Stable nitroxyl radicals with triple bonds: 4-acetylenyl-3-imidazoline-3-oxide-1-oxyls

Article abstract of DOI:10.1016/j.tet.2006.02.036

Cross-coupling reaction of 1-hydroxy-2,2,5,5-tetramethyl-4-[2-(p-iodophenyl)vinyl]-3-imidazoline-3-oxide with copper(I) salts of 1-aryl(hetaryl)alkynes leads to the corresponding 2,2,5,5-tetramethyl-4-[2-(p-aryl(hetaryl)ethynylphenyl)vinyl]-3-imidazoline-3-oxide-1-oxyls in high yields.

Full text of DOI:10.1016/j.tet.2006.02.036

Tetrahedron 62 (2006) 4597–4602
Stable nitroxyl radicals with triple bonds:
4-acetylenyl-3-imidazoline-3-oxide-1-oxyls
a
a
b
Sergei F. Vasilevsky,a, Svetlana V. Klyatskaya, Olga L. Korovnikova, Svetlana A. Amitina,
*
Dmitri V. Stass,a,c Igor A. Grigor’evb,c, and Jose Elguero
d,
*
*
´
aInstitute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Science,
630090 Novosibirsk, Russian Federation
bNovosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk,
Russian Federation
cNovosibirsk State University, 630090 Novosibirsk, Russian Federation
d
´
´
Instituto de Quımica Medica (CSIC), Juan de la Cierva 3, E-28006 Madrid, Spain
Received 9 January 2006; revised 10 February 2006; accepted 13 February 2006
Available online 20 March 2006
Abstract—Cross-coupling reaction of 1-hydroxy-2,2,5,5-tetramethyl-4-[2-(p-iodophenyl)vinyl]-3-imidazoline-3-oxide with copper(I) salts
of 1-aryl(hetaryl)alkynes leads to the corresponding 2,2,5,5-tetramethyl-4-[2-(p-aryl(hetaryl)ethynylphenyl)vinyl]-3-imidazoline-3-oxide-
1-oxyls in high yields.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
unpaired electron is isolated from the substituent by single
bonds within the radical itself, thus providing the desired
attenuation of ‘electron spin conductivity’ outside the radical
moiety of the spin-labeled molecule.
A recent extension of the spin-labeling methodology in
physicochemical studies consists of the preparation of model
systems to gain insight into the phenomenonof spin catalysis,1
that is, the effect of the ‘external’ spin on the evolution of a
correlated spin system. A reasonable way to accomplish this is
the augmentation of a photo- or radiation generated spin-
correlated radical pair with a third spin—the spin of a stable
radical moiety introduced in the precursor of one of the pair
partners. Recently,2 we have reported the synthesis and
physicochemical study of a series of aromatic charge
acceptors and luminophores containing a stable 2-imidazoline
radical fragment, which under X-irradiation in non-polar
solvents, produced biradical ions that are partners in spin-
correlated radical ion pairs. An important outcome of this
study was the realization that the exchange coupling between
the two unpaired spins of the short-lived biradical ion was too
strong and must be reduced to allow for more quantitative
studies going beyond the mere observation of the effect. In the
present paper, we report the synthesis of a series of acetylenic
derivatives of 3-imidazoline-1-oxyls. In this way, as opposed
to 2-imidazoline radicals, the NO fragment bearing the
We have already published a preliminary communication
devoted to the synthesis of acetylene-containing nitroxides
of the 3-imidazoline series.3 In this work, we will report the
synthesis of these compounds and provide additional
examples of the preparation of spin-labeled acetylenyl
nitroxides as well as their diamagnetic derivatives, in full
detail with all spectral and analytical data.
Our attempts to use the classical method for the synthesis of
the desired acetylenes,4 dehydrobromination of the corre-
sponding 1,2-dibromoethane, were unsuccessful. Reaction
of 1 with either KOH in boiling EtOH, KOH in the presence
of TBAB (tetrabutylammonium bromide), or KOH in
DMSO in a wide interval of temperatures (20–100 8C) led
to a large number of by-products, from which acetylene 2
could not be isolated (Scheme 1).
O
O
KOH, EtOH
Br
N
N
Keywords: Acetylenes; 3-Imidazoline nitroxides; Cross-coupling reaction;
Copper acetylides.
N
N
(KOH/TBAB)
O
O
*
Corresponding authors. Fax: C7 383 3307350 (S.F.V.); fax: C34 91
5644853 (J.E.);
Br
1
2
e-mail addresses: vasilev@ns.kinetics.nsc.ru; grig@nioch.nsc.ru;
iqmbe17@iqm.csic.es
Scheme 1. Attempts of dehydrobromination of dibromoethane 1.
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.02.036

4598
S. F. Vasilevsky et al. / Tetrahedron 62 (2006) 4597–4602
For the preparation of a series of both diamagnetic and
paramagnetic acetylenic derivatives of 3-imidazoline-3-
oxide-1-oxyl we thought of using the key ethynyl
derivatives 5 (6). These compounds are obtained by
condensation of 1-hydroxy-2,2,4,5,5-pentamethyl-3-
imidazoline-3-oxide 3 with p-ethynyl benzaldehyde 4
(Scheme 2).
O
N
NaIO4
N
11
I
O
H2O, CHCl3
12
Scheme 4. Oxidation of hydroxylamine 11 into nitroxyl 12 in the presence
of NaIO4.
O
O
H
However, we failed to perform cross-coupling of the spin-
labeled bromo derivative 10 with both phenylacetylene 13a
and 2-methylbut-3-yn-2-ol 13b. In both cases the reaction
resulted in the obtention of diamagnetic derivatives 9,
accompanied by formation of the homo-coupling product of
1-alkynes—1,4-disubstituted-1,3-diynes 14a,b (Scheme 5).
Even the use of the more active, for cross-coupling
reactions, iodo compounds 11 or 12, was unsuccessful.
N
N
O
4
N
N
OH(O )
NaOH, MeOH
OH
3
5 (6)
Scheme 2. Condensation of hydroxylamine 3 with the aldehyde 4.
O
However, we observed strong polymerization and the
mixture of hydroxylamine 5 and nitroxyl 6 was isolated in
low yields (2.4 and 3.0%, respectively).
N
PdCl2(Ph3P)2 - CuI
N
R
+
10
Br
HO
Et3N
Then we tried another approach to the synthesis of
acetylenic derivatives of 3-imidazoline-3-oxide-1-oxyl,
based on the Sonogashira cross-coupling reaction5 of the
corresponding iodo(bromo)-imidazolines with acetylenyl-
arenes, a reaction that has been successfully applied to the
preparation of a series of acetylenyl derivatives of
2-imidazoline nitroxides.6
13a,b
9
+
R
R
14a,b
R = a: Ph
b: -C(CH3)2OH
Scheme 5. Cross-coupling of bromonitroxyl 10 with terminal acetylenes
13a and 13b.
The starting halogeno-arylimidazolines were synthesized by
condensation of 2,2,4,5,5-pentamethyl-imidazoline 3 with
p-bromobenzaldehyde 7 or p-iodobenzaldehyde 8. In the
case of the bromo derivative 7 both para- (10, 10%) and
diamagnetic (9, 36%) (bromophenyl)vinylimidazolines
were isolated. On the other hand, only the iodo derivative
11 was isolated in 28% yield in the case of iodoaldehyde 8
(Scheme 3).
We tried to avoid these complications by protecting the
hydroxyl group in the starting halogen derivatives with ethyl
vinyl ether 15.7 The starting bromide was prepared as shown
below (Scheme 6).
O
H
O
O
Br
O
N
O
Br
N
H
15
7
3
N
N
Br
N
H+
NaOH, MeOH
O
O
O
O
O
7
16
17
N
N
Br
OH(O )
NaOH, MeOH
Scheme 6. Protection of the hydroxy group in hydroxylamine 3 followed by
condensation of 16 with p-bromobenzaldehyde 7.
9 (10)
O
3
H
O
I
N
In case of success, this way could open a route to the
synthesis of the diamagnetic acetylenyl-3-imidazolines
and the corresponding paramagnetic derivatives. This is
important because the study of the phenomenon of spin
catalysis requires the determination of quantum yields
of luminescence of both dia- and paramagnetic
compounds.8
8
I
OH
NaOH, MeOH
11
Scheme 3. Condensation of imidazoline 3 with p-halogeno benzaldehydes
7 and 8 in the presence of NaOH.
The paramagnetic iodo derivative 12 was synthesized by
oxidation of 11 in the presence of NaIO4. It is necessary to
emphasize that this is the first successful application of the
system NaIO4–H2O–CHCl3 for preparing 3-imidazoline
nitroxyls. The yield of the desired radical 12 was 72%
(Scheme 4).
Thus protected bromo-imidazoline 17 reacted with terminal
acetylenes 13a,b under standard conditions [Pd(PPh3)2Cl2–
CuI–NEt3, 55–80 8C] to afford the desired diamagnetic
cross-coupling products 18a,b in 60–70% yield (Scheme 7).
The mono substituted acetylene derivative 18c was obtained
by alkaline cleavage of 18b.

S. F. Vasilevsky et al. / Tetrahedron 62 (2006) 4597–4602
4599
O
O
N
N
PdCl2(Ph3P)2 - CuI
Et3N
Py
N
R
C
C
Cu
R
+
11
17 + 13a,b
O
N
R
20a-g
a
O
21a-g
KOH
b
c
d
e
f
g
f
O
18a,b
N
O
O
18c
18b
O
N
p-MeO-C6H4-,
,p-Br-C6H4-
R = Ph-, Ph-O-CH2-,
H+
,
O
O
N
O
O
3
3
O
N
Scheme 9. Cross-coupling of diamagnetic iodo-imidazoline 11 with the
copper salt of phenylacetylenes 20a–g.
a, R = Ph
b, R = C(CH3)2OH
c, R = H
N
R
HO
The series of acetylenic nitroxides 21a–e, were obtained in
good yields (90–95%), and even in the worst case of low
reactive crown ether 20f or the bromo derivative 20g the
yields of 21f,g were 50 and 60%.
19a-c
Scheme 7. Cross-coupling of acetal 17 with terminal acetylenes 13a,b
followed by attempts to eliminate the protecting group and the cleavage of
carbinol 18b.
Thus, new methods for the acetylide synthesis of
aryl(hetaryl)ethynylphenyl-3-imidazoline nitroxides have
been developed.
Next we tried to remove the protecting group, followed by
oxidation of the hydroxyl group. However, deprotection of
the acetal group from the acetylenic derivatives in the
presence of trace amounts of HCl led only to the formation
of a gum.
We suppose that the successful application of cross-
coupling in the 2-imidazoline series and the negative result
of the same reaction for 3-imidazolines is related to stronger
oxidative properties of the nitroxide group in 3-imidazoline-
3-oxide-1-oxyls as compared with 2-imidazoline-3-oxide-1-
oxyl derivatives.9 On the other hand, this result is connected
also with the low reactivity of the bromine atom in the aryl
moiety due to CM-effect of the N-oxide fragment.10 This
effect of the N–O group for 3-imidazolines is confirmed by
the data from 13C NMR spectra.11
For this reason, and taking into account the difference in the
mechanisms of Cu- and Pd-catalyzed cross-coupling
reaction of alk-1-ynes,12 we supposed that the described
difficulties could be overcome by using the acetylide
synthesis to obtain the desired products.
As a model, the copper salt of phenylacetylene 20a
was allowed to react with paramagnetic iodo-imidazoline
12 in boiling pyridine to afford product 21a in 83% yield
(Scheme 8).
O
N
c
Py
N
+
12
Cu
O
20a
21a
Scheme 8. Cross-coupling of paramagnetic iodo-imidazoline 12 with the
copper salt of phenylacetylene 20a.
It is important to note that the diamagnetic analogue, the
iodo-imidazoline 11 was also successfully used in the
cross-coupling reaction affording the radical 21a.
The transformation of the reaction products directly into
radicals 21a–g probably takes place during the work-up of
the reaction mixture (Scheme 9). We observed similar
transformations in the condensation of 1-hydroxy-
2,2,4,5,5-pentamethyl-3-imidazoline-3-oxide 3 with p-bromo-
benzaldehyde 7.
3346 3348 3350 3352 3354 3356 3358
Magnetic Field, G
Figure 1. (a) X-band CW ESR spectrum of 10K5 M 21d in degassed
toluene, room temperature, microwave power 2 mW, modulation 0.1 G
100 kHz, single scan of 40 min; (b) simulation (shifted), ANZ4.09 G,
Að13CÞðCH Þ Z5:71 G, AHðCH Þð12HÞZ0:23 G; (c) expanded view of the
3
3
low-field line. The structure from minor coupling with 12 methyl hydrogens
is clearly seen both for the main line and for the 13C satellites.

4600
S. F. Vasilevsky et al. / Tetrahedron 62 (2006) 4597–4602
ESR spectra of the nitroxides are typical for 3-imidazoline
radicals with spin density localized mostly at the NO
fragment (Fig. 1). All spectra show a dominant triplet at N
atom in the first position with splitting of about 14.1 G (in
toluene) and weaker satellites from 13C nuclei of the four
methyl groups in natural abundance (splitting about 5.7 G).
Minor splittings of 0.23 G from 12 nearly equivalent methyl
protons are also neatly resolved (Fig. 1c).
layer was separated and dried over K2CO3 and evaporated to
dryness under reduced pressure. Purification of the crude
product by column chromatography on Al2O3 (elution with
chloroform) and following recrystallization gave 80 mg
(72%) compounds 12, mp 180.5–182.0 8C (from mixture
of hexane–benzene). IR, cmK1: nmaxZ1306 (N/O), 1362
(N–%O). HRMS, m/z (%): 384.8 [M]C (16.84), 337.8
(73.54), 295.0 (19.22), 240.8 (21.97), 170.0 (99.63), 155.9
(57.73), 141.0 (69.80), 129.0 (50.06), 115.0 (49.39). Found:
m/z 385.03914 [M]C. C15H18IN2O2. Calcd: MZ385.04148.
ESR, G: gisoZ2.0060 (DHDPPH Z4.05 G), ANZ14.10
2. Conclusions
A
HðCH Þð12HÞZ0:23, A(13C)Z5.78. Solvent: toluene.
3
A synthetic approach to acetylenic derivatives of 3-imida-
zoline nitronyl nitroxide radicals (NNR) has been found.
Unlike nitronyl nitroxides of the 2-imidazoline series,
Sonogashira cross-coupling reaction is unsuitable for the
synthesis of 3-imidazoline nitroxides. It was found that
coupling reaction of Cu(I)-salts of 1-alkynes with the
corresponding iodo-containing 3-imidazolines leads to
disubstituted spin-labeled acetylenes in good yield. We
have investigated the cross-coupling of copper acetylides
with both spin-labeled 12 and diamagnetic 11 iodo-
imidazolines. In both cases cross-coupling leads to
paramagnetic derivatives 21a–g in 50–90% yields. ESR-
spectra of the prepared compounds are typical for
3-imidazoline radicals with spin density localized mostly
at the nitroxyl fragment.
3.1.2. 1-(O-Ethoxyethyl)-2,2,4,5,5-pentamethyl-3-imida-
zoline-3-oxide (16). A solution of imidazoline 3 (6.1 g,
35.3 mmol) and freshly distilled ethoxyethene 15 (5.1 mL,
52.9 mmol) in benzene (7 mL) was stirred at 45–50 8C in
the presence of traces of HCl for 3.5–4 h till absence of 3
(TLC-control). The reaction mixture was neutralized and
dried over K2CO3, filtered through A12O3, and concentrated
under reduced pressure. The final yellowish oil was purified
by vacuum distillation to give 8.2 g (95%) of the title
compound as a colorless oil, bp 110–111 8C/0.5 Torr, n1D7Z
1.4750. 1H NMR (CDCl3) d 1.09–1.53 (m, 18H, –CH–CH3,
–OCH2–CH3, 2,2,5,5-CH3), 1.90 (s, 3H, 4-CH3), 3.52–3.75
(two q, 2H, –OCH2–CH3, JZ5 Hz), 4.77 (q, 1H, –CH–CH3,
JZ9 Hz). Anal. Calcd for C12H24N2O3: C, 58.98; H, 9.86;
N,11.46. Found: C, 58.35; H, 9.48; N, 10.97.
3. Experimental
3.1. General
3.1.3. 1-Hydroxy-4-[2-(p-ethynylphenyl)vinyl]-2,2,5,5-
tetramethyl-3-imidazoline-3-oxide (5) and 4-[2-(p-ethy-
nylphenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-3-
oxide-1-oxyl (6). A solution of NaOH (440 mg, 11 mmol),
imidazoline derivative 3 (1.72 g, 10 mmol), and aldehyde 4
(1.3 g, 10 mmol) in MeOH (7 mL) was stirred at 45–50 8C
in argon atmosphere for 3.5–4 h till absence of aldehyde
(TLC-control). CHCl3 (30 mL) and water (40 mL) were
then added. The organic layer was separated and dried over
K2CO3 and evaporated to dryness under reduced pressure.
Purification of the mixture of 5 and 6 (420 mg, 15%) by
column chromatography on Al2O3 (elution with chloro-
form) followed by recrystallization gave the corresponding
compounds 5 and 6.
Melting points were determined with a hot-stage microscope.
Column chromatography was performed on Al2O3. The Rf
values were measured on aluminium backed TLC plates of
silica gel 60 F254 (Merck, 0.2 mm) with the indicated eluent.
1H NMR spectra were recorded on a Bruker DRX 400 (9.4 T,
200.13 MHz) spectrometer. Chemical shifts (d in parts per
million) are given from internal CHCl3 (7.24). Coupling
constants (J in Hertz) were accurate to G0.2 Hz for 1H. Mass
spectra (HRMS) were measured on a Finnigan SSQ-710 at
70 eV using electron impact modes. The IR-spectra were
recorded on a Bruker IFS 66 spectrometer (potassium
bromide). CW ESR spectra were taken in degassed solutions
on a Bruker EMX CW ESR spectrometer, all hyperfine
coupling constants and field offsets from standard DPPH line
are given in Gauss with accuracy G0.02 G, except for the
couplings with methyl carbon-13 for which the accuracy is G
0.1 G, concentration of radicals 10K5–10K4 M in the
indicated solvent. Compounds1,13 3,9 46 and 78 were prepared
by previously reported methods. Copper(I) acetylides (20a–g)
werepreparedaccordingtothepublishedprocedure12 fromthe
corresponding acetylenes. Commercial ethoxyethene 15 was
used freshly distilled over sodium and pyridine over NaOH;
phenylacetylene was used freshly distilled. Compound 16 and
PdCl2(PPh3)2 were used without additional purification.
For 5 the yield was 68 mg (2.4%), mp 169.0–171.0 8C (from
mixture of benzene–hexane). IR, cmK1: nmaxZ1295 (N/
O), 2105 (–C^C–), 3251 (C^C–H), 3441 (br, OH). H
1
NMR (CDCl3) d, 1.48 (s, 6H, 2,2-CH3), 1.59 (s, 6H, 5,5-
CH3), 3.15 (s, 1H, H–C^C), 4.77 (s br, 1H, OH), 6.65 (d,
–CH]CH-Ar, JZ16 Hz), 7.49 (s, 4H, HAr), 8.38 (d,
–CH]CH-Ar, JZ16 Hz). Anal. Calcd for C17H20N2O2: C,
71.81; H, 7.09; N, 9.85. Found: C, 71.65; H, 6.96; N, 9.98.
For 6 the yield was 85 mg (3%), mp 182.0–184.0 8C (from
mixture of benzene–hexane). IR, cmK1: nmaxZ1275 (N/
O), 1355 (N–%O), 2104 (–C^C–); 3250 (^C–H). Anal.
Calcd for C17H19N2O2: C, 72.06; H, 6.76; N, 9.89. Found:
C, 72.25; H, 6.55; N, 9.86. ESR, G: gisoZ2.0058 ANZ13.81
A
HðCH Þð12HÞZ0:24, A(13C)Z5.74. Solvent: n-hexane.
3.1.1. 4-[2-(p-Iodophenyl)vinyl]-2,2,5,5-tetramethyl-3-
imidazoline-3-oxide-1-oxyl (12). A mixture of 11 (0.11 g,
0.28 mmol) and NaIO4 (0.09 g, 4.2 mmol) in chloroform
(7 mL) and water (7 mL), was stirred at room temperature
for 2–2.5 h till absence of 11 (TLC-control). The organic
3
3.1.4. 1-Hydroxy-4-[2-(p-bromophenyl)vinyl]-2,2,5,5-tet-
ramethyl-3-imidazoline-3-oxide (9) and 4-[2-(p-bromo-
phenyl)vinyl]-2,2,5,5-tetramethyl-3-imidazoline-3-

S. F. Vasilevsky et al. / Tetrahedron 62 (2006) 4597–4602
4601
oxide-1-oxyl (10). For 9 the yield was 1.67 g (49%),
mp 153.0–154.0 8C (from mixture of hexane–benzene). IR,
cmK1: nmaxZ1320(N/O), 3241(br, OH). 1H NMR (CDCl3)
d, 1.44 (s, 6H, 2,2-CH3), 1.58 (s, 6H, 5,5-CH3), 5.29 (s br, 1H,
OH), 6.61–6.65 (d, 1H, –CH]CH-Ar, JZ16 Hz), 7.35–7.49
(d, d, 4H, HAr), 8.30–8.34 (d, 1H, –CH]CH-Ar, JZ16 Hz).
HRMS, m/z (%): 338.0 [M]C (7.90), 265.0 (8.19), 237.0
(8.97), 236.0 (8.40), 157.0 (15.24), 156.0 (100.0), 141.1
(30.46), 115.1 (9.83), 74.1 (10.60). Found: m/z 338.06344
[M]C. C15H19BrN2O2. Calcd: MZ338.06299.
CH3), 3.45–3.75 (m, 2H, –OCH2–CH3), 4.74 (q, 1H,
–CH–CH3), 6.41–6.49 (d, –CH]CH-Ar, JZ16 Hz), 7.21–
7.41 (m, 9H, Har), 8.31 (d, 1H, –CH]CH-Ar, JZ16 Hz).
Anal. Calcd for C27H32N2O3: C, 74.97; H, 7.46; N, 6.48.
Found: C, 74.83; H, 7.28; N, 6.30.
3.1.8. 1-(O-Ethoxyethyl)-2,2,5,5-tetramethyl-4-{2-[p-(3-
methyl-3-hydroxybutyn-1-yl)phenyl]vinyl}-3-imidazo-
line-3-oxide (18b). The yield of compound 18b was 580 mg
(48%) obtained from 1.23 g (3.0 mmol) of 17, mp 104.0–
106.0 8C (from hexane). IR, cmK1: nmaxZ1278 (N/O),
2220 (–C^C–), 3406 (br, OH). 1H NMR (CDCl3) d, 1.18 (t,
3H, –OCH2–CH3, JZ6 Hz), 1.21 (d, 3H, –CH–CH3, JZ
7 Hz), 1.31–1.65 (m, 18H, 2,2,5,5-CH3, –C(CH3)OH),
2.035 (s br, –C(CH3)OH), 3.51–3.91 (two q, 2H, –OCH2–
CH3, JZ6 Hz), 4.80–4.91 (q, 1H, –CH–CH3, JZ7 Hz),
6.54–6.65 (d, –CH]CH-Ar, JZ16 Hz), 7.32–7.47 (dd, 4H,
Har), 8.37–8.48 (d, –CH]CH-Ar, JZ16 Hz). HRMS, m/z
(%): 414.1 [M]C (10.04), 343.0 (25.46), 342.1 (77.46),
295.2 (14.03), 239.0 (17.93), 98.0 (19.81), 73.0 (100.0),
56.1 (13.72), 45.1 (82.62). Found: m/z 414.25148 [M]C.
C24H34N2O4. Calcd: MZ414.25184.
For 10 the yield was 480 mg (14%), mp 189.5–192.0 8C
(from mixture of benzene–hexane). IR, cmK1: nmaxZ1279
(N/O), 1363 (N–%O). HRMS, m/z (%): 337.0 [M]C (6.14),
291.8 (51.08), 290.0 (25.81), 247.9 (14.43), 236.9 (2.73),
170.1 (100.0), 156.0 (56.52), 141.1 (58.93), 115.1 (32.81),
102.1 (26.81). Found: m/z 337.05547 [M]C.
C15H18BrN2O2. Calcd: MZ337.05521. ESR: gisoZ2.0059
(DHDPPHZ3.97 G), ANZ13.86 G, AHðCH Þð12HÞZ0:22 G,
3
A(13C)Z5.62 G. Solvent: toluene.
3.1.5. 1-Hydroxy-4-[2-(p-iodophenyl)vinyl]-2,2,5,5-tetra-
methyl-3-imidazoline-3-oxide (11). The yield of com-
pound 11 was 2.15 g (28%), mp 175 (decomp.) 8C (from
ethylacetate). IR, cmK1: nmaxZ1310 (N/O), 3233 (br,
3.1.9. 1-(O-Ethoxyethyl)-2,2,5,5-tetramethyl-4-[2-(p-
ethynylphenyl)vinyl]-3-imidazoline-3-oxide (18c). A
mixture of 18b (150 mg, 0.36 mmol) and KOH (130 mg,
0.33 mmol) in 10 mL of toluene was stirred at 80–85 8C for
14 h till absence of alcohol (TLC-control). The reaction
mixture was filtered off through Al2O3 (elution with
chloroform), and evaporated to dryness under reduced
pressure. The crude product was purified by column
chromatography on Al2O3 (elution with chloroform) and
following recrystallization gave 74 mg (62%) of compound
18c, mp 93.0–94.5 8C (from mixture of hexane–benzene).
IR, cmK1: nmaxZ1325 (N/O), 2099 (–C^C–), 3221
(C^C–H), 1H NMR (CDCl3) d, 1.18–1.25 (t, 3H, –OCH2–
CH3, JZ4 Hz), 1.31–1.34 (d, 3H, –CH–CH3, JZ3 Hz),
1.43–1.65 (m, 12H, 2,2,5,5-CH3), 3.13 (s, 1H, C^C–H),
3.50–3.92 (two q, 2H, –OCH2–CH3, JZ4 Hz), 4.80–4.92 (q,
1H, –CH–CH3, JZ3 Hz), 6.55–6.63 (d, –CH]CH-Ar, JZ
16 Hz), 7.43–7.45 (s br, 4H, Har), 8.42–8.53 (d, –CH]CH-
Ar, JZ16 Hz). HRMS, m/z (%): 356.0 [M]C (1.07), 355.9
(3.78), 283.8 (58.09), 268.8 (4.17), 236.8 (9.31), 180.8
(11.41), 164.8 (15.12), 72.9 (100.0), 45.1 (86.33). Found:
m/z 356.20998 [M]C. C21H28N2O3. Calcd: MZ356.20999.
1
OH). H NMR (CDCl3) d, 1.44 (s, 6H, 2,2-CH3), 1.55 (s,
6H, 5,5,-CH3), 5.46 (s br, 1H, OH), 6.64 (d, 1H, –CH]CH-
Ar, JZ8 Hz), 7.22 (d, 2H, 2,6-HAr, JZ4 Hz), 7.65 (d, 2H,
3,5-HAr, JZ4 Hz), 8.27 (d, –CH]CH-Ar, JZ8 Hz). Anal.
Calcd for C15H19IN2O2: C, 46.65; H, 4.96; N, 7.25; I, 32.86.
Found: C, 47.00; H, 5.40; N, 6.92; I, 32.39.
3.1.6. 1-(O-Ethoxyethyl)-4-[2-(p-bromophenyl)vinyl]-
2,2,5,5-tetramethyl-3-imidazoline-3-oxide (17). The
yield of compound 17 was 1.50 g (36%, viscous liquid).
IR, cmK1: nmaxZ1298 (N/O). 1H NMR (CDCl3) d, 1.15–
1.54 (m, 18H, 2,2,5,5-CH3, –OCH2–CH3, –CH–CH3), 3.54–
3.85 (m, 2H, –CH2–CH3), 4.79 (q, 1H, –CH–CH3, JZ9 Hz),
6.39–6.47 (d, 1H, –CH]CH-Ar, JZ16 Hz), 7.31–7.43 (q,
4H, Har), 8.30–8.38 (d, 1H, –CH]CH-Ar, JZ16 Hz).
HRMS, m/z (%): 409.9 [M]C (12.41), 339.8 (63.51), 337.8
(64.89), 156.0 (58.47), 140.9 (40.75), 98.0 (41.37), 73.0
(100.0), 56.0 (35.40), 45.0 (89.33). Found: m/z 410.12611
[M]C. C19H27BrN2O3. Calcd: MZ410.12054.
3.1.7. 1-(O-Ethoxyethyl)-2,2,5,5-tetramethyl-4-{2-[4-
(p-phenylethynyl)phenyl)vinyl}-3-imidazoline-3-oxide
(18a). A mixture of the halogen compound 17 (171 mg,
0.4 mmol), alkyne 13a (43 mg, 0.43 mmol), PdCl2(PPh3)2
(40 mg) and CuI (20 mg) and Et3N or piperidine (10 mL)
was stirred under argon stream at 80 8C for 3 h. The solvent
was removed with an oil pump (0.1 Torr) at 20 8C, the
residue was dissolved in benzene, the solution was filtered
through a thin-layer of Al2O3 and evaporated to dryness
under reduced pressure. The crude product was purified by
column chromatography on Al2O3, and the solvent was
distilled off. Purification of the crude product by column
chromatography on Al2O3 (elution with chloroform) and
following crystallization gave the corresponding compound
18a. The yield of compound 18a was 125 mg (72%), mp
138–140 8C (from hexane). IR, cmK1: nmaxZ1325 (N/O),
3.1.10. 2,2,5,5-Tetramethyl-4-{2-[4-(p-phenylethynyl)
phenyl]vinyl}-3-imidazoline-3-oxide-1-oxyl (21a). A mix-
ture of copper(I) salt of acetylenes 20a (60 mg, 0.36 mmol)
and diamagnetic (11) or spin-labeled iodide (12) (130 mg,
0.33 mmol) in 10 mL of pyridine was stirred at 80–85 8C in
argon atmosphere for 3.5–4 h till absence of iodide (TLC-
control). Then CHCl3 (30 ml) and water (40 mL) were
added. The organic layer was separated, the water layer was
extracted with CHCl3 (2!25 mL), and the combined
organic layers were washed with 25% NH3aq (2!15 mL),
dried over K2CO3, filtered off and evaporated to dryness
under reduced pressure. The crude product was purified by
column chromatography on Al2O3 (elution with chloro-
form) and following recrystallization gave 100 mg (85%)
of nitroxide 21a, mp 197.5–198.5 8C (from benzene). IR,
cmK1: nmaxZ1315 (N/O), 1364 (N–%O), 2216 (C^C).
Anal. Calcd for C23H23N2O2: C, 76.85; H, 6.45; N, 7.79.
1
2220 (–C^C–). H NMR (CDCl3) d, 1.12–1.16 (m, 6H,
–CH–CH3, –OCH2–CH3), 1.26–1.43 (m, 12H, 2,2,5,5-

4602
S. F. Vasilevsky et al. / Tetrahedron 62 (2006) 4597–4602
Found: C, 76.63 H, 6.51 N, 7.87 ESR: gisoZ2.0058
3.1.16. 2,2,5,5-Tetramethyl-4-{2-[4-(p-bromophenyl-
ethynyl)phenyl]vinyl}-3-imidazoline-3-oxide-1-oxyl
(21g). The yield of compound 21g was 100 mg (69%), mp
192.5–193.5 8C (from benzene). IR, cmK1: nmaxZ1314 (N/
O), 1361 (N–%O), 2212 (C^C). HRMS, m/z (%): 437.0 [M]C
(6.34), 410.1 (7.24), 407.0 (35.07), 394.0 (39.32), 391.9
(100.00), 350.9 (37.18), 349.9 (45.67), 294.9 (37.56), 257.1
(9.18), 239.1 (50.58), 176.0 (23.43), 150.0 (11.40), 135.1
(30.55), 98.1 (24.57). Found: m/z 437.08795 C23H22N2O2Br.
Calcd: MZ437.08651. ESR: gisoZ2.0057 (DHDPPHZ3.6 G),
(DHDPPHZ3.79 G), ANZ14.05 G, AHðCH Þð12HÞZ0:23 G,
3
A(13C)Z5.66 G. Solvent: toluene.
From spin-labeled iodide 12: the yield of compound 21a
was 50 mg (85%) obtained from 65 mg (0.165 mmol) of 12,
mp 197.5–198.5 8C (from benzene).
3.1.11. 2,2,5,5-Tetramethyl-4-{2-[4-(3-phenoxyprop-1-
ynyl)phenyl]vinyl}-3-imidazoline-3-oxide-1-oxyl (21b).
The yield of compound 21b was 120 mg (92%), mp
161.5–163.5 8C (from mixture of benzene–hexane). IR,
cmK1: nmaxZ1318 (N/O), 1360 (N–%O), 2225 (C^C).
HRMS, m/z (%): 389.0 [MC] (24.15), 222.0 (27.09), 221.0
(15.41), 207.9 (11.70), 194.9 (39.90), 94.0 (11.80), 73.1
(43.77), 72.0 (63.66), 67.0 (14.59). Found: m/z 389.18652
ANZ14.09 G, AHðCH Þð12HÞZ0:23 G, A(13C)Z5.72 G. Sol-
3
vent: toluene.
Acknowledgements
[MC]. C24H25N2O3. Calcd: MZ389.18650. ESR: giso
Z
This work was supported by RFBR grant No 02-03-32265,
grant CRDF REC No 008-XI. The Chemical Service Center
of SB RAS. D.V.S. is grateful to the Science Support
Foundation for awarding a personal scholarship.
2.0059
HðCH Þð12HÞZ0:23 G, A(13C)Z5.81 G. Solvent: toluene.
(DHDPPHZ4.00 G),
ANZ14.13 G,
A
3
3.1.12. 4-{2-[p-(N-Ethoxyethyl-1H-pyrazol-4-ylethynyl)-
phenyl]vinyl}-2,2,5,5-tetramethyl-3-imidazoline-3-oxide-
1-oxyl (21c). The yield of compound 21c was 111 mg (80%),
mp 169.0–170.0 8C (from benzene). IR, cmK1: nmaxZ1310
(N/O), 1351 (N–%O), 2214 (C^C). Anal. Calcd for
C24H29N4O3: C, 68.39; H, 6.93; N, 11.39. Found: C, 66.35;
H, 7.07; N, 12.09. ESR: gisoZ2.0060 (DHDPPHZ4.10 G),
References and notes
1. Buchachenko, A. L.; Berdinsky, V. L. Chem. Rev. 2002, 102,
603–612.
ANZ14.11 G, AHðCH Þð12HÞZ0:23 G, A(13C)Z5.93 G. Sol-
2. Sviridenko, F. V.; Stass, D. V.; Kobzeva, T. V.; Tretyakov,
E. V.; Klyatskaya, S. V.; Mshvidobadze, E. V.; Vasilevsky,
S. F.; Molin, Yu. N. J. Am. Chem. Soc. 2004, 126, 2807–2819.
3. Vasilevsky, S. F.; Klyatskaya, S. V.; Korovnikova, O. L.;
Stass, D. V.; Amitina, S. A.; Grigor’ev, I. A.; Elguero, J.
Tetrahedron Lett. 2004, 45, 7741–7743.
3
vent: toluene.
3.1.13. 2,2,5,5-Tetramethyl-4-{2-[4-(p-methoxyphenyl
ethynyl)phenyl]vinyl}-3-imidazoline-3-oxide-1-oxyl
(21d). The yield of compound 21d was 120 mg (92%), mp
172.0–173.0 8C (from mixture of benzene–hexane). IR,
cmK1: nmaxZ1295 (N/O), 1343 (N–%O), 2212 (C^C).
Anal. Calcd for C24H25N2O3: C, 74.01; H, 6.47; N, 7.19.
Found: C, 74.15; H, 6.58; N, 7.12. ESR: gisoZ2.0058
4. Klein, J.; Gurfinkel, E. Tetrahedron 1970, 26, 2127–2131.
5. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 50, 4467–4470. (b) Brandsma, L.; Vasilevsky, S. F.;
Verkruijsse, H. D. Application of Transition Metal Catalysts in
Organic Synthesis; Springer: Berlin, New York, 1998.
6. Klyatskaya, S. V.; Tretyakov, E. V.; Vasilevsky, S. F. Izv.
Akad. Nauk, Ser. Khim. 2002, 122–127. Russ. Chem. Bull., Int.
Ed. 2002, 51, 128–133.
(DHDPPHZ3.71 G), ANZ14.09 G, AHðCH Þð12HÞZ0:23 G,
3
A(13C)Z5.71 G. Solvent: toluene.
3.1.14. 2,2,5,5-Tetramethyl-4-{2-[p-(2-pyridinylethynyl)
phenyl]vinyl}-3-imidazoline-3-oxide-1-oxyl (21e). The
yield of compound 21e was 84 mg (90%) obtained from
100 mg (0.239 mmol) of 11, mp 179.5–180.0 8C (from
mixture of benzene–hexane). IR, cmK1: nmaxZ1283 (N/
O), 1365 (N–%O), 2221 (C^C). Anal. Calcd for C22H22N3O2:
C, 73.31; H, 6.15; N, 11.66. Found: C, 73.33; H, 6.60; N,
11.20. ESR: gisoZ2.0059 (DHDPPHZ4.05 G), ANZ13.81 G,
7. Vasilevsky, S. F.; Klyatskaya, S. V.; Tretyakov, E. V.;
Elguero, J. Hererocycles 2003, 60, 879–886.
8. Tretyakov, E. V.; Novikova, T. V.; Korolev, V. V.;
Usov, O. M.; Vasilevsky, S. F.; Molin, Yu. N. Izv. Akad.
Nauk, Ser. Khim. 2000, 1415–1420. Russ. Chem. Bull., Int. Ed.
2000, 49, 1409–1414.
9. Imidazoline Nitroxides; Volodarsky, L. B., Ed.; Synthesis
and Properties; CRC: Boca Raton, Florida, 1988; Vol. 1;
pp 171–214.
A
HðCH Þð12HÞZ0:23 G, A(13C)Z5.60 G. Solvent: toluene.
3
3.1.15. 2,2,5,5-Tetramethyl-4-{2-[p-(2,3,5,6,8,9,11,12-
octahydro-1,4,7,10,13-pentaoxabenzocyclopentadecen-
15-yl-ethynyl)phenyl]vinyl}-3-imidazoline-3-oxide-1-
oxyl (21f). The yield of compound 21f was 90 mg (50%),
mp 178.5–180.0 8C (from mixture of benzene–hexane).
IR, cmK1: nmaxZ1253 (N/O), 1363 (N–%O), 2205
(C^C). HRMS, m/z (%): 549.2 [M]C (15.31), 534.1
(31.71), 504.1 (24.31), 502.2 (45.38), 448.3 (12.07),
447.3 (35.54), 343.1 (11.61), 295.2 (18.03), 189.2 (6.38),
180.1 (23.58), 163.1 (33.76), 98.2 (28.67). Found: m/z
549.25942 [M]CC31H37N2O7. Calcd: MZ549.26006.
ESR: gisoZ2.0059 (DHDPPHZ4.10 G), ANZ3.74 G,
10. Volodarsky, L. B.; Grigor’ev, I. A.; Grigor’eva, L. N.;
Kirilyuk, I. A. Tetrahedron Lett. 1984, 25, 5809–5812.
11. Grigor’ev, I. A.; Martin, V. V.; Schukin, G. I.; Mamatyuk, V. I.;
Volodarsky, L. B. Khim Geter. Soed. 1985, 2, 247–251
(Russ. Ed.). Grigor’ev, I. A.; Martin, V. V.; Schukin, G. I.;
Mamatyuk, V. I.; Volodarsky, L. B. Khim. Geter. Soed. 1985, 2,
205–209.
12. Tretyakov, E. V.; Knight, D. W.; Vasilevsky, S. F. J. Chem.
Soc., Perkin Trans. 1 1999, 3713–3720.
13. An Atlas of IR Spectra of Aromatic and Heterocyclic
Compounds; Koptyug, V. A., Ed.; Institute of Organic
Chemistry of Siberian Branch of Russian Academy of
Sciences; Novosibirsk: Russia, 1979; Vol. 17.
A
HðCH Þð12HÞZ0:22 G, A(13C)Z5.57 G. Solvent: toluene.
3