An efficient Br?nsted–Lewis acidic ionic liquid catalyzed tetrahydropyranylation of alcohols

Article abstract of DOI:10.1016/j.tetlet.2016.09.099

An imidazolium based Br?nsted–Lewis acidic ionic liquid has been shown to be an excellent catalyst and reaction medium for the tetrahydropyranylation of various alcohols in good to excellent yields with short reaction times. Selective protection of benzyl

Full text of DOI:10.1016/j.tetlet.2016.09.099

Accepted Manuscript
An efficient Brønsted–Lewis acidic ionic liquid catalyzed tetrahydropyranyla-
tion of alcohols
Najmedin Azizi, Masumeh Abdoli-Senejani, Faezeh Abbasi
PII:
S0040-4039(16)31292-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.09.099
TETL 48169
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
8 August 2016
19 September 2016
29 September 2016
Please cite this article as: Azizi, N., Abdoli-Senejani, M., Abbasi, F., An efficient Brønsted–Lewis acidic ionic liquid
catalyzed tetrahydropyranylation of alcohols, Tetrahedron Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.
2016.09.099
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An efficient Brønsted–Lewis acidic ionic
liquid catalyzed tetrahydropyranylation of
alcohols
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Najmedin Azizi, Masumeh Abdoli-Senejani, Faezeh Abbasi

1
Tetrahedron Letters
An efficient Brønsted–Lewis acidic ionic liquid catalyzed tetrahydropyranylation of
alcohols
Najmedin Azizia,  Masumeh Abdoli-Senejanib and Faezeh Abbasib
a Department of Green chemistry, Chemistry and Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
b Department of Chemistry, Islamic Azad University-Arak Branch, P.O. BOX 38135-567, Arak, Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An imidazolium based Brønsted–Lewis acidic ionic liquid has been shown to be an excellent
catalyst and reaction medium for the tetrahydropyranylation of various alcohols in good to
excellent yields with short reaction times. Selective protection of benzyl alcohol in the presence
of phenol was achieved. The novel ionic liquid was prepared from readily available starting
materials and could be easily recovered and reused several times without significant
deterioration in catalytic activity.
Available online
Keywords:
tetrahydropyranylation
alcohols
2009 Elsevier Ltd. All rights reserved.
acidic ionic liquid
green chemistry
Protection
Protecting groups play a pivotal role in the multi-step
synthesis of structurally complicated natural products.1 Among
the protecting groups, the tetrahydropyranyl (THP) protection of
hydroxy compounds with 3,4-dihydro-2H-pyran (DHP) is
attractive due to its low cost, ease of deprotection and stability
under a variety of reaction conditions such as strongly basic
such as water solubility, recyclablity, high acid density and easy
separation.9
Herein, we report the convenient tetrahydropyranylation of
alcohols using
a
Brønsted–Lewis acidic IL as an
environmentally-friendly catalyst and reaction medium.
media,
oxidative
conditions
and
reducing
agents.2
The Brønsted–Lewis acidic IL was prepared by treatment of
the known sulfonic acid-functionalized Brønsted acidic IL HSO3-
pmim]+Cl− 10 with 2 eq. of ZnCl2 at 80 °C. After water removal
under vacuum the Brønsted–Lewis acidic IL was obtained
(Scheme 1).
Tetrahydropyranylation has generally been achieved using both
Brønsted acid and Lewis acid catalysts.3,4 However, some of
these methods have drawbacks such as elevated temperatures,
long reaction times and the use of harmful organic solvents.
Green chemistry has emerged as a new research area in the
chemical sciences as well as industry.5 Volatile organic solvents,
especially halogenated solvents, as well as industrial catalysts
that are used in large quantities are significant sources of
pollution.6 Ionic liquids (IL) are molten salts with melting points
below 100 °C, that came into the spotlight during the last decade,
based on their possible use as alternatives to conventional
organic solvents due to their unique properties, such as low vapor
pressure, high thermal stability, recyclability, and non-
flammability.7 The characteristics of IL can be controlled through
various combinations of cations and anions, allowing the design
of IL with unique properties. Additionally, by incorporating
functional groups, it is possible to form task-specific IL that have
dual properties.8 In this context, the introduction of acidic
functional groups may offer a convenient solution to both the
problem of solvent use and recycling. Furthermore, acidic IL
possess the advantages of both liquid and solid acid catalysts
Scheme 1. Synthesis of the acidic IL.
To explore the feasibility of using the acidic IL for
tetrahydropyranylation, the model reaction of benzyl alcohol with
DHP was selected (Table 1, entry 1). The reaction was carried
out at room temperature under solvent-free conditions with low
catalyst loading (0.5 mol%) to give the corresponding THP ether
———
 Corresponding author. Tel.: +98-21-44787775; fax: ++98-21-44787775; e-mail: azizi@ccerci.ac.ir

2
Tetrahedron
in 97% isolated yield. Under identical conditions, IL1 and IL1
with one equivalent of ZnCl2 showed low catalytic activity
(Table 1, entry 1) in comparison to IL2. Furthermore, compared
with the commercial Lewis acid ZnCl2 as well as Brønsted acids
p-toluenesulfonic acid (p-TsOH) and methanesulfonic acid
(MsOH), IL2 produced the THP product with a better result
(Table 1, entry 1).
Next, we examined the protection of
a variety of
commercially available alcohols using this methodology (Table
1). Primary, secondary, tertiary, allylic, furyl and benzylic
alcohols underwent facile tetrahydropyranylation to afford the
corresponding ethers. Acid-sensitive alcohols, such as tert-
butanol, benzhydrol and menthol, which are sterically hindered,
underwent tetrahydropyranylation with no dehydration being
observed (Table 1, entries 9, 11, 12 ).
Figure 1. Recycling of the Brønsted-Lewis acidic IL2
Furthermore, we examined the acidic IL for the selective
protection of hydroxyl groups, and excellent chemoselectivity
was observed for benzyl alcohol in the presence of phenol
(Scheme 2).
Further investigation involved examining the reusability of the
Brønsted-Lewis acidic IL for the tetrahydropyranylation of
benzyl alcohol on a 5 mmol scale in the presence of 3 mol%
catalyst (Fig. 1). After reaction completion, the product was
extracted with Et2O and the remaining catalyst left in the reaction
vessel washed with Et2O and dried under vacuum. The catalyst
was used directly without further treatment for the next run after
being charged with fresh starting materials. Using this procedure,
the Brønsted-Lewis acidic IL could be reused up to four times
without significant loss of the initial catalytic activity (Fig. 1).
Scheme 2. Chemoselective protection of benzyl alcohol in the
presence of phenol
Table 1. Tetrahydropyranylation of various alcohols in the presence of IL2
Entry
1
Alcohol
Product
Time (min.)
40
Yield 3 (%)a,b
97 (80, 88, 72, 84, 68)c
3a
2
45
97
3b
3
4
5
60
80
45
90
82
92
3c
3d
3e
6
7
45
45
60
92
90
97
95
3f
3g
3h
8
9
60
80
3i
3j
10
70

3
11
12
90
80
74
72
3k
3l
aReaction conditions: alcohol (5 mmol), DHP (5 mmol), catalyst (0.5 mol%), rt. bIsolated yield. cYields refer to the use of 2 mol% IL1,
IL1 with ZnCl2 (1 equiv.), ZnCl2, MeSO3H and p-TSOH.
Chakraborti, A. K. Green Chem. 2013, 15, 798-810; (h) Kommi, D.
N.; Kumar, D.; Bansal, R.; Chebolu, R.; Chakraborti, A. K. Green
In summary, a novel Brønsted-Lewis acidic IL was
investigated
as
a
reusable
catalyst
for
the
Chem. 2012, 14, 3329-3335.
tetrahydropyranylation of various alcohols in good to high
yields with short reaction times. The advantages are high
catalytic activity under mild reaction conditions, low cost and a
readily available IL, easy separation of the catalyst by simple
extraction, and selectivity for alcohols over phenols.11
6.
(a) Parikh, N.; Kumar, D.; Roy, S. R.; Chakraborti, A. K. Chem.
Commun. 2011, 1797-1799; (b) Manabe, K.; Mori, Y.; Wakabayashi,
T.; Nagayama, S.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 7202-
7207; (c) Tanwar, B.; Purohit, P.; Raju, B. N.; Kumar, D.; Kommi,
D. N.; Chakraborti, A. K. RSC Adv. 2015, 5, 11873-11883; (d) Jia,
Z.; Zhou, F.; Liu, M.; Li, X.; Chan, A. S. C.; Li, C.-J. Angew. Chem.
Int. Ed. 2013, 52, 11871-11874; (e) Kommi, D. N.; Kumar, D.; Seth,
K.; Chakraborti, A. K. Org. Lett. 2013, 15, 1158-1161; (f) Liu, W.;
Li, L.; Li, C.-J. Nat. Commun. 2015, 6, 6526-6534.
(a) Sarkar, A.; Roy, S. R.; Parikh, N.; Chakraborti, A. K. J. Org.
Chem. 2011, 76, 7132-7140; (b) Sarkar, A.; Roy, S. R.; Chakraborti,
A. K. Chem. Commun. 2011, 4538-4540; (c) Chakraborti, A. K.;
Roy, S. R. Green Chem. 2008, 10, 1111-1118; (d) Roy, S. R.;
Chakraborti, A. K.. Org. Lett. 2010, 12, 3866-3869; (e) Chakraborti,
A. K.; Roy, S. R. J. Am. Chem. Soc. 2009, 131, 6902–6903.
(a) Chaturvedi, D. Cur. Org. Chem. 2011, 15, 1236-1248; (b)
Chaturvedi, D. Cur. Org. Synth. 2011, 8, 438-471; (c) Raha Roy, S.;
Jadhavar, P. S.; Seth, K.; Sharma, K. K.; Chakraborti, A. K.
Synthesis 2011, 2261-2267; (d) Chen, X.; uo, H.; Abdeltawab, A. A.;
Guan, Y.; Al-Deyab, S. S.; Yu, G.; Yu, L. Energy Fuels, 2015, 29,
2998-3003; (e) Chen, X.; Yuan, S.; Abdeltawab, A. A.; Al-Deyab, S.
S.; Zhang, J.; Yu, L.; Yu, G. Sep. Purif. Technol. 2014, 133, 187-
193; (F) Chen, X.; Song, D.; Asumana, C.; Yu, G. J. Mol. Catal. A:
Chem. 2012, 359, 8-13; (g) Wei, Y.; Keke, C.; Xiaofang, Z.;
Yingying, K.; Xiujuan, T.; Xiaoxiang, H. J. Ind. Eng. Chem. 2015,
29, 185-193; (h) Gogoi, P.; Kumar Dutta, A.; Sarma, P.; Borah, R.
Appl. Catal., A Gen. 2015, 492, 133-139; (i) Tran, P. H.; Hansen, P.
E.; Hoang, H. M.; Chau, D. K. N.; Le, T. N. Tetrahedron Lett. 2015,
56, 2187-2192.
Acknowledgments
Financial support of this work by the Chemistry and
Chemical Engineering Research Center of Iran.
7.
8.
References and notes
1.
Greene, T. W.; Wuts, P. G. M. Protective groups in organic
synthesis, 2nd ed., Wiley, New York, 1991, 346.
2.
3.
Kiyoshi, T.; Tsuneo, S. Org. Prep. Proc. Int. 2016, 48, 72-80.
(a) Palaniappan, S.; Sai Ram, M.; Amarnath, C. A. Green Chem.
2002, 4, 369-371; (b) Wang, M.; Song, Z.; Wan, X.; Zhao, S. RSC
Adv. 2011, 1, 1698-1700; (c) Namboodiri, V. V.; Varma, R. S. Chem.
Commun. 2002, 342-343; (d) Singh Yadav, J.; Subba Reddy, B. V.;
Gnaneshwar, D. New J. Chem. 2003, 27, 202-204; (e) Heravi, M. M.;
Behbahani, F. K.; Oskooie, H. A.; Hekmat Sho, R. Tetrahedron Lett.
2005, 46, 2543-2545; (f) Prabhavathi Devi, B.L.A.; Gangadhar,
K.N.; Siva Kumar, K.L.N.; Shiva Shanker, K.; Prasad, R.B.N.; Sai
Prasad, P. S. J. Mol. Catal. A: Chem. 2011, 345, 96-100; (g) Ballini,
R.; Bigi, F.; Carloni, S.; Maggi, R.; Sartori, G. Tetrahedron Lett.
1997, 38, 4169-4172; (h) Bodipati, N.; Rao Palla, S.; Komera, V.;
Peddinti, R. K. Tetrahedron Lett. 2014, 50, 6878-6881; (i) Wang,
M.-K.; Zhou, Z.-L.; Tang, R.-Y.; Zhang, X.-G.; Deng, C.-L. Synlett.
2013, 24, 737-740; (j) Duan, Z.; Gu, Y.; Deng, Y. Synth. Commun.
2005, 35, 1939; (k) Singh, J.; Gupta, N.; Kad, G. L. Synth. Commun.
2006, 36, 2893; (l) Hajipour, A. R.; Nasresfahani, Z. Synth. Commun.
2012, 42, 1995; (m) Shirini, F.; Abedini, M.; Mahmoodi, N.; Biglari,
M.; Safarpoor Nikoo Langrudi, M. Phosphorus Sulfur Silicon Relat
Elem. 2015, 11, 1912-1921.
(a) Kotke, M.; Schreiner, P. R. Synthesis 2007, 779-790; (b) Khan, A.
T.; Parvin, T.; Choudhury, L. H. Synthesis 2006, 2497-2502; (c)
Stephens, J. R.; Butler, P. L.; Clow, C. H.; Oswald, M. C.; Smith, R.
C.; Mohan, R. S. Eur. J. Org. Chem. 2003, 3827-3831; (d) Sanz, R.;
Martinez, A.; Alvarez-Gutierrez, J. M.; Rodriquez, F. Eur. J. Org.
Chem. 2006, 1383-1386; (e) Azizi, N.; Mirmashhori, B.; Saidi, M.R.
Catal. Commun. 2007, 8, 2193-2203; (f) Wang, Y. G.; Wu, X. X.;
Jiang, Z. Y. Tetrahedron Lett. 2004, 45, 2973-2976; (g) Naik, S.;
Gopinath, R.; Patel, B. K. Tetrahedron Lett. 2001, 42, 7679; (h)
Pachamuthu, K.; Vankar, Y. D. J. Org. Chem. 2001, 66, 7511-7516;
(i) Khan, A. T.; Ghosh, S.; Choudhury, L. H. Eur. J. Org. Chem.
2005, 4891-4896; (j) Narender, N.; Reddy, K. S. K.; Kumar M. A.;
Rohitha C. N. Kulkarni, S. J. Catal. Lett. 2010, 134, 175-179.
(a) Li, C.-J.; Chen, L. Chem. Soc. Rev. 2006, 35, 68-82; (b) Khatik,
G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006, 8, 2433-2436;
(c) Chankeshwara, S. V.; Chakraborti, A. K. Org. Lett. 2006, 8,
3259-3262; (d) Pirrung, M. C.; Sarma, K. D. J. Am. Chem. Soc. 2004,
126, 444-445; (e) Chakraborti, A. K.; Rudrawar, S.; Jadhav, K. B.;
Kaura, G.; Chankeshwara, S. V. Green Chem. 2007, 9, 1335-1340;
(f) Kommi, D. N.; Kumar, D.; Chakraborti, A. K.. Green Chem.
2013, 15, 756-767; (g) Kommi, D. N.; Jadhavar, P. S.; Kumar, D.;
9.
(a) Srinivas Reddy, A.; Laali, K. K. Tetrahedron Lett. 2015, 56 5495-
5499; (b) Vafaeezadeh, M.; Alinezhad, H. J. Mol. Liq. 2016, 218, 95-
105; (c) Cao, Y.; Zhou, H.; Li, J. Renew. Sust. Energ. Rev. 2016, 58,
871-875; (d) Mjalli, F. S. J. Taiwan Inst. Chem. 2016, 61, 64-74. (e)
Yue, C.; Fang, D.; Liu, L.; Yi, T.-F. J. mol. Liq. 2011, 163, 99-121.
10. (a) Wiredu, B.; Amarasekara, A. S. Catal. Commun. 2015, 70, 82-
85; (b) Liu, S.; Chen, C.; Yu, F.; Li, L.; Liu, Z.; Yu, S.; Xie, C.; Liu,
F. Fuel. 2015, 159, 803-809; (c) Yu, F.; Liu, C.; Yuan, B.; Xie, P.;
Xie, C.; Yu, S. Fuel, 2016, 177, 39-45; (d) Liu, S.; Xie, C.;Yu, S.;
Liu, F. Catal. Commun. 2008, 10, 2030-2034; (e) Amarasekara, A. S.
Chem. Rev. 2016, 116, 6133-6183; (f) Amarasekara, A. S.; Wiredu,
B. Catal. Commun. 2016, 81, 41-44. (g) Amarasekara, A. S.; Hasan,
M. A. Tetrahedron Lett. 2014, 55, 3319 – 3321.
11. Preparation of catalyst: The acidic IL was synthesized using a
modified literature method.10 1-Methylimidazole (1.57 mL, 20 mmol)
was added to a 50 mL round-bottom flask. Under vigorous magnetic
stirring, 1,4-butane sultone (2.04 mL, 20 mmol) was added dropwise
at room temperature. The mixture was continuously stirred at 80 °C
for 6 h to afford the white solid zwitterion after repeated washing
with Et2O which was further converted into the acidic IL upon
acidification with HCl (37%) at r.t. for 4 h. The mixture was distilled
under vacuum for 4 hours to remove residual water and acid to give
IL1 (3.78 g, 74%, 14.8 mmol). 1H NMR: (500 MHz; D2O): 1.59-1.62
(m, 2H), 1.84-1.91 (m, 2H), 2.82 (t, 2H), 3.77 (s, 3H), 4.10 (t, J =
7.01 Hz, 2H), 7.34-7.36 (m, 2H), 8.58 (s, 1H). 13C NMR: (125 MHz;
D2O): 20.8, 27.9, 35.5, 48.6, 49.9, 121.0, 123.5, 135.8. Anhydrous
ZnCl2 (28 mmol) was added to the reaction mixture and heated at 80
4.
5.

4
Tetrahedron
°C for 8 h to give IL2 (7.82 g, 14.0 mmol, M = 527.37 g/mol) as a
dark honey like viscous oil (Scheme 1).
12. General procedure: A test tube, equipped with a magnetic stirrer bar,
was charged with benzyl alcohol (0.51 mL, 5.0 mmol), DHP (0.45
mL, 5.0 mmol), and catalyst (15 mg, 0.5 mol%, M = 527 g/mol). The
resulting mixture was stirred at room temperature until reaction
completion (40-90 min, GC and TLC). The crude product was
dissolved in Et2O (for compounds 8, 9, 11, EtOAc was used) and
purified by passing through a short column of silica gel using
hexane–ethyl acetate as eluent or recrystallized from EtOH or Et2O to
give pure products. All products are known compounds and identical
to literature reports.3

5
Highlights
► Tetrahydropyranylation of alcohols in
excellent yields and short reaction times
► The method used a mild and efficient
Brønsted–Lewis acidic ionic liquid catalyst.
► Selective protection of benzyl alcohol in the
presence of a phenol was achieved.