Microwave-mediated selective monotetrahydropyranylation of symmetrical diols catalyzed by iodine

Article abstract of DOI:10.1021/jo000863a

Selective protection of one hydroxyl group as its tetrahydropyranyl ether in 1, n-symmetrical diol is achieved by iodine-catalyzed reaction of the diol with dihydropyranyl ether under microwave irradiation.

Full text of DOI:10.1021/jo000863a

J . Org. Chem. 2001, 66, 1947-1948
1947
Micr ow a ve-Med ia ted Selective Mon otetr a h yd r op yr a n yla tion of
Sym m etr ica l Diols Ca ta lyzed by Iod in e
Nabajyoti Deka and J adab C Sarma*
Organic Chemistry Division (NPC), Regional Research Laboratory, J orhat -785006, Assam, India
natprod@csir.res.in
Received J une 6, 2000
Selective protection of one hydroxyl group as its tetrahydropyranyl ether in 1,n-symmetrical diol
is achieved by iodine-catalyzed reaction of the diol with dihydropyranyl ether under microwave
irradiation.
Protection of hydroxyl groups by the preparation of
tetrahydropyranyl ethers is quite common and an ad-
1
vantageous reaction in organic synthesis. Although
1
several reagents are available for protection of alcohols
as their tetrahydropyranyl ethers, the selective protection
of one of two identical hydroxyl groups in a symmetrical
molecule is very limited. Only a few recent reports from
Nishiguchi et al. have described the use of metallic
2
sulfate supported on silica gel or some acidic ion-
3
exchange resins as suitable catalyst for this purpose. In
general monoetherification of symmetrical diol is achieved
4
by the Williamson synthesis, by the use of alumina and
5
diazomethane or via cyclic acetals in a two-step proce-
6
dure. In the acetal-opening process the reaction needs
to be done at very low temperature (-78 °C), and the
yield is also low. The process involving metallic sulfate
2
supported on silica gel has the drawback as to when to
terminate the reaction for getting optimum yield. Herein
we report a microwave-mediated reaction for selective
protection of one hydroxyl as a tetrahydropyranyl ether
in a symmetrical 1,n-diol. During the course of our
F igu r e 1. Yield vs reaction time. Reaction of ethane-1,2-diol
with DHP under reflux in THF. Curve Abedef is for diether
and ABCDEF is for monoether.
7
Ta ble 1. Mon op r otection of 1,n -Diols
studies on iodine-catalyzed reactions in organic synthe-
sis we have observed that iodine is a very good catalyst
for tetrahydropyranylation of hydroxyl groups under
microwave irradiation.8
power time temp
yield (%)
substrate
(W)
(s)
(°C) of monoether diether
ethane-1,2-diol
propane-1,3-diol
butane-1,4-diol
hexane-1,6-diol
600
600
600
600
150
150
160
160
170
67
67
67
67
67
78
77
75
76
77
17
17
16
16
15
DHP/l2
HO-(CH ) -OH THF, MW8
2
n
cyclohexane-1,4-diol 600
THPO-(CH ) -OH + ......
2
n
7
5% or greater isolated yield of the monoprotected diol
within 3 min. When the same reaction was carried out
under reflux, the conversion was quantitative within 30
min, but selectivity was very poor. The isolated yield of
the monoether was 43% and that of the diether was 51%.
Even at room temperature the reaction proceeded slowly
without any selectivity (product ratio monoether:diether
In the present method, the diol in dry THF was
irradiated in a microwave oven in the presence of 3,4-
dihydro-2H-pyran and catalytic amount of iodine to afford
(
3.
1) Kocienski, P. J . Protecting Groups; Thieme: Stuttgart, 1994; p
8
(2) Nishiguchi, T.; Kawamine, K.; Ohtsuka, T. J . Chem. Soc., Perkin
1
:1). Figure 1 depicts the progress of the reaction of
Trans. 1 1992, 153.
3) Nishiguchi, T.; Fujisaki, S.; Kuroda, M.; Kajisaki, K.; Saitoh, M.
J . Org. Chem. 1998, 63, 8183.
4) (a) Bouzide, A.; Sauve, G. Tetrahedron Lett. 1997, 38, 5945. (b)
(
ethane-1,2-diol with DHP under reflux in THF.
Table 1 presents our observations along with the
optimum parameters for obtaining the best yields of
monotetrahydropyranylated diol.
Figure 2 shows the dependence of the product yield on
the microwave power in the monotetrahydropyranylation
of ethane-1,2-diol at a reaction period of 120 s. It may be
seen that above 40% (180 W) of power output the yield
remains between 60 and 65%. At higher energy the yield
of monoether is a little less due to the formation of the
(
Bessodes, M.; Boukarim, C. Synlett 1996, 1119. (c) Kalinowski, H. O.;
Crass, G.; Seebach, D. Chem. Ber. 1981, 114, 477.
(5) Ogawa, H.; Ichimura, Y.; Chihara, T.; Teratani, S.; Taya, K. Bull.
Chem. Soc. J pn. 1986, 59, 2481.
(
6) Barton, D. H. R.; Zhu, J . Tetrahedron 1992, 48, 8337.
(7) (a) Kalita, D. J .; Borah, R.; Sarma, J . C. Tetrahedron Lett. 1998,
3
9, 4573. (b) Deka, N.; Kalita, D. J .; Borah, R.; Sarma, J . C. J . Org.
Chem. 1997, 62, 1563. (c) Borah, R.; Deka, N.; Sarma, J . C. J . Chem.
Res. (S) 1997, 110.
(
8) Deka, N.; Sarma, J . C. Synth. Commun. 2000, 30 (24), 4435.
1
0.1021/jo000863a CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/28/2001

1
948 J . Org. Chem., Vol. 66, No. 6, 2001
Deka and Sarma
Ta ble 2. Cor r ela tion of Rea ction Tem p er a tu r e w ith
Tim e a t Sp ecified P ow er
time (s)
power (W)
temp (°C)
2
3
6
20
20
20
20
20
0
0
0
90
90
90
36
50
52
58
65
67
67
68
1
1
1
1
1
90
180
360
600
800
From Figures 1-3 as well as the Tables 1 and 2, it
can be inferred that the product yields and selectivities
of the reactions are microwave-specific and depend on
both the power of the microwave oven selected and the
total reaction time. These two factors in turn determine
the temperature of the reaction mixture. At lower tem-
perature the yield of the monoether is less in comparison
to the yield at higher temperature. Interestingly the yield
of the diether varies around 15 to 20% in all the reactions.
F igu r e 2. Yield vs microwave power. Reaction of ethane-1,2-
diol with DHP carried out for 120 s at different level. Graph
ABCDE for monoether. Graph abcde for diether.
Exp er im en ta l Section
In a typical reaction, a solution of 1 mmol (62 mg) of ethane-
1
,2-diol in dry THF (0.8 mL) was mixed with 1.25 mmol (106
mg) of 3,4-dihydro-2H-pyran and 0.2 mmol of iodine. The
mixture was added to a 50 mL conical flask, and a small funnel
was placed over it to reduce any possible evaporation of solvent
9
(
CAUTION). The flask as such was placed in a microwave
oven (kitchen type, Brand LG, Model ‘Multiwave’ MS-283MC)
and irradiated at 600 W of power for 150 s. Immediately on
completion, the flask was taken out, and the temperature of
the mixture was recorded with a thermometer. The mixture
was diluted with chloroform (50 mL) and washed with a dilute
solution of sodium thiosulfate followed by water. The organic
layer was dried over anhydrous sodium sulfate and evaporated
under reduced pressure. Purification by coloumn chromatog-
raphy (1:2 EtOAc:hexane) gave 78% (114 mg) of the monoether
F igu r e 3. Yield vs reaction time. Reaction of ethane-1,2-diol
with DHP at constant power. Graph ABCDE at 800 W power
and Graph abcde at 90 W power.
along with 17% (39 mg) of the diether. All the products are
already known in the literature2 and were characterized by
spectral analysis and by comparing with authentic material
prepared by reported methods.
corresponding diethers. In all the cases, the reactions are
not complete and around 10% of the diol remains unre-
acted. Figure 3 shows the variation of product yield at
different reaction times at a particular power of 20% (90
W) and 100% (800 W), respectively. At 90 W of power
the reaction remains incomplete, and the yields are also
low. Even at the highest power (800 W) the product yield
varies with time.
Ack n ow led gm en t. Authors are thankful to the
Director Dr. J S Sandhu FNA for providing the facilities,
and N.D. thanks CSIR, New Delhi, for a Senior Re-
search Fellowship.
J O000863A
(
9) CAUTION: Fire may break out when organic solvents, especially
Table 2 shows the temperature of the reaction mixture
corresponding to a range of power of the microwave oven
for a given period of time.
flammable ones, are heated in a domestic microwave oven. Of course,
in the present setup in small scale the reaction proceeded without any
mishaps.