2
Journal of Chemistry
−
OH
(ESI-TOF) m/z: calcd for C H ClO [M−H] 141.0185, found
OH
7
6
141.0107.
HCl, O2, CuCl2
R1
Microwave irradiation
R1
3. Results and Discussion
R2
R2
Cl
3.1. Oxychlorination of Phenols. Oxychlorination of vari-
ous phenols was performed to investigate the reactivities
(Table 1). Under microwave irradiation, 4-chlorophenol was
prepared with high efficiency (93.4%) and perfect selec-
tivity (96.6%), and the reaction was finished only in 60
minutes at 50∘C (Entry 1) with minor amounts of ortho-
substituted products being detected. Oxychlorination of
phenols substituted by electron donating groups (methyl,
methoxyl, isopropyl, etc.) at ortho- and meta-positions was
accomplished with higher conversion rates, lower reaction
time, and excellent selectivity. In particular, compound 6a,
simultaneously substituted by methyl and isopropyl groups
at ortho- and meta-positions, completed the conversion with
100% efficiency and 99.8% selectivity (Entry 6). Furthermore,
oxychlorination of ortho-substituted phenol with aldehyde
group was still finished with high efficiency and excellent
selectivity (Entry 5) but in 50 minutes. Substituting phenol
with methoxyl group (3a) at para-position, the oxychlorina-
tion reaction occurred at ortho-position with lower conver-
sion rate and poor selectivity due to the dual-orienting effect
(Entry 3).
Scheme 1: Microwave-promoted oxychlorination of phenols.
Technology Development Co., Ltd., Beijing, China) and
measured by a gas chromatography (GC) using a Shimadzu
GC-2014C instrument.
2.1. General Methods. Phenols (78 mmol) and a catalytic
amount of CuCl (7.8 mmol) were dissolved in 100 mL of
2
aqueous hydrochloric acid solution (6 mol/L), and the mix-
ture was bubbled with dioxygen (22 mL/min). e reaction
was performed on a microreactor at 50∘C and measured by
gas chromatography (GC). Afer GC showed the disappear-
ance of the starting material, the reaction was extracted with
dichloromethane (100 mL × 2), and the organic layer was
washed with water (50 mL × 2) and fractionated to give the
desired product.
1H NMR and HRMS spectra can be seen in the
.org/10.1155/2016/2960414.
3.2. Proposed Reaction Mechanism. Different conditions were
researched to investigate the proposed reaction mechanism
in oxychlorination of phenol. As it is shown in Table 2, with-
out addition of hydrochloric acid, there was no chlorination
product detected in this reaction, and the chlorination effi-
1
Compound 1b: H NMR (400 MHz, CDCl ) ꢀ 7. 24–7. 17
3
(m, 2H, Ph), 6.77–6.74 (m, 2H, Ph), 5.27 (s, 1H, OH); HRMS
−
(ESI-TOF) m/z: calcd for C H ClO [M−H] 127.0029, found
6
4
126.9956.
Compound 2b: 1H NMR (400 MHz, DMSO-ꢁ6) ꢀ 9.20 (s,
1H, OH), 6.95 (d, ꢂ = 2.0 Hz, 1H, Ph), 6.79–6.75 (m, 2H,
Ph), 3.78 (s, 3H, OCH ); HRMS (ESI-TOF) m/z: calcd for
ciency was only 10.3% when hydrochloric acid was replaced
with sulfuric acid, which indicated that hydrochloric acid was
performed as chlorine source. As the catalyst, CuCl played
3
2
−
−
C H ClO [M − H] 157.0135, found 157.0056.
an essential role in chlorination reaction. In the absence of
7
7
6
2
Compound 3b: 1H NMR (400 MHz, DMSO-ꢁ6) ꢀ 9.55 (s,
CuCl , no product was formed and no other reactions were
2
1H, OH), 6.94–6.90 (m, 2H, Ph), 6.76 (dd, ꢂ = 3.2, 8.8 Hz,
1H, Ph), 3.69 (s, 3H, OCH ); HRMS (ESI-TOF) m/z: calcd for
occurred, and replacement of CuCl by lithium chloride still
2
could not promote the reaction. Furthermore, the conversion
3
C H ClO [M − H] 157.0135, found 157.0059.
rate was relatively low when the procedure was not bubbled
with dioxygen, which proved its participation in oxidation.
6
2
Compound 4b: 1H NMR (400 MHz, DMSO-ꢁ6) ꢀ 9.51 (s,
1H, OH), 7.16 (d, ꢂ = 8.8 Hz, 1H, Ph), 6.74 (d, ꢂ = 2.4 Hz,
1H, Ph), 6.62 (dd, ꢂ = 2.8, 8.8 Hz, 1H, Ph), 2.24 (s, 3H, CH );
A proposed reaction mechanism is depicted in Scheme 2.
As conventional mechanism of phenol chlorination [9], one
electron transfers from Cu(II) to phenoxy radical B via the
complex A and simultaneously generates copper(I) chloride
3
−
HRMS (ESI-TOF) m/z: calcd for C H ClO [M−H] 141.0185,
7
6
found 141.0116.
Compound 5b: 1H NMR (400 MHz, DMSO-ꢁ6) ꢀ 10.93
(s, 1H), 10.23 (s, 1H), 7.60 (d, ꢂ = 2.8 Hz, 1H, Ph), 7.54 (dd, ꢂ =
2.8, 8.8 Hz, 1H, Ph), 7.05 (d, ꢂ = 8.8 Hz, 1H, Ph); HRMS (ESI-
(CuCl). en, radical B converts to the tautomeric structure
C, followed by chlorination with CuCl to form intermediate
2
product D and CuCl. Tautomerization of D affords the
−
TOF) m/z: calcd for C H ClO [M − H] 154.9978, found
desired product 4-chlorophenol, and CuCl generated in this
7
4
2
154.9898.
reaction converts to CuCl in the presence of hydrochloric
2
1
Compound 6b: H NMR (400 MHz, DMSO-ꢁ6) ꢀ 9.39
acid and dioxygen. Our previous experiments revealed that
insufficient concentration of [H+] caused the transformation
of radical C to benzoquinone. Furthermore, major byproduct
monitored in this reaction was 2-chlorophenol which was
generated from tautomerization of radical C into E, and
further conversions as the similar procedure to form 4-
chlorophenol gave the ortho-substituted product. It seems
that the key step of the reaction is the formation of radicals
(s, 1H, OH), 7.04 (s, 1H, Ph), 6.72 (s, 1H, Ph), 3.15–3.12
(m, 1H, CH(CH ) ), 2.19 (s, 3H, CH ), 1.12 (d, ꢂ
=
1H, OH), 7.10 (d, ꢂ3=22.4 Hz, 1H, Ph), 7.01 (dd, ꢂ = 2.8, 8.4 Hz,
3
6.8 Hz, 6H, CH(CH ) ); HRMS (ESI-TOF) m/z: calcd for
3 2
−
C H ClO [M − H] 183.0655, found 183.0579.
10 13
Compound 7b: 1H NMR (400 MHz, DMSO-ꢁ6) ꢀ 9.52 (s,
1H, Ph), 6.78 (d, ꢂ = 8.8 Hz, 1H, Ph), 2.11 (s, 3H, CH ); HRMS
3