BULLETIN OF THE
Article
Synthesis and Screening of Thiazolium Salts
KOREAN CHEMICAL SOCIETY
pressure using phosphorus pentoxide. To this residue, triiso-
propyl orthoformate (9.1 mmol, 2.0 mL) was added before
the reaction mixture was heated to 130 C and maintained at
this temperature for 25 h, after which the triisopropyl orthofor-
mate was removed under reduced pressure. The residue was
dissolved in ethyl acetate and methanol, and the mixture
was filtered through basic alumina and concentrated to give
3-Isopropyl-4-methylthiazol-3-ium tetrafluoroborate
(5). Aqueous tetrafluoroboric acid (1.82 mmol, 0.237 mL)
was added to 4-methylthiazole (1.82 mmol, 0.166 mL) at
ꢀ
ꢀ
0 C, and thewater subsequently removed underreducedpres-
sure using phosphorus pentoxide. Triisopropyl orthoformate
(9.1 mmol, 2.0 mL) was added to the residue, and the reaction
ꢀ
mixture was heated to 130 C. The temperature was main-
the resulting product (1.73 mmol, 396 mg) in 94% yield.
tained at this level for 25 h before the triisopropyl orthofor-
mate was removed under reduced pressure. The residue was
dissolved in ethyl acetate and methanol, and filtered through
basic alumina prior to concentrating it to recover the resulting
1
H NMR (300 MHz, DMSO-d ): δ = 1.55 (d, J = 6.6 Hz,
6
6
1
2
H) 2.59 (s, 3H) 4.87 (septet, J = 6.6 Hz, 1H) 8.04 (s, 1H)
13
0.21 (s, 1H); C NMR (75 MHz, DMSO-d ): δ = 12.74,
6
2.51, 59.00, 132.67, 140.40, 156.41.
product (1.71 mmol, 391 mg) in 94% yield.
1
3-Butyl-5-methylthiazol-3-ium tetrafluoroborate (3).
H NMR (300 MHz, DMSO-d ): δ = 1.54 (d, J = 6.6, Hz
6
Aqueous tetrafluoroboric acid (1.82 mmol, 0.237 mL) was
added to 4-methylthiazole (1.82 mmol, 0.166 mL) at 0 C,
after which the water was removed under reduced pressure
using phosphorus pentoxide. Tributyl orthoformate
6H) 2.56 (s, 3H) 4.98 (septet, J = 6.6 Hz, 1H) 8.49 (s, 1H)
10.02 (s, 1H); C NMR (75 MHz, DMSO-d ): δ = 13.28,
22.64, 55.81, 122.14, 146.30, 157.07.
ꢀ
13
6
3-Butyl-4-methylthiazol-3-ium tetrafluoroborate (6).
Aqueous tetrafluoroboric acid (1.82 mmol, 0.237 mL) was
(
9.1 mmol, 2.4 mL) was added to the residue, and the reaction
ꢀ
ꢀ
mixture was heated to 140 C and maintained at this temper-
ature for 48 h. The tributyl orthoformate was removed under
reducedpressure, andtheresiduewasdissolved inacetonitrile.
The mixture was filtered through basic alumina and concen-
trated to give the resulting product (1.78 mmol, 433 mg) in
added to 4-methylthiazole (1.82 mmol, 0.166 mL) at 0 C,
and the water was removed under reduced pressure using
phosphorus pentoxide. Tributyl orthoformate (9.1 mmol,
2.4 mL) was added to the residue, and the reaction mixture
ꢀ
was heated to 140 C. After 30 h, the tributyl orthoformate
9
8% yield.
was removed under reduced pressure. The residue was dis-
solved in acetonitrile, and the mixture was filtered through
basic alumina and concentrated to give the resulting product
1
H NMR (300 MHz, DMSO-d ): δ = 0.90 (t, J = 7.3 Hz,
6
3
2
H) 1.25 (sextet, J = 7.3 Hz, 2H) 1.82 (quintet, J = 7.3 Hz,
H) 2.55 (s, 3H) 4.46 (t, J = 7.3 Hz, 2H) 8.34 (s, 1H) 10.00
(1.76 mmol, 429 mg) in 97% yield.
13
1
(
1
s, 1H); C NMR (75 MHz, DMSO-d ): δ = 12.59, 13.69,
H NMR (300 MHz, DMSO-d ): δ = 0.92 (t, J = 7.3 Hz,
6
6
9.22, 31.83, 54.78, 134.58, 140.22, 157.77.
3H) 1.32 (sextet, J = 7.3 Hz, 2H) 1.79 (quintet, J = 7.3 Hz,
2H) 2.55 (s, 3H) 4.43 (t, J = 7.3 Hz, 2H) 8.01 (s, 1H) 10.10
3,4-Dimethylthiazol-3-ium tetrafluoroborate (4). Aque-
1
3
ous tetrafluoroboric acid (1.82 mmol, 0.237 mL) was added to
(s, 1H); C NMR (75 MHz, DMSO-d ): δ = 13.03, 13.77,
6
ꢀ
4-methylthiazole (1.82 mmol, 0.166 mL) at 0 C, followed by
19.37, 31.23, 52.55, 122.34, 146.30, 159.40.
the removal of the water under reduced pressure using phos-
phorus pentoxide. Trimethyl orthoformate (9.1 mmol, 1 mL)
was added to the residue, and the resulting mixture was heated
3,4,5-Trimethylthiazol-3-ium tetrafluoroborate (7).
Aqueous tetrafluoroboric acid (1.82 mmol, 0.237 mL) was
added to 4,5-dimethylthiazole (1.82 mmol, 0.19 mL) at
ꢀ
ꢀ
to 110 C. After 23 h at this temperature, the trimethyl ortho-
0 C, after which the water was removed under reduced pres-
formate was removed under reduced pressure and the residue
was dissolved in methanol. This mixture was filtered through
basic alumina and concentrated to give the resulting product
sure using phosphorus pentoxide. Trimethyl orthoformate
(9.1 mmol, 1 mL) was added to the residue, and the reaction
mixture was heated to and maintained at 110 C for 24 h.
ꢀ
(
1.76 mmol, 355 mg) in 97% yield.
The trimethyl orthoformate was removed under reduced pres-
sure. The crude product was recrystallized using ethyl acetate
and hexane. The solvents were removed under reduced pres-
sure, and the resulting product (1.74 mmol, 374 mg) was iso-
1
H NMR (300 MHz, DMSO-d ): δ = 2.48 (s, 3H) 4.05 (s,
6
1
3
3
H) 7.93 (s, 1H) 10.00 (s, 1H); C NMR (75 MHz,
DMSO-d ): δ = 13.03, 40.01, 121.53, 146.67, 159.69.
6
3,4-Dimethylthiazol-3-ium trifluoromethanesulfonate
lated in 96% yield.
1
(4–1). 4-Methylthiazole (1.82 mmol, 0.166 mL) and trifluor-
H NMR (300 MHz, DMSO-d ): δ = 2.37 (s, 3H) 2.46 (s,
6
13
omethanesulfonic acid (1.82 mmol, 0.159 mL) were mixed
with trimethyl orthoformate (9.1 mmol, 1 mL). The reaction
mixture was heated to 110 C and maintained at this temper-
ature for 23 h, after which the trimethyl orthoformate was
removed under reduced pressure. The crude product was
recrystallized using ethyl acetate and diethyl ether. The result-
3H) 4.04 (s, 3H) 9.87 (s, 1H); C NMR (75 MHz, DMSO-
d6): δ = 11.28, 12.23, 40.65, 132.77, 142.62, 156.04.
ꢀ
3-Butyl-4,5-dimethylthiazol-3-ium tetrafluoroborate
(8). Aqueous tetrafluoroboric acid (1.82 mmol, 0.237 mL)
was added to 4,5-dimethylthiazole (1.82 mmol, 0.19 mL) at
ꢀ
0 C, andthe water was removed under reduced pressure using
ing product (1.72 mmol, 453 mg) was collected in 95% yield.
phosphorus pentoxide. Tributyl orthoformate (9.1 mmol,
2.4 mL) was added to the residue, and the reaction mixture
was heated to 140 C. After 24 h at this temperature, the tribu-
1
H NMR (300 MHz, DMSO-d ): δ = 2.48 (s, 3H) 4.06 (s,
6
1
3
ꢀ
3
H) 7.94 (s, 1H) 10.02 (s, 1H); C NMR (75 MHz,
DMSO-d ): δ = 13.06, 47.27, 114.67, 118.94, 121.57,
tyl orthoformate was removed under reduced pressure. The
residue was dissolved in acetonitrile and filtered through basic
6
1
23.21, 127.48, 146.83, 159.73.
Bull. Korean Chem. Soc. 2015
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.bkcs.wiley-vch.de
2