Hydrogen Bonding in the Activation of Nucleophiles
J . Org. Chem., Vol. 67, No. 8, 2002 2547
GCMS) of an authentic sample. In most cases the product was
isolated in pure form and, whenever required, purification was
accomplished through crystallization (EtOAc-hexane) or chro-
matography (silica gel, eluent 15% EtOAc-hexane).
in a catalytic amounts in the presence of dipolar aprotic
solvents with high dielectric constant, high molecular
polarizability, high DN, and low AN. Chemoselective
deprotection of alkyl/aryl esters and aryl alkyl ethers are
carried out by thiophenol in the presence of catalytic
quantities of KF under nonhydrolytic and neutral condi-
tions via a “demand-based” in situ generation of thiolate
anion. No competitive aromatic/aliphatic nucleophilic
substitution, reduction and Michael addition could be
observed for substrates susceptible to undergo such side
reactions. Aryl esters could be deprotected selectively in
the presence of alkyl esters and aryl methyl ethers during
intramolecular competitions.
Rep r esen ta tive P r oced u r e for Dep r otection of a n Ar yl
Alk yl Eth er . A mixture of 2-methoxynaphthalene (395.5 mg,
2.5 mmol), PhSH (0.27 g, 2.5 mmol), and KF (15 mg, 0.25
mmol, 10 mol %) in NMP (2.5 mL) were heated under reflux
for 60 min under N2. The cooled reaction mixture was made
alkaline with 5% aqueous NaOH (25 mL) and extracted with
Et2O (3 × 15 mL) to separate any neutral component (GCMS
of these combined ethereal extracts showed the presence of
PhSMe). The aqueous part was acidified in the cold (ice bath)
with 6 N HCl and extracted with Et2O (3 × 15 mL). The
combined Et2O extracts were washed with brine (15 mL), dried
(Na2SO4), and concentrated under vacuo to afford a brown solid
which on passing through a column of silica gel (230-400, 1
g) and elution with 5% EtOAc-hexane (200 mL) afforded the
product (288 mg, 80%) which was in full agreement with mp
Exp er im en ta l Section
The esters studied were either available commercially or
prepared by standard procedures.2,40 The solvents were dis-
tilled before use. DMA, DMPU, DMEU, DEF, DEA, DMSO,
sulfolane, formamide, PhSH, 4-Me-C6H4SH, 4-MeO-C6H4SH,
4-NH2-C6H4SH, 2-NH2-C6H4SH, PhCH2SH, EtSH, 2-mercap-
tobenzthiazole, 2-mercaptothiazoline, LiOAc, CsF, LiF, TBAF‚
xH2O, Me4NF‚4H2O, Me3PhCH2NF‚xH2O, and NH4HF2 were
purchased from Aldrich, St. L. KF, KHF2, NaF, KCl, KBr, KI,
NaCl, NaBr, NaI, NH4Cl, KOAc, KOCOPh, DMF, and NMP
were procured from S. d. Fine chemicals, India.
1
and spectral data (IR, H NMR, and GCMS) of an authentic
sample of 2-naphthol.
Rep r esen ta tive P r oced u r e for Dep r otection of a n Ar yl
Ester . A mixture of 2-naphthyl benzoate (0.62 g, 2.5 mmol)
and KF (15 mg, 0.25 mmol, 10 mol %) in NMP (2.5 mL) were
heated under reflux for 30 min under N2. The cold reaction
mixture was diluted with 5% aqueous NaOH (10 mL) and
extracted with Et2O (3 × 20 mL) to separate any neutral
component (the GCMS results showed the presence of Ph-
SCOPh indicating the nucleophilic attack at the carbonyl
carbon of the substrate). The aqueous layer was acidified with
ice-cooling (6 M HCl) and extracted with Et2O (3 × 20 mL).
The combined ethereal extracts were washed with saturated
aqueous NaHCO3 (2 % 20 mL) to separate the liberated benzoic
acid and brine (20 mL), dried (Na2SO4), and concentrated to
afford 2-naphthol (332 mg, 92%) which was in full agreement
with mp and spectral data (IR, 1H NMR, and GCMS) of an
authentic sample of 2-naphthol. 2-Naphthol (289 mg, 80%)
could be obtained by carrying out the reaction at 100 °C for
60 min.
The 1H NMR and IR spectra of the following compounds
were in complete agreement with those of the authentic
samples: benzoic acid, 2-chlorobenzoic acid, 4-chlorobenzoic
acid, 2-nitrobenzoic acid, 4-nitrobenzoic acid, 3-nitrobenzoic
acid, 2-hydroxybenzoic acid, 4-hydroxybenzoic acid, phenoxy-
acetic acid, thiophenoxyacetic acid, phenylacetic acid, 1-naph-
thylacetic acid, 2-furoic acid, cinnamic acid, 2-nitrocinnamic
acid, 2-naphthol, 4-nitrophenol, 4-hydroxyacetophenone, 4-hy-
droxybenzaldehyde, 4-cyanophenol, 4-chloro-3-methylphenol,
4-hydroxy-3-methoxybenzaldehyde, methyl 4-hydroxybenzoate,
ethyl 4-hydroxybenzoate, propyl 4-hydroxybenzoate, (Aldrich),
trans-4-hydroxystilbene (Acros Organics), trans-4-hydroxy-
chalcone, trans-4′-hydroxychalcone (Lancaster).
Gen er a l P r oced u r e for Dep r otection . Exa m p le of th e
Gen er a l P r oced u r e Dep r otection of Alk yl Ester s. A
mixture of methyl benzoate (0.34 g, 2.5 mmol), PhSH (0.27 g,
2.5 mmol), and KF (15 mg, 0.25 mmol, 10 mol %) in NMP (2.5
mL) were heated under reflux for 10 min under N2. The cold
reaction mixture was diluted with saturated aqueous NaHCO3
(25 mL) and extracted with Et2O (2 % 20 mL) to separate the
neutral component (the GCMS of these combined ethereal
extracts showed the presence of PhSMe supporting the nu-
cleophilic attack at the carbinol carbon). The aqueous part was
acidified (6 M HCl) with ice-cooling and extracted with Et2O
(3 % 20 mL) to afford the product (274.5 mg, 90%) which was
in full agreement with mp and spectral data (IR, 1H NMR,
and GCMS) of an authentic sample of benzoic acid.
Rep r esen ta tive P r oced u r e for Dep r otection of a n Ar yl
Ester in th e P r esen ce of a n Alk yl Ester . A mixture of
methyl 4-benzoyloxybenzoate (0.64 g, 2.5 mmol) and KF (15
mg, 0.25 mmol, 10 mol %) in NMP (2.5 mL) were heated at
100 °C for 60 min under N2. The cold reaction mixture was
diluted with 2% aqueous NaOH (10 mL) and extracted with
Et2O (3 × 20 mL) to separate any neutral component. The
aqueous layer was acidified with ice-cooling (6 M HCl) and
extracted with Et2O (3 × 20 mL). The combined ethereal
extracts were washed with saturated aqueous NaHCO3 (2 ×
20 mL) to separate the liberated benzoic acid, and brine (20
mL), dried (Na2SO4), and concentrated in vacuo to afford the
product (339 mg, 89%) which was in full agreement with mp
1
and spectral data (IR, H NMR, and GCMS) of an authentic
sample of methyl 4-hydroxybenzoate.
This generalized method was followed for ethyl 4-benzoyl-
oxybenzoate and propyl 4-benzoyloxybenzoate and in each
occasion the product was found to be in full agreement with
the spectral data (IR, 1H NMR and GCMS) of an authentic
sample. In most cases the product was isolated in pure form
or, when required, purification was accomplished through
crystallization (EtOAc-hexane) or chromatography (silica gel,
eluent 15% EtOAc-hexane).
This generalized method was followed for the remaining
substrates, and on each occasion the product was found to be
in full agreement with the spectral data (1H NMR, FTIR, and
(40) Furniss, B. R.; Hannaford, A. J .; Rogers, V.; Smith, P. W. G.;
Tatchell, A. R. Vogel’s Textbook of Practical Organic Chemistry;
Longman: London, 1996.
(41) Pouchart, C. J .; J acqlynn, B. The Aldrich Libraray of 13C and
1H FT NMR Spectra, 1st ed.; Aldrich Chemical Co. Inc.: Milwaukee,
1993; vol. II.
Ack n ow led gm en t. L.S. thanks CSIR, New Delhi,
for award of senior research fellowship.
(42) Cirovic, M. M. Properties of Organic Compounds; CRC Press
Inc.: Boca Raton, 1996; POC-personal ed., version 5.1.
(43) Hseih, H.-K.; Lee, T.-H.; Wang, J .-P.; Wang, J .-J .; Lin, C.-N.
Pharmacol. Res. 1998, 15, 39.
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