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Structures and ring closures of compounds from the mothproofing agent eulan wa neu
Analytica Chimica Acta, 155 (1983) 293-298 Elsevier Science Publishers B.V., Amsterdam - Printed in The Netherlands
Short Communication
STRUCTURES AND RING CLOSURES OF COMPOUNDS FROM THE MOTHPROOFING AGENT EULAN WA NEU
GUNNEL WESTGG, KOIDU NORBN* and B6RJE
EGESTAD
Department
Institute,
of Physiological
Chemistry,
Karolinska
Stockholm
(Sweden)
LENA PALMBR Department
of Toxicology,
Karolinska
Institute,
Stockholm
(Sweden)
GUN BLOMKVIST Swedish
National
Food Administration,
Uppsala (Sweden)
(Received 16th March 1983)
Summary. The main active ingredients of the mothproofing agent Eulan WA Neu are the N-chloromethylsulphone derivatives of 2’,3,4,4’,5-pentachloro-2-aminodiphenyl ether and 2’,3,4,4’,5,6-hexachloro-2-aminodiphenyl ether. The structures of the pentachloro-2aminodiphenyl ether and some related compounds are discussed on the basis of n.m.r. spectroscopic data. Orientating ring closure experiments were done by heating some of the Eulan WA Neu compounds to about 390°C. The results of g.c./m.s. studies indicated the formation of polychlorinated dibenzodioxins, dibenxofurans and phenoxaxines.
The contamination of fish by two polychlorinated aminodiphenyl ethers, 2’,3,4,4’,5-pentachloro-2aminodiphenyl ether (I) and 2’,3,4,4’,5,6_hexachloro-2aminodiphenyl ether (II), was demonstrated in 1977 [ 11. These compounds emanated from the mothproofing agent Eulan WA Neu (Farbenfabriken Bayer AC), the main active constituents of which are the N-chloromethylsulphone derivatives (III, IV) of these amines. In 1979, Wells [2]
(‘1
\,’
“ill
IX
\
reported that fish from a water area into which Eulan WA Neu was discharged contained, in addition to two polychlorinated aminodiphenyl ethers, the N-chloromethylsulphone derivatives at levels up to 0.6 mg kg-’ in fish muscle and 5.7 mg kg-’ in fish liver. Using Wells’ method of analysis [2] , we found
0 1983 Elsevier Science Publishers B.V.
294
Based on n.m.r. and g.c./m,s. studies, Wells [ 21 suggested structures V and VI, having a hydrogen atom in the ortho position to the amino group for the pentachloro-2-aminodiphenyl ether and its N-chloromethylsulphone derivative. He also concluded that his data were in accordance with previously reported structures I and III [l] (having a hydrogen atom in the metu position to the amino group). Structures V and VI were also used in later reports [3-51. However, they are incompatible with the chlorination experiments done [l] with 2’,4,4’,5-tetrachloro-2-aminodiphenyl ether (VII) and its NJdiacetyl derivative. In the first case, the Eulan WA Neu compound I was easily formed, whereas in the second case there was no reaction. The acetylation should suppress an electrophilic substitution by chlorine in the ortho position to the amino group in VII, whereas substitution in the metu position should be mainly unaffected. (In the dichlorophenyl ring, Wells sometimes [2] placed the chlorine atom, that should be paru to the oxygen, in the metu position, but this probably happened accidentally and is not discussed here.) In the present investigation, nuclear magnetic resonance spectroscopy (n.m.r.) was used to confirm structures I and III for the compounds present in Eulan WA Neu. This mothproofing agent was also heated to high temperature to see if it would form potentially more toxic compounds such as polychlorinated dibenzofurans. Discussion of s true tures A pentachloro-2aminodiphenyl ether was prepared by reducing the product obtained by coupling 1,2-dinitro-3,4,5-trichlorobenzene and 2,4-d& chlorophenol. From the method of synthesis, it must have either structure I
or V. This pentachloro-2-aminodiphenyl ether (m.p. 139.8”C) has a g.c. retention time of 1.29 relative to the pentachloro-2-aminodiphenyl ether I (m.p. 94.8”C) present in Eulan WA Neu and thus cannot have the structure I. Furthermore, in contrast to compound I, it reacted easily with chlorine with the formation of the previously [l] described 2’,3,4,4’,5,6-hexachloro-2aminodiphenyl ether (II). The amino group strongly promotes an electrophilic substitution by chlorine in the ortho position, which is available in structure V but not in structure I. The synthesized compound thus must have structure V. The pentachloro-2-aminodiphenyl ether, I, from Eulan WA Neu, its isomer V prepared as above, and the previously [l] synthesized compound, 2’,4,4’,5tetrachloro-2-aminodiphenyl ether (VII), were studied by ‘H-n.m.r. The data, compiled in Table 1, can be interpreted as follows. The NH2 resonance in
295
TABLE 1 ‘H-n.m.r. data for the three polychloro-2-aminodiphenyl
HP
H,
I
ethers studied (6 values)
Compound I: X = Cl, Y = H cI Compound V: X = H, Y = Cl Compond VII. X = H, Y = H
Proton
Compound Ia
Compound V
Compound VII
X (s) Y (s) H, (d)b H, (dd)b H, (d)b NH, (br s)
6.68 6.94 7.25 7.49 4.42
6.89 6.50 7.09 7.46 3.95
6.89 6.75 6.89 7.21 7.47 3.94
aFrom Eulan WA Neu. bFor the three compounds, J,, = 8.8 Hz, J,, not observed.
= 2.4 Hz, and J,, was
compound I from Eulan WA Neu was shifted downfield relative to the NH2 resonances for compounds V and VII. This shift should be caused by the chlorine substituent ortho to the amino group in compound I. In compound V, the resonances for H1, and to some extent Hz, (Table 1) were shifted upfield compared to the corresponding resonances in compounds I and VII. This must be explained as an effect of the chlorine atom in position 6 (Y = Cl) in compound V. Thus these n.m.r. data provide conclusive evidence that the previously demonstrated [l] structure I is correct for the pentachloro-2aminodiphenyl ether found in Eulan WA Neu. Accordingly, III (not VI) is the structure of its N-chloromethylsulphone derivative. Consequently, also in Wells’ reaction sequences [2] starting from V and VI, the intermediates and reaction products have one chlorine atom in the wrong position.
Ring closures
Structures I-IV for the compounds present in Eulan WA Neu indicate that U.V. radiation or high temperature might cause ring closure (cf. [6] ) with the formation of highly toxic polychlorinated dibenzofurans (IX). Polychlorinated phenoxazines (X) are also likely to be formed. Some ring closure experiments were therefore done. Compound II was heated to 390°C in a glass tube, sealed without previous removal of air. Analysis of the product mixture by g.c./m.s. indicated the formation of hexachlorodibenzofuran (IX). When a mixture of compounds III and IV or their sodium salts was heated in the same way, various ring closures occurred. The g.c. peaks from several pyrolysis experiments (two chromatograms are shown in Fig. 1) were analyzed by m.s. The molecular ions and the typical fragments expelled are reported in Table 2. Some of the m.s. patterns are in accordance with the observations made by Nagayama et al.
296
A
B
11
5
IO Retention
time
0
15
5
(men)
15
IO Retention
time
(I-NIT)
Fig. 1. Total ion current chromatograms from g.c./m.s. of compounds formed in pyrolysis experiments with III and IV (B, excess of IV) or their sodium salts (A, excess of III).
[ 71 and Bowes et al. [ 81 for tetrachlorodibenzofurans, others with observations by Nilsson et al. [6] for polychlorinated dibenzodioxins (VIII). Fragments probably resulting from loss of HCl + Cl and CO + Cl agree with the presence of polychlorinated phenoxazines (X). The g.c./m.s. data indicated the formation of two tetrachlorodibenzodioxins (VIII), one pentachlorodibenzodioxin (VIII), two pentachlorodibenzofurans (IX), one hexachlorodibenzofuran (IX), two pentachlorophenoxazines (X) and one hexachlorophenoxazine (X). Traces of a tetrachlorodibenzofuran (IX) and a tetrachlorophenoxazine (X) were also observed. The formation of the pentachloro isomers of the tricyclic compounds could be explained by ring closure to either of the ortho positions of the oxygen at the dichlorophenyl ring of the compounds III and IV. TABLE 2 G.c./m.s. data for the main tricyclic compounds and IV (B) or their sodium salts (A) Compounds found
Polychlorinated dibenzodioxins, VIII Polychlorinated dibenzofurans, IX Polychlorinated phenoxszines, X
Retention timea (min)
3.3(B) 3.8(B), 5.9(B) 4.2(B) 4.7(B), 7.3(B) 6.5(B) 12.4(B),
%See Fig. 1.
found in pyrolysis experiments with III
Number of Cl atoms
Mass of molecular ion, M+
Main fragmentslost
4
320
63(CO + Cl) + 63(CO + Cl)
5 5
354 338
63(CO + Cl) + 63(CO + Cl) 63(Cl + CO) + 7O(Cl + Cl)
6 5
372 353
63(Cl+ CO) + 7O(Cl+ Cl) 71(HCl+ Cl) + 63(CO + Cl)
6
387
71(HCl + Cl) + 63(CO + Cl)
from M+
3.8(A)
4.8 (A) 7.6(A) 12.7(A)
297
Formation of compounds I (ta = 6.8 min; Fig. 1A) and II (ta = 9.7 min; Fig. 1B) occurred during the pyrolysis of III and IV (mass spectra have been reported [l] ). Other compounds were also formed, but their structures were not established. Experimental A pentachloro-2aminodiphenyl ether (m.p. 139.8”C; 49.7% Cl found, 49.6% required for C,,H,ONCl,) was prepared by coupling 1,2-dinitro3,4,5trichlorobenzene with 2,4dichlorophenol and reducing the pentachloro-2nitrodiphenyl ether formed according to general methods [1] . Chlorination. This pentachloro-2aminodiphenyl ether (16.2 mg) was chlorinated by adding a solution (3.0 ml) of chlorine (3.2 mg ml-l) in carbon tetrachloride. After 12 min at room temperature, the solution was diluted to 50.0 ml with heptane. After further dilution, it was analysed by g.c. which showed that 2’,3,4,4’,5,6-hexachloro-2aminodiphenyl ether (II) had been formed (93% yield). The same chlorination procedure was used for the pentachloro-2-aminodiphenyl ether from Eulan WA Neu. No hexachloro-2-aminodiphenyl ether (II) could be detected by gc.; 89% of the starting material remained unchanged. Pyrolysis. For the pyrolysis experiments, compound II, a mixture of III and IV, or a mixture of the sodium salts of III and IV (about 2 mg) in a glass tube, sealed without previous removal of the air, was gradually heated in an oven during 25 min until 390°C was reached. The heating was then switched off, and after 10 min the tubes were cooled to room temperature. The reaction mixtures were dissolved in heptane (2 ml) and subjected to g.c./m.s. (Fig. 1, Table 2). Apparatus. For g.c., a Varian Aerograph 1200 with a tritium source electron capture detector was used. The glass column (3 mm X 1.8 m) was packed with a mixture of 3% SF-96 and 6% QF-1 [l] . N.m.r. spectra were obtained with a JEOL FX-100 instrument; the substances were dissolved in chloroform-d. For g.c./m.s., an LKB 2091 instrument connected to an LKB 2130 data system was used. The glass column (2 mm X 2 m) was packed with a mixture of 2% OV-1 and 3% QF-1. The temperature of the column and the separator was 225°C. The ion source was kept at 220°C and the electron energy was 70 eV. Financial support from the Swedish Products Control Board and the Swedish Council for Planning and Coordination of Research (Grant No. 81/2137) is gratefully acknowledged. We also wish to thank Dr. L. Kenne, University of Stockholm, for running the n.m.r. spectra.
298
REFERENCES 1 2 3 4 5 6
G. WestoS and K. Norbn, Ambio, 6 (1977) 232. D. E. Wells, Anal. Chim. Acta, 104 (1979) 253. D. E. Wells, Anal. Proc., 17 (1980) 116. D. E. Wells and S. J. Johnstone, J. Chromatogr. Sci., 19 (1981) 137. D. E. Wells and A. A. Cowan, Analyst, 106 (1981) 862. C. A. Nilsson, K. Andersson, C. Rappe and S. 0. Westermark, J. Chromatogr., 96 (1974) 137. 7 J. Nagayama, M. Kuratsune and Y. Masuda, Bull. Environ. Contam. Toxicol., 15 (1976) 9. 8 G. W. Bowes, M. J. Mulvihill, B. R. T. Simoneit, A. L. Burlingame and R. W. Risebrough, Nature, 256 (1975) 305.
Short Communication
STRUCTURES AND RING CLOSURES OF COMPOUNDS FROM THE MOTHPROOFING AGENT EULAN WA NEU
GUNNEL WESTGG, KOIDU NORBN* and B6RJE
EGESTAD
Department
Institute,
of Physiological
Chemistry,
Karolinska
Stockholm
(Sweden)
LENA PALMBR Department
of Toxicology,
Karolinska
Institute,
Stockholm
(Sweden)
GUN BLOMKVIST Swedish
National
Food Administration,
Uppsala (Sweden)
(Received 16th March 1983)
Summary. The main active ingredients of the mothproofing agent Eulan WA Neu are the N-chloromethylsulphone derivatives of 2’,3,4,4’,5-pentachloro-2-aminodiphenyl ether and 2’,3,4,4’,5,6-hexachloro-2-aminodiphenyl ether. The structures of the pentachloro-2aminodiphenyl ether and some related compounds are discussed on the basis of n.m.r. spectroscopic data. Orientating ring closure experiments were done by heating some of the Eulan WA Neu compounds to about 390°C. The results of g.c./m.s. studies indicated the formation of polychlorinated dibenzodioxins, dibenxofurans and phenoxaxines.
The contamination of fish by two polychlorinated aminodiphenyl ethers, 2’,3,4,4’,5-pentachloro-2aminodiphenyl ether (I) and 2’,3,4,4’,5,6_hexachloro-2aminodiphenyl ether (II), was demonstrated in 1977 [ 11. These compounds emanated from the mothproofing agent Eulan WA Neu (Farbenfabriken Bayer AC), the main active constituents of which are the N-chloromethylsulphone derivatives (III, IV) of these amines. In 1979, Wells [2]
(‘1
\,’
“ill
IX
\
reported that fish from a water area into which Eulan WA Neu was discharged contained, in addition to two polychlorinated aminodiphenyl ethers, the N-chloromethylsulphone derivatives at levels up to 0.6 mg kg-’ in fish muscle and 5.7 mg kg-’ in fish liver. Using Wells’ method of analysis [2] , we found
0 1983 Elsevier Science Publishers B.V.
294
Based on n.m.r. and g.c./m,s. studies, Wells [ 21 suggested structures V and VI, having a hydrogen atom in the ortho position to the amino group for the pentachloro-2-aminodiphenyl ether and its N-chloromethylsulphone derivative. He also concluded that his data were in accordance with previously reported structures I and III [l] (having a hydrogen atom in the metu position to the amino group). Structures V and VI were also used in later reports [3-51. However, they are incompatible with the chlorination experiments done [l] with 2’,4,4’,5-tetrachloro-2-aminodiphenyl ether (VII) and its NJdiacetyl derivative. In the first case, the Eulan WA Neu compound I was easily formed, whereas in the second case there was no reaction. The acetylation should suppress an electrophilic substitution by chlorine in the ortho position to the amino group in VII, whereas substitution in the metu position should be mainly unaffected. (In the dichlorophenyl ring, Wells sometimes [2] placed the chlorine atom, that should be paru to the oxygen, in the metu position, but this probably happened accidentally and is not discussed here.) In the present investigation, nuclear magnetic resonance spectroscopy (n.m.r.) was used to confirm structures I and III for the compounds present in Eulan WA Neu. This mothproofing agent was also heated to high temperature to see if it would form potentially more toxic compounds such as polychlorinated dibenzofurans. Discussion of s true tures A pentachloro-2aminodiphenyl ether was prepared by reducing the product obtained by coupling 1,2-dinitro-3,4,5-trichlorobenzene and 2,4-d& chlorophenol. From the method of synthesis, it must have either structure I
or V. This pentachloro-2-aminodiphenyl ether (m.p. 139.8”C) has a g.c. retention time of 1.29 relative to the pentachloro-2-aminodiphenyl ether I (m.p. 94.8”C) present in Eulan WA Neu and thus cannot have the structure I. Furthermore, in contrast to compound I, it reacted easily with chlorine with the formation of the previously [l] described 2’,3,4,4’,5,6-hexachloro-2aminodiphenyl ether (II). The amino group strongly promotes an electrophilic substitution by chlorine in the ortho position, which is available in structure V but not in structure I. The synthesized compound thus must have structure V. The pentachloro-2-aminodiphenyl ether, I, from Eulan WA Neu, its isomer V prepared as above, and the previously [l] synthesized compound, 2’,4,4’,5tetrachloro-2-aminodiphenyl ether (VII), were studied by ‘H-n.m.r. The data, compiled in Table 1, can be interpreted as follows. The NH2 resonance in
295
TABLE 1 ‘H-n.m.r. data for the three polychloro-2-aminodiphenyl
HP
H,
I
ethers studied (6 values)
Compound I: X = Cl, Y = H cI Compound V: X = H, Y = Cl Compond VII. X = H, Y = H
Proton
Compound Ia
Compound V
Compound VII
X (s) Y (s) H, (d)b H, (dd)b H, (d)b NH, (br s)
6.68 6.94 7.25 7.49 4.42
6.89 6.50 7.09 7.46 3.95
6.89 6.75 6.89 7.21 7.47 3.94
aFrom Eulan WA Neu. bFor the three compounds, J,, = 8.8 Hz, J,, not observed.
= 2.4 Hz, and J,, was
compound I from Eulan WA Neu was shifted downfield relative to the NH2 resonances for compounds V and VII. This shift should be caused by the chlorine substituent ortho to the amino group in compound I. In compound V, the resonances for H1, and to some extent Hz, (Table 1) were shifted upfield compared to the corresponding resonances in compounds I and VII. This must be explained as an effect of the chlorine atom in position 6 (Y = Cl) in compound V. Thus these n.m.r. data provide conclusive evidence that the previously demonstrated [l] structure I is correct for the pentachloro-2aminodiphenyl ether found in Eulan WA Neu. Accordingly, III (not VI) is the structure of its N-chloromethylsulphone derivative. Consequently, also in Wells’ reaction sequences [2] starting from V and VI, the intermediates and reaction products have one chlorine atom in the wrong position.
Ring closures
Structures I-IV for the compounds present in Eulan WA Neu indicate that U.V. radiation or high temperature might cause ring closure (cf. [6] ) with the formation of highly toxic polychlorinated dibenzofurans (IX). Polychlorinated phenoxazines (X) are also likely to be formed. Some ring closure experiments were therefore done. Compound II was heated to 390°C in a glass tube, sealed without previous removal of air. Analysis of the product mixture by g.c./m.s. indicated the formation of hexachlorodibenzofuran (IX). When a mixture of compounds III and IV or their sodium salts was heated in the same way, various ring closures occurred. The g.c. peaks from several pyrolysis experiments (two chromatograms are shown in Fig. 1) were analyzed by m.s. The molecular ions and the typical fragments expelled are reported in Table 2. Some of the m.s. patterns are in accordance with the observations made by Nagayama et al.
296
A
B
11
5
IO Retention
time
0
15
5
(men)
15
IO Retention
time
(I-NIT)
Fig. 1. Total ion current chromatograms from g.c./m.s. of compounds formed in pyrolysis experiments with III and IV (B, excess of IV) or their sodium salts (A, excess of III).
[ 71 and Bowes et al. [ 81 for tetrachlorodibenzofurans, others with observations by Nilsson et al. [6] for polychlorinated dibenzodioxins (VIII). Fragments probably resulting from loss of HCl + Cl and CO + Cl agree with the presence of polychlorinated phenoxazines (X). The g.c./m.s. data indicated the formation of two tetrachlorodibenzodioxins (VIII), one pentachlorodibenzodioxin (VIII), two pentachlorodibenzofurans (IX), one hexachlorodibenzofuran (IX), two pentachlorophenoxazines (X) and one hexachlorophenoxazine (X). Traces of a tetrachlorodibenzofuran (IX) and a tetrachlorophenoxazine (X) were also observed. The formation of the pentachloro isomers of the tricyclic compounds could be explained by ring closure to either of the ortho positions of the oxygen at the dichlorophenyl ring of the compounds III and IV. TABLE 2 G.c./m.s. data for the main tricyclic compounds and IV (B) or their sodium salts (A) Compounds found
Polychlorinated dibenzodioxins, VIII Polychlorinated dibenzofurans, IX Polychlorinated phenoxszines, X
Retention timea (min)
3.3(B) 3.8(B), 5.9(B) 4.2(B) 4.7(B), 7.3(B) 6.5(B) 12.4(B),
%See Fig. 1.
found in pyrolysis experiments with III
Number of Cl atoms
Mass of molecular ion, M+
Main fragmentslost
4
320
63(CO + Cl) + 63(CO + Cl)
5 5
354 338
63(CO + Cl) + 63(CO + Cl) 63(Cl + CO) + 7O(Cl + Cl)
6 5
372 353
63(Cl+ CO) + 7O(Cl+ Cl) 71(HCl+ Cl) + 63(CO + Cl)
6
387
71(HCl + Cl) + 63(CO + Cl)
from M+
3.8(A)
4.8 (A) 7.6(A) 12.7(A)
297
Formation of compounds I (ta = 6.8 min; Fig. 1A) and II (ta = 9.7 min; Fig. 1B) occurred during the pyrolysis of III and IV (mass spectra have been reported [l] ). Other compounds were also formed, but their structures were not established. Experimental A pentachloro-2aminodiphenyl ether (m.p. 139.8”C; 49.7% Cl found, 49.6% required for C,,H,ONCl,) was prepared by coupling 1,2-dinitro3,4,5trichlorobenzene with 2,4dichlorophenol and reducing the pentachloro-2nitrodiphenyl ether formed according to general methods [1] . Chlorination. This pentachloro-2aminodiphenyl ether (16.2 mg) was chlorinated by adding a solution (3.0 ml) of chlorine (3.2 mg ml-l) in carbon tetrachloride. After 12 min at room temperature, the solution was diluted to 50.0 ml with heptane. After further dilution, it was analysed by g.c. which showed that 2’,3,4,4’,5,6-hexachloro-2aminodiphenyl ether (II) had been formed (93% yield). The same chlorination procedure was used for the pentachloro-2-aminodiphenyl ether from Eulan WA Neu. No hexachloro-2-aminodiphenyl ether (II) could be detected by gc.; 89% of the starting material remained unchanged. Pyrolysis. For the pyrolysis experiments, compound II, a mixture of III and IV, or a mixture of the sodium salts of III and IV (about 2 mg) in a glass tube, sealed without previous removal of the air, was gradually heated in an oven during 25 min until 390°C was reached. The heating was then switched off, and after 10 min the tubes were cooled to room temperature. The reaction mixtures were dissolved in heptane (2 ml) and subjected to g.c./m.s. (Fig. 1, Table 2). Apparatus. For g.c., a Varian Aerograph 1200 with a tritium source electron capture detector was used. The glass column (3 mm X 1.8 m) was packed with a mixture of 3% SF-96 and 6% QF-1 [l] . N.m.r. spectra were obtained with a JEOL FX-100 instrument; the substances were dissolved in chloroform-d. For g.c./m.s., an LKB 2091 instrument connected to an LKB 2130 data system was used. The glass column (2 mm X 2 m) was packed with a mixture of 2% OV-1 and 3% QF-1. The temperature of the column and the separator was 225°C. The ion source was kept at 220°C and the electron energy was 70 eV. Financial support from the Swedish Products Control Board and the Swedish Council for Planning and Coordination of Research (Grant No. 81/2137) is gratefully acknowledged. We also wish to thank Dr. L. Kenne, University of Stockholm, for running the n.m.r. spectra.
298
REFERENCES 1 2 3 4 5 6
G. WestoS and K. Norbn, Ambio, 6 (1977) 232. D. E. Wells, Anal. Chim. Acta, 104 (1979) 253. D. E. Wells, Anal. Proc., 17 (1980) 116. D. E. Wells and S. J. Johnstone, J. Chromatogr. Sci., 19 (1981) 137. D. E. Wells and A. A. Cowan, Analyst, 106 (1981) 862. C. A. Nilsson, K. Andersson, C. Rappe and S. 0. Westermark, J. Chromatogr., 96 (1974) 137. 7 J. Nagayama, M. Kuratsune and Y. Masuda, Bull. Environ. Contam. Toxicol., 15 (1976) 9. 8 G. W. Bowes, M. J. Mulvihill, B. R. T. Simoneit, A. L. Burlingame and R. W. Risebrough, Nature, 256 (1975) 305.