Solvent-free tetrahydropyranylation of alcohols catalyzed by amine methanesulfonates

Article abstract of DOI:10.1007/s11164-010-0222-6

A comparative study of tetrahydropyranylation of alcohols under various solvents or solvent-free conditions using different amine methanesulfonates as catalysts shows that tetrahydropyranyl ethers of alcohols are obtained under solvent-free conditions in good yields using catalytic amounts of triethylenediamine methanesulfonate, 1,6-hexanediamine methanesulfonate, diethylenetriamine methanesulfonate and pyridine methanesulfonate, respectively. The reaction occurs readily in short times at room temperature catalyzed by these catalysts, especially triethylenediamine methanesulfonate. Some of the major advantages of this procedure are that the catalysts are environmentally friendly, highly effective, and easy to prepare and handle. The reaction is also clean and needs no solvent, and the work-up is very simple.

Full text of DOI:10.1007/s11164-010-0222-6

Res Chem Intermed (2011) 37:61–67
DOI 10.1007/s11164-010-0222-6
Solvent-free tetrahydropyranylation of alcohols
catalyzed by amine methanesulfonates
•
Rui Wang MingZhu Sun Heng Jiang
•
Received: 14 September 2010 / Accepted: 29 October 2010 / Published online: 24 November 2010
ꢀ Springer Science+Business Media B.V. 2010
Abstract A comparative study of tetrahydropyranylation of alcohols under
various solvents or solvent-free conditions using different amine methanesulfonates
as catalysts shows that tetrahydropyranyl ethers of alcohols are obtained under
solvent-free conditions in good yields using catalytic amounts of triethylenediamine
methanesulfonate, 1,6-hexanediamine methanesulfonate, diethylenetriamine meth-
anesulfonate and pyridine methanesulfonate, respectively. The reaction occurs
readily in short times at room temperature catalyzed by these catalysts, especially
triethylenediamine methanesulfonate. Some of the major advantages of this pro-
cedure are that the catalysts are environmentally friendly, highly effective, and easy
to prepare and handle. The reaction is also clean and needs no solvent, and the
work-up is very simple.
Keywords Methanesulfonates ꢀ Tetrahydropyranylation ꢀ Catalysts ꢀ Solvent-free ꢀ
Alcohols ꢀ Protection
Introduction
Tetrahydropyranylation is an attractively protective method that is often used for
protection of alcohol moieties, in particular natural products, due to the remarkable
stability of tetrahydropyranyl (THP) ethers under various reaction conditions such
as strongly basic media, oxidation, reduction with hydride, reactions involving
R. Wang (&) ꢀ H. Jiang
School of Chemistry and Materials Science, Liaoning Shihua University, 113001 Fushun,
Liaoning, People’s Republic of China
e-mail: wr_wrwr@hotmail.com
M. Sun
School of Petrochemical Engineering, ShenYang University of Technology, 111003 Liaoyang,
Liaoning, People’s Republic of China
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R. Wang et al.
Grignard reagents and alkyllithiums [1]. Acid catalysts play a predominant role in
organic synthesis, in particular tetrahydropyranylation. Due to its ease of handling
and recovering, various solid acids were introduced, which include protic acids
[2, 3], Lewis acids [4, 5], ion exchange resins [6, 7], solid silica-based sulfonic acid
[8], zeolites [9, 10], hetropolyacids [11, 12], and clays [13, 14]. The main problems
associated with solid acids are the complicated preparation procedure, corrosive-
ness, the expense, the harsh reaction conditions, the need for solvents such as
CH2Cl2, as well as unsatisfactory product yields, etc. Therefore, for both
environmental and economical reasons, there is an ongoing effort to develop new
acid catalysts.
Methanesulfonic acid, which is a readily biodegradable and environmentally
friendly material [15], has been studied as an acid catalyst in esterification,
condensation, and alkylation reactions [16–18]. In our study, methanesulfonic acid,
used as a tetrahydropyranylation catalyst, has been found, like many strongly acidic
catalysts [19], to produce polymeric products of 3,4-dihydro-2H-pyran (DHP). In
recent years, methanesulfonates as catalysts have attracted great interest throughout
scientific communities [20–22]. This is mainly due to the distinct advantages such
as their non-toxicity, low cost, non-corrosiveness, and ease of preparation and
recovery. In this direction, we now wish to report amine methanesulfonates (AMS),
which acted as Brønsted acid, are excellent and effective catalysts for tetrahydro-
pyranylation of alcohols under mild conditions.
Experimental
General
The products were characterized by comparison of their physical data with those of
known samples. GC analysis was carried out on an Auto System XL series gas
chromatograph instrument from Perkin-Elmer. Fourier transform infrared (FTIR)
1
spectra were obtained on a Perkin-Elmer Spectrum GX. H NMR spectra were
recorded on Bruker AVANCE 600 spectrometer in CDCl3 using TMS as an internal
standard. Melting points were determined using RY-1 micromelting point
apparatus.
Typical procedure for preparation of AMS
Stoichiometric methanesulfonic acid and triethylenediamine with 2:1 M ratio were
mixed in an agate mortar at room temperature. After grinding for about 1–2 h, a
small amount of alcohol was added. The solid was filtered off and dried in an oven
at 353 K. The resultant salt (triethylenediamine methanesulfonate, TEDAMS) was
obtained. Using the above procedure, other AMS catalysts (Table 1) could also be
synthesized.
123

Solvent-free tetrahydropyranylation of alcohols
63
Table 1 Comparison the activity of various catalysts in the tetrahydropyranylation of benzyl alcohol
under solvent-free conditions
AMS
CH2OH
CH2O
Solvent-Free, r.t.
O
O
Entry
1
Catalysts
Time/h
0.2
Yield/%a
94
[CH3SO3] HN
NH[CH3SO3]
2
3
0.2
6
93
90
[CH3SO3] H3N(CH2)6NH3 [CH3SO3]
[CH3SO3] H3N(CH2)2
NH2[CH3SO3]
[CH3SO3] H3N(CH2)2
4
5
6
7
4.5
3
91
2
NH [CH3SO3]
CH3
Cl
NH3[CH3SO3]
NH3[CH3SO3]
3
2
3
2
CH3
C
NH2[CH3SO3]
2
CH3
Benzyl alcohol (20 mmol), DHP (24 mmol), catalyst (0.8 mmol)
a
Yields based on the isolated products
General procedure for the tetrahydropyranylation of alcohols
Protection was carried out mixing the alcohol (20 mmol), 2.02 g DHP (24 mmol,
1.2 equiv.) and the stated quantity of TEDAMS (Table 3). The suspension was
stirred at room temperature, and the progress of the reaction was monitored by GC.
After completion of the reaction, the mixture was diluted with benzene (10 ml). The
catalyst was filtered off and then washed with benzene (2 9 10 ml). The filtrate was
washed with 1 M NaOH and then dried over anhydrous Na2SO4 and evaporated.
Further purification was achieved by column chromatography on silica gel to obtain
the corresponding THP ether.
Results and discussion
Tetrahydropyranylation reactions of alcohols were catalyzed by a variety of AMS
under similar reaction conditions. The results of the tetrahydropyranylation of benzyl
alcohol are summarized in Table 1. The protection methodology using the above AMS
(Table 1, entries 1–4) as catalysts is successful and gives satisfactory yields.
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R. Wang et al.
Moreover, a vigorous reaction takes place in the presence of a catalytic amount of
p-toluidine methanesulfonate (Table 1, entry 5), resulting in the formation of a deep
reddish brown viscous liquid (probably resulting from the polymerization of
dihydropyran). The yield of the corresponding tetrahydropyranyl ether from this
reaction mixture is very low and most of the alcohol remains unreacted. The same
thing also takes place when 4,40-bis (a, a-dimethylbenzyl) diphenylamine methane-
sulfonate and p-chloroaniline methanesulfonate (Table 1, entries 6–7) are utilized to
protect alcohols in the same reaction conditions. The possible reason for this is that
their (Table 1, entries 5–7) acidity is stronger than the others’ (Table 1, entries 1–4).
Among the described AMS catalysts, the activities of TEDAMS (Table 1, entry 1)
and 1,6-hexanediamine methanesulfonate (Table 1, entry 2), especially TEDAMS
(Table 1, entry 1), are superior to the others’. Investigation of applications of
TEDAMS (Table 1, entry 1) and 1,6-hexanediamine methanesulfonate [23] (Table 1,
entry 2) as highly active catalysts is of practical importance.
In order to optimize the reaction conditions, we attempted the conversion of
benzyl alcohol (20 mmol) to the corresponding THP ether with different amount of
DHP and TEDAMS (0.8 mmol) under various solvents and solvent-free conditions
at room temperature. The results (Table 2) indicate that the yield of the
tetrahydropyranylation reaction of benzyl alcohol with DHP (molar ratio 1:1.2)
under solvent-free condition is higher and the reaction time is shorter.
Several examples illustrating this novel and rapid procedure for tetrahydropyr-
anylation of alcohols using TEDAMS as catalyst under the optimal condition are
presented in Table 2. Isomeric alcohol (Table 3, entries 4, 8, 10, 12), aromatic
alcohol (Table 3, entries 15, 16), furfuryl alcohol (Table 3, entry 18) and optically
active alcohol (-)-menthol (Table 3, entry 19) by using TEDAMS undergo facile
tetrahydropyranylation to form THP ethers in good to excellent yields. Notably, the
increase of carbon number in primary alcohols (Table 3, entries 1–3, 5, 9, 11, 13,
Table 2 Tetrahydropyranylation of benzyl alcohol under different condition using TEDAMS as catalyst
[CH3SO3] HN
NH[CH3SO3]
CH2OH
CH2O
O
O
Entry
nbenzyl alcohol : nDHP
Solventsa
Time/h
Yield/%b
1
2
3
4
5
6
7
8
a
1:1.1
1:1.1
1:1.2
1:1.2
1:1.2
1:1.2
1:1.3
1:1.3
Benzene
None
0.5
0.5
0.5
0.6
0.8
0.2
0.5
0.3
87
89
87
91
91
94
91
94
Benzene
Tetrahydrofuran
Dichloromethane
None
Benzene
None
The reaction was carried out in 10 ml of solvent
Yields based on the isolated products
b
123

Solvent-free tetrahydropyranylation of alcohols
65
Table 3 TEDAMS catalyzed tetrahydropyranylation of alcohols under solvent-free conditions
[CH3SO3] HN
NH[CH3SO3]
OH
R
Solvent-Free, r.t.
O
O
OR
Entry
Alcohols
Cat: DHP (mmol: mmol)
Time/h
Yield/%a
Refs.b
1
CH3OH
0.8:24
0.8:24
2:24
0.5
0.5
2
93
93
90
80
89
78
69
90
88
93
85
91
77
80
94
94
79
90
86
[24]
2
C2H5OH
[24]
3
n-C3H7OH
i-C3H7OH
n-C4H9OH
s-C4H9OH
t-C4H9OH
i-C4H9OH
n-C5H11OH
[24]
4
0.8:24
1.3:24
2:24
2.5
1.3
7
[13]
5
[24]
6
[13]
7
2:24
10
1
[25]
8
1.3:24
1.3:24
1.3:24
2:24
[13]
9
2
[26]
10
11
12
13
14
15
16
17
18
19
a
(CH3)2CHCH2CH2OH
n-C8H17OH
1
[13]
2
[13]
i-C8H17OH
0.8:24
2:24
1.5
4.5
14
0.2
0.3
5
[13]
n-C12H25OH
n-C16H33OH
PhCH2OH
[13]
2:24
[5]
0.8:24
0.8:24
2:24
[13, 24]
[27]
PhCH2CH2OH
c-C6H11OH
[13, 19]
[13, 24]
[28]
Furfuryl alcohol
(-)-menthol
0.8:24
1.3:24
1
1
Yields based on the isolated pure products and confirmed by comparison with authentic samples (GC,
IR and 1H NMR)
b
References for spectroscopic data of products
14) decreases the yields of THP ethers. The protection of secondary alcohol
(Table 3, entry 6), tertiary alcohol (Table 3, entry 7), and cyclic saturated alcohol
(Table 3, entry 17) afforded the corresponding THP ethers in low yields at long
reaction time in the same conditions. The absence of by-product obtained by GC
analysis shows the high selectivity of TEDAMS catalyst.
Based on our results, the plausible mechanism for the protection of alcohols is
shown in scheme 1. It is assumed that DHP protonated with Brønsted acid sites of
TEDAMS. The intermediate product further reacts with alcohol to give corre-
sponding THP ether.
Conclusions
In conclusion, tetrahydropyranylation of alcohols has been carried out successfully
using the new AMS catalyst, specifically TEDAMS. High effectivity and easy of
123

66
R. Wang et al.
[CH3SO3] HN
NH[CH3SO3]
O
O
O
O
H
R
[CH3SO3] HN
NH[CH3SO3]
O
O
H
O
OR
R
Scheme 1 The plausible mechanism for the protection of alcohols
preparation and handling of the catalyst with its environmentally friendly nature
should make the method particularly attractive. Most importantly, work-up
procedures in our study have been simplified due to the absence of solvent.
Because of the outstanding advantages, this method is expected to have wide
applicability for the protection of various hydroxyl compounds.
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