Synthesis of nitrones using the methyltrioxorhenium/hydrogen peroxide system

Article abstract of DOI:10.1021/jo961252e

Secondary amines are oxidized by the methyltrioxorhenium/hydrogen peroxide system to the corresponding nitrones in excellent yield. The results provide a further example of the parallel between the chemistry of this metal system and that of the dioxiranes.

Full text of DOI:10.1021/jo961252e

J . Org. Chem. 1996, 61, 8099-8102
8099
Syn th esis of Nitr on es Usin g th e Meth yltr ioxor h en iu m /Hyd r ogen
P er oxid e System
Robert W. Murray* and Kaliappan Iyanar
Department of Chemistry, University of MissourisSt. Louis, St. Louis, Missouri 63121
J ianxin Chen and J ames T. Wearing
Pulp and Paper Research Institute of Canada, Vancouver Laboratory, Vancouver, BC, Canada, V6S 2L9
Received J uly 2, 1996X
Secondary amines are oxidized by the methyltrioxorhenium/hydrogen peroxide system to the
corresponding nitrones in excellent yield. The results provide a further example of the parallel
between the chemistry of this metal system and that of the dioxiranes.
In tr od u ction
phines,7 arsines,7 stibines,7 arenes,8 sulfur compounds,9
benzaldehyde,10 alkynes,11 anilines,12 and alcohols.13 The
rhenium system has been shown by Herrmann14 and
Espenson15 to give two adducts, 1 and 2 (eq 1), either of
Nitrones are important organic compounds because of
their use in organic synthesis1 and their use as spin
traps.2,3 The latter usage includes nitrones as scavengers
of radicals in the biomedical area. A number of nitrone
syntheses have been described.1,4 Many of these methods
involve the oxidation of hydroxylamines which generally
are not readily accessible. We have reported4a that the
oxidation of secondary amines with dimethyldioxirane
provides a convenient high-yield synthesis of hydroxyl-
amines. Furthermore, we have demonstrated5 that some
of these hydroxylamines are rapidly and, in most cases,
quantitatively converted to nitrones by dimethyldiox-
irane.
which could be responsible for the chemistry we observe.
Under our experimental conditions we expect the major
oxidant to be 2.
We reported earlier16 that the MTO/H2O2 system is
capable of accomplishing C-H bond insertion reactions
which parallel those of dimethyldioxirane. As part of our
effort to further compare this metal system with dimeth-
yldioxirane, we have reported17 the oxidation of a variety
of organonitrogen compounds using the MTO/H2O2 sys-
tem. Again, we observed a remarkable parallel to the
dioxirane chemistry. Included in the group of compounds
studied was a secondary amine, dibenzylamine, which
gave primarily the expected hydroxylamine. However,
the reaction also gave a small amount of nitrone which
prompted us to study the use of this system as a general
preparative method for nitrones. The results of that
study are described here.
We have become interested in the methyltrioxorhe-
nium/hydrogen peroxide (MTO/H2O2) system because of
the similarity of its chemistry to that of dioxirane
chemistry. This metal system has been shown to oxidize
a variety of organic substrates including alkenes,6 phos-
X Abstract published in Advance ACS Abstracts, November 1, 1996.
(1) (a) Patai, S. The Chemistry of the Carbon-Nitrogen Double Bond;
Wiley: New York, 1970. (b) Tennant, G. In Comprehensive Organic
Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: New
York, 1979; Vol. 2. (c) Sandler, S. R.; Karo, W. Organic Functional
Group Preparations; Academic Press: New York, 1972; Vol. 3. (d)
Padwa, A. 1,3-Dipolar Cycloaddition Chemistry; Wiley: New York,
1984; Vol. 2, p 83. (e) Confalone, P. N.; Huie, E. M. The [3+2] Nitrone-
Olefin Cycloaddition Reaction. In Organic Reactions; Wiley: New York,
1988; Vol. 36. (f) Hamer, J .; Macaluso, A. Chem. Rev. 1964, 64, 473.
(g) Delpierre, G. R.; Lamchen, M. Q. Rev., Chem. Soc. 1965, 19, 329.
(h) Tufariello, J . J . Acc. Chem. Res. 1979, 12, 396. (i) Torsell, K. B. G.
Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis; VCH
Publishers: New York, 1988.
Resu lts a n d Discu ssion
Generally we have followed the procedures described
by Herrmann14 and Espenson15 to prepare the MTO/H2O2
(6) (a) Herrmann, W. A.; Fischer, R. W.; Marz, D. W. Angew. Chem.,
Int. Ed. Engl. 1991, 30, 1638. (b) Boehlow, T. R.; Spilling, C. D.
Tetrahedron Lett. 1996, 37, 2727.
(2) Evans, C. A. Spin Trapping. Aldrichimica Acta 1979, 12, 23.
(3) J anzen, E. G. Acc. Chem. Res. 1971, 4, 31.
(4) (a) Murray, R. W.; Singh, M. Synth. Commun. 1989, 19, 3509.
(b) De La Mare, H. E.; Coppinger, G. M. J . Org. Chem. 1963, 28, 1068.
(c) Murahashi, S. L.; Shiota, T. Tetrahedron Lett. 1987, 28, 2383. (d)
Mitsui, H.; Zenki, S.; Shiota, T.; Murahashi, S. I. J . Chem. Soc., Chem.
Commun. 1984, 874. (e) Markowicz, T.; Skolimoski, J .; Skowronski,
R. Pol. J . Chem. 1981, 55, 2505. (f) Murahashi, S. I.; Mitsui, H.;
Watanabe, T.; Zenki, S. Tetrahedron Lett. 1983, 24, 1049. (g) Berry,
D. W.; Bryant, R. W.; Smith, J . K.; Landolt, R. G. J . Org. Chem. 1970,
35, 845. (h) Christensen, D.; J orgensen, K. A. J . Org. Chem. 1989, 54,
126. (i) Boyd, D. R.; Coulter, P. B.; McGuckin, M. R.; Sharma, N. D.;
J ennings, W. D.; Wilson, V. E. J . Chem. Soc., Perkin Trans. 1 1990,
301. (j) Ogata, Y.; Sawaki, Y. J . Am. Chem. Soc. 1973, 95, 4687, 4692.
(k) Katritzky, A. R.; Lagowski, M. In Chemistry of the Macrocyclic
N-Oxides; Academic Press: London, 1971. (l) Lee, T. D.; Keana, J . F.
W. J . Org. Chem. 1976, 41, 3237. (m) Pandey, G.; Kumaraswamy, G.;
Krishna, A. Tetrahedron Lett. 1987, 28, 2649. (n) Gorrad, J . W.;
Gooderham, N. J . Arch. Pharm. (Weinheim, Ger.) 1986, 319, 261. (o)
Huie, R.; Cherry, W. R. J . Org. Chem. 1985, 50, 1531. (p) Haire, D. L.;
Hilborn, J . W.; J anzen, E. G. J . Org. Chem. 1986, 51, 4298. (q) Zajac,
W. W., J r.; Walters, T. R.; Darcy, M. G. J . Org. Chem. 1988, 53, 5856.
(5) Murray, R. W.; Singh, M. J . Org. Chem. 1990, 55, 2954.
(7) Abu-Omar, M. M.; Espenson, J . H. J . Am. Chem. Soc. 1995, 117,
272.
(8) (a) Adam, W.; Herrmann, W. A.; Lin, J .; Saha-Moller, C. R.;
Fischer, R. W.; Correia, J . D. G. Angew. Chem., Int. Ed. Engl. 1994,
33, 2475. (b) Adam. W.; Herrmann, W. A.; Lin, J ; Saha-Moller, C. R.
J . Org. Chem. 1994, 59, 8281.
(9) (a) Huston, P.; Espenson, J . H.; Bakac, A. Inorg. Chem. 1993,
32, 4517. (b) Adam, W,; Mitchell, C. M.; Saha-Moller, C. R. Tetrahedron
1994, 50, 13121.
(10) Yamazaki, S. Chem. Lett. 1995, 127.
(11) Zhu, Z.; Espenson, J . H. J . Org. Chem. 1995, 60, 7728.
(12) Zhu, Z.; Espenson, J . H. J . Org. Chem. 1995, 60, 1326.
(13) Zhu, Z.; Espenson, J . H. J . Org. Chem. 1996, 61, 324.
(14) Herrmann, W. A.; Fischer, R. W.; Scherer, W.; Rauch, M. U.
Angew. Chem., Int. Ed. Engl. 1993, 32, 1157.
(15) Yamazaki, S.; Espenson, J . H.; Huston, P. Inorg. Chem. 1993,
32, 4683.
(16) Murray, R. W.; Iyanar, K.; Chen, J .; Wearing, J . T. Tetrahedron
Lett. 1995, 36, 6415.
(17) Murray, R. W.; Iyanar, K.; Chen, J .; Wearing, J . T. Tetrahedron
Lett. 1996, 37, 805.
S0022-3263(96)01252-2 CCC: $12.00 © 1996 American Chemical Society

8100 J . Org. Chem., Vol. 61, No. 23, 1996
Murray et al.
we have followed the literature procedure18,19 for the
synthesis of the pyrrolidine precursor to the required
nitrone. For the nitrone synthesis we used the MTO/
H2O2 system instead of the SeO2/H2O2 used in the
earlier18 method. The current procedure gave an 80%
yield of the nitrone as compared with 60% yield in the
earlier synthesis.
Ta ble 1. Oxid a tion of Secon d a r y Am in es w ith Hyd r ogen
P er oxid e in th e P r esen ce of MTO Ca ta lysta
We described earlier5 a synthesis of nitrones using
dimethyldioxirane. The method is rapid, simple, and
high yield. The results described here using the MTO/
H2O2 adduct 2 indicate that the latter method is quite
competitive with the dioxirane method. Furthermore, it
has the advantage of being catalytic as opposed to being
stoichiometric, as is the case with the dioxirane method.
This new nitrone synthesis further indicates the parallel
between the chemistry of 2 and that of the dioxirane
systems. The reaction proceeds through the hydroxyl-
amine, as demonstrated in the case of dibenzylamine
where we have isolated the hydroxylamine and then
oxidized it to the nitrone (eq 2). In their study of the
reaction of the MTO/H2O2 system with anilines, Zhu and
Espenson12 used a Hammett plot to show that the
reaction was electrophilic in character. A number of
studies have demonstrated20 that dimethyldioxirane also
behaves in an electrophilic manner in a variety of
oxidations. We plan to continue our studies that are
directed at a comparison of the dioxirane and MTO/H2O2
systems. Results similar to those reported here have
been obtained with another metal system. The sodium
tungstate/H2O2 system oxidizes secondary amines to give
the corresponding nitrones in good yield.21
Exp er im en ta l Section
a
General experimental procedure followed. b Partial decomposi-
tion occurs during isolation. c Urea-hydrogen peroxide adduct used.
Ma ter ia ls. Methylrhenium trioxide was prepared following
the literature procedure22 using Re2O7 and Sn(CH3)4. Diben-
zylamine (Aldrich), 2-methylpiperidine (Aldrich), di-n-butyl-
amine (Fisher), 1,2,3,4-tetrahydroisoquinoline (Aldrich), N-tert-
butylbenzylamine (Aldrich), proline methyl ester (Aldrich),
N-phenylbenzylamine (Aldrich), tetramethyltin (Aldrich), per-
fluoroglutaric anhydride (Aldrich), dirhenium heptoxide (Al-
drich), urea-hydrogen peroxide (Aldrich), L-(+)-tartaric acid
(Aldrich), benzylamine (Aldrich), palladium hydroxide on
carbon (Aldrich), boron trifluoride etherate (Aldrich), Celite
(Aldrich), Florisil (Aldrich), and silica gel 60 (PF254, containing
gypsum, Merck) were used as received. Anhydrous sodium
sulfate, sodium fluoride, sodium borohydride, sodium chloride,
and hydrogen peroxide (50%) were obtained from Fisher and
used as such. Ethyl acetate (Fisher), methanol (Fisher),
2-methoxyethyl ether (Aldrich), and ethanol (Fisher) were
purified by distillation prior to use. Methylene chloride
(Fisher), chloroform (Fisher), and hexane (Fisher) were frac-
tionally distilled over calcium hydride.
adducts. Oxidations using the adducts generally followed
the methods used in our earlier work17 with organoni-
trogen compounds. A number of secondary amines of
varying structural types were treated with 2. The
reactions were run at room temperature and usually for
30 min. An example of this oxidation is shown in eq 2.
Usually, the product nitrones were obtained in high yield
(>80%, Table 1). The products are known materials
which were identified by NMR and GC-MS methods.
Oxidation of N-phenylbenzylamine using the general
procedure gave the hydrolysis products nitrosobenzene
and benzaldehyde. However, a good yield (50%) of the
derived nitrone could be obtained by using urea-
hydrogen peroxide (UHP) as the source of hydrogen
peroxide and methylene chloride as the solvent. With
the proline derivative (entry 6), the nitrone was obtained
regiospecifically, presumably because of the acidity of the
proton involved. Of particular interest is the synthesis
of (3S,4S)-3,4-bis(methoxymethoxy)-1-pyrroline N-oxide
(entry 8). This nitrone has proven to be useful in the
synthesis of the antibiotic (-)-anisomycin.18 Generally
In str u m en ta tion . 1H and 13C NMR spectra were mea-
sured on a 300 MHz NMR spectrometer. Mass spectra were
recorded on an EI quadrupole mass spectrometer interfaced
with a gas chromatograph fitted with an Ultra-1 (cross-linked
methyl silicone) column. Chromatographic separations on the
Chromatotron were accomplished using 2 mm Kieselgel 60PF
254 plates. Melting points were determined on a capillary
melting point apparatus and are uncorrected.
Gen er a l P r oced u r e for th e Syn th esis of Nitr on es. The
literature procedure6,14,17 for the preparation of the MTO/H2O2
(19) Nagel, U.; Kinzel, E.; Andrade, J .; Prescher, G. Chem. Ber. 1986,
119, 3326.
(20) For
a summary of Hammett studies on dimethyldioxirane
reactions, see: Curci, R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem.
1995, 67, 811.
(21) Murahashi, S.-I.; Mitsui, H.; Shiota, T.; Tsuda, T.; Watanabe,
S. J . Org. Chem. 1990, 55, 1736.
(18) Ballini, R.; Marcantoni, E.; Petrini, M. J . Org. Chem. 1992, 57,
1316.
(22) Herrmann, W. A.; Kuhn, F. E.; Fischer, R. W.; Thiel, W. R.;
Romo, C. C. Inorg. Chem. 1992, 31, 4431.

Synthesis of Nitrones
J . Org. Chem., Vol. 61, No. 23, 1996 8101
adduct was followed. To a stirred solution of amine (5 mmol)
in ethanol (25 mL) was added MTO (0.04 g, 0.16 mmol) in H2O2
(6 mL in ethanol, 50 mmol), and the reaction continued to stir
at room temperature for 0.5 h. Water (25 mL) was then added
to the reaction mixture followed by the addition of a saturated
aqueous solution of NaCl (10 mL). The reaction mixture was
then extracted with methylene chloride. The organic layer was
separated, washed with saturated NaCl solution (10 mL), and
dried over anhydrous sodium sulfate. The drying agent was
filtered off, and the solvent was removed on the rotary
evaporator. The crude product was purified by either chro-
matography or crystallization and characterized spectroscopi-
cally (1H and 13C NMR spectroscopy and GC-MS).
data are the same as those previously reported.21 13C NMR
(CDCl3): δ 25.8, 30.7, 48.7, 61.7, 174, 179.1. Mass spectrum
(EI, 70 eV): 143 (M+, 79), 85 (base peak), calcd for C6H9NO3:
143.14.
N-Ben zyliden eph en ylam in e N-Oxide. Oxidation of 0.183
g (1 mmol) of N-phenylbenzylamine with urea-hydrogen
peroxide (UHP, 2.24 g, 20 mmol) and MTO (20 mg, 0.08 mmol)
in CH2Cl2 (6 mL) gave a brown-colored mixture after stirring
for 2 h at room temperature. The reaction mixture was dried
(Na2SO4), and the solvent was removed to give a cream-colored
solid. This material was purified on the Chromatotron using
a silica gel plate and hexane-ethyl acetate (80:20) to elute.
This process gave 0.098 g (50% yield) of the pure nitrone, mp
110-112 °C, lit.24 mp 112-114 °C. 1H NMR (CDCl3): δ 7.45-
7.50 (m, 2H), 7.75-7.78 (m, 2H), 7.91 (s, 1H), 8.37-8.41 (m,
2H). 13C NMR (CDCl3): δ 121.8, 128.7, 129.1, 129.2, 130,
130.9, 130.9, 131.0, 134.8, 149.0. Mass spectrum (EI, 70 eV):
197 (M+, 15), 91 (base peak), calcd for C13H11NO: 197.24.
(3R,4R)-1-Ben zyl-3,4-d ih yd r oxy-2,5-p yr r olid in d ion e.
Benzylamine (11 mL, 1 mmol) and L-(+)-tartaric acid (15 g, 1
mmol) were mixed in a 300 mL round bottom flask containing
80 mL of xylene. The mixture was heated at reflux for 3 h,
and the water (∼3.6 mL, 2 mmol) was collected using a Dean-
Stark apparatus. Since crystals collect during the reaction,
care must be taken to avoid bumping. After the reaction
mixture was cooled, the solid was filtered off, washed with
acetone, and recrystallized from ethanol (81% yield), mp 196-
198 °C, lit.19 mp 196 °C.
N-Bu tylid en ebu tyla m in e N-Oxid e. Oxidation of di-n-
butylamine (0.646 g, 5 mmol) following the general procedure
given above produced a pale yellow liquid. This was purified
by distillation at 110-120 °C (2 mmHg), lit.21 bp 110-120 °C
(2 mmHg), to give 0.680 g (95% yield) of product. 1H NMR
(CDCl3): δ 0.95 (t, 3H), 0.98 (t, 3H), 1.2-2.0 (m, 6H), 2.47 (dt,
2H), 3.72 (t, 2H), 6.74 (t, 1H). 13C NMR (CDCl3): δ 13.4, 13.8,
18.8, 19.4, 28.4, 29.1, 64.9, 141.9. Mass spectrum (EI, 70 eV):
m/ z 143 (M+, 3.1), 100 (base peak), calcd for C8H17NO 143.23.
N-Ben zylid en eben zyla m in e N-Oxid e. The general pro-
cedure was followed using dibenzylamine (0.986 g, 5 mmol).
Solvent removal gave a solid which was chromatographed on
silica gel using ethyl acetate-hexane (15:85) as the eluent.
This gave a white solid (0.90 g, 85%), mp 79-81 °C, lit.4b mp
82-83 °C. 1H NMR (CDCl3): δ 5.31 (s, 2H), 7.31-7.51 (m,
9H), 8.17-8.25 (m, 2H). 13C NMR (CDCl3): δ 71.2, 128.4,
128.6, 128.9, 129.1, 130.3, 130.4, 133.2, 134.3. Mass spectrum
(EI, 70 eV): 211 (M+, 4.7), 91 (base peak), calcd for
C14H13NO: 211.26. In a separate experiment the general
procedure was used to oxidize 0.213 g (1 mmol) of N,N-
dibenzylhydroxylamine with MTO (10 mg, 0.04 mmol) and
hydrogen peroxide (50%, 2 mL, 30 mmol). Removal of the
solvent gave a solid which was purified on the Chromatotron
using a silica gel plate and ethyl acetate-petroleum ether (15:
85) to elute. This gave 0.2 g (94% yield) of the pure product.
N-Ben zylid en e-ter t-bu tyla m in e N-Oxid e. Oxidation of
N-tert-butylbenzylamine (0.816 g, 5 mmol) and removal of the
solvent gave a white solid. Recrystallization from ethyl
acetate-hexane gave the pure nitrone as white crystals (0.80
g, 90% yield), mp 72-74 °C, lit.23 mp 75-76 °C. 1H NMR
(CDCl3): δ 1.61 (s, 9H), 7.38-7.45 (m, 3H), 7.54 (s, 1H), 8.27-
8.30 (m, 2H). 13C NMR (CDCl3): δ 28.5, 70.9, 128.4, 128.8,
130.1, 130.2, 131. Mass spectrum (EI, 70 eV): 177 (M+, 15.5),
57 (base peak), calcd for C11H15NO: 177.25.
(3S,4S)-1-Ben zyl-3,4-p yr r olid in ed iol. Boron trifluoride
etherate (7.4 mL, 59 mmol) and 2-methoxyethyl ether (30 mL)
were combined in a round bottom flask and cooled to 0 °C.
The dione (3.3 g, 15 mmol) was added to this mixture. After
the reaction mixture was stirred for 10 min, sodium borohy-
dride (1.5 g, 39 mmol) was added slowly. The diborane that
was generated was collected by passing it through acetone.
After the addition was complete, the mixture was heated to
70 °C and stirred for 2 h. The mixture was cooled to room
temperature, and 20 mL of 6 N HCl was added slowly. The
mixture was heated to 70 °C and stirred for 15 min. The
reaction mixture was cooled to room temperature, and 9.2 g
of sodium fluoride was added at once followed by stirring at
100 °C for 30 min. The solution was cooled to 20 °C, and 19
mL of an aqueous sodium hydroxide solution (20%) was added.
The aqueous phase was separated, and the organic phase was
evaporated to dryness in vacuo. The residue was dissolved in
12 mL of water and extracted with ether continuously for 24
h. Evaporation of the ether gave the diol as a crystalline solid
(52% yield), mp 98-100 °C, lit.19 mp 100 °C. [R]20 +31.4 (c
D
3,4-Dih yd r oisoqu in olin e N-Oxid e. The general proce-
dure was followed using 0.66 g (5 mmol) of 1,2,3,4-tetrahy-
droisoquinoline. Removal of the solvent gave a brown, oily
liquid. This material was dissolved in ethyl acetate-hexane
(80:20) and chromatographed on the Chromatotron using a
silica gel plate. Elution with the same solvent combination
gave a yellow, oily liquid (0.662 g, 90% yield). The 1H NMR
data are the same as those previously reported.21 13C NMR
(CDCl3): δ 27.7, 57.7, 125.7, 127.2, 127.6, 128, 129.7, 130.2,
134.9. Mass spectrum (EI, 70 eV): 147 (M+, 100), calcd for
C9H9NO: 147.17.
4, methanol), lit.18 [R]20 +31.9 (c 4, methanol).
D
(3S ,4S )-1-Be n zyl-3,4-b is(m e t h oxym e t h oxy)p yr r oli-
d in e. The diol (0.3 g, 1.55 mmol) in dimethoxymethane (10
mL) was cooled to 0 °C, and P2O5 (1.1 g, 7.75 mmol) was added
slowly with stirring over a period of 1 h. The reaction mixture
was then stirred at room temperature for 2 days. The solvent
was evaporated, and the residue was again cooled to 0 °C. The
residue was treated with 20% methanolic KOH (7.5 mL). The
resulting suspension was filtered over Florisil, and the metha-
nol was evaporated. The crude residue was purified on the
Chromatotron using silica gel and eluting with hexane/ethyl
acetate (3:2) to give the diether as a colorless oil. The 1H NMR
spectrum is essentially the same as that in the literature.18
13C NMR (CDCl3): δ 138.1, 129.1, 128.4, 127.2, 95.8, 81.7, 60.5,
58.8, 55.7. Mass spectrum (EI, 70 eV): 281 (M+, 0.36), 91
(base peak), calcd for C15H23O4N: 281.35.
(3S,4S)-3,4-Bis(m eth oxym eth oxy)p yr r olid in e. The di-
ether (0.229 g, 0.812 mmol) and Pd(OH)2 on carbon (0.05 g)
were mixed in methanol (10 mL). The suspension was
hydrogenated at room temperature and 1 atm for 3 h. The
catalyst was removed by filtration through Celite and was
washed with methanol. The solvent was evaporated to give
the crude product which was purified on the Chromatotron
using silica gel and elution with hexane/ethyl acetate/ethanol/
NH4OH (4:4:1.8:0.2) to give 0.109 g (70%) of pure material.
6-Meth yl-2,3,4,5-tetr a h yd r op yr id in e N-Oxid e. The gen-
eral procedure was followed to oxidize 0.4959 g (5 mmol) of
2-methylpiperidine. Solvent removal gave a pale yellow oil.
This material was chromatographed using the Chromatotron
using a silica gel plate and chloroform-methanol (97:3) as the
1
eluent to give 0.509 g (90% yield) of the product. The H NMR
data are the same as those previously reported.21 13C NMR
(CDCl3): δ 18.7, 18.9, 23.2, 30.9, 57.5, 148.8. Mass spectrum
(EI, 70 eV): 113 (M+, 100), 54 (79), calcd for C6H11NO: 113.15.
Meth yl 1-P yr r olin e-2-ca r boxyla te N-Oxid e. The gen-
eral procedure was followed using 0.828 g (5 mmol) of L-proline
methyl ester. Removal of the solvent gave a pale yellow oil.
The oil was purified on the Chromatotron using a silica gel
plate and chloroform-methanol (97:3) as the eluent. This
1
process gave 0.573 g (80% yield) of the nitrone. The H NMR
(24) (a) Utzinger, G. E. Ann. 1944, 556, 50. (b) Wheeler, O. H.; Gore,
P. H. J . Am. Chem. Soc. 1956, 78, 3363.
(23) Emmons, W. D. J . Am. Chem. Soc. 1957, 79, 5739.

8102 J . Org. Chem., Vol. 61, No. 23, 1996
Murray et al.
1
The H NMR spectrum is essentially the same as that in the
Note Ad d ed in P r oof: Since submission of this paper
a report has appeared describing similar results; see:
Gobi, A.; Nanelli, L. Tetrahedron Lett. 1996, 37, 6025.
literature.18 13C NMR (CDCl3): δ 95.6, 81.8, 55.7, 52.0. Mass
spectrum (EI, 70 eV): 191 (M+, 0.12), 45 (base peak), calcd
for C8H17NO4: 191.23.
(3S,4S)-3,4-Bis(m et h oxym et h oxy)-1-p yr r olin e N-Ox-
id e. Urea-hydrogen peroxide (0.146 g, 1.57 mmol) and me-
thyltrioxorhenium were mixed in CH2Cl2 (5 mL), and the
mixture was stirred for 5 min. The solution became yellow
colored. (3S,4S)-3,4-Bis(methoxymethoxy)pyrrolidine (30 mg,
0.157 mmol) was dissolved in CH2Cl2. This solution was added
Ack n ow led gm en t. The project described was sup-
ported by Grant ES01984 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 work at the Pulp and Paper Research
Institute of Canada was supported by Industry Canada,
DuPont Canada, Inc., and FMC Corp. The Varian XL-
300 NMR Spectrometer was purchased with support
from the National Science Foundation.
to the UHP-MTO solution, and the combined solution was
1
stirred for
/ h. The general workup procedure was used
2
followed by solvent removal. The crude product was purified
by column chromatography on silica gel with elution by
hexane/ethyl acetate/ethanol (4:5:1) which gave 25 mg (80%
yield) of pure product. The 1H NMR spectrum is essentially
the same as that in the literature.18 13C NMR (CDCl3): δ 132.6,
95.2, 81.3, 55.2, 51.6. Mass spectrum (EI, 70 eV): 205 (M+,
0.7), 45 (base peak), calcd for C8H15NO5: 205.21.
J O961252E