A convenient method for converting hydroxyacetophenones into their ethylene or trimethylene acetals

Article abstract of DOI:10.1055/s-0028-1088025

Various types of hydroxyacetophenones are efficiently converted into the corresponding ethylene acetals in the presence of ethane-1,2-diol, triisopropyl orthoformate, and a catalytic amount of cerium(III) trifluoromethanesulfonate under mild reaction conditions. The homologous trimethylene acetals can be also prepared in the same way. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1088025

1318
PAPER
A Convenient Method for Converting Hydroxyacetophenones into Their
Ethylene or Trimethylene Acetals
H
ydroxyaceto
u
phenone
E
th
m
ylene or
T
rimethyle
i
ne
A
ce
a
tals ki Ono, Hirotaka Takenaka, Toshikazu Fujikawa, Masaki Mori, Tsuneo Sato*
Department of Life Science, Kurashiki University of Science and the Arts, Kurashiki 712-8505, Japan
Fax +81(86)4401062; E-mail: sato@chem.kusa.ac.jp
Received 6 November 2008; revised 24 December 2008
(CH2)n
Abstract: Various types of hydroxyacetophenones are efficiently
converted into the corresponding ethylene acetals in the presence of
ethane-1,2-diol, triisopropyl orthoformate, and a catalytic amount
of cerium(III) trifluoromethanesulfonate under mild reaction condi-
tions. The homologous trimethylene acetals can be also prepared in
the same way.
O
O
O
Ce(OTf)3 (1 mol%)
HC(Oi-Pr)3
(CH2)n
OH
+
HO
n = 2
n = 3
HO
HO
1 n = 2
2 n = 3
Key words: acetal, cerium(III) trifluoromethanesulfonate, hy-
droxyacetophenone, Lewis acid, protecting group
Scheme 1
of cerium(III) trifluoromethanesulfonate (1 mol%) in hex-
Cyclic acetals (ethylene or trimethylene acetals) are one ane at 40 °C (Table 1, entry 1). After 18 hours, the usual
of the most widely used and versatile protecting groups workup of the reaction mixture gave the desired 2-(2-hy-
for ketones in organic synthesis because of their stability droxyphenyl)-2-methyl-1,3-dioxolane (1a) in 95% isolat-
under basic or slightly acidic conditions.1 Although the ed yield as the sole product.8 When this reaction was
cyclic acetalization of acetophenone usually presents few attempted in the absence of cerium(III) trifluoromethane-
problems,2 hydroxyacetophenones cannot undergo acetal- sulfonate or triisopropyl orthoformate, ethylene acetaliza-
ization under acid-catalyzed conditions in satisfactory tion did not proceed at all (entries 2 and 3). A screening of
yields. For example, the p-toluenesulfonic acid catalyzed orthoformates revealed that triisopropyl orthoformate
condensation of 4-hydroxy-2-methylacetophenone with gave the best result (entries 1, 4, and 5). The effect of other
ethane-1,2-diol is reported to afford only 3-methylphenol, solvents such as toluene, tetrahydrofuran, ethyl acetate,
a deacetylation product, in 83% yield.3 Thus, they are usu- acetonitrile, and nitromethane were also studied, but in
ally prepared by first protecting the phenolic group, then comparison with hexane the yields were found to be con-
acetalization, followed by removing the protecting group, siderably lower, probably because the cerium active site is
which generates the desired phenolic acetal.4 Although occupied by solvent molecules (entries 6–10). Among
Venanzi et al.5 reported the preparation of hydroxy- metal triflates tested, cerium(III) trifluoromethane-
acetophenone cyclic acetals from the parent ketones sulfonate was the most effective in this acetalization (en-
and ethane-1,2-diol or propane-1,3-diol using tries 1 and 11–16). In addition, traditional Brønsted acids
[Ru(MeCN)3(triphos)](OTf)2 as a Lewis acid catalyst in and Lewis acids were less active or inert (entries 17–23).
refluxing benzene, this involves some annoying prob-
Next, we investigated substrate generality in the ceri-
lems: (1) longer reaction times; (2) failure to afford the de-
um(III) trifluoromethanesulfonate catalyzed ethylene ace-
sired product in the trimethylene acetalization of 4-
talization of hydroxyacetophenones with ethane-1,2-diol
hydroxyacetophenone; (3) the use of an expensive Lewis
(1.5 equiv) and triisopropyl orthoformate (1.5 equiv) in
acid catalyst, etc. Thus, the development of more conve-
hexane (Table 2). The reactions proceeded not only for o-
hydroxyacetophenone, but also m- and p-isomers to give
nient and efficient methods for the preparation of phenolic
cyclic acetals are still being pursued.6 Herein we report an
the corresponding acetals 1a–c in high to excellent yields
efficient and versatile procedure for the cyclic acetaliza-
tion of various hydroxyacetophenones using ethane-1,2-
diol or propane-1,3-diol and triisopropyl orthoformate in
(entries 1–3).9 It is worthy to note that 4-hydroxy-2-meth-
ylacetophenone can be acetalized to give 1d in quantita-
tive yield under the described reaction conditions without
the presence of a catalytic amount of cerium(III)
formation of 3-methylphenol (entry 4), which was ob-
trifluoromethanesulfonate7 (1 mol%) (Scheme 1).
tained in substantial amounts when the acetalization was
Initially, we examined the reaction of 2-hydroxyacetophe- carried out by the conventional p-toluenesulfonic acid/
none as a model substrate with ethane-1,2-diol (1.5 equiv) ethane-1,2-diol method.3 In addition, the properties of the
and triisopropyl orthoformate (1.5 equiv) in the presence substituent groups in the aromatic ring, whether electron-
donating group (entry 5) or electron-withdrawing group
(entry 6), had no obvious effect on the acetalization under
SYNTHESIS 2009, No. 8, pp 1318–1322
Advanced online publication: 25.03.2009
DOI: 10.1055/s-0028-1088025; Art ID: F23108ST
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
9
these conditions. The homologous derivatives 2a–f (tri-
methylene acetals) could also be made using our protocol,
by substituting propane-1,3-diol for ethane-1,2-diol, in

PAPER
Hydroxyacetophenone Ethylene or Trimethylene Acetals
1319
Table 1 Ethylene Acetalization of 2-Hydroxyacetophenone in the
Table 2 Ethylene or Trimethylene Acetalization of Hydroxyace-
Presence of Various Lewis Acidsa
tophenones Using Cerium(III) Trifluoromethanesulfonatea
(CH2)n
O
O
O
O
O
O
HO(CH2)nOH, Ce(OTf)3
HC(Oi-Pr)3
HO(CH2)2OH, Lewis acid
HC(OR)3
OH
OH
HO
HO
1a
1a–f n = 2
2a–f n = 3
Entry Lewis acid
Solvent
hexane
hexane
hexane
hexane
hexane
toluene
THF
HC(OR)3
Yieldb (%)
Entry Substrate
n
Temp, time
Product Yieldb
(%)
1
Ce(OTf)3
–
HC(Oi-Pr)3
HC(Oi-Pr)3
–
98 (95)
0
2c
1
2
3
o-HOC6H4COMe
2
2
2
40 °C, 18 h
1a
1b
1c
95
99
97
3d Ce(OTf)3
0
m-HOC6H4COMe
p-HOC6H4COMe
COMe
25 °C, 1 h
25 °C, 2 h
4
5
Ce(OTf)3
Ce(OTf)3
Ce(OTf)3
Ce(OTf)3
Ce(OTf)3
Ce(OTf)3
Ce(OTf)3
TMSOTf
Sc(OTf)3
In(OTf)3
HC(OMe)3
HC(OEt)3
80
80
65
37
46
0
4
5
2
2
25 °C, 4 h
25 °C, 1 h
1d
1e
100
91
6
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HC(Oi-Pr)3
HO
7
COMe
8
EtOAc
MeCN
MeNO2
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
HO
9
OMe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
12
68
17
24
0
COMe
6
2
25 °C, 2 h
1f
99
HO
COOMe
7
8
9
o-HOC6H4COMe
3
3
3
40 °C, 20 h
25 °C, 1 h
2a
2b
2c
90
98
88
m-HOC6H4COMe
p-HOC6H4COMe
La(OTf)3
Gd(OTf)3
Yb(OTf)3·2H2O
p-TsOH·H2O
TfOH
25 °C, 1.5 h
0
COMe
2
10
11
3
3
25 °C, 4 h
25 °C, 3 h
2d
2e
95
5
HO
COMe
79
3
98c
BF3·OEt2
AlCl3
HO
OMe
0
COMe
Ce(NO3)3·6H2O
CeCl3·7H2O
CeI3·9H2O
0
12
3
25 °C, 2 h
2f
98
HO
0
COOMe
0
a Conditions: substrate (2.0 mmol), diol (3.0 mmol), HC(Oi-Pr)3 (3.0
mmol), Ce(OTf)3 (0.02 mmol), hexane (4 mL).
b Isolated yield.
a Conditions: o-HOC6H4COMe (2.0 mmol), HO(CH2)2OH (3.0
mmol), HC(OR)3 (3.0 mmol), Lewis acid (0.02 mmol), solvent (4
mL), 40 °C, 18 h, unless otherwise noted.
c Isolated as the acetate after acetylation (Ac2O/pyridine) because
deacetalization was observed during purification.
b The yield was determined by 1H NMR analysis of the crude prod-
ucts. Isolated yields are given in parentheses.
c In the absence of Ce(OTf)3.
Finally, in order to extend the scope of our methodology
further, the ethylene or trimethylene acetalization of hy-
droxypropiophenones was investigated. As shown in
Table 3, the reactions proceeded smoothly to give the de-
sired cyclic acetals 3 and 4 in excellent yields without any
other side products.
Our protocol is superior to Venanzi’s method,5 which has
been claimed to be the best of the previously available
procedures for the conversion of hydroxyacetophenones
d In the absence of HC(Oi-Pr)3.
high to excellent yields (entries 7–12). In particular, it
should be noted that 4-hydroxyacetophenone, which un-
dergoes trimethylene acetalization with difficulty by
Venanzi’s method,5 could be easily converted into the
corresponding trimethylene acetal 2c in 88% yield (entry
9).
Synthesis 2009, No. 8, 1318–1322 © Thieme Stuttgart · New York

1320
F. Ono et al.
PAPER
Melting points were determined on a Büchi 535 melting point appa-
ratus and are uncorrected. The NMR spectra were recorded on a Jeol
JNM-LA 500 instrument. Chemical shifts are given as d values with
reference to TMS as an internal standard. Mass spectra were ob-
tained on a Jeol JMS-70 employing EI. Column chromatography
was performed on Merck silica gel 60 (70–230 mesh). Et3N (0.1%)
was always used as a mobile-phase additive to prevent deacetaliza-
tion. All chemicals were purchased from commercial suppliers and
used without purification prior to use; Ce(OTf)3 was purchased
from Alfa Aesar.
Table 3 Ethylene or Trimethylene Acetalization of Hydroxypro-
piophenones Using Cerium(III) Trifluoromethanesulfonatea
(CH2)n
O
O
O
HO(CH2)nOH, Ce(OTf)3
HC(Oi-Pr)3
Et
Et
HO
HO
3a,b n = 2
4a,b n = 3
Entry Substrate
n
Temp, time
ProductYieldb
(%)
2-(4-Hydroxyphenyl)-2-methyl-1,3-dioxolane (1c); Typical Pro-
cedure
To a mixture of 4-hydroxyacetophenone (273 mg, 2.0 mmol),
ethane-1,2-diol (187 mg, 3.0 mmol), and Ce(OTf)3 (11.8 mg, 0.02
mmol) in hexane (4 mL) was added HC(Oi-Pr)3 (571 mg, 3.0 mmol)
at 25 °C. The mixture was stirred for 2 h and the mixture was
quenched with Et3N (101 mg, 1.0 mmol) and sat. NaHCO3. The or-
ganic materials were extracted with Et2O containing 0.1% Et3N,
washed with sat. NaCl, dried (Na2SO4), and evaporated. Column
chromatography of the residue (silica gel, 7% EtOAc–hexane con-
taining 0.1% Et3N) afforded 1c (350 mg, 97%); mp 73.9–76.1 °C
(Lit.5 80–82 °C).
1
2
3
4
o-HOC6H4COEt
2
2
3
3
40 °C, 48 h
3a
3b
4a
4b
95
98
94
94
p-HOC6H4COEt
o-HOC6H4COEt
p-HOC6H4COEt
25 °C, 2.5 h
40 °C, 48 h
25 °C, 6 h
a Conditions: substrate (2.0 mmol), diol (3.0 mmol), HC(Oi-Pr)3 (3.0
mmol), Ce(OTf)3 (0.02 mmol), hexane (4 mL).
b Isolated yield.
1H NMR (500 MHz, CDCl3): d = 1.65 (s, 3 H), 3.75–3.83 (m, 2 H),
into their respective cyclic acetals. Comparative data are
summarized in Table 4.
4.00–4.07 (m, 2 H), 6.79 (d, J = 8.6 Hz, 2 H), 7.35 (d, J = 8.6 Hz, 2
H).
13C NMR (125 MHz, CDCl3): d = 27.4, 64.2, 109.1, 115.0, 126.7,
134.7, 155.6.
MS (EI, 70 eV): m/z = 180 [M]+.
In conclusion, we have demonstrated an efficient and ver-
satile method for the ethylene or trimethylene acetaliza-
tion of hydroxyacetophenones using ethane-1,2-diol or
propane-1,3-diol and triisopropyl orthoformate catalyzed
by cerium(III) trifluoromethanesulfonate. This new meth-
od has the following advantages: (1) cerium(III) trifluo-
romethanesulfonate is commercially available, (2) highly
catalytic activity, (3) wide applicability, (4) operational
simplicity, (5) mild reaction conditions, (6) high yields.
2-(2-Hydroxyphenyl)-2-methyl-1,3-dioxolane (1a)
Mp 61.6–63.2 °C (Lit.5 61.5–63.5 °C).
1H NMR (500 MHz, CDCl3): d = 1.69 (s, 3 H), 3.83–3.91 (m, 2 H),
4.06–4.13 (m, 2 H), 6.86 (t, J = 8.0 Hz, 2 H), 7.19 (t, J = 8.0 Hz, 1
H), 7.29 (d, J = 8.0 Hz, 1 H), 8.19 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 26.5, 64.3, 109.9, 117.1, 120.0,
126.1, 126.4, 129.9, 154.4.
Table 4 Comparison of Protocols for the Ethylene or Trimethylene Acetalization of Hydroxyacetophenones
(CH2)n
O
O
O
HO
HO
+
(CH2)n
HO
HO
1a–c n = 2
2a–c n = 3
Entry
Substrate
n
Product
This worka
Temp, time
Venanzi’s workb
Temp, time
Yield (%)
Yield (%)
1
2
3
4
5
6
o-HOC6H4COMe
o-HOC6H4COMe
m-HOC6H4COMe
m-HOC6H4COMe
p-HOC6H4COMe
p-HOC6H4COMe
2
3
2
3
2
3
1a
2a
1b
2b
1c
2c
40 °C, 18 h
40 °C, 20 h
25 °C, 1 h
25 °C, 1 h
25 °C, 2 h
25 °C, 1.5 h
95
90
99
98
97
88
reflux, 136 h
reflux, 144 h
reflux, 168 h
reflux, 23 h
reflux, 19 h
n.r.d
93
95
94c
99
95
0
a Molar ratio: substrate/diol/HC(Oi-Pr)3/Ce(OTf)3 (1:1.5:1.5:0.01), hexane.
b Molar ratio: substrate/diol/[Ru(MeCN)3(triphos)](OTf)2 (1:5.0:0.0005), benzene, unless otherwise noted.
c Molar ratio: substrate/[Ru(MeCN)3(triphos)](OTf)2 (1:0.001).
d No reaction.
Synthesis 2009, No. 8, 1318–1322 © Thieme Stuttgart · New York

PAPER
Hydroxyacetophenone Ethylene or Trimethylene Acetals
1321
MS (EI, 70 eV): m/z = 180 [M]+.
13C NMR (125 Hz, CDCl3): d = 25.3, 32.2, 61.3, 100.9, 113.5,
114.8, 118.8, 130.2, 142.6, 156.6.
2-(3-Hydroxyphenyl)-2-methyl-1,3-dioxolane (1b)
MS (EI, 70 eV): m/z = 194 [M]+.
Mp 89.1–90.9 °C (Lit.5 88–90 °C).
1H NMR (500 MHz, CDCl3): d = 1.65 (s, 3 H), 3.76–3.84 (m, 2 H),
4.01–4.08 (m, 2 H), 5.30 (s, 1 H), 6.77 (d, J = 7.6 Hz, 1 H), 6.99 (s,
1 H), 7.05 (d, J = 7.6 Hz, 1 H), 7.22 (t, J = 7.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 27.4, 64.4, 108.9, 112.3, 114.9,
117.4, 129.6, 144.8, 155.8.
2-(4-Hydroxyphenyl)-2-methyl-1,3-dioxane (2c)
Mp 143.0–145.6 °C.
1H NMR (500 MHz, CDCl3): d = 1.26 (d-like, J = 11.3 Hz, 1 H),
1.50 (s, 3 H), 2.05–2.17 (m, 1 H), 3.78–3.89 (m, 4 H), 5.30 (br, 1 H),
6.87 (d, J = 8.6 Hz, 2 H), 7.30 (d, J = 8.6 Hz, 2 H).
MS (EI, 70 eV): m/z = 180 [M]+.
13C NMR (125 MHz, CDCl3): d = 25.4, 32.4, 61.6, 100.8, 115.6,
128.2, 132.5, 155.5.
2-(4-Hydroxy-2-methylphenyl)-2-methyl-1,3-dioxolane (1d)
Mp 97.0–100.2 °C.
1H NMR (500 MHz, CDCl3): d = 1.66 (s, 3 H), 2.44 (s, 3 H), 3.69–
3.77 (m, 2 H), 3.98–4.05 (m, 2 H), 4.91 (br, 1 H), 6.61 (dd, J = 2.8,
8.6 Hz, 1 H), 6.63 (d, J = 2.8 Hz, 1 H), 7.40 (d, J = 8.6 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 20.6, 26.4, 63.8, 109.5, 112.1,
118.5, 127.7, 132.7, 137.5, 155.2.
MS (EI, 70 eV): m/z = 179 [M – CH3]+.
HRMS (EI): m/z [M – CH3]+ calcd for C10H11O3: 179.0708; found:
MS (EI, 70 eV): m/z = 194 [M]+.
HRMS (EI): m/z [M]+ calcd for C11H14O3: 194.0943; found:
194.0950.
2-(4-Hydroxy-2-methylphenyl)-2-methyl-1,3-dioxane (2d)
Mp 129.4–131.6 °C.
1H NMR (500 MHz, CDCl3): d = 1.25 (d-like, J = 12.8 Hz, 1 H),
1.51 (s, 3 H), 2.09–2.20 (m, 1 H), 2.36 (s, 3 H), 3.76 (t-like, J = 12.2
Hz, 2 H), 3.85 (dd-like, J = 5.2, 10.4 Hz, 2 H), 4.70 (s, 1 H), 6.67
(d, J = 2.8 Hz, 1 H), 6.69 (dd, J = 2.8, 8.6 Hz, 1 H), 7.33 (d, J = 8.6
Hz, 1 H).
179.0715.
2-(4-Hydroxy-3-methoxyphenyl)-2-methyl-1,3-dioxolane (1e)
Mp 104.4–108.7 °C.
13C NMR (125 MHz, CDCl3): d = 21.0, 25.4, 30.3, 61.0, 101.6,
112.9, 119.0, 130.0, 138.2, 155.1.
1H NMR (500 MHz, CDCl3): d = 1.65 (s, 3 H), 3.78–3.82 (m, 2 H),
3.90 (s, 3 H), 4.01–4.05 (m, 2 H), 5.61 (s, 1 H), 6.87 (d, J = 8.9 Hz,
1 H), 6.97–7.03 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 27.7, 55.9, 64.3, 108.0, 108.8,
114.0, 118.2, 136.3, 145.2, 146.2.
MS (EI, 70 eV): m/z = 208 [M]+.
HRMS (EI): m/z [M]+ calcd for C12H16O3: 208.1100; found:
208.1093.
2-(4-Acetoxy-3-methoxyphenyl)-2-methyl-1,3-dioxane (2e)
Mp 136.6–138.2 °C.
MS (EI, 70 eV): m/z = 210 [M]+.
1H NMR (500 MHz, CDCl3): d = 1.27 (d, J = 13.5 Hz, 1 H), 1.51 (s,
3 H), 2.07–2.17 (m, 1 H), 2.33 (s, 3 H), 3.81–3.90 (m, 4 H), 3.84 (s,
3 H), 7.00–7.06 (m 3 H).
HRMS (EI): m/z [M]+ calcd for C11H14O4: 210.0892; found:
210.0884.
2-[4-Hydroxy-3-(methoxycarbonyl)phenyl]-2-methyl-1,3-di-
oxolane (1f)
13C NMR (125 MHz, CDCl3): d = 20.7, 25.3, 32.4, 56.0, 61.2,
100.3, 110.8, 119.1, 122.9, 139.1, 140.2, 151.4, 169.1.
Mp 51.5–53.3 °C.
MS (EI, 70 eV): m/z = 266 [M]+.
HRMS (EI): m/z [M]+ calcd for C14H18O5: 266.1154; found:
1H NMR (500 MHz, CDCl3): d = 1.63 (s, 3 H), 3.76–3.79 (m, 2 H),
3.95 (s, 3 H), 4.02–4.05 (m, 2 H), 6.95 (d, J = 8.6 Hz, 1 H), 7.57 (dd,
J = 2.5, 8.6 Hz, 1 H), 7.95 (d, J = 2.5 Hz, 1 H), 10.75 (s, 1 H).
266.1148.
13C NMR (125 MHz, CDCl3): d = 27.4, 52.2, 64.4, 108.3, 111.7,
117.4, 126.6, 132.8, 134.3, 161.2, 170.4.
2-[4-Hydroxy-3-(methoxycarbonyl)phenyl]-2-methyl-1,3-diox-
ane (2f)
Mp 76.0–77.1 °C.
MS (EI, 70 eV): m/z = 238 [M]+.
1H NMR (500 MHz, CDCl3): d = 1.28 (d-like, J = 13.2 Hz, 1 H),
1.49 (s, 3 H), 2.06–2.16 (m, 1 H), 3.77 (t-like, J = 13.4 Hz, 2 H),
3.88 (dd, J = 4.9, 12.2 Hz, 2 H), 3.97 (s, 3 H), 7.02 (d, J = 8.6 Hz, 1
H), 7.52 (dd, J = 2.5, 8.6 Hz, 1 H), 7.90 (d, J = 2.5 Hz, 1 H), 10.77
(s, 1 H).
13C NMR (125 MHz, CDCl3): d = 25.4, 32.1, 52.3, 61.1, 100.0,
112.4, 118.0, 128.3, 132.0, 134.3, 161.0, 170.5
HRMS (EI): m/z [M]+ calcd for C12H14O5: 238.0841; found:
238.0838.
2-(2-Hydroxyphenyl)-2-methyl-1,3-dioxane (2a)
Mp 61.8–63.6 °C (Lit.5 62.5–64.5 °C).
1H NMR (500 MHz, CDCl3): d = 1.35 (d-like, J = 13.4 Hz, 1 H),
1.57 (s, 3 H), 2.13–2.24 (m, 1 H), 3.87–3.99 (m, 4 H), 6.92 (t-like,
J = 8.6 Hz, 2 H), 7.22–7.29 (m, 2 H), 8.16 (s, 1 H).
MS (EI, 70 eV): m/z = 252 [M]+.
13C NMR (125 MHz, CDCl3): d = 24.9, 29.9, 61.6, 101.6, 117.1,
120.1, 123.3, 128.0, 129.9, 154.9.
HRMS (EI): m/z [M]+ calcd for C13H16O5: 252.0998; found:
252.0990.
MS (EI, 70 eV): m/z = 194 [M]+.
2-Ethyl-2-(2-hydroxyphenyl)-1,3-dioxolane (3a)
Mp 38.2–39.5 °C.
2-(3-Hydroxyphenyl)-2-methyl-1,3-dioxane (2b)
Mp 143.4–144.9 °C (Lit.5 143–145 °C).
1H NMR (500 MHz, CDCl3): d = 0.93 (t, J = 7.3 Hz, 3 H), 1.96 (q,
J = 7.3 Hz, 2 H), 3.86–3.93 (m, 2 H), 4.05–4.12 (m, 2 H), 6.84–6.88
(m, 2 H), 7.20 (dt–like, J = 1.5, 7.7 Hz, 1 H), 7.25 (dd, J = 1.5, 7.7
Hz, 1 H), 8.27 (s, 1 H).
1H NMR (500 MHz, CDCl3): d = 1.27 (d-like, J = 13.1 Hz, 1 H),
1.52 (s, 3 H), 2.07–2.19 (m, 1 H), 3.82–3.91 (m, 4 H), 5.63 (br, 1 H),
6.81 (d, J = 7.7 Hz, 1 H), 6.98 (s, 1 H), 7.01 (d, J = 7.7 Hz, 1 H),
7.28 (t, J = 7.7 Hz, 1 H).
Synthesis 2009, No. 8, 1318–1322 © Thieme Stuttgart · New York

1322
F. Ono et al.
PAPER
Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W., Eds.;
Pergamon: Oxford, 1995, 159. (d) Kocienski, P. J.
Protecting Groups, 3rd ed; Georg Thieme Verlag: New
York, 2004, Chap. 2. (e) Wuts, P. G. M.; Greene, T. W.
Greene’s Protective Groups in Organic Synthesis, 4th ed.;
Wiley: New York, 2007, Chap. 4.
13C NMR (125 MHz, CDCl3): d = 7.5, 32.5, 64.5, 112.0, 116.9,
119.7, 125.3, 127.1, 129.8, 154.8.
MS (EI, 70 eV): m/z = 194 [M]+.
HRMS (EI): m/z [M]+ calcd for C11H14O3: 194.0943; found:
194.0937.
(2) For ethylene acetalization of acetophenone, see: (a) Reddy,
B. M.; Reddy, V. R.; Giridhar, D. Synth. Commun. 2001, 31,
1819. (b) Kawabata, T.; Mizugaki, T.; Ebitani, K.; Kaneda,
K. Tetrahedron Lett. 2001, 42, 8329. (c) Firouzabadi, H.;
Iranpoor, N.; Shaterian, H. R. Bull. Chem. Soc. Jpn. 2002,
75, 2195. (d) Leonard, N. M.; Oswald, M. C.; Freiberg, D.
A.; Nattier, B. A.; Smith, R. C.; Mohan, R. S. J. Org. Chem.
2002, 67, 5202. (e) Palaniappan, S.; Narender, P.;
Saravanan, C.; Rao, V. J. Synlett 2003, 1793. (f) Khan, A.
T.; Mondal, E.; Ghosh, S.; Islam, S. Eur. J. Org. Chem.
2004, 2002. (g) Gregg, B. T.; Golden, K. C.; Quinn, J. F.
Tetrahedron 2008, 64, 3287. For trimethylene acetalization
of acetophenone, see: (h) Karimi, B.; Ebrahimian, G. R.;
Seradj, H. Org. Lett. 1999, 1, 1737. (i) Firouzabadi, H.;
Iranpoor, N.; Karimi, B. Synlett 1999, 321. (j) Firouzabadi,
H.; Iranpoor, N.; Karimi, B. Synth. Commun. 1999, 29,
2255. (k) Gopinath, R.; Haque, S. J.; Patel, B. K. J. Org.
Chem. 2002, 67, 5842. (l) Karimi, B.; Golshani, B.
Synthesis 2002, 784. (m) Karimi, B.; Hazarkhani, H.;
Maleki, J. Synthesis 2005, 279.
2-Ethyl-2-(4-hydroxyphenyl)-1,3-dioxolane (3b)
Mp 72.5–75.7 °C.
1H NMR (500 MHz, CDCl3): d = 0.87 (t, J = 7.3 Hz, 3 H), 1.90 (q,
J = 7.3 Hz, 2 H), 3.75–3.82 (m, 2 H), 3.97–4.04 (m, 2 H), 6.79 (d,
J = 8.9 Hz, 2 H), 7.31 (d, J = 8.9 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 8.0, 33.3, 64.4, 111.0, 114.8,
127.2, 134.1, 155.4.
MS (EI, 70 eV): m/z = 165 [M – C2H5]+.
HRMS (EI): m/z [M – C2H5]+ calcd for C9H9O3: 165.0552; found:
165.0543.
2-Ethyl-2-(2-hydroxyphenyl)-1,3-dioxane (4a)
Mp 43.1–44.7 °C.
1H NMR (500 MHz, CDCl3): d = 0.87 (t, J = 7.3 Hz, 3 H), 1.34 (d-
like, J = 13.4 Hz, 1 H), 1.83 (q, J = 7.3 Hz, 2 H), 2.12–2.23 (m, 1
H), 3.87–3.99 (m, 4 H), 6.88–6.93 (m, 2 H), 7.19–7.26 (m, 2 H),
8.20 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 7.1, 25.1, 35.3, 61.5, 103.4,
117.0, 119.7, 122.1, 128.9, 129.8, 155.2.
MS (EI, 70 eV): m/z = 208 [M]+.
HRMS (EI): m/z [M]+ calcd for C12H16O3: 208.1100; found:
(3) Grözinger, K.; Hess, F. Synthesis 1977, 411.
(4) Kuboki, A.; Yamamoto, T.; Ohira, S. Chem. Lett. 2003, 32,
420.
(5) Ma, S.; Venanzi, L. M. Synlett 1993, 751.
(6) Zeolite HSZ-360-catalyzed ethylene acetalization of 3-
hydroxyacetophenone was reported: Ballini, R.; Bosica, G.;
Frullanti, B.; Maggi, R.; Sartori, G.; Schroer, F. Tetrahedron
Lett. 1998, 39, 1615.
208.1107.
2-Ethyl-2-(4-hydroxyphenyl)-1,3-dioxane (4b)
Mp 115.2–118.2 °C.
1H NMR (500 MHz, CDCl3): d = 0.79 (t, J = 7.4 Hz, 3 H), 1.24 (d-
like, J = 13.1 Hz, 1 H), 1.74 (q, J = 7.4 Hz, 2 H), 2.06–2.16 (m, 1
H), 3.78–3.88 (m, 4 H), 5.16 (br, 1 H), 6.87 (d, J = 8.6 Hz, 2 H),
7.26 (d, J = 8.6 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 7.3, 25.7, 37.4, 61.0, 102.6,
115.3, 129.1, 131.0, 155.4.
MS (EI, 70 eV): m/z = 179 [M – C2H5]+.
HRMS (EI): m/z [M – C2H5]+ calcd for C10H11O3: 179.0708; found:
(7) For the use of Ce(OTf)3 in other types of reactions, see: for
acylation: (a) Dalpozzo, R.; De Nino, A.; Maiuolo, L.;
Procopio, A.; Nardi, M.; Bartoli, G.; Romeo, R. Tetrahedron
Lett. 2003, 44, 5621. (b) Bartoli, G.; Dalpozzo, R.; De Nino,
A.; Maiuolo, L.; Nardi, M.; Procopio, A.; Tagarelli, A.
Green Chem. 2004, 6, 191. (c) Bartoli, G.; De Nino, A.;
Dalpozzo, R.; Maiuolo, L.; Nardi, M.; Procopio, A.;
Tagarelli, A. Lett. Org. Chem. 2005, 2, 51. For cyclization:
(d) Keh, C. C. K.; Namboodiri, V. V.; Varma, R. S.; Li, C.-
J. Tetrahedron Lett. 2002, 43, 4993. For deprotection:
(e) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Procopio, A.;
Tagarelli, A.; Sindona, G.; Bartoli, G. J. Org. Chem. 2002,
67, 9093. (f) Bartoli, G.; Dalpozzo, R.; De Nino, A.;
Maiuolo, L.; Nardi, M.; Procopio, A.; Tagarelli, A. Eur. J.
Org. Chem. 2004, 2176.
179.0717.
References
(1) (a) Meskens, F. A. J. Synthesis 1981, 501. (b) Sandler, S.
R.; Karo, W. Organic Functional Group Preparations, 2nd
ed., Vol. III; Academic: New York, 1989, Chap. 1.
(8) No reaction took place when the reaction was carried out in
the absence of ethane-1,2-diol.
(9) Cyclic acetalization of normal ketones such as octan-2-one
and acetophenone proceeded smoothly under similar
reaction conditions.
(c) Macpherson, D. T.; Harshad, K. R. In Comprehensive
Organic Functional Group Transformations, Vol. 4;
Synthesis 2009, No. 8, 1318–1322 © Thieme Stuttgart · New York