Purification-Free, Small-Scale Synthesis of Isothiocyanates
2
3
to approximately 5 bar of pressure. All heating must be conducted
in custom-built glassware or reaction vessels that are provided by
the manufacturer and rated to at least 10 bar.
(ddd, JH,H = 13.4 Hz, JH,H = 7.1, 3.6 Hz, 2 H), 1.80–1.60 (m, 4
H), 1.55–1.30 (m, 4 H) ppm. IR: ν
= 2103 (br. s) cm–1.
˜
max
Supporting Information (see footnote on the first page of this arti-
cle): Characterization data for 7a and 7b as well as H NMR and
4-Methoxyphenyl Isothiocyanate (1a):[8,9] The title compound
(5.2 mg, 71% based on loading of 0.44 mmolg–1) was isolated from
polymer-supported 5,5-diphenoxy-3-[4-methoxyphenyl]-1,4,2-oxa-
thiazole (100 mg) after heating under microwave conditions. 1H
1
IR spectroscopic analysis of the optimized solution-phase fragmen-
tation studies; microwave heating, pressure, and energy profile for
optimized fragmentation conditions; IR spectra to accompany each
transformation shown in Scheme 3 (for compound 1c); 1H NMR
spectra of crude cleavage mixtures for 10a–10i; and 1H NMR spec-
tra for products obtained from 3-year-old samples of 10b–10d and
10i.
3
NMR (400 MHz, CDCl3): δ = 7.17 (d, JH,H = 9.0 Hz, 2 H), 6.85
3
(d, JH,H = 9.0 Hz, 2 H), 3.81 (s, 3 H) ppm. IR: ν
= 2109
˜
max
(s) cm–1.
β-Phenethyl Isothiocyanate (1b):[30] The title compound (3.1 mg,
86% based on loading of 0.44 mmolg–1) was isolated from poly-
mer-supported
3-β-phenethyl-5,5-diphenoxy-1,4,2-oxathiazole
Acknowledgments
(50 mg) after heating under microwave conditions. 1H NMR
(400 MHz, CDCl3): δ = 7.30–7.12 (Ar, 5 H), 3.73 (t, 3JH,H = 7.0 Hz,
2 H), 3.00 (t, 3JH,H = 7.0 Hz, 2 H) ppm. IR: νmax = 2185 (m), 2110
Funding from the Agency for Science, Technology and Research
(A*STAR) is gratefully acknowledged.
˜
(s) cm–1.
Phenyl Isothiocyanate (1c):[8,9] The title compound (2.7 mg, 53%
based on loading of 0.45 mmolg–1) was isolated from polymer-sup-
ported 5,5-diphenoxy-3-phenyl-1,4,2-oxathiazole (80 mg) after
heating under microwave conditions. 1H NMR (400 MHz, CDCl3):
δ = 7.38–7.33 (m, 2 H), 7.30–7.27 (m, 1 H), 7.25–7.21 (m, 2
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= 2064 (s) cm–1.
˜
max
[3] K. K. Brown, M. B. Hampton, Biochim. Biophys. Acta 2011,
4-Methylphenyl Isothiocyanate (1d):[8,9] The title compound
(3.2 mg, 61% based on loading of 0.44 mmolg–1) was isolated from
polymer-supported 3-[4-methylphenyl]-5,5-diphenoxy-1,4,2-oxathi-
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1
azole (80 mg) after heating under microwave conditions. H NMR
(400 MHz, CDCl ): δ = 7.13 (m, 4 H), 2.35 (s, 3 H) ppm. IR: ν
˜
3
max
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4-Nitrophenyl Isothiocyanate (1e):[8,9] The title compound (7.4 mg,
76% based on theoretical loading of 0.60 mmolg–1) was isolated
from polymer-supported 3-[4-nitrophenyl]-5,5-diphenoxy-1,4,2-
12187–12196.
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1
oxathiazole (90 mg) after heating under microwave conditions. H
3
NMR (400 MHz, CDCl3): δ = 8.24 (d, JH,H = 9.0 Hz, 2 H), 7.35
3
(d, JH,H = 9.0 Hz, 2 H) ppm. IR: ν
= 2099 (s), 1585 (s), 1336
˜
max
(s) cm–1.
4-Fluorophenyl Isothiocyanate (1f):[8,9] The title compound (2.0 mg,
30% based on loading of 0.44 mmolg–1) was isolated from poly-
mer-supported 3-[4-fluorophenyl]-5,5-diphenoxy-1,4,2-oxathiazole
(100 mg) after heating under microwave conditions. 1H NMR
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(400 MHz, CDCl ): δ = 7.13 (m, 2 H), 7.04 (m, 2 H) ppm. IR: ν
˜
3
max
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= 2101 (m), 2053 (s) cm–1.
tert-Butyl Isothiocyanate (1g):[9] The title compound (1.7 mg, 33%
based on loading of 0.45 mmolg–1) was isolated from polymer-sup-
ported 3-tert-butyl-5,5-diphenoxy-1,4,2-oxathiazole (100 mg) after
heating under microwave conditions. 1H NMR (400 MHz, CDCl3):
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δ = 1.43 (s, 9 H) ppm. IR: ν
= 2080 (s), 1976 (m) cm–1.
˜
max
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n-Hexyl Isothiocyanate (1h):[8,31] The title compound (1.7 mg, 27%
based on loading of 0.44 mmolg–1) was isolated from polymer-sup-
ported 3-hexyl-5,5-diphenoxy-1,4,2-oxathiazole (100 mg) after
heating under microwave conditions. 1H NMR (400 MHz, CDCl3):
3
3
δ = 3.51 (t, JH,H = 6.7 Hz, 2 H), 1.69 (dq, JH,H = 8.4, 6.7 Hz, 2
H), 1.48–1.23 (m, 6 H), 0.89 (t, J = 6.7 Hz, 3 H) ppm. IR: ν
=
˜
max
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2130 (br. s) cm–1.
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Cyclohexyl Isothiocyanate (1i):[8,9] The title compound (1.1 mg,
22% based on loading of 0.44 mmolg–1) was isolated from poly-
mer-supported
3-cyclohexyl-5,5-diphenoxy-1,4,2-oxathiazole
(80 mg) after heating under microwave conditions. 1H NMR
3
(400 MHz, CDCl3): δ = 3.69 (tt, JH,H = 7.8, 3.7 Hz, 1 H), 1.89
Eur. J. Org. Chem. 2014, 1053–1058
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