2-Iodoxybenzoic acid/tetraethylammonium bromide/water: An efficient combination for oxidative cleavage of acetals

Article abstract of DOI:10.1055/s-0028-1087986

A simple and efficient procedure has been developed for the oxidation of cyclic and acyclic acetals to the corresponding hydroxyalkyl carboxylic esters and simple esters, respectively. 2-Iodoxybenzoic acid (IBX) in the presence of tetraethylammonium bromide was employed for the reaction in aqueous media. The salient features of the protocol include short reaction time, environmentally benign reagents and solvent, and moderate to high yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087986

PAPER
929
2-Iodoxybenzoic Acid/Tetraethylammonium Bromide/Water: An Efficient
Combination for Oxidative Cleavage of Acetals
o
-Iodoxybenzoic
h
A
cid/Tetraet
u
hylammoniu
t
m
Brom
i
ide/W
m
ater Combination a Kuhakarn,*a Waraporn Panchan,a Supanimit Chiampanichayakul,a Natthapol Samakkanad,a
Manat Pohmakotr,a Vichai Reutrakul,a Thaworn Jaipetchb
a
Department of Chemistry and Center for Innovation in Chemistry, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok
10400, Thailand
Fax +66(2)3547151; E-mail: scckk@mahidol.ac.th
Mahidol University, Kanchanaburi Campus, Saiyok, Kanchanaburi 71150, Thailand
b
Received 27 June 2008; revised 2 December 2008
cy, and ease of preparation.16 The synthetic utility of o-
iodoxybenzoic acid as an efficient oxidizing reagent for
elegant oxidative transformations has been demonstrated
by several groups.17 In continuation of our interest in the
Abstract: A simple and efficient procedure has been developed for
the oxidation of cyclic and acyclic acetals to the corresponding hy-
droxyalkyl carboxylic esters and simple esters, respectively. 2-Io-
doxybenzoic acid (IBX) in the presence of tetraethylammonium
bromide was employed for the reaction in aqueous media. The sa- development of novel synthetic applications of o-iodoxy-
benzoic acid,18 we disclose herein an efficient approach to
lient features of the protocol include short reaction time, environ-
mentally benign reagents and solvent, and moderate to high yields.
hydroxyalkyl carboxylic esters by oxidative cleavage of
Key words: o-iodoxybenzoic acid, acetals, oxidations, hydroxy-
alkyl esters, alcohols
cyclic acetals mediated by 2-iodoxybenzoic acid in the
presence of tetraethylammonium bromide19 in water.
Initially, the effect of various reaction parameters was ex-
amined, and for this 1,3-dioxolane 1a derived from 4-ni-
trobenzaldehyde was utilized as the model substrate
(Table 1). In the absence of tetraethylammonium bromide
(entries 1–8), reactions performed at room temperature
under various conditions gave unsatisfactory results, and
mostly starting material was recovered (entries 1–5). Sig-
nificant amounts of hydrolysis product 3a was obtained
when the reactions were carried out at elevated tempera-
ture in the absence of tetraethylammonium bromide (en-
tries 6–8). Much to our delight, the addition of
tetraethylammonium bromide (0.5 equiv) to the reaction
mixture dramatically altered the situation; hydroxyalkyl
ester 2a formed in moderate to excellent conversion (en-
tries 9–12). More importantly, water can be used as the
solvent for this reaction (entry 12), providing the corre-
sponding hydroxyalkyl ester 2a in excellent conversion
(97%). When the experiments were performed either at
room temperature or with less tetraethylammonium bro-
mide (0.25 equiv), the reactions remained incomplete and
significant conversion to hydrolysis product occurred (en-
tries 13 and 16). It should also be mentioned that no reac-
tion took place in aqueous media in the presence of only
o-iodoxybenzoic acid or only tetraethylammonium bro-
mide (entries 14 and 15). Additionally, only moderate
conversion occurred when the reaction of 1a was carried
out under our previously established biphasic conditions
(CH2Cl2–H2O, 1:1) (entries 17 and 18).18
Cyclic acetals are often used in organic synthesis, partic-
ularly as carbonyl protecting groups,1 as well as for the
synthesis of hydroxyalkyl carboxylic esters (Scheme 1),
which are commercially important products serving as the
cross-linking agents for polyesters as well as fungicides.2
A number of oxidizing agents are used for the conversion
of cyclic and acyclic acetals, and include molecular oxy-
gen–cobalt(II),3 di-tert-butyl peroxide,4 tert-butyl hydro-
peroxide in combination with transition metals,5 tert-butyl
hydroperoxide–pyridinium dichromate,6 tert-butyl hydro-
peroxide–iodine(III) compounds,7 potassium permangan-
ate,8
electrochemical
oxidation,9
ozonolysis,10
electrophilic halogen,11 m-chloroperbenzoic acid in the
presence of 2,2¢-bipyridinium chlorochromate or boron
trifluoride–diethyl ether,12 sodium perborate in acetic an-
hydride,13 and oxone.14
O
n
oxidative cleavage
OH
n
O
R
O
R
O
H
1
2
Scheme 1 Cleavage of cyclic acetals to form hydroxyalkyl carboxy-
lic esters
Recently, the use of hypervalent iodine reagents in organ-
ic synthesis has attracted considerable interest owing to
their mild, selective, and environmentally friendly proper-
ties.15 2-Iodoxybenzoic acid (IBX), despite its explosive
properties, is a versatile oxidizing reagent due to its stabil-
ity to air and moisture, mild reaction conditions, efficien-
The effect of the type of phase-transfer catalyst was also
evaluated, as shown in Table 2. It is obvious that the type
of the halide anion of the phase-transfer reagent has a con-
siderable effect on this conversion. The presence of the
bromide anion was found vital for the conversion of 1a
into 2a. Tetraethylammonium bromide gave the best con-
version (entry 1), while tetrabutylammonium bromide and
cetyltrimethylammonium bromide (CTMAB) led to com-
SYNTHESIS 2009, No. 6, pp 0929–0934
x
x
.
x
x
.2
0
0
9
Advanced online publication: 02.03.2009
DOI: 10.1055/s-0028-1087986; Art ID: P07108SS
© Georg Thieme Verlag Stuttgart · New York

930
C. Kuhakarn et al.
PAPER
Table 2 Evaluation of Phase-Transfer Catalysts for the Transforma-
tion of 1a into 2aa
Table 1 Optimization of Reagents and Reaction Conditions for the
Oxidation of Acetal 1a
O
O
O
O
IBX, PTC
O
O
H
O
O
H
+
OH
OH
Ar
H
H2O, 65 °C, 1 h
+
Ar
O
Ar
O
Ar
H
Ar
Ar
1a
Ar = 4-O2NC6H4
2a
3a
1a
Ar = 4-O2NC6H4
2a
3a
Conversionb (%)
Entry IBX/Et4NBr Conditions
(equiv)
Conversiona
(%)
Entry
Phase-transfer reagent
2a
97
89
75
0
3a
0
2a
0
3a
0
1
2
3
4
5
6
Et4NBr
Bu4NBr
CTMABc
Et4NCl
Et4NI
1
2
1.1:0
CH2Cl2–H2O (4:1), r.t., 24 h
acetone–H2O (4:1), r.t., 24 h
EtOAc–H2O (4:1), r.t., 24 h
MeCN–H2O (4:1), r.t., 24 h
DMSO–H2O (4:1), r.t., 24 h
MeCN–H2O (4:1), 65 °C, 24 h
DMSO–H2O (4:1), 65 °C, 24 h
0
1.1:0
0
0
0
3
1.1:0
0
2
56
1
4
1.1:0
0
6
0
5
1.1:0
0
5
Bu4NI
0
2
6
1.1:0
0
57
53
96
0
a Reagents and conditions: IBX (1.1 equiv), phase-transfer reagent
(0.5 equiv).
7
1.1:0
0
b Calculated from 1H NMR (300 MHz) integration.
c CTMAB = cetyltrimethylammonium bromide.
8
1.1:0
DMSO–H2O (4:1), 100 °C, 24 h
MeCN–H2O (3:1), 65 °C, 1 h
MeCN–H2O (1:3), 65 °C, 1 h
EtOAc–H2O (1:3), 65 °C, 1 h
H2O, 65 °C, 1 h
9
1.1:0.5
1.1:0.5
1.1:0.5
1.1:0.5
1.1:0.5
0:0.5
67
93
96
97
41
0
moderate to good yields (entries 8–11). 1,3-Dioxane de-
rivatives reacted with the reagents with almost equal facil-
ity, leading to corresponding g-hydroxypropyl esters in
comparable yields (entries 12–21). Unlike the reactions
mediated by ozone,10 electrochemical oxidation,9 and hy-
pervalent iodine(III),7 the reactions of acyclic dialkyl ace-
tals proceeded readily to give simple alkyl esters in
moderate yields (entries 22 and 23). It should also be
pointed out that the reaction of 1,3-dioxolane-derived 4-
nitroacetophenone under standard conditions exclusively
led to simple hydrolysis to the corresponding carbonyl
compound.
10
11
12
13
14
15
16
17
18
1
0
0
H2O, r.t., 1 h
2
H2O, 65 °C, 1 h
0
1.1:0
H2O, 65 °C, 1 h
0
0
1.1:0.25
1.1:0.5
1.1:0.5
H2O, 65 °C, 3 h
63
55
52
24
0
CH2Cl2–H2O (1:1), r.t., 1 h
CH2Cl2–H2O (1:1), r.t., 4 h
Oxidation of unsymmetrical cyclic acetals under similar
reaction conditions was also evaluated as shown in
Scheme 2. Even though moderate to good yields were ob-
served, an approximately 1:1 inseparable isomeric mix-
ture of the hydroxyalkyl esters was obtained.
0
a Calculated from 1H NMR (300 MHz) integration.
paratively lower conversions (entries 2 and 3). Unexpect-
edly, the chloride and iodide anions did not give the
expected hydroxyalkyl ester 2a, and the hydrolysis prod-
uct 3a was obtained in moderate to low yields (entries 4–
6).
O
R2
IBX (1.1 equiv)
Et4NBr (0.5 equiv)
n
O
OH
O
R1
O
H2O, 65 °C
R1
H
R3
Having established the optimal reaction conditions [IBX
(1.1 equiv), Et4NBr (0.5 equiv), H2O, 65 °C], we then ex-
amined the scope and the generality of the reaction, and
the results are summarized in Table 3. 1,3-Dioxolane- and
1,3-dioxane-derived aldehydes representing several struc-
tural varieties were prepared according to previously re-
ported procedures20 and were screened for their reactivity
(entries 1–21). In general, aromatic 1,3-dioxolanes under-
went oxidative cleavage, yielding b-hydroxyethyl esters
in good yields (55–81%, entries 1–7). Oxidation of ali-
phatic 1,3-dioxolanes gave the corresponding esters in
7aa; R1 = 4-O2NC6H4, R2 = Me, R3 = H, 39%
7ab; R1 = 4-O2NC6H4, R2 = H, R3 = Me, 39%
7ba; R1 = 2-O2NC6H4, R2 = Me, R3 = H, 30%
7bb; R1 = 2-O2NC6H4, R2 = H, R3 = Me, 24%
6a; R1 = 4-O2NC6H4
6b; R1 = 2-O2NC6H4
Scheme 2 Oxidation of unsymmetrical acetals
On the basis of the experimental results and literature pre-
cedents on similar acetal cleavage, a plausible reaction
pathway for the formation of hydroxyalkyl esters is as-
sumed to involve the following steps: (a) oxidation of the
bromide anion by 2-iodoxybenzoic acid to give electro-
Synthesis 2009, No. 6, 929–934 © Thieme Stuttgart · New York

PAPER
o-Iodoxybenzoic Acid/Tetraethylammonium Bromide/Water Combination
931
Table 3 Oxidation of Acetals with o-Iodoxybenzoic Acid and
n
n
Tetraethylammonium Bromide in Watera
n
O
IBX
H2O
O
R
O
O
O
O
R
Et4NBr
+
O
H
OH
n
R
IBX, Et4NBr
1
OH
n
O
R
O
H
A
B
R
O
H2O, 65 °C
1
2
O
Entry Acetal R
n
Et4NBr Time
(equiv) (h)
2
Yieldb
(%)
OH
R
O
n
2
1
2
1a
1b
1c
1d
1e
1f
4-O2NC6H4
2-O2NC6H4
4-BrC6H4
3-ClC6H4
4-FC6H4
Tol
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
–
–
0.5
0.5
0.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
0.5
1.0
0.5
0.5
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1
5
2
1
1
1
1
2
1
1
1
3
2
1
1
1
1
2
1
1
1
1
2.5
2a
2b
2c
2d
2e
2f
81
71
75
70
63
55
58
81
76
62
59
50
78
78
61
42
59
83
79
86
79
60
56
Scheme 3 Plausible reaction pathway for 2-iodoxybenzoic acid/
tetraethylammonium bromide mediated oxidative cleavage of acetals
3
ters and simple esters, respectively, using the combination
of 2-iodoxybenzoic acid and tetraethylammonium bro-
mide in water. The method has general scope, and a clean
reaction occurs, giving the products in moderate to high
yields; the short reaction time in aqueous media can be of
great synthetic utility in organic synthesis. The oxidative
hydrolysis of acetals and ketals by 2-iodoxybenzoic acid
as well as other hypervalent iodine(III) reagents is cur-
rently being investigated and will be reported in due
course.
4
5
6
7
1g
1h
1i
Ph
2g
2h
2i
8
Bn
9
CHMePh
n-C8H17
n-C13H27
4-O2NC6H4
4-BrC6H4
3-ClC6H4
4-FC6H4
Tol
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
2j
All known compounds were characterized by 1H and 13C NMR, IR,
and mass spectroscopy, and their spectroscopic data were identical
to those reported in the literature. All new compounds were charac-
terized by 1H and 13C NMR, IR, and high-resolution mass spectros-
copy. 1H and 13C NMR spectra were run on Bruker DPX-300 and
Bruker Avance 500 spectrometers. IR spectroscopy was carried out
on a Perkin Elmer GX FT-IR System spectrometer, and HRMS was
carried out on a Bruker micro TOF spectrometer.
1k
1l
2k
2l
1m
1n
1o
1p
1q
1r
1s
2m
2n
2o
2p
2q
2r
2s
Hydroxyalkyl Carboxylic Esters 2; General Procedure
IBX (154 mg, 0.55 mmol) was added to a suspension of acetal 1 or
4 (0.5 mmol) and Et4NBr (52.5 mg, 0.25 mmol) in H2O (2 mL), and
the reaction mixture was vigorously stirred at 65 °C for the time pe-
riod shown in Table 3. Upon completion of the reaction, the reac-
tion mixture was quenched by the addition of sat. aq Na2S2O3 (5
mL), and basified with sat. aq NaHCO3 (5 mL); further stirring was
followed by extraction with EtOAc (3 × 5 mL). The combined or-
ganic extracts were washed with H2O (10 mL) and brine (10 mL),
dried (Na2SO4), filtered, and concentrated (aspirator). The residue
was purified by column chromatography (silica gel) to furnish the
analytically pure product.
Ph
Bn
CHMePh
n-C8H17
n-C13H27
–
1t
2t
1u
4ac
4bc
2u
5ac
5bc
–
2-Hydroxyethyl 4-Bromobenzoate (2c)
a Reagents and conditions: IBX (1.1 equiv), H2O, 65 °C, in air.
b Isolated yield.
Compound 2c was prepared by the general procedure from 1c
(114.5 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2
cm; hexanes–EtOAc, 1:0 to 7:3) gave the title compound.
c Phenylacetaldehyde dimethyl acetal (4a); 2-phenylpropanal dimeth-
yl acetal (4b); methyl phenylacetate (5a), methyl 2-phenylpropanoate
(5b).
Yield: 92.0 mg (75%); colorless liquid; Rf = 0.26 (hexanes–EtOAc,
7:3).
IR (neat): 3419 (O–H), 1722 (C=O) cm–1.
philic bromine; (b) oxidation of the acetal carbon to pro-
vide stabilized acetal carbocation A; (c) nucleophilic
attack by water to give hemiorthoester B; and (d) ring
opening of hemiorthoester B to provide, finally, hydroxy-
alkyl ester 2 (Scheme 3).
1H NMR (300 MHz, CDCl3): d = 7.91 (d, J = 8.5 Hz, 2 H), 7.58 (d,
J = 8.5 Hz, 2 H), 4.45 (t, J = 4.7 Hz, 2 H), 3.96 (t, J = 4.7 Hz, 2 H),
2.05 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 166.2, 131.8, 131.2, 128.8, 128.3,
66.8, 61.3.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9BrO3Na:
266.9633; found: 266.9659.
In summary, we have developed an efficient and simple
method for the oxidative cleavage of cyclic and acyclic
acetals to their corresponding hydroxyalkyl carboxylic es-
Synthesis 2009, No. 6, 929–934 © Thieme Stuttgart · New York

932
C. Kuhakarn et al.
PAPER
2-Hydroxyethyl 3-Chlorobenzoate (2d)
HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H14O3Na: 217.0841;
found: 217.0892.
Compound 2d was prepared by the general procedure from 1d (92.3
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 3:2) gave the title compound.
2-Hydroxyethyl Nonanoate (2j)
Compound 2j was prepared by the general procedure from 1j (93.0
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 7:3) gave the title compound.
Yield: 70.0 mg (70%); pale yellow liquid; Rf = 0.30 (hexanes–
EtOAc, 7:3).
IR (neat): 3419 (O–H), 1723 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 8.04 (t, J = 1.8 Hz, 1 H), 7.95
(ddd, J = 7.9, 1.5, 1.1 Hz, 1 H), 7.55 (ddd, J = 7.9, 2.1, 1.1 Hz, 1 H),
7.39 (td, J = 7.9, 0.3 Hz, 1 H), 4.47 (t, J = 4.7 Hz, 2 H), 3.97 (t,
J = 4.7 Hz, 2 H), 2.42 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 165.7, 134.5, 133.1, 131.6, 129.68,
129.66, 127.8, 66.9, 61.1.
Yield: 62.6 mg (62%); colorless liquid; Rf = 0.23 (hexanes–EtOAc,
7:3).
IR (neat): 3423 (O–H), 1737 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 4.19 (t, J = 4.7 Hz, 2 H), 3.81 (t,
J = 4.7 Hz, 2 H), 2.75 (br s, 1 H), 2.33 (t, J = 7.6 Hz, 2 H), 1.70–1.55
(m, 2 H), 1.40–1.20 (m, 10 H), 0.87 (t, J = 6.6 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 174.2, 65.8, 61.1, 34.1, 31.7,
29.11, 29.05, 29.01, 24.8, 22.5, 14.0.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9ClO3Na:
223.0138; found: 223.0145.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H22O3Na: 225.1467;
2-Hydroxyethyl 4-Fluorobenzoate (2e)
found: 225.1466.
Compound 2e was prepared by the general procedure from 1e (84.0
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 1:1) gave the title compound.
2-Hydroxyethyl Tetradecanoate (2k)
Compound 2k was prepared by the general procedure from 1k
(128.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2
cm; hexanes–EtOAc, 7:3) gave the title compound.
Yield: 58.0 mg (63%); pale yellow liquid; Rf = 0.26 (hexanes–
EtOAc, 7:3).
Yield: 80.2 mg (59%); colorless solid; mp 44–45 °C; Rf = 0.32
(hexanes–EtOAc, 7:3).
IR (KBr): 3367 (O–H), 1737 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): d = 4.23 (t, J = 4.7 Hz, 2 H), 3.85 (t,
J = 4.7 Hz, 2 H), 2.37 (t, J = 7.6 Hz, 2 H), 1.70–1.55 (m, 2 H), 1.40–
1.20 (m, 21 H), 0.90 (t, J = 6.9 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 174.2, 65.9, 61.3, 34.2, 31.9,
29.64, 29.61, 29.57, 29.43, 29.32, 29.23, 29.12, 24.9, 24.7, 22.7,
14.1.
IR (neat): 3424 (O–H), 1719 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 8.11–8.04 (m, 2 H), 7.15–7.09 (m,
2 H), 4.44 (t, J = 4.7 Hz, 2 H), 3.94 (t, J = 4.7 Hz, 2 H), 2.73 (br s,
1 H).
13C NMR (75 MHz, CDCl3): d = 165.9, 165.8 (d, J = 252.9 Hz),
132.2 (d, J = 9.4 Hz), 126.1 (d, J = 2.9 Hz), 115.5 (d, J = 21.9 Hz),
66.6, 61.2.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C9H9FO3Na: 207.0433;
found: 207.0444.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C16H32O3Na: 295.2249;
2-Hydroxyethyl 2-Phenylethanoate (2h)
found: 295.2299.
Compound 2h was prepared by the general procedure from 1h (72.9
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 7:3) gave the title compound.
3-Hydroxypropyl 4-Nitrobenzoate (2l)
Compound 2l was prepared by the general procedure from 1l (104.5
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 3:2) gave the title compound.
Yield: 73.0 mg (81%); pale yellow liquid; Rf = 0.22 (hexanes–
EtOAc, 7:3).
Yield: 56.3 mg (50%); pale yellow liquid; Rf = 0.14 (hexanes–
EtOAc, 7:3).
IR (neat): 3416 (O–H), 1724 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 8.29 (d, J = 8.7 Hz, 2 H), 8.21 (d,
J = 8.7 Hz, 2 H), 4.54 (t, J = 6.1 Hz, 2 H), 3.81 (t, J = 6.1 Hz, 2 H),
2.05 (quin, J = 6.1 Hz, 2 H), 2.03 (br s, 1 H).
13C NMR (75 MHz, CDCl3): d = 164.9, 150.5, 135.5, 130.7, 123.5,
62.8, 59.0, 31.6.
IR (neat): 3418 (O–H), 1732 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.27 (m, 5 H), 4.25 (t,
J = 4.7 Hz, 2 H), 3.81 (t, J = 4.7 Hz, 2 H), 3.70 (s, 2 H), 2.10 (br s,
1 H).
13C NMR (75 MHz, CDCl3): d = 171.9, 133.8, 129.2, 128.6, 127.2,
66.4, 61.0, 41.2.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H12O3Na: 203.0684;
found: 203.0667.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H11NO5Na:
2-Hydroxyethyl 2-Phenylpropanoate (2i)
248.0535; found: 248.0533.
Compound 2i was prepared by the general procedure from 1i (89
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 9:1 to 7:3) gave the title compound.
3-Hydroxypropyl 3-Chlorobenzoate (2n)
Compound 2n was prepared by the general procedure from 1n (99.3
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 1:1) gave the title compound.
Yield: 73.7 mg (76%); colorless liquid; Rf = 0.24 (hexanes–EtOAc,
7:3).
Yield: 83.7 mg (78%); pale yellow liquid; Rf = 0.27 (hexanes–
EtOAc, 7:3).
IR (neat): 3423 (O–H), 1720 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): d = 8.00 (t, J = 1.8 Hz, 1 H), 7.92 (dt,
J = 7.9, 1.1 Hz, 1 H), 7.54 (ddd, J = 7.9, 2.1, 1.1 Hz, 1 H), 7.39 (t,
J = 7.9 Hz, 1 H), 4.49 (t, J = 6.2 Hz, 2 H), 3.79 (t, J = 6.2 Hz, 2 H),
2.45 (br s, 1 H), 2.02 (quin, J = 6.2 Hz, 2 H).
IR (neat): 3426 (O–H), 1732 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): d = 7.37–7.32 (m, 4 H), 7.30–7.26 (m,
1 H), 4.24–4.16 (m, 2 H), 3.79 (q, J = 7.2 Hz, 1 H), 3.76–3.71 (m, 2
H), 2.19 (br s, 1 H), 1.53 (d, J = 7.2 Hz, 3 H).
13C NMR (125 MHz, CDCl3): d = 174.8, 140.4, 128.6, 127.3, 127.2,
66.2, 60.9, 45.4, 18.4.
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o-Iodoxybenzoic Acid/Tetraethylammonium Bromide/Water Combination
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13C NMR (125 MHz, CDCl3): d = 165.7, 134.5, 133.0, 131.8, 129.7,
129.6, 127.7, 62.2, 59.0, 31.7.
(quin, J = 6.1 Hz, 2 H), 1.70–1.52 (m, 2 H), 1.40–1.15 (m, 10 H),
0.87 (t, J = 6.6 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H11ClO3Na:
237.0294; found: 237.0286.
13C NMR (75 MHz, CDCl3): d = 174.3, 61.1, 59.1, 34.3, 31.7 (2 C),
29.13, 29.07, 29.03, 24.9, 22.5, 14.0.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C12H24O3Na: 239.1623;
found: 239.1606.
3-Hydroxypropyl 4-Fluorobenzoate (2o)
Compound 2o was prepared by the general procedure from 1o (91
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 1:1) gave the title compound.
3-Hydroxypropyl Tetradecanoate (2u)
Compound 2u was prepared by the general procedure from 1u
(135.0 mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2
cm; hexanes–EtOAc, 85:15) gave the title compound.
Yield: 60.5 mg (61%); colorless liquid; Rf = 0.26 (hexanes–EtOAc,
7:3).
IR (neat): 3407 (O–H), 1716 (C=O) cm–1.
Yield: 113.0 mg (79%); colorless liquid; Rf = 0.30 (hexanes–
EtOAc, 7:3).
IR (neat): 3297 (O–H), 1736 (C=O) cm–1.
1H NMR (500 MHz, CDCl3): d = 4.24 (t, J = 6.1 Hz, 2 H), 3.69 (t,
J = 6.1 Hz, 2 H), 2.32 (t, J = 7.6 Hz, 2 H), 1.87 (quin, J = 6.1 Hz, 2
H), 1.65–1.59 (m, 2 H), 1.36–1.23 (m, 21 H), 0.88 (t, J = 6.8 Hz, 3
H).
1H NMR (300 MHz, CDCl3): d = 8.07–8.02 (m, 2 H), 7.14–7.08 (m,
2 H), 4.47 (t, J = 6.1 Hz, 2 H), 3.77 (t, J = 6.1 Hz, 2 H), 2.47 (br s,
1 H), 2.01 (quin, J = 6.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 165.9, 165.8 (d, J = 252.6 Hz),
132.1 (d, J = 9.3 Hz), 126.3 (d, J = 3.0 Hz), 115.5 (d, J = 21.9 Hz),
62.0, 59.0, 31.8.
HRMS (ESI-TOF): m/z [M + H+] calcd for C10H12O3F: 199.0770;
found: 199.0740.
13C NMR (125 MHz, CDCl3): d = 174.3, 61.1, 59.1, 34.3, 31.9,
31.7, 29.62 (2 C), 29.58, 29.54, 29.4, 29.3, 29.2, 29.1, 24.9, 22.6,
14.0.
3-Hydroxypropyl 2-Phenylethanoate (2r)
HRMS (ESI-TOF): m/z [M + Na+] calcd for C17H34O3Na: 309.2406;
found: 309.2404.
Compound 2r was prepared by the general procedure from 1r (89
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 1:1) gave the title compound.
Methyl 2-Phenylpropanoate (5b)
Yield: 80.6 mg (83%); colorless liquid; Rf = 0.21 (hexanes–EtOAc,
7:3).
IR (neat): 3416 (O–H), 1731 (C=O) cm–1.
Compound 5b was prepared by the general procedure from 4b (90
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 1:0 to 3:2) gave the title compound.
Yield: 46.0 mg (56%); pale yellow liquid; Rf = 0.44 (hexanes–
EtOAc, 9:1).
IR (neat): 1738 (C=O) cm–1.
1H NMR (300 MHz, CDCl3): d = 7.34–7.28 (m, 5 H), 4.24 (t,
J = 6.1 Hz, 2 H), 3.64 (s, 2 H), 3.61 (t, J = 6.1 Hz, 2 H), 2.49 (br s,
1 H), 1.84 (quin, J = 6.1 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 171.8, 133.8, 129.0, 128.4, 126.9,
61.8, 58.8, 41.2, 31.4.
1H NMR (500 MHz, CDCl3): d = 7.38–7.26 (m, 5 H), 3.75 (q,
J = 7.2 Hz, 1 H), 3.69 (s, 3 H), 1.53 (d, J = 7.2 Hz, 3 H).
HRMS (ESI-TOF): m/z [M + Na+] calcd for C11H14O3Na: 217.0841;
found: 217.0833.
13C NMR (125 MHz, CDCl3): d = 175.0, 140.6, 128.6, 127.5, 127.1,
52.0, 45.4, 18.6.
HRMS (ESI-TOF): m/z [M + Na+] calcd for C10H12O2Na: 187.0735;
found: 187.0728.
3-Hydroxypropyl 2-Phenylpropanoate (2s)
Compound 2s was prepared by the general procedure from 1s (96
mg, 0.5 mmol). Column chromatography (silica gel, 13 × 2 cm;
hexanes–EtOAc, 9:1 to 4:1) gave the title compound.
Acknowledgment
Yield: 82.2 mg (79%); colorless liquid; Rf = 0.27 (hexanes–EtOAc,
7:3).
IR (neat): 3416 (O–H), 1732 (C=O) cm–1.
We thank the Thailand Research Fund (RMU5180040), Center for
Innovation in Chemistry (PERCH-CIC), and the Commission on
Higher Education (CHE-RES-RG) for financial support.
1H NMR (500 MHz, CDCl3): d = 7.36–7.26 (m, 5 H), 4.26–4.19 (m,
2 H), 3.75 (q, J = 7.2 Hz, 1 H), 3.59–3.51 (m, 2 H), 2.15 (br s, 1 H),
1.81 (quin, J = 6.1 Hz, 2 H), 1.52 (d, J = 7.2 Hz, 3 H).
References
13C NMR (125 MHz, CDCl3): d = 174.9, 140.4, 128.5, 127.3, 127.1,
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HRMS (ESI-TOF): m/z [M + Na+] calcd for C12H16O3Na: 231.0997;
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Synthesis 2009, No. 6, 929–934 © Thieme Stuttgart · New York