Reaction of 2,3-epoxypropyl ethers with 1-butanol

Article abstract of DOI:10.1023/B:RUJO.0000044537.64421.dd

Nucleophilic opening of the oxirane ring in 2,3-epoxypropyl ethers with alcohols in the presence of titanium alkoxides and other catalysts was studied. The mechanism of catalysis by titanium alkoxides was discussed on the basis of comparison with acid-bas

Full text of DOI:10.1023/B:RUJO.0000044537.64421.dd

Russian Journal of Organic Chemistry, Vol. 40, No. 6, 2004, pp. 769–772. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 6, 2004,
pp. 810–813.
Original Russian Text Copyright © 2004 by Yatluk, Suvorov, Khrustaleva, Chernyak.
Dedicated to Full Member of the Russian Academy of Sciences
O.N. Chupakhin on his 70th Anniversary
Reaction of 2,3-Epoxypropyl Ethers with 1-Butanol
Yu. G. Yatluk, A. L. Suvorov, E. A. Khrustaleva, and S. V. Chernyak
Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences,
ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia
e-mail: eop@ios.uran.ru
Received January 23, 2004
Abstract—Nucleophilic opening of the oxirane ring in 2,3-epoxypropyl ethers with alcohols in the presence of
titanium alkoxides and other catalysts was studied. The mechanism of catalysis by titanium alkoxides was
discussed on the basis of comparison with acid–base catalysts.
Addition of alcohols to alkyl 2,3-epoxypropyl
ethers in the presence of sodium alkoxides yields
1,3-dialkoxy-2-propanols, while under catalysis with
boron trifluoride–ether complex insignificant amounts
of 2,3-dialkoxy-1-propanol are also formed [1]. In
the reaction of 2,3-epoxypropyl phenyl ether with
1-butanol, 2-butoxy-3-phenoxy-1-propanol was isolat-
ed together with the major product, the corresponding
secondary alcohol [2]. It should be noted that no
quantitative estimation of the product ratio was per-
formed in [1, 2]. Kuvamura [3] reported on the
formation of secondary alcohol as the only product in
the presence of sulfuric acid. Caron and Sharpless in
their classical work [4] showed that titanium iso-
propoxide ensures highly selective ring opening in
2,3-epoxy-1-hexanol with a large number of nucleo-
philes; on the other hand, the corresponding methyl
ether failed to react under analogous conditions. It is
known that organic titanium compounds act as curing
agents toward epoxy resins, i.e., they are capable of
catalyzing opening of epoxy ring with hydroxy
compounds [5].
equimolar amounts with respect to the substrate. The
products were identified by GLC. Generally, the reac-
tion can occur both according to the Krasuskii rule and
contrary to it (Scheme 1). The results are summarized
in Table 1.
Scheme 1.
Catalyst
CH2OR
III
RO
OBu
+
BuOH
O
OH
Ia–Ic
II
IVa–IVc
RO
OH
+
OBu
Va–Vc
I, IV, V, R = C4H9 (a), CH2=CHCH2 (b), C6H5 (c).
It is seen that titanium butoxide at 140°C exhibits
a weak catalytic activity in the reaction of butyl
2,3-epoxypropyl ether with 1-butanol, as compared to
acid and base catalysts. The overall yield of dialkoxy-
propanols ranges from 9 to 16%, and a considerable
amount of the initial ether is recovered from the
reaction mixture. Probable isomerization products,
such as butoxyacetone and 3-butoxypropanal were not
detected. The yield increases in going to boron tri-
fluoride–ether complex and benzyldimethylamine as
catalysts. The maximal yield was obtained in the
presence of sulfuric acid. Taking into account that the
substrate conversion was complete (initial butyl
2,3-epoxypropyl ether was not detected among the
The goal of the present work was to compare the
efficiency and selectivity of oxirane ring opening in
2,3-epoxypropyl ethers in the presence of titanium
alkoxides and other catalysts. We examined the reac-
tion of 2,3-epoxypropyl ethers with 1-butanol as
a model. The reactions were carried out at different
reactant ratios using titanium butoxide, sulfuric acid
(protic acid), boron trifluoride–ether complex (Lewis
acid), and benzyldimethylamine (base) as catalysts.
Titanium butoxide was added in both catalytic and
1070-4280/04/4006-0769 © 2004 MAIK “Nauka/Interperiodica”

YATLUK et al.
Table 1. Reactions of 2,3-epoxypropyl ethers I with 1-butanol (II) in the presence of catalysts III; temperature 140°C
770
R in I
Butyl
Butyl
Butyl
Butyl
Butyl
Butyl
Butyl
Allyl
Catalyst III
Molar ratio I:II:III
1:4:0
Overall yield (IV + V), %
Ratio IV:V, %
95:50
–
04.5
64.0
39.0
43.0
09.1
16.0
09.8
15.0
15.0
H2SO4
1:4:0.06
1:4:0.06
1:4:0.06
1:4:0.06
1:4:1
78:22
BF3–Et2O
85:15
C6H5CH2N(CH3)2
Ti(OC4H9)4
Ti(OC4H9)4
Ti(OC4H9)4
Ti(OC4H9)4
Ti(OC4H9)4
98:20
90:10
88:12
1:0:1
60:40
1:4:1
91:90
Phenyl
1:4:1
94:60
products), the low yields may be due to concurrent
polymerization of butyl 2,3-epoxypropyl ether. This
was confirmed by the presence of a considerable
amount of undistillable products.
In order to raise the yield of the addition products,
the reaction of 2,3-epoxypropyl ethers with 1-butanol
was carried out at higher temperature. The results
given in Table 2 show that the overall yield of products
IV and V in the reaction catalyzed by titanium
butoxide considerably increases as the temperature
rises from 140 to 200°C; the above relations holding in
the selectivity of the process are generally conserved.
The yield of the addition products increases with
rise in the amount of titanium butoxide from catalytic
to equimolar. In the absence of 1-butanol, the yield
decreases, indicating that the addition of titanium
butoxide itself is ineffective. The addition of 1-butanol
in the absence of a catalyst occurs with a very poor
yield. The nature of the R radical in 2,3-epoxypropyl
ether almost does not affect the yield.
Scheme 2.
CH2OH
+
Ti(OR)4
O
–ROH
O
O
Ti(OR)3
Under catalysis by benzyldimethylamine, the major
product is 1,3-dialkoxy-2-propanol, whereas almost no
primary alcohol is formed. The yield of the latter
increases in the presence of sulfuric acid. Boron tri-
fluoride–ether complex occupies an intermediate place
between the base and acid catalysts; it approaches
titanium butoxide in the selectivity but is superior to
Ti(OBu)4 in the product yield. Increase in the amount
of titanium butoxide from catalytic to equimolar
almost does not affect the product ratio. The high
selectivity in the absence of a catalyst is likely to result
from leaching of glassware. The substituent in the
substrate has no appreciable effect on the product ratio.
Reactions of titanium alkoxides with 2,3-epoxy-1-
propanol involve intermediate formation of a complex
shown in Scheme 2 [4]. Such structure cannot be
obtained from 2,3-epoxypropyl ethers. Let us consider
possible mechanisms of alcohol addition to 2,3-epoxy-
propyl ethers in the presence of titanium alkoxides
with account taken of the complexing power of the
catalyst toward the substrate and the product ratio.
Gut [6] studied complex formation in the system
Ti(OMe)4–MeOH and found that the dissociation
constant of the alkoxide is so small that it could not be
measured.
Ti(OMe)4
Ti(OMe)+3
+
MeO–
Table 2. Reaction of butyl 2,3-epoxypropyl ether (Ia) with
1-butanol (II) in the presence of titanium butoxide at 200°C
Therefore, participation of titanium alkoxides in
the catalytic process as bases seems to be improbable.
On the other hand, it was shown [6] that titanium
methoxide with methanol forms an acidic complex:
Molar ratio
Ia:II:III
Ratio
IV:V, %
Overall yield (IV + V), %
1:4:0
21
51
52
23
97:30
88:12
92:80
72:28
[Ti2(OMe)9]–
+
H+
1:4:0.06
1:4:1
H[Ti2(OMe)9]
We previously studied in detail [7] complex forma-
tion in alkanol–titanium alkoxide systems and showed
1:0:1
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

REACTION OF 2,3-EPOXYPROPYL ETHERS WITH 1-BUTANOL
771
Scheme 3.
Bu
H
O
RO
RO
RO
OH
–H+
O
OBu
CH2OR
CH2OR
H
H+
BuOH
O
O
H
Bu
O
RO
H
OBu
–H+
O
H
OH
Scheme 4.
Bu
H
O
RO
RO
OH
–Ti(OBu)4
O
OBu
CH2OR
CH2OR
Ti(OBu)4
Ti(OBu)4
BuOH
O
O
Bu
O
Ti(OBu)4
RO
H
RO
OBu
–Ti(OBu)4
O
OH
Ti(OBu)4
that the complex derived from 1-butanol and titanium
butoxide (which is the most acidic) dissociates accord-
ing to the following scheme:
inner-sphere coordination of epoxide and outer-sphere
coordination of alcohol (A, B) and with inner-sphere
coordination of alcohol and outer-sphere coordination
of epoxide (C, D).
Ti(OBu)4
+
BuOH
H+
H[Ti(OBu)5]
[Ti(OBu)5]–
Bu
H
O
A
Bu
Bu
H
O
B
Bu
O
O
O
O
+
Ti(OBu)3
Ti(OBu)3
Thus titanium butoxide, being a weak Lewis acid,
reacts with 1-butanol to give a complex Meerwein
acid, and the subsequent addition of the alcohol can
follow the acid catalysis pattern (Scheme 3). However,
in this case the regioselectivity should be the same as
under catalysis by sulfuric acid. Provided that the
amount of titanium butoxide increases (or the amount
of 1-butanol decreases), the alkoxide can act as Lewis
acid (Scheme 4). Then the regioselectivity should
approach that observed in the presence of Lewis acids,
i.e., boron trifluoride–ether complex. In fact, titanium
alkoxide gives rise to higher regioselectivity, as com-
pared to both H2SO4 and BF3–Et2O.
RO
RO
(OR)3
Ti
(OR)3
Ti
Bu
Bu
Bu
Bu
O
O
O
O
H
O
H
O
RO
RO
C
D
Taking into account that complexes of titanium
alkoxides with alcohols are more stable, the latter
version of the coordination–acid catalysis is preferred
(Scheme 5). Undoubtedly, steric hindrances to forma-
tion of the complex giving rise to secondary alcohol
are greater; therefore, the corresponding primary
alcohol is formed as the major product.
We showed in [8] that ethers, including epoxy
derivatives, are capable of forming complexes with
titanium butoxide, although such complexes with
ethers are weaker than those derived from alcohols.
Two pairs of transition complexes can be formed: with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004

YATLUK et al.
772
Scheme 5.
Ti(OBu)4
+
BuOH
H[Ti(OBu)5]
(OR)3
Ti
Bu
Bu
O
O
H
RO
RO
OBu
–BuOH
O
OTi(OBu)3
O
RO
H[Ti(OBu)5]
RO
(OR)3
Ti
Bu
Bu
O
O
OTi(OBu)3
–BuOH
H
O
OBu
RO
BuOH
Ti(OBu)3[C3H5(OR)(OBu)]
+
C3H5(OR)(OBu)(OH)
+
Ti(OBu)4
Thus reactions of 2,3-epoxypropyl ethers with
1-butanol in the presence of titanium alkoxides give
addition products both according and contrary to the
Krasuskii rule. The overall yield increases as the
temperature rises, and the selectivity approaches 90%.
Analysis of the selectivity observed under catalysis by
titanium butoxide, base, mineral acid, and Lewis acid
suggests that the coordination–acid mechanism of
catalysis is preferred.
hydrochloric acid (to remove titanium butoxide). The
organic phase was separated, dried over sodium
sulfate, and subjected to fractional distillation under
reduced pressure. The target fraction was analyzed by
GLC. The reaction at 200°C was carried out in a sealed
ampule.
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were added to 0.2 mol of 1-butanol. The mixture was
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 6 2004