valuable intermediates for the synthesis of bioactive and
industrially important compounds. No organic solvent is
required during the ꢀ-elimination procedure, pure products can
be isolated quickly by phase separation followed by distillation,
and only nonhazardous and inexpensive compounds are used.
We anticipate that the mild conditions employed in the new
procedure will allow it to be used for the large-scale synthesis
of a large number of substrates.
dd, J 1.3 and 5.1).13C NMR (CDCl3): 29.8, 37.4, 69.7, 124.5,
126.2, 127.0, 138.12.
2-Pyridineethanol O-Methanesulfonate (14). 2-Pyridine
ethanol (13) (12.3 g, 0.1 mol) was dissolved in CH2Cl2 (50
mL) and cooled in a water/ice cooling bath. Et3N (12.1 g, 0.12
mol) was added, and methanesulfonyl chloride (13.7 g, 0.12
mol) was added dropwise over 15 min at the same temperature.
After stirring at room temperature for 3 h, the reaction mixture
was diluted with sat. NaHCO3, and the two phases were
separated. The aqueous phase was extracted with CH2Cl2 (20
mL), and the combined extracts were washed with water (20
mL) and dried over Na2SO4; the solvent was removed at
reduced pressure to give 14 (19.7 g, 98%) as a colourless oil
(Calcd for C8H11NO3S: C, 47.75; H, 5.44, N, 6.96. Found: C,
Experimental Section
General Remarks. Substrates 4,10, and 13 are commercially
available. Pellets of NaOH were ground in a mortar before use.
NMR spectra were recorded on a Bruker AC 300 or AC 200
spectrometer, operating at 300.13 or 200.13 MHz for 1H NMR
and 75.3 or 50 MHz for 13C NMR. Chemical shifts are reported
by using CHCl3 as an external standard (δ ) 7.24 ppm for 1H
NMR and 77.0 for 13C NMR). The coupling constants J are
given in hertz. APT experiments were used in the assignment
of carbon spectra.
1
47.86; H, 5.42, N, 6.94); H NMR (CDCl3): δ 2.91 (3 H, s),
3.26 (2 H, t, J 6.3), 4.67 (2 H, t, J 6.3), 7.15–7.21 (2 H, m),
7.62 (1 H, dt, J 1.9 and 7.7), 8.57 (1 H, m).
4-Methyl-5-vinylthiazole (6). To a mixture of mesylate 5
(37.62 g, 0.17 mol) and Et3BnN+Cl- (1.94 g, 0.085 mol) was
added 50% NaOH (45 mL) with vigorous magnetic stirring at
<40 °C. After 2.5 h, the reaction mixture was cooled to 0–5
°C, and water (80 mL) was dropwise added over 15 min at
<15 °C. After dilution with water (50 mL) the organic phase
was separated, diluted with CH2Cl2 (20 mL) and washed with
sat. NH4Cl. The organic phase was separated, phenothiazine
was added as a polymerization inhibitor, and the mixture was
distilled under vacuum (bp 65 °C, 20 mmHg; lit.,7b 78–80 °C,
25 mmHg) to give 6 (19.15 g, 90%) as a colourless oil (Anal.
Calcd for C6H7NS: C, 57.56; H, 5.64; N, 11.19. Found: C,
57.65; H, 5.62; N, 11.16); 1H NMR (CDCl3): δ 2.46 (3 H, s),
5.28 (1 H, d, J 10.9), 5.50 (1 H, d, J 17.2), 6.82 (1 H, dd, J
10.9 and 17.2), 8.55 (1 H, s).
2-Vinylthiophene (12). Under the same reaction conditions
as described for the synthesis of 6, 50% NaOH (13.2 mL) was
added dropwise to a mixture of 11 (10.31 g, 50 mmol) and
Et3BnN+Cl- (0.57 g, 2.5 mol). The reaction mixture was stirred
at 40 °C for 5 h. After the usual workup, the residue was
distilled (64–65 °C, 50 mmHg; lit,17 65.5–66.5 °C, 48 mmHg)
to give 12 (4.52 g, 82%) as a colourless oil. (Anal. Calcd for
C6H6NS: C, 65.41; H, 5.49; N, 29.10. Found: C, 65.53; H, 5.47;
N, 29.17.). 1H NMR (CDCl3): δ 5.13 (1 H, d, J 10.9), 5.56 (1
H, d, J 17.4), 6.80 (1 H, dd, J 10.9 and 17.4), 6.96 (2 H, m),
7.17 (1 H, m). 13C NMR (CDCl3): δ 113.2, 124.3, 125.7, 127.2,
129.8, 143.03.
4-Methyl-5-thiazoleethanol O-Methanesulfonate (5).
Method A. 4-Methyl-5-thiazoleethanol (4) (25.1 g, 0.18 mol)
was dissolved in CH2Cl2 (70 mL) and cooled in a water/ice
cooling bath. After addition of Et3N (20.24 g, 0.20 mol)
methanesulfonyl chloride (22.9 g, 0.20 mol) was added drop-
wise over 15 min at the same temperature. After stirring at room
temperature for 4 h, the reaction mixture was diluted with sat.
NaHCO3, and the two phases were separated. The aqueous
phase was extracted with CH2Cl2 (15 mL), and the combined
extracts were washed with water and dried over Na2SO4; the
solvent was removed at reduced pressure to give 5 (38.30 g,
99%) as a colourless oil that solidified on standing at 0 °C
(Calcd for C7H11NO3S2: C, 37.99; H, 5.01; N, 6.33. Found: C,
1
38.1; H, 5.02; N, 6.35.); H NMR (CDCl3): δ 2.43 (3 H, s),
2.96 (3 H, s), 3.23 (2 H, t, J 9.9), 4.36 (2 H, t, J 9.9), 8.63 (1
H, s).
Method B. 4-Methyl-5-thiazoleethanol (4) (25.1 g, 0.18 mol)
was cooled to 0 °C, and Et3N (20.24 g, 0.20 mol) was added
dropwise over 15 min. Methanesulfonyl chloride (22.9 g, 0.20
mol) was added dropwise over 60 min at the same temperature.
After stirring at room temperature for 4 h, the reaction mixture
was diluted with sat. NaHCO3, and the two phases were
separated. The organic phase was washed with brine (20 mL)
and dried over Na2SO4 to give 5 (35.6 g, 92%) as a yellowish
oil.
2-Vinylpyridine (15). Under the same reaction conditions as
described for the synthesis of 6, 50% NaOH (13.2 mL) was
added dropwise to a mixture of 14 (10.06 g, 50 mmol) and
Et3BnN+Cl- (0.57 g, 2.5 mol). The reaction mixture was stirred
at 40 °C for 2 h (TLC AcOEt/PE, 1:4). After the usual workup,
the residue was distilled (64–65 °C, 21 mmHg; lit,18 68.5 °C,
23 mmHg) to give 15 (4.21 g, 80%) as a colourless oil (Anal.
Calcd for C7H7N: C, 79.97; H, 6.71; N, 13.32. Found: C, 80.12;
H, 6.68; N, 13.35). 1H NMR (CDCl3): δ 5.48 (1 H, dd, J 1.1
and 10.8), 6.20 (1 H, dd, J 1.1 and 17.5), 6.83 (1 H, dd, J 10.8
and 17.5), 7.15 (1 H, m), 7.35 (1 H, m), 7.65 (1 H, dt,
J 1.8 and 7.7), 8.58 (1 H, m).
2-Thiopheneethanol O-Methanesulfonate (11). 2-Thiop-
hene ethanol (10) (12.8 g, 0.1 mol) was dissolved in CH2Cl2
(50 mL) and cooled in a water/ice cooling bath. Et3N (12.1 g,
0.12 mol) was added, and then methanesulfonyl chloride (13.7
g, 0.12 mol) was added dropwise over 15 min at the same
temperature. After stirring at room temperature for 2 h the
reaction mixture was diluted with sat. NaHCO3, and the two
phases were separated. The aqueous phase was extracted with
CH2Cl2 (20 mL), and the combined extracts were washed with
water (20 mL) and dried over Na2SO4; the solvent was removed
at reduced pressure to give 11 (20.4 g, 99%) as a colourless oil
(Calcd for C7H10O3S2: C, 40.76; H, 4.89. Found: C, 40.86; H,
4.91); 1H NMR (CDCl3): δ 2.46 (3 H, s), 2.93 (3 H, s), 3.28 (2
H, t, J 6.7), 4.42 (2 H, t, J 6.7), 6.91–6.96 (2 H, m), 7.20 (1 H,
(17) Schick, J. W.; Hartough, H. D. J. Am. Chem. Soc. 1948, 70, 1646–
1647.
(18) Bauer, L.; Gardella, L. A. J. Org. Chem. 1961, 26, 82–85.
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Vol. 12, No. 4, 2008 / Organic Process Research & Development