Hot water as a mild Bronsted acid catalyst in ring opening reactions of epoxides

Article abstract of DOI:10.1007/s11426-011-4323-x

Ring opening of extremely hydrophobic epoxides with water, amines, sodium azide and thiophenol was realized in the mixture solvent of water and 1, 4-dioxane under reflux condition. Hot water was believed to act as a mild Bronsted acid catalyst in the epoxide-opening reactions.

Full text of DOI:10.1007/s11426-011-4323-x

SCIENCE CHINA
Chemistry
November 2011 Vol.54 No.11: 1718–1725
doi: 10.1007/s11426-011-4323-x
• ARTICLES •
Hot water as a mild Brønsted acid catalyst in ring opening
reactions of epoxides
XU ZhaoBing & QU Jin*
State Key Laboratory and Institute of Elemento-organic Chemistry; Nankai University, Tianjin 300071, China
Received February 26, 2011; accepted April 5, 2011
Ring opening of extremely hydrophobic epoxides with water, amines, sodium azide and thiophenol was realized in the mixture
solvent of water and 1, 4-dioxane under reflux condition. Hot water was believed to act as a mild Brønsted acid catalyst in the
epoxide-opening reactions.
epoxide-opening reaction, 1,4-dioxane, hot water, Brønsted acid catalyst
the epoxide toward ring-opening reactions [12–14]. In 2007,
1 Introduction
the elegant work from Jamison’s group revealed that the
cascade epoxide-openings of tetrahydropyran-templated
polyepoxides occurred smoothly in hot water (70 °C) to
generate the ladder polyether [15], and later on an in-water
hydrogen bond mechanism was proposed to explain the
special regioselectivity [16]. Recently, we also reported the
practical ring-opening reactions of epoxides or aziridines
with water or other heteroatom nucleophiles such as amines,
sodium azide, and thiophenol in hot water (60–100 °C) [17].
Based on the comparison of the selectivities of the reactions,
we believed that the role of water in the reaction is a mild
acid catalyst. In our previous paper, the aqueous solubilities
of the substrates are acceptable since in most cases there are
hydrophilic substituent groups present in the molecules.
Some relatively small hydrocarbon compounds also have
appreciable aqueous solubilities in hot water. Further study
on the substrates scope of the reaction revealed that, howev-
er, extremely hydrophobic epoxides with very long aliphatic
chains were inert in hot water even after prolonged refluxing.
For example, though the hydrolysis of 10,11-epoxyundecyl-
1-ol (1a) could occur effectively in refluxing water, 1-
dodecene oxide (2a) was completely unreactive under the
same condition (Scheme 1). As an extension of our previous
study, herein the ring-opening of extremely hydrophobic
In recent years, green chemistry has become an important
research area and much attention has been focused on
searching more ‘green’ or environmentally friendly chemi-
cal processes [1–3]. Water is a cheap, non-toxic, non-
flammable, and environmentally benign solvent but it is not
commonly used in organic reactions majorly due to the poor
aqueous solubilities of organic reactants. Since Breslow et
al. observed an exceptional acceleration of the Diels-Alder
reaction in water in 1980 [4], the use of water as the solvent
or the co-solvent in organic reactions has attracted great
attention from the organic community and a number of re-
ports have emerged [5–8]. Interestingly, when water is
added to the reaction system, some reactions display differ-
ent characteristics (rates, yields or selectivities) compared
with those carried out solely in organic solvents [9–11].
Ring-opening of epoxides with nucleophiles provides a
valuable protocol in organic synthesis to construct vicinal
bifunctional groups. Brønsted acids or Lewis acids are
commonly-used catalysts in the epoxide-opening reactions,
yet it was reported that water was also capable of activating
*Corresponding author (email: qujin@nankai.edu.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com www.springerlink.com

Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
1719
1.29–1.17 (m, 28H), 0.85 (t, J = 6.8 Hz, 3H); 13C NMR
(DMSO-d6, 75 MHz) δ (ppm) 71.52, 66.43, 33.84, 31.69,
29.70, 29.50, 29.44, 29.09, 25.57, 22.48, 14.32.
Dec-9-ene-1,2-diol (4b) [34]
1
Pale yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm)
5.86–5.76 (m, 1H), 5.02–4.92 (m, 2H), 3.70 (m, 1H), 3.65
(d, J = 11.2 Hz, 1H), 3.43 (dd, J = 10.8 and 8.0 Hz, 1H),
2.38 (br s, 2H), 2.04 (q, J = 6.8 Hz, 2H), 1.44–1.32 (m,
10H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 138.98,
114.16, 72.30, 66.67, 33.69, 32.99, 29.46, 28.98, 28.79,
25.51.
Scheme 1 Hydrolysis of 1a and 2a in pure water under reflux. Reaction
condition: 2 mmol of epoxide (1a or 2a) in refluxing water (12 mL)
for indicated time, the yield of 1b was obtained by flash column chroma-
tography.
epoxides was further investigated in the mixture solvent of
water and 1,4-dioxane under reflux. Furthermore, the role
water played in the reaction was considered as a mild
Brønsted acid which was consistent with our previous point.
(1S,2S,4R)-1-Methyl-4-(prop-1-en-2-yl)cyclohexane-1,2-diol
(5b) [35]
1
White crystalline solid, mp: 70–71 °C. H NMR (CDCl3,
400 MHz) δ (ppm) 4.74 (s, 2H), 3.65 (m, 1H), 2.31–2.23 (m,
1H), 1.97–1.90 (m, 1H), 1.81–1.75 (m, 1H), 1.74 (s, 3H),
1.71–1.65 (m, 1H), 1.60–1.52 (m, 5H), 1.28 (s, 3H); 13C
NMR (CDCl3, 150 MHz) δ (ppm) 149.13, 108.97, 73.72,
71.43, 37.39, 33.84, 33.61, 26.35, 26.05, 21.06.
2 Experimental
2.1 General
The melting points recorded are uncorrected. 1H NMR
spectra were obtained at 300 MHz or 400 MHz in CDCl3 or
DMSO-d6. Coupling constants (J) are given in Hz. 13C
NMR spectra were obtained at 75, 100 and 150 MHz in
CDCl3 or DMSO-d6. HRMS spectra were recorded by ESI
method. GC analysis was recorded using Rtx-5 column.
Commercially obtained reagents were used without further
purification. Flash column chromatography was performed
using petroleum ether and ethyl acetate as eluent on silica
gel (200–300 mesh).
2-Methyl-6-methylene-oct-7-en-2,3-diol (6b) [36]
1
Pale yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm) 6.38
(dd, J = 10.8 and 17.6 Hz, 1H), 5.27 (d, J = 17.6 Hz, 1H),
5.09 (d, J = 10.8 Hz, 1H), 5.05 (s, 1H), 5.04 (s, 1H), 3.41
(dd, J = 10.6 and 1.4 Hz, 1H), 2.58–2.51 (m, 1H), 2.40 (s,
1H), 2.32–2.24 (m, 1H), 2.10 (s, 1H), 1.72–1.64 (m, 1H),
1.56–1.47 (m, 1H), 1.21 (s, 3H), 1.16 (s, 3H); 13C NMR
(CDCl3, 75 MHz) δ (ppm) 146.16, 138.67, 115.93, 113.52,
78.23, 73.10, 30.21, 28.54, 26.50, 23.26.
2.2 Preparation and analytic data of substrates
(1RS,2RS)-1,2-Diphenylpropane-1,2-diol (7b) [37]
1
General procedure of hydrolysis of epoxides in mixed
solvent of water and 1,4-dioxane: To a 25 mL round
bottom flask equipped with a condenser was added a solu-
tion of epoxides (2a–15a, 0.4 mmol) in distilled water (6
mL) and 1,4-dioxane (6 mL). The reaction mixture was
heated to reflux and was monitored by TLC. After com-
pletion, the mixture was extracted by EtOAc to give the
crude product which was purified by flash column chro-
matography.
White crystalline solid, mp: 90–92 °C. H NMR (CDCl3,
400 MHz) δ (ppm) 7.33–7.23 (m, 8H), 7.09 (m, 2H), 4.78 (s,
1H), 2.78 (br s, 1H), 2.75 (br s, 1H), 1.34 (s, 3H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 144.94, 139.09, 128.03, 127.74,
127.65, 127.62, 127.18, 125.81, 80.74, 77.32, 23.95; HRMS
(ESI) for C15H16O2: calcd for [M+Na]+ m/z 251.1043, found
251.1041.
10,11-Dihydroxyundecyl acetate (8b)
1
White solid, mp: 40–42 °C. H NMR (CDCl3, 400 MHz) δ
Dodecane-1,2-diol (2b) [32]
(ppm) 4.05 (t, J = 6.6 Hz, 2H), 3.70–3.64 (m, 2H), 3.43 (t, J
= 9.6 Hz, 1H), 2.41 (br s, 2H), 2.05 (s, 3H), 1.60 (q, J = 6.4
Hz, 2H), 1.43 (m, 3H), 1.29 (m, 11H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 171.21, 72.11, 66.51, 64.47, 32.89,
29.46, 29.27, 29.24, 29.01, 28.36, 25.67, 25.41, 20.78;
HRMS (ESI) for C13H26O4: calcd for [M+Na]+ m/z
269.1723, found 269.1727.
White solid, mp: 6264 °C. 1H NMR (CDCl3, 400 MHz) δ
(ppm) 3.713.63 (m, 2H), 3.453.40 (m, 1H), 2.67 (br s,
2H), 2.05 (s, 3H), 1.43 (m, 3H), 1.26 (m, 15H), 0.88 (t, J =
6.8 Hz, 3H); 13C NMR (CDCl3, 150 MHz) δ (ppm) 72.34,
66.80, 33.14, 31.88, 29.64, 29.59, 29.54, 29.31, 25.55,
22.66, 14.09.
N-Cyclohexyl-10,11-dihydroxyundecanamide (9b)
Octadecane-1,2-diol (3b) [33]
White solid, mp: 78–80 °C. 1H NMR (DMSO-d6, 400 MHz)
δ (ppm) 4.41 (t, J = 5.6 Hz, 1H), 4.33 (d, J = 4.8 Hz, 1H),
3.38–3.34 (m, 1H), 3.27–3.17 (m, 2H), 1.40–1.38 (m, 2H),
1
White solid, mp: 78–81 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) 5.71 (d, J = 7.6 Hz, 1H), 3.75–3.61 (m, 3H),
3.44–3.31 (m, 3H), 2.13 (t, J = 7.2 Hz, 2H), 1.91–1.88 (m,

1720
Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
2H), 1.72–1.69 (m, 2H), 1.60 (m, 3H), 1.42–1.29 (m, 14H),
1.17–1.11 (m, 3H); 13C NMR (CDCl3, 100 MHz) δ (ppm)
172.48, 72.21, 66.75, 48.08, 36.89, 33.08, 33.03, 29.43,
29.20, 29.10, 29.06, 25.75, 25.44, 24.80; HRMS (ESI)
for C17H33NO3: calcd for [M+Na]+ m/z 322.2353, found
322.2355.
0.97 (m, 8H), 0.90 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 6.0 Hz,
6H), 0.68 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ (ppm)
171.00, 76.13, 75.54, 71.42, 56.33, 55.81, 45.26, 42.72,
39.92, 39.47, 38.25, 36.86, 36.16, 35.80, 34.51, 32.13, 30.18,
28.20, 27.95, 26.68, 24.11, 23.93, 22.76, 22.52, 21.40, 21.07,
18.64, 16.63, 12.12; HRMS (ESI) for C29H50O4: calcd for
[M+Na]+ m/z 485.3601, found 485.3596.
(5RS,6SR)-Decane-5,6-diol (10b)
White crystalline solid, mp: 127–129 °C. 1H NMR (CDCl3,
400 MHz) δ (ppm) 3.61 (m, 2H), 1.83 (s, 2H), 1.50–1.44 (m,
6H), 1.39–1.31 (m, 6H), 0.92 (t, J = 6.0 Hz, 6H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 74.71, 30.86, 28.19, 22.71,
14.00; HRMS (ESI) for C10H22O2: calcd for [M+Na]+ m/z
197.1512, found 197.1514.
24(R,S)-3β-acetoxy-24,25-dihydroxy-5α-lanost-8-ene (15b)
[41]
White solid, mp: 181–183 °C. 1H NMR (CDCl3, 400 MHz)
δ (ppm) 4.50 (dd, J = 4.0 and 11.2 Hz, 1H), 3.35–3.28 (m,
1H), 2.05 (s, 3H), 2.04 (m, 5H), 1.91 (m, 2H), 1.75–1.66 (m,
8H), 1.52–1.46 (m, 3H), 1.41–1.31 (m, 5H), 1.22 (s, 3H),
1.17 (s, 3H), 1.14 (m, 2H), 1.00 (s, 3H), 0.90 (d, J = 6.0 Hz,
3H), 0.88 (s, 9H), 0.70 (s, 3H); 13C NMR (CDCl3, 100 MHz)
δ (ppm) 171.03, 134.40, 134.19, 80.92, 79.55, 78.68, 73.16,
73.11, 50.53, 50.43, 50.39, 49.76, 49.74, 44.43, 37.74,
36.83, 36.69, 36.25, 35.21, 33.51, 33.09, 30.93, 30.74,
28.65, 28.35, 28.24, 28.12, 27.85, 26.48, 26.46, 26.32,
24.20, 24.11, 23.19, 23.11, 21.28, 20.94, 19.13, 18.78,
18.49, 18.06, 16.48, 15.73.
(4SR,5SR)-4,5-Dihydroxydecyl acetate (11b)
1
Pale yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm) 4.11
(t, J = 6.0 Hz, 2H), 3.42 (s, 2H), 2.34 (s, 1H), 2.12 (s, 1H),
2.05 (s, 3H), 1.87–1.82 (m, 1H), 1.76–1.70 (m, 2H),
1.54–1.32 (m, 9H), 0.90 (br s, 3H); 13C NMR (CDCl3, 100
MHz) δ (ppm 171.26, 74.33, 73.75, 64.40, 33.32, 31.70,
29.68, 25.18, 24.81, 22.43, 20.78, 13.85; HRMS (ESI) for
C12H24O4: calcd for [M+Na]+ m/z 255.1567, found
255.1572.
General procedure of the ring-opening reactions of
1-dodecene oxide by other nucleophiles in equal volume
of water and 1,4-dioxane: To a stirred solution of
1-dodecene oxide (92 mg, 0.5 mmol) in distilled water (6
mL) and 1,4-dioxane (6 mL) was added the nucleophiles
(2.5 mmol) in a 25 mL flask with a condenser, the resulting
mixture was heated to reflux and was monitored by TLC.
After completion, the mixture was extracted by EtOAc, and
the crude product was purified by flash column
chromatography to give the corresponding product.
(9SR,10SR)-Octadecane-1,9,10-triol (12b) [38]
1
White solid, mp: 82–83 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) 3.63 (br s, 2H), 3.39 (br s, 2H), 2.27 (br s, 2H),
1.47–1.29 (m, 29H), 0.88 (s, 3H); 13C NMR (CDCl3, 100
MHz) δ (ppm) 74.51, 74.47, 62.96, 33.61, 33.58, 32.71,
31.85, 29.67, 29.53, 29.46, 29.28, 29.25, 25.66, 25.60,
22.63, 14.07; HRMS (ESI) for C18H38O3: calcd for [M+Na]+
m/z 325.2713, found 325.2698.
1-(Phenylamino)-2-dodecanol (2c) [42]
(3S,5R,6R,8R,9R,10R,13S,14R,17S)-17-Acetyl-5,6-dihydrox
y-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanth
ren-3-yl acetate (13b) [39]
1
White solid, mp: 43–45 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) 7.21–7.17 (m, 2H), 6.75–6.72 (m, 1H), 6.67–6.65 (m,
2H), 3.98 (br s, 1H), 3.83 (br s, 1H), 3.27 (dd, J = 12.8 and
2.8 Hz, 1H), 3.00 (dd, J = 12.8 and 8.8 Hz, 1H), 1.93 (br s,
1H), 1.56–1.47 (m, 3H), 1.31–1.27 (m, 15H), 0.88 (t, J =
6.8 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 148.31,
129.24, 117.83, 113.26, 70.38, 50.30, 35.11, 31.88, 29.64,
29.57, 29.29, 25.61, 22.64, 14.06.
White solid, mp: 223–225 °C. 1H NMR (CDCl3, 300 MHz)
δ (ppm) 5.20–5.10 (m, 1H), 3.63–3.55 (m, 1H), 2.54 (t, J =
11.4 Hz, 1H), 2.24–2.18 (m, 2H), 2.12 (s, 3H), 2.03 (s, 3H),
1.91–1.56 (m, 13H), 1.52–1.42 (m, 4H), 1.31–1.19 (m, 2H),
1.19 (s, 3H), 0.63 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ
(ppm) 209.54, 170.92, 76.06, 75.62, 71.11, 63.74, 56.08,
45.28, 44.33, 38.97, 38.37, 37.02, 34.57, 32.11, 31.47,
30.28, 26.64, 24.34, 22.83, 21.40, 21.08, 16.60, 13.49;
HRMS (ESI) for C23H36O5: calcd for [M+Na]+ m/z
415.2455, found 415.2458.
1-(N,N-Diethylamino)-2-dodecanol (2d) [43]
Pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ (ppm)
3.59–3.54 (m, 1H), 3.57 (br s, 1H), 2.63 (m, 2H), 2.48 (m,
2H), 2.41 (dd, J = 12.8 and 3.2 Hz, 1H), 2.23 (dd, J = 12.4
and 10.4 Hz, 1H), 1.48–1.39 (m, 2H), 1.36–1.26 (m, 16H),
1.02 (t, J = 7.2 Hz, 6H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) δ (ppm) 66.70, 59.64, 47.05, 35.02,
31.85, 29.81, 29.56, 29.27, 25.73, 22.61, 14.01, 11.98.
(3S,5R,6R,8S,9S,10R,13R,14S,17R)-5,6-Dihydroxy-10,13-
dimethyl-17-((R)-6-methylheptan-2-yl)hexadecahydro-1H-
cyclopenta[a]phenanthren-3-yl acetate (14b) [40]
White solid, mp: 201–203 °C. 1H NMR (CDCl3, 400 MHz)
δ (ppm) 5.15 (m, 1H), 3.53 (m, 1H), 2.17 (t, J = 12 Hz, 1H),
2.02 (s, 3H), 1.97 (s, 1H), 1.85 (m, 2H), 1.71–1.62 (m, 6H),
1.57–1.50 (m, 4H), 1.42–1.24 (m, 8H), 1.19 (s, 3H), 1.19–
1-(4-Morpholino)-2-dodecanol (2e) [43]
1
Pale yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm)
3.76–3.67 (m, 5H), 3.39 (br s, 1H), 2.67–2.63 (m, 2H),

Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
1721
2.39–2.25 (m, 4H), 1.45–1.26 (m, 18H), 0.88 (t, J = 6.6 Hz,
3H); 13C NMR (CDCl3, 75 MHz) δ (ppm) 66.97, 65.93,
64.76, 53.64, 34.80, 31.82, 29.70, 29.52, 29.24, 25.50,
22.59, 14.00.
no product was obtained when 2a was heated in the 1:1
mixture of water/1,4-dioxane at 70 ºC for 12 h.
Under the optimized reaction condition, the scope of the
reaction was examined. Several hydrophobic epoxides
were checked with the results summarized in Table 2. The
reactions generally gave 90%–99% isolated yields in the
time scale ranging from 0.5 to 48 h. Terminal epoxides
with long aliphatic chains could be hydrolyzed effectively
in high yields (entries 1 and 2, Table 2). The 1:1 mixture
of trans/ cis-(R)-(+)-limonene oxides could be hydrolyzed
in 95% yield in 10 h under the optimal conditions (entry 3),
compared with that 90% yield obtained in 36 h in pure
water [17].
1-Azido-2-hydroxydodecane (2f) [44]
1
Pale yellow oil. H NMR (CDCl3, 400 MHz) δ (ppm) 3.76
(br s, 1H), 3.38 (dd, J = 12.4 and 3.2 Hz, 1H), 3.25 (dd, J =
12.4 and 7.2 Hz, 1H), 1.97 (d, J = 4.0 Hz, 1H), 1.50–1.44
(m, 3H), 1.26 (m, 15H), 0.88 (t, J = 6.8 Hz, 3H); 13C NMR
(CDCl3, 75 MHz) δ (ppm) 70.78, 59.07, 34.28, 31.82, 29.50,
29.45, 29.24, 25.38, 22.59, 13.99.
2-Azido-1-hydroxydodecane (2g) [45]
Pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ (ppm)
3.72–3.67 (m, 1H), 3.58–3.52 (m, 1H), 3.50–3.44 (m, 1H),
1.86 (m, 1H), 1.65–1.27 (m, 18H), 0.88 (t, J = 6.6 Hz, 3H);
13C NMR (CDCl3, 75 MHz) δ (ppm) 65.24, 64.50, 31.88,
30.58, 29.55, 29.51, 29.41, 29.28, 26.00, 22.65, 14.07.
The acceleration of the reaction was also observed for
trisubstituted myrcene oxide (Entry 4), for which 90% yield
of product was obtained in 0.5 h while 13 h was needed in
pure water. 2-Methyl-2,3-diphenyloxirane could be hydro-
lyzed in 4 h with almost quantitative transformation (Entry
5). The acetyl protected 11,12-epoxycitronellol and cyclo-
hexyl amino protected 10,11-epoxyundecanoic acid could
be hydrolyzed without the removal of protective groups
(entries 6 and 7). Disubstituted aliphatic epoxides also af-
forded excellent yields (entries 8–10). For the hydrolysis of
epoxides on the fused rings or at the side chain of steroids,
1-(Phenylthio)-2-dodecanol (2h) [46]
1
White solid, mp: 39–41 °C. H NMR (CDCl3, 400 MHz) δ
(ppm) 7.40–7.38 (m, 2H), 7.31–7.27 (m, 2H), 7.23–7.19 (m,
1H), 3.66 (m, 1H), 3.15 (dd, J = 13.8 and 3.2 Hz, 1H), 2.83
(dd, J = 13.6 and 8.8 Hz, 1H), 2.40 (s, 1H), 1.54–1.50 (m,
2H), 1.45–1.41 (m, 1H), 1.26–1.24 (m, 15H), 0.88 (t, J =
6.7 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 135.42,
129.93, 129.00, 126.48, 69.37, 42.16, 36.11, 31.88, 29.57,
29.52, 29.30, 25.64, 22.66, 14.10; HRMS (ESI) for
C18H30SO: calcd for [M+Na]+ m/z 317.1910, found
317.1914.
Table 1 Hydrolysis of 1-dodecene oxide (2a) in water or 1:1 mixture of
water and organic solvent a)
3 Results and discussion
Epoxide 2a, bearing a long aliphatic hydrocarbon chain, is
extremely hydrophobic and can not be dispersed in water.
So it was hard to undergo the hydrolysis reaction in “on
water” condition [18–21]. If the inertness of 2a was owing
to its extremely poor aqueous solubility, adding a water
miscible organic solvent may benefit the dispersion of 2a in
water. A variety of water-miscible organic co-solvents were
screened in the hydrolysis of 2a in the equal volume of the
organic co-solvent and water under refluxing condition (Ta-
ble 1). When CH3CN, acetone, DMF or DMSO were used
as the organic co-solvents, very low yields of 2a were ob-
served. The employment of alcoholic co-solvents such as
MeOH, EtOH, i-PrOH, ethylene glycol, or PEG-400 also
gave low transformations. Using THF as the co-solvent led
to a terribly slow reaction while using another ether, 1,4-
dioxane, as the co-solvent gave relatively fast reaction. Di-
methoxymethane, dimethoxyethane, and diethylene glycol
dimethyl ether, with increasing boiling point afforded grad-
ually increased yields. It was found that the reaction tem-
perature was also critical for the hydrolysis reaction since
a) Reaction conditions: 0.8 mmol of epoxide in 1:1 mixture of water (6
mL) and organic solvent (6 mL) was heated under reflux for 12 h; b) iso-
lated yield; c) Reaction conditions: 0.4 mmol of epoxide in 1:1 mixture of
water (6 mL) and 1,4-dioxane (6 mL) was heated under reflux for 16 h.

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Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
Table 2 Hydrolysis of epoxides in water/1,4-dioxane mixed solvent a)
the reactions also gave high yields with prolonged reaction
time (entries 11–13).
Other heteroatom nucleophiles such as amines, sodium
azide, and thiophenol could also react with epoxide under
the same condition while the reactions in pure water pro-
ceeded very slowly. In all cases, it was priority that the ter-
minal carbon of 2a was attacked by the nucleophile. The
reactions were fast and clean with the desired products ob-
tained in good to excellent yields (Table 3). Aniline, di-
ethylamine and morpholine could be rapidly and effectively
added to 1-dodecene oxide (entries 1 to 3). Cheap and water-
soluble NaN3 could be added to 2a in 5 h, giving two az-
idolysis products in high yield (entry 4). Moreover, thio-
phenol was also an appropriate nucleophile used for ring-
opening of 1-dodecene oxide without additional catalyst,
affording 84% of sulfur attacking product accompanying
with the diol byproduct (entry 5).
Then the role water played in the reaction was further
investigated. Generally the activation using ambient water is
Table 3 Epoxide-opening reactions of 1-dodecene oxide (2a) with het-
eroatom nucleophiles in the 1:1 mixture of water and 1, 4-dioxane a)
a) The reaction was conducted with 0.4 mmol of epoxide in 12 mL 1:1
mixture of water and 1,4-dioxane under reflux; b) isolated yield; c) the
reaction was conducted with 0.4 mmol of epoxide in 6 mL of water and 12
mL of 1,4-dioxane.
a) The reaction was conducted with 0.5 mmol of epoxide and 2.5 mmol
of nucleophile in 12 mL 1:1 mixture of water and 1,4-dioxane under reflux;
b) isolated yield; c)under nitrogen atmosphere.

Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
1723
categorized as the hydrogen bond catalysis. On the other
hand, there were computational [22, 23] and experimental
studies [24, 25] suggesting that water at ambient tempera-
ture can also act as a dual acid/base catalyst to promote or-
ganic reactions. In addition, it is believed that water can act
as an acid, base or dual acid/base catalyst at near-critical
temperature [26] as the ionization of water enhances with
temperature rises (pKw = 11.2 at 250 °C [27]), providing a
significant increase in the concentration of H+ and OH−.
The self-ionization of water enhances rapidly in the range
from 0 °C to 100 °C (pKw = 15 at 0 °C and pKw = 12.3 at
100 °C [27]) and the pKw value of water at 100 °C is closer
to that of near-critical water than water at ambient temper-
ature [28, 29]. On the contrary, the hydrogen bond interac-
tion in water is considerably weakened as temperature rises
[30] and even strongly hydrogen-bonded molecules like the
complimentary double strand DNA fall apart in hot water.
So water acts more potentially as a Brønsted acid at high
temperature.
changes from 14 in pure water to 14.60 in 20% 1,4-dioxane
aqueous solution [31]. For 10,11-epoxyundecyl-1-ol (Figure
1(a)) and 6,7-epoxygeranyl acetate (Figure 1(b)) with ac-
ceptable aqueous solubilities in hot water, the conversions
of the reactions dropped upon the addition of 1,4-dioxane
and the reaction did not proceed when the proportion of
1,4-dioxane was too high (the pKa* value of water is 16 in
60% of 1,4-dioxane aqueous solution at room temperature
[31]). For extremely hydrophobic 1-dodecene oxide (Figure
1(c)) and 1,2-diphenylpropene oxide (Figure 1(d)), 1,4-
dioxane facilitated the dissolution of the hydrophobic epox-
ides and the rates of the reaction went higher upon the addi-
tion of a small amount of 1,4-dioxane initially. After a cer-
tain point (this point varies depending on the aqueous solu-
bility of epoxides), the conversions of the reactions de-
creased with further addition of 1,4-dioxane. The experi-
ments above suggested that for epoxides with acceptable
aqueous solubilities in hot water, the highest hydrolysis
rates were obtained in pure water as the ionization of water
was maximal then. While for extremely hydrophobic epox-
ides, the reactions only took place when suitable amounts of
1,4-dioxane were added as the dissolution of the substrates
were needed for their hydrolysis. The reaction rates of ex-
tremely hydrophobic epoxides decreased when excessive
amounts of 1,4-dioxane were added as 1,4-dioxane could
disturb the ionization. Though the hydrogen bond catalysis
The rates of the hydrolysis reaction of different types of
epoxides were also examined in the mixture of water and
1,4-dioxane with different ratios. The pKa* value (Ka* is
the apparent ionization constant of water) increases with the
increase of the 1,4-dioxane in the solvent system because
the dielectric constant of the mixed solvent decreases during
this process. At room temperature, the pKa* value of water
Figure 1 Hydrolysis of epoxides in water/1,4-dioxane solvent system with increasing volume of 1,4-dioxane. (a) 10,11-Epoxyundecyl-1-ol (1.0 mmol) in
refluxing water/1,4-dioxane mixture solvent (10 mL) for 2 h. The conversions were determined by flash column chromatography; (b) 6,7-epoxygeranyl
acetate (0.14 mmol) in water/1,4-dioxane mixture solvent (5 mL, 70 oC) for 1 h. The conversions were determined by GC; (c) 1-dodecene oxide (0.22 mmol)
in refluxing water/1,4-dioxane mixture solvent (12 mL) for 12 h. The conversions were determined by GC; (d) 2-methyl-2,3-diphenyloxirane (0.5 mmol) in
refluxing water/1,4-dioxane mixture solvent (10 mL) for 1 h. The conversions were determined by flash column chromatography.

1724
Xu ZB, et al. Sci China Chem November (2011) Vol.54 No.11
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This work was financially supported by the National Natural Science
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High-tech Research & Development Program of China (863 Projcect,
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