Alkoxyamines of stable aromatic nitroxides: N-O vs. C-O bond homolysis

Article abstract of DOI:10.1002/hlca.200690215

A series of stable 2,2-disubstituted 3-(phenylimino)indol-1-oxyls, the alkoxyamines 3, were prepared, characterized, and tested as possible candidates in controlled radical polymerization (CRP). The sturctures of 3d and 10 were additionally solved by X-ra

Full text of DOI:10.1002/hlca.200690215

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Helvetica Chimica Acta – Vol. 89 (2006)
Alkoxyamines of Stable Aromatic Nitroxides: NÀO vs. CÀO Bond Homolysis
by Didier Gigmes*a), Anouk Gaudel-Sirib), Sylvain R. A. Marquea), Denis Bertina), Paul Tordoa), Paola
Astolfic), Lucedio Greci*c), and Corrado Rizzolid)
a) UMR 6517 case 542, UniversitØ de Provence, Avenue Escadrille Normandie-Niemen, F-13397 Mar-
seille Cedex 20 (fax: +33-4-91-28-87-58; e-mail: didier.gigmes@up.univ-mrs.fr)
b) UMR-CNRS 6178, UniversitØ Paul CØzanne/Aix-Marseille, FacultØ des Sciences et Techniques, Case
D12, F-13397 Marseille Cedex 20
c) Dipartimento di Scienze dei Materiali e della Terra, Università Politecnica delle Marche, via Brecce
Bianche, I-60131 Ancona (fax: +39-071-2204714; e-mail: l.greci@univpm.it)
d) Dipartimento di Chimica Generale ed Inorganica, Chimica Analitica, Chimica Fisica, Università, viale
G. P. Usberti, I-43100 Parma
Dedicated to the memory of Professor Hanns Fischer
A series of stable 2,2-disubstituted 3-(phenylimino)indol-1-oxyls, the alkoxyamines 3, were pre-
pared, characterized, and tested as possible candidates in controlled radical polymerization (CRP).
The sturctures of 3d and 10 were additionally solved by X-ray diffraction. The lability of the NÀO(C)
and (N)OÀC bonds of compounds 3 were compared, and the possibility of NÀO vs. OÀC bond cleavage
was evaluated by thermal degradation, ESR spin trapping, MS experiments, and DFT calculations.
Alkoxyamines with a primary- or secondary-alkyl group bound to the O-atom of the nitroxide function
(hexyl and i-Pr) mainly underwent (undesired) NÀO bond homolysis. When the O-alkyl radical was a
tertiary or a benzyl group (crotonyl or styryl), OÀC bond cleavage occurred as the main process, thus
suggesting a possible use of these compounds in CRP processes.
1. Introduction. – Two decades ago, Rizzardo and co-workers [1], as well as Georges
et al. [2] showed that it is possible to prepare well-defined polymers by using nitroxyl
radicals or alkoxyamines as catalysts. Nitroxide-mediated polymerization (NMP)
was, thus, born [3][4], and it inspired several studies with the aim to understand the
mechanism [5] and kinetics of polymerization [6–11], to prepare new polymers
[3][12–14], and to develop more-efficient initiators/controllers [15–22].
Among the few commercially available nitroxides, TEMPO (=2,2,6,6-tetramethyl-
piperidinooxy radical) has been widely used, although it proved to be efficient only in
the polymerization of styrene derivatives [23]. To overcome this limitation, the synthe-
sis of new nitroxides has been developed. The use of TEMPO-based nitroxides and,
above all, of acyclic nitroxides having a H-atom on one of the a-C-atoms, such as
TIPNO [17] and SG1 [24], and their corresponding alkoxyamines 1, represents a break-
through in the field of NMP. After the development of these new nitroxide radicals, it is
now possible to polymerize acrylates, acrylamides, 1,3-dienes, and acrylonitrile mono-
mers [23] with accurate control.
Up to now, the major drawback of NMP has been the difficulty in controlling the
polymerization of methacrylate derivatives [25]: livingness and control could be
ꢀ 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
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reached only in the presence of a small amount of co-monomer [26]. Recently, we over-
came this limitation by using alkoxyamines based on DPAIO (2a) nitroxides, which
allowed us to control the polymerization of methyl methacrylate at 1008, with 60% con-
version [27]. Compound 2a belongs to the family of ꢁindolinonic nitroxidesꢂ [28], aro-
matic nitroxides with the nitroxide function being in conjugation with the benzene ring.
Usually, these radical species are more stable than tetramethylpiperidino- and tetrame-
thylpyrrolidino derivatives. In particular, nitroxides 2a–c do not significantly decom-
pose when heated at 2008 in Dowtherm solution [29]. Compounds 2f–h are less stable
due to the easy elimination of alkyl radicals (i-Pr, t-Bu, Bn) from the C-atom in position
2 [28]. The nitroxides 2g and 2h have a low thermal stability, and they decompose even
at 1008.
To evaluate the efficiency of these nitroxides in NMP, the alkoxyamines 3a–d were
synthesized by alkylation of 2a, which is one of the most stable compounds among the
above selection. In particular, compound 3a was synthesized to study its activity in the
polymerization of ethylene (=ethene) [30], which is normally carried out at 2508 under
a pressure of 2000 atmospheres. The alkoxyamine 3d was designed for the controlled
polymerization of methyl methacrylate. Finally, the alkoxyamines 3e–g were synthe-
sized from 2d–f, respectively, to ascertain the role, if any, of the alkyl group at C(2).
2. Results. – 2.1. Synthesis. The alkoxyamines 3a–g (with the exception of 3d) were
prepared from the nitroxides 2a, 2e, and 2f, which were reduced in situ with phenylhy-
drazine in the presence of a stoichiometric amount of potassium tert-butoxide (tBuOK)
to give the corresponding hydroxylamine anions (Scheme 1). Addition of the appropri-
ate alkyl halide to these anions led to the formation of the desired alkoxyamines 3.
Compound 3d was easily prepared from 2a according to the atom-transfer radical-addi-

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tion (ATRA) method [31] using the corresponding activated bromide in the presence of
CuI and a small amount of Cu0 (Scheme 1). In all cases, the yields were very high, rang-
ing from 80 to 91% (see Exper. Part).
Scheme 1
The alkoxyamines 3a–g were identified on the basis of their spectroscopic data.
Both the IR and 1H-NMR spectra were very similar for all the compounds synthesized.
In particular, the IR spectra showed two characteristic bands typical of the indoline
structures [32], one at ca. 1650 cmÀ1 for the C=Ngroup, the other, the so-called Witkop
band, at ca. 1595 cmÀ1 for the PhÀNÀ(OR)ÀC group. Compound 3d showed an addi-
tional IR band at 1732 cmÀ1 for the C=O group. In the 1H-NMR spectra, as expected,
the same pattern was evident for the aromatic H-atoms of each alkoxyamine. However,
compounds 3b and 3c did not show well-resolved peaks for the Me groups, most likely
due to hindered rotation of the alkyl group about the NÀOÀR bonds.
2.2. X-Ray Crystallographic Analyses. 2.2.1. Structure of 3d. The bond distances and
angles in 3d were as expected (see Table 1 and Fig. 1). The distance N(2)ÀC(2) (1.270
Š) and the C(2)ÀN(2)ÀC(13) angle (120.08) are in agreement with the interaction of a
double bond. The indoline ring is not planar, with maximum deviations from planarity
of À0.240(3) and 0.222(2) Š for C(1) and N(1), respectively. The three Ph rings (C(13)
to C(18), C(19) to C(25), and C(25) to C(30)) form with the mean plane of the indoline
ring dihedral angles of 81.4, 89.2, and 76.78, respectively. Van der Waals interactions are
the main contacts among the molecules in the crystal. The two intermolecular interac-
tions between O(2), N(2), and CÀH of two Ph rings may be interpreted as weak H-
bonds: a) C(16)···O(2)i, 3.581(3) Š; H(16)···O(2)i, 2.72 Š; C(16)ÀH(16)···O(2)i,
154.28; b) C(29)···N(2)ii, 3.676(4) Š; H(29)···N(2)ii, 2.81 Š; C(29)ÀH(29)···N(2)ii,
155.28 (i=1+x, y, 1+z; ii=1.5Àx, Ày, À0.5+z).
2.2.2. Structure of 10. The structure of 10 (see below) could also be solved by X-ray
crystallography (Fig. 2). Bond distances and angles again fell in the expected range
(Table 1). The indoline ring is approximately planar, with maximum deviations from
planarity of À0.092 and 0.071 Š for C(2) and N(1), respectively. The dihedral angles
formed by the Ph rings (C(9) to C(14), C(15) to C(20), and C(21) to C(26)) with the
mean plane of the indoline ring are 86.9, 88.4, and 68.58, respectively. Two weak
CÀH···Nintramolecular H-bond interactions are observed: a) C(22)···N(1), 2.795 Š;
H(22)···N(1), 2.43 Š; C(22)ÀH(22)···N(1), 103.58; b) C(26)···N(2) 3.028 Š;
H(26)···N(2), 2.60 Š; C(26)ÀH(26)···N(2), 108.98.
Here, the crystal packing is mainly determined by Van der Waals contacts.
2.3. Mass Spectrometry. The mass spectra of compounds 3a–d were very significant,
the fragmentation pattern depending on the nature of the O-alkyl group. In fact, 3a and
3b (both having a primary O-alkyl group) showed very low intensities of the molecular-

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Table 1. Selected Bond Distances (in Š) and Angles (in 8) for 3d and 10
3d
O(1)ÀN(1)
O(1)ÀC(9)
O(2)ÀC(10)
O(3)ÀC(10)
O(3)ÀC(11)
N(1)ÀC(1)
N(1)ÀC(8)
N(2)ÀC(2)
N(2)ÀC(13)
10
1.432(2)
1.459( 2)
1.195(4)
1.320(3)
1.468(4)
1.512(3)
1.414(3)
1.270(3)
1.419(2)
N(1)ÀO(1)ÀC(9)
C(10)ÀO(3)ÀC(11)
O(1)ÀN(1)ÀC(1)
O(1)ÀN(1)ÀC(8)
C(1)ÀN(1)ÀC(8)
C(2)ÀN(2)ÀC(13)
113.0(1)
118.8(2)
113.3(1)
112.1(1)
107.0(1)
120.0(2)
O(1)ÀC(7)
O(1)ÀC(27)
N(1)ÀC(1)
N(1)ÀC(8)
N(2)ÀC(2)
N(2)ÀC(9)
1.374(5)
1.425(5)
1.486(5)
1.386(5)
1.259(5)
1.411(5)
C(7)ÀO(1)ÀC(27)
C(1)ÀN(1)ÀC(8)
C(2)ÀN(2)ÀC(9)
116.6(3)
109.1(3)
120.8(3)
Fig. 1. X-Ray crystal structure of 3d. ORTEP View (40%-probability ellipsoids).
ion peak in their mass spectra, the most important peak in both cases appearing at m/z
359, which corresponds to the fragment originating from the parent alkoxyamine after
loss of an hexyloxy or an isopropyloxy group, respectively. Compounds 3c and 3d gave
mass spectra in which the molecular-ion peaks were clearly visible. Other well-defined
peaks were found at m/z 375 and 359, corresponding to the fragments derived from the
cleavage of the OÀC and NÀO bonds of the alkoxyamine moiety, respectively (see
below).
2.4. ESR Spin-Trapping Experiments and Thermal Stability of 3a–g. The stability of
the nitroxides 2a–h has already been described [29]. The data reported in the literature

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Fig. 2. X-Ray crystal structure of 10. ORTEP View (40%-probability ellipsoids).
indicate that the thermal stability of these nitroxides depends on the nature of the sub-
stituent R at C(2) of the indole moiety. The higher the stabilization of the radical R, the
lower the stability of the nitroxide. For this reason, 2g and 2h having a t-Bu and a Bn
group at C(2), respectively, are less stable and decompose at temperatures <1008.
Nitroxide 2a, in which two Ph groups are present at C(2), is very stable, similar as nitro-
xides with a primary alkyl group at C(2). For this reason, we focused our attention on
alkoxyamines derived from 2a.
To gain information on the stabilities of the alkoxyamines 3a–d, their benzene sol-
utions were heated at 808 directly inside the ESR cavity, and the identification of alkyl
or alkoxy radicals eventually formed was achieved by means of the spin-trapping tech-
nique, with ꢁtert-butyl-a-phenylnitroneꢂ (PBN, 4)1) being used as the spin trap. Thermal
decomposition may occur according to two different pathways (Scheme 2).
The radical adduct formed from the trapping of the aminyl radical 6 by PBN( 4) was
not detected because it is thermally unstable and, if formed, would have rapidly decom-
posed. In addition, its formation could be inhibited by crowding around the radical cen-
ter. The different radical species generated during the thermal decomposition of 3a–d
in the presence of PBN( 4) were identified from the experimental ESR spectra with the
aid of computer simulations [33]. The results are summarized in Table 2.
From Table 2, it is clear that different radical adducts were formed (in different
ratios) from the various alkoxyamines depending on the nature of the alkyl group
Rꢁ. In particular, the ESR spectrum of 3a (not shown) was found to be the superposition
of two different signals in a 95 :5 ratio, one corresponding to that of the nitroxide 7a, the
other belonging to the acyl nitroxide 8, respectively.
1
)
Systematic name: N-(1,1-dimethylethyl)-N-(phenylmethylidene)amine oxide.

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Scheme 2
Table 2. Product Distribution (in %) of the Different Radical Species Observed by ESR During Thermal
Decomposition of Alkoxyamines 3. Conditions: in benzene solution for 40 min at 808 in the presence of
PBN( 4).
Starting material
2a
5
7
8
3a
3b
3c
3d
3da)
–
–
43
79
60
–
–
15
7
40
95
92
–
14
–
5
8
42
–
–
a) After 10 min of heating.
The same radical adducts were obtained from the thermal decomposition of com-
pound 3b in the presence of PBN( 4), and in fact, nitroxides 7b and 8 were obtained
in a 92 :8 ratio, respectively (Fig. 3). Simulation of the experimental spectrum recorded
from alkoxyamine 3c was in agreement with the superposition of three different signals
due to nitroxides 2a, 5c, and 8 (Fig. 4). A similar behavior was observed for compound
3d: after 40 min of heating, a composite spectrum exhibiting the signals of nitroxides 2a,
5d, and 7d in a ratio of 79 :7:14, respectively, was recorded (not shown). In this last
case, after 10 min of heating, a spectrum was formed only by the signal of 2a and 5d
(Fig. 5). The hyperfine-coupling constants of the formed nitroxides are collected in
Table 3. Note that compounds 3e–g, when heated at 808, behave like compound 3a.

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Fig. 3. Experimental (exp.) vs. simulated (sim.) ESR spectra for the radical adducts formed in the ther-
mal decomposition of 3b in the presence of PBN (4) after 40 min at 808
Fig. 4. Experimental (exp.) vs. simulated (sim.) ESR spectra for the radical adducts formed in the ther-
mal decomposition of 3c in the presence of PBN (4) after 40 min at 808
2.5. Preparative-Scale Thermal Decomposition. Compound 3a was thermally
decomposed on a preparative scale by heating a tert-butylbenzene solution of the
alkoxyamine under reflux for 1.5 h. In agreement with the ESR spin-trapping experi-
ment, DPAIO was not formed, and compound 9 (70%) was the main product, together
with 10 (30%).
2.6. Bond-Dissociation-Enthalpy (BDE) Calculations. The BDE values for the
alkoxyamines 3a–d were calculated to compare the lability of the corresponding NÀ

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Fig. 5. Experimental (exp.) vs. simulated (sim.) ESR spectra for the radical adducts formed in the ther-
mal decomposition of 3d in the presence of PBN (4) after 10 min at 808
Table 3. ESR Hyperfine Coupling Constants (in mT) for Selected Compounds. Conditions: in benzene at
808 (see Exper. Part).
Radical
a(N)
a(H)
2aa)
5d
7a
7d
7c
0.943
1.443
1.405
1.393
1.400
0.811
–
0.313
0.229
0.203
0.232
–
8
a) Values for other atoms: aH(5) =0.314, aH(7) =0.303, aH(4) =aH(6) =0.104, aN(exo) =0.072.
O(C) and (N)OÀC bonds. The BDEs for the two competitive pathways at 298 K are
defined by Eqns. 1 and 2:
BDECÀO =DHof (nitroxide)+DHfo (RC)ÀDHof (N-alkoxyamine)
BDENÀO =DHof (aminyl)+DHfo (ROC)ÀDHof (N-alkoxyamine)
(1)
(2)
Density-functional-theory (DFT) calculations were performed with the Gaussian03
software package [34]. Recently [35][36], various standard functionals have been
tested to calculate BDE values of CÀX and XÀY bonds belonging to a large panel
of compounds. The best results were obtained with the B3P86 functional, and the
best correlation constants between the experimental and calculated values were

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obtained at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d) level. Herein, the geometry
optimization and the calculation of vibrational frequencies were performed at the
B3LYP/6-31G(d) level, and a single point at the B3P86/6-311++G(d,p) level was
used to calculate the energy. All minima were confirmed by a calculation of vibrational
frequencies. For thermodynamic calculations, as recommended by Wong [37], a scale
factor of 0.9804 was applied to the vibrational frequencies. The BDEs were then calcu-
lated according to Eqn. 3 (for T=298 K):
BDE=DHor =De +D(ZPE)+DHtrl +DHrot +DHvib +RT
(3)
Here, De is the classical electronic bond-dissociation energy, D(ZPE) is the differ-
ence in zero-point energy between the products and the N-alkoxyamine, and DHtrl,
DHrot, and DHvib are the contributions from translational, rotational, and vibrational
degrees of freedom, respectively. The results of these studies are reported in Table 4.
Table 4. Comparison of the Bond-Dissociation Enthalpies (BDE) for the (N)OÀC vs. NÀO(C) Cleavage
of 3 at 298 K. All values calculated at the B3P86/6-311++G(d,p)//B3LYP/6-31G(d) level.
Compound
BDE [kJ molÀ1
]
(N)OÀC
NÀO(C)
3a
3b
3c
3d
175
173
118
102
136
141
137
126
3. Discussion. – According to the experiments carried out on the thermal decompo-
sition of 3a–d, as described above, it is clear that the pathway followed in the thermal
homolysis is related to the nature of the Rꢁ group. When Rꢁ is a nonstabilized alkyl
group, as in 3a,b, the bond-dissociation enthalpy (BDE) for the NÀO(C) bond is
lower than that for the (N)OÀC bond. When Rꢁ is a stabilized substituent, the BDEs
for the two bonds are closer to each other, as in the case of 3c. For compound 3d,
the BDE for the (N)OÀC bond is smaller than for NÀO(C). These data are in agree-
ment with those obtained from the MS analyses of the different alkoxyamines (see
above). In fact, the most-important mass peaks in the spectra of all studied compounds
(with the exception of 3c and 3d) are due to the aminyl radical 6 formed from the start-
ing alkoxyamine after NÀO(C) bond cleavage, with loss of the O-alkyl moiety. This
result is also supported by the thermal-decomposition experiment. When 3a was
refluxed in tert-butylbenzene, no DPAIO was recovered, and the main product isolated
corresponded to 9 (70%) derived from the aminyl fragment 6. The second product,
compound 10, was also formed via the intermediate aminyl radical. Compounds 3c
and 3d, i.e., O-styryl and O-methylcrotonate, showed in their mass spectra both the
peaks of the nitroxide 2a and of the aminyl fragment 6 (R=Ph), the latter being less
intense than that of the nitroxide in the case of 3d.
The thermal decomposition of 3a–d at 808 in the presence of PBN( 4) inside the
ESR cavity were also convincing. With the exception of 3c and 3d, the spectra recorded
during the decomposition of all the other alkoxyamines correspond to the O-alkylÀ

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PBNspin adduct 7 and to the acyl nitroxide 8, its thermal decomposition product (see
Fig. 3). In the case of 3c and 3d, the ESR spectrum of 2a was also detected, thus indi-
cating that OÀC bond cleavage occurs. In particular, in the case of 3d, the spin adduct
5d was observed (see Fig. 5). The spin adducts 5 and 7 were identified on the basis of the
hyperfine coupling for the a-H-atom, which should be ca. 0.3 mTwhen an alkyl group is
attached to the same C-atom, and ca. 0.2 mT when an alkoxy group is present [38].
The above data may be rationalized by the observation that NÀO(C) bond cleavage
easily occurs because of the formation of the resonance-stabilized aminyl radical 6;
however, when the radical bonded to the O-atom in these aromatic nitroxides is suffi-
ciently stabilized, as in the case of styryl and methyl crotonate-1-yl, the cleavage of the
OÀC bond also occurs (3c and 3d). With 3d, (N )OÀC cleavage is favored compare to 3c
due to an increase of the steric hindrance of the released alkyl fragment. Compared to
3a and 3b, the (N)OÀC cleavage of 3c is the main process due to both increased steric
hindrance and stabilization of the released alkyl part; DFT calculations support these
experimental results (Table 4). In fact, the calculated BDENÀO values are quite constant
(DBDENÀO =19 kJ molÀ1), while the calculated BDEOÀC values are strongly influenced
by the nature of the substituents attached to the C-atom (DBDEOÀC =73 kJ molÀ1).
For 3a and 3b, the BDENÀO values are significantly lower than the BDEOÀC ones
(DBDE ca. 35 kJ molÀ1), and in fact, amine and alkoxy radicals are formed, being
the sole products observed. In the case of 3c and 3d, the (N)OÀC bond is the most
labile, and its homolysis is favored with respect to NÀO(C) homolysis. This can be
rationalized by the released radical being stabilized by p-electron delocalization,
whereas the parent alkoxyamine is destabilized by steric hindrance. As already pointed
out [35], the combination of both steric and electron-withdrawing effects for the
released radical (3d) leads to a significant decrease in the BDEOÀC value. For 3c,d, a
small gap (ca. 20 kJ molÀ1) between BDEOÀC and BDENÀO was observed, which justifies
the detection of both aminyl and nitroxyl radicals in the ESR spin-trapping experi-
ments. The gap between the BDE values for the two different bonds is larger for 3d,
with BDEOÀC being considerably lower than BDENÀO, and, indeed, a higher ratio of
nitroxyl/aminyl radicals was detected.
Introduction of an alkyl group, i.e., Pr, i-Pr, or Bu on C(2) of the indole ring, as in
alkoxyamines 3e–g, does not affect the behavior of these compounds. As in the case of
3a, during their thermal decomposition, the aminyl radical was mainly formed, which
suggests that, for the studied compound, it is the nature of the group attached to the
O-atom of the nitroxide function that determines the particular kind of homolysis,
i.e., NÀO(C) vs. (N )OÀC cleavage, with no influence by the other groups present on
the indole ring.
4. Conclusions. – During our investigation on the use of DPAIO alkoxyamines in
NMP, we discovered that the thermal decomposition may occur in two different ways
(Scheme 3). Thereby, there may be a competition between (N)OÀC and NÀO(C)
bond cleavage. The possibility and the extent of bond cleavage depend on the nature
of the alkyl moiety R3 bound to the O-atom of the nitroxide function, as deduced by
detailed studies of the thermal decomposition of the alkoxyamines 3a–d by means
of ESR spin-trapping experiments, MS analyses, laboratory-scale experiments, and
DFT calculations.

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 3
It is obvious that, except for 3d, the studied alkoxyamines 3 are not suitable to medi-
ate controlled radical polymerization since their thermal decomposition occurs pre-
dominantly between the NÀO(C) bond. However this alkoxyamines can afford an
interesting way to produce alkoxy radicals at medium-to-high temperatures. In a forth-
coming paper, we will present a successful living controlled radical polymerization of a
different substrate (MMA) using 3d-type initiators/controllers [27].
University of Provence and CNRS are kindly acknowledged for financial support.
Experimental Part
1. General. The nitroxides 2a–h were prepared starting from 2-phenyl-3-phenylimino-3H-indole N-
oxide [39] according to a procedure reported previously [28]. Solvents and chemicals were purchased
from Carlo Erba and Sigma-Aldrich and used as received. Melting points (m.p.) were measured with
an electrothermal apparatus; uncorrected. IR Spectra: Perkin-Elmer Spectrum MGX1 spectrophotome-
ter equipped with a Spectra Tech ꢁCollectorꢂ for DRIFT measurements; in cmÀ1. 1H-NMR Spectra: Var-
ian Gemini-200 spectrometer; at r.t. in CDCl3 soln.; d in ppm rel. to Me4Si, D in Hz. ESR Spectra:
G
upgraded Bruker ER-200D spectrometer. GC/MS: Carlo Erba QMD-1000 mass spectrometer equipped
with a Fisons GC-8060 chromatograph; in m/z.
2. Synthesis of 3a–c and 3e–g (General Procedure). To a soln. of 2a (1 mmol) and the appropriate
alkyl halide (6 mmol) in THF (10 ml) was added phenylhydrazine (1 mmol) under Ar gas. Upon reduc-
t
tion, the color changed from red to yellowish. Then, BuOK (2 mmol) was added, and the mixture was
stirred at r.t. for 1 h. The mixture was diluted with Et2O (25 ml) and washed with dist. H2O (3”20
G
ml). The org. phase was dried (Na2SO4) and evaporated, and the residue was crystallized from the appro-
priate solvent (see below).
N-[1-(Hexyloxy)-1,2-dihydro-2,2-diphenyl-3H-indol-3-ylidene]aniline (3a). Yield: 89%. M.p. 85–868
1
(ligroin, b.p. 40–608). IR: 1652 (C=N), 1596 (PhÀN(OÀhexyl)ÀC). H-NMR (200 MHz, CDCl3): 0.86
(unresolved t, 3 H); 1.20–1.25 (m, 6 H); 1.48–1.62 (m, 2 H); 3.85 (t, J=6.8, 2 H); 6.40 (d, J=6.8, 1
H); 6.62 (t, J=7.2, 1 H); 6.79 (d, J=7.2, 2 H); 7.05–7.15 (m, 2 H); 7.27–7.36 (m, 10 H); 7.51–7.56 (m,
3 H). EI-MS (pos.): 461 (2.5, [M+1]+), 375 (5), 361 (30), 359 (100), 283 (18), 254 (14), 205 (26) 165
(39), 152 (44). Anal. calc. for C32H32N2O: C 83.44, H 7.0, N6.08; found: C 84.47, H 7.04, N6.12.
N-{1,2-Dihydro-1-[(1-methylethyl)oxy]-2,2-diphenyl-3H-indol-3-ylidene}aniline (3b). Yield: 90%.
1
M.p. 152–1538 (ligroin, b.p. 60–1008). IR: 1657 (C=N), 1596 (PhÀN(OiPr)ÀC). H-NMR (200 MHz,
CDCl3): 1.17 (br. s, 6 H,); 3.93 (sept., 1 H); 6.40 (d, J=7.8, 1 H); 6.61 (t, J=7.2, 1 H); 6.79 (d, J=7.2, 2
H); 7.08–7.13 (2 arom. H); 7.28–7.34 (9 arom H); 7.50–7.59 (br. s, 4 H). EI-MS (pos.): 418 (1.3, M+),
375 (1.2), 361 (30), 360 (100), 2.81 (7), 254 (8), 205 (18). Anal. calc. for C29H26N2O: C 83.22, H 6.26, N
6.69; found: C 83.14, H 6.22, N6.71.
N-{1,2-Dihydro-2,2-diphenyl-1-[(1-phenylethyl)oxy]-3H-indol-3-ylidene}aniline (3c). Yield: 91%.
M.p. 162–1638 (benzene/petroleum ether). IR: 1657 (C=N), 1596 (PhÀN(OÀstyryl)ÀC). 1H-NMR
(200 MHz, CDCl3): 1.36 (br. s., 3 H); 4.61 (q, J=7.8, 1 H); 6.34 (d, J=8.9, 1 H); 6.55 (t, J=7.8, 1 H);

Helvetica Chimica Acta – Vol. 89 (2006)
2323
7.03–7.38 (m, 15 H); 7.53–7.65 (m, 4 H); 7.73 (d, J=7.8, 2 H). EI-MS (pos.): 480 (7, M+), 376 (27), 375
(30), 362 (17), 360 (52), 299 (38), 285 (23), 284 (100), 205 (33), 165 (19). Anal. calc. for C34H28N2O: C
84.97, H 5.87, N5.83, found: C, 84.95, H 5.91, N5.87.
N-[1-(Hexyloxy)-1,2-dihydro-2-phenyl-2-propyl-3H-indol-3-ylidene]aniline (3e). M.p. 64–668
(ligroin, b.p. 60–1008). IR: 1661(C=N), 1598(PhÀN(OPr)ÀC). 1H-NMR (200 MHz, CDCl3): 0.87 (t,
J=6, 3 H); 0.98 (t, J=6, 3 H); 1.15–1.56 (m, 12 H); 2.43 (m, 1 H); 2.51–2.61 (m, 1 H); 3.71–3.79 (m,
1 H); 3.83–3.90 (m, 1 H); 6.34 (d, J=9, 1 H); 6.57 (t, J=9, 1 H); 6.77 (d, J=9, 2 H) 7.05–7.10 (m, 2
H); 7.23–7.35 (m, 6 H); 7.52 (d, J=9, 2 H). EI-MS (pos.): 426 (3, M+), 325 (100), 283 (17). Anal. calc.
for C29H34N2O: C 81.43, H 8.86, N6.40; found: C 81.65, H 8.83, N6.57.
N-[2-Butyl-1-(hexyloxy)-1,2-dihydro-2-phenyl-3H-indol-3-ylidene]aniline (3f). M.p. 44–458 (ligroin,
b.p. 60–1008). IR: 1661(C=N), 1597(PhÀN(OBu)ÀC). 1H-NMR (200 MHz, CDCl3): 0.87 (t, J=6, 3 H);
0.92 (t, J=6, 3 H); 1.16–1.42 (m, 10 H); 1.52–1.64 (m, 2 H); 2.35–2.45 (m, 1 H); 2.54–2.63 (m, 1 H);
3.73–3.80 (m, 1 H); 3.84–3.91 (m, 1 H); 6.35 (t, J=9, 1 H); 6.58 (t, J=6, 1 H); 6.77 (d, J=6, 2 H);
7.05–7.11 (m, 2 H); 7.23–7.35 (m, 6 H); 7.51 (d, J=6, 2 H). EI-MS (pos.): 440 (10, M+), 384 (13), 340
(100), 295 (45), 283 (39). Anal. calc. for C30H36N2O: C 81.78, H 8.24, N6.36; found: C 81.97, H 8.36, N
6.15.
N-[1-(Hexyloxy)-1,2-dihydro-2-(1-methylethyl)-2-phenyl-3H-indol-3-ylidene]aniline
(3g).
M.p.
109–1108 (ligroin, b.p. 60–1008). IR: 1667(C=N), 1597 (PhÀN(OiPr)ÀC). 1H-NMR (200 MHz,
CDCl3): 0.90 (t, J=6, 3 H); 1.07 (t, J=6, 3 H); 1.15 (d, J=6, 3 H); 1.25–1.45 (m, 6 H); 1.61–1.70 (m,
2 H); 3.15–3.29 (t, J=6, 1 H); 3.91–4.08 (m, 2 H); 6.31 (d, J=9, 1 H); 6.52 (t, J=9, 1 H); 6.78 (d,
J=9, 2 H); 7.02–7.11 (m, 2 H); 7.25–7.31 (m, 6 H); 7.60 (d, J=9, 2 H). EI-MS (pos.): 426 (9, M+),
383 (86), 325 (100), 299 (62), 282 (75). Anal. calc. for C29H34N2O: C 81.43, H 8.86, N6.40; found: C
81.49, H 8.78, N6.53.
The Nitroxides 2d–f were transformed into the corresponding hexyl-substituted compounds 8e–g as
reported for compounds 3a–c.
3. Synthesis of Ethyl 2-{[2,3-Dihydro-2,2-diphenyl-3-(phenylimino)-1H-indol-1-yl]oxy}-2-methylpro-
panoate (3d). Compound 2a (1 mmol) and ethyl 2-bromoisobutyrate (2 mmol) were dissolved in anh. tol-
uene (5 ml) in a 50-ml round-bottom flask, and degassed with Ar. In another 50-ml flask, Cu (2 mmol)
and CuBr (2 mmol) were suspended in anh. toluene (5 ml), degassed for 10 min with Ar, and then treated
with pentamethyl-diethylenetriamine (PMDETA; 1 mmol), and finally degassed again for another 10
min. Next, the content of the first flask was poured into that of the second under Ar atmosphere. The
resulting reaction mixture was stirred for 30 min and then diluted with Et
was washed with H2O (3”20 ml), dried (Na2SO4), and evaporated. The residue was purified by column
chromatography (CC) (SiO2; petroleum ether/Et2O 9 :1) and recrystallized from ligroin. Yield of 3d:
80%. M.p. 106–1078 (ligroin, b.p. 60–1008). IR: 1732 (C=O), 1660 (C=N), 1594 (PhÀN(OCMe2CO2-
2O (60 ml). The org. layer
AHCTREUNG
AHCTREUNG
Et)ÀC). 1H-NMR (200 MHz, CDCl3): 1.19 (t, J=7.5, 3 H); 1.32 (s, 6 H); 3.88 (br. s, 2 H); 6.4 (d,
J=7.5, 1 H); 6.67 (t, J=7.5, 1 H); 6.78 (d, J=8.2, 2 H); 7.03–7.14 (q-like, 1 H); 7.28–7.33 (m, 10 H);
7.41 (br. s, 4 H). EI-MS (pos.): 490 (8, M+), 375 (45), 360 (13), 299 (11), 283 (40), 205 (18), 165 (18),
78 (100). Anal. calc. for C32H30N2O3: C 78.34, H 6.16, N5.71; found: C 78.39, H 76.21, N5.76. X-Ray crys-
tal structure: see Fig. 1, Exper. 6.1, and Table 5.
4. ESR Measurements. A soln. of the appropriate compound 3 (2 mg) and PBN( 4; 2 mg) in anh. ben-
zene (1 ml) was transferred to an ESR tube, accurately degassed by bubbling with Ar gas, and heated at
808. The final spectra resulted from ten accumulations in 40 min. Computer-simulated ESR spectra were
calculated with the WinSim program in the NIEHS public ESR software-tools package (see http://
www.epr.niehs.nih.gov/) [33].
5. Thermal Decomposition of 3a. Compound 3a (100 mg) was heated at 1608 in 5 ml of tert-butylben-
zene for 1.5 h. After this time, the reaction soln. was reduced to a small volume (ca. 1 ml) and then sub-
jected to prep. TLC (SiO2; cyclohexane/AcOEt 95 :5). Compound 9 was obtained in 70% yield, together
with 10 (30%). Compound 9 was identified by comparison with an authentic sample [40]; compound 10
was characterized spectroscopically (see below).
Data of N-[7-(Hexyloxy)-1,2-dihydro-2,2-diphenyl-3H-indol-3-ylidene]aniline (10). M.p. 100–1018
(ligroin, b.p. 40–608). IR: 1657(C=N), 1591(PhÀN(OÀhexyl)ÀC). 1H-NMR (200 MHz, CDCl3):

2324
Helvetica Chimica Acta – Vol. 89 (2006)
Table 5. X-Ray Diffraction Data for 3d and 10
Compound
3d
10
Formula
Mr
Space group
a [Š]
b [Š]
c [Š]
a, b, g [8]
V [Š3]
Z
C32
490.6
P212121
10.272(2)
28.347(4)
9.056(2)
90
A
N2
O3
C32
460.6
Pbcn
38.136(6)
7.2893(11)
18.683(3)
90
5193.4(14)
8
U
G
G
2636.9(9)
4
T [8C]
l [Š]
23(2)
1.54178
1.236
25(2)
0.71073
1.178
1calc [g cmÀ3
]
m [cmÀ1
]
6.30
0.71
Transmission coefficient
Ra)
0.978–1.000
0.037
0.994–1.000
0.037
wR2
0.094
0.044
GOF
1.019
0.646
Observed refl.
Independent refl. (I>2s(I))
Refined refl.
Variables
3936
4747
4747
335
991
3734
3734
320
7.05–7.15 (m, 2 H); 7.27–7.41 (m, 10 H); 7.48–7.63 (m, 3 H). EI-MS (pos.): 461(2, M+), 260 (92.15), 384
(26), 383 (100), 299 (64), 221 (32), 167 (45), 165 (29), 77 (48). Anal. calc. for C32H32N2O: C 83.44, H 7.0, N
6.08; found: C 84.41, H 7.15, N6.18.
6. X-Ray Crystallography2). 6.1. Compound 3d. C32H30N2O3, Mr 490.6, orthorhombic, space group
P212121; a=10.272(2), b=28.347(4), c=9.056(2) Š, V=2636.9(9) Š3, Z=4; 1=1.236 g cmÀ3
;
l(CuKa)=1.54178 Š, m(CuKa)=6.30 cmÀ1; colorless prism (0.14”0.15”0.20 mm). The structure was
solved by direct methods (SIR97 [41]) and anisotropically refined for all non-H atoms. The H-atoms
were located from a difference Fourier map and thereafter treated as riding atoms, the isotropic displace-
ment parameter Uiso
N
N
using the weighting scheme w=1/[s2(Fo2)+(0.0515 P)2], where P=(Fo2 +2 Fc2)/3). For 4747 unique
reflections having I>0 collected at T=296(2) K on an Enraf-Nonius CAD4 diffractometer
(3<2q<1408), the final R value was 0.037 (wR2 =0.094; S=1.019). See also Table 5.
6.2. Compound 10. C32H32N2O, Mr 460.6, orthorhombic, space group Pbcn; a=38.136(6),
b=7.2893(11), c=18.683(3) Š, V=5193.4(14) Š3, Z=8; 1=1.178 g cmÀ3
; l(MoKa)=0.71072 Š,
m(MoKa)=0.71 cmÀ1; yellow plate (0.03”0.09”0.15 mm). The structure was solved by direct methods
(SIR 97 [41]) and anisotropically refined for all the non-H-atoms. The H-atom bound to N(1) was located
from a difference Fourier map and refined isotropically. All other H-atoms were located from a differ-
ence Fourier map and thereafter treated as riding atoms, the isotropic displacement parameter Uiso
ACHTREUNG
set at 1.2 Ueq
ACHTREUNG
2
)
The crystallographic data of 3d and 10 have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication numbers CCDC-605374 and CCDC-605375, resp. Copies
of the data can be obtained, free of charge, via the internet at http://www.ccdc.cam.ac.uk/data_
request/cif.

Helvetica Chimica Acta – Vol. 89 (2006)
2325
weighting scheme w=1/[s2(Fo2 )]. For 3734 unique reflections with I>0 collected at 298(2) K on a Bruker
SMART CCD diffractometer (2.8<2q<45.68), the final R value was 0.037 (wR2 =0.044; S=0.646). See
also Table 5.
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