Graphite oxide: A simple and efficient solid acid catalyst for the ring-opening of epoxides by alcohols

Article abstract of DOI:10.1016/j.tetlet.2014.10.050

A simple, efficient, and general procedure for the ring-opening of epoxides with various alcohols to give the corresponding β-alkoxy alcohols using graphite oxide (GO) as the catalyst, under very mild reaction conditions is described. The method proceeds in good to excellent yields and in short reaction times at room temperature under metal-free conditions.

Full text of DOI:10.1016/j.tetlet.2014.10.050

Accepted Manuscript
Graphite oxide: a simple and efficient solid acid catalyst for the ring-opening of
epoxides by alcohols
Maryam Mirza-Aghayan, Mahdi Alizadeh, Mahdieh Molaee Tavana, Rabah
Boukherroub
PII:
S0040-4039(14)01733-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2014.10.050
TETL 45279
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
7 July 2014
10 September 2014
8 October 2014
Please cite this article as: Mirza-Aghayan, M., Alizadeh, M., Tavana, M.M., Boukherroub, R., Graphite oxide: a
simple and efficient solid acid catalyst for the ring-opening of epoxides by alcohols, Tetrahedron Letters (2014),
doi: http://dx.doi.org/10.1016/j.tetlet.2014.10.050
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphite oxide: a simple and efficient solid acid catalyst for the
ring-opening of epoxides by alcohols
Maryam Mirza-Aghayan, Mahdi Alizadeh, Mahdieh Molaee Tavana, Rabah Boukherroub
A simple, efficient and general procedure for the ring-opening of epoxides with various alcohols to give the
corresponding β-alkoxy alcohols using graphite oxide (GO) as the catalyst under very mild reaction conditions is
described.

Graphite oxide: a simple and efficient solid acid
catalyst for the ring-opening of epoxides by alcohols
Maryam Mirza-Aghayana,*, Mahdi Alizadeh,a Mahdieh Molaee Tavanaa,
Rabah Boukherroubb
a Chemistry and Chemical Engineering Research Center of Iran
(CCERCI), P. O. BOX 14335-186, Tehran, Iran
b Institut de Recherche Interdisciplinaire (IRI, USR 3078), Parc de la Haute Borne, 50
Avenue de Halley-BP 70478, 59658 Villeneuve d’Ascq, France
Abstract
A simple, efficient and general procedure for the ring-opening of epoxides with
various alcohols to give the corresponding β-alkoxy alcohols using graphite oxide
(GO) as the catalyst, under very mild reaction conditions is described. The method
proceeds in good to excellent yields and in short reaction times at room temperature
under metal-free conditions.
Keywords: Epoxide; Ring-opening; Graphite oxide; Metal-free conditions.
Epoxides are useful and valuable intermediates because of their versatility and
reactivity with a large range of nucleophiles such as alcohols, amines and thiols.1 The
ring-opening of epoxides by the addition of alcohols leads to synthetically important
β-alkoxy alcohols.2 This reaction can be catalyzed under basic or acidic conditions.
Several Lewis2a-c,3a-d and Brønsted acids,2e,3e porphyrin complexes,3f perchlorates3g
and triflates3h have been used as catalysts for the activation of epoxides to
nucleophilic attack. For example, bis(cyclopentadienyl)zirconium dichloride
catalyzed ring-opening reactions of epoxides to give β-alkoxy alcohols occur in good
to excellent yields.2b Bradley and co-workers found that Al(OTf)3 (at ppm levels) was
an effective catalyst for the ring-opening of epoxides using a wide range of alcohols.2d
* Corresponding author: m.mirzaaghayan@ccerci.ac.ir
Tel.: +98 21 44580720; Fax: +98 2144580777

Heterogeneous catalysts such as metal-organic frameworks,4a mesoporous
aluminosilicate,4b mesoporous activated carbon,4c propylsulfonic acid functionalized
SBA-15 (SBA-15-pr-SO3H)4d and mesoporous AlKIT-54e have also been investigated
for the ring-opening of epoxides.
Graphite oxide (GO), prepared by exhaustive oxidation of graphite, has been used as a
heterogeneous catalyst for several organic transformations.5 We have reported on the
use of GO as a highly efficient reagent for the oxidation of 1,4-dihydropyridines into
pyridine derivatives.6 More recently, GO and Oxone have been successfully applied
for the direct oxidative ester formation from aldehydes and alcohols under
ultrasonication.7 The surface of GO comprises different oxygen-containing groups
such as hydroxyl, epoxy and carbonyl, which confer an acidic character to the
material. This property has recently been applied for the esterification of organic acids
with alcohols under mild conditions.8 In continuation of our investigations on the use
of GO for organic transformations,6-10 we report herein a new and simple method for
the ring-opening of epoxides by various alcohols using GO as a solid acid catalyst
under very mild metal-free reaction and conditions (Scheme 1).
Scheme 1. Alcoholysis of epoxides using GO.
The experimental procedure is quite simple and straightforward. Initially, we tested
the efficacy of GO, a readily available and inexpensive material, for this chemical
transformation by screening the reaction of styrene oxide (1 mmol) with n-butanol (3
mmol) under different conditions. The resulting mixture was stirred for the time
indicated in Table 1 prior to GC/MS analysis. The reaction of styrene oxide (1 mmol)
with n-butanol (3 mmol) in the absence of GO led to recovery of the starting
materials, even after stirring at room temperature for 24 hours (entry 1, Table 1).
When the reaction of styrene oxide (1 mmol) with n-butanol (3 mmol) was performed
in the presence of 50 mg or 25 mg of GO, an exothermic reaction took place and the
corresponding alcohol, 2-butoxy-2-phenylethanol, was obtained in 59% and 66%
yield after 5 minutes, respectively (entries 2 and 3, Table 1). It should be noted that
several unknown compounds were observed in the GC/MS spectra. Decreasing the
3

amount of GO to 12 mg and 1 mg gave 2-butoxy-2-phenylethanol in 79% and 90%
yields after 30 minutes and 105 minutes, respectively (entries 4 and 5, Table 1). Thus
1 mg of GO was found to be sufficient for this reaction. We also investigated this
reaction in dichloromethane as the solvent and the obtained results indicated a
decrease in the yield to 64% and an increase of the reaction time to 195 minutes (entry
6, Table 1). Using 5 mmol of n-butanol (instead of 3 mmol) led to an increase of the
reaction yield to 94% and a decrease of the reaction time to 90 minutes for the
alcoholysis of styrene oxide using GO (1 mg) under solvent-free conditions (entry 7,
Table 1).
Table 1. Optimization of the reaction conditions for the ring-opening of styrene oxide
with n-butanol.a
Entry
GO
(mg)
-
n-Butanol
(mmol)
3
Time
(min)
24
Yield
(%)
-
1
2
50
3
5
59
25
12
3
4
3
3
5
66
79
30
5
6
7
1
1
1
3
3
5
105
195
60
90
64b
94
a Conditions: a mixture of styrene oxide (1 mmol), n-butanol and GO was stirred at room temperature
for the time indicated.
b The reaction was performed in CH2Cl2 as the solvent.
Under the optimized conditions, a wide range of epoxides (1 mmol) was converted
into the corresponding alcohols in good to excellent yields by treatment with various
alcohols (5 mmol) in the presence of GO (1 mg) at room temperature for the time
indicated in Table 2.11 Under these experimental conditions, the methanolysis of
styrene oxide in the presence of GO afforded 2-methoxy-2-phenylethanol in 94%
yield after 30 minutes (entry 1, Table 2). Similarly, the alcoholysis of styrene oxide
with ethanol, n-propanol, allyl alcohol, n-butanol and n-pentanol gave 2-ethoxy-2-
4

phenylethanol, 2-propoxy-2-phenylethanol, 2-(allyloxy)-2-phenylethanol, 2-butoxy-
2-phenylethanol and 2-(pentyloxy)-2-phenylethanol in 56-94% yields after 30-120
minutes (entries 2, 3, 5, 6 and 9, Table 2). We also investigated the alcoholysis of
styrene oxide with acyclic and cyclic secondary alcohols such as i-propanol, 2-
butanol and cyclohexanol. The results obtained indicated that a long reaction time
was required for epoxide ring-opening with secondary alcohols. Indeed, 2-iso-
propoxy-2-phenylethanol, 2-(sec-butoxy)-2-phenylethanol and 2-(cyclohexyloxy)-2-
phenylethanol were obtained in 86%, 84% and 94% yields after 5, 6 and 4.5 hours,
respectively (entries 4, 7 and 10, Table 2). The efficiency of this procedure was also
demonstrated for the alcoholysis of styrene oxide with the tertiary alcohol, t-butanol,
and 2-(tert-butoxy)-2-phenylethanol was isolated in 91% yield after 7 hours (entry 8,
Table 2). The reaction of benzyl alcohol with styrene oxide afforded 2-(benzyloxy)-
2-phenylethanol in 70% yield after two hours at room temperature (entry 11, Table
2).
It should be noted that the alcoholysis of styrene oxide was remarkably
regioselective and occurred at the more highly substituted carbon atom of the
epoxide ring.2d, 3b-c The nucleophilic attack on the sterically more hindered position
of the epoxide suggests that the reaction is controlled by electronic effects. In this
case, electronic effects dominate over steric effects; the transition state carbocation at
the secondary carbon atom is stabilized through resonance with the phenyl ring,
thereby promoting nucleophilic attack at this position. Indeed, the regioselectivity of
this reaction can be proved by analysis of the MS spectra. We observed a mass ion
[M-CH2OH]+ due to the Marknikov-type products in the mass spectrum, which
would not be observed for anti-Marknikov-type products.
In contrast, the methanolysis of 2-ethyloxirane provided two isomers: 2-
methoxybutan-1-ol and 1-methoxybutan-2-ol in 38% and 58% yield (1:1.5 mole
ratio), respectively. In this case, the reaction is not regioselective and two isomers
resulting from attack at either end of the epoxide ring were observed.
Furthermore, we investigated the methanolysis of 2-(butoxymethyl)oxirane, 2-
[(allyloxy)methyl]oxirane and 2-(phenoxy)methyloxirane under similar conditions.
1-Butoxy-3-methoxypropan-2-ol, 1-(allyloxy)-3-methoxypropan-2-ol and 1-
methoxy-3-phenoxypropan-2-ol were isolated in 81%, 25% and 38% yields after 5, 2
and 2 hours, respectively (entries 13-15, Table 2). The results obtained suggest that
5

alcoholysis of the epoxide is regioselective and that nucleophilic attack occurs at the
less hindered carbon atom of the epoxide ring. In these cases, steric effects dominate
over electronic effects. Increasing the amount of GO to 10 mg led to higher yields of
the expected products (entries 14 and 15, Table 2).
Table 2. Alcoholysis of epoxides catalyzed by GO.a
Entry
Epoxide
Alcohol
methanol
ethanol
Product
Time
(h)
Yieldb
(%)
1
2
3
0.5
0.5
0.5
943e
724b
904b
n-propanol
4
i-propanol
5
864b
5
6
allyl alcohol
0.5
1
5612
942d
n-butanol
7
2-butanol
6
843e
8
t-butanol
7
912d
84
9
n-pentanol
cyclohexanol
2
10
11
4.5
943h
2
1
5
7013
benzyl alcohol
methanol
38/582d
8114
12
13
14
15
methanol
2
2
2515
67c
methanol
methanol
2
2
384b
72c
a Conditions: a mixture of epoxide (1 mmol), alcohol (5 mmol) and GO (1 mg) was reacted at room temperature
for the time indicated in Table 2.
6

b Isolated yield.
c 10 mg of GO was used.
In summary, the described procedure using graphite oxide as a solid acid catalyst
provides a very simple and efficient method for the ring-opening of a wide range of
epoxides by a variety of alcohols at room temperature. The alcoholysis of epoxides
in the presence of GO afforded the corresponding alcohols in good to very high
yields and in short reaction times, under metal-free and mild conditions with
excellent regioselectivity.
References
1. (a) Robinson, M. W. C.; Buckle, R.; Mabbett, I.; Grant, G. M.; Graham, A. E.
Tetrahedron Lett. 2007, 48, 4723; (b) Yarapathi, R. V.; Reddy, S. M.;
Tammishetti, S. React. Funct. Polym. 2005, 64, 157; (c) Huang, J.; Akita, T.;
Faye, J.; Fujitani, T.; Takei, T.; Haruta, M. Angew. Chem. Int. Ed. 2009, 48, 7862;
(d) Ollevier, T.; Lavie-Compin, G. Tetrahedron Lett. 2004, 45, 49.
2. (a) Chandrasekhar, S.; Reddy, Ch. R.; Babu, B. N.; Chandrashekar, G.
Tetrahedron Lett. 2002, 43, 3801; (b) Kantam, M. L.; Aziz, K.; Jeyalakshmi, K.;
Likhar, P. R. Catal. Lett. 2003, 89, 95; (c) Prestat, G.; Baylon, C.; Heck, M.-P.;
Mioskowski, C. Tetrahedron Lett. 2000, 41, 3829; (d) Bradley, G.; Williams, D.;
Lawton, M. Org. Biomol. Chem. 2005, 3, 3269; (e) Gallo, J. M. R.; Teixeira, S.;
Schuchardt, U. Appl. Catal. A 2006, 311, 199; (f) Solodenko, W.; Jas, G.; Kunz,
U.; Kirschning, A. Synthesis 2007, 583; (g) Iranpoor, N.; Baltork, I. M.
Tetrahedron Lett. 1990, 31, 735;
3. (a) Barluenga, J.; Vázquez-Villa, H.; Ballesteros, A.; González, J. M. Org. Lett.
2002, 4, 2817; (b) Kim, B. H.; Piao, F.; Lee, E. J.; Kim, J. S.; Jun, Y. M.; Lee, B.
M. Bull. Korean Chem. Soc. 2004, 25, 881; (c) Moghadam, M.; Tangestaninejad,
S.; Mirkhani, V.; Shaibani, R. Tetrahedron 2004, 60, 6105; (d) Firouzabadi, H.;
Iranpoor, N.; Jafari, A. A.; Makarem, S. J. Mol. Catal. A: Chem. 2006, 250, 237;
(e) Weil, T.; Kotke, M.; Kleiner, C. M.; Schreiner, P. R. Org. Lett. 2008, 10,
1513; (f) Zakavi, S.; Karimipour, G. R.; Gharab, N. G. Catal. Commun. 2009, 10,
388; (g) Salehi, P.; Seddighi, B.; Irandoost, M.; Behbahani, F. K. Synth. Commun.
2000, 30, 2967; (h) Likhar, P.; Kumar, M.; Bandyopadhyay, A. Synlett 2001,
1196.
7

4. (a) Dhakshinamoorthy, A.; Alvaro, M.; Garcia, H. Chem. Eur. J. 2010, 16, 8530;
(b) Robinson, M. W. C.; Davies, A. M.; Buckle, R.; Mabbett, I.; Taylor, S. H.;
Graham, A. E. Org. Biomol. Chem. 2009, 7, 2559; (c) Matos, I.; Neves, P. D.;
Castanheiro, J. E.; Perez-Mayoral, E.; Martin-Aranda, R.; Duran-Valle, C.; Vital,
J.; Botelho do Rego, A. M.; Fonseca, I. M. Appl. Catal., A 2012, 439–440, 24; (d)
Saikia, L.; Satyarthi, J. K.; Srinivas, D.; Ratnasamy, P. J. Catal. 2007, 252, 148;
(e) Chakravarti, R.; Oveisi, H.; Kalita, P.; Pal, R. R.; Halligudi, S. B.; Kantam, M.
L.; Vinu, A. Microporous Mesoporous Mater. 2009, 123, 338.
5. (a) Vijay Kumar, A.; Rama Rao, K. Tetrahedron Lett. 2011, 52, 5188; (b) Dreyer,
D. R.; Bielawski, C. W. Chem. Sci. 2011, 2, 1233; (c) Dreyer, D. R.; Jia, H.-P.;
Bielawski, C. W. Angew. Chem. Int. Ed. 2010, 49, 6686; (d) Jia, H.-P.; Dreyer, D.
R.; Bielawski, C. W. Tetrahedron 2011, 67, 4431; (e) Jia, H.-P.; Dreyer, D. R.;
Bielawski, C. W. Adv. Synth. Catal. 2011, 353, 528; (f) Dreyer, D. R.; Jia, H.-P.;
Todd, A. D.; Geng, J.; Bielawski, C. W. Org. Biomol. Chem. 2011, 9, 7292; (g)
Dreyer, D. R.; Jarvis, K. A.; Ferreira, P. J.; Bielawski, C. W. Polym. Chem. 2012,
3, 757; (h) Dreyer, D. R.; Jarvis, K. A.; Ferreira, P. J.; Bielawski, C. W.
Macromolecules 2011, 44, 7659.
6. Mirza-Aghayan, M.; Boukherroub, R.; Nemati, M.; Rahimifard, M. Tetrahedron
Lett. 2012, 53, 2473.
7. Mirza-Aghayan, M.; Zonoubi, S.; Molaee Tavana, M.; Boukherroub, R. Ultrason.
Sonochem. 2014, 22, 359.
8. Mirza-Aghayan, M.; Rahimifard, M.; Boukherroub, R. Turk. J. Chem. 2014, 38,
859.
9. Mirza-Aghayan, M.; Kashef-Azar, E.; Boukherroub, R. Tetrahedron Lett. 2012,
53, 4962.
10. Mirza-Aghayan, M.; Molaee Tavana, M.; Boukherroub, R. Tetrahedron Lett.
2014, 55, 342.
11. General procedure for the alcoholysis of epoxides: To a solution of epoxide (1
mmol) and alcohol (5 mmol) was added 1 mg of graphite oxide (GO) at room
temperature and the mixture stirred for the time indicated in Table 2 prior to
GC/MS analysis. CH2Cl2 was added and the mixture was filtered and evaporated
under reduced pressure. Pure products were isolated by flash column
chromatography using hexane/EtOAc (6/1) as eluent. The products were
1
characterized by IR, H NMR and 13C NMR spectroscopy and mass spectrometry.
8

Spectroscopic data for 2-(pentyloxy)-2-phenylethanol (entry 9, Table 2): Colorless
oil, 1H NMR (80 MHz, CDCl3): δ = 0.8 (m, 3H, CH3), 1.4 (m, 6H, CH2CH2CH2),
3.3 (m, 3H, OCH2, OH), 3.5 (m, 1H, CH2OH), 4.25 (dd, J=1.6 Hz, 0.8 Hz, 1H,
CH2OH), 4.7 (dd, J=1.6 Hz, 0.8 Hz, 1H, CH), 7.3 (m, 5H, Ar); 13C NMR (125
MHz, CDCl3): δ = 14.43, 22.93, 28.76, 29.97, 67.91, 69.70, 83.28, 127.22,
128.42, 128.91, 139.44; MS (EI) (70 eV), m/z (%): 177 (32) [M-CH2OH]+, 121
(100), 107 (53), 91 (5), 71 (5); IR (KBr): ν = 3440, 2931, 2866, 1455, 1103, 1042,
913, 744, 701 cm-1.
12. Kumar, G. D. K.; Baskaran, S. J. Org. Chem. 2005, 70, 4520.
13. Otera, J.; Yoshihisa, N.; Hitosi, N. Tetrahedron 1991, 47, 7625.
14. Garcia, J. I.; Garcia-Marin, H.; Mayoral, J. A.; Perez, P. Green Chem. 2010, 12,
426.
15. Jeyakumar, K.; Chand, D. K. Synthesis 2008, 807.
9