Selective monotetrahydropyranylation of 1,n-diols catalyzed by aqueous acids

Article abstract of DOI:10.1016/S0040-4039(00)01742-1

1,n-Diols with 3-12 carbon atoms gave selectively the corresponding monotetrahydropyranyl ethers in higher yields than 80% in the reaction catalyzed by hydrogen ion in the water layer which is in contact with DHP-toluene or DHP-hexane layer. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01742-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 9843–9846
Selective monotetrahydropyranylation of 1,n-diols catalyzed
by aqueous acids
Takeshi Nishiguchi,a,* Seiji Hayakawa,a Yoshihiro Hirasakab and Masahiko Saitohb
aFaculty of Agriculture, Yamaguchi University, Yamaguchi 753-5815, Japan
bFaculty of Education, Yamaguchi University, Yamaguchi 753-8513, Japan
Received 29 June 2000; revised 8 September 2000; accepted 29 September 2000
Abstract
1,n-Diols with 3–12 carbon atoms gave selectively the corresponding monotetrahydropyranyl ethers in
higher yields than 80% in the reaction catalyzed by hydrogen ion in the water layer which is in contact
with DHP–toluene or DHP–hexane layer. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: selective reaction; tetrahydropyranyl ether; etherification; diol.
Methods for the selective protection of one of two identical functional groups, which exist in
symmetrical positions in a molecule, are important in organic synthesis.1 Since the protection of
hydroxyl groups by etherificaion is quite common in organic syntheses,2 it will be worth
developing the methods to obtain monohydroxyethers selectively from symmetrical diols. In
some cases, the monoetherification of symmetrical diols can be achieved by Williamson
reaction,3 by the use of alumina and diazomethane,4 and via cyclic compounds.5 It has also been
reported that the monotetrahydro-2H-pynanyl (THP) ether was obtained in 85% yield from
1,8-octanediol in the reaction catalyzed by iodine.6 We have already reported the selective
monotetrahydropyranylation of symmetrical diols in 3,4-dihydro-2H-pyran (DHP)–hydrocar-
bon catalyzed by metallic sulfates supported on silica gel7 and by acidic ion-exchange resins
which contain water.8 In the former reaction diethers begin to form rapidly when diols have
almost been consumed,7 therefore close observation is required to decide when to terminate the
reaction. This weak point is improved in the latter reaction.8 However, the catalytic ion-
exchange resins used in the reaction are expensive and the performance of the catalysts often
changes as the reaction proceeds, because the amounts of water contained in the resins tend to
decrease in the course of the etherification.
* Corresponding author.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01742-1

9844
Here we would like to report the selective monotetrahydropyranylation of 1,n-diols in which
the disadvantages mentioned above are overcome. This reaction was carried out by stirring a
diol, an acidic aqueous solution, and a mixture of DHP and a hydrocarbon.
+
+
HO-(CH2)n-OH ꢀꢀꢀꢀꢀHꢀ3ꢀOꢀꢀꢀꢀꢀꢁ THPO-(CH2)n-OH ꢀꢀꢀꢀꢀHꢀ3ꢀOꢀꢀꢀꢀꢀꢁ [THPO-(CH2)n-OTHP]
DHP−hydrocarbon
DHP−hydrocarbon
Fig. 1 shows an example of the dependence of the yields of the products on the reaction
period in the etherification of 1,6-hexanediol (1 mmol) using aqueous NaHSO4 (5 M, 0.2 ml)
and DHP–toluene (5:95 (v/v), 6 ml). This reaction was followed by the use of GLC. The yield
of the diether was 2% when that of the monoether reached 94%. The yield of the diether did not
increase rapidly even after the yield of the monoether reached its maximum. The result described
above enhances the value of this reaction because the timing to terminate the successive
etherification is not so important in this reaction as in the reaction catalyzed by the supported
sulfates.7
Figure 1. Yield of the monoether ( ) and the diether (ꢀ) versus reaction time. 1,6-Hexanediol (1 mmol), aqueous
NaHSO4 (5 M, 0.2 ml) and DHP/toluene (5:95, 6 ml) were stirred at 30°C
The yield of 1,6-bis(tetrahydropyranyloxy)hexane in the reaction of 6-(tetrahydropyranyloxy)-
1-hexanol, which was the starting material, was much lower than the yield of the monoether in
the reaction of 1,6-hexanediol. The ratio of the reaction rate of the diether formation from the
monoether to that of the monoether formation from the diol was roughly 1:80 under similar
reaction conditions.
We presume that the selectivity for the monoether formation arises from the following
assumed factors: (1) the percentage of the diol existing in the water layer is much higher than
that of the monoether existing there; (2) the diol reacts in the aqueous layer which contains
DHP and hydronium ion; (3) the formed monoether migrates from the aqueous layer into the
surrounding aprotic organic layer which does not contain the catalytic species.
Assumption (1) is supported by the result that 6-(tetrahydropyranyloxy)-1-hexanol hardly
existed in the water layer, while 1,6-hexanediol existed mainly there when (1 mmol) stirred well
along with water (0.6 ml) and DHP–toluene (6 ml) at 30°C (Fig. 2).

9845
Figure 2. The percentage of 1,6-hexanediol ( ) and 6-(tetrahydropyranyloxy)-1-hexanol (ꢀ) in the water layer (0.6
ml) which was kept in contact with DHP–toluene (6 ml) at 30°C
Tetrahydropyranyl ethers are usually hydrolyzed to the corresponding alcohols in dilute
aqueous acids.2 However, the yield of the monoether is high in this reaction, probably because
the monoether, even if its amount is small in the acidic water layer, moves into the surrounding
organic layer immediately after its formation, as inferred by Fig. 2.
Table 1 shows that some 1,n-diols with 3–12 carbon atoms gave the corresponding mono-
tetrahydropyranyl ethers in higher yields than 80% in the reaction catalyzed by aqueous
NaHSO4. In the reaction of 1,10-decanediol using DHP–toluene, the yield of the monoether was
low. The yield was increased by changing DHP–toluene into DHP–hexane and by adding
DMSO (0.2 ml). In the reaction of 1,12-dodecanediol, the yield of the monoether was somewhat
lower than the yields of the monoethers in the reactions of the diols with not more than 10
carbon atoms.
Table 1
a
Selective monotetrahydropyranyration of HO-(CH2)n-OH with DHP catalyzed by aqueous NaHSO4
n
NaHSO4 (ml)
DHP (vol.%)
Temp. (°C)
T (min)
Yield (%)b
Monoether
Diether
3
6
10
0.2
0.2
0.2
1.0
1.0
1.0
1.0
40
5
3
3
3
30
30
30
40
40
40
50
50
130
480
960
720
300
420
93
92
66
81
83
88
80
2
2
26
11
9
10
10c
10c,d
12c,d
3
5
4
3
a Diol (1.0 mmol), aqueous NaHSO4 solution (5 M), and DHP–toluene (6 ml) were stirred.
b GLC yields obtained by the use of internal standards.
c The solvent was a DHP–hexane mixture.
d DMSO (0.2 ml) was added.

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Each diol had a particular DHP/hexane or DHP/toluene ratio that gives the highest
selectivity. In the reaction of 1,6-hexanediol, the percentages of DHP at which the highest
selectivity was realized were about 5 and 60% in the reaction in DHP–toluene and DHP–hexane,
respectively. The highest yield of the monoether from 1,6-hexanediol in the reaction of
DHP–toluene was higher than in the reaction of DHP–hexane. In the reaction of 1,10-decane-
diol, the selectivity for the monoether was higher when the percentage of DHP in DHP–hexane
was 3% than when it was 5%. When the number of carbon atoms of the diols is large, the
organic layers whose ability to dissolve diols must be low to realize the high selectivity.
As described previously, the addition of DMSO increased the selectivity in the reaction of
1,10-decanediol. The increase of the selectivity may be explained by the presumption that the
strongly polar additive is distributed mainly in the water layer and that the dissolving power of
the water layer for the diol is enhanced by the addition to a greater extent than for the
monoether.8 For catalysts, aqueous NH4HSO4, KHSO4 and Fe2(SO4)3, and diluted hydrochloric
acid (0.2 M) were as effective as aqueous NaHSO4.
This method of selective etherification is suitable for large-scale preparations because the
catalysts described above are inexpensive and harmless to a natural environment, and the
experimental operation in this method is quite simple. Further, the reproducibility of results in
this reaction is much higher than that in the reactions catalyzed by acidic ion-exchange resins,8
in which amounts of water contained in the catalysts are not always settled even when the resins
are purchased and change in the course of the reaction.
Supplementary material: An example of monoetherification of 1,n-diols. The etherification of
hexane-1,6-diol is typical. A mixture of hexane-1,6-diol (0.118 g, 1 mmol), aqueous 5 M
NaHSO4 (02 ml), 1-octadecene (GLC internal standard, 40 ml), and 5:95 (vol/vol) DHP–toluene
(6 ml) was stirred at 30 1°C. Samples of the supernatant liquid were then removed periodically
and analyzed by GLC. The retention times of the monoether and the diether were identical to
those of authentic samples prepared by the conventional method described in the previous
paper.6,7 The yields of monoethers at a particular yield of diethers were derived from plots of
product yield versus time, such as those shown in Fig. 1.
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