A. K. Prasad et al. / Bioorg. Med. Chem. 13 (2005) 4467–4472
4471
of all NH2-bearing nucleosides in an ionic liquid as
this media has very high polarizability and polarizes
(practically ionizes) the –O–H bond, thereby making
the hydroxy group more nucleophilic than the amino
group of the nucleosides. However in pyridine, such
polarization (or ionization) of –O–H function does not
occur and both amino and hydroxy functions of nucleo-
sides undergo acylation. The great solubilizing nature of
IL MoeMIM.Ms made it possible to carry out the
benzoylation of ribo-nucleosides at room temperature.
The present study has also revealed that by careful selec-
tion of acylating agent, high efficiency and selectivity
can be achieved in IL.
were not matching with those reported in literature,
however we have confirmed the structures of all our
compounds unequivocally from their complete spectral
data. We report herein the complete spectral data
of the new compound, 2-benzamidobenzyl benzoate
and the 1H and 13C NMR spectral data of the
1
benzoylated nucleosides 2e, 4c and 4e; the H and 13C
NMR spectral data of all other nucleosides have been
reported by us earlier.28
4.1.1. 30,50-Di-O-benzoyl-20-deoxyguanosine (2e). White
solid (309 mg, 65%); mp 150 ꢁC (dec) [lit.36 mp 214 ꢁC
(dec)]; 1H NMR (300 MHz, CDCl3): d 2.71 (1H, dd, J =
13.7 and 4.4 Hz, C-20Ha), 3.10–3.15 (1H, m, C-20Hb),
4.54–4.65 (3H, m, C-40H and C-50H), 5.74 (1H, br s,
C-30H), 6.30 (1H, t, J = 6.9 Hz, C-10H), 6.47 (2H, s,
NH2), 7.49–8.06 (11H, m, 10 aromatic protons and
C-8H) and 10.66 (1H, s, NH); 13C NMR (75 MHz,
CDCl3): d 36.60 (C-20), 65.17 (C-50), 76.17 (C-30),
82.28 (C-40), 83.79 (C-10), 117.85 (C-2), 129.64, 130.11
and 130.24 (C-200, C-2000, C-300, C-3000, C-500, C-5000, C-600
and C-6000), 134.35 and 134.55 (C-400 and C-4000), 136.11
(C-100 and C-1000), 151.90 (C-4), 154.61 (C-5), 157.55
(C-8), 166.07 (2 · ester CO) and 166.34 (C-6).
4. Experimental
Melting points were determined on a Mettler FP 62
instrument or in a sulfuric acid bath and are uncor-
rected. The IR spectra were recorded on a Perkin–Elmer
model 2000 FT-IR spectrometer by making KBr discs
1
for solid samples and thin films for oils. The H and
13C NMR spectra were recorded on a Bruker AC-300
Avance spectrometer at 300 and at 75 MHz, respec-
tively, using TMS as internal standard. Analytical TLCs
were performed on pre-coated Merck silica gel 60 F254
plates; the spots were detected either under UV light
or by charring with 4% alcoholic H2SO4. Benzoyl cya-
nide and DMAP were purchased either from Aldrich
Chemical Co. or Fluka Chemicals Co., USA and used
without further purification. The ionic liquid 1-meth-
oxyethyl-3-methylimidazolium methanesulfonate (Moe-
MIM.Ms) was obtained as a gift from Sai Life
Sciences Laboratories Ltd, Hyderabad, India.
4.1.2. 20,30,50-Tri-O-benzoylcytidine (4c). White solid
(389 mg, 70%); mp 183–188 ꢁC (lit.40 mp 185–187 ꢁC);
1H NMR (300 MHz, CDCl3): d 1.90 (2H, br s, NH2),
4.63–4.81 (3H, m, C-40H and C-50H), 5.81–5.87 (1H,
m, C-30H), 5.96 (1H, t, J = 5.6 Hz, C-20H), 6.21 (1H,
d, J = 4.2 Hz, C-10H) and 7.32–8.09 (17H, m, 15
aromatic protons, C-5H and C-6H); 13C NMR (75
MHz, CDCl3): d 63.71 (C-50), 71.06 (C-30), 74.37
(C-40), 79.73 (C-20), 90.28 (C-10), 95.72 (C-5), 128.35,
128.48, 129.62, 129.71 and 129.81 (C-6, C-200, C-2000,
C-20000, C-300, C-3000, C-30000, C-500, C-5000, C-50000, C-600,
C-6000 and C-60000), 133.26 and 133.44 (C-400, C-4000 and
C-40000), 141.36 (C-100, C-1000 and C-1000), 155.39 (C-4),
165.19, 165.30 and 165.85 (3 · ester CO) and 166.08
(C-2).
4.1. General experimental procedure for benzoylation of
nucleosides, phenols, aromatic amines, benzyl alcohol,
aliphatic diols, 3-aminophenol and 2-aminobenzyl alcohol
The starting compound (1 mM) was dissolved in the io-
nic liquid MoeMIM.Ms (1 ml) followed by the addition
of DMAP (10 mg) and BzCN (1.0–1.16 equiv/OH group
in nucleosides; 1.0 equiv/OH and/or NH2 group in other
compounds). The reaction mixture was allowed to stir at
room temperature (25–35 ꢁC) and the progress of the
reaction was followed by TLC. Upon completion, water
(20 ml) was added to the reaction mixture and the prod-
uct was extracted with ethyl acetate (3 · 20 ml). The
combined organic layer was then washed with distilled
water (25 ml) and concentrated under vacuum to get
the crude product, which was purified on silica gel col-
umn using chloroform/methanol as eluent in increasing
order of polarity to afford the benzoylated product.
The structures of all the products were unambiguously
established on the basis of their spectral analysis (IR,
1H, 13C NMR and High Resolution Mass spectral data).
All the benzoylated products were found to be known in
the literature, except 2-benzamidobenzyl benzoate
obtained from 2-aminobenzyl alcohol. The structures
of known compounds were further confirmed by
comparison of their melting points and/or spectral data
with those reported in the literature.33–46 In some cases
the observed melting points of benzoylated compounds
4.1.3. 20,30,50-Tri-O-benzoylguanosine (4e). White solid
(417 mg, 70%); mp 250 ꢁC (dec) (lit.41 mp 252–256 ꢁC);
1H NMR (300 MHz, CDCl3): d 4.68–4.84 (3H, m,
C-40H and C-50H), 6.20 (1H, t, J = 4.9 Hz, C-30H),
6.29–6.35 (2H, m, C-20H and C-10H), 6.45 (2H, s,
NH2), 7.40–8.03 (16H, m, 15 aromatic protons and
C-8H) and 10.76 (1H, s, NH); 13C NMR (75 MHz,
CDCl3): d 64.08 (C-50), 71.63 (C-30), 73.80 (C-40),
79.67 (C-20), 86.31 (C-10), 117.61 (C-2), 128.41, 128.61,
128.72, 128.90, 129.62 and 129.68 (C-200, C-2000, C-20000,
C-300, C-3000, C-30000, C-500, C-5000, C-50000, C-600, C-6000 and
C-60000), 133.62, 133.96 and 134.08 (C-400, C-4000 and
C-40000), 136.36 (C-100, C-1000 and C-10000), 151.23 (C-4),
154.19 (C-5), 157.10 (C-8), 164.81 and 164.96 (3 · ester
CO) and 165.75 (C-6).
4.1.4. 2-Benzamidobenzyl benzoate. White solid
(321 mg, 97%); mp 112–115 ꢁC; IR: (KBr) 3274.9
(NH), 1716.5 (COO), 1649.0 (CONH), 1604.7, 1521.7,
1490.9, 1440.7, 1307.5, 1274.9, 1259.4, 1093.6, 1068.5
and 1026.1 cmꢀ1; UV (CHCl3) kmax: 275 and 212 nm;
1H NMR (300 MHz, CDCl3): d 5.38 (2H, s, CH2),