Alkylation of 2-methylimidazole with iodomethyl ketones of the aliphatic, aromatic, and heteroaromatic series

Full text of DOI:10.1134/S1070428013030287

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 3, pp. 475–477. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © N.O. Yarosh, L.V. Zhilitskaya, L.G. Shagun, I.A. Dorofeev, L.I. Larina, M.G. Voronkov, 2013, published in Zhurnal Organicheskoi
Khimii, 2013, Vol. 49, No. 3, pp. 486–488.
SHORT
COMMUNICATIONS
Dedicated to Full Member of the Russian Academy of Sciences
I.P. Beletskaya on her jubilee
Alkylation of 2-Methylimidazole with Iodomethyl Ketones
of the Aliphatic, Aromatic, and Heteroaromatic Series
N. O. Yarosh, L. V. Zhilitskaya, L. G. Shagun, I. A. Dorofeev, L. I. Larina,
and M. G. Voronkov
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: shag@irioch.irk.ru
Received December 15, 2012
DOI: 10.1134/S1070428013030287
Imidazole derivatives exhibit a broad spectrum of
pharmacological activity [1–3]. They constitute base
fragments of biologically active compounds [4] and
“green” fertilizers [5] and are used as solvents and
catalysts in organic reactions [6]. Substituted imidaz-
oles catalyze curing of epoxy resins and are com-
ponents of curing agents [7].
For this purpose, we examined the reactions of
2-methyl-1H-imidazole (I) with 1-iodopropan-2-one
(IIa), 1-(biphenyl-4-yl)-2-iodoethanone (IIb), and
2-iodo-1-(2-thienyl)ethanone (IIc) in acetone at 40°C.
These reactions led to the formation of mixtures of
2-methyl-1,3-bis(2-oxopropyl)-3H-imidazol-1-ium,
1,3-bis[2-(biphenyl-4-yl)-2-oxoethyl]-2-methyl-3H-
imidazol-1-ium, and 2-methyl-1,3-bis-[2-oxo-2-(2-
thienyl)ethyl]-3H-imidazol-1-ium iodides IIIa–IIIc
with the corresponding triiodides IVa–IVc. The ratio
of iodides III and triiodides IV is determined by the
ability of iodo ketones IIa–IIc to undergo reduction
with hydrogen iodide liberated as a result of first
alkylation. Triiodide ion is formed via addition of
iodide ion to molecular iodine arising from the reduc-
tion of ketones IIa–IIc with hydrogen iodide.
A classical procedure for the synthesis of N-alkyl-
imidazoles is based on the reaction of imidazole with
alkyl halides under pressure at 100–150°C [8]. Reac-
tions of imidazoles with alkyl halides, α-bromo(chloro)
ketones, and chloroalkyl formates in the presence of
bases or phase-transfer catalysts give both N1-mono-
[2, 3, 9] and N1,N3-dialkylation products [10]. Alkyla-
tion of imidazole derivatives with α-iodo ketones in
the absence of a base and catalyst has not been re-
ported so far. There are grounds to believe that α-iodo
ketones can be successfully used in the synthesis of
diazolyl ketones in one preparative step due to high
reactivity of the C–I bond therein.
Electron-donor methyl group in 1-iodopropan-2-
one (IIa) favors reduction of the iodomethyl group and
hence the formation of triiodide IVa, so that the yield
of IVa attains 67%. Replacement of methyl group by
O
O
O
O
O
N
40°C
–HI
+
3
I–
+
I3
R
I
R
O
R
R
N
N
N
N
Me
R
N
H
Me
Me
I
IIa–IIc
IIIa–IIIc
IVa–IVc
IIa–IIc
+
HI
+
I2
I2
+
I–
I3
R
Me
R = Me (a), biphenyl-4-yl (b), thiophen-2-yl (c).
475

YAROSH et al.
476
biphenylyl or thienyl decreases the yield of triiodides
IVb and IVc to 21 and 19%, respectively.
C10H15I3N2O2. Calculated, %: C 20.85; H 2.63;
I 66.10; N 4.86.
1,3-Bis[2-(biphenyl-4-yl)-2-oxoethyl]-2-methyl-
3H-imidazol-1-ium iodide (IIIb). Yield 59%, yellow
crystals, mp 278–279°C. IR spectrum: ν 1689 cm–1
Thus the alkylation of 2-methylimidazole with
iodomethyl ketones of the aliphatic, aromatic, and
heteroaromatic series in the absence of a base gives
1,3-dialkylimidazolium iodides (triiodides).
1
(C=O). H NMR spectrum, δ, ppm: 2.50 s (3H, CH3),
6.16 s (4H, CH2), 7.42–8.13 m (18H, Harom), 7.69 s
(2H, 4-H, 5-H). 13C NMR spectrum, δC, ppm: 9.67
(CH3), 55.08 (CH2), 123.77–146.86 (Carom), 129.87
(C4, C5), 148.23 (C2), 191.71 (C=O). 15N NMR spec-
trum: δN –211.1 ppm. Found, %: C 64.14; H 4.31;
I 21.59; N 4.54. C32H27IN2O2. Calculated, %: C 64.17;
H 4.55; I 21.21; N 4.68.
The structure of imidazolium iodides IIIa–IIIc and
triiodides IVa–IVc was determined on the basis of
1
their H, 13C, and 15N NMR, IR, and UV spectra and
elemental compositions. All compounds III and IV
displayed in the 1H–15N HMBC two-dimensional spec-
tra cross peaks between the nitrogen nuclei (δN –209.8
to –211.8 ppm) and protons in the imidazole ring (4-H,
5-H), CH2 groups, and 2-CH3 group. In the UV spectra
of IVa–IVc we observed absorption bands in the
regions λ 291–293 and 361–362 nm, which are typical
of triiodide ion.
1,3-Bis[2-(biphenyl-4-yl)-2-oxoethyl]-2-methyl-
3H-imidazol-1-ium triiodide (IVb). Yield 21%, dark
brown crystals, mp 205–210°C. IR spectrum:
ν 1689 cm–1 (C=O). 1H NMR spectrum, δ, ppm: 2.31 s
(3H, 2-CH3), 5.93 s (4H, CH2), 7.25–7.94 m (18H,
Harom), 7.57 s (2H, 4-H, 5-H). 13C NMR spectrum, δC,
ppm: 9.90 (2-CH3), 55.11 (CH2), 119.13–139.05
(Carom), 128.92 (C4, C5), 146.28 (C2), 191.06 (C=O).
15N NMR spectrum: δN –211.2 ppm. Found, %:
C 44.15; H 3.07; I 44.49; N 3.51. C32H27I3N2O2. Cal-
culated, %: C 45.09; H 3.19; I 44.67; N 3.29.
Imidazolium iodides IIIa–IIIc and triiodides
IVa–IVc (general procedure). A solution of 18 mmol
of iodo ketone II in 2 ml of acetone was added
dropwise under stirring in an argon atmosphere to
a solution of 6 mmol of 2-methylimidazole (I) in 7 ml
of acetone, and the mixture was stirred for 10–12 h at
40°C until the initial ketone disappeared. The precip-
itate of iodide III was filtered off, washed with
acetone, and dried under reduced pressure. The filtrate
was evaporated to a volume of 5 ml, 30 ml of hexane
was added, and the precipitate of triiodide IV was
filtered off, reprecipitated thrice from acetone with
hexane (1:10), and dried under reduced pressure.
2-Methyl-1,3-bis[2-oxo-2-(2-thienyl)ethyl]-3H-
imidazol-1-ium iodide (IIIc). Yield 63%, light yellow
crystals, mp 247°C. IR spectrum: ν 1668 cm–1 (C=O).
1H NMR spectrum, δ, ppm: 2.52 s (3H, 2-CH3), 6.05 s
(4H, CH2), 7.40 d.d (2H, 4′-H, 3J = 4.9, 4.0 Hz), 7.70 s
(2H, 4-H, 5-H), 8.20 m (4H, 3′-H, 5′-H). 13C NMR
spectrum, δC, ppm: 9.59 (2-CH3), 54.21 (CH2), 122.77
(C4, C5), 129.33 (C4′), 135.08 (C3′), 136.73 (C5′),
139.73 (C2′), 147.30 (C2), 184.16 (C=O). 15N NMR
spectrum: δN –211.2 ppm. Found, %: C 41.56; H 3.27;
I 25.47; N 6.01; S 13.50. C16H15IN2O2S2. Calculated,
%: C 41.92; H 3.30; I 27.69; N 6.11; S 13.99.
2-Methyl-1-(2-oxopropyl)-3H-imidazol-1-ium
iodide (IIIa). Yield 13%, yellow crystals, mp 148–
1
150°C. IR spectrum: ν 1731 cm–1 (C=O). H NMR
spectrum, δ, ppm: 2.36 s (3H, 2-CH3), 2.25 s (6H,
CH3), 5.33 s (4H, CH2), 7.47 s (2H, 4-H, 5-H).
13C NMR spectrum, δC, ppm: 9.69 (2-CH3), 57.16
(CH2), 27.59 (CH3), 122.64 (C4, C5), 148.59 (C2),
200.17 (C=O). 15N NMR spectrum: δN –211.8 ppm.
Found, %: C 36.58; H 3.86; I 40.02; N 9.71.
C10H15IN2O2. Calculated %: C 37.28; H 4.70; I 39.38;
N 8.69.
2-Methyl-1,3-bis[2-oxo-2-(2-thienyl)ethyl]-3H-
imidazol-1-ium triiodide (IVc). Yield 19%, brown
crystals, mp 160°C. IR spectrum: ν 1669 cm–1 (C=O).
1H NMR spectrum, δ, ppm: 2.80 s (3H, 2-CH3), 6.20 s
(4H, CH2), 7.40 d.d (2H, 4′-H, 3J = 4.9, 4.0 Hz), 7.82 s
(2H, 4-H, 5-H), 8.15 (2H, 5′-H, 3J = 4.9 Hz), 8.21 (2H,
3
3′-H, J = 4.0 Hz). 13C NMR spectrum, δC, ppm: 9.67
2-Methyl-1-(2-oxopropyl)-3H-imidazol-1-ium
triiodide (IVa). Yield 67%, dark brown crystals,
mp 122–124°C. IR spectrum: ν 1720 cm–1 (C=O).
1H NMR spectrum, δ, ppm: 2.25 s (6H, CH3), 2.37 s
(3H, 2-CH3), 5.37 s (4H, CH2), 7.50 s (2H, 4-H, 5-H).
13C NMR spectrum, δC, ppm: 9.35 (2-CH3), 27.25
(CH3), 56.82 (CH2), 122.28 (C4, C5), 146.24 (C2),
199.86 (C=O). 15N NMR spectrum: δN –210.7 ppm.
Found, %: C 21.18; H 2.75; I 65.92; N 5.48.
(2-CH3), 54.48 (CH2), 122.92 (C4, C5), 129.04 (C4′),
134.47 (C3′), 136.19 (C5′), 139.94 (C2′), 147.90 (C2),
183.10 (C=O). 15N NMR spectrum: δN –209.8 ppm.
Found, %: C 27.33; H 2.10; I 52.84; N 3.96; S 9.08.
C16H15I3N2O2S2. Calculated %: C 26.98; H 2.12;
I 53.46; N 3.39; S 9.01.
The IR spectra were recorded on a Bruker Vertex
1
70 spectrometer (KBr, film). The H, 13C, and 15N
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 3 2013

ALKYLATION OF 2-METHYLIMIDAZOLE WITH IODOMETHYL KETONES
477
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