Hot water-promoted ring-opening of epoxides and aziridines by water and other nucleopliles

Article abstract of DOI:10.1021/jo702401t

Effective hydrolysis of epoxides and aziridines was conducted by heating them in water at 60 or 100 °C. Other types of nucleophile such as amines, sodium azide, and thiophenol could also efficiently open epoxides and aziridines in hot water. It was proposed that hot water acted as a modest acid catalyst, reactant, and solvent in the hydrolysis reactions.

Full text of DOI:10.1021/jo702401t

Hot Water-Promoted Ring-Opening of Epoxides and Aziridines by
Water and Other Nucleopliles
Zhi Wang, Yong-Tao Cui, Zhao-Bing Xu, and Jin Qu*
The State Key Laboratory of Elemento-Organic Chemistry, Nankai UniVersity,
Tianjin 300071, People’s Republic of China
qujin@nankai.edu.cn
ReceiVed NoVember 10, 2007
Effective hydrolysis of epoxides and aziridines was conducted by heating them in water at 60 or 100 °C.
Other types of nucleophile such as amines, sodium azide, and thiophenol could also efficiently open
epoxides and aziridines in hot water. It was proposed that hot water acted as a modest acid catalyst,
reactant, and solvent in the hydrolysis reactions.
SCHEME 1. Epoxide-Opening Cascades Promoted by
Water
Introduction
Although water is cheap, safe, and clean compared with
organic solvents, water is not a regular choice for the medium
of organic reactions because of the insolubility of reactants and
incompatibility of reaction intermediates. In certain situations,
the special physical and chemical properties of water, such as
high dielectric constant, high heat capacity, hydrophobic interac-
tions between reactants, hydrogen bond formation between water
and reactant, and acid or base characters may be utilized to
promote organic reactions. In the early 1980s, Breslow’s group
reported that Diels-Alder reaction was remarkably accelerated
in water owing to the hydrophobic effect.1 This important
finding dramatically changed chemists’ attitudes toward the use
of water as solvent for organic reactions. After that, a number
of organic reactions were found to proceed very well in water.2
A very recent work from Jamison’s research group revealed
that the cascade epoxide-opening yielding ladder polyether could
be promoted by water. This finding presented a highly efficient
synthesis of natural trans-fused polycyclic ethers as well as
provided new evidence for the biosynthesis of this kind of
natural products (Scheme 1).3 In this paper, we report that the
ring-opening reactions of epoxides and aziridines can be
promoted by hot water. A general acid-catalyzed mechanism
was proposed based on the observed selectivity of the reactions
in hot water.
Results and Discussion
Hydrolysis of epoxides is a pivotal protocol for making
synthetically useful vicinal diols. Compared with the use of
protic acid,4 the hydrolysis of epoxides now can be conducted
under milder condition by using solid or solid-supported Lewis
acids,5 one-electron-transfer reagents,6 and other newly discov-
ered reagents.7 In the course of our research to finding catalysts
for enantioselective ring-opening of epoxides, we accidentally
found that styrene oxide could be hydrolyzed in hot water
(60 °C) within 3.5 h and the corresponding vicinal diol was
obtained in 98% yield (Scheme 2). A literature search showed
that in 1993, Kotsuki’s group reported a catalyst-free hydrolysis
(4) (a) Olah, G. A.; Fung, A. P.; Meidar, G. Synthesis 1981, 280. (b)
Parker, R. E.; Isaacs, N. S. Chem. ReV. 1959, 59, 737.
(5) (a) Iranpoor, N.; Tarrian, T.; Movahedi, Z. Synthesis 1996, 1473.
(b) Baltork, I. M.; Aliyan, S. T. H.; Mirkhani, V. Synth. Commun. 2000,
30, 2365. (c) Iranpoor, N.; Adibi, H. Bull. Chem. Soc. Jpn. 2000, 73, 675.
(d) Salehi, P.; Seddighi, B.; Irandoost, M.; Behbahani, F. K. Synth. Commun.
2000, 30, 2967.
(6) (a) Iranpoor, N.; Baltork, I. M.; Zardaloo, F. S. Tetrahedron 1991,
47, 9861. (b) Iranpoor, N.; Zardaloo, F. S. Synth. Commun. 1994, 24, 1959.
(7) (a) Yadav, J. S.; Reddy, B. V. S.; Harikishan, K.; Madan, Ch.;
Narsaiah, A. V. Synthesis 2005, 2897. (b) Fan, R.-H.; Hou, X.-L. Org.
Biomol. Chem. 2003, 1, 1565. (c) Mirkhani, V.; Tangestaninejad, S.;
Yadollahi, B.; Alipanah, L. Tetrahedron 2003, 8213. (d) Iranpoor, N.;
Tamami, B.; Niknam, K. Can. J. Chem. 1997, 75, 1913.
(1) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102, 7816.
(2) For recent reviews on organic reactions in water, see: (a) Organic
Reactions in Water; Lindstrom, U. M., Ed.; Blackwell: Oxford, UK, 2007.
(b) Li, C. J. Chem. ReV. 2005, 105, 3095. (c) Lindstro¨m, U. M. Chem. ReV.
2002, 102, 2751.
(3) Vilotijevic, I.; Jamison, T. F. Science 2007, 317, 1189.
10.1021/jo702401t CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/21/2008
2270
J. Org. Chem. 2008, 73, 2270-2274

Hot Water-Promoted Ring-Opening of Epoxides and Aziridines
SCHEME 2. Hydrolysis of Styrene Oxide in Hot Water
obtained. Acyclic aliphatic terminal epoxides (entries 7 to 9)
could be hydrolyzed efficiently at 100 °C. A large-scale reaction
was carried out by applying 6 mmol of 6,7-epoxycitronellol in
12 mL of water, and the epoxide could be transformed to the
corresponding triol in 97% yield. The acetyl-protected 6,7-
epoxycitronellol (entry 11) could also be hydrolyzed without
removal of the acetyl group. R-Hydroxyl epoxides (entries 12
to 14) also reacted smoothly with excellent yields. Cyclopentene
oxide and cyclohexene oxide were hydrolyzed with excellent
stereoselectivity since only trans vicinal diols were detected
(entries 15 and 16). For trisubstituted 1,2-epoxylimonene (entry
17), 36 h of reaction in boiling water gave the hydrolyzed
product in 90% yield. Cyclic R,â epoxy ketone (entry 18) was
hydrolyzed to trans-diol in 77% yield (compared to 47% in
Kotsuki’s method).8
Further studies showed that this method is suitable for the
hydrolysis of aziridines as well.10 As shown in Table 3, various
aziridines, including aromatic, aliphatic, and cyclic aliphatic
aziridines, could be hydrolyzed successfully and the yields were
excellent. For N-tosyl-2-phenylaziridine (entry 1), exclusive
product was obtained from water attacking at the benzylic
position. The alkyl terminal aziridine (entry 2) was preferentially
attacked at the less substituted position. In the case of cycloalkyl
aziridines (entries 3, 4, and 5), the stereochemistry of the
products was determined to be trans by comparing with the
reported data. Nonactivated aziridines such as N-benzylcyclo-
hexanoaziridine were also tested, but the reactions were very
slow.
Recently the ring-opening reactions of epoxides or aziridines
with various types of nucleophiles have been extensively
studied.11 Several methods with different catalysts employed
water as solvent and it was believed that water was essential
for the success of the reactions.12 In 2005, Saidi’s group reported
an effective aminolysis of epoxides in water around room
temperature without additional catalyst.13 To extend the general-
ity of our simple method, three representative substrates were
treated with different nucleophiles in hot water without ad-
ditional catalyst (Table 4). In Saidi’s report, the additions of
aromatic amines to alkyl epoxides were sluggish at room
temperature. We found that at 60 °C, both benzylamine and
aniline could equally and effectively add to styrene oxide and
cyclohexene oxide.14 Moreover, the addition of amines to
N-tosylcyclohexanoaziridine proceeded very well and gave
quantitative yield of products.15 Instead of using expensive
TMSN3, cheap and water-soluble NaN3 could be added to both
TABLE 1. Hydrolysis of Styrene Oxide and Cyclohexene Oxide in
Water or a 1:1 Mixture of Water and Other Solventsa
entry
epoxides
other solvents
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14c
15c
16c
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
styrene oxide
cyclohexene oxide
cyclohexene oxide
cyclohexene oxide
pure water
MeOH
EtOH
i-PrOH
t-BuOH
ethylene glycol
CH3CN
THF
acetone
DMF
98
70
60
40
50
96
9
1
20
6
38
40
95
89
47
85
DMSO
PEG400
1,4-dioxane
pure water
1,4-dioxane
ethylene glycol
Reaction conditions: 2 mmol of epoxides in water or a 1:1 mixture of
water and organic solvent was heated at 60 °C for 3.5 h. b GC yield. c The
reaction was carried out at 80 °C for 12 h, isolated yield.
of epoxides in the mixed solvent of acetone and water at 60 °C
under 10 kbar, but the substrate scope was limited and the yield
was unsatisfied.8
Solvent screening was carried out by employing an equal
volume of water and water miscible organic solvent (Table 1).
For the hydrolysis of styrene oxide, water gave the highest yield
while the introduction of CH3CN, THF, DMF, acetone, or
DMSO gave little conversion of styrene oxide. The addition of
different alcohols gave moderate conversion. It seemed that a
1:1 mixture of water and 1,4-dioxane or ethylene glycol was
also a good solvent system in which a similar yield was obtained
compared with that of water. However, when a relatively inert
substrate cyclohexene oxide was hydrolyzed, an 89% yield of
1,2-dihydroxycyclohexane was obtained in water compared with
an 47% and 85% yield in the mixture of water and 1,4-dioxane
or ethylene glycol, respectively. Thereby, water is the choice
of solvent.
We also found that the amount of water had a significant
influence on reaction rate. As shown in Figure 1a, for the
hydrolysis of styrene oxide, the product yield climbed higher
following the increase of water amount and the curve went to
a plateau after the ratio of water to substrate was raised to 6
mL of water per millimole of substrate. This critical amount of
water requirement was also observed in recently reported N-tert-
butyloxycarbonylation of amines in which water was also used
as solvent.9 Temperature effect was also examined with cyclo-
hexene oxide being a test substrate; superior yield was obtained
at higher temperature and the reaction rate reached a maximum
in boiling water (Figure 1b).
(10) For resent examples of hydrolysis of aziridines, see: (a) Srinivas,
B.; Kumar, V. P.; Sridhar, R.; Surendra, K.; Nageswar, Y. V. D.; Rao, K.
R. J. Mol. Catal. A 2007, 261, 1. (b) Chakraborty, T. K.; Ghosh, A.; Raju,
T. V. Chem. Lett. 2003, 32, 82. (c) Chandrasekhar, S.; Narsihmulu, Ch.;
Sultana, S. S. Tetrahedron Lett. 2002, 43, 736. (d) Prasad, B. A. B.; Sekar,
G.; Singh, V. K. Tetrahedron Lett. 2000, 41, 4677.
(11) For recent reviews on ring-opening reactions of epoxides, see:
Smith, J. G. Synthesis 1984, 629. For recent reviews on ring-opening
reactions of aziridines, see: Hu, X. E. Tetrahedron 2004, 60, 2701.
(12) (a) Fringuelli, F.; Piermatti, O.; Pizzo, F.; Vaccaro, L. J. Org. Chem.
1999, 64, 6094. (b) Fan, R.-H.; Hou, X.-L. J. Org. Chem. 2003, 68, 726.
(13) Azizi, N.; Saidi, M. R. Org. Lett. 2005, 7, 3649.
(14) For resent examples of aminolysis of epoxides, see: (a) Pujala, S.
B.; Chakraborti, A. K. J. Org. Chem. 2007, 72, 3713. (b) Das, U.; Crousse,
B.; Kesavan, V.; Bonnet-Delpon, D.; Be´gue´, J.-P. J. Org. Chem. 2000, 65,
6749. (c) Desai, H.; D’Souza, B. R.; Foether, D.; Johnson, B. F.; Lindsay,
H. A. Synthesis 2007, 902. (d) Yadav, J. S.; Reddy, A. R.; Narsaiah, A. V.;
Reddy, B. V. S. J. Mol. Catal. A: Chem. 2007, 261, 207. (e) Wu, J.; Xia,
H.-G. Green Chem. 2005, 7, 708. (f) Tan, W.; Zhao, B.-X.; Sha, L.; Jiao,
P.-F.; Wan, M.-S. Synth. Commun. 2006, 36, 1353. (g) Azizi, N.; Saidi, M.
R. Tetrahydron 2007, 63, 888.
A variety of epoxides could be hydrolyzed by heating them
in water (Table 2). All aromatic epoxides (entries 1 to 6) showed
high reactivity and nearly quantitative yields of diols were
(8) Kotsuki, H.; Kataoka, M.; Nishizawa, H. Tetrahedron Lett. 1993,
34, 4031.
(9) Chankeshwara, S. V.; Chakraborti, A. K. Org. Lett. 2006, 8, 3259.
J. Org. Chem, Vol. 73, No. 6, 2008 2271

Wang et al.
FIGURE 1. (a) A 2 mmol sample of styrene oxide was hydrolyzed in the indicated volume of water at 60 °C for 3.5 h and the yields were
analyzed by GC. (b) A 2 mmol sample of cyclohexene oxide was hydrolyzed in 12 mL of water at the indicated temperature for 12 h and the yields
were analyzed by GC.
epoxides and aziridines, giving azidolysis products at neutral
condition.16 It has been reported that thiophenol could be
efficiently added to epoxides in water around room tempera-
ture.17 We found that the ring-opening of aziridine by thiophenol
could proceed in neutral hot water without catalyst and gave
73% of sulfur attacking product accompanied by the diol
byproduct.15a-c,18
Efforts were also made to understand the role of hot water
in the above reactions. One possibility is that the hydrogen-
bonding formation between epoxide oxygen and water may
activate epoxides based on the reports, showing that the
hydrogen bond between alcohol (or phenol) and epoxide can
accelerate their ring-opening reactions.14b,19 In several reported
catalytic ring-opening reactions of epoxides or aziridines
operating in ambient water, including the newly published
cascade epoxide-opening in water at 70 °C, the hydrogen bond
between water and epoxide or aziridine was also used to explain
the rate enhancement.3,12b,13 But in the present studies, the rates
of hydrolysis reaction reached the maximum in boiling water,
while actually the hydrogen bond donating ability of water drops
quickly from 25 to 100 °C because the hydrogen-bonding
formation is exothermic.20 An alternative and more likely
explanation of the rate acceleration in hot water may be that
the self-ionization of water enhances as temperature rises, the
-log Kw (Kw is the self-ionization constant of water) value of
water at 100 °C is 12,21 where both H+ and OH- are 10 times
more abundant than that in ambient water (-log Kw ) 14 at
25 °C), therefore water itself can act as a modest acid or base
catalyst.22 It was reported that some traditionally acid- or base-
catalyzed reactions, such as hydrolysis of esters and ethers23
and dehydration of alcohols,24 could take place in neutral high-
temperature water (>200 °C, -log Kw ) 11 at 200 °C) without
additional acid or base. As the ring-opening reactions of
epoxides or aziridines are conventional acid or base catalyzed,
it seems reasonable to assume that it can also be facilitated where
the self-ionization of water is progressively enhanced along with
the increase of temperature. Acid catalysis dominates the
reported organic reactions in high-temperature water.23a,c The
observed cis/trans ratio of diol products of entries 4 and 5 in
Table 2 was found to be similar with the product distribution
in the protic acid-catalyzed hydrolysis (cis-diols are predominant
in the hydrolyzed products).25 If hot water acts as a modest acid,
we predicted that an intramolecular hydroxyl group should open
epoxide in hot water, with higher reaction rate since these
reactions are also traditionally acid catalyzed.
To test our hypothesis, two simple epoxides with a hydroxyl
group at the terminal site were prepared. Both trans-4,5-
epoxyhexanols 1 and cis-4,5-epoxyhexanols 3 were cyclized in
water at 60 °C in 0.5 h with almost quantitative yield. The 5-exo-
opening of epoxide was preferred and the observed ratio of
oxalane to oxane product produced from trans and cis substrates
was exactly the same compared with the reported product
distribution from the BF3‚Et2O-catalyzed cyclization of the same
substrates (Scheme 3).26 The ratio of oxalane to oxane product
was not changed in the reactions conducted in water at 0 °C
(15) For recent examples of aminolysis of aziridines, see: (a) Hou, X.-
L.; Fan, R.-H.; Dai, L.-X. J. Org. Chem. 2002, 67, 5295. (b) Wu, J.; Sun,
X.; Sun, W. Org. Biomol. Chem. 2006, 4, 4231. (c) Wu, J.; Sun, X.; Li, Y.
Eur. J. Org. Chem. 2005, 4271. (d) Nadir, U. K.; Singh, A. Tetrahedron
Lett. 2005, 46, 2083.
(16) For recent examples of azidolysis of epoxides and aziridines, see:
(a) Sabitha, G.; Babu, R. S.; Rajkumar, M.; Yadav, J. S. Org. Lett. 2002,
4, 343. (b) Minakata, S.; Okada, Y.; Oderaotoshi, Y.; Komatsu, M. Org.
Lett. 2005, 7, 3509. (c) Minakata, S.; Kano, D.; Oderaotoshi, Y.; Komatsu,
M. Angew. Chem., Int. Ed. 2004, 43, 79. (d) Wu, J.; Sun, X.; Xia, H.-G.
Eur. J. Org. Chem. 2005, 4269. (e) Das, B.; Reddy, V. S.; Tehseen, F.;
Krishnaiah, M. Synthesis 2007, 666. (f) Sabitha, G.; Babu, R. S.; Reddy,
M. S. K.; Yadav, J. S. Synthesis 2002, 2254. (g) Kishore Kumar, G. D.;
Baskaran, S. Synlett 2004, 1719. (h) Yadav, J. S.; Reddy. B. V. S.;
Jyothirmai, B.; Murty, M. S. R. Tetrahedron Lett. 2005, 46, 6559. (i)
Iranpoor, N.; Firouzabadi, H.; Shekarize, M. Org. Biomol. Chem. 2003, 1,
724.
(17) (a) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. AdV. Synth.
Catal. 2002, 344, 379. (b) Pironti, V.; Colonna, S. Green Chem. 2005, 7,
43.
(18) For resent examples of thiolysis of aziridines, see: (a) Reddy, M.
S.; Narender, M.; Rao, K. R. Synlett 2005, 489. (b) Wu, J.; Hou, X.-L.;
Dai, L.-X. J. Chem. Soc., Perkin Trans. 1 2001, 1314. (c) Yadav, J. S.;
Reddy, B. V. S.; Baishya, G.; Reddy, P. V.; Narsaiah, A. V. Catal. Commun.
2006, 7, 807.
(20) Lu, J.; Brown, J. S.; Liotta, C. L.; Eckert, C. A. Chem. Commun.
2001, 665.
(21) Akiya, N.; Savage, P. E. Chem. ReV. 2002, 102, 2725.
(22) For resent reviews on organic reactions in high-temperature water,
see: (a) Liotta, C. L.; Hallett, J. P.; Pollet, P.; Eckert, C. A. In Organic
Reactions in Water; Lindstrom, U. M., Ed.; Blackwell: Oxford, UK, 2007;
p256. (b) Katritzky, A. R.; Nichols, D. A.; Siskin, M.; Murugan, R.;
Balasubramanian, M. Chem. ReV. 2001, 101, 837.
(23) (a) Lesutis, H. P.; Gla¨ser, R.; Liotta, C. L.; Eckert, C. A. Chem.
Commun. 1999, 2063. (b) Krammer, P.; Vogel, H. J. Supercrit. Fluids 2000,
16, 189. (c) Penninger, J. M. L.; Kersten, R. J. A.; Baur, H. C. L. J.
Supercrit. Fluids 1999, 16, 119.
(24) (a) Hunter, S. E.; Ehrenberger, C. E.; Savage, P. E. J. Org. Chem.
2006, 71, 6229. (b) Kuhlmann, B.; Arnett, E. M.; Siskin, M. J. Org. Chem.
1994, 59, 3098.
(25) (a) Battistini, C.; Balsamo, A.; Berti, G.; Crotti, P.; Macchia, B.;
Macchia, F. J. Chem. Soc., Chem. Commun. 1974, 712. (b) Berti, G.; Camici,
G.; Macchia, B.; Macchia, F.; Monti, L. Tetrahedron Lett. 1972, 2591. (c)
Whalen, D. L.; Ross, A. M. J. Am. Chem. Soc. 1976, 98, 7859.
(19) (a) Hine, J.; Linden, S.-M.; Kanagasabapathy, V. M. J. Am. Chem.
Soc. 1985, 107, 1082. (b) Omoto, K.; Fujimoto, H. J. Org. Chem. 2000,
65, 2464.
2272 J. Org. Chem., Vol. 73, No. 6, 2008

Hot Water-Promoted Ring-Opening of Epoxides and Aziridines
TABLE 2. Hydrolysis of Epoxides in Hot Watera
TABLE 3. Hydrolysis of Aziridines in Hot Watera
a The reaction was conducted with 2 mmol of aziridine in 12 mL of
water at 100 °C. b Isolated yield; the ratio of the isomers was determined
1
by integrations of the signals in the H NMR
TABLE 4. Ring-Opening Reactions of Epoxides and Aziridines in
Hot Watera
a The reaction was conducted with 2 mmol of epoxide in 12 mL of water
at the indicated temperature. b Isolated yield; the ratio of the isomers was
determined by integrations of the signals in the 1H NMR spectrum. c Threo/
erythro: 60/40. d Trans/cis: 25/75. e Trans/cis: 25/75. f Threo/erythro: 75/
25. g 6 mmol of epoxide in 12 mL of water. h 1 mmol of a 1:1 mixture of
trans-(R)-(+)-limonene oxide and cis-(R)-(+)-limonene oxide in 12 mL of
water.
a The reaction was conducted with 1 mmol of substrate and 2 mmol of
nucleophile in 6 mL of water at 60 °C. b Isolated yield.
of five-member-ring product 6b, which was parallel with the
result from BF3-etherate-promoted cyclization. The same reac-
tion could also complete in water at 100 °C within 10 min or
more than 24 h at 0 °C with the same product distribution. This
but more than 15 h was required for completion of the same
reactions. Another reported Lewis acid-catalyzed cyclization of
diepoxide was also tested in hot water.27 A diastereomeric
mixture of 1,5-diepoxides 528 was completely consumed in water
at 60 °C in 0.5 h (Scheme 4). Acylation of the resulting crude
mixture gave 44% of seven-member-ring product 6a and 24%
(27) (a) McDonald, F. E.; Wang, X.; Do, B.; Hardcastle, K. I. Org. Lett.
2000, 2, 2917. (b) McDonald, F. E.; Bravo, F.; Wang, X.; Wei, X.; Toganoh,
M.; Rodr´ıguez, J. R.; Do, B.; Neiwert, W. A.; Hardcastle, K. I. J. Org.
Chem. 2002, 67, 2515. (c) Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.;
Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224.
(26) Coxon, J. M.; Hartshorn, M. P.; Swallow, W. H. Aust. J. Chem.
1973, 26, 2521.
J. Org. Chem, Vol. 73, No. 6, 2008 2273

Wang et al.
SCHEME 3. Hydroxy-Epoxide Cyclization in Water at
60 °C
manageable hot water (60-100 °C) rather than high-temperature
water (>200 °C) makes the present reactions safe and practical.
Experiment Section
A Typical Procedure of Hydrolysis of Epoxide in Hot Water
(Table 2, entry 1). The suspension of styrene oxide (1 mmol, 120
mg) in distilled water (6 mL) in a 10 mL flask with a condenser
was stirred at 60 °C and monitored by TLC. After completion, the
mixture was extracted with EtOAc, washed with brine, dried over
MgSO4, and then concentrated to give the crude product. Purifica-
tion by silica gel flash column chromatography provided diol
product (135 mg, 98%).
1-Phenyl-1, 2-ethanediol: 1H NMR (400 MHz, CDCl3) δ 7.31-
7.37 (m, 5H), 4.83 (dd, J ) 3.2, 8.0 Hz, 1H), 3.76 (dd, J ) 3.0,
11.4 Hz, 1H), 3.66 (dd, J ) 8.2, 11.1 Hz, 1H), 2.69 (br s, 1H),
2.27 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 140.34, 128.36,
127.77, 126.00, 74.63, 67.88.
SCHEME 4. Oxacyclization of 1,5-Diepoxide
A Typical Procedure of Hydrolysis of 2-Phenyl-1-tosylaziri-
dine in Hot Water (Table 3, entry 1). The suspension of 2-phenyl-
1-tosylaziridine (2 mmol, 546 mg) in distilled water (12 mL) in a
25 mL flask with a condenser was stirred at 100 °C and monitored
by TLC. After completion, the mixture was extracted with EtOAc,
washed with brine, dried over MgSO4, and then concentrated to
give the crude product. Purification by silica gel flash column
chromatography provided product (576 mg, 99%).
2-(N-Tosylamino)-1-phenyl-1-ethanol: 1HNMR (400 MHz,
CDCl3) δ 7.69 (d, J ) 8.0 Hz, 2H), 7.23-7.25 (m, 7H), 5.68 (s,
1H), 4.76 (dd, J ) 2.4, 8.4 Hz, 1H), 3.48 (br s, 1H), 3.14-3.17
(m, 1H), 2.94-3.00 (m, 1H), 2.37 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.40, 140.76, 136.48, 129.65, 128.39, 127.89, 126.94,
125.78, 72.58, 50.18, 21.39.
evidence implies that the ring-opening reactions in hot water
was acid catalyzed.
The dielectric constant of ambient water is 80 and this number
quickly reduces to 55 at 100 °C, which implies that water is
more like a polar organic solvent at high temperature. Therefore,
some substrates that were originally water insoluble dissolve
and react at elevated temperatures.29
A Typical Procedure of the Ring-Opening Reactions of
Epoxides or Aziridines by Other Nucleophiles (Table 4, entry
4). To a stirred suspension of cyclohexene oxide (1 mmol, 98 mg)
in distilled water (6 mL) was added the sodium azide (2 mmol,
130 mg) in a 10 mL flask with a condenser; the resulting mixture
was stirred at 60 °C and was monitored by TLC. After completion,
the mixture was extracted with EtOAc, washed with brine, dried
over MgSO4, and then concentrated to give the crude product.
Purification by silica gel flash column chromatography provided
product (137 mg, 97%).
In conclusion, efficient hydrolysis of epoxides and aziridines
has been achieved by just heating them in water. Other
nucleophiles such as amines, sodium azide, and thiophenol could
also effectively open epoxides and aziridines in hot water.
Hydroxyl epoxides could also undergo cyclization to give cyclic
ether in hot water. Simple workup (without the wash step) or
direct evaporation of water led to pure ring-opening products
and the yields are generally over 90% for a variety of substrates.
Moreover, the present method avoided the use and subsequent
disposal of additional catalyst, which will satisfy both laboratory
and industrial operations. Furthermore, the present finding
revealed another type of organic reaction that may benefit from
the enhanced self-ionization of water. The utilization of
1
2-Azidocyclohexanol: H NMR (400 MHz, CDCl3) δ 3.42-
3.35 (m, 1H), 3.22-3.15 (m, 1H), 2.52 (s, 1H), 2.07-2.00 (m,
2H), 1.78-1.72 (m, 2H), 1.36-1.19 (m, 4H).
Acknowledgment. This work was financially supported by
The National Natural Science Foundation of China (Nos.
20402007 and 20421202), NanKai University, the 111 Project
(B06005), and the Project 863 of the Ministry of Science and
Technology of China (No. 2006AA020502). We thank Prof.
Chi Zhang for helpful discussions. We thank Mr. Xiangcai Ge
for involvement in some early works.
(28) Compound 5 is an inseparable 3.7:1 mixture of two diastereomers.
It was prepared from geranylacetone by Shi enantioselective double
epoxidation. Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am.
Chem. Soc. 1997, 119, 11224.
Supporting Information Available: General experimental
1
procedures and H NMR and 13C NMR spectra of compounds in
(29) Styrene oxide was not soluble in water at room temperature but it
dissolved at 60 °C. (a) Akerlof, G. C.; Oshry, H. I. J. Am. Chem. Soc.
1950, 72, 2844. (b) Miller, D. J.; Hawthorne, S. B. J. Chem. Eng. Data
2000, 45, 78.
Tables 2-4 and Schemes 3 and 4. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO702401T
2274 J. Org. Chem., Vol. 73, No. 6, 2008