10.1002/chem.201605238
Chemistry - A European Journal
FULL PAPER
Synthesis of 1,3-dimethyl-1H-benzo[d]imidazole-2(3H)-thione (4). To
a solution of N-methyl benzimidazole (0.9 g, 6.80 mmol) in ethyl acetate,
methyl iodide (0.67 mL, 10.15 mmol) was added dropwise at 0°C.
Reaction mixture was stirred for 4 h to produce the corresponding salt as
a white solid (0.75 g, 5.06 mmol) which was isolated after the reaction
and, then, dissolved in dry methanol (50 mL). The sulfur powder (0.24 g,
7.60 mmol) and anhydrous potassium carbonate (1.05 g, 7.60 mmol) was
added to the above methanol solution and the reaction mixture was
allowed to reflux for 20 h. The solution was then filtered in hot condition
through celite. Filtrate was evaporated under reduced pressure to yield
yellow crude which was purified by column chromatography packed with
silica ethyl acetate/hexane as mobile phase (0.3%).The desired product
was obtained as a white crystalline solid. Yield: 0.76 g (63%). 1H NMR
(CD3OD) δ (ppm) = 3.74 (s, 6H), 7.24-7.29 (m, 2H), 7.30-7.33 (m, 2H),
13C NMR (CD3OD) δ (ppm) = 31.4, 110.2, 124.1, 133.6, 170.9. HR-
ESIMS (m/z): calcd for [M+H]+ C9H10N2S = 179.0637, found: 179.0644.
Synthesis
of
1-(2-hydroxyethyl)-3-methyl-1H-benzo[d]imidazol-
2(3H)-one (11). Procedure 1: A mixture of 1 (9.4 mg, 45 µmol) and 4-
(hydroxymercuri)benzoic acid sodium salt (16.2 mg, 45 µmol, Ar1HgOH,
Ar1 = p-C6H4CO2Na) was stirred in 3 mL of water/acetonitrile solution
(1:1) for 2 h at 37°C. After 2h, the black HgS nanoparticles were washed
several times with acetonitrile followed by with water and characterized
by TEM, SEM and EDX analysis. The supernatant part was evaporated
under vacuum and the compound 11 was extracted with chloroform and
purified by column chromatography, yield: 3.5 mg (40%).
Procedure 2:
A mixture of compound 1 (9.4 mg, 45 µmol) and
methylmercury chloride (11.3 mg, 45 µmol) or ethylmercury chloride
(11.9 mg, 45 µmol) or 4-chloromercuribenzoic acid (ArHgCl, Ar = p-
C6H4CO2H) (16.0 mg, 45 µmol) was stirred in 3 mL of water/acetonitrile
mixture (1:1) for 1 h at 37°C. After 1 h, aqueous KOH (45 µmol) was
added to the above reaction mixture and was continued to stir for another
2 h. The black HgS nanoparticles were washed several times with
acetonitrile followed by with water and characterized by several
techniques as mentioned above. Supernatant part was extracted with
organic solvent as mentioned above and compound 11 was purified by
column chromatography, yield = 3.2 mg (37%). Characterization data of
11: 1H NMR (CDCl3) δ (ppm) = 3.37 (s, 3H), 3.95 (t, J = 5.20 Hz, 2H),
4.03 (t, J = 5.20 Hz, 2H), 6.96-7.06 (m, 3H), 7.06-7.12 (m, 1H), 13C NMR
(CDCl3) δ (ppm) = 27.2, 44.4, 61.4, 107.7, 107.9, 121.5, 121.5, 129.7,
130.1, 155.2. HR-ESIMS (m/z): calcd for [M+H]+ C10H12N2O2 = 193.0972,
Found : 193.0974. calcd for [M+Na]+ = 215.0791, found: 215.0789.
Synthesis of 1-(2-methoxyethyl)-3-methyl-1H-benzo[d]imidazole-
2(3H)-thione (5). 1-methylbenzimidazole (0.5 g, 3.78 mmol) and 2-
chloroethylmethylether (0.35 g, 3.78 mmol) was heated at 80 C. After 4
days the white salt (0.66 g) was taken in anhydrous methanol (50 mL)
and treated with elemental sulfur (0.12 g, 3.78 mmol), anhydrous
potassium carbonate (0.52 g, 3.78 mmol). The reaction mixture was
allowed to reflux for 20 h. The solution was then filtered in hot condition
through celite. Filtrate was evaporated under reduced pressure to yield
yellow crude which was purified by column chromatography packed with
silica ethyl acetate/hexane as mobile phase (50 %). The desired product
was obtained as a white crystalline solid. Yield: 0.52 g (63%). 1H NMR
(CDCl3) δ (ppm) = 3.30 (s, 3H), 3.77 (s, 3H), 3.78 (t, J = 5.60 Hz, 2H),
4.49-4.52 (t, J = 5.60 Hz, 2H), 7.15-7.18 (m, 1H), 7.21-7.23 (m, 2H),
7.30-7.33 (m, 1H), 13C NMR (CDCl3) δ (ppm) = 31.2, 45.1, 59.1, 70.3,
108.8, 110.1, 122.9, 123.0, 132.4, 132.8, 169.5. HR-ESIMS (m/z): calcd
for [M+H]+ C11H14N2OS = 223.0900, found: 223.0906.
General procedure for the synthesis of 1:1 RHg-conjugated
complexes (18-20):
Synthesis of 18: A mixture of compound 1 (9.4 mg, 45 μmol) and 4-
chloromercuribenzoic acid (16.1 mg, 45 μmol; ArHgCl, Ar = p-C6H4CO2H)
was stirred in 3 ml of water/ acetonitrile mixture (1:1) for 1 h. Solvent was
evaporated completely under vacuum to obtain 18 as yellow solid. 1H
NMR of 18 (DMSO-d6) δ (ppm) = 3.71 (s, 3H), 3.74 (t, J = 5.6 Hz, 2H),
4.33 (t, J = 5.6 Hz, 2H), 7.23-7.92 (m, 8H), 13C NMR (CD3OD) δ (ppm)
=30.8, 46.8, 58.3, 109.2, 110.1, 122.5, 122.6, 128.0, 128.4, 129.9, 131.8,
132.3, 136.8, 138.1, 158.0, 167.4, 168.5. 199Hg NMR (DMSO-d6) δ (ppm)
-1186. HR-ESIMS (m/z): calcd for [M]+ C17H17HgN2OS = 531.0661,
found: 531.0674.
Synthesis of 1-(2-hydroxyethyl)-1H-benzo[d]imidazole-2(3H)-thione
(7). For the synthesis compound 7, the nucleophilic sulfur center of 6 is
protected with trityl group following the literature procedure and used for
next step.
To the dispersed solution
of 2-(tritylthio)-1H-
benzo[d]imidazole (1 g, 2.54 mmol) in dry acetone (25 ml), potassium
hydroxide (0.71 g, 1.27 mmol) was added and stirred for 5 min, then 2-
bromoethonal (0.38 g, 3.08 mmol) was added dropwise at 0°C and
stirred for 8 h. After 8 h the mixture was poured into 25 ml of water and
extracted with ethyl acetate (2×45ml) and washed with brine and dried
over Na2SO4 and filtered. Filtrate was evaporated under reduced
pressure to yield solid which was dissolved in 5% acetic acid in methanol
and reflux for 30 min. The solution was concentrated and washed with
NaHCO3 solution and the expected compound was extracted with ethyl
acetate. Organic layer was concentrated under reduced pressure to yield
crude which was purified by column chromatography packed with silica
and ethyl acetate/hexane as mobile phase (35%). The desired compound
Synthesis of 19: A mixture of compound 1 (9.4 mg, 45 μmol) and EtHgCl
(11.9 mg, 45 μmol) was stirred in 3 ml of water/ acetonitrile mixture (1:1)
for 1 h. Solvent was evaporated completely under reduced pressure to
yield 19 as white solid. 1H NMR 19 (CD3OD) δ (ppm) = 1.33 (t, J =7.9Hz,
3H), 1.84 (q, J =7.9Hz, 2H), 3.80 (s, 3H), 3.93 (t, J = 5.7 Hz, 2H), 4.47 (t,
J = 5.7 Hz, 2H), 7.28-7.31 (m, 2H) , 7.37-7.48 (m, 2H), 13C NMR
(CD3OD) δ (ppm) = 14.0, 22.7, 31.6, 48.2, 60.4, 110.4, 111.2, 124.3,
124.3, 133.73, 133.9,169.3. 199Hg NMR (DMSO-d6) δ (ppm) -1009. HR-
ESIMS (m/z): calcd for [M]+ C12H17HgN2OS = 439.0762, found: 439.0702.
º
was obtained as a white crystalline solid upon cooling at 4 C. Yield: 0.29
g (59%). 1H NMR of 7 (CD3OD) δ (ppm) = 3.93 (t, J = 5.60 Hz, 2H), 4.40
(t, J = 5.60 Hz, 2H), 7.19-7.23 (m, 3H), 7.37-7.39 (m, 1H). 13C NMR
(CD3OD) δ (ppm) = 47.3, 60.6, 110.7, 111.1, 123.6, 124.1, 132.2, 135.1,
169.7. HR-ESIMS (m/z): calcd for [M+H]+C9H10N2OS= 195.0587, found:
195.0588.
Synthesis of 20: A mixture of compound 1 (9.4 mg, 45 μmol) and MeHgCl
(11.3 mg, 45 μmol) was stirred in 3 ml of water/ acetonitrile mixture (1:1)
for 1 h. Solvent was evaporated completely under vacuum to obtain 20
1
as white solid. H NMR 20 (CD3OD) δ (ppm) = 0.91(s, 3H), 3.79 (s, 3H),
3.93 (t, J = 5.7 Hz, 2H), 4.47 (t, J = 5.7 Hz, 2H), 7.28-7.30 (m, 2H) , 7.36-
7.47 (m, 2H); 13C NMR (CD3OD) δ (ppm) = 3.73,31.58, 48.17, 60.49,
110.37, 111.18, 124.28, 124.31, 133.71, 134.0,169.60. 199Hg NMR
(DMSO-d6) δ(ppm) -848. HR-ESIMS (m/z): calcd for [M]+ C11H15HgN2OS
= 425.0605, found: 425.061.
Synthesis of 1-methyl-1H-benzo[d]imidazole-2(3H)-thione (8).
Compound 8 is synthesized following literature procedure.[10] 1H NMR of
8: (DMSO d6) δ (ppm) = 3.65 (s, 3H), 7.18-7.19 (m, 3H), 7.35-7.36 (m,
1H), 13C NMR (DMSO d6) δ (ppm) = 30.0, 109.4, 109.5, 122.1, 122.8,
130.6, 133.1, 168.5. HR-ESIMS (m/z): calcd for [M+H]+ C8H8N2S=
165.0480, found: 165.0485.
Synthesis of 28: Method 1: Compound 28 was obtained as a by-product
in the form of white crystalline material from a reaction solution of EtHgCl
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