Selective acylation of the phenolic hydroxyl of (hydroxyalkyl)phenols
1353
affording results similar to that with vinyl acetate, though
the times needed for complete consumption of the parent
diol were different. The acylation with 2,2-dimethylpropa-
noic acid vinyl ester proceeded regiospecifically to give
only the phenyl ester, though a longer reaction time was
necessary for complete consumption of the parent diol. On
the contrary, isopropenyl acetate did not work as an acyl
donor in the presence of RbF.
Table 4 Acylation of phenol (2) and 2-phenylethanol (3) with vinyl
acetate in the presence of RbF
Substrates
Time/min
Yields/%
Phenyl ester
Alkyl ester
2
45
60
45
60
100
–
–
3
10.4
3.8
7.8
2 ? 3
82.8
98.8
The chlorides, bromides, and iodides of cesium and
rubidium were completely ineffective for acylation. The
occurrence of acylation in the presence of cesium and
rubidium fluorides can be rationalized in terms of the
‘‘naked’’ fluoride anion from the corresponding salts facil-
itated by the electropositive character and large ionic radius
of the cesium and rubidium ions [13, 14, 21]. Moreover, the
fact that only vinyl esters can act as good acyl donors
suggests that their carbonyl groups can effectively be acti-
vated by the cesium or rubidium ion in the presence of the
vinyl group. The large activity of CsF compared with RbF
ascribed to the larger ionic radius of the cesium ion would
be responsible for the observed smaller selectivity when
CsF was employed. Furthermore, it is quite interesting to
know that the use of KF (0.1 mol equiv.) in the presence of
18-crown-6 (0.1 mol equiv.) resulted in the formation of the
phenyl ester in 84.7 % yield, together with the diester
(12.1 % yield), in 60 min, as compared with the afore-
mentioned result obtained with KF alone.
Reactions were conducted in acetonitrile at 80 °C using 1 mol equiv.
each of the substrates and 2 mol equiv. vinyl acetate in the presence
of RbF (0.1 mol equiv.)
selectivity observed was akin to that obtained with the diol
1a. With the diol 1d bearing a substituent ortho to the
phenolic hydroxyl in 1b, the reaction was rather slow and
afforded the phenyl ester in 83 % yield in 2 h accompanied
by a greater amount of the diester. With the diol 1e having
the meta reciprocal position between the phenolic hydroxyl
and the alkyl chain or the diol 1f bearing a substituent ortho
to the phenolic hydroxyl in 1e, the yield of the phenyl ester
was around 80 %, though a fair amount of the diester was
produced. With b-estradiol (1g) the reaction proceeded
regiospecifically to afford the phenyl ester quantitatively in
60 min in the presence of 0.1 mol equiv. RbF.
As shown in Table 4, when phenol (2) and 2-phenyl-
ethanol (3) were allowed to react with vinyl acetate in the
presence of RbF (0.1 mol equiv.), 2 was acetylated quan-
titatively in 45 min, while the yield of the acylated product
of 3 was only 10 % after 60 min. When a mixture of
equimolar amounts of 2 and 3 was treated in the same
manner as above, 2 was acetylated in more than 80 % yield
in 45 min and almost quantitatively in 60 min, while the
yield of the acylated product of 3 was less than 8 %. Thus,
the results of this competition reaction resemble those
obtained with the diol 2a.
Next, we set about examining the general applicability
of this novel acylation method using vinyl carboxylates and
RbF for selective acylation of the phenolic hydroxyl of
(hydroxyalkyl)phenols. The results are compiled in
Table 3. Quite a similar result was observed in the acety-
lation of 3-(4-hydroxyphenyl)propanol (1c) bearing a
longer alkyl chain. Although the reaction of (4-hydroxy-
phenyl)methanol (1b) was rather slow in the presence of
0.1 mol equiv. RbF and 1 mol equiv. was necessary for
complete consumption of the parent diol in 30 min, the
Conclusion
Table 3 Acylation of (hydroxyalkyl)phenols (1) with vinyl acetate in
the presence of RbF
With (hydroxyalkyl)phenols carrying both an alcoholic and
a phenolic hydroxyl, highly selective acylation of the
phenolic hydroxyl can be achieved without resorting to
specially devised reagents, but by using the more con-
ventional acyl donors, vinyl carboxylates, with the
assistance of RbF. Therefore, the present method should be
an attractive alternative to the existing methods.
Diol Mol equiv. RbF Time/min Yield/%
Phenyl ester Alkyl ester Diester
1b 0.1
60
30
8.2
0
0
0
0
0
0
0
0
1
92.7
96.0
83.3
78.3
78.8
100
7.3
4.0
11.6
13.9
19.6
0
1c
1d
1e
1f
0.1
1
30
120
25
1
1
30
Experimental
1g 0.1
60
Typical acylation procedure is as follows: a mixture of
a (hydroxyalkyl)phenol (0.4 mmol) and vinyl acetate
Reactions were conducted in acetonitrile at 80 °C using 2 mol equiv.
vinyl acetate
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