Microwave-assisted cleavage of epoxides with amines in the presence of the catalytic Zn(OAc)2/1,7-bis(2-benzoic acid)-1,4,7-trioxaheptane (ZnBBATOH)

Article abstract of DOI:10.1081/SCC-200050944

We describe a highly regioselective ring opening of epoxides with aromatic amines in the presence of a catalytic amount of Zn(OAc)₂ and 1,7-bis(2-benzoic acid)-1,4,7-trioxaheptane under microwave irradiation. The yields of the amino alcohols ar

Full text of DOI:10.1081/SCC-200050944

This article was downloaded by: [The University of Manchester Library]
On: 23 November 2014, At: 13:45
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
Microwave‐Assisted Cleavage of Epoxides
with Amines in the Presence of the
Catalytic Zn(OAc)2/1,7‐Bis(2‐Benzoic
Acid)‐1,4,7‐Trioxaheptane (ZnBBATOH)
Hossein Eshghi a , Mohammad Rahimizadeh a & Abolhassan Shoryabi b
a Department of Chemistry , Ferdowsi University of Mashhad , Mashhad, Iran
b Department of Chemistry , Sistan and Baluchestan University , Zahedan,
Iran
Published online: 20 Aug 2006.
To cite this article: Hossein Eshghi , Mohammad Rahimizadeh & Abolhassan Shoryabi (2005)
Microwave‐Assisted Cleavage of Epoxides with Amines in the Presence of the Catalytic
Zn(OAc)2/1,7‐Bis(2‐Benzoic Acid)‐1,4,7‐Trioxaheptane (ZnBBATOH), Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:6, 791-798, DOI: 10.1081/
SCC-200050944
To link to this article: http://dx.doi.org/10.1081/SCC-200050944
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
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. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 35: 791–798, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200050944
Microwave-Assisted Cleavage of Epoxides
with Amines in the Presence of the Catalytic
Zn(OAc)2/1,7-Bis(2-Benzoic Acid)-1,4,7-
Trioxaheptane (ZnBBATOH)
Hossein Eshghi and Mohammad Rahimizadeh
Department of Chemistry, Ferdowsi University of Mashhad,
Mashhad, Iran
Abolhassan Shoryabi
Department of Chemistry, Sistan and Baluchestan University,
Zahedan, Iran
Abstract: We describe a highly regioselective ring opening of epoxides with aromatic
amines in the presence of a catalytic amount of Zn(OAc)2 and 1,7-bis(2-benzoic acid)-
1,4,7-trioxaheptane under microwave irradiation. The yields of the amino alcohols are
mostly good and the recovered catalyst could be reused several times.
Keywords: Amines, amino-alcohols, epoxide, microwave irradiation, ring opening
The b-amino alcohols are a major class of functional group in many important
biologically active natural and synthetic products.[1] Several clinically useful
skeletones, which exhibit a broad range of biological activities in anti-
obesity[2] and anti-hypertensives,[3] contains the b-amino-alcohol functional-
ity. The classical method for the preparation of b-amino alcohol involves
heating an epoxide in a protic solvent with excess amine. Although this non-
catalytic reaction is satisfactory in many cases, it has a number of limitations.
Received in the U.K. August 19, 2004
Address correspondence to Hossein Eshghi, Department of Chemistry,
Ferdowsi University of Mashhad, Mashhad 91775-1436, Iran. E-mail: heshghi@
hamoon.usb.ac.ir

792
H. Eshghi, M. Rahimizadeh, and A. Shoryabi
For example, the cleavage of epoxides by anilines using classical procedures
are difficult.[4] The reaction requires an excess of strong inorganic base or a
long reaction time, or both, and the yields of the corresponding secondary
alcohols are low.[5] Recently, new methods using activators or promoters
have been developed. These include Lewis acids such as BiCl3,[6]
CeCl3 7H2O-NaI,[7] TaCl5,[8] SmCl3,[9] diisopropoxyaluminium trifluoroace-
.
tate,[10] Cu(OTf)2, and Sn(OTf)2,[11] and other activating agents such as
alumina,[12] and trifluoroethanol, hexafluoro-2-propanol.[13] However, there
are still some limitations with these methods, such as the failure of deactivated
aromatic amines and some sterically hindered aromatic amines to open the
epoxides, the need for an excess of reagents and reflux temperature, and
sluggish reactions.
The efficiency of microwave irradiation in organic synthesis is recently
under intensive study.[14] There are only a few publications describing the
use of microwave irradiation for the ring opening of epoxides by amines.[15]
In conjunction with ongoing work in our laboratory on the macrocyclic
crown ethers (synthesis,[16] formation of complexes,[17] and catalytic regiose-
lective ring opening of epoxides,[18] we found that 1,7-bis(2-benzoic acid)-
1,4,7-trioxaheptane (BBATOH) efficiently catalyzed the ring opening of
epoxides with anilines under microwave irradiation with high regioselectivity.
Recently, we have prepared[16a] BBATOH and used it as a starting dicar-
boxylic acid material for the preparation of corresponding macrocyclic
diamides. In this study, we report the results of the reactions of some
epoxides with anilines in the presence of a catalytic amount of Zn(OAc)2
and BBATOH (ZnBBATOH, for short) (Scheme 1, Table 1).
The results of the reactions of cyclohexene oxide with aniline in the
presence of the ZnBBATOH catalyst are summarized in Table 1. They are
Scheme 1.

Cleavage of Epoxides with Amines
793
Table 1. Ring opening of cyclohexene oxide with aniline
Entry
Catalyst (mol%)
Reaction conditions
Yield (%)a
1
2
3
4
5
6
7
8
—
Zinc tartarate (10)
CH2Cl2/7 days
CH2Cl2/28 days
CH2Cl2/7 days
CH2Cl2/7 days
CH2Cl2/7 days
Solvent-free/15 min
MW/3 min
0
53[19]
95[19]
40
Zinc tartarate (50)
Zinc acetate (10)
Zinc acetate, BBATOH (10)
Zinc acetate, BBATOH (10)
Zinc acetate, BBATOH (10)
Zinc acetate (10)
96
94
98
67
MW/3 min
aYields refer to isolated yield.
compared with the corresponding results obtained by other applied catalysts.
Cleavage of the epoxide ring occurs in each case, and the corresponding amino
alcohol is obtained upon simple workup. The cleavage behaviors of cyclohex-
ene oxide with aniline in the absence or presence of catalyst are compared.
The yields of ring opening with this methodology are quite good, as shown
in Table 1. ZnBBATOH is a more effective catalyst under solvent-free con-
ditions and/or microwave irradiation than in solution; short reaction time
and lower catalyst loading (10 mol% versus 50 mol%) could be used. The
catalyst was easily recovered and could be reused several times. Generally,
the optimum amounts of the catalyst were found to be 0.1 mol per 1 mol of
epoxide and aniline.
The results obtained with some representative epoxides in the presence of
ZnBBATOH as the catalyst under microwave irradiation are summarized
in Table 2. With only the exception of styrene oxide (entries 10–12), when
unsymmetric epoxides were allowed to react in the presence of ZnBBATOH,
the ring opening took place in a completely regioselective fashion. The
attack at the less substituted oxirane carbon afforded the desired compound
as the only product. However, when styrene oxide was used in CH2Cl2, two
regioisomers in a 60:40 ratio were obtained, whereas, in the solvent-free
condition, mainly one isomer was obtained (90:10). On the other hand,
under microwave irradiation, the ring opening took place in a completely
regioselective fashion, by attacks to the benzylic carbon of the epoxide.
This observed reverse regioselectivity could be attributed to ionic nature of
styrene oxide reactions. This is confirmed by the observation that the
reaction of sterically hindered aromatic amine, for example, 2-acetylaniline,
with styrene oxide, in which the ring opening took place in a completely regio-
selective fashion (by attack at the benzylic carbon).
The stereoselectivity of the aminolysis reactions was anti as demonstrated
by the reaction of cyclohexane oxide with 2-acetylaniline, which exclusively
gave corresponding trans amino alcohols and confirmed by the coupling

794
H. Eshghi, M. Rahimizadeh, and A. Shoryabi
Table 2. Ring opening of various epoxides with amines catalyzed by ZnBBATOH
under microwave irradiation
Entry/product
number
Yield
(%)a
Epoxides
Products
1
2
98
87
3
4
80
78
5
6
76
87
7
8
78
88
(continued)

Cleavage of Epoxides with Amines
795
Table 2. Continued
Entry/product
number
Yield
(%)a
Epoxides
Products
9
75
10
11
83b
(40:60)
85c
(10:90)
12
13
85
89
aIsolated yield of pure product after column chromatography [(peterelium ether/
EtOAc (9:1)].
bThe reaction took place in CH2Cl2 for 7 days.
cThe reaction took place in solvent-free conditions for 20 min.
constants of the peaks at 3.3 ppm (CHNHAr) (ddd, J ¼ 10.3, 10.1, and 5.5 Hz)
1
and 3.5 ppm (CHOH) (ddd, 10.1, 8.5, and 4.1 Hz) in H-NMR (100 MHz)
1
spectra. All the compounds are fully characterized by H-NMR, IR, and
mass spectral data by comparison with the known compounds.[10–12,19,20] It
is interesting to note that in the above studies, aliphatic amines such as
n-buthyl amine, benzylamine, and iso-propylamine failed to react with
epoxides in the presence of a catalytic amount of ZnBBATOH under
microwave irradiation. This may be due to stronger complexation of
aliphatic amines with the catalyst because of their higher basicity (highly
exothermic reactions were observed in preliminarly grinding of reactants).
This type of behavior has been previously reported[6–9,11] with metal
catalysts. Evaporation of aliphatic amines in microwave conditions may be
another reason to stop the reaction.

796
H. Eshghi, M. Rahimizadeh, and A. Shoryabi
The cleavage of epoxides with aromatic amines is unique and highly
useful in organic synthesis. To the best of our knowledge, the above
catalyst is not used in ring-opening reactions of epoxides. A variety of
chiral derivatives of BBATOH can be complexed with zinc acetate for asym-
metric versions of these reactions, which are in progress in our laboratory.
EXPERIMENTAL SECTION
All materials and solvents were obtained from Merck chemical company
(Germany) and Fluka (Switzerland). IR spectra were recorded on a
Shimadzu-IR 470 spectrophotometer. 1H-NMR spectra were recorded on
Bruker-80 and 100 MHz instruments using tetramethylsilane (TMS) as an
internal standard. Mass spectra were determined on a Shimadzu GCMS-QP
1000 EX instrument at 70 eV. Irradiation was carried out in a domestic
microwave oven (Electra, 2450 MHz, and 800 W) for optimized time.
Elemental analyses were performed at the Research Institute of Petroleum
Industry of Iran. Columns chromatography was carried out on short
columns of silica gel 60 (230–400 mesh) in glass columns (2–3 cm
diameter) using 15–30 g of silica gel per 1 g of crude mixture. BBATOH
was obtained according to literature.[16a]
Cleavage of Epoxides with Aromatic Amines: General Procedure
.
A mixture of the Zn(OAc)2 2H2O (0.2 mmol) and 1,7-bis(2-benzoic acid)-
1,4,7-trioxaheptane (BBATOH) (0.2 mmol) was grounded in a mortar for
5 min. Then, epoxide (2 mmol) and aniline (2 mmol) were added to the
catalyst and the mixture was ground thoroughly in the mortar. Usually an
immediate color change was observed. The mortar was covered with a
watch glass and put inside the microwave oven. The mixture was irradiated
for 3 min. The completion of the reaction was monitored by TLC. After the
completion of the reaction, the mortar was removed from the oven, the
mixture was cooled to room temperature, and then chloroform (15 mL) was
added and the catalyst filtered off. The filtrate was washed with water
(2 ꢀ 15mL), passed through anhydrous MgSO4, and the solvent was distilled
off to give the respective amino alcohol. These were further purified by
column chromatography [silica gel, peterelium ether/EtOAc (9:1)]. Physical
properties of the products thus obtained were in good agreement with
reported data.[8–12,19–23] Spectral data of unknown compunds are given below.
1-[2-(2-Hydroxy-cyclohexylamino)-phenyl]-ethanone (2)
mp ¼ 99 8C (Lit.[8] semi solid). IR (neat): n ¼ 3400, 3300, 1630, 1240,
1160 cm21
.
1H-NMR (100 MHz, CDCl3): d ¼ 1.2–1.5 (m, 4H), 1.6–1.9

Cleavage of Epoxides with Amines
797
(m, 2H), 1.9–2.3 (m, 2 H), 2.45 (bs, 1H, OH), 2.54 (s, 3H), 3.30 (ddd, 1H,
J1 ¼ 10.3 Hz, J2 ¼ 10.1 Hz, J3 ¼ 5.5 Hz), 3.50 (ddd, 1H, J1 ¼ 10.1 Hz,
J2 ¼ 8.5 Hz, J3 ¼ 4.1 Hz), 6.6 (t, 1H, J ¼ 8 Hz), 6.9 (d, 1H, J ¼ 8 Hz), 7.3
(dt, 1H, J1 ¼ 8 Hz, J2 ¼ 1.5 Hz), 7.7 (dd, J1 ¼ 8. Hz, J2 ¼ 1.5 Hz), 8.9
(d, 1H, J ¼ 6.5 Hz). MS: m/z 233 (Mþ).
1-(2-Methoxy-phenoxy)-3-phenylamino-propan-2-ol (4)
Viscous liquid. IR (neat): n ¼ 3500, 3400, 1250, 1120 cm21
.
1H-NMR
(80 MHz, CDCl3): d ¼ 3.2–3.4 (m, 2H), 3.4–3.7 (m, 2H), 3.8 (s, 3H), 3.9–
4.3 (m, 3H), 6.5–6.8 (m, 3H), 6.9 (s, 4H), 7.0–7.3 (m, 2H). MS: m/z 273
(Mþ). Anal. calcd. for C16H19 NO3: C, 70.31; H, 7.01; N, 5.12. Found C,
70.35; H, 7.04; N, 5.32.
1-Phenylamino-3-o-tolyloxy-propan-2-ol (5)
1
Viscous liquid. IR (neat): n ¼ 3450, 1250, 1120 cm21. H-NMR (80 MHz,
CDCl3): d ¼ 2.2 (s, 3H), 2.8–3.4 (m, 2H), 3.4–3.7 (m, 2H), 3.7–4.4
(m, 3H), 6.3–6.9 (m, 5H), 6.9–7.3 (m, 4H). MS: m/z 257 (Mþ). Anal.
calcd. for C16H19 NO2: C, 74.68; H, 7.44; N, 5.44. Found C, 74.71; H, 7.50;
N, 5.48.
1-Phenylamino-3-m-tolyloxy-propan-2-ol (6)
viscous liquid. IR (neat): n ¼ 3500, 3400, 1250, 1150 cm21
.
1H-NMR
(80 MHz, CDCl3): d ¼ 2.3 (s, 3H), 3.0 (b, 2H), 3.1–3.6 (m, 2H), 3.8–4.4
(m, 3H), 6.4–6.8 (m, 5H), 6.9–7.3 (m, 4H). MS: m/z 257 (Mþ). Anal.
calcd. for C16H19 NO2: C, 74.68; H, 7.44; N, 5.44. Found C, 74.70; H, 7.47;
N, 5.47.
1-[2-(2-Hydroxy-1-phenyl-ethylamino)-phenyl]-ethanone (13)
mp ¼ 74–758C. IR (neat): n ¼ 3400, 3300, 1630, 1240, 1160 cm21. 1H-NMR
(100 MHz, CDCl3): d ¼ 2.5 (s, 3H), 3.0 (b, 1H), 3.8–4.06 (m, 2H), 4.6 (dd,
1H, J1 ¼ 12 Hz, J2 ¼ 5.5 Hz), 6.4–6.6 (m, 2H), 7.0–7.4 (m, 6H), 7.8 (dd,
1H, J1 ¼ 8.7 Hz, J2 ¼ 1.7 Hz), 9.52 (d, 1H, J ¼ 6 Hz). MS: m/z 255 (Mþ).
Anal. calcd. for C16H17 NO2: C, 75.27; H, 6.71; N, 5.49. Found C, 75.50;
H, 6.75; N, 5.52.
ACKNOWLEDGMENTS
We are thankful to Sistan and Baluchestan University for the partial support of
this work.

798
H. Eshghi, M. Rahimizadeh, and A. Shoryabi
REFERENCES
1. (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835;
(b) Kobayashi, S.; Ishitani, H.; Ueno, M. J. Am. Chem. Soc. 1998, 120, 431;
(c) Corey, E. J.; Zhang, F. Y. Angew. Chem., Int. Ed. Engl. 1999, 38, 1931;
(d) Rogers, G. A.; Parsons, S. M.; Anderson, D. C.; Nilsson, L. M.; Bahr, B. A.;
Kornreich, W. D.; Kaufman, R.; Jacobs, R. S.; Kirtman, B. J. Med. Chem. 1989,
32, 1217.
2. Gehlert, D. R.; Goldstein, D. J.; Hipskind, P. A. Ann. Rep. Med. Chem. 1999, 201.
3. Johannes, C. W.; Visser, M. S.; Weatherhead, G. S.; Hoveyda, A. H. J. Am. Chem.
Soc. 1998, 120, 8340.
4. Moller, F. Methoden der Organische Chemie (Houbenweyl), 4th Ed.; Muller, E.,
Ed.; Thieme-verlag: Sturttgart, 1957; Vol. 11/1, pp. 311–326.
5. (a) Posner, G. H.; Rogers, D. Z. J. Am. Chem. Soc. 1977, 99, 8208;
(b) Posner, G. H. Angew. Chem., Int. Ed. Engl. 1978, 17, 487.
6. Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2002, 43, 7891.
7. Rajender Reddy, L.; Arjun Reddy, M.; Bhanumathi, N.; Rama Rao, K. Synthesis
2001, 831.
8. Chandrasekhar, S.; Ramachandar, T.; Jaya Prakash, S. Synthesis 2000, 1817.
9. Fu, X.-L.; Wu, S.-H. Synth. Commun. 1997, 27, 1677.
10. Rampalli, S.; Chandhari, S. S.; Akamanchi, K. G. Synthesis 2000, 78.
11. Sekar, G.; Singh, V. K. J. Org. Chem. 1999, 64, 287.
12. Harrak, Y.; Pujol, M. D. Tetrahedron Lett. 2002, 43, 819.
´ ´
13. Das, U.; Crousse, B.; Kesavan, V.; Bonnet-Delpon, D.; Begue, J. P. J. Org. Chem.
2000, 65, 6749.
14. (a) Caddick, S. Tetrahedron. 1995, 51, 10403; (b) Loupy, A.; Petit, A.; Hamelin, J.;
Texier-Boullet, F.; Jacquault, P.; Mathe, D. Synthesis 1998, 1213.
15. Lidstrom, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron. 2001, 57, 9225.
16. (a) Sharghi, H.; Eshghi, H. Tetrahedron 1995, 51, 913; (b) Sharghi, H.; Eshghi, H.
J. Sci. I.R. Iran 1998, 9, 238; (c) Rahimizadeh, M.; Eshghi, H.; Rostami, F.;
Faghihi, H. Pol. J. Chem. 2005, 79, 73.
17. (a) Shamsipur, M.; Fakhari, A. R.; Sharghi, H.; Eshghi, H.; Ganjali, M. R. Pol.
J. Chem. 2002, 76, 1665; (b) Shamsipur, M.; Rouhani, S.; Ganjali, M. R.;
Sharghi, H.; Eshghi, H. Sens. Actuators, B 1999, 59, 30; (c) Shamsipur, M.;
Rouhani, S.; Sharghi, H.; Ganjali, M. R.; Eshghi, H. Anal. Chem. 1999, 71, 4938.
18. (a) Sharghi, H.; Massah, A. R.; Eshghi, H.; Niknam, K. J. Org. Chem. 1998, 63,
1455; (b) Eshghi, H.; Tayyari, S. F.; Sanchuli, E. Monatsh Chem. 2004, 135, 1101.
19. Yamashita, H. Bull. Chem. Soc. Jpn. 1988, 61, 1213.
20. Hou, X. I.; Wu, L.; Dai, L. X.; Xia, L. J.; Tang, M. H. Tetrahedron Asymmetry
1998, 9, 1747.
21. Sabitha, G.; Reddy, G. S.; Kumar, K.; Reddy, K. B.; Yadav, J. S. Synthesis 2003,
2298.
22. Zhao, P.-Q.; Xu, L.-W.; Xia, C.-G. Synlett 2004, 846.
23. Furukawa, M.; Ohkawara, T.; Noguchi, Y. Chem. Pharm. Bull. 1978, 26, 3556.