Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl ethers

Article abstract of DOI:10.1016/j.tet.2018.01.048

B-Alkylpinacolboranes, derived from rhodium-catalyzed hydroboration of allyl ethers with pinacolborane, react with 1,4-benzoquinone under acidic, oxidizing conditions, to afford, after subsequent hydrogenation, 2-substituted hydroquinones in isolated, pur

Full text of DOI:10.1016/j.tet.2018.01.048

Tetrahedron xxx (2018) 1e6
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Tetrahedron
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Synthesis of 2-substituted hydroquinone derivatives from 1,4-
benzoquinone and allyl ethers
Kevin J. Kaurich, Paul A. Deck*
Department of Chemistry, Virginia Tech, Blacksburg, VA, 24061, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
B-Alkylpinacolboranes, derived from rhodium-catalyzed hydroboration of allyl ethers with pinacolbor-
ane, react with 1,4-benzoquinone under acidic, oxidizing conditions, to afford, after subsequent hydro-
genation, 2-substituted hydroquinones in isolated, purified yields of about 50% based on 1,4-
benzoquinone. The product hydroquinones have potential use as precursors to poly(arylene ether) and
related aromatic polymers.
Received 4 December 2017
Received in revised form
24 January 2018
Accepted 26 January 2018
Available online xxx
© 2018 Elsevier Ltd. All rights reserved.
Keywords:
Hydroboration
Hydroquinone
Benzoquinone
Wilkinson's catalyst
1. Introduction
with larger R groups, researchers have resorted to derivatizing the
hydroquinone to enable a separation.10 Third, alkene hydroboration
Alkylated hydroquinones and benzoquinones are found in na-
ture and can have important cytotoxic and antioxidant activities.1,2
Hydroquinones are also important constituents of aromatic poly-
mers such as poly(arylene ether)s and polyesters.3e5 Traditional
synthetic approaches to alkylated hydroquinones include Friedel
Crafts and free-radical alkylations as well as oxidation of
substituted phenols.6e8 While procedurally simple, these methods
often afford low yields or complex mixtures of products.
Trialkylboranes, conveniently generated by alkene hydro-
boration, can transfer one alkyl group to 1,4-benzoquinone to afford
alkylated hydroquinones,9 usually in the presence of dioxygen.10
Either primary or secondary alkyl groups may be transferred, and
the method tolerates functional groups that are compatible with
BH3 (halogens, esters, ethers, and nitriles).10 Although overall yields
in these reactions are usually high, there are three frustrating
complications. First, only one alkyl group from the trialkylborane is
transferred, thereby wasting two equivalents of the starting alkene.
Second, the borinic acid byproduct (R2BOH) is difficult to separate
from the desired hydroquinone. When R is relatively small (i.e., C6
or less), the borinic acid can be removed by steam distillation, but
with BH3 (or with BH3$SMe2) is not highly regioselective, especially
for alkenes having electron-withdrawing substituents near the
double bond.11 Although the initial hydroboration may afford
mostly primary borane, the higher migratory aptitude of secondary
radicals12 can lead to significant contamination by the branched
alkyl group in the hydroquinone,13 and then recrystallization is
needed to obtain a pure regioisomer.
Recent advances in the preparation of organoboranes have
partly alleviated these problems. Using catecholborane instead of
BH3 should, in principle, eliminate the problem of wasting two
thirds of the alkene.14 B-Alkylcatecholboranes derived from various
unfunctionalized alkenes will transfer a primary or secondary alkyl
group to 1,4-benzoquinone. A recently reported method of pre-
paring B-alkylcatecholboranes uses catecholborane in the presence
of N,N-dimethylacetamide (DMAC), however this method has about
the same regioselectivity for simple terminal alkenes as one would
obtain using BH3.15 Moreover, the optimized conditions for alkyl
transfer to 1,4-benzoquinone requires a twofold excess of the B-
alkylcatecholborane, ostensibly to outpace the natural tendency of
the alkylated hydroquinone product to reduce the 1,4-
benzoquinone reactant in situ. In this case the product hydroqui-
none must be separated from by-product catechol derivatives,
likely including catecholboronic acid, o-C6H4O2BOH.14,16 In pre-
liminary experiments we found these kinds of separations difficult
and inefficient.
* Corresponding author. Virginia Tech, 406 Davidson Hall, Blacksburg, VA 24061
USA.
E-mail address: pdeck@vt.edu (P.A. Deck).
https://doi.org/10.1016/j.tet.2018.01.048
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
ethers, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.048

2
K.J. Kaurich, P.A. Deck / Tetrahedron xxx (2018) 1e6
The challenge of product isolation in these procedures is not to
ethers are the more precious of the two main reactants. Yields
based on the allyl ethers are only about one third of the yields based
on benzoquinone because only one alkyl group of the trialkylbor-
ane intermediate is transferred.
One factor in the low yields obtained for 2d-f could be the low
regioselectivity for hydroboration of allyl ethers noted by Brown
and co-workers. Rather than question or repeat their work in this
area, we moved on different hydroboration reagents. Even if we had
obtained better yields for 2d-f, the necessity of removing the
byproduct borinic acid (R2BOH) by steam distillation would tend to
limit the range of useable allyl ethers. Moreover there is still the
issue of wasting two-thirds of the alkene reactant.
be underestimated. Renaud developed a tetrahydroisoquinoline-
derived catecholborane that facilitated removal of the byproducts
by acidic aqueous extraction upon workup, however the needed
catechol derivative is not commercially available and the overall
procedure is complicated.16 Cole and co-workers generated tri-
alkylboranes having the formula RBMe2, which transfer primary
and secondary alkyl groups to benzoquinone in strong preference
to the methyl groups.17 However, preparing those trialkylboranes
requires hydroboration with HBCl2 (generated in situ from HSiEt3
and BCl3) followed by substitution of the BCl2 moiety with MeMgBr,
a pathway that excludes most other functional groups because of
reagent incompatibilities.18 In another recent advance, alkyl- and
arylboronic acids were combined with 1,4-benzoquinone to give 2-
substituted 1,4-benzoquinones in moderate to high yields.19
Boronic acids are not always the most conveniently prepared syn-
thetic intermediates.
In the course of our ongoing work on functionalized aromatic
polymers we wanted to develop a general synthetic method for
monosubstituted hydroquinones that would start with selective
anti-Markovnikov hydroboration of an allyl ether and then transfer
the 3-alkoxypropyl group to 1,4-benzoquinone. Because allyl ethers
are readily prepared by Williamson synthesis, such a method
would give us rapid access to a wide range of functional 2-
substituted hydroquinone derivatives.
Preliminary efforts using BH3$SMe2 and catecholborane, with
allyl ethyl ether as the substrate, afforded poor yields of the desired
2-(3-ethoxypropyl)hydroquinone. We then thought to use pina-
colborane, which is not only more stable than catecholborane20 but
might also afford better regioselectivity because of its greater steric
bulk and lower overall electrophilicity. However, the utility of B-
alkylpinacolboranes in radical-transfer processes has met with
mixed results. In particular, alkyl transfer to 1,4-benzoquinone was
shown to be quite sluggish, even in the presence of K2S2O8 and
AgNO3.19 On the other hand, a related fluorination with Select-
Fluor™ showed better efficiency in the presence of CF3COOH (TFA).
We reasoned that TFA might facilitate the desired alkyl transfer to
1,4-benzoquinone as well. Such a procedure under oxidizing con-
ditions (K2S2O8, AgNO3, and TFA) would ideally give an interme-
diate 2-substituted 1,4-benzoquinone, which we could then reduce
to the corresponding hydroquinone derivative by catalytic hydro-
genation, possibly with minimal workup between steps, thereby
approaching one-pot efficiency. We now describe our efforts to
explore these possibilities.
We next explored monohydroborating agents and their use in
generating substituted hydroquinones. As noted above, halobor-
anes such as HBCl2 were ruled out entirely because they form
strong complexes with ethers. Table 2 shows the results of our
studies using catecholborane and Wilkinson's catalyst, (Ph3P)3RhCl,
to effect hydroboration of four alkene substrates, followed by
reductive alkyl transfer from the alkylboron intermediate to 1,4-
benzoquinone. Yields are somewhat improved relative to those
shown in Table 1, but “atom economy” with respect to the alkene is
still low (2 equiv of B-alkylcatecholborane is needed), and the
chromatographic separation of the product from catecholboronic
acid and other by-products required large volumes of eluting sol-
vents. Importantly, using one of our most urgently desired sub-
strates, allyl phenyl ether (1g), the initial hydroboration was
extremely sluggish and unpredictable, and in four attempts with
the typical adjustments to conditions and isolation procedures, we
obtained no yield of the corresponding 3-phenoxypropyl-1,4-
hydroquinone (2g) whatsoever. Analysis of the reaction mixture
by NMR spectroscopy after the initial hydroboration step revealed
mostly unreacted allyl phenyl ether e an unacceptable result for us.
Still hoping to conserve alkene starting materials and improve
the scope of our method, we switched to hydroboration with
pinacolborane, which gives selective anti-Markovnikov addition to
terminal alkenes using Wilkinson's catalyst.20 Using 1-hexene (1a)
for initial screening (Table 3), Rh-catalyzed hydroboration suc-
ceeded either in THF or dichloromethane solution, but the subse-
quent alkylation of benzoquinone entirely failed using aqueous THF
(entry 1). Slightly more promising results for the alkylation step
were obtained using a water-dichloromethane biphasic mixture
(entry 5), but the reaction still afforded a very poor yield. Others
have also found that alkyl transfer from B-alkylpinacolboranes to
1,4-benzoquinone is sluggish,19 so based on related findings21 in
the area of fluorinations of B-alkylpinacolboranes, we reasoned that
TFA might help facilitate alkyl transfer (entry 4). In contrast to that
prior work, we found that TFA alone, rather than 4:1 TFA:H3PO4,
gave the highest yields. Longer reaction time resulted in no
improvement, so we considered the reaction to be optimized at the
yields shown in Table 3. The final hydrogenation is not yield-
limiting, as we optimized hydrogenation conditions separately.
Next we extended our method to allyl ethers (Table 3, entries
5e11). Variations in reaction time, proportions of reagents, etc.
were explored, but isolated yields were reliably close to about 50%
for the 2-alkylated hydroquinones after chromatographic purifi-
cation. When we started with allyl 4-bromophenyl ether (1h, R ¼ 4-
C6H4Br), 1H NMR spectroscopic analysis of the chromatographically
purified product showed contamination with about 30% of the
debrominated product (2g, R ¼ C6H5), not a surprising result for a
sequence that includes a noble-metal-catalyzed hydrogenation.22
We found, however, that the 3-aryloxypropyl-substituted 1,4-
benzoquinones could be isolated (ca. 73% for R ¼ C6H5; 60% for
R ¼ 4-C6H4Br). They are not especially stable, but reduction of the
benzoquinone derivative bearing the pendant 4-bromophenyl
group was effected cleanly using dissolving zinc in about 90%
2. Results and discussion
Our efforts in the area of functionalized aromatic polymers have
led us to develop a general synthetic approach to monosubstituted
hydroquinones starting with anti-Markovnikov hydroboration of
an allyl ether as the origin of the substituent that is then transferred
from boron to 1,4-benzoquinone in a free-radical process. Like
others before us, we started with BH3$SMe2 because of its
simplicity and low cost. Even though we knew we would lose two
thirds of our alkene to byproducts, we wanted to ensure that we
could reproduce the results of others with our own hands. Table 1
shows the results of these preliminary studies. Yields obtained with
1-hexene and 1-octene (1a and 1b, entries 1 and 2, respectively) are
for purified products and are consistent with crude yields previ-
ously reported.13 Cyclooctene (1c, entry 3) gives a higher yield,
possibly due to the enhanced migratory aptitude of the secondary
alkyl group.12
Allyl ethers however, gave disappointing results (1d-f, entries
4e6). While a yield of 30% might seem tolerable, one must recall
that this yield is based on 1,4-benzoquinone, whereas the allyl
Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
ethers, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.048

K.J. Kaurich, P.A. Deck / Tetrahedron xxx (2018) 1e6
3
Table 1
Yields of hydroquinones derived from trialkylboranes.
Entry
Alkene
R
yield (%)a
1
2
3
4
5
6
1-hexene (1a)
1-octene (1b)
cyclooctene (1c)
allyl ethyl ether (1d)
allyl 2,2,2-trifluoroethyl ether (1e)
(CH2)5CH3
(CH2)7CH3
cyclo-C8H15
(CH2)3OCH2CH3
(CH2)3OCH2CF3
2a
2b
2c
2d
2e
2f
72
70
88
33
30
29
allyl 2,2,3,3,3-pentafluoropropyl ether (1f)
(CH2)3OCH2CF2CF3
a
Isolated yields based on 1,4-benzoquinone.
Table 2
Yields of hydroquinones derived from B-alkylcatecholboranes.
Table 3
Yields of hydroquinones derived from B-alkylpinacolboranes.
Entry
Alkene
R
yield (%)a
1
2
3
4
5
1-hexene (1a)
1-octene (1b)
allyl ethyl ether (1d)
allyl 2,2,2-trifluoroethyl ether (1e)
allyl phenyl ether (1g)
(CH2)5CH3
(CH2)7CH3
(CH2)3OCH2CH3
(CH2)3OCH2CF3
(CH2)3OPh
2a
2b
2d
2e
2g
58
59
53
52
e
a
Isolated yields based on 1,4-benzoquinone.
Entry Alkene
R
Solvent
Yield
(%)a
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1d
1e
1f
1g
1g
1h
1h
(CH2)5CH3
(CH2)5CH3
(CH2)5CH3
(CH2)5CH3
(CH2)3OCH2CH3
(CH2)3OCH2CF3
(CH2)3OCH2CF2CF3 CH2Cl2/H2O/TFA
(CH2)3OC6H5
(CH2)3OC6H5
(CH2)3OC6H4Br
(CH2)3OC6H4Br
THF/H2O
CH2Cl2/H2O
CH2Cl2/H2O/TFA
CH2Cl2/H2O/TFA
CH2Cl2/H2O/TFA
CH2Cl2/H2O/TFA
2a
0
isolated yield. For all the other derivatives, both the hydroboration
and benzoquinone-alkylation steps are carried out in a single pot,
as the organic solvent for the hydroboration step and the alkylation
step is the same (dichloromethane). After a short aqueous workup,
the crude 2-substituted 1,4-benzoquinone intermediate can be
subjected directly to catalytic hydrogenation with Raney nickel
(1 atm, 25 ꢀC, 1 h) to afford the desired 2-substituted hydroquinone
after silica gel chromatographic purification. While 50% yield is not
ordinarily cause for celebration, the improvement in yield with
respect to the alkene has improved compared to using BH3$SMe2.
Our yields are comparable to those obtained by Baran and co-
workers using boronic acids as the alkylating reagent.19 We
cannot rule out the possibility that our pinacolboranes are hydro-
lyzed to the corresponding boronic acids in situ, since our reaction
conditions include aqueous TFA. Likewise we could imagine con-
verting our pinacolboranes to boronic acids or potassium alkyltri-
fluoroborates, but based on results obtained by Baran and co-
workers, we would not anticipate significant improvements in
yield, and those conversions would involve additional synthetic
steps. An important feature of our methods is its experimental
simplicity, especially starting from allyl ethers as the source of the
alkyl group. This feature will allow us to extend the scope of the
alkylating agent widely because allyl ethers themselves are easily
prepared.
2a 10
2a 52
2a 50
2d 50
2e 49
2f
2g 73
49
CH2Cl2/H2O/TFA
CH2Cl2/H2O/4:1 TFA:H3PO4 2g 64
CH2Cl2/H2O/TFA
CH2Cl2/H2O/TFA
9
10
11
2h 44b
2h 54c
a
Yields based on 1,4-benzoquinone after product purification by silica gel
chromatography.
b
Total yield of 44% representing a 3:2 mixture of R ¼ 4-C6H4Br (2g) and R ¼ C6H5
(2h).
c
Yield of pure 2h using
a dissolving-zinc reduction instead of catalytic
hydrogenation.
3. Conclusion
In summary we have developed a simplified and apparently
general method for the synthesis of 2-substituted hydroquinones
derived from allyl ethers. Further development of this work,
particularly in the formation of derivatives having much longer
Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
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4
K.J. Kaurich, P.A. Deck / Tetrahedron xxx (2018) 1e6
fluorous substituents attached to the ether oxygen atom are un-
derway, as are studies of these hydroquinone derivatives as
monomers for poly(arylene ether)s.
2 mL of THF to ensure that the all of the catalyst entered the reac-
tion mixture. The dark red solution was stirred overnight at room
temperature. Water (0.1 mL) was then added and the mixture
stirred for 15 min to quench any unreacted catecholborane. To the
brown mixture was added THF (5 mL), DMPU (2.0 mmol) and 1,4-
benzoquinone (1.0 mmol). The dark mixture was stirred for 2 h at
room temperature. The reaction was then worked up by diluting
with ether (60 mL), washing with water (2 ꢁ 20 mL) and brine
(20 mL), drying over MgSO4, filtering, and concentrating by rotary
evaporation to afford a dark reddish-brown oil. Silica gel column
chromatography, eluting with 30% ethyl acetate in hexanes to
afford, after evaporation of the eluent, the pure 2-
alkylhydroquinone as a white solid.
4. Experimental section
General: Pinacolborane (Alfa-Aesar), catecholborane (Sigma-
Aldrich), Wilkinson's catalyst (Strem), borane dimethyl sulfide
(Oakwood), allyl ethyl ether (Sigma-Aldrich), allyl phenyl ether
(Sigma-Aldrich), potassium persulfate (Oakwood), Raney nickel
(Oakwood), and silver nitrate (Sargent Welch) were used as
received. 1,4-Benzoquinone was prepared according to literature
procedures23 and sublimed prior to use. Allyl 2,2,2-trifluoroethyl
ether,24 allyl 2,2,3,3,3-pentafluoropropyl ether,25 and allyl 4-
bromophenyl ether26 were prepared according to literature pro-
cedures. Tetrahydrofuran and dichloromethane were distilled from
calcium hydride. Melting points were taken on a Buchi Melting
Point M-560 and are uncorrected. NMR spectra were collected us-
ing Agilent (Varian) U4-DD2 and Agilent (Varian) MR4 spectrom-
eters (1H at 400 MHz, 19F at 376 MHz, and 13C at 101 MHz). A line
broadening window function (0.5 Hz) was applied to the FIDs prior
to Fourier transformation, and Whittaker baseline corrections were
applied to frequency-domain spectra. High-resolution mass spectra
were collected using an Agilent 6220 with electrospray ionization
(ESI) and time-of-flight (TOF) mass analysis; samples were intro-
duced by direct infusion of a methanol solution containing 1%
formic acid.
4.3. 2-Alkylhydroquinone synthesis method C (using
pinacolborane)
A
flame-dried 100-mL Schlenk flask was charged with
1.95 mmol of pinacolborane and 3 mL of dichloromethane. Liquid
alkene (1.77 mmol) was added to the flask followed by 0.040 mmol
(36 mg) of Wilkinson's catalyst. The neck of the flask was rinsed
with about 2 mL of dichloromethane to ensure that the all of the
catalyst entered the reaction mixture. The reddish solution was
stirred for about 15 h under a nitrogen atmosphere. Water (5 mL)
was then added and stirred for 10 min to quench any unreacted
pinacolborane. Then 1,4-benzoquinone (127 mg, 1.18 mmol) was
dissolved in 2 mL of dichloromethane and added to the flask. Silver
nitrate (40 mg, 0.24 mmol) and potassium persulfate (960 mg,
3.54 mmol), and the neck of the flask was rinsed with about 5 mL of
water to ensure that the all of the reagents had entered the reaction
mixture. Trifluoroacetic acid (5 mL) was then added and the flask
was opened to air. The biphasic mixture was stirred under reflux
(50 ꢀC) for 24 h. The mixture was then cooled to RT, diluted with
20 mL of dichloromethane, separated, and extracted with addi-
tional dichloromethane (2 ꢁ 20 mL). The organic layers were
combined, washed with water (3 ꢁ 20 mL), dried over MgSO4,
filtered, and concentrated by rotary evaporation to afford a dark oil.
The crude intermediate 2-alkyl-1,4-benzoquinone was dissolved in
15 mL of THF and 0.7 g Raney nickel was added. A balloon of
hydrogen was fitted, and the mixture was stirred at room tem-
perature under a hydrogen atmosphere for 1 h. The solution was
then diluted with 40 mL of ether, filtered through diatomaceous
earth, dried over MgSO4, and concentrated by rotary evaporation to
yield a dark brown oil. Silica gel column chromatography using
flash-grade absorbent and eluting with 30% ethyl acetate in hex-
anes, afforded after evaporation of the eluent, the pure 2-
alkylhydroquinone as a white solid.
4.1. 2-Alkylhydroquinone synthesis method A (using BH3SMe2)
The following procedure was adapted from a published pro-
cedure.13 A flame-dried three-neck 500-mL round-bottomed flask
was charged with 0.050 mol of borane dimethylsulfide (neat liquid)
and 50 mL ether. A nitrogen inlet, dropping funnel, magnetic stir
bar, and condenser were fitted to the flask. Liquid alkene (0.15 mol)
was added to the dropping funnel and added dropwise to the
stirred mixture, using 10 mL of ether to rinse the funnel. The re-
action can be slightly exothermic, depending on the alkene, and
induce reflux. Once all of the alkene was added and reflux had
subsided, the solvent was removed by distillation using a steam
bath. 1,4-Benzoquinone (4.32 g, 0.040 mol) was then dissolved in
125 mL of ether and added dropwise to the solution using the
addition funnel. Upon complete addition of the 1,4-benzoquinone
the nitrogen inlet was removed, and the ether was removed by
distillation using a steam bath. Water (350 mL) was added to the oil,
and steam distillation was used to remove the dialkylborinic acid
byproduct (R2BOH). Several additions of DI water were required for
the steam distillation to completely remove the borinic acid
byproduct, depending on the alkene, until the distillate showed no
signal in an 11B-NMR spectroscopic analysis. The reaction flask was
then cooled using an ice bath, causing the oily crude 2-
alkylhydroquinone to precipitate as a chunky tan or brown solid.
The solid was collected on a Buchner funnel, washed with water
(100 mL), and dried briefly under air. Analytically pure samples
were obtained as white powders by recrystallization from toluene
and hexanes (1:1).
4.4. Previously reported compounds
2eHexylhydroquinone (2a)17 was prepared using Methods A
(72%), B (58%) and C (52%) as described in Sections 4.1, 4.2, 4.3,
respectively); mp 82.1e84.1 ꢀC; lit.17 mp 81.5e82.7. TLC (silica gel,
30% EtOAc/Hexanes) Rf ¼ 0.43.2eOctylhydroquinone (2b)14 was
prepared using Methods A (71%) and B (59%); mp 89.2e92.1 ꢀC;
lit.14 mp 92e94 ꢀC). TLC (silica gel, 30% EtOAc/Hexanes) Rf ¼ 0.45.2-
Cyclooctylhydroquinone (2c)9 was prepared using Method A (88%);
mp 144.5e146.3 ꢀC). TLC (silica gel, 30% EtOAc/Hexanes) Rf ¼ 0.36.
4.2. 2-Alkylhydroquinone synthesis method B (using
catecholborane)
4.5. Previously unreported compounds
This procedure was adapted from a literature procedure.14
A
flame-dried 100-mL Schlenk flask was charged with catecholbor-
ane (300 mg, 2.5 mmol) and diluted with 3 mL of THF. Liquid alkene
(2.0 mmol) was added to the flask followed by 0.040 mmol (37 mg)
Wilkinson's catalyst. The neck of the flask was rinsed with about
4.5.1. 2-(3-Ethoxypropyl)-1,4-hydroquinone (2d)
Compound 2d was prepared using Methods A, B, and C (33%,
53%, and 50%, respectively, mp 115.9e118.9 ꢀC); 1H NMR (400 MHz,
DMSO-d6)
d
8.50 (s, 1H, OH), 8.46 (s, 1H, OH), 6.55 (d, 3J ¼ 9 Hz, 1H,
Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
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K.J. Kaurich, P.A. Deck / Tetrahedron xxx (2018) 1e6
5
aromatic CH), 6.44 (d, 4J ¼ 3 Hz, 1H, aromatic CH), 6.38 (dd,
3J ¼ 9 Hz, 4J ¼ 3 Hz, 1H, aromatic CH), 3.39 (q, 3J ¼ 7 Hz, 2H, CH2),
3.33 (t, 3J ¼ 7 Hz, 2H), 2.48e2.41 (m, 2H), 1.77e1.64 (m, 2H), 1.10 (t,
phenyl derivative). 1H NMR (400 MHz, DMSO-d6)
d
8.54 (s, 1H, OH),
8.53 (s, 1H, OH), 7.46e7.39 (m, 2H), 6.91e6.88 (m, 2H), 6.60e6.53
(m, 1H, CH), 6.50e6.44 (m, 1H, CH), 6.40 (dd, 3J ¼ 9 Hz, 4J ¼ 3 Hz, 1H,
CH), 3.98e3.89 (m, 2H, CH2), 2.62e2.52 (m, 2H, CH2), 1.99e1.87 (m,
3J ¼ 7 Hz, 3H, CH3). 13C{1H} NMR (101 MHz, DMSO-d6)
d 149.6 (ar-
omatic C), 147.5 (aromatic C), 128.5 (aromatic C), 116.3 (aromatic
CH), 115.4 (aromatic CH), 112.8 (aromatic CH), 69.4 (CH2), 65.2
(CH2), 29.4 (CH2), 26.5 (CH2), 15.2 (CH3). HRMS ESI (þ) Calc for
2H, CH2). 13C{1H} NMR (101 MHz, DMSO-d6)
d 158.0 (aromatic C),
149.6 (aromatic C), 147.5 (aromatic C), 132.1 (aromatic CH), 129.5
(aromatic CH), 128.0 (aromatic CH), 120.4 (aromatic CH), 116.7
(aromatic CH), 116.4 (aromatic CH), 115.4 (aromatic CH), 114.4 (ar-
omatic C), 113.0 (aromatic CH), 111.7 (aromatic CH), 67.3 (CH2), 28.6
(CH2), 26.3 (CH2). Rf (30% EtOAc/Hexane) ¼ 0.24.
C
11H16O3 (M*þ) 196.1094; Found 196.1098. Rf (30% EtOAc/
Hexanes) ¼ 0.23.
4.5.2. 2-[3-(2,2,2-Trifluoroethoxy)propyl]-1,4-hydroquinone (2e)
Compound 2e was prepared using Methods A, B and C (30%, 52%,
49%, respectively; mp 98.2e100.4 ꢀC). 1H NMR (400 MHz, DMSO-
4.5.6. 2-[3-(4-Bromophenoxy)propyl]-1,4-hydroquinone (2h)
Compound 2h was prepared using Method C, but the interme-
diate benzoquinone was not subjected to catalytic hydrogenation.
Instead, it was directly purified by silica gel chromatography (20%
ethyl acetate in hexanes) to obtain the purified 2-[3-(4-
bromophenoxy)propyl]-1,4-benzoquinone in 63% yield: mp
d6)
d
8.51 (s, 1H, OH), 8.50 (s, 1H, OH), 6.56 (d, 3J ¼ 9 Hz, 1H, aro-
matic CH), 6.45 (d, 4J ¼ 3 Hz, 1H, aromatic CH), 6.39 (dd, 3J ¼ 9,
4J ¼ 3 Hz, 1H, aromatic CH), 4.02 (q, JHF ¼ 10 Hz, 2H, CH2CF3), 3.56
3
(t, J ¼ 7 Hz, 2H, CH2), 2.48e2.43 (m, 2H, CH2), 1.79e1.70 (m, 2H,
CH2). 13C{1H} NMR (101 MHz, DMSO-d6)
d
149.6 (aromatic C), 147.5
80.2e82.4 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.41e7.29 (m, 2H, aro-
(aromatic C), 128.2 (aromatic C), 125.0 (q, 1JCF ¼ 278 Hz, CF3), 116.3
matic CH), 6.81e6.68 (m, 4H), 6.64e6.55 (m, 1H), 3.96 (t, 3J ¼ 6 Hz,
(aromatic CH), 115.4 (aromatic CH), 113.0 (aromatic CH), 71.4 (CH2),
2H), 2.62 (ddd, 3J ¼ 9 Hz, 3J ¼ 6 Hz, 4J ¼ 1 Hz, 2H), 2.06e1.94 (m, 2H).
67.0 (q, JCF ¼ 32 Hz, CH2CF3), 29.1 (CH2), 26.1 (CH2). 19F NMR
13C NMR (101 MHz, CDCl3)
d 187.7 (CO), 187.4 (CO), 157.9 (aromatic
2
(376 MHz, DMSO-d6)
d
ꢂ72.85 (t, 3JHF ¼ 10 Hz, CF3). The assignment
C), 148.8 (alkene C), 136.9 (alkene CH), 136.5 (alkene CH), 132.8
(alkene CH), 132.4 (aromatic CH), 116.3 (aromatic CH), 113.1 (aro-
matic C), 67.2 (CH2), 27.6 (CH2), 26.2 (CH2). Rf (20% EtOAc/hex-
anes) ¼ 0.31. We were not able to obtain adequate MS or
microanalytical data on this benzoquinone derivative. A 50-mL
round bottom flask was charged with (0.250 g, 0.78 mmol 2-(3-
(4-bromophenoxy)propyl)-1,4-benzoquinone dissolved in THF
(5 mL). Water (5 mL) was added to the flask followed by the addi-
tion of granular zinc (0.31 g, 4.68 mmol) and ammonium chloride
(0.21 g 3.9 mmol). The reaction was stirred for 30 min, during
which time the yellow color gradually faded. The reaction was
allowed to stir for an additional 30 min. The mixture was diluted
with ether (20 mL), washed with water (3 ꢁ 10 mL), dried over
MgSO4, filtered, and concentrated by rotary evaporation to afford a
light brown oil. The light brown oil was then recrystallized from
toluene and hexanes (1:1) to yield the pure hydroquinone (90% for
the reduction, 54% overall from 1,4-benzoquinone): mp
of the CF3 group was confirmed by 13C{19F} NMR (101 MHz, DMSO-
3
d6):
d
125.0 (t, JFH ¼ 5 Hz, CF3). HRMS ESI (þ) Calc for C12H18O3
(M*þ) 250.0811; Found 250.0810. Rf (30% EtOAc/Hexanes) ¼ 0.23.
4.5.3. 2-[3-(2,2,3,3,3-Pentafluoropropoxy)propyl]-1,4-
hydroquinone (2f)
Compound 2f was prepared using Methods A and C (29% and
49%, respectively, mp 102.6e103.9 ꢀC); 1H NMR (400 MHz)
d 8.53 (s,
2H, OH), 6.56 (d, 3J ¼ 9 Hz, 1H, aromatic CH), 6.45 (d, 4J ¼ 3 Hz, 1H,
aromatic CH), 6.39 (dd, 3J ¼ 9, 4J ¼ 3 Hz, 1H, aromatic CH), 4.10 (tq,
3JHF ¼ 14 Hz, 4JHF ¼ 1 Hz, 2H, CH2CF2CF3), 3.57 (t, 3J ¼ 7 Hz, 2H, CH2),
2.45 (t, 3J ¼ 7 Hz, 2H, CH2), 1.81e1.69 (m, 2H). 13C{1H} NMR
(101 MHz, dmso)
d 150.1 (aromatic C), 147.9 (aromatic C), 128.6
(aromatic C), 116.8 (aromatic CH), 115.9 (aromatic CH), 113.4 (aro-
2
matic CH), 72.0 (CH2), 66.5 (t, JCF ¼ 26 Hz, CH2CF2CF3), 29.5 (CH2),
26.5 (CH2). The CF2 and CF3 groups were located in the 13C{19F}
NMR (101 MHz, DMSO-d6):
d
118.6 (s, CF3) and 113.5 (CF2). 19F NMR
119.0e122.6 ꢀC. 1H NMR (400 MHz, DMSO-d6)
d 8.57 (s, 1H, OH),
(376 MHz, dmso)
d
ꢂ82.68 (s, 3F), ꢂ122.47 (t, 3JHF ¼ 14 Hz, 2F, CF2).
8.56 (s, 1H, OH), 7.46e7.38 (m, 2H, aromatic CH), 6.93e6.85 (m, 2H,
aromatic CH), 6.57 (d, J ¼ 9 Hz, 1H, CH), 6.47 (d, J ¼ 3 Hz, 1H, CH),
6.40 (dd, J ¼ 9, 3 Hz, 1H, CH), 3.93 (t, J ¼ 3 Hz, 2H, CH2), 2.62e2.52
(m, 2H, CH2), 1.98e1.87 (m, 2H, CH2). 13C NMR (101 MHz, DMSO-d6)
HRMS ESI (þ) Calc for
C
12H13F5O3 (M*þ) 300.0779; Found
300.0797. Rf (30% EtOAc/Hexanes) ¼ 0.31.
4.5.4. 2-(3-Phenoxypropyl)-1,4-hydroquinonone (2g)
Compound 2g was prepared using Method
d 158.0 (aromatic C), 149.7 (aromatic C), 147.6 (aromatic C), 132.2
C
(73%, mp
(aromatic CH), 128.1 (aromatic C), 116.8 (aromatic CH), 116.5 (aro-
matic CH), 115.5 (aromatic CH), 113.1 (aromatic C), 111.8 (aromatic
CH), 67.4 (CH2), 28.7 (CH2), 26.3 (CH2). Rf (30% EtOAc/Hex-
ane) ¼ 0.20. We were unable to obtain a suitable ESI-MS spectrum
of this compound and therefore we sent a sample for microanalysis.
Anal. Calcd for C15H15BrO3: C, 55.75; H, 4.68. Found: C, 55.69; H,
4.73.
102.2e103.4 ꢀC). 1H NMR (400 MHz, DMSO-d6)
d 8.55 (s, 1H, OH),
8.53 (s, 1H, OH), 7.27 (t, 8 Hz, 2H, aromatic CH), 6.96e6.87 (m, 3H,
aromatic CH), 6.58 (d, 3J ¼ 9 Hz, 1H, aromatic CH), 6.49 (d, 4J ¼ 3 Hz,
1H, aromatic CH), 6.41 (dd, 3J ¼ 9, 4J ¼ 3 Hz, 1H, aromatic CH), 3.94
(t, 3J ¼ 7 Hz, 2H, CH2), 2.59 (t, 3J ¼ 7.2 Hz, 2H, CH2), 2.00e1.86 (m,
2H, CH2). 13C{1H} NMR (101 MHz, DMSO-d6)
d 158.7 (aromatic C),
149.7 (aromatic C), 147.6 (aromatic C), 129.5 (aromatic C), 128.2
(aromatic CH), 120.4 (aromatic CH), 116.4 (aromatic CH), 115.5 (ar-
omatic CH), 114.4 (aromatic CH), 113.0 (aromatic CH), 66.9 (CH2),
28.8 (CH2), 26.4 (CH2). HRMS ESI (þ) Calc for C12H18O3 (M*þ)
244.1094; Found 244.1096. Rf (30% EtOAc/Hexanes) ¼ 0.24.
4.5.7. 2-(3-Phenoxypropyl)-1,4-benzoquinone (3g)
Compound 3g was prepared using Method C, but the interme-
diate benzoquinone derivative was purified by silica gel chroma-
tography instead of subjecting it to hydrogenation. A 73% yield was
obtained: mp 83.2e84.9 ꢀC. 1H NMR (400 MHz, CDCl3)
d 7.30e7.24
4.5.5. 2-[3-(4-Bromophenoxy)propyl]-1,4-hydroquinone (2h)
(m, 2H, aromatic CH), 6.94 (tt, 3J ¼ 7 Hz, 4J ¼ 1 Hz, 1H, aromatic CH)
6.89e6.83 (m, 2H, aromatic CH), 6.81e6.69 (m, 2H, alkene CH), 6.62
(dt, 3J ¼ 3 Hz, 4J ¼ 1 Hz, 1H, alkene CH), 4.01 (t, 3J ¼ 6 Hz, 2H, CH2),
Compound 2h was prepared using Method C (45%). This com-
pound was formed as a mixture of the desired compound (70%) and
the debrominated analogue 2-(3-phenoxypropyl)benzene-1,4-diol
(30%). By comparing the NMR spectra of the mixture to the NMR
spectra of the pure phenyl derivative, we were able to assign the
spectrum of the bromophenyl derivative (pendant aryl group only;
all of the other signals were coincident with the signals of the
2.64 (td, 3J ¼ 8 Hz, 4J ¼ 1 Hz, 2H, CH2), 2.07e1.97 (m, 2H, CH2). 13
C
{1H} NMR (101 MHz, CDCl3)
d 187.7 (CO),187.5 (CO),158.7 (aromatic
C), 149.0 (aromatic C), 136.9 (alkene CH), 136.5 (alkene CH), 132.8
(alkene CH), 129.6 (aromatic CH), 121.0 (aromatic CH), 114.6 (aro-
matic CH), 66.8 (CH2), 27.7 (CH2), 26.3 (CH2). HRMS-APCI (þ) Calc
Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
ethers, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.048

6
K.J. Kaurich, P.A. Deck / Tetrahedron xxx (2018) 1e6
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for C15H14O3 (M*þ) 242.0937; Found 242.0936. Rf (20% EtOAc/
Hexanes) ¼ 0.48.
Declaration of interests
None.
11. Brown HC, Cope OJ. J Am Chem Soc. 1964;86:1801e1807.
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Acknowledgments
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We thank Ken Knott for 19F-decoupled 13C NMR measurements
and Bill Bebout for collecting our MS data. This research did not
receive any specific grant from funding agencies in the public,
commercial, or not-for-profit sectors.
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Appendix A. Supplementary data
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Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2018.01.048.
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Please cite this article in press as: Kaurich KJ, Deck PA, Synthesis of 2-substituted hydroquinone derivatives from 1,4-benzoquinone and allyl
ethers, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.048