Aminonitrone-N-hydroxyaminoimine tautomeric equilibrium in the series of 1-hydroxy-2-imidazolines

Article abstract of DOI:10.1016/j.molstruc.2004.02.028

A series of 2-substituted 1-hydroxy-4,4,5,5-tetramethyl-4,5-dihydro-1H- imidazoles have been synthesized. Various effects on the state of the aminonitrone-N-hydroxyaminoimine tautomeric equilibrium, including solvent effects and substituent effect in the 2 position of heterocycle, have been studied.

Full text of DOI:10.1016/j.molstruc.2004.02.028

Journal of Molecular Structure 697 (2004) 49–60
www.elsevier.com/locate/molstruc
Aminonitrone-N-hydroxyaminoimine tautomeric equilibrium in the series
of 1-hydroxy-2-imidazolines
Sergey A. Popova, Rodion V. Andreevb, Galina V. Romanenkoa, Viktor I. Ovcharenkoa,
Vladimir A. Reznikovb,
*
aInternational Tomography Center, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russian Federation
bN.N. Vorozhtsov Institute of Organic Chemistry Siberian Branch, Russian Academy of Sciences, Lavrentev Ave. 9, Novosibirsk, Russian Federation
Received 9 January 2004; revised 9 January 2004; accepted 18 February 2004
Abstract
A series of 2-substituted 1-hydroxy-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazoles have been synthesized. Various effects on the state of
the aminonitrone-N-hydroxyaminoimine tautomeric equilibrium, including solvent effects and substituent effect in the 2 position of
heterocycle, have been studied.
q 2004 Elsevier B.V. All rights reserved.
Keywords: Tautomerism; Ab initio calculations; 2-Imidazoline; 4,5-Dihydro-1H-imidazole; Nitrone
1. Introduction
the possibility of existence in two tautomeric forms:
aminonitrone (A) and N-hydroxyaminoimino (B) [6].
The 1,3-dipolar cycloaddition reaction is a powerful tool
for the design of heterocyclic structures. This is a useful
approach to syntheses of complex structures with adjusted
geometry in view of the high regio- and stereo-selectivity of
this reaction. Further transformations of the initially formed
cycloadducts make this strategy highly versatile [1].
Nitrones are typical examples of 1,3-dipoles easily partici-
pating in cycloaddition reactions. 1,3-Cycloaddition reac-
tion is well studied for nitrones in the series of 2,5-dihydro-
1H-imidazole-3-oxides and are still being investigated [2].
Data on cycloadditions of 4,5-dihydro-1H-imidazoles are
scarce [3,4]; there is only one instance of the involvement of
4,5-dihydro-1H-imidazole with a nitrone group in the
heterocycle as a dipole into cycloaddition reaction [5] No
data are available on participation of 4,5-dihydro-1H-
imidazole-3-oxide without substituents at the second
nitrogen atom in this reaction.
Of these two forms, only A can act as a 1,3-dipole;
in its reactions with dipolarophiles, form B can only act
as a nucleophile. Therefore, reactions of compounds of
this type with activated alkenes or alkynes as dipolar-
ophiles will probably occur as nucleophilic additions or
cycloadditions. Since cycloadditions are generally con-
sidered to be concerted processes, the reaction kinetics
must depend on the content of the nitrone form;
however, no data are available in the literature
concerning the state of the A Y B tautomeric equili-
brium. According to the data published in ref.6, the
major form of imidazoline 1d in ethanolic solutions is
aminonitrone. Imidazoline 1c exists in chloroform
The distinguishing feature of 4,5-dihydro-1H-imidazole-
3-oxide with an unsubstituted nitrogen atom is
*
Corresponding author. Tel.: þ7-383-234-2387; fax: þ7-383-234-2387.
E-mail addresses: mslf@nioch.nsc.r (V.A. Reznikov), serge@nioch.
nsc.ru (S.A. Popov).
0022-2860/$ - see front matter q 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2004.02.028

50
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
solutions mainly in N-hydroxyaminoimino form [7].
Thus, the available data preclude any conclusions
about the composition of the tautomeric mixture,
affecting the reactions of 4,5-dihydro-1H-imidazole-3-
oxide derivatives with dipolarophiles. The aim of the
present work, therefore, is investigation of the influence
of the structure and nature of the solvent on the state of
the A Y B tautomeric equilibrium.
between the forms. At temperatures lowered to 290 8C,
one can only observe the broadening of the signals of the
methyl protons, which may result from the retardation of
the imidazoline heterocycle inversion.
The ratio between the tautomeric forms was deter-
mined using the position of the metathetical signal
relative to the respective signals of ‘fixed tautomers’
3Aa–k and 3Ba–k in the 13C NMR spectra; 1B ¼ 1
A ¼ Dd1=Dd2: The C-2 atom was shown to be
most sensitive to tautomeric transformations (Dd is
maximal). Synthesis of ‘models’ 3B and 3A is shown
in Scheme 1.
2. Results and discussion
Aminonitrone-N-hydroxyaminoimine tautomerism is
considered to be an acid-base equilibrium with the ratio
between the forms dictated by the ratio of their acidity
constants. The state of the ½AŠ Y ½BŠ tautomeric equili-
brium depends on the balance between the stabilizing and
destabilizing factors.
Replacement of the proton at N-1 to the methyl group
or of the hydroxy group to the methoxy group can
obviously lead to noticeable changes in the positions of
the signals of the nearest atoms (1–4 bonds). These
changes must be taken into account in determining the
ratio between the tautomeric forms (b-, g- and d-effects
of substituent). Using the chemical shifts of C-10 for this
purpose seems to be justified despite their lower
sensitivity to tautomeric transformations, because the
substituent introduced at that atom into the model
The ratio between the tautomeric forms was determined
by 13C NMR. In this case, as well as in most acid–base
equilibria, proton transfer from one form to another is fast
on the NMR time scale, precluding NMR observation of
each form separately and direct determination of the ratio
Scheme 1.

S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
51
molecule usually has minor effect compared to the
substitutent at C-2.
calculation of methyl group effects and the higher
sensitivity of the former to tautomeric transformations.
The solvent has a pronounced effect on the compo-
sition of the tautomeric mixture (Table 2). According to
calculations, nitrone form A is more polar than N-
hydroxyaminoimino
form
B
(HF/6-31G(d,p),
mð1AcÞ ¼ 5:43 D, mð1BcÞ ¼ 2:35 D); hence, polar sol-
vents stabilize form A more effectively than form B.
Thus, the content of nitrone form 1Ac grows noticeably
with solvent inductivity in the order CCl4 , CDCl3 ,
CD2Cl2. To evaluate the solvent effect, specific solvation
effects must be taken into account along with solvent
inductivity. Thus, protic solvents such as methanol are
capable of forming hydrogen bonds, which are more
important for the nitrone form (structure 7). Aprotic
solvents (DMSO) form solvates of type 8, stabilizing N-
hydroxyaminoimino form B.
The b- and g-effects of the methyl group for the
series of N-methyl-substituted 4,4,5,5-tetramethyl-2-imi-
dazoline-1-oxides 3Aa–k were evaluated from
literature data for structurally related compounds 5 and
6 (Table 1).
Based on the values of the g-effect of the methyl group in
molecule 5 (Table 1), the g-effect of the methyl group in 2-
substituted 1-methoxy-4,4,5,5-tetramethyl-4,5-dihydro-1H-
imidazoles 3B is expected to be 0–1.0 ppm. Replacement of
the methyl group by acyl in 2b–e,g changes the chemical
shift of C-2 by only 0.5–1.0 ppm. Moreover, replacement of
hydrogen at nitrogen atom to the methyl group of imidazo-
line 1a, which in chloroform solutions exists almost entirely
in N-hydroxyaminoimino form B (see below), shifts the
signal of C-2 (g-position) in the 13C NMR spectrum by
20.81 ppm, in which case the d-effect is shown to be
insignificant.
Thus, in the case of methanol as a solvent, nitrone
form A is stabilized by both high inductivity and
hydrogen bonding. In DMSO, these are counter-effects.
This leads to an anomalously high content of form 1Bc
in DMSO-d6 and immeasurably low content in CD3OD
(Table 2).
Based on the values of the b- and g-effect (for 3Ac,
b ¼ 1:1 ppm, g ¼ 21:6 ppm; for 3Bc, g ¼ 0:5 ppm and
d ¼ 0:0 ppm), we determined the composition of the 1Ac
1Bc tautomeric mixture using 13C NMR spectra. The C-2
and C-10 chemical shifts of 1c along with those of
models 3AC and 3BC and the tautomer ratio are
summarized in Table 2 for different solvents. The
tautomer ratios obtained from the C-2 chemical
shifts seem to be more reliable than those obtained
from the C-10 chemical shifts due to the correct
Intramolecular hydrogen bonding is even more
essential to the A : B ratio than intermolecular
hydrogen bonding. Thus, in contrast to 1b and 1c,
imidazolines 1i and 1j exist in nitrone form A even in
crystals due to intramolecular hydrogen bonding between
the aromatic hydroxyl group and the nitrone oxygen
atom [8].
Since in some solvents imidazoline 1c exists in only one
tautomeric form, the b-, g-, and d-effects may be evaluated
more accuratelyfor each substituent R. Thus, the difference
between the C-2 and C-10 chemical shifts of imidazoline 1c
in N-hydroxyaminoimino form B (in CCl4 as a solvent) and
the corresponding methoxy derivative 3Bc actually equals
the values of the g- and d-effects of the methyl
group attached to the oxygen atom. In methanol, 1c exists
in nitrone form, permitting one to calculate the effect of
the methyl group attached to nitrogen atom. This assump-
tion gives bð3AcÞ ¼ 0:2 ppm, gð3AcÞ ¼ 21:6 ppm,
gð3BcÞ ¼ 1:0 ppm, and dð3BcÞ ¼ 0:2 ppm. For 1a,
Table 1
b and g effects of the methyl group for 5 and 6 based on literature data
[9–12]
5
6
R ¼ H
2.8
R ¼ Me
0.2
R ¼ Ph
0.5
b
g
1.1
–
22.4
0.1
–

52
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
Table 2
13C NMR chemical shifts of C2 and C1 atoms in compounds 3Ac, 3Bc, and 1c in different solvents
0
1a
C2
0
C1
3Ac
1c
3Bc
B/A
3Ac
1c
3Bc
B/A
CCl4
2.23
149.37
146.35
154.50
153.08
151.63
165.14
159.27
157.67
152.88
161.68
164.11
163.48
163.84
166.26
162.91
q 10
9.69
8.74
9.78
8.30
9.12
13.49
12.52
12.15
9.89
13.28
13.11
13.49
12.70
13.47
q 10
CDCl3
4.70
8.9
2.97 (2.50)
0.64 (0.47)
p 0.1
3.64 (2.74)
0.58 (0.50)
p 0.1
CD2Cl2
CH3OD
DMSO-d6
32.6
49
6.45 (4.54)
13.07
5.88 (3.87)
The values in parentheses calculated using the corrected values of b; g and d effects.
Dielectric constants for non-deuterated solvents.
a
similar calculations give gð3BaÞ ¼ 0:81 ppm and
with molecule 1. To calculate the ratio between forms B and
A, we used the averaged values of effects: b ¼ 1:1 ppm and
g ¼ 0:1 ppm for 3A (for 3Ac, g ¼ 21:6 ppm); g ¼ 0:5 ppm
and d ¼ 0:0 ppm for 3B. The accuracy of these estimations is
only important if the difference in the concentrations offorms
very large.
dð3BaÞ ¼ 0:15 ppm.
The form concentrations obtained from the C-2 and C-10
chemical shifts are in good agreement with each other
(Fig. 1). For 2-aryl-substituted compound 1 (R ¼ Ph,
p-NO2-Ph, etc.), where B : A , 1; the inverse proportion,
A : B; is more appropriate.
The substituent effect at the C-2 atom of imidazoline
seems to be the result of the action of several factors
(inductive or mesomeric effects, polarity, etc.). One of
possible reasons for the shift of the tautomeric equilibrium is
unequal modification of the acidity constants of the
tautomeric forms. The degree of stabilization must be
proportional to changes in electron density on the atoms
bearing the acid proton (N-3 and O). Increased electron
density results in increased X–H bond order, stabilizing the
structures. Decreased electron density acts oppositely. The
inductive effect is known to decrease noticeably on
the distance. The distances between the N- and O-acidic
centers and the R substituent differ in tautomers B and A:
three and two bonds, respectively. The ability of a bond to
transmit polarization effect increases with bond order,
changing oppositely with the length of the bond. Typical
This refinement of the b-, g-, and d-effects does not
markedly change the calculated ratio of forms, but improves
the correlation between the data obtained for the C-2 and
C-10 atoms (Table 2).
The nature of the substituent in the 2 position of the
imidazoline heterocycle markedly influences the state of the
tautomeric equilibrium. Interaction of the substituent with
the p-system changes the acid-base properties of both
heteroatomic fragments. Substituent effects on the tauto-
meric equilibrium were investigated in chloroform (Table 3),
because this solvent is not involved in specific interactions
Table 3
13C NMR chemical shifts of C2 and C1 atoms (chloroform) of 3A, 3B, and 1 and the B:A ratio
0
0
C1
R
C2
3A
1
3B
B:A
3A
1
3B
B:A
a
b
c
136.5a
155.6
153.34
159.27
147.67
148.05
144
154.79
156.32
163.84
164.95
163.14
164.96b
165.38
165.06b
162.07b
q 10
4.72
2.97
0.17
0.26
,0.1
0.81
0.38
0.25
111.2a
–
117.44
–
117.29
–
q 10
–
138a
146.35
145.79
145.05
147.05
147.35
148
8.736
12.515
126.38
132.69
118.18
125.49
123.88
110.77
13.114
131.299
137.55
122.72
128.31
127.73
115.59
3.64
0.20
0.30
0.18
1.18
0.59
0.35
d
e
125.49
131.33
117.18
122.25
121.7
f
g
h
k
155.05
152
142.82
145.89
109.16
a
Calculated from the experimental values of substituent a-effects (aH ¼ 0 ppm; aCF3 < 21:5 ppm).
b
NMR of acyl-substituted derivatives 2f, h, k. The difference between the g-effects was taken into account ðDg < 1:0 ppmÞ:

S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
53
Fig. 2. The spatial structure of 1Ab (ab initio calculations) and 1Bb (X-ray
analysis data).
between the atomic orbitals of N1 and N3 and the p-system
of the substituent.
The spatial structure of 1Bb and 1Ab according to
X-ray analysis data and ab initio calculations is shown in
Fig. 2. The hydroxyl oxygen atom in tautomer 1Bb and
the hydrogen atom of the N–H bond in 1Ab are out of
the plane of p-conjugation (N1–C2–N3), which hinders
effective involvement of the lone electron pairs of
nitrogen and oxygen in conjugation (Table 5). The N1–
C2 bond in form B is long, the bond order being thus
lower than that of C2–N3 in form A (Table 4). For N1–
O, the bond order is slightly higher than single (Table 4),
indicating that the p-overlap is insignificant and the
transmission of the mesomeric effect from substituent to
this center is inefficient. Hence, the mesomeric effect of
substituent does not change electron density on oxygen
as greatly as it does on N-3. This is confirmed by the
calculated Mulliken charges on N-3 and O (Table 6).
Fig. 1. The values of 1B(b-k): 1A(b-k) and C2 (C1) correlation.
˚
bond lengths reported in the literature are C–N 1.514 (A),
˚
CyN 1.281 (A), [13] N–O 1.460 (A), [14] and NyO 1.197
˚
˚
(A) [15]. On the other hand, according to X-ray analysis data
and quantum-mechanical calculations (Table 4), N1–C2 and
N1–O in 2 and C2–N3 in 1A are very nearly single bonds.
Hence, the inductive effect of substituent R is greater on
nitrogen compared to oxygen, and the substituent with a
negative (2I) inductive effect, will destabilize the nitrone
form more effectively compared to the N-hydroxyaminoi-
mino form. Substituents with a positive (þI) inductive effect
will stabilize nitrone form A. Thus, the content of the nitrone
form changes as follows: CH3 . H . CF3 (Table 3).
The substituent attached to an sp2-hybridized carbon
displays a 2I effect. At the same time, it can have a strong
mesomeric effect. The larger the overlap integral, the higher
the efficiency of the transmission. According to X-ray
analysis data and quantum-mechanical calculations
(Table 4), the bond order for N1–C2 in form B and C2–
N3 in form A is higher than single, leading to an overlap
According to calculations, charge variation is 0.017 e on
ꢀ
oxygen and 0.048 e on N-3. Hence, when we introduce a
ꢀ
substituent with a positive (þM) mesomeric effect,
greater stabilization is achieved for the nitrone form.
Introduction of phenyl or substituted phenyl groups into
Table 4
˚
N1–C2, C2–N3, and N1–O bond lengths (A) in 1A(a–k) and 1B(a–k)
Table 5
N1C2N3H and N3C2N1O dihedral angles in 1A(a–k) and 1B(a–k)
according to X-ray data and HF/6-31G (d,p) ab initio quantum-mechanical
calculations
according to X-ray data and HF/6-31G (d,p) ab initio quantum-mechanical
calculations
R
A
B
R
A
B
Ab initio
C2–N3
X-ray
Ab initio
N1–C2
X-ray
/N1C2N3H
Ab initio
/N3C2N1O
Ab initio
C2–N3
N1–O
N1–C2
N1–O
X-ray
X-ray
a
b
c
d
e
f
1.384
1.383
1.385
1.391
1.392
1.391
1.388
1.388
1.377a
1.367
1.389
1.395
1.394
1.403
1.408
1.405
1.408
1.410
1.407
1.402a
1.391
1.405
1.383
1.386
1.386
1.386
1.386
1.386
1.386
1.385
1.383a
1.387
1.385
a
b
c
d
e
f
147.40
146.37
147.33
143.74
143.21
143.49
147.29
146.61
147.21a
152.85
146.61
148.93
148.98
149.88
146.83
146.62
147.22
146.38
147.93
147.53a
145.97
150.03
1.357
1.394
1.407
1.415
153.26
150.74
g
h
I
g
h
I
1.357
1.346
155.94
164.02
j
j
k
k
a
a
The bromine atom was exchanged for chlorine for simplification of
calculations.
Bromine atom was exchanged for chlorine for the simplification of
calculations.

54
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
Table 6
Table 7
0
0
The values of Mulliken charges at N-3 and O for A and B in eꢀ; calculated ab
initio HF/6-31G(d,p)
Dihedral angles N1C2C1 C2 in 1A(d–k) and 1B(d–k) according to X-ray
analysis data and quantum-mechanical calculations ab initio HF/6-31G
(d,p)
R
A (N3)
B (O)
R
A
B
a
b
c
d
e
f
20.670
20.655
20.675
20.701
20.701
20.703
20.674
20.679
20.701
20.685
20.691
20.490
20.497
20.496
20.488
20.488
20.488
20.489
20.491
20.482
20.499
20.494
Ab initio
X-ray
Ab initio
X-ray
35.38
d
e
f
18.78
19.28
17.80
53.27
63.03
32.18a
27.83
2.57
30.53
30.74
27.37
41.34
83.98
14.95a
7.71
g
h
I
g
h
ia
j
33.82
27.24
j
k
9.12
k
a
a
Bromine atom was exchanged for chlorine for the simplification of
Bromine atom was exchanged for chlorine for the simplification of
calculations.
calculations.
a molecule 1 is the different spatial hindrance for coming
into being planar for different tautomers 1Ad–k and 1Bd–k.
Thus, according to quantum-mechanical calculations for
tautomers 1Bd–h, k, the bulky hydroxy group is a greater
obstacle than the oxygen atom of the nitrone group in 1Ad–
molecule 1 significantly increases the content of nitrone
form A (Table 3). Introduction of a substituent with an
appreciable 2M (NO2) or þM (OCH3) effect into the
para-position of the phenyl group markedly changes the
p-donor properties of the substituent, incidentally chan-
ging its inductive effect. The para-nitrophenyl group
decreases the content of the nitrone form because of its
minor stabilization effect, whereas the para-methoxypne-
nyl group provides additional stabilization of this form
compared to the unsubstituted phenyl group (Table 3).
The spatial structure of the molecule, namely, the
planarity of the R substituent is another factor essential to
the state of the tautomeric equilibrium. According to
quantum-mechanical calculations, the phenyl group and the
heteroatom fragment cannot be planar because of steric
hindrance (Fig. 3). As the dihedral angle between the phenyl
ring and the N1–C2–N3 plane increases, the efficiency of
conjugation decreases along with the degree of stabilization
of the respective form. The distinctive peculiarity of
0
0
h, k (Table 7). Hence, the smaller N1C2C1 C2 dihedral angle,
typically found in the nitrone form, provides more efficient
stabilization of this form compared to the N-hydroxyami-
noimino form.
Sequential introduction of methyl groups into the ortho-
position of the phenyl ring results in increased steric
0
0
hindrance and hence in increased N1C2C1 C2 dihedral
angle. Thus, the hypsochromic shift of the long-wave
maximum in the UV spectra of the series of nitroxides 4d
(596 nm) . 4g (556 nm) . 4h (537 nm) is obviously
0
0
caused by an increase in the N1C2C1 C2 dihedral angle.
Another evidence for this is an upfield shift of the proton
signals of the acyl group in 2g (1.70 ppm) relative to 2d
(1.95 ppm), of the methoxy group in 3Bg (d 3.43 ppm)
relative to 3Bd (3.68 ppm), and of the N-methyl group in 3Ag
(d 2.45 ppm) relative to 3Ad (d 2.59 ppm), obviously
resulting from the turning of the cone of magnetic anisotropy
for the phenyl group.
0
0
As the N1C2C1 C2 dihedral angle increases, the effi-
ciency of conjugation in molecules 1g, h decreases
compared to 1d; this results in less resonance stabilization
of the nitrone form, whose content in these compounds is
thus lower than that in 1d (Table 3). In 1h, however, the
content of the nitrone form is higher than that in 1g; the
reason for this is the different symmetry of substituents.
Molecule 1g with a 2,4-dimethylphenyl group can exist as
two different conformers, one of which, s-trans 1Bg, is more
0
0
stable (Fig. 3). In this conformer, the N1C2C1 C2 dihedral
angle is smaller than that in s-cis1 1Ag; this results in less
destabilization of 1Bg compared to 1Ag.
1
s-trans and s-cis conformers are considered here regarding to the
position relatively to the plane ðXYÞ of methyl groups in phenyl ring and
nitrone oxygen atom in tautomer A or hydroxyl group in tautomer B.
Fig. 3. The spatial structure of s-cis and s-trans conformers of 1Ag and 1Bg
(ab initio calculations).

S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
55
Table 8
Experimental and calculated (HF/6-31G(d,p)) DEcomb: for B and A
3. Conclusions
Thus, the state of the aminonitrone-N-hydroxyaminoi-
mino tautomeric equilibrium in the series of 1-hydroxy-
2-imidazolines in solutions depends on various factors,
including the nature of the solvent and the structure of
the substituent in the 2-position of heterocycle. The
increase of the inductivity of a solvent and its protic
character leads to the increase of the content of nitrone
form. On the contrary, aprotic solvents increase the
content of N-hydroxyaminoimino form due to specific
solvation. Electron-donating substituents (particularly
those with the þM effect) stabilize the aminonitrone
form, whereas the N-hydroxyaminoimino form is stabil-
ized by electron-withdrawing substituents. The planarity
of the whole p-system, including the aryl substituent, is
also a very important factor affecting the state of the
tautomeric equilibrium.
R
HF/6-31G (d,p)
Experimental,
DEcomb:
(kcal/mol)
Ecomb: (a.u.) 1 Ecomb: (a.u.) 10 DEcomb: (kcal/mol) C2
C1
0
a
b
c
d
e
f
2792.554374 2792.527966 216.572
2456.939488 2456.916487 214.434
2495.988442 2495.968135 212.743
25.32
23.59
22.52 22.98
–
–
2686.500728
686.485036 29.848
4.13
3.09
5.32
0.70
2.26
–
3.70
2.78
3.93
0.23
1.21
–
2889.970252 2889.953368 210.595
2800.385015 2800.369650 29.642
2764.578012 2764.561751 210.205
2803.615043 2803.597985 210.704
g
h
ia 21220.26753 21220.26025
24.568
24.474
2763.392777 2763.375949 210.560
j
2777.36469
2777.35756
–
–
k
3.20
2.39
a
Bromine atom was exchanged for chlorine for the simplification of
calculations.
Therefore, it is believed that varying of a substituent at
position 2 of the 2-imidazoline heterocycle and the nature of
the solvent may change the path in reactions of these
compounds with dipolarophiles. Further studies are under
way to investigate these effects.
The moving aside of the bulky phenyl group with
preservation of the conjugate chain prevents rotation of
the conjugation plane relative to the imidazoline ring in
molecule 1k. In this case, in both A and B, the
0
0
N1C2C1 C2 dihedral angles become smaller (Table 7),
resulting in relatively more efficient stabilization of N-
hydroxyaminoimino form 1Bk compared to nitrone form
1Ak (cf. 1Bk : 1Ak and 1Bd : 1Ad, Table 3).
4. Experimental
IR spectra were recorded on a Bruker IFS 66 spec-
trometer for KBr pellets (concentration 0.25%, pellet
thickness 1 mm). UV spectra were measured on a Specord
M-40 spectrophotometer in EtOH. NMR spectra were
recorded on Bruker WP 200 SY, Bruker AC-200, and
Bruker AM-400 spectrometers for 5% solutions using the
solvent as the internal standard. For 19F NMR, C6F6 was
used as internal standard. High-resolution mass spectra were
recorded on a Finnigan MAT 8200 mass spectrometer with
direct sample injection at a resolution of 10,000. The
melting points were measured on a ‘Boetius’ plate and are
uncorrected. Thin layer chromatography control was carried
out with the use of Aluminum oxide TLC-cards (Fluka) with
chloroform or chloroform–methanol (30:1 or 20:1) as
eluent. The solutions were evaporated in vacuo in all cases.
2-Substituted 4,4,5,5-tetramethylimidazolidine-1,3-diols
were synthesized according to Ref. [17]; imidazolines 1c,
d, according to Ref. [7]. Imidazolines 1i, j were kindly
granted by Dr E. V. Tretyakov [8].
The B : A ratio is determined from the difference
between the formation heats of the forms DEcomb according
to the equation B : A ¼ exp½2DEcomb=RTŠ: The N-hydro-
xyaminoimino form is generally preferable according to
calculations, so that in the crystalline state imidazolines 1b,
d exist in this form. Hence, substituents capable of
stabilizing the nitrone form relative to the N-hydroxyami-
noimino form lead to decreased values of DEcomb (Table 8).
A comparison of the calculated and experimental values of
DEcomb shows that they change symbatically, confirming
that the state of equilibrium depends on the nature of the
substituent and not only on solvation effects (Fig. 4).
For single crystals 1c, d, data were collected on a Smart
Apex Bruker AXS automatic diffractometer at room
temperature using the standard procedure (Mo radiation,
2 , u , 258). The structures were solved by direct
methods. Full-matrix least-squares refinement was per-
formed anisotropically for nonhydrogen atoms and iso-
tropically for hydrogens. H atoms were localized in
difference electron density syntheses. All structure solution
and refinement calculations were carried out with
SHELXTL software.
Fig. 4. The comparison of calculated and experimental DEcomb: (according
to C-2 and C-10).

56
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
Crystal data for 1c: C7H14N2O, M ¼ 142:20; orthorhom-
cm21: 3124 (OH), 1627 (CyN), 1187, 1163 (CF3). m.p.
144–146 8C (from an ethyl acetate–hexane mixture).
Found: C 45.7, H 6.2, F 27.1, N 13.3. Calculated for
C8H13F3N2O: C 45.7, H 6.2, F 27.1, N 13.2.
bic, space group Pna21; a ¼ 13:066ð2Þ; b ¼ 6:3291ð8Þ;
3
˚
˚
c ¼ 10:372ð1Þ A,
V ¼ 857:7ð2Þ A ,
Z ¼ 4;
Dc ¼ 1:101 g cm3, m ¼ 0:075 mm21, 3390 reflections col-
lected, 1061 unique ðRint ¼ 0:0456Þ; 148 parameters,
Goof ¼ 0:994; R1 ¼ 0:0305; wR2 ¼ 0:0704ðI . 2sðIÞÞ;
R1 ¼ 0:0329; wR2 ¼ 0:0719 for all data (CCDC 215579).
Crystal data for 1d: C13H18N2O, M ¼ 218:29; mono-
4.2. 4,4,5,5-Tetramethyl-4,5-dihydro-1H-imidazol-1-ol 1b
Procedure A: A solution of 4,4,5,5-tetramethylimidazo-
lidine-1,3-diol (2.69 g, 16.8 mmol) in toluene (30 ml) was
boiled for 10 h while bubbling air through the solution.
After solvent removal, the residue was recrystallized from
an ethyl acetate–hexane mixture to give 1.2 g (41%) of 1b.
Procedure B: A solution of NaNO2 (1.62 g, 25.8 mmol)
in water (20 ml) was added to a solution of 4b (2.25 g,
14.34 mmol) in chloroform (50 ml). To the resulting
mixture, hydrochloric acid (5% solution, 1 ml) was added
dropwise while vigorously stirring the solution. The stirring
was continued for 30 min, the organic layer was separated,
and the aqueous solution extracted with chloroform
(2 £ 50 ml). The combined extracts were dried with
MgSO4, and the solvent was removed. The residue was
dissolved in anhydrous tetrahydrofuran (15 ml), a catalyst
(0.15 g, 5% Pd on charcoal) was added, and the mixture was
hydrogenated with hydrogen while stirring for 4 h at 20 8C.
The catalyst was filtered off and the solvent removed to give
(96%) pure 1b (2.0 g), which could be additionally purified
by recrystallization from an ethyl acetate–hexane mixture.
1H NMR (CDCl3, 200.13 MHz, d, ppm): 1.14 (s, 12H, 4,5-
(CH3)2), 6.34.(s, 1H, OH), 7.19 (s, 1H, CHy). 13C NMR
(CDCl3, 50.32 MHz, d, ppm): 18.5, 23.6 (4,5-(CH3)2), 67.7
(C-4), 71.0 (C-5), 153.3 (C-2). lmax; (ethanol), nm ðlog 1Þ :
269 (4.71). n; cm21: 3100 (OH), 1596 (CyN).
clinic, space group C2=c; a ¼ 17:435ð3Þ; b ¼ 13:748ð2Þ;
3
˚
˚
c ¼ 11:014ð2Þ A, b ¼ 110:977ð4Þ8; V ¼ 2465:0ð7Þ A , Z ¼
8; Dc ¼ 1:176 g cm3, m ¼ 0:075 mm21, 5223 reflections
collected, 1783 unique ðRint ¼ 0:1101Þ; 218 parameters,
Goof ¼ 0:840; R1 ¼ 0:0508; wR2 ¼ 0:0972ðI . 2sðIÞÞ;
R1 ¼ 0:0931; wR2 ¼ 0:1148 for all data (CCDC 215580).
All computations were carried out with the GAMESS
program package [16]. Full geometry optimization was
carried out at the Hartree–Fock (HF) level of theory. The
standard 6-31G (d, p) basis set was employed, which is 6-
31G quality plus six d-like polarization functions on heavy
atoms and three p-like polarization functions on hydrogen
atoms. The basis set used (HF/6-31G (d, p)) was chosen by
comparing the experimental (X-ray) data with the geo-
metrical characteristics and energies of compounds 1
(Tables 4, 5, 7 and 8). The harmonic vibration frequencies
were determined by analytic second derivative methods at
the 6-31G (d, p) level for equilibrium geometries 2(b,c,d,g).
4.1. 4,4,5,5-tetramethyl-2-(trifluoromethyl)-4,
5-dihydro-1H-imidazol-1-ol 1a
Trifluoroacetaldehyde hydrate (3.61 g, 31.1 mmol)
emulsion in chloroform (10 ml) was slowly added dropwise
with stirring to a boiling solution of 2,3-bis(hydroxyamino)-
2,3-dimethylbutane (2.97 g, 20.05 mmol) in chloroform
(15 ml). The reaction mixture was boiled for 5 h, then
cooled to 20 8C, and washed with brine (2 £ 15 ml). The
chloroform solution was dried with MgSO4, the solvent
removed, and the residue chromatographed on alumina with
a (1:20) methanol-chloroform mixture as eluent to give
4,4,5,5-tetramethyl-2-(trifluoromethyl)imidazolidine-
1,3-diol. Yield 1.9 g (65% after recrystallization from
4.3. 4,4,5,5-Tetramethyl-2-(4-nitrophenyl)-4,
5-dihydro-1H-imidazol-1-ol 1e
A solution of 4,4,5,5-tetramethyl-2-(4-nitrophenyl)imi-
dazolidine-1,3-diol (0.677 g, 2.41 mmol) (Ref. [18]) in
chloroform (25 ml) was stirred with MnO2 (3 g) for 1 h at
20–25 8C. Manganese oxides were filtered off and a water
solution (10 ml) containing NaNO2 (0.25 g, 3.62 mmol) was
added to the filtrate; then 5% hydrochloric acid (0.4 ml) was
added dropwise with vigorous stirring. The stirring
was continued for 1 h at 20 8C, the organic solution was
separated, and the water solution extracted with chloroform
(3 £ 20 ml). The combined extract was dried with MgSO4
and the residue obtained after solvent removal was
dissolved in a methanol solution (10 ml) containing
hydroxylamine hydrochloride (0.83 g, 12.05 mmol) and
sodium methoxide (0.39 g, 7.23 mmol). The resulting
solution was kept for 24 h at 10 8C, the solvent was
removed, and the residue dissolved in water (10 ml) and
extracted with chloroform (3 £ 20 ml). The combined
extract was dried with MgSO4, and the residue (after
solvent removal) recrystallized from an ethyl acetate-
hexane mixture to give 0.54 g (85%) of imidazoline 1e.
1
hexane). H NMR (CDCl3, 200.13 MHz, d; ppm): 1.05 (s,
6H), 1.15 (s, 6H, 4,5-(CH3)2), 4.33 (q, 1H, JH–C–C–
¼ 5.9 Hz, 4-H), 5.29 (s, 2H, NOH).
F
A solution of 4,4,5,5-tetramethyl-2-(trifluoromethyl)imi-
dazolidine-1,3-diol (0.170 g, 0.75 mmol) in toluene (10 ml)
with MgSO4 (0.5 g) was boiled for 3 h with stirring and air
bubbling. MgSO4 was filtered off, and the solvent removed
to give imidazoline 1a, which was recrystallized from an
ethyl acetate–hexane mixture; yield 0.10 g (60%).
1H NMR (CDCl3, 200.13 MHz, d, ppm): 1.14 (s, 6H),
1.15 (s, 6H, 4,5-(CH3)2), 5.9 (s, 1H, OH). 13C NMR (CDCl3,
50.32 MHz, d, ppm): 18.1, 22.8 (4,5-(CH3)2), 68.4 (C-4),
73.4 (C-5), 117.5 (q. JC–F 275.8 Hz, CF3), 155.6 (q. JC–C–F
35.5 Hz, C-2). 19F NMR (CDCl3, 188.28 MHz, d, ppm):
92.8 (s, CF3). lmax; (ethanol), nm ðlog 1Þ : 246 (4.21), n;

S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
57
1H NMR (CDCl3, 200.13 MHz, d, ppm): 1.22 (s, 6H), 1.23
(s, 6H, 4,5-(CH3)2), 5.82 (s, 1H, OH), 8.07 (dd, 2H, J3 9 Hz,
J4 2 Hz, 20-H, Ph), 8.29 (dd, J3 9 Hz, J4 2 Hz, 30-H, Ph). The
spectrum also contains signals of the ethyl acetate crystal-
line solvate. 13C NMR (CDCl3, 50.32 MHz, d, ppm): 19.2,
23.9 (4,5-(CH3)2), 62.7 (C-4), 74.3 (C-5), 123.1 (C30), 128.2
(C20), 132.7 (C10), 148.0 (C-2), 148.1 (C40). m.p. 115–
116 8C. Found: C 59.00, H 6.65, N 14.52. Calculated for
C13H17N3O3 £ (1/4)C4H8O2: C 58.93, H 6.71, N 14.73.
(C40). m.p. 196–198 8C (in a sealed capillary). Found, m=z:
248.15320. Calculated for C14H20N2O2, m=z: 248.15247.
4.5. 2-(2,4-Dimethylphenyl)-4,4,5,5-tetramethyl-4,5-
dihydro-1H-imidazol-1-ol 1g
2,3-Bis(hydroxyamino)-2,3-dimethylbutane sulphate
(2.45 g, 9.28 mmol), sodium acetate (1.4 g, 17.1 mmol),
and 2,4-dimethylbenzaldehyde (1.13 g, 8.43 mmol) in a
(1:1) water–methanol mixture (30 ml) was boiled for 48 h.
Methanol was evaporated, and the 2-(2,4-dimethylphenyl)-
4,4,5,5-tetramethylimidazolidine-1,3-diol precipitate was
filtered off and washed with water and hexane. Yield
4.4. 2-(4-Methoxyphenyl)-4,4,5,5-tetramethyl-4,
5-dihydro-1H-imidazol-1-ol 1f
A solution of 2,3-bis(hydroxyamino)-2,3-dimethylbu-
tane sulphate (1.13 g, 4.28 mmol) and 4-methoxybenzalde-
hyde (0.47 ml, 3.9 mmol) in a (1:1) water–methanol
mixture (20 ml) was boiled for 72 h. Sodium acetate
(0.7 g, 8.54 mmol) was added after cooling and methanol
was evaporated. The precipitate was filtered off and washed
with water and hexane to give 0.76 g (75%) of crude 2-(4-
methoxyphenyl)-4,4,5,5-tetramethylimidazolidine-1,3-diol
(cf. Ref. [19]), which was used without further purification.
1H NMR (CDCl3, 200.13 MHz, d, ppm): 1.26 (s, 6H), 1.28
(s, 6H, 4,5-(CH3)2), 3.93 (s, 3H, CH3O), 4.75 (s, 1H, 2-H),
7.00 ppm (d, J ¼ 8.4 Hz, 20-H, Ph), 7.61.(d, J ¼ 8.4 Hz, 30-
H, Ph), 7.78 (s, 1H, OH).
1
1.18 g (53%). H NMR (DMSO-d6, 200.13 MHz, d, ppm):
1.04 (s, 6H), 1.07 (s, 6H, 4,5-(CH3)2), 2.23 (s, 3H), 2.33 (s,
3H, 2,4-(CH3)2Ph), 4.84 (s, 1H, 2-H), 7.2 ppm (s, 1H, 30-H,
Ph), 6.96 (d, 1H, J ¼ 7.8 Hz, 50-H, Ph), 7.5 ppm (d, 1H,
J ¼ 7.8 Hz, 60-H, Ph), 7.60 (s, 2H, OH).
A solution of 2-(2,4-dimethylphenyl)-4,4,5,5-tetra-
methylimidazolidine-1,3-diol (0.90 g, 3.41 mmol) in
chloroform (40 ml) was stirred with MnO2 (5 g) for 2 h at
20 8C. Manganese oxides were filtered off, and the filtrate
was evaporated to dryness to give nitronylnitroxide 4g,
20 mg of which was purified chromatographically on
alumina with chloroform as eluent. lmax; (ethanol), nm
ðlog 1Þ: 207 (4.23), 253 nm. (3.95), 327 (3.85), 556 (2.99).
The remainder of 4g was converted into imidazoline 1g in
the same manner as described for 1f; yield 0.53 g (63%). 1H
NMR (CDCl3, 200.1 MHz, d, ppm): 1.31 (s, 6H), 1.33 (s,
6H, 4,5-(CH3)2), 2.50 (s, 3H), 2.52 (s, 6H, 2,4-(CH3)2Ph),
5.71 (s, 1H, OH), 7.21 (d, 1H J ¼ 7.6 Hz), 7.24 (s, 1H), 7.35
(d, 1H, J ¼ 7.6 Hz, Ph). 13C NMR (CDCl3, 50.3 MHz, d,
ppm): 18.6, 23.5 (4,5-(CH3)2), 19.5, 20.9 (2,4-(C H3)2Ph),
63.4 (C-4), 71.8 (C-5), 125.1 (C10), 125.5 128.4 130.5 (C30,
C50, C60), 137.1, 139.1 (C20, C40), 154.6 (C-2). m.p. 193–
195 8C (from an ethyl acetate–hexane mixture). Found: C
73.00, H 9.41, N 11.37. Calculated for C15H22N2O: C 73.13,
H 9.00, N 11.37.
A mixture of 2-(4-methoxyphenyl)-4,4,5,5-tetramethyli-
midazolidine-1,3-diol (0.12 g, 0.45 mmol) and MnO2 (3 g)
in chloroform (10 ml) was stirred for 30 min at 20–25 8C.
Manganese oxides were filtered off, and an aqueous solution
(5 ml) containing NaNO2 (0.1 g, 1.45 mmol)was added to
the filtrate; then 5% hydrochloric acid (0.1 ml) was added
with stirring to the resulting mixture. The stirring was
continued for 30 min, the organic layer was separated, and
the aqueous solution extracted with chloroform (3 £ 10 ml).
The combined organic extract was dried with MgSO4, and
the residue obtained after solvent evaporation, 2-(4-
methoxyphenyl)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imi-
dazole-1-oxyl, was purified by flash chromatography on
alumina with chloroform as eluent. The eluate containing
iminonitroxide was evaporated, and the residue was
dissolved in anhydrous tetrahydrofuran (7 ml). A catalyst
(5% Pd on charcoal, 0.1 g) was added, and the mixture was
hydrogenated with hydrogen with stirring for 1 h at 20 8C.
The catalyst was filtered off and the solvent removed to give
crude 1f, which was purified chromatographically on
alumina with chloroform as eluent to remove traces of the
starting iminonitroxide and then with a (10:1) chloroform-
methanol mixture. The eluate containing 1f was evaporated
to give (after recrystallization from chloroform) 0.070 g
(63%) of pure 1f. 1H NMR (CDCl3, 200.13 MHz, d, ppm):
1.18.(s, 6H), 1.23 (s, 6H, 4,5-(CH3)2), 3.73.(s, 3H, OCH3),
4.77(s, OH), 6.77 (d, J ¼ 9 Hz, 20-H, Ph), 8.18 (d, J ¼ 9 Hz,
30-H, Ph). 13C NMR (CDCl3, 50.32 MHz, d, ppm): 19.3,
24.2 (4,5-(CH3)2), 55.2 (OCH3), 61.0 (C-4), 73.7 (C-5),
113.6 (C30), 118.2 (C10), 128.9 (C20), 144.0 (C-2), 161.2
2-Mesityl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-
1-ol 1h and nitroxide 4h were obtained as described for 1g
and 4g, respectively. The yield of 2-mesityl-4,4,5,5-
tetramethylimidazolidine-1,3-diol was 10%.
4h: lmax; (ethanol), nm ðlog 1Þ : 240 (4.09), 319 (3.87),
537 (3.13).
1
1h: Yield 58%. H NMR (CDCl3, 200.1 MHz, d, ppm):
1.28 (s, 6H), 1.32 (s, 6H, 4,5-(CH3)2), 2.26 (s, 6H), 2.95 (s,
3H) (20, 40, 60-CH3), 6.83 (s, 2H, 3,5-H, mesityl). 13C NMR
(CDCl3, 50.3 MHz, d, ppm): 19.4, 24.4 (4,5-(CH3)2), 21.2
(2,4,6-(C H3)3Ph), 63.3 (C-4), 72.4 (C-5), 123.9 (C10), 128.3
(C30), 137.4 (C20), 139.5 (C40), 152.0 (C-2). m.p. 215–
217 8C (from an ethyl acetate–hexane mixture). Found: C
73.81, H 9.72, N 10.68. Calculated for C16H24N2O: C 73.81,
H 9.29, N 10.76.

58
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
4.6. 4,4,5,5-Tetramethyl-2-[(E)-2-phenylvinyl]-4,
5-dihydro-1H-imidazol-1-ol 1k
NMR (CDCl3, 200.1 MHz, d, ppm): 0.95 (s, 6H), 0.97 (s,
6H, 4,5-(CH3)2), 3.53 (s, OCH3). 13C NMR (CDCl3,
50.3 MHz, d, ppm): 18.8, 23.0 (4,5-(CH3)2), 64.0 (OCH3),
69.6 (C-4), 70.8 (C-5), 156.32 (C-2). Found, m=z :
156.12671. Calculated for C8H16N2O, m=z : 156.12626.
A solution of hydroxylamine obtained by alkalization of
a solution of hydroxylamine hydrochloride (0.07 g, 1 mmol)
in anhydrous methanol (5 ml) with sodium methoxide to pH
8–9 was added dropwise to a solution of 4,4,5,5-
tetramethyl-2-[(E)-2-phenylvinyl]-4,5-dihydro-1H-imida-
zol-1-oxyl (0.090 g, 0.37 mmol) (for synthesis, see Ref.
[17]) in anhydrous methanol (10 ml) at 5 8C with stirring
until the color vanished. The solvent was removed and
imidazoline 1k was purified chromatographically on
alumina with chloroform as eluent to remove traces of the
starting iminonitroxide and then with a (10:1) chloroform-
methanol mixture. The eluate containing 1k was evaporated
4.9. 1-Methoxy-2,4,4,5,5-pentamethyl-4,5-dihydro-1H-
imidazole 3Bc
A solution of 1c (0.265 g, 1.70 mmol) and dimethyl
sulphate (0.162 ml, 1.71 mmol) in anhydrous chloroform
(4 ml) was kept for 30 min at 20 8C, then washed with a 5%
water solution of KHCO3, dried with MgSO4 and evapor-
ated. Imidazoline 3Bc was isolated by flash chromatography
on alumina with chloroform as eluent; yield 90 mg (31%).
1
to give 0.080 g (89%) of pure 1k. Oil H NMR (CDCl3,
1
200.1 MHz, d, ppm): 1.18.(s, 6H), 1.23 (s, 6H 4,5-(CH3)2),
5.10 (s, 1H, OH), 7.05 (d, J ¼ 16.8 Hz), 7.32 (d,
J ¼ 16.8 Hz, HCyCH), 7.17–7.41 (m, Ph). NMR 13C
(CDCl3, 50.3 MHz, d, ppm): 19.1, 23.8 (4,5-(CH3)2), 61.2
(C-4), 72. ppm (C-5), 110.8 (C10), 126.9, 128.3 (C40, C50),
128.8 (C60), 135.2 (C30), 136.4 (C20), 145.9 (C-2). Found,
m=z : 244.15700. Calculated for C15H20N2O, m=z :
244.15756.
Oil. H NMR (CDCl3, 200.1 MHz, d, ppm): 0.99 (s, 6H),
1.01 (s, 6H, 4,5-(CH3)2), 1.86 (s, 3H, 2-CH3), 3.59 (s,
OCH3). 13C NMR (CDCl3, 50.3 MHz, d, ppm): 13.1 (2-
CH3), 18.3, 23.4 (4,5-(CH3)2), 63.3 (OCH3), 65.5 (C-4),
70.1 (C-5), 163.5 (C-2). Found, m=z : 170.14175. Calculated
for C9H18N2O, m=z : 170.14191.
4.10. 1-Methoxy-4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-
1H-imidazole 3Bd
4.7. 1-Methoxy-4,4,5,5-tetramethyl-2-(trifluoromethyl)-4,5-
dihydro-1H-imidazole 3Ba
1-Methoxy-4,4,5,5-tetramethyl-2-phenyl-4,5-dihydro-
1H-imidazole 3Bd was synthesized similarly to imidazoline
A solution of dimethyl sulphate (0.028 ml, 0.29 mmol) in
anhydrous tetrahydrofuran (2 ml) was added to a solution of
1a (0.056 g, 0.27 mmol) in anhydrous tetrahydrofuran
(5 ml) with stirring, while the temperature was kept below
10 8C. The stirring was continued for 1 h at this temperature,
and the solvent was carefully removed (imidazoline 3Ba is
volatile). The residue was flash-chromatographed on
alumina with chloroform as eluent. Yield 40 mg (67%).
Oil 1H NMR (CDCl3, 200.1 MHz, d, ppm): 1.14(s, 6H), 1.18
(s, 6H 4,5-(CH3)2), 3.70 (s, OCH3). NMR 13C (CDCl3,
50.3 MHz, d, ppm): 18.8, 22.4 (4,5-(CH3)2), 64.2 (OCH3),
68.6 (C-4), 73.6 (C-5), 117.3 (q. JC–F ¼ 275.6 Hz, CF3),
154.8 (q. JC – C – F 35.6 Hz, C-2). 19F NMR (CDCl3,
188.2 MHz, d, ppm): 92.9 (CF3). Found, m=z : 224.11361.
Calculated for C9H15F3N2O, m=z : 224.11365.
1
3b. Reaction time was 24 h at 10 8C; yield 80%. Oil. H
NMR (CDCl3, 200.1 MHz, d, ppm): 1.16 (s, 6H), 1.20 (s,
6H, 4,5-(CH3)2), 3.68 (s, OCH3), 7.33–7.36 (m, 3H), 7.64
(dd. 2H, J ¼ 7.9 Hz, J ¼ 1.7 Hz, ortho-H, Ph). 13C NMR
(CDCl3, 50.3 MHz, d, ppm): 19.5, 23.2 (4,5-(CH3)2), 63.7
(OCH3), 66.9 (C-4), 71.9 (C-5), 127.7, 127.8 (C20, C30),
129.6 (C40), 131.3 (C10), 164.9 (C-2). lmax; (ethanol), nm
ðlog 1Þ : 227 (3.76). n; cm21: 2815 (OCH3), 1629 (CyN),
1601, 1576.5 (CyC, Ph). Found, m=z : 232.15800. Calcu-
lated for C14H20N2O, m=z : 232.15755.
4.11. 1-Methoxy-4,4,5,5-tetramethyl-2-(4-nitrophenyl)-4,5-
dihydro-1H-imidazole 3Be
4.8. 1-Methoxy-4,4,5,5-tetramethyl-4,5-dihydro-1H-
imidazole 3Bb
1-Methoxy-4,4,5,5-tetramethyl-2-(4-nitrophenyl)-4,5-
dihydro-1H-imidazole 3Be was synthesized similarly to
imidazoline 3Bb. Reaction time was 1 h at 20 8C; yield
Sodium hydride (0.030 g, 1.25 mmol) was added to a
solution of 1b (0.166 g, 1.17 mmol) in anhydrous tetrahy-
drofuran (5 ml). The resulting mixture was stirred for 5 min,
and a solution of dimethyl sulphate (0.12 ml, 1.27 mmol) in
tetrahydrofuran (3 ml) was added dropwise with stirring at a
temperature below 15 8C. The stirring was continued for
10 min, the solvent was carefully evaporated, and imidazo-
line 3Bb was purified by flash chromatography on alumina
1
85%. Oil. H NMR (CDCl3, 200.1 MHz, d, ppm): 1.19 (s,
6H), 1.23 (s, 6H, 4,5-(CH3)2), 3.70 (s, 3H, OCH3), 7.83 (t,
2H, J3 ¼ 9.0 Hz, J4 ¼ 2.1 Hz, 20-H, Ph), 8.22 (t, 2H,
J3 ¼ 9.0 Hz, J4 ¼ 2.1 Hz, 30-H, Ph). NMR 13C (CDCl3,
50.3 MHz, d, ppm): 19.5, 23.1 (4,5-(CH3)2), 63.8 (OCH3),
67.9 (C-4), 72.6 (C-5), 123.0 (C30), 129.0 (C20), 137.6 (C10),
148.5 (C40), 163.1 (C-2). Found, m=z : 277.14288. Calcu-
lated for C14H19N3O3, m=z : 277.14263.
1
with chloroform as eluent. Yield 0.090 g (50%). Oil H

S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
59
4.12. 2-(2,4-Dimethylphenyl)-1-methoxy-4,4,5,5-
tetramethyl-4,5-dihydro-1H-imidazole 3Bg
3.76 (s, 3H, OCH3), 6.83 (dd, J3 ¼ 8.9 Hz, J4 ¼ 2.5 Hz, 20-
H, Ph), 7.46 (dd, J3 ¼ 8.9 Hz, J4 ¼ 2.5 Hz, 30-H, Ph). 13C
NMR (CDCl3, 50.3 MHz, d, ppm): 18.6 (CH3CO), 19.7,
23.9 (4,5-(CH3)2), 55.0 (OCH3), 68.0 (C-4), 72.2 (C-5),
113.5 (C30), 122.7 (C10), 128.9 (C20), 161.1 (C40), 163.5 (C-
2), 169.1 (CyO).
2-(2,4-Dimethylphenyl)-1-methoxy-4,4,5,5-tetramethyl-
4,5-dihydro-1H-imidazole 3Bg was synthesized similarly to
imidazoline 3Bb. Reaction time was 1 h at 100 8C (dioxane
1
1
as solvent); yield 69%. Oil. H NMR (CDCl3, 200.1 MHz,
2g. Yield 85%. H NMR (CDCl3, 200.1 MHz, d, ppm):
d, ppm): 1.19 (s, 6H), 1.22 (s, 6H, 4,5-(CH3)2), 2.30 (s, 3H),
2.34 (s, 3H, 2,4-(CH3)2-Ph), 3.43 (s, 3H, OCH3), 6.97 (d,
1H, J3 ¼ 7.6 Hz, 50-H, Ph) 6.99 (s, 1H, 30-H, Ph), 7.13 (d,
1H, J3 ¼ 7.6 Hz, 60-H, Ph). 13C NMR (CDCl3, 50.3 MHz, d,
ppm): 19.3, 23.2 (4,5-(CH3)2), 19.1, 21.0 (2,4-(C H3)2-Ph),
63.5 (OCH3), 67.4 (C-4), 71.0 ppm (C-5), 128.3 (C10),
125.4, 128.0, 130.4 (C30, C50, C60), 136.1, 138.2 (C20, C30),
165.4 (C-2). Found, m=z : 260.18885. Calculated for
C16H24N2O, m=z : 260.18886.
1.08 (s, 6H), 1.16(s, 6H, 4,5-(CH3)2), 1.70 (CH3CO), 2.15
(s, 3H, 40-CH3Ph), 2.23 (s, 3H, 20-CH3Ph), 6.81 (d, 1H,
J ¼ 7.8 Hz, 50-H, Ph), 6.86 (s, 1H, 30-H, Ph), 6.98 (d, 1H,
J3 ¼ 7.8 Hz, 60-H, Ph); 13C NMR (CDCl3, 50.3 MHz, d;
ppm): 18.8 (C H3CO), 19.2, 23.3 (4,5-(CH3)2), 20.7, 21.5
(4,5-(C H3)Ph), 68.0 (C-4), 71.6 (C-5), 126.6 (C10), 125.4,
127.6, 130.6 (C30, C50, C60), 136.3, 138.6 (C20, C40), 163.9
(C-2), 168.1 (CyO).
1
2k. Yield 90%. H NMR (CDCl3, 200.1 MHz, d, ppm):
1.12 (s, 6H), 1.21 (s, 6H, 4,5-(CH3)2), 2.16 (s, 3H, CH3CO),
6.37 (d, 1H, J3 ¼ 16.3 Hz, HCyCH–Ph), 7.46 (d, 1H,
J3 ¼ 16.3 Hz, HCyCH–Ph), 7.24–7.31 (m, 3H), 7.39–
7.4 ppm (m, 2H, Ph). 13C NMR (CDCl3, 50.32 MHz, d,
ppm): 18.5 (CH3CO), 19.1, 20.5 (4,5-(CH3)2), 67.5 (C-4),
72.1 (C-5), 114.8 (C10), 127.0, 128.3 (C40, C50), 128.8 (C60),
135.2 (C30), 138.0 (C20), 161.1 (C-2), 168.8 (CyO).
4.13. 1-(Acetyloxy)-2,4,4,5,5-pentamethyl-4,5-dihydro-1H-
imidazole 2c
Acetic anhydride (0.47 ml, 4.99 mmol) was added
dropwise with stirring to a solution of 1c (0.26 g,
1.66 mmol) in anhydrous chloroform (5 ml). The stirring
was continued for 30 min; the solution was washed with an
aqueous solution of KHCO3, water, and then dried with
MgSO4. After solvent removal, 2c (0.311 g, 94%) was
4.15. 1-(Acetyloxy)-2-mesityl-4,4,5,5-tetramethyl-4,5-
dihydro-1H-imidazole 2h
1
obtained. H NMR (CDCl3, 200.1 MHz, d, ppm): 1.03 (s,
6H), 1.09 (s, 6H, 4,5-(CH3)2), 1.83 (s, 3H, 2-CH3), 2.09 (s,
3H, CH3–CO). 13C NMR (CDCl3, 50.3 MHz, d, ppm): 13.6
(2-CH3), 18.2 (CH3–CO), 18.9, 23.1 (4,5-(CH3)2), 66.9 (C-
4), 71.7 (C-5), 162.8 (C-2), 168.4 (CyO). n; cm21: 1796
(CyO), 1652 (CyN).
A solution of acetic anhydride (0.075 ml, 0.74 mmol)
and triethylamine (0.20 ml, 1.35 mmol) in anhydrous
chloroform (2 ml) was added dropwise with stirring to a
solution of 1h (0.080 g, 0.31 mmol) in anhydrous chloro-
form (3 ml). The stirring was continued for 1 h at 20 8C, the
solvent was removed, and the residue dissolved in
anhydrous ether (10 ml). The triethylammonium acetate
precipitate was filtered off and the filtrate evaporated.
Imidazoline 2h was purified by chromatography on alumina
4.14. 2-R-1-(Acetyloxy)-4,4,5,5-tetramethyl-4,5-dihydro-
1H-imidazoles 2d,e,f,g,k
1
2-R-1-(Acetyloxy)-4,4,5,5-tetramethyl-4,5-dihydro-1H-
imidazoles 2d,e,f,g,k were obtained similarly.
with chloroform as eluent. Yield 0.050 g (54%). H NMR
(CDCl3, 200.1 MHz, d, ppm): 1.22 (s, 6H), 1.28 (s, 6H, 4,5-
(CH3)2), 1.76 (s, 3H, CH3CO), 2.21 (s, 3H, 40-CH3Ph, 2.24
(s, 6H, 20,60-(CH3)2Ph), 6.75 (s, 3H). 13C NMR (CDCl3,
50.3 MHz, d, ppm): 18.2 (CH3CO), 19.2, 23.8 (4,5-(CH3)2),
20.3, 20.9 (20,40,60-(CH3)3Ph), 68.7 (C-4), 71.2 (C-5), 126.7
(C10), 127.6 (C30), 136.6 (C20), 138.2 (C40), 163.5 (C-2),
168.2 (CyO).
1
2d. Yield 82%. H NMR (CDCl3, 200.1 MHz, d, ppm):
1.16 (s, 6H), 1.25 (s, 6H, 4,5-(CH3)2), 1.95 (s, 3H, CH3CO),
7.31–7.38 (m, 3H, Ph), 7.52 (dd, 2H, J3 ¼ 7.9 Hz,
J5 ¼ 1.7 Hz, 20-H, Ph. 13C NMR (CDCl3, 50.3 MHz, d,
ppm): 18.6 (C H3CO), 19.7, 23.9 (4,5-(CH3)2), 68.3 (C-4),
72.4 (C-5), 127.3, 128.1 (C20,C30), 130.1 (C40), 130.5 (C10),
164.0 (C-2), 168.9 (CyO). lmax; (ethanol), nm ðlog 1Þ :
229 nm (4.02). n; cm21: 3064 (Ar–H), 1779 (CyO), 1630
(CyN), 1602, 1578 (CyC).
4.16. 1,2,4,4,5,5-Hexamethyl-4,5-dihydro-1H-imidazole 3-
oxide 3Ac
1
2e. Yield 95%. H NMR (CDCl3, 200.1 MHz, d, ppm):
1.18 (s, 6H), 1.27 (s, 6H, 4,5-(CH3)2), 1.99 (s, 3H, CH3CO),
7.71 (dd, 2H J3 ¼ 9.0 Hz, J4 ¼ 2.1 Hz, 20-H, Ph), 8.20 (dd,
2H, J3 ¼ 9.0 Hz, J4 ¼ 2.1 Hz, 30-H, Ph). 13C NMR (CDCl3,
50.3 MHz, d, ppm): 18.6 (C H3CO), 19.7, 23.8 (4,5-(CH3)2),
69.4 (C-4), 73.0 (C-5), 123.4 (C30), 128.5 (C20), 136.7 (C10),
148.9 (C40), 162.5 (C-2), 168.8 (CyO);
A solution of 2c (0.311 g, 1.57 mmol) and dimethyl
sulphate (0.44 ml, 4.65 mmol) in anhydrous ether (9 ml)
was kept for 48 h at 10 8C. The precipitate was filtered off
and washed with anhydrous ether to give 0.411 g of 1-
(acetyloxy)-2,3,4,4,5,5-hexamethyl-4,5-dihydro-1H-imida-
zol-3-ium methylsulphate. The latter was dissolved in 5%
NaOH (5 ml) and the resulting solution was kept for 10 min
at 20 8C. The solution was extracted with chloroform
1
2f. Yield 90%. H NMR (CDCl3, 200.1 MHz, d, ppm):
1.14 (s, 6H), 1.22 (s, 6H, 4,5-(CH3)2), 1.97 (s, 3H, CH3CO),

60
S.A. Popov et al. / Journal of Molecular Structure 697 (2004) 49–60
(4 £ 10 ml), and the combined extract was dried with
1
(80%) of nitrone 3Ac. Oil. H NMR (CDCl3, 200.1 MHz,
(N–C H3), 65.4 (C-4), 72.5 (C-5), 121.7 (C10), 128.4 (C30),
MgSO4. Subsequent solvent evaporation gave 0.214 g
137.2 (C20), 139.9 (C40), 148.0 (C-2).
1
3Ak. Yield 60%. Oil. H NMR (CDCl3, 200.1 MHz, d,
ppm): 1.14 (s, 6H), 1.29 (s, 6H, 4,5-(CH3)2), 2.44 (s, 3H, N–
CH3), 6.45 (d, 1H, J3 ¼ 16.0 Hz, HCyCHPh), 7.27–7.36
(m, 3H), 7.48–7.53 (m, 2H, Ph), 9.06 (d, 1H, J3 ¼ 16.0 Hz,
HCyCH Ph). 13C NMR (CDCl3, 50.3 MHz, d, ppm): 19.1,
19.2 (4,5-(CH3)2), 28.3 (N–C H3), 64.9 (C-4), 72.6 (C-5),
109.2 (C10), 127.2, 128.6 (C40, C50), 128.9 (C60), 136.7
(C30), 139.7 (C20), 142.8 (C-2); Found, m=z : 258.17320.
Calculated for C16H22N2O, m=z : 258.17321.
d, ppm): 1.04 (s, 6H), 1.16 (s, 6H, 4,5-(CH3)2), 1.99 (s, 3H,
2-CH3), 2.58.(s, 3H, N-CH3). 13C NMR (CDCl3, 50.3 MHz,
d, ppm): 8.7 (2-CH3), 18.5, 18.7 (4,5-(CH3)2), 27.1 (N–
CH3), 64.8 (C-4), 71.0 (C-5), 146.4 (C-2); Found, m=z :
170.14300. Calculated for C9H18N2O, m=z : 170.14190.
4.17. 2-R-1,4,4,5,5-Pentamethyl-4,5-dihydro-1H-imidazole
3-oxides 3A(d–k)
2-R-1,4,4,5,5-pentamethyl-4,5-dihydro-1H-imidazole 3-
oxides 3A(d–k) were synthesized similarly.
Acknowledgements
3Ad. Yield 65%. 1H NMR (CDCl3, 200.1 MHz, d, ppm):
1.20 (s, 6H), 1.32 (s, 6H, 4,5-(CH3)2), 2.59 (s, 3H, N-CH3),
7.34–7.42 (m, 3H), 7.60–7.65 (m, Ph); 13C NMR (CDCl3,
50.3 MHz, d, ppm): 19.3, 19.5 (4,5-(CH3)2), 29.5 (N–CH3),
64.9 (C-4), 72.8 ppm (C-5), 125.5 (C10), 128.1, 129.0 (C20,
C30), 129.8 (C40), 145.8 (C-2). mp 90–92 8C; Found: C
72.2, H 8.7, N 11.9. Calculated for C14H20N2O: C 72.4, H
8.7, N 12.1.
This work was supported by RFBR grants (02-03-33112,
03-03-32518) and ‘Integration’ programs.
References
[1] J.J. Tufariello, in: A. Padwa (Ed.), 1,3-Dipolar Cycloaddition
Chemistry, vol. 2, Wiley–Interscience, New York, 1984, pp.
122–127, Chapter 9.
3Ae. Yield 72%. 1H NMR (CDCl3, 200.1 MHz, d, ppm):
1.26 (s, 6H), 1.36.(s, 6H, 4,5-(CH3)2), 2.66 (s, 3H, NCH3),
7.89 (dd, 2H, J3 ¼ 9 Hz, J4 ¼ 2.1 Hz, 20-H, Ph, 8.30 (dd,
2H, J3 ¼ 9 Hz, J4 ¼ 2.1 Hz, 30-H, Ph). 13C NMR (CDCl3,
50.3 MHz, d, ppm): 19.5, 19.7 (4,5-(CH3)2), 29.8 (N–CH3),
65.5 (C-4), 73.7 (C-5), 123.5 (C30), 130.2 (C20), 131.3 (C10),
145.1 (C-2), 148.2 (C40). m.p. 165.5–166.5 8C; Found, m=z :
277.142631. Calculated for C14H19N3O3, m=z : 277.14264.
3Af. Yield 85%. 1H NMR (CDCl3, 200.1 MHz, d, ppm):
1.20(s, 6H), 1.31 (s, 6H, 4,5-(CH3)2), 2.62 (s, 3H, N–CH3),
3.79 (s, 3H, OCH3), 6.92 (dd, 2H, J3 ¼ 9.0 Hz, J4 ¼ 2.5 Hz,
20-H, Ph), 7.59 (dd, 2H, J3 ¼ 9.0 Hz, J4 ¼ 2.5 Hz, 30-H, Ph).
13C NMR (CDCl3, 50.3 MHz, d, ppm): 19.3 19.5 (4,5-
(CH3)2), 29.4 (N–CH3), 55.2 (OCH3), 65.0 (C-4), 72.4 (C-
5), 113.6 (C30), 117.2 (C10), 130.7 (C20), 147.1 (C-2), 160.8
(C40). m.p. 142–143 8C; Found, m=z : 262.16956. Calcu-
lated for C15H22N2O2, m=z : 262.16812.
[2] N. Coscun, M. Ay, Heterocycles 48 (3) (1998) 537.
[3] R.C.F. Jones, K.J. Howard, J.S. Snaith, Tetrahedron Lett. 37 (10)
(1996) 1707.
[4] R.C.F. Jones, K.J. Howard, J. Chem. Soc., Perkin Trans. 1 (1993)
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Hursthouse, Chem. Commun. (2000) 1949.
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[7] P.A. Petrov, S.V. Fokin, G.V. Romanenko, Y.G. Shvedenkov, V.A.
Reznikov, V.I. Ovcharenko, Mendeleev Commun. (2001) 179–181.
[8] E.V. Tretyakov, I.V. Eltsov, S.V. Fokin, Y.G. Shvedenkov, G.V.
Romanenko, V.I. Ovcharenko, Polyhedron (2004) in press.
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[11] M. Begtrup, Acta Scand. 27 (1973) 3101.
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1
[14] L.E. Sutton (Eds.), Tables of Interatomic Distances and Configuration
in Molecules and Ions, The Chemical Society Special Publication No.
11, London, 1958.
3Ag. Yield 80%. Oil. H NMR (CDCl3, 200.1 MHz, d,
ppm): 1.22 (s, 6H), 1.33 (s, 6H, 4,5-(CH3)2), 2.45 (s, 3H, N–
CH3), 2.28 (s, 6H, 2,4-(CH3)2Ph), 7.01–7.05 (m, 2H), 7.23
(s, 1H, 30-H, Ph). 13C (CDCl3, 50.3 MHz, d, ppm): 18.9,
19.1, 19.2, 19.3, 21.2 (4,5-(CH3)2, 2,4-(CH3)2Ph), 28.1 (N–
CH3), 65.3 (C-4), 72.5 (C-5), 122.3 (C10), 126.4, 128.5,
131.0 (C30, C50, C60), 137.9, 140.1 (C20, C40), 147.3 (C-2).
Found, m=z : 260.18910. Calculated for C16H24N2O, m=z :
260.18885.
[15] L.B. Gurvich, G.A. Khackuruzof, V.A. Medvedev, I.V. Veinz, G.A.
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1
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3Ah. Yield 60%. Oil. H NMR (CDCl3, 200.1 MHz, d,
ppm): 1.25 (s, 6H), 1.3 ppm (s, 6H, 4,5-(CH3)2), 2.19 (s,
6H), 2.26 (s, 3H, 2,4,6-(CH3)3Ph), 2.44 (s, 3H, N-CH3), 6.86
(s, 3H, Ph). 13C NMR (CDCl3, 50.3 MHz, d, ppm): 19.1,
19.2 (CH3), 19.5, 21.0 (4,5-(CH3)2, 2,4,6-(C H3)3Ph), 27.1
[18] K. Awaga, T. Inabe, U. Nagashima, Y. Maruyama, J. Chem. Soc.,
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