Silica sulfuric acid (SSA) as a highly efficient heterogeneous catalyst for persilylation of purine and pyrimidine nucleobases and other N-heterocycles using HMDS

Article abstract of DOI:10.1080/10426500903383952

Purine and pyrimidine nucleobases and other N-heterocycles have been silylated with HMDS in excellent yields in the presence of a catalytic amount of silica sulfuric acid (SSA) as a heterogeneous catalyst. SSA utilizes a shorter reaction time and higher yields of silylated nucleobases. SSA is reusable for several times without a decrease in reactivity or yield of silylated adducts. Copyright

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Phosphorus, Sulfur, and Silicon and the
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Silica Sulfuric Acid (SSA) as a Highly
Efficient Heterogeneous Catalyst for
Persilylation of Purine and Pyrimidine
Nucleobases and Other N-Heterocycles
Using Hmds
Mohammad Navid Soltani Rad a , Ali Khalafi-Nezhad b , Masoumeh
Divar b & Somayeh Behrouz b
a Department of Chemistry, Faculty of Basic Sciences, Shiraz
University of Technology, Shiraz, Iran
b Department of Chemistry, College of Sciences, Shiraz University,
Shiraz, Iran
Version of record first published: 25 Aug 2010.
To cite this article: Mohammad Navid Soltani Rad , Ali Khalafi-Nezhad , Masoumeh Divar & Somayeh
Behrouz (2010): Silica Sulfuric Acid (SSA) as a Highly Efficient Heterogeneous Catalyst for Persilylation
of Purine and Pyrimidine Nucleobases and Other N-Heterocycles Using Hmds, Phosphorus, Sulfur, and
Silicon and the Related Elements, 185:9, 1943-1954
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Phosphorus, Sulfur, and Silicon, 185:1943–1954, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903383952
SILICA SULFURIC ACID (SSA) AS A HIGHLY EFFICIENT
HETEROGENEOUS CATALYST FOR PERSILYLATION OF
PURINE AND PYRIMIDINE NUCLEOBASES
AND OTHER N-HETEROCYCLES USING HMDS
Mohammad Navid Soltani Rad,1 Ali Khalafi-Nezhad,2
Masoumeh Divar,2 and Somayeh Behrouz2
1Department of Chemistry, Faculty of Basic Sciences, Shiraz University
of Technology, Shiraz, Iran
2Department of Chemistry, College of Sciences, Shiraz University,
Shiraz, Iran
Purine and pyrimidine nucleobases and other N-heterocycles have been silylated with HMDS
in excellent yields in the presence of a catalytic amount of silica sulfuric acid (SSA) as a
heterogeneous catalyst. SSA utilizes a shorter reaction time and higher yields of silylated
nucleobases. SSA is reusable for several times without a decrease in reactivity or yield of
silylated adducts.
Keywords HMDS; nucleobase; persilylation; silica sulfuric acid (SSA)
INTRODUCTION
Trimethylsilylation of organic compounds having labile hydrogen atoms is finding
increasing use in analytical and in preparative organic chemistry.1 It is a frequently used
protection method in multistep synthesis due to its enhanced stability under a variety of
conditions, solubility in nonpolar solvents, thermal stability, and the ease of removal of the
protecting group, which is simply carried out by acid- or base-induced hydrolysis, giving
only unreactive siloxane as a byproduct. Several silylating agents such as chlorotrimethyl-
silane,2 hexamethyldisiloxane,3 N-(trimethylsilyl) imidazoles,4 and ethyl(trimethylsilyl)
acetate5 have been used for the introduction of a trimethylsilyl group onto hydrogen labile
hydroxyl and thio substrates. Hexamethyldisilazane (HMDS), as a stable, cheap, and com-
mercially available reagent,6,7 has been frequently used for this purpose. HMDS handling is
easy, and its workup from the reaction mixture is rarely time consuming; however, the low
Received 12 July 2009; accepted 2 October 2009.
We wish to thank the Shiraz University of Technology and Shiraz University Research Councils for partial
support of this work.
Address correspondence to Mohammad Navid Soltani Rad, Department of Chemistry, Faculty of Basic
Sciences, Shiraz University of Technology, Modaress Blvd., Shiraz 71555-313, Iran. E-mail: soltani@sutech.ac.ir
and Ali Khalafi-Nezhad, Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran.
E-mail: khalafi@chem.susc.ac.ir
1943

1944
M. N. S. RAD ET AL.
silylating power of HMDS is the main drawback for its application.8 Therefore, a variety
of catalysts have been reported for the activation of HMDS.9–16
Acyclic nucleosides constitute a special class of nucleoside analogues, which have
attracted great interest due to their broad spectrum of antiviral and anticancer activities.17
The most common route into nucleoside synthesis involves the N-alkylation of nucleobases
with various carbon electrophiles.18–23 The N-alkylation of purine and pyrimidine nucle-
obases is often achieved using two general methods: so-called direct18–23 and persilylated24
methods.
The former method has several drawbacks, including low solubility of nucleobases,
especially that of purine nucleobases in organic solvents, lack of regioselectivity in the case
of ambident nucleobase, low yields of products, harsh reaction condition, tedious workup,
and cumbersome separation process. The latter method possesses the apparent advantages
of remarkable increment in solubility of nucleobase in organic solvents, enhancement in
regioselectivity of the N-alkylation site, higher yields of products, milder reaction con-
ditions, and easier workup procedure. Many silylating reagents are used for silylation of
hydroxyl compounds such as phenols and alcohols, but HMDS is the most common sily-
lating agent used for nucleobases. Due to the weak silylating power of HMDS and less
nucleophilic behavior of nucleobases, the reaction of HMDS with nucleobases requires
efficient Lewis or Brønsted acid catalysts. Up to now, ammonium sulfate and/or TMSCl24
combined with HMDS have been widely employed for the silylation of nucleobases. How-
ever, the employment of these acid catalysts is usually accompanied with several limitations
and drawbacks. For example, (NH4)2SO4 and TMSCl are quite sensitive to moisture and
could decompose during prolonged reflux conditions. Additionally, they are nonrecoverable
and nonreusable. Furthermore, these catalysts do not efficiently convert the nucleobases
to their corresponding silyl ethers, especially in the case of purine derivatives, even if the
reaction time is prolonged. Hence finding an efficient heterogeneous Lewis or Brønsted
acids catalyst to establish a facile and effective method for silylation of nucleobases is an
interesting challenge.
Silica sulfuric acid (SSA) is a heterogeneous acid that currently is largely used for
many organic transformations as a solid acid catalyst under various conditions.25 The wide
application of SSA is due to its strong acidity, chemical and thermal stabilities, low cost,
reusability, ease of handling, and environmentally benign nature with fewer disposals prob-
lems. Encouraged by suitable performance and usefulness of SSA in organic synthesis, and
also in continuation of our interest in design and synthesis of novel carboacyclic nucle-
osides,18–20,26,27 in this article we report SSA as a highly efficient solid acid catalyst for
presilylation of nucleobases as well as the other N-heterocycles using HMDS (Scheme 1).
HMDS, SSA (cat.)
(1)
(2)
[B]
H
[B] SiMe3
[B] CE
reflux, 10min-24h
CE, TBAF
THF, reflux, 2-24h
[B] SiMe3
B : purin, pyrimidine nucleobases &, N-heterocycles
CE : carbon electrophile
Scheme 1

SSA AS CATALYST FOR PERSILYLATION OF NUCLEOBASES
1945
In the second part of this work, to demonstrate the efficiency of SSA and HMDS for silyla-
tion of nucleobases, the presilylated nucleobases attained by this method were condensed
with various sources of carbon electrophiles to produce various carboacyclic nucleosides
(Scheme 1).
RESULTS AND DISCUSSION
Initially, silylation of uracil was carried out in the presence of a catalytic amount
of SSA (0.05 g, 0.13 mmol) as an active heterogeneous acid catalyst in refluxing HMDS
(Scheme 2). Uracil was successfully converted to its corresponding trimethylsilyl ether in
quantitative yield in a short reaction time.
O
OSiMe3
N
NH
HMDS, SSA (cat.)
reflux, 0.5h
N
H
O
N
OSiMe3
Scheme 2
The generality and versatility of this method was demonstrated by extension to
various purine and pyrimidine nucleobases and other N-heterocycles (Table I). As the
results in Table I indicate, trimethylsilylation of nucleobases was easily carried out in
the presence of SSA in refluxing HMDS in almost quantitative yields. The depicted data
in Table I indicate this method is highly efficient and suitable for pyrimidine (Table I,
entries 1–4) and purine nucleobases and/or purine-like scaffolds (Table I, entries 5–9).
Interestingly, guanine as the most unreactive and insoluble purine nucleobase was efficiently
converted to its corresponding trimethylsilyl ether (Table I, entry 6) after refluxing for 24 h.
SSA
+
(Me3Si)2NH
[B]-H
[B]-SiMe3
(Me3Si)2NH2
(I)
(Me3Si)2NH
[B]-SiMe3
H-[B]-SiMe3
Me3SiNH3
(II)
(III)
[B]-H
NH3
Scheme 3

1946
M. N. S. RAD ET AL.
Table I Silylation of pyrimidine and purine nucleobases and other N-heterocycles using SSA/HMDS
Entry
1
Substrate
Product
Time (h)
0.5
Yielda (%)
100
OSiMe3
N
O
NH
N
H
O
N
OSiMe3
2
3
4
5
0.5
2
100
100
100
100
O
OSiMe3
N
NH
N
N
N
H
O
N
OSiMe3
OSiMe3
N
O
NH
N
H
S
N
SSiMe3
0.5
3
O
OSiMe3
N
O2N
O2N
NH
N
H
O
N
OSiMe3
NHSiMe3
NH2
N
N
N
N
N
N
N
N
H
SiMe3
6
7
24
90
O
OSiMe3
N
N
N
N
NH
NH2
N
H
N
N
NHSiMe3
Me3Si
1.5
100
SiMe3
N
O
O
N
N
NH
N
N
N
N
H
Me3Si
8
9
1
2
100
100
O
O
Me3Si
H
N
N
N
N
N
O
N
N
O
O
N
OSiMe3
N
N
N
N
N
NH
N
O
N
O
10
11
0.5
2
100
100
N
N
N
SiMe3
N
H
O2N
O2N
N
N
N
N
H
SiMe3
12
13
0.16
0.5
100
100
N
N
N
H
N
SiMe3
N
N
N
N
H
SiMe3

SSA AS CATALYST FOR PERSILYLATION OF NUCLEOBASES
1947
Table I Silylationof pyrimidineand purinenucleobasesand other N-heterocyclesusing SSA/HMDS (Continued)
Entry
14
Substrate
Product
Time (h)
0.33
Yielda (%)
100
O
Me3SiO
N
NH
HN
N
N
O
OSiMe3
15
2
100
O
Me3SiO
NH
N
HN
S
SSiMe3
aGC yield.
Table II Comparison of some of the results obtained by silylation of nucleobases and other N-heterocycles with
HMDS in the presence of SSA, TMSCl, and (NH4)2SO4
Time (h)/Yielda (%)
Entry
1
Substrate
SSA
TMSCl
3.5/100
(NH4)2SO4
2/100
0.5/100
O
NH
N
H
O
O
2
0.5/100
4/100
2/100
NH
N
N
H
O
3
4
3/100
24/90
24/80
48/50
12/95
80/63
NH2
N
N
N
N
H
O
N
NH
N
H
N
NH2
5
6
0.5/100
0.66/100
0.5/100
1/100
N
N
H
0.16/100
0.75/100
N
N
H
aGC yield.
Table III The reusability of SSA for presilylation of uracil and adenine
Time (h)/Yielda (%)
Entry
1
Substrate
1
2
3
4
5
0.5/100
0.67/100
1/95
1.67/91
1.25/88
O
NH
N
H
O
2
3/100
3.33/100
3.75/94
4.17/86
4.5/82
NH2
N
N
N
H
N
aGC yield.

1948
M. N. S. RAD ET AL.
Table IV N-Alkylated nucleobases and other N-heterocycles
EntryRef.
1
Substrate
Electrophile
Product
Mp (◦C)
167
Yielda (%)
85
OSiMe3
N
Br
O
NH
N
OSiMe3
N
O
2
180
156
85
87
O
OSiMe3
N
C
N
Cl
O
NH
N
O
N
OSiMe3
N
319
OSiMe3
N
O
N
OPh
OPh
NH
N
OSiMe3
O
OPh
OH
419
Oil
80
OSiMe3
N
O
O
N
NH
N
N
N
OSiMe3
O
OPh
OH
5
6
80
85
80
OSiMe3
N
O
N
O
O
O
NH
O
N
SSiMe3
S
O
137
NHSiMe3
NH2
OPh
N
N
N
N
N
N
N
N
SiMe3
PhO
OH
727
104
188
75
90
O
N
Me3Si
Br
O
N
N
N
N
N
O
N
N
O
8
O
O
Me3Si
N
N
N
N
Br
N
N
O
O
N
O
O
N
N
O
O
O
9
129
58
87
90
O
O
Me3Si
Me3Si
OPh
N
N
N
N
PhO
N
N
OH
O
N
O
O
O
N
10
O
N
N
O
O
N
N
N
N
N
O
11
oil
80
N
N
N
N
Br
SiMe3

SSA AS CATALYST FOR PERSILYLATION OF NUCLEOBASES
1949
Table IV N-Alkylated nucleobases and other N-heterocycles (Continued)
EntryRef.
12
Substrate
Electrophile
Product
Mp (◦C)
58
Yielda (%)
90
N
N
N
N
C
N
Cl
O
SiMe3
N
13
14
114
130
90
90
N
N
N
O
N
SiMe3
O
O
O
Me3SiO
O
N
OPh
N
N
HN
OSiMe3
HO
OPh
O
aIsolated yield.
Additionally, the optimized conditions were also applied to other N-heterocycles, including
benzimidazole, 2-methyl-4-nitro-1H-imidazole, imidazole, 2-phenyl imidazole, hydantoin,
and thiohydantoin (Table I, entries 10–15).
To demonstrate the efficiency of the present method, we compared some of our results
using SSA with those attained by TMSCl and (NH4)2SO4 (Table II). As the data in Table II
indicate, higher yields of silylated nucleobases and/or shorter reaction times were obtained
when SSA was used.
The reusability of the catalyst was tested in presilylation of uracil and adenine
(Table III). As shown in Table III, the catalyst was recovered after each run, washed three
times with acetone, dried in a vacuum oven at 100◦C for 30 min prior to use, and tested for
its activity in the subsequent run and fresh catalyst was not added. The catalyst was tested
for five runs. It was seen that the catalyst displayed favorable reusability.
The mechanism of the reaction is not clear; however on the basis of our observations
related to the fast evolution of NH3 gas from the reaction mixture and the reusability of
the catalyst without any considerable loss of its catalytic activity, we have proposed a
mechanism that is shown in Scheme 3.9
On the basis of this mechanism, acid–base interaction between SSA and HMDS
polarizes the Si-N bond in HMDS to produce the reactive silylating agent (I). A reaction of
purine and pyrimidine nucleobases as well as other N-heterocycles with (I) results in the
formation of ammonium silylating species (II) with concomitant release of the correspond-
ing silyl ether. Irreversible cleavage of (II) with a nucleobase or other N-heterocycles leads
to the fast evolution of NH3 and also formation of the unstable protonated silyl ether (III).
Release of H+ as catalyst from intermediate (III) re-enters catalytic cycle (Scheme 3).
To demonstrate the effectiveness of SSA in the persilylation reaction of nucleobases,
the silyl ethers of nucleobases as well as other N-heterocycles prepared by present method
were condensed with different sources of carbon electrophiles including alkyl halides,
epoxides, and Michael acceptors by using tetra-n-butylammonium fluoride (TBAF) as a
desilylating agent (Scheme 1). The structures of the synthesized compounds are shown in
Table IV. As the data in Table IV indicate, high yields of corresponding acyclic nucleosides
were attained. The good yield of acyclic nucleosides is evidence for efficient persilylation
of nucleobases using SSA.

1950
M. N. S. RAD ET AL.
CONCLUSION
In summary, a convenient method for trimethylsilylation of various nucleobases and
other N-heterocycles using SSA and HMDS has been established. SSA has proven to
be an efficient heterogeneous acid catalyst for presilylation of nucleobases and showed
a favorable reusability after many runs. Higher yields of the silyl ethers, shorter reaction
times, and easier workup procedure are the main advantages of the described method.
EXPERIMENTAL
All reagents were purchased from Merck and Fluka and were used without further
purification. The progress of the reactions was followed with TLC using silica gel SILG/UV
254 plates. Silica gel 60, 0.063–0.200 mm (70–230 mesh ASTM) was used for column
chromatography. IR spectra were run on a Shimadzu FTIR-8300 spectrophotometer. The
1H NMR (250 MHz) and 13C NMR (62.5 MHz) spectra were run on a Bru¨ker Avanced
DPX-250 FT-NMR spectrometer, δ in ppm, J in Hz. GC analysis was run with Shimadzu
GC-14A. Melting points (mp) were recorded on a Bu¨chi 510 apparatus in open capillary
tubes and are uncorrected.
Preparation of Silica Sulfuric Acid
SSA was prepared by the method described in the literature.28
Typical Procedure for SSA-Catalyzed Silylation of Nucleobases
and Other N-Heterocycles in the Presence of HMDS
In a 250-mL round-bottom flask, a mixture of the appropriate nucleobase or other
N-heterocycle (10 mmol), SSA (0.05 g), and HMDS (100 mL) was heated at reflux until a
clear solution was obtained (Table I). Then the catalyst was filtered off, and the filtrate was
evaporated under vacuum to remove the solvent (HMDS). The resulting crude was pure
enough as indicated by GC analysis to be used for any synthetic application and does not
require further purification or characterization.
Typical Procedure for N-Alkylation of Silylated Nucleobases
and Other N-Heterocycles
To a double-necked 250-mL round-bottom flask equipped with a condenser contain-
ing an appropriate amount of persilylated nucleobase (0.01 mol) and electrophile (15 mmol)
diluted in freshly distilled, anhydrous THF (100 mL), anhydrous TBAF (2.62 g, 10 mmol)
in THF solution (20 mL) was gradually added over 20 min. Then, the mixture was heated
at reflux (TLC control). The solvent was evaporated at reduced pressure, and the residue
was dissolved in CHCl3 (200 mL) and washed with H2O (3 × 100 mL). The organic layer
was dried (10 g of Na2SO4) and concentrated to afford the crude product.
Spectral Data for1-Benzylpyrimidine-2,4(1H,3H)-dione
(Table III, Entry 1)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:1)
afforded white crystals (1.7 g, 85%). Mp = 167◦C. Rf (EtOAc/n-hexane 1:1) (0.66). IR

SSA AS CATALYST FOR PERSILYLATION OF NUCLEOBASES
1951
(KBr) cm−1: 3350, 3089, 2855, 1730, 1705. δH (250 MHz, DMSO-d6) 11.53 (1H, s, NH
exchangeable with D2O), 7.71 (1H, d, J = 7.8 Hz, C(6) H), 7.35–7.26 (5H, m, Ph), 5.58
(1H, d, J = 7.8 Hz, C(5) H), 4.86 (2H, s, CH2). δC (62.5 MHz, DMSO-d6) 163.68, 150.99,
145.57, 136.79, 128.58, 127.59, 127.35, 101.31, 50.23. Anal. Calcd for C11H10N2O2: C,
65.34; H, 4.98; N, 13.85%. Found: C, 65.30; H, 4.91; N, 13.94%.
Spectral Data for 2-(2,4-Dioxo-3,4-dihydropyrimidin-1(2H)-
yl)acetonitrile (Table IV, Entry 2)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:1)
afforded white crystals (1.2 g, 85%). Mp = 180◦C. Rf (EtOAc/n-hexane 1:1) (0.68). IR
(KBr) cm−1: 3300, 3080, 2842, 2195, 1725, 1700. δH (250 MHz, DMSO-d6) 11.48 (1H, s,
NH exchangeable with D2O), 7.51 (1H, d, J = 7.7 Hz, C(6) H), 5.66 (1H, d, J = 7.7 Hz,
C(5) H), 4.74 (2H, s, CH2). δC (62.5 MHz, DMSO-d6) 161.93, 150.49, 141.79, 115.93,
99.31, 27.48. Anal. Calcd for C6H5N3O2: C, 47.69; H, 3.33; N, 27.81%. Found: C, 47.72;
H, 3.38; N, 27.75%.
Spectral Data for Butyl 3-(6-Oxo-1,6-dihydropyrimidin-2-
ylthio)propanoate (Table IV, Entry 5)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.1 g, 85%). Mp = 80◦C. Rf (EtOAc/n-hexane 1:2) (0.58). IR
(KBr) cm−1: 3200, 3050, 2895, 1750, 1725, 1300. δH (250 MHz, DMSO-d6) 12.54 (1H,
s, NH exchangeable with D2O), 7.84 (1H, d, J = 6.5 Hz, C(6) H), 6.08 (1H, d, J = 6.5
Hz, C(5) H), 4.00 (2H, t, J = 6.4 Hz, OCH2), 3.26 (2H, t, J = 6.6 Hz, SCH2), 2.71 (2H,
t, J = 6.6 Hz, O CCH2), 1.55–1.47 (2H, m, CH2), 1.34–1.25 (2H, m, CH2), 0.83 (3H,
t, J = 7.2 Hz, CH3). δC (62.5 MHz, DMSO-d6) 175.96, 171.21, 153.70, 146.44, 109.61,
63.82, 33.58, 30.07, 24.96, 18.52, 13.43. Anal. Calcd for C11H16N2O3S: C, 51.54; H, 6.29;
N, 10.93; S, 12.51%. Found: C, 51.58; H, 6.33; N, 10.90; S, 12.55%.
Spectral Data for 1-(6-Amino-9H-purin-9-yl)-3-phenoxypropan-2-ol
(Table IV, Entry 6)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.2 g, 80%). Mp = 137◦C. Rf (EtOAc/n-hexane 1:2) (0.53). IR
(KBr) cm−1: 3500, 3350, 3090, 1350, 1300, 1050. δH (250 MHz, DMSO-d6) 8.42 (1H, s,
C(8) H), 8.30 (1H, s, C(2) H), 7.51–7.45 (5H, m, Ph), 7.14 (2H, br s, NH, exchangeable
with D2O), 4.47 (1H, s, OH, exchangeable with D2O), 4.44–4.38 (1H, m, CH), 4.30 (2H,
dd, J = 3.7, 10.2 Hz), 4.14 (2H, dd, J = 6.2,10.2 Hz). δC (62.5 MHz, DMSO-d6) 158.56,
156.32, 152.76, 150.05, 141.92, 129.85, 121.11, 119.09, 114.64, 70.07, 69.48, 46.72. Anal.
Calcd for C14H15N5O2: C, 58.94; H, 5.30; N, 24.55%. Found: C, 58.97; H, 5.24; N, 24.59%.
Spectral Data for 1,3-Dimethyl-7-(2-oxo-2-phenyl-ethyl)-3,7-dihydro-
purine-2,6-dione (Table IV, Entry 8)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.6 g, 90%). Mp = 188◦C. Rf (EtOAc/n-hexane 1:2) (0.60). IR

1952
M. N. S. RAD ET AL.
(KBr) cm−1: 3085, 2910, 1725, 1715, 1705. δH (250 MHz, CDCl3) 7.98–7.95 (2H, m,
Ph), 7.62 (1H, s, C(8) H), 7.52–7.46 (3H, m, Ph), 5.77 (2H, s, NCH2), 3.58 (3H, s, N-
Me), 3.30 (3H, s, N-Me). δC (62.5 MHz, CDCl3) 191.12, 155.34, 151.54, 148.43, 142.37,
134.39, 133.85, 129.00, 128.04, 107.02, 51.81, 29.72, 27.74. Anal. Calcd for C15H14N4O3:
C, 60.40; H, 4.73; N, 18.78%. Found: C, 60.49; H, 4.70; N, 18.72%.
Spectral Data for 7-(2-Hydroxy-3-phenoxypropyl)-1,3-dimethyl-1H-
purine-2,6(3H,7H)-dione (Table IV, entry 9)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.8 g, 87%). Mp = 129◦C. Rf (EtOAc/n-hexane 1:2) (0.69). IR
(KBr) cm−1: 3500, 3100, 2943, 1725, 1710, 1303, 1055. δH (250 MHz, CDCl3) 7.66 (1H,
s C(8) H), 7.32–7.25 (2H, m, Ph), 7.01–6.87 (3H, m, Ph), 4.65 (2H, dd, J = 2.5, 13.4
Hz, OCH2), 4.51–4.48 (1H, m, CH), 4.18 (1H, s, OH exchangeable with D2O), 4.07–3.95
(2H, dd, J = 3.5, 13.4 Hz, NCH2), 3.56 (3H, s, N-Me), 3.37 (3H, s, N-Me). δC (62.5 MHz,
CDCl3) 158.04, 155.59, 151.29, 148.75, 142.66, 129.49, 121.36, 114.35, 106.97, 68.82,
68.68, 49.65, 29.76, 27.96. Anal. Calcd for C16H18N4O4: C, 58.17; H, 5.49; N, 16.96%.
Found: C, 58.24; H, 5.45; N, 16.98%.
Spectral Data for Butyl 3-(1,3-Dimethyl-2,6-dioxo-1,2,3,6-
tetrahydropurin-7-yl)propanoate (Table IV, Entry 10)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.7 g, 90%). mp = 58◦C. Rf (EtOAc/n-hexane 1:2) (0.59). IR
(KBr) cm−1: 3085, 2895, 1730, 1718, 1704, 1350, 1310. δH (250 MHz, CDCl3) 7.59 (1H,
s, C(8) H), 4.40 (2H, t, J = 6.5 Hz, OCH2), 3.89 (2H, t, J = 6.1 Hz, NCH2), 3.43 (3H, s,
N-Me), 3.25 (3H, s, N-Me), 2.80 (2H, t, J = 6.1 Hz, O CCH2), 1.49–1.37 (2H, m, CH2),
1.25–1.13 (2H, m, CH2), 0.73 (3H, t, J = 7.30 Hz, CH3). δC (62.5 MHz, CDCl3) 170.70,
154.95, 151.47, 148.92, 142.08, 106.40, 64.78, 42.57, 34.78, 30.36, 29.62, 27.81, 18.90,
13.50. Anal. Calcd for C14H20N4O4: C, 54.54; H, 6.54; N, 18.17%. Found: C, 54.62; H,
6.51; N, 18.23%.
Spectral Data for 1-Allyl-1H-benzo[d]imidazole (Table IV, Entry 11)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded a colorless oil (1.2 g, 80%). Rf (EtOAc/n-hexane 1:2) (0.62). IR (film) cm−1
:
3090, 2943, 1350. δH (250 MHz, CDCl3) 8.62 (1H, s, C(2) H), 7.46–7.41 (2H, m, aryl),
6.88–6.82 (2H, m, aryl), 5.43–5.39 (1H, m, CH), 4.79 (2H, dd, J = 8.4, 16.5 Hz, CH2),
4.11 (2H, d, J = 5.7 Hz, NCH2). δC (62.5 MHz, CDCl3) 143.55, 142.84, 133.60, 131.79,
122.66, 121.87, 119.86, 118.01, 109.93, 46.88. Anal. Calcd for C10H10N2: C, 75.92; H,
6.37; N, 17.71%. Found: C, 75.95; H, 6.42; N, 17.78%.
Spectral Data for 2-(1H-Benzo[d]imidazol-1-yl)acetonitrile
(Table IV, Entry 12)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.7 g, 90%). Mp = 58◦C. Rf (EtOAc/n-hexane 1:2) (0.59). IR

SSA AS CATALYST FOR PERSILYLATION OF NUCLEOBASES
1953
(KBr) cm−1: 3090, 2880, 2200, 1350. δH (250 MHz, DMSO-d6) 8.37 (1H, s, C(2) H),
7.78–7.61 (2H, m, aryl), 7.39–7.18 (2H, m, aryl), 5.69 (2H, s, NCH2). δC (62.5 MHz,
DMSO-d6) 143.99, 129.12, 122.40, 122.06, 121.84, 119.47, 116.14, 111.17, 46.77. Anal.
Calcd for C9H7N3: C, 68.78; H, 4.49; N, 26.74%. Found: C, 68.73; H, 4.56; N, 26.72%.
Spectral Data for Butyl 3-(1H-Benzo[d]imidazol-1-yl)propanoate
(Table IV, Entry 13)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.1 g, 90%). Mp = 114◦C. Rf (EtOAc/n-hexane 1:2) (0.55). IR
(film) cm−1: 3088, 2860, 1735, 1350, 1305. δH (250 MHz, CDCl3) 7.84 (1H, s, C(2) H),
7.71–7.67 (2H, m, aryl), 7.29–7.13 (2H, m, aryl), 4.30 (2H, t, J = 6.5 Hz, OCH2), 3.90
(2H, t, J = 6.7 Hz, NCH2), 2.69 (2H, t, J = 6.7 Hz, O CCH2), 1.47–1.35 (2H, m, CH2),
1.23–1.09 (2H, m, CH2), 0.73 (3H, t, J = 7.3 Hz, CH3). δC (62.5 MHz, CDCl3) 170.64,
143.73, 143.31, 133.32, 122.92, 122.11, 120.33, 109.32, 64.93, 40.26, 34.30, 30.36, 18.91,
13.55. Anal. Calcd for C14H18N2O2: C, 68.27; H, 7.37; N, 11.37%. Found: C, 68.29; H,
7.45; N, 11.32%.
Spectral Data for 3-(2-Hydroxy-3-phenoxypropyl)imidazolidine-2,4-
dione (Table IV, Entry 14)
Purification by column chromatography on silica gel using EtOAc/n-hexane (1:2)
afforded white crystals (2.25 g, 90%). Mp = 130◦C. Rf (EtOAc/n-hexane 1:2) (0.55). IR
(KBr) cm−1: 3350, 3200, 3050, 2885, 1715, 1705, 1315, 1057. δH (250 MHz, CDCl3)
7.21–7.10 (2H, m, Ph), 6.83 (1H, s, NH, exchangeable with D2O), 6.80–6.72 (3H, m, Ph),
4.22–4.15 (5H, complex, OCH2, NCH2C O), 3.79 (1H, s, OH, exchangeable with D2O),
3.56 (2H, dd, J = 6.35, 14.47 Hz, NCH2). δC (62.5 MHz, CDCl3) 171.56, 158.83, 158.48,
129.62, 121.22, 114.50, 70.43, 68.11, 46.48, 42.10. Anal. Calcd for C12H14N2O4: C, 57.59;
H, 5.64; N, 11.19%. Found: C, 57.54; H, 5.71; N, 11.13%.
REFERENCES
1. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 3rd ed. (Wiley, New
York, 1999).
2. S. H. Langer, S. Connell, and I. Wender, J. Org. Chem., 23, 50 (1958).
3. H. W. Pinnick, B. S. Bal, and N. H. Lajis, Tetrahedron Lett., 4261 (1978).
4. E. J. Corey and A. Venkateswarlu, J. Am. Chem. Soc., 94, 6190 (1972).
5. E. Nakamura, K. Hashimoto, and I. Kuwajima, Bull. Chem. Soc. Jpn., 54, 805 (1981).
6. J. Cossy and P. Pale, Tetrahedron Lett., 6093 (1978).
7. S. Tarkelson and C. Anisworth, Synthesis, 722 (1976).
8. C. A. Bruynes and T. K. Jurrines, J. Org. Chem., 47, 3966 (1982).
9. H. R. Shaterian, F. Shahrekipoor, and M. Ghashang, J. Mol. Catal. A: Chem., 272, 142 (2007).
10. A. Khazaei, M. A. Zolfigol, A. Rostami, and A. Ghorbani Choghamarani, Catalysis Commun.,
8, 543 (2007).
11. B. Karimi and B. Golshani, J. Org. Chem., 65, 7228 (2000).
12. D. Zareyee and B. Karimi, Tetrahedron Lett., 48, 1277 (2007).
13. N. Azizi, R. Yousefi, and M. R. Saidi, J. Organomet. Chem., 691, 817 (2006).
14. H. Firouzabadi, N. Iranpoor, S. Sobhani, and S. Gassamipour, Synthesis, 595 (2005).
15. V. H. Tillu, V. H. Jadhav, H. B. Borate, and R. D. Wakharkar, Arkivoc, XIV, 83 (2004).

1954
M. N. S. RAD ET AL.
16. N. Azizi and M. R. Saidi, Organometallics, 23, 1457 (2004).
17. E. De Clercq, In Advances in Antiviral Drug Design, N. G. Johnsson, ed. (JAI Press, Greenwich,
CT, 1993).
18. A. Khalafi-Nezhad, M. N. Soltani Rad, A. A. Moosavi-Movahedi, and M. Kosari, Helv. Chim.
Acta, 90, 730 (2007).
19. A. Khalafi-Nezhad, M. N. Soltani Rad, and A. Khoshnood, Synthesis, 583 (2004).
20. A. Khalafi-Nezhad, A. Zarea, M. N. Soltani Rad, B. Mokhtari, and A. Parhami, Synthesis, 419
(2005).
21. J.-R. Choi, D.-G. Cho, K. Y. Roh, J.-T. Hwang, S. Ahn, H. S. Jang, W.-Y. Cho, K. W. Kim, Y.-G.
Cho, J. Kim, and Y.-Z. Kim, J. Med. Chem., 47, 2864 (2004).
22. F. Amblard, S. P. Nolan, R. F. Schinazi, and L. A. Agrofoglio, Tetrahedron, 61, 537 (2005).
23. Y.-K. Han and L. A. Paquette, J. Org. Chem., 44, 3733 (1979).
24. C. K. Chu and S. J. Cutler, J. Heterocycl. Chem., 23, 289 (1986).
25. P. Salehi, M. A. Zolfigol, F. Shirini, and M. Baghbanzadeh, Current. Org. Chem., 10, 2171
(2006).
26. M. N. Soltani Rad, A. Khalafi-Nezhad, S. Behrouz, M. A. Faghihi, A. Zare, and A. Parhami,
Tetrahedron, 64, 1778 (2008).
27. M. N. Soltani Rad, A. Khalafi-Nezhad, S. Behrouz, Z. Asrari, M. Behrouz, and Z. Amini,
Synthesis, 3067 (2009).
28. M. A. Zolfigol, Tetrahedron, 57, 9509 (2001).