Electron spin resonance study of phosphorus-nitroxides from 1,3-additions of silicon-phosphorus reagents to nitrones

Article abstract of DOI:10.1002/mrc.1436

This article explores a new, convenient route to β-phosphorus nitroxides. Specifically, the reaction sequence involves the novel 1,3-addition of trimethylsilyl phosphites (e.g. diethyl) or trimethylsilyl phosphines (e.g. diphenyl) to aldo-nitrones [e.g. α

Full text of DOI:10.1002/mrc.1436

MAGNETIC RESONANCE IN CHEMISTRY
Magn. Reson. Chem. 2004; 42: 835–843
Published online 10 August 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1436
Electron spin resonance study of phosphorus-
nitroxides from 1,3-additions of silicon-
phosphorus reagents to nitrones
D. Lawrence Haire,1∗ Edward G. Janzen,1 Valerie J. Robinson2 and Ivan Hrvoic3
1
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada
Department of Chemistry and Biochemistry, Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, NMR Centre, University of
2
Guelph, Guelph, ON, N1G 2W1, Canada
3
Gem Systems, 52 West Beavercreek Road, Unit 14, Richmond Hill, ON, L4B 1L9, Canada
Received 3 February 2004; Revised 14 May 2004; Accepted 19 May 2004
This article explores a new, convenient route to b-phosphorus nitroxides. Specifically, the reaction
sequence involves the novel 1,3-addition of trimethylsilyl phosphites (e.g. diethyl) or trimethylsilyl
phosphines (e.g. diphenyl) to aldo-nitrones [e.g. a-phenyl-N-tert-butylnitrone (PBN) or 5,5-dimethyl-l-
pyrroline-N-oxide (DMPO)] or keto-nitrones [e.g. 2-ethyl-5,5-dimethyl-1 pyrroline-N-oxide (2-Et-DMPO)
or 2-phenyl-5,5-dimethyl-l-pyrroline-N-oxide (2-Ph-DMPO)] to form a-phosphityl- or a-phosphinyl-O-
silylhydroxylamines. Acidic hydrolysis provides the corresponding hydroxylamines that are easily
oxidized to the title b-phosphorus-nitroxides. ESR spectroscopic analysis revealed some very large b-
phosphorus hyperfine splittings (i.e. in excess of 5 mT). For this reason and their remarkable stability
(persistence) some of these nitroxides show promise as integral components in new, improved weak-field
dynamic nuclear polarization (DNP) magnetometers. Copyright  2004 John Wiley & Sons, Ltd.
KEYWORDS: ESR; ˇ-phosphorus-nitroxides (aminoxyls); ˛-phosphorus-O-silylhydroxylamines; nitrones; magnetometry
amplified by the presence of trace amounts of persistent
free radicals. This is the well-known Abragam Overhauser
effect.4
INTRODUCTION
Weak-field magnetometers measure magnetic fields on land,
sea, air and space. Geology,1 aerospace exploration,2 as well
as archaeology3 are just a few fields in which these devices
find current usage. Our interest in magnetometers, however,
stems from the fact that stable (persistent) free radicals play
a critical role in their sensitivity. Specifically, our search is
for new free radical molecules that can provide enhanced
magnetometric sensitivity. In addition to their persistence,
the free radical should also exhibit a large hyperfine
splitting (a) in its electron spin resonance (or ESR) spectrum.
The ESR parameter ‘a’ is associated with a phenomenon
known as the dynamic nuclear polarization (DNP) effect.
Dynamic nuclear polarization is a double magnetic resonance
technique in which there is a transfer of electron spin
polarization to the nuclear spins when the electron spin
transition is stimulated. These DNP magnetometers may
be thought of as NMR spectrometers in which the applied
magnetic field is absent. Thus, the magnetic field of interest
(e.g. from the geological site, etc.) generates the NMR
signal. DNP magnetometers usually operate via detection
of the 1H NMR signal of solvent nuclei that has been
Due to their remarkable persistence, nitroxides have
become the ‘gold standard’ for use in commercial DNP
magnetometers. Two factors contribute to this stability.
The first is the resonance stabilization afforded by the
more polar and less polar canonical forms (Fig. 1). A
second factor is steric hindrance. The bulkiness of the
nitroxide flanking groups (i.e. R1, to R6) also enhances
the free radical’s lifetime (Fig. 1). This is because when
nitroxides are attached to two bulky ˛-groups (e.g. di-tert-
alkyls) a major decay route known as disproportionation
is slowed or prevented altogether (Scheme 1). It is worth
mentioning that some nitroxides with one ˇ-hydrogen also
may exhibit relatively long half-lives (i.e. from months to
years). Spin trapping5 with the two most popular nitrone spin
traps [˛-phenyl-N-tert-butylnitrone (PBN) and 5,5-dimethyl-
l-pyrroline-N-oxide (DMPO) (Fig. 3)] may also yield spin
adduct nitroxides of uncommon stability. Examples of
such spin adducts that may be chromatographed (e.g. by
HPLC) and/žor analysed by mass spectrometry (MS) include
ž
the methyl ( CH3 ), 2-cyano-2-propyl [ C-ꢀCH3ꢁ2CN]7 and
6
trichloromethyl (žCCl3)8,9 adducts of PBN as well as the 2-
cyano-2-propyl [žC-ꢀCH3ꢁ2CN]7 and various alkoxyl (žOR)
adducts of DMPO.10
ŁCorrespondence to: Dr D. Lawrence Haire, Department of Clinical
Studies, Ontario Veterinary College, University of Guelph, Guelph,
ON, N1G 2W1, Canada. E-mail: lhaire@uoguelph.ca
Contract/grant sponsor: Natural Sciences and Engineering
Research Council of Canada.
It should be noted, however, that to date virtually
all the nitroxides patented for use in magnetometers are
Copyright  2004 John Wiley & Sons, Ltd.

836
D. L. Haire et al.
Figure 1. Resonance structures for nitroxide (or aminoxyl)
free radicals.
Figure 2. Structures of various nitroxides patented for use in
DNP magnetometers.
Scheme 1. Decay of nitroxides by disproportionation.
cyclic di-tert-alkylnitroxides (Fig. 2). The first three are
pyrrolidine-N-oxyls (1),11 piperidine-N-oxyls (2),11 as well
as oxazolidine-N-oxyls (3),12 respectively. The next gener-
ation of nitroxides for magnetometry are deuterated and
15N-labelled versions [(4)13 and (5)13–15] of the original
nitroxides (1 and 2). Another deuterated and 15N-labelled
nitroxide, an isoindoline-N-oxyl (6)16,17 has also recently
arrived on the magnetometry scene. Nitroxide (6) was syn-
thesized and found to be superior to nitroxide (5) (the
current radical of choice), especially in higher tempera-
ture magnetometry applications (unpublished observations).
Deuteration is advantageous in magnetometry because it
sharpens the ESR lines that otherwise would display long-
1
range unresolved H hyperfine splittings. It is worth men-
tioning that free radicals for magnetometry are generally
smaller molecules because the larger ones are associated
with wider ESR lines due to immobilization/anisotropy.
Labelling a nitroxide with 15N may help in two ways.
First, it generally provides a larger ESR hyperfine split-
ting (a15N ¾ 2.1 mT vs a14N ¾ 1.5 mT). Second, it leads to
fewer ESR lines (2 vs 3 for 15N vs 14N, respectively). It
is noteworthy, however, that the DNP effect is complex18
(higher at lower magnetic fields for 14N nitroxides). Even
ESR studies at low magnetic fields are complicated. For
instance, 14N nitroxides may be favoured over their 15N
counterparts.19 Therefore, some new free radicals for low-
field magnetometry may require field-testing to fully gauge
their utility (sensitivity). Nevertheless, because of their
large (>5.0 mT) ˇ-31P hyperfine splittings ˇ-phosphorus-
nitroxides (7) (Fig. 2) have captured the interest of our
group20,21 and others.22
Scheme 2. Addition of silicon-phosphorus reagents to carbonyl
compounds and nitrones.
comes from a contraction of the term nitrogen-ketone.23
A
couple of papers24,25 have described the reaction of car-
bonyl compounds (8) with silicon-phosphorus reagents (10)
(Scheme 2). A check of the nitrone literature,23,26–34 how-
ever, revealed that no one has examined the analogous
reactions with nitrones (Scheme 2). While the carbonyl (8)
and nitrone (9) reactions with silicon-phosphorus reagents
(10 and 11) are likely mechanistically similar, the former
is a 1,2-addition while the latter is a 1,3-addition. The
This paper examines new routes to some new and
known ˇ-phosphorus-nitroxides derived from aldo- and
keto-nitrones. The sequence was discovered by recognition
that the chemistries of carbonyl compounds and nitrones
often parallel each other. The name of the latter actually
Copyright  2004 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2004; 42: 835–843

ESR of phosphorus-nitroxides 837
carbonyl and nitrone adducts thus are an ˛-phosphityl-
O-silylether (12) and an ˛-phosphityl-O-silylhydroxylamine
(13), respectively. Because silyl ethers (e.g. 12) are generally
hydrolysable (HC) to alcohols (e.g. 14)25 it was reasoned that
O-silylhydroxylamine (13) should also be easily convertible
to the N,N-hydroxylamine (15) which in turn should be eas-
ily oxidizable to the desired nitroxide (16). Fortunately, this
turns out to be the general case and will be discussed in
detail later.
(21 and 23) and related compounds (22 and 24) are
listed in Table 2. Key 1H, 13C and 31P NMR spectro-
scopic data for phosphorus adducts (25) and (26) (Fig. 5)
derived from the 1,3-addition of diethyl trimethylsilyl
phosphite (21) and diphenyl (trimethyl) phosphine (23)
to nitrone (17) (PBN), respectively, are listed in Table 3.
The ESR spectral data for the various ˇ-phosphityl-
and ˇ-phosphinyl-nitroxides (27–35) (Fig. 6) derived from
nitrones (17–20) are presented in Table 4. Representative
ESR spectra of some phosphorus-nitroxides from the 1,3-
additions (i.e. 27, 31 and 32) are given in Figs 7–9, respec-
tively.
RESULTS AND DISCUSSION
In this study the reaction of four nitrones (Fig. 3) with
two silicon-phosphorus compounds (Fig. 4) was examined.
The two aldo-nitrones were ˛-phenyl-N-tert-butylnitrone
(PBN) (17) and 5,5-dimethyl-l-pyrroline-N-oxide (DMPO)
(18), whereas the two keto-nitrones were 2-ethyl-5,5-
dimethyl- l-pyrroline-N-oxide (2-Et-DMPO) (19) and 2-
phenyl-5,5-dimethyl-l-pyrroline-N-oxide (2-Ph-DMPO) (20).
The silicon-phosphorus compounds used were diethyl
trimethylsilyl phosphite (21) and diphenyl(trimethylsilyl)
phosphine (23) (Fig. 4). The 1H and 13C NMR data for
the nitrones (17–20) are collected in Table 1 while the
1H, 13C and 31P NMR data for the silicon-phosphorus
EXPERIMENTAL
The aldo-nitrones ˛-phenyl-N-tert-butylnitrone (PBN) (17)
and 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) (18) were
purchased from the Aldrich chemical company. The
Figure 4. Structures of the silicon-phosphorus reagents and
Figure 3. Structures of the nitrones used in this study.
related compounds.
Table 1. The 1H and 13C NMR data for the nitrones (17–20)a,b
Nitrone 17 (PBN)
1H NMR: 1.26 (s, 9H, methyls), 7.17–7.23 (m, 4H, nitronyl, and meta, and para-aryls), 8.47 (d, 2H,
ortho-aryls, J1H-1H D 8.20 Hz)
13C NMR:28.16 (methyls), 70.53 (tert-butyl quaternary), 127.82, 128.31,128.57,128.75,129.62 (nitronyl and
aryls except aryl quaternary), 132.43 (aryl quaternary)
Nitrone 18 (DMPO)
1H NMR:1.16 (s, 6H, 5-methyls), 1.42 (t, 2H, C4, J1H-1H D 7.20 Hz), 1.80 (t of d, 2H, C3, J1H-1H D 7.20 Hz,
1
1
1
J H-1H D 2.67 Hz), 6.40 (t, 1H, nitronyl, J H ꢀ H D 2.67 Hz)
13C NMR: 23.92 (C3), 25.24 (5-methyls), 33.81 (C4), 72.75 (C5), 129.00 (nitronyl)
Nitrone 19 (2-Et-DMPO) 1H NMR: 0.82 (t, 3H, ethyl CH3, J1H-1H D 7.60 Hz), 1.21 (s, 6H, 5-methyls), 1.40 (t, 2H, C4,
J1H-1H D 7.40 Hz), 1.94 (t, 2H, C3, J1H-1H D 7.20 Hz), 2.35 (q, 2H, ethyl CH2, J1H-1H D 7.74 Hz)
13C NMR: 9.25 (ethyl CH3), 20.36 (ethyl CH2), 25.18 (5-methyls), 25.48 (C3), 32.13 (C4), 72.77 (C5), 141.82
(nitronyl)
Nitrone 20 (2-Ph-DMPO) 1H NMR: 1.24 (s, 6H, 5-methyls), 1.38 (t, 2H, C4, J1H-1H 7.40 Hz), 2.32 (t, 2H, C3, J1H-1H D 7.40 Hz), 7.18
(m, 3H, meta- and para- aryls), 8.56 (d, 2H, ortho-aryls, J1H-1H D 8.26 Hz)
13C NMR: 25.61 (5-methyls), 26.25 (C3), 31.64 (C4), 75.31 (C5), 127.09, 128.44, 129.40 (aryls except aryl
quaternary), 131.15 (aryl quaternary), 135.30 (nitronyl)
1
a The chemical shifts (υ) in ppm for the H and 13C spectra are relative to external ꢀCH3ꢁ4Si and/or internal C6D6. All spectra were
recorded at room temperature.
b The NMR parameters for these nitrones have been reported previously in the literature (c.f. references 20, 21 and references
cited therein).
Copyright  2004 John Wiley & Sons, Ltd.
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838
D. L. Haire et al.
Table 2. The 1H, 13C, and 31P NMR data for the silicon-phosphorus reagents (21 and 23) and related compounds (22 and 24)a,b
Silicon-phosphorus compound (21) (diethyl trimethylsilyl phosphite)
1H NMR: 0.19 (s, 9H, Si-CH3), 1.09 (t, 6H, ethyl CH3, J1H-1H D 7.00 Hz), 3.76 (m, 4H, ethyl CH2)
13C NMR: 1.43 (s, Si-CH3), 17.11 (d, ethyl CH3, J13C-31P D 4.72 Hz), 56.67 (d, ethyl CH2, J13C-31P D 9.33 Hz)
51P NMR: ꢀ7.70 (p, phosphityl P, J31P-1H D 8.29 Hz)
Silicon-phosphorus compound (22) (diethyl phosphite)
1H NMR: 0.96 (t, 6H, ethyl CH3, J1H-1H D 7.00 Hz), 3.78 (m, 4H, ethyl CH2), 6.60 (d, 1H, phosphityl H, J1H-31P D 683.83 Hz)
13C NMR: 16.24 (d, ethyl CH3, J13Cꢀ31P D 6.01 Hz), 61.20 (d, ethyl CH2, J13C-31P D 5.50 Hz)
31P NMR: 7.32 (d of p, phosphityl P, J31P-1H D 683.93 Hz, J31P-1H D 9.23 Hz) Silicon-phosphorus compound (23) [diphenyl
(trimethylsilyl)phosphine]
1H NMR: 0.13 (d, 9H, Si-CH3, J1H-31P D 4.80 Hz), 7.02 to 7.09 (m, 6H, aryls), 7.49 to 7.53 (m, 4H, aryls)
13C NMR: ꢀ1.11 (d, Si-CH3, J13C-31P D 12.59 Hz), 127.69 to 137.27 (aryls)
31P NMR: ꢀ56.32 (s, phosphinyl P)
Silicon-phosphorus compound (24) (diphenylphosphine)
1H NMR: 7.00 to 7.60 (m, l0 H, aryls)
13C NMR: 127 to 137 (aryls, estimated)
31P NMR: ꢀ40.29 (d of multiplets, phosphinyl P, J31P-1H D 215.59 Hz)
a The chemical shifts (υ) in ppm for the 1H and 13C spectra are relative to external ꢀCH3ꢁ4Si and/or internal C6D6. The chemical shifts
for the 31P spectra are relative to external H3PO4. All spectra were recorded at room temperature in C6D6.
Table 3. The key 1H, 13C, and 31P parameters for the ˛-phosphorus-O-silylhydroxylamines (25 and 26) derived from nitrone (17)
(PBN) and the silicon-phosphorus compounds (21 and 23)a
˛-Phosphorus-O-silylhydroxylamine (25)
1H NMR: 4.19 (d, diastereomeric CH, J1H-31P D 25.15 Hz), 4.21 (d, diastereomeric CH, J1H-31P D 25.16 Hz). Note: the 31
P
coupling disappeared upon 31P decoupling
13C NMR: 56.79 (d, CH, J13C-31P D 31.09 Hz)
31P NMR: 24.06 (broad s, phosphityl P)
˛-Phosphorus-O-silylhydroxylamine (26)
1H NMR: 5.19 (d, CH, J1H-31P D 4.40 Hz). Note: the 31P coupling disappeared upon 31P decoupling
13C NMR: 69.43 (broads, CH)
31P NMR: ꢀ9.44 (broad s, phosphinyl P)
a The chemical shifts (υ) in ppm for the 1H and 13C spectra are relative to external ꢀCH3ꢁ4Si and/or internal C6D6. The chemical shifts
for the 31P spectra are relative to external H3PO4. All spectra were recorded at room temperature in C6D6.
Figure 5. Structures of the ˛-phosphorus-O-silylhydroxy-
lamines derived from ˛-phenyl-N-tert-butylnitrone (PBN) and
silicon-phosphorus reagents detected by NMR spectroscopy.
keto-nitrones 2-ethyl- 5,5-dimethyl-l-pyrroline-N-oxide (2-
Et-DMPO) (19) and 2-phenyl-5,5-dimethyl-l-pyrroline-N-
oxide (2-Ph-DMPO) (20) were synthesized as described,
respectively in two previous papers.21,35 The two
Figure 6. Structures of the 0-31P phosphityl- and
phosphinyl-nitroxide adducts (PA D phosphorus addend).
silicon-phosphorus reagents diethyl trimethylsilyl phosphite
(21) and diphenyl(trimethylsilyl)phosphine (23) were
obtained from the Aldrich chemical company. Since
diethyl trimethylsilyl phosphite (21)36 may be synthesized
Copyright  2004 John Wiley & Sons, Ltd.
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ESR of phosphorus-nitroxides 839
Table 4. ESR hyperfine splittings for the [ˇ-31P] phosphityl and phosphinyl nitroxide adducts in
benzene at room temperaturea
Nitrone
Nitroxide
31P adduct
aN
aˇH
aˇ31P
Refs.
PBN
PBN
PBN
PBN
PBN
PBN
DMPOb
DMPO
2-Et-DMPO
2-Et-DMPO
2-Et-
2-Ph-
2-Ph-DMPOc
2-Ph-
27
27
27
27
28
29
30
31
32
32
33
34
34
34
35
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(Ph)2
PꢀC6H11ꢁ2
P(O)(OEt)2
P(Ph)2
P(O)(OEt)2
P(O)(OEt)2
P(Ph)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(Ph)2
1.448
1.465
1.450
1.475
1.425
1.439
1.32
1.391
1.350
1.350
1.381
1.353
1.367
1.347
1.349
0.3075
0.306
0.294
0.318
0.325
0.335
1.69
1.846
—
—
—
—
—
2.445
2.433
2.431
2.475
1.838
1.211
4.50
3.729
5.400
5.425
4.250
3.429
3.459
3.458
2.727
This work
66
20
67
This work
66
68
This work
This work
21
This work
This work
51
—
—
20
2-Ph-DMPO
This work
a The hyperfine splittings (a) are listed in millitesla (mT).
ž
b This ˇ-phosphityl nitroxide was not observed. Instead, DMPOX (2-oxo-5,5-dimethylpyrrolidine-
N-oxyl) was seen (aN D 0.650 mT, aꢂ2H D 0.325 mT).
c This nitroxide was formed by the addition of phenyl radicals (from benzoyl peroxide) to 2-
(diethylphosphityl)-5,5-dimethyl-1-pyrroline-N-oxide.
Figure 7. ESR spectrum of the diethylphosphityl-nitroxide adduct of PBN (27) in C6H6.
from sodium diethylphosphite [Na P(O) (OEt2)] and
trimethylsilyl chloride (Me3SiC1) other non-commercially
available silicon-phosphorus reagents should be available
by variation of the alkyl groups (e.g. ethyl vs methyl, etc.).
as follows: an equimolar (1.25 mmol) solution of the silicon-
phosphorus reagent and nitrone (as well as a catalytic
amount of ZnI237) in 5 ml of C6D6 was refluxed for 3 h.
The crude reaction mixture was analysed by 1H, 13C and
31P NMR.
Syntheses for NMR examination
Syntheses for ESR examination
Production of the 1,3-adducts (˛-phosphorus-O-silylhydroxy
lamines) (25 and 26) (Fig. 5) from the silicon-phosphorus
reagents (21 and 23) and nitrone (17) (PBN) was conducted
An equimolar (0.125 mmol) solution of the silicon-
phosphorus reagent and nitrone (including a catalytic
amount of ZnI237) in 5 ml of C6H6 was refluxed for 3 h.
Copyright  2004 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2004; 42: 835–843

840
D. L. Haire et al.
Figure 8. ESR spectrum of the diphenylphosphinyl-nitroxide adduct of DMPO (31) in C6H6.
Figure 9. ESR spectrum of the diethylphosphityl-nitroxide adduct of 2-Et-DMPO (32) in C6H6.
After cooling to room temperature the mixture was treated
with 5 ml of 0.1 M HCl. The organic layer was separated
and treated with several milligrams of lead dioxide and
anhydrous Na2SO4 (0.25 g). The filtered C6H6 solution was
placed into a round, quartz ESR cell and purged with argon
(g) for 15 min. The mixture was then examined by ESR.
ER 200 D instrument operating at around 9.8 GHz (i.e. X-
band) and centre field (337.5 mT).
NMR results
Since the 1,3-addition of silyl-phosphorus reagents to
nitrones is virtually unknown in the literature, it was decided
to use NMR spectroscopy to identify some of these adducts.
In contrast to some related studies where the 1,3-addition
of trimethylsilyl cyanide to nitrones proceeds in high yield
(95%)37 the reaction of silicon-phosphorus reagents (21 and
23) (Fig. 4) to nitrone (17) (PBN) gave 25 and 26 (Fig. 5)
in low yield (<10%) and relatively complex NMR spectra.
It is noteworthy though that no attempt was made to
NMR and ESR spectroscopy
The 1H, 13C and 31P spectra were obtained at ambient
temperature using a Bruker spectrometer operating at
approximately 400, 100 and 162 MHz, respectively. The ESR
spectra were recorded at room temperature using a Bruker
Copyright  2004 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2004; 42: 835–843

ESR of phosphorus-nitroxides 841
optimize the yields. Nevertheless, by recording the NMR
spectra (1H and 13C) of the nitrones (Table 1) and the
silicon-phosphorus reagents (1H, 13C and 31P) (Table 2) in
the reaction solvent (i.e. benzene) it was possible to identify
the 1,3-adducts of PBN (25 and 26) by focusing on the
corresponding phosphinyl adduct (33) has a ˇ -phosphorus
splitting of 4.3 mT.
Finally, the phosphityl (34) and phosphinyl (35) adducts
of 2-Ph-DMPO show ˇ-phosphorus splittings around 3.5 mT
and 2.7 mT, respectively. In summary, the ˇ-phosphorus
hyperfine splitting is consistently and significantly larger
for the phosphityl versus the phosphinyl nitroxide adducts
of the respective nitrone. As mentioned in the Introduction
Section some ESR parameters influence the performance
of a free radical in magnetometry applications. And since
the ˇ-phosphorus hyperfine splitting for the phosphorus-
nitroxides from the cyclic nitrones (30–35) (2.7–5.4 mT) are
larger than those from PBN (27–29) (1.2–2.5 mT) the former
are favoured. Among the phosphorus adducts from the
cyclic nitrones those from 2-Et-DMPO and 2-Ph-DMPO (i.e.
32–35) are expected to elicit a stronger DNP effect than
those from the corresponding ones from DMPO (30, 31)
because they display fewer ESR lines (6 vs 12). A further
consideration is the persistence of the various phosphorus-
nitroxide adducts. Nitroxide adducts of DMPO (30, 31) are
expected to be less persistent, especially because they are
prone to decomposition by disproportionation Scheme 1.
Keto-nitrone adducts (32–35) cannot degrade via this route.
The most persistent phosphorus-nitroxides are 2-Et-
DMPO-Rž (32, 33) and 2-Ph-DMPO-Rž (34, 35) whose
stabilities are very similar. The next most stable are the
adducts of PBN (27–29) with those of DMPO (30, 31) the
least stable. Qualitatively, the phosphorus adducts of the
aldo-nitrones (27–31) were ESR detectable for hours to days
while the corresponding ones for the keto-nitrones (32–35)
were observable for weeks to months. Little difference
in persistence was observed between the phosphityl and
phosphinyl adducts of the same nitrones. In summary, of
all the phosphorus-nitroxides synthesized in this study,
the best candidate for magnetometry would appear to be
the phosphityl-nitroxide adduct of 2-Et-DMPO (32). Related
phosphorus adducts of 2-alkyl-DMPO20–22 have also been
synthesized for these purposes.
1
methine (i.e. CH) peak in the H and 13C NMR spectra and
the phosphityl and phosphinyl peaks in the 31P NMR spectra
(Table 3). Though the 1,3-adducts (25 and 26) are new to the
literature, comparison with the 31P NMR chemical shifts of
related compounds was helpful in the assignment of these
peaks.38 For instance, diethyl phosphityl compounds of the
R-P(O)ꢀOEtꢁ2 type (R D alkyl) exhibit 31P NMR peaks around
21 ppm (š10). This compares favourably with the observed
peak at 24.06 ppm for compound 25. Diphenyl phosphinyl
compounds[R-PꢀC6H5ꢁ2] ꢀR D alkylꢁ show 31P NMR peaks
around ꢀ12 ppm ꢀš10ꢁ. This is also close to the observed
peak at ꢀ9.44 ppm for compound 26.
ESR results
The phosphorus-nitroxides (27–35, except 29 and 30) (Fig. 6)
were synthesized according to the 1,3-addition, acidic
hydrolysis, oxidation sequence outlined in Scheme 2. The
ESR spectral data are collected in Table 4. Specifically, diethyl
phosphityl (27, 32, 34) and diphenyl phosphinyl (28, 31,
33, 35) nitroxide adducts of all the aldo- and keto-nitrones
except for the diethyl phosphityl adduct of DMPO (30) were
observed. In place of the expected adduct (30) the oxidation
product, an acyl nitroxide or nitroxone, known as DMPOXž
(2-oxo-5,5-dimethyl-pyrrolidine-N-oxyl) was detected. The
ESR hyperfine splittings (aN D 0.650 mT, aꢂ2H D 0.325 mT in
C6H6) are well known. This result reflects the susceptibility of
aldo-nitrones to oxidation at the nitronyl-carbon [–CH NC
(Oꢀ)]. Formation of an oxo (C O) group at the nitronyl-
carbon of keto-nitrones is blocked. That DMPO is oxidized
to DMPOXž while PBN is not oxidized to PBNOXž is likely
due to the overall higher lability of DMPO versus PBN.5
The phosphorus-nitroxides from the aldo-nitrones (27–31)
all exhibit 12 line triplet of doublet of doublet patterns
due to the nitrogen, ˇ-hydrogen (hfs), and ˇ-phosphorus
nuclei (Table 4). Examples of these ESR spectral patterns are
illustrated in Figs 7 and 8 (the diethylphosphityl adduct of
PBN (27) and the diphenylphosphinyl adduct of DMPO (31)).
The phosphorus-nitroxides from the keto-nitrones
(32–35) show 6 line triplet of doublet patterns due to the
nitrogen and (3-phosphorus nuclei (Table 4). A case in point
is the diethylphosphityl adduct of 2-Et-DMPO (32) (Fig. 9).
(A small peak in the centre of the spectrum is due to a di-tert-
alkyl nitroxide of unspecific structure.) While the nitrogen
(and ˇ-hydrogen where applicable) hyperfine splittings for
all the phosphorus adducts did not vary much between
the phosphityl and phosphinyl adducts, significant changes
were observed in the ˇ-phosphorus splittings. Phosphorus
adducts of PBN exhibited ˇ-phosphorus splittings around
2.5 mT (27), whereas those of phosphinyl adducts varied
from 1.2 mT (29) to 1.8 (28). DMPO phosphityl adducts (e.g.
30) show a robust ˇ-phosphorus splitting (4.5 mT) while the
phosphinyl adduct (31) is significantly smaller at 3.7 mT.
An even larger (ˇ-phosphorus splitting (around 5.4 mT) is
observed for the phosphityl adduct of 2-Et-DMPO (32). The
CONCLUSIONS
The design and synthesis of phosphorus-nitroxides (mainly
ˇ-31P nitroxides) is an active research field. New ˇ-31P
labelled spin traps20,21,39–51 and spin probes46,52–54 have
recently appeared in the literature. At least three papers20–22
deal specifically with magnetometry. Controlled/living
stable free radical mediated polymerization using ordinary
nitroxide spin probes such as 2,2,6,6 tetramethyl-piperidine-
1- oxyl(TEMPO)55–58 and TMIO (1,1,3,3,-tetramethyl-
isoindoline-N-oxyl59 have been studied by ESR and HPLC,
respectively. 15N NMR has also been used to investigate
polymerizations using 15N-labelled TEMPO derivatives.60
Interestingly, some cyclic and non-cyclic ˇ-phosphorus
nitroxides have found their way to the scientific and
industrial forefronts.61,62 Our study here has shown that
new and known ˇ-phosphityl- and ˇ-phosphinyl-nitroxides
may be conveniently prepared by a novel 1,3-addition (of
silicon-phosphorus reagents), acidic hydrolysis, oxidation
sequence. In the case of PBN (17) it was possible to identify
Copyright  2004 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2004; 42: 835–843

842
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the intermediate ˛-phosphityl (25) and ˛-phosphinyl (26)
1
silylhydroxylamines by H, 13C and 31P NMR spectroscopy
(Table 3). These assignments were made much easier
by recording the 1H and 13C of the nitrones (Table 1)
as well as the silicon-phosphorus reagents (Table 2).
The ESR spectral parameters of the phosphorus-nitroxide
adducts (27–35) from diethyl trimethylsilyl phosphite (21)
and diphenyl(trimethylsilyl)phosphine (23) and the aldo-
nitrones [PBN (17) and DMPO (18)] and the keto-nitrone
[2-Et-DMPO (19) and 2-Ph-DMPO (20) were recorded and
are collected in Table 4. It is noteworthy that the phosphityl
adduct of DMPO (30) was not observed. In its place the
oxidation product DMPOXž (2-oxo-5,5-dimethylpyrrolidine-
N-oxyl) was seen. In terms of persistence, the number of
ESR lines, and the relatively large (ˇ-phosphorus hyperfine
splitting, it appears that the phosphityl adduct of 2-Et-DMPO
(32) represents the best prototypical nitroxide examined here
for use in magnetometry. Finally, it is worth mentioning that
we are currently searching for phosphorus-centred radicals
(e.g. žPR2, etc.) because these species may exhibit even larger
hyperfine splittings (10–100 mT).63 The challenge, so far,
has been to synthesize phosphorus-centred radicals64,65 with
sufficient persistence to be useful in real life magnetometric
applications. Finally, it should be noted that the ESR
hyperline splittings (hfs) of some known ˇ-phosphorus
nitroxides are collected in Table 4.51,55–68 High magnitude
ESR lines such as those from 31P nuclei (spin 1/2) generally
lead to better DNP responses, although the effect may be
complicated.
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Acknowledgements
This work is supported by the Natural Sciences and Engineering
Research Council of Canada (NSERC). Grateful acknowledgement is
hereby made. Special thanks are due to Mrs Moira Simpson-McPake
and Miss Beverley Healy for helping to type the manuscript.
34. Tufariello JJ. Acc. Chem. Res. 1979; 12: 396.
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