Synthesis of 1,3-dialkylimidazolium and 1,3-dialkylbenzimidazolium salts

Article abstract of DOI:10.1023/B:RUJO.0000010563.79902.47

A number of N-alkylimidazoles and N-alkylbenzimidazoles were synthesized by reactions of imidazole and benzimidazole with alkyl halides. The reaction rate increases by a factor of 2 to 3 under conditions of microwave activation. Subsequent treatment of the resulting N-alkylazoles with alkyl halides afforded the corresponding 1,3-dialkylimidazolium and 1,3-dialkylbenzimidazolium halides.

Full text of DOI:10.1023/B:RUJO.0000010563.79902.47

Russian Journal of Organic Chemistry, Vol. 39, No. 10, 2003, pp. 1467 1470. Translated from Zhurnal Organicheskoi Khimii, Vol. 39, No. 10, 2003,
pp. 1536 1539.
Original Russian Text Copyright
2003 by Starikova, Dolgushin, Larina, Ushakov, Komarova, Lopyrev.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on the 65th Anniversary of His Birth
Synthesis of 1,3-Dialkylimidazolium and 1,3-Dialkyl-
benzimidazolium Salts
O. V. Starikova, G. V. Dolgushin, L. I. Larina, P. E. Ushakov,
T. N. Komarova, and V. A. Lopyrev
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: ktn@irioch.irk.ru
Received June 23, 2003
Abstract A number of N-alkylimidazoles and N-alkylbenzimidazoles were synthesized by reactions of
imidazole and benzimidazole with alkyl halides. The reaction rate increases by a factor of 2 to 3 under condi-
tions of microwave activation. Subsequent treatment of the resulting N-alkylazoles with alkyl halides afforded
the corresponding 1,3-dialkylimidazolium and 1,3-dialkylbenzimidazolium halides.
Several methods for the synthesis of N-alkylazoles
and N-alkylbenzazoles are known [1 4]. N-Allenyl-
azoles were obtained from the corresponding azoles
and 2-propynyl chloride or 1,2,3-trichloropropane in
one preparative step [2]. Monosubstituted imidazoles
were synthesized under conditions of phase-transfer
catalysis in a solid liquid system [3]. Monoalkylated
imidazoles exhibit surfactant properties and are pre-
cursors of 1,3-dialkylimidazolium salts which are used
as hygroscopic ionic liquids with low melting points
(from 30 C to ambient) [1, 4, 5]. In addition, di-
alkylazolium salts are used in the synthesis of stable
heterocyclic carbenes [6, 7].
alkylating agents we used i-PrBr, i-BuBr, i-BuI, and
BzlCl. The corresponding N-alkylimidazoles were
thus obtained in good yields (60 80%). For com-
parison, the alkylation of imidazole was carried out
under conditions of microwave activation. The reac-
tion of imidazole with isobutyl bromide in DMSO
gave 33% of 1-isobutylimidazole in 1 h. When this
reaction was carried out in DMF, 26% of the product
was formed in 7 min. The yield increased to 56% on
prolonging the reaction to 60 min.
An analogous pattern was observed in the alkyla-
tion with benzyl bromide: the yield of the product was
15% in 7 min and 68% in 60 min.
Microwave activation of organic reactions attracts
increasing interest of chemists working in the field of
organic synthesis [8, 9]. Studies on the N-alkylation
of imidazoles, pyrroles, indoles, and carbazoles with
butyl bromide and decyl chloride in the presence of
K2CO3/KOH and a catalytic amount of tetrabutyl-
ammonium bromide under microwave irradiation have
been reported [10 12]. Imidazole and its 4-substituted
derivatives are known to relatively readily react with
various alkylating agents to give N1-substituted
imidazoles in high yields [13]. On the other hand,
the yields of alkylation products from benzimidazole
are sometimes poor.
Benzimidazole was alkylated both by the procedure
described in [2] and under microwave irradiation. By
the classical reaction of benzimidazole with isobutyl
bromide 1-isobutylbenzimidazole (V) was isolated
in 29% yield. The microwave-activated reaction was
carried out in different solvents: acetonitrile, methyl
alcohol, DMSO, and DMF. The best results were
obtained in DMF in the presence of KOH. Here, as
in the microwave-activated reaction with imidazole,
the yield of the product increased from 39 to 67% on
prolonging the reaction from 15 to 60 min. No ap-
preciable increase in the product yield was attained
by variation of the solvent (in particular, using aceto-
nitrile, methanol, or DMSO), reaction time, and radia-
tion power, as well as by replacement of KOH by
t-BuOK. We also made an attempt to modify the
We performed alkylation of unsubstituted imid-
azole according to the procedure reported in [2]. The
reaction readily occurred at the nitrogen atom. As
1070-4280/03/3910-1467$25.00 2003 MAIK Nauka/Interperiodica

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STARIKOVA et al.
synthetic procedure: alkyl halide was added dropwise
to a mixture of benzimidazole and alkali in approp-
riate solvent. In the reaction with isobutyl bromide,
the yield of 1-isobutylbenzimidazole was 47%, and
the yield of 1-isopropylbenzimidazole in the reaction
with isopropyl bromide was 54%.
tion of 0.01 mol of imidazole or benzimidazole in
20 ml of DMSO, the mixture was stirred for 30 min
at 18 20 C, and 0.01 mol of the corresponding alkyl
halide was added dropwise under vigorous stirring and
cooling with a water bath. After 2 h, the mixture was
diluted with 200 ml of water and extracted with
chloroform (6 25 ml), the combined extracts were
washed with water and dried over MgSO4, the solvent
was distilled off, and the residue was either distilled
under reduced pressure or recrystallized from hexane.
b. The reaction was carried out in a one-neck
round-bottom flask equipped with a reflux condenser,
which was placed in an LG Electronics MS-192A
household microwave oven. The flask was charged
with 0.01 mol of imidazole or benzimidazole, 0.84 g
(0.015 mol) of potassium hydroxide, 20 ml of DMF,
and 0.01 mol of alkyl halide, and the mixture was
irradiated for 60 min at a power of 90 W. The mixture
was then cooled and treated as described in a.
1-Isopropylimidazole (I). Method a. Yield 80%.
Colorless viscous liquid, bp 68 72 C (3 mm); pub-
lished data [15]: 62 C (2 mm).
1-Isobutylimidazole (II). Yield 60% (a), 56% (b).
Colorless viscous liquid, bp 78 C (3 mm); published
data [15]: bp 92 C (2 mm).
I, IV, R = i-Pr; II, V, R = i-Bu; III, VI, R = CH2Ph;
I VI, Hlg = I, Br, Cl; X = H; VII, XI, R = R = i-Pr,
Hlg = Br; VIII, XIII, R = R = i-Bu, Hlg = Br; IX, XIV,
R = R = i-Bu, Hlg = I; X, XV, R = R = PhCH2, Hlg = Cl;
XII, R = Me, R = i-Bu, Hlg = Br; I III, VII X, X = H;
IV VI, XI XV, XX = CH CH CH CH.
According to Jones and Young [14], treatment of
imidazole with 2 equiv of acrylic acid in methanol
or water directly afforded zwitterionic imidazolium-
1,3-diacetate. We failed to obtain the corresponding
1,3-dialkyldiazolium salts by treatment of imidazole
or benzimidazole with 2 equiv of alkylating agent.
The reaction gave a mixture of monoalkylated azole,
dialkylazolium salt, and potassium halide, which was
difficult to separate. Therefore, 1,3-dialkylazolium
salts were obtained in two steps. Initially, N-alkyl-
azoles were synthesized and isolated and were then
treated with 3 equiv of alkyl halide. As a result, the
N,N -dialkyl derivatives were formed in good yields.
1-Benzylimidazole (III). Yield 77% (a), 68% (b).
Colorless crystals, mp 69 70 C (from hexane); pub-
lished data [15]: mp 70 71.5 C.
1-Isopropylbenzimidazole (IV). Yield 79% (a).
1
Colorless viscous liquid, bp 135 140 C (1 mm). H
NMR spectrum, , ppm: 8.39 (2-H), 7.85 (4-H), 7.26
(5-H), 7.28 (6-H), 7.55 (7-H), 4.6 (CH), 1.47 (CH3).
13C NMR spectrum, C, ppm: 144.06 (C2), 141.4(C9),
133.3 (C8), 122.15 (C6), 121.48 (C5), 119.76 (C4),
110.66 (C7), 47.2 (CH), 22.1 (CH3). Found, %:
C 75.03; H 7.62; N 17.44. C10H12N2. Calculated, %:
C 74.97; H 7.55; N 17.48.
The IR spectra of the products contain absorption
bands due to stretching vibrations of the endocyclic
1-Isobutylbenzimidazole (V). Yield 29% (a), 67%
(b). Colorless viscous liquid, bp 155 165 C (1 mm),
which crystallized at room temperature to give color-
1
C C and C N bonds (1468 1547 cm ), CH and
1
1
CH2 groups ( C H 2873 2934 cm ), and CH3
less crystals with mp 49 50 C. H NMR spectrum, ,
1
groups ( C H 2962 2977 cm ).
ppm: 8.19 (2-H), 7.64 (4-H), 7.18 (5-H), 7.23 (6-H),
7.58 (7-H), 4.05 (2-H), 2.14 (CH), 1.47 (CH3).
13C NMR spectrum, C, ppm: 144.31 (C2), 143.33
EXPERIMENTAL
(C9), 134.07 (C8), 122.12 (C6), 121.26 (C5), 119.35
The IR spectra were recorded on a Bruker IFS-25
(C4), 110.5 (C7), 51.2 (CH2), 29.1 (CH), 20.2 (CH3).
Found, %: C 75.73; H 8.06; N 16.21. C11H14N2. Cal-
culated, %: C 75.82; H 8.10; N 16.08.
1
spectrometer in KBr. The H and 13C NMR spectra
were obtained on a Bruker DPX-400 instrument at
400.13 and 100.61 MHz, respectively, from solutions
in DMSO-d6.
N-Alkylazoles (general procedure). a. Potassium
hydroxide, 0.84 g (0.015 mol), was added to a solu-
1-Benzylbenzimidazole (VI). Yield 85% (a).
Colorless crystals, mp 106 108 C; published data
[16]: mp 116 118 C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 10 2003

SYNTHESIS OF 1,3-DIALKYLIMIDAZOLIUM
1469
1,3-Dialkylimidazolium and 1,3-dialkylbenz-
imidazolium halides (general procedure). Alkyl
halide, 0.3 mol, was added dropwise under vigorous
stirring to a mixture of 0.1 mol of 1-alkylazole or
1-alkylbenzimidazole in 20 ml of appropriate solvent
which was dried by standard procedure [17]. The mix-
ture was stirred for 8 36 h at a temperature indicated
below, the solvent was distilled off, the residue was
ground with anhydrous THF, and the precipitate was
filtered off and dried under reduced pressure.
powder, mp 124 126 C. 1H NMR spectrum
(DMSO-d6), , ppm: 9.91 (2-H), 8.15 (4-H), 7.7
(5-H), 7.7 (6-H), 8.15 (7-H), 5.1 (CH), 1.7 (CH3).
13C NMR spectrum (DMSO-d6), C, ppm: 139.07
(C2), 130.5(C8), 130.5 (C9), 126.4 (C5), 126.4 (C6),
114.02 (C4), 114.02 (C7), 53.1 (CH), 28.2 (CH2), 19.3
(CH3). Found, %: C 55.09; H 6.65; Br 28.55; N 9.71.
C13H19BrN2. Calculated, %: C 55.13; H 6.76;
Br 28.21; N 9.89.
1-Isobutyl-3-methylbenzimidazolium bromide
(XII). Reaction time 17 h (toluene). Yield 46%.
Colorless powder, mp 185 186 C. 1H NMR spectrum,
, ppm: 9.88 (2-H), 8.13 (4-H), 7.68 (5-H), 7.7 (6-H),
8.03 (7-H), 4.37 (CH2), 4.06 (NCH3), 2.26 (CH), 0.98
(CH3). 13C NMR spectrum, C, ppm: 144.04 (C2),
132.96 (C9), 132.47 (C8), 127.67 (C6), 127.61 (C5),
114.89 (C4), 114.81 (C7), 54.25 (CH), 34.5 (NCH3),
29.57 (CH2), 20.58 (CH3). Found, %: C 53.56;
H 6.76; Br 29.35; N 10.33. C12H17BrN2. Calculated,
%: C 53.54; H 6.36; Br 29.68; N 10.41.
1,3-Diisopropylimidazolium bromide (VII). Re-
action time 12 h (toluene). Yield 60%. Colorless
1
powder, mp 136 138 C. H NMR spectrum, , ppm:
4
4
9.35 t (2-H, J = 1.7 Hz), 7.94 d (4-H, J = 1.6 Hz),
4
7.94 d (5-H, J = 1.6 Hz), 4.63 (CH), 1.49 (CH3).
13C NMR spectrum (DMSO-d6), C, ppm: 133.65
(C2), 120.71 (C4), 120.71 (C5), 52.3 (CH), 22.4
(CH3). Found, %: C 46.55; H 7.18; Br 34.25;
N 12.02. C9H17BrN2. Calculated, %: C 46.36; H 7.35;
Br 34.27; N 12.01.
1,3-Diisobutylimidazolium bromide (VIII). Reac-
1,3-Diisobutylbenzimidazolium bromide (XIII).
tion time 18 h (2-propanol). Yield 65%. Colorless
Reaction time 18 h (acetonitrile). Yield 29%. Color-
1
powder, mp 84 86 C. H NMR spectrum, , ppm:
1
less powder, mp 176 179 C. H NMR spectrum, ,
9.27 s (2-H), 7.82 d (4-H, J = 1.6 Hz), 7.82 d (5-H,
J = 1.6 Hz), 4.04 (CH2), 2.12 (CH), 0.85 (CH3).
13C NMR spectrum, C, ppm: 136.47 (C2), 122.96
(C4), 122.96 (C5), 55.63 (CH2), 28.81 (CH), 19.16
(CH3). Found, %: C 51.02; H 8.10; Br 29.83;
N 11.05. C11H21BrN2. Calculated, %: C 50.58;
H 8.10; Br 30.59; N 10.72.
ppm: 9.9 (2-H), 8.13 (4-H), 7.69 (5-H), 7.69 (6-H),
8.13 (7-H), 4.36 (CH2), 2.24 (CH), 0.99 (CH3).
13C NMR spectrum, C, ppm: 142.5 (C2), 131.3 (C8),
131.3 (C9), 126.5 (C5), 126.5 (C6), 113.9 (C4), 113.9
(C7), 53.1 (CH), 28.2 (CH2), 19.3 (CH3). Found, %:
C 57.87; H 7.64; Br 25.64; N 8.85. C15H23BrN2. Cal-
culated, %: C 57.88; H 7.45; Br 25.67; N 9.00.
1,3-Diisobutylimidazolium iodide (IX). Reaction
1,3-Diisobutylbenzimidazolium iodide (XIV).
time 8 h (acetonitrile). Yield 66%. Colorless powder,
1
Reaction time 36 h (acetonitrile). Yield 70%. Color-
mp 118 120 C. H NMR spectrum, , ppm: 9.27 s
1
less powder, mp 158 160 C. H NMR spectrum, ,
(2-H), 7.82 d (4-H, J = 1.6 Hz), 7.82 d (5-H, J =
1.6 Hz), 4.04 (CH2), 2.12 (CH), 0.85 (CH3). 13C
NMR spectrum, C, ppm: 136.47 (C2), 122.96 (C4),
122.96 (C5), 55.63 (CH2), 28.81 (CH), 19.16 (CH3).
Found, %: C 43.02; H 7.10; I 40.98; N 8.90.
C11H21IN2. Calculated, %: C 42.87; H 6.87; I 41.18;
N 9.09.
1,3-Dibenzylimidazolium chloride (X). Reaction
time 11 h (toluene). Yield 85%. Colorless hygroscopic
powder which quickly liquified on exposure to air.
1H NMR spectrum, , ppm: 9.78 s (2-H), 7.9 m (4-H),
7.9 m (5-H), 5.49 (NCH2) 7.43 m (Ph). 13C NMR
spectrum, C, ppm: 136.52 (C2); 128.72 (C4); 128.72
(C5); 122.83, 128.94, 128.53, 135.06 (Ph); 51.84
(CH2). Found, %: C 71.14; H 6.20; Cl 12.65; N 10.01.
C17H17ClN2. Calculated, %: C 71.69; H 6.02;
Cl 12.45; N 9.84.
ppm: 9.9 (2-H), 8.13 (4-H), 7.69 (5-H), 7.69 (6-H),
8.13 (7-H), 4.36 (CH2), 2.24 (CH), 0.99 (CH3).
13C NMR spectrum, C, ppm: 142.5 (C2), 131.3 (C8),
131.3 (C9), 126.5 (C5), 126.5 (C6), 113.9 (C4), 113.9
(C7), 53.1 (CH), 28.2 (CH2), 19.3 (CH3). Found, %:
C 50.50; H 6.20; I 35.28; N 8.02. C23H15IN2. Calcu-
lated, %: C 50.29; H 6.47; I 35.42; N 7.82.
1,3-Dibenzylbenzimidazolium chloride (XV).
Reaction time 13 h (toluene). Yield 87%. Colorless
1
powder, mp 210 212 C. H NMR spectrum, , ppm:
10.4 (2-H), 7.98 (4-H), 7.62 (5-H), 7.62 (6-H), 7.98
(7-H), 5.83 (CH2), 7.55 (o-H), 7.4 (p-H, m-H). 13C
NMR spectrum, C, ppm: 142.96 (C2), 131.12 (C8),
131.12 (C9), 126.84 (C5), 126.84 (C6), 114.12 (C4),
114.12 (C7), 134.1 (Ci), 129.1 (Co), 128.8 (Cp), 128.4
(Cm), 50.06 (CH2). Found, %: C 75.29; H 5.80;
Cl 10.48; N 8.42. C21H19ClN2. Calculated, %:
C 75.32; H 5.72; Cl 10.58; N 8.37.
1,3-Diisopropylbenzimidazolium bromide (XI).
Reaction time 26 h (toluene). Yield 31%. Colorless
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STARIKOVA et al.
8. Bates, E.D., Mayton, R.D., Ntai, I., and Davis, J.H.,
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