Mg(ClO4)2, an efficient catalyst for synthesis of β-amino alcohols by ring opening of epoxides with amines under solvent-free conditions

Article abstract of DOI:10.1080/00397911003629473

Commercially available magnesium perchlorate is reported as an extremely efficient catalyst for the ring-opening reaction of epoxide with various primary and secondary amines, especially diphenyl amine, under solvent-free conditions at room temperature.

Full text of DOI:10.1080/00397911003629473

This article was downloaded by: [Illinois State University Milner Library]
On: 06 December 2012, At: 22:12
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
Mg(ClO4)2, an Efficient Catalyst for
Synthesis of β-Amino Alcohols by Ring
Opening of Epoxides with Amines under
Solvent-Free Conditions
Abbas Ali Jafari a & Moradgholi a
a Department of Chemistry, Faculty of Science, Yazd University,
Yazd, Iran
Version of record first published: 02 Feb 2011.
To cite this article: Abbas Ali Jafari & Moradgholi (2011): Mg(ClO4)2, an Efficient Catalyst for
Synthesis of β-Amino Alcohols by Ring Opening of Epoxides with Amines under Solvent-Free
Conditions, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 41:4, 594-602
To link to this article: http://dx.doi.org/10.1080/00397911003629473
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation
that the contents will be complete or accurate or up to date. The accuracy of any
instructions, formulae, and drug doses should be independently verified with primary
sources. The publisher shall not be liable for any loss, actions, claims, proceedings,
demand, or costs or damages whatsoever or howsoever caused arising directly or
indirectly in connection with or arising out of the use of this material.

Synthetic Communications1, 41: 594–602, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003629473
Mg(ClO4)2, AN EFFICIENT CATALYST FOR SYNTHESIS
OF b-AMINO ALCOHOLS BY RING OPENING OF
EPOXIDES WITH AMINES UNDER SOLVENT-FREE
CONDITIONS
Abbas Ali Jafari and Moradgholi
Department of Chemistry, Faculty of Science, Yazd University, Yazd, Iran
Abstract Commercially available magnesium perchlorate is reported as an extremely
efficient catalyst for the ring-opening reaction of epoxide with various primary and second-
ary amines, especially diphenyl amine, under solvent-free conditions at room temperature.
Keywords Amines; b-amino alcohols; epoxides; Mg(ClO4)2; ring opening; solvent-free
INTRODUCTION
Epoxides are versatile building blocks for the synthesis of many bioactive
natural products. They are an ideal source for diversity because they can be opened
with nucleophiles. They are well-known carbon electrophiles, and their ability to
undergo regioselective ring-opening reactions contributes to their synthetic
value.[1–4] Regioselective ring opening of epoxides with amines is an important
reaction in organic and medicinal chemistry as the resultant b-amino alcohols are
versatile intermediates. Thay have been used in biologically active natural products,
synthetic amino acids, b-blockers, insecticidal agents, chiral auxiliaries, and oxazo-
lines.[5,6] The classical synthesis of b-amino alcohols involves the heating of epoxide
with an excess of amines at elevated temperature.[7] However, these conditions are
not ideal, becuse epoxides are not tolerant with certain functional groups. Recently,
various methods have been reported using metal salts,[8–13] metal triflates,[14–17] and
some heterogeneous catalysts.[18–26] However, there are some limitations such as
Received October 25, 2009.
Address correspondence to Abbas Ali Jafari, Department of Chemistry, Faculty of Science, Yazd
University, Yazd 89195-741, Iran. E-mail: Jafari@yazduni.ac.ir
594

SYNTHESIS OF b-AMINO ALCOHOLS
595
longer reaction times, poor yields, use of expensive reagents in stoichiometric
quantities, use of hazardous organic solvents, and poor regioselectivity.
Since the beginning of the new century, green chemistry[27,28] has become a
major driving force in organic chemistry with pressure to develop environmentally
benign synthetic routes to materials. Performing reactions under solvent-free con-
ditions with solid catalysts could enhance their efficiency from an economic as well
as an ecological point of view, so solvent-free chemical reactions have received much
attention. These reaction conditions offer several advantages in preparative proce-
dures such as environmental compatibility, simplification of workup, formation of
cleaner products, enhanced selectivity, reduction of by-products and waste products,
and improved reaction rates. Therefore, there is a need to develop new methods for
the synthesis of b-amino alcohols using less hazardous solvents, or better, those that
do not need solvents at all. In addition, there is further scope to search for better
catalysts in terms of operational simplicity.
Magnesium perchlorate has emerged as a potential catalyst in various organic
transformations[29–31] because of its high catalytic activity, availability, and economic
viability. In this investigation, we report the catalytic potential of Mg(ClO4)2 for the
synthesis of b-amino alcohols at room temperature under solvent-free conditions.
RESULTS AND DISCUSSION
To determine the best experimental conditions, the reaction of phenyl glysidyl
ether (2 mmol) with 4-bromo-aniline (2.1 mmol) in the presence of a catalytic amount
of Mg(ClO4)2 in different solvents was the model reaction (Table 1). We observed
that the reaction did not proceed properly in solvent and that the desired product,
1-(4-bromophenylamino)-3-phenoxypropan-2-ol, was obtained in less than 80%
yield even after 24 h. In addition, because of the current challenges for developing
solvent-free and environmentally benign protocols,[13] we have studied the reaction
under solvent-free conditions in the presence of this catalyst. We have found that
solvent-free conditions were extremely suitable and efficient in which a lesser amount
of Mg(ClO4)2 (0.01 g, 2 mol%) was sufficient to complete the reaction in a very short
Table 1. Effect of solvent during the Mg(ClO4)2-catalyzed ring-opening reaction of phenyl glysidyl ether
(2 mmol) with 4-bromo-aniline (2.1 mmol) at room temperature
Entry
Solvent
Cat. (mol%)
Time
Yield (%)
1
2
3
4
8
6
7
5
CH2Cl2
CH3CN
5
5
24 h
24 h
80
50
n-Hexane
EtOH
5
24 h
24 h
60
65
5
Solvent-free
Solvent-free
Solvent-free
Solvent-free
5
5 min
15 min
1 h
90
93
2
1
—
90
NR
24 h

596
A. A. JAFARI AND MORADGHOLI
Table 2. Ring opening of epoxides with various amines catalyzed by Mg(ClO4)2 under solvent-free con-
ditions at room temperature
Yieldb
Entry
1
Epoxide
Amine
Producta
Time
4 min
(%)
97
2
4 min
90
3
4
15 min
93
96
7 h
5
6
60 min
15 min
97
98
7c
120 min
81
8
9
5 h
87
80
150 min
10
(PhCH2)2NH
30 min
97
(Continued )

SYNTHESIS OF b-AMINO ALCOHOLS
Table 2. Continued
597
Yieldb
(%)
Entry
Epoxide
Amine
Producta
Time
4.5 h
11
83
12
13
14
45 min
90 min
6 min
96
89
93
15c
120 min
74
16
17
5 min
93
93
30 min
18
8 min
98
19
180 min
97d
(Continued )

598
A. A. JAFARI AND MORADGHOLI
Table 2. Continued
Yieldb
(%)
Entry
20
Epoxide
Amine
Producta
Time
30 min
92
89
21
45 min
aAll the products were fully characterized by the usual spectroscopic techniques.
bYields refer to isolated yield.
c10 mol% Mg(ClO4)2 was used.
dThe ratio of a=b was 54=46.
time (15 min) with excellent regioselectivity. In the absence of the catalyst, a similar
reaction did not proceed under solvent-free conditions (Table 1, entry 5) even after
24 h. The results of this study are summarized in Table 1.
After this success, we employed similar reaction conditions to the ring opening
of phenyl glysidyl ether with different aromatic and aliphatic amines. All reactions
proceeded well in excellent yields with excellent regioselectivity, which the epoxide
rings were opened from the less-hindered site in the appropriate reaction times. This
type of ring opening shows that steric hindrance plays a major role in the ring-
opening reactions. The results of this investigation are summarized in Table 2
(entries 1–13). Primary and secondary amines react very rapidly. Aniline and its
derivatives with electron-donating substituents also react quite fast. However,
aminolysis of epoxides by anilines with electron-withdrawing substituents and
sterically hindered anilines required prolonged reaction times.
Further, to generalize this methodology, allyl and isopropyl glysidyl ether (as
electron-deficient epoxides), styrene oxide (as an aromatic substituted epoxide),
and cyclohexene oxide were treated with various amines in the presence of 2 mol%
Mg(ClO4)2 under these conditions (Table 2, entries 14–21). When cyclohexene oxide
was treated with anilines (entries 20 and 21), trans b-hydroxy substituted amine
products were obtained in excellent yields. The reaction of styrene oxide with aniline
Scheme 1. Proposed mechanism of the reaction of epoxide with amine catalyzed by Mg(ClO4)2.

SYNTHESIS OF b-AMINO ALCOHOLS
599
Table 3. Comparison of the ring-opening reaction of phenyl glysidyl ether with aniline catalyzed by
Mg(ClO4)2 and some other reported catalyst
Entry
Cat. (mol%)
Solvent
Temp. (ꢀC) Time (min) Yield (%) Ref.
1
2
3
4
5
6
7
8
9
H2NSO3H (10)
Montmorillonite K10 (30 mg)
NaY zeolite (50 mg)
Cu(BF4)2 (10)
—
—
rt
rt
90
180
300
12
90
100
95
25
26
21
12
11
23
9
—
—
35
rt
97
91
SnCl4 (5)
Bi(OTf)3 (2)
—
Molten TBAB
50
70
rt
600
15
84
ZrCl4 (5)
FeCl3 ꢁ 6H2O (5)
Mg(ClO4)2 (2)
—
—
—
15
100
88
50
rt
720
4
11
—
97
proceeded well, and the epoxide ring was opened from the more hindered cite with
excellent regioselectivity in a short reaction time. In the case of the reaction of styr-
ene oxide with morpholine, because of the steric effect, the mixture of two products
was produced in 54=46 ratio (Table 2, entry 19). The ring-opening reaction from the
more hindered site of styrene oxide indicates the carbocationic character of the inter-
mediate during the progress of the reaction. The results of this study are tabulated in
1
Table 2. The regioselectivity was determined by H and 13C NMR.
The possible mechanism of the reaction involved activation of the epoxide ring
and is presented in Scheme 1. Mg(ClO4)2 activated the epoxide ring through coordi-
nation with oxygen of epoxide to increase the susceptibility of the epoxide ring to
nucleophilic attack of the nitrogen atom.
This protocol is versatile; both aromatic and aliphatic amines could be
employed in contrast to a large number of reports that describe the epoxide opening
only by aromatic amines. The most important contribution is probably the success in
the aminolysis of epoxide with diphenylamine for the synthesis of new b-amino alco-
hols derived from diarylamine in good yields (Table 2, entries 7 and 15).
To show the merit of Mg(ClO4)2 in comparison with the other catalysts used
for a similar reaction, we have tabulated some of the results in Table 3. As is evident
from the results, the required ratio for most catalysts used for this purpose is
>2 mol% and the required reaction times are much longer (12 h).
CONCLUSION
In conclusion, the present procedure provides an efficient methodology for the
synthesis of b-amino alcohols via ring-opening reaction of epoxide with amine. The
notable advantages offered by this method are the use of relatively cheap commercially
available Mg(ClO4)2, short reaction time, applicability to both aromatic and aliphatic
amines, good yields of products, excellent regioselectivity, and solvent-free conditions.
EXPERIMENTAL
General Remarks
Chemicals were purchased from Merck and Fluka Chemical Companies. All
the products are known and were characterized by comparison of their physical data

600
A. A. JAFARI AND MORADGHOLI
with those reported in the literature. Infrared (IR) spectra were run on a Shimadzu
model 8300 Fourier transform (FT)–IR spectrophotometer. NMR spectra were
recorded on a Bruker Avance DPX 250- or 500-MHz instrument. The purity of
the products and the progress of the reactions were monitored by thin-layer
chromatography (TLC) on silica-gel polygram SILG=UV254 plates.
General Procedure for the Reactions of Epoxide with Amine
Catalyzed by Mg(Clo4)2 Under Solvent-Free Conditions
Mg(ClO4)2 (4.5 mg, 2 mol%) was added to a magnetically stirred mixture of
epoxide (2.0 mmol) and amine (2.1 mmol) under solvent-free conditions for the
appropriate reaction time (Table 2). The progress of the reaction was monitored
by TLC. After completion of the reaction, 10 mL of an organic solvent (Et2O or
EtOAc) were added to the reaction mixture, and the organic layer was washed with
10 mL of water and dried over anhydrous Na2SO4. Evaporation of the solvent under
diminished pressure resulted in almost-pure products in good to excellent yields
(Tables 2). For further purification (especially entries 7, 13, and 15 of Table 2),
the collected products were purified by column chromatography on silica gel eluted
with EtOAc = petroleum ether to afford the highly pure products.
Selected Spectral Data for New Compounds
1-Diphenylamino-3-phenoxy-propan-2-ol (Table 1, Entry 7). 1H NMR
(500 MHz, CDCl3): 7.36–7.32 (m, 6H), 7.15 (dd, J1 ¼ 8.6 Hz, J2 ¼ 1.0 Hz, 4H),
7.06–7.03 (m, 3H), 6.95 (dd, J1 ¼ 8.6 Hz, J2 ¼ 1.0 Hz, 2H), 4.42–4.38 (m, 1H),
4.14–4.06 (m, 3H), 4.02 (dd, J1 ¼ 15.0 Hz, J2 ¼ 7.1 Hz, 1H), 2.56 (br, 1H, OH)
ppm; 13C NMR (125.8, CDCl3): 158.9, 148.7, 130.0, 129.9, 122.4, 121.8, 121.7,
115.1, 70.1, 68.5, 55.6 ppm; IR (KBr): n ¼ 3452, 3060, 2925, 1589, 1495, 1456 cmꢂ
1. C21H21NO2 (319.40): calcd. C, 78.97; H, 6.63. Found: C, 78.85; H, 6.56.
1-Diphenylamino-3-isopropoxy-propan-2-ol (Table 1, Entry 15). 1H
NMR (500 MHz, CDCl3): 7.37–7.34 (m, 4H), 7.17 (d, J ¼ 7.7 Hz, 4H), 7.05 (t,
J ¼ 7.3 Hz, 2H), 4.17–4.13 (m, 1H), 4.01 (dd, J1 ¼ 14.9 Hz, J2 ¼ 6.4 Hz, 1H), 3.90
(dd, J1 ¼ 14.9 Hz, J2 ¼ 6.5 Hz, 1 H), 3.66–3.60 (m, 2H), 3.53 (dd, J1 ¼ 9.5 Hz,
J2 ¼ 5.5 Hz, 1H), 2.78 (br, 1H, OH), 1.24 (t, J ¼ 6.1 Hz, 6H) ppm; 13C NMR
(125.8, CDCl3): d ¼ 148.8, 129.8, 122.0, 121.7, 72.7, 70.1, 68.9, 55.5, 22.5; IR
(KBr): n ¼ 3452, 3060, 2925, 1589, 1495, 1456 cmꢂ1. C18H23NO2 (285.38): calcd.
C, 75.76; H, 8.12. Found: C, 75.23; H, 8.05.
ACKNOWLEDGMENT
The authors are thankful to the Research Council of Yazd University for finan-
cial support.
REFERENCES
1. Parker, R. E.; Isaacs, N. S. Mechanisms of epoxide reactions. Chem. Rev. 1959, 59, 737–799.
2. Bonini, C.; Righi, G. Regio- and chemoselective synthesis of halohydrines by cleavages of
oxiranes with metal halides. Synthesis 1994, 225–238.

SYNTHESIS OF b-AMINO ALCOHOLS
601
3. Rao, A. S.; Paknikar, S. K.; Kirtane, J. G. Recent advances in the preparation and
synthetic applications of oxiranes. Tetrahedron 1983, 39, 2323–2367.
4. Smith, J. G. Synthetically useful reactions of epoxides. Synthesis 1984, 629–656.
5. Ager, D. J.; Prakash, I.; Schaad, D. R. 1,2-Amino alcohols and their heterocyclic
derivatives as chiral auxiliaries in asymmetric synthesis. Chem. Rev. 1996, 96, 835–875.
6. Bose, D. S.; Narsaiah, A. V. An efficient asymmetric synthesis of (S)-atenolol: Using
hydrolytic kinetic resolution. Bioorg. Med. Chem. 2005, 627–630.
7. Deyrup, J. A.; Moyer, C. L. 1,2,3-Oxathiazolidines heterocyclic system. J. Org. Chem.
1969, 34, 175–179.
8. Reddy, L. R.; Reddy, M. A.; Bhanumati, N.; Rao, K. R. Cerium chloride–catalysed
cleavage of epoxides with aromatic amines. Synthesis 2001, 831–832.
9. Chakraborti, A. K.; Kondaskar, A. ZrCl4 as a new and efficient catalyst for the opening of
epoxide rings by amines. Tetrahedron Lett. 2003, 44, 8315–8319.
10. Firouzabadi, H.; Iranpoor, N.; Khoshnood, A. Aluminum tris (dodecyl sulfate) trihydrate
Al(DS)3 ꢁ 3H2O as an efficient Lewis acid–surfactant-combined catalyst for organic reac-
tions in water: Efficient conversion of epoxides to thiiranes and to amino alcohols at room
temperature. J. Mol. Catal. A: Chem. 2007, 274, 109–115.
11. Zhao, P. Q.; Xu, L. W.; Xia, C. G. Transition metal–based Lewis acid – catalyzed ring
opening of epoxides using amines under solvent-free conditions. Synlett 2004, 846–850.
12. Kamal, A.; Ramu, R.; Azhar, M. A.; Khanna, G. B. R. Copper(II) tetrafluoroborate–
catalyzed ring-opening of epoxides by amines. Tetrahedron Lett. 2005, 46, 2675–2677.
13. Maheswara, M.; Rao, K. S. V. K.; Do, J. Y. Regioselective ring opening of epoxides with
amines using Zn(ClO4)2–Al2O3 as a heterogeneous and recyclable catalyst. Tetrahedron
Lett. 2008, 49, 1795–1800.
14. Ollevier, T.; Lavie-Compin, G. Bismuth triflate–catalyzed mild and efficient epoxide
opening by aromatic amines under aqueous conditions. Tetrahedron Lett. 2004, 45, 49–52.
15. Procopio, A.; Gaspari, M.; Nardi, M.; Oliverio, M.; Rosati, O. Highly efficient and
versatile chemoselective addition of amines to epoxides in water catalyzed by erbium(III)
triflate. Tetrahedron Lett. 2008, 49, 2289–2293.
16. Mancilla, G.; Femenıa-Rıos, M.; Macıas-Sanchez, A. J.; Collado, I. G. Sn(OTf)2-
catalysed regioselective styrene oxide ring opening with aromatic amines. Tetrahedron
2008, 64, 11732–11737.
17. Ollevier, T.; Nadeau, E. Microwave-enhanced bismuth triflate–catalyzed epoxide opening
with aliphatic amines. Tetrahedron Lett. 2008, 49, 1546–1550.
18. Curini, M.; Epifano, F.; Marcotullio, C. M.; Rosati, O. Zirconium sulfophenyl phospho-
nate as a heterogeneous catalyst in the preparation of b-amino alcohols from epoxides.
Eur. J. Org. Chem. 2001, 4149–4152.
19. Danafar, H.; Yadollahi, B. (TBA)4PFeW11O39 ꢁ 3H2O-catalyzed efficient and facile
ring-opening reaction of epoxides with aromatic amines. Catal. Commun. 2009, 10,
842–847.
20. Hosseini-Sarvari, M.; Sharghi, H. Sulfamic acid – catalyzed ring opening of epoxides with
amines under solvent-free conditions. J. Iran. Chem. Soc. 2008, 5, 384–393.
21. Kureshy, R. I.; Singh, S.; Khan, N. H.; Razi Abdi, S. H.; Suresh, E.; Jasra, R. V. Efficient
method for ring opening of epoxides with amines by NaY zeolite under solvent-free
conditions. J. Mol. Catal. A: Chem. 2007, 264, 162–169.
22. Reddy, Y. V.; Saraswathy, M.; Rao, B. V.; Shekaram, T. Polymer-supported copper
sulphate – promoted aminolysis of epoxides with aromatic amines. Catal. Commun.
2006, 7, 466–471.
23. Khodaei, M. M.; Khosropour, A. R.; Ghozati, K. A powerful, practical, and chemoselec-
tive synthesis of 2-anilinoalkanols catalyzed by Bi(TFA)3 or Bi(OTf)3 in the presence of
molten TBAB. Tetrahedron Lett. 2004, 45, 3525–3529.

602
A. A. JAFARI AND MORADGHOLI
24. Bhanushali, M. J.; Nandurkar, N. S.; Bhor, M. D.; Bhanage, B. M. Y(NO3)3 ꢁ 6H2O-
catalyzed regioselective ring opening of epoxides with aliphatic, aromatic, and heteroaro-
matic amines. Tetrahedron Lett. 2008, 49, 3672–3676.
25. Kamal, A.; Prasad, B. R.; Reddy, A. M., Khan, M. N. A. Sulfamic acid as an efficient and
recyclable catalyst for the ring opening of epoxides with amines and anilines: An easy
synthesis of b-amino alcohols under solvent-free conditions. Catal. Commun. 2007, 8,
1876–1880.
26. Chakraborti, A. K.; Kondaskar, A.; Rudrawar, S. Scope and limitations of montmoril-
lonite K-10 – catalysed opening of epoxide rings by amines. Tetrahedron 2004, 60,
9085–9091.
27. Tanaka, K.; Toda, F. Solvent-free organic synthesis. Chem. Rev. 2000, 100, 1025–1074.
28. Varma, R. S. Solvent-free organic syntheses using supported reagents and microwave
irradiation. Green Chem. 1999, 43–55.
29. Bhagat, S.; Chakraborti, A. K. An extremely efficient three-component reaction of
aldehydes=ketones, amines, and phosphites (Kabachnik–Fields reaction) for the synthesis
of a-aminophosphonates catalyzed by magnesium perchlorate. J. Org. Chem. 2007, 72,
1263–1270.
30. Wu, J.; Sun, W.; Xia, H.-G.; Sun, X. A facile and highly efficient route to a-amino
phosphonates via three-component reactions catalyzed by Mg(ClO4)2 or molecular iodine.
Org. Biomol. Chem. 2006, 4, 1663–1666.
31. Bartoli, G.; Bosco, M.; Dalpozzo, R.; Marcantoni, E.; Massaccesi, M.; Rinaldi, S.;
Sambria, L. Mg(ClO4)2 as a powerful catalyst for the acylation of alcohols under
solvent-free conditions. Synlett 2003, 39–42.