668
Chemistry Letters Vol.38, No.7 (2009)
Phosphorofluoridic Acid-catalyzed Condensation Reaction of Carboxylic Acids
with 1-Arylalkyl Alcohols Leading to Esters under Solvent-free Conditions
Toshiaki Murai,Ã1 Nagisa Tanaka,1 Shinji Higashijima,2 and Hidetoshi Miura2
1Department of Chemistry, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193
2Chemicrea Inc., Tsukuba Center Inc. D-14, 2-1-6 Sengen, Tsukuba 305-0047
(Received April 8, 2009; CL-090348; E-mail: mtoshi@gifu-u.ac.jp)
O
P
2
O
P
O
Phosphorofluoridic acid with an L-menthyl group catalyzed
Bu4NF
THF
Bu4N+
−O
F
HO
F
PhO
PhO
P
1
condensation reaction between carboxylic acids and 1-arylalkyl
alcohols under solvent-free conditions to give esters in moderate
to high yields. Results using aliphatic acids are shown.
OR
OR
OR
Scheme 1.
Table 1. Acid-catalyzed condensation between 3a and 4aa
Catalyst
5 mol%
O
Condensation reactions between carboxylic acids and alco-
hols leading to esters are some of the most fundamental chemical
processes.1 Recently, attention has been focused on these reac-
tions using acid-sensitive substrates mediated by nonmetal
Brønsted acid catalysts. For example, ammonium2 and phospho-
nium3 salts of sulfonic acids have been developed to achieve
these reactions. In these cases, it is not necessary to remove
water, which is a coproduct of condensation reactions, from
the reaction vessels. However, the reaction has to be performed
in organic solvents. From an environmental perspective, it would
be more preferable if the reactions could be carried out under
solvent-free conditions. Instead of organic solvents, ionic liquids
have been used as a reaction media under microwave-irradia-
tion.4 Alternatively, ammonium tribromide has been used to me-
diate the condensation reaction, but large excess amounts of al-
cohols were used.5 Very recently, Ishihara et al. reported that
sulfuric, toluenesulfonic, and camphorsulfonic acid-catalyzed
condensation reaction under open air effectively gave the corre-
sponding esters.6 Nevertheless, even these systems do not
always mediate the esterification with high efficiency. For exam-
ple, the use of alcohols, such as 1-arylethyl alcohols, which read-
ily undergo acid-catalyzed dehydration, results in the formation
of esters in only low yields.7 The acid catalysts that have been
developed to date mainly have sulfonic acid moieties. In con-
trast, less attention has been paid to those with phosphoric acid
moieties. This may partly be due to their lower acidities com-
pared to those of sulfonic acids. The introduction of electron-
withdrawing groups at the phosphorus atom might be expected
to provide stronger acids. Furthermore, the introduction of hy-
drophobic sites to the oxygen atoms of phosphoric acids makes
it possible to remove water from the reactive centers while main-
taining high catalytic activities. While phosphorofluoridic acids
with various alkyl substituents have been described,8 to the best
of our knowledge there has been no report on their application as
acid catalysts, most likely due to their complicated syntheses.
Very recently, we found that fluoridative hydrolysis ofO,O-di-
aryl phosphoric acid esters gave phosphorofluoridic acid salts 1,9
which can be converted to the corresponding acids 2 (Scheme 1).
We report herein the first example of a phosphorofluoridic
acid-catalyzed condensation reaction of carboxylic acids and 1-
arylalkyl alcohols leading to esters under solvent-free conditions.
Initially, to clarify the catalytic ability of phosphorofluoridic
acids 2, the reaction between 2-bromobutanoic acid (3a) and
1-phenylethyl alcohol (4a) was carried out in the presence of
+
OH
HO
+
Ph
temp, time
+
3a
4a
Br
O
Ph
O
Ph
Ph
Ph
O
Ph
7
5
6
Br
Temp Time
Yield /%
Entry
Catalyst
/°C
/h
5
6
7
0
29
1
24
0
0
0
None
80
80
80
1
2
3
4
5
6
7
60
27
0
H2SO4
TsOH
2
40
51
77
38
54
0
22.5
26
6
0
PhOP(O)(OH)2 80
0
42
27
30
PhP(O)(OH)2
PhP(O)(OH)2
PhP(O)H(OH)
80
100
80
0
0
22
0
0
3
1
21
3
51
57
75
76
37
13
35
44
80
100
100
100
8
O
9
10
11
HO
F
P
O
5.5
22.5
2a
aThe reaction mixture of 3a (2 mmol) and 4a (3 mmol) was heat-
ed with stirring in the presence of a catalyst (0.1 mmol).
a variety of acids under solvent-free conditions (Table 1). The
reaction in the presence of H2SO4 catalyst was complete within
1 h, but mainly gave alkene 7,10 which may be formed via
two molecules of styrene derived from the dehydration of 4a
(Entry 2). The p-toluenesulfonic acid-catalyzed condensation
reaction gave the desired product 5 to some extent, but also pro-
duced some inseparable impurities (Entry 3). Phosphoric acid
analogues were then used to catalyze the reaction (Entries 4–
7). The reaction for more than 20 h gave 5 in yields of more than
50%, but the reaction at a higher temperature and for a shorter
reaction time gave 5 in a reduced yield (Entry 6).
The catalytic activity of phosphorofluoridic acid 2a for the
esterification was then examined. The reaction at 80 ꢀC for
21 h gave 5 in 51% yield, and that at 100 ꢀC for 5.5 h gave 5
in 75% yield, although ether 6 was also formed as a by-product.
Various combinations of acids 3 and 1-arylethyl alcohols 4
were subjected to an acid 2a-catalyzed condensation reaction
(Table 2). In most cases, acid 2a catalyzed the condensation re-
Copyright Ó 2009 The Chemical Society of Japan
Murai, Toshiaki
