D. M. S. Buyens, P. Mangondo, I. Cukrowski, and L. A. Pilcher
Vol 000
EXPERIMENTAL
7.40 (m, 2H, C H ), 7.39–7.23 (m, 3H, C H ), 5.51 (s,
6 5 6 5
13
2
H, CH2). C NMR (101 MHz, DMSO-d , 25°C)
6
1
Instrumentation. The H NMR spectra were recorded
δ = 154.9 (1C, C6), 152.3 (1C, C8), 149.6 (1C, C4),
1
43.5 (1C, C2), 136.1 (1C, C , C H ), 128.6 (2C, C H ),
at 400.13 MHz with a Bruker 400 AVANCE ultrashield+.
0 6 5 6 5
1
3
The decoupled C NMR spectra were recorded at
01 MHz using the Bruker 400 AVANCE ultrashield+.
128.1 (2C, C H ), 128.1 (1C, C H ), 120.1 (C5), 52.1
6 5 6 5
+
1
(CH
Crystal data for N9-Bn. CCDC ref no. 1451434.
, Mrel = 225.26, T = 150 K, monoclinic, space
group P 2 /c, a 11.7874(4) Å b 12.4129(4) Å c 7.1279(2)
2
), MS (+ESI): m/z 226.11 (M + H) .
1
H NMR spectra were calibrated using residual non-
deuterated solvent signals (DMSO-d6 at 2.50 ppm,
C H N
12 11 5
13
MeOD-d at 3.31 ppm, and CDCl at 7.24 ppm). The
C
1
4
3
3
Å, α 90 β 90.7760(11) γ 90, V = 1042.83 Å , R-factor
(%) = 3.87.
NMR spectra were calibrated using solvent signals
(DMSO-d6 at 39.5 ppm, MeOD-d4 at 49.2 ppm, and
CDCl at 77.2 ppm). All melting points were performed
Crystal data for N3-Bn. CCDC ref no. 1451435.
3
C H N , M = 225.26, T = 150 K, monoclinic, space
on single crystals using a Stuart melting point apparatus
SMP10 and are uncorrected. All flash column
chromatography was performed with silica gel 60 from
Merck, Darmstadt, Germany (No. 64271). X-ray
diffraction to obtain the crystal structures reported was
performed on a Bruker D8 Venture (copper radiation). IR
spectra were recorded in KBr using a Perkin Elmer
Spectrum RXI FTIR spectrometer. Mass spectra were
12 11
5
rel
group P 2
/c, a 7.2996(4) Å b 11.7426(6) Å c 12.4520(7)
1
3
Å, α 90 β 100.998 γ 90, V = 1047.74 Å , R-factor
(%) = 3.41.
The aforementioned synthetic procedure was repeated
using the relevant bases and solvents reported in this
article. The DMSO and DMF used for obtaining
N9-benzyladenine as a single product were dried over
activated molecular sieves, 4 Å.
®
recorded using a Waters Synapt G2 high-definition mass
spectrometry system (Waters Inc., Milford, MA, USA) in
ESI positive mode operating at a capillary voltage of
Computational methods. The crystal structure of the
N9-Bn and self-constructed structures of the N7-Bn and
N3-Bn were optimized in ADF [27,28] 2010 software.
The B3LYP level of theory was used in conjunction
with an augmented triple-ζ basis set with valence shell
polarization (ATZP) [28,29], in the COSMO [30,31]
(conductor-like screening model) implicit solvation
model using DMSO as a solvent. NMR [27,32–34]
calculations were performed using ADF software to
2
.8 kV using FIA (5 μL).
Synthesis. N9-benzyladenine and N3-benzyladenine.
KOtBu (0.436 g, 3.89 mmol) and adenine (0.499 g,
3.70 mmol) were added to DMF (30 ml) and stirred for
3
0 min at room temperature, forming a white precipitate
ꢀ
+
(
adenine K salt). Benzyl bromide (0.44 ml, 5.8 mmol)
was added, and the solution was heated to 125°C and
stirred for 24 h. The reaction mixture was filtered, and the
13
13
obtain the C NMR chemical shifts. The calculated
C
NMR spectra for adenine, N9-Bn, N3-Bn, and N7-Bn
were calibrated using the DMSO solvent signal (ppm)
as a reference to give the absolute computed values.
solvent was removed from the filtrate by an N (g) stream at
2
5
0°C. The precipitate was rinsed with ethyl acetate, and the
products were isolated by gradient flash chromatography,
ethyl acetate CH Cl hexane (1:1:0.5); ethyl
acetate : CH Cl : hexane (1:1:0.5), methanol (10%); and
:
:
2
2
2
2
ethyl acetate : CH Cl : hexane (1:1:0.5), methanol
Acknowledgments. The authors gratefully acknowledge David
C. Liles and Petrus H. van Rooyen the crystallographic team at
the University of Pretoria for solving the crystal structures, Eric
Palmer for the NMR spectroscopy service, and Lusanda Fikeni
for conducting the dried DMSO experiment. We thank the NRF
and the University of Pretoria for financial support.
2
2
(12.5%). The pure compounds were recrystallized from
CH Cl and methanol (1:1).
2
2
N9-benzyladenine. White. Yield: 30% (0.251 mg). mp:
ꢀ
1
2
3
7
35–236°C (lit. [8] 233–235°C). IR (KBr, cm ): 3399,
298, 3091, 1645, 1596, 1572, 1485, 1325, 1300, 1246,
31. H NMR (400 MHz, DMSO-d , 25°C) δ = 8.26
1
6
(
s, 1H, C8-H), 8.16 (s, 1H, C2-H), 7.38–7.17 (m, 7H, NH ,
2
13
REFERENCES AND NOTES
C H ), 5.37 (s, 2H, CH ). C NMR (101 MHz, DMSO-d6,
6
5
2
2
1
1
5°C) δ = 156.1 (1C, C6), 152.8 (1C, C2), 149.6 (1C, C4),
[
1] Raboisson, P.; Lugnier, C.; Muller, C.; Reimund, J.-M.;
41.0 (1C, C8), 137.2 (1C, C , C H ), 128.8 (2C, C H ),
Schultz, D.; Pinna, G.; Le Bec, A.; Basaran, H.; Desaubry, L.;
Gaudiot, F.; Seloum, M.; Bourguignon, J.-J. Eur J Med Chem 2003, 38,
0
6
5
6 5
27.9 (1C, C H ), 127.6 (2C, C H ), 118.8 (1C, C5), 46.3
6
5
6 5
199.
+
(1C, CH ), MS (+ESI): m/z 226.11 (M + H) .
2
[2] Bourguignon, J.-J.; Désaubry, L.; Raboisson, P.; Wermuth,
C.-G.; Lugnier, C. J Med Chem 1997, 40, 1768.
N3-benzyladenine. White. Yield: 4% (0.030 mg). mp:
ꢀ
1
2
3
6
1
79–281°C, (lit. [21] 280–281°C). IR (KBr, cm ): 3319,
099, 1658, 1617, 1567, 1455, 1405, 1226, 1176, 1014,
56. H NMR (400 MHz, DMSO-d , 25°C) δ = 8.57 (s,
H, C2-H), 7.96 (s, 2H, NH ), 7.78 (s, 1H, C8-H), 7.50–
[3] Hakimelahi, G. H.; Ly, T. W.; Moosavi-Movahedi, A. A.;
Jain, M. L.; Zakerinia, M.; Davari, H.; Mei, H.-C.; Sambaiah, T.;
Moshfegh, A. A.; Hakimelahi, S. J Med Chem 2001, 44, 3710.
[4] Phadtare, S.; Kessel, D.; Corbett, T. H.; Renis, H. E.; Court, B. E.;
Zemlicka, J. J Med Chem 1991, 34, 421.
1
6
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet