Chem. Res. Toxicol. 1998, 11, 449-453
449
Oxidative Transformations of 1-Nitropyrene under Simulated Environmental Conditions† Robert W. Murray* and Megh Singh Department of Chemistry, University of Missouri-St. Louis, St. Louis, Missouri 63121 Received September 4, 1997
The oxidation of 1-nitropyrene (1-NP), adsorbed on silica gel, with dimethyldioxirane (DMD) leads to the formation of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide in a ratio of 74/26 (4,5-oxide/9,10-oxide). When the adsorbed 1-NP is exposed to the products of the gasphase reaction of tetramethylethylene (TME) with ozone at -40 °C, the same oxides are produced in a ratio of 72/28. The fact that the ratio of the oxides is essentially the same in these two different types of experiments is highly significant. We have speculated that the gas-phase ozonolysis of TME produces an energy-rich form of the carbonyl oxide, acetone oxide. Some of this carbonyl oxide may cyclize to the isomeric DMD which, we propose, is responsible for oxide formation in the TME/ozone experiment. This proposal is supported by the observation that using ozone alone to oxidize 1-NP does not lead to oxide formation. Thus the oxidant responsible for oxide formation in the TME/ozone experiment must be produced in the ozonolysis. We suggest that this oxidant is DMD.
Introduction 1-Nitropyrene (1-NP)1 is a widely distributed environmental pollutant which is highly mutagenic in both bacterial strains and mammalian cells (1-4) and carcinogenic in experimental animals (1). It is one of the most abundant of the larger class of nitrated polycyclic aromatic hydrocarbons. As a class nitroarenes have received attention as widespread environmental pollutants only in about the last 15 years. They are formed in combustion reactions and in atmospheric reactions involving polycyclic aromatic hydrocarbons (PAH) and nitrogen oxides (1, 2). 1-Nitropyrene is metabolized by both oxidative and reductive routes (5). Two of the mutagenic metabolites produced in oxidative metabolism of 1-nitropyrene are the K-region oxides: 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide (6). It has been established that many PAHs are metabolized in humans to mutagenic and carcinogenic metabolites (7). We have been attempting to identify oxidants in polluted atmospheres that can mimic these enzymecatalyzed oxidations. This effort is prompted by the observations that oxygenated portions of atmospheric samples can contain mutagens and carcinogens (8-11). Our research has led us to suggest that oxidants produced in ozone-alkene reactions may be responsible for converting PAH to mutagenic/carcinogenic products in these atmospheres (12-17). We have now included nitroPAH in these studies.
Experimental Section Materials. 1-Nitropyrene and silica gel (Merck, 35-70 mesh, 40 Å) were purchased from Aldrich Chemical Co. (Milwaukee, † This is paper number 36 in the series “Chemistry of Dioxiranes”. For number 35, see: Murray, R. W., Singh, M., and Rath, N. (1997) J. Org. Chem. 62, 8794-8799. 1 Abbreviations: 1-NP, 1-nitropyrene; TME, tetramethylethylene; DMD, dimethyldioxirane; PAH, polycyclic aromatic hydrocarbon; EI, electron ionization.
WI) and were used as received. Tetramethylethylene (TME) was purchased from Aldrich and was purified by passing it through a column of alumina (Brockman neutral, activity grade 1, 80-320 mesh; purchased from Fisher). Acetone (Fisher reagent grade) was fractionally distilled over anhydrous potassium carbonate. Methylene chloride and hexane were obtained from Fisher and were distilled from calcium hydride before use. Oxone (DuPont), 2KHSO5‚KHSO4‚K2SO4, was obtained from Aldrich and used as such. The dimethyldioxirane (DMD) solution in acetone was prepared according to the literature procedure (18, 19) and was assayed for dioxirane content using phenyl methyl sulfide and the GLC method, or concentration was determined using a calibration curve of DMD concentration versus UV absorbance at 335 nm. TLC (thin-layer chromatography) analyses were performed on EM silica gel plates, 60 PF254 (Alltech Assoc., Deerfield, IL). Preparative TLC was performed on Analtech silica gel GF uniplates (20 × 20 cm, 1000 µm). Methods. 1H NMR spectra were obtained on a Varian XL300 MHz NMR spectrometer with tetramethylsilane (TMS, 0.00 ppm) as internal reference in CDCl3 or acetone-d6 as the solvent. All NMR data are reported in ppm or δ values downfield from TMS, and coupling constants, J, are reported in Hz. Electron impact (EI) ionization mass spectra were recorded, at 70 eV ionizing voltage, on a Hewlett-Packard 5988A twin EI and CI (chemical ionization) quadrupole mass spectrometer connected to a Hewlett-Packard 5890 gas chromatograph fitted with a Hewlett-Packard 12- × 0.2-mm × 0.33-µm Ultra-1 (cross-linked methyl silicone) column. UV-vis spectra were obtained on a Hitachi 3110 UV-vis spectrometer. HPLC (high-performance liquid chromatography) analyses were performed with a Varian 5000 liquid chromatograph equipped with a Valco loop valve injector and a Varian VARI-CHROM UV-vis detector. The detector was interfaced with a Hewlett-Packard 3390A integrator. Analytical separations were carried out using an RSIL C18 10-µm reversed-phase column (25 cm × 4.6 mm; Alltech Assoc., Deerfield, Il) by eluting with 70/30 methanol/water at a flow of 1.0 mL/min. Ozone was produced in a Welsbach laboratory ozone generator (Model T-408, Welsbach Corp., Philadelphia, PA) with the concentration being measured using iodometry. The concentration used in these studies was 5000 ppm. Reaction of 1-Nitropyrene with Dimethyldioxirane in Acetone Solution. To a magnetically stirred solution of
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450 Chem. Res. Toxicol., Vol. 11, No. 5, 1998 1-nitropyrene (65.5 mg, 0.265 mmol) in acetone (2 mL) was added a solution of dimethyldioxirane (0.066 M) in acetone (12 mL, 10.79 mmol). The reaction mixture was stirred at room temperature in the dark for 15 h. The solvent was removed on the rotary evaporator, and the residue was dried in vacuo for 1 h to give a dark-orange residue. TLC analysis (silica gel/CH2Cl2) of the residue shows two spots, one due to unreacted 1-NP and one due to a mixture of 1-NP oxides. The residue was dissolved in CDCl3 for NMR analysis. The 1H NMR spectrum of the residue shows the presence of two 1-NP oxides (16%) and unreacted 1-NP (84%). The ratio of 1-nitropyrene 4,5-oxide to 1-nitropyrene 9,10-oxide was determined by NMR to be 60/40. 1-Nitropyrene 9,10-oxide shows the characteristic NMR absorptions at δ 5.23 (C10H, d, J ) 3.93 Hz) and 4.66 (C9H, d, J ) 4.01 Hz). 1-Nitropyrene 4,5-oxide has absorptions at δ 4.75 (C4H, d, J ) 3.85 Hz) and 4.69 (C5H, d, J ) 3.88 Hz). These 1H NMR spectra are identical to those reported in the literature (20). Reaction of 1-Nitropyrene, Adsorbed on Silica Gel, with Dimethyldioxirane. 1-Nitropyrene (25 mg) was dissolved in a small amount of methylene chloride/acetone (50/50). Silica gel (5 g) was added to this solution. The solvent was removed on the rotary evaporator and the residue dried in vacuo. The silica gel-adsorbed 1-NP was packed into a 6-in. air condenser. A stream of DMD vapors was carried into the reactor for 2 h using argon as carrier gas. After reaction the silica gel was extracted with acetone (50 mL). The solvent was removed on the rotary evaporator, and the residue was dried in vacuo for 1 h to give an orange crystalline solid (0.0302 g). TLC analysis (silica gel/CH2Cl2) shows two spots, one due to unreacted 1-NP and the other to a mixture of 1-NP oxides. The 1H NMR spectrum of the residue also shows the presence of two 1-NP oxides as well as unreacted 1-NP. The relative ratio of the total oxides and unreacted 1-NP was determined to be 19/81 (19% conversion) by 1H NMR analysis. 1-Nitropyrene 4,5-oxide shows the characteristic NMR absorptions at δ 4.75 (d, J ) 3.85 Hz) and 4.69 (d, J ) 3.88 Hz). 1-Nitropyrene-9,10-oxide shows the characteristic NMR absorptions at δ 5.23 (d, J ) 3.93 Hz) and 4.66 (d, J ) 4.01 Hz). The 1H NMR spectra of the oxides were identical with those in the literature (20). The ratio of 4,5-oxide to 9,10-oxide was determined to be 74/26 by NMR. Reaction of Silica Gel-Adsorbed 1-NP with the Products of Gas-Phase Ozonolysis of TME. 1. Room Temperature. 1-NP (22 mg) was dissolved in a small amount of methylene chloride/acetone. Silica gel (5 g) was added to this solution. The solvent was removed on the rotary evaporator, and the residue was dried in vacuo. The silica gel-adsorbed 1-NP was packed into a 6-in. air condenser. TME, carried by argon, and ozone (0.16 mmol/min) were brought together at room temperature in a Y connector at one end of the condenser. The other end of the condenser was connected to a trap containing a fresh solution of KI (5%). The TME/ozone stream was passed through the reactor for 90 min. After reaction the silica gel was extracted with acetone. The solvent was removed on the rotary evaporator, and the residue was dried in vacuo for 1 h. TLC analysis of the residue showed no oxides present, but only polar materials. The residue was dissolved in CDCl3 and was analyzed by NMR and GC/MS. The 1H NMR spectrum of the reaction mixture showed the presence of several reaction products, but no evidence for either the 1-NP 4,5-oxide or the 1-NP 9,10-oxide. However GC/MS (column, HP-1; temperature 1, 150 °C; time 1, 2 min; rate, 20 °C/min; temperature 2, 320 °C; time 2, 10 min; injector and source temperature, 250 °C) analysis of the reaction mixture indicated the presence of the diols arising from the oxides. The mass spectra of the diols were identical to those reported in the literature (21). The spectra also indicated the presence of several other products which were not identified further. 2. Low Temperature. The procedure described in part 1 above was repeated except that the air condenser was placed into a plastic jacket and cooled with dry ice (-40 °C). TME and ozone were brought together in a Y connector as before. The TME/ozone stream was passed through the reactor for 60 min.
Murray and Singh
Figure 1. Example of NMR spectrum used to obtain the ratio of 1-NP 4,5-oxide to 9,10-oxide in the O3/TME experiment. After reaction the silica gel was extracted with acetone. The solvent was removed on the rotary evaporator and the residue dried in vacuo for 1 h. The residue was dissolved in CDCl3 for NMR analysis. The 1H NMR spectrum of the reaction mixture showed several peaks in the δ 3.00-6.00 region. The spectrum showed the characteristic peaks at ca. δ 4.76 (two doublets). The peaks expected for the 1-NP 9,10-oxide were masked by other peaks. A mixture of the 1-NP oxides was isolated by preparative TLC (silica gel/methylene chloride) and analyzed by HPLC. Analysis of this sample by NMR showed the oxides to be present in a 72/28 ratio (4,5-oxide/9,10-oxide) (Figure 1). The HPLC analysis indicated the presence of the two oxides. The ratio of the oxides was found to be 77/23 (4,5-oxide/9,10-oxide). The experiment was repeated three times giving the 4,5-oxide as 74.33 ( 2.52%. The retention times of the oxides were 13.9 and 15.4 min for the 9,10- and 4,5-oxides, respectively. The identity of the oxides was confirmed by co-injecting a mixture of the oxides obtained from the experiment using DMD and observing coincidence of the peaks. Reaction of Silica Gel-Adsorbed 1-NP with Ozone Alone. 1. Room Temperature. The procedure described under part 1 above was followed except that ozone alone was passed into the reactor. The orange color of the 1-NP started to fade immediately and turned to pale yellow in 2-3 min. The ozone was passed for 30 min at room temperature. The silica gel was extracted with a 1/1 mixture of methylene chloride and acetone (50 mL) containing a trace of methanol (1 mL). The solvent was removed on the rotary evaporator to afford an orange-yellow residue (0.0154 g). Analysis of the residue by 1H NMR in acetone-d6 and GC/MS indicated the absence of the two 1-NP oxides and 1-NP. TLC analysis showed only a baseline spot. 2. Low Temperature. The procedure under part 1 above was repeated except that the air condenser was placed in a plastic jacket and cooled with dry ice (-40 °C). Ozone alone was passed through the reactor for 30 min. After 2-3 min of ozone passage, the orange color of the 1-NP began to fade and the silica gel turned a dirty-yellow color. The silica gel was extracted with 50 mL of a 1/1 mixture of methylene chloride and acetone containing a trace (1 mL) of methanol. The solvent was removed on the rotary evaporator to afford an orange-yellow residue. Analysis of the residue by 1H NMR showed the absence of 1-NP oxides and 1-NP.
Oxidative Transformations of 1-NP
Chem. Res. Toxicol., Vol. 11, No. 5, 1998 451
Results In the experiments conducted here we have attempted to determine whether 1-NP is oxidized under simulated atmospheric conditions. For some time we have been attempting to identify the atmospheric oxidation process or processes which apparently can mimic metabolic oxidations of polycyclic aromatic hydrocarbons (PAH) (12-17). It is known that metabolic activation of some PAHs produces metabolites which are mutagenic and carcinogenic (7). Since oxygenated fractions of samples collected from polluted air which contains PAH are also found to be mutagenic and carcinogenic (8-11), there must be atmospheric oxidation processes which can mimic the enzyme-catalyzed reactions involved in metabolic activation of these PAHs. Our efforts have led us to devise a laboratory reactor which permits us to simulate atmospheric oxidations, particularly those in which the substrates are adsorbed on models for atmospheric particulate matter. The results obtained from use of this reactor have led us to propose that the atmospheric oxidants which are capable of activating PAH in the same manner as observed in the in vivo studies may be those produced from reactions of ozone and alkenes in these atmospheres (15). In the current work we first have adsorbed 1-NP on silica gel as a model for atmospheric particulate matter. The silica gel is then packed into the reactor and exposed to a gas stream containing DMD. The silica gel is removed from the reactor and extracted with acetone. Removal of the acetone gave a residue which was subjected to TLC analysis. This analysis showed the presence of unreacted 1-NP as well as two other spots which were eventually shown to be due to the oxides, 1-NP 4,5-oxide and 1-NP 9,10-oxide, by comparing their 1 H NMR spectra with the published data (20). The ratio of the two oxides was determined by 1H NMR to be 74/ 26 (4,5-oxide/9,10-oxide). We next repeated this same experiment except that the silica gel-adsorbed 1-NP was exposed to the products of the ozonolysis of TME while in the reactor. When this experiment was carried out at room temperature, analysis of the reaction mixture showed only the presence of the diols derived from the epoxides. The diols related to 1-NP 4,5-oxide were identified by comparing their mass spectral data with the published values (21). When the TME/ozone experiment is conducted with the reactor cooled to -40 °C, the reaction mixture showed the characteristic 1H NMR peaks of 1-NP 4,5-oxide. The peaks of the 1-NP 9,10oxide could not be observed since the pertinent region of the NMR spectrum contained many masking absorptions. A sample obtained by preparative TLC analysis of the reaction mixture showed the oxides to be present in a ratio of 72/28 (4,5-oxide/9,10-oxide). HPLC analysis of
Table 1. Ratio of 1-NP Oxides in Oxidative Transformations of 1-NP conditions
1-NP 4,5-oxide (%)
1-NP 9,10-oxide (%)
1. guinea pig liver microsomesa 2. MCPBA oxidationa 3. 1-NP/silica gel + DMD vapors 4. 1-NP/silica gel + TME/ozone 5. NP + DMD (solution)
80 60 74 72 60
20 40 26 28 40
a
Reference 20.
the reaction mixture showed peaks at the correct retention times for the oxides. Their identity was confirmed by co-injecting the mixture of oxides obtained in the DMD experiment and observing coincidence of the peaks. The ratio of the peaks obtained in the TME/ozone experiment was essentially also the same (72/28 4,5-oxide/9,10-oxide) as that found in the DMD experiment. The results of these experiments as well as some related ones from the literature are summarized in Table 1. In the next set of experiments the procedure for the TME/ozone experiments was followed except that no TME was used. In this case no oxides were formed at either room temperature or -40 °C. We have also separately determined the ratio of 1-NP oxides produced by solution reaction of 1-NP with DMD. In this case the ratio of oxides was found to be 60/40 (4,5-oxide/9,10-oxide).
Discussion The oxidation of 1-NP (1) with gaseous DMD in a simulated atmospheric reactor led to the formation of the two oxides 1-NP 4,5-oxide (2) and 1-NP 9,10-oxide (3) (Scheme 1). Interestingly, the ratio of the oxides obtained in this oxidation is closer to that found in one metabolic study (20) than the ratio given by m-chloroperbenzoic acid (MCPBA) oxidation of 1 (20). The solution-phase oxidation of 1-NP also gives a ratio of the oxides which is different from that obtained when gas-phase DMD is used to oxidize the silica gel-adsorbed 1-NP (Table 1). We suggest that the latter conditions are more closely related to those in the metabolic studies which may explain why the oxide ratios given by these two reaction conditions are almost the same and different from the solution results. While it is true that the oxide isomer ratio is dependent on the microsomal system used (22), we think that it is remarkable that these two conditions give a similar ratio of oxide isomers. When 1 is oxidized by the products of the gas-phase ozonolysis of TME in the same reactor, the product composition depends on the temperature of the reactor. At room temperature the products are the diols derived from reaction of the oxides with water. Beland et al. have shown (20) that inclusion of the epoxide hydrase inhibitor 1,2-epoxy-3,3,3-trichloropropane (TCPO) in the incubation of 1 with guinea pig
Scheme 1. Oxidation of 1 under Various Conditions
452 Chem. Res. Toxicol., Vol. 11, No. 5, 1998
Murray and Singh
Scheme 2. Proposed Mechanism for 1-NP Oxide Formation by TME/O3
liver microsomes leads to a decrease in the formation of the diols and an increase in the formation of the oxides in these incubations. Thus we speculate that the diols we observe are derived from the precursor oxides which are unstable under the conditions used. This speculation is supported by the observation that when the TME/ozone experiment is conducted at a reactor temperature of -40 °C, then the oxides are found to be present in the reaction mixture (Figure 1). The significance of the experiments involving ozone alone, where there is no oxide formation, is that the oxidant responsible for the epoxidation must be produced in the ozonolysis of TME. We have proposed previously (15) that the ozonolysis of TME in our atmospheric reactor proceeds as shown in Scheme 2. In this proposal carbonyl oxide (4) is seen as being formed in a highly energetic state as a result of the large exothermicity of the ozonolysis reaction. Under these circumstances we suggest that some 4 cyclizes to DMD. The DMD then oxidizes 1 in the same manner as in the experiment involving gaseous DMD in the reactor. Because this proposal has the DMD being formed under conditions where it is rapidly converted to acetone by reaction with the very reactive TME to give TME epoxide, we have been unable to obtain spectroscopic evidence for the intervention of the DMD in this process. The fact that the TME/ozone experiment gives the oxides of 1 in the same ratio (Table 1) as obtained in the DMD experiment is highly significant since it is the first confirmatory evidence for our proposal that DMD may be involved in the ozonolysis experiment. Indeed this observation has even a deeper significance for our understanding of the chemistry of polluted atmospheres since DMD is such a reactive species. A number of groups have presented evidence for the involvement of radicals, particularly OH radicals, in gasphase ozonolysis reactions (23-26). We feel that radical reactions are not responsible for arene oxide production in our experiments. It should be noted that the reaction conditions used in those cases where radicals are invoked are quite different than those used here. The previous work was done under conditions which encourage radical production, that is, using moist air, adding (NO)x, or generating the O3 under conditions where (NO)x could be produced. In our conditions pure, dry oxygen is used to prepare ozone. We also note that our reaction mixtures are clean, usually containing only arene oxides and starting 1-NP. In some cases there are slight traces of other materials. We would expect many more products if radicals were involved. The reactions of gas-phase PAHs with OH radicals in the presence of NOx have been studied (27). Arene oxides were not among the observed
products. Several groups (28, 29) have used cyclohexane as an indicator of the presence of OH radicals in O3alkene reactions. The reaction gives cyclohexanone and cyclohexanol. We note that use of cyclohexane as a detector of OH radicals in our system is complicated by the fact that dioxiranes also react (30-32) with cyclohexane to give cyclohexanone and cyclohexanol.
Acknowledgment. The project described was supported by Grant Number ESO1984 from the National Institute of Environmental Health Sciences, NIH. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIH. The Varian NMR spectrometer was purchased with support from the National Science Foundation.
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Oxidative Transformations of 1-NP
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dimethyldioxirane. In Polynuclear Aromatic Hydrocarbons: A Decade of Progress (Cooke, M., and Dennis, A. J., Eds.) pp 595607, Battelle Press, Columbus, OH. Murray, R. W., Rajadhyaksha, S. N., and Jeyaraman, R. J. (1990) Activation of PAH by ozone derived oxidants. Polycyclic Aromat. Compd. 1, 213-219. Murray, R. W., Pillay, M. K., and Snelson, M. J. (1991) Oxidation of polycyclic aromatic hydrocarbons by atmoaspheric oxidants. In Polynuclear Aromatic Hydrocarbons: Measurements, Means, and Metabolism (Cooke, M., Loening, K., and Merritt, J., Eds.) pp 615-628, Battelle Press, Columbus, OH. Murray, R. W., and Kong, W. (1994) Activation of PAH by ozone derived oxidants: results at ambient conditions. Polycyclic Aromat. Compd. 5, 139-147. Murray, R. W., and Singh, M. (1995) Quantitative synthesis and formation of cyclopenta[cd]pyrene 3,4-oxide under simulated atmospheric conditions. Chem. Res. Toxicol. 8, 239-243. Murray, R. W., and Singh, M. (1997) Activation of PAH by ozone derived oxidants: results using fly ash as particulate. Polycyclic Aromat. Compd. 12, 51-60. Murray, R. W., and Jeyaraman, R. J. (1985) Dioxiranes: synthesis and reactions of methyldioxiranes. J. Org. Chem. 50, 2847-2853. Singh, M., and Murray, R. W. (1992) Chemistry of dioxiranes. 21. thermal reactions of dioxiranes. J. Org. Chem. 57, 4263-4270. Fifer, E. K., Howard, P. C., Heflich, R. H., and Beland, F. A. (1986) Synthesis and mutagenicity of 1-nitropyrene-4,5-oxide and 1-nitropyrene-9,10-oxide, microsomal metabolites of 1-nitropyrene. Mutagenesis 1, 433-438. El-Bayoumy, K., Villuci, P., Roy, A. K., and Hecht, S. S. (1986) Synthesis of K-region derivatives of the carcinogen 1-nitropyrene. Carcinogenesis 7, 1577-1580. Djuric, Z., Fifer, E. K., Howard, P. C., and Beland, F. A. (1986) Oxidative microsomal metabolism of 1-nitropyrene and DNAbinding of oxidized metabolites following nitroreduction. Carcinogenesis 7, 1073-1079.
Chem. Res. Toxicol., Vol. 11, No. 5, 1998 453 (23) Atkinson, R. (1990) Gas-Phase tropospheric chemistry of organic compounds: a review. Atmos. Environ. 24A, 1-41. (24) Grosjean, E., Grosjean, D. (1996) Rate constants for the gas-phase reaction of ozone with 1,2-disubstituted alkenes. Int. J. Chem. Kinats. 27, 461-466. (25) Atkinson, R., and Carten, W. P. L. (1984) Kinetics and mechanism of the gas-phase reactions of ozone with organic compounds under atmospheric conditions. Chem. Rev. 84, 437-470. (26) Paulson, S. E., and Orlando, J. J. (1996) The reaction of ozone with alkenes - an important source of HOX in the boundary layer. Geophys. Res. Lett. 23, 3727-3730. (27) Atkinson, R., and Aray, J. (1994) Atmospheric chemistry of gasphase polycyclic aromatic hydrocarbons: formation of atmospheric mutagens. Environ. Health Perspect. 102, 117-126. (28) Atkinson, R., and Ashmann, S. M. (1993) OH radical production from the gas-phase reactions of O3 with a series of alkenes under atmospheric conditions. Environ. Sci. Technol. 27, 1357-1363. (29) Grosjean, D., Grosjean, E., and Williams, E. L., III (1994) Atmospheric chemistry of olefins: a product study of the ozonealkene reaction with cyclohexane added to scavenge OH. Environ. Sci. Technol. 28, 186-196. (30) Murray, R. W., Jeyaraman, R., and Mohan, L. (1986) Chemistry of dioxiranes. 4. oxygen atom insertion into carbon-hydrogen bonds by dimethyldioxirane. J. Am. Chem. Soc. 108, 2470-2472. (31) Asensio, G., Mello, R., Gonzalez-Nunez, M. E., Boxi, C., and Royo, J. (1997) The oxidation of alkanes with dimethyldioxirane: a new mechanistic insight. Tetetrahedron Lett. 38, 2373-2376. (32) Murray, R. W., and Singh, M. Unpublished results. Interestingly the gas-phase reaction of cyclohexane with dimethyldioxirane gave cyclohexanone and cyclohexanol in a ratio of 1.2 which is similar to that found28 in the OH radical reaction with cyclohexane (0.8-1.2).
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