Esterification of 2,4-dihydroxybenzoic acid

Full text of DOI:10.1134/S1070428014120252

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1845–1847. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © L.G. Derkach, N.S. Novikova, A.V. Mazepa, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 12,
pp. 1861–1863.
SHORT
COMMUNICATIONS
Esterification of 2,4-Dihydroxybenzoic Acid
L. G. Derkach, N. S. Novikova, and A. V. Mazepa
Bogatsky Physicochemical Institute, National Academy of Sciences of Ukraine,
Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine
e-mail: nadyanovikova@rambler.ru; office.physchem@nas.gov
Received June 26, 2014
DOI: 10.1134/S1070428014120252
We previously synthesized methyl 4-[4-(4-hexa-
decyloxybenzoyloxy)benzoyloxy]-2-hydroxybenzoate
whose coordination compound with terbium(III) chlo-
ride showed strong luminescence [1]. Initial methyl
2,4-dihydroxybenzoate was obtained by esterification
in the presence of sulfuric acid [2]. When the reaction
time was 12 h, the yield of the ester did not exceed
35% (after recrystallization). According to [3], the syn-
thesis of ethyl and propyl 2,4-dihydroxybenzoates is
even more difficult (reaction time 22 h).
benzoyloxy)-2-hydroxybenzoyloxy]-2-hydroxybenzoic
acid (III, [M]+ 425) (Scheme 1). Obviously, inter-
mediate 2,4-dihydroxybenzoyl chloride acylates the
initial acid and its acylation product II at the 4(4′)-hy-
droxy group. Variation of the reaction conditions
showed that room temperature is optimum for the
predominant formation of acid II. It was isolated, and
its structure was confirmed by the 1H NMR and mass
spectra.
We also tried to protect the hydroxy groups in I
with trifluoroacetyl group to ensure carbodiimide
esterification and subsequent deprotection under mild
conditions. The reaction of 2,4-dihydroxybenzoic acid
(I) with trifluoroacetic anhydride in pyridine at ~20°C
produced a complex mixture of products which we
failed to isolate and identify. When the reaction was
We tried to synthesize phenyl 2,4-dihydroxyben-
zoate through 2,4-dihydroxybenzoyl chloride which
was reported in [4]. However, attempted reproduction
of the procedure described in [4] resulted in the forma-
tion of a mixture of 4-(2,4-dihydroxybenzoyloxy)-
2-hydroxybenzoic acid (II) and 4-[4-(2,4-dihydroxy-
Scheme 1.
O
O
6
SOCl2, DMF, 20°C
1
2
Cl
5
4
O
OH
13
10
COOH
8
9
HO
OH
7
12
I
O
OH
3
O
O
11
HO
OH
HO
OH
(CF3CO)2O
pyridine, –20°C
I
II
O
CF3
HO
OH
O
O
O
OH
Cl
OH
O
O
OH
HO
O
OH
HO
OH
III
1845

DERKACH et al.
1846
Scheme 2.
O
6
3
1
2
5
4
O
H
4-C10H21OC6H4COOH
DCC, DMAP
CHO
13
10
POCl3, DMF
8
7
12
O
OH
HO
OH
HO
OH
9
11
C10H21
O
IV
V
VI
OMe
O
O
4-MeOC6H4OH
DCC, DMAP
O
OH
O
O
Jones reagent
O
OH
O
OH
C10H21
O
C10H21O
VII
VIII
carried out at reduced temperature (–20°C), we isolat-
ed 2-hydroxy-4-(2,4-dihydroxybenzoyloxy)benzoic
acid (II) which was identified by mass spectrometry
and the mixture was stirred for 3 h at 20°C. The
yellow–green solid was filtered off, washed with anhy-
drous hexane (3×50 mL), and treated with boiling dis-
tilled water. After cooling, the precipitate was filtered
off and dried. Yield 1.9 g (33%), mp 260°C.
1
and H NMR. We presumed that the reaction involves
intermediate formation of mixed 2,4-dihydroxybenzoic
trifluoroacetic anhydride and subsequent acylation of
the 4-hydroxy group (Scheme 1).
b. A solution of 1.54 g (0.01 mol) of 2,4-dihydroxy-
benzoic acid in 20 mL of anhydrous pyridine was
cooled to –20°C, 2.8 mL (0.02 mol) of trifluoroacetic
anhydride cooled to 0°C was added dropwise under
stirring, and the mixture was stirred for 0.5 h and
poured onto crushed ice (150 mL). The precipitate was
filtered off, repeatedly washed with distilled water,
dried, and recrystallized from anhydrous benzene.
The synthesis of 4-methoxyphenyl 4-(4-decyloxy-
benzoyloxy)benzoate (VIII) by the carbodiimide
method is illustrated by Scheme 2. 2,4-Dihydroxy-
benzaldehyde (V) was synthesized by the Vilsmeier
formylation [5] of resorcinol (IV). Carbodiimide
coupling of V with 4-decyloxybenzoic acid gave
4-(4-decyloxybenzoyloxy)-2-hydroxybenzaldehyde
(VI) which was oxidized with the Jones reagent [6] to
2-hydroxy-4-(4-decyloxybenzoyloxy)benzoic acid
(VII), and the subsequent carbodiimide esterification
with 4-methoxyphenol afforded targeted ester VIII.
1
Yield 1.56 g (54%), mp 257°C. H NMR spectrum, δ,
ppm: 6.20–7.20 m (4H, 3-H, 5-H, 10-H, 12-H), 7.70–
8.40 m (2H, 6-H, 13-H), 10.10–11.86 m (4H, OH,
COOH). Mass spectrum (EI), m/z (Irel, %): 290 [M]+,
154 (15.2), 138 (8.0), 137 (28.9), 136 (28.9), 110 (5.9),
108 (12.7), 81 (7.6), 80 (6.7), 79 (8.7), 53 (6.5), 52
(9.2), 51 (6.3). Found, %: C 57.79; H 3.59. C14H10O7.
Calculated, %: C 57.93; H 3.45.
The structure of compounds VI–VIII was con-
1
firmed by their H NMR and mass spectra. In the
1H NMR spectrum of VI, the aldehyde proton signal
resonated as a broadened singlet at δ 11.08 ppm, and
the COOH signal of acid VII was a singlet at
δ 11.25 ppm. Compound VIII displayed in the
1H NMR spectrum a singlet at δ 3.86 ppm from the
methoxy group, and signals from aromatic protons in
the ortho positions with respect to the methoxy group
were displaced upfield and overlapped by those
belonging to other aromatic protons.
4-(4-Decyloxybenzoyloxy)-2-hydroxybenzalde-
hyde (VI). 2,4-Dihydroxybenzaldehyde (V), 3.036 g
(0.022 mol), was dissolved in 50 mL of anhydrous
methylene chloride, 4.4 g (0.011 mol) of 4-decyloxy-
benzoic acid and 0.14 g (0.0011 mol) of 4-(dimethyl-
amino)pyridine (DMAP) were added at room tempera-
ture, the mixture was stirred for 10 min, and 2.3 g
(0.011 mol) of N,N′-dicyclohexylcarbodiimide (DCC)
was added. The mixture was stirred for 25 h at room
temperature, the precipitate was filtered off and
washed with anhydrous methylene chloride, the
solvent was removed under reduced pressure, and the
residue was crystallized from ethanol–benzene (10:1).
4-(2,4-Dihydroxybenzoyloxy)-2-hydroxybenzoic
acid (II). a. Thionyl chloride, 24.8 g (0.21 mol), was
added under stirring at 20°C to 3.08 g (0.02 mol) of
2,4-dihydroxybenzoic acid, 0.45 g (0.06 mol) of anhy-
drous dimethylformamide was then added dropwise,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014

ESTERIFICATION OF 2,4-DIHYDROXYBENZOIC ACID
1847
1
Yield 2.0 g (46%), mp 85°C. H NMR spectrum, δ,
mixture was stirred for 20 h at room temperature. The
precipitate was filtered off, the filtrate was evaporated
under reduced pressure, and the residue was washed
with acetonitrile and dried. Yield 0.148 g (32%). Phase
transition temperatures: Cr→N 74.8, N→I 112.0°C.
3
ppm: 0.86 t (3H, CH3, J = 6.75 Hz), 1.11–1.52 m
(14H, CH2), 1.63–1.86 m (2H, CH2CH2O), 4.09 t (2H,
CH2O, J = 5.97 Hz), 6.77–7.04 m (2H, 3-H, 5-H),
7.12 d (2H, 10-H, 12-H, J = 8.05 Hz), 7.75 d (1H,
6-H, J = 8.30 Hz), 8.07 d (2H, 9-H, 13-H, J = 8.56),
10.25 s (1H, CHO), 11.08 br.s (1H, OH). Mass spec-
trum (FAB), m/z (Irel, %): 399 (5.0) [M + H]+, 262
(14.7), 261 (100), 121 (47.3). Found, %: C 72.60;
H 7.74. C24H30O5. Calculated, %: C 72.36; H 7.54.
3
3
3
3
3
1H NMR spectrum, δ, ppm: 0.91 t (3H, CH3, J =
6.31 Hz), 1.20–1.60 m (14H, CH2), 1.76–1.95 m (2H,
3
CH2CH2O), 3.86 s (3H, CH3), 4.07 t (2H, CH2O, J =
5.49 Hz), 6.80–7.25 m (8H, Harom), 8.05–8.25 m (3H,
6-H, 9-H, 13-H), 10.70 s (1H, OH). Mass spectrum
(FAB), m/z (Irel, %): 522 (6.3), 521 (18.1) [M + H]+,
262 (12.0), 261 (67.7), 121 (100). Found, %: C 71.58;
H 7.95. C31H36O7. Calculated, %: C 71.69; H 6.92.
4-(4-Decyloxybenzoyloxy)-2-hydroxybenzoic
acid (VII) was synthesized by oxidation of 0.4 g
(1 mmol) of aldehyde VI with 2 mL of freshly
prepared Jones reagent. The product was recrystallized
from diethyl–ether–hexane (2:1). Yield 0.302 g (73%).
Phase transition temperatures*: Cr→Sm 111.7, Sm→N
150.5, N→I 172.9°C. H NMR spectrum, δ, ppm:
0.89 t (3H, CH3, J = 6.31 Hz), 1.10–1.65 m (14H,
CH2), 1.70–2.00 m (2H, CH2CH2O), 4.05 t (2H,
CH2O, J = 5.49 Hz), 6.70–7.15 m (4H, 3-H, 5-H,
The electron impact (EI) mass spectra (70 eV) were
recorded on an MKh-1321 spectrometer with direct
sample admission into the ion source (220°C). The fast
atom bombardment (FAB) mass spectra were obtained
on a VG 70-70EQ instrument (xenon beam, 8 kV;
m-nitrobenzyl alcohol and polypropylene glycol as
1
3
1
3
matrix). The H NMR spectra were measured from 5–
10% solutions in CDCl3 or DMSO-d6 on a Bruker
Avance DRX-500 spectrometer (500.13 MHz) using
tetramethylsilane as internal reference.
10-H, 12-H), 7.90–8.25 m (3H, 6-H, 9-H, 13-H),
10.57 s (1H, OH), 11.25 s (1H, COOH). Mass spec-
trum (FAB), m/z (Irel, %): 415 (5.1) [M + H]+, 262
(18.3), 261 (100), 259 (7.4), 123 (9.9), 122 (30.0), 121
(95.0), 109 (9.8), 108 (6.2), 107 (7.8), 106 (5.0), 97
(5.4), 93 (8.1), 92 (8.4), 91 (12.8). Found, %: C 69.78;
H 7.44. C24H30O6. Calculated, %: C 69.56; H 7.25.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 12 2014