2,5-Dihydro-1H-imidazole-based nitroxides as prospective mediators in living radical polymerization

Article abstract of DOI:10.1002/hlca.200690218

A number of spectroscopic methods were applied to obtain kinetic parameters of reactions modelling the 2,5-dihydro-1H-imidazole 1-oxide mediated living polymerization of acrylates. The homolysis rate constants of alkoxyamines based on five nitroxides were

Full text of DOI:10.1002/hlca.200690218

Helvetica Chimica Acta – Vol. 89 (2006)
2341
2,5-Dihydro-1H-imidazole-Based Nitroxides as Prospective Mediators in
Living Radical Polymerization
by Dmitry Zubenkoa), Igor Kirilyukb), Galina Roshchupkinab), Irina Zhurkob), Vladimir Reznikovb),
Sylvain R. A. Marquec), and Elena Bagryanskaya*a)
a) International Tomography Center SB RAS, Institutskaya 3A, 630090 Novosibirsk, Russia
(phone: +7-3833333425; fax: +7-3838331399; e-mail: elena@tomo.nsc.ru)
b) Institute of Organic Chemistry SB RAS, Institutskaya 3A, 630090 Novosibirsk, Russia
c) UniversitØ de Provence, UMR-6517 Chimie, Biologie, Radicaux Libres, Case 542, Avenue Escadrille
Normandie-Niemen, F-13397 Marseille Cedex 20
Dedicated to the memory of Professor Hanns Fischer
A number of spectroscopic methods were applied to obtain kinetic parameters of reactions model-
ling the 2,5-dihydro-1H-imidazole 1-oxide mediated living polymerization of acrylates. The homolysis
rate constants of alkoxyamines based on five nitroxides were measured by EPR spectroscopy at different
temperatures. The recombination rate constants kc between the corresponding alkyl radicals and the
nitroxides were measured by means of laser flash photolysis. The time-resolved chemically induced
dynamic nuclear polarization (TR-CIDNP) experiments revealed the negligible contribution of dispro-
portionation in the recombination reaction. In addition, the thermodecomposition of alkoxyamines in
the NMR probe showed the absence of intramolecular elimination of hydroxylamines from the corre-
sponding alkoxyamines. Analysis of the kinetic parameters showed that the 2,5-dihydro-1H-imidazole
1-oxide type radicals are promising mediators for the living polymerization of acrylates and methacry-
lates.
Introduction. – Nitroxide-mediated polymerization [1][2] (NMP) is a fine synthetic
technique, which allows for the design of new types of homo- and copolymers with well-
defined architectures and narrow molecular-mass distributions [3]. The principal mech-
anism of NMP (Scheme 1) involves the reversible dissociation of a dormant nitroxide
end-capped polymer chain with rate constant kd, the propagation of C-centered radi-
cals with rate constant kp, the cross-coupling reaction between the nitroxide and the
growing polymer chain with rate constant kc, and simultaneous irreversible self-termi-
nation reactions of the C-centered radicals with rate constant kt.
Scheme 1
ꢀ 2006Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
The main contribution to the understanding of the NMP mechanism has been done
by Fischer [4][5] and Goto and Fukuda [6]. It has been shown [7][8] that the equili-
brium constant K=kd/kc should fall in the range from 10ꢀ7 to 10ꢀ11 mol lꢀ1 for efficient
NMP of common monomers. Despite the fact that NMP of monomers based on styrene
(=ethenylbenzene) and acrylate (=prop-2-enoate) using a large variety of nitroxides
became a routine procedure [3][9], the development of new mediators to be used in
the (co)polymerization of methacrylates (=2-methylprop-2-enoates), acrylamides
(=2-prop-2-enamides), and dienes [10] still remains a challenging task for many
research groups [11–13].
Stable 2,5-dihydro-1H-imidazol-1-yloxy radicals with different bulky substituents at
the positions 2 and 5 of the imidazole ring (Fig. 1) are efficient [14] as pH probes in bio-
logical systems, but the overall suitability of these nitroxides for the purposes of NMP
has not yet been determined. Aiming at possible applications of this type of nitroxides
(Fig. 1) as mediators in NMP of acrylate-type monomers, we studied the model reaction
occurring during decomposition/reformation of the corresponding alkoxyamines. The
present communication deals with the application of a number of experimental spectro-
scopic techniques to acquire maximum kinetic information on these processes.
Results and Discussion. – The Coupling Rate Constants kc1. For the measurements
of radical cross-termination rate constants kc, we applied the same approach as previ-
Fig. 1. Model nitroxides 1–5, alkyl radicals a–c, and corresponding alkoxyamines

Helvetica Chimica Acta – Vol. 89 (2006)
2343
ously published by Sobek and Fischer [15], and Ingold and co-workers [16–18]. The C-
centered radicals a–c (MP=methyl propionate-2-yl (=2-methoxy-1-methyl-2-
oxoethyl), MiB=methyl isobutyrate-2-yl (=2-methoxy-1,1-dimethyl-2-oxoethyl), and
tBiB=ꢁtert-butyl isobutyrate-2-ylꢂ (=2-(tert-butoxy)-1,1-dimethyl-2-oxoethyl), respec-
tively) were generated by laser pulse photolysis of the corresponding symmetric
ketones RꢀCOꢀR. These radicals are the simplest models of propagating radicals
formed during the polymerization of methyl or tert-butyl methacrylate and methyl ac-
rylate. The photochemistry of the ketones is known [19]. After the excitation of the
n–p* transition and intersystem crossing, the ketones undergo a-cleavage from the trip-
let state yielding geminate (in-cage) acyl-alkyl radical pairs. The geminate reactions of
recombination and disproportionation result in the restoration of the initial ketone Rꢀ
COꢀR and in the formation of aldehyde RꢀCHO and alkene R(ꢀH). The escaped
acyl radicals undergo a fast decarbonylation reaction with the rate constant
k
CO =2·107 sꢀ1 for MP (a) [20] and kCO =8·106 sꢀ1 for MiB (b) [21]. The consequent
bulk reactions of radical termination kt rise to the formation of products RꢀR, RH,
and R(ꢀH). In the presence of nitroxide, these reactions are partly or entirely replaced
by the formation of alkoxyamine RꢀY due to the coupling of C-centered radicals R
with the nitroxide Y, and by the formation of the hydroxylamine YꢀH and the alkene
due to the H-abstraction from the C-centered radicals by the nitroxide [15][22]. In the
absence of niꢀtr1oxides, the C-centered radicals decay in a second-order reaction with
ꢀ1
kt =1.8·109
M
sꢀ1 for MiB and kt =1.2·109
M
sꢀ1 for MP. With the nitroxide added,
the kinetic curves become first-order decay. The observed pseudo-first-order rate con-
stant km was found to be proportional to the nitroxide concentration, km =k0 +kc ·[Y]
(k0 for the processes observed in the absence of nitroxide). The concentration depend-
encies of km are shown in Fig. 2, and the calculated values of kc are listed in Table 1. One
can see that kc values decrease with increasing congestion around both the nitroxide
moiety and the alkyl-radical centre, in accordance with previously observed trends
for other nitroxides [23–25].
Table 1. Coupling Rate Constants for the Reaction of Nitroxides 1–3 and 5 with Alkyl Radicals a–c in
Benzene at Room Temperature
ꢀ1
Nitroxide
Radical
kc [108
M
sꢀ1
]
1
1
2
2
3
5
a
c
a
b
a
c
16.0(2.0)
4.8(1.5)
12.0(2.0)
6.3(1.4)
4.6(1.8)
1.2(0.3)
EPR Measurements of Homolysis Rate Constants kd. The rate constants of the
alkoxyamines decay kd were obtained by monitoring the appearance of the nitro-
xide-radical EPR signal during decomposition of the corresponding alkoxyamines
[26]. The chlorobenzene solution was used with O2 as a scavenger for the C-centered
radicals. The growth of nitroxide-radical concentration obeyed to the expected first-
order kinetic law. The evaluation of the activation energy of homolysis was made by

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Helvetica Chimica Acta – Vol. 89 (2006)
Fig. 2. Concentration dependencies of the apparent rate constant km for the cross-coupling of radicals
a–c with nitroxides 1–3 and 5 in benzene at room temperature
using the averaged frequency factor A=2.4·1014 sꢀ1 [27–29]. The DEa (8.7 kJ/mol,
Table 2) measured for homolysis of the CꢀON bond between 1a and 4a is close to
the value expected (DEa =11.0 kJ/mol estimated for the styrene fragment)
[23][26][29].
Table 2. Experimentally Measured Rate Constants of Thermal Decomposition of Alkoxyamines 1a, 2a, 4a,
and 5c in C6H5Cl
T [8]
kd [sꢀ1] [1208]a)
Ea [kJ/mol]
1a
2a
4a
5c
140
140
130
80–120
1.4·10ꢀ5
1.1·10ꢀ5
1.9·10ꢀ4
6.8·10ꢀ3
144.8
145.5
136.1
124.5
a)
Estimated with A=2.4·1014 sꢀ1, see [23][26][27].
Time-Resolved Chemically Induced Dynamic Nuclear Polarization (TR-CIDNP)
Experiments and Side Reactions. The photolysis of the ketones in the magnetic field
of the NMR spectrometer [24] led to the formation of highly intensive CIDNP (Fig.
3). The absorption CIDNP signals are observed for the initial compound RꢀCOꢀR
(I in Fig. 3,a), and the emission signals for the escape products RꢀR and RH (IV
and III, resp., in Fig. 3,a), as predicted by Kapteinꢂs rules [30] (Dg>0, A(Me)>0).
The alkene R(ꢀH) (II in Fig. 3,a) can be formed both in geminate reactions and in
the bulk. Therefore, immediately after the laser pulse, the signal from the Me group
of R(ꢀH) is in emission [24], which then decays on the microsecond timescale due
to the compensation by absorptively polarized molecules of R(ꢀH) formed in the
bulk (the so-called CIDNP cancellation effect [31]). In the presence of nitroxides,
both the CIDNP spectra (Fig. 3,b) and the kinetics change significantly [24]. Strong

Helvetica Chimica Acta – Vol. 89 (2006)
2345
Fig. 3. CIDNP Spectrum taken 100 microsecond after laser pulse photolysis of ketone I a) in the
absence and b) in the presence of nitroxide 2. I=MeOOCC(Me)2COC(Me)2COOMe,
II=MeOOCC(Me)=CH2, III=MeOOCCH(Me)2, IV=MeOOCC(Me)2C(Me)2COOMe, and
V=MeOOCC(Me)2Y (Y derived from nitroxide 2)
A
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
emissive signals are observed at d 1.4–1.5, which correspond to the Me group of the
coupling product RꢀY (V in Fig. 3,b). The polarization shows the fast growth in inten-
sity at short time delays, and then reaches a plateau after ca. 1–2 ms. The presence of the
nitroxide inhibits the formation of bulk products RꢀR, RH and R(ꢀH), as indicated by
the absence of any emissive bulk polarization on these products. The absence of bulk
polarization from the products R(ꢀH) and YH, demonstrates the negligible contribu-
tion of H-abstraction in the reaction between R and Y (<2%). A typical CIDNP spec-
trum for nitroxide 2 and alkyl radical b is shown in Fig. 3.
Thermal Decomposition of Alkoxyamines in NMR Probe. The most important pro-
cess which can interfere with the reactions shown in Scheme 1 [22][32][33] is the trans-
fer of HꢀC(b) from the alkyl radical to the nitroxide. This process leads to the forma-
tion of a polymeric chain with a terminal C=C bond and a hydroxylamine and can occur
due to a radical cross-disproportionation (vide supra) or a nonradical hydroxylamine
elimination [22]. To check contributions of these reactions, the thermal decomposition
of the three alkoxyamines 1a, 2a, and 4a was studied by means of 1H-NMR in degassed
solution and in the absence of other scavengers. The analysis of the experimental NMR
spectra revealed no formation of methyl acrylate after 10 h of homolysis at 12081),
which agrees with the CIDNP experiments and also allows us to neglect the nonradical
decomposition of alkoxyamines.
Fischerꢀs Diagram Approach. For the prediction of the NMP result, Fischer
[8][34][35] developed the phase-diagram approach (Fig. 4) based on Eqns. 1–3, pro-
1
)
This time corresponds to roughly 50% decomposition under scavenging conditions.

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Helvetica Chimica Acta – Vol. 89 (2006)
viding both the living fraction (0<Fꢁ1 being the percentage of dead chains, Eqn. 1),
the polydispersity index (PDI with d=PDIꢀ1 (PDI>1.1), Eqn. 2), and the time of
polymerization (t90% being the time for 90% monomer conversion, Eqn. 3). For a
given monomer (kp and kt), the success of the NMP experiments, i.e., high livingness
(F>80%) and high control (PDI<1.5), depends on the kd and kc values of the dormant
species. Hence, applying Eqns. 1–3 for given experimental conditions – polymerization
temperature, polymerization time, conversion, chain length – it is possible to predict the
feasibility of the polymerization or not. Therefore, this approach requires an accurate
determination of kd and kc. The values of kp and kt were given by Buback and co-work-
ers [36][37] as averaged values from PLP-SEC experiments, where the monomer con-
version did not exceed 3%.
kp ꢂ ½alkoxyamineŠ
kd
kc
0
ꢁ
ꢂ F2
(1)
2ln10 ꢂ kt
p ꢂ k3 ꢂ ½alkoxyamineŠ
1
d2
0
p
kd ꢂ kc ꢃ
ꢂ
(2)
(3)
kt
3
kd
ꢃ
kc
ð2ln10Þ ꢂkt
9 ꢂ k3p ꢂ ½alkoxyamineŠ0ꢂt920%
Fig. 4. Fischerꢀs phase diagram for NMP of methyl methacrylate. Parameters for Eqns. 1–3: T 808,
[alkoxyamine]0 =5·10ꢀ2 mol/l, kp =1298 l molꢀ1 sꢀ1, kt =3.21·107 l molꢀ1 sꢀ1 (see [8]), values of kc1 and
kd from Table 3.
As it was shown by Tordo and co-workers [38], the correct calculation of NMP
could be done only by taking account of the kd and kc dependence on the length of
the polymer chain. Therefore, kd and kc values implemented in the phase diagrams

Helvetica Chimica Acta – Vol. 89 (2006)
2347
(Figs. 4 and 5) were corrected for the account of the penultimate effect on homolysis in
cases of methyl methacrylate (MMA) [28][39] and butyl acrylate [40] polymerizations,
as well as for the account of the chain-length effect on the recombination [41][42]. The
phase-diagram approach (Fig. 4) predicts possible successful NMP of MMA lasting one
day for nitroxide 1–3 at 808, achieving 90% conversion, and 80% of living chains, and
very low PDI. In the case of the methyl acrylate (Fig. 5), successful NMP is predicted
for nitroxides 3 and 4, reaching 90% conversion in one day, and higher PDI (1.4), and
80% living chains. Aiming at slightly higher PDI, successful NMP of methyl acrylate
would be possible with nitroxides 1 and 2.
Fig. 5. Fischerꢀs phase diagram for NMP of methyl acrylate. Parameters for Eqns. 1–3: T 1408,
[alkoxyamine]0 =10ꢀ3 mol/l, kp =114.2·103 l molꢀ1 sꢀ1, kt =5.05·107 l molꢀ1 sꢀ1 (see [8]), values of kc1
and kd from Table 3.
Conclusions. – We showed, that for the proper ratio of homolysis/reformation rate
constants kd and kc in the absence of side reactions (hydroxylamine elimination), the
nitroxides studied can be promising mediators in polymerization of acrylate and meth-
acrylate monomers. In both cases, the living fraction is expected to be above 80% at
90% conversion at a reasonable reaction time (24 h), and with the PDI values in the
acceptable range of 1.1–1.4. The polymerization experiments are in progress, and
the results will be published in a subsequent report.
We are very thankful to Dr. G. Ananchenko for very helpful discussions and to Dr. Yu. Tsentalovich
for help with the laser-flash photolysis experiments. This work was supported by RFBR (grant Nos. 05-03-
32370 and 04-03-32299). D. Z. acknowledges a grant from INTASYSN (No. 05-109-5102). E. B. is very
grateful to the University of Provence.

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Helvetica Chimica Acta – Vol. 89 (2006)
Table 3. Estimated kc1 and kd for the Phase Diagrams for the Polymerization of Methyl Methacrylate and
Methyl Acrylate
ꢀ1
ꢀ1
kc1a) [106
M
sꢀ1
]
Ea ) [kJ/mol]
kd ) [s ]
b
c
Reaction
160(2)d)
120(2)d)
144.8
3.5·10ꢀ4
2.8·10ꢀ4
3.0·10ꢀ3
4.4·10ꢀ3
4.3·10ꢀ3
3.4·10ꢀ3
6.3·10ꢀ3
)
)
)
)
)
)
)
e
e
e
e
1+aÐ1a
2+aÐ2a
3+aÐ3a
4+aÐ4a
1+bÐ1b
2+bÐ2b
3+bÐ3b
145.5
137.4f)
136.1
125.7j)
126.4l)
124.5m)
46(1.8)d)
46(1.8)d)g)
4.8(1.5)h)i)
6.3(1.4)h)
k
k
k
1.2(0.3)h)m)
a) kc are given at room temperature. It was assumed that no significant changes occur with T, see
[15–18][23][24]. b) Given in Table 2 unless otherwise mentioned. c) Estimated with A=2.4·1014 sꢀ1, see
[26][27][29]. d) To take into account the chain-length effect, kc1 =kc/10 (see [41]). kc given in Table 1
e
unless otherwise mentioned.
) Chain-length effect was assumed around a factor three, i.e.,
kd =3·Aexp(ꢀEa/RT), see [40]. f) Estimated from Ea
A
yl group as sterically demanding as two Et groups. g) Aweak polar effect was assumed as exemplified with
1 and 2 (Table 1).h) To take into account the chain-length effect, kc1 =kc/100 (see [42]). kc given in Table 1
unless otherwise mentioned. i) The influence of the ester-group size on kc was assumed to be insignificant,
j
see [25]. ) Estimated from Ea
G
kd =70·Aexp(ꢀEa/RT), see [39]. ) Estimated from Ea
(2a)ꢀ19.1 kJ/mol (see [28]). m) kc1
(3b)=kc1(5c)
and kd(3b)=kd(5c) assuming the same steric effect for two Et groups and the cyclohexyl group, see [29].
A
ACHTREUNG
Experimental Part
General. The solvents benzene, chlorobenzene, and MeCN were distilled prior to use. CC=Column
chromatography. UV Spectra: HP-Agilent-8453 spectrometer; EtOH solns.; in nm (log e). IR Spectra:
1
Bruker-Vector-22-FT-IR spectrometer; KBr pellets (concentration 0.25%; pellet thickness 1 mm). H-
NMR Spectra: Bruker-AV300 (300.1 MHz) spectrometer; 5% solns.; with the solvent signal as the stan-
dard; d in ppm, J in Hz. 13C-NMR Spectra: Bruker-AV300 (75.5 MHz) and Bruker-AM-400 (100.6MHz)
spectrometers; 5–10% solns. at 300 K, with the solvent signal as the standard; d in ppm. High-resolution
(HR) MS: Finnigan-8200 spectrometer; in m/z. Element analyses were performed in the Microanalysis
Laboratory of NIOCh, Novosibirsk.
Materials. Ketone concentrations were 20 mM in the case of 2,4-dimethyl-3-oxopentanedioic acid
dimethyl ester, 2,2,4,4-tetramethyl-3-oxopentanedioic acid dimethyl ester (I), and 2,2,4,4-tetramethyl-
3-oxopentanedioic acid di(tert-butyl) ester. The concentrations of the nitroxides were varied from 2 to
10 mM. The ketones were synthesized according to [43][44] and purified by column chromatography.
The nitroxides 1 [45], 2 [45] and 4 [14] were prepared by the published procedures. The nitroxides 3
and 5 were synthesized according to Scheme 2 from 6 via 7–9 by using two subsequent ethylmagnesium
bromide additions to 2H-imidazole 1-oxides and oxidation steps. Similar syntheses of 2,5-dihydro-1H-
imidazole-1-oxy radicals by using organometallic-reagent additions to 2H-imidazole 1-oxides have
been described earlier [46].
The alkoxyamines 1a, 2a, 4a, and 5c were prepared by the method developed by Matyjaszewski and
co-workers [47], see Scheme 3.
General Procedure for Alkoxyamine Preparation. A mixture of the nitroxide 1, 2, 4, or 5 (2.2 mmol),
2-bromo-2-methylpropanoic acid tert-butyl ester (0.5 g, 2.25 mmol), Cu powder (140 mg, 2.25 mmol),
4,4’-di(tert-butyl)-2,2’-bipyridine (24 mg, 0.09 mmol), Cu(OTf)2 (8 mg, 0.023 mmol; TfO=CF3SO3),
and benzene (5 ml) was placed in a Schlenk flask and degassed by three freeze-pump-thaw cycles. The
soln. was heated to 758 and stirred for 24 h. The benzene was evaporated and the residue separated by
CC (Al2O3, hexane/Et2O 10 :1).
A
2-Phenyl-1,4-diazaspiro[4.5]deca-1,3-diene 4-oxide (7a) was prepared according to the method
described in [48].

Helvetica Chimica Acta – Vol. 89 (2006)
2349
Scheme 2
Scheme 3
2,2-Diethyl-4-phenyl-2H-imidazole 1-oxide (7b) was prepared similarly to 7a. A mixture of 2-oxo-2-
phenylacetaldehyde oxime (6) (3 g, 20 mmol), pentan-3-one (5 ml, 71 mmol), ammonium acetate (9 g,
117 mmol), and AcOH (10 ml) was stirred at 408 for 8 h (TLC (Silufol UV 254, Et2O/hexane 1:2) mon-
N
itoring of 6). The mixture was poured into H2O (200 ml) and extracted with CHCl3. The CHCl3 extract
was washed with 5% NaOH soln. and dried (MgSO4), the solvent evaporated, and the residue separated
by CC (alumina, CH2Cl2): 7b (2.4 g, 55%). Pinkish crystals. M.p. 45–478 (hexane). UV/VIS (EtOH): 233
(4.27), 277 (4.20). IR (KBr): 3077 (N=CꢀH), 2974, 2935, 2881 (CH3, CH2), 1605, 1590, 1563, 1514 (C=N).
1H-NMR (400 MHz, CDCl3): 0.59 (t, J=7.2, 2 MeCH2); 1.92, 2.08 (AB(q), JAB =14, 3J=7.2, 2 MeCH2);
7.40 (m, 2 Hm, Hp); 7.70 (s, HꢀC(5)); 7.82 (m, 2 Ho). 13C-NMR (100 MHz, CDCl3): 6.6 (MeCH2); 29.9
(MeCH2); 107.3 (C(2)); 126.5 (C(5)); 127.0 (Co); 128.8 (Cm); 131.1 (Cipso); 131.4 (Cp); 165.9 (C(4)).
Anal. calc. for C13H16N2O: C 72.19, H 7.46, N 12.95; found: C 72.05, H 7.30, N 13.03.
2,2,5-Triethyl-2,5-dihydro-1-hydroxy-4-phenyl-1H-imidazole (8b). A soln. of 7b (3.25 g, 15 mmol) in
dry THF (30 ml) was added to 1M EtMgBr in Et2
ACHTREUNG
mixture was quenched with H2O. The aq. layer was extracted with Et2
A
ACHTREUNG

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Helvetica Chimica Acta – Vol. 89 (2006)
(MgSO4), the solvent evaporated, and the residue recrystallized from hexane: 8b (1.67 g, 45%). Colorless
crystals. M.p. 137–1408. UV/VIS (EtOH): 237 (4.17). IR (KBr): 3167 (OH), 3032 (=CꢀH), 2979, 2962,
1
2922, 2879, 2838 (Me, CH2), 1631 (C=N). H-NMR (200 MHz, CDCl3): 0.74 (t, J=7.4, MeCH2ꢀC(5));
0.87, 0.88 (2t, J=7.4, 2 MeCH2ꢀC(2)); 1.85 (m, 3 CH2); 4.47 (dd, J=3.6, 6, HꢀC(5)); 6.79 (br. s, OH);
7.34 (m, 2 Hm, Hp); 7.54 (m, 2 Ho). 13C-NMR (100 MHz, CDCl3): 7.8 (MeCH2ꢀC(5)); 8.6, 8.9
(MeCH2ꢀC(2)); 24.4, 27.3 (MeCH2ꢀC(2)); 31.8 (MeCH2ꢀC(5)); 74.9 (C(5)); 95.2 (C(2)); 127.0 (Co);
128.2 (Cm), 130.1 (Cp); 133.3 (Cipso); 171.4 (C(4)). Anal. calc. for C15H22N2O: C 73.13, H 9.00, N 11.37;
found: C 73.42, H 9.21, N 11.44.
2,2,4-Triethyl-5-phenyl-2H-imidazole 3-Oxide (9b). Lead dioxide 15 g (63 mmol) was added portion-
wise to a stirred soln. of 8b (3.2 g, 12.4 mmol) in CHCl3 (30 ml), the mixture was stirred for 2 h, lead
oxides were filtered off, CHCl3 was evaporated, and the residue was separated by CC (silica gel 60
(Merck), hexane/tBuOMe 4 :1): 9b (2.8 g, 89%). Brownish oil. UV/VIS (EtOH): 231 (4.01), 273 (3.89).
IR (neat): 3062 (=CꢀH, Ph), 2974, 2936, 2880 (CH3, CH2), 1515, 1566 (C=N, C=C). 1H-NMR (400
MHz, CD
A
J
AB =14, J=7.2, 2 MeCH2ꢀC(2)); 2.80 (q, J=7.6, MeCH2ꢀC(4)); 7.58 (m, 2 Hm, Hp); 7.80 (m, 2 Ho).
13C-NMR (100 MHz, CD3
A
(MeCH2ꢀC(2)); 104.6(C(2)); 128.2 (C o); 129.6(C m); 131.7 (Cp); 132.9 (Cipso); 144.4 (C(4)); 168.8
(C(5)). Anal. calc. for C15H20N2O: C 73.74, H 8.25, N 11.47; found: C 73.32, H, 8.01, N 11.14.
2,2,5,5-Tetraethyl-2,5-dihydro-4-phenyl-1H-imidazol-1-yloxy (3). A soln. of 9b (1.6g, 6.6mmol) in
dry Et
A
ACHTREUNG
for 0.5 h and quenched with H2O. The aq. layer was extracted with Et2
AHCTREUNG
dried (MgSO4). Then MnO2 (5 g, 57 mmol) was added, and the mixture was stirred for 2 h. The precip-
itate was filtered off, the solvent evaporated, and the residue separated by CC (silica gel 60 (Merck), hex-
ane/Et
A
2972, 2939, 2880 (CH3, CH2), 1601, 1572 (C=N, C=C). Anal. calc. for C17H25N2O: C 74.68, H 9.22, N
10.25; found: C 75.48, H 9.16, N, 9.98.
2,2-Diethyl-3-phenyl-1,4-diazaspiro[4.5]dec-3-en-1-yloxy (5). A 1M soln. of EtMgBr in Et2
was added dropwise to a stirred soln. of 7a (2 g, 8.8 mmol) in dry THF (20 ml). The soln. was stirred for
0.5 h and then poured into the vigorously stirred cold (08) mixture of Et2O (65 ml) and AcOH (14 ml).
Then H2O (200 ml) was added to the mixture, the aq. phase extracted with Et2O, and the combined
A
AHCTREUNG
AHCTREUNG
extract washed with sat. NaHCO3 soln. and dried (MgSO4): crude soln. of 3-ethyl-4-hydroxy-2-phenyl-
1,4-diazaspiro[4.5]dec-1-ene (8a). Colorless crystals were obtained from AcOEt. M.p. 184–186.58. UV/
1
VIS (EtOH): 241 (4.14). IR (KBr): 3175 (OH), 2987, 2962, 2928, 2852 (CH3, CH2), 1621 (C=N). H-
NMR (200 MHz, CD
(m, 7 H, MeCH2, (CH2)); 1.88 (m, 1 H, (CH2)5); 4.16( dd, J=10, 4, HꢀC(3)); 7.12 (m, 2 Hm, Hp); 7.35
(m, 2 Ho). 13C-NMR (50 MHz, CD3
OD/CDCl3 1:10): 10.4 (MeCH2); 22.7, 22.8, 25.0, 25.2, 31.1, 37.5
E
AHCTREUNG
(MeCH2, (CH2)5); 78.4 (C(3)); 92.3 (C(5)); 127.4 (Co); 128.0 (Cm); 130.0 (Cp); 132.7 (Cipso); 171.1
(C(3)). Anal. calc. for C16H22N2O: C 74.38, H 8.58, N 10.84; found: C 74.11, H 8.58, N 10.70.
The crude soln. of 8a was stirred with MnO2 (15 g, 170 mmol) for 1 h. The oxidant was filtered off and
the solvent evaporated: crude 2-ethyl-3-phenyl-1,4-diazaspiro[4.5]deca-1,3-diene 1-oxide (9a). A sample
was purified by CC (silica gel 60 (Merck) hexane/tBuOMe 4 :1): brownish oil. UV/VIS (EtOH): 229
1
(3.90), 269 (3.73). IR (neat): 3062 (=CꢀH, Ph), 2937, 2858 (CH3, CH2), 1564, 1515 (C=N, C=C). H-
NMR (200 MHz, CDCl3): 1.07 (t, J=7.6, MeCH2); 1.83 (m, 8 H, (CH2)5); 2.17 (m, 2 H, (CH2)5); 2.69
(q, J=7.6, MeCH2); 7.44 (m, 2 Hm, Hp); 7.67 (m, 2 Ho). 13C-NMR (50 MHz, CDCl3): 9.6( MeCH2);
17.4, 23.0, 34.8 ((CH2)5); 24.6(Me CH2); 101.5 (C(5)); 127.5 (Co); 128.7 (Cm); 130.6(C ); 132.7 (Cipso);
p
140.8 (C(2)); 166.5 (C(3)). Anal. calc. for C16H20N2O: C 74.97, H 7.86, N 10.93; found: C 74.68, H
8.31, N 10.34.
The crude 9a was dissolved in dry Et
2O (80 ml). The resulting mixture was stirred for 1 h and quenched with sat. aq. NH4Cl soln. The aq.
phase was extracted with Et2O and the combined extract dried (MgSO4). Then MnO2 (10 g, 114 mmol)
2O (20 ml), and the soln. was added dropwise to 1M EtMgBr in
Et
ACHTREUNG
AHCTREUNG
was added and the mixture stirred for 1 h. The oxidant was filtered off, the solvent evaporated, and the
residue separated by CC (silica gel 60 (Merck), hexane/CHCl3 2 :1): 5 (1 g, 40%). Yellow crystals. M.p.
97–998. UV/VIS (EtOH): 245 (4.19). IR (KBr): 3060, 3024 (HꢀC=, Ph), 2978, 2962, 2933, 2856 (CH3,

Helvetica Chimica Acta – Vol. 89 (2006)
2351
CH2), 1598, 1571 (C=N, C=C). Anal. calc. for C18H25N2O: C 75.75, H 8.83, N 9.82; found: C 75.36, H 8.61,
N 9.68.
Methyl 2-[(2,5-Dihydro-2,2,4,5,5-pentamethyl-1H-imidazol-1-yl)oxy]propanoate (1a). Yield 45%.
1
Colorless oil, a mixture of diastereoisomers. IR (neat): 1754 (C=O), 1656 (C=N). H-NMR(200 MHz,
CDCl3): 4.28 (m, OCHMe); 3.67 (s, MeO); 1.83 (s, MeꢀC(4)); 1.34, 1.30, 1.28 1.29, 1.25, 1.18, 1.14 (2
MeꢀC(2)), 2 MeꢀC(5)). 13C-NMR (50 MHz, CDCl3): 15.2 (MeꢀC(4)); 15.8 (OCHMe); 17.05, 17.1,
23.2, 23.5 (MeꢀC(5)); 27.0, 28.2, 30.3, 31.5 (MeꢀC(2)); 51.4 (MeO); 72.9 (C(5)); 79.6, 79.8 (OCHMe);
90.8, 90.9 (C(2)); 172.7 (C(4)); 173.8, 174.1 (C=O). HR-MS: 242.16286 (C
A
G
N
Methyl 2-[(2,5-Dihydro-2,2,5,5-tetramethyl-4-phenyl-1H-imidazol-1-yl)oxy]propanoate (2a). Yield
30%. Colorless oil, a mixture of diastereoisomers. UV/VIS (EtOH): 237 (3.90). IR (neat): 1755 (C=
O), 1617 (C=N). 1H-NMR(200 MHz, CDCl3): 1.55, 1.50, 1.49, 1.48, 1.45, 1.43, 1.41, 1.38, 1.36, 1.35
(10s, 2 MeꢀC(2), 2 MeꢀC(5), OCHMe); 3.71, 3.72 (2s, MeO); 4.37 (m, OCHMe); 7.35 (m, 3 arom.
H); 7.65 (m, 2 arom. H). 13C-NMR (50 MHz, CDCl3): 17.0 (OCHMe); 21.1, 21.3, 23.0, 23.3 (Meꢀ
C(5)); 28.1, 29.2, 30.0, 31.2 (MeꢀC(2)); 51.3 (MeO); 72.55, 72.6(C(5)); 79.6, 79.9 (O CHMe); 90.1,
90.3 (C(2)); 127.4, 127.9, 129.5 (Co, Cm, Cp); 133.4, 133.5 (Cipso); 172.0, 172.8 (C=N); 173.5, 173.8 (C=
O). HR-MS: 304.17939 (C17
A
G
N
Methyl 2-[(2,2,5,5-Tetraethyl-2,5-dihydro-4-methyl-1H-imidazol-1-yl)oxy]propanoate (3a). Yield
1
30%. Colorless oil, a mixture of diastereoisomers. IR (neat): 1755 (C=O), 1663 (C=N). H-NMR (200
MHz, CDCl3): 0.62–0.72 (m, 1 Me); 0.79–0.97 (m, 3 Me); 1.23 (m, 1 Me); 1.37–1.82 (m, 6H, CH 2);
1.81, 1.78 (s, MeC=N); 1.86–1.98 (m, 2 H, CH2); 3.64, 3.63 (s, MeO); 4.22 (m, OCHMe). 13C-NMR
(50 MHz, CDCl3): 8.8, 8.9, 9.0, 9.3, 10.2, 10.25, 10.3, 10.35, 16.8, 16.9, 17.0 (MeCH2ꢀC(2), MeCH2ꢀ
C(5), MeꢀC(4), OCHMe); 27.0, 27.2, 27.6, 28.5, 28.6, 29.7, 30.3, 31.4 (MeCH2ꢀC(2), MeCH2ꢀC(5));
51.2, 51.3 (MeO); 78.3, 78.6(O CHMe); 79.4, 80.0 (C(5)); 95.1, 95.6(C(2)); 172.0, 172.4 (C =N); 173.7,
174.3 (C=O). HR-MS: 298.22582 (C
A
G
N
tert-Butyl 2-Methyl-2-[(2,2-diethyl-3-phenyl-1,4-diazaspiro[4.5]dec-3-en-1-yl)oxy]propanoate (5c).
Yield 84%. Colorless oil. IR (neat): 3058 (=CꢀH, Ph), 2935, 2858 (CH3, CH2), 1732 (C=O), 1630,
1576(C =N, C=C). 1H-NMR(400 MHz, CDCl3): 0.75 (t, J=8, 1 MeCH2); 0.89 (t, J=8, 1 MeCH2); 1.40,
t
1.41 (2s, OC(Me)
G
H, (CH2)5); 2.27 (m, 1 H, MeCH2); 7.36( m, 2 Hm, Hp); 7.73 (m, 2 Ho). 13C-NMR (75 MHz, CDCl3):
9.5, 11.4 (MeCH2); 25.0, 25.1 (OC(Me)2CO); 28.0 (Me3C); 24.0, 24.6, 26.3, 27.9, 31.1, 33.7, 39.5 (CH2);
80.8 (C(2)); 81.8 (Me3C); 93.8 (C(5)); 127.8 (Co); 128.3 (Cm); 129.5 (Cp); 135.2 (Cipso); 166.8 (C=N);
173.5 (C=O). Anal. calc. for C26H40N2O3: C 72.86, H 9.41, N 6.54; found: C 72.51, H 8.93, N 6.66.
Time-Resolved(TR)-CIDNP and NMR Experiments. A sample, purged with Ar and sealed in a stan-
dard NMR Pyrex tube, was irradiated by a COMPEX-Lambda-Physik excimer laser (wavelength 308
nm, pulse energy up to 150 mJ) in the probe of an Avance-200 NMR spectrometer. TR-CIDNP experi-
ments were carried out with the usual pulse sequence: presaturation–laser pulse–evolution time–detec-
tion pulse–free induction decay. Because the background signals in CIDNP spectra were suppressed by
the presaturation pulses, only signals of the polarized products formed during the variable delay between
the laser and NMR radio frequency (rf) pulse appeared in the CIDNP spectra. The rf pulse used had a
duration of 3 ms, which corresponds to a flip angle of 308.
Decomposition of alkoxyamines at 1208 were performed in sealed NMR tubes in the probe of the
NMR spectrometer. Samples were degassed by three freeze–pump–thaw cycles and sealed in a standard
NMR Pyrex tube. NMR Spectra were detected during decomposition every 15 min during 10 h.
Laser Flash Photolysis. A detailed description of our laser-flash-photolysis experiments has been
published earlier [49]. Solns. in a rectangular cell with inner dimensions 10 mm”10 mm were irradiated
with a Lambda-Physik-EMG-101 excimer laser 308 nm, pulse energy up to 100 mJ, pulse duration 15–20
ns. The monitoring system included a DKSh-150 xenon short-arc lamp connected to a high-current
pulser, a home-made monochromator, a 9794B photomultiplier (Electron Tubes Ltd.), and a LeCroy-
9310A digitizer. The monitoring light, concentrated in a rectangular of 3 mm height and 1 mm width,
passed through the cell along the front of the laser-irradiated window. Thus, in all experiments, the exci-
tation optical length was 1 mm, and the monitoring optical length was 8 mm. To obtain one kinetic trace,
15–20 signals were averaged. All solns. were bubbled with Ar for 15 min prior to, and all the time during
the experiments.

2352
Helvetica Chimica Acta – Vol. 89 (2006)
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Received April 28, 2006