Silver ion-mediated coupling of 4-bromo-2,6-di-tert-butylcycohexa-2,5- dienone with phenols

Full text of DOI:10.1021/jo981356k

J . Org. Chem. 1998, 63, 10031-10034
10031
in DME was carried out in the presence of excess Na2-
CO3 (4 molar equiv), and the formation of 5 was found
to be indeed minimized (3%), while that of 4 was
substantially increased (60%).3 Symmetrically substi-
tuted 4,4′-biphenols 6a or 6b were not obtained. 4,4′-
Diphenoquinones 7a , 7b, or 7c, the products of dehydro-
genation of 6a , 6b, or 4, respectively, were not obtained
either.
Silver Ion -Med ia ted Cou p lin g of
4-Br om o-2,6-d i-ter t-bu tylcycoh exa -2,5-d ien on e
w ith P h en ols
Kanji Omura*
College of Nutrition, Koshien University, Momijigaoka,
Takarazuka, Hyogo 665, J apan
Received J uly 13, 1998
Recently, we have shown that the Ag ion can induce
nucleophilic displacement of 4-bromo-2,6-di-tert-butylcy-
clohexa-2,5-dienone (1) with alcohols.1 We were then
prompted to study the Ag ion-promoted displacement of
1 with phenolic nucleophiles. The products expected were
3,5-di-tert-butyl-4,4′- or 4,2′-biphenols which are not
easily accessible by the conventional coupling reactions.
This paper deals with the results of such a study.
Compound 1 was allowed to react at 0 °C for a short
period with excess 2,6-diisopropylphenol (3) (4 mol equiv)
in DME containing AgClO4 (1 molar equiv). 3,5-Di-tert-
butyl-3′,5′-diisopropyl-4,4′-biphenol (4) was, as antici-
pated, obtained in 37% yield (eq 1).2 The major product
The success of preparation of 4 led us to investigate
the coupling of 1 with other phenols by using AgClO4/
Na2CO3 in DME. The phenolic nucleophiles chosen were
mainly alkyl-substituted ones. The results are shown in
Table 1. From 4-unsubstituted 2,6-dialkylphenols 8, 9,
11, 13 and 15, 3,5-di-tert-butyl-3′,5′-dialkyl-4,4′-biphenols
6b, 10, 12, 14, and 16, respectively, were generated in
50-68% yield. The coupling with 6-unsubstituted 2,4-
dialkylphenols 17, 20, and 22 afforded 3,5-di-tert-butyl-
3′,5′-dialkyl-4,2′-biphenol 19, 21, and 24, respectively, in
53-69% yield, along with the 3,5-di-tert-butyl-4-phenoxy-
phenols, the products of C-O coupling, as the minor
products. From the reaction of 2,6-unsubstituted 4-alkyl-
phenols 25 and 28, both the 4,2′-biphenols and the
4-phenoxyphenols were produced, the amounts of the
latter products having been principal or substantial. All
of the three possible coupling products, 34, 35, and 36,
were obtained from the reaction of 3,5-dimethylphenol
(33). In contrast, the reaction of 3,5-di-tert-butylphenol
(31) afforded only 4-phenoxyphenol 32. Neither the 4,4′-
nor the 4,2′-biphenol was produced. Bulky tert-butyl
groups at the 3- and 5-positions in 31 may prohibit attack
by cation 2 on the ring carbons. While no or little C-O
coupling took place in the reaction of 4-unsubstituted 2,6-
dimethylphenols 9, 13, and 15, the reaction of 2,4,6-
trimethylphenol (37) gave 4-phenoxyphenol 38, albeit in
a fair yield.
The reaction of some phenols bearing a substituent(s)
other than an alkyl group was also investigated. The
reaction of 2,6-dimethoxyphenol (39) afforded 4,4′-biphe-
nol 40. 4,3′-Biphenol 41 and 4,4′-diphenoquinones 42 and
7b were obtained in addition. The obtention of 41 as the
principal C-C coupling product may probably indicate
that the 3- and 5-positions in 39 are the most activated
sites toward electrophilic attack by cation 2. Bromination
of 39 with Br2 has been reported to give 3-bromo-2,6-
dimethoxyphenol exclusively or almost exclusively rather
than the 4-bromo isomer.4 The reaction of 4-chlorophenol
(43), 4-acetylphenol (46), and 4-nitrophenol (49) gave
both the expected 4-phenoxyphenols and the 4,2′-biphe-
was 4-bromo-2,6-di-tert-butylphenol (5) (47%). A small
amount of 2,6-di-tert-butylphenol (8) (6%) was also
produced. Prototropic rearrangement of 1 to give 5 was
presumed to have been caused by catalysis with HClO4,
which was likely generated during the course of the
reaction (eq 2, cf. eq 1). Neutralization of the HClO4 as
it was generated, therefore, was expected to suppress the
formation of 5. The AgClO4-induced reaction of 1 with 3
* Corresponding author Phone 0797-87-5111. Fax 0797-87-5666.
(1) Omura, K. J . Org. Chem. 1996, 61, 7156.
(2) A similar reaction with AgOCOCF3, another Ag salt soluble in
DME, in place of AgClO4 provided only a few percent of 4. The 1H NMR
spectrum of the crude reaction product suggested that it contained
significant amounts of 4-(trifluoroacetoxy)-2,6-di-tert-butylphenol and
its tautomer, 4- (trifluoroacetoxy)-2,6-di-tert-butylcyclohexa-2,5-di-
enone. Cf. ref 1.
(3) The reaction with 2 molar equiv (in place of 4 mol equiv) of 3
gave 4 in 49% yield.
(4) Giles, R. G.; Hughes, A. B.; Sargent, M. V. J . Chem. Soc., Perkin
Trans. 1 1991, 1581.
10.1021/jo981356k CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/05/1998

10032 J . Org. Chem., Vol. 63, No. 26, 1998
Ta ble 1. Cou p lin g of Br om o Dien on e 1 w ith P h en ols
Notes
nols. However, the total yields of the coupling products
obtained from the strongly deactivated phenols (46 and
49) were limited.
Of the biphenolic products listed in Table 1, sym-
metrically substituted 4,4′-biphenol 6b can be prepared
by dehydrogenative dimerization of 8.5 The other biphe-
nols (except 41) may in principle be producible by a one-
electron cooxidation of 8 and the appropriate phenols.
The biphenols from this cross-coupling, however, may
necessarily be accompanied by the biphenolic products
from dehydrogenative dimerization of 8 and/or of the
phenols employed. Moreover, further dehydrogenation of
(5) (a) Ley, K.; Mu¨ller, E.; Mayer, R.; Scheffler, K. Chem. Ber. 1958,
91, 2670. (b) Kharasch, M. S.; J oshi, B. S. J . Org. Chem. 1957, 22,
1439. (c) Omura, K. J . Org. Chem. 1991, 56, 921. (d) Okada, K.; Okubo,
K.; Oda, M.; Murai, H. Chem. Lett. 1995, 845.

Notes
J . Org. Chem., Vol. 63, No. 26, 1998 10033
mg, 8%) and 2,6-di-tert-butyl-4-bromophenol (5)5a (18 mg, 3%)
as analyzed by GC and 1H NMR spectroscopy.
the biphenolic products to give the diphenoquinones may
not be avoided. As a result, formation of the biphenols
by the cross-coupling may not be very selective. For
instance, cooxidation of 8 with 9, 15, or 39 with manga-
nese complexes has been shown to give mixtures of
products, from which 10, 16, or 40, respectively, are
isolable in low yields.6
A convenient method for preparation of 3,5-di-tert-
butyl-4-phenoxyphenols 53 may be the acid-catalyzed de-
tert-butylation of 2,4,6-tri-tert-butyl-4-phenoxycyclohexa-
2,5-dienones 52 (eq 3),7 which are obtained by reaction
of 2,4,6-tri-tert-butylphenoxy radical with phenols.8 In-
deed 32 has been prepared by using this method.7 It
3,5-Di-ter t-bu tyl-3′,5′-d iisop r op yl-4,4′-bip h en ol (4): 460
mg (60%) from 3; colorless crystals from hexane; mp 150-151.5
1
°C; H NMR δ 7.31 (s, 2 H), 7.18 (s, 2 H), 5.16 (s, 1 H), 4.74 (s,
1 H), 3.20 (hept, J ) 6.8 Hz, 2 H), 1.49 (s, 18 H), 1.32 (d, J ) 7.0
Hz, 12 H); 13C NMR δ 152.7, 148.8, 135.8, 134.9, 133.5, 133.4,
123.7, 122.3, 34.4, 30.3, 27.4, 22.7; IR 3610, 3590 cm-1. Anal.
Calcd for C26H38O2: C, 81.62; H, 10.01. Found: C, 81.37; H,
10.16.
3,5,3′,5′-Tetr a -ter t-bu tyl-4,4′-bip h en ol (6b): 465 mg (57%)
from 8; light yellow crystals from hexane, identical with an
authentic sample5c (1H NMR and TLC); mp 185-186.5 °C (lit.5c
mp 184.5-185.5 °C); 1H NMR δ 7.30 (s, 4 H), 5.15 (s, 2 H), 1.49
(s, 18 H); 13C NMR δ 152.6, 135.8, 133.7, 123.9, 34.4, 30.3.
3,5-Di-ter t-bu tyl-3′,5′-d im eth yl-4,4′-bip h en ol (10): 374 mg
(57%) from 9; light yellow crystals from EtOH; mp 198.5-200
°C (lit.6 mp 198.5-200 °C). The 1H NMR and IR spectra were
in accordance with those reported for 10.6 13C NMR δ 152.7,
151.0, 135.9, 134,5, 132.4, 127.1, 123.5, 123.0, 34.4, 30.4, 16.0.
Anal. Calcd for C22H30O2: C, 80.93; H, 9.26. Found: C, 80.85;
H, 9.42.
3,5,3′-Tr i-ter t-bu tyl-5′-m eth yl-4,4′-bip h en ol (12): 450 mg
(61%) from 2-tert-butyl-6-methylphenol (11); colorless crystals
from hexane; mp 177-178 °C; H NMR δ 7.30 (s, 2H), 7.26 (d,
J ) 2.3 Hz, 1 H), 7.13 (d, J ) 2.3 Hz, 1 H), 5.15 (s, 1 H), 4.71 (s,
1 H), 2.29 (s, 3 H), 1.48 (s, 18 H), 1.46 (s, 9 H); 13C NMR δ 152.6,
151.4, 135.8, 135.5, 134.1, 133.0, 127.0, 123.9, 123.6, 123.0, 34.6,
34.4, 30.3, 29.8, 16.1; IR 3615, 3590 cm-1. Anal. Calcd for
should, however, be noted that the reaction to give 52
does not always proceed smoothly.9 In addition, selectiv-
ity of the formation of 53 from 52 is not always high.7
The results shown above may suffice to prove that 1
can couple with a wide variety of phenols when mediated
by AgClO4/Na2CO3. Exhaustive de-tert-butylation of the
coupling products obtained here may be expected to
furnish a number of new 4,4′- and 2,4′-biphenols as well
as 4-phenoxyphenols.10
1
C
25H36O2: C, 81.47, H, 9.85. Found: C, 81.32; H, 9.82.
3,5-Di-ter t-bu tyl-2′,3′,5′-tr im eth yl-4,4′-bip h en ol (14): 459
mg (68%) from 13; colorless crystals from hexane; mp 137.5-
138 °C; 1H NMR δ 7.06 (s, 2 H), 6.90 (s, 1 H), 5.13 (s, 1 H), 4.59
(s, 1 H), 2.24 (s, 6 H), 2.16 (s, 3 H), 1.46 (s, 18 H); 13C NMR δ
152.1, 150.6, 135.4, 135.1, 133.4, 132.8, 129.3, 126.1, 122.1, 119.5,
34.4, 30.4, 17.5, 15.8, 12.3; IR 3615, 3590 cm-1. Anal. Calcd for
Exp er im en ta l Section
C
23H32O2: C, 81.13; H, 9.47. Found: C, 80.93; H, 9.72.
1H (90 MHz) and 13C (22.6 MHz) NMR and IR spectra were
taken in CDCl3 and in CHCl3, respectively. Column chromatog-
raphy was conducted on Merck SiO2 60 using gradient elution
(100% petroleum ether to 100% benzene). TLC was run on SiO2.
GC analyses were performed at 150 °C on a column packed with
10% FAP-S on Chromosorb W.
3,5-Di-t er t -b u t yl-2′,3′,5′,6′-t e t r a m e t h yl-4,4′-b ip h e n ol
(16): 357 mg (50%) from 15; colorless crystals from hexane; mp
1
208-210 °C (lit.6 mp 199-200 °C). The H NMR and IR spectra
were in accordance with those reported for 16.6 13C NMR δ 151.8,
150.3, 135.7, 135.4, 133.1, 133.1, 126.2, 118.8, 34.4, 30.6, 17.9,
12.3.
Gen er a l P r oced u r e for Rea ction s in Ta ble 1. To a
mixture of powdered 4-bromo-2,6-di-tert-butylcyclohexa-2,5-di-
enone (1) (570 mg, 2 mmol) and finely powdered anhydrous Na2-
CO3 (0.85 g, 8 mmol) was added in one portion a cold (0 °C)
solution of a phenol (8 mmol) and AgClO4 (415 mg, 2 mmol) in
DME (10 mL), and the resulting mixture was stirred magneti-
cally for 10 min at 0 °C. The mixture was filtered into a flask
containing water. The contents of the flask were extracted with
ether. The extract was washed with water, dried over anhydrous
Na2SO4, and evaporated to dryness. The residue was chromato-
graphed. The residues obtained from the reactions of 2,6-
dimethylphenol (9), 2,3,6-trimethylphenol (13), and 2,3,5,6-
tetramethylphenol (15) were sublimed (85 °C, 21 mmHg) to
recover the unreacted phenols as the sublimates, and the
residues were chromatographed. The residue obtained from the
reaction of 2,6-dimethoxyphenol (39) was washed with petroleum
ether, affording 3,5-di-tert-butyl-3′,5′-dimethoxy-4,4′-dipheno-
quinone (42) as purple crystals (50 mg, 7%): mp 240-242 °C
(lit.11 mp 240-242 °C). The washings were evaporated, and the
residue was chromatographed. Chromatography of the residue
obtained from the reaction of 2,6-diisopropylphenol (3) provided,
as the first fraction, a mixture of 2,6-di-tert-butylphenol (8) (35
3,5-Di-t er t -b u t yl-4-(2,4-d i-t er t -b u t ylp h e n oxy)p h e n ol
(18): 76 mg (9%) from 2,4-di-tert-butylphenol (17); colorless oil;
1H NMR δ 7.37 (d, J ) 2.6 Hz, 1 H), 7.06 (dd, J ) 2.4 Hz, 8.6
Hz, 1 H), 6.83 (s, 2 H), 6.59 (d, J ) 8.6 Hz, 1 H), 4.94 (s, 1 H)
1.47 (s, 9 H), 1.41 (s, 18 H), 1.31 (s, 9 H); 13C NMR δ 155.0,
149.5, 148.8, 143.6, 137.9, 137.2, 123.7, 123.2, 116.7, 116.2, 34.9,
34.5, 34.3, 31.6, 30.2, 30.1; IR 3620 cm-1. HRMS calcd for
C28H42O2 410.3185, found 410.3159.
3,5,3′,5′-Ter a -ter t-bu tyl-4,2′-bip h en ol (19): 495 mg (60%)
from 17; colorless crystals from MeOH, identical with an
authentic sample12 (1H and 13C NMR, IR and TLC); mp 189-
190.5 °C (lit.12 mp 189-190.5 °C).
3,5,3′-Tr i-ter t-bu tyl-5′-m eth yl-4,2′-bip h en ol (21): 511 mg
(69%) from 2-tert-butyl-4-methylphenol (20); colorless crystals
from hexane; mp 137.5-139 °C; 1H NMR δ 7.20 (s, 2 H), 7.06
(d, J ) 2.3 Hz, 1 H), 6.9-6.8 (m, 1 H), 5.41 (s, 1 H), 5.28 (s, 1
H), 2.30 (s, 3 H), 1.46 (s, 18 H), 1.44 (s, 9 H); 13C NMR δ 153.4,
148.8, 136.8, 135.4, 129.3, 128.3, 128.2, 128.0, 126.6, 126.0, 34.8,
34.5, 30.3, 29.7, 20.8; IR 3615, 3525 cm-1. Anal. Calcd for
C
25H36O2: C, 81.47; H, 9.85. Found: C,81.32; H, 9.94.
3,5-Di-ter t-bu tyl-4-(2,4-d im eth ylp h en oxy)p h en ol (23): 77
mg (12%) from 2,4-dimethylphenol (22); light yellow oil; 1H NMR
δ 7.1-6.6 (m, 3 H), 6.79 (s, 2 H), 4.89 (s, 1 H), 2.28 (s, 3 H), 2.25
(s, 3 H), 1.40 (s, 18 H); 13C NMR δ 153.7, 149.5, 149.1, 137.2,
131.6, 131.5, 127.0, 116.9, 115.1, 34.5, 30.2, 20.6, 16.2; IR 3620
cm-1; HRMS calcd for C22H30O2 326.2247, found 326.2238.
3,5-Di-ter t-bu tyl-3′,5′-d im eth yl-4,2′-bip h en ol (24): 346 mg
(53%) from 22; colorless crystals from hexane; mp 167.5-169
°C; 1H NMR δ 7.21 (s, 2 H), 7.0-6.8 (m, 2 H), 5.28 (s, 1 H), 5.20
(s, 1 H), 2.27 (s, 6 H), 1.46 (s, 18 H); 13C NMR δ 153.4, 148.3,
136.7, 130.4, 128.8, 128.1, 127.9, 125.6, 123.9, 34.5, 30.3, 20.4,
(6) Nishino, H.; Itoh, N.; Nagashima, M.; Kurosawa, K. Bull. Chem.
Soc. J pn. 1992, 65, 620.
(7) Rieker, A.; Zeller, N. Terahedron Lett. 1968, 4969.
(8) (a) Mu¨ller, E.; Ley, K.; Schlechte, G. Chem. Ber. 1957, 90, 2660.
(b) Becker, H.-D. J . Org. Chem. 1964, 29, 3068.
(9) Matsuura, T.; Nishinaga, A.; Ogura, K.; Omura, K. J . Org. Chem.
1969, 34, 550.
(10) (a) Olah, G. A.; Surya Prakash, G. K.; Iyer, P. S.; Tashiro, M.;
Yamato, T. J . Org. Chem. 1987, 52, 1881. (b) Tashiro, M.; Yoshiya,
H.; Yamato, T. Synthesis 1978, 399.
(11) Boldt, P.; Michaelis, W.; Lackner, H.; Krebs, B. Chem. Ber.
1971, 104, 220.
(12) Omura, K. Terahedron 1995, 51, 6901.

10034 J . Org. Chem., Vol. 63, No. 26, 1998
Notes
16.1; IR 3620, 3535 cm-1. Anal. Calcd for C22H30O2: C,80.94, H,
9.26. Found: C, 80.92; H, 9.44.
kindly provided by Dr. Nishino; mp 145.5-147 °C (lit.6,13 mp
201-201.5 °C). 13C NMR δ 153.0, 147.0, 136.1, 134.0, 133.8,
132.9, 123.7, 104.2, 56.4, 34.4, 30.3.
3,5-Di-ter t-bu tyl-2′,4′-d im eth oxy-4,3′-bip h en ol (41): 282
mg (39%) from 39; light yellow oil; 1H NMR δ 7.36 (s, 2 H), 6.83
(AB, J ) 8.6 Hz, 1 H), 6.69 (AB, J ) 8.6 Hz, 1 H), 5.75 (s, 1 H),
5.19 (s, 1 H), 3.89 (s, 3 H), 3.60 (s, 3 H), 1.47 (s, 18 H); 13C NMR
δ 152.7, 146.4, 144.5, 138.6, 135.4, 128.9, 128.6, 125.4, 120.1,
106.8, 60.2, 56.2, 34.4, 30.4; IR 3620, 3520 cm-1; HRMS calcd
for C22H30O4 358.2145, found 358.2147.
3,5,3′,5′-Tetr a -ter t-bu tyl-4,4′-d ip h en oqu in on e (7b): 36 mg
(9%) from the reaction of 39; reddish brown crystals from
benzene, identical with an authentic sample14 (1H NMR and
TLC); mp 246-248 °C (lit.14 mp 240-241 °C).
3,5-Di-ter t-bu tyl-4-(4-ch lor op h en oxy)p h en ol (44): 379 mg
(57%) from 4-chlorophenol (43); colorless crystals from hexane;
mp 82.5-83.5 °C; 1H NMR δ 7.3-7.1 (m, 2 H), 6.9-6.7 (m, 2
H), 6.86 (s, 2 H), 5.01 (s, 1 H), 1.41 (s, 18 H); 13C NMR δ 157.3,
150.1, 148.2, 137.5, 129.2, 126.7, 118.2, 116.4, 34.5, 30.2; IR 3615
cm-1. Anal. Calcd for C20H25O2Cl; C, 72.17; H, 7.57; Cl, 10.65.
Found: C, 72.30; H, 7.73; Cl, 10.45.
3,5-Di-ter t-bu tyl-5′-ch lor o-4,2′-biph en ol (45): 152 mg (23%)
from 43; colorless crystals from hexane; mp 107-108 °C; 1H
NMR δ 7.3-7.1 (m, 2 H), 7.19 (s, 2 H), 7.0-6.8 (m, 1 H), 5.34 (s,
1 H), 5.27 (s, 1 H), 1.46 (s, 18 H); 13C NMR δ 153.9, 151.1, 137.0,
130.3, 129.6, 128.1, 126.4, 125.4, 125.1, 116.6, 34.5, 30.2; IR 3620,
3530, 3300 cm-1. Calcd for C20H25O2Cl: C, 72.17; H, 7.57; Cl,
10.65. Found: C, 72.04; H, 7.62; Cl, 10.72.
3,5-Di-ter t-bu tyl-4-(4-a cetylp h en oxy)p h en ol (47): 158 mg
(23%) from 4-acetylphenol (46); colorless crystals from diisopro-
pyl ether; mp 128-130 °C; 1H NMR δ 8.0-7.8 (m, 2 H), 7.0-6.8
(m, 2 H), 6.89 (s, 2 H), 5.09 (s, 1 H), 2.55 (s, 3 H), 1.43 (s, 18 H);
13C NMR δ 196.4, 163.0, 150.6, 147.1, 137.7, 131.0, 130.4, 117.0,
116.0, 34.5, 30.2, 26.3; IR 3620, 1673 cm-1. Anal. Calcd for
3,5-Di-ter t-bu tyl-4-(4-ter t-bu tylp h en oxy)p h en ol (26): 472
mg (67%) from 4-tert-butylphenol (25); colorless crystals from
1
hexane; mp 139-140 °C; H NMR δ 7.4-7.1 (m, 2 H), 7.0-6.7
(m, 2 H), 6.88 (s, 2 H), 4.97 (s, 1 H), 1.41 (s, 18 H), 1.31 (s, 9 H);
13C NMR δ 156.3, 149.8, 148.4, 144.3, 137.2, 126.1, 116.6, 116.1,
34.5, 34.1, 31.5, 30.2; IR 3620 cm-1. Anal. Calcd for C24H34O2:
C, 81.31; H, 9.67. Found: C, 81.02; H, 9.51.
3,5,5′-Tr i-ter t-bu tyl-4,2′-bip h en ol (27): 190 mg (27%) from
1
25; colorless crystals from hexane; mp 136-137 °C; H NMR δ
7.4-7.1 (m, 2 H), 7.24 (s, 2 H), 7.0-6.8 (m, 1 H), 5.30 (s, 1 H),
5.15 (s, 1 H), 1.47 (s, 18 H), 1.33 (s, 9 H); 13C NMR δ 153.4,
150.1, 143.1, 136.7, 128.2, 128.1, 126.9, 125.7, 125.3, 114.8, 34.5,
34.1, 31.6, 30.3; IR 3620, 3540, 3300 cm-1. Anal. Calcd for
C
24H34O2; C, 81.31; H, 9.67. Found: C, 81.05; H, 9.86.
3,5-Di-ter t-bu tyl-4-(4-m eth ylp h en oxy)p h en ol (29): 188
mg (30%) from 4-methylphenol (28); colorless crystals from
hexane; mp 98-99 °C; 1H NMR δ 7.2-7.0 (m, 2 H), 6.9-6.6 (m,
2 H), 6.86 (s, 2 H), 4.95 (s, 1 H), 2.30 (s, 3 H), 1.41 (s, 18 H); 13
C
NMR δ 156.2, 149.6, 148.9, 137.2, 131.2, 129.8, 117.1, 116.1, 34.5,
30.2, 20.6; IR 3615 cm-1. Anal. Calcd for C21H28O2: C, 80.73; H,
9.03. Found: C, 80.77; H, 9.00.
3,5-Di-ter t-b u t yl-5′-m et h yl-4,2′-b ip h en ol (30): 245 mg
(39%) from 28; colorless crystals from hexane; mp 50-54 °C; 1H
NMR δ 7.22 (s, 2 H), 7.1-6.8 (m, 3 H), 5.29 (s, 1 H), 5.14 (s, 1
H), 2.31 (s, 3 H), 1.47 (s, 18 H); 13C NMR δ 153.4, 150.2, 136.7,
130.5, 129.5, 128.8, 128.5, 127.8, 125.5, 115.1, 34.5, 30.3, 20.5;
IR 3620, 3520, 3300 cm-1. Anal. Calcd for C21H28O2: C, 80.73;
H, 9.03. Found: C, 80.66; H, 9.15.
3,5-Di-ter t-bu tyl-4-(3,5-d i-ter t-bu tylp h en oxy)p h en ol (32):
638 mg (78%) from 3,5-di-tert-butylphenol (31); colorless crystals
from hexane; mp 119.5-121 °C (lit.7 mp 112-114 °C); 1H NMR
δ 7.09 (t, J ) 1.7 Hz, 1 H), 6.89 (s, 2 H), 6.82 (d, J ) 1.7 Hz, 2
H), 4.93 (s, 1 H), 1.41 (s, 18 H), 1.29 (s, 18 H); 13C NMR δ 157.3,
152.1, 149.2, 148.8, 137.1, 116.0, 115.6, 111.8, 34.9, 34.5, 31.4,
C
22H28O3: C, 77.61; H, 8.29. Found: C, 77.51; H, 8.47.
3,5-Di-ter t-bu tyl-5′-acetyl-4,2′-biph en ol (48): 121 mg (18%)
30.2; IR 3620 cm-1
.
from 46; colorless crystals from MeOH/hexane; mp 169-170 °C;
1H NMR δ 8.0-7.8 (m, 2 H), 7.22 (s, 2 H), 7.1-6.9 (m, 1 H), 5.98
(s, 1 H), 5.37 (s, 1 H), 2.57 (s, 3 H), 1.47 (s, 18 H); 13C NMR δ
196.8, 157.0, 153.9, 137.1, 131.0, 130.2, 129.4, 129.0, 126.5, 125.6,
115.3, 34.5, 30.2, 26.3; IR 3620, 3515, 3250, 1668 cm-1. Anal.
Calcd for C22H28O3: C, 77.61; H, 8.29. Found: C, 77.53; H, 8.43.
3,5-Di-ter t-bu tyl-4-(4-n itr op h en oxy)p h en ol (50): 217 mg
(32%) from 4-nitrophenol (49); light yellow crystals from hexane;
mp 131-132 °C; 1H NMR δ 8.2-8.0 (m. 2 H), 7.0-6.8 (m, 2 H),
6.90 (s, 2 H), 5.15 (s, 1 H), 1.44 (s, 18 H); 13C NMR δ 164.2,
151.0, 146.6, 141.9, 137.9, 125.7, 117.1, 116.0, 34.5, 30.1; IR 3615
cm-1. Anal. Calcd for C20H25O4N: C, 69.95; H, 7.34; N, 4.08.
Found: C, 69.88; H, 7.31; N, 3.79.
3,5-Di-ter t-bu tyl-5′-n itr o-4,2′-bip h en ol (51): 28 mg (4%)
from 49; light yellow crystals from hexane; mp 135-138 °C; 1H
NMR δ 8.2-8.0 (m, 2 H), 7.20 (s, 2 H), 7.1-6.9 (m, 1 H), 6.00 (s,
1 H), 5.43 (s, 1 H), 1.48 (s, 18 H); 13C NMR δ 158.1, 154.4, 141.4,
137.4, 129.5, 126.0, 125.4, 125.1, 124.5, 115.7, 34.5, 30.2; IR 3620,
3515, 3200 cm-1. Anal. Calcd for C20H25O4N: C, 69.95; H, 7.34;
N, 4.08. Found: C, 70.00; H, 7.33; N, 4.13.
3,5-Di-ter t-bu tyl-4-(3,5-dim eth ylph en oxy)ph en ol (34): 127
mg (19%) from 3,5-dimethylphenol (33); colorless crystals from
hexane; mp 54-55 °C; 1H NMR δ 6.87 (s, 2 H), 6.65 (s, 1 H),
6.56 (s, 2 H), 4.97 (s, 1 H), 2.26 (s, 6 H), 1.41 (s, 18 H); 13C NMR
δ 158.5, 149.7, 148.5, 139.1, 137.2, 123.5, 116.4, 114.7, 34.5, 30.2,
21.3; IR 3620 cm-1. Anal. Calcd for C22H30O2: C, 80.93; H, 9.26.
Found: C, 80.96, H, 9.16.
3,5-Di-ter t-bu tyl-2′,6′-d im eth yl-4,4′-bip h en ol (35) was ob-
tained as a mixture with 33 (starting phenol) upon chromatog-
raphy. A solution of the mixture in diisopropyl ether was shaken
with aqueous NaOH. The organic layer was washed with water,
dried, and evaporated to leave 35 (152 mg, 23%). Colorless
crystals from diisopropyl ether/hexane: mp 214-240 °C; 1H
NMR δ 6.88 (s, 2 H), 6.58 (s, 2 H), 5.11 (s, 1 H), 4.63 (s, 1 H),
2.01 (s, 6 H), 1.44 (s, 18 H); 13C NMR δ 153.6, 152.0, 138.1, 135.5,
131.2, 125.9, 113.8, 34.4, 30.5, 21.1; IR 3620, 3585, 3325 cm-1
.
Anal. Calcd for C22H30O2: C, 80.93; H, 9.26. Found: C, 80.73;
H, 9.48.
3,5-Di-ter t-bu tyl-4′,6′-d im eth yl-4,2′-bip h en ol (36): 292 mg
(45%) from 33; colorless crystals from hexane; mp 171-172 °C;
1H NMR δ 7.04 (s, 2 H), 6.68 (s, 2 H), 5.28 (s, 1 H), 4.92 (s, 1 H),
2.31 (s, 3 H), 2.05 (s, 3 H), 1.45 (s, 18 H); 13C NMR δ 153.4,
152.9, 137.9, 137.1, 136.8, 126.7, 125.9, 125.5, 122.5, 112.8, 34.5,
30.3, 21.2, 20.4; IR 3620, 3520, 3300 cm-1. Anal. Calcd for
Ack n ow led gm en t. The author is grateful to Dr.
Hiroshi Nishino (Kumamoto University) for providing
1
a sample of compound 40 as well as its H NMR and IR
C
22H30O2: C, 80.93; H, 9.26. Found: C, 80.83; H, 9.43.
spectra, and to Professor Isao Saito (Kyoto University)
for measurement of HRMS. He is thankful to Tohru
Nakata, Seiko Araki, Kaori Kobayashi, and Daisuke
Itoh (students) for their experimental contributions.
3,5-D i-t er t -b u t y l-4-(2,4,6-t r im e t h y lp h e n o x y )p h e n o l
(38): 236 mg (35%) from 2,4,6-trimethylphenol (37); colorless
crystals from hexane; mp 104-105 °C; 1H NMR δ 6.85 (s, 2 H),
6.57 (s, 2 H), 4.71 (s, 1 H), 2.28 (s, 3 H), 2.08 (s, 6 H), 1.36 (s, 18
H); 13C NMR δ 150.8, 149.1, 147.5, 137.0, 133.5, 130.9, 129.2,
110.8, 34.5, 30.2, 20.8, 16.4; IR 3625 cm-1. Anal. Calcd for
J O981356K
C
23H32O2: C, 81.13; H, 9.47. Found: C, 80.98; H, 9.51.
3,5-Di-ter t-bu tyl-3′,5′-d im eth oxy-4,4′-bip h en ol (40): 156
(13) Dr. Nishino corrected the melting point to 148.5-149.0 °C
(private communication)
(14) Omura, K. J . Org. Chem. 1984, 49, 3046.
mg (22%) from 39; light yellow crystals from diisopropyl ether,
identical with an authentic sample (1H NMR, IR, and TLC)