink-colored solid (0.31 g, 84%) was
obtained. GC analysis indicated isomer 3 (-90%) and some lower congeners. Treatment with Norit and recrystallization (lx) from ether produced off-white crystals, mp. 178-181 "C, with a purity >97% as judged by GC. 1,2,3,5,6,7(1,2,3,4,6,7)-Hexachloronaphthalenes, 4 (5). (A) Partially pure (>90 % ) octachloronaphthalene (2.0 g, 5.0 mmol) dissolved in dry THF (75 mL) was treated with fresh LiAlH4 (0.21g, 5.5 mmol) and processed as in method A for the 1H-heptachlor0 isomer, 3, to yield a white solid (1.70 g). GC analysis indicated the composition to be -75% of one "hexa" peak and -20% of the 1H hepta isomer. Repeated recrystallizations from ether or dichloromethane could never increase the isomericpurity beyond 90% "hexachloro" as judged by GC. (B)Commercial Halowax 1051 (1.0 g, 2.5 mmol) was dissolved in glacial acetic acid (50 mL) and treated with Zn dust (0.5 g). After stirring 12 h a t reflux, the metal was filtered off, the filtrate was treated with water (500 mL), and the precipitated solid, 0.72 g, was collected by filtration. Analysis by GC indicated >90 9% purity with some lower congeners. Recrystallization (2X) from diethyl ether gave white, fluffy needles, showing one peak >98% pure by GC. mp, 178181 "C, lit. no data (9,22); IH NMR, 8.39, 8.32 (ratio approximately 1:l); 13C NMR, 134.1, 133.4, 132.1, 131.5, 131.0,129.2,129.05,129.04,126.7,124.6 (bothstrong); MS, M+ cluster 336(81), 334(100), 332(53), plus 264(36); retention times: GC, 14.52; HPLC, 11.48(10.10,10.32). 1,2,3,4,5,6-Hexachlor0-7-nitronaphthalene, 7. As reported earlier (25),2-nitronaphthalene (10.0 g, 0.58 mmol) was treated with chlorine gas, iron powder (0.5 g), and iron(II1) chloride (0.5 g) in tetrachloroethane (75 mL) for 2.5 h a t 100 "C to produce yellowish needles (16.0 g, 72%), which could be recrystallized from dichloromethane or acetone. mp, 187-189 "C, lit. 188 "C (25);lH NMR, 8.72; I3C NMR, 147.8, 137.6, 133.6, 132.6, 131.3, 129.3, 129.2, 129.0,127.0,120.4 (strong); MS, 383(30),381(69),379(84), 377(45), 335(37), 333(47), 331(24), 323(28), 302(21), 300(64), 298(100),296(63),228(27),226(29);HRMS, calcd for CloH02NCl6, 376.8141; found: 376.81165. Retention time: GC, 18.70. 1,2,3,4,5,6-Hexachloro-7-aminonaphthalene, 8. As reported earlier (%),the hexachloronitronaphthalene,7, (3.0 g, 8.0 mmol) was refluxed for 18 h with stirring in l-pentanol(40 mL) and aqueous 20 % sodium metabisulfite solution (50 mL). The reaction mixture was cooled and filtered, and the solid was washed with hot water before drying to yield a whitish solid (2.01 g, 72%). Recrystallization, if necessary, could be achieved from acetone or dichloromethane. mp, 163-165 "C, lit. 165 "C (25);1H NMR (DMSO-&), 7.47 (8, 11, 6.65 (bs, 2); 13C NMR (DMSO-&), 145.8,131.2,129.5,128.4,127.5,127.0,126.7, 125.5, 118.7, 104.3 (strong); MS, 353(33), 351(80), 349(1001, 347(53), 287(24); HRMS, calcd for CloHsNCk, 346.8400; found: 346.83893. Retention time: GC, 22.15. 1,2,3,4,5,6-Hexachloronaphthalene, 9. Following the Doyle procedure (261,the amine (0.35 g, 1 mmol) in anhydrous dimethylformamide (10 mL) was added to a rapidly stirred solution of isoamylnitrite (0.2 g, 17 mmol) in anhydrous DMF (40 mL) a t 60 "C. After addition of the amine, heating was continued for a further 30 min. The reaction mixture was then cooled, diluted with HzO (500 mL), and extracted with CHzClz(3 X 40 mL). The combined organic phases were washed successively with dilute aqueous HCl(1 X 50 mL) and water (2 X 50 mL). After drying and completely removing solvents, a pinkEnviron. Sci. Technol., Vol. 27, No. 8, 1883
1675
CI
CI
CI
IO
CI
"2 11
CI
CI
II
I2
I
1
CI
CI I4
Figure 2. Synthesis scheme for 10-14.
colored solid was obtained (0.27 g, 80%),which consisted of -90% of a single hexachloronaphthalene as judged by GUMS. Treatment with decolorizingcharcoal and a single crystallization from ether produced white needles with a purity of >97%. mp, 132-134 "C, lit. no data (14,19); lH NMR, 8.23 (d, 1J= 10 Hz), 7.69 (d, 1J= 10 Hz); 13CNMR, 136.7,134.7,131.4,130.6,130.5,129.8(strong), 128.9,128.8, 128.5,125.3 (strong); MS, 338(43),336(100), 334(60),264(31),262(24);HRMS, calcd for CloHzCle, 331.8290; found: 331.8279. Retention times: GC, 16.20; HPLC, 9.69(8.37). The synthesis scheme for compounds 10-14 is shown in Figure 2. 3,4,5,6,7,8-Hexachloronaphtho[l,8-cdll,2-dithiole, 10. Octachloronaphthalene (5.0 g, 12.4 mmol) was suspended in refluxing ethanol (40 mL) and then treated with a solution of NazS-9H20 (3.9 g, 16.3 mmol) and sulfur (0.53 g, 16.3 mmol) in boiling ethanol (20 mL). The mixture was heated to reflux to give a homogeneous,orange-browncolored solution. Reflux was maintained for 3 h, and on cooling, the solution deposited an orange-brown solid, 4.4 g (88%). This solid could be recrystallized from 1,4dioxane yielding orange-colored crystals: mp, 282-4 "C, lit. 283-5 "C (15);1H NMR, no peaks; MS, 400(36), 398(73), 396(100), 326(29); retention time: GC, 22.17. 2,3,4,5,6,7-HexachloronaphthaZene, 11. Several unsuccessfulattempts were made to repeat the original patent literature (20)before devising a successful modification. The Raney nickel employed was a gray powder, suspended in water and supplied by W. R. Grace (Division Chemical Division), grade no. 28. (a) As originally described, the dithiole derivative, 10 (1.2 g) dissolved in hot diethylaminoethanol (45mL) was treated carefully with excess Raney nickel (2.0 g, wet). After being refluxed (165 "C) for 60 min, the hot solution was decanted from the nickel powder and treated with water (500 mL), and the cooled solution was extracted with CH2C12 (3 X 100 mL). The combined organic layers were backwashed with H20 (2 X 50 mL) and dried, and the solvent was removed, yielding a dark oil (-50 mg) which solidified on standing. The nickel powder was dissolved in 20 % aqueous HCl, and the green solution was extracted with CH2C12, but no additional organic material was recovered. Analyses of the residue by GC/MS indicated a complex mixtures of penta-, tetra-, tri-, and even dichlorinated naphthalenes but little or no hexachloro isomers. (B)The orange-brown-colored suspension of the dithiole derivative, 10 (500 mg) in THF (75 mL) was stirred with wet Raney nickel (1g). After stirring at room temperature for 10 min, the catalyst was filtered off, and the yellow solution evaporated to dryness to produce a yellow solid which, by GC/MS analysis, was composed primarily of one hexachloro isomer ( 85 5% 1 N
1676 Envlron. Scl. Technol., Vol. 27, No. 8, 1993
and one pentachloro isomer (-12% ). Successive recrystallization from ether and acetone could produce the hexa isomer in 95% purity, or prep RP-HPLC would yield material of >98% purity as determined by GC. mp, 158160 "C, lit. no data (20);'H NMR, 7.79; 13CNMR, 134.6, 132.8,132.1,130.6,127.0,126.8(strong);MS, 338(36),336(82),334(100), 332(55),264(37), 262(29),132(21);HRMS, calcd for CloHaCle, 331.8290; found 331.82980. Retention times: GC, 16.64; HPLC, 7.67(7.27). 2,3,4,5,6-Pentachloronaphthalene, 12. Purification of the hexachloro congener by prep RP-HPLC also yielded a fraction containing the pentachloro side product, and final recrystallization from acetone or dichloromethane produced white crystals with purity >98% by GC. mp, 115-117 "C; 'H NMR, 7.86 [~,11,7.614,7.592,7.589,7.567 [dd,21; 13C NMR, 135.7, 134.4, 132.8, 131.8, 130.4, 129.3 (strong), 128.4, 128.1 (strong), 127.6 (strong), 125.6; MS, 302(62),300(100), 299(58), 230(32),228(30);HRMS, calcd for CloHaCls, 297.8680; found, 297.86520. Retention times: GC, 14.24; HPLC, 5.46(5.39). Attempted Preparation of 1,2,4,5,6,7-Hezachloronaphthalene. As originally reported (9)1,5-diaminonaphthalene (0.50 g, 1.9 mmol) was dissolved in dry acetonitrile (50mL) and treated with anhydrous CuClz (2.5 g, 19mmol). After being stirred and heated at 65 OC for 2 h, this suspension was treated slowly with a solution of isoamylnitrite (4 mL) in dry acetonitrile (25 mL) over 15 min. The temperature was then increased to 95 "C and held for 2 h, at which time the mixture was cooled, treated with water (500 mL), and acidified with dilute HC1. The organic material was extracted with CHzClz (3 X 50 mL), and the combined organic extracts were back-washed with 10% aqueous sodium bicarbonate (2 X 40 mL) and water (1X 50 mL). Drying and removing the solvent produced a brownish, solid residue (0.32 g). GC/MS analysis indicated this product to be a complex mixture of tri-, tetra-, and pentachloronaphthalenes plus a small amount of a hexachloro isomer. Many variations on order of the addition of reagents and temperature gave no useful results. 1,2,4,5,6,8-Hexachloronaphthalene, 14 (seeref17). (A) 1,5-Ditosylaminonaphthalene. The 1,5-diaminonaphthalene (5.3 g, 33.4 mmol) was dissolved in dry pyridine (300 mL) and treated with fresh tosyl chloride (15.8 g, 83 mmol) at reflux for 24 h (17,lO).The solution was cooled to room temperature and diluted with H20 (1 L). The light purple-colored solid was filtered, washed with water, and air-dried to yield the ditosyl derivative, 14.7 g (95% 1. mp, 300-305 "C dec.; 'H NMR, 10.2 (s, l),7.9 (m, l),7.6 (m, 2), 7.3 (m, 3), 7.1 (m, l),3.7 (8, 3); MS, 313(23), 312(loo), 158(45),157(93),155(20),130(98),129(32),103(27), 79(47). (B)2,4,6,8Tetrachloro-l,5-ditosylaminonaphthalene, 13. A suspension of the ditosyl derivative (10.0 g, 21.5 mmol) in glacial acetic acid (300 mL) under stirring at 95 "C was treated slowly over 20 min with a solution of chlorine gas (6.4 g, 90 mmol) in acetic acid (100 mL) (10). The solution turned dark red in color, and after 10 min, still at 95 OC, was treated with more chlorine (0.4 g) in acetic acid (10mL). A mass of crystalline material formed, and after a further 15-30-min the mixture was filtered while hot. The orange-colored solid was washed to neutrality with water and air-dried to give 6.4 g (50% ). The water washings caused more solid to precipitate from
the filtrate, and when collected and dried, this produced an additional 0.52 g of reddish brown solid. MP, 290-300 “C dec.; lit. 290-292 OC (10); MS, 604(6), 602(4), 570(5), 568(5), 155(28), 91(100). (C) Hydrolysis of Tosyl Groups of 13and Subsequent Sandmeyer Displacement t o 14. As originally described (17),the tetrachloroditosylderivative, 13 (2.0g, 3.3mmol), was treated with concentrated H2S04 (10 mL) at room temperature for 36 h to hydrolyze the tosyl groups and was subsequently treated with NaN02/CuC1 to give a dark grey solid, 0.43 g (45% ). GC/MS analysis of this material indicated -70% of a single hexachloro isomer together with -20% of two pentachloro isomers and some other minor components. Repeated recrystallization from ether, acetone, or dichloromethane could achieve only -85% purity of the hexachloro isomer. Prep RP-HPLC could produce material of >97 % . mp, 176-177 “C, lit. 175-177 NMR, 134.4, 132.9 (strong), “C (17);IH NMR, 7.80; 130.5, 130.2, 128.3; MS, 338(35), 336(81), 334(100), 332(53), 264(38), 262(30), 132(25), 129(43);HRMS, calcd for CloHzCls, 331.8290; found: 331.8302. Retention times: GC, 15.66; HPLC, 9.78(8.26). Discussion
Purity and Isomer Differentiation. I t has been our experience that melting points especially give little indication of product purity. Frequently, one obtains crude mixtures containing 70-80 % of a single isomer as indicated by capillary GC and several recrystallizations will raise the isomeric purity to 85-90% but no further. Not much change is noted in the range or sharpness of the melting temperature, for example, a mixture of 4 and 5 has only a 3O melting range. This phenomenon has been noted in the literature (18). Generally, the most discriminating solvents are chloroform or dichloromethane followed by acetone, diethyl ether, then hexane, and finally ethanol or methanol, but still the propensity for cocrystallization of 10-20% of other congeners is highly probable. The best techniques for determining isomeric purity are capillary GC and RP-HPLC. Although the DB-5 coating has been reported to separate most congeners (4, 9),we have found that DB-17 is more effective;for instance, such GC columns can provide “baseline separation” of the two heptachloro isomers, 3 and 6. The sole exception observed by us and others (9,221 thus far is the inability to distinguish between the hexachloro isomers 4 and 5. Normal-phase HPLC can often separate hexas from heptas from octa, but it is virtually useless in distinguishing regioisomers containing the same number of chlorines (4). Reverse-phase conditions, e.g., Lichrosorb RP-8 with methanol or acetonitrile in water (85:15), have been reported to provide baseline separation of the two heptachloro isomers as well as octachloronaphthalene (4,14, 23). We have found that C18 columns with pure methanol permit baseline separations not only of the two heptachloro isomers but also of most of the hexachloro isomers that we have prepared. Similar conditions, i.e., S5ODS in methanol or methanol/water, have been reported to distinguish between 1 and 2 (24). This opportunity to achieve isomer separation without the use of water is absolutely crucial for the final purifications of various isomers employing preparative-scale columns. For example, if even 10 mL of a solution containing PCNs is injected into methanol containing a few percent water,
the compounds immediately precipitate, and the RPHPLC column becomes clogged and, thus, inoperative. Depending on structure, the PCNs usually have solubilities in methanol of 20-50 mg/100 mL, and we have had good success for final purifications, Le., removing the final 1015% of cocrystallizing impurities by utilizing approximately 40 mg/injection. In our experience to date, only the two hexachloro isomers, 4 and 5, cannot be distinguished by analyticalscale C18 RP-HPLC in methanol or methanol/water. However, we now have observed not quite baseline resolution of these two isomers using analytical-scale C18 RP-HPLC with neat acetonitrile as solvent, see also ref 22. Synthetic Procedures. The reductive dechlorination of octachloronaphthalene is very facile with LiAlH4. Unlike previous reports which propose large excesses of LiAlH4, e.g., 4 equiv for hepta (13),24 equiv for hexas (9) in refluxing THF (see, however, ref 141, we have found it necessary to use almost stoichiometric amounts of the reductant to prevent significant overreduction to pentachloro- and lower congeners, see also ref 22. Even under optimum conditions one never obtains crude product containing more than -70% of the desired congener. In our opinion this practical complication favors the modified Sandmeyer chlorination route for the preparation of 3 from 8 (28). This common intermediate, Le., 8, can also be diverted to produce directly the 1,2,3,4,5,6-hexachloro congener, 9 (261,which has never been characterized (14, 19). In both instances the crude products containing >90% of the desired isomer as judged by GC could be purified to >97 % by one crystallization. We have discovered that Zn dust in refluxing acetic acid is the preferred technique for obtaining the identical (by GC/MS, mp, IH NMR, NMR) hexachloronaphthalene mixture of 4 and 5 reportedly obtained by LiAlH4reduction of 1; (9,22). The ratio (roughly 1:l)of these two isomers will vary somewhat depending on the method of preparation. Synthesis of octachloronaphthalene,2, has been achieved usually by elimination of Cl2 thermolytically (-200 “C) from the decachlorodihydronaphthalene,1 (4,6,7) or by using SnCl2 reduction (7).We have found that this technique to produce a material containing -80% octachloronaphthalene plus other congeners, Le., a mixture quite similar to Halowax 1051 by GC examination. We investigated two other elimination procedures (27) with interesting results. Treatment of 1 with Zn dust in refluxing methanol produced in -80% yield a crude mixture of polychloronaphthalenes of which the 1Hhepta isomer, 3, was the major component. On the other hand treatment of 1with NaI in acetone yielded a crude product containing 85 % octachloronaphthalene in overall yield of 85-90%. Clearly the latter method would be preferred for preparation of octachloronaphthalene, 2. Our attempts to prepare 2,3,4,5,6,7-hexachloronaphthalene, 11 from the corresponding dithiole, 10 using selective desulfurization with Raney nickel in refluxing diethylaminoethanol as originally described (20), were totally unsuccessful. We obtained minuscule amounts of crude products showing only mixtures of di-, tri-, and tetrachloronaphthalenes by GC/MS. Perhaps our Raney nickel was much more active. We eventually developed sufficiently mild conditions to produce a good yield a mixture containing predominantly one hexachloro conN
Envlron. Sci. Technol., Vol. 27, No. 8, l W 3 1077
gener, Le., 11, and one pentachloro isomer, 12. Despite some additional modification of conditions, e.g., time, temperature, and Raney nickel activity, we could not prevent the formation of this pentachloro impurity, presumably formed by hydrodechlorination of the major product. Final purification was thus complicated and could be most readily achieved by prep RP-HPLC. The 1,2,4,5,6,8-hexachloronaphthalene, 14, can in principle be obtained from 1,5-diaminonaphthalene by directed 0- and p-substitution of four chlorine atoms followed by Sandmeyer substition of the two amino groups, e.g, see ref 17. According to a recent Swedish report (9, IO), these two reactions can be combined into one experimental procedure utilizing the Doyle conditions of CuClz and isoamylnitrite in acetonitrile (28). Our many attempts to repeat this one-pot procedure invariably led to low overall yields of mixtures containing only small amounts of a hexachloronaphthalene but predominantly several pentaand tetrachloro congeners. Thus, we were forced to revert to a stepwise procedure from 1,5-diaminonaphthalene involving bistosylation, tetrachlorination, hydrolysis of the protecting groups, and Sandmeyer displacement by chlorine of the two free amino groups. This sequence has been reported previously but with little characterization of intermediates (17,29). We were never able to obtain unambiguous spectral data of the various intermediates due to insolubility and apparent lability of the tosyl groupsunder MS conditions. However, a crude polychloronaphthalene product was obtained containing, by GCt MS, a single hexachloro product but two pentachloro congeners as major impurities. Final purification of the hexachloro congener could be achieved by prep RP-HPLC, but the two pentachloro compounds were never purified sufficiently for identification. These major impurities had not been reported in the original publication and perhaps represent incomplete ring chlorination that is not detected due to difficulty in characterization of the various intermediates in the sequence. Also, despite many attempts, we were unable to obtain any useful amount of the 1,2,4,5,7,8-hexachloronaphthalene from 1,8-diaminonaphthalene either directly as previously reported (9) or indirectly via a sulfur-bridged intermediate (30). In view of these various observations illustrating the ease of hydrodechlorination of polychlorinated naphthalenes by Zn dust, one should be very concernedtskeptical about the integrity of chlorine substitution when using Zn for reduction of the NO2 group in this series of molecules, see, for example, ref 19; we would recommend the milder dithionite conditions (25) or others (31). Even catalytic reduction conditions, e.g., Pd/HZ (131,should be carefully evaluated because of our experiences with Raney nickel and other reports (32). Structure Proof. Most of the existing structure proof for the hexa- and heptachloro isomers are based on the presumed regioselectivity of the reaction sequences used to prepare these compounds. For example, the structures of the two heptachloro isomers rest on the assumption that the nulceophilic hydride ion will attack at the a-position (9,13). These compounds are chromatographically different (4, 9) and also exhibit different lH NMR chemical shift values, namely, 8.4 for the 1H isomer, 3, and 7.8 for the 2H isomer, 6 (4,14). We feel the structure of 3 is now unambiquously established since the substitution patterns of its precursors, i.e., 7 and 8, can be 1678 Envlron. Scl. Technol., Vol. 27, No. 8, 1993
unequivocally assigned from their NMR spectra here available for the first time. Although the lH NMR shift differences have been used to "characterize" protons on the a- or @-carbons(19),we believe that the 13C NMR spectra, accumulation for the first time in this study, seem to be equally diagnostic or perhaps even more reliable as illustrated below. From the 13C NMR spectra of the two heptachloro isomers, it appears that an a-carbon with attached proton resonates at higher field (125.2)than a @-carbonwith attached proton at 132.6. These are the only intense peaks in the spectrum. This trend is consistent with all our data and, in conjunction with other data (12, 22), would indicate the following ranges: for aC(H) 125-129 and for @C(H)129135. The unequivocal structure of isomer 9 follows from its NMR spectra, i.e., one aCH and one @CHwith a J value indicating ortho coupling, plus the method of preparation from 8. The structure of isomer 14 follows unambiguously from the NMR spectra. Its unique symmetry is confirmed by only five lines in the 13C NMR, and the presence of only a @CHis implied by both lH and 13Cchemical shift values. That the product of reduction of octachloronaphthalene, 2, by LiAlH4 or preferably Zn/acetic acid is a mixture of isomers 4 and 5 can be readily deduced from the NMR data. Only uncoupled aCH's are indicated both by 'H and 13Cchemical shifts. This product was clearly not the isomer 11for which we had data, and the implied symmetry of any other structure would predict a 13CNMR spectrum of only five lines rather than the 10 observed. We were also pleased to finally device chromatographic conditions that would differentiate these isomers. The Swedish investigators have recently isolated the two isomers (22), thus, correcting their earlier assumptions (9). The lH NMR spectrum of the 2,3,4,5,6,7-hexachloronaphthalene, 11, has now introduced an anomaly to the usual lH NMR shift designations. The a-protons now appear as a singlet at 7.79, a value supposedly indicative of @-protons,but the 13CNMR spectrum shows six different peaks of which the one large peak, Le., the carbon with attached H, occurs at 127.0, which is indicative of aC(H). Probably the absence of a peri-situated chlorine has a substantial effect (12). To confirm this structure assignment for 11, we include an X-ray crystallographic study with comments to follow. Data for the pentachloronaphthalene impurity, 12, display the same ambiguity, namely, 'H NMR shifts in the 7.8-7.5 range, seemingly indicative of three protons only in @-positionswhen its method of preparation infers otherwise. Close inspection reveals the absorption at 7.5 to be an extremely unsymmetrical doublet of doublets with J = 8 and 1Hz. The size of this coupling constant strongly suggests vicinal protons, thus implying one aand one @-hydrogen.This is corroborated by the 13CNMR which displays three intense peaks, on @CH(129.3) and two aCH (128.0,127.6). Furthermore, these designations correspond to the calculated values based on Ad additivities (12),and thus the structure for this compound must be 2,3,4,5,6-~entachloronaphthalene, 12. Consequently, we urge caution when using lH NMR data to assign a- or @-hydrogensin these types of molecules. It would appear that 13CNMR spectra are most unambiguously diagnostic. X-ray Crystallographyof 11. The needle-like crystal was formed by recrystallization from acetone. Systematic
~~~
Table 11. Atomic Parameters x, y, and z and € .4,
Table I. Crystal Data empirical formula formula weight crystal shape crystal dimensions (mm) crystal system no. of reflections used for unit cell dimension (26 range) lattice parameters space group Z value D d o( ~ c m - ~ ) F(000) fim(mm-1) no. of reflections measured no. of reflections unique no. of reflections observed no. of atoms no. of variables Rf(sign refl) R, (sign refl) Rf(all refl) R , (all refl) goodness of fit last difference fourier map max peak min peak
CioHzCle 334.84 needles 0.1, 0.1,0.4 orthorhombic 24 40,50 a = 11.2187 (13) b = 14.7768 (22) c = 6.898 (3) P212121 4 1.945 659.27 1.48 1191 1191 944 18 146 0.034 0.024 0.055 0.024 1.78 0.310 4.320
m
Flgure 3. X-ray structure of 2,3,4,5,6,7-hexachloronaphthalene, 11.
absences indicated a space group P212121. The lattice parameters were obtained by least-squares calculations based on setting angles of 24 reflections. The data was corrected for Lorentz and polarization effects (33),and an absorption correction was done using +scan. The minimum and maximum transmission factors are 0.630690 and 0.715550. The crystal data for 11is found in Table I. The structure was solved by the direct method using the program NRCVAX crystal structure package (34),and the model was refined by full-matrix least-squares. Figure 3 represents an ORTEP drawing, and it was found that the six chlorines lie essentially in the same plane as the naphthalene ring (k0.029A from the plane). All the atoms were found by electron density map and refined anisotropically; the hydrogen positions were also found by difference fourier but were refined isotropically. The weighting scheme employedwas determined from counting statistics. There were no changes larger than 0.0026 in any of the parameters in the last least-square cycle. All the final coordinates are given in Table I1 while bond distances and angles are listed in Table 111. A list of
X
C11 C12 C13 C14 C15 C16 C1 C2 C3 C4 C5 C6 C7 C8 C9 C10 H6 H7
0.67428(13) 0.64769(13) 0.40587(14) -0.00813(14) -0.05785(13) 0.14223(13) 0.5353(5) 0.5206(5) 0.4087(5) 0.3039(4) 0.3205(5) 0.4360(5) 0.2222(5) 0.1090(5) 0.0886(4) 0.1817(5) 0.447 0.239
Y
t
Bi,
0.40344(11) 0.61268(11) 0.70234(9) 0.33140(11) 0.53752(12) 0.67429(10) 0.4519(4) 0.5458(4) 0.5854(4) 0.5312(4) 0.4345(4) 0.3967(4) 0.3739(4) 0.4067(4) 0.5006(4) 0.5610(4) 0.324 0.300
0.1113(4) 0.1154(4) 0.1162(4) 0.1188(4) 0.1107(4) 0.1030(4) 0.1128(14) 0.1132(14) 0.1123(15) 0.1140(12) 0.1123(13) 0.1146(15) 0.1141(14) 0.1121(15) 0.1120(12) O.llOO(13) 0.118 0.115
3.22(9) 3.11(8) 2.85(8) 3.15(8) 2.82(8) 2.89(8) 1.9(3) 1.9(3) 1.8(3) 1.6(3) 1.5(3) 2.1(3) 2.2(3) 2.1(3) 1.9(3) 1.8(3) 2.8 2.9
Bho is the mean of the principal axes of the thermal ellipsoid. The last digit in parentheses refers to standard error deviation.
Table 111. Structural Parameters Cll-c1 c12-c2 C13-Cl6 C13-C3 C14-C8 C15-C9 C16-C10 Cl-C2 Cl-C6 C2-C3 C16-C13-C3 C13-Cl6-ClO c11-c1-c2 C11-C1-C6 C12-Cl-C6 c12-c2-c1 c12-c2-c3 Cl-C2-C3 c13-c3-c2 c13-c3-c4 c2-c3-c4 c3-c4-c5 C3-C4-C10 C5-C4-C10 C4-C5-C6 c4-c5-c7
Atomic Bond Lengths (A) 1.716(5) c3-c4 1.735(5) c4-c5 2.9881(21) C4-ClO 1.729(6) C5-C6 1.722(6) c5-c7 1.731(5) C6-H6 1.732(6) C7-C8 1.397(8) C7-H7 1.380(8) C&C9 1.385(8) C9-ClO Bond Angles (deg) 83.04(20) C6-C5-C7 83.11(21) Cl-C6-C5 121.5(4) Cl-C6-H6 119.1(4) C5-C6-H6 119.4(5) C5-C7-C8 117.9(4) C5-C7-H7 120.3(4) C8-C7-H7 121.7(5) C14-C8-C7 116.0(4) C14-C8-C9 123.2(4) C7-C&C9 120.8(5) C15-C9-C8 116.8(5) C15-C9-C10 127.9(5) C8-C9-C10 115.3(5) C16-ClO-C4 120.7(5) C16-ClO-C9 121.6(5) C4-ClO-C9
1.423(8) 1.441(8) 1.440(8) 1.411(8) 1.421(8) 1.086(5) 1.359(9) 1.106(5) 1.406(8) 1.374(8) 117.6(5) 120.5(5) 119.6(5) 119.9(5) 120.0(5) 119.4(5) 120.6(5) 118.8(5) 120.9(5) 120.2(5) 117.7(4) 121.1(4) 121.2(5) 122.7(4) 115.7(4) 121.661
structure factors and anisotropic thermal parameters are available as required from one of the authors (C.B.). Conclusions The detailed toxicologicaland analytical investigations that are long overdue for the polychlorinated naphthalenes (see refs 2 and 22) are dependent on the availability of adequate amounts, ca. >lo0 mg, of material. Obviously these compounds must be rigorously characterized and of high, ca. >98%, isomeric purity. We believe this paper details preparation and purification methods that can provide such compounds together with their necessary description. We are continuing to investigate new methods of synthesizing adequate amounts of the remaining unknown PCNs, including the ecologically interesting hexachloro isomers 4 and 5 (10, 22). Environ. Sci. Technol., Vol. 27, No. 8, 1993
1679
Acknowledgments
We thank Professor G. W, Buchanan and K. Bourque of Carleton University for assistance with NMR spectra and Dr. R. Burk of the Centre for Environmental and Analytical Chemistry, Carleton University, for assistance with all chromatographic instrumentation including GC/ MS. Financial support for much of this work was provided by a contract with Health and Welfare Canada. Literature Cited Jansson, B.; Asplund, L.; Olsson, M. Chemosphere 1984,
13,33. Hanberg, A.; Waern, F.; Asplund, L.; Haglund, E.; Safe, S. Chemosphere 1990,20, 1161. Suschitzky, H., Ed. Polychoroaromatic Compounds, 1sted.; Plenum Press: London/New York, 1974,pp 32-36,411. Brinkman, U. A. Th.; Reymer, H. G. M. J. Chromatogr.
1976,127,203.
Clark,J.;Maynard, R.;Wakefield,B. J. J.Chem.SOC.,Perkin Trans. 2 1976,73. Mosby, W. L. J. Am. Chem. SOC.1955,77,759. Ballester, M.; Castaner, J.; Riera, J.; Pares, J. Anal. Quim. Ser. C 1981,76,157. Brintzinger, J.; Orth, H. Monatsch. Chem. 1954,85,1015. Haglund, E.;Bergman, A. Chemosphere 1989,19,195. Asplund, L.; Jansson, B.; Sundstrom, G.; Brandt, I.; Brinkman, U. A. Th. Chemosphere 1986,15,619. Herbstein, F. H. Acta Crystallogr. B 1979,35,1661. Wileon, N. K.; Zehr, R. D. J. Org. Chem. 1978,43,1768. Brady, J. H.; Tahir, N.; Wakefield, B. J. J . Chem. SOC., Perkins Trans 1 1984,2425. Campbell, M. A.; Bandiera, S.; Robertson, L.; Parkinson, A.; Safe, S. Toxicology 1983,26,193.
1680 Environ. Scl. Technoi., Vol. 27, No. 8, 1993
(15) Klingsberg, E. Tetrahedron 1972,28,963. (16)Brinkman, U.A. Th.; deKok, A. J. Chromatogr. 1976,129, 451. (17) Reimlinger, H.; King, G. Chem. Ber. 1962,95,1043. (18) Sundstrom, G. Chemosphere 1976,5,191. (19) RUZO,L.; Jones, D.; Safe, S.; Hutzinger, 0. J. Agric. Food Chem. 1976,24,581. (20) Klingsberg, E. U.S.Patent 1973,3769276;Chem. Abstr. 1972,76,P142391w. Safe, S.;Zitko, V. Int. J.Environ. Anal. Chem. (21) Hutzinger, 0.; 1972,2, 95. (22) Jakobsson, E.; Eriksson,L.; Bergman, A. Acta Chem.Scand. 1992,46,527.We thank Dr. Bergman for a preprint of this manuscript.
(23) Brinkman, U.A. Th.; deKok, A. J. Chromatogr. 1976,129, 451. (24) Ivanov, Z.; Magee, R. J.; Markovec, L. Talanta 1983,30, 277. (25)Fenyes, J. G. E. J. Chem. SOC.(C)1968,5. (26)Doyle, M. P.; Dellaria, J. F.; Siegfried, B.; Bishop, S. W. J. Org. Chem. 1977,42,3494. (27) For a leading reference, see: Larock, R. C. Organic Transformations,lsted.; VCH Publishers: New York, 1989; p 133. (28) Doyle, M.P.; Siegfried, B.; Dellaria, J. F. J. Org. Chem. 1977,42,2426. (29)Whitehurst, J. S.J. Chem. SOC.1951,220. (30)See ref 27,p 412. (31) Behr'inger, J.; Leiritz, K. Chem. Ber. 1965,98,3196. (32) Cooke, M.;Robert, D. J. J. Chromatogr. 1980,193,437. (33) Gabe, E. J.; Lee, F. L.; LePage, Y. J. Appl. Crystallogr. 1989,22,384. (34) Grant, D. F.; Gabe, E. J. J.Appl. Crystallogr. 1978,11,114. Received for review April 20, 1993.Accepted April 27, 1993.
