Zirconyl nitrate mediated regioselective ring opening of epoxides and aziridines: an easy synthesis of β-nitrato-alcohols and -sulfonamides

Article abstract of DOI:10.1016/j.tetlet.2006.06.114

Epoxides and aziridines are cleaved efficiently and regioselectively in the presence of zirconyl nitrate at room temperature to afford the corresponding β-nitrato-alcohols and -sulfonamides, respectively, in high yields.

Full text of DOI:10.1016/j.tetlet.2006.06.114

Tetrahedron Letters 47 (2006) 6027–6029
Zirconyl nitrate mediated regioselective ring opening of
epoxides and aziridines: an easy synthesis of b-nitrato-alcohols
and -sulfonamidesI
Biswanath Das,* Maddeboina Krishnaiah and Katta Venkateswarlu
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 26 April 2006; revised 12 June 2006; accepted 22 June 2006
Abstract—Epoxides and aziridines are cleaved efficiently and regioselectively in the presence of zirconyl nitrate at room temperature
to afford the corresponding b-nitrato-alcohols and -sulfonamides, respectively, in high yields.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Ring-opening reactions of epoxides and aziridines have
extensively been studied with a large number of nucleo-
philes.1 However, there are few applications of the
nitrate ion as the nucleophile for these reactions.2
Alkyl nitrates are versatile synthetic intermediates.3
b-Nitrato-alcohols and -sulfonamides are examples of
functionalized alkyl nitrates and could be utilized in
organic synthesis. b-Nitrato-alcohols have been previ-
ously prepared from epoxides by treatment with concen-
trated HNO3,2a CAN,2b or NO in air.2c However, the
first method suffered from low yields and strongly acidic
conditions, which might effect other functional groups.
The reaction of CAN with epoxides was generally
carried out at high temperatures (80 ꢁC) and with
styrene oxide, the reaction afforded benzaldehyde as
the major product. Moreover, the regioselectivity of
the opening of some epoxides was poor.2b The reaction
of NO with epoxides2c and aziridines3 was found to re-
quire long reaction times (12–32 h). Thus an improved
method for ring opening of both epoxides and aziridines
with nitrate ions is still required.
In continuation of our work,4 on the development of
useful synthetic methodologies, we have found that
zirconyl nitrate can be utilized efficiently for the ring
opening of epoxides and aziridines to form the corres-
ponding b-nitrato-alcohols and -sulfonamides, respec-
tively (Scheme 1).
OH
O
ZrO(NO3)
O
2 . xH2O
O
ONO2
MeCN
r.t., 5 h
MeO
MeO
85%
1a
1h
2a
ZrO(NO3)
NHTs
2 . xH2O
NTs
MeCN
ONO2
r.t., 8 h
94%
2h
Scheme 1.
Keywords: Epoxide; Aziridine; Zirconyl nitrate; Ring opening; b-Nitrato-alcohols and -sulfonamides.
q Part 93 in the series, ‘Studies on novel synthetic methodologies.’ IICT Communication No. 060516.
*
Corresponding author. Tel./fax: +91 40 27160512; e-mail: biswanathdas@yahoo.com
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.06.114

6028
B. Das et al. / Tetrahedron Letters 47 (2006) 6027–6029
Table 1. Zirconyl nitrate mediated ring opening of epoxides and aziridinesa
Entry
a
Epoxide/aziridine 1
Product 2
Time (h)
5
Isolated yield (%)
85
OH
O
O
O
O
ONO2
MeO
MeO
Cl
OH
O
O
ONO2
b
4.5
87
Cl
OH
Cl
O
c
1
1
90
83
Cl
ONO2
OH
O
d
ONO2
ONO2
O
OH
e
f
0.5
1
94
80
90
O
O
ONO
2O
OH
ONO2
O
g
0.5
OH
ONO2
h
i
0.5
8
92
94
O
OH
NHTs
NTs
ONO2
NHTs
NTs
j
8
91
ONO2
ONO2
NTs
NHTs
k
l
1
70b
84
ONO2
NHTs
NTs
NTs
4.5
4.5
ONO2
m
83
NHTs
a The structures of the products were established from their spectral (IR, 1H, 13C NMR and MS) and analytical data and by comparison of the values
with those reported earlier for the known compounds.2,3
b The corresponding b-N-tosyl amino alcohol (18%) was also produced.
Several epoxides and N-tosylaziridines underwent ring
cleavage smoothly with zirconyl nitrate in MeCN at
room temperature (Table 1).5 Zirconyl nitrate is inex-
pensive and nontoxic. The reaction conditions are mild
and the experimental procedure is simple. No additional
catalyst was required for the reaction. The b-nitrato-
alcohols and -sulfonamides were produced in high
yields. The ring opening of both epoxides and aziridines
occurred with excellent regioselectivity. 2-Alkylepoxides
and N-tosyl-2-alkylaziridines yielded the products
formed by cleavage at the 3-position while 2-arylepox-
ides and N-tosyl-2-arylaziridines afforded the products
formed by opening at the benzylic position. Bicyclic
epoxides (Table 1, entries g and h) and aziridines (entries
l and m) were also cleaved efficiently with zirconyl
nitrate. In those cases, the nitrate ion approached from

B. Das et al. / Tetrahedron Letters 47 (2006) 6027–6029
6029
was added zirconyl nitrate (1.2 mmol). The mixture was
stirred at room temperature and the reaction was moni-
tored by TLC. After completion, the reaction was quenched
with water (10 mL) and the mixture was extracted with
EtOAc (3 · 5 mL). The combined organic extracts were
dried and concentrated to afford a crude product, which
was subjected to column chromatography (silica gel,
hexane–EtOAc, 9:1) to obtain pure b-nitrato-alcohols or
-sulfonamides.
the axial direction. The ring opening was completely
anti-stereoselective forming only the trans-isomers.5
The structures of the products were established from
1
13
their spectral (IR, H and C NMR and MS) data5
and by comparison of the values with those reported
1
for the known compounds.2,3 In the H NMR spectra,
the –CH2ONO2, >CHONO2 and Ar–CH(ONO2)– pro-
tons of similar systems related to the products are
known to resonate around d 4.5, 4.8 and 5.8, respec-
tively.2,3 The structures of the b-nitrato-alcohols and
-sulfonamides formed in the present conversion were
clearly derived with the help of these reported spectral
values.5 The 13C NMR spectra also supported the
The spectral (IR, 1H, 13C NMR and MS) and analytical
data of some representative products are given below.
Product 2a: Rf: 0.47 (silica gel, hexane–EtOAc, 7:3); IR
(KBr): mmax 3389, 1636, 1512, 1458 cmÀ1; 1H NMR (CDCl3,
200 MHz): d 7.12 (2H, d, J = 8.0 Hz), 6.80 (2H, d,
J = 8.0 Hz), 4.69–4.51 (2H, m), 4.23 (1H, m), 4.01 (2H, d,
J = 5.2 Hz), 3.52 (2H, t, J = 7.0 Hz), 3.31 (3H, s), 2.78 (2H,
t, J = 7.0 Hz), 2.02 (1H, br s); 13C NMR (CDCl3, 75 MHz);
d 157.2, 132.5, 130.0, 114.8, 73.8, 73.2, 68.7, 67.2, 58.8, 35.3;
FABMS: m/z 272 [M+H]+Å; Anal. Calcd for C12H17NO6:
C, 53.14; H, 6.27; N, 5.17%. Found: C, 53.27; H, 6.32; N,
5.12%.
Product 2e: Rf: 0.51 (silica gel, hexane–EtOAc, 7:3); IR
(KBr): mmax 3410, 1637, 1530, 1453 cmÀ1; 1H NMR (CDCl3,
200 MHz): d 7.41–7.28 (5H, m), 5.86 (1H, dd, J = 8.3,
3.8 Hz), 3.91 (1H, dd, J = 12.8, 8.3 Hz), 3.79 (1H, dd,
J = 12.8, 3.8 Hz), 2.18 (1H, br s); 13C NMR (CDCl3,
75 MHz); d 133.6, 129.2, 127.3, 127.0, 85.4, 67.3; FABMS:
m/z 184 [M+H]+Å; EIMS: m/z (%) 121 (M+ÅÀONO2)(12),
104(48); Anal. Calcd for C8H9NO4: C, 52.46; H, 4.92; N,
7.65%. Found: C, 52.63; H, 4.83; N, 7.72%.
1
proposed structures.2,3,5 In the H NMR spectra of the
nitrato-compounds derived from bicyclic epoxides and
aziridines, the coupling constants of the ring protons
adjacent to the –ONO2 and –OH (or –NHTs) groups
clearly suggested their trans-configuration.5 For exam-
ple, the J values of these two protons for 2g are 10.0,
9.2 and 4.3 Hz and 9.8, 9.2 and 4.3 Hz. The molecular
weight of each product was deduced from its FAB mass
spectrum. The EI mass spectra for products 2e and 2i
were also studied. These spectra showed m/z signals
corresponding to [M+ÅÀONO2].5
In conclusion, we have developed a simple and efficient
method for the preparation of b-nitrato-alcohols and
-sulfonamides by the ring opening of epoxides and azir-
idines using zirconyl nitrate at room temperature. High
yields and excellent regio- and stereoselectivity are the
advantages of this protocol.
Product 2g: Rf: 0.58 (silica gel, hexane–EtOAc, 7:3); IR
(KBr): mmax 3364, 1633, 1439 cmÀ1 1H NMR (CDCl3,
;
200 MHz): d 4.76 (1H, ddd, J = 10.0, 9.2, 4.3 Hz), 3.61 (1H,
ddd, J = 9.8, 9.2, 4.3 Hz), 2.92 (1H, br s), 2.22–2.02 (2H,
m), 1.88–1.63 (2H, m), 1.42–1.21 (2H, m); 13C NMR
(CDCl3,75 MHz); d 79.4, 75.2, 31.0, 28.6, 20.8; FABMS:
m/z 148 [M+H]+Å; Anal. Calcd for C5H9NO4: C, 40.82; H,
6.12; N, 9.52%. Found: C, 40.85; H, 6.21; N, 9.63%.
Product 2i: Rf: 0.53 (silica gel, hexane–EtOAc, 7:3); IR
Acknowledgments
(KBr): mmax 3392, 1612, 1483 cmÀ1 1H NMR (CDCl3,
;
The authors thank the CSIR and the UGC, New Delhi,
for financial assistance.
200 MHz): d 7.72 (2H, d, J = 8.0 Hz), 7.31 (2H, d,
J = 8.0 Hz), 5.41 (1H, d, J = 8.3 Hz), 4.32 (2H, d,
J = 5.3 Hz), 3.46 (1H, m), 2.44 (3H, s), 1.65 (1H, m), 1.44
(1H, m), 1.28 (1H, m), 1.21–1.02 (3H, m), 0.77 (3H, t,
J = 7.0 Hz); 13C NMR (CDCl3, 75 MHz); d 144.1, 137.5,
129.4, 127.0, 76.2, 56.1, 31.8, 26.2, 22.4, 13.8; FABMS: m/z
317 [M+H]+Å; EIMS: m/z (%) 254 (M+ÅÀONO2)(8), 170(6),
146(4); Anal. Calcd for C13H20N2O5S: C, 49.37; H, 6.33; N,
8.86%. Found: C, 49.13; H, 6.42; N, 8.71%.
Product 2k: Rf: 0.52 (silica gel, hexane–EtOAc, 7:3); IR
(KBr): mmax 3412, 1638, 1465, 1405 cmÀ1; 1H NMR (CDCl3,
200 MHz): d 7.67 (2H, d, J = 8.0 Hz), 7.31–7.18 (7H, m),
5.73 (1H, dd, J = 8.3, 5.3 Hz), 5.21(1H, t, J = 6.8 Hz),
3.32–3.18 (2H, m), 2.38 (3H, s); 13C NMR (CDCl3,
75 MHz); d 144.2, 136.6, 134.5, 129.4, 129.1, 128.7, 127.1,
126.2, 83.7, 45.4, 21.3; FABMS: m/z 337 [M+H]+Å; Anal.
Calcd for C15H16N2O5S: C, 53.57; H, 4.76; N, 8.33%.
Found: C, 53.32; H, 4.83; N, 8.14%.
Product 2m: Rf: 0.48 (silica gel, hexane–EtOAc, 7:3); IR
(KBr): mmax 3378, 1629, 1452, 1401 cmÀ1; 1H NMR (CDCl3,
200 MHz): d 7.79 (2H, d, J = 8.0 Hz), 7.31 (2H, d,
J = 8.0 Hz), 5.86 (1H, d, J = 6.8 Hz), 5.05 (1H, ddd,
J = 9.8, 9.1, 4.5 Hz), 3.56 (1H, m), 2.42 (3H, s), 2.12 (1H,
m), 1.88 (1H, m), 1.81–1.62 (2H, m), 1.58–1.47 (2H, m),
1.29–1.21 (2H, m); 13C NMR (CDCl3, 75 MHz); d 144.0,
137.2, 129.5, 127.1, 83.0, 53.6, 32.5, 28.7, 23.6, 23.2, 21.2;
FABMS: m/z 315 [M+H]+Å; Anal. Calcd for C13H18N2O5S:
C, 49.68; H, 5.73; N, 8.92%. Found: C, 49.91; H, 5.88; N, 8.70%.
References and notes
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5. General experimental procedure for the synthesis of b-
nitrato-alcohols and -sulfonamides: To a solution of
epoxide or N-tosylaziridine (1 mmol) in MeCN (5 mL)