Mild regiospecific alcoholysis and aminolysis of epoxides catalyzed by zirconium(IV) oxynitrate

Article abstract of DOI:10.1016/j.tetlet.2015.09.031

A regiospecific method for the ring-opening reaction of epoxides by the primary, secondary, tertiary alcohols, and aryl, aliphatic amines has been developed using non-toxic metal nitrate salt as a catalyst. The best results were obtained using zirconium(IV) oxynitrate among the various screened metal nitrate salts. The reported protocol works efficiently for styrene epoxide and aliphatic as well.

Full text of DOI:10.1016/j.tetlet.2015.09.031

Accepted Manuscript
Mild Regiospecific Alcoholysis and Aminolysis of Epoxides Catalyzed by Zir-
conium(IV) oxynitrate
Sandip S. Shinde, Madhukar S. Said, Trupti B. Surwase, Pradeep Kumar
PII:
S0040-4039(15)30073-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.09.031
TETL 46703
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 August 2015
10 September 2015
11 September 2015
Please cite this article as: Shinde, S.S., Said, M.S., Surwase, T.B., Kumar, P., Mild Regiospecific Alcoholysis and
Aminolysis of Epoxides Catalyzed by Zirconium(IV) oxynitrate, Tetrahedron Letters (2015), doi: http://dx.doi.org/
10.1016/j.tetlet.2015.09.031
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Mild Regiospecific Alcoholysis and Aminolysis of Epoxides Catalyzed by Zirconium(IV) oxynitrate
Leave this area blank for abstract info.
Sandip S. Shinde,* Madhukar S. Said, Trupti B. Surwase and Pradeep Kumar*
Mild regiospecific method has been developed for ring-opening of epoxides with various general alcohols and amines using
zirconium(IV)oxynitrate as catalyst under solvent-free condition.

1
Tetrahedron Letters
Mild Regiospecific Alcoholysis and Aminolysis of Epoxides Catalyzed by
Zirconium(IV) oxynitrate
Sandip S. Shinde,* Madhukar S. Said, Trupti B. Surwase and Pradeep Kumar*
Organic Chemistry Division, National Chemical Laboratory, Dr. Homi Bhabha Road, Pune-411008, India.
Email: ss.shinde@ncl.res.in
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A regiospecific method for the ring-opening reaction of epoxides by the primary, secondary, tertiary
alcohols, and aryl, aliphatic amines has been developed using non-toxic metal nitrate salt as a catalyst.
The best results were obtained using zirconium(IV)oxynitrate among the various screened metal
nitrate salts. The reported protocol works efficientyl both for styrene epoxide and aliphatic as well.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Epoxide, Zirconia, Lewis acid,
Alcoholysis
Aminolysis
Introduction
advantageous as they are heterogeneous redox catalyst in
Epoxides represent an intrigue building block in bioscience
and organic research due to their reactivity and versatility as
an intermediate of numerous natural products.1
Stereoselective epoxidation followed by regio-specific
epoxide opening reactions are the key steps in construction
of the polyketide skeleton. Recent ionophore polyketide
biosynthesis of lasalocid, demonstrated that regioselective
epoxide opening affords natural type mono- or di-epoxides
in a sequential manner in enzyme catalyzed synthesis of
Lasalocid.2 In general, the ring opening of epoxide with
alcohols requires either strongly acidic or basic conditions
due to the poor nucleophilicity of alcohols.3 Numerous
methods have been developed to open the epoxide ring with
amines or alcohols as a nucleophile in the presence of Lewis
nature and have capability to activite the substrate by
coordination with the oxygen.16
In continuation of our research interest on developing a
more practical and new catalytic protocol for nucleophilic
substitution reactions,17 we herein report the epoxide
opening reaction with a variety of alcohols and amines in the
presence of various metal nitrates hydrates as catalyst.
Results and discussion,
The activity of various metal nitrates as a catalyst was examined
for the ring opening of epoxides using 2-[(Naphthalen-2-
yloxy)methyl]oxirane as a model substrate in tert-butanol (t-
BuOH) solvent at 45 C. The results are summarized in Table 1.
6
acids such as BF3.OEt2,4 Cu(BF4)2,5 Fe(Cp)2BF4/PF6,
8
Er(OTf)3,7 and Al(OTf)3 etc. However, many catalytic
Table 1. Alcoholysis of 2-[(Naphthalen-2-
yloxy)methyl]oxirane catalyzed by Metal
Nitrates.a
systems are associated with drawabacks such as tedious
work-up procedure, long reaction time and disposal of
hazardous chemicals, which prompted the organic researcher
to develop a simple and environmentally benign methods.9
Zirconium salt is reported as a green catalyst in various
organic transformation. 9, 10 Major attempts have focused on
making various solid-supported catalyst including Zircono-
silicate-nano
material
(Zr-Nano(PrTES)-ZSM-5),11
sulphated-Y-Zr salt12 as heterogeneous catalyst for the ring
opening of epoxides with alcohols. However, these methods
suffer from the tedious catalyst preparation, and also with
their limited application to aryl alcohols only.
Entry M(NO3) (20
mol%)
Yield Selectivity
comments
1
of 2a
ratio (%)c
(%)b
2a:2b
Recently, Y(NO3)2,13 ZrCl414 have been reported for epoxide
opening with amines. More recently, ZrO(NO3)2 has been
employed for ring opening reaction of epoxide in aprotic
solvent conditions.15 In addition, these metal nitrates are
1
2
-
100
32
-
Mg(NO3)2
6H2O
15
80:20
6% 2b

2
Tetrahedron
3
Ca(NO3)2
4H2O
-
40
58
62
90
76
53
72:28
89:11
93:7
8% 2b
Entry
R (alcohols)
Time (min)
Yield (%)b
4
5
6
7
8
Ni(NO3)2
6H2O
32
28
-
trace 2-
naphthol
1
2
methanol
5
98
97
Cu(NO2)2
6H2O
trace 2-
n-butanol
20
naphthol
ZrO(NO3)2
nH2O
96:4
3
4
5
benzyl alcohol
allyl alcohol
i-propanol
20
20
30
94
96
94
La(NO3)3
H2O
9
81:19
88:12
6
7
t-BuOH
40
80
87
91
ZrO(NO3)2
nH2O (1
mol%)
6
cyclohexanol
aAll reactions were carried out under same reaction condition
b
of entry 6 of table 1. isolated yield
9
ZrO(NO3)2
nH2O (0.5
equiv)
87
97: 3
96: 4
As illustrated in Table 2, the optimized conditions were
further extended to the ring opening of styrene epoxide with
various primary, secondary, and tertiary alcohols to examine
the scope of ZrO(NO3)2 nH2O as catalyst. These results
prove that several derivatives of primary alcohols, such as
benzylic, allylic and aliphatic, can easily be prepared
10d
ZrO(NO3)2
nH2O
trace 82
aAll reactions were carried out on a 1.0 mmol scale of epoxide
following
this
approach.
Similarly,
compounds
with t-BuOH (3 mL) in the presence of 20 mol% M(NO3)n nH2O
incorporating more hindered hydroxyl functionality can be
also accessed through this mild and simple approach.
Opening of styrene epoxide at benzylic position is favored
due to the stable carbo-cation generated leading to the β-
alkoxy alcohol as the major product.
b
at 45 C for 60 min. Isolated yield. cSelectivity determined by
d
crude 1H-NMR. Reaction carried out in CH2Cl2 (3 ml) using 10
equiv of t-BuOH for 4h.
Reactions catalyzed by alkaline earth Mg and Ca nitrate hydrates,
afforded 2a with other regio-isomer 2b in 6 to 8% respectively
(entries 2-3). Same reaction without use of catalyst did not give
any product and only starting material was recovered back (entry
1). Comparatively, the transition metal nitrates such as nickel,
copper and zirconyl showed moderate to good conversion with
high selectivity (entries 4-6). Reaction using nickel and copper
nitrate consumed >50% of SM to afford 58 and 62 % yield of the
desired product 2a respectively with byproduct 2-naphthol
detected in trace amount (entries 4-5). Zirconium(IV) oxynitrate
showed higher conversion with 96% regioselectivity for product
2a (entry 6). The reaction with less amount of zirconium (IV)
oxynitrate (1 mol %), resulted in only moderate yield of product,
even after prolonged reaction time (entry 8). Increase in the
catalyst amount did not affect the regio-selectivity and yield of
product significantly (entry 9). Co-solvent is known to be
excellent media for epoxide opening with Lewis acid catalyst,4
thus the same reaction was examined using t-BuOH (10 equiv)
and CH2Cl2 as co-solvent. However, it took longer time (4h) to
give the desired product 2a in 82% yield with excellent
regioselectivity (entry 10).
To extend the scope of reaction and examine the efficacy of
ZrO(NO3)2 nH2O, the alcoholysis was carried out with various
epoxides using different alcohols as shown in Table 3. It is
noteworthy that in case of naphthyloxy, phenyloxy substituted
epoxide reactions; ring opening takes place from less substituted
side of epoxide to afford the corresponding -alkoxy alcohols in
excellent yield (entries 1-5). However, tert-alcohol slightly took
longer time than primary alcohols but the regio-selectivity was
not affected. Linear alkyl substituted substrates provided
moderate yield (38-52%) of desired -alkoxy alcohols (entires 6-
8), which could probably be due to the competition of
mechanistic pathway for such type of aliphatic nucleophilic
epoxide ring opening.18 Further we carried out the ring opening
reactions on internal epoxides such as cyclopentyl and
cyclohexyl epoxides with primary secondary and tertiary
alcohols, the reaction resulted in exclusive formation of the trans-
products in quantitative yield (entries 9-12).
Table 2. Alcoholysis of Styrene Epoxide with various
Alcohols Catalyzed by Zirconium (IV) oxynitrate.a

3
Table 3. Alcoholysis of Epoxides Catalyzed by Zirconium (IV) oxynitrate at 45C.a
Entry Epoxised
Alcohol
Time(min) product
Yieldb
86
1
MeOH
20
2
3
i-propanol
n-pentanol
40
30
84
90
4
5
t-BuOH
50
55
86
83
6
EtOH
13h
21h
14h
50
44
38
52
94
83
7
8
EtOH
9
EtOH
10
i-propanol
120
11
12
t-BuOH
120
60
96
98
MeOH
a Unless otherwise indicated, all reactions were carried out on a 1.0 mmol scale of SM under same condition of entry 6 of Table 1.
bIsolated yield.

4
Tetrahedron
Table 4. Aminolysis of Epoxides Catalyzed by Zirconium(IV) Oxynitrate.a
Entry Epoxide
Amine
Product
Yield(%)b
86
1
2
3
87
82
4
5
6
7
91
94
83
82
8
9
91
78
10
93
11
97
aUnless otherwise indicated, all reactions were carried out on 1.0 mmol scale of SM with amine (1. 5 mmol) stirring at 45C for 20
min.

5
† Electronic Supplementary Information (ESI) available: [1H
Table 4 shows the extended scope of this protocol for ring
opening of epoxide with amines, such as aryl and cyclic
and 13C NMR of new compounds spectral data].
amine at 45 C for 20min. In the reaction of epoxide with
1
2
For Review on Epoxide opening sees: Bonini, C.; Righi,
G. Synthesis 1994, 225-238.
aryl amine, morpholine. the nucleophilic addition occurred
from the less-subsituted side, affording selectively β-
hydroxy amine products (entries 1-3). In contrast, the
reaction of styrene epoxide with morpholine or other aryl
amines afforded β-amino alcohols as single regio-selective
products (entries 4-8). The results obtained with respect to
regioselectivity are in agreement with earlier report of
zirconium phosphonate catalyzed ring opening of
epoxides.19 Notably, ring opening of epoxide was found to
be more efficient and general with diverse range of the
cyclic and heterocyclic amines such as morpholine, aniline,
2-amino naphthalene and imidazole efficiently leading to the
corresponding amino alcohol in excellent yield. the
cyclohexene epoxide was also successfully converted to
trans-β-hydroxy amine in quantitative yield (entry 10-11).
From the experiment, it is evident that, in case of aliphatic
epoxides steric effect predominates over electronic-
controlled factor thereby facilitating the attack at the less
hindered carbon atom of the epoxide ring. Overall, the
epoxide ring opening with amine and alcohol indicates that
ZrO(NO3)2 nH2O has shown best catalytic activity with wide
substrate scope as compared to the previously reported
bismuth triflate20 or Zr-silicate-nano particles.1
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Conclusion
An efficient ring-opening of epoxides by variety of alcohols and
amines is developed using zirconium oxynitrate hydrated salt as
catalyst. We believe this will present a better environmentally
benign protocol and should find widespread application in green
chemical reactions.
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677-682
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General procedure of alcoholysis and amynolysis: A mixture of
styrene epoxide (120 mg, 1.0 mmol) and t-butyl alcohol (3 ml)
[or morpholine (0.5 mL)] and ZrO(NO3)2 nH2O (46 mg, 20
mol%). The mixture was heated under stirring at 45 C. The
progress of reaction was monitored by GC-MS and TLC. After
completion, the reaction mixture was concentrated under the
reduced pressure. Then crude product was purified using column
cromatography (20% ethyl acetate:pet ether, rf 0.6) to afford
168.7 mg (87 %) of 2-tert-butoxy-2-phenylethanolas a white
solid. obs mp 76-78 C, reported mp 77-79 C; 6 1H NMR (500
MHz, CDCl3): δ = 7.39–7.28 (m, 5H), 4.65 (dd, J = 8.05, 4.39
Hz, 1H), 3.56–3.50 (m, 2H), 1.21 (s, 9H). 13C NMR (125 MHz,
CDCl3) 28.7, 67.8, 74.8, 75.1, 126.3, 127.2, 128.1, 142.2; HRMS
(EI) calcd for C12H18O2 (M+) 194.3068, found 194.3066.
Acknowledgements
S. S. Shinde would like to thank Department of Science and
Technology (DST), India for financial support in form of the Fast
Track Young scientist (SB/FT/CS-042/2013) and Ramanujan
fellowship (SR/S2/RJN-111/2012). We are grateful to Director
CSIR-NCL for his constant support and encouragement.
References and notes
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43, 7891-7893. (b) Ollevier, T.; Lavie-Compin, G.
Tetrahedron Lett. 2004, 45, 49-52.
Organic Chemistry Division, National Chemical Laboratory
(CSIR-NCL), Dr. Homi Bhabha Road, Pashan, Pune 411008,
India. Fax: +91- 020-25902627; Tel: +91-020-25902329; E-
mail: ss.shinde@ncl.res.in