N-alkylation products of substituted imidazoles and dihydropyrimidinediones with dibromoalkanes

Article abstract of DOI:10.1007/s10593-008-0016-6

The reactions of N-containing heterocycles with dihaloalkanes were studied. All structures were determined by NMR and mass techniques.

Full text of DOI:10.1007/s10593-008-0016-6

Chemistry of Heterocyclic Compounds, Vol. 44, No. 1, 2008
N-ALKYLATION PRODUCTS
OF SUBSTITUTED IMIDAZOLES
AND DIHYDROPYRIMIDINEDIONES
WITH DIBROMOALKANES
K. Brokaitė, V. Mickevičius, R. Vaickelionienė
The reactions of N-containing heterocycles with dihaloalkanes were studied. All structures were
determined by NMR and mass techniques.
Keywords: N-alkylation, benzimidazole, dihydropyrimidinedione, dibromoalkane, heterocycles,
imidazole.
For a long time heterocycles have constituted one of the largest areas of research in organic chemistry.
Heterocycles play an important role in biochemical processes and are of interest in biology, pharmacology,
microelectronics and optoelectronic material sciences.
The imidazole, benzimidazole, and pyrimidinedione moieties represent important substructures of a wide
variety of bioactive compounds [1-4].
In modern microelectronics and optoelectronics, there are signs that the way is paved for the application of new
organic materials evolving from the art of molecular design and synthetic chemistry. The possibility of
introducing various functionalities into molecules, which is the strong point of organic synthesis, offers a
boarder range of optical and electrical properties than for traditional semiconductors [5].
Organic charge-transporting materials required by modern technologies have to exhibit a high enough
carrier mobility, a suitable ionization potential, and electron affinity for energy level matching, light absorption,
electrochemical stability, good film forming properties, and thermal and morphological stability (no
crystallization of amorphous materials should occur).
According to Naito and Miura [6] who examined the relations between thermal properties and
thermodynamic parameters, morphologically stable molecular glasses require a high Tg (glass-transition
temperature), a low maximum crystal-growth velocity, and a high temperature of maximum crystal growth.
One rather straightforward way to get glass-forming functional molecules is the connection of dyes to
''dimeric'' twin molecules. In the simplest case, if the electronic structure of each half is to be maintained, the
connection is made by an alkyl spacer. Care must be taken that not too much flexibility is introduced, which may
reduce Tg. Thus, short spacers like methylene linkages are most suitable.
In the present work, we investigated alkylation of nitrogen heterocycles with dibromoalkanes. The
reactions of appropriate imidazoles, benzimidazoles, and dihydropyrimidinediones (Het) with dibromoalkanes
__________________________________________________________________________________________
Kaunas University of Technology, LT 50254 Kaunas, Lithuania; e-mail: Vytautas.Mickevicius@ktu.lt.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 31-34, January, 2007. Original article
submitted April 6, 2007.
0009-3122/08/4401-0025©2008 Springer Science+Business Media, Inc.
25

under basic conditions afforded N-substituted bisheterocycles 1-6 with four, five, or six methylene groups.
Alkylation was carried out in acetone in the presence of a catalytic amount of tetrabutylammonium iodide. The
obtained products were purified by column chromatography or recrystallized from an appropriate solvent.
Me
Me
N
O
O
Me
Me
N
N
N
O
O
5
Me
O
Me
O
N
N
N
N
Me
Me
Cl
O
Cl
O
6
O
O
N
N
N
N
N
N
N
N
N
N
4
Het
1a
Cl
Cl
O
O
N
N
N
N
N
N
N
N
N
N
1b
3
N
N
N
N
2
1a,b Het = 2,4,5-triphenyl-1H-imidazole; 2 Het = 4,5-diphenyl-1H-imidazole;
3 Het = 4-(1H-benzimidazol-2-yl)-1-(3-chlorophenyl)pyrrolidin-2-one;
4 Het = 4-(1H-benzimidazol-2-yl)-1-(3-chloro-4-methylphenyl)pyrrolidin-2-one;
5 Het = 1-(2,4-dimethylphenyl)dihydropyrimidine-2,4(1H,3H)-dione;
6 Het = 1-(4-methylphenyl)dihydropyrimidine-2,4(1H,3H)-dione.
The structures of 1-6 were confirmed by 1H NMR spectroscopy and mass spectrometry. In the 1H NMR
spectra of the synthesized compounds we observed all proton signals of aromatic rings, heterocyclic rings and
methylene groups, and did not observe protons of the NH group of heterocyclic rings of the initial compounds.
26

EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on the Varian Unity Inova-300 (300 and 75 MHz
respectively) instrument; chemical shifts are reported in ppm on the δ scale with tetramethylsilane as the internal
reference. Mass spectra were determined on the Waters ZQ 2000 spectrometer (ESI, 20 V). Silica gel plates
(Silufol UV-254) were used for analytical purposes. Elemental analysis was carried out on the C, H, N Analyzer
CE 440, and the melting point was determined on the auto probe analyzer APA 1.
2,4,5-Triphenyl-1-[6-(2,4,5-triphenyl-1H-1-imidazolyl)alkyl]-1H-imidazoles (1a,b) and 4,5-Diphenyl-
1-[6-(4,5-diphenyl-1H-1-imidazolyl)hexyl]-1H-imidazole (2) (General Method). To a solution of the
corresponding imidazole (10 mmol) in acetone (150 ml), corresponding dihaloalkane (3.3 mmol) and a catalytic
amount (∼0.1 mmol) of tetrabutylammonium iodide were added. The mixture was stirred to reflux until it
became homogenous. Then, of potassium hydroxide (80%) (0.46 g, 6.6 mmol) was added. The reaction mixture
was refluxed for 4 h. Then the inorganic components were filtered off. The solvent was evaporated.
2,4,5-Triphenyl-1-[6-(2,4,5-triphenyl-1H-1-imidazolyl)butyl]-1H-imidazole (1a). 1.7 g (80% yield),
mp 170°C, purified by column chromatography on silica gel; Rf 0.57 (eluent ethyl acetate−hexane, 1:2). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 7.5-7.1 (30H, m, ArH); 3.56 (4H, t, J = 7.2, 2NCH2); 0.9-0.8 (4H, m, 2CH2).
Mass spectrum, m/z (I, %): 646 [M + H]+ (100). Found, %: C 85.21; H 5.69; N 8.79. C46H38N4. Calculated, %: C
85.42; H 5.92; N 8.66.
2,4,5-Triphenyl-1-[6-(2,4,5-triphenyl-1H-1-imidazolyl)hexyl]-1H-imidazole (1b). 1.6 g (70% yield),
1
mp 224-225°C (diethylether). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.7-7.1 (30H, m, ArH); 3.75 (4H, t,
J = 7.5, 2NCH2); 1.2-1.0 (4H, m, 2CH2); 0.7-0.5 (4H, m, 2CH2). Mass spectrum, m/z (I, %): 674 [M + H]+ (100).
Found, %: C 85.31; H 6.11; N 8.45. C48H42N4. Calculated, %: C 85.43; H 6.27; N 8.30.
4,5-Diphenyl-1-[6-(4,5-diphenyl-1H-1-imidazolyl)hexyl]-1H-imidazole (2). 2.1 g (87% yield), mp
1
233-234°C (ethyl methyl ketone). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.6-7.1 (22H, m, ArH and 2
=CH−); 3.71 (4H, t, J = 7.2, 2NCH2); 1.5−1.3 (4H, m, 2CH2); 1.1-0.9 (4H, m, 2CH2). Mass spectrum, m/z (I, %):
523 [M + H]+ (100). Found, %: C 82.59; H 6.71; N 10.58. C36H34N4. Calculated, %: C 82.72; H 6.56; N 10.72.
Compounds 3, 4 (General Method). To a solution of corresponding benzimidazole (10 mmol) in acetone
(30 ml), of 1.5-dibromopentane (0.74, g 3.2 mmol), of potassium carbonate (0.44 g, 3.2 mmol), and a catalytic
amount of tetrabutylammonium iodide were added. The mixture was stirred to reflux until it became
homogenous. Then, of (80%) potassium hydroxide (0.9 g, 12.8 mmol) was added. The reaction mixture was
refluxed for 4 h. Then the inorganic components were filtered off. The solvent was evaporated.
1-(3-Chlorophenyl)-4-[1-(5-{2-[1-(3-chlorophenyl)-2-oxotetrahydro-1H-4-pyrrolyl)-1H-benzo-
[d]imidazol-1-yl}pentyl)-1H-benzo[d]imidazol-2-yl]-2-pyrrolidinone (3). 1.16 g (52% yield), mp 182-183°C
1
(ethanol). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.7-7.1 (16H, m, ArH); 4.58 and 4.07 (4H, 2t, J = 9.0,
2NCH2); 4.2-4.0 (4H, m, 2CH2Nhet); 3.9-3.8 (2H, m, 2CHhet); 3.1-2.9 (4H, m, 2CH2CO); 1.9-1.8 (4H, m, 2CH2);
1.5-1.4 (2H, m, CH2). Mass spectrum, m/z (I, %): 691 [M + H]+ (100), 693 [M + 2 + H]+ (70). Found, %:
C 67.59; H 5.41; N 12.28. C39H36Cl2N6O2. Calculated, %: C 67.73; H 5.25; N 12.15.
1-(3-Chloro-4-methylphenyl)-4-[1-(5-{2-[1-(3-chloro-4-methylphenyl)-2-oxotetrahydro-1H-3-
pyrrolyl)-1H-benzo[d]imidazol-1-yl}pentyl)-1H-benzo[d]imidazol-2-yl]-2-pyrrolidinone (4). 1.34 g (61%
1
yield), mp 99−100°C (from ethanol). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 7.8−7.2 (14H, m, ArH); 4.59
and 4,09 (4H, 2t, J = 9.0, 2NCH2); 4.2−4.0 (4H, m, 2CH2Nhet); 3.9−3.6 (2H, m, 2CHhet); 3.1−2.9 (4H, m,
2CH2CO); 2.34 (6H, s, 2CH3); 1.9−1.8 (4H, m, 2CH2); 1.6−1.4 (2H, m, CH2). Mass spectrum, m/z (I, %): 719 [M
+ H]+ (100), 721 [M + 2 + H]+ (80). Found, %: C 68.65; H 5. 78; N 11.42. C41H40Cl2N6O2. Calculated, %:
C 68.42; H 5.60; N 11.68.
Compounds 5, 6 (General Method). To a solution of corresponding pyrimidinedione (10 mmol) in
acetone (30 ml), of 1.5-dibromopentane (0.74 g, 3.2 mmol), of potassium carbonate (2 g, 14.5 mmol), and a
catalytic amount of tetrabutylammonium iodide were added. The mixture was stirred to reflux until it became
27

homogeneous. Then, of potassium hydroxide (80%) (0.9 g, 12.8 mmol) was added. The reaction mixture was
refluxed for 4 h. Then the inorganic components were filtered off. The solvent was evaporated.
1-(2,4-Dimethylphenyl)-3-{5-[1-(2,4-dimethylphenyl)-2,4-dioxohexahydro-3-pyrimidinyl]pentyl}-
1
hexahydro-2,4-pyrimidinedione (5). 0.6 g (30% yield), mp 175-176°C (ethanol). H NMR spectrum (CDCl3),
δ, ppm (J, Hz): 7.1-7.0 (6H, m, ArH); 3.82 (4H, t, J = 7.3, 2CH2Nhet); 3.7-3.4 (4H, m, 2NCH2); 2.81 (4H, t,
J = 7.3, 2COCH2); 2.32 (6H, s, 2CH3); 2.18 (6H, s, 2CH3); 1.7−1.6 (4H, m, 2CH2); 1.4-1.3 (2H, m, CH2). Mass
spectrum, m/z (I, %): 505 [M + H]+ (100). Found, %: C 68.82; H 6.97; N 11.34. C29H36N4O4. Calculated, %:
C 69.02; H 7.19; N 11.10.
1-(4-Methylphenyl)-3-{5-[1-(4-methylphenyl)-2,4-dioxohexahydro-3-pyrimidinyl]pentyl}hexahydro-
2,4-pyrimidinedione (6). 1.34 g (46.5% yield), mp 179-180°C (ethanol). 1H NMR spectrum (CDCl3), δ, ppm (J,
Hz): 7.3-7.1 (8H, m, ArH); 3.81 (4H, t, J = 7.2, 2CH2Nhet); 3.9-3.7 (4H, m, 2NCH2); 2.84 (4H, t, J = 7.3,
2COCH2); 2.34 (6H, s, 2CH3); 1.7−1.5 (4H, m, 2CH2); 1.4−1.3 (2H, m, CH2). Mass spectrum, m/z (I, %): 477 [M + H]+
(100). Found, %: C 67.92; H 6.49; N 11.50. C27H32N4O4. Calculated, %: C 68.05; H 6.77; N 11.76.
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