Hydrolysis of diazonium salts using a two-phase system (CPME and water)

Article abstract of DOI:10.1002/hc.21275

A new method for the hydrolysis of diazonium salts, without the formation of tar, was developed. A two-phase system consisting of cyclopentyl methyl ether (CPME) and water is very effective for the hydrolysis of diazonium salts. Using this solvent system, the diazonium salt prepared from 3-(4-nitrophenoxy)aniline gave 3-(4-nitrophenoxy)phenol in high yield (96%) within 20 min. The synthesized phenol is an industrially important raw material in polymer syntheses. Furthermore, the use of the present two-phase system of CPME and water successfully brought about the efficient conversions of several m-substituted anilines into the corresponding m-substituted phenols. This is the first example of hydrolysis of diazonium salts using the two-phase system (CPME and water).

Full text of DOI:10.1002/hc.21275

Heteroatom Chemistry
Volume 26, Number 6, 2015
H
ydrolysis of Diazonium Salts Using a
Two-Phase System (CPME and Water)
1,2
1
1
Toshihide Taniguchi, Mitsutaka Imoto, Motonori Takeda,
Takeo Nakai, Masatoshi Mihara, Toshiyuki Iwai, Takatoshi Ito,
3
3
3
3
3
2
2
Takumi Mizuno, Akihiro Nomoto, and Akiya Ogawa
1
Seika Corporation, Wakayama, 641-0007, Japan
2Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
Sakai, Osaka, 599-8531, Japan
3Osaka Municipal Technical Research Institute, Joto-ku, Osaka, 536–8553, Japan
Received 23 April 2015; revised 26 May 2015
3
-phenoxyphenols and 4-phenoxyphenols have re-
ABSTRACT: A new method for the hydrolysis of di-
azonium salts, without the formation of tar, was de-
veloped. A two-phase system consisting of cyclopentyl
methyl ether (CPME) and water is very effective for
the hydrolysis of diazonium salts. Using this sol-
vent system, the diazonium salt prepared from 3-(4-
nitrophenoxy)aniline gave 3-(4-nitrophenoxy)phenol
in high yield (96%) within 20 min. The synthe-
sized phenol is an industrially important raw ma-
terial in polymer syntheses. Furthermore, the use
of the present two-phase system of CPME and wa-
ter successfully brought about the efficient conver-
sions of several m-substituted anilines into the cor-
responding m-substituted phenols. This is the first
example of hydrolysis of diazonium salts using the
two-phase system (CPME and water). ꢀC 2015 Wi-
ceived much attention as monomers of polypheny-
lene oxide because they are more reactive than
unsubstituted phenol, and less isomer formation oc-
curs during the coupling reaction [1,2].
In our project concerning the production
of a raw material for functional plastics (poly-
imide resin), 3-(4-aminophenoxy)phenol and 3-(4-
nitrophenoxy)phenol (3a) are very significant com-
pounds [3, 4]. Thus, many synthetic methods for
3
a have been reported. Among them, 3a has typi-
cally been synthesized through the aromatic nucle-
ophilic substitution of resorcinol with 4-halogenated
nitrobenzenes [5]. However, this reaction required
high temperature and prolonged reaction time, and
the yields were moderate. Generally, the synthesis
of 3-substituted phenols is difficult, because phe-
nol has ortho-/para-directing property due to the
electron-donating hydroxyl group. For ortho- and
para-functionalization of phenols, many methodolo-
gies are well investigated. However, this strong di-
recting effect prevents the selective direct function-
alization of phenols at the meta position [6].
ley Periodicals, Inc. Heteroatom Chem. 26:411–
416, 2015; View this article online at wileyonlineli-
brary.com. DOI 10.1002/hc.21275
INTRODUCTION
To develop a safe, simple, low-cost, and high-
yielding synthetic method, the synthesis of 3a using
the hydrolysis of diazonium salt 2a prepared from
Phenoxyphenols play a key role in the field
of aromatic polymer materials. In particular,
3
-(4-nitrophenoxy)aniline (1a) was examined [7].
However, the classical reactions described in text-
books are not always practical and industrially fea-
sible. In such reaction systems, large amounts of tar
Correspondence to: Toshihide Taniguchi; e-mail: t-taniguchi@
waseika.com.
ꢀ
2015 Wiley Periodicals, Inc.
C
411

412 Taniguchi et al.
O
N2+ OSO H-
O
OH
3
H O
2
+
Unreacted 2a
O N
2
O N
2
2
a
3a
3a (46%)
+
Azo Compounds (Tar)
SCHEME 1 Synthesis of 3a.
formed in the aqueous phase, is converted into 3a,
which is immediately extracted by organic solvent.
Using this two-phase system (organic solvent and
water), it is possible to avoid the diazo coupling re-
action between the diazonium salt 2a and obtained
3a
Organic solvent
3a.
2a
3a
2a
3a
Diazonium salt 2a was prepared from 1a and
Tar
(Coupling compounds)
X
Water
Water
sodium nitrite in concentrated sulfuric acid. The so-
lution of 2a was poured into a mixture of an organic
solvent and water, and then the resulting solution
was refluxed (Method A, see Experimental section).
The hydrolysis reaction using toluene as a co-
solvent gave 3a in low yield (26%) (Entry 1). As
toluene has an electron-donating Me group, it can
act as a good coupler for the diazo coupling reaction.
Therefore, it was considered that the diazo coupling
reaction of 2a with toluene proceeded preferentially.
Next, using ethyl acetate, the yield of 3a improved to
SCHEME 2 Expected effect of two-phase system.
are formed during the reaction, making the reason-
able access of suitable experimental manipulation
difficult. To solve this problem, the use of a two-
phase system comprising a mixture of an organic
solvent and water was envisioned. After intensive
examinations of the hydrolysis of 2a prepared from
1
a using a variety of two-phase systems, we herein
6
7% (Entry 2). In the case of ethyl acetate, the two-
report the surprising effect of a two-phase system
consisting of cyclopentyl methyl ether (CPME) and
water. To the best of our knowledge, this is the first
example of the hydrolysis of diazonium salts using
the two-phase system.
phase system was maintained at the initial stage,
but became monophasic at the end of the hydrolysis
reaction. This is because of the hydrolysis of ethyl
acetate with sulfuric acid, which affords acetic acid
and ethanol. Keeping the good result of ethyl ac-
etate (Entry 2) in mind, tolerance of several esters
under the strong acidic conditions was examined
RESULTS AND DISCUSSION
(
Entries 3–6). Butyl acetate and s-butyl acetate gave
3
a in high yields (Entries 4 and 5). After the reac-
At the outset, we attempted to synthesize 3a accord-
ing to a literature method [7] (Scheme 1). The dia-
zonium salts 2a, which was prepared from 1a using
sodium nitrite and sulfuric acid, was poured into
a dilute solution of sulfuric acid under heating at
reflux temperature. In this hydrolysis procedure, tar
was formed, and the yield of 3a was 46% (Scheme 1).
In thin layer chromatography analysis, many polar
compounds were observed. The tar formation sug-
gested that a competitive reaction of 3a with unre-
acted 2a occurred in the aqueous phase. In other
words, the tar polymer or oligomer may be formed
via diazo coupling of the diazonium salt 2a with the
resulting phenol 3a before the nucleophilic substitu-
tion of 3a with water takes place.
tion, however, acetic acid was formed. Chlorinated
solvents and nitrobenzene were also examined. In
these cases, tar was formed and 3a was produced in
moderate yields (64–71%) (Entries 7–11). In the hy-
drolysis of 2a with water, product 3a and tar tend to
float at the surface of water. Hence, the extractive ef-
fect for 3a with heavier solvents such as chlorinated
solvents might be lower than that in lighter solvents.
Also, chlorinated solvents are industrially less ac-
cessible. Ketones were also examined as cosolvents.
The hydrolysis of 2a proceeded with excellent yields
in ketones (88–89%) (Entries 12–14). However, a
highly unpleasant odor was occasionally generated
as a result of oxidation of the ketones. Therefore, ke-
tones are not suitable as cosolvents for the industrial
production of phenols 3. Then, the effect of ethers
was examined (Entries 15–17). To our surprise, the
To prevent the diazo coupling reaction, a two-
phase system of organic solvent and water was de-
vised (Scheme 2 and Table 1). Diazonium salt 2a,
Heteroatom Chemistry DOI 10.1002/hc

Hydrolysis of Diazonium Salts Using a Two-Phase System (CPME and Water) 413
TABLE 1 Optimization of Organic Solvents for the Two-Phase System
Entry
Solvent
Yield (%)a
Entry
Solvent
Yield (%)a
b
1
2
3
4
5
6
7
8
9
Toluene
Ethyl acetate
Isopropyl acetate
Butyl acetate
s-Butyl acetate
f-Butyl acetate
Chloroform
1,2-Dichloroethane
Chlorobenzene
1,2-Dichlorobenzene
Nitrobenzene
26
67
13
14
15
16
17
18
19
20
21
22
23
Methyl isobutyl ketone
Diisobutyl ketone
2-Methy itetra hydrofuran
Methyl f-butyl ether
Cyclopentyl methyl ether (CPME)
Methyl alcohol
Acetonitrile
Isopropyl alcohol
f-Butyl alcohol
89
88
77
b
b
78
84
85
62
64
b
96
63
60
66
70
71
b
64
64
68
70
71
88
10
11
12
Sulfolane
Tetrahydrofuran
b
80
2-Pentanone
a
HPLC yields.
Isolated yields.
b
reaction using CPME proceeded smoothly to give 3a
in almost quantitative yield (Entry 17). In diazotiza-
tions, few examples using a mixture of an organic
solvent and water have been reported [8, 9]. How-
ever, this is the first example of the hydrolysis of
diazonium salts 2 in two-phase system (CPME and
water).
benzyloxyaniline (1c), 3c was obtained in moder-
ate yield (64%) (Entry 3). The anilines featuring
meta-substituted electron-donating group (1d–1f)
and meta-substituted electron-withdrawing group
(1g, 1i, and 1j) afforded the corresponding phe-
nols (3d–3g, 3i, and 3j) in excellent yields (91–98%)
(Entries 4–7, 9, and 10). For the synthesis of m-
nitrophenol (3h), higher reaction temperature was
required and the yield of 3h was lowered. Then, the
use of pseudocumene (bp 169°C) as a cosolvent af-
forded 3h in reasonable yield (Entry 8). These results
show that a simple and useful synthetic method for
m-substituted phenols was established successfully.
Furthermore, the syntheses of ortho- and para-
substituted phenols 3k–3n from the anilines 1k–1n
were investigated (Table 3). The corresponding prod-
ucts 3k–3n were obtained in high yields (82–96%)
(Entries 1–4). Also, aniline (1o) was smoothly con-
verted into phenol (3o) in 93% yield (Entry 5). Fi-
nally, 3-aminopyridine (1p) was converted into 3-
hydroxypyridine (3p) quantitatively (Entry 6).
Finally, solvents that are miscible with water
were investigated (Entries 18–23). The formation of
3a in moderate yields (60–80%) was observed. How-
ever, tar was also formed in these reactions. The use
of immiscible organic solvents with water is more
effective for selective synthesis of 3a than that of
miscible solvents.
These results suggest that the ideal organic
solvent for the two-phase system is immiscible
with water, acid resistant, and lighter than water.
CPME is the best cosolvent for this two-phase
system. CPME has recently received much attention
because of high boiling point (106°C), resistance
to peroxide formation, extremely easy dehydration,
and high solubility with organic compounds. Also,
CPME is applicable for a variety of synthetic
methods using organolithium reagents, Grignard
reactions, and various cross-coupling reactions in
the presence of Pd catalysts [10–17].
With the optimized reaction conditions in hand,
the scope and limitations of the syntheses of vari-
ous phenols (3a–3j) from anilines (1a--1j) through
the hydrolyses of diazonium salt (2a–2j) using
method A (see Scheme 2) or method B were ex-
amined. In method B, the syntheses of diazonium
salts 2 were performed by reacting anilines 1 with
sodium nitrite in sulfuric acid and CPME (see
Experimental section). The results are shown in
Table 2. The meta-substituted phenoxyanilines (1a
and 1b) gave 3a and 3b in almost quantitative
yields (Entries 1 and 2). However in the case of
CONCLUSIONS
In summary, a useful synthetic method for various
phenols 3 without the formation of tar was devel-
oped. The hydrolysis of diazonium salts 2 prepared
from anilines 1 gave 3 in good to excellent yields us-
ing the two-phase system of CPME and water. From
the practical and industrial viewpoints, the present
method for producing a variety of phenols 3 is very
noteworthy because of the use of easily available and
cheap reagents and solvents, and mild reaction con-
ditions.
EXPERIMENTAL
Melting points were determined with a YAMATO
MP-21 instrument (Yamato Scientific Co., Ltd.,
Heteroatom Chemistry DOI 10.1002/hc

414 Taniguchi et al.
TABLE 2 Synthesis of m-Substituted Phenols (3a–j) in the Two-Phase System (CPME and Water)
R
NH2
N2+ OSO H-
R
OH
R
3
H SO , NaNO
CPME, H O
2
2
4
2
1
a-j
2a-j
3a-j
Entry
R
Product
3a
Yield (%)a
Method
O N
O
2
1
2
96
95
A
B
O
3b
O
3
4
5
6
7
8
9
3c
3d
3e
3f
64
96
93
91
92
56, 75
94
98
B
B
B
B
B
B
A
A
i-Pr
Me
MeO
Ac
3g
3h
3i
b
N0
CF
COOH
2
3
10
3j
a
Isolated yields.
Cosolvent is pseudocumene.
b
TABLE 3 Synthesis of 3k–p in the Two-Phase System (CPME and Water)
R1
R1
R1
NH2
N2+ OSO H-
OH
3
H SO , NaNO
2
CPME, H O
2
2
4
R2
Y
k-p
R2
R2
Y
2k-p
Y
3k-p
1
Entry
R1
Me
COOH
H
H
H
H
R2
H
H
Me
COOH
H
Y
Product
3k
Yield (%)a
1
2
3
4
5
6
CH
CH
CH
CH
CH
N
83
89
82
96
93
31
3m
3n
3o
3p
H
100
aMethod B was used. Isolated yields.
Tokyo, Japan) and were uncorrected. 1H and 13
NMR spectra were obtained on JEOL JNM-AL300
300 MHz, 75 MHz) and JEOL JNM-ECX400 (400
MHz, 100 MHz) instruments (JEOL Ltd., Tokyo,
Japan). Mass spectra were measured on GC-MS Var-
ian 3400 with Varian SATURN 2000 (Agilent Tech-
nologies, Inc., Santa Clara, USA) and Shimadzu
LCMS-2020 featuring a DART (Direct Analysis Real
Time) source (SHIMADZU CORPORATION, Kyoto,
Japan).
C
temperature and stirred for additional 1 h to pro-
duce diazonium salt 2. Next, the diazonium salt solu-
tion was poured into another flask containing water
(40 mL) and CPME (35 mL) with stirring. The mix-
ture was refluxed for 15–20 min. After the reaction,
the product was extracted with AcOEt and dried over
MgSO4. After evaporation of organic solvents, prod-
uct 3 was obtained by purification using silica gel
column chromatography.
(
Method B. To a mixture of ice (26 g) and con-
centrated sulfuric acid (8.0 mL), aniline (5.0 mmol)
was added slowly and stirred for several minutes at
room temperature. CPME (35 mL) was added to the
solution. An aqueous solution (14 mL) of sodium
nitrite (0.38 g, 5.5 mmol) was added dropwise over
10 min, and the mixture was refluxed for 15–20 min.
After completion of the reaction, the resulting solu-
tion was allowed to cool to room temperature, and
General Procedure for the Synthesis of Phenols 3
Method A. Into the concentrated sulfuric acid
(
8.0 mL), aniline 1 (5.0 mmol) was added carefully.
A mixture of 1 and sulfuric acid was cooled with
an ice bath with stirring. To the yellow or color-
less solution, sodium nitrite (0.38 g, 5.5 mmol) was
added at 5°C. The solution was warmed to room
Heteroatom Chemistry DOI 10.1002/hc

Hydrolysis of Diazonium Salts Using a Two-Phase System (CPME and Water) 415
then extracted with AcOEt and dried over MgSO4.
After purification by silica gel column chromatogra-
phy, phenol 3 was obtained.
J = 8.1, 2.3, 0.9 Hz, 1H), 7.12 (t, J = 7.9 Hz, 1H).
13
C NMR (CDCl3) δ (ppm): 55.4, 101.7, 106.6, 108.0,
+
130.3, 156.8, 160.9. MS (EI) m/z (%): 124 (M , 100),
94 (61), 81 (33), 66 (33), 53 (62), 41 (18).
3
-(4-Nitrophenoxy)phenol (3a). Yield 1.110 g
1
(
(
1
96%), mp 95–96°C (Lit. [18] 96–97°C). H NMR
CDCl3) δ (ppm): 5.26 (s, 1H, OH), 6.59 (t, J = 2.4 Hz,
3-Acetylphenol (3g). Yield 0.629 g (92%), mp
1
95–96°C (Lit. [24] 96°C). H NMR (CDCl3) δ (ppm):
2.61 (s, 3H, CH3), 6.85 (s, 1H, OH), 7.12 (ddd, J = 8.0,
2.7, 0.9 Hz, 1H), 7.34 (t, J = 8.0 Hz, 1H), 7.51 (dt, J =
H), 6.65 (ddd, J = 8.2, 2.4, 0.8 Hz, 1H), 6.72 (ddd, J
=
8.2, 2.4, 0.8 Hz, 1H), 7.04 (dt, J = 9.2, 2.1 Hz, 2H),
1
3
7
.27 (t, J = 8.2 Hz, 1H), 8.20 (dt, J = 9.2, 2.1 Hz, 2H).
8.0, 0.9 Hz, 1H), 7.55–7.56 (m, 1H). C NMR (CDCl3)
1
3
C NMR (CDCl3) δ (ppm): 108.0, 112.6, 112.7, 117.4,
δ (ppm): 26.9, 114.8, 121.0, 121.2, 130.0, 138.4, 156.5,
+
1
26.1, 131.1, 142.7, 155.9, 157.4, 163.2. MS (EI) m/z
199.5. MS (EI) m/z (%): 136 (M , 62), 121 (91), 93
(65), 65 (49), 43 (100).
+
(
%): 231 (M , 100), 207 (24), 128 (52), 65 (82).
3
-Phenoxyphenol (3b). Yield 0.882 g (95%), oil
3-Nitrophenol (3h). Yield 0.519 g (75%), mp 95–
96°C (Lit. [7] 95–96°C). H NMR (CDCl3) δ (ppm):
1
1
(
Lit. [19]). H NMR (CDCl3) δ (ppm): 4.84 (s, 1H,
OH), 6.48 (t, J = 2.4 Hz, 1H), 6.56 (dd, J = 8.2,
5.39 (s, 1H, OH), 7.18 (ddd, J = 8.2, 2.3, 0.9 Hz, 1H),
2
7
8
.4, 1H), 6.58 (dd, J = 8.2, 2.4 Hz, 1H), 7.03 (d, J =
7.41 (t, J = 8.2 Hz, 1H), 7.70 (t, J = 2.3 Hz, 1H), 7.82
1
3
.3 Hz, 2H), 7.12 (t, J = 7.3 Hz, 1H), 7.17 (t, J =
(ddd, J = 8.2, 2.3, 0.9 Hz, 1H). C NMR (CDCl3)
1
3
.2 Hz, 1H), 7.34 (t, J = 7.3 Hz, 2H). C NMR
δ (ppm): 110.6, 116.0, 122.1, 130.4, 149.2, 156.3. MS
+
(
CDCl3) δ (ppm): 106.0, 110.2, 111.1, 119.4, 123.7,
(EI) m/z (%): 139 (M , 70), 93 (42), 81 (24), 65 (100),
1
29.9, 130.5, 156.8, 156.9, 158.8. MS (EI) m/z (%):
53 (40).
+
186 (M , 100), 157 (21), 129 (27), 77 (35), 51 (94).
3
-Trifluoromethylphenol (3i). Yield 0.760 g
1
3
-Benzyloxyphenol (3c). Yield 0.643 g (64%),
(94%), oil (Lit. [25]). H NMR (CDCl3) δ (ppm): 5.04
(s, 1H, OH), 7.01 (dd, J = 2.3, 8.2 Hz, 1H), 7.08
(s, 1H), 7.20 (dd, J = 8.2, 2.3 Hz, 1H), 7.36 (t, J =
1
mp 49–50°C (Lit. [20] 50–51°C). H NMR (CDCl3)
δ (ppm): 4.71 (s, 1H, OH), 5.04 (s, 2H, CH2), 6.44
1
3
(
ddd, J = 8.2, 2.4, 0.9, 1H), 6.48 (t, J = 2.4 Hz, 1H),
8.2 Hz, 1H). C NMR (CDCl3) δ (ppm): 112.5 (q, J
= 3.7 Hz), 117.8, (q, J = 3.7 Hz), 119.0, 124.0 (q, J =
274 Hz), 130.4, 132.3 (q, J = 33 Hz), 155.8. MS (EI)
6
1
7
1
9
.57 (ddd, J = 8.2, 2.4, 0.9 Hz, 1H), 7.14 (t, J = 8.2 Hz,
H), 7.33–7.44 (m, 5H). 13C NMR (CDCl3) δ (ppm):
0.1, 102.6, 107.5, 108.2, 127.6, 128.1, 128.7, 130.3,
+
m/z (%): 162 (M , 100), 143 (33), 112 (24), 63 (18).
+
36.9, 156.7, 160.2. MS (EI) m/z (%): 200 (M , 11),
1 (100), 65 (15), 51 (6).
3-Hydroxybenzoic acid (3j). Yield 0.678
98%), mp 197–198°C (Lit. [26] 199–200°C).
g
H
1
(
3
-Isopropylphenol (3d). Yield 0.652 g (96%), oil
NMR (DMSO-d6) δ (ppm): 7.01 (ddd, J = 7.9, 2.4, 1.2
Hz, 1H), 7.31 (t, J = 7.9 Hz, 1H), 7.35 (t, J = 2.4 Hz,
1H), 7.40 (d, J = 7.9 Hz, 1H), 9.77 (s, 1H, OH), 12.8
1
(
Lit. [21]). H NMR (CDCl3) δ (ppm): 1.23 (d, J = 6.9
Hz, 6H, CH3), 2.86 (sep, J = 6.9 Hz, 1H, CH), 4.76
1
3
(
(
s, 1H, OH), 6.65 (ddd, J = 7.7, 2.2, 0.9 Hz, 1H), 6.71
t, J = 2.2 Hz, 1H), 6.81 (d, J = 7.7 Hz, 1H), 7.16 (t,
(brs, 1H, COOH). C NMR (DMSO-d6) δ (ppm):
116.3, 120.4, 120.5, 130.1, 132.5, 157.9, 167.8. MS
1
3
−
J = 7.7 Hz, 1H). C NMR (CDCl3) δ (ppm): 24.0,
(Neg-DART) m/z: 137 ([M – H] ).
3
(
(
4.1, 112.7, 113.4, 119.1, 129.5, 151.1, 155.6. MS
+
EI) m/z (%): 136 (M , 38), 121 (100), 103 (15), 91
23), 77 (24), 65 (11), 51 (15), 41 (21).
o-Cresol (3k). Yield 0.449 g (83%), oil (Lit. [22]).
1
H NMR (CDCl ) δ (ppm): 2.25 (s, 3H, CH ), 4.72 (s,
3
3
1
H, OH), 6.76 (d, J = 7.7 Hz, 1H), 6.85 (td, J = 7.7,
13
m-Cresol (3e). Yield 0.504 g (93%), oil (Lit.
1.2 Hz, 1H), 7.06–7.13 (m, 2H). C NMR (CDCl3) δ
1
[
4
8
22]). H NMR (CDCl3) δ (ppm): 2.30 (s, 3H, CH3),
(ppm): 15.9, 115.0, 120.9, 123.9, 127.3, 131.2, 153.8.
MS (EI) m/z (%): 108 (M , 100), 107 (83), 90 (25), 79
(42), 51 (45), 40 (12).
+
.78 (s, 1H, OH), 6.62–6.66 (m, 2H), 6.75 (d, J =
1
3
.0 Hz, 1H), 7.12 (t, J = 8.0 Hz, 1H). C NMR (CDCl3)
δ (ppm): 21.4, 112.4, 116.2, 121.8, 129.6, 140.0, 155.4.
+
MS (EI) m/z (%): 108 (M , 100), 107 (97), 90 (17), 79
41), 51 (35), 40 (21).
Salicylic acid (3l). Yield 0.614 g (89%), mp
1
(
157.5–158.5°C (Lit. [27] 157.5–158°C). H NMR
(
DMSO-d6) δ (ppm): 6.92 (t, J = 7.2 Hz, 1H), 6.95
3
-Methoxyphenol (3f). Yield 0.565g (91%), oil
(d, J = 7.2 Hz, 1H), 7.51 (td, J = 7.6, 0.6 Hz, 1H),
1
13
(
Lit. [23]). H NMR (CDCl3) δ (ppm): 3.77 (s, 3H,
7.79 (dd, J = 7.6, 1.6 Hz, 1H), 11.50 (brs, 1H).
C
CH3), 5.15 (s, 1H, OH), 6.41–6.44 (m, 2H), 6.50 (ddd,
NMR (DMSO-d6) δ (ppm): 113.5, 117.6, 119.7, 130.8,
Heteroatom Chemistry DOI 10.1002/hc

416 Taniguchi et al.
1
36.2, 161.7, 172.5. MS (Neg-DART) m/z: 137 ([M –
[6] Luo, J.; Preciado, S.; Larrosa, I. J Am Chem Soc 2014,
136, 4109–4112.
−
H] ).
[
[
7] Manske, R. H. F. Org Synth Coll 1941, 1, 404–406.
8] Yamashita, T.; Kawai, N.; Tokuyama, H.; Fukuyama,
T. J Am Chem Soc 2005, 127, 15038–15039.
p-Cresol (3m). Yield 0.444 g (82%), oil (Lit.
1
[
22]). H NMR (CDCl3) δ (ppm): 2.27 (s, 3H, CH3),
[9] Tokukura, Y.; Nagatomi, T. Jpn Kokai Tokkyo Koho
2000, 53626.
[10] Watanabe, K.; Goto, K. J Synth Org Chem Jpn 2003,
61, 806–808.
11] Watanabe, K.; Yamagiwa, N.; Torisawa, Y. Org Pro-
cess Res Dev 2007, 11, 251–258.
4
.75 (s, 1H, OH), 6.73 (dd, J = 8.2, 2.0 Hz, 2H), 7.03
13
(
1
d, J = 8.2 Hz, 2H). C NMR (CDCl3) δ (ppm): 20.6,
+
15.2, 130.2, 153.2. MS (EI) m/z (%): 108 (M , 94),
[
107 (100), 90 (12), 77 (33), 51 (42), 40 (11).
[
12] Watanabe, K. Molecules 2013, 18, 3184–3194.
4
-Hydroxybenzoic acid (3n). Yield 0.660 g
[13] Antonucci, V.; Coleman, J.; Ferry, J. B.; Johnson, N.;
Mathe, M.; Scott, J. P.; Xu, J. Org Process Res Dev
1
(
96%), mp 209.5–210.5°C (Lit. [28] 210–211°C). H
2
011, 15, 939–941.
NMR (DMSO-d6) δ (ppm): 6.82 (d, J = 8.6 Hz, 2H),
[
14] Kobayashi, S.; Kuroda, H.; Ohtsuka, Y.; Kashihara,
T.; Masuyama, A.; Watanabe, K. Tetrahedron 2013,
69, 2251–2259.
[15] Okabayashi, T.; Iida, A.; Takai, K.; Nawate, Y.; Mis-
aki, T.; Tanabe, Y. J Org Chem 2007, 72, 8142–8145.
16] Shimada, T.; Suda, M.; Nagano, T.; Kakiuchi, K. J
Org Chem 2005, 70, 10178–10181.
7
1
1
.78 (d, J = 8.6 Hz, 2H), 10.2 (brs, 1H, OH), 12.4 (brs,
13
H, COOH). C NMR (DMSO-d6) δ (ppm): 115.6,
21.9, 132.1, 162.1, 167.7. MS (Neg-DART) m/z: 137
−
(
[M – H] ).
[
Phenol (3o). Yield 0.435 g (93%), mp 40.5–
[
17] Roche, M.; Bignon, J.; Brion, J.-D.; Hamze, A.; Alami,
M. J Org Chem 2014, 79, 7583−7592.
1
4
4
7
1.5°C (Lit. [29] 41–43°C). H NMR (CDCl3) δ (ppm):
.82 (s, 1H, OH), 6.81–6.85 (m, 2H), 6.93 (t, J =
[18] Ikawa, K. Yakugaku Zasshi 1959, 79, 1498–1502.
[19] Sax, K. J.; Saari, W. S.; Mahoney, C. L.; Gordon, J.
M. J Org Chem 1960, 25, 1590–1595.
.4 Hz, 1H), 7.22–7.27 (m, 2H). 1 C NMR (CDCl3)
3
δ (ppm): 115.4, 120.9, 129.8, 155.5. MS (EI) m/z (%):
9
[
20] Fitton, A. O.; Ramage, G. R. J Chem Soc 1962, 4870–
874.
+
4 (M , 100), 66 (39), 55 (18), 40 (39).
4
[21] Joshi-Pangu, A.; Ganesh, M.; Biscoe, M. R. Org Lett
2011, 13, 1218–1221.
3
-Hydroxypyridine (3p). Yield 0.479 g (100%),
1
[22] Kendall, J.; Beaver, J. J. J Am Chem Soc 1921, 43,
853–1867.
23] Thakur, K. G.; Sekar, G. Chem Commun 2011, 47,
692–6694.
[24] Gogoi, P.; Sarmah, G. K.; Konwar, D. J Org Chem
2004, 69, 5153–5154.
mp 126–127°C (Lit. [30] 127°C). H NMR (Acetone-
d6) δ (ppm): 7.20 (t, J = 2.1 Hz, 2H), 8.08 (t, J = 3.2
Hz, 1H), 8.21 (t, J = 1.6 Hz, 1H), 8.92 (brs, 1H, OH).
1
[
6
1
3
C NMR (Acetone-d6): δ (ppm) 121.9, 124.0, 138.1,
+
1
4
40.9, 153.7. MS (EI) m/z (%): 95 (M , 100), 67 (24),
0 (79).
[
[
[
[
25] Chatterjee, N.; Chowdhury, H.; Sneh, K.; Goswami,
A. Tetrahedron Lett 2015, 56, 172–174.
26] Ungnade, H. E.; Henick, A. S. J Am Chem Soc 1942,
64, 1737–1738.
27] Hauptschein, M.; Saggiomo, A. J.; Stokes, C. S. J Am
Chem Soc 1955, 77, 2284–2287.
28] Kikuchi, M.; Sato, K.; Shiraishi, Y.; Nakayama, R.;
Watanabe, R.; Sugiyama, M. Yakugaku Zasshi 1990,
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Heteroatom Chemistry DOI 10.1002/hc