First synthesis of alkylthio-substituted 4,4'-biphenoquinones and 4,4'- biphenohydroquinones (4,4-biphenyldiols)

Full text of DOI:10.1021/jo962058v

7464
J . Org. Chem. 1997, 62, 7464-7468
Notes
The key steps for the synthesis of new 4,4′-bipheno-
F ir st Syn th esis of Alk ylth io-Su bstitu ted
hydroquinones 1 and new 4,4′-biphenoquinones 2 are as
follows: for 1, direct methylthiolation of 4,4′-biphenyldiol,
cross-coupling reaction of aryl bromide with arylstan-
nane, and bromine-sulfur exchange reaction of a tetra-
bromo compound with thiolate nucleophile; and for 2,
oxidative coupling reaction of phenols.
As reported by Ranken and McKinnie,5 methylthio-
substituted phenols are conveniently prepared by direct
methylthiolation from the corresponding phenols and
(MeS)2. We utilized this method for the preparation of
methylthio-substituted 4,4′-biphenohydroquinones. Mono-
and bis(methylthio) derivatives 1a ,b were obtained as
main products by treating 4,4′-biphenyldiol with a large
excess of (MeS)2 in the presence of 1 and 2 equiv of AlCl3
in 17% and 22% yields, respectively. Oxidation of 1a
using 2 equiv of CAN6 in a mixture of CH2Cl2-H2O and
of 1b using excess of K3Fe(CN)6 in benzene-KOH (aq)
gave mono- and bis(methylthio)biphenoquinones 2a ,b7 as
reddish-black powders in 73% and 84% yields, respec-
tively.
In addition, synthesis of unsymmetrical derivatives
1c,d and 2c,d has been accomplished by the palladium-
catalyzed coupling reaction of aryl bromide with aryl-
stannane (the Stille reaction8) as a key step. The
preparation of the starting aryl bromide and arylstan-
nanes 3b-d is summarized in Table 1 (entries 1-3).
Cross-coupling reactions of 3b with arylstannanes 3c,d
were conducted in the presence of 6 equiv of LiCl, 10
mol % Pd(PPh3)4, and 4 mol % 2,6-di-tert-butyl-4-meth-
ylphenol (BHT) in 1,4-dioxane. The coupling products
4a ,b were obtained in 46% and 27% yields, respectively.
Deprotection of these compounds by TsOH‚H2O in
MeOH afforded the desired 4,4′-biphenohydroquinone
derivatives 1c,d in 93% and 77% yields, respectively.
The biphenoquinones 2c,d were obtained from 1c,d by
using 5 equiv of K3Fe(CN)6 in 52% and 56% yields,
respectively.
4,4′-Bip h en oqu in on es a n d
4,4′-Bip h en oh yd r oqu in on es
(4,4′-Bip h en yld iols)
Yasushi Morita,* Atsushi Kashiwagi, and
Kazuhiro Nakasuji*
Department of Chemistry, Graduate School of Science,
Osaka University, Toyonaka, Osaka 560, J apan
Received November 4, 1996 (Revised Manuscript Received
J uly 7, 1997)
1,4-Benzoquinhydrone is a hydrogen-bonded charge-
transfer (CT) complex between quinone and hydro-
quinone. Since a new phase transition of the complex
was found under high pressure, we have been interested
in chemical modification of the quinhydrone-type CT
complexes to explore new molecular materials having
interesting solid state properties.1 Our recent studies on
the 1,4-benzoquinones with donor and acceptor substit-
uents made clear their amphoteric redox nature and the
substituent effects of π-donor groups.3 In the present
study, we have designed and synthesized new extended
conjugated quinones and hydroquinones having the donor
and acceptor substituents to decrease the intermolecular
CT gap.2,4 In this paper, we report the first synthesis of
11 new 4,4′-biphenoquinone derivatives 2 and 11 new
4,4′-biphenohydroquinone derivatives 1 with alkylthio
and halogen substituents.
(4) CT complexes based on the tetrachloro- or tetrabromo-4,4′-
biphenoquinones are reported: (a) Iida, Y. Bull. Chem. Soc. J pn. 1972,
45, 105. (b) Matsunaga, Y.; Narita, Y. Bull. Chem. Soc. J pn. 1972, 45,
408. (c) Golovkina, I. F.; Krivoshei, I. V.; Starodub, V. A.; Aleshin, V.
G.; Gella, I. M.; Nemoshkalenko, V. V.; Senkevich, A. I.; Surov, Y. N.
Teor. Eksp. Khim. 1979, 15, 181. (d) Starikova, Z. A.; Shchegoleva, T.
M.; Trunov, V. K.; Lantratova, O. B.; Pokrovskaya, I. E. Zh. Strukt.
Khim. 1980, 21, 73. (e) Shchegoleva, T. M.; Starikova, Z. A.; Trunov,
V. K.; Lantratova, O. B.; Pokrovskaya, I. E. Zh. Strukt. Khim. 1981,
22, 93. (f) Starodub, V. A.; Gluzman, E. M.; Golovkina, I. F.; Zaslavskaya,
G. S.; Krivoshei, I. V. Zh. Obshch. Khim. 1981, 51, 2306. (g) Lau, C.-
P.; Singh, P.; Cline, S. J .; Seiders, R.; Brookhart, M.; Marsh, W. E.;
Hodgson, D. J .; Hatfield, W. E. Mol. Cryst. Liq. Cryst. 1982, 86, 131.
(h) Starodub, V. A.; Gluzman, E. M.; Golovkina, I. P. Zh. Obshch. Khim.
1983, 53, 1127. (i) Akutagawa, T.; Saito, G. Bull. Chem. Soc. J pn. 1995,
68, 1753.
(5) (a) Ranken, P. F.; McKinnie, B. G. Synthesis 1984, 117. (b)
McKinnie, B. G.; Ranken, P. F. Eur. Patent 122,203, 1984; Chem. Abstr.
1985, 102, 28149d.
(6) CAN is known as an effective oxidizing agent for both hydro-
quinone and sulfide to the quinone and sulfoxide, respectively; see for
review: Ho, T.-L. In Cerium(IV) Oxidation of Organic Compounds;
Mijs, W. J ., de J onge, C. R. H. I., Eds.; Plenum Press: New York, 1986;
Chapter 11, p 569.
(7) This biphenoquinone was obtained as a mixture of stereoisomers.
(8) Reviews: (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986,
25, 508. (b) Mitchell, T. N. Synthesis 1992, 803.
(9) This MOM-protected phenol was prepared from the correspond-
ing phenol, MOMCl (1.1-1.5 equiv), and NaH (1.1-1.8 equiv) in THF
at rt in quantitative yield; see: Supporting Information.
* To whom correspondence should be addressed: fax, 81-06-850-
5392.
(1) (a) Nakasuji, K.; Sugiura, K.; Kitagawa, T.; Toyoda, J .; Okamoto,
H.; Okaniwa, K.; Mitani, T.; Yamamoto, H.; Murata, I. J . Am. Chem.
Soc. 1991, 113, 1862. (b) Mitani, T.; Saito, G.; Urayama, H. Phys. Rev.
Lett. 1988, 60, 2299. (c) Sugiura, K.; Toyoda, J .; Okamoto, H.; Okaniwa,
K.; Mitani, T.; Kawamoto, A.; Tanaka, J .; Nakasuji, K. Angew. Chem.,
Int. Ed. Engl. 1992, 31, 852.
(2) Viehe, H. G.; J anousek, Z.; Merenyi, R.; Stella, L. Acc. Chem.
Res. 1985, 18, 148.
(3) Kitagawa, T.; Toyoda, J .; Nakasuji, K.; Yamamoto, H.; Murata,
I. Chem. Lett. 1990, 897.
S0022-3263(96)02058-0 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 21, 1997 7465
Ta ble 1. P r ep a r a tion of Alk ylth io-Su bstitu ted P h en ol Der iva tivesa
entry
products
starting materials
reagents and conditions
yield, %
41
1
2
3b
3a b
a. 5 equiv of n-BuLi, pentane, -20 °Cc
b. 5 equiv of (MeS)2, -30-0 °C
a. n-BuLi, THF, -78 °C
b. Bu3SnCl, -78 °C
a. 2 equiv of t-BuLi, THF, -95 °C
b. Bu3SnCl, -95 °C
excess (MeS)2
cat. Al powder, 110 °C, 5 days
3 equiv of Cu(I)SPrh
quinoline-pyridine, 160 °C, 5.5 h
4 equiv of Cu(I)S-t-Buk
quinoline-pyridine, 160 °C, 6 h
excess (MeS)2
AlCl3, 100 °C, 4 h
excess (MeS)2
AlCl3, 110 °C, 5 h
cat. TsOH‚H2O
MeOH, 65 °C, 8 h
cat. TsOH‚H2O
MeOH, 65 °C, 2 h
3c
4-bromophenol MOM etherd
89
85
16
83
79
15
16
92
98
72
40
3
3d
5a f
5b
5c
4-bromo-2,6-dimethylphenol MOM ethere
4
phenol
5
2,6-dibromophenolg
6
2,6-dibromophenolg
7
5d
5ei
5fj
5g
6c
2-fluorophenol
8
2-chlorophenol
9
6c
10
11
12
6d
6a b
6bb
a. 2 equiv of t-BuLi, THF, -95 °C
b. (MeS)2, 0.5 h
a. 2 equiv of t-BuLi, THF, -95 °C
b. (MeS)2, 0.5 h
6d
a
b
g
See Supporting Information for full details. Reference 9. c Reference 10. dReference 11. e Reference 12. f Reference 5. Reference
h
i
j
k
16. Reference 17. Reference 15. Reference 18. Reference 20.
tions. In such circumstances we have found that DDQ14
is a very effective and convenient oxidant for the syn-
thesis of the desired 4,4′-biphenoquinones 2e,f,h -k
from the alkylthio-substituted phenols 5a ,b,d -g in good
yield.
Synthesis of tetrasubstituted biphenoquinones 2e,f,h -k
has been accomplished by the oxidative coupling reaction
of phenols. Alkyl, phenyl, and methoxy derivatives of
4,4′-biphenoquinones were prepared from the corre-
sponding substituted phenols by using a variety of
reagents, such as metal oxidants and organic oxidants,
and by electrochemical oxidation.13 However, the prod-
ucts are mostly complex mixtures of compounds such as
the 1,4-benzoquinone, 4,4′-biphenohydroquinone, and
polymeric phenol ether as well as the desired 4,4′-
biphenoquinone.13 Furthermore, in the case of alkylthio-
substituted phenol as substrate, sulfoxide compounds
are also produced under the oxidative coupling condi-
The preparation of the starting phenols 5a ,b,d -g is
shown in Table 1 (entries 4, 5, 7-12). These phenols
were treated with 1 equiv of DDQ in MeOH at rt, and
then the resulting black precipitate was filtered and
washed with MeOH to afford the desired, analytically
pure 4,4′-biphenoquinones 2e,f,h 7-k 7 as bluish-black
(14) Only a limited number of reports are known about DDQ as a
phenol oxidative coupling agent: (a) Becker, H.-D. J . Org. Chem. 1965,
30, 982. (b) Boldt, P.; Michaelis, W.; Lackner, H.; Krebs, B. Chem. Ber.
1971, 104, 220. (c) Cardillo, G.; Cricchio, R.; Merlini, L. Tetrahedron
1971, 27, 1875. For DDQ review: (d) Walker, D.; Hiebert, J . D. Chem.
Rev. 1967, 67, 153.
(15) Winkler, A. DE 2644591, 1978; Chem. Abstr. 1978, 89, 23960q.
(16) Pearson, D. E.; Wysong, R. D.; Breder, C. V. J . Org. Chem. 1967,
32, 2358.
(10) For ortho-selective lithiation of 2,4,6-tribromophenyl methyl
ether, see: Green, K. J . Org. Chem. 1991, 56, 4325.
(11) Kipping, F. B.; Wren, J . J . J . Chem. Soc. 1957, 3246.
(12) Borror, A. L.; Cincotta, L.; Ellis, E. W.; Foley, J . W.; Kampe,
M. M. U.S. 4,181,660, 1980; Chem. Abstr. 1980, 92, 146747.
(13) For review: (a) Boldt, P. In Methoden der Organischen Chemie
(Houben-Weyl); Mu¨ller, E., Bayer, O., Eds.; Georg Thieme Verlag:
Stuttgart, 1979; Bd. 7, 3b, p 188. (b) Whiting, D. A. In Comprehensive
Organic Synthesis; Pattenden, G., FRS, Ed.; Pergamon Press: Oxford,
1991; Vol. 3, Chapter 2.9, p 659.
(17) Ford, P. W.; Davidson, B. S. J . Org. Chem. 1993, 58, 4522.
(18) Lertratanangkoon, K.; Horning, M. G. Drug Metab. Dispos.
1987, 15, 1.

7466 J . Org. Chem., Vol. 62, No. 21, 1997
Ta ble 2. Selected P h ysica l a n d Cyclic Volta m m etr ic Da ta (V vs SCE)a of Bip h en oqu in on es 2
2b 2c 2d 2e 2f 2g 2h 2i 2j
Notes
2a
2k
IR,b
cm-1
UV,c
1621, 1580, 1612, 1594, 1623, 1592, 1587, 1559, 1588, 1513 1605, 1592, 2960, 1625, 1611, 1526 1619, 1519 1616, 1514 1610, 1509
1559
274, 402,
512
1543
266, 402,
564
1509
1508
1510
1508
250, 288,
326, 492
248, 288,
332, 496
256, 304, 258, 308,
262, 304,
428, 568
266, 422, 242, 284,
244, 288,
248, 298,
494, 576
nm
562
-0.25
-0.52
570
572
-0.07
-0.33
452, 582 462, 582
red
red
E1
E2
-0.22
-0.45
-0.23
-0.50
-0.21
-0.45
-0.31
-0.55
-0.37
-0.10
-0.39
-0.02
-0.29
-0.01
-0.30
-0.02
-0.28
a
b
Measured against the saturated calomel electrode (SCE) in CH3CN with 0.1 M n-Bu4NClO4 as supporting electrolyte at rt. KBr
pellet. c CH2Cl2 solution.
were dried over Na2SO4, then filtered, and concentrated under
reduced pressure. The residual white powder was subjected
to silica gel column chromatography with a 10:1 to 2:1 mixture
of hexane and ethyl acetate as eluant, yielding crude 1a . This
crude product was further purified by silica gel column
chromatography with CH2Cl2 as eluant, to give 1a (433 mg,
powders in 80%, 60%, 52%, 70%, 64%, and 84% yields,
respectively. Na2S2O4 reduction of 2e,f,h -k gave the
corresponding biphenohydroquinones 1e,19f,h -k in 73%,
42%, 79%, 94%, 96%, and 99% yields, respectively. Since
oxidation of 2,6-bis(tert-butylthio)phenol (5c) (Table 1,
entry 6) with DDQ did not give the desired 2g, we
prepared tetrakis(tert-butylthio) derivative (1g) by treat-
ing 3,3′,5,5′-tetrabromo-4,4′-biphenohydroquinone21 with
excess of Cu(I)S-t-Bu20 in 14% yield. Oxidation of 1g
using excess of K3Fe(CN)6 gave tetrakis(tert-butylthio)-
biphenoquinone 2g in 86% yield.
The biphenoquinones 2 are stable in the solid state.
The tetrasubstituted derivatives 2d -f are stable in
solution. The monosubstituted derivative 2a is not stable
in CDCl3: for example, it decomposed to the extent of
more than 50% within several days. Selected physical
data and redox potentials of these biphenoquinones are
shown in Table 2.
1
17%) as a white powder: mp 105 °C; H NMR (DMSO-d6) δ
2.42 (s, 3, SMe), 6.80 (d, 2, J ) 8.6 Hz, 3′-, 5′-H), 6.82 (d, 1, J
) 8.1 Hz, 5-H), 7.16 (dd, 1, J ) 2.1, 8.1 Hz, 6-H), 7.22 (d, 1, J
) 2.1 Hz, 2-H), 7.39 (d, 2, J ) 8.6 Hz, 2′-, 6′-H), 9.37 (s, 1,
OH), 9.76 (s, 1, OH); IR (KBr) 3300, 1494 cm-1; UV (CH3CN)
252 nm; MS m/ z 232 (M+, 100). Anal. Calcd for C13H12O2S:
C, 67.21; H, 5.21. Found: C, 66.87; H, 5.16.
3-(Meth ylth io)-4,4′-bip h en oqu in on e (2a ). Hydroquinone
1a (100.3 mg, 0.432 mmol) was placed in a 50-mL round-
bottomed flask and dissolved in CH2Cl2 (15 mL) and H2O (15
mL) at rt. To this mixture was added CAN (473.7 mg, 0.864
mmol) in one portion, and the mixture was stirred at rt for 3
min. The dark-red-colored organic layer was separated,
washed with H2O (15 mL × 2), and then dried over Na2SO4.
After being filtered and washed with CH2Cl2, the resulting
dark-red solution was concentrated under reduced pressure
and dried in vacuo at rt to give crude 2a as a reddish-black
powder. This crude product was subjected to deactivated silica
gel column chromatography with a 2:1 to 1:1 mixture of hexane
and ethyl acetate as eluant, yielding biphenoquinone 2a (72.4
mg, 73%) as a reddish-black powder: mp 165-168 °C dec; 1H
NMR (CDCl3) δ 2.49 (s, 3), 6.60-6.75 (m, 3), 7.34 (d, 1, J )
2.6 Hz), 7.85-8.00 (m, 3); MS m/ z 232 (M+ + 2H, 100); HRMS
m/ z calcd for C13H12O2S (M+ + 2H) 232.0559, found 232.0533.
In conclusion, our synthetic procedures provide a
simple and convergent approach for the preparation of
4,4′-biphenoquinones and 4,4′-biphenohydroquinones sub-
stituted with alkylthio and halogen groups. We are
currently investigating further applications of these
methods for the synthesis of new bipheno compounds.
Exp er im en ta l Section
Gen er a l. 1H and 13C NMR spectra were recorded at 270
and 68 MHz, respectively, with CDCl3, acetone-d6, or DMSO-
d6 as solvent and Me4Si or residual solvent as an internal
standard. Infrared spectra were recorded using KBr plates
or Cl2CdCCl2 solution. Electronic spectra were recorded using
CH3CN or CH2Cl2 solution. Mass spectra analyses were
recorded by electron impact at 70 eV. The cyclic voltammetries
were carried out at rt under argon. Melting points were
measured with a hot-stage apparatus and are uncorrected.
Elemental analyses were performed at the Graduate School
of Science at Osaka University. Silica gel 60 (100-200 mesh)
was used for column chromatography. Deactivated silica gel
was prepared by mixing with 6% water. Solvents were dried
(drying agent in parentheses) and distilled under argon prior
to use: THF (Na-benzophenone ketyl), 1,4-dioxane (Na),
MeOH (Mg(OMe)2), CH3CN, CH2Cl2 (CaH2), Cl2CdCCl2 (P4O10),
quinoline (Na2SO4 then Zn powder). All reactions requiring
anhydrous conditions were conducted under argon atmosphere.
3-(Meth ylth io)-4,4′-bip h en oh yd r oqu in on e (1a ). 4,4′-
Biphenyldiol (2.09 g, 11.2 mmol), (MeS)2 (20.2 mL, 225 mmol),
and AlCl3 (1.50 g, 11.2 mmol) were placed in a 100-mL round-
bottomed flask, and this mixture was heated at 110 °C. After
being stirred at this temperature for 0.5 h, this reaction
mixture was cooled to rt and then poured into a chilled 1 M
HCl aqueous solution (100 mL) and ether (50 mL). The
organic layer was separated, and the aqueous layer was
extracted with ether (50 mL). The combined organic extracts
3,3′-Bis(m et h ylt h io)-4,4′-b ip h en oh yd r oq u in on e (1b ).
This compound was prepared by a similar procedure as for
the synthesis of 1a using 4,4′-biphenyldiol (2.14 g, 11.5 mmol),
(MeS)2 (41.4 mL, 460 mmol), and AlCl3 (3.07 g, 23.0 mmol):
1
grayish-yellow-green powder, yield 22%; mp 68 °C; H NMR
(CDCl3) δ 2.38 (s, 6), 6.64 (s, 2), 7.03 (d, 2, J ) 8.3 Hz), 7.42
(dd, 2, J ) 8.3, 2.3 Hz), 7.66 (d, 2, J ) 2.3 Hz); IR (KBr) 3320,
1421 cm-1; UV (CH3CN) 248, 275(sh), 305(sh) nm; MS m/ z
278 (M+, 100). Anal. Calcd for C14H14O2S2: C, 60.40; H, 5.07.
Found: C, 60.18; H, 4.83.
3,3′-Bis(m eth ylth io)-4,4′-bip h en oqu in on e (2b).7 Hyd-
roquinone 1b (221.8 mg, 0.797 mmol) was placed in a 100-mL
round-bottomed flask and mixed with benzene (30 mL). To
this mixture was added a solution of K3Fe(CN)6 (2651 mg, 7.97
mmol) and KOH (2634 mg, 39.9 mmol) in H2O (30 mL) in one
portion, and the mixture was stirred at rt for 5 min. The black
precipitate was filtered and washed with H2O (300 mL) and
MeOH (100 mL), successively. The resulting reddish-black
powder was dried in vacuo at rt for 4 h, yielding bipheno-
quinone 2b (186.0 mg, 84%) as a reddish-black powder: mp
>300 °C; 1H NMR (CDCl3) δ 2.56 (s, 6), 2.60 (s, 6), 6.61 (br s,
4), 7.70 (br dd, 4, J ) 8.9, 2.3 Hz), 8.23 (d, 2, J ) 8.1 Hz), 8.37
(d, 2, J ) 8.1 Hz); MS m/ z 278 (M+ + 2H, 100). Anal. Calcd
for C14H12O2S2: C, 60.84; H, 4.38. Found: C, 60.68; H, 4.24.
3,5-Bis(m eth ylth io)bip h en yl-4,4′-d iyl Bis(m eth oxym -
eth yl) Eth er (4a ). Bromophenol derivative 3b (1.29 g, 4.18
mmol), arylstannane 3c (1.78 g, 4.18 mmol), Pd(PPh3)4 (483
mg, 0.418 mmol), BHT (37.7 mg, 0.171 mmol), and LiCl (1.06
g, 25.0 mmol) were placed in a 500-mL round-bottomed flask
and suspended in 1,4-dioxane (150 mL). This mixture was
stirred at 110-115 °C for 8.5 h and then cooled to rt. To this
reaction mixture was added satd aqueous KF solution (50 mL),
and the resulting suspension was filtered. The organic layer
was separated, and the aqueous layer was extracted with
(19) This hydroquinone was also obtained by the homocoupling
reaction of 3b (NiCl2(PPh3)2 (1 equiv), active Zn powder (1 equiv), and
PPh3 (1.7 equiv) in DMF at -20-0 °C, yield 28%) and subsequent
deprotection of MOM groups (cat. TsOH‚H2O in THF-MeOH at 60
°C, yield 89%); see: Supporting Information.
(20) Adams, R.; Ferretti, A. J . Am. Chem. Soc. 1959, 81, 4927.
(21) Magatti, G. Chem. Ber. 1880, 13, 224.

Notes
J . Org. Chem., Vol. 62, No. 21, 1997 7467
ether. The combined organic extracts were washed with satd
aqueous NaCl solution (50 mL), dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residual oil
was subjected to silica gel column chromatography with a
100:1 to 10:1 mixture of hexane and ethyl acetate as eluant,
yielding coupling product 4a (706 mg, 46%) as a pale-yellow
oil: 1H NMR (CDCl3) δ 2.47 (s, 6), 3.51 (s, 3), 3.74 (s, 3), 5.18
(s, 2), 5.22 (s, 2), 7.09 (s, 2), 7.11 (br d, 2, J ) 8.9 Hz), 7.46 (br
d, 2, J ) 8.9 Hz). The product was used without further
purification in the following reaction.
was stirred at rt for 75 min and then filtered, washed with
MeOH, and dried in vacuo at rt for 4 h, yielding bipheno-
quinone 2e (1.67 g, 80%) as a bluish-black powder: mp 220-
222 °C dec; 1H NMR (acetone-d6) δ 2.43 (s, 12), 6.38 (s, 4); MS
m/ z 370 (M+ + 2H, 100). Anal. Calcd for C16H16O2S4: C,
52.14; H, 4.38. Found: C, 51.88; H, 4.33.
3,3′,5,5′-Te t r a k is(p r op ylt h io)-4,4′-b ip h e n oq u in on e
(2f): bluish-black powder, yield 60%; mp 192-194 °C dec; 1H
NMR (CDCl3) δ 1.12 (t, 12, J ) 7.3 Hz), 1.82 (sextet, 8, J )
7.3 Hz), 2.91 (t, 8, J ) 7.4 Hz), 7.35 (s, 4); MS m/ z 482 (M+
+
3,5-Bis(m eth ylth io)-4,4′-biph en oh ydr oqu in on e (1c). Bis-
(MOM)-protected biphenol derivative 4a (706 mg, 1.93 mmol)
was placed in a 300-mL round-bottomed flask and dissolved
in THF (50 mL) and MeOH (50 mL). To this mixture was
added TsOH‚H2O (20.0 mg, 0.105 mmol), and the mixture was
stirred at rt for 14 h and then at 90 °C for 28 h. After being
cooled to rt, most of the solvent was removed in vacuo at rt.
pH 7.0 phosphate buffer solution (0.1 M solution, 20 mL) and
ethyl acetate (20 mL) were added to this residual oil. The
organic layer was separated, and the aqueous layer was
extracted with ethyl acetate (10 mL × 2). The combined
organic extracts were dried over MgSO4, filtered, and concen-
trated under reduced pressure. The residual oil was subjected
to deactivated silica gel column chromatography with a 100:1
to 5:1 mixture of hexane and ethyl acetate as eluant, yielding
1c (446 mg, 83%) as a yellowish-gray powder: mp 126-127
2H, 100). Anal. Calcd for C24H32O2S4: C, 59.96; H, 6.71.
Found: C, 59.88; H, 6.65.
3,3′-D i flu o r o -5,5 ′-b i s (m e t h y lt h i o )-4,4 ′-b i p h e n o -
qu in on e (2h ):7 dark-grayish-blue powder, yield 52%; mp >300
1
°C; H NMR (DMSO-d6) δ 2.57 (s, 6), 2.59 (s, 6), 7.49 (s, 2),
7.64 (s, 2), 8.16 (d, 2, J ) 10.8 Hz), 8.34 (d, 2, J ) 10.8 Hz);
MS m/ z 314 (M+ + 2H, 100). Anal. Calcd for C14H10F2O2S2:
C, 53.83; H, 3.23. Found: C, 53.27; H, 3.25.
3,3′-D i c h lo r o -5,5′-b i s (m e t h y lt h i o )-4,4′-b i p h e n o -
qu in on e (2i):7 bluish-black powder, yield 70%; mp >300 °C;
1H NMR (acetone-d6) δ 2.63 (s, 6), 2.66 (s, 6), 7.74 (d, 2, J )
2.6 Hz), 7.75 (d, 2, J ) 2.6 Hz), 8.56 (d, 2, J ) 2.6 Hz), 8.58 (d,
2, J ) 2.6 Hz); MS m/ z 346 (M+ + 2H, 100). Anal. Calcd for
C14H10Cl2O2S2: C, 48.70; H, 2.92. Found: C, 48.60; H, 2.95.
3,3′-D i b r o m o -5,5′-b i s (m e t h y lt h i o )-4,4′-b i p h e n o -
qu in on e (2j):7 grayish-black powder, yield 64%; mp >300 °C
dec; 1H NMR (acetone-d6) δ 2.63 (s, 6), 2.65 (s, 6), 7.74 (d, 2, J
) 2.6 Hz), 7.77 (d, 2, J ) 2.6 Hz), 8.79 (d, 2, J ) 3.0 Hz), 8.81
(d, 2, J ) 3.0 Hz); MS m/ z 436 (M+ + 2H, 2.2). Anal. Calcd
for C14H10Br2O2S2: C, 38.73; H, 2.32. Found: C, 39.13; H, 2.41.
3,3′-Diiod o-5,5′-b is(m et h ylt h io)-4,4′-b ip h en oq u in on e
(2k ):7 black powder, yield 84%; mp >300 °C; 1H NMR (DMSO-
d6) δ 2.56 (s, 6), 2.58 (s, 6), 7.62 (s, 4), 9.06 (d, 2, J ) 2.3 Hz),
9.13 (d, 2, J ) 2.3 Hz); MS m/ z 530 (M+ + 2H, 43). Anal.
Calcd for C14H10I2O2S2: C, 31.84; H, 1.91. Found: C, 32.28;
H, 1.90.
1
°C; H NMR (CDCl3) δ 2.44 (s, 6), 4.83 (s, 1), 6.89 (d, 2, J )
8.8 Hz), 7.04 (s, 1), 7.41 (d, 2, J ) 8.8 Hz), 7.41 (s, 1); IR (KBr)
3441, 3332, 1450, 1435 cm-1; UV (CH3CN) 254, 320 nm; MS
m/ z 278 (M+, 100). Anal. Calcd for C14H14O2S2: C, 60.40; H,
5.07. Found: C, 59.99; H, 5.01.
3,5-Bis(m eth ylth io)-3′,5′-dim eth ylbiph en yl-4,4′-diyl Bis-
(m eth oxym eth yl) Eth er (4b). This compound was prepared
by a similar procedure as for the synthesis of 4a using 3b (524
mg, 1.67 mmol), 3d (772 mg, 1.67 mmol), Pd(PPh3)4 (196 mg,
0.170 mmol), BHT (18.7 mg, 0.085 mmol), and LiCl (431 mg,
10.2 mmol): yield 27%; 1H NMR (CDCl3) δ 2.36 (s, 6), 2.48 (s,
6), 3.64 (s, 3), 3.73 (s, 3), 5.00 (s, 2), 5.18 (s, 2), 7.08 (s, 2), 7.17
(s, 2); MS m/ z 394 (M+, 52), 349 (M+ - SCH3 + 2H, 100). The
product was used without further purification in the following
reaction.
3,5-Bis(m eth ylth io)-3′,5′-d im eth yl-4,4′-bip h en oh yd r o-
qu in on e (1d ). This compound was prepared by a similar
procedure as for the synthesis of 1c using 4b (403 mg, 1.02
mmol) and TsOH‚H2O (13.9 mg, 0.073 mmol): yield 64%; mp
108-111 °C; 1H NMR (CDCl3) δ 2.31 (s, 6), 2.45 (s, 6), 7.02 (s,
2), 7.14 (s, 2), 7.41 (s, 2); IR (KBr) 3475, 3316, 1456 cm-1; UV
(CH3CN) 256, 320(sh) nm; MS m/ z 306 (M+, 100). Anal.
Calcd for C16H18O2S2: C, 62.71; H, 5.92. Found: C, 62.24; H,
5.81.
3,5-Bis(m eth ylth io)-4,4′-biph en oqu in on e (2c). This com-
pound was prepared by a similar procedure as for the synthesis
of 2b using 1c (136 mg, 0.488 mmol), K3Fe(CN)6 (803 mg, 2.44
mmol), and KOH (548 mg, 9.76 mmol): brownish-black
powder, yield 56%; mp 195-199 °C dec; 1H NMR (CDCl3) δ
2.49 (s, 6), 6.66 (d, 2, J ) 9.9 Hz), 7.34 (d, 2, J ) 13.9 Hz),
7.95 (d, 2, J ) 9.9 Hz); MS m/ z 278 (M+ + 2H, 100). Anal.
Calcd for C14H12O2S2: C, 60.84; H, 4.38. Found: C, 60.80; H,
4.38.
Gen er a l P r oced u r e for th e 3,3′,5,5′-Tetr a su bstitu ted
4,4′-Bip h en oh yd r oq u in on es fr om t h e Cor r esp on d in g
4,4′-Bip h en oqu in on es: 3,3′,5,5′-Tetr a k is(m eth ylth io)-4,4′-
bip h en oh yd r oqu in on e (1e). Biphenoquinone 2e (539 mg,
1.46 mmol) was placed in a 200-mL round-bottomed flask and
suspended in ether (50 mL). A solution of Na2S2O4 (3.56 g,
20.5 mmol) in 1 M NaOH (75 mL) was added to this mixture
in one portion. After being stirred at rt for 30 min, the reaction
mixture was acidified by slow addition of concd HCl. The
organic layer was separated, and the aqueous layer was
extracted with ethyl acetate (50 mL × 2). The combined
organic extracts were dried over MgSO4, filtered, and concen-
trated under reduced pressure at 40 °C. The residual yellow-
ish-pink powder was subjected to silica gel column chroma-
tography with a 10:1 to 2:1 mixture of hexane and ethyl acetate
as eluant, yielding 1e (393 mg, 73%) as a beige-white powder:
1
mp 128-129 °C; H NMR (CDCl3) δ 2.45 (s, 12), 7.08 (s, 2),
7.40 (s, 4); IR (KBr) 3367, 2916, 1443 cm-1; UV (CH3CN) 252,
310 nm; MS m/ z 370 (M+, 100). Anal. Calcd for C16H18O2S4:
C, 51.86; H, 4.90. Found: C, 51.85; H, 4.86.
3,3′,5,5′-T e t r a k is (p r o p y lt h io )-4,4′-b ip h e n o h y d r o -
qu in on e (1f): colorless oil, 42% yield; 1H NMR (CDCl3) δ 1.03
(t, 12, J ) 7.3 Hz), 1.66 (sextet, 8, J ) 7.3 Hz), 2.84 (t, 8, J )
7.3 Hz), 7.19 (s, 2), 7.44 (s, 4); IR (Cl2CdCCl2) 3388, 2964, 2932,
1432 cm-1; UV (CH3CN) 256, 310 nm; MS m/ z 482 (M+, 100).
Anal. Calcd for C24H34O2S4: C, 59.71; H, 7.10. Found: C,
60.11; H, 7.18.
3,3′-Diflu or o-5,5′-b is(m et h ylt h io)-4,4′-b ip h en oh yd r o-
qu in on e (1h ): pale-beige powder, 79% yield; mp 128-130 °C;
1H NMR (CDCl3) δ 2.44 (s, 6), 6.26 (s, 2), 7.20 (br dd, 2, J )
2.3, 11.2 Hz), 7.35 (br t, 2); IR (KBr) 3423, 1473 cm-1; UV
(CH3CN) 250, 300(sh) nm; MS m/ z 314 (M+, 100). Anal.
Calcd for C14H12F2O2S2: C, 53.49; H, 3.85. Found: C, 53.59;
H, 3.93.
3,5-B i s (m e t h y lt h i o )-3′,5′-d i m e t h y l-4,4′-b i p h e n o -
qu in on e (2d ). This compound was prepared by a similar
procedure as for the synthesis of 2b using 1d (177 mg, 0.579
mmol), K3Fe(CN)6 (953 mg, 2.90 mmol), and KOH (650 mg,
11.6 mmol): dark-grayish-olive powder, yield 88%; mp 158-
1
160 °C dec; H NMR (CDCl3) δ 2.18 (s, 6), 2.50 (s, 6), 7.35 (s,
2), 7.69 (s, 2); MS m/ z 304 (M+, 64), 306 (M+ + 2H, 54). Anal.
Calcd for C16H16O2S2: C, 63.13; H, 5.30. Found: C, 63.23; H,
5.46.
Gen er a l P r oced u r e for th e Tetr a su bstitu ted 4,4′-Bi-
p h en oqu in on es fr om 2,6-Disu bstitu ted P h en ols: 3,3′,5,5′-
Tetr akis(m eth ylth io)-4,4′-biph en oqu in on e (2e). DDQ (2.59
g, 11.4 mmol) was placed in a 100-mL round-bottomed flask
and dissolved in MeOH (25 mL). To this mixture was added
a solution of 2,6-bis(methylthio)phenol (5a ) (2.12 g, 11.4 mmol)
in MeOH (10 mL) in one portion, and the mixture was rinsed
with MeOH (10 mL). The resulting bluish-black suspension
3,3′-Dich lor o-5,5′-b is(m et h ylt h io)-4,4′-b ip h en oh yd r o-
qu in on e (1i): pale-yellow powder, 94% yield; mp 116-117
1
°C; H NMR (CDCl3) δ 2.45 (s, 6), 6.61 (s, 2), 7.42 (d, 2, J )
2.3 Hz), 7.44 (d, 2, J ) 2.3 Hz); IR (KBr) 3346, 2923, 1456
cm-1; UV (CH3CN) 254, 305(sh) nm; EI-MS m/ z 346 (M+, 100).

7468 J . Org. Chem., Vol. 62, No. 21, 1997
Notes
Anal. Calcd for C14H12Cl2O2S2: C, 48.42; H, 3.48. Found: C,
48.42; H, 3.50.
chromatography with a 100:1 to 10:1 mixture of hexane and
ethyl acetate as eluant, yielding 1g (813 mg, 14%) as a white
powder: mp 176-178 °C; 1H NMR (CDCl3) δ 1.36 (s, 36), 7.47
(s, 2), 7.66 (s, 4); IR (KBr) 3375, 3341, 2973, 1422 cm-1; UV
(CH3CN) 220, 266, 310(sh) nm; MS m/ z 538 (M+, 9), 450 (M+
- S-t-Bu + H, 18). Anal. Calcd for C28H42O2S4: C, 62.40; H,
7.86. Found: C, 62.34; H, 7.82.
3,3′-Dib r om o-5,5′-b is(m et h ylt h io)-4,4′-b ip h en oh yd r o-
qu in on e (1j): beige-white powder, 96% yield; mp 122-123
1
°C; H NMR (CDCl3) δ 2.44 (s, 6), 6.69 (s, 2), 7.48 (d, 2, J )
2.3 Hz), 7.57 (d, 2, J ) 2.0 Hz); IR (KBr) 3424, 3333, 2919,
1455 cm-1; UV (CH3CN) 256, 305(sh) nm; MS m/ z 436
(M+, 100). Anal. Calcd for C14H12Br2O2S2: C, 38.55; H, 2.77.
Found: C, 38.87; H, 2.85.
3,3′,5,5′-Tet r a k is(ter t-b u t ylt h io)-4,4′-b ip h en oq u in on e
(2g). This compound was prepared by a similar procedure as
for the synthesis of 2b using 1g (398 mg, 0.739 mmol),
K3Fe(CN)6 (2.40 g, 7.39 mmol), and KOH (2.07 g, 37.0 mmol):
dark-grayish-violet powder, yield 86%; mp 190-191 °C dec;
3,3′-Diiod o-5,5′-b is(m e t h ylt h io)-4,4′-b ip h e n oh yd r o-
qu in on e (1k ): yellowish-white powder, 99% yield; mp 178-
180 °C; 1H NMR (CDCl3) δ 2.42 (s, 6), 6.93 (s, 2), 7.54 (d, 2, J
) 2.3 Hz), 7.78 (d, 2, J ) 2.0 Hz); IR (KBr) 3356, 2923, 1429
cm-1; UV (CH3CN) 234, 260, 305(sh) nm; MS m/ z 530 (M+,
100). Anal. Calcd for C14H12I2O2S2: C, 31.71; H, 2.28.
Found: C, 32.08; H, 2.31.
1H NMR (CDCl3) δ 1.51 (s, 36), 7.97 (s, 4); MS m/ z 538 (M+
2H, 25). Anal. Calcd for C28H40O2S4: C, 62.64; H, 7.51.
Found: C, 62.57; H, 7.46.
+
3,3′,5,5′-Tet r a k is(ter t-b u t ylt h io)-4,4′-b ip h en oh yd r o-
qu in on e (1g). 3,3′,5,5′-Tetrabromo-4,4′-biphenohydroquinone
(5.57 g, 11.1 mmol) and Cu(I)S-t-Bu (13.6 g, 88.8 mmol) were
placed in a 500-mL round-bottomed flask and mixed with
quinoline (75 mL) and pyridine (25 mL). This mixture was
warmed up to 160 °C and stirred at this temperature for 2.5
h. After being cooled to rt, the resulting suspension was
poured into a chilled 2 M HCl aqueous solution (100 mL). After
addition of ethyl acetate (100 mL) to this mixture, the organic
layer was separated and the aqueous layer was extracted with
ethyl acetate. The combined organic extracts were washed
with 2 M HCl aqueous solution (100 mL × 2), dried over
Na2SO4, filtered, and concentrated under reduced pressure.
The residual brown oil was subjected to silica gel column
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research from the Ministry
of Education, Science and Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Spectroscopic data
(1H NMR, IR, MS, and Anal. Calcd) and experimental proce-
dures for the preparation of compounds 3a -d , 5b-g, and
6a -d and homocoupling reaction of 3b (4 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microfilm version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O962058V