Reactions of cyclic α-methoxy nitrones with nucleophilic reagents

Article abstract of DOI:10.1023/A:1009528126552

Reactions of cyclic α-methoxy nitrones, which are derivatives of imidazole or dihydroimidazole N-oxides, with amines, KOH, or KSH result in the replacement of the MeO group to form cyclic α-amino nitrones, hydroxamic acids, or thiohydroxamic acids, respectively. Analogous reactions occur with C-nucleophiles.

Full text of DOI:10.1023/A:1009528126552

Russian Chemical Bulletin, International Edition, Vol. 49, No. 12, December, 2000
2031
Reactions of cyclic α-methoxy nitrones with nucleophilic reagents
I. A. Grigor´ev, S. M. Bakunova,« and I. A. Kirilyuk
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752. E-mail: sveta@nioch.nsc.ru
Reactions of cyclic α-methoxy nitrones, which are derivatives of imidazole or
dihydroimidazole N-oxides, with amines, KOH, or KSH result in the replacement of the MeO
group to form cyclic α-amino nitrones, hydroxamic acids, or thiohydroxamic acids, respec-
tively. Analogous reactions occur with Ñ-nucleophiles.
Key words: α-alkoxy nitrones (imidate N-oxides), nucleophilic substitution, cyclic α-amino
nitrones, cyclic hydroxamic acids, cyclic thiohydroxamic acids, 2H-imidazole N-oxides,
4H-imidazole 3-oxides.
Scheme 1
α-Alkoxy nitrones (imidate N-oxides) are difficultly
accessible and generally unstable compounds. These com-
pounds attract interest because of their high reactivity in
nucleophilic substitution and 1,3-dipolar cycloaddi-
tion.1—4 Recently,5 we have reported a new procedure
for the synthesis of N-oxides of 1,5-dihydro-2H-imida-
zole, 2Í-imidazole, and 4Í-imidazole containing the
α-methoxy nitrone fragment in the ring. In the present
work, we studied the reactions of these compounds with
N-, O-, S-, and Ñ-nucleophiles.
Ph
Ph
N
N
RNH2
RHN
MeO
N
O
N
O
1
5a,b
R = H (a), Me (b)
Previously,2,6 we have demonstrated that the reac-
tions of 4-methoxy-1,5-dihydro-2H-imidazole 3-oxides
and acyclic α-methoxy nitrones with amines or ammo-
nia resulted in the replacement of the methoxy group by
the amino group to form the corresponding α-amino
nitrones. Cyclic α-methoxy nitrones 1 and 2 and com-
pound 3, which (according to the NMR spectral data)
exists in solutions in equilibrium with α-methoxy nitrone
4,5 behave analogously (Scheme 1). α-Amino nitrones
5à,b, 6a,b, and 7a,b were isolated in the free state as
crystalline yellow (5 and 7) or red (6) compounds. The
Ph
Ph
N
N
RR´NH
OMe
NRR´
N
N
O
O
6a,b
2
R = H, R´ = Me (a); R + R´ = (CH2)5 (b)
IR spectra of these compounds have broad intense bands
O
O
Ph
Ph
–1
at 1680—1650 cm
characteristic of Ñ=N stretching
N
N
vibrations of α-amino nitrones.2 Previously, it has
been demonstrated6 that the contribution of the
hydroxylamino-imine tautomeric form in the case of
α-amino nitrones is insignificant. Apparently, the chemi-
cal shifts of the carbon atoms of the N—C=N→O
fragment in the 13Ñ NMR spectra of amino nitrone 6b
(δ 146.9) and compounds 5a,b, 6a, and 7a,b capable of
undergoing tautomerization (δ 142—151) indicate that
these compounds also exist primarily as α-amino nitrones.
Unlike the reactions of acyclic α-methoxy nitrones
and 4,5-dihydrooxazole N-oxides,3,5,7 the reactions of
compounds 1, 2, and 3 and 1,2,2,5,5-pentamethyl-4-
methoxy-2,5-dihydroimidazole 3-oxide (8) with a solu-
tion of KOH in aqueous ethanol resulted in the forma-
MeO
MeO
–MeOH
MeOH
RNH2
MeO
N
N
OH
O
3
4
O
Ph
N
RHN
N
O
7a,b
R = H (a), Me (b)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2066—2071, December, 2000.
1066-5285/00/4912-2031 $25.00 © 2000 Plenum Publishing Corporation

2032
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Grigor´ev et al.
Scheme 2
Ph
Ph
N
N
–
HX
1
HX
X
N
O
N
OH
9a,b
OCD3
N
OH
Ph
Ph
D
Ph
H
N
N
CD3OD
–
HX
2
XH
XD
XH
H2O
N
O
N
O
N
O
OCD3
N
OH
Ph
Ph
H
Ph
D
N
N
X
X
X
N
N
N
OH
OH
OD
10a,b
13a,b
14a,b
O
O
Ph
Ph
N
N
–
HX
3
N
N
O
X
HX
OH
11a,b
O
OH
X
MeO
O
HX
N
N
N
–
HX
N
N
N
12a,b
8
X = O (a), S (b)
tion of cyclic hydroxamic acids 9a—12à rather than in
the hydrolytic cleavage of the Ñ=N bond (Scheme 2).
The reactions of compounds 1, 2, 3, and 8 with KSH
gave analogous results, viz., afforded thiohydroxamic
acids 9b—12b, respectively. Previously, compounds 12a,b
have been prepared from 4-cyano-1,2,2,5,5-pentamethyl-
2,5-dihydroimidazole 3-oxide.6,8
Interestingly, the reactions of 4Í-imidazole 2 with
KOH or KSH were accompanied by the covalent hydra-
tion of the Ph—C=N bond. Analysis of the NMR
spectra of the resulting 1,4-dihydroxy-5,5-dimethyl-4-
phenylimidazolidin-2-one (10a) and -imidazolidine-2-
thione (10b) demonstrated that these compounds, like
4-hydroxy-1-methoxy-5,5-dimethyl-4-phenylimidazoli-
din-2-one described previously,5 reversibly eliminate the
water molecule in CD3OD solutions. The contents of
1-hydroxy-5,5-dimethyl-4-phenyl-2,5-dihydroimidazol-
2(1Í)-one (13a) and 1-hydroxy-5,5-dimethyl-4-phenyl-
2,5-dihydroimidazole-2(1Í)-thione (13b) in CD3OD
were ∼5%. Storage of these solutions resulted in the
replacement of the hydroxy group at position 4 of the
heterocycle by the ÎCD3 group to form compounds
14à,b, respectively. The degree of conversion at 25 °Ñ
reached ∼60% in 20 h.
For compounds 9—14, tautomeric equilibrium
(rapid within the NMR time scale) between α-hydr-
oxy(α-mercapto) nitrones and hydroxamic (thiohydroxa-
mic) acids can occur.6 The chemical shifts of the carbo-
nyl carbon atoms in the spectra of hydroxamic acids 9a,
10a, and 11a (δ 158.49, 163.52, and 162.05, respec-
tively) are very similar to those of the corresponding
atoms in the spectra of fixed models, which cannot

Reactions of cyclic α-methoxy nitrones
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000 2033
undergo tautomerization, viz., of methyl esters of the
above-mentioned hydroxamic acids (δ 159.60, 164.43,
and 163.91, respectively).5 The signals for the carbon
atoms of the —C=N→O group in the spectra of methoxy
nitrones 1 and 2 are observed at δ 148.8 and 152.78,
respectively. Therefore, the contribution of the α-hydr-
oxy nitrone tautomeric form is insignificant, as in the
case of 3-hydroxy-2,2,5,5-tetramethylimidazolidin-
4-ones.6
For compounds 9b, 10b, 11b, and 14b, the tauto-
meric equilibrium is shifted to α-mercapto nitrone to a
somewhat greater extent than in the case of compound
12b.6 In the 13Ñ NMR spectra of methanolic solutions
of these compounds, the signals for the carbon atoms of
the —C=N→O group are observed at δ 170.1, 183.4,
179.5, and 183.5, respectively, whereas the signals of the
C=S groups of N-methoxy thioamides are observed at
δ 190—195 and 137—148 for thiones and mercapto
nitrones, respectively.6 Therefore, the contribution of
the tautomeric form of α-mercapto nitrone in CD3OD
can reach 20—40%.
that these reactions will result in the replacement of the
methoxy group to form either α-(β-hydroxyvinyl) nitrones
or β-hydroxy nitrones (N-hydroxy enamino ketones). It
is known that11 hydroxy enamino ketones exist as a
mixture of three tautomeric forms two of which give one
set of signals in the NMR spectra due to the rapid
intrachelate tautomerism.
We found that compound 1 readily entered into
condensation with acetophenone in the presence of
sodium hydride to form stable compound 18 existing as
tautomeric forms A—C (Scheme 4). Colorless crystals
(18A) slowly precipitated upon storage of yellow liquid
samples of compound 18 or its solutions in diethyl ether.
A yellow solution was again obtained after dissolution of
these crystals. The UV spectrum of compound 18 in
ethanol has a long-wavelength maximum at 390 nm,
whereas the UV spectrum of a crystalline sample of 18À
in ÊÂr has only a shoulder at 285 nm (in the region
corresponding to absorption of 2Í-imidazole 1-oxides12)
and shows no absorption in the longer-wavelength re-
1
gion. The H NMR spectra of compound 18 have two
The reactions of cyclic α-alkoxy nitrones, which are
dihydrooxazole or dihydrooxazine derivatives, with
Grignard reagents are successfully used in the prepara-
tion of nitroxyl radicals, which are employed as spin
probes.9 The behavior of acyclic and cyclic α-methoxy
nitrones under the action of organometallic compounds
has not been studied previously.
The reactions of compounds 1 and 2 with an excess
of methylmagnesium iodide followed by oxidation af-
forded the same nitroxyl radical, viz., 2,2,5,5-tetramethyl-
4-phenyl-2,5-dihydroimidazole-1-oxyl (15), in ∼30%
yield (Scheme 3). Apparently, the reactions proceeded
through the formation of methylnitrones 16 and 17,
respectively. It is known10 that the addition of organo-
metallic compounds to 2,4,4-trimethyl-5-phenyl-4Í-imi-
dazole 3-oxide (17) occurs predominantly at position 2
of the heterocycle.
sets of signals. Their ratios in (CD3)2CO and (CD3)2SO
are 2 : 1 and 3 : 2, respectively. The spectra of the major
component have a singlet for two methylene protons at
δ 4.59 and a singlet for the protons of the methyl groups
at δ 1.49 (in the region characteristic of 2Í-imidazole
1-oxides) along with a multiplet for the protons of the
phenyl groups. The spectra of the minor component
have a signal for the methine proton at δ 5.81. The
signals for the protons of the geminal methyl groups are
shifted downfield (δ 1.60) like in the spectra of dimethyl
2-(2,2-dimethyl-4-phenyl-1,5-dihydro-2Í-imidazol-5-
ylidene)-3-oxosuccinate,13 hydroxamic acid 9à, and its
methyl ester.5 From these data it follows that compound
18 is a mixture of tautomers, viz., 5-benzoylmethyl-
2,2-dimethyl-4-phenyl-2Í-imidazole 1-oxide (18À),
4-(2-hydroxy-2-phenylvinyl)-2,2-dimethyl-5-phenyl-2Í-
imidazole 1-oxide (18Â), and 5-benzoylmethylidene-1-
hydroxy-2,2-dimethyl-4-phenyl-2,5-dihydro-1Í-imid-
azole (18Ñ).
The reactions of α-alkoxy nitrones with enolate an-
ions have not been studied previously. One would expect
Scheme 3
Scheme 4
Ph
Ph
Ph
N
N
N
MeÌgI
MeÌgI
1
MeCOPh
1
N
O
N
N
NaH, THF
OH
Ph
O
O
MeÌgI
16
Ph
18A
MnO2
Ph
Ph
Ph
N
N
N
N
MeÌgI
2
N
N
O
N
N
•
Ph
OH
O
O
Ph
O
OH
15
17
18B
18C

2034
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Grigor´ev et al.
spectra was made based on analysis of intensities, on the spectra
measured in the J-modulation mode, and using the data re-
ported previously.5,6 Column chromatography was carried out
on silica gel Kieselgel 60 (Merck).
Therefore, the behavior of cyclic α-methoxy nitrones
in reactions with N-, O-, S-, and Ñ-nucleophiles is
analogous to the behavior of esters, i.e., they give prod-
ucts of replacement of the methoxy group by the amino,
hydroxy, or methoxy groups, enter into the Claisen
condensation, and can add Grignard reagents at the
carbon atom of the nitrone group.
Synthesis of amino nitrones 5à,b—7a,b. A saturated solution
of amine in MeOH (10 mL) was added to a solution of
α-methoxy nitrones 1—3 (2 mmol) in MeOH (2 mL). After the
starting compound was consumed (TLC control), the solvent
was evaporated in vacuo. Analogously, the addition of piperi-
dine to a methanolic solution of compound 2 afforded 4,4-di-
methyl-5-phenyl-2-piperidino-4Í-imidazole 3-oxide (6b).
5-Amino-2,2-dimethyl-4-phenyl-2Í-imidazole 1-oxide (5à) and
5-amino-2,2-dimethyl-4-phenyl-2Í-imidazole 1,3-dioxide (7à)
were recrystallized from acetone. 5-Methylamino-2,2-dimethyl-
4-phenyl-2Í-imidazole 1-oxide (5b) was recrystallized from
ethyl acetate. 5-Methylamino-2,2-dimethyl-4-phenyl-2Í-imid-
azole 1,3-dioxide (7b) was recrystallized from a 2 : 1 ethyl
acetate—hexane mixture. 2-Methylamino-4,4-dimethyl-5-phe-
nyl-4Í-imidazole 3-oxide (6à) and 4,4-dimethyl-5-phenyl-2-
Experimental
The IR spectra were recorded on Specord M-80 and Bruker
IFS-66 spectrometers in KBr pellets (the concentration was
0.25%; the pellet thickness was 1 mm). The UV spectra were
measured on a Specord Ì-40 spectrometer in ethanol. The
spectral data are given in Table 1. The 1H and 13Ñ NMR
spectra were recorded on a Bruker AC-200 spectrometer for
1–5% solutions using the signal of the solvent as the standard
(Table 2). The assignment of the signals in the 13Ñ NMR
Table 1. Characteristics of the compounds synthesized
Com-
pound
Yield
(%)
M.p./°Ñ
Found
Calculated
Molecular
formula
IR spectrum
(in KBr),
UV spectrum
(EtOH),
(%)
–1
ν/cm
λ
max/nm (log ε)
Ñ
Í
N
5a
5b
6a
90
85
90
185—187
143—145
175—179
62.2
62.3
66.3
66.4
63.6
63.7
6.6
6.6
7.1
6.9
7.0
7.1
19.6
19.8
19.4
19.4
18.5
18.6
C11H13N3O•0.5 H2O
C12H15N3O
1670 (N—C=N);
1550 (C=N)
1675 (N—C=N);
1560 (C=N)
218 (4.54);
242 (4.52)
248 (4.23);
360 (3.70)
245 (3.82);
273 (3.92);
409 (3.34)
271 (4.29);
510 (3.69)
250 (4.11);
293 (3.58);
391 (3.23)
227 (3.54);
252 (4.04);
285 (4.00);
398 (3.26)
262 (4.18)
C12H15N3O•0.5 H2O
1670 (N—C=N)
6b
7a
40
85
147—149
157—160
68.6
68.5
60.4
60.3
7.6
7.9
6.3
5.9
15.1
15.0
18.8
19.2
C16H21N3O•0.5 H2O
C11H13N3O2
1630 (N—C=N)
1670 (N—C=N);
1550 (C=N)
7b
70
151—153
61.7
61.8
6.5
6.4
18.0
18.0
C12H15N3O2
1660 (N—C=N);
1530 (C=N)
9a
95
65
40
90
81—84
114—117
127—129
84—87
64.5
64.7
59.6
60.0
55.4
55.0
53.4
53.4
5.9
5.9
5.4
5.5
6.8
6.7
6.0
6.1
13.6
13.7
12.5
12.7
11.7
11.7
C11H12N2O2
C11H12N2OS
1725 (C=O);
1590 (C=N)
1610 (C=N)
9b
242 (4.00);
272 (3.93)
263.2 (2.96)
10a
10ba
C11H14N2O3•H2O
1722 (C=O);
3381 (OH)
3580, 3480 (OH)
11.3 C11H14N2O2S•0.5 H2O
11.3
250 (KBr);
251 (4.20);
295 shb (3.94)
231 (4.18);
285 (4.01)
334.6 (4.23);
334.1 (4.10)c
237 (KBr);
285 shb (KBr);
390 (3.66);
276 (4.23);
241 (4.32)
11a
11b
18
90
85
65
143—146
137—140
92—95
60.4
60.0
55.6
55.9
75.0
74.5
5.7
5.5
5.1
5.1
6.1
5.9
12.7
12.7
11.6
11.9
9.0
C11H12N2O3
C11H12N2O2S
C19H18N2O2
1717(C=O);
1550 (C=N)
1550 (C=N)
1691 (C=O);
9.2
1594, 1596 (C=N);
1730d, 1695 (C=O)d;
1606d, 1573 (C=N)d
a Found (%): S, 12.6. Calculated (%): S, 12.9.
b Shoulder.
c Heptane as the solvent.
d In CCl4.

ì → m
Reactions of cyclic α-methoxy nitrones
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000 2035
Table 2. Data of 1H and 13C NMR spectroscopy of the compounds synthesized
Com-
pound
Solvent
δ (J/Hz)
1Í
13C
5a
5b
6a
6b
CD3OD
CD3OD
CDCl3
1.61 (s, 6 Í, gem-Me); 7.63, 7.86 (both m,
3 Í and 2 Í, N=C—Ph)
23.81 (gem-Me); 94.40 (ÑMe2); 143.06
(NH2—C=N); 161.82 (Ph—C=N); Ph: 131.81 (Ci);
128.82 (Co); 130.21 (Cm); 132.90 (Cp)
23.91 (gem-Me); 29.93 (N—Me); 94.70 (ÑMe2);
142.86 (NH2—C=N); 165.52 (Ph—C=N); Ph:
132.31 (Ci); 129.02 (Co); 130.11 (Cm); 132.53 (Cp)
21.91 (gem-Me); 25.79 (N—Me); 75.07 (ÑMe2);
150.81 (N—C=N); 182.08 (Ph—C=N); Ph: 129.98
(Ci); 127.68 (Co); 128.86 (Cm); 132.24 (Cp)
1.60, 1.61 (both s, 3 H each, gem-Me); 3.18 (c,
3 H, NH—Me); 7.61, 7.70 (both m, 3 Í and
2 Í, N=C—Ph)
1.64 (s, 6 Í, gem-Me); 3.19 (c, 3 H, NH—Me);
7.48, 7.97 (both m, 3 Í and 2 Í, N=C—Ph)
(CD3)2CO
(1H);
(CD3)2SO
(13C)
1.55 (s, 6 Í, gem-Me); 1.58; 3.93 (both m, 6 Í
and 4 Í, piperidyl); 7.50, 8.03 (both m, 3 Í
and 2 Í, N=C—Ph)
23.2 (gem-Me); 24.0; 25.6; 46.2 (piperidyl); 76.6
(ÑMe2); 146.9 (N—C=N); 177.9 (Ph—C=N); Ph:
129.7 (Ci); 127.4 (Co); 129.1 (Cm); 132.0 (Cp)
7a
CD3OD
1.79 (s, 6 Í, gem-Me); 7.61, 7.96 (both m, 3 Í
and 2 Í, N=C—Ph)
23.81 (gem-Me); 94.26 (ÑMe2); 144.87 (N—C=N);
132.95 (Ph—C=N); Ph: 124.91 (Ci); 132.44
(Co); 129.60 (Cm); 130.00 (Cp)
7b
CD3OD
CD3OD
CD3OD
CD3OD
CD3OD
CD3OD
CD3OD
1.79 (s, 6 Í, gem-Me); 3.13 (s, 3 H, NH—Me);
7.61, 7.71 (both m, 3 Í and 2 Í, N=C—Ph)
23.95 (gem-Me); 30.99 (N—Me); 94.43 (ÑMe2);
144.49 (N—C=N); 134.38 (Ph—C=N); Ph: 125.01
(Ci); 130.07 (Co); 130.44 (Cm); 132.37 (Cp)
24.30 (gem-Me); 84.43 (ÑMe2); 158.49 (C=O);
163.12 (P—C=N); Ph: 132.01 (Ci); 128.91 (Co);
129.64 (Cm); 132.00 (Cp)
23.70 (gem-Me); 93.50 (ÑMe2); 170.12 (C=S);
165.51 (Ph—C=N); Ph: 133.11 (Ci); 128.98 (Co);
130.40 (Cm); 132.32 (Cp)
9a
1.57 (s, 6 Í, gem-Me); 7.53, 8.34 (both m, 3 Í
and 2 Í, N=C—Ph)
9b
1.63 (s, 6 Í, gem-Me); 7.52, 8.34 (both m, 3 Í
and 2 Í, N=C—Ph)
10a
10b
11a
11b
0.72, 1.43 (both s, 3 H each, gem-Me); 7.40, 7.56 18.71, 20.87 (gem-Me); 69.98 (ÑMe2); 93.51
(both m, 3 Í and 2 Í, Ph)
(Ph—C—N); 163.52 (C=O); Ph: 141.05 (Ci);
127.71 (Co); 128.11 (Cm); 129.82 (Cp)
0.72, 1.47 (both s, 3 H each, gem-Me); 7.43, 7.55 18.15, 21.32 (gem-Me); 72.94 (ÑMe2); 91.52
(both m, 3 Í and 2 Í, Ph)
(Ph—C—N); 183.42 (C=S); Ph: 140.13 (Ci); 127.44
(Co); 128.14 (Cm); 129.52 (Cp)
23.84 (gem-Me); 99.37 (ÑMe2); 140.45 (Ph—C=N);
162.05 (C=O); Ph: 127.15 (Ci); 128.73 (Co);
129.27 (Cm); 132.17 (Cp)
23.40 (gem-Me); 93.84 (ÑMe2); 138.76 (Ph—C=N);
179.48 (C=S); Ph: 126.78 (Ci); 128.66 (Co);
131.07 (Cm); 131.68 (Cp)
1.73 (s, 6 Í, gem-Me); 7.53, 8.67 (both m, 3 Í
and 2 Í, N=C—Ph)
1.78 (s, 6 Í, gem-Me); 7.50, 8.24 (both m, 3 Í
and 2 Í, N=C—Ph)
13a
13b
CD3OD
CD3OD
1.68 (s, 6 Í, gem-Me)
1.70 (s, 6 Í, gem-Me); 7.60, 8.20 (both m, 3 Í
and 2 Í, N=C—Ph)
23.91 (gem-Me)
22.77 (gem-Me); 77.01 (ÑMe2)
14a
14b
18A
CD3OD
CD3OD
0.69, 1.42 (both s, 3 H each, gem-Me);
7.47 (m, 5 Í, Ph)
18.37, 20.74 (gem-Me); 70.8 (ÑMe2); 93.50
(Ph—C—N); 163.82 (C=O); Ph: 137.54 (Ci);
128.46 (Co); 129.51 (Cm); 129.82 (Cp)
17.78, 21.05 (gem-Me); 74.01 (ÑMe2); 95.64
(Ph—C—N); 183.50 (C=S); Ph: 136.48 (Ci); 128.21
(Co); 129.54 (Cm); 130.00 (Cp)
0.67, 1.44 (both s, 3 H each, gem-Me);
7.46 (m, 5 Í, Ph)
(CD3)2SO
(CD3)2SO
1.49 (s, 6 Í, gem-Me); 4.59 (s, 2 Í, ÑÍ2);
7.41—7.99 (m, 10 Í, 2 Ph)
1.60 (s, 6 Í, gem-Me); 5.81 (s, Í, ÑÍ);
7.41—7.99 (m, 10 Í, 2 Ph)
18B
(18Ñ)
piperidino-4Í-imidazole 3-oxide (6b) were isolated by chroma-
tography on SiO2 with the use of the 10 : 1 CHCl3—MeOH
mixture as the eluent and recrystallized from hexane.
Synthesis of hydroxamic (9a—12a) and thiohydroxamic ac-
ids (9b—12b). A solution of ÊÎÍ (4 mmol) in aqueous metha-
nol (5 mL) or a solution of ÊSH (5 mmol) in MeOH (2 mL)
was added to a solution of α-methoxy nitrone (1—3 or 8;
2 mmol) in MeOH (2 mL). After the starting compound was
consumed (TLC control, Silufol UV-254, CHCl3—MeOH,
50 : 1), the solvent was evaporated in vacuo. Water (10 mL) was
added to the residue. The resulting solution was washed with
tert-butyl methyl ether and acidified with 10% HCl to ðÍ 5. The
product was extracted with ÑÍÑl3. The extract was dried with
Na2SO4, the solvent was evaporated, and the residue was recrys-
tallized. 1-Hydroxy-2,2-dimethyl-4-phenyl-1,2-dihydroimidazol-
5-one (9à) was recrystallized from the 4 : 1 hexane—acetone

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Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Grigor´ev et al.
mixture. 1-Hydroxy-2,2-dimethyl-4-phenyl-1,2-dihydroimid-
azole-5-thione (9b) was recrystallized from the 2 : 1 ethyl
acetate—hexane mixture. 1-Hydroxy-2,2-dimethyl-4-phenyl-1,2-
dihydroimidazol-5-one 3-oxide (11à) and 1-hydroxy-2,2-di-
methyl-4-phenyl-1,2-dihydroimidazole-5-thione 3-oxide (11b)
were recrystallized from ethyl acetate. 1,4-Dihydroxy-5,5-di-
methyl-4-phenylimidazolidin-2-one (10à) and 1,4-dihydroxy-5,5-
dimethyl-4-phenylimidazolidine-2-thione (10b) were recrystal-
lized from water. 3-Hydroxy-1,2,2,5,5-pentamethylimidazolidin-
3-one (12a) and 3-hydroxy-1,2,2,5,5-pentamethylimidazolidine-
3-thione (12b) were isolated as described previously.6,8
2. G. I. Shchukin, I. A. Grigor´ev, L. A. Vishnivetskaya, and
L. B. Volodarskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1988,
1944 [Bull. Acad. Sci. USSR, Div. Chem. Sci., 1988, 37,
1743 (Engl. Transl.)].
3. J. A. Warshaw, D. E. Gallis, B. J. Acken, O. J. Gonzales,
and D. R. Crist, J. Org. Chem., 1989, 54, 1736.
4. S. P. Ashburn and R. M. Coates, J. Org. Chem., 1985,
50, 3076.
5. S. M. Bakunova, I. A. Grigor´ev, I. A. Kirilyuk, and L. B.
Volodarskii, Izv. Akad. Nauk, Ser. Khim., 1999, 2160 [Russ.
Chem. Bull., 1999, 48, 2136 (Engl. Transl.)].
Reactions of compounds 1 and 2 with MeMgI. A solution of
α-methoxy nitrone 1 or 2 (0.3 g, 1.4 mmol) in THF (10 mL)
was added dropwise with stirring to a solution of MeMgI, which
has been prepared from Mg (100 mg, 4 mg-at.), MeI (0.6 g),
and diethyl ether (20 mL). The reaction mixture was stirred at
∼20 °Ñ for 1 h and quenched with water (15 mL). The organic
phase was separated and the aqueous solution was extracted
with tert-butyl methyl ether (3½15 mL). Then MnO2 (1 g) and
anhydrous MgSO4 (1 g) were added to the combined extracts.
The mixture was stirred for 2 h and filtered. The solvent was
evaporated in vacuo and the residue was chromatographed on a
column with SiO2 using CHCl3 as the eluent. The nitroxyl
radical 2,2,5,5-tetramethyl-4-phenyl-2,5-dihydro-1Í-imidazole-
1-oxyl (15) was obtained in yields of 95 and 85 mg in the case
of compounds 1 and 2, respectively, m.p. 79–80 °Ñ. The IR
spectra of the resulting samples were identical with the spec-
trum published previously.14
5-Benzoylmethyl-2,2-dimethyl-4-phenyl-2Í-imidazole
1-oxide (18). A solution of α-methoxy nitrone 1 (450 mg,
2 mmol) and acetophenone (0.3 mL, 2.5 mmol) in THF (5 mL)
was added dropwise with stirring to a suspension of 60% sodium
hydride (170 mg, 4 mmol) in dry THF (5 mL). The reaction
mixture was stirred at ∼20 °Ñ for 4 h and quenched with AcOH
(1 mL) and water (10 mL). Then the reaction mixture was
extracted with tert-butyl methyl ether (3½10 mL), the extract
was dried with MgSO4, the solvent was evaporated, and the
reside was chromatographed on a column with silica gel using
CHCl3 as the eluent.
6. G. I. Shchukin, I. A. Grigor´ev, and L. B. Volodarskii,
Khim. Geterotsikl. Soedin., 1990, 478 [Chem. Heterocycl.
Compd., 1990 (Engl. Transl.)].
7. M. Guyot and M. Dvolaisky, J. Chem. Research (S),
1977, 132.
8. G. I. Shchukin, I. A. Grigor´ev, and L. B. Volodarskii, Izv.
Sib. Otd. Akad. Nauk SSSR, Ser. Khim. [Bull. Sib. Branch
Acad. Sci. USSR, Div. Chem. Sci.], 1984, 81 (in Russian).
9. T. D. Lee and J. F. W. Keana, J. Org. Chem., 1976,
41, 3237.
10. V. A. Reznikov and L. B. Volodarskii, Izv. Akad. Nauk, Ser.
Khim., 1993, 933 [Russ. Chem. Bull., 1993, 42, 891 (Engl.
Transl.)].
11. V. A. Reznikov and L. B. Volodarskii, Khim. Geterotsikl.
Soedin., 1991, 192 [Chem. Heterocycl. Compd., 1991 (Engl.
Transl.)].
12. I. A. Kirilyuk, I. A. Grigor´ev, and L. B. Volodarskii, Izv.
Akad. Nauk SSSR, Ser. Khim., 1991, 2113 [Bull. Acad. Sci.
USSR, Div. Chem. Sci., 1991, 40, 1871 (Engl. Transl.)].
13. S. M. Bakunova, I. A. Kirilyuk, and I. A. Grigor´ev, Izv.
Akad. Nauk, Ser. Khim., 2001, in press [Russ. Chem. Bull.,
Int. Ed. Engl., 2001, 50, in press (Engl. Transl.)].
14. E. I. Lebedeva, I. A. Grigor´ev, and M. M. Mitasov, Atlas
spektrov aromaticheskikh i geterotsiklicheskikh soedinenii,
Vyp. 27, IK-spektry i spektry KR nitroksil´nykh radikalov
ryada 3-imidazolina, ikh diamagnitnykh predshestvennikov i
analogov, soderzhashchikh D i 15N [Atlas of Spectra of Aro-
matic and Heterocyclic Compounds. 27. IR and Raman Spec-
tra of Nitroxyl Radicals of the 3-Imidazoline Series, Their
Diamagnetic Precursors, and D- and 15N-Containing Ana-
logs], Ed. V. A. Koptyug, Novosibirsk Institute of Organic
Chemistry of the Siberian Branch of the Russian Academy
of Sciences, Novosibirsk, 1983 (in Russian).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 97-03-
32864a).
References
1. Houben-Weil, Methoden der Organischen Chemie, George
Thieme Verlag, Stuttgart—New York, 1990, E 146/2, 1372.
Received February 23, 2000;
in revised form June 13, 2000