Dienone tautomers of 4-alkoxy-2,6-di-terf-butylphenols

Article abstract of DOI:10.1021/jo9609945

Generation and isolation of 4-alkoxycyclohexa-2,5-dienones 9, the tautomeric forms of the title phenols (10), is described. They are generated efficiently by the Ag ion mediated reaction of 4-bromocyclohexa-2,5-dienone 3b with simple alcohols, although they can be irreversibly isomerized into 10 under the reaction conditions. Crude materials with high amounts of 9 can be obtained by conducting the reaction with AgClO₄ in the presence of Na₂CO₃ or with AgOCOCF₃ and by interrupting the reaction shortly after the formation of 9 is complete. The AgOCOCF₃ reaction produces labile 4-(trifluoroacetoxy)cyclohexa-2,5-dienone 11 also, the formation of which becomes significant as the alcohol becomes bulky. All of 9 prove to be very much susceptible to the prototropic rearrangement into 10 by catalysis with base, acid, or SiO₂. Crude dienones 9 can be conveniently prepared directly from phenol 6 by treatment for a short time with Br₂ in alcohols containing AgClO₄ and Na₂CO₃. A one-pot synthesis from 6 of 4-oxyfunctionalized 2,6-di-tert-butylphenols, including 10, is also described.

Full text of DOI:10.1021/jo9609945

7156
J . Org. Chem. 1996, 61, 7156-7161
Dien on e Ta u tom er s of 4-Alk oxy-2,6-d i-ter t-bu tylp h en ols
Kanji Omura
College of Nutrition, Koshien University, Momijigaoka, Takarazuka, Hyogo 665, J apan
Received May 29, 1996X
Generation and isolation of 4-alkoxycyclohexa-2,5-dienones 9, the tautomeric forms of the title
phenols (10), is described. They are generated efficiently by the Ag ion mediated reaction of
4-bromocyclohexa-2,5-dienone 3b with simple alcohols, although they can be irreversibly isomerized
into 10 under the reaction conditions. Crude materials with high amounts of 9 can be obtained by
conducting the reaction with AgClO4 in the presence of Na2CO3 or with AgOCOCF3 and by
interrupting the reaction shortly after the formation of 9 is complete. The AgOCOCF3 reaction
produces labile 4-(trifluoroacetoxy)cyclohexa-2,5-dienone 11 also, the formation of which becomes
significant as the alcohol becomes bulky. All of 9 prove to be very much susceptible to the prototropic
rearrangement into 10 by catalysis with base, acid, or SiO2. Crude dienones 9 can be conveniently
prepared directly from phenol 6 by treatment for a short time with Br2 in alcohols containing AgClO4
and Na2CO3. A one-pot synthesis from 6 of 4-oxyfunctionalized 2,6-di-tert-butylphenols, including
10, is also described.
Cyclohexadienones 1a or 1b are the tautomeric forms
of phenols 2a or 2b, respectively. In most cases, these
species only exist transiently since they readily undergo
prototropic rearrangement into more stable, phenol
forms. Therefore, it is usual that they can not be isolated,
Isolation of simple dienones of type 1a where X is an
oxyfunctional group appears to be hitherto unknown,
although their intermediacy has been or may be reason-
ably postulated to account for the formation of the
products from a number of reactions such as (i) reactions
of phenols with oxygen electrophiles,6 (ii) reactions of
phenoxy radicals with oxygen radicals,7 and (iii) reactions
of chemically or electrochemically generated phenox-
enium ions or related species with oxygen nucleophiles.8
In this article, the generation and isolation of 4-alkoxy-
2,6-di-tert-butylcyclohexa-2,5-dienones (9), the tautomeric
forms of 4-alkoxy-2,6-di-tert-butylphenols (10), is de-
scribed. Their generation was expected from 4-bromo-
2,6-di-tert-butylcyclohexa-2,5-dienone (3b) by a reaction
analogous to the Ag ion induced nucleophilic displace-
although they may be detectable by spectroscopic means
under appropriate conditions.1 4-Halocyclohexa-2,5-di-
enones 3 and bis(cyclohexadienone)s 4 are among rare
examples of dienones of type 1a which can be isolated.
Dienones 3 and 4 are obtained by electrophilic phenol
halogenation2 and phenoxy radical coupling,3 respec-
tively. Even these isolatable dienones are susceptible to
irreversible isomerization into the corresponding phenols
by catalysis with base, acid, or SiO2. They also isomerize
in polar media such as EtOH. 4-tert-Butyl-cyclohexa-2,5-
dienone 5 has been isolated from irradiation of an
isomeric cyclohexa-2,5-dienone.4 It is noticeable that
these isolatable dienones bear tert-butyl groups in the
2- and 6-positions. Simple dienones of type 1b do not
appear to have been isolated.5
(5) For specifically substituted phenols including hydroxy derivatives
of polycondensed aromatic hydrocarbons, the tautomeric cyclohexadi-
enone forms of type 1a or 1b are known, which are isolable in the
individual state or exist in an appropriate solvent. Some of these
dienone forms are energetically favored over the phenol forms, and in
limited cases only the dienone forms are known. The actual cyclohexa-
dienone-phenol tautomerism, as a mobile equilibrium, has been rarely
observed experimentally. See: (a) Ershov, V. V.; Nikiforov, G. A. Russ.
Chem. Rev. 1966, 35, 817. (b) Forse´n, S.; Nilsson, M. In The Chemistry
of the Carbonyl Group; Patai, S., Ed.; Wiley: New York, 1970; Vol. 2,
p 157. (c) Crozier, R. F.; Hewitt, D. G. Aust. J . Chem. 1972, 25, 183.
(d) Highet, R. J .; Chou, F. E. J . Am. Chem. Soc. 1977, 99, 3538. (e)
Teuber, H.-J .; Go¨tz, N. Chem. Ber. 1956, 89, 2654. (f) Teuber, H.-J .;
Thaler, G. Chem. Ber. 1959, 92, 667.
(6) (a) Chambers, R. D.; Goggin, P.; Musgrave, W. K. R. J . Chem.
Soc. 1959, 1804. (b) McClure, J . D. J . Org. Chem. 1963, 28, 69.
(7) (a) Pfoertner, K.; Bo¨se, D. Helv. Chim. Acta 1970, 53, 1553. (b)
van Dort, H. M.; Geursen, H. J . Recueil 1967, 86, 520. (c) Armstrong,
D. R.; Breckenridge, R. J .; Cameron, C.; Nonhebel, D. C.; Pauson, P.
L.; Perkins, P. G. Tetrahedron Lett. 1983, 24, 1071. (d) Ngo, M.; Larson,
K. R.; Mendenhall, G. D. J . Org. Chem. 1986, 51, 5390.
X Abstract published in Advance ACS Abstracts, September 15, 1996.
(1) (a) Lasne, M.-C.; Ripoll, J .-L.; Denis, J .-M. Tetrahedron Lett.
1980, 21, 463. (b) Capponi, M.; Gut, I.; Wirz, J . Angew. Chem., Int.
Ed. Engl. 1986, 25, 344.
(2) (a) Ershov, V. V.; Volod’kin, A. A. Izv. Akad. Nauk SSSR, Otd.
Khim. Nauk 1962, 730. (b) Volod’kin, A. A.; Ershov, V. V. Izv. Akad.
Nauk SSSR, Otd. Khim. Nauk 1962, 2022. (c) Fyfe, C. A.; Van Veen,
L., J r. J . Am. Chem. Soc. 1977, 99, 3366. (d) Pearson, D. E.;
Venkataramu, S. D.; Childers, W. E., J r. Synth. Commun. 1979, 9, 5.
(e) Baciocchi, E.; Bocca, P. L. Ric. Sci. 1969, 39, 68.
(8) (a) Ronla´n, A. J . Chem. Soc. D 1971, 1643. (b) Nilsson, A.;
Palmquist, U.; Pettersson, T.; Ronla´n, A. J . Chem. Soc., Perkin Trans.
1 1978, 696. (c) Endo, Y.; Shudo, K. Yakugaku Zasshi 1994, 114, 565.
(d) Pelter, A.; Elgendy, S. M. A. J . Chem. Soc., Perkin Trans. 1 1993,
1891. (e) Mckillop, A.; Perry, D. H.; Edwards, M. J . Org. Chem. 1976,
41, 282.
(3) (a) Kharasch, M. S.; J oshi, B. S. J . Org. Chem. 1957, 22, 1439.
(b) Ley, K.; Mu¨ller, E.; Mayer, R.; Scheffler, K. Chem Ber. 1958, 91,
2670. (c) Omura, K. J . Org. Chem. 1991, 56, 921.
(4) Matsuura, T.; Ogura, K. J . Am. Chem. Soc. 1967, 89, 3846.
S0022-3263(96)00994-2 CCC: $12.00 © 1996 American Chemical Society

Dienone Tautomers of 4-Alkoxy-2,6-di-tert-butylphenols
J . Org. Chem., Vol. 61, No. 20, 1996 7157
Ta ble 1. Alk oxy Dien on es 9 fr om Br om o Dien on e 3ba
(Scheme 1). An 1H NMR study confirmed that in the
absence of AgClO4 the prototropic rearrangement of 3b
in MeOH-d4 was fast and was not accompanied by
solvolysis of 3b.12 Solvolysis of 4-bromo-4-alkyl-2,6-di-
tert-butylcyclohexa-2,5-dienones with alcohols can take
place in the absence13 or presence14 of base.
Enrichment of 9a in the crude product was tried by
modifying the reaction conditions. It was presumed that
the isomerization of 9a was facilitated not only by MeOH
but also by HClO4, which is likely generated during the
course of the AgClO4-induced reaction of 3b with MeOH
(cf. Scheme 1). Neutralization of the HClO4 as it was
generated was expected to retard the isomerization and
thus to increase the content of 9a . The reaction of 3b
with AgClO4 in MeOH was conducted in the presence of
excess Na2CO3 (4 molar equiv). The crude product
obtained was analyzed in a manner analogous to that
described above for the reaction without Na2CO3. As
expected, the amount of 9a in the crude product was
remarkably increased (71%) while that of 10a was
substantially decreased (15%) (Table 1, run 2).
product (yield,b %)
run
alcohol
Ag salt
additive
9
10
1
2
3
4
5
6
7
8
9
MeOH
MeOH
MeOH
MeOH
AgClO4
AgClO4
AgClO4
AgOCOCF3
AgClO4
AgClO4
AgClO4
AgClO4
AgOCOCF3
9a (35)
9a (71)
9a (54)
9a (82)
9b (80)
9c (81)
9d (41)
9d (79)
9d (30)
9e (74)
9e (88)
10a (54)
10a (15)
10a (24)
10a (6)
10b (6)
10c (7)
10d (49)
10d (14)
10d (1)
10e (16)
10e (3)
Na2CO3
H2Oc
EtOH
Na2CO3
Na2CO3
i-PrOH
t-BuOHd
t-BuOHd
t-BuOHd
Na2CO3
Na2CO3
10
11
t-AmOHe AgClO4
t-AmOHe AgClO4
a
Unless stated otherwise, the reaction was carried out for 2
min at 0 °C by using 3b (2 mmol), AgClO4 or AgOCOCF3 (2 mmol),
and an alcohol (30 mL). The amount of Na2CO3 employed as an
optional additive was 8 mmol. b 1H NMR spectroscopically deter-
mined yields of 9 and 10 contained in the crude product. Com-
pound 9 was converted into 10 when chromatographed on SiO2.
See Experimental Section for products obtained by chromatogra-
phy. c Conducted for 10 min with a solvent mixture of MeOH (28
d
mL) and H2O (4 mL). Conducted at 27 °C. e Conducted for 4 min.
Enrichment in the content of 9a could also be brought
about by conducting the reaction of 3b with AgClO4 in a
7:1 (v/v) mixture of MeOH and H2O (in the absence of
Na2CO3). The reaction time was extended due to the
limited solubility of 3b in the medium, and 9a constituted
the major component (54% yield) (Table 1, run 3). The
prototropic rearrangement of 3b in a mixture of AcOH
and H2O (containing HBr) is slow as the proportion of
H2O becomes high.2c
The reaction between 3b and MeOH was investigated
also with AgOCOCF3 (in the absence of Na2CO3), which
was expected to generate CF3CO2H, a much weaker acid
than HClO4. The oily product was estimated to contain
9a in as high as 82% yield (Table 1, run 4). Attempted
purification of crude 9a thus obtained by crystallization
from nonpolar solvents such as hexane proved unsuc-
cessful: chilling the solution slowly deposited only a
crystalline mixture of 9a and 10a , and the proportion of
9a to 10a in it was always lower than that in the original
oil. The isomerization of 9a into 10a progressed, though
gradually, even in the nonpolar solvents.
We turned our attention to preparation of 9 other than
9a by conducting similarly the reaction of 3b in other
alcohols with AgClO4 and Na2CO3 or with AgOCOCF3.
The reaction with AgClO4 and Na2CO3 was carried out
in EtOH, i-PrOH, or t-AmOH (tert-amyl alcohol) at 0 °C
or in t-BuOH at 27 °C. As shown in Table 1 (runs 5, 6,
8, and 11), all of the products from these reactions
contained 9 (see below for their NMR data) in satisfactory
amounts (79-88%). The 9/10 (including 9a /10a ) ratio
obtained from the reaction at 0 °C tended to be high when
the alcohol was bulky. Further examples of the de-
creased yield of 9 upon omission of Na2CO3 are also
shown in the table (compare runs 7 and 10 with runs 8
and 11, respectively). The crude product of 4-ethoxy- (9b)
or 4-isopropoxy-2,6-di-tert-butylcyclohexa-2,5-dienone (9c)
obtained from run 5 or 6, respectively, was oily. Their
purification by crystallization from hexane or CCl4 has
ment of 4-bromo-4-alkyl-2,6-di-tert-butylcyclohexa-2,5-
dienones with an alcohol.9
Resu lts a n d Discu ssion
A solution of AgClO4 (1 molar equiv) in MeOH was
added in one portion to solid 3b, and the mixture was
vigorously stirred for a few minutes at 0 °C. As 3b
dissolved, yellow deposits of insoluble AgBr formed. The
1H NMR spectrum (in CDCl3) of the isolated organic
product exhibited singlets ascribable to 4-methoxy-2,6-
di-tert-butylphenol (10a ) and weak singlets assignable to
4-bromo-2,6-di-tert-butylphenol (7), while the starting
material (3b) was undetectable. In addition, the spec-
trum displayed new signals, which appeared at δ 6.69
(d, J ) 3.1 Hz), 4.42 (t, J ) 3.1 Hz), 3.40 (s), and 1.24 (s)
with relative intensities of ca. 2:1:3:18. Upon addition
of pyridine-d5 to the CDCl3 solution, these new signals
disappeared rapidly from the spectrum, and the singlets
due to 10a were intensified. Column chromatography
of the crude product on SiO2 isolated 10a and 7 in 89%
and 5% yields, respectively, but did not afford the product
responsible for the new NMR signals. The product,
therefore, contained a labile new substance, and this
appeared to be 4-methoxy-2,6-di-tert-butylcyclohexa-2,5-
dienone (9a ), which underwent prototropic rearrange-
ment into 10a by catalysis with pyridine-d5 or SiO2. The
NMR signals at δ 6.69, 4.42, 3.40, and 1.24 are assignable
to vinyl, methine, methoxy, and tert-butyl protons, re-
spectively. Combination of the analyses by 1H NMR
spectroscopy and chromatography suggested that the
crude product contained 9a and 10a in 35% and 54%
yields, respectively (Table 1, run 1).10,11 The result
suggests that Ag ion mediated removal of the bromide
ion from 3b to generate carbocationic intermediate 8 (a
resonance form of the phenoxenium ion), which combines
with solvent to give 9a , is so efficient that it overwhelms
the competing prototropic rearrangement of 3b into 7
(12) Dienone 3b (43 mg) was allowed to dissolve in MeOH-d4 (0.6
mL) in ca. 80 s at 30 °C, and the progress of its decay at ca. 30 °C was
followed by 1H NMR spectroscopy. After 3 min about one-half of the
3b was found to survive, and after 25 min only singlets due to 7 were
observed.
(9) Ronla´n, A.; Parker, V. D. J . Chem. Soc. C 1971, 3214.
(10) The isomerization of 9a into 10a upon chromatography on SiO2
was assumed to be quantitative.
(11) Very recently, we have found that 9a is contained, albeit in a
small quantity, in the product obtained from the reaction of 2,6-di-
tert-butylphenol (6) with I2 and H2O2 in MeOH. See: Omura, K. J .
Org. Chem. 1996, 61, 2006.
(13) Coppinger, G. M.; Campbell, T. W. J . Am. Chem. Soc. 1953,
75, 734.
(14) (a) Mu¨ller, E.; Ley, K.; Kiedaisch, W. Chem. Ber. 1954, 87, 1605.
(b) Tashiro, M.; Fukata, G.; Yoshiya, H. Synthesis 1979, 988.

7158 J . Org. Chem., Vol. 61, No. 20, 1996
Omura
Sch em e 1
Ta ble 2. 1H NMR Da ta for Alk oxy Dien on es 9 in CDCl3
δ (multiplicity, J in hertz)
compd
H-3 and H-5
H-4
2- and 6-t-Bu
4-alkoxy
9a a
9ba
9ca
9d b
9eb
6.69 (d, 3.1)
6.70 (d, 3.2)
6.65 (d, 3.1)
6.52 (d, 3.1)
6.53 (d, 3.2)
4.42 (t, 3.1)
4.46 (t, 3.2)
4.47 (t, 3.1)
4.54 (t, 3.1)
4.55 (t, 3.1)
1.24 (s)
1.24 (s)
1.23 (s)
1.22 (s)
1.22 (s)
3.40 (s)
3.61 (q, 7.0), 1.26 (t, 6.9)
3.83 (hept, 6.1), 1.25 (d, 6.1)
1.34 (s)
1.62 (q, 7.5), 1.27 (s), 0.97 (t, 7.4)
a
b
Crude product obtained from run 4, 5, or 6, Table 1. Analytically pure product obtained from run 8 or 11, Table 1.
been unsuccessful: at -20 °C, it progressed extremely
reluctantly and slow isomerization of 9b or 9c into
4-ethoxy- (10b) or 4-isopropoxy-2,6-di-tert-butylphenol
(10c), respectively, was observed. The crude product of
4-tert-butoxy-2,6-di-tert-butylcyclohexa-2,5-dienone (9d )
obtained from run 8 was crystalline. We were pleased
to find that pure 9d was readily isolated by simple
recrystallization from hexane. Microanalysis of the
compound, obtained as colorless crystals, suggested it to
be isomeric with 4-tert-butoxy-2,6-di-tert-butylphenol
neighborhood of those in 9d or 9e. Stability was tested
on the pure specimens of 9d and 9e. As proved by H
1
NMR spectroscopy, they were considerably stable in
CDCl3: 9d or 9e suffered little isomerization into 10d
or 4-(tert-amyloxy)-2,6-di-tert-butylphenol (10e), respec-
tively, after allowing the solution to stand at ca. 35 °C
for 15 h. In CDCl3 containing pyridine-d5, they were
converted into the phenols very rapidly, as anticipated.
In MeOH-d4, they were unstable and their isomerization
was completed within 15 min at ca. 35 °C. It was
confirmed that 9d and 9e were quantitatively recovered
as 10d and 10e, respectively, when chromatographed on
SiO2 with nonpolar eluents. In the solid states, both 9d
and 9e remained unchanged for months when stored at
-20 °C.
As cited above, a high amount of 9a in the crude
product was obtained from the reaction of 3b with
AgOCOCF3 in MeOH. The reactions to give 9 with
AgOCOCF3 and other alcohols, however, proved not to
be quite successful, owing to occurrence of a competing
reaction generating a new, labile dienone, 4-(trifluoro-
acetoxy)-2,6-di-tert-butylcyclohexa-2,5-dienone (11). Com-
pound 11 was not isolable, but its formation was supported
by the following representative observations. The 1H
NMR spectrum (in CDCl3) of the crude product from the
reaction in t-BuOH (at 27 °C) (run 9, Table 1) suggested
that it contained, in addition to 9d and 10d , two new
compounds. One of them (minor component) was found
to be 4-(trifluoroacetoxy)-2,6-di-tert-butylphenol (12). The
other (major component) showed signals at δ 6.53 (d, J
1
(10d ). Product identification by H NMR spectroscopy
was straightforward (Table 2). The 13C NMR spectrum
was also compatible with structure 9d . The IR (1658 and
1639 cm-1; Nujol mull) as well as UV [236 nm (log ꢀ 3.92)
in cyclohexane] spectra also supported the cyclohexa-2,5-
dienone structure.15 Purification by recrystallization of
the crystalline crude product of 4-(tert-amyloxy)-2,6-di-
tert-butylcyclohexa-2,5-dienone (9e), obtained from run
11, was also facile. Structure 9e for the compound was
unambiguously demonstrated similarly from the 1H
(Table 2) and 13C NMR, IR (1661 and 1639 cm-1; Nujol
mull), and UV [239 nm (log ꢀ 3.95) in cyclohexane]
spectra as well as microanalysis. Table 2 lists the 1H
NMR data of 9a -c also. It is rational that the reso-
nances of vinyl, methine (in the 4-position), and tert-butyl
(in the 2- and 6-positions) protons in 9a -c appear in the
(15) The spectral properties of cyclohexadienones have been de-
scribed in detail. See: (a) Rieker, A.; Rundel, W.; Kessler, H. Z.
Naturforsch 1969, 24b, 547. (b) Rieker, A.; Berger, S. Org. Magn. Reson.
1972, 4, 857.

Dienone Tautomers of 4-Alkoxy-2,6-di-tert-butylphenols
J . Org. Chem., Vol. 61, No. 20, 1996 7159
Ta ble 3. Alk oxy Dien on es 9 fr om P h en ol 6a
) 3.2 Hz) (overlapped with the doublet due to 9d ), 5.98
(t, J ) 3.2 Hz), and 1.25 (s). In CDCl3 containing
product (yield,b %)
1
pyridine-d5, the H NMR spectrum of the product con-
alcohol
9
10
sisted exclusively of singlets due to 10d and 12. Column
chromatography of the product on SiO2 provided four
compounds almost excusively, 10d , 12, 2,6-di-tert-butyl-
hydroquinone (13), and 2,6-di-tert-butyl-p-benzoquinone
(14). Compounds 13 and 14 were artifacts formed from
12 during the chromatography.16 It is thus reasonable
MeOH
EtOH
i-PrOH
t-BuOHc
t-AmOH
9a (75)
9b (86)
9c (83)
9d (91)
9e (82)
10a (14)
10b (7)
10c (6)
10d (3)
10e (3)
a
Unless stated otherwise, the reaction was carried out for 2
min at 0 °C by using 6 (2 mmol), Br2 (2 mmol), AgClO4 (4 mmol),
and Na2CO3 (8 mmol) in a mixture of an alcohol (30 mL) and DME
(7 mL). b 1H NMR spectroscopically determined yields of 9 and 10
contained in the crude product. c Conducted for 3 min in a mixture
of t-BuOH (20 mL) and DME (17 mL in total: see Experimental
Section).
10a in 84% yield as well as AgBr (2 molar equiv).20 The
actual species for brominating 6 must be Br2 itself.
However, BrClO4 (or BrOMe after its reaction with
MeOH) generated from the reaction between Br2 and
AgClO4 may as well be responsible for the bromination
of 6. Indeed, addition of Br2 to methanolic AgClO4 (1
molar equiv) immediately discharged the Br2 color and
precipitated AgBr (1 molar equiv, isolated by filtration),
and the filtrate was capable of brominating 6 rapidly.
Hence 10a was obtained also by adding 6 to a mixture
of Br2 (1 molar equiv) and AgClO4 (2 molar equiv) in
MeOH. Electrophilic halogenation of aromatic substrates
with a combination of molecular halogen and Ag ion has
been documented.21 The same methoxylation could be
achieved by adding Br2 to a solution of 6 and AgClO4 in
DME containing a limited amount (12 molar equiv) of
MeOH, without much sacrifice to the yield of 10a (79%).
4-Alkoxyphenols 10b, 10c, and 10d were obtained in 76-
79% yields from similar reactions with limited amounts
(8-10 molar equiv) of EtOH, i-PrOH, and t-BuOH,
respectively. The reaction with H2O (28 molar equiv)
provided 13 (79%). Acetoxylation of 6 to give 4-acetoxy-
2,6-di-tert-butylphenol (15) was successful (78%) only
when a large quantity of AcOH was employed. Examples
of synthesis of oxyfunctionalized phenols directly from
phenols are scarce because substantial overoxidation
takes place usually.8b,d,e,22
to assume that the crude product contained 11, to which
the aforementioned new NMR signals are ascribable, and
that 11 underwent prototropic rearrangement by base,
acid, or SiO2, providing 12. Similarly, the crude products
obtained from the reactions (at 0 °C) of 3b with Ag-
OCOCF3 in other alcohols (including MeOH) contained
11 and 12 in addition to 9 and 10. The (9 + 10)/(11 +
12) molar ratios were estimated to be 30, 8.0, 2.6, 0.5,
and 0.5 for the reactions in MeOH, EtOH, i-PrOH,
t-BuOH, and t-AmOH, respectively: the 9/10 ratios and
the 11/12 ratios were in general high. The formation of
11 may be the result of the reaction of carbocation 8,
generated from the interaction between 3b and Ag-
OCOCF3, with the freed CF3CO2 anion (Scheme 1).17
Competition for 8 between CF3CO2 anion (giving 11) and
an alcohol (giving 9) is shown to become in favor of the
former as the alcohol becomes bulky.18 Generation of 9
by displacement reaction of 11 with an alcohol is unlikely,
since extending the time of the reaction in t-BuOH,
described above, altered neither the total yield of 9d and
10d nor that of 11 and 12, although the 9d /10d and 11/
12 ratios were both decreased.
It was found that 9 can be conveniently obtained
directly from 2,6-di-tert-butylphenol (6), by brominating
it to generate 3b in situ in an alcohol containing AgClO4
and Na2CO3 (cf. Scheme 1). Molecular bromine (1 molar
equiv) in DME was added quickly to a vigorously stirred
solution (0 °C) of 6 and AgClO4 (2 molar equiv) in an
alcohol19 containing excess Na2CO3 (4 molar equiv), and
the stirring was continued for a few minutes at 0 °C. As
shown in Table 3, the crude product contained 9 in a yield
comparable to that obtained from the corresponding
reaction of 3b with AgClO4 and Na2CO3. Success of the
process is indebted to the rapidity and selectivity of both
the bromination and the subsequent debromination. Half
of the AgClO4 employed was consumed in the bromina-
tion step.
In summary, 4-alkoxycyclohexa-2,5-dienones 9, the
tautomeric forms of 4-alkoxyphenols 10, can be obtained
as crude products from the fast reaction of 4-bromo-
cyclohexa-2,5-dienone 3b either with AgClO4 and Na2CO3
in alcohols or with AgOCOCF3 in the same solvents. They
can also be obtained directly from phenol 6 by treatment
with Br2 in alcohols containing AgClO4 and Na2CO3.
Crude 4-tert-alkoxycyclohexa-2,5-dienones 9d and 9e can
be purified facilely by recrystallization, and they are fully
It is natural that a one-pot synthesis of 10 from 6 was
also possible. Quick addition of methanolic Br2 (1 molar
equiv) to a stirred solution of 6 and AgClO4 (2 molar
equiv) in MeOH (not containing Na2CO3) readily afforded
(16) Compounds 13 and 14 were also obtained in small quantities
from the reactions with AgClO4 (see Experimental Section).
(17) An alternative mechanism may not be excluded in which 3b is
attacked by Ag ion and by an alcohol or CF3CO2 anion concertedly
and free cation 8 accordingly is not generated.
(18) The reaction at 0 °C of 3b with AgClO4 in an equimolar mixture
of MeOH and t-BuOH (not containing Na2CO3) gave rise to 10a and
10d in 76% and 14% yields, respectively, after chromatography of the
crude product.
(20) If Br2 was added slowly, namely, over a period of 6 min, the
yield of 10a was reduced to 56% while recovery of 6 (21%) and
formation of 14 (14%) became significant. Compound 10a was oxidized
rapidly by Br2 in MeOH containing or not containing AgClO4, giving
14 quantitatively.
(21) (a) Galli, C. J . Org. Chem. 1991, 56, 3238. (b) Derbyshire, D.
H.; Waters, W. A. J . Chem. Soc. 1950, 3694. (c) Myhre, P. C.; Owen,
G. S.; J ames, L. L. J . Am Chem. Soc. 1968, 90, 2115. (d) Sy, W.-W.
Synth. Commun. 1992, 22, 3215.
(19) In the reaction with t-BuOH, DME was employed as a cosolvent
to avoid freezing (see Experimental Section).
(22) Becker, H.-D.; Gustafsson, K. J . Org. Chem. 1979, 44, 428.

7160 J . Org. Chem., Vol. 61, No. 20, 1996
Omura
(89%, run 1), 10a (78%, run 3), 10d (90%, run 7), or 10e (90%,
run 10)], 13 [0-15 mg (3%)], and 14 (trace to 6%).
characterized. Dienones 9 are susceptible to (irrevers-
ible) tautomerization into phenols 10 by catalysis with
base, acid, or SiO2. A one-pot synthesis of 4-oxyfunc-
tionalized 2,6-di-tert-butylphenols from 6 is achieved.
With AgOCOCF 3. The procedure described above for the
reaction with AgClO4 in the presence of Na2CO3 was followed
except that AgOCOCF3 (442 mg, 2 mmol) replaced AgClO4 and
Na2CO3 was omitted. MeOH (run 4), EtOH, i-PrOH, t-BuOH
(run 9), or t-AmOH was employed as the alcohol. The reaction
mixture obtained from run 9, containing fine particles of AgBr
(passable through a filter paper) was poured into brine (200
mL) for the subsequent extractive workup. Column chroma-
tography of the product obtained from run 4 afforded 7 (4%),
10a (88%), 13 (1%), and 14 (2%). Column chromatography of
the product obtained from run 9 provided successively 7 (2%),
4-(trifluoroacetoxy)phenol 12 (190 mg, 30%), a mixture of 10d
Exp er im en ta l Section
1H (90 MHz) and 13C (22.6 MHz) NMR spectra were taken
in CDCl3. Column chromatography was conducted on Merck
SiO2 60 by using gradient elution (100% petroleum ether to
50%/50% petroleum ether/benzene). TLC was run on SiO2. GC
analyses were performed at 150 °C on a column packed with
10% FAP-S on Chromosorb W. Commercially available Ag-
ClO4 (Wako) and AgOCOCF3 (Aldrich) were used as received.
Reactions with the Ag salts were carried out in a stoppered
vial.
1
(31%) and 14 (5%) as analyzed by H NMR spectroscopy, and
13 (141 mg, 32%). Compounds 12 and 13 were purified by
recrystallization from hexane.
Silver Ion In d u ced Rea ction of Br om o Dien on e 3b
w ith Alcoh ols (Ta ble 1). With AgClO4 in th e P r esen ce
of Na 2CO3 (Ru n s 2, 5, 6, 8, a n d 11). To a mixture of
powdered 3b2c (570 mg, 2 mmol) and finely powdered anhy-
drous Na2CO3 (0.85 g, 8 mmol) was added at once a cold (0
°C) solution of AgClO4 (415 mg, 2 mmol) in an alcohol (30 mL),
and the resulting mixture was stirred magnetically for 2 min
at 0 °C. The reaction with t-BuOH (run 8) was run at 27 °C.
The reaction with t-AmOH (run 11) was carried out for 4 min.
The mixture was filtered into a flask containing stirred, cold
water (200 mL). The contents of the flask were extracted with
petroleum ether (200 mL × 2). The extract was washed with
water, dried over anhydrous Na2SO4, and evaporated to
dryness under reduced pressure below 30 °C. The residual
product (containing alkoxy dienone 9 and 4-alkoxyphenol 10)
was readily subjected to analysis by 1H NMR spectroscopy.
Column chromatography of the product provided successively
4-bromophenol 7 (15-33 mg, 3-6%), 10 (see below for the
yield), p-benzoquinone 14 (3-24 mg, 1-5%), and hydroquinone
13 (none or trace). Compound 10d or 10e was in part obtained
as a mixture with 14, and the amounts of 10d or 10e and of
14 in the mixture were estimated by 1H NMR spectroscopy.
Compounds 7, 10a -e, and 14 were purified by recrystalliza-
tion from hexane or MeOH.
Compound 12: colorless crystals; mp 46-47 °C; 1H NMR δ
6.97 (s, 2H), 5.22 (s, 1H), 1.43 (s, 18H); IR (CHCl3) 3620, 1790
cm-1. Anal. Calcd for C16H21O3F3: C, 60.37; H, 6.65. Found:
C, 60.55; H, 6.66. Ester 12 was also obtained in nearly
quantitative yield by treating 13 with excess (CF3CO)2O at
rt. Ester 12 suffered significant degradation upon chroma-
tography, giving 13 and 14.
Compound 13: identical with an authentic sample prepared
by NaBH4 reduction of 14 (1H NMR and TLC); mp 105-106
°C (lit.23 mp 110-111 °C). Hydroquinone 13 suffered partial
degradation into 14 upon chromatography.
Isola tion a n d Id en tifica tion of ter t-Alk oxy Dien on es
9d a n d 9e. Analytically pure 9d and 9e were obtained by
recrystallizing the crude products obtained from runs 8 and
11, Table 1, respectively.
Compound 9d : colorless crystals from hexane (227 mg,
41%); mp 107-109 °C; 13C NMR δ 185.9, 146.9, 139.7, 75.1,
64.6, 34.7, 29.3, 28.1. Anal. Calcd for C18H30O2: C, 77.65; H,
10.86. Found: C, 77.40; H, 11.01.
Compound 9e: colorless crystals from hexane (267 mg,
46%); mp 84-86.5 °C; 13C NMR δ 186.0, 146.9, 139.8, 77.5,
64.3, 34.7, 33.6, 29.3, 25.4, 8.8. Anal. Calcd for C19H32O2: C,
78.03; H, 11.03. Found: C, 77.99; H, 10.99.
The 1H NMR, IR, and UV spectra of 9d and 9e as well as
their stability are described in the text.
Compound 7: identical with an authentic sample3b (1H NMR
and TLC); mp 82-84 °C (lit.3b mp 80-82 °C).
On e-P ot Syn th esis of Cr u d e Alk oxy Dien on es 9 fr om
P h en ol 6 (Ta ble 3). A cold (0 °C) solution of Br2 (320 mg, 2
mmol) in DME (7 mL) was added in one portion to a vigorously
stirred, cold, heterogeneous mixture of 6 (412 mg, 2 mmol),
AgClO4 (830 mg, 4 mmol), finely powdered anhydrous Na2CO3
(0.85 g, 8 mmol), and an alcohol (30 mL). The Br2 color was
discharged immediately. The stirring was continued for 2 min
at 0 °C. The mixture was filtered into a flask containing
stirred, cold water (200 mL). The reaction with t-BuOH was
performed at 0 °C for 3 min by using the Br2 solution in DME
and a mixture of 6, AgClO4, Na2CO3, t-BuOH (20 mL), and
DME (10 mL), and the reaction mixture was filtered into a
flask containing a stirred, cold solution of NaCl (25 g) in water
(200 mL). The contents of the flask were extracted with
petroleum ether (200 mL × 2). The extract was washed with
water, dried (Na2SO4), and evaporated to dryness under
reduced pressure below 30 °C. The amount of 9 (as well as
that of 10) in the residual product was estimated readily by
1H NMR spectroscopy.
Compound 10a : obtained from run 2 (407 mg, 86%);
identical with a commercially available sample (from Aldrich)
of 10a (1H NMR and TLC); mp 105-106 °C (lit.23 mp 106-
107 °C).
Compound 10b: obtained from run 5 (432 mg, 86%); mp
84.5-85.5 °C (lit.24 mp 83-84 °C).
Compound 10c: obtained from run 6 (463 mg, 88%); mp 60-
62.5 °C (lit.25 mp 59-60 °C).
Compound 10d : obtained from run 8 (515 mg, 93%); mp
99.5-100 °C (lit.26 mp 99-100 °C).
Compound 10e obtained from run 11 (532 mg, 91%);
colorless crystals from hexane; mp 64.5-65 °C; 1H NMR δ 6.76
(s, 2H), 4.85 (s, 1H), 1.63 (q, J ) 7.2 Hz, 2H), 1.41 (s, 18H),
1.21 (s, 6H), 1.00 (t, J ) 7.2 Hz, 3H); IR (CHCl3) 3620 cm-1
;
UV (cyclohexane) 283 nm (log ꢀ 3.40), 203 (4.47). Anal. Calcd
for C19H32O2: C, 78.03; H, 11.03. Found: C, 77.76; H, 11.19.
Compound 14: identical with an authentic sample27 (1H
NMR and TLC); mp 65-67 °C (lit.23 mp 67-68 °C).
Recrystallization from hexane of the products obtained from
the reactions with t-BuOH and t-AmOH afforded spectroscopi-
cally (1H NMR) homogeneous 9d (220 mg, 40%) and 9e (295
mg, 51%), respectively.
With AgClO4 in th e Absen ce of Na 2CO3 (Ru n s 1, 3, 7,
a n d 10). The procedure described above for the reaction with
AgClO4 in the presence of Na2CO3 was followed except that
Na2CO3 was omitted. The reaction in a mixture of MeOH (28
mL) and H2O (4 mL) (run 3) was carried out for 10 min.
Column chromatography of the product gave 7 (3-5%), 10 [10a
On e-P ot Syn th esis of 4-Oxyfu n ction a lized 2,6-Di-ter t-
b u t ylp h en ols fr om P h en ol 6. 4-Met h oxyp h en ol 10a .
Ru n A. To a stirred, cold (0°C) solution of 6 (412 mg, 2 mmol)
and AgClO4 (830 mg, 4 mmol) in MeOH (30 mL) was added
quickly a cold solution of Br2 (320 mg, 2 mmol) in MeOH (7
mL). The Br2 color was discharged immediately, and yellow
precipitates began to form soon. The stirring was continued
for 3 min at 0 °C. The mixture was filtered to give AgBr (0.73
g, 97%). The filtrate was poured into water (200 mL) and
extracted with petroleum ether (200 mL × 2). The extract was
washed with water, dried (Na2SO4), and evaporated under
(23) Mu¨ller, E.; Ley, K. Chem. Ber. 1955, 88, 601.
(24) Cook, C. D.; Kuhn, D. A.; Fianu, P. J . Am. Chem. Soc. 1956,
78, 2002.
(25) Plekhanova, L. G.; Nikiforov, G. A.; Ershov, V. V. Izv. Akad.
Nauk SSSR, Ser. Khim. 1969, 961.
(26) Cook, C. D.; Woodworth, R. C.; Fianu, P. J . Am. Chem. Soc.
1956, 78, 4159.
(27) Omura, K. J . Org. Chem. 1989, 54, 1987.

Dienone Tautomers of 4-Alkoxy-2,6-di-tert-butylphenols
J . Org. Chem., Vol. 61, No. 20, 1996 7161
reduced pressure, leaving a crystalline residue. Recrystalli-
zation from MeOH provided 10a (340 mg, 72%). The filtrate
from the recrystallization was evaporated, and the residue was
chromatographed to give successively a mixture of 6 (22 mg,
5% recovery) and 7 (5 mg, 1%) as analyzed by GC, an
additional crop of 10a (58 mg, 84% in total), and 14 (10 mg,
2%).20
Ru n B. The reaction was conducted with a solution of 6 (2
mmol), AgClO4 (4 mmol), and MeOH (1 mL, 25 mmol) in DME
(15 mL) and a solution of Br2 (2 mmol) in DME (7 mL), and
the reaction mixture was worked up, in the manner described
above for run A, giving 6 (5% recovery), 7 (5%), 10a (79% in
total), and 14 (8%).
Ru n C. To a stirred, cold solution of AgClO4 (4 mmol) in
MeOH (20 mL) was added a cold solution of Br2 (2 mmol) in
MeOH (7 mL). The Br2 color was discharged immediately, and
yellow precipitates began to form soon. After 1 min, a cold
solution of 6 (2 mmol) in MeOH (10 mL) was added quickly to
the stirred mixture. The stirring was continued for 5 min at
0 °C. The reaction mixture was worked up in the manner
described above for run A, giving 6 (3% recovery), 7 (5%), 10a
(80% in total), and 14 (5%).
Ru n D. To a stirred, cold solution of AgClO4 (2 mmol) in
MeOH (25 mL) was added a cold solution of Br2 (2 mmol) in
MeOH (7 mL). After the stirring was continued for 30 s, the
mixture was filtered into a flask containing a solution of 6 (2
mmol) in MeOH (5 mL). The filtration collected AgBr (98%).
The contents of the flask were allowed to stand for 3 min at rt
and poured into water. Extractive workup with petroleum
ether provided a yellow oil (0.57 g), which was a 2.3:1 mixture
of 3b and 7 as estimated by 1H NMR spectroscopy. A small
amount of 6 (2% recovery) was also found. Phenol 10a was
not found.
Oth er 4-Oxyfu n ction a lized 2,6-Di-ter t-bu tylp h en ols.
The procedure described above for the synthesis of 10a , run
B, was followed except that EtOH (1 mL, 17 mmol), i-PrOH
(1.5 mL, 20 mmol), t-BuOH (1.5 mL, 16 mmol), or H2O (1 mL,
56 mmol) replaced MeOH. Acetoxylation was conducted with
a solution of 6 and AgClO4 in a 3:1 (v/v) mixture of AcOH and
DME (30 mL) and a solution of Br2 in the same solvent mixture
(7 mL). Recrystallization of the product from hexane provided
9b (318 mg, 64%), 9c (290 mg, 55%), 9d (380 mg, 68%), 13
(302 mg, 68%), or 4-acetoxyphenol 15 (322 mg, 61%). Ad-
ditional crops of the 4-oxyfunctionalized phenols were obtained
by chromatography of the filtrates from the recrystallization,
and their total yields amounted to 76-79%.
Compound 15: mp 91-92 °C (lit.28 mp 87-88 °C).
Ack n ow led gm en t. The author is thankful to Tohru
Nakata and Makiko Terada (students) for experimental
contributions.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 9d ,e, 10a -e, 12, and products containing com-
pounds 9a -c and 11; 13C NMR spectra of compounds 9d and
9e (14 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 O9609945
(28) Mu¨ller, E.; Rieker, A.; Mayer, R.; Scheffler, K. J ustus Liebigs
Ann. Chem. 1961, 645, 36.