Activated Carbon-Promoted Dehydrogenation of Hydroquinones to Benzoquinones, Naphthoquinones, and Anthraquinones under Molecular Oxygen Atmosphere

Article abstract of DOI:10.1021/acs.joc.8b02961

We found that the activated carbon-molecular oxygen system promotes the conversion of hydroquinones to benzoquinones, naphthoquinones, and anthraquinones, which are often found in natural products and pharmaceuticals. In particular, the one-pot synthesis of naphthoquinones and anthraquinones involving a Diels-Alder reaction is a useful protocol for this purpose.

Full text of DOI:10.1021/acs.joc.8b02961

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Note
Activated Carbon-Promoted Dehydrogenation of
Hydroquinones to Benzoquinones, Naphthoquinones, and
Anthraquinones under Molecular Oxygen Atmosphere
Sanghun Kim, Ryosuke Matsubara, and Masahiko Hayashi
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02961 • Publication Date (Web): 07 Feb 2019
Downloaded from http://pubs.acs.org on February 9, 2019
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Activated
Carbon-Promoted
Dehydrogenation
of
Hydroquinones to Benzoquinones, Naphthoquinones, and
Anthraquinones under Molecular Oxygen Atmosphere
Sanghun Kim, Ryosuke Matsubara*, and Masahiko Hayashi*
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Department of Chemistry, Graduate School of Science, Kobe University, Kobe 657-
8501, Japan
Supporting Information Placeholder
ABSTRACT: We found activated carbon-molecular oxygen system promotes the
conversion of hydroquinones to benzoquinones, naphthoquinones, and anthraquinones,
which are often found in natural products and pharmaceuticals. In particular, the one-pot
synthesis of naphthoquinones and anthraquinones involving a Diels-Alder reaction is a
useful protocol for this purpose.
Benzoquinones, naphthoquinones, and anthraquinones are remarkable scaffolds in the
synthesis of natural products and pharmaceutical compounds. For example,
benzoquinone has been considered a privileged structure in compounds that show
antitumor, antimalarial or leishmanicidal activity, such as coenzyme Q10,1 embelin,2 and
geldanamycin.3 The naphthoquinone skeleton is also found in the precursors of bioactive
molecules that have antimalarial,4 anticancer,5 antitumor,6 wound healing,7 antiparasitic8
and antibacterial propertiess9 (Figure 1).
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Figure 1. Benzoquinone and naphthoquinone moieties found in natural products and
pharmaceuticals.
As shown in Scheme 1, numerous catalysts and promotors have been developed for the
conversion of hydroquinones to benzoquinones, including cerium ammonium nitrate
(CAN),10 chromium (VI),11 or metal complexes12 In 2008, Kobayashi and co-workers
reported the aerobic oxidation of hydroquinone derivatives to quinones catalyzed by a
polymer-incarcerated gold catalyst (PI Pt).13 They also reported a polymer incarcerated
platinum catalyst (PI Au) system.14 In 2014, Namboothiri, Doris, and co-workers
reported the aerobic oxidation of phenols, and related compounds, including
hydroquinones to 1,4-benzoquinones using a carbon nanotube-gold nanohybrid catalyst
(AuCNT).15 More recently, Stahl and co-workers reported the Co(salophen)-catalyzed
aerobic oxidation of p-hydroquinones.16
Scheme 1. Previously reported methods for conversion of hydroquinone to
benzoquinone.
In this paper, we report the synthesis of 1,4-benzoquinones from hydroquinones to
quinones using an activated carbon__ molecular oxygen system.17 Furthermore, we carried
out the one-pot synthesis of naphthoquinones via a dehydrogenation, Diels-Alder
reaction, and dehydrogenation sequence (Scheme 2).
Scheme 2. One-pot synthetic strategy for naphthoquinone .
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First, we attempted the reaction of hydroquinone with activated carbon in xylene under
molecular oxygen atmosphere at 120 ºC for 24 h. As shown in entries 1 to 4 in Table 1,
the concentration of the hydroquinone is a crucial factor to obtain high yields of
benzoquinone. This may be because of the formation of quinhydrone, which is a 1:1
molecular complex of benzoquinone and hydroquinone, in high concentration.18 The
results in entries 5 and 6 indicated that neither activated carbon nor molecular oxygen
was powerful enough to promote the reaction when used alone.
Table 1. Optimization and control experiments for dehydrogenation of
hydroquinone to benzoquinone
a Activated carbon (TCI-2), Tokyo Chemical Industry Co. specific surface area (~1400
m2/g), pore volume (1.3 mL/g). b Isolated yield by silica-gel column chromatography.
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Under the optimized conditions, various substituted hydroquinones (1a-1j) were
converted to the corresponding benzoquinones (2a-2j) in high to excellent yields (Table
2). Notable, 1,2-benzoquinone derivative 2j was obtained in 70% yield. Hydroquinones
possessing a variety of group, such as COCH3, CO2CH3, OH, NO2, CN and 1,4-
dihydroxynaphthalene afforded the corresponding quinines in low yield. Then, we
investigated the recyclability of the activated carbon. As shown in Table 3, the activated
carbon could be recycled and reused at least five times to obtain the corresponding
benzoquinone without loss of yield.
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Table 2. Synthesis of benzoquinones from hydroquinonesa
a Isolated yield by silica-gel column chromatography. b Activated carbon (TCI-2), Tokyo
Chemical Industry Co.
Table 3. Recyclability of activated carbon.
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a Activated carbon (TCI-2), Tokyo Chemical Industry Co.
b Determined by GC analysis using pentadecane as the internal standard.
We next carried out one-pot synthesis of naphthoquinones. The reaction of benzoquinones
(1a-1j) with 2,3-dimethyl-1,3-butadiene or 1,3-butadiene proceeded smoothly to afford
the corresponding naphthoquinone derivatives (4a-4l) in good to high yields except for
2-chloro-6,7-dimethyl-1,4-naphthoquinone (4f) and 2-bromo-6,7-dimethyl-1,4-
naphthoquinone (4g), which gave low yield (27% and 40% yield, respectively) (Table 4).
The reaction involves dehydrogenation of hydroquinone by the activated
carbon__molecular oxygen system to give benzoquinone, followed by Diels-Alder
reaction with 1,3-butadiene to form tetrahydronaphthoquinone, and finally,
dehydrogenation by the activated carbon__ molecular oxygen system to give the desired
naphthoquinones.
Table 4. One-pot synthesis of naphthoquinone derivatives
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a Activated carbon (TCI-2), Tokyo Chemical Industry Co. b Sufficient pure without further
c
d
purification. Isolated yield by silica-gel column chromatography. Isolated yield by
recrystallization.
During the investigation of the synthesis of naphthoquinones, we found that when we
used excess amount of 1,3-dienes, anthraquinone derivatives were obtained including two
times of Dield-Alder reaction. After optimization, we established the conditions for one-
pot synthesis of anthraquinones in excellent yield (Scheme 3).19
Scheme 3. One-pot synthesis of anthraquinones from hydroquinones.
a Activated carbon (TCI-2) Tokyo Chemical Industry Co. b15 % (w/w) of 1,3-butadiene
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solution in toluene. c Isolated yield by silica-gel column chromatography.
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As for the role of activated carbon, we previously reported the relationship between the
nature of activated carbon and reactivity in the oxidation reaction. We have shown in a
number of previous studies that the key role of activated carbon in these oxidations is not
associated with metal contaminants, specific surface area, pore volume, or the mean pore
diameter. Instead, it is associated with oxygenated functional groups in the pore, for
example, carbonyl and carboxyl groups.17d
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In conclusion, we have developed a simple and environment-friendly method for the
synthesis of benzoquinones, naphthoquinones, and anthraquinones from hydroquinones
using an activated carbon__molecular oxygen system. Further investigation toward the
application of this protocol to natural product synthesis is on-going.
EXPERIMENTAL SECTION
General experiment. All reactions were carried out in flame-dried and well cleaned
glasswares with magnetic stirring. Dehydrogenation of hydroquinones to benzqouinones
was conducted in a two-neck test tube with balloon which is filled with oxygen gas, unless
otherwise noted. Dehydrogenation of hydroquinones to naphthoquinones and
anthraquinones was conducted in a 30 mL Schlenk flask which is filled with oxygen gas.
In the case of the synthesis of benzoquinones, all of reagents were added under dry argon
atmosphere then the atmosphere was changed from argon to oxygen by vacuum
techniques thrice. In the case of the synthesis of naphthoquinones and anthraquinones, all
of the reagents were added under dry argon atmosphere then the atmosphere was changed
from argon to oxygen in an ice bath to prevent evaporation of diene derivatives. All
starting materials were obtained from commercial sources. Melting points were measured
on a Yanaco MP-500D and are not corrected. 1H and 13C{1H} NMR were recorded on a
Bruker Avance lll HD 400 using TMS (0 ppm) and CDCl3 (13C{1H}: 77.0 ppm) as an
internal standard, respectively (1H NMR, 400 MHz; 13C{1H}NMR, 100 MHz). The
following abbreviations are used in connection with NMR; s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet. Mass spectra were measured using an IsoleraTM Dalton
Mass Detector. HRMS spectra were measured using a JOEL JMS-T100LP (DART
ionization method, TOF analyzer). GC analyses were performed using a Hitachi G-5000
or Shimazu GC-2025 gas chromatograph equipped with GL Science InertCAP 5.
Preparative column chromatography was performed using Kanto Chemical silica gel 60
N (spherical, neutral), Fuji Silysia BW: 10MH silica gel or YMC_GEL Silica gel 60
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F254aluminiym sheets. Safety precautions: Although we have not experienced explosion
after hundreds times of oxidation experiments, mixing volatile hydrocarbons with pure
oxygen has a potential risk for explosion. Safety measures against static discharge should
be taken.
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General Procedure
General method for the dehydrogenation of hydroquinones to benzoquinones (2a-
2j)
A flame-dried two-necked test tube was prepared with balloon connected via three
ways cock. After cooling down to room temperature, hydroquinone derivatives (0.5-5.0
mmol, 1.0 eq.) and activated carbon (100% w/w) were added under argon atmosphere.
Then, xylene (5-50 mL, 0.1 M) was slowly added with stirring. After addition of all of
reagents, the atmosphere was changed from argon to oxygen by using vacuum technique
for 3 times. The reaction solution was heated up to 120 ℃ with oil bath and carefully
stirred for 24 h. The reaction was monitored by TLC and GC. After confirmation of
completion of the reaction, the reaction mixture was cooled down to room temperature
and filtered through Celite by washing with dichloromethane. Then, the yellow solution
was evaporated with reduced pressure because benzoquinone derivatives were volatile.
After evaporation, the obtained residue was purified by the silica-gel column
chromatography.
Recyclability of activated carbon
Firstly, substrate (1b) was dehydrogenated by activated carbon—O2 promoting system
and 91% of desired benzoquinone (2b) was obtained by gas chromatography (GC)
analysis with pentadecane as an internal standard. After the reaction, the activated carbon
was filtered through the Büchner funnel by washing with enough ethyl acetate and
hexane. Then the washed activated carbon was dried overnight in vacuum. This recycling
process was investigated for 5 times (Table 3).
General method for the dehydrogenation of hydroquinones to naphthoquinones
with 2,3-dimethyl-1,3-butadiene (4a-4g)
A flame-dried 30 mL Schlenk flask was prepared. After cooling down to room
temperature, hydroquinone derivatives (0.5-1.2 mmol, 1.25 eq.) and activated carbon
(100% w/w) were added under argon atmosphere. Then, xylene (5-12 mL, 0.1 M based
on hydroquinone derivatives) was slowly added with stirring. The reaction solution was
cooled down in an ice bath before introduction of 2,3-dimethylbutadiene. After cooling
down, 2.3-dimehylbutadiene (0.4-0.96 mmol, 1.0 eq.) was added dropwise into the
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reaction mixture. After addition of 2,3-dimethylbutadiene, the reaction atmosphere was
changed to oxygen by using three ways cock (one is for balloon with oxygen, another is
for vacuum pump and the other is for Schlenk flask). The atmosphere was changed for
10 times by quickly converting the cock position. After changing the atmosphere, the
reaction mixture was heated up to 120 ℃ with oil bath and carefully stirred for 36 h. The
reaction was monitored by TLC and GC. After confirmation of completion of the reaction,
the reaction mixture was cooled down to room temperature and filtered through Celite by
washing with ethyl acetate. Then, all of solvents were removed under reduced pressure.
After removal of solvents, the obtained residue was purified by recrystallization or silica-
gel column chromatography.
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General method for the dehydrogenation of hydroquinones to naphthoquinones
with 1,3-butadiene (4h-4l)
A flame-dried 30 mL Schlenk flask was prepared. After cooling down to room
temperature, hydroquinone derivatives (0.5 mmol, 1.0 eq.) and activated carbon (100%
w/w) were added under argon atmosphere. Then, xylene (5 mL, 0.1 M) was slowly added
with stirring. The reaction solution was cooled down in an ice bath before introduction of
1,3-butadiene. After cooling down, 15% w/w of 1.3-butadiene in toluene (2.0 mmol, 4.0
eq.) was added dropwise into the reaction mixture. After addition of 1,3-butadiene, the
reaction atmosphere was changed to oxygen by using three ways cock (one is for balloon
with oxygen, another is for vacuum pump and the other is for Schlenk flask). The
atmosphere was changed 5 times by quickly changing the position of the cock. After
changing atmosphere, the reaction mixture was heated up to 120 ℃ with oil bath and
carefully stirred for 36 h. The reaction was monitored by TLC and GC. After confirmation
of completion of the reaction, the reaction mixture was cooled down to room temperature
and filtered through Celite by washing with ethyl acetate. Then, the solvent was removed
under reduced pressure. After removal of solvents, the obtained residue was purified by
recrystallization or silica-gel column chromatography.
General method for the dehydrogenation of hydroquinones to anthraquinone
A flame-dried 30 mL Schlenk flask was prepared. After cooling down to room
temperature, hydroquinone derivatives (0.5 mmol, 1.0 eq.) and activated carbon (100
w/w%) were added under argon atmosphere. Then, xylene (5 mL, 0.1 M) was slowly
added with stirring. The reaction solution was cooled down in ice bath before introduction
of diene. After cooling down, 15 w/w% of 1.3-butadiene in toluene (10 mmol, 20 eq.)
was added dropwise into the reaction mixture. After addition of diene, the reaction
atmosphere change to oxygen by using three ways cock (one is for balloon with oxygen,
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another is for vacuum pump and the other is for Schlenk flask). The atmosphere was
changed for 5-10 times by quickly converting the cock position. After changing
atmosphere, the reaction mixture were heated up to 120 ℃ with oil bath and carefully
stirred for 48 h. The reaction was monitored by TLC and GC. After confirmation of
completion of the reaction, the reaction mixture was cooled down to room temperature
and filtered through Celite by washing with ethyl acetate. Then, the solvent was removed
under reduced pressure. After evaporation, the obtained residue was purified by silica-gel
column chromatography (CHCl3/hexane = 1:1).
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p-benzoquinone 2a. Yield: 95% (510 mg, 4.75 mmol). Yellow solid, Mp: 113.3__114.2
℃ (lit.20 Mp: 114__116 ℃); IR (neat) 501, 505, 742, 887, 941, 1072, 1082, 1305, 1342,
1364, 1590, 1641, 1677; 1H NMR (400 MHz, CDCl3), δ = 6.79 (s, 4H); 13C{1H} NMR
(100 MHz, CDCl3) δ = 187.2, 136.5.
2-methly-p-benzoquinone 2b. Yield: 100% (610 mg, 5.0 mmol). Yellow solid, Mp:
67.7__68.1 ℃ (lit.21 Mp: 68__69 ℃); IR (neat) 531, 536, 680, 822, 884, 922, 998, 1094,
1141, 1300, 1347, 1372, 1597, 1643, 3055, 3071; 1H NMR (400 MHz, CDCl3), δ = 6.72
(dd, J = 10.1, 2.4 Hz, 1H), 6.63 (dq, J = 3.2, 1.6 Hz, 1H), 6.77 (d, J = 10.1 Hz, 1H), 2.07
13
(d, J = 1.6 Hz, 3H); C{1H} NMR (100 MHz, CDCl3) δ = 187.7, 187.6, 145.8, 136.5,
136.4, 133.3, 15.8.
2-methoxy-p-benzoquinone 2c. Yield: 100% (276 mg, 2.0 mmol). Yellow solid, Mp:
124.6__125.2 ℃ (lit.22 Mp: 138__139 ℃); IR (neat) 556, 593, 632, 694, 793, 843, 879,
982, 1109, 1176, 1313, 1357, 1377, 1445, 1461, 1588, 1617, 1643, 1674, 2947, 2982,
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3067; H NMR (400 MHz, CDCl3), δ = 6.72 (d, J = 1.5 Hz, 2H), 5.95 (s, 1H), 3.84 (s,
13
3H); C{1H} NMR (100 MHz, CDCl3) δ = 187.4, 181.7, 158.5, 137.2, 134.4, 107.7,
56.2.
2,3-dimethyl-p-benzoquinone 2d. Yield: 100% (50 mg, 0.36 mmol). Yellow solid, Mp:
51.0__52.1 ℃ (lit.23 Mp: 54__55 ℃); IR (neat) 624, 754, 803, 840, 1064, 1136, 1307,
1365, 1380, 1600, 1651, 2955, 3052; 1H NMR (400 MHz, CDCl3), δ = 6.72 (s, 2H), 2.03
(s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ = 187.2, 140.9, 136.1, 12.1.
2-tert-butyl-p-benzoquinone 2e. Yield: 90% (74 mg, 0.45 mmol). Yellow solid, Mp:
54.2__55.1 ℃ (lit.24 Mp: 54__56 ℃); IR (neat) 536, 590, 652, 791, 844, 880, 934, 1010,
1042, 1107, 1116, 1198, 1257, 1289, 1337, 1365, 1391, 1459, 1482, 1589, 1651, 2869,
2960, 3055, 3254, 3297; 1H NMR (400 MHz, CDCl3), δ = 6.68 (d, J = 1.2 Hz, 2H), 6.60
13
(t, J = 1.2 Hz, 1H), 1.28 (s, 9H); C{1H} NMR (100 MHz, CDCl3), δ = 188.2, 187.3,
155.8, 138.5, 134.8, 131.4, 35.1, 29.0.
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2,3,6-trimethyl-p-benzoquinone 2f. Yield: 83% (62 mg, 0.42 mmol). Yellow solid, Mp:
36.1__36.5 ℃ (lit.25 Mp: 36 ℃); IR (neat) 674, 697, 756, 807, 879, 990, 1030, 1101, 1187,
1260, 1314, 1374, 1434, 1616, 1643, 2918; 1H NMR (400 MHz, CDCl3), δ = 6.55 (q, J =
1.6 Hz, 1H), 2.04 (d, J = 1.6 Hz, 3H), 2.03–2.02 (m, 3H), 2.02–1.98 (m, 3H); 13C{1H}
NMR (100 MHz, CDCl3), δ = 187.7, 187.3, 145.2, 140.7, 140.6, 132.9, 15.7, 12.2, 11.9.
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2-phenyl-p-benzoquinone 2g. Yield: 95% (88 mg, 0.48 mmol). Yellow solid, Mp:
115.6__116.2 ℃ (lit.26 Mp: 113__114 ℃); IR (neat) 534, 610, 623, 692, 799, 841, 912,
936, 976, 1000, 1077, 1099, 1254, 1276, 1297, 1314, 1342, 1444, 1492, 1572, 1589, 1643,
1
3036, 3058; H NMR (400 MHz, CDCl3), δ = 7.52–7.41 (m, 5H), 6.88 (d, J = 6.7 Hz,
1H), 6.87 (d, J = 1.1 Hz, 1H), 6.84 (dd, J = 10.2, 2.2 Hz, 1H); 13C{1H} NMR (100 MHz,
CDCl3), δ = 187.6, 186.6, 145.9, 137.0, 136.2, 132.6, 132.6, 130.1, 129.2, 128.5.
2-bromo-p-benzoquinone 2h. Yield: 65% (39 mg, 0.33 mmol). Brown solid, Mp:
50.2__50.7℃ (lit.27 mp 56.5 ℃); IR (neat) 527, 532, 540, 547, 553, 559, 565, 778, 830,
915, 972, 1096, 1109, 1197, 1280, 1315, 1372, 1577, 1642, 1658, 3044, 3054; 1H NMR
(400 MHz, CDCl3), δ = 7.32 (d, J = 2.4 Hz, 1H), 6.97 (d, J = 10.1 Hz, 1H), 6.83 (dd, J =
13
10.1, 2.4 Hz, 1H); C{1H} NMR (100 MHz, CDCl3), δ = 184.5, 179.1, 138.1, 137.5,
136.6, 135.8.
2-chloro-p-benzoquinone 2i. Yield: 67% (476 mg, 3.4 mmol). Brown solid, Mp:
48.2__48.7 ℃ (lit.28 Mp 51__54 ℃); IR (neat) 562, 636, 782, 829, 844, 910, 998, 1105,
1200, 1285, 1320, 1370, 1588, 1651, 1677, 3051; 1H NMR (400 MHz, CDCl3), δ = 7.02
(d, J = 2.4 Hz, 1H), 6.93 (d, J = 10.1 Hz, 1H), 6.82 (dd, J = 10.1, 2.4 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3), δ = 184.9, 179.2, 144.0, 136.7, 136.0, 133.6.
3,5-di-tert-butyl-o-benzoquinone 2j. Yield: 70% (77 mg, 0.35 mmol). Darkish green
solid, Mp 103.4__103.8 ℃ (lit.29 Mp 111__112 ℃); IR (neat) 531, 541, 581, 656, 734, 811,
889, 931, 951, 1023, 1069, 1207, 1244, 1274, 1366, 1373, 1392, 1464, 1478, 1567, 1621,
1651, 1659, 1673, 2870, 2954, 3063; 1H NMR (400 MHz, CDCl3), δ = 6.93 (d, J = 2.3
Hz, 1H), 6.21 (d, J = 2.3 Hz, 1H), 1.27 (s, 9H), 1.22 (s, 9H); 13C{1H} NMR (100 MHz,
CDCl3), δ = 180.9, 179.9, 163.2, 149.7, 133.4, 121.9, 35.9, 35.3, 29.1, 27.7.
2,6,7-trimethyl-1,4-naphthoquinone 4a. Yield: 90% (216 mg, 1.1 mmol). Yellow solid,
Mp: 107.1__107.5 ℃ (lit.30 Mp 107.5__108.5 ℃); IR (neat) 586, 649, 680, 699, 733, 805,
876, 919, 985, 1021, 1067, 1209, 1276, 1298, 1319, 1340, 1381, 1450, 1595, 1623, 1664,
2917, 2945, 3053; 1H NMR (400 MHz, CDCl3), δ = 7.83 (s, 1H), 7.80 (s, 1H), 6.76 (q, J
13
= 1.5 Hz, 1H), 2.39 (d, J = 2.0 Hz, 6H), 2.17 (d, J = 1.6 Hz, 3H); C{1H} NMR (100
MHz, CDCl3), δ = 185.5, 185.1, 147.7, 143.2, 143.2, 135.3, 130.0, 129.9, 127.3, 126.9,
20.0, 20.0, 16.3.
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2-methoxy-6,7-dimethyl-1,4-naphthoquinone 4b. Yield: 82% (89 mg, 0.41 mmol).
Brown solid, Mp: 170.6__170.8 ℃ (lit.31 Mp: 169__171 ℃); IR (neat) 587, 673, 716,
741, 803, 873, 916, 898, 996, 1013, 1076, 1154, 1185, 1196, 1250, 1305, 1325, 1358,
1389, 1451, 1567, 1597, 1650, 1685, 2839, 2948, 3051; 1H NMR (400 MHz, CDCl3), δ
= 7.88 (s, 1H), 7.83 (s, 1H), 6.10 (s, 1H), 3.89 (s, 3H), 2.39 (d, J = 2.5 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3), δ = 185.1, 180.1, 160.2, 144.2, 142.9, 129.8, 128.8,
127.6, 127.1, 109.5, 56.3, 20.2, 19.9.
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2,3,6,7-tetramethyl-1,4-naphthoquinone 4c. Yield: 74% (79 mg, 0.37 mmol). Yellow
solid, Mp: 174.5__175.0 ℃ (lit.32 Mp: 167__168.5 ℃); IR (neat) 661, 720, 747, 895, 901,
922, 998, 1028, 1087, 1149, 1191, 1217, 1304, 1324, 1367, 1454, 1590, 1613, 1650, 2915,
1
2947, 3031; H NMR (400 MHz, CDCl3), δ = 7.82 (s, 2H), 2.38 (s, 6H), 2.15 (s, 6H);
13C{1H} NMR (100 MHz, CDCl3), δ = 185.2, 143.1, 143.0, 130.1, 127.2, 20.1, 12.8.
2-tert-butyl-6,7-dimethyl-1,4-naphthoquinone 4d. Yield: 64% (77 mg, 0.32 mmol).
Yellow solid, Mp. 110.3__110.8 ℃; IR (neat) 589, 639, 685, 705, 733, 818, 890, 932, 994,
1042, 1095, 1190, 1227, 1258, 1299, 1335, 1356, 1378, 1363, 1378, 1449, 1557, 1573,
1598, 1656, 2866, 2915, 2950, 2966, 3047; 1H NMR (400 MHz, CDCl3), δ = 7.82 (s, 1H),
13
7.77 (s, 1H), 6.77 (s, 1H), 2.39 (d, J = 3.3 Hz, 6H), 1.36 (s, 9H); C{1H} NMR (100
MHz, CDCl3), δ = 186.1, 185.1, 157.9, 143.4, 142.9, 133.6, 131.4, 129.4, 127.8, 126.4,
35.6, 29.3, 20.2, 20.0; HRMS (DART): m/z [M+H]+ calcd for C16H19O2: 243.1385;
Found: 243.1379.
2-phenyl–6,7-dimethyl-1,4-naphthoquinone 4e. Yield: 72% (94 mg, 0.36 mmol).
Yellow solid, Mp. 83.4__84.4 ℃; IR (neat) 547, 693, 701, 715, 761, 780, 810, 843, 892,
1073, 1190, 1294, 1355, 1344, 1444, 1567, 1598, 1652, 1666, 2978, 2950, 2996, 3031;
1H NMR (400 MHz, CDCl3), δ = 7.92 (s, 1H), 7.86 (s, 1H), 7.60–7.52 (m, 2H), 7.51–7.44
(m, 3H), 7.01 (s, 1H) 2.43 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3), δ = 185.2, 184.3,
147.6, 143.6, 143.5, 134.9, 133.5, 130.2, 129.9, 129.7, 129.3, 128.3, 127.8, 126.7, 20.1,
20.1; HRMS (DART): m/z [M+H]+ calcd for C18H15O2: 263.1072; Found: 263.1057.
2-chloro–6,7-dimethyl-1,4-naphthoquinone 4f. Yield: 27% (31 mg, 0.14 mmol).
Yellow solid, Mp: 141.2__142.0 ℃ (lit.33 Mp: 145__147 ℃); IR (neat) 575, 626, 711, 891,
999, 1023, 1200, 1258, 1282, 1310, 1329, 1375, 1448, 1594, 1659, 1672, 2885, 2918,
1
2942, 3036, 3060; H NMR (400 MHz, CDCl3), δ = 7.91 (s, 1H), 7.83 (s, 1H), 7.15 (s,
13
1H), 2.41 (s, 6H); C{1H} NMR (100 MHz, CDCl3), δ = 183.0, 178.1, 146.1, 144.6,
144.1, 135.7, 129.7, 129.2, 128.5, 127.7, 20.3, 20.2.
2-bromo–6,7-dimethyl-1,4-naphthoquinone 4g. Yield: 40% (53 mg, 0.2 mmol).
Yellow solid, Mp: 155.6__156.0 ℃ (lit.34 Mp: 155__156 ℃); IR (neat) 560, 613, 678, 705,
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797, 812, 892, 993, 1023, 1200, 1260, 1277, 1327, 1311, 1375, 1448, 1566, 1592, 1659,
1671, 2889, 2912, 2939, 3033, 3055; 1H NMR (400 MHz, CDCl3), δ = 7.91 (s, 1H), 7.83
(s, 1H), 7.45 (s, 1H), 2.41 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3), δ = 182.6, 177.9,
144.5, 144.1, 140.1, 139.9, 129.6, 128.8, 128.8, 127.8, 20.2, 20.2.
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2-methyl-1,4-naphthoquinone 4h. Yield: 63% (55 mg, 0.32 mmol). Yellow solid, Mp:
104.1__104.9 ℃ (lit.33 Mp 106__107 ℃); IR (neat) 642, 650, 666, 690, 719, 749, 777, 900,
939, 1156, 1192, 1259, 1299, 1352, 1589, 1621, 1661, 1682, 2920, 2961, 3068; 1H NMR
(400 MHz, CDCl3), δ = 7.85–7.72 (m, 2H), 7.64–7.52 (m, 2H), 3.82 (s, 1H), 1.60 (s, 3H);
13C{1H} NMR (100 MHz, CDCl3), δ = 185.5, 184.9, 148.1, 135.6, 133.6, 133.5, 132.2,
132.1, 126.5, 126.0, 16.5.
2-methoxy-1,4-naphthoquinone 4i. Yield: 83% (78 mg, 0.42 mmol). Brown solid, Mp:
153.5__154.3 ℃ (lit.35 Mp: 147 ℃); IR (neat) 645, 670, 692, 722, 780, 865, 924, 1022,
1043, 1086, 1118, 1156, 1193, 1213, 1241, 1265, 1335, 1445, 1577, 1590, 1602, 1643,
1680, 2848, 2947, 2988, 3047; 1H NMR (400 MHz, CDCl3), δ = 8.18–8.06 (m, 2H), 7.80–
7.67 (m, 2H), 6.18 (s, 1H), 3.91 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3), δ = 184.8,
180.1, 160.4, 134.3, 133.3, 132.0, 131.0, 126.7, 126.2, 109.9, 56.4.
2,3-dimethyl-1,4-naphthoquinone 4j. Yield: 70% (65 mg, 0.35 mmol). Yellow solid,
Mp: 126.3__127.4 ℃ (lit.36 Mp: 126 ℃); IR (neat) 533, 538, 552, 566, 617, 660, 695, 789,
889, 1004, 1189, 1258, 1292, 1313, 1371, 1334, 1592, 1620, 1656, 2848, 2923; 1H NMR
(400 MHz, CDCl3), δ = 8.09 (dd, J = 5.7, 3.3 Hz, 2H), 7.69 (dd, J = 5.8, 3.3 Hz, 2H), 2.19
(s, 6H); 13C{1H} NMR (100 MHz, CDCl3), δ = 184.7, 143.3, 133.2, 132.0, 126.1, 12.8.
2-tert-butyl-1,4-naphthoquinone 4k. Yield: 67% (72 mg, 0.33 mmol). Yellow solid,
Mp: 76.0__76.6 ℃ (lit.37 Mp: 76__77 ℃); IR (neat) 626, 670, 719, 785, 891, 903, 1125,
1201, 1248, 1307, 1340, 1330, 1591, 1654, 1663, 2869, 2958, 2969, 3068; 1H NMR (400
MHz, CDCl3), δ = 8.13–8.00 (m, 2H), 7.78–7.65 (m, 2H), 6.85 (s, 1H), 1.37 (s, 9H);
13C{1H} NMR (100 MHz, CDCl3), δ = 185.9, 184.9, 158.3, 133.8, 133.7, 133.5, 133.3,
131.5, 126.9, 125.6, 35.7, 29.4.
2-phenyl-1,4-naphthoquinone 4l. Yield: 72% (84 mg, 0.36 mmol). Yellow solid, Mp:
107.5__108.9 ℃ (lit.38 Mp: 107__108 ℃); IR (neat) 569, 669, 694, 714, 756, 849, 898,
909, 1014, 1044, 1118, 1204, 1244, 1306, 1332, 1442, 1485, 1569, 1588, 1650, 1663; 1H
NMR (400 MHz, CDCl3), δ = 7.84–7.74 (m, 2H), 7.62–7.54 (m, 2H), 7.52–7.44 (m, 3H),
7.09 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3), δ = 185.1, 184.4, 148.1, 135.2, 133.9,
133.8, 133.4, 132.4, 132.1, 130.0, 129.4, 128.4, 127.0, 126.0.
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2,3,6,7-tetramethylanthraquinone 5a. Yield: 98% (129 mg, 0.49 mmol). Light yellow
powder, Mp: 331.6__332.5 ℃ (lit.39 Mp: 330 ℃); IR (neat) 593, 717, 908, 927, 967, 1028,
1197, 1299, 1373, 1449, 1556, 1588, 1665; 1H NMR (400 MHz, CDCl3), δ = 8.03 (s, 4H),
2.43 (s, 12H); 13C{1H} NMR (100 MHz, CDCl3), δ = 183.6, 143.7, 131.6, 128.0, 20.2.
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Anthraquinone 5b. Yield: 98% (102 mg, 0.49 mmol). Light yellow powder, Mp:
218.7__219.5 ℃ (lit.40 Mp: 269__271 ℃); IR (neat) 620, 808, 817, 892, 935, 1168, 1205,
1282, 1331, 1573, 1673; 1H NMR (400 MHz, CDCl3), δ = 8.33 (dd, J = 5.8, 3.3 Hz, 4H),
13
7.82 (dd, J = 5.8, 3.3 Hz, 4H); C NMR (100 MHz, CDCl3), δ = 183.1, 134.1, 133.5,
127.2.
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website
at DOI: copies of 1H and 13C NMR spectra.
AUTHOR INFORMATION
Corresponding Author
*E-mail: mhayashi@kobe-u.ac.jp: matsubara.ryosuke@people.kobe-u.ac.jp. Website:
http://www2.kobe- u.ac.jp/~mhayashi/
ORCID
Masahiko Hayashi: 0000-0002-1716-6686
Ryosuke Matsubara: 0000-0001-8941-2391
Notes
The authors declare no competing financial interest.
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