1,3-Dipolar cycloaddition reaction of 4,5-dihydro-1H-imidazole 3-oxides with alkynes

Article abstract of DOI:10.1002/jhet.5570430206

4,5-Dihydro-1H-imidazole 3-oxides bearing different substituents at positions 1 and 2 of the heterocycle were shown to react with a wide range of acceptor-substituted alkynes forming corresponding cycloadducts - derivatives of 1,2,3,7a-tetrahydroimidazo[1

Full text of DOI:10.1002/jhet.5570430206

Mar-Apr 2006
277
1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole
3-oxides with Alkynes
a∗
b
c
a
Sergey A. Popov , Nikita V. Chukanov , Galina V. Romanenko , Tatjana V. Rybalova ,
a
a
Yuri V. Gatilov and Vladimir A. Reznikov
a
N. N. Vorozhtsov Institute of Organic Chemistry, Siberian Branch of Russian Academy of Sciences, Akad.
Lavrent'ev ave. 9, 630090 Novosibirsk, Russia.
b
Novosibirsk State University, 630090 Novosibirsk, Pirogova str. 2, Russia.
c
International Tomography Center, Siberian Branch of Russian Academy of Sciences, Institutskaya str. 3a,
630090 Novosibirsk, Russia
∗
E-mail: serge@nioch.nsc.ru
Received May 16, 2005
4,5-Dihydro-1H-imidazole 3-oxides bearing different substituents at positions 1 and 2 of the heterocycle
were shown to react with a wide range of acceptor-substituted alkynes forming corrsponding cycloadducts –
derivatives of 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole. High regioselectivity of this process stipulated by
conjugation of the nitrogen atom with the nitrone group was revealed.
J. Heterocyclic Chem., 43, 277 (2006).
Introduction.
Scheme 1
Over the past decades, reactions of 1,3-dipolar
cycloaddition have been attracting attention due to the
great possibilities of this synthetic approach. One of the
advantages of this methodology is the vast variety of
compounds of different classes taking part in this reac-
tion as dipoles and dipolarophiles. This allows a wide
spectrum of cycloadducts as well as products of their
subsequent transformations to be obtained. Since the
60-s of the last century, scientists dealing with 1,3-dipo-
lar cycloaddition reactions pay the highest attention to
nitrones as 1,3-dipoles. The numerous approaches to
obtaining compounds of different classes have been
developed, which are based on cycloaddition of various
dipolarophiles to nitrones. It should be mentioned that
over the past few years, chemistry of isolated nitrones
containing no functional substituents at the nitrogen or
α-carbon atom as well as cycloaddition reactions of
such nitrones have been thoroughly investigated [1-
12].Unlike this, the nitrone group attached to the het-
eroatomic substituent at the α-carbon atom is a poorly
studied, though interesting, target [13-18]. Derivatives
of 4,5-dihydro-1H-imidazole 3-oxide, which can be
considered as α-aminonitrones, are just such objects.
The lone pair of the amino group is conjugated with the
π-electron system of nitrone influencing the chemical
properties of the latter.
It should be pointed out that the authors have investi-
gated only 4,5-dihydro-1H-imidazole 3-oxide 1, con-
taining the benzyl fragment at the nitrogen atom and
hydrogen at position 2, i.e. compounds 1 can be related
to cyclic aldonitrones, which are known to be more
reactive than cyclic ketonitrones [22]. Besides, N-
unsubstituted derivatives of 4,5-dihydro-1H-imidazole
3-oxide, as we showed previously [24], exist in solu-
tion as a mixture of two tautomeric forms - aminoni-
trone A and N-hydroxyaminoimine B. Only aminoni-
trone A is capable of taking part in the cycloaddition
reaction, while N-hydroxyaminoimine B can act only
†
as nucleophile (R = H, Scheme 2). It is not, therefore,
1
obviously that N-non-substituted derivatives of 4,5-
dihydro-1H-imidazole 3-oxide containing a substituent
at position 2 of heterocycle can be involved in the reac-
tion of 1,3-dipolar cycloaddition and this reaction is
not described for related systems, apart from our previ-
ous paper [23].
The first attempts of using the derivative of the 4,5-dihy-
dro-1H-imidazole 3-oxide in 1,3-dipolar cycloaddition
reactions have been recently made (Scheme 1) [19-21].

278
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
Results and Discussion.
cycloaddition, despite these compounds exist in the solid
state usually as tautomeric form B [24].
Methods for the preparation of a wide variety of 2-sub-
stituted derivatives of 4,5-dihydro-1H-imidazole 3-oxide
2-12 were reported earlier [24]. In the present paper these
substances have been investigated as 1,3-dipoles in the
reactions with a number of mono and disubstituted alkynes
(Scheme 2).
Alkynes containing no strong electron withdrawing sub-
stituents (dimethylacetylene, phenylacetylene, dipheny-
lacetylene, propargyl alcohol) do not react even with the
most active nitrones under investigation. Formation of
cycloaddition products, for example, was not registered
Scheme 2
when 2a was kept with the excess of dimethylacetylene as
a solvent at 80 °C for 15 days.
The reaction was carried out in homogeneous (in solu-
tion) or heterogeneous (when crystal sample of nitrone was
kept in dipolarophile vapours) modes. In the most cases the
reaction in solution occurs very rapidly at room tempera-
ture (during several minutes) leading to compounds 13-21
with a high, often quantitative, yield. Since the reaction is
exothermic, it was carried out on cooling in case of very
active dipoles and dipolarophiles. The reaction in hetero-
geneous conditions was carried out at 50-70 °C during
several days up to several weeks depending on dipo-
larophile vapours pressure. Cycloaddition products of the
same structure and with a comparable yield are formed
when the reaction is carried out both in heterogeneous and
in homogeneous conditions.
The distinguishing feature of derivatives of 4,5-dihydro-
1H-imidazole 3-oxide is their high regioselectivity in
cycloaddition reactions with alkynes: in case of asymmet-
ric alkynes, only one regioisomer containing more electron
withdrawing substituent at position 4 of the 2,3-dihy-
droisoxazole cycle is formed (Scheme 2).
The structures of regioisomers 14-21 are proved by
1
13
NMR ( H and C) data. Chemical shifts as well as
multiplicity of the signals of carbon atom at positions 6
and 7 of the 1,2,3,7a-tetrahydroimidazo[1,2-b]isoxa-
zoles in NMR spectra unambiguously indicate posi-
tions of substituents in 2,3-dihydroisoxazole cycle for
structures 14a, 14g, 17a and 18e (Figure 1). Position of
It is important to note that the reaction of N-non-substi-
tuted derivatives of 4,5-dihydro-1H-imidazole 3-oxide with
alkynes in heterogeneous conditions occurs exclusively as
13
the ester group in 14d is determined by C-NMR data
(J-modulation). The signal at 153.5 ppm (C-6) is

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
279
Scheme 3
doublet that corresponds to regioisomer structure 14d
(Figure1).
alkenes destruction and polymerization or products of
nucleophilic addition of oxygen atom of the hydroxy-
lamine group in tautomer B to the activated double bond
of asymmetrically substituted alkene. Reaction of acry-
lonitrile with 3a in chloroform, for example, results in
formation of compound 22 (Scheme 3).
Product 22 is formed due to the peculiarity of N-non-
substituted derivatives of 4,5-dihydro-1H-imidazole 3-
oxide distinguishing them from the majority of nitrones
and even from their N-substituted analogues. These com-
pounds, as it is mentioned above, exist in solution as mix-
tures of two tautomeric forms - aminonitrone A and N-
13
Figure 1. Spin-spin interaction and chemical shifts in C-NMR spectra
(mono resonance or J-modulation).
The structure of cycloadducts 14h, 16c, 17g and 18j is
confirmed by X-ray diffraction analysis (Figure 2).
Examples of reaction of derivatives of 4,5-dihydro-1H-
imidazole 3-oxide with alkenes are described in literature
[20,21]. Our efforts to obtain cycloadducts by the reac-
tion of 2a, 3a,b, 6a,b with alkenes in different conditions
were failed. Compounds containing a double bond which
are the most active dipolarophiles towards the isolated
nitrone group (acrylonitrile, phenylisocyanate, diethyla-
zodicarboxylate, norboren, norbornadiene, maleic anhy-
dride, N-phenylmaleimide) do not participate in the
cycloaddition reaction with derivatives of 4,5-dihydro-
1H-imidazole 3-oxide 2a, 3a,b, 6a,b even upon pro-
hydroxyaminoimine B (R = H, scheme 3) [24]; form B
1
plays the role of nucleophile towards the activated multi-
ple bond. In spite of this fact, alkynes, unlike alkenes, react
with N-non-substituted derivatives giving predominantly,
and in most cases solely, corresponding cycloadducts.
Regioselectivity of the reaction is not changed even in
the presence of considerable steric hindrance. Thus,
although the reaction rate of imidazolines 2, 3, 5-8 with
methyl propiolate noticeably decreases in the presence of a
bulky substituent at position 2 of the 4,5-dihydro-1H-imi-
dazole ring, the other - less hindered regioisomer is not
formed (Scheme 4).
longed heating in different solvents (CHCl , toluene or
3
corresponding alkene) (Scheme 3). In most cases, the
result of such interaction is the formation of products of
Introduction of one or two methyl groups in ortho-posi-
Scheme 4

280
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
Figure 2. Crystal structure of 14h (1,2,2,3,3,7a-hexamethyl-6-phenyl-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-7-carbaldehyde, CCDC 260688), 16c
((7a-tert-butyl-2,2,3,3-tetramethyl-6-phenyl-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazol-7-yl)(phenyl)methanone, CCDC 260687), 17g (6,7a-diphenyl-
1,2,2,3,3-pentamethyl-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-7-carbaldehyde, CCDC 260355), 18j ((1,2,2,3,3-pentamethyl-6-phenyl-7a-(4-nitro-
phenyl)-1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazol-7-yl)(phenyl)methanone, CCDC 260689).

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
281
tion of the phenyl ring in compounds 7 and 8 results in the
twisting of the phenyl group from the plane of the 4,5-
dihydro-1H-imidazole ring. As a result, the appreciable
steric blocking of the nitrone group completely prevents
the reaction with methyl propiolate. The introduction of
two methyl groups in ortho-position of the phenyl ring
leads to complete inactivation of the nitrone 8 even
towards the most active dipolarophiles, such as dimethyl
acetylenedicarboxylate (DMAD).
High regioselectivity of the reactions of the studied
compounds with alkynes can be explained applying the
theory of frontier molecular orbitals (FMO theory) widely
used for the consideration of 1,3-dipolar cycloaddition
reactions. In the overwhelming majority of the cases this
reaction is the concerted process guided with the
Woodward-Hoffman rule. According to ab initio HF/6-
31G (d,p) calculations, the interaction of HOMO of 4,5-
dihydro-1H-imidazole 3-oxide with LUMO of alkyne is
determinative (Figure 3a). Thus, nitrone is donor and
alkyne is acceptor of electrons. This is confirmed by the
fact that the strengthening of the acceptor properties of
substituents in alkyne is accompanied by the increase of
the cycloaddition rate.
of nitrogen atom conjugated with the nitrone group. The
nitrogen atom is π-donor that leads to raising the energy levels
of frontier orbitals HOMO and LUMO in comparison with
that of isolated nitrones. These increase the contribution of the
interaction HOMO (nitrone) – LUMO (alkyne) and make less
favourable the interaction LUMO (nitrone) – HOMO
(alkyne). This fact stipulates higher regioselectivity of the
studied system as compared to nitrones of similar structure.
Thus, compounds 24 and 25 are formed in the reaction of N-
methyl-C-phenylnitrone 23 with methyl in the ratio 58:42,
Scheme 5
Figure 3. a - Interaction of HOMO of 4,5-dihydro-1H-imidazole 3-oxide with LUMO of alkyne; b - ab initio calculations in HF/6-31G (d,p) basis of the
interaction of frontier orbitals of 3a and methyl propiolate.
High regioselectivity of the studied reaction is the result
of the significant difference of coefficients squares of
atomic wave functions at reaction centres in LUMO of
respectively [22], while compounds 6 give the only regioiso-
mer 17(c, j) (Scheme 5).
The cycloadducts synthesized are stable and capable of
being stored for a long time at room temperature in the
case of R ≠ H. When R = H, cycloadducts initially
2
2
asymmetrically substituted alkynes (ϕ and ϕ ) and in
1
2
2
2
HOMO of the nitrone group (ϕ and ϕ ). The results of ab
3
4
2
2
initio calculations of frontier orbitals interaction of 3a and
methyl propionate fulfilled on HF/6-31G(d,p) basis are rep-
resented on Figure 3b. Interaction of the centres with maxi-
formed spontaneously transform to enaminones 13
(Scheme 2). As a rule, this process is very fast but when
cycloaddition reaction is carried out at about 0 °C, forma-
tion of the corresponding cycloadducts can be registered
2
mum values of ϕ is preferred. Maximum atomic coeffi-
i
1
cients in the interacting molecular orbitals pertain to the
by H NMR spectroscopy. The opening of 2,3-dihy-
2
oxygen atom of the nitrone group and to the carbon atom C
droisoxazole ring in cycloadduct 26 (Scheme 6) is so
kinetically hindered that cycloadduct 26 can be isolated by
chromatography at 0 °C [23]. Cycloadduct 26 is quickly
transformed at room temperature to enaminone 13C with a
quantitative yield.
in alkyne (Figure 3b). Regioisomer 14d is formed as a result
of such overlapping, that is observed in the experiment.
As it is mentioned above, derivatives of 4,5-dihydro-1H-
imidazole 3-oxide differ from acyclic nitrones by the presence

282
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Scheme 6
Vol. 43
by analytic second derivative methods at the 6-31G (d, p) level
for equilibrium geometries 2-12.
Conclusion.
Derivatives of 4,5-dihydro-1H-imidazole 3-oxide, both
with and without substituents at the nitrogen atom at posi-
tion 1, and with different substituents at position 2 of hete-
rocycle have been demonstrated to react with acceptor-
substituted alkynes giving corresponding cycloadducts,
i.e. the derivatives of 1,2,3,7a-tetrahydroimidazo[1,2-
b]isoxazole. High regioselectivity of this process is
revealed, that is explained by the presence of the nitrogen
atom conjugated with nitrone group. Alkenes are shown
not to be dipolarophiles in the reaction with the studied
substrates.
2-Substituted 4,4,5,5-tetramethylimidazolidine-1,3-diols - the
precursors of 2-substituted 4,4,5,5-tetramethyl-4,5-dihydro-1H-
imidazol-1-ol 3-oxides were synthesized according to ref. [26,27]
2-Substituted 4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-ol
3-oxides were synthesized according to ref. [24] Synthesis of 13c
was published in ref. [23].
4,4,5,5-Tetramethyl-4,5-dihydro-1H-imidazol-1-ol 3-oxide (2c)
[28].
MnO (0.43 g, 5.0 mmol) was added to a solution of 0.20 g
2
(1.25 mmol) of 4,4,5,5-tetramethylimidazolidine-1,3-diol in 10
ml CHCl at –5-0 °C and the mixture was stirred at this tempera-
3
ture for 30 min (TLC monitoring). The oxidant was filtered off
and filtrate was evaporated to dryness. The residue was treated
EXPERIMENTAL
with hexane and a precipitate of 2c 0.15 g (75 %) was filtered off
1
1
13
and was used without further purification; NMR H (CDCl ,
NMR H and C spectra were recorded on Bruker AC–200,
3
1
13
1
19
200.13 MHz, δ, ppm): 1.14, 1.21 (s, 6H, 2-CH , 3-CH ), 7.28 (s,
AM–400 ( H, C) and WP-200 ( H, F) spectrometers; sol-
vents were used as internal standards. Hexafluorobenzene was
used as internal standard for NMR F. IR spectra were recorded
3 3
1H, N=C-H), 9.19 (broad s, 1H, NOH).
19
4,4,5,5-Tetramethyl-2-(trifluoromethyl)-4,5-dihydro-1H-imida-
zol-1-ol 3-oxide (4c).
with a Bruker IFS 66 spectrometer for KBr pellets (concentration
0.25%, pellet thickness 1 mm). UV spectra were measured with
Specord M-40 spectrophotometer in EtOH. High-resolution mass
spectra were recorded on a Finnigan MAT 8200 mass spectrome-
ter with direct sample injection at a resolution of 10000 with ion-
isation power 70 eV. Melting points were measured in a sealed
capillary. The yields are given for pure substances after recrystal-
lization. Thin layer chromatography monitoring was carried out
on alumina plates (Fluka, Switzerland) with chloroform and
chloroform-MeOH mixtures (from 50:1 to 20:1) as eluents. The
solutions were evaporated in vacuo in all cases. X-ray data were
measured on a Bruker P4 and Smart Apex diffractometers with
graphite monochromated Mo-Kα radiation. Atomic coordinates,
thermal parameters, bond lengths and bond angles have been
deposited at the Cambridge Crystallographic Data Centre;
CCDC's contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge at
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) + 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
All computations were carried out with the GAMESS program
package [25]. 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 polariza-
tion functions on hydrogen atoms. The basis set used (HF/6-31G
(d, p)) was chosen by comparing of the experimental (X-ray) data
with the geometrical characteristics and energies of compounds
(cf. [24]). The harmonic vibration frequencies were determined
This compound was synthesized similarly to that described
above for 2c. Reaction time was 40 min, the yield was 60%;
NMR H (CDCl , 200.13 MHz, δ, ppm): 1.30 (s, 12H, 4,4,5,5-
(CH ) ), 6.76 (broad s, 1H, NOH). NMR F (CDCl , 188.28
1
3
19
3 4
3
MHz, δ, ppm): 95.4 (s. CF ).
3
2-tert-Butyl-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole 3-
oxide (5a).
A solution of NaNO (1.05 g, 15.2 mmol) in water (20 ml) was
2
added to solution of 2-tert-butyl-4,4,5,5-tetramethyl-3-oxy-4,5-
dihydroimidazole-1-oxyl (1.10 g, 5.05 mmol) in chloroform (30
ml). Hydrochloric acid (5 % aqueous solution, 1 ml) was added
dropwise to the resulting mixture on vigorous stirring. After stir-
ring for 30 min, the organic layer was separated, and the aqueous
solution was extracted with chloroform (2×30 ml). The combined
extracts were dried with MgSO , and the solvent was evaporated
4
after removing of desiccant. The residue was dissolved in anhy-
drous tetrahydrofuran (10 ml), a catalyst (5% Pd on charcoal,
0.100 g) was added, and the mixture was hydrogenated with
hydrogen upon stirring for 4 h at 20 °C. The catalyst was filtered
off, and the solvent was removed to give 0.90 g (90 %) pure 5a.
The product can be additionally purified by recrystallization from
the ethyl acetate – hexane mixture; NMR H (CDCl , 200.13
MHz, δ, ppm): 1.18, 1.19 (s, 6H, 4-CH , 5-CH ), 1.32 (s, 9H, C-
(CH ) ), 4.50 (broad s, 1H, NH). NMR C (CDCl , 50.32 MHz,
1
3
3
3
13
3 3
3
δ, ppm): 18.1, 23.2 (2-CH , 3-CH ), 25.1 (C-(CH ) ), 32.0 (C-
3
3
3 3
(CH ) ), 61.1 (C-5), 71.9 (C-4), 157.9 (C-2). λ , (ethanol), nm
3 3
max
(lg ε): 264 (3.78). IR (KBr): ν = 3098, 2975, 2929, 2868, 2813,

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
283
1587, 1468, 1444, 1387, 1361, 1333, 1204, 1172, 1150, 1134,
1086, 743 cm . m.p. 170-171 °C (from ethyl acetate – hexane
mixture).
The reaction was carried out at room temperature up to the disap-
pearance of starting 1 (TLC monitoring). After the completion of
the reaction, the solvent was removed and a product was isolated
by chromatography and purified by recrystallization.
-1
Anal. Calcd. for C
H N O: C 66.62, H 11.18, N 14.23.
11 22 2
Found: C 66.63, H 11.52, N 14.23.
Reaction of 2-Substituted 4,4,5,5-Tetramethyl-4,5-dihydro-1H-
imidazole 3-oxides with Alkynes in Heterogeneous Conditions
(General Procedure, Method B).
2-tert-Butyl-1,4,4,5,5-pentamethyl-4,5-dihydro-1H-imidazole 3-
oxide (5b).
Finely powdered substrate 2-12 (0.1 mmol) was placed in one
round-bottom flask (5 ml volume), and 1 mmol of alkyne was
placed into another round-bottom flask (5 ml volume). These flasks
were connected to two-joint cow receiver, supplied with stopcock.
All the system was evacuated to 1 mm Hg and kept for 7-20 days at
60-70 °C (TLC monitoring). Reaction product was isolated by chro-
Acetic anhydride (0.156 ml, 1.66 mmol) was added dropwise
upon stirring to the solution of 5a (0.109 g, 0.55 mmol) in anhy-
drous chloroform (10 ml). After stirring for 30 min, the reaction
mixture was washed successively with aqueous solution of
KHCO and water and dried with MgSO . After filtration of des-
3
4
iccant and removal of the solvent, 1-(acetyloxy)-2-tert-butyl-
4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole was obtained. The
solution of this compound and dimethyl sulphate (0.157 ml, 1.66
mmol) in anhydrous ether (10 ml) was kept for 120 h at room
temperature. The precipitate was collected by filtration and
washed with anhydrous ether to give 0.060 g of 1-(acetyloxy)-2-
tert-butyl-3,4,4,5,5-pentamethyl-4,5-dihydro-1H-imidazol-3-
ium methylsulphate. The latter was dissolved in 5% water solu-
tion of NaOH (5 ml) and the resulting solution was kept for 10
min at 20 °C, then was extracted with chloroform (2×15 ml), and
matography on alumina with CHCl as eluent and then purified by
3
recrystallization from hexane – ethyl acetate mixture.
Methyl 3-Oxo-2-(4,4,5,5-tetramethylimidazolidin-2-ylidene)-
propanoate (13a).
Solution of 1.74 mmol methyl propiolate in 2 ml CHCl was
3
added to frozen solution (below -60 °C) of 0.21 g (1.45 mmol) of
2a in 4 ml CHCl , and a mixture was allowed to warm slowly up
3
to room temperature. After two hours the solvent was removed,
and the residue was recrystallized to give 0.216 g 13a (66 %);
the combined extract was dried with MgSO . After filtration of
4
1
NMR H (CDCl , 200.13 MHz, δ, ppm): 1.17 (s, 12H, 4,4,5,5-
desiccant the solvent was removed to give crude 5b, which was
purified by chromatography on alumina with chloroform as elu-
ent to remove traces of the starting iminonitroxide and then with
a (20:1) chloroform-methanol mixture. The eluate was evapo-
rated to give 0.043 g (37 %) of nitrone 5b as colourless oil; NMR
3
(CH ) ), 3.65 (s, 3H, CO CH ), 7.73, 9.13 (broad s, 1H, NH),
3 4
2
3
9.56 (s, 1H, CHO). λ , (ethanol), nm (lg ε): 232 (4.31), 268
max
(4.28). IR (KBr): ν = 3314, 3250, 2954, 2842, 1681, 1616, 1577,
-1
1548, 1437, 1395, 1370, 1328, 1264, 1184, 1099 cm . m.p. 132-
1
133 °C (from ethyl acetate – hexane mixture).
H (CDCl , 200.13 MHz, δ, ppm): 1.04, 1.13 (s, 6H, 4-CH , 5-
3
3
13
Anal. Calcd. for C
H N O : C 58.39, H 8.02, N 12.38.
CH ), 1.39 (s, 9H, C-(CH ) ), 2.74 (s, 3H, N-CH ). NMR
C
11 18 2 3
3
3 3
3
Found: C 57.85, H 8.13, N 12.08.
(CDCl , 50.32 MHz, δ, ppm): 19.2, 19.6 (2-CH , 3-CH ), 26.9
3
3
3
(C-(CH ) ), 28.1 (C-(CH ) ), 31.3 (N-CH ), 65.0 (C-5), 71.7 (C-
3 3
3 3
3
Dimethyl 2-oxo-3-(4,4,5,5-tetramethylimidazolidin-2-
ylidene)succinate (13b).
4), 152.6 (C-2).
4,4,5,5-Tetramethyl-2-phenyl-4,5-dihydro-1H-imidazol-1-ol 3-
oxide (6c) [26].
This compound was synthesized similarly to 13a with the yield
1
63%; NMR H (CDCl , 200.13 MHz, δ, ppm): 1.23 (s, 12H,
3
4,4,5,5-(CH ) ), 3.66, 3.80 (s, 3H, CO CH ), 7.97, 9.16 (broad s,
This compound was synthesized as it was pointed out for 2c;
3 4
2
3
1
1H, NH). λ , (ethanol), nm (lg ε): 233 (4.15), 272 (4.11).
reaction time was 20 min, the yield was 40%; NMR
H
max
(KBr): ν = 3362, 3292, 2995, 2974, 2953, 1737, 1662, 1597,
([D ]DMSO, 200.13 MHz, δ, ppm): 1.27 (s, 12H, 4,4,5,5-
6
-1
1559, 1437, 1400, 1336, 1280, 1234, 1192, 1155, 1102 cm . m.p.
(CH ) ), 7.39-7.50 (m, 3H, Ph), 8.31-8.35 (m, 2H, Ph), 9.15
3 4
168-170 °C (from ethyl acetate – hexane mixture).
(broad s, 1H, N-OH).
Anal. Calcd. for C
C 54.93, H 7.00, N 9.87.
H N O : C 54.92, H 7.09, N 9.85. Found:
13 20 2 5
4,4,5,5-Tetramethyl-2-(3-nitrophenyl)-4,5-dihydro-1H-imida-
zole 3-oxide (10a).
2,2,3,3,7a-Pentamethyl-6-phenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carbaldehyde (14a).
This compound was synthesized similarly to 5a with the yield
1
90 %; NMR H ([D ]acetone, 200.13 MHz, δ, ppm): 1.30, 1.33
6
(s, 6H, 4-CH , 5-CH ), 4.20 (broad s, 1H, NH), 7.56 (t, J =8.2
A solution of 3-phenylprop-2-ynal 0.167 ml (1.37 mmol) and
3
3
3
Hz, 1H, Ar), 8.21 (d.m, J =8.2 Hz, 1H, Ar), 8.75 (broad s, 1H,
3a 0.178 g (1.14 mmol) in 5 ml CHCl was kept 3 h at room tem-
3
3
Ar), 8.85 (broad s, 1H, Ar). λ , (ethanol), nm (lg ε): 225 (4.35),
perature and then the solvent was removed. Cycloadduct 14a was
max
isolated by flash chromatography on alumina with CHCl as elu-
343 (3.58). IR (KBr): ν = 3089, 2982, 2791, 2677, 1627, 1597,
3
-1
ent and purified by recrystallization from hexane – ethyl acetate
1534, 1441, 1347, 1159, 1063, 833, 812, 756, 729, 706 cm . m.p.
1
mixture. The yield was 0.186 g (57 %); NMR H (CDCl , 200.13
192-194 °C (from ethyl acetate – hexane mixture).
3
MHz, δ, ppm): 1.06, 1.11, 1.16, 1.31 (each s, 3H, 2-CH , 3-CH ),
Anal. Calcd. for C
Found: C 59.37, H 6.49, N 15.64.
H N O : C 59.30, H 6.51, N 15.96.
3
3
13 17 3 3
1.81 (s, 3H, 7a-CH ), 2.33 (broad s, 1H, NH), 7.41-7.54 (m, 5H,
3
13
Ph), 9.65 (s, 1H, CHO). NMR C-mono (CDCl , 50.32 MHz, δ,
ppm): 19.4, 25.1, 25.4, 25.6 (qqq, J =127.7 Hz, J =4.5 Hz, J =1.0
3
Reaction of 2-Substituted 4,4,5,5-Tetramethyl-4,5-dihydro-1H-
imidazole 3-oxides with Alkynes in Solution (General Procedure,
Method A).
1
3
4
Hz, 2-CH , 3-CH ), 28.7 (q, J =128.6, 7a-CH ), 64.0 (m, C-2),
3
3
1
3
71.9 (m, C-3), 89.9 (dq, J =5.5, J =5.0, C-7a), 118.7 (dq,
3
2
J =24.5, J =3.0, C-7), 126.4 (t, J =7.4, Ph, C-1'), 128.7 (dm,
Solution of 0.12 mmol of alkyne in 1 ml of CHCl was added to
2
3
2
3
J =163.0, Ph, C-2' , C-3'), 131.5 (dt, J =161.5, J =7.5, Ph, C-4'),
cooled (-10 - 0 °C) solution of 2-12 (0.1 mmol) in 3 ml of CHCl .
1
1
2
3

284
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
168.6 (t, J =4.0, C-6), 185.9 (d, J =174.3, -CHO). λ
,
1.13, 1.15, 1.19, 1.28 (each s, 3H, 2-CH , 3-CH ), 1.80 (s, 3H, 7a-
3 3
3
1
max
(ethanol), nm (lg ε): 260 (3.91), 300 (3.88). IR (KBr): ν = 3314,
CH ), 2.34 (broad s, 1H, NH), 3.63 (s, 3H, CO CH ), 7.33-7.42 (m,
3
2
3
13
3007, 2989, 2969, 2941, 2837, 2764, 1648, 1631, 1596, 1492,
1477, 1397, 1371, 1346, 1167, 1112, 800, 771, 738, 699 cm .
m.p. 125-125 °C (from ethyl acetate – hexane mixture).
3H, Ph), 7.56 (d.m, J = 7.5 Hz, 2H, Ph). NMR C (CDCl , 50.32
3 3
-1
MHz, δ, ppm): 19.2, 25.2, 25.3, 25.8 (2-CH , 3-CH ), 29.9 (7a-
3 3
CH ), 50.8 (CO CH ), 63.3 (C-2), 71.9 (C-3), 90.3 (C-7a), 107.0 (C-
3 2 3
Anal. Calcd. for C
H
N O : C 71.30, H 7.74, N 9.78. Found:
7), 127.7 (C-2', Ph), 128.2 (C-1', Ph), 128.8 (C-3', Ph), 130.3 (C-4',
17 22
2 2
Ph), 162.3 (CO CH ), 164.3 (C-6). λ , (ethanol), nm (lg ε): 233
C 71.52, H 7.54, N 9.68.
2
3
max
(3.90), 244 (3.90). IR (KBr): ν = 3322, 3001, 2980, 2938, 1694,
1-(2,2,3,3,7a-Pentamethyl-6-phenyl-1,2,3,7a-tetrahydroimidazo-
[1,2-b]isoxazol-7-yl)ethanone (14b).
-1
1646, 1430, 1368, 1346, 1176, 1123, 1068, 796, 768, 702 cm . m.p.
149-151 °C (from ethyl acetate – hexane mixture).
This compound was synthesized similarly to 14a; reaction
Anal. Calcd. for C
C 67.99, H 8.16, N 8.64.
H N O : C 68.33, H 8.65, N 8.85. Found:
18 24 2 3
1
time was 20 h, the yield was 60 %; NMR H (CDCl , 200.13
3
MHz, δ, ppm): 1.10, 1.20 (each s, 3H, 2-CH , 3-CH ), 1.07 (s,
3
3
Dimethyl 2,2,3,3,7a-pentamethyl-1,2,3,7a-tetrahydroimidazo-
[1,2-b]isoxazole-6,7-dicarboxylate (14f).
6H, 2-CH , 3-CH ), 1.71 (s, 3H, COCH ), 1.81 (s, 3H, 7a-CH ),
3
3
3
3
13
2.90 (broad s, 1H, NH), 7.35 (s, 5H, Ph). NMR C-mono
(CDCl , 50.32 MHz, δ, ppm): 19.2, 25.3, 25.4, 25.8 (qqq,
This compound was synthesized similarly to 13a; reaction
3
1
J =127.3 Hz, J =4.5 Hz, J =1.0 Hz, 2-CH , 3-CH ), 29.4 (q,
time was 30 min, the yield was 71 %; NMR H (CDCl , 200.13
1
3
4
3
3
3
J =127.9 Hz, 7a-CH ), 29.8 (q, J =128.2 Hz, COCH ), 63.3 (m,
MHz, δ, ppm): 1.12, 1.14, 1.24, 1.28 (each s, 3H, 2-CH , 3-CH ),
1
3
1
3
3
3
C-2), 71.7 (m, C-3), 90.8 (q, J =4.5 Hz, C-7a), 118.7 (m, C-7),
1.74 (s, 3H, 7a-CH ), 2.24 (broad s, 1H, NH), 3.73, 3.86 (s, 3H,
2
3
13
128.9 (m, C-1'), 128.5, 128.7 (d.m, J =162.0 Hz, C-2' , C-3'),
CO CH ). NMR C-mono (CDCl , 50.32 MHz, δ, ppm): 19.2,
1
2
3
3
130.5 (dt, J =162.0 Hz, J =7.5 Hz, C-4'), 162.8 (m, C-6), 193.9
25.2, 25.3, 25.8 (qqq, J =127.7 Hz, J =4.5 Hz, J =1.0 Hz, 2-CH ,
1
2
1 3 4 3
(q, J =6.0 Hz, COCH ). λ , (ethanol), nm (lg ε): 239 (3.80),
3-CH ), 29.1 (q, J =128.8, 7a-CH ), 51.6 , 53.0 (q. J =147.2,
3 1 3 1
2
3
max
291 (3.74). IR (KBr): ν = 3319, 3059, 3002, 2982, 2939, 1637,
CO CH ), 63.9 (m, C-2), 72.3 (m, C-3), 89.9 (q, J =5.0, C-7a),
2
3
2
1594, 1481, 1444, 1367, 1338, 1245, 1181, 1167, 1118, 792, 777,
110.9 (q, J =2.8, C-7), 152.5 (s, C-6), 159.9, 162.8 (q, J =4.0,
3 3
-1
710 cm . m.p. 131.5-133.5 °C (from hexane).
CO CH ). λ , (ethanol), nm (lg ε): 274 (3.61). IR (KBr): ν =
2 3 max
Anal. Calcd. for C
H
N O : C 71.97, H 8.05, N 9.33. Found:
3327, 3011, 2986, 2953, 1753, 1713, 1653, 1527, 1435, 1373,
18 24
2 2
-1
1348, 1303, 1237, 1179, 1149, 1137, 1098, 1072, 823 cm . m.p.
C 71.82, H 8.07, N 9.34.
122-113 °C (from ethyl acetate – hexane mixture).
(2,2,3,3,7a-Pentamethyl-6-phenyl-1,2,3,7a-tetrahydroimidazo-
[1,2-b]isoxazol-7-yl)(phenyl)methanone (14c).
Anal. Calcd. for C
H N O : C 56.36, H 7.43, N 9.39. Found:
14 22 2 5
C 56.35, H 7.56, N 9.31.
This compound was synthesized similarly to 14a; reaction
Ethyl 2,2,3,3,6,7a-hexamethyl-1,2,3,7a-tetrahydroimidazo[1,2-
b]isoxazole-7-carboxylate (14g).
1
time was 10 h, the yield was 30 %; NMR H (CDCl , 200.13
3
MHz, δ, ppm): 1.16, 1.19, 1.26, 1.34 (each s, 3H, 2-CH , 3-CH ),
3
3
1.84 (s, 3H, 7a-CH ), 1.96 (broad s, 1H, NH), 6.97-7.17 (m, 8H,
A solution of 0.32 mmol methyl propiolate in 1 ml CHCl was
3
3
Ph), 7.40 (d.m, J =7.5 Hz, 2H, Ph). λ , (ethanol), nm (lg ε):
added to the frozen solution of 0.046 g (1.45 mmol) of 3a in 5 ml
3
max
248 (4.09), 319 (3.86). IR (KBr): ν = 3442, 3319, 3055, 3019,
CHCl . Reaction mixture turns colourless immediately. The mix-
3
-1
2977, 2935, 1622, 1596, 1577, 1446, 1350, 1160, 883, 856 cm .
ture was allowed to warm slowly to room temperature, the sol-
m.p. 125.5-126.5 °C (from heptane).
vent was removed, and cycloadduct 14g was isolated from the
Anal. Calcd. for C
H
N O : C 76.21, H 7.23, N 7.73. Found:
residue by flash chromatography on alumina with CHCl as elu-
23 26
2
2
3
ent. The yield was 0.06 g (63 %). Compound 14g can be addi-
tionally purified by sublimation in vacuo (2 mm Hg, 50 °C);
C 76.26, H 7.41, N 7.78.
Methyl 2,2,3,3,7a-pentamethyl-1,2,3,7a-tetrahydroimidazo[1,2-b]-
isoxazole-7-carboxylate (14d).
1
NMR H (CDCl , 200.13 MHz, δ, ppm): 1.06, 1.11, 1.13, 1.27
3
(each s, 3H, 2-CH , 3-CH ), 1.27 (t, J =7.1 Hz, 3H, OCH CH ),
3
3
3
2
3
This compound was synthesized similarly to 14a; reaction
1.74 (s, 3H, 7a-CH ), 2.19 (broad s, 1H, NH), 4.23 (q, 2H,
3
1
19
time was 24 h, the yield was 88 %; NMR H (CDCl , 200.13
OCH CH ). NMR F (CDCl , 188.28 MHz, δ, ppm): 99.6 (s.
3
2
3
3
13
MHz, δ, ppm): 1.03, 1.06, 1.09, 1.22 (each s, 3H, 2-CH , 3-CH ),
CF ). NMR C-mono (CDCl , 50.32 MHz, δ, ppm): 13.7 (qt,
J =127.4, J =4.5, OCH CH ), 18.9, 25.2, 25.3, 25.8 (qqq,
3
3
3
3
1.68 (s, 3H, 7a-CH ), 2.19 (broad s, 1H, NH), 3.67 (s, 3H,
3
1
2
2
3
13
CO CH ), 7.20 (s, 1H, C=CH). NMR C (CDCl , 50.32 MHz,
J =127.7 Hz, J =4.5 Hz, J =1.0 Hz, 2-CH , 3-CH ), 29.3 (q,
2
3
3
1
3
4
3
3
δ, ppm): 19.2, 24.9, 25.3, 25.8 (2-CH , 3-CH ), 29.1 (7a-CH ),
J =129.0, 7a-CH ), 60.8 (tq, J =148.3, J =4.5, OCH CH ), 63.7
3
3
3
1
3
1
2
2
3
50.8 (CO CH ), 64.2 (C-2), 71.6 (C-3), 88.0 (C-7a), 112.8 (C-7),
(m, C-2), 72.4 (m, C-3), 91.0 (q, J =4.8, C-7a), 112.1 (q, J =2.6,
2
3
2
3
153.5 (C-6), 163.8 (CO CH ). λ , (ethanol), nm (lg ε): 268
C-7), 117.7 (q, J (C-F)=275.0, CF ), 148.6 (q, J (C-F)=39.6, C-
2
3
max
1
3
2
(4.00). IR (KBr): ν = 3318, 3074, 3019, 3003, 2987, 2968, 1689,
6), 161.3 (t, J =4.1, CO Et). λ , (ethanol), nm (lg ε): 277
3
2
max
-1
1632, 1440, 1329, 1182, 1164, 1135, 1093, 1070, 801 cm . m.p.
(3.69). IR (KBr): ν = 3343, 2984, 2939, 1715, 1666, 1469, 1448,
-1
90-91.5 °C (from ethyl acetate – hexane mixture).
1394, 1374, 1346, 1311, 1234, 1176, 1096, 1069, 833 cm . m.p.
Anal. Calcd. for C
H N O : C 59.98, H 8.39, N 11.66.
29-30 °C (after sublimation). Found, m/z: 322,15068. Calculated
12 20 2 3
Found: C 60.15, H 8.16, N 11.57.
for C H F N O , m/z: 322,15041.
14 21 3 2 3
Methyl 2,2,3,3,7a-pentamethyl-6-phenyl-1,2,3,7a-tetrahydroimi-
1,2,2,3,3,7a-Hexamethyl-6-phenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carboxylate (14e).
dazo[1,2-b]isoxazole-7-carbaldehyde (14h).
This compound was synthesized similarly to 14a; reaction time
This compound was synthesized similarly to 14a; reaction
1
1
was 24 h, the yield was 50; NMR H (CDCl , 200.13 MHz, δ, ppm):
time was 2 h, the yield was 59 %; NMR H (CDCl , 200.13
3
3

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
285
MHz, δ, ppm): 0.80, 0.90, 1.17, 1.19 (each s, 3H, 2-CH , 3-CH ),
19
3
3
(s, 3H, CO CH ), 5.31 (broad s, 1H, N-OH). NMR F (CDCl ,
2 3 3
1.64 (s, 3H, 7a-CH ), 2.36 (s, 3H, N-CH ), 3.63 (s, 3H,
3
3
188.28 MHz, δ, ppm): 87.2 (s. CF ). λ , (ethanol), nm (lg ε):
3 max
CO CH ), 7.32-7.48 (m, 5H, Ph), 9.52 (s, 1H, CHO). m.p. 110-
2
3
267 (3.54). IR (KBr): ν = 3461, 3016, 2958, 2790, 1757, 1738,
111 °C (from ethyl acetate – hexane mixture). Found: C 72.16, H
7.79, N 9.29. Calculated for C N O : C 71.97, H 8.05, N
1652, 1440, 1351, 1322, 1290, 1221, 1196, 1165, 1141, 1098,
H
-1
18 24
2
2
1016, 983, 829, 800 cm . m.p. 161-163 °C (from ethyl acetate –
9.33; X-ray crystallography (CCDC 260688): C
H N O , FW
18 24 2 2
hexane mixture).
300.39, triclinic, P¯1, a 6.747(2), b 10.585(4), c 12.164(4) Å, α
Anal. Calcd. for C
H F N O : C 45.65, H 5.20, F 15.47, N
14 19 3 2 6
3
86.834(6), β 76.813(6), γ 76.165(5) °, V 821.3(5) Å , Z 2, D
C
7.61. Found: C 45.65, H 4.96, F 15.67, N 8.00.
3
-1
1.215 g/cm , µ(Mo-Kα) 0.079 mm , θ 1.72-23.28°, 3555 reflec-
tions collected, 2356 unique, R = 0.0551, data/parameters
7a-tert-Butyl-2,2,3,3-tetramethyl-6-phenyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-7-carbaldehyde (16a).
int
2356/296, Goof 0.983, R indices (I> 2σ(I)):R1 0.0411, wR2
0.1175; R indices (all data):R1 0.0449, wR2 0.1218.
This compound was synthesized by Method B with the 45%
yield; NMR H (CDCl , 200.13 MHz, δ, ppm) 1.03 (s, 9H,
C(CH ) ), 1.09 (s, 6H, 2-CH , 3-CH ), 1.23, 1.28 (s, 3H, 2-CH ,
3-CH ), 2.56 (broad s, 1H, N-H), 7.45-7.53 (m, 3H, Ph), 7.63-
7.67 (m, 2H, Ph), 9.65 (s, 1H, CHO). λ , (ethanol), nm (lg ε):
227 (4.03), 273 (3.86), 309 (3.86). IR (KBr): ν = 3340,
3077,3013, 2993, 2978, 2960, 2870, 2768, 1635, 1615, 1595,
1479, 1464, 1449, 1401, 1379, 1336, 1256, 1226, 1156, 1046,
1
3
Methyl 1,2,2,3,3,7a-hexamethyl-1,2,3,7a-tetrahydroimidazo[1,2-
b]isoxazole-7-carboxylate (14i).
3 3
3
3
3
3
This compound was synthesized similarly to 14a; reaction
max
time was 4 h, the yield was 60 %.
1
NMR H (CDCl , 200.13 MHz, δ, ppm): 0.85, 0.91 (each s,
3
3H, 2-CH , 3-CH ), 1.14 (s, 6H, 2-CH , 3-CH ), 1.56 (s, 3H, 7a-
3
3
3
3
-1
CH ), 2.33 (s, 3H, N-CH ), 3.64 (s, 3H, CO CH ), 7.26 (s, 1H,
888, 835, 781, 755, 713 cm . m.p. 118-120 °C (from hexane).
Anal. Calcd for C H N O : C 73.14, H 8.59, N 8.53. Found:
3
3
2
3
C=CH). λ , (ethanol), nm (lg ε): 266 (3.77). IR (KBr): ν =
max
20 28 2 2
C 73.04, H 8.37, N 8.32.
3050, 3011, 2986, 2950, 2874, 2804, 1714, 1620, 1467, 1438,
-1
1374, 1365, 1333, 1199, 1157, 1118, 1106, 1076, 867, 831 cm .
7a-tert-Butyl-1-(2,2,3,3-tetramethyl-6-phenyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazol-7-yl)ethanone (16b).
m.p. 83.5-84.5 °C (from heptane).
Anal. Calcd. for C
H N O : C 61.39, H 8.72, N 11.01.
13 22 2 3
Found: C 61.44, H 8.80, N 10.99.
This compound was synthesized similarly to 14a; reaction
1
time was 20 h, the yield was 45 %; NMR H ([D ]acetone,
6
Dimethyl 1,2,2,3,3,7a-hexamethyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-6,7-dicarboxylate (14j).
200.13 MHz, δ, ppm): 1.00 (s, 9H, C(CH ) ), 1.14 (s, 3H, 2,3-
3 3
(CH ) ), 1.22 (s, 9H, 2,3-(CH ) ), 2.05 (s, 3H, COCH ), 3.33 (s,
3 2
3 2
3
This compound was synthesized similarly to 14a; reaction
time was 1 h, the yield was 65 %; NMR H (CDCl , 200.13
1H, NH), 7.50-7.60 (m, 5H, Ph). λ , (ethanol), nm (lg ε): 226
max
1
(3.89), 293 (3.80). IR (KBr): ν = 3335, 2995, 2958, 2864, 1642,
3
MHz, δ, ppm): 0.89, 0.92, 1.13, 1.15 (each s, 3H, 2-CH , 3-CH ),
1479, 1447, 1386, 1362, 1326, 1151, 1109, 1073, 1054, 952, 800,
3
3
-1
1.57 (s, 3H, 7a-CH ), 2.31 (s, 3H, N-CH ), 3.66, 3.80 (s, 3H,
775, 762. 702 cm . m.p. 104.5-105.5 °C (from hexane).
3
3
CO CH ). λ , (ethanol), nm (lg ε): 272 (3.62). IR (KBr): ν =
Anal. Calcd for C
H N O : C 73.65, H 8.83, N 8.18. Found:
2
3
max
21 30 2 2
2995, 2953, 2848, 2803, 1750, 1717, 1646, 1436, 1371, 1343,
C 73.69, H 8.99, N 8.28.
-1
1309, 1221, 1156, 1103, 1072, 787 cm . m.p. 40-42 °C (from
heptane).
(7a-tert-Butyl-2,2,3,3-tetramethyl-6-phenyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazol-7-yl)(phenyl)methanone (16c).
Anal. Calcd. for C
H N O : C 57.68, H 7.74, N 8.97. Found:
15 24 2 5
C 57.76, H 7.79, N 8.72.
This compound was synthesized similarly to 14a; reaction
1
time was 20 h, the yield was 43 %; NMR H (CDCl , 200.13
3
Dimethyl 2,2,3,3-tetramethyl-7a-(trifluoromethyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (15a).
MHz, δ, ppm): 1.05 (s, 9H, C(CH ) ), 1.09, 1.15, 1.25, 1.27 (each
3 3
s, 3H, 2-CH , 3-CH ), 1.70 (broad s, 1H, N-H), 7.01-7.12 (m,
3
3
This compound was synthesized similarly to 14g; reaction
8H, Ph), 7.60 (d.m, J =7.5 Hz, 2H, Ph). λ , (ethanol), nm (lg
3
max
time was 2 h, the yield was 58 %.
ε): 255 (4.11), 322 (3.81). IR (KBr): ν = 3336, 3068, 3031, 3005,
1
NMR H (CDCl , 200.13 MHz, δ, ppm): 1.16 (each s, 3H, 2-
2977, 2962, 1639, 1618, 1596, 1577, 1447, 1385, 1366, 1337,
3
-1
CH , 3-CH ), 1.17 (s, 6H, 2-CH , 3-CH ), 1.24 (s, 3H, 2-CH , 3-
1144, 1045, 873, 811 cm . m.p. 147-148 °C (from hexane); X-
3
3
3
3
3
CH ), 2.74 (broad s, 1H, N-H), 3.78, 3.91 (s, 3H, CO CH ).
ray crystallography (CCDC 260687): C
H N O , FW 404.54,
3
2
3
26 32 2 2
19
NMR F (CDCl , 188.28 MHz, δ, ppm): 81.8 (s. CF ). λ
,
monoclinic, P2 /c, a 12.011(8), b 10.767(7), c 17.986(11) Å, β
3
3
max
1
3
3
(ethanol), nm (lg ε): 264 (3.72). IR (KBr): ν = 3360, 2994, 2961,
91.813(14) °, V 2325(3) Å , Z 4, D 1.155 g/cm , µ(Mo-Kα)
C
-1
2928, 2859, 1758, 1721, 1655, 1441, 1380, 1347, 1295, 1216,
0.073 mm , θ 2.20-23.32°, 9597 reflections collected, 3332
-1
1190, 1167, 1136, 1114, 1055, 1030, 984, 788, 778, 735 cm .
unique, R = 0.1095, data/parameters 3332/400, Goof 0.940, R
int
m.p. 83-85 °C (from ethyl acetate – hexane mixture).
indices (I> 2σ(I)):R1 0.0653, wR2 0.1443; R indices (all data):R1
0.1108, wR2 0.1699.
Anal. Calcd. for C
H F N O : C 47.73, H 5.44, F 16.18, N
14 19 3 2 5
7.95. Found: C 47.85, H 5.53, F 15.77, N 7.65.
Anal. Calcd. for C
H N O : C 77.19, H 7.97, N 6.92. Found:
26 32 2 2
C 77.21, H 8.09, N 6.95.
Dimethyl 1-hydroxy-2,2,3,3-tetramethyl-7a-(trifluoromethyl)-
1,2,3,7a-tetrahydroimidazo [1,2-b]isoxazole-6,7-dicarboxylate
(15b).
Methyl 7a-tert-Butyl-2,2,3,3-tetramethyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carboxylate (16d).
This compound was synthesized similarly to 13a; reaction
This compound was synthesized similarly to 14a; reaction
1
1
time was 10 h, the yield was 71 %; NMR H (CDCl , 200.13
time was 4 h, the yield was 52 %. NMR H (CDCl , 200.13 MHz,
3
3
MHz, δ, ppm): 1.12, 1.22 (each s, 6H, 2-CH , 3-CH ), 3.76, 3.90
δ, ppm): 0.99 (s, 9H, C(CH ) ), 1.12 (s, 3H, 2-CH , 3-CH ),
3
3
3 2
3
3

286
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
1.15 (s, 6H, 2-CH , 3-CH ), 1.20 (s, 3H, 2-CH , 3-CH ), 1.73
This compound was synthesized similarly to 14a; reaction
3
3
3
3
1
(broad s, 1H, N-H), 3.71 (s, 3H, CO CH ), 7.37 (s, 1H, C=CH).
time was 20 h, the yield was 67 %. NMR H ([D ]acetone,
2
3
6
λ
, (ethanol), nm (lg ε): 223 (3.38), 265 (3.75). IR (KBr): ν =
200.13 MHz, δ, ppm): 1.04, 1.14, 1.31, 1.35 (each s, 3H, 2,3-
max
3340, 3011, 2983, 2965, 2915, 1709, 1626, 1479, 1440, 1402,
1381, 1351, 1325, 1194, 1145, 1129, 1109, 1037, 927, 894, 879
(CH ) ), 3.50 (broad s, 1H, N-H), 7.00-7.37 (m, 13H, Ph), 7.86
3 2
(d.m, J = 8.0 Hz, 2H, Ph). λ , (ethanol), nm (lg ε): 254 (4.17),
3
max
-1
cm . m.p. 72-73 °C (from hexane).
316 (3.81). IR (KBr): ν = 3356, 3336, 3059, 1634, 1614, 1597,
Anal. Calcd. for C
H
N O : C 63.80, H 9.28, N 9.92. Found:
1577, 1490, 1447, 1367, 1344, 1217, 1151, 1073, 1024, 911, 884,
15 26
2 3
-1
863, 816 cm . m.p. 169-170 °C (from ethyl acetate – hexane
C 63.94, H 9.66, N 9.59.
mixture).
Anal. Calcd. for C
C 79.15, H 6.50, N 6.60.
Dimethyl 7a-tert-Butyl-2,2,3,3-tetramethyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-6,7-dicarboxylate (16e).
H N O : C 79.22, H 6.65, N 6.60. Found:
28 28 2 2
This compound was synthesized similarly to 14a; reaction
Methyl 2,2,3,3-Tetramethyl-7a-phenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carboxylate (17c).
1
time was 4 h, the yield was 74 %. NMR H (CDCl , 200.13 MHz,
3
δ, ppm): 0.96 (s, 9H, C(CH ) ), 1.09, 1.15, 1.17, 1.18 (each s,
3 3
This compound was synthesized similarly to 14a; reaction
time was 20 h, the yield was 42 % or by Method B with the yield
3H, 2-CH , 3-CH ), 2.59 (broad s, 1H, N-H), 3.75, 3.84 (s, 3H,
3
3
CO CH ). λ , (ethanol), nm (lg ε): 225 (3.57), 273 (3.59). IR
2
3
max
1
20%. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.84, 0.96, 1.10,
(KBr): ν = 3359, 3009, 2964, 2874, 1746, 1712, 1669, 1436,
3
-1
1.21 (each s, 3H, 2-CH , 3-CH ), 2.74 (broad s, 1H, N-H), 3.47
1381, 1367, 1322, 1259, 1208, 1173, 1130, 1104, 1061 cm . m.p.
3
3
(s, 3H, CO CH ), 7.10-7.23 (m, 3H, Ph), 7.63 (d, J =7.5 Hz, 2H,
49-50.5 °C (from hexane).
2
3
3
Ph). λ , (ethanol), nm (lg ε): 255 (3.92). IR (KBr): ν = 3091,
Anal. Calcd. for C
C 59.94, H 8.31, N 8.19.
H N O : C 59.98, H 8.29, N 8.23. Found:
max
17 28 2 5
3059, 2955, 1722, 1623, 1438, 1340, 1256, 1198, 1152, 1026,
-1
760, 700 cm . m.p. 76-77 °C (from hexane-benzene mixture).
Methyl 7a-tert-Butyl-1,2,2,3,3-pentamethyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-7-carboxylate (16f).
Anal. Calcd. for C
H N O : C 67.53, H 7.33, N 9.26. Found:
17 22 2 3
C 67.43, H 7.61, N 9.15.
This compound was synthesized similarly to 14a; reaction
Methyl 2,2,3,3-Tetramethyl-6,7a-diphenyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-7-carboxylate (17d).
1
time was 6 h, the yield was 60 %. NMR H ([D ]acetone, 200.13
6
MHz, δ, ppm): 0.94 (s, 6H, 2,3-(CH ) ), 1.04 (s, 9H, C(CH ) ),
3 2
3 3
This compound was synthesized similarly to 14a; reaction
1.14, 1.18 (each s, 3H, 2,3-(CH ) ), 2.66 (s, 3H, N-CH ), 3.66 (s,
3 2
3
1
time was 40 h, the yield was 53 %. NMR H (CDCl , 200.13
3H, CO CH ), 7.65 (s, 1H, C=CH). λ , (ethanol), nm (lg ε):
3
2
3
max
MHz, δ, ppm): 1.00, 1.10, 1.25, 1.34 (each s, 3H, 2-CH , 3-CH ),
269 (3.67). IR (KBr): ν = 3069, 3016, 2996, 2962, 1708, 1610,
3
3
1.83 (broad s, 1H, N-H), 3.46 (s, 3H, CO CH ), 7.17-7.45 (m,
1438, 1365, 1311, 1195, 1176, 1155, 1115, 1055, 1025, 878, 804
2
3
-1
6H, Ph), 7.64-7.66 (m, 4H, Ph). λ , (ethanol), nm (lg ε): 248
cm . m.p. 47-48 °C (from hexane).
max
(4.00). IR (KBr): ν = 3349, 3056, 2978, 2948, 1688, 1629, 1598,
Anal. Calcd. for C
H N O : C 64.83, H 9.52, N 9.45. Found:
16 28 2 3
1492, 1435, 1366, 1346, 1218, 1187, 1165, 1115, 1090, 1074,
C 64.77, H 9.56, N 9.34.
-1
1028, 811 cm . m.p. 100-101 °C (from heptane).
1-(2,2,3,3-Tetramethyl-6,7a-diphenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazol-7-yl)ethanone (17a)
Anal. Calcd. for C
H N O : C 72.99, H 6.92, N 7.40. Found:
23 26 2 3
C 73.18, H 7.01, N 7.36.
This compound was synthesized similarly to 14a; reaction
Dimethyl 2,2,3,3-Tetramethyl-7a-phenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-6,7-dicarboxylate (17e).
1
time was 20 h, the yield was 56 %. NMR H ([D ]acetone,
6
200.13 MHz, δ, ppm): 1.04, 1.06, 1.28, 1.34 (each s, 3H, 2-CH ,
3
This compoundwas synthesized similarly to 14a; reaction time
3-CH ), 1.71 (s, 3H, COCH ), 3.33 (s, 1H, NH), 7.20-7.33 (m,
3
3
1
was 20 h, the yield was 84 %. NMR H (CDCl , 200.13 MHz, δ,
3
3H, Ph), 7.54-7.57 (m, 3H, Ph), 7.63-7.67 (m, 2H, Ph), 7.63-7.80
ppm): 0.90, 1.05, 1.20, 1.30 (each s, 3H, 2-CH , 3-CH ), 3.55
13
3
3
(m, 2H, Ph). NMR C-mono ([D ]acetone, 50.32 MHz, δ, ppm):
6
3.84 (s, 3H, CO CH ) 7.62-7.66 (m, 2H, Ph) 7.19-7.31 (m, 3H,
2
3
19.1, 24.9, 25.7, 26.5 (q. q. q, J = 127.0 Hz, J = 5.0 Hz, J = 1.0
1
3
4
Ph). λ , (ethanol), nm (lg ε): 273 (3.72). IR (KBr): ν = 3352,
max
Hz, 2,3-(CH ) ), 29.7 (q. J = 127.5 Hz, COCH ), 63.8 (m. C-2),
3 2
1
3
3003, 2982, 2956, 1753, 1723, 1659, 1450, 1437, 1369, 1341,
1299, 1211, 1173, 1131, 1099, 1089, 1074, 971, 915, 876, 830
73.2 (m. C-3), 93.6 (t. q. J = 4.0 Hz, J = 1.0 Hz, C-7a), 121.3 (q.
3
4
t. J =1.1 Hz, C-7), 127.6 (t, J = 162.6 Hz, C-1'), 127.8 (d.m, J
3
1
1
-1
cm .m.p 141-142 °C (from heptane).
= 157.6 Hz, C-3"), 128.1 (dd, J = 158.5 Hz, J = 7.6 Hz, C-2“),
1
2
Anal. Calcd. for C
H N O : C 63.32, H 6.71, N 7.77. Found:
19 24 2 5
129.5 (dd, J = 162.6 Hz, J = 6.5 Hz, C-2'), 130.0 (dt, J = 161.7
1
2
1
C 63.42, H 6.88, N 7.60.
Hz, J = 6.5 Hz, C-3'), 131.7 (d. t. t, J = 162.6 Hz, J = 7.1 Hz, J
2
1
2
3
=1.0 Hz, C-4'), 147.8 (t. J = 7.1 Hz, C-1”), 162.7 (t. J = 3.5 Hz,
2
3
1,2,2,3,3-Pentamethyl-7a-phenyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carbaldehyde (17f).
C-6), 192.9 (q. J = 6.1 Hz, COCH ). λ , (ethanol), nm (lg ε):
2
3
max
245 (3.93), 300 (3.78). IR (KBr): ν = 3284, 3060, 2983, 1663,
This compound was synthesized similarly to 13a; reactants
1651, 1637, 1588, 1569, 1489, 1446, 1367, 1332, 1249, 1217,
1
ratio was 1:2, reaction time was 2 h, the yield was 83 %. NMR H
-1
1171, 1107, 1076, 770, 754, 702 cm . m.p. 92.5-94.5 °C (from
(CDCl , 200.13 MHz, δ, ppm): 0.92, 1.01, 1.09, 1.33 (each s, 3H,
3
hexane).
2-CH , 3-CH ), 2.42 (s, 3H, N-CH ), 7.22 (s, 1H, C=CH), 7.25-
3
3
3
Anal. Calcd. For C
H N O : C 76.21, H 7.23, N 7.73.
23 26 2 2
7.34 (m, 2H, Ph), 7.53-7.57 (m, 3H, Ph), 9.45 (s, 1H, CHO). m.p
87-88 °C (from hexane).
Found: C 76.06, H 7.49, N 7.59.
(2,2,3,3-Tetramethyl-6,7a-diphenyl-1,2,3,7a-tetrahydroimi-
Anal. Calcd. for C
H N O : C 71,30, H 7.74, N 9.78. Found:
17 22 2 2
dazo[1,2-b]isoxazol-7-yl)(phenyl)methanone (17b).
C 71.02, H 8.09, N 9.60.

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
287
6,7a-Diphenyl-1,2,2,3,3-pentamethyl-1,2,3,7a-tetrahydroimi-
dazo[1,2-b]isoxazole-7-carbaldehyde (17g).
This compound was synthesized by Method B with the 45%
1
yield. NMR H (CDCl , 200.13 MHz, δ, ppm ) 0.90, 1.08, 1.10,
3
1.31 (each s, 3H, 2-CH , 3-CH ), 2.56 (s, 3H, N-CH ), 3.27 (s,
3
3
3
This compound was synthesized by Method B with the 52%
3H, CO CH ), 7.24-7.29 (m, 2H, Ph), 7.38-7.44 (m, 5H, Ph),
1
2
3
yield. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.96, 1.04,
3
7.61-7.64 (m, 3H, Ph). λ , (ethanol), nm (lg ε): 246 (4.08); IR
max
1.12, 1.36 (each s, 3H, 2-CH , 3-CH ), 2.54 (s, 3H, N-CH ),
3
3
3
(KBr): ν = 3086, 3058, 3011, 2995, 2959, 2871, 2846, 2801,
7.2-7.7 (m, 10H, Ph), 9.53 (s, 1H, CHO). λ , (ethanol), nm
max
1704, 1636, 1598, 1492, 1464, 1446, 1342, 1219, 1189, 1150,
(lg ε): 206 (4.32), 255 (4.09). IR (KBr): ν = 3060, 2992, 2966,
-1
1119, 1075, 1027, 1001, 749, 697 cm . m.p. 143-144 °C (from
2941, 2847, 2802, 2762, 1656, 1617, 1594, 1574, 1492, 1446,
hexane).
-
1344, 1221, 1152, 1110, 1001, 984, 866, 840, 749, 699 cm
Anal. Calcd. for C
H N O : C 73.44, H 7.19, N 7.14. Found:
1
24 28 2 3
.m.p. 129-130 °C (from hexane). X-ray Crystallography
C 73.64, H 7.24, N 7.15.
(CCDC 260355): C
H N O , FW 362.46, triclinic, P¯1, a
23 26 2 2
11.330(2), b 13.739(3), c 14.905(3) Å, α 66.66(1), β 80.89(1),
Dimethyl 1,2,2,3,3-Pentamethyl-7a-phenyl-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-6,7-dicarboxylate (17l).
3
3
γ 71.50(2)°, V 2018.7(7) Å , Z 4, D 1.193 g/cm , µ(Mo-Kα)
C
-1
0.076 mm , θ 1.79-24.99°, 7329 reflections collected, 6941
unique, R = 0.026, data/parameters 6941/643, Goof 0.959, R
This compound was synthesized similarly to 14a; reaction
int
1
time was 20 h, the yield was 56 %. NMR H ([D ]methanol,
4
indices (I> 2σ(I)):R1 0.0537, wR2 0.1122; R indices (all
data):R1 0.1139, wR2 0.1359.
200.13 MHz, δ, ppm ): 0.92, 1.16, 1.18, 1.35 (each s, 3H, 2-CH ,
3
3-CH ), 2.52 (s, 3H, NCH ), 3.51 , 3.95 (s, 3H, CO CH ), 7.24-
3
3
2
3
Anal. Calcd. for C
H N O : C 76.21, H 7.23, N 7.73. Found:
23 26 2 2
7.28 (m, 1H, Ph), 7,32-7,37 (m, 2H, Ph), 7,55-7,58 (m, 2H, Ph);
C 75.72, H 7.17, N 7.51.
13
NMR C ([D ]methanol, 50.32 MHz, δ, ppm): 19.7 , 21.2, 25.8,
4
26.2 (2-CH , 3-CH ), 30.6 (N-CH ), 52.8, 54.8 (CO CH ), 68.0
1-(1,2,2,3,3-Pentamethyl-6,7a-diphenyl-1,2,3,7a-tetrahydroimi-
3
3
3
2
3
(C-2), 74.2 (C-3), 96.5 (C-7a), 112.0 (C-7), 129.3 (C-4”), 129.4,
129.7 (C-2” , C-3”), 145.0 (C-1”), 157.5 (C-6), 162.2, 165.0
(CO CH ). λ , (ethanol), nm (lg ε): 276 (3.58). IR (KBr): ν =
dazo[1,2-b]isoxazol-7-yl)ethanone (17h).
This compound was synthesized by Method B with the 73%
2
3
max
1
yield. NMR H ([D ]acetone, 200.13 MHz, δ, ppm): 0.86, 1.14,
6
2988, 2952, 2890, 2806, 1755, 1722, 1644, 1438, 1341, 1307,
1.16, 1.29 (each s, 3H, 2-CH , 3-CH ), 1.64 (s, 3H, COCH ),
3
3
3
-1
1217, 1129, 1082, 1059, 1032, 989, 834, 810 cm . m.p. 84.5-86
2.58 (s, 3H, NCH ), 7.15-7.30 (m, 3H, Ph), 7.60-7.64 (m, 5H,
3
°C (from hexane).
Ph), 7.66-7.69 (m, 2H, Ph). λ , (ethanol), nm (lg ε): 245 (4.09).
max
Anal. Calcd. for C
H N O : C 64.15, H 7.00, N 7.48. Found:
20 26 2 5
IR (KBr): ν = 3058, 3000, 2977, 2932, 2875, 2844, 2802, 1643,
C 64.47, H 7.30, N 7.49.
1618, 1591, 1491, 1447, 1366, 1332, 1218, 1150, 1096, 981, 754,
-1
706, 694 cm . m.p. 160-161.5 °C (from hexane).
Anal. Calcd. for C
C 76.32, H 7.59, N 7.45.
H N O : C 76.56, H 7.50, N 7.44. Found:
Methyl 1,2,2,3,3-Pentamethyl-7a-phenyl-6-(trifluoromethyl)-
1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate
(17m).
24 28 2 2
(1,2,2,3,3-Pentamethyl-6,7a-diphenyl-1,2,3,7a-tetrahydroimi-
This compoundwas synthesized similarly to 14g; reaction time
dazo[1,2-b]isoxazol-7-yl)(phenyl)methanone (17i).
1
was 20 min, the yield was 97 %. NMR H (CDCl , 200.13 MHz,
3
This compound was synthesized similarly to 14a; reaction
δ, ppm): 0.89 (s, 3H, 2-CH , 3-CH ), 1.01 (t, J = 7.1 Hz, 3H,
3
3
3
1
time was 20 h, the yield was 83 %. NMR H (CDCl , 200.13
3
OCH CH ), 1.09, 1.12, 1.34 (each s, 3H, 2-CH , 3-CH ), 2.52 (s,
2
3
3
3
MHz, δ, ppm): 0.95, 1.15, 1.16, 1.42 (each s, 3H, 2-CH , 3-CH ),
3
3
3H, N-CH ), 3.98 (q, J = 7.1 Hz, 2H, OCH CH ), 7.23-7.25 (m,
3
3
2
3
2.70 (s, 3H, N-CH ), 6.91-7.37 (m, 13H, Ph), 7.75 (d.m, J = 7.5
3
3
1H, Ph), 7.31 (t, J = 7.5 Hz, 2H, Ph), 7.55 (t, J = 7.5 Hz, 2H,
3
3
Hz, 2H, Ph). λ , (ethanol), nm (lg ε): 250 (4.14). IR (KBr): ν =
max
19
Ph). NMR F (CDCl , 188.28 MHz, δ, ppm): 99.9 (s. CF ).
3
3
3059, 3022, 2959, 2867, 2841, 2800, 1613, 1592, 1575, 1491,
λ
, (ethanol), nm (lg ε): 280 (3.56). IR (KBr): ν = 2983, 2945,
max
-1
1446, 1346, 1218, 1166, 1148, 1001, 986, 889, 853, 814 cm .
m.p. 176.5-177.5 °C (from ethyl acetate – hexane mixture).
2810, 1714, 1647, 1467, 1447, 1392, 1370, 1340, 1306, 1258,
-1
1224, 1175, 1113, 1080, 1039, 1005, 840 cm . m.p. 43-44 °C
Anal. Calcd. for C
H N O : C 79.42, H 6.89, N 6.39. Found:
29 30 2 2
(from hexane).
C 79.41, H 6.75, N 6.39.
Anal. Calcd. for C
H F N O : C 60.29, H 6.32, F 14.31, N
20 25 3 2 3
Methyl 1,2,2,3,3-Pentamethyl-7a-phenyl-1,2,3,7a-tetrahydroimi-
7.03. Found: C 59.96, H 6.77, F 14.77, N 7.20.
dazo[1,2-b]isoxazole-7-carboxylate(17j).
Dimethyl 1-Hydroxy-2,2,3,3-tetramethyl-7a-phenyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (17n).
This compound was synthesized similarly to 14a, reaction time
1
was 5 h, the yield was 52 %. NMR H (CDCl , 200.13 MHz, δ,
3
This compound was synthesized similarly to 14g; reaction
ppm): 0.89, 1.04, 1.09, 1.32 (each s, 3H, 2-CH , 3-CH ), 2.47 (s,
3
3
1
time was 2 h, the yield was 25 %. NMR H ([D ]acetone, 200.13
6
3H, N-CH ), 3.52 (s, 3H, CO CH ), 7.20-7.34 (m, 3H, Ph), 7.54
3
2
3
MHz, δ, ppm): 0.97, 1.05, 1.25, 1.36 (each s, 3H, 2-CH , 3-CH ),
3
3
(s, 1H, C=CH), 7.57 (d.m, J = 7.0 Hz, 2H, Ph). λ , (ethanol),
3
max
3.45 , 3.88 (each s, 3H, CO CH ), 7.27-7.31 (m, 3H, Ph), 7.37
2
3
nm (lg ε): 270 (3.58); IR (KBr): ν = 3063, 2990, 2952, 2846,
(broad s, 1H, N-OH), 7.73 (dm, J = 7.6 Hz, 2H, Ph). λ
,
3
max
2802, 1719, 1617, 1442, 1366, 1332, 1225, 1195, 1166, 1123,
(ethanol), nm (lg ε): 261 (3.52), 267 (3.53). IR (KBr): ν = 3418,
-1
1032, 1001, 984 cm . m.p. 89-90 °C (from hexane).
3014, 2992, 2951, 1756, 1713, 1650, 1436, 1367, 1347, 1307,
Anal. Calcd. for C
H N O : C 68.33, H 7.65, N 8.85. Found:
18 24 2 3
-1
1210, 1173, 1145, 1088, 1070 cm . m.p 124-126 °C (from ethyl
C 67.94, H 8.04, N 8.79.
acetate – hexane mixture).
Methyl 6,7a-Diphenyl-1,2,2,3,3-pentamethyl-1,2,3,7a-tetrahy-
Anal. Calcd. for C H N O : C 60.63, H 6.43, N 7.44. Found:
19 24 2 6
droimidazo[1,2-b]isoxazole-7-carboxylate (17k).
C 60.70, H 6.41, N 7.41.

288
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-6-phenyl-1,2,3,7a-
Anal. Calcd. for C H N O : C 58.78, H 6.09, N 12.10.
17 21 3 5
tetrahydroimidazo[1,2-b]isoxazole-7-carbaldehyde (18a)
Found: C 58.35, H 6.31, N 11.88.
This compound was synthesized similarly to 14a; reaction
Methyl 2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-6-phosphino-
1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (18e).
1
time was 20 h, the yield was 69 %. NMR H (CDCl , 200.13
3
MHz, δ, ppm): 1.03, 1.06, 1.19, 1.35 (each s, 3H, 2-CH , 3-CH ),
3
3
This compound was synthesized similarly to 14a; reaction
2.73 (broad s, 1H, NH), 7.44-7.63 (m, 5H, Ph), 8.00 (dt, J =9.0
3
time was 50 h at 60 °C, the yield was 61 %.
Hz, J =2.1 Hz, 2H, Ar), 8.15 (dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar),
4
3
4
1
NMR H (CDCl , 200.13 MHz, δ, ppm): 1.03, 1.04, 1.25, 1.32
3
13
9.53 (s, 1H, CHO). NMR C-mono (CDCl , 50.32 MHz, δ,
ppm): 18.4, 24.1, 25.0, 25.6 (qqq, J =127.7 Hz, J =4.5 Hz, J =1.0
3
(each s, 3H, 2-CH , 3-CH ), 2.87 (broad s, 1H, NH), 3.49 (s, 3H,
3
3
1
3
4
CO CH ), 7.41-7.48 (m, 3H, Ph), 7.65-7.70 (m, 2H, Ph), 7.96
2
3
Hz, 2-CH , 3-CH ), 63.8 (m, C-2), 72.9 (m, C-3), 91.3 (dt,
3
3
(dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar), 8.15 (dt, J =9.0 Hz, J =2.1
3
4
3
4
J =5.6 Hz, J =3.5 Hz, C-7a), 119.1 (d, J =25.9 Hz, C-7), 122.8
3
3
2
13
Hz, 2H, Ar). NMR C-mono (CDCl , 50.32 MHz, δ, ppm):
18.5, 24.2, 25.3, 25.8 (qqq, J =127.7 Hz, J =4.5 Hz, J =1.0 Hz,
3
(d, J =169.0 Hz, C-3''), 125.7 (t, J =7.2 Hz, C-1'), 127.6 (dd,
1
2
1
3
4
J =167.0 Hz, J =6.5 Hz, C-2''), 128.9 (d.m, J =165.4 Hz, C-2' or
1
2
1
2-CH , 3-CH ), 50.9 (q, J =147.2 Hz, CO CH ), 63.1 (m, C-2),
3
3
1
2
3
C-3'), 129.0 (dm, J =163.0 Hz, C-2' or C-3'), 132.1 (dtt, J =161.5
1
1
72.8 (m, C-3), 91.8 (t, J =3.5 Hz, C-7a), 107.9 (s, C-7), 122.6 (d,
3
Hz, J =7.5 Hz, J =1.0 Hz, C-4'), 147.0 (m, C-4''), 151.9 (t, J =7.3
2
3
2
J =168.8 Hz, C-3''), 127.2 (t, J =7.4 Hz, C-1'), 127.8 (d, J =172.1
1
2
1
Hz, C-1''), 169.0 (t, J =4.0 Hz, C-6), 184.8 (d, J =176.4 Hz,
3
1
Hz, C-2''), 128.0 (d.m, J =165.4 Hz, C-2'), 129.0 (d.m, J =163.0
1
1
CHO). λ , (ethanol), nm (lg ε): 273 (4.39). IR (KBr): ν = 3297,
max
Hz, C-3'), 131.1 (dtt, J =161.5 Hz, J =7.5 Hz, J =1.0 Hz, C-4'),
1
2
3
3108, 3069, 2979, 2939, 2874, 1648, 1622, 1595, 1515, 1447,
147.0 (m, C-4''), 153.2 (t, J =7.5 Hz, C-1''), 163.1 (t, J =4.1 Hz,
-1
2
3
1392, 1370, 1345, 1316, 1218, 1158, 1145, 862, 850 cm . m.p.
C-6), 163.3 (q, J =4.1 Hz, CO CH ). λ , (ethanol), nm (lg ε):
3
2
3
max
156-157 °C (from hexane).
270 (4.27). IR (KBr): ν = 3354, 3068, 2978, 2951, 1688, 1635,
Anal. Calcd. for C
H N O : C 67.16, H 5.89, N 10.68.
22 23 3 4
-1
1599, 1516, 1492, 1437, 1347, 1188, 1175, 1112, 1073, 851 cm .
Found: C 67.14, H 5.94, N 10.55.
m.p. 126-128 °C (from hexane).
1-(2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-6-phenyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazol-7-yl)ethanone (18b).
Anal. Calcd. for C
H N O : C 65.24, H 5.95, N 9.92. Found:
23 25 3 5
C 65.08, H 6.24, N 9.80.
This compound was synthesized similarly to 14a; reaction
Dimethyl 2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (18f).
1
time was 20 h, the yield was 50 %. NMR H ([D ]acetone,
6
200.13 MHz, δ, ppm): 1.00, 1.08, 1.29, 1.37 (each s, 3H, 2-CH ,
3
was synthesized similarly to 14a; reaction time was 1 h, the
3-CH ), 1.67 (s, 3H, COCH ), 3.47 (s, 1H, NH), 7.58-7.69 (m,
3
3
1
yield was 49 %. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.92,
3
5H, Ph), 8.05-8.09 (dt, J = 9.0 Hz, J = 2.0 Hz, 2H, Ar), 8.15-
3
4
0.95, 1.16, 1.23 (each s, 3H, 2-CH , 3-CH ), 2.81 (broad s, 1H,
3
3
8.19 (dt, J = 8.7 Hz, J = 2.0 Hz, 2H, Ar). λ , (ethanol), nm (lg
3
4
max
N-H), 3.52, 3.83 (each s, 3H, CO CH ), 7.84 (dt, J =9.0 Hz,
2
3
3
ε) 272 (4.19). IR (KBr): ν = 3355, 2984, 1631, 1605, 1593, 1516,
J =2.1 Hz, 2H, Ar), 8.08 (dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar).
-1
4
3
4
1490, 1446, 1370, 1347, 1160, 1107, 864, 850, 700 cm . m.p.
λ
, (ethanol), nm (lg ε): 269 (4.18). IR (KBr): ν = 3353, 2981,
max
144-146 °C (from hexane).
2959, 1755, 1713, 1651, 1523, 1438, 1348, 1306, 1213, 1175,
Anal. Calcd. for C
H N O : C 67.80, H 6.18, N 10.31.
23 25 3 4
-1
1138, 1090, 851 cm . m.p. 116-117 °C (from hexane).
Found: C 66.92, H 6.17, N 10.25.
Anal. Calcd. for C
H N O : C 56.29, H 5.72, N 10.37.
19 23 3 7
(2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-6-phenyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazol-7-yl)(phenyl)methanone
(18c).
Found: C 56.43, H 5.91, N 10.30.
1,2,2,3,3-Pentamethyl-7a-(4-nitrophenyl)-1,2,3,7a-tetrahydroim-
idazo[1,2-b]isoxazole-7-carbaldehyde (18g).
This compound was synthesized similarly to 14a; reaction
1
This compound was synthesized similarly to 13a; the yield
time was 20 h, the yield was 76 %. NMR H (CDCl , 200.13
3
1
was 24 %. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.84, 1.01,
MHz, δ, ppm ): 1.00, 1.13, 1.26, 1.35 (each s, 3H, 2-CH , 3-
3
3
1.08, 1.33 (each s, 3H, 2-CH , 3-CH ), 2.41 (s, 3H, N-CH ),
CH ), 2.60 (s, 1H, N-H), 9.94-7.70 (m, 8H, Ar), 8.04-8.23 (m,
3
3
3
3
7.58 (s, 1H, C=CH), 7.72 (dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar), 8.14
6H, Ar). λ , (ethanol), nm (lg ε): 262 (4.29); IR (KBr): ν =
3
4
max
(dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar), 9.50 (s, 1H, CHO). m.p. 71.5-
3439, 3346, 3063, 2981, 2947, 2874, 1622, 1597, 1577, 1518,
3
4
-1
72.5 °C (from hexane).
1491, 1447, 1369, 1347, 1217, 1154, 887, 871, 849, 810 cm .
Anal. Calcd. for C
H N O : C 61.62, H 6.39, N 12.68.
m.p. 129-130 °C (from ethyl acetate – hexane mixture).
17 21 3 4
Found: C 61.58, H 6.67, N 12.67.
Anal. Calcd. for C
H N O : C 71.62, H 5.80, N 8.95. Found:
28 27 3 4
C 71.42, H 5.45, N 9.27.
1,2,2,3,3-Pentamethyl-6-phenyl-7a-(4-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-7-carbaldehyde (18h).
Methyl 2,2,3,3-Tetramethyl-7a-(4-nitrophenyl)-1,2,3,7a-tetrahy-
droimidazo[1,2-b]isoxazole-7-carboxylate (18d).
This compound was synthesized by Method B with the 68%
1
yield. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.88, 1.03, 1.12,
This compound was synthesized similarly to 14a; reaction time
3
1
1.37 (each s, 3H, 2-CH , 3-CH ), 2.54 (s, 3H, N-CH ), 7.47-7.68
was 5 h, the yield was 76 %. NMR H (CDCl , 200.13 MHz, δ,
3
3
3
3
(m, 5H, Ph), 7.78-7.82 (d.m, J = 8.7 Hz, 2H, Ar), 8.13-8.17
ppm ): 0.93, 0.95, 1.14, 1.21 (each s, 3H, 2-CH , 3-CH ), 3.00
3
3
3
(d.m, J = 8.7 Hz, 2H, Ar), 9.53 (s, 1H, CHO). λ , (ethanol),
(broad s, 1H, N-H), 3.53 (s, 3H, CO CH ), 7.37 (s, 1H, C=CH),
3
max
2
3
nm (lg ε): 271 (4.28). IR (KBr): ν = 3066, 2991, 2955, 2826,
7.87 (d, J = 8.5 Hz, 2H, Ar), 8.09 (d, J = 8.5 Hz, 2H, Ar). λ ,
3
3
max
2804, 2751, 1663, 1620, 1595, 1524, 1490, 1446, 1395, 1342,
(ethanol), nm (lg ε): 270 (4.15). IR (KBr): ν = 3312, 3056, 2991,
-1
1214, 1152, 1109, 985, 862, 851, 771, 702 cm . m.p. 161-163 °C
2956, 1710, 1616, 1603, 1513, 1438, 1372, 1345, 1217, 1166, 1129,
-1
(from hexane).
1106, 1081, 865, 853, 836 cm . m.p. 141-143 °C (from hexane).

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
289
Anal. Calcd. for C
H
N O : C 67.80, H 6.35, N 10.23.
(2-CH , 3-CH ), 29.2 (N-CH ), 50.5 (CO CH ), 66.1 (C-2), 71.7
3 3 3 2 3
23 25
3
4
(C-3), 94.8 (C-7a), 105.2 (C-7), 122.8 (C-3”), 127.8 (C-1'), 127.9
(C-2”), 128.2 (C-2'), 129.3 (C-3'), 131.0 (C-4'), 146.8 (C-4”),
152.5 (C-1”), 163.7 (C-6), 165.4 (-CO CH ). λ , (ethanol),
Found: C 67.82, H 6.35, N 10.23.
1-(1,2,2,3,3-Pentamethyl-6-phenyl-7a-(4-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazol-7-yl)ethanone (18i).
2
3
max
nm (lg ε): 270 (4.18). IR (KBr): ν = 3061, 2995, 2952, 2807,
This compound was synthesized similarly to 14a; reaction
time was 20 h, the yield was 58 %. NMR H ([D ]acetone,
1699, 1634, 1595, 1520, 1492, 1440, 1367,1346, 1273, 1218,
1
-1
1198, 1124, 1037, 987, 865, 847, 792, 767, 750, 709 cm . m.p.
6
200.13 MHz, δ, ppm): 0.84, 1.16, 1.18, 1.32 (each s, 3H, 2-CH ,
169.5-171 °C (from hexane).
3
3-CH ), 1.67 (s, 3H, COCH ), 2.58 (s, 3H, NCH ), 7.61-7.73 (m,
Anal. Calcd. for C
H N O : C 65.89, H 6.22, N 9.60. Found:
3
3
3
24 27 3 5
5H, Ph), 7.90-7.95 (dt, J = 9.0 Hz, J = 2.0 Hz, 2H, Ar), 8.13-
C 66.21, H 6.46, N 9.41.
3
4
8.18 (dt, J = 8.7 Hz, J = 2.0 Hz, 2H, Ar). λ , (ethanol), nm
3
4
max
Dimethyl 1,2,2,3,3-Pentamethyl-7a-(4-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (18m).
(lg ε): 275 (4.25). IR (KBr): ν = 3058, 2995, 2952, 2882, 2802,
1645, 1626, 1592, 1520, 1367, 1345, 1270, 1216, 1150, 1112,
-1
1097, 1011, 983, 866, 846, 772, 698 cm . m.p. 200-202 °C (from
This compound was synthesized by Method B with the 61%
1
yield. NMR H (CDCl , 200.13 MHz, δ, ppm ) 0.81, 1.32 (each s,
hexane).
3
3H, 2-CH , 3-CH ), 1.09, (s, 6H, 2-CH , 3-CH ), 2.47 (s, 3H, N-
Anal. Calcd. for C
H N O : C 68.39, H 6.46, N 9.97. Found:
3
3
3
3
24 27 3 4
CH ), 3.50, 3.91 (each s, 3H, CO CH ), 7.75 (dm, J = 8.7 Hz,
C 68.21, H 6.50, N 9.62.
3
2
3
3
2H, Ar), 8.15 (dm, J = 8.7 Hz, 2H, Ar). λ , (ethanol), nm (lg
3
max
(1,2,2,3,3-Pentamethyl-6-phenyl-7a-(4-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazol-7-yl)(phenyl)methanone (18j).
ε): 271 (4.12). IR (KBr): ν = 3074, 2995, 2960, 1761, 1717,
1651, 1519, 1441, 1345, 1308, 1222, 1064, 864, 849, 794, 777,
-1
This compound was synthesized similarly to 14a; reaction
742 cm . m.p. 126.5-127.5 °C (from hexane).
1
time was 20 h, the yield was 79 %. NMR H ([D ]acetone,
Anal. Calcd. for C
H N O : C 57.27, H 6.01, N 10.02.
6
20 25 3 7
200.13 MHz, δ, ppm): 0.91, 1.21, 1.25, 1.44 (each s, 3H, 2,3-
Found: C 56.91, H 6.26, N 9.87.
(CH ) ), 2.70 (s, 3H, N-CH ), 6.99-7.38 (m, 10H, Ph), 8.05 (dt,
3 2
3
1-(2,2,3,3-Tetramethyl-6-phenyl-7a-(3-nitrophenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazol-7-yl)ethanone (19a).
J = 9.1 Hz, J = 2.1 Hz, 2H, Ar), 8.19 (dt, J = 9.1 Hz, J = 2.1
3
4
3
4
Hz, 2H, Ar). λ , (ethanol), nm (lg ε): 271 (4.28). IR (KBr): ν =
max
3062, 3003, 2945, 2890, 2804, 1615, 1595, 1576, 1518, 1491,
This compound was synthesized similarly to 14a; reaction
time was 20 h, the yield was 65 %. NMR H ([D ]acetone,
-1
1
1423, 1345, 1218, 1159, 988, 892, 865 cm . m.p. 182.5-183.5 °C
6
(from ethyl acetate – hexane mixture). X-ray crystallography
200.13 MHz, δ, ppm): 1.01, 1.08, 1.30, 1.38 (s, 3H, 2-CH , 3-
3
(CCDC 260689): C
H
N O , FW 483.55, monoclinic, C2/c, a
CH ), 1.67 (s, 3H, CO CH ), 7.55-7.69 (m, 6H, Ph), 8.11 (dm, J
29 29
3
4
3 3 3
26.144(3), b 13.2308(14), c 19.256(2) Å, β 129.236(2)°, V
= 8.0 Hz, 1H, Ar), 8.21 (dm, J = 8.0 Hz, 1H, Ar), 8.73 (t, J = 1.8
3 4
3
3
-1
5158.9(10) Å , Z 8, D 1.245 g/cm , µ(Mo-Kα) 0.084 mm , θ
Hz, 1H, Ar). λ , (ethanol), nm (lg ε): 263 (4.17). IR (KBr): ν =
C
max
1.84-23.28°, 10964 reflections collected, 3710 unique, R
=
3433, 3087, 2987, 2873, 1633, 1594, 1527, 1491, 1447, 1368,
int
-1
0.0857, data/parameters 3710/439, Goof 1.1100, R indices (I>
2σ(I)):R1 0.0761 wR2 0.1644; R indices (all data):R1 0.1274,
wR2 0.1845.
1349, 1162, 1108, 1091, 770, 743, 728, 706 cm . m.p. 146-148
°C (from hexane).
Anal. Calcd. for C
H N O : C 67.80, H 6.18, N 10.31.
23 25 3 4
Anal. Calcd. for C
H N O : C 72.03, H 6.04, N 8.69. Found:
Found: C 67.25, H 6.15, N 10.29.
29 29 3 4
C 71.74, H 5.99, N 8.65.
Methyl 2,2,3,3-Tetramethyl-7a-(3-nitrophenyl)-1,2,3,7a-tetrahy-
Methyl 1,2,2,3,3-Pentamethyl-7a-(4-nitrophenyl)--1,2,3,7a-
droimidazo[1,2-b]isoxazole-7-carboxylate(19b).
tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (18k).
This compound was synthesized similarly to 14a; reaction
1
This compound was synthesized similarly to 14a; reaction
time was 20 h, the yield was 80 %. NMR H (CDCl , 200.13
3
1
time was 40 h, the yield was 46 %. NMR H (CDCl , 200.13
MHz, δ, ppm ): 0.95 (s, 6H, 2-CH , 3-CH ), 1.16, 1.22 (each s,
3
3
3
MHz, δ, ppm ): 0.79, 1.02, 1.06, 1.29 (each s, 3H, 2-CH , 3-
3H, 2-CH , 3-CH ), 2.89 (broad s, 1H, N-H), 3.54 (s, 3H,
3
3 3
CH ), 2.45 (s, 3H, N-CH ), 3.51 (s, 3H, CO CH ), 7.55 (s, 1H,
CO CH ), 7.38 (s, 1H, C=CH), 7.38-7.46 (m, 1H, Ar), 8.03-8.06
2 3
3
3
2
3
C=CH), 7.73 (dt, J =9.0 Hz, J =2.1 Hz, 2H, Ar), 8.12 (dt, J =9.0
(m, 2H, Ar), 8.56 (s, 1H, Ar). λ , (ethanol), nm (lg ε): 265
3
4
3
max
Hz, J =2.1 Hz, 2H, Ar). λ , (ethanol), nm (lg ε): 270 (4.17). IR
(4.07). IR (KBr): ν = 3333, 3095, 3001, 2978, 2874, 1711, 1622,
4
max
(KBr): ν = 2987, 2949, 2850, 2804, 1719, 1618, 1522, 1439,
1528, 1434, 1378, 1367, 1351, 1336, 1287, 1159, 1146, 1130,
-1
-1
1367, 1346, 1214, 1196, 1156, 1123, 1032, 986, 862, 853 cm .
1089, 1066, 903, 887, 808 cm . m.p. 130.5-131.5 °C (from
m.p. 108-110 °C (from hexane).
hexane).
Anal. Calcd. for C
H N O : C 59.82, H 6.41, N 11.63.
Anal. Calcd. for C
H N O : C 58.78, H 6.09, N 12.10.
17 21 3 5
18 23 3 5
Found: C 59.69, H 6.60, N 11.57.
Found: C 58.39, H 6.01, N 11.95.
Methyl 1,2,2,3,3-Pentamethyl-6-phenyl-7a-(4-nitrophenyl)-
Dimethyl 2,2,3,3-Tetramethyl-7a-(3-nitrophenyl)-1,2,3,7a-
1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (18l).
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (19c).
This compound was synthesized by Method B with the 76%
This compound was synthesized similarly to 14a; reaction
1
1
yield. NMR H (CDCl , 200.13 MHz, δ, ppm) 0.85, 1.09, 1.12,
time was 20 h, the yield was 76 %. NMR H (CDCl , 200.13
3
3
1.33 (each s, 3H, 2-CH , 3-CH ), 2.57 (s, 3H, NCH ), 3.32 (s,
MHz, δ, ppm): 0.93, 0.97, 1.18, 1.25 (each s, 3H, 2-CH , 3-CH ),
3
3
3
3
3
3H, CO CH ), 7.42-7.47 (m, 3H, Ph), 7.62-7.67 (m, 2H, Ph),
2.78 (broad s, 1H, N-H), 3.53, 3.84 (each s, 3H, CO CH ), 7.43
2
3
2 3
7.83 (d.m, J = 9.0 Hz, 2H, Ar), 8.16 (dm, J = 9.0 Hz, 2H, Ar).
(t, J = 8.0 Hz, 1H, Ar), 8.01 (tm, J = 8.0 Hz, 2H, Ar), 8.54 (s,
3 3
3
3
13
NMR C (CDCl , 50.32 MHz, δ, ppm): 18.8, 20.1, 24.6, 24.9
1H, Ar). λ , (ethanol), nm (lg ε): 265 (4.05). IR (KBr): ν =
3
max

290
S. A. Popov, N. V. Chukanov, G. V. Romanenko, T. V. Rybalova, Y. V. Gatilov and V. A. Reznikov
Vol. 43
3339, 2990, 2958, 1756, 1724, 1651, 1524, 1439, 1371, 1350,
1297, 1202, 1143, 1094, 1044, 897, 789, 774, 758, 738 cm , 725.
Methyl 7a-(4-Methoxyphenyl)-1,2,2,3,3-pentamethyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (20e).
-1
m.p. 118-119 °C (from hexane).
This compound was synthesized similarly to 14a; reaction
Anal. Calcd. for C
H N O : C 56.29, H 5.72, N 10.37.
19 23 3 7
1
time was 10 h, the yield was 50 %. NMR H (CDCl , 200.13
3
Found: C 56.44, H 5.85, N 9.96.
MHz, δ, ppm): 0.83, 0.96, 1.00, 1.24 (each s, 3H, 2-CH , 3-CH ),
3
3
2.38 (s, 3H, N-CH ), 3.47 (s, 3H, CO CH ), 3.69 (s, 3H, OMe),
1-(2,2,3,3-Tetramethyl-6-phenyl-7a-(4-methoxyphenyl)-
1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazol-7-yl)ethanone (20a).
3
2
3
6.75 (d, J =9.0 Hz, 2H, Ar), 7.40 (d, J =9.0 Hz, 2H, Ar), 7.47 (s,
3
3
1H, C=CH). λ , (ethanol), nm (lg ε): 228 (4.11), 270 (3.83). IR
max
This compound was synthesized similarly to 14a; reaction time
was 30 h, the yield was 54 %. NMR H ([D ]acetone, 200.13 MHz,
(KBr): ν = 2997, 2949, 2844, 2802, 1715, 1618, 1512, 1464,
1
6
-1
1439, 1331, 1243, 1194, 1160, 1122, 1034, 982, 847 cm . m.p.
δ, ppm): 1.03, 1.07, 1.27, 1.33 (each s, 3H, 2-CH , 3-CH ), 1.73 (s,
3
3
120-122 °C (from hexane).
3H, COCH ), 3.78 (s, 3H, OCH ), 6.82-6.87 (dm, J = 8.7 Hz, 2H,
3
3
3
Anal. Calcd. for C
H N O : C 65.87, H 7.56, N 8.09. Found:
19 26 2 4
Ar), 7.55-7.65 (m, 5H, Ph), 7.66-7.70 (dm, J = 8.7 Hz, 2H, Ar).
3
C 66.08, H 7.90, N 8.04.
λ
, (ethanol), nm (lg ε): 228 (4.26), 275 (3.89), 282 (3.89). IR
max
Dimethyl 7a-(4-Methoxyphenyl)-1,2,2,3,3-pentamethyl-
1,2,3,7a-tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate
(20f).
(KBr): ν = 3059, 2980, 2933, 2839, 1633, 1609, 1593, 1511, 1489,
1444, 1372, 1335, 1302, 1248, 1171, 1101, 1067, 1031, 839, 770,
704, 611 cm . m.p. 125-126.5 °C (from heptane).
-1
Anal. Calcd. for C
C 73.42, H 7.39, N 7.19.
H N O : C 73.44, H 7.19, N 7.14. Found:
24 28 2 3
This compound was synthesized similarly to 14a; reaction
1
time was 6 h, the yield was 60 %. NMR H ([D ]acetone, 200.13
6
MHz, δ, ppm): 0.89, 1.11, 1.13, 1.30 (each s, 3H, 2-CH , 3-CH ),
Methyl 7a-(4-Methoxyphenyl)-2,2,3,3-tetramethyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (20b).
3
3
2.48 (s, 3H, NCH ), 3.49 (s, 3H, CO Me), 3.78 (s, 3H, OCH ),
3
2
3
3.91(s, 3H, CO Me), 6.85-6.90 (dm, J = 9.0 Hz, 2H, Ar), 7.42-
2
3
This compound was synthesized similarly to 14a; reaction
7.47 (dm, J = 9.0 Hz, 2H, Ar). λ , (ethanol), nm (lg ε): 227
3
max
1
time was 10 h, the yield was 40 %. NMR H (CDCl , 200.13
3
(4.29), 275 (3.91). IR (KBr): ν = 3085, 3006, 2951, 2840, 2794,
MHz, δ, ppm): 0.89, 1.00, 1.13, 1.24 (each s, 3H, 2-CH , 3-CH ),
3
3
1752, 1694, 1648, 1607, 1508, 1469, 1433, 1339, 1315, 1251,
2.64 (broad s, 1H, N-H), 3.52 (s, 3H, CO CH ), 3.70 (s, 3H,
-1
2
3
1210, 1173, 1126, 1110, 1061, 847, 772 cm . m.p. 105.5-107.5
OMe), 6.77 (d, J =9.0 Hz, 2H, Ar), 7.26 (s, 1H, C=CH), 7.58 (d,
3
°C (from hexane).
J =9.0 Hz, 2H, Ar). λ , (ethanol), nm (lg ε): 226 (3.99), 273
3
max
Anal. Calcd. for C
H N O : C 62.36, H 6.98, N 6.93. Found:
21 28 2 6
(3.82). IR (KBr): ν = 3311, 2998, 2960, 1701, 1630, 1619, 1439,
C 62.44, H 7.28, N 6.92.
-1
1344, 1247, 1178, 1163, 1127, 1107, 1084, 828, 766 cm . m.p.
Methyl 2,2,3,3-Tetramethyl-7a-[(E)-2-phenylvinyl]-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-7-carboxylate (21a).
103-104 °C (from hexane).
Anal. Calcd. for C
H N O : C 65.04, H 7.28, N 8.43. Found:
18 24 2 4
C 65.18, H 7.52, N 8.41.
This compound was synthesized similarly to 14a; reaction
1
time was 16 h, the yield was 33 %. NMR H (CDCl , 200.13
3
Dimethyl 7a-(4-Methoxyphenyl)-2,2,3,3-tetramethyl-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (20c).
MHz, δ, ppm): 1.07 (s, 6H, 2-CH , 3-CH ), 1.10, 1.29 (each s,
3
3
3H, 2-CH , 3-CH ), 2.60 (broad s, 1H, N-H), 3.66 (s, 3H,
3
3
This compound was synthesized similarly to 14a; reaction
time was 10 h, the yield was 58 %. NMR H (CDCl , 200.13
MHz, δ, ppm): 0.82, 0.96, 1.11, 1.20 (each s, 3H, 2-CH , 3-CH ),
2.68 (broad s, 1H, N-H), 3.46, 3.63 (each s, 3H, CO CH ), 3.74
CO CH ), 6.67, 6.80 (each d, J =15.8 Hz, 2H, CH=CH-Ph),
2
3
3
1
3
7.15-7.37 (m, 5H, Ph). λ , (ethanol), nm (lg ε): 256 (4.32). IR
max
3
3
(KBr): ν = 3309, 3079, 3055, 3022, 2978, 2954, 1687, 1648,
-1
2
3
1629, 1477, 1441, 1332, 1199, 1160, 1132, 1060, 972 cm . m.p.
(s, 3H, OMe), 6.71 (d, J =9.0 Hz, 2H, Ar), 7.47 (d, J =9.0 Hz,
3
3
127-129 °C (from hexane).
2H, Ar). λ , (ethanol), nm (lg ε): 225 (4.09), 275 (3.78). IR
max
Anal. Calcd. for C
H N O : C 69.49, H 7.37, N 8.53. Found:
19 24 2 3
(KBr): ν = 3321, 3011, 2973, 2955, 2833, 1748, 1727, 1651,
C 69.62, H 7.60, N 8.40.
1609, 1510, 1439, 1343, 1312, 1248, 1213, 1177, 1134, 1076,
Dimethyl 2,2,3,3-Tetramethyl-7a-[(E)-2-phenylvinyl]-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-6,7-dicarboxylate (21b)
-1
1030, 840 cm . m.p. 114-115 °C (from hexane).
Anal. Calcd. for C
H N O : C 61.53, H 6.71, N 7.18. Found:
20 26 2 6
C 61.50, H 7.30, N 7.07.
This compound was synthesized similarly to 14a; reaction time
1
was 10 h, the yield was 40 %. NMR H (CDCl , 200.13 MHz, δ,
3
1,2,2,3,3-Pentamethyl-6-phenyl-7a-(4-methoxyphenyl)-1,2,3,7a-
tetrahydroimidazo[1,2-b]isoxazole-7-carbaldehyde (20d).
ppm): 1.04, 1.06, 1.11, 1.28 (each s, 3H, 2-CH , 3-CH ), 2.64
3
3
(broad s, 1H, N-H), 3.65, 3.79 (each s, 3H, CO CH ), 6.58, 6.81
2
3
This compound was synthesized by Method B with the 53%
(each d, J =15.8 Hz, 2H, CH=CH-Ph), 7.13-7.33 (m, 5H, Ph).
3
1
yield. NMR H (CDCl , 200.13 MHz, δ, ppm): 0.97, 1.02, 1.11,
λ
, (ethanol), nm (lg ε): 256 (4.26). IR (KBr): ν = 3321, 3060,
3
max
1.35 (each s, 3H, 2-CH , 3-CH ), 2.52 (s, 3H, N-CH ), 3.76 (s,
3006, 2978, 2952, 1754, 1708, 1645, 1439, 1343, 1315, 1211,
3
3
3
3
-1
3H, OMe), 6.80-6.85 (d.m, J = 8.9 Hz, 2H, Ar), 7.50-7.54 (d.m,
1176, 1139, 1072, 987, 803 cm . m.p. 138-139 °C (from hexane).
3
J = 8.9 Hz, 2H, Ar), 7.50-7.54 (m, 3H, Ph), 7.63-7.68 (m, 2H,
Anal. Calcd. for C
H N O : C 65.27, H 6.78, N 7.25. Found:
21 26 2 5
Ph), 9.53 (s, 1H, CHO). λ , (ethanol), nm (lg ε): 231 (4.28). IR
C 65.00, H 7.17, N 7.28.
max
(KBr): ν = 3058, 2938, 2833, 2803, 2765, 1652, 1619, 1508,
3-[(2,4,4,5,5-Pentamethyl-4,5-dihydro-1H-imidazol-1-yl)oxy]-
propanenitrile (22).
1462, 1445, 1342, 1243, 1169, 1108, 1040, 984, 845, 776, 704
-1
cm . m.p. 147-147.5 °C (from hexane).
Anal. Calcd. for C
H N O : C 73.44, H 7.19, N 7.14. Found:
Solution of 0.326 g (2.09 mmol) of 3a and 0.80 ml (12 mmol)
24 28 2 3
C 72.90, H 7.32, N 6.92.
acrylonitrile in 5 ml CHCl was refluxed for 6 h. Then the solvent
3

Mar-Apr 2006 1,3-Dipolar Cycloaddition Reaction of 4,5-Dihydro-1H-imidazole 3-oxides with Alkynes
291
Comprehensive Organic Synthesis. (Ed.: B. M. Trost and I. Fleming),
Oxford, Pergamon Press. 4.9 (1991), 1069-1109.
[8] L. Fisera, U. A. R. Altimari, et al. in Cycloaddition Reactions
in Carbohydrate Chemistry. (Ed.: R. M. Giuliano), Washington, DC, Am.
Chem. Soc. (1992), 158-171.
[9] L. Raimondi, Gazz. Chim. Ital., 4, 167 (1997).
[10] K. V. Gothelf and K. A. Jorgensen, Chem. Rev., 2, 863-909
(1998).
[11] K. V. Gothelf, and K. A. Jorgensen, J. Chem. Soc., Chem.
Commun., 16, 1449-1458 (2000).
[12] R. C. F. Jones, J. N. Martin in Nitrones (Ed.: A. Padwa), John
Wiley & Sons, Ltd (2002), 1-81.
was removed, and 22 was isolated by flash chromatography on
alumina with ether as eluent. The yield was 0.081 g (19 %). NMR
1
H (CDCl , 200.13 MHz, δ, ppm): 1.01, 1.06 (each s, 6H, 2-CH ,
3
3
3-CH ), 1.92 (s, 3H, 2-CH ), 2.60 (t, J =6.0 Hz, 2H, CH CN),
3.97 (t, J =6.0 Hz, 2H, CH CN). NMR C (CDCl , 50.32 MHz,
3
3
3
2
13
3
2
3
δ, ppm): 14.3 (2-CH ), 17.5 (CH -CN), 23.2 (2-CH , 3-CH ),
3
2
3
3
66.6 (C-4), 70.1 (O-CH ), 71.5 (C-5), 117.2 (-CN), 164.0 (C-2).
2
λ
, (ethanol), nm (lg ε): 228 (3.72). IR (KBr): ν = 2988, 2971,
max
2931, 2904, 2257, 1640, 1468, 1446, 1385, 1368, 1312, 1162,
-1
1079, 1053, 760, 702, 652 cm . m.p. 81-83 °C (from ethyl
acetate – hexane mixture).
[13] F. Saczewski, T. Debowski, M. Gdaniec, and Z. Gdaniec, J.
Org. Chem., 61, 5425-5429 (1996).
[14] S. P. Ashburn, and R. M. Coates, J. Org. Chem., 17, 3127-
3133 (1984).
Anal. Calcd. for C
H N O: C 63.13, H 9.15, N 20.08.
11 19 3
Found: C 63.19, H 9.38, N 19.98.
Dimethyl 1-Hydroxy-2,2,3,3-tetramethyl-1,2,3,7a-tetrahydroimi-
[15] S.P. Ashburn, and R.M. Coates, J. Org. Chem., , 18, 3076-
3081 (1985).
[16] T. Hisano, K. Harano, T. Matsuoka, S. Watanabe, and T.
Matsuzaki, Chem. Pharm. Bull., 4, 907-911 (1989).
[17] S. Takahashi, and H. Kano, Tetrahedron Lett., 25, 1687-1691
(1963).
[18] S. Takahashi, and H. Kano, J. Org. Chem., 4, 1118-1122
(1965).
[19] R. C. F. Jones, J. N. Martin, P. Smith, T. Gelbrich, M. E. Light,
and M. B. Hursthouse, Chem. Commun., 19, 1949-1951 (2000).
[20] R. C. F. Jones, J. N. Martin, and P. Smith, J. Heterocyclic
Chem., 3, 481-486 (2000).
dazo[1,2-b]isoxazole-6,7-dicarboxylate (26).
1
This compound was identified by NMR H of reaction mixture
formed in the reaction of imidazoline 2c with DMAD in CHCl
at –10 °C. Warming to 25 °C of this reaction mixture during 3 h
3
resulted in almost quantitative formation of 13c (cf. [23]). NMR
1
H (CDCl , 200.13 MHz, δ, ppm): 1.25 (s, 12H, 4,4,5,5-(CH ) ),
3
3 4
3.58, 3.71 (each s, 1H, CO CH ), 5.38 (s, 1H, C-H), 6.11 (broad
2
3
s, 1H, N-OH).
Acknowledgments.
The work was supported by BRHE (NO-008-X1) grant and
RAS and SB RAS integration programs.
[21] R. C. F. Jones, J. N. Martin, and P. Smith, Synlett., 7, 967-970
(2000).
[22] R. Huisgen, H. Seidl, and I. Brüning, Chem. Ber., 102, 1102-
1116 (1969).
REFERENCES AND NOTES
[23] V. A. Reznikov, G. I. Roshchupkina, D. G. Mazhukin, P. A.
Petrov, S. A. Popov, S. V. Fokin, G. V. Romanenko, T. V. Rybalova, Y. V.
Gatilov, Y. G. Shvedenkov, I. G. Irtegova, L. A. Shundrin, V. I.
Ovcharenko, Eur. J. Org. Chem., 749-765 (2004).
[24] S. A. Popov, R. V. Andreev, G. V. Romanenko, V. I.
Ovcharenko, V. A. Reznikov, Journal of Molecular Structure, 697 (1-3),
49 (2004).
[25] M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M.
S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J. Su,
T. L. Windus, M. Dupuis, J. A. Montgomery, J. Comput. Chem., 11,
1347-1363 (1993).
†
The details of the influence of tautomeric equilibrium state on
the reaction path with dipolarophiles see in our next paper.
[1] A. Padwa, Angew. Chem., 5, 131 (1976).
[2] R. A. Firestone, Tetrahedron,, 33, 3009 (1977).
[3] J. J. Tufariello in 1,3-Dipolar Cycloaddition Chemistry (Ed.:
A. Padwa), Wiley-Interscience, New York, (1984), chapter 9, 83-167.
[4] R. Huisgen in Steric Course and Mechanism of 1,3-Dipolar
Cycloadditions. Advances in Cycloaddition. (Ed.: D. P. Curran),
Greenwich, CT, Jai Press Inc. Chapter 1 (1988).
[5] A. Padwa and A. M. Schoffstall in Intramolecular 1,3-Dipolar
Cycloaddition Chemistry. Advances in Cycloaddition. (Ed.: D. P.
Curran), Greenwich, CT, Jai Press Inc. chapter 2 (1990).
[6] P. A. Wade in Intramolecular 1,3-Dipolar Cycloadditions.
Comprehensive Organic Synthesis. (Ed.: B. M. Trost and I. Fleming),
Oxford, Pergamon Press. 4.10 (1991), 1111-1168.
[26] F. E. Ullman, J. H. Osiecki, D. G. B. Boocock and R. Darcy, J.
Am. Chem. Soc., 20, 7049-7059 (1972).
[27] P. A. Petrov, S. V. Fokin, G. V. Romanenko, Y. G.
Shvedenkov, V. A. Reznikov and V. I. Ovcharenko, Mendeleev Commun.,
179-181 (2001).
[28] R. Weiss, N. Kraut, F. Hampel, J. Organomet. Chem. 2001,
617, 473 - 482.
[7] A. Padwa Intramolecular 1,3-Dipolar Cycloadditions.