N,N-diarylammonium pyrosulfate as a highly effective reverse micelle-type catalyst for hydrolysis of esters

Article abstract of DOI:10.1021/ol301290c

Reverse micelle-type N,N-diarylammonium pyrosulfate (3-5 mol %) efficiently catalyzes the hydrolysis of esters (up to 100 mmol scale) under organic solvent-free conditions. The present method is successfully applied to the hydrolysis of various esters without the decomposition of the base-sensitive moieties and without any loss of optical purity for α-heterosubstituted carboxylic acids.

Full text of DOI:10.1021/ol301290c

ORGANIC
LETTERS
2
012
Vol. 14, No. 12
194–3197
N,N-Diarylammonium Pyrosulfate as a
Highly Effective Reverse Micelle-Type
Catalyst for Hydrolysis of Esters
3
†
Yoshiki Koshikari, Akira Sakakura, and Kazuaki Ishihara*
‡
,†,§
Graduate School of Engineering and EcoTopia Science Institute, Nagoya University,
Furo-cho, Chikusa, Nagoya, 464-8603, Japan, and JST, CREST, Furo-cho, Chikusa,
Nagoya 464-8603, Japan
ishihara@cc.nagoya-u.ac.jp
Received May 10, 2012
ABSTRACT
Reverse micelle-type N,N-diarylammonium pyrosulfate (3À5 mol %) efficiently catalyzes the hydrolysis of esters (up to 100 mmol scale) under
organic solvent-free conditions. The present method is successfully applied to the hydrolysis of various esters without the decomposition of the
base-sensitive moieties and without any loss of optical purity for r-heterosubstituted carboxylic acids.
The hydrolysis of esters is one of the most fundamental
transformations in organic synthesis since esters are used
not only as substrates for the synthesis of carboxylic acids
but also as protecting groups for carboxylic acids or
alcohols. In general, the hydrolysis of esters is irreversibly
conducted using Brønsted bases such as LiOH and NaOH
2
in a homogeneous solution. Since the resulting carboxylic
acids neutralize the Brønsted base, stoichiometric amounts
of Brønsted bases are required to complete the reaction. In
addition, after the reaction, stoichiometric amounts of
strong Brønsted acids are required to acidify the resultant
reaction mixture to obtain the carboxylic acids.
In sharp contrast, Brønsted acids catalytically promote
3
the hydrolysis of esters. Under organic/aqueous bilayer
conditions, most Brønsted acid catalysts are ineffective
4
because of their high solubility in water, while solid acids
1
5
such as Amberlite or zeolite can be used as catalysts.
When hydrophobic esters are hydrolyzed to hydrophobic
carboxylic acids and hydrophilic alcohols or tohydrophilic
carboxylic acids and hydrophobic alcohols, the reverse
esterification should be suppressed under acidic organic/
aqueous bilayer conditions, since the hydrophilic products
are selectively removed to the aqueous layer. For this reaction
system, oil-soluble hydrophobic small-molecule Brønsted
acids would be more effective than these solid acid catalysts.
Indeed, Okahata and colleagues reported that a lipid-coated
lipase dissolved in the organic layer and showed 40- to
†
Graduate School of Engineering.
EcoTopia Science Institute.
CREST.
‡
§
6
(
1) Wuts, P. G.; Greene, T. W. Greene’s Protective Groups in Organic
Synthesis, 4th ed.; Wiley-VCH: Weinheim, 2006.
2) (a) Larock, R. C. Comprehensive Organic Transformations, 2nd
100-fold greater catalytic activity than the native lipase.
(
ed.; Wiley-VCH: New York, 1999. (b) Theodorou, V.; Skobridis, K.;
(4) Izumi, Y. Catal. Today 1997, 33, 371.
Tzakosb, A. G.; Ragoussis, V. Tetrahedron Lett. 2007, 48, 8230.
(5) For examples of the solid acid-catalyzed hydrolysis of esters, see:
(a) Ogawa, H.; Tensai, K.; Taya, K.; Chihara, T. J. Chem. Soc., Chem.
Commun. 1990, 1246. (b) Kimura, M.; Makato, T.; Okuhara, T. Appl.
Catal., A 1997, 165, 227. (c) Iimura, S.; Manabe, K.; Kobayashi, S.
J. Org. Chem. 2003, 68, 8723. (d) Delgado, P.; Sanz, M. T.; Beltr ꢀa n, S.
Chem. Eng. J 2007, 126, 111.
(
3) For examples of the acid-catalyzed hydrolysis of esters under the
homogeneous conditions, see: (a) Skeean, R. W.; Goel, O. P. Synthesis
990, 628. (b) Yamaguchi, S.; Mutoh, M.; Shimakura, M.; Tsuzuki, K.;
1
Kawase, Y. J. Heterocycl. Chem 1991, 28, 119. (c) H o€ dl, C.; Raunegger,
K.; Strommer, R.; Ecker, G.; Kunert, O.; Sturm, S.; Seger, C.; Haslinger,
E.; Steiner, R.; Strauss, W. S. L.; Schramm, H.-W. J. Med. Chem. 2009,
(6) Mori, T.; Kishimoto, S.; Ijiro, K.; Kobayashi, A.; Okahata, Y.
Biotechnol. Bioeng. 2001, 76, 157.
52, 1268.
1
0.1021/ol301290c r 2012 American Chemical Society
Published on Web 05/30/2012

We recently reported that oil-soluble N,N-diarylammo-
nium pyrosulfate 1 (Figure 1), which was prepared by
mixing an equimolar amount of sulfuric acid and N-(2,4,6-
triisopropylphenyl)-N-(2,6-diphenylphenyl)amine (2) at
Table 1. Catalytic Activities for the Hydrolysis of Methyl
Laurate
a
8
tion reactions between hydrophobic carboxylic acids and
0 °C for 0.5 h, was an efficient catalyst for ester condensa-
7
,8
hydrophobic alcohols under aqueous conditions. The
high catalytic activity is attributed to the hydrophobic
9
,10
effect of the bulky aryl groups of the catalyst. We report
here a highly efficient hydrolysis of esters catalyzed by 1
under organic/aqueous bilayer conditions.
b
entry
catalyst
X (mol %)
yield (%)
c
1
1
1
1
1
5
5
56
86
82
84
17
4
2
d,e
3
5
f
4
g
1
5
Amberlite IR 120-H
SO
5
6
7
8
9
H
2
4
5
DBSA
LiOH
5
77
h
100
100
4 (6)
Me
3
SnOH
4
a
The reaction of methyl laurate (2 mmol) was conducted with a
b
1
catalyst (X mol %) in water (8 mL) at 60 °C for 20 h. Determined by H
NMR analysis. The reaction was conducted in water (1 mL). Com-
c
d
pound 1 was prepared by mixing an equimolar amount of sulfuric acid
CNÀhexane (1:1 v/v) under azeotropic reflux conditions
and 2 in CH
3
e
f
for 0.5 h. For 8 h. For 68 h. The reaction was conducted under reflux
g
Figure 1. N,N-Diarylammonium pyrosulfate 1.
h
4
conditions. In the presence of Bu NBr (5 mol %).
We first examined the catalytic activity of 1 for the
hydrolysis of methyl laurate under aqueous conditions
1
2
acid (DBSA) catalyzed the hydrolysis of methyl laurate
entry 7). The reaction mixture catalyzed by DBSA also
(
Table 1). When the reaction of methyl laurate (2 mmol)
was conducted in the presence of 1 (5 mol %) and water
1 mL) at 60 °C for 20 h, lauric acid was obtained in 56%
(
formed an oil-in-water emulsion. In contrast to the 1-
catalyzed reaction, the addition of NaOH (5 mol %) to
the reaction mixture did not give a clear separation of the
two layers, since the sodium salt of DBSA might act as a
surfactant. The initial rates of 1-catalyzed hydrolysis were
independent of the amounts of water (Figure 2A). On
the other hand, the initial rates of DBSA-catalyzed
hydrolysis significantly depended on the amounts of
water. The use of less amounts of water showed greater
initial rates although yields of carboxylic acids were low
because of the unfavorable equilibrium (Figure 2B). It
is conceivable that catalyst 1 forms reverse micelles in
(
yield (entry 1). The yield was not improved by prolonging the
reaction time. The low yield could be attributed to the
rather low solubility of methanol in the aqueous layer. The
use of 8 mL of water successfully improved the yield of
lauric acid (86% yield, entry 2). Although the reaction
mixture was an oil-in-water emulsion, the addition of
NaOH (5 mol %) gave a clear separation of the organic
1
1
1
3
1
1
substrate layer and the aqueous layer. Thus, the crude
lauric acid was easily obtained by simple decantation.
When 1 was prepared under azeotropic reflux conditions
1
1
7
in CH CNÀhexane (1:1 v/v), the catalytic activity in-
3
organic layer to promote the hydrolysis. In contrast,
surfactant-type DBSA might promote the hydrolysis on
creased (entry 3). Only 1 mol % of 1 was sufficient to give
the lauric acid in 84% yield (entry 4).
On the other hand, Amberlite IR 120-H was ineffec-
tive even under reflux conditions (entry 5). Hydrophilic
sulfuric acid was almost inert under organic/aqueous
bilayer conditions (entry 6). p-Dodecylbenzenesulfonic
1
2
the surface of the oil-in-water emulsion. Since the use
of larger amounts of water made the emulsion droplets
smaller, the concentration of DBSA on the surface
should decrease, which could result in lower reactivity
in the DBSA-catalyzed hydrolysis.
5
Under organic/aqueous bilayer conditions, a conventional
Brønsted base such as lithium hydroxide (100 mol %)
was almost inert (entry 8). The addition of Bu NBr, a
(
7) Sakakura, A.; Koshikari, Y.; Akakura, M.; Ishihara, K. Org.
Lett. 2012, 14, 30.
8) Igarashi, T.; Yagyu, D.; Naito, T.; Okumura, Y.; Nakajo, T.;
Mori, Y.; Kobayashi, S. Appl. Catal., B 2012, 119À120, 304.
9) (a) Ishihara, K.; Nakagawa, S.; Sakakura, A. J. Am. Chem. Soc.
005, 127, 4168. (b) Sakakura, A.; Nakagawa, S.; Ishihara, K. Tetra-
4
(
(
(12) (a) Manabe, K.; Sun, X.-M.; Kobayashi, S. J. Am. Chem. Soc.
2001, 123, 10101. (b) Kobayashi, S.; Iimura, S.; Manabe, K. Chem. Lett.
2002, 31, 10. (c) Manabe, K.; Iimura, S.; Sun, X.-M.; Kobayashi, S.
J. Am. Chem. Soc. 2002, 124, 11971. (d) Aoyama, N.; Kobayashi, S.
Chem. Lett. 2006, 35, 238. (e) Shirakawa, S.; Kobayashi, S. Org. Lett.
2007, 9, 311.
2
hedron 2006, 62, 422. (c) Sakakura, A.; Watanabe, H.; Nakagawa, S.;
Ishihara, K. Chem. Asian J. 2007, 2, 477. (d) Sakakura, A.; Nakagawa,
S.; Ishihara, K. Nat. Protoc. 2007, 2, 1746.
(
10) (a) Wakasugi, K.; Misaki, T.; Yamada, K.; Tanabe, Y. Tetra-
hedron Lett. 2000, 41, 5249. (b) Funatomi, T.; Wakasugi, K.; Misaki, T.;
Tanabe, Y. Green Chem. 2006, 8, 1022. (c) Gacem, B.; Jenner, G.
Tetrahedron Lett. 2003, 44, 1391. (d) Mercs, L.; Pozzi, G.; Quici, S.
Tetrahedron Lett. 2007, 48, 3053.
(13) In contrast to the hydrolysis of esters, the reactivity of 1-
catalyzed ester condensation in water became lower as the amounts of
7
water increased. The carboxylic acid used as a substrate might act as a
surfactant in the early stage of the ester condensation to decrease the
reactivity when larger amounts of water were used.
(11) See the Supporting Information for details.
Org. Lett., Vol. 14, No. 12, 2012
3195

Table 2. 1-Catalyzed Hydrolysis of Esters Composed of Hy-
drophobic Carboxylic Acids and Hydrophilic Alcohols
a
Figure 2. Plot of conversion versus time for the hydrolysis of
methyl laurate: (A) catalyzed by 1; (B) catalyzed by DBSA. Key:
green, H O (8 mL); blue, H O (4 mL); red, H O (2 mL); black,
2
2
2
H
2
O (1 mL).
1
4
phase-transfer catalyst, did not improve the reactivity.
Trimethyltin hydroxide (100 mol %), a mild and effective
1
5
promoter for the hydrolysis of esters in organic solvent,
was also inert (entry 9). The low activities of these alkaline
catalysts might be attributed to their low solubilities in the
organic substrate layer.
a
The reaction of ester (1 mmol) was conducted with 1 (5 mol %) in
b
1
c
water (4 mL) at 60 °C. Determined by H NMR analysis. At 80 °C.
d
e
The reaction was conducted in water (8 mL/mmol). The reaction of
triolein (100 mmol) was conducted with 1 (3 mol %) in water (400 mL) at
0 °C for 56 h.
To explore the generality and scope of the present 1-
catalyzed method, the hydrolysis of various esters, com-
posed of hydrophobic carboxylic acids and hydrophilic
alcohols, were examined (Table 2). In these reactions, the
hydrophilic alcohols were removed to the aqueous layer
and the hydrophobic carboxylic acids remained as the
organic substrate layer. The solubility of the generated
alcohol in water was important for obtaining the corre-
sponding carboxylic acid in high yield. Methyl, ethyl, and
ethylene glyceryl esters (1 mmol) were smoothly hydro-
lyzed in the presence of water (4 mL) and gave the corres-
ponding carboxylic acids in good yields (entries 1À3). A
larger amount of water (8 mL) was required for the efficient
hydrolysis of isopropyl laurate (1 mmol), since isopropyl
alcohol is less soluble in water than methanol (entry 4). The
present method could also be applied to the hydrolysis of
8
1
7
basic conditions and easily racemized. For example, the
conventional alkaline hydrolysis (method B) of (S)-methyl
O-methylmandelate (entry 2), N-Cbz-L-phenylglycine
1
8
methyl ester (entry 4), and N-Cbz-O-benzyl-L-serine
methyl ester (entry 6) resulted in epimerization, although
the corresponding carboxylic acids were obtained in high
yields. In contrast, 1-catalyzed hydrolysis of these esters
(method A) gave the corresponding carboxylic acids
without any loss of optical purity (entries 1, 3, and 6). The
present protocol could be conducted on a gram scale: 25 g
of N-Cbz-L-phenylglycine was obtained in a single reaction
(entry 4).
The present method could also be applied to esters
bearing a base-sensitive group. For example, N-Fmoc-
protected L-phenylalanine methyl ester was successfully
hydrolyzed without cleavage of the Fmoc group by method
A (entry 8). In contrast, under alkaline conditions (method
B), the Fmoc group was completely removed and unpro-
1
6
triacylglycerols in high yields without the isomerization
of carbonÀcarbon double bonds (entries 5À8). The pre-
sent protocol could be applied to a gram-scale reaction.
The hydrolysis of triolein (89 g, 100 mmol) catalyzed by 1
(
3 mol %) gave oleic acid in 82% yield (entry 7).
2
Next, we examined the hydrolysis of chiral R-heterosub-
stituted esters (Table 3). These esters are unstable under
tected L-phenylalanine was generated (entry 9). When the
substrates and/or products were solid under the reaction con-
ditions, the addition of a small amount of organic solvent
(
14) Crouch, R. D.; Burger, J. S.; Zietek, K. A.; Cadwallader, A. B.;
Bedison, J. E. Synlett 2003, 991.
15) (a) Furlan, R. L. E.; Mata, E. G.; Mascaretti, O. A. J. Chem.
(
(17) Kaestle, K. L.; Anwer, M. K.; Audhya, T. K.; Goldstein, G.
Tetrahedron Lett. 1991, 32, 327.
Soc., Perkin Trans. 1 1998, 355. (b) Furlan, R. L. E.; Mata, E. G.;
Mascaretti, O. A.; Pena, C.; Coba, M. P. Tetrahedron 1998, 54, 13023.
(18) (a) Lovri ꢀc , M.; Cepanec, I.; Litvi ꢀc , M.; Bartolin ꢀc i ꢀc , A.; Vinkovi ꢀc ,
V. Croat. Chem. Acta 2007, 80, 109. (b) Maegawa, Y.; Agura, K.;
Hayashi, Y.; Ohshima, T.; Mashima, K. Synlett 2012, 137.
(19) (a) Orita, A.; Hamada, Y.; Nakano, T.; Toyoshima, S.; Otera, J.
Chem.;Eur. J. 2001, 7, 3321. (b) Iwasaki, T.; Agura, K.; Maegawa, Y.;
Hayashi, Y.; Ohshima, T.; Mashima, K. Chem.;Eur. J. 2010, 16, 11567.
(20) Otera, J. Acc. Chem. Res. 2004, 37, 288.
(
(
c) Furlan, R. L. E.; Mascaretti, O. A. Aldrichimica Acta 1997, 30, 55.
d) Furlan, R. L. E.; Mata, E. G.; Mascaretti, O. A. Tetrahedron Lett.
1
996, 37, 5229. (e) Nicolaou, K. C.; Estrada, A. A.; Zak, M.; Lee, S. H.;
Safina, B. S. Angew. Chem., Int. Ed. 2005, 44, 1378.
16) Beal, G. D. Organic Synthesis; Wiley: New York, 1941; Collect.
Vol. I, p 379.
(
3
196
Org. Lett., Vol. 14, No. 12, 2012

p-methoxybenzyl (PMB) (entry 8) groups afforded the
corresponding alcohols without cleavage of these protecting
Table 3. Hydrolysis of Base-Sensitive Optically Active Methyl
Esters
2
groups. However, highly acid-sensitive protecting groups
such as tert-butyldimethylsilyloxy (TBSO) and tetrahydro-
pyranyloxy (THPO) groups hydrolyzed more rapidly than
11
an acetoxy group under the present reaction conditions.
Table 4. 1-Catalyzed Hydrolysis of Esters Composed of Hy-
drophobic Alcohols and Hydrophilic Carboxylic Acids
a
a
Conditions A: The reaction of methyl ester (1 mmol, >99% ee) was
conducted with 1 (5 mol %) in water (4 mL) at 80 °C for 9 h. Conditions
B: The reaction of methyl ester (1 mmol, >99% ee) was conducted with
LiOH (100 mol %) in waterÀMeOHÀTHF (2:2:1 v/v, 2.5 mL) at rt for
b
c
d
2
À4 h. Isolated yield. For 20 h. The reaction of N-Cbz-L-phenylgly-
cine methyl ester (100 mmol) was conducted in the presence of 1 (1 mol %)
e
in water (400 mL) at 80 °C for 9 h. WaterÀEtNO
2
(13:1 v/v, 4.3 mL) was
used as a solvent.
such as nitroethane was effective for dissolving the ester and
promoting the hydrolysis (entry 8).
a
Next, the 1-catalyzed hydrolysis of esters composed of
hydrophobic alcohols and hydrophilic carboxylic acids
The reaction of ester (1 mmol) was conducted with 1 (5 mol %) in
b 1 c d
water (4 mL). Determined by H NMR analysis. For 6 h. For 4 h.
e
f
Isolated yield of L-lactic acid. Yield of dicinnamyl ether.
1
9
was examined (Table 4). In this case, the hydrophilic
carboxylicacidswereremoved tothe aqueouslayer and the
hydrophobic alcohols remained as the organic substrate
layer. A variety of acetates and propionates were successfully
converted to the corresponding alcohols (entries 1À3).
The 1-catalyzed hydrolysis of dodecyl isobutyrate gave
In conclusion, reverse micelle-type N,N-diarylammo-
nium pyrosulfate 1 highly efficiently catalyzed the hydro-
lysis of various esters under organic/aqueous bilayer con-
ditions to give the corresponding carboxylic acids and/or
alcohols in good yields. The present method was success-
fully applied to the hydrolysis of base-sensitive esters to
give the corresponding carboxylic acids without decom-
position of the base-sensitive moieties and without any loss
of optical purity for R-heterosubstituted carboxylic acids.
1
-dodecanol in only 38% yield (entry 4). This is because
isobutyric acid is not sufficiently soluble in water to transfer
to the aqueous layer. The hydrolysis of 1-dodecyl L-lactate
gave 1-dodecanol in 87% yield as the organic layer, while L-
lactic acid was obtained from the aqueous layer after
11
purification by ion-exchange chromatography (entry 5).
Acknowledgment. Financial support for this project
was partially provided by JSPS.KAKENHI (20245022
and 23350039), NEDO, Yazaki Memorial Foundation
for Scienceand Technology, and the GlobalCOE Program
of MEXT.
In general, allylic esters and allylic alcohols are acid-
sensitive, and the acid-catalyzed hydrolysis of allylic esters
generates a significant amount of diallylic ethers as by-
products. In fact, the 1-catalyzed hydrolysis of cinnamyl
2
0
acetate at 60 °C gavedicinnamyl ether in 15% yield along
with cinnamyl alcohol (82%). When the same reaction
was conducted at 40 °C, the yield of dicinnamyl ether was
reduced to 2% and the desired cinnamyl alcohol was
obtained in 92% yield (entry 6). The hydrolysis of ace-
tates bearing tert-butyldiphenylsilyl (TBDPS) (entry 7) or
Supporting Information Available. Detailed experimen-
tal procedures. This material is available free of charge via
the Internet at http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 14, No. 12, 2012
3197