K. Liu et al. / Tetrahedron xxx (2015) 1e4
3
Table 2 (continued )
insecticides. It can also be transformed into a variety of other useful
functionalized compounds.
Entry
Styrene
Product
Yield(%)b
4. Experimental section
4.1. General
17e
3r N.Dc
All reactions were carried out in oxygen atmosphere. 1H NMR
(400 MHz or 300 MHz) and 13C NMR (150 or 100 MHz) spectra were
determined with CDCl3 or DMSO-d6 as solvent and tetramethylsi-
lane (TMS) as internal standard. Chemical shifts were reported in
a
Styrene (2.0 equiv), NH4SCN (1.0 equiv) in HOAc (3 mL) at 25 ꢀC for 8 h in oxygen
atmosphere.
b
c
Isolated yield.
N.D. means no reaction.
40 ꢀC.
60 ꢀC for 24 h.
parts per million from internal TMS (d), all coupling constants (J
d
e
values) were reported in Hertz (Hz). High resolution mass spectra
were recorded on a TOF machine (ESI). Column chromatography
was performed with 300e400 mesh silica gel using flash column
techniques. All of the reagents were used directly as obtained
commercially unless otherwise noted.
aryl is necessary for oxythiocyanation of alkenes since the aryl
moiety can stabilize the carbon radical formed.
4.2. General procedure for the preparation of compound 3
The mixture of styrene (2.0 mmol) and ammonium thiocyanate
(1.0 mmol) in HOAc (3 mL) was stirred in an oxygen atmosphere at
25 ꢀC for 8 h. After removal of solvent under reduced pressure, the
residue was purified by flash silica-gel column chromatography
(eluted with petroleum ether/acetone from 50/1 to 8/1 (v:v)) to
afford the desired phenacylthio-cyanate 3.
Scheme 1. The structure of a- or b-substituted styrenes and non-conjugated terminal
alkenes.
4.3. Characterization
To understand the reaction mechanism, TEMPO (2,2,6,6-
tetramethyl-1-piperidinyloxy, 1.2 equiv) was added to the re-
action of styrene with ammonium thiocyanate and it was found
that oxythiocyanation reaction did not take place. This confirmed
that the reaction proceeded through a free radical process. Based on
this finding, a reaction mechanism was proposed in Scheme 2.
Thiocyanate radical 4 derived from 2 selectively adds to the ter-
minal end of the C]C double bond of 1 to form benzyl radical 5,
which interacts with O2 to form peroxy radical 6 that further ab-
stracts hydrogen to afford hydroperoxide 7, followed by fragmen-
tation to give product 3.8
4.3.1. 2-Thiocyanatoacetophenone (3a).5a Yellow oil (139 mg, 79%
yield). 1H NMR (400 MHz, CDCl3):
d
7.95 (d, J¼8.0 Hz, 2H),7.68 (t,
J¼8.0 Hz, 1H), 7.54 (t, J¼8.0 Hz, 2H), 4.75 (s, 2H). 13C NMR (150 MHz,
CDCl3):
d 190.8, 134.8, 133.9, 129.1, 128.4, 111.8, 43.0. HRMS (ESI-
TOF) m/z: (MþH)þ calcd for C9H8NOS 178.0327, found 178.0320.
4.3.2. 20-Methyl-2-thiocyanatoacetophenone (3b).4e White solid
(148 mg, 78% yield), mp 80e82 ꢀC. 1H NMR (400 MHz, CDCl3):
d
7.92
(d, J¼8.0 Hz, 1H), 7.53 (t, J¼8.0 Hz, 1H), 7.38 (t, J¼8.0 Hz, 2H), 5.05 (s,
2H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3):
195.6, 138.9, 134.8,
d
133.2, 132.5, 130.4, 126.6, 113.4, 44.2, 21.4. HRMS (ESI-TOF) m/z:
(MþH)þ calcd for C10H10NOS 192.0483, found 192.0480.
4.3.3. 30-Methyl-2-thiocyanatoacetophenone
(3c).9 Yellow
7.73 (d, J¼12.0 Hz,
oil
(120 mg, 63% yield). 1H NMR (400 MHz, CDCl3):
d
2H), 7.48 (d, J¼8.0 Hz, 1H), 7.41 (t, J¼8.0 Hz, 1H), 4.73 (s, 2H), 2.44 (s,
3H). 13C NMR (100 MHz, CDCl3):
d 191.0, 139.2, 135.6, 133.9, 129.0,
128.9,125.7,111.9, 43.2, 21.3. HRMS (ESI-TOF) m/z: (MþH)þ calcd for
C10H10NOS 192.0483, found 192.0476.
4.3.4. 40-Methyl-2-thiocyanatoacetophenone
(3d).10 Yellow oil
(152 mg, 80% yield). 1H NMR (400 MHz, CDCl3):
d
7.86 (d, J¼8.0 Hz,
2H), 7.34 (d, J¼8 Hz, 2H), 4.75 (s, 2H), 2.47 (s, 3H). 13C NMR (100 MHz,
CDCl3): d 190.4, 146.1, 131.5, 129.8, 128.6, 112.0, 43.1, 21.9. HRMS (ESI-
Scheme 2. Proposed mechanism for molecular oxygen induced free radical oxy-
thiocyanation of styrenes leading to a-oxothiocyanates.
TOF) m/z: (MþH)þ calcd for C10H10NOS 192.0483, found 192.0478.
4.3.5. 40-Acetoxybenzoic acid (3h).11 Yellow oil (54 mg, 30% yield).
3. Conclusion
1H NMR (400 MHz, CDCl3):
d
9.99 (s, 1H), 7.92 (d, J¼8.0 Hz, 2H), 7.28
(d, J¼8.0 Hz, 2H), 2.34 (s, 3H). 13C NMR (150 MHz, CDCl3):
d 190.9,
A facile and efficient protocol of oxythiocyanation of styrenes
with ammonium thiocyanate has been developed. The reaction
proceeded under mild conditions to afford the phenacylth-
iocyanates in moderate to good yields. This method is straightfor-
ward, green and cost-effective, requires no catalyst, additives or
other oxidant except O2. The phenacylthiocyanates obtained can be
directly applied in syntheses of important medicinal agents such as
anticancer, antiasthmatic drugs, DNA topoisomerase inhibitors, and
168.7, 155.3, 134.0, 131.2, 122.4, 21.2. MS (ESI-TOF) m/z: (MþH)þ
calcd for C9H9O4 181.0, found 181.0.
4.3.6. 20-Fluoro-2-thiocyanatoacetophenone
(3i).3c Yellow
7.99 (t, J¼8.0 Hz,
oil
(55 mg, 28% yield). 1H NMR (400 MHz, CDCl3):
d
1H), 7.65 (dd, J¼16.0, 8.0 Hz, 1H), 7.32 (t, J¼8.0 Hz, 1H), 7.25e7.17
(m, 1H), 4.65 (s, 2H). 13C NMR (100 MHz, CDCl3):
188.5, 162.4 (d,
J¼255.3 Hz), 136.7 (d, J¼9.4 Hz), 136.1, 125.2, 122.3 (d, J¼12.2 Hz),
d