Multicomponent assembling of imidazole N-oxides, aldehydes and CH-acids: A simple and efficient approach to newly functionalized imidazole derivatives

Article abstract of DOI:10.1016/j.tet.2017.10.026

An efficient and simple method for C2-functionalization of 2-unsubstituted imidazole N-oxides has been developed. It consists at the condensation of 2-unsubstituted imidazole N-oxides with aldehydes and CH-acids. This method permits broad variations in th

Full text of DOI:10.1016/j.tet.2017.10.026

Accepted Manuscript
Multicomponent assembling of imidazole N-oxides, aldehydes and CH-acids: A
simple and efficient approach to newly functionalized imidazole derivatives
Vitaly S. Mityanov, Anton V. Kutasevich, Michail M. Krayushkin, Boris V. Lichitsky,
Arkady A. Dudinov, Andrey N. Komogortsev, Tatyana Yu. Koldaeva, Valery P.
Perevalov
PII:
S0040-4020(17)31041-4
10.1016/j.tet.2017.10.026
TET 29029
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 22 July 2017
Revised Date: 24 September 2017
Accepted Date: 9 October 2017
Please cite this article as: Mityanov VS, Kutasevich AV, Krayushkin MM, Lichitsky BV, Dudinov AA,
Komogortsev AN, Koldaeva TY, Perevalov VP, Multicomponent assembling of imidazole N-oxides,
aldehydes and CH-acids: A simple and efficient approach to newly functionalized imidazole derivatives,
Tetrahedron (2017), doi: 10.1016/j.tet.2017.10.026.
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Multicomponent assembling of imidazole N-
oxides, aldehydes and CH-acids: a simple
and efficient approach to newly
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functionalized imidazole derivatives.
a,b
a,*
b
b
Vitaly S. Mityanov , Anton V. Kutasevich , Michail M. Krayushkin , Boris V. Lichitsky , Arkady A.
b
b
a
a
Dudinov , Andrey N. Komogortsev , Tatyana Yu. Koldaeva , Valery P. Perevalov .
a
Department of Fine Organic Synthesis and Chemistry of Dyes, D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Sq., 9, Moscow
1
25047, Russian Federation
b
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Pr., 47, Moscow 119991, Russian Federation

1
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Tetrahedron
journal homepage: www.elsevier.com
Multicomponent assembling of imidazole N-oxides, aldehydes and CH-acids: a
simple and efficient approach to newly functionalized imidazole derivatives
a,b
a*
b
b
b
Vitaly S. Mityanov , Anton V. Kutasevich , Michail M. Krayushkin , Boris V. Lichitsky , Arkady A. Dudinov ,
b
a
a
Andrey N. Komogortsev , Tatyana Yu. Koldaeva and Valery P. Perevalov .
a
Department of Fine Organic Synthesis and Chemistry of Dyes, D. Mendeleyev University of Chemical Technology of Russia, Miusskaya Sq., 9, Moscow 125047,
Russian Federation
b
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Pr., 47, Moscow 119991, Russian Federation
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient and simple method for C2-functionalization of 2-
unsubstituted imidazole N-oxides has been developed. It consists at the
condensation of 2-unsubstituted imidazole N-oxides with aldehydes and
CH-acids. This method permits broad variations in the structure of starting
materials.
Available online
2
017 Elsevier Ltd. All rights reserved.
Keywords:
Imidazole N-oxides
CH-acids
Multicomponent reaction
CH-functionalization
1
. Introduction
especially at the C2-position, it allows efficient
regioselective C2-functionalization. However, C2-
Imidazole N-oxides are interesting compounds due to
functionalization of imidazole N-oxides with preservation of
the N-oxide group is known only in case of using transition
their applications as building blocks in advanced heterocyclic
1,2
8
chemistry,3
natural product synthesis, coordination
metal catalysis. Examples of functionalization without
4
9
chemistry, and catalysis. In addition, imidazole derivatives
play a significant role in various biochemical processes and
catalysis are mostly accompanied by deoxygenation.
In our earlier work we have described C2-
functionalization of 1-benzyl-4,5-dimethylimidazole N-oxide
via condensation with aldehydes and Meldrum’s acid
5,6
exhibit a diverse scope of biological activities. The
imidazole core is present in many natural compounds such as
histidine and the related hormone histamine.
In this context, development of new effective methods
for the synthesis of imidazole derivatives is therefore of great
importance. There are two fundamentally different
approaches for their synthesis. The first way involves
preparation of imidazoles from acyclic precursors using
10
proceeding under mild conditions. In the present study, we
have expanded this reaction to the broad scope of CH-acids
and imidazole N-oxides
.
2
. Results and discussion
7
various cyclocondensation reactions. The second way
It was found that 2-unsubstituted imidazole N-oxides 1
reacts with various CH-acids 2 and aldehydes 3 with the
entails direct C-H functionalization of the imidazole ring
using mostly transition metal-catalyzed reactions. It is known
that the N-oxide group imparts a great increase in reactivity
in reactions with electrophilic reagents at all positions, and
formation
of
products
4a-w
(Table
1).

ACCEPTED MANUSCRIPT
2
Table 1. Synthesis of compounds 4a-w.
O
O
HN NH
N
N
O
O
=
O
O
O
O O
O O
O O
O O
OH O
OH
CHꢀacids
3
a
3b
3c
3d
3e
3f
3
OHO H
N
N
O
NH
N
O
4
f
OH
S
1%b
9
OHO H
N
N
O
NH
N
O
4i
N
8
5%b
O
O

ACCEPTED MANUSCRIPT
3
OHO
N
O
N
O
4u
OH
3
7%c
a
b
used as 37% aqueous solution. Reaction conditions: imidazole N-oxide 1 (2 mmol), barbituric acid 3а (2 mmol), aldehyde (2
c
mmol) was refluxed for 8 h in mixture MeCN (5 mL) and H O (2 mL). imidazole N-oxide (2 mmol), CH-acid 3b-f (2 mmol),
2
and aldehyde 2 (2 mmol) in MeCN (5 mL) was refluxed for 6 h.
of using CH-acids such as 4-hydroxycoumarin and 4-
Various 2-unsubstituted 1-alkyl-4,5-dimethylimidazole
N-oxides (1a-f), 1-arylimidazole N-oxide 1g and 1-alkyl-2,4-
unsubstituted 1h and various aldehydes, including aromatic
hydroxy-6-methylpyrone, which are known not to form
stable enones in reaction with aldehydes.
11
In the case of using thiazolidine-2,4-dione 5 as CH-acid,
the reaction stops at the formation of enone 6, which can be
isolated from the reaction mixture. This fact can be explained
by the lack of activity of this enone as a Michael acceptor.
Attempts to use acyclic β-dicarbonyl compounds such as
acetylacetone 5a, diethylmalonate 5b and ethyl acetoacetate
(2a,b), heteroaromatic (2c-e), aliphatic (2f) and
formaldehyde (as 37% water solution) were selected. CH-
acids were represented by barbituric acid 3a, 1,3-
dimethylbarbituric acid 3b, dimedone 3c, 1,3-indandione 3d,
4
-hydroxy-6-methyl-2H-pyran-2-one
3e
and
4-
hydroxycoumarin 3f. Assembling various combinations of
these building blocks, we were able to prepare a library of
functionalized imidazole derivatives. It should be noted that
in case of N-oxide 1h which has two available positions, only
the product of reaction on position C2 was obtained (4o).
The yields of the discussed condensation are practically
independent of nature of both the imidazole N-oxide and the
CH-acid, but are determined by the ease of the pure product
isolation (Table 1).
5
c also failed. Most probably corresponding enones do not
form under the reaction conditions (Scheme 2) and only the
starting N-oxide 1b was isolated from the reaction mixture.
Scheme 2. Reaction of imidazole N-oxide and aldehyde
with thiazolidine-2,4-dione and acyclic β-dicarbonyl
compounds.
Most probably, the reaction begins with nucleophilic
addition of CH-acid to the aldehyde with the formation of the
corresponding enone, followed by the Michael-type addition
of imidazole N-oxide (Scheme 1).
Scheme 1. Plausible reaction mechanism.
1
The molecular structures of 4a-w were established by H
13
1
and C NMR spectrometry and HRMS. The H NMR
spectra of all compounds 4 displayed a very characteristic
singlet at 16-18 ppm for the N-OH proton. Similar signals
1
can also be observed in H NMR spectra of products of
condensation of 1-benzyl-4,5-dimethylimidazole N-oxide
with aldehydes and Meldrum’s acid which were reported in
our earlier work.
In addition, it is necessary to note that in this three-
component reaction product can be obtained even in the case
10

ACCEPTED MANUSCRIPT
3
Imidazole N-oxides were obtained in analogy to the
already described procedures. 1,3,5-Triazinanes 9a-b were
obtained by treatment of the corresponding amines 8 with
paraformaldehyde in methanol at room temperature. The
crude products were used for the further reaction with
butane-2,3-dione monooxime 11 in refluxing EtOH without
purification. Under these conditions, triazines are known to
undergo dissociation, and the monomeric formaldehyde
imines (N-methyleneamines) reacts with 11 to give
imidazole N-oxides 1e,f. Imidazole N-oxides 1g,h were
prepared as shown in the scheme below (Scheme 3).
were performed with Merck Silica Gel 60 F254 precoated
plates. IR spectra were recorded on a Shimadzu IRAffinity-1
FTIR spectrophotometer. The melting points were
determined on a Kofler hot stage.
4
.2. General procedure of preparation compounds 4a-w
Method A. A mixture of appropriate imidazole N-oxide (2
mmol), aldehyde (2 mmol) (or equivalent amount of 37%
aqueous solution of formaldehyde in case of compounds
4a,e) and barbituric acid 3a (2 mmol) in mixture MeCN (5
mL) and water (2 mL) was refluxed for 8 h. The solvent was
removed under reduced pressure and the residue was
crystallized from IPA or its mixture with water to give the
corresponding product.
Scheme 3. Synthesis of imidazole N-oxides 1e-h.
Method B. A mixture of appropriate imidazole N-oxide
(
2mmol), CH acid (2 mmol) and aldehyde (2 mmol) (or
equivalent amount of 37% aqueous solution of formaldehyde
in case of compound 4k,q,u) in MeCN (5 mL) was refluxed
for 6 h. The solvent was removed under reduced pressure and
the residue was crystallized from IPA or its mixture with
water to give the corresponding product.
4
.2.1. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)methyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-
olate (4a). White powder; yield 88% (method A); mp >300
1
°
C; H NMR (300 MHz, DMSO-d ), δ: 10.16 (s, 2H), 7.38-
6
7
2
.27 (m, 3H), 7.11 (d, J = 6 Hz, 2H), 5.40 (s, 2H), 3.78 (s,
H), 2.12 (s, 3H), 2.01 (s, 3H); C NMR (75 MHz, DMSO-
13
d ) δ: 165.0, 150.6, 139.4, 135.2, 128.9, 127.9, 126.4, 122.5,
6
–
1
1
3
1
1
22.0, 81.4, 47.5, 16.2, 8.2, 6.7. IR spectrum, ν, cm : 3434,
114, 3035, 2973, 2832, 2757, 2498, 1685, 1612, 1481,
455, 1383, 1356, 1303, 1293, 1225, 1186, 1106, 1045,
031, 858, 821, 776, 698, 659, 576, 565, 539, 518, 444, 436.
+
HRMS: Calculated for C H N O [M+H] : 343.1406.
17
19
4
4
Found: 343.1398.
.2.2. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)(4-methoxyphenyl)methyl)-2,6-dioxo-1,2,3,6-
4
3
. Conclusion
tetrahydropyrimidin-4-olate (4b). White powder; yield 96 %
In conclusion, we described the new condensation of 2-
unsubstituted imidazole N-oxides with aldehydes and CH-
acids. The described procedure is operationally simple and
chromatography free. A diverse scope of starting materials
combined with an operationally simple, chromatography-free
procedure make this a useful synthetic method for C2-
functionalization of imidazole N-oxides.
1
(method A); mp 283-285 °C; H NMR (300 MHz, DMSO-
d6), δ: 17.19 (s, 1H), 10.34 (s, 2H), 7.45-7.33 (m, 3H), 7.26
(d, J = 7.2 Hz, 2H), 6.77 (s, 4H), 6.07 (s, 1H), 5.52 (d, J =
1
3
1
1
6.8 Hz, 1H), 5.37 (d, J = 16.8 Hz, 1H), 3.70 (s, 3H), 2.24 (s,
13
H), 2.13 (s, 3H); C NMR (75 MHz, DMSO-d ) δ: 165.2,
6
58.0, 150.6, 140.0, 135.3, 129.1, 128.1, 127.7, 127.6,
26.4, 123.0, 122.7, 113.6, 83.9, 55.0, 47.6, 32.4, 8.5, 6.8.
–1
4
. Experimental
IR spectrum, ν, cm : 3440, 3137, 3033, 2997, 2963, 2832,
2
1
7
760, 1690, 1601, 1510, 1473, 1457, 1391, 1352, 1300,
273, 1248, 1220, 1169, 1093, 1042, 976, 884, 832, 801,
4
.1. General
88, 772, 753, 705, 660, 574, 543, 536, 454, 436. HRMS:
Unless otherwise noted, all the reagents were purchased
+
Calculated for C H N O [M+H] : 449.1825. Found:
449.1819.
4.2.3. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)(thiophen-2-yl)methyl)-2,6-dioxo-1,2,3,6-
tetrahydropyrimidin-4-olate (4c). White powder; yield 73%
from commercial suppliers, and used without further
purification. Imidazole N-oxides 1a-d
24 25
4
5
12-14
15
and oxime 13
1
were prepared according to the reported procedures. H and
13
C NMR spectra were recorded on a Bruker Avance 300
MHz spectrometer or on a Bruker DRX500 500 MHz
spectrometer in DMSO-d , chemical shift (δ) values for H
and C NMR spectra are reported in parts per million (ppm)
with the solvent resonance as the internal standard. High-
resolution mass spectra (HRMS) were registered on Bruker
MicrOTOF ESI-TOF mass spectrometer. The TLC analysis
1
(method A); mp 281-283 °C (dec.); H NMR (300 MHz,
1
6
DMSO-d ), δ: 17.38 (s, 1H), 10.34 (s, 2H), 7.45-7.33 (m,
6
13
3
H), 7.29 (d, J = 5.1 Hz, 1H), 7.21 (d, J = 7.5 Hz, 2H), 6.87
t, J = 4.2 Hz, 1H), 6.57 (d, J = 2.7 Hz, 1H) 6.23 (s, 1H),
5.49 (d, J = 16.8 Hz, 1H), 5.40 (d, J = 16.8 Hz, 1H), 2.22 (s,
(
13
3H), 2.15 (s, 3H); C NMR (75 MHz, DMSO-d ) δ: 164.9,
6

ACCEPTED MANUSCRIPT
4
1
1
50.5, 140.6, 138.5, 135.0, 129.1, 128.2, 126.8, 126.2, 124.7,
24.6, 123.3, 122.9, 85.6, 47.6, 40.3, 29.5, 8.4, 6.8. IR
DMSO-d ) δ: 165.2, 158.0, 150.7, 139.7, 137.4, 127.7, 127.6,
6
127.5, 127.4, 127.3, 123.0, 122.3, 113.7, 83.9, 55.0, 43.1,
–1
–1
spectrum, ν, cm : 3429, 3133, 3062, 2984, 2849, 2774,
32.4, 8.5, 6.7. IR spectrum, ν, cm : 3436, 3151, 3050, 2960,
1
1
7
696, 1597, 1498, 1476, 1456, 1403, 1356, 1273, 1235,
206, 1154, 1132, 1089, 1027, 1001, 974, 902, 865, 831,
2836, 2774, 1693, 1601, 1511, 1462, 1405, 1353, 1302,
1249, 1179, 1069, 1033, 880, 831, 800, 788, 771, 716, 575,
+
86, 699, 660, 632, 576, 553, 531, 467, 459, 440. HRMS:
538, 453. HRMS: Calculated for C H N O S [M+H] :
22
23
4
5
+
Calculated for C H N O S [M+H] : 425.1284. Found:
4
455.1389. Found: 455.1370.
4.2.8. 5-((1-(carboxymethyl)-3-hydroxy-4,5-dimethyl-1H-
21
21
4
4
25.1278.
4
.2.4.
5-((3-hydroxy-1-(2-hydroxyethyl)-4,5-dimethyl-1H-
imidazol-3-ium-2-yl)(4-methoxyphenyl)methyl)-2,6-dioxo-
imidazol-3-ium-2-yl)(4-methoxyphenyl)methyl)-2,6-dioxo-
,2,3,6-tetrahydropyrimidin-4-olate (4d). Pale yellow
powder; yield 45 % (method A); mp 276-278 °C (dec.); H
1,2,3,6-tetrahydropyrimidin-4-olate (4h). White powder;
yield 72 % (method A); mp 266-268 °C; H NMR (300
1
1
1
MHz, DMSO-d ), δ: 17.16 (s, 1H), 10.23 (s, 2H), 6.98 (d, J =
6
8
=
.4 Hz, 2H), 6.82 (d, J = 8.4 Hz, 2H), 5.91 (s, 1H), 5.08 (d, J
18.3 Hz, 1H ), 4.94 (d, J = 18.3 Hz, 1H), 3.69 (s, 3H), 2.14
NMR (300 MHz, DMSO-d ), δ: 17.08 (s, 1H), 10.24 (s, 2H),
6
7
1
.05 (d, J = 9.9 Hz, 2H), 6.85 (d, J = 9.9 Hz, 2H), 6.21 (s,
H), 5.30 (t, J = 4.5 Hz, 1H), 4.35-4.19 (m, 2H), 3.74-3.68
13
(s, 3H), 2.06 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
6
13
168.4, 165.2, 158.1, 150.7, 140.6, 127.8, 127.6, 122.9, 122.4,
(m, 5Н), 2.26 (s, 3H), 2.09 (s, 3H); C NMR (75 MHz,
–1
1
3
1
8
13.7, 83.6, 55.0, 45.8, 32.3, 8.1, 6.6. IR spectrum, ν, cm :
420, 3170, 2997, 2959, 2838, 2542, 1696, 1610, 1465,
360, 1302, 1248, 1178, 1106, 1106, 1033, 984, 884, 834,
DMSO-d ) δ: 165.2, 157.9, 150.6, 140.4, 128.4, 127.9, 122.7,
6
1
22.1, 113.5, 83.8, 59.4, 55.0, 47.0, 32.4, 8.5, 6.6. IR
–1
spectrum, ν, cm : 3474, 3173, 3067, 2923, 2837, 1701,
02, 789, 773, 740, 683, 600, 582, 543, 448. HRMS:
Calculated for C H N O [M+H] : 417.1410. Found:
+
1
1
6
608, 1507, 1454, 1354, 1302, 1250, 1176, 1163, 1087,
031, 979, 943, 884, 862, 833, 799, 786, 765, 754, 715, 680,
19
21
4
7
417.1398.
56, 609, 584, 543, 511, 491, 419. HRMS: Calculated for
4.2.9. 5-((3-hydroxy-4,5-dimethyl-1-(2-morpholinoethyl)-1H-
imidazol-3-ium-2-yl)(4-methoxyphenyl)methyl)-2,6-dioxo-
+
C H N O [M+H] : 403.1618. Found: 403.1612.
19
23
4
6
1
,2,3,6-tetrahydropyrimidin-4-olate (4i). White powder;
4
.2.5.
5-((3-hydroxy-1-(2-hydroxyethyl)-4,5-dimethyl-1H-
1
yield 85 % (method A); mp 290-291 °C (dec.); H NMR
imidazol-3-ium-2-yl)methyl)-2,6-dioxo-1,2,3,6-
(
300 MHz, DMSO-d ), δ: 17.05 (s, 1H), 10.24 (s, 2H), 7.03
tetrahydropyrimidin-4-olate (4e). White powder; yield 52%
6
1
(d, J = 8.4 Hz, 2H), 6.85 (d, J = 8.4 Hz, 2H), 6.16 (s, 1H),
(
method A); mp 246-248 °C; H NMR (300 MHz, DMSO-
4
3
2
1
8
.40-4.32 (m, 1H), 4.12 (d, J = 15.0 Hz, 1H), 3.73 (s, 3H),
d ), δ: 10.14 (s, 2H), 5.12 (br. s, 1H), 4.25 (s, 2H), 3.84 (s,
6
13
.38-3.33 (m, 4H), 2.76-2.54 (m, 4H), 2.36-2.33 (m, 2H),
2
H), 3.62 (s, 2H), 2.18 (s, 3H), 2.13 (s, 3H); C NMR (75
13
.25 (s, 3H), 2.08 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
MHz, DMSO-d ) δ:165.0, 150.7, 139.6, 122.1, 121.6, 81.5,
6
6
–1
65.2, 157.9, 150.7, 140.3, 128.2, 127.9, 122.3, 122.2, 113.4,
3.8, 65.7, 57.9, 54.9, 53.6, 42.0, 32.5, 8.2, 6.6. IR spectrum,
5
3
1
8
9.7, 47.0, 16.2, 8.2, 6.8. IR spectrum, ν, cm : 3536, 3481,
443, 3197, 3048, 3002, 2929, 2788, 1696, 1623, 1465,
394, 1359, 1283, 1217, 1180, 1069, 993, 955, 923, 873,
–1
ν, cm : 3430, 3139, 3096, 2990, 2971, 2927, 2872, 2842,
2
1
8
4
4
4
801, 1724, 1584, 1513, 1490, 1464, 1394, 1361, 1351,
304, 1285, 1249, 1166, 1144, 1115, 1075, 1026, 930, 912,
42, 821, 771, 713, 660, 651, 607, 582, 544, 518, 548, 425.
+
HRMS: Calculated for C H N O [M+H] : 297.1199.
12
17
4
5
83, 858, 825, 789, 766, 723, 713, 660, 619, 608, 569, 538,
Found: 297.1188.
.2.6. 5-((3-hydroxy-1-(2-hydroxyethyl)-4,5-dimethyl-1H-
imidazol-3-ium-2-yl)(thiophen-3-yl)methyl)-2,6-dioxo-
,2,3,6-tetrahydropyrimidin-4-olate (4f). Off-white powder;
+
58, 418. HRMS: Calculated for C H N O [M+H] :
4
23 30
5
6
72.2196. Found: 472.2191.
.2.10. 5-((4-hydroxy-3-methoxyphenyl)(3-hydroxy-4,5-
1
1
dimethyl-1-(1H-1,2,4-triazol-5-yl)-1H-imidazol-3-ium-2-
yl)methyl)-2,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate
yield 91 % (method A); mp 253-255 °C; H NMR (300
MHz, DMSO-d ), δ: 17.23 (s, 1H), 10.23 (s, 2H), 7.43 (m,
6
(
4j). White powder; yield 71 % (method A); mp 258-260
1
H), 7.12 (s, 1H), 6.85 (d, J = 4.5 Hz, 1H), 6.19 (s, 1H), 5.30
1
(dec.) °C; H NMR (300 MHz, DMSO-d ), δ: 17.91 (s, 1H),
(
t, J = 4.8 Hz, 1H), 4.35-4.18 (m, 2H), 3.76-3.66 (m, 2H),
6
13
1
4.83 (br. s, 1H), 10.22 (s, 2H), 8.88 (s, 1H), 6.68 (d, J = 8.1
2
1
1
3
1
1
7
.25 (s, 3H), 2.10 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
6
Hz, 1H), 6.61 (s, 1H), 6.50 (d, J = 8.1 Hz, 1H), 5.87 (s, 1H),
65.0, 150.7, 139.7, 137.5, 127.4, 125.6, 122.5, 122.3,
13
–1
3
.64 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H); C NMR (75 MHz,
21.7, 85.0, 59.4, 47.0, 29.9, 8.4, 6.7. IR spectrum, ν, cm :
446, 3164, 3108, 3081, 3025, 2841, 2767, 2360, 1691,
601, 1507, 1487, 1457, 1387, 1352, 1302, 1247, 1187,
142, 1107, 1081, 955, 927, 887, 867, 841, 786, 777, 738,
DMSO-d ) δ: 164.4, 151.2, 150.4, 147.4, 146.1, 145.6, 140.4,
6
1
3
2
27.2, 124.0, 123.1, 119.6, 115.5, 111.6, 84.1, 55.8, 38.7,
2.5, 8.7, 6.7. IR spectrum, ν, cm : 3498, 3440, 3284, 3135,
926, 2853, 2362, 1730, 1680, 1616, 1532, 1517, 1472,
–1
19, 678, 664, 622, 612, 569, 547, 535, 452, 441. HRMS:
+
1448, 1402, 1386, 1363, 1343, 1264, 1223, 188, 1147, 1122,
Calculated for C H N O S [M+H] : 379.1076. Found:
16
19
4
5
1
4
4
4
027, 976, 904, 874, 810, 786, 707, 644, 591, 565, 536, 503,
3
4
1
79.1071.
+
78, 457, 422. HRMS: Calculated for C H N O [M+H] :
19
20
7
6
.2.7. 5-((3-hydroxy-4,5-dimethyl-1-(thiophen-2-ylmethyl)-
H-imidazol-3-ium-2-yl)(4-methoxyphenyl)methyl)-2,6-
42.1475. Found: 442.1481.
.2.11. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
dioxo-1,2,3,6-tetrahydropyrimidin-4-olate
powder; yield 78 % (method A); mp 238-240 °C (dec.); H
(4g).
White
1
ium-2-yl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-
tetrahydropyrimidin-4-olate (4k). White powder; yield 81%
NMR (300 MHz, DMSO-d ), δ: 17.17 (s, 1H), 10.32 (s, 2H),
6
1
(
method B); mp 244-246 °C; H NMR (300 MHz, DMSO-
7
.58 (d, J = 5.1 Hz, 1H), 7.24 (d, J = 2.7 Hz, 1H), 7.06-7.03
d6), δ: 16.96 (br. s, 1H), 7.37-7.26 (m, 3H), 7.10 (d, J = 7.2
Hz, 2H), 5.45 (s, 2H), 3.88 (s, 2H), 3.07 (s, 6H), 2.14 (s, 3H),
(
(
m, 1H), 6.80 (s, 4H), 6.24 (s, 1H), 5.66-5.54 (m, 2H), 3.70
s, 3H), 2.29 (s, 3H), 2.08 (s, 3H); C NMR (75 MHz,
13

ACCEPTED MANUSCRIPT
5
1
3
2
1
2
2
1
6
.02 (s, 3H); C NMR (75 MHz, DMSO-d ) δ: 163.0, 151.3,
83.3, 55.0, 40.0, 39.8, 39.5, 39.2, 38.9, 33.9, 33.3, 27.9. IR
–1
6
39.6, 135.0, 128.8, 127.8, 126.2, 122.3, 81.4, 47.6, 38.7,
spectrum, ν, cm : 3447, 3065, 2954, 1695, 1603, 1549,
1510, 1459, 1401, 1382, 1362, 1350, 1314, 1256, 1186,
1154, 1083, 1061, 1018, 841, 802, 789, 754, 706, 619, 571,
515, 480, 453, 423. HRMS: Calculated for C H N O
5
–1
7.6, 17.6, 8.1, 6.7. IR spectrum, ν, cm : 3236, 3347, 3037,
973, 2930, 2292, 1686, 1597, 1518, 1457, 1357, 1298,
280, 1212, 1159, 1103, 1058, 980, 911, 851, 782, 759, 739,
99, 672, 639, 619, 596, 573, 495, 461, 453, 423. HRMS:
Calculated for C H N O [M+H] : 371.1719 Found:
23
24
5
+
[M+H] : 450.1777. Found: 450.1772.
+
4.2.16. 5-(1-(3-hydroxy-1,4,5-trimethyl-1H-imidazol-3-ium-
19
23
4
4
3
4
71.1712.
.2.12. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
2-yl)-3-methylbutyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-
tetrahydropyrimidin-4-olate (4p). White powder; yield 66 %
1
ium-2-yl)(4-methoxyphenyl)methyl)-1,3-dimethyl-2,6-dioxo-
,2,3,6-tetrahydropyrimidin-4-olate (4l). White powder;
(
method B); mp 235-237 °C; H NMR (300 MHz, DMSO-
1
d6), δ: 17.16 (s, 1H), 4.92 (t, J = 7.8 Hz, 1H), 3.67 (s, 3H),
.14 (s, 6H), 2.18-2.15 (m, 7H), 1.88-1.79 (m, 1H), 1.42-1.33
1
yield 71% (method B); mp 227-228 °C; H NMR (300 MHz,
DMSO-d ), δ: 16.61 (s, 1H), 7.42-7.30 (m, 3H), 7.21 (d, J =
3
6
13
(m, 1H), 0.90-0.84 (m, 6H); C NMR (75 MHz, DMSO-d6)
7
1
2
1
1
8
1
1
5
.2 Hz, 2H), 6.75 (s, 4H), 6.18 (s, 1H), 5.48 (d, J = 16.8 Hz,
H), 5.40 (d, J = 16.8 Hz, 1H), 3.68 (s, 3H), 3.14 (s, 6H),
δ: 162.7, 139.9, 122.7, 121.6, 85.8, 36.8, 31.4, 28.1, 27.7,
–1
13
25.8, 22.4, 22.0, 8.2, 6.6. IR spectrum, ν, cm : 3443, 2957,
.23 (s, 3H), 2.14 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
6
2
1
311, 1684, 1606, 1516, 1472, 1447, 1386, 1368, 1257,
239, 1202, 1149, 1104, 1058, 994, 963, 926, 840, 814, 783,
63.2, 158.0, 151.3, 140.1, 135.1, 128.9, 128.0, 127.6, 127.4,
26.3, 123.0, 122.8, 113.6, 84.0, 55.0, 47.7, 38.7, 33.8, 27.9,
–1
.4, 6.8. IR spectrum, ν, cm : 3436, 2929, 2831, 1684, 1601,
512, 1468, 1457, 1442, 1350, 1303, 1250, 1214, 1167,
132, 1112, 1061, 1031, 1002, 958, 945, 806, 781, 760, 710,
73, 521, 509, 456, 423. HRMS: Calculated for C H N O
768, 758, 709, 635, 600, 573, 507, 492, 455, 424. HRMS:
+
Calculated for C17
351.2027.
H
27
N
4
O
4
[M+H] : 351.2032. Found:
26
29
4
5
4.2.17. 2-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
+
[
M+H] : 477.2138. Found: 477.2133.
ium-2-yl)methyl)-5,5-dimethyl-3-oxocyclohex-1-en-1-olate
1
4
.2.13. 5-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
(
4q). White powder; yield 41%; mp 148-150 °C; H NMR
ium-2-yl)(furan-2-yl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-
tetrahydropyrimidin-4-olate (4m). Black powder; yield 51 %
(
300 MHz, DMSO-d ), δ: 7.41-7.30 (m, 3H), 7.08 (d, J = 7.2
6
Hz, 2H), 5.36 (s, 2H), 3.78 (s, 2H), 2.13-2.11 (m, 7H), 2.03
1
(method B); mp 231-232 (dec.) °C; H NMR (300 MHz,
13
(
s, 3H), 0.95 (s, 6H); C NMR (75 MHz, DMSO-d ) δ:
6
DMSO-d ), δ: 16.73 (s, 1H), 7.51 (s, 1H), 7.42-7.30 (m, 3H),
7
5
6
1
37.3, 135.7, 128.9, 127.7, 126.1, 122.7, 121.0, 106.0, 47.3,
.17 (d, J = 7.5 Hz, 2H), 6.34 (s, 1H), 6.15 (d, J = 9 Hz, 2H),
13
47.0, 45.3, 31.0, 28.0, 27.6, 15.4, 8.2, 6.8. IR spectrum, ν,
.43 (s, 2H), 3.13 (s, 6H), 2.15 (s, 6H); C NMR (75 MHz,
–1
cm : 3443, 2949, 2921, 2875, 1614, 1581, 1565, 1498, 1476,
454, 1412, 1368, 1358, 1320, 1298, 1263, 1212, 1196,
1139, 1119, 1086, 978, 957, 934, 855, 806, 741, 701, 603,
DMSO-d ) δ: 162.9, 151.3, 148.6, 142.5, 138.0, 134.6,
6
1
1
3
1
1
6
28.9, 128.0, 126.0, 123.2, 123.0, 110.4, 107.7, 82.8, 47.5,
–1
0.2, 27.8, 8.3, 6.7. IR spectrum, ν, cm : 3447, 2965, 2897,
682, 1606, 1473, 1451, 1354, 1281, 1230, 1217, 1154,
135, 1058, 1005, 952, 853, 784, 762, 746, 726, 719, 707,
588, 562, 484, 458. HRMS: Calculated for C21
H
27
N
O
3
2
+
[M+H] : 355.2021. Found: 355.2026.
69, 600, 658, 504, 458. HRMS: Calculated for C H N O
23
25
4
5
4.2.18. 2-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)(4-methoxyphenyl)methyl)-5,5-dimethyl-3-
+
[
M+H] : 437.1825. Found: 437.1826.
4
.2.14. 5-((3-hydroxy-1,4,5-trimethyl-1H-imidazol-3-ium-2-
oxocyclohex-1-en-1-olate (4r). White powder; yield 38%; mp
1
yl)(4-methoxyphenyl)methyl)-1,3-dimethyl-2,6-dioxo-1,2,3,6-
156-158 °C; H NMR (300 MHz, DMSO-d ), δ: 17.52 (s,
6
tetrahydropyrimidin-4-olate (4n). White powder; yield 40 %
1H), 7.43-7.31 (m, 3H), 7.17 (d, J = 7.5 Hz, 2H), 6.76-6.69
(m, 4H), 6.24 (s, 1H), 5.42 (d, J = 17.1 Hz, 1H), 5.27 (d, J =
1
(method B); mp 252-253 °C; H NMR (300 MHz, DMSO-
1
1
7.1 Hz, 1H), 3.69 (s, 3H), 2.31 (s, 2H), 2.20-2.08 (m, 8H),
d6), δ: 16.36 (s, 1H), 7.00 (d, J = 6.7 Hz, 2H), 6.81 (d, J = 6.7
13
.08-0.97 (m, 6H); C NMR (75 MHz, DMSO-d ) δ: 168.4,
Hz, 2H), 6.24 (s, 1H), 3.71 (s, 3H), 3.70 (s, 3H), 3.14 (s, 6H),
6
1
3
165.2, 158.0, 150.7, 140.6, 127.8, 127.6, 122.9, 122.4, 113.7,
2
1
8
.19 (s, 3H), 2.07 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
6
–1
8
2
1
6
3.6, 55.1, 45.8, 32.3, 8.1, 6.6. IR spectrum, ν, cm : 3434,
952, 2927, 2362, 1062, 1570, 1512, 1459, 1362, 1302,
250, 1176, 1147, 1121, 1038, 945, 876, 855, 826, 758, 707,
60, 596, 55, 507, 459. HRMS: Calculated for C H N O
4
63.1, 158.0, 151.5, 139.8, 128.0, 127.9, 123.0, 121.7, 113.6,
3.6, 55.0, 40.3, 33.7, 31.8, 27.8, 8.3, 6.6. IR spectrum, ν,
cm : 3439, 2958, 2929, 1684, 1613, 1510, 1457, 1363, 1286,
–1
2
8
33
2
1
7
248, 1208, 1174, 1108, 1058, 1023, 994, 961, 880, 835,
80, 759, 578, 516, 423. HRMS: Calculated for C H N O
+
[
M+H] : 461.2440. Found: 461.2431.
20
25
4
5
4.2.19. 2-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)(thiophen-2-yl)methyl)-5,5-dimethyl-3-oxocyclohex-
+
[
M+H] : 401.1825. Found: 401.1826.
4
.2.15.
5-((3-hydroxy-1-methyl-5-(pyridin-3-yl)-1H-
1-en-1-olate (4s). Off-white powder; yield 57%; mp 194-196
1
imidazol-3-ium-2-yl)(4-methoxyphenyl)methyl)-1,3-dimethyl-
,6-dioxo-1,2,3,6-tetrahydropyrimidin-4-olate (4o). White
(dec.) °C; H NMR (300 MHz, DMSO-d ), δ: 17.69 (s, 1H),
6
2
7.43-7.30 (m, 3H), 7.23 (d, J = 5.1 Hz, 1H), 7.16 (d, J = 7.5
Hz, 2H), 6.83 (t, J = 4.5 Hz, 1H), 6.49-6.48 (m, 1H), 6.42 (s,
1H), 5.40 (d, J = 16.8 Hz, 1H), 5.27 (d, J = 16.8 Hz, 1H),
1
powder; yield 67% (method B); mp 226-227 °C; H NMR
300 MHz, DMSO-d ) δ: 17.01 (s, 1H), 8.82 (s, 1H), 8.76 (d,
(
6
13
J = 4.8 Hz, 1H), 8.11 (d, J = 8.1 Hz, 1H), 8.02 (s, 1H), 7.65-
2.31-2.10 (m, 10H), 1.07 (s, 3H), 0.97 (s, 3H); C NMR (75
7
2
.61 (m, 1H), 7.14 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.4 Hz,
MHz, DMSO-d ) δ: 193.8, 181.4, 141.0, 136.9, 135.4, 129.0,
6
13
H), 6.38 (s, 1H), 3.84 (s, 3H), 3.77 (s, 3H), 3.21 (s, 6H);
C
127.9, 126.5, 126.0, 124.3, 124.0, 123.4, 122.2, 109.5, 49.3,
NMR (75 MHz, DMSO-d ) δ: 163.2, 158.1, 151.4, 150.5,
47.1, 46.4, 30.8, 29.3, 28.3, 26.9, 8.4, 6.8. IR spectrum, ν,
6
–1
1
49.9, 142.4, 137.2, 128.1, 127.4, 123.7, 122.6, 117.1, 113.6,
cm : 3443, 3065, 2943, 2864, 1647, 1604, 1559, 1497, 1456,

ACCEPTED MANUSCRIPT
6
1
8
366, 1356, 1303, 1221, 1207, 1144, 1030, 980, 949, 867,
4.3. General procedure for preparation N-oxides 1e,f.
47, 785, 741, 711, 667, 651, 590, 579, 562, 493, 455.
To a solution of amine 8 (10 mmol) in methanol (10 mL)
was added paraformaldehyde (0.3 g, 10 mmol) and stirred at
room temperature for 8 h, then solvent removed under
reduced pressure. To the residue was added ethanol (10 mL)
and butane-2,3-dione monooxime (1.01 g, 10 mmol). The
resulting solution was refluxed for 4 h, then solvent was
removed under reduced pressure and the residue was treated
with acetone (10 mL), filtered and washed with acetone (10
mL).
+
HRMS: Calculated for C H N O S [M+H] : 437.1898.
25
29
2
3
Found: 437.1889.
.2.20. 2-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
ium-2-yl)(4-methoxyphenyl)methyl)-1-oxo-1H-inden-3-olate
4
1
(4t). Yellow powder; yield 49 %; 198-200 mp °C; H NMR
(300 MHz, DMSO-d ), δ: 17.96 (s, 1H), 7.37-7.22 (m, 9H),
6
6
5
3
1
1
6
2
1
.83-6.74 (m, 4H), 5.65 (d, J = 16.8 Hz, 1H), 5.57 (s, 1H),
.20 (d, J = 16.8 Hz, 1H), 3.69 (s, 3H), 2.25 (s, 3H), 2.15 (s,
13
H); C NMR (75 MHz, DMSO-d ) δ: 158.1, 139.4, 135.1,
4.3.1. 4,5-dimethyl-1-(thiophen-2-ylmethyl)-1H-imidazole 3-
oxide (1f). White powder; yield 74%, mp 206-208 °C, H
6
1
30.7, 129.0, 128.5, 128.1, 126.6, 123.7, 122.4, 118.7, 113.5,
03.5, 55.0, 47.6, 40.1, 39.8, 39.5, 39.2, 38.9, 38.7, 31.7, 8.5,
NMR (300 MHz, DMSO-d ), δ: 8.18 (s, 1H), 7.51 (d, J = 5.1
6
–1
.8. IR spectrum, ν, cm : 3447, 3060, 2997, 2921, 2836,
Hz, 1H), 7.11-7.10 (m, 1H), 7.03 (t, J = 4.2 Hz, 1H), 5.30 (s,
13
361, 1635, 1589, 1509, 1463, 1351, 1243, 1181, 1166,
2H), 2.14 (s, 3H), 1.99 (s, 3H), C NMR (75 MHz, DMSO-
035, 936, 883, 828, 809, 769, 730, 702, 580, 533, 477.
d ) δ: 139.0, 127.1, 126.8, 126.5, 125.5, 123.6, 120.7, 42.9,
6
+
–1
HRMS: Calculated for C H N O [M+H] : 467.1970.
8.3, 6.9. IR spectrum, ν, cm : 3443, 3147, 3099, 2925, 2360,
29
27
2
4
Found: 467.1959.
.2.21. 3-((3-hydroxy-1-(2-hydroxyethyl)-4,5-dimethyl-1H-
imidazol-3-ium-2-yl)methyl)-6-methyl-2-oxo-2H-pyran-4- 1
olate (4u). Off-white powder; yield 37%, mp 198-200 °C, H
1623, 1469, 1441, 1389, 1369, 1306, 1225, 1168, 1142,
1080, 965, 855, 829, 745, 725, 689, 668, 651, 602, 471, 418.
4
+
HRMS: Calculated for C H N OS [M+H] : 209.0748.
10
13
2
Found: 209.0748.
NMR (300 MHz, DMSO-d ), δ: 5.78 (s, 1H), 5.12 (br. s,
4.3.2. 4,5-dimethyl-1-(2-morpholinoethyl)-1H-imidazole 3-
oxide (1e). White powder; yield 87%, mp 216-218 °C, H
6
1
1
H), 4.22 (t, J = 5.4 Hz, 2H), 3.92 (s, 2H), 3.63 (t, J = 5.4
13
Hz, 2H), 2.18 (s, 3H), 2.11 (s, 3H), 2.08 (s, 3H), C NMR
75 MHz, DMSO-d ) δ: 173.3, 165.3, 159.8, 137.3, 122.0,
NMR (300 MHz, DMSO-d ), δ: 8.07 (s, 1H), 3.92 (s, 2H),
6
(
3.38 (s, 2H), 2.50 (s, 4H), 2.41 (s, 4H), 2.12 (s, 3H), 1.96 (s,
6
1
3
1
21.8, 103.8, 93.9, 59.8, 46.9, 19.0, 17.5, 8.2, 6.8. IR
3H), C NMR (75 MHz, DMSO-d ) δ: 123.8, 66.1, 57.8,
6
–1
–1
spectrum, ν, cm : 3330, 2986, 2926, 1681, 1617, 1534,
53.1, 41.5, 8.7, 6.9. IR spectrum, ν, cm : 3432, 3010, 2957,
1
9
443, 1359, 1288, 1269, 1203, 1159, 1081, 1055, 1004, 953,
2853, 2812, 2360, 1624, 1455, 1400, 1389, 1372, 1338,
1158, 1149, 1115, 1071, 1039, 1024, 929, 857, 832, 773,
728, 648, 621, 603, 587, 558, 515, 423. HRMS: Calculated
15, 876, 836, 753, 622, 586, 532, 511. HRMS: Calculated
+
for C H N O [M+H] : 295.1294. Found: 295.1292.
4
14
19
2
5
+
.2.22. 3-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
for C H N O [M+H] : 226.1555. Found: 226.1562.
11
20
3
2
ium-2-yl)(4-methoxyphenyl)methyl)-6-methyl-2-oxo-2H-
4.4. 4,5-dimethyl-1-(1,2,4-triazol-3-yl)-1H-imidazole 3-oxide
(1g). A mixture of butane-2,3-dione monooxime 11 (1.01 g,
10 mmol), 1H-1,2,4-triazol-3-amine (0.84 g, 10 mmol) and a
37% water solution of formaldehyde (0.81 g, 10 mmol) in
glacial acetic acid (10 mL) was refluxed for 5 h, then solvent
was removed under reduced pressure and the residue was
pyran-4-olate (4v). White powder; yield 29%; mp 211-212
1
°
C; H NMR (300 MHz, DMSO-d ), δ: 17.70 (s, 1H), 7.42-
6
7
2
.30 (m, 3H), 7.18 (d, J = 7.5 Hz, 2H), 6.73 (d, J = 8.7 Hz,
H), 6.65 (d, J = 8.7 Hz, 2H), 5.96 (s, 1H), 5.83 (s, 1H), 5.49
(
2
d, J = 17.1 Hz, 1H), 5.27 (d, J = 17.1 Hz, 1H), 3.67 (s, 3H),
.22 (s, 3H), 2.11-2.09 (m, 6H); C NMR (75 MHz, DMSO-
13
crystallized from IPA. Off-white powder; yield 67%, mp
1
d6) δ: 173.2, 165.9, 159.8, 158.0, 137.8, 135.4, 129.0, 128.0,
244-246 °C, H NMR (300 MHz, DMSO-d ), δ: 8.61 (s, 1H),
6
13
1
4
2
1
6
27.5, 127.0, 126.2, 123.3, 122.7, 113.6, 104.6, 95.6, 55.0,
8.53 (s, 1H), 2.40 (s, 3H), 2.12 (s, 3H), C NMR (75 MHz,
–1
7.4, 34.1, 19.0, 8.5, 6.8. IR spectrum, ν, cm : 3455, 2961,
928, 1683, 1646, 1545, 1512, 1456, 1355, 1294, 1249,
199, 1174, 1155, 1031, 990, 881, 846, 826, 781, 706, 668,
DMSO-d ) δ: 154.1, 144.7, 122.8, 122.5, 10.4, 6.9. .IR
6
–1
spectrum, ν, cm :3420, 3124, 3096, 2930, 2521, 2361, 1869,
1635, 1560, 1546, 1481, 1382, 1374, 1313, 1300, 1256,
1212, 1189, 1121, 1066, 945, 904, 875, 803, 735, 639, 584,
17, 597, 570, 555, 534, 418. HRMS: Calculated for
+
+
C H N O [M+H] : 447.1920. Found: 447.1910.
408. HRMS: Calculated for C H N O [M+H] : 180.0885.
26
27
2
5
7
10
5
4
.2.23. 3-((1-benzyl-3-hydroxy-4,5-dimethyl-1H-imidazol-3-
Found: 180.0880.
ium-2-yl)(4-methoxyphenyl)methyl)-2-oxo-2H-chromen-4- 1
4.5. 1-methyl-5-(pyridin-3-yl)-1H-imidazole 3-oxide (1h). A
mixture of oxime 13 (1.0 g, 6.7 mmol) and 1,3,5-trimethyl-
1,3,5-triazinane (0.3 g, 2.3 mmol) in glacial acetic acid (10
mL) was stirred overnight, then solvent was removed under
reduced pressure and the residue was crystallized from
olate (4w). White powder; yield 39%; mp 213-215 °C; H
NMR (300 MHz, DMSO-d ), δ: 17.95 (s, 1H), 7.90 (d, J =
6
7
7
.8 Hz, 1H), 7.57 (t, J = 6.9 Hz, 1H ), 7.40-7.26 (m, 5H),
.21 (d, J = 7.2 Hz, 2H), 6.74 (s, 4H), 6.17 (s, 1H), 5.53 (d, J
=
17.1 Hz, 1H), 5.34 (d, J = 17.1 Hz, 1H), 3.67 (s, 3H), 2.23
13
mixture of acetone with Et O. Off-white powder; yield 42%,
2
(s, 3H), 2.15 (s, 3H); C NMR (75 MHz, DMSO-d ) δ:
1
6
mp 216-218 °C, H NMR (300 MHz, DMSO-d ), δ: 8.73 (d,
6
1
1
1
3
1
1
4
69.5, 164.4, 158.0, 152.4, 138.2, 135.2, 131.9, 129.0, 128.1,
27.6, 126.7, 126.2, 124.5, 123.4, 123.3, 123.1, 119.5, 115.8,
13.7, 96.6, 55.0, 47.6, 40.3, 40.1, 39.8, 39.5, 39.2, 38.9,
J = 1.8 Hz, 1H),8.62 (d, J = 4.8 Hz, 1H), 8.35 (s,1H), 7.97
(
3
1
d, J = 7.8 Hz, 1H), 7.54-7.49 (m, 1H), 7.43 (s,1H), 3.63 (s,
13
–1
H). C NMR (75 MHz, DMSO-d ) δ: 149.5, 148.9, 135.8,
6
4.7, 8.5, 6.8. IR spectrum, ν, cm : 3443, 2929, 1670, 1606,
558, 1512, 1456, 1355, 1303, 1278, 1249, 1194, 1177,
167, 1107, 1032, 898, 818, 763, 704, 676, 637, 599, 542,
–
1
28.1, 123.7, 120.4, 40.3 , 33.3. IR spectrum, ν, cm : 3438,
3245, 3081, 2360, 1653, 1583, 1559, 1329, 1255, 1233,
1189, 1163, 1086, 1051, 1012, 960, 938, 857, 812, 787, 708,
+
31. HRMS: Calculated for C H N O [M+H] : 483.1919.
29
27
2
5
Found: 483.1908.

ACCEPTED MANUSCRIPT
7
6
78, 668, 624, 592, 498, 418. HRMS: Calculated for
+
C H N O [M+H] : 176.0823. Found: 176.0822.
9
10
3
5
. References
1
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Laperle, M.; Villemure, E.; Sun, H. Y.; Lasserre, S.;
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1