Pesric. Sci. 1980, 11, 451-457

The Photolysis of Quinomethionate in Benzene Solution

Terence Clark and R. S. Thomas Loeffler

University of Bristol, Long Ashton Research Station, Bristol BS18 9AF

(Revised manuscript received 19 February 1980)

The photolysis of quinomethionate in benzene solution was found to result in complete cleavage of the dithiole ring with loss of both sulphur atoms. Products isolated and identified were those arising from the reaction of intermediate radicals with oxygen and with the solvent. They were identified, by gas chromatography-mass spectro- metry and by comparison with authentic samples synthesised by known methods, as 6-methyl-l,2,3,4-tetrahydroquinoxaline-2,3-dione and 6- and 7-methyl-3-phenyl-l,2- dihydroquinoxalin-2-one. A mechanism that accounts for the formation of these products is presented.

1. Introduction

Quinomethionate (6-methyl-1,3-dithiolo[4,5-b]quinoxalin-2-one) (I, Figure 1) is a fungicide used specifically against powdery mildews.’ It has been reported2 to be stable to acid but quickly hydro- lysed, with ring opening, by aqueous alkalies. Light has been said to have no detectable effect on quinomethionate except when moisture and oxidising substances are present2 More recently, however, quinomethionate has been irradiated in benzene solution in a nitrogen atmosphere, and dimethylthieno[2,3-b:4,5-b’]diquinoxaline (11, Figure l), dimethyl[l,4]dithiino[2,3-b:5,6-b’]- diquinoxaline (111, Figure 1) and elemental sulphur were identified as the products.3

A benzene solution of a standard mixture of fungicides, containing triadimefon, vinclozolin, dichlofluanid and quinomethionate, re-analysed after being kept for one month in the laboratory (Cooke, B. K., personal communication), contained no quinomethionate although the other fungicides were present in their original quantities. The possible involvement of light in this disappearance of quinomethionate, and the identification of the decomposition products is described in this paper.

2. Materials

Quinomethionate, obtained by Soxhlet extraction of ‘Morestan’ (Bayer AG; 25 % w.P.) with dry benzene, was recrystallised from methanol+ benzene (1 + 4 by volume) and had m.p. of 168- 170°C (lit. 172°C).4 Biphenyl and diethyl oxalate were purchased from BDH Chemicals Ltd, toluene-3,4-diamine and benzoylformic acid from Aldrich Chemical Co. Ltd, and sodium methoxide from Hopkin and Williams Ltd.

3. Experimental 3.1. Photolyses 3.1 .l. Irradiation of quinomethionate Magnetically-stirred solutions of quinomethionate (0.1 g) in benzene (370 ml) were irradiated for 8 h using a medium pressure lamp (400 W) in a borosilicate glass system. The brown solid which was formed was filtered off, washed from the filter paper using methanol and combined with the methanol washings of the lamp water-jacket. The benzene solution and the methanol washings

0031-613X/80/1000-0451 $02.00 0 1980 Society of Chemical Industry

31 451

452 T. Clark and R. S. T. Loeffler

were evaporated separately to dryness using a rotary evaporator (40°C). The residue (60 mg) from the benzene was redissolved in bznzene (25 ml), and the residue (85 mg) from the methanol, in methanol (50 ml); the irradiation products contained in these solutions were determined by gas- liquid chromatography (g.1.c.) and high-performance liquid chromatography (h.p.l.c.), respectively. Under the same conditions no reaction occurred in the dark.

3.1.2. Irradiation of dimethyl[I,4Jdithiino[2,3-6: 5,6-b’JdiquinoxaIine (111)

Compound 111 (25 mg) in benzene (370 ml) was irradiated as described in section 3.1.1 for 10 h, after which time a small amount ( < I mg) of a white solid had appeared. The solution was concen- trated in a rotary evaporator (40°C) to approximately 2 ml, allowed to stand for 1 h, and the benzene then decanted from the white solid.

3.2. Thin-layer chromatography (t.1.c.) T.1.c. and preparative t.1.c. work was done on silica gel G (Merck Type 60, 0.3 mm thick) plates; development was in chloroform + methanol (3 + 1 by volume, solvent A), or in benzene + methanol (4+ 1 by volume, solvent B), or in dichloromethane (solvent C).

3.3. Gas-liquid chromatography Analyses by g.1.c. were obtained using a stainless-steel column (1.8 m x 3.2 mm 0.d.) containing 1 % OV 17 on Gaschrom Q , and a flame-ionisation detector. The temperature was programmed from 120 to 320°C at 6°C min-l; the carrier gas was nitrogen at a flow-rate of 30 ml min-I.

3.4. Mass spectrometry Probe and gas chromatography-mass spectra were obtained on a Finnigan 4000 instrument, at 70 eV using electron impact ionisation. Helium was used as carrier gas for the g.c. analysis. The results were processed by an Incos 2100 data system.

3.5. High-performance liquid chromatography Separations were obtained using a Partisil 10 (Whatman) column (25 cm x 4.6 mm i.d.) with linear gradient elution from 10 to 80% ethanol by volume in hexane in 20 min at I ml min-l. Detection was by absorption at 254 and 280 nm.

3.6. Proton magnetic resonance (p.m.r.) spectroscopy P.m.r. spectra were obtained using the following spectrometers: Perkin-Elmer R.32 (90 MHz continuous wave), JEOL PS-100 (100 MHz continuous wave), JEOL PFT-I00 (100 MHz Pulsed Fourier Transform).

3.7. Syntheses 3.7.1. 6-Methyl-l,2,3,4-tetrahydroquinoxaline-2,3-dione5 (IV, Figure 1 ) Toluene-3,4-diamine (6.1 1 g) and diethyl oxalate (40 ml; excess) were heated under reflux in an oil bath at 170-190°C for 3 h. The cooled mixture was filtered, and the solid washed repeatedly with light petroleum (b.p. 40-60°C). Yield : 9.4 g (quantitative). Recrystallisation from methanol gave colourless crystals of 1V m.p. > 300°C. P.m.r. [(CD&SO]: 6 11 37, broad s, removed by D2O treatment, 2H(N-H); 6.8-7.15, m, 3H (arom. H); 2.27, s, 3H (CH3). Mass spectrum: m/e (rel. int. above 20%) 176 (Mf 99), 148 (56), 147 (IOO), 120 (29), 119 (27), 106 (26), 105 (36), 93 (32), 92 (25), 77 (42), 66 (28), 65 (55) , 63 (251, 52 (62), 51 (651, 50 (32).

3.7.2. 2,3-Dichloro-6-methylquinoxaline This compound was made as described by Curd et U Z . ; ~ yield 84%, m.p. 112-1 13°C ( k 5 : 114°C) P.m.r.(CDC13): 67.90,d(J=8Hz), lH(H-8);7.77,m, lH(H-5);7.60,dofd(Ji=8Hz,Jz=2Hz), 1 H (H-7); 2.60, s, 3H (CH3). Mass spectrum: m/e above 70 (rel. int. above 10%). M+ 212 (68,2-CI), 177(43, 1-Cl), 141 (13), 116(59), 115(15), 114(16), 90(23), 89(100), 76(16), 75(19).

Photolysis of quinomethionate 453

H

H I

Figure 1. (I), Quinomethionate; (II), dimethylthieno[2,3-b:4,5-b’]diquinoxaline; (III), dimethyI[l,4]dithiino- [2,3-b :5,6-b’]diquinoxaline; (IV), 6-methyl-] ,2,3,4-tetrahydroquinoxaline-2,3-dione; (V), 6- and 7-rnethyl-3-phenyl- I ,2-dihydroquinoxalin-2-ones; (VI), possible irradiation product of 111.

3.7.3. Dimethyl[l,4]dithiino[2,3-b :5,6-b’]diquinoxaline (111)

6-Methyl-1,2,3,4-tetrahydroquinoxaline-2,3-dithione was prepared from 2,3-dichlor0-6-methyl- quinoxaline as described by Gaillard et aL6 P.m.r. [(CD&CO]: 7.25-7.5, m, 2H; 7.0-7.2, d of d (Jl=9 Hz, J2= 1.5 Hz), 1H; 5.95, broad s, disappears with DzO, 2H; 2.34, s, 3H. The reaction of the dithione (I mmol) with 2,3-dichloro-6-methylquinoxaline ( I mmol) in refluxing ethanol for 2 h gave yellow crystals, which were collected by filtration and dried in air; m.p. 311-315°C (lit.:3 292-300°C). Mass spectrum: m/e (re]. int. above 20%): 348 (57,M+), 206 (27), 174 (48), 173 (35), 148 ( 5 3 , 116(100), 115 (28), 89 (50), 45 (22), 44(43), 40(21).

3.7.4. 2,3-Dimethoxy-6-methylquinoxaline (IX, Figure 2) Excess of sodium methoxide (0.2 g) was added to a solution of 2,3-dichloro-6-methy1quinoxaline (0.2g) in methanol (4ml) and the mixture heated on a water-bath for 2 h. The methanol was evaporated, diethyl ether (10 ml) added to the residue and the insoluble sodium salts were filtered off. The filtrate, evaporated to dryness, gave the dimethoxy compound IX, m.p. 80-82°C

Figure 2. Methylation products of 6-methyl-l,2,3,4-tetrahydroquinoxaline-2,3-dione (IV): (IX), 2,3-dimethoxy- 6-methylquinoxaline; (X), 3-methoxy-l,6(or 7)-dimethyl-l,2-dihydroquinoxalin-2-one; (XI), 1,4,6-trimethyl-l,2,3,4- tetrahydroquinoxaline-2,3-dione.

454 T. Clark and R. S. T. Loeffler

82-83°C). Yield: 0.18 g (94%). P.m.r. (CDC13): 67.65, d ( J=8 Hz), IH (H-8); 7.56, m, 1H (H-5); 7.30, d of d (J1=8 Hz, J2=2 Hz), 1H (H-7); 4.12, S, 6H (OCH3); 2.49, s, 3H (arom. -CH3). Mass spectrum: m/e (rel. int. above 10%) 204 (M+, loo), 203 (25), 189 (12), 176 (lo), 175 (75), 174(37), 173(14), 161 (lo), 145(17), 144(22), 143(11), 133(11), 132(15), 11S(12), 117(16), 102 (lo), 91 (12), 77 (11), 51 (10).

3.7.5. 1,4,6-Tyimethyl-l,2,3,4-tetrahydroquinoxaline-2,3-dione (XI, Figure 2) Compound X I was prepared from the dioxo compound IV by the method described5 for the 6-bromo analogue of XI: m.p. 202-204" (lit. :5 205-206°C). Yield: 60% P.m.r. [(CD&SO]: 66.7- 7.3, m, 3H; 3.45, s, 6H; 2.33, s, 3H. Mass spectrum: m/e (rel. int. above 10%). M+204(100), 176 (33), 175 (98), 133 (13), 77 (13), 65 (16), 44 (32), 39 (12).

3.7.6. 6- and 7-Methyl-3-phenyl-l,2-dihydroquinoxalin-2-ones (V, Figure 1 ) Toluene-3,4-diamine (0.01 1 mole) and benzoylformic acid (0.010 mole) were allowed to react as described by Nie l~en ;~ an 87 "/o yield of yellow crystals, m.p. 203-205°C (lit.:* 198°C) was obtained. P.m.r. (CDCI3): 612.37, broad s, lH, disappears on DzO treatment (N-H); 8.35-8.45, m, 2H; 7.82, d, 1H; 7.45-7.65, m, 3H; 7.10-7.35, m, 2H; 2.47, s, 3H (CH3). Mass spectrum. m/e (rel. int. above 10%): 237 (lo), 236 (M-, 64), 209 (13), 208 (90), 207 (IOO), 118 (17), 105 (16), 104 (82), 103 (36), 89 (15), 78 (461, 77 (931, 76 (18), 63 (151, 52 (201, 51 (781, 44 (34), 43 (11). RF (solvent B): 0.60; G.1.c. retention time 23 min. Mass spectrum of trimethylsilyl (TMS) derivative: m/e (rel. int. above 20%): M+ 308 (23), 293 (741, 231 (4% 139 (61), 135 (311, 104 (36), 89 (63), 77 (99), 73 (loo), 45 (56).

3.8. Methylation and trimethylsilylation methods Methylation was achieved overnight using an excess of a diazomethane solution in diethyl ether with a trace of methanol. Trimethylsilyl derivatives were made using excess pyridine and N , o - bis(trimethylsilyl)acetamide (BSA), ( I + 1 by volume) in a stoppered tube in an oil bath at 60°C for 1 h.

4. Results and discussion

4.1. Identification of products in the benzene residue Gas chromatography-mass spectrometry (g.c.-rn.s.1 data of the benzene residue as described in section 3.1.1 and given in Table I , indicated only one major peak, corresponding to quino-

Table 1. Gas chromatographic and mass spectral data of the main photolysis products obtained by irradiation of quinomethionate in benzene, before and

after methylation

Retention time (min)

Before After ion Identified Component methylation methylation (44 structure

Parent - -

2 15 23 * * ND c

8

t

2 15

16 21

6 12.5 20

c

*

152 234 236 250 250 176 204 204 204

Biphenyl I V VII VIII IV IX X XI

*=Compound not present. ND = Compound not detected.

Photolysis of quinomethionate 455

methionate (component B, 46 mg). On concentration to approximately 2 ml, two further peaks appeared, components A and C. The mass spectrum of A and that of an authentic sample of biphenyl were identical. The mass spectrum of component C had a parent ion m/e 236 with two strong peaks m/e 207 and 208 indicating loss of 29 and 28 mass units, possibly due to HCO and CO. The F.T.-p.m.r. spectrum of component C (isolated by preparative t.l.c., solvent A) showed a methyl peak at 62.47 and several multiplets of aromatic protons. The integral indicated a ratio of eight aromatic to three methyl protons which suggested that the addition of a phenyl group had occurred. This was confirmed by the mass spectrum (using g.c.-m.s.) of the TMS derivative of C which had a parent ion m/e 308 and a strong peak at mle 231, a loss of 77 units. The addition of solvent molecules on photolysis in benzene is well known.gJO

On methylating the benzene residue with excess diazomethane, components A and B were unchanged but C was converted into components D and E. The mass spectra of these components confirmed that mono-methylation had occurred, and structures VII and VIII (Figure 3) were assigned to components D and E, respectively. Similar results were obtained by methylation of a synthetic sample of V. The mass and p.m.r. spectra of the synthetic sample of V and compound C were identical and C was concluded to have structure V. Determination of A and C by g.1.c. showed less than 1 mg of each to be present.

CH<

CIj , , 0-CH, cHJa;b la::$ ( V W (VIII) \

Figure 3. Methylation products of 6- and 7-methyl-3-phenyl-l,2-dihydroquinoxalin-2-ones (V).

4.2. Identification of products in the methanol residue The methanol residue as described in section 3.1 .1 showed no peak on g.1.c. and only two on h.p.1.c. After methylation three g.1.c. peaks appeared (components G, H and J); g.c.-m.s. showed these to be isomers (all had a parent ion at m/e 204 and ions at m/e 189 (M-15), 175 (M-29). From their mass spectra G, H and J were postulated to have structures IX, X and XI, respectively (Figure 2). Compounds with structures 1X and XI were synthesised (see sections 3.7.4 and 3.7.5) and their g.c.-m.s. spectra were found to be identical to those for components G and J.

Preparative t.1.c. (solvent B) of the methanol residue yielded a fraction (component F) which had an h.p.1.c. retention time (10 min) identical to that obtained for the synthetic product of structure IV. It was concluded that component F had structure IV because an authentic specimen had identical mass and p.m.r. spectra, did not give a peak on g.1.c. and gave the same three products when methylated. H.p.1.c. showed 15 mg of compound IV to be present in the methanol residue.

The probe mass spectrum of the white solid produced on irradiation of dimethyl[l,4]dithiino- [2,3-b:5,6-b’]diquinoxaline (111) in benzene (see section 3.1.2) had M+ m/e 259 which suggested V1 (Figure 1) as a possible structure.

5. Conclusions 5.1. Identification of the products From spectroscopic investigations on derivatives of quinoxalines, the tautomeric equilibrium between the ‘amide form’ (NH-C=O) and the ‘iminol form’ (N=C-OH) is known to favour the f0rmer.l’ In spite of the absence of detectable amounts of the ‘iminol form’ in solution, methylation with diazomethane gives rise to mixtures of all possible products.12 This was confirmed for the phenylated 0x0 compound V, which gave rise to two methylated products, and for the dioxo compound IV, which gave three dimethyl derivatives. In the latter case, four products are theo- retically possible, because two alternative N,O-dimethyl compounds (6-methyl and 7-methyl) are

456 T. Clark and R. S. T. Loeffler

possible; the chromatographic techniques used in this work did not separate them, although it is almost certain that compound X was a mixture.

For the dioxo compound, the assignment of the g.c.-m.s. peaks G, H and J to compounds IX, X and XI, respectively, follows from the g.1.c. retention times of synthetic samples of IX and XI. The 0,O-dimethyl compound was found to be the most volatile and eluted first on g.1.c. and the N,N-dimethyl was least volatile and eluted last; it is reasonable to argue that the N,O-dimethyl compound should be intermediate in volatility and retention time.

A similar argument was applied to the two methylation products of the phenylated 0x0 compound V; the earlier eluting peak was ascribed to the 0-methyl compound VII and the later one to the N-methyl compound VIII. However, when compound V was treated with BSA + pyridine, only the 0-TMS derivative was formed as has been reported previously.'3

The other compound identified in the benzene residue, biphenyl, was a by-product probably formed by oxidative dimerisation of benzene solvent molecules.

The identification of the product of the photolysis of the [1,4]dithiin 111 as the fused quinolino- quinoxaline VI is based solely on the mass spectrum. The small quantities available and the presence of a mixture of isomers (four would be expected from the proposed structure) precluded identification by p.m.r. and 13C-n.m.r. spectroscopy.Themain object of this irradiation was achieved, in that the solid was proved not to be the dioxo compound IV isolated from the photolysis of quinomethionate, thus ruling out compound 111 as an intermediate in its formation.

5.2. The fate of the sulphur atoms of quinomethionate The major products found by Gray et aL3 in the photolysis of a benzene solution of quinomethionate in an atmosphere of nitrogen, the dithiin I11 and the corresponding thiene 11, were not found in the present investigation. As discussed above, compound I11 was shown not to be a precursor of the observed products, thereby ruling out any mechanism by which it could be formed and broken down rapidly to further products. The other product found by the earlier investigator^,^ elemental sulphur, was not detected in any of the photolyses reported here, suggesting that it was not formed or that it was bound tightly in the matrix of the large amount of polymeric material formed. The latter postulate received support from the results of the elemental composition analysis, which showed that 8.72% S was present in the total base-line material from the preparative t.1.c. (solvent C) of the total crude photolysis product (benzene+ methanol residues). When the presence of the dioxo compound IV (14 mg) in this material is taken into account, the total sulphur in the residue amounted to 9.9 %. This leads to the conclusion that, from the unrecovered quinomethionate, 50% of the original sulphur was present in the polymeric material. Therefore half the sulphur in quinomethionate became part of the material that was immobile on preparative t.l.c., presumably as polymeric material, whereas the other half must have escaped in the form of volatile products, such as carbonyl sulphide or sulphur dioxide.

A possible decomposition product of quinomethionate, the dithio analogue of compound (IV), which has been detected as a metabolite in rats,6 was not found.

5.3. Mechanism of the decomposition of quinomethionate A mechanism to rationalise the formation of the products observed in the present investigation is illustrated in Figure 4. The probable primary photochemical process is loss of carbon monoxide (by analogy with the known loss of carbon monoxide from a vinylene dithiocarbonate to give a dithione14), followed by rapid loss of sulphur, either as the element or after oxidation, to form the quinoxalinethio diradical XI1 (Figure 4). In the absence of oxygen, this can dimerise to give the [ 1,4]dithiin 111 reported by Gray et aZ.3 as the minor product of the photolysis of quinomethionate; when oxygen is present, as in the photolysis described in this work, the diradical XI1 is converted into the key intermediate, the diradical XIV, possibly by addition of oxygen followed by loss of the elements of sulphur monoxide from the hypothetical intermediate XI11 (Figure 4). The diradical XIV can then give rise to the observed products by reacting with benzene to yield, after net shift of a hydrogen radical, the phenylated quinoxalinone V or with oxygen, to yield, after decom- position of an intermediate peroxo diradical, the dione IV.

Photolysis of quinomethionate. 457

( X W Figure 4. Proposed mechanism for the photodecomposition of quinomethionate in benzene.

Gray et a1.3 used a similar mechanism to explain the formation of compound 111 as a minor product in the photolysis of quinomethionate under nitrogen, without rationalising the formation of the diradical XII. Because Gray et aL3 were able to show that the dithiin I11 is not the precursor of the major product in the photolysis (the thiene II), they proposed that the latter compound is formed by an alternative mechanism in which the diradical XI1 dimerises to form a disulphide bond, and the resulting [1,2]dithiin loses an atom of sulphur with ring contraction.

No detailed mechanistic investigations were made either in the present work or in the work of the earlier investigators,3 and the mechanism shown in Figure 4 must be treated as tentative. The difference in the products observed in this work and in the earlier work must be due to the different photolysis conditions; the work of Gray et al. was performed by bubbling nitrogen into the photo- lytic reactor, whereas in the present work no attempt was made to exclude air.

Acknowledgements The authors wish to thank Dr D. A. M. Watkins for his constant interest, discussion, advice and patience, Dr D. Woodcock for his interest and technical advice and Mr M. West for the sulphur analysis.

References I . 2. 3. 4. 5 . 6. 7. 8. 9.

10. 1 I . 12. 13. 14.

Pesticide Manual (Worthing, C. R., Ed.) British Crop Protection Council, Croydon, 6th edn, 1979, p. 463. Sasse, K. Hoefihen-Briefe (now PJunzenscliurz-Nuckr. Buyer) 1960, 13, 197-207. Gray, W. F.; Pomerantz, 1. H.; Ross, R. D. J . Heterocycl. Chem. 1972, 9, 707-71 1. Grewe, F.; Kaspers, H. Pjlanzenschutz-Nachr. Bayer 1965, 18, 1-23. Curd, F. H. S.; Davey, D. G.; Stacey, G. J. J. Chem. Soc. 1949, 1271-1277. Gaillard, D . ; Chamoiseau, G.; Derache, R. Arch. Environ. Contam. Toxicol. 1977, 5, 403-413. Nielsen, K. H. 1. Chromatogr. 1963, 10, 463-472. Hinsberg, 0. Justus Liebigs Ann. Chem. 1887, 237, 327-372. Loeffler, R. S. T. Pestic. Sci. 1978, 9, 310-312. White, E. R.; Kilgore, W. W.; Mallett, G. J. Agric. Food Chem. 1969, 17, 585-588. Cheeseman, G. W. H. J . Chem. Soc. 1958, 108-113. Cheeseman, G. W. H. J. Chem. Soc. 1955, 1804-1809. Langenbeck, U.; Mohring, H.-U.; Hinney, B.; Spiteller, M. Biomed. Mass Spectrum. 1977, 4, 197-202. Kusters, W.; de Mayo, P. J. Am. Chem. Soc. 1973, 95, 2383-2384.