Preparation and crystal structures of purine 2,2′-, 6,6′-, and 8,8′-dimers

Article abstract of DOI:10.1002/ejoc.200800017

Treatment of 9- or 7-substituted 6-, 2-, or 8-iodopurine derivatives with copper(I) thiophene-2-carboxylate or copper(I) 3-methylsalicylate in N,N-dimethylformamide affords the corresponding 6,6′-, 2,2′-, and 8,8′-purine dimers in high yield. Cross-dimeri

Full text of DOI:10.1002/ejoc.200800017

FULL PAPER
DOI: 10.1002/ejoc.200800017
Preparation and Crystal Structures of Purine 2,2Ј-, 6,6Ј-, and 8,8Ј-Dimers
[a]
[b]
[b]
[a]
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Tomás Tobrman, Petr Stepnicka, Ivana Císarová, and Dalimil Dvorák*
Keywords: Nucleobases / Dimerization / Copper / Nitrogen heterocycles / X-ray diffraction
Treatment of 9- or 7-substituted 6-, 2-, or 8-iodopurine deriv-
atives with copper(I) thiophene-2-carboxylate or copper(I) 3-
were obtained. The crystal structures of 9,9Ј-dibenzyl- (1a)
and 9,9Ј-bis(1-methylethyl)-9H,9ЈH-[6,6Ј]bipurinyl (1c) and
methylsalicylate in N,N-dimethylformamide affords the cor- the salt [1aH2]Br2 were determined by single-crystal X-ray
responding 6,6Ј-, 2,2Ј-, and 8,8Ј-purine dimers in high yield.
Cross-dimerization reactions of different iodo derivatives
were attempted, but only mixtures containing the cross-cou-
pled products, homodimers, or dehalogenation products
diffraction analysis, which revealed extensive hydrogen
bonding and π···π stacking interactions.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
rectly by a C–C bond between the ring carbon atoms (6–6Ј,
2–2Ј, 8–8Ј) have been reported. Moreover, as the purine
bases are known to coordinate transition metals,[7] the pu-
rine dimers may serve as interesting donors for metal ions.
Introduction
The effect of many clinically used antitumor agents relies
on their ability to crosslink[1] or intercalate[2] DNA. With
an aim of extending the scope of antitumor-active com-
pounds, a number of diverse purine–purine conjugates were
designed and synthesized featuring linkages (9–9, 8–8, 9–
8, 9–7, 9–6, and 6–6) of various lengths and with various
connecting groups, including all-carbon chains attached to
the carbon atoms of the purine and pyrimidine heterocy-
cles.[3] In contrast, directly connected purine C–C dimers
still remain practically unknown.
Nucleoside C–C 8,8Ј-dimers were reported as products
of oxidative DNA damage.[4] The synthesis of some
C–C 6,8Ј-purine dimers, 6,8Ј,6Ј,8ЈЈ-purine trimers,
6,8Ј,6Ј,8ЈЈ,6ЈЈ,8ЈЈ-purine tetramers, and a Pd complex of the
corresponding cyclic tetramer based on Negishi cross-coup-
ling reaction has been described.[5] Recently, we reported
the formation of 6,6Ј-purine dimers in an attempted Heck
reaction involving 6-iodopurines.[6] Although this method-
ology can be utilized for the preparation of purine 6,6Ј-
dimers, the reaction is complicated by the formation of dif-
ficult-to-remove byproducts, the separation of which results
in substantial decrease in the yield of the coupling products.
This led us to search for a more convenient and general
approach to C–C purine dimers. To the best of our knowl-
edge, neither a practical preparative method nor the bio-
logical evaluation of simple purine dimers connected di-
Results and Discussion
Our observation that traces of 9,9Ј-dibenzyl-9H,9ЈH-
[6,6Ј]bipurinyl (1a) are formed during the preparation of
(9-benzylpurine-6-yl)magnesium halides[8] encouraged us to
study dimerization of magnesiated purines. Unfortunately,
attempts at Pd0- and Ni0-catalyzed coupling of 9-benzyl-6-
iodopurine (2a) with (9-benzylpurin-6-yl)magnesium chlo-
ride were unsuccessful. For instance, the CuI-mediated di-
merization of (9-benzylpurin-6-yl)magnesium chloride af-
forded a modest yield (42%) of dimer 1a and so did the
simple thermal decomposition of (9-benzylpurin-6-yl)mag-
nesium chloride at 50 °C in THF (yield of 1a: 28%).
Finally, we found that copper(I) thiophene-2-carboxylate
(CuTC) introduced by Liebeskind for Ullmann reductive
coupling of aromatic iodides and bromides[9] is a suitable
reagent for purine coupling. Heating of 2a in DMF at 50 °C
in the presence of CuTC (3 equiv.) gave the desired dimer
1a in excellent isolated yield (Scheme 1; Table 1, Entry 1).
High yields of symmetrical dimers were also obtained with
other 9-substituted 6-iodopurines (Table 1). In contrast,
CuTC was completely inactive in the case of riboside 2d.
However, copper(I) 3-methylsalicylate (CuMeSal),[10] which
was also reported to be active in this coupling, afforded
the corresponding purine dimer 1d in good yield (Table 1,
Entry 4). 7-Benzyl-6-iodopurine furnished the correspond-
ing dimer 3 in only moderate yield regardless of the catalyst
used (CuTC or CuMeSal).
[a] Department of Organic Chemistry, Institute of Chemical Tech-
nology, Prague
Technická 5, 2166 28 Prague 6, Czech Republic
Fax: +420-224-354-288
E-mail: dvorakd@vscht.cz
[b] Department of Inorganic Chemistry, Faculty of Science,
Charles University
The same methodology was also applied for the dimer-
ization of 2- and 8-iodopurine. Thus, 2-iodo-9-isopropyl-6-
methoxypurine (4) afforded the corresponding 2,2Ј-dimer 5
Hlavova 2030, 128 40 Prague 2, Czech Republic
Fax: +420-221-951-253
E-mail: stepnic@natur.cuni.cz
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FULL PAPER
uct, which could be isolated by tedious chromatography.
For example, the reaction of equimolar amounts of 6-iodo-
9-isopropylpurine (2c) and 2-iodo-9-isopropyl-6-meth-
oxypurine (4) gave Ϫ besides the mixed 2–6Ј bis(purine) de-
rivative 8 (26%) – the symmetrical dimers 1c (69%) and 5
(18%) (Scheme 3). Similarly, the mixture of 6-iodo-9-iso-
propylpurine (2c) and 2-iodo-9-isopropyl-6-methoxypurine
(6) afforded the unsymmetrical 6–8Ј dimer 9 (30%) together
with the homocoupling products 1c (65%) and 7 (50%)
(Scheme 4). Interestingly, when 8-iodo-9-isopropyl-6-meth-
oxypurine (6) and 2-iodo-9-isopropyl-6-methoxypurine (4)
were submitted to reductive cross-coupling in the presence
of CuTC, only formation of the 2,8Ј-mixed dimer (14%)
together with the symmetrical 8,8Ј-dimer 7 (21%) was ob-
Scheme 1. Dimerization of 9-substituted 6-iodopurines.
Table 1. Preparation of purine 6,6Ј-dimers (Scheme 1).
[a] Isolated yields. [b] With CuTC. [c] With CuMeSal.
Scheme 3. Mixed dimerization of 6-iodopurine 2c and 2-iodo-
purine 4.
in 87% yield with both catalysts (CuTC or CuMeSal). On
the contrary, CuTC gave significantly better results in the
dimerization of 8-iodo-9-isopropyl-6-methoxypurine (6)
and provided the 8,8Ј-dimer 7 in almost quantitative yield,
whereas the CuMeSal-catalyzed reaction resulted in only
29% isolated yield (Scheme 2).
Scheme 4. Mixed dimerization of 6-iodopurine 2c and 8-iodo-
purine 6.
Scheme 2. Products and yields of the dimerization of 7-benzyl-6-
iodopurine, 2-iodopurine 4, and 8-iodopurine 6.
Cross-coupling of two different iodopurine derivatives
under the above conditions was addressed next. Generally,
such cross-coupling reactions gave mixtures of all possible
Scheme 5. Mixed dimerization of 2-iodopurine 4 and 8-iodo-
regioisomers with only low selectivity for the mixed prod- purine 6.
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Eur. J. Org. Chem. 2008, 2167–2174

Preparation and Crystal Structures of Purine 2,2Ј-, 6,6Ј-, and 8,8Ј-Dimers
served. The 2,2Ј-dimer was not detected in this case but
instead a product of dehalogenation of 4, viz. 9-isopropyl-
6-methoxypurine (11) was isolated in 39% yield (Scheme 5).
X-ray Crystallography
The solid-state structures of 1a, 1c, and the salt [1aH2]-
Br2 were determined by single-crystal X-ray diffraction. The
molecular structures shown in Figures 1, 2, and 3 are rather
unexceptional as far as molecular geometry is concerned.
In all cases, the imposed crystallographic symmetry results
in anti arrangement of the purine moieties and renders the
dimers planar. Far more interesting, however, are the crystal
assemblies that may serve as a unique example of variable
and synergic cooperation between C–H···X hydrogen bond-
ing, π···π stacking of the heterocyclic rings, and hydro-
phobic interactions.
Figure 3. A view of the molecular structure of [1aH2]Br2 showing
only one, structurally independent bromide ion. Displacement el-
lipsoids are shown with 30% probability. Selected distances [Å] and
angles [°]: N(1)–C(2) 1.335(6), N(1)–C(6) 1.337(6), N(3)–C(2)
1.338(6), N(3)–C(4) 1.330(6), N(7)–C(5) 1.374(6), N(7)–C(8)
1.324(6), N(9)–C(4) 1.380(6), N(9)–C(8) 1.344(6), N(9)–C(10)
1.479(6), C(4)–C(5) 1.392(6), C(5)–C(6) 1.400(6), C(6)–C(6iii)
1.462(6); N(9)–C(10)–C(11) 111.0(4). Inner ring angles: six-mem-
bered ring, from 118.8(4) [C(2)–N(3)–C(4)] to 128.4(4) [N(1)–C(2)–
N(3)]; five-membered ring, from 106.9(4) [N(9)–C(4)–C(5)] to
111.6(4) [N(7)–C(8)–N(9)]. Symmetry code: iii. 1/2 – x, 1/2 – y,
1/2 – z.
Figure 1. Molecular structure of 1c. Displacement ellipsoids are
shown with 30% probability. Selected distances [Å] and angles [°]:
N(1)–C(2) 1.336(2), N(1)–C(6) 1.350(2), N(3)–C(2) 1.337(2), N(3)–
C(4) 1.334(2), N(7)–C(5) 1.387(2), N(7)–C(8) 1.315(2), N(9)–C(4)
1.372(2), N(9)–C(8) 1.375(2), N(9)–C(10) 1.476(2), C(4)–C(5)
1.414(2), C(5)–C(6) 1.401(2), C(6)–C(6i) 1.4818(2). Inner ring
angles: six-membered ring, from 111.4(1) [C(2)–N(3)–C(4)] to
128.8(1) [N(1)–C(2)–N(3)]; five-membered ring, from 106.2(1)
[N(9)–C(4)–C(5)] to 114.3(1) [N(7)–C(8)–N(9)]. Symmetry code: i.
1/2 – x, 1/2 – y, – z.
Figure 2. Molecular structure of 1a. Displacement ellipsoids are
shown with 30% probability. Selected distances [Å] and angles [°]:
N(1)–C(2) 1.337(2), N(1)–C(6) 1.348(2), N(3)–C(2) 1.337(2), N(3)–
C(4) 1.325(2), N(7)–C(5) 1.391(2), N(7)–C(8) 1.319(2), N(9)–C(4)
1.368(2), N(9)–C(8) 1.365(2), N(9)–C(10) 1.475(2), C(4)–C(5)
1.411(2), C(5)–C(6) 1.403(2), C(6)–C(6ii) 1.489(2). Inner ring
angles: six-membered ring, from 111.4(1) [C(2)–N(3)–C(4)] to
128.2(1) [N(1)–C(2)–N(3)]; five-membered ring, from 104.1(1)
[C(5)–N(7)–C(8)] to 114.3(1) [N(7)–C(8)–N(9)]. Symmetry code: ii.
1 –x, 1 – y, 1 – z.
The molecules of 1c assemble into tilted columns
through graphite-like π···π interactions of their aromatic
rings. The interacting purine moieties are parallel but offset
and mutually rotated by 180° (crystallographic inversion
operation; Figure 4a), which ensues in 15···26/16···25 pairing
of the fused heterocyclic rings (Xn: X is used to distinguish
the purine units and n the rings therein). The distance of
the centroids of the interacting five- and six-membered
Figure 4. (a) Schematic drawing of the crystal assembly of 1c show-
ing π interactions of the aromatic rings (dotted lines) and hydrogen
bonds (C–HǞN). The isopropyl groups are shown as black circles.
(b) Projection of the unit cell onto the ac plane (i.e., along the π-
rings Cg(5)···Cg(6iv) is 3.6876(7) Å, and the perpendicular stacked columns) showing the hydrogen bonds as dashed lines.
Eur. J. Org. Chem. 2008, 2167–2174
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FULL PAPER
distance of the ring planes separation is ca. 3.5 Å, which
corresponds with an offset of about 1.3 Å (iv. 1/2 – x,
–1/2 – y, –z).
The unit cell contains two pairs of such stacks differing
in orientation (Figure 4b); molecules in the neighboring
stacks are mutually rotated at a dihedral angle of 82°. Indi-
vidual columns are interconnected by C–H···N hydrogen
bonds: C(8)–H(8)···N(7v), C(8)···N(7v) 3.253(2) Å, angle at
H(8) 161°, v. 1/2 – x, –1/2 + y, 1/2 – z (Figure 4a and Fig-
ure 4b). Hydrogen-bond formation brings the nonpolar
substituents at N(9) into proximity, which leads to the for-
mation of alternating polar and hydrophobic domains (Fig-
ure 4b). It is also worth noting that the structure can alter-
natively be looked upon as if consisting of zig–zag folded
ribbons involving hydrogen-bonded, mutually rotated mole-
cules that are piled up at distances corresponding to the
π···π stacking interactions and interlinked by hydrogen
bonds (see horizontal slices in Figure 4a).
Although the interactions operating in crystals of 1a are
similar to those in 1c, the crystal assemblies differ. In the
structure of 1a, each purine moiety takes part in three-cen-
tered hydrogen bonds from C(8)–H(8) to N(1) and N(5) in
an adjacent bis(purine) molecule (Figure 5a): C(8)···N(7vi)
3.269(2) Å, angle at H(8) 129°; C(8)···N(1vii) 3.258(2) Å, an-
gle at H(8) 155° (vi. 1 – x, –1/2 + y, 1/2 – z; vii. x, 1/2 – y,
–1/2 + z). Because the purine units forming one molecule Figure 5. (a) A view of the hydrogen bonded sheets in the structure
of 1a along the columnar stacks. The hydrogen bonds are shown
are rotated by 180° along the 6–6Ј line, the bis(purine)
as dashed lines. For clarity, the phenyl groups were replaced with
molecules act as bridges between four other proximal mole-
black circles. (b) A side view of the π-stacked columns. The arrow
cules: two as twofold hydrogen-bond donors [from H(8)
indicating how the tilted columnar assembly propagates is identical
and H(8Ј)] and two as twofold acceptors [to N(1)/N(5Ј) and
to N(1Ј)/N(5)]. This gives rise to infinite folded sheets that
are layered at the distances dictated by π···π stacking inter-
actions of the purine units, which similar are to that in 1c
(Figure 5b): Cg(5)···Cg(6viii) 3.7031(8) Å, interplanar dis-
tance 3.29 Å (viii. 1 – x, –y, 1 – z). The formed molecular
assembly is further aided by relatively weaker C–H(phenyl)
···π-ring(purine) interactions [C(14)–H(14)···Cg(6ix): C(14)
···Cg(6ix) 3.567(2) Å, angle at H(14) 143°; and C(15)–H(15)
···Cg(5ix): C(15)···Cg(5ix) 3.518(2) Å, angle at H(15) 127°;
ix. –x, –1/2 + y, 1/2 – z].
to the viewing direction used to obtain the diagram shown in Fig-
ure 5a.
The salt [1aH2]Br2 crystallizes with the symmetry of the
tetragonal space group I41/a (Figure 6). The bis(purine)
units are doubly protonated at both N(7) atoms and form
three-centered hydrogen bridges from N(7)–H(7) to neigh-
boring bromide ions [intermolecular; N(7)–H(7)···Brx,
N(7)···Brx 3.258(4) Å, angle at H(7) 155°; x. 1/4 – y, 1/4 +
x, 5/4 – z] and to the N(1) atom in the second bonded pu-
rine moiety [intramolecular; N(7)–H(7)···N(1xi), N(7)···
N(1xi) 2.927(5) Å, angle at H(7) 110°; xi. 1/2 – x, 1/2 – y,
1/2 – z]. Thus, each bis(purine) unit behaves as a fourfold
hydrogen-bond donor and a twofold hydrogen-bond ac-
ceptor.[11] This leads to the formation of hollow helical as-
semblies along the crystallographic fourfold axes. Albeit the
cylindrical channels are nearly 5 Å wide, they do not host
other molecules (e.g., the solvents), very likely due to satu-
ration of the groups prone to hydrogen bonding.[12,13]
In addition to the mentioned polar interactions, the six-
Figure 6. Projection of the unit cell of [1aH2]Br2 onto the ab plane
showing important intermolecular interactions [hydrogen bonds
(dashed lines), π···π stacking of the aromatic rings (–π–), and C–
H···π-ring interactions (Ǟ)] and structural voids (large empty
membered ring of the protonated bis(purine) units in circles).
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Eur. J. Org. Chem. 2008, 2167–2174

Preparation and Crystal Structures of Purine 2,2Ј-, 6,6Ј-, and 8,8Ј-Dimers
9-Isopropyl-6-iodopurine
(2c):[20]
6-Iodopurine[17]
(5.24 g,
[1aH2]Br2 take part in π···π stacking with phenyl rings from
adjacent molecules: the ring centroid distance Cg(6)···
Cg(Phxii) is 3.652(3) Å and the interplanar separation is
about 3.5 Å (xii. 1/4 + y, 1/4 – x, 1/4 + z); the least-squares
ring planes are rotated by ca. 6°. Finally, each phenyl ring
enters into C–H···π-system interaction as both the donor
and acceptor (see Figure 4); the parameters are as follows:
21.3 mmol) was added to a suspension of dry K2CO3 (8.83 g,
63.9 mmol) in dry DMF (100 mL). The mixture was stirred at room
temperature for 30 min and then treated with 2-iodopropane
(4.3 mL, 42.6 mmol). After stirring for 16 h, the mixture was fil-
tered through Celite, which was subsequently washed with dry ace-
tone. Evaporation of the solvents in vacuo and chromatography on
silica (hexane/ethyl acetate, 2:1) afforded 2c (4.52 g, 74%) as a
white solid. M.p. 94–98 °C (toluene). 1H NMR (300 MHz, CDCl3):
δ = 1.66 (d, J = 6.9 Hz, 6 H, CH3), 4.91 [m, 1 H, CH(CH3)2], 8.18
(s, 1 H, 8-H), 8.62 (s, 1 H, 2-H) ppm. The data agree with those in
ref.[24] Formation of the 7-isomer was not observed.
C(14)–H(14)···Cg(Phxiii), C(14)···Cg(Phxiii
)
3.609(6) Å,
angle at H(14) 150° (xiii. 1/4 – y, – 1/4 + x, –1/4 + z).
Conclusions
2-Amino-9-isopropyl-6-methoxypurine: Sodium (0.274 g, 10.74
mmol) was added to MeOH (20 mL), and the resulting mixture
was stirred until sodium disappeared. 2-Amino-6-chloro-9-isopro-
pylpurine (1.894 g, 8.95 mmol) was then added, and stirring was
continued at ambient temperature. After 2 h, the reaction mixture
was evaporated with silica and purified by flash chromatography
(ethyl acetate/methanol, 9:1) to the product (1.84 g, 99%). M.p.
166–169 °C. 1H NMR (300 MHz, DMSO): δ = 1.47 (d, J = 6.6 Hz,
6 H, CH3), 3.96 (s, 3 H, OCH3), 4.58 [m, 1 H, CH(CH3)2], 6.38 (s,
2 H, NH2), 7.97 (s, 1 H, 8-H) ppm. 13C NMR (75 MHz, DMSO):
δ = 22.0 (CH3), 45.8 [CH(CH3)2], 53.1 (OCH3), 114.1 (C-5), 137.5
Symmetrical 6,6Ј-, 2,2Ј-, and 8,8Ј-purine dimers can be
conveniently prepared by CuTC- or CuMeSal-mediated di-
merization of the corresponding iodopurines. Cross dimer-
ization is also possible but lacks selectivity and gives mix-
tures of all the possible products. Complexation behavior
of the purine dimers is currently under study in our
laboratories.
Experimental Section
(C-8), 153.6 (C-4), 159.5 (C-4), 160.6 (C-6) ppm. IR (KBr): ν =
˜
3338, 3189, 1644, 1606, 1586, 1517, 1480, 1463, 1409, 1395, 1254,
1052 cm–1. C9H13N5O (207.23): calcd. C 52.16, H 6.32, N 33.79;
found C 52.42, H 6.59, N 34.17.
General Comments: NMR spectra were measured with a Varian
Gemini 300 (1H, 300.07 MHz; 13C, 75.46 MHz), Bruker AMX3 400
(1H, 400.13 MHz and 13C, 100.62 MHz), or Bruker DRX 500 Av-
ance (1H, 500.13 MHz and 13C, 125.77 MHz) spectrometers at
298 K. The assignment of the NMR signals is based on 13C{1H},
13C APT, COSY, 13C HMQC, and 13C HMBC spectra. IR spectra
were recorded with a Nicolet 750 FTIR spectrometer. Mass spectra
were measured with a ZAB-SEQ (VG Analytical).
2-Iodo-9-isopropyl-6-methoxypurine (4): A mixture of 2-amino-9-
isopropyl-6-methoxypurine (0.525 g, 2.53 mmol), iodine (0.642 g,
2.53 mmol), Cu2I2 (0.506 g, 2.65 mmol), CH2I2 (2.1 mL,
26.1 mmol), isoamyl nitrite (1.1 mL, 7.8 mmol), and THF (10 mL)
was heated at reflux for 2 h. After cooling, the reaction mixture
was washed with a saturated solution of Na2S2O3. The water layer
was washed with CH2Cl2 (3ϫ15 mL), and the combined organic
portion was dried with Na2SO4. Chromatography on silica with
hexane removed the excess amount of CH2I2. A subsequent elution
with hexane/ethyl acetate (1:2) furnished 4 (0.371 g, 46%) as a
white solid. M.p. 140–146 °C (toluene). 1H NMR (300 MHz,
CDCl3): δ = 1.59 (d, J = 6.8 Hz, 6 H, CH3), 4.16 (s, 3 H, OCH3),
4.86 [m, 1 H, CH(CH3)2], 7.88 (s, 1 H, 8-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 22.7 (CH3), 47.4 [CH(CH3)2], 54.9 (OCH3),
The solvents were dried and degassed by standard procedures; sil-
ica gel (ICN SiliTech, 32–63 mesh) was used for column
chromatography. 9-Benzyl-6-iodopurine[14] (2a), 6-iodo-9-(2,3,5-tri-
O-acetyl-β--ribofuranosyl)purine[15] (2d), 9-(3,5-di-O-p-toluoyl-2-
deoxy-β--erythro-pentofuranosyl)-6-iodopurine[16] (2e), and 7-
benzyl-6-iodopurine[14] were prepared by the reported procedures.
9-Allyl-6-iodopurine (2b) and 9-isopropyl-6-iodopurine (2c) were
prepared by alkylation of 6-iodopurine[17] with allyl bromide or 2-
iodopropane, respectively. 9-Isopropyl-2-iodo-6-methoxypurine (4)
was prepared from 2-amino-6-chloro-9-isopropylpurine.[18] It was
at first converted into 2-amino-9-isopropyl-6-methoxypurine by the
reaction with CH3OH in the presence of K2CO3, and the amino
group was subsequently replaced with iodine. Preparation of 8-
iodo-9-isopropyl-6-methoxypurine (6) started from 6-chloro-9-iso-
propylpurine,[19] which was converted into 9-isopropyl-6-meth-
oxypurine and then iodinated. Other compounds were purchased.
139.6 (C-8), 117.3, 121.7, 159.9 ppm. IR (CHCl ): ν = 2999, 1595,
˜
3
1564, 1464, 1376, 1328, 1308, 1282, 1222, 1202, 1159, 1146, 1040,
900 cm–1. HRMS (EI): calcd. for C9H11IN4O 317.9978; found
317.9991.
9-Isopropyl-6-methoxypurine: 6-Chloro-9-isopropylpurine[19] (1.76 g,
8.95 mmol) was added to
a solution of sodium (0.274 g,
10.74 mmol) in dry methanol (20 mL), and the reaction mixture
solution was stirred for 2 h at room temperature. Methanol was
then evaporated in vacuo, and the residue was purified by
chromatography on silica (hexane/ethyl acetate, 1:2) to give 9-iso-
propyl-6-methoxypurine (1.71 g, 99%) as a yellow oil. 1H NMR
(300 MHz, CDCl3): δ = 1.61 (d, J = 6.77 Hz, 6 H, CH3), 4.17 (s, 3
H, OCH3), 4.87 [m, 1 H, CH(CH3)2], 7.97 (s, 1 H, 8-H), 8.56 (s, 1
H, 2-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 22.5 (CH3), 47.4
and 54.0 [CH(CH3)2 and OCH3], 121.9 (C-5), 139.7 (C-8), 151.5
9-Allyl-6-iodopurine (2b): Dry acetonitrile was added to a mixture
of 6-iodopurine (246 mg, 1 mmol) and K2CO3 (3 mmol, 415 mg)
followed by the addition of allyl bromide (181 mg, 1.5 mmol). The
resulting mixture was heated at reflux for 2 h. The reaction mixture
was cooled to room temperature, evaporated with silica, and puri-
fied by flash chromatography (hexane/ethyl acetate, 1:2) to afford
2b (220 mg, 77%) as white solid. Formation of the 7-isomer was
not observed. 1H NMR (300 MHz, CDCl3): δ = 4.89 (m, 2 H,
CH2), 5.27 (d, J = 17.3 Hz, 1 H, =CH2), 5.38 (d, J = 10.3 Hz, 1
H, =CH2), 6.04 (m, 1 H, -CH=), 8.13 (s, 1 H, 8-H), 8.65 (s, 1 H,
2-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 46.0, 119.7, 121.9,
(C-4), 151.7 (C-2), 161.1 (C-6) ppm. IR (CHCl ): ν = 2988, 1604,
˜
3
1575, 1479, 1402, 1350, 1323, 1306, 1197, 1042 cm–1. HRMS (EI):
calcd. for C9H12N4O 192.1011; found 192.1016.
130.7, 138.1, 144.1, 144.8, 147.6, 151.7 ppm. IR (CHCl ): ν = 3000,
8-Iodo-9-isopropyl-6-methoxypurine (6): BuLi (1.6  in hexanes,
˜
3
1583, 1554, 1491, 1428, 1400, 1333 cm–1. HRMS (EI): calcd. for 3.8 mL, 6.03 mmol) was added to a stirred solution of diisopropyl-
C8H7IN4 285.9715; found 285.9713.
amine (0.85 mL, 6.03 mmol) in THF (5 mL) at –80 °C. After 5 min,
Eur. J. Org. Chem. 2008, 2167–2174
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2171

ˇ
T. Tobrman, P. Steˇpnicˇka, I. Císarˇová, D. Dvorˇák
FULL PAPER
9-isopropyl-6-methoxypurine (0.58 g, 3.02 mmol) dissolved in THF
(5 mL) was added dropwise. After 80 min at –80 °C, a solution of
iodine (2.30 g, 9.05 mmol) in THF (10 mL) was introduced, and
the mixture was stirred for another 10 min. It was then quenched
by the addition of a saturated solution of Na2S2O3 (20 mL). The
water layer was separated and washed with CH2Cl2 (3ϫ10 mL).
The combined organic extract was dried with MgSO4 and evapo-
rated in vacuo. Chromatography on silica (hexane/ethyl acetate,
1:2) gave 6 (0.719 g, 74%) as white crystals. M.p. 156–162 °C (tolu-
= 2991, 1734, 1579, 1567, 1488, 1422, 1397, 1329 cm–1. HRMS
(EI): calcd. for C16H14N8 318.1341; found 318.1324.
9,9Ј-Diisopropyl-9H,9ЈH-[6,6Ј]bipurinyl (1c): General procedure
starting from 2c (308 mg, 1.06 mmol) and CuTC (606 mg,
3.18 mmol) in dry DMF (5 mL). After quenching with a saturated
solution of NH4Cl (15 mL) and ammonia (2 mL), flash chromatog-
raphy (EtOAc/MeOH, 9:1) afforded dimer 1c (143 mg, 84%) as yel-
low solid. M.p. 187–192 °C. 1H NMR (300 MHz, CDCl3): δ = 1.71
(d, J = 6.7 Hz, 12 H, CH3), 5.05 [m, 2 H, CH(CH3)2], 8.33 (s, 2 H,
8-H), 9.28 (s, 2 H, 2-H) ppm. 13C NMR (75 MHz, CDCl3): δ =
1
ene). H NMR (300 MHz, CDCl3): δ = 1.72 (d, J = 6.9 Hz, 6 H,
CH3), 4.14 (s, 3 H, OCH3), 4.78 [m, 1 H, CH(CH3)2], 8.42 (s, 1 H,
2-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 20.9 (CH3), 53.5 and
54.1 [CH(CH3)2 and OCH3], 151.1 (C-2), 102.5, 125.0, 152.8, 159.6
22.5, 47.6, 132.8, 144.1, 151.9, 152.3 152.8 ppm. IR (CHCl ): ν =
˜
3
2986, 1590, 1576, 1490, 1483, 1460, 1407, 1391, 1375, 1331 cm–1.
HRMS (EI): calcd. for C16H18N8 322.1654; found 322.1644.
(C-6, C-5, C-4, C-8) ppm. IR (CHCl ): ν = 2996, 1602, 1573, 1484,
˜
3
9,9Ј-Bis(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-9H,9ЈH-[6,6Ј]bipurin-
1443, 1335, 1318, 1290, 1270, 1221, 1215, 1086, 1041 cm–1. HRMS
yl (1d): General procedure starting from 2d (101 mg, 0.20 mmol)
and CuMeSal (129 mg, 0.60 mmol) in dry DMF (3 mL). After
quenching with a saturated solution of NH4Cl (15 mL) and ammo-
nia (2 mL), flash chromatography (EtOAc/MeOH, 9:1) gave dimer
(EI): calcd. for C9H11IN4O 317.9978; found 317.9974.
General Procedure for the Dimerization of Iodopurines: Iodopurine
(1 equiv.) and CuTC or CuMeSal (3 equiv.) were placed in a flask
equipped with a rubber septum. After three vacuum/argon cycles,
dry DMF was added, and the resulting mixture was stirred under
an argon atmosphere at 50 °C overnight (14–16 h). It was then co-
oled to room temperature and quenched by the addition of a mix-
ture of a saturated aqueous solution of NH4Cl and concentrated
ammonia. The resulting mixture was stirred at ambient tempera-
ture for 30 min. The organic phase was separated, and the aqueous
layer was extracted with dichloromethane. The combined organic
extract was dried with MgSO4, the solvents were removed in vacuo,
and the solid residue was purified by flash chromatography on sil-
ica.
1
1d (59 mg, 78%) as a yellow foam. H NMR (300 MHz, CDCl3):
δ = 2.09 (s, 6 H, COCH3), 2.14 (s, 6 H, COCH3), 2.17 (s, 6 H,
COCH3), 4.44 (m, 4 H, OCH2), 4.51 (m, 2 H, CH2CHO), 5.68 (m,
2 H, CHOAc), 6.01 (t, J = 5.8 Hz, 2 H, CHOAc), 6.37 (d, J =
5.8 Hz, 2 H, CH), 8.45 (s, 2 H, 8-H), 9.30 (s, 2 H, 2-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 20.3, 20.5,20.7, 63.0, 70.7, 73.0, 80.6,
86.1, 133.0, 144.7, 152.0, 152.8, 152.9, 169.2, 169.5, 170.2 ppm. IR
(CHCl ): ν = 2869, 1752, 1673, 1581, 1491, 1437, 1388, 1330, 1266,
˜
3
1226 cm–1. HRMS (EI): calcd. for C32H34N8O14 754.2194; found
754.2168.
9,9Ј-Bis(3,5-di-O-p-toluoyl-2-deoxy-β-D-ribofuranosyl)-9H,9ЈH-[6,6Ј]-
9,9Ј-Dibenzyl-9H,9ЈH-[6,6Ј]bipurinyl (1a): General procedure start-
ing from 2a (67 mg, 0.20 mmol) and CuTC (114 mg, 0.60 mmol) in
dry DMF (5 mL). After quenching with a saturated solution of
NH4Cl (15 mL) and ammonia (2 mL), flash chromatography
(EtOAc/MeOH, 9:1) gave dimer 1a (38 mg, 90%) as a yellow solid.
bipurinyl (1e): General procedure starting from 2e (50 mg,
0.08 mmol) and CuTC (48 mg, 0.25 mmol) in dry DMF (3 mL).
After quenching with a saturated solution of NH4Cl (15 mL) and
ammonia (2 mL), flash chromatography (EtOAc/MeOH, 9:1) gave
dimer 1e (23 mg, 14%) as a brown amorphous solid. 1H NMR
(300 MHz, CDCl3): δ = 2.38 (s, 6 H, CH3), 2.44 (s, 6 H, CH3), 2.91
(dd, J1 = 4.3 Hz, J2 = 13.2 Hz, 2 H, 2-Ha), 3.18 (m, 2 H, 2-Hb),
4.68 (m, 4 H, 4-H, 5-Hb), 4.78 (m, 2 H, 5-Ha), 5.85 (d, J = 6.3 Hz,
2 H, 3-H), 6.71 (m, 2 H, 1-H), 7.22 (d, J = 7.9 Hz, 4 H, ArH), 7.30
(d, J = 7.9 Hz, 4 H, ArH), 7.91 (d, J = 7.9 Hz, 4 H, ArH), 7.99 (d,
J = 7.9 Hz, 4 H, ArH), 8.43 (s, 2 H, 8-H), 9.22 (s, 2 H, 2-H) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.65, 21.74, 38.0, 64.0, 75.1,
83.2, 84.9, 126.3, 126.6, 129.3, 129.3, 129.6, 129.8, 133.0, 144.2,
1
M.p. 236–240 °C. H NMR (300 MHz, CDCl3): δ = 5.54 (s, 4 H,
CH2Ph), 7.36 (br. s, 10 H, ArH), 8.23 (s, 2 H, 8-H), 9.31 (s, 2 H,
2-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 47.5, 127.8, 128.6,
129.1, 132.2, 134.7, 146.2, 151.8, 153.1, 152.7 ppm. IR (CHCl ): ν
˜
3
= 2992, 1578, 1568, 1498, 1457, 1438, 1397, 1329, 1254, 1201,
1174 cm–1. HRMS (EI): calcd. for C24H18N8 418.1654; found
418.1643.
Preparation of [1aH2]Br2: Compound 1a (42 mg, 0.10 mmol) was
dissolved in a mixture of water (10 mL), ethanol (5 mL), and HBr
(47%, 1 mL). The mixture was briefly boiled, whereupon most of
the solid dissolved; the formed solution was filtered while hot. Sub-
sequent crystallization induced by slow cooling to room tempera-
ture and then completed by storing at +4 °C for several days gave
crystalline product, which was filtered off, washed with 50% etha-
nol and water (2ϫ2 mL each), and dried in air. Yield: 47 mg
(81%), yellow solid. MS (ESI): m/z = 441 [1a + Na]+. The com-
pound gives erratic elemental analyses, probably due to incomplete
combustion.
144.6, 144.7, 151.9, 152.7, 165.9, 166.1 ppm. IR (CDCl ): ν = 2929,
˜
3
2853, 1721, 1612, 1578, 1489, 1441, 1409, 1329, 1271, 1179,
1101 cm–1. HRMS (ES): calcd. for C52H47N8O10 [M+ H]+
943.3415; found 943.3591.
7,7Ј-Dibenzyl-7H,7ЈH-[6,6Ј]bipurinyl (3): General procedure start-
ing from 6-iodo-7-benzylpurine (67 mg, 0.20 mmol) and CuTC
(114 mg, 0.6 mmol) in dry DMF (5 mL). After quenching with a
saturated solution of NH4Cl (15 mL) and ammonia (2 mL), flash
chromatography (EtOAc/MeOH, 4:1) gave dimer 3 (18 mg, 43%)
1
as a yellow foam. H NMR (300 MHz, CDCl3): δ = 5.18 (s, 4 H,
CH2), 6.57 (d, J = 6.7 Hz, 4 H, ArH), 7.07 (m, 6 H, ArH), 8.18 (s,
2 H, 8-H), 9.25 (s, 2 H, 2-H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 123.2, 126.8, 128.4, 128.8, 133.8, 146.3, 149.9, 151.8, 162.9 ppm.
9,9Ј-Diallyl-9H,9ЈH-[6,6Ј]bipurinyl (1b): General procedure starting
from 2b (280 mg, 0.98 mmol) and CuTC (561 mg, 2.94 mmol) in
dry DMF (5 mL). After quenching with a saturated solution of
NH4Cl (15 mL) and ammonia (2 mL), flash chromatography
(EtOAc/MeOH, 9:1) furnished dimer 1b (130 mg, 83%) as yellow
IR (CDCl ): ν = 2934, 1605, 1580, 1553, 1497, 1479, 1455, 1371,
˜
3
1334, 1173 cm–1. HRMS (EI): calcd. for C24H18N8 418.1654; found
418.1664.
1
solid. M.p. 183–188 °C. H NMR (300 MHz, CDCl3): δ = 5.00 (d,
J = 4.69 Hz, 4 H, CH2), 5.32 (d, J = 16.8 Hz, 2 H, =CH2), 5.39 (d, By following the same procedure and by using CuMeSal (161 mg,
J = 10.8 Hz, 2 H, =CH2), 6.10 (m, 2 H, CHCH=), 8.29 (s, 2 H, 8- 0.60 mmol) and 6-iodo-7-benzylpurine (84 mg, 0.25 mmol) in dry
H), 9.32 (s, 2 H, 2-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 45.9,
DMF (5 mL) gave, after quenching with a saturated solution of
NH4Cl (15 mL) and ammonia (2 mL) followed by flash chromatog-
119.7, 131.1, 132.3, 146.3, 151.9, 152.7, 153.1 ppm. IR (CHCl ): ν
˜
3
2172
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2167–2174

Preparation and Crystal Structures of Purine 2,2Ј-, 6,6Ј-, and 8,8Ј-Dimers
raphy (EtOAc/MeOH, 9:1) a mixture (53 mg) of 3 and 7-benzylpu-
rine contaminated with dimer 3 (25 mg, 48%; on the basis of NMR
spectroscopic data).
9,9Ј-Diisopropyl-6,6Ј-dimethoxy-9H,9ЈH-[2,8Ј]bipurinyl (10): Gene-
ral procedure starting from 6 (64 mg, 0.20 mmol), 4 (64 mg,
0.20 mmol), and CuTC (229 mg, 1.20 mmol) in dry DMF (3 mL).
After quenching with a saturated solution of NH4Cl (15 mL) and
ammonia (2 mL), flash chromatography (EtOAc/Hexane, 2:1) gave
8,8Ј-dimer 7 (8 mg, 14%). Subsequent elution (EtOAc/MeOH, 9:1)
afforded successively 9-isopropyl-6-methoxypurine (11; 30 mg,
39%) and 2,8Ј-dimer 10 (11 mg, 14%) as white amorphous solid.
Data for 10: 1H NMR (300 MHz, CDCl3): δ = 1.65 (d, J = 6.9 Hz,
6 H, CH3), 1.83 (d, J = 6.9 Hz, 6 H, CH3), 4.20 (s, 6 H, OCH3),
4.27 (s, 6 H, OCH3), 5.07 [m, 1 H, CH(CH3)2], 5.59 [m, 1 H,
CH(CH3)2], 8.11 (s, 2 H, 8-H), 8.58 (s, 2 H, 2-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.2, 22.9, 47.4, 50.5, 54.0, 54.6, 121.5,
121.9, 141.2, 149.0, 150.8, 151.7, 152.0, 153.2, 160.7, 161.5 ppm.
9,9Ј-Diisopropyl-6,6Ј-dimethoxy-9H,9ЈH-[2,2Ј]bipurinyl (5): General
procedure starting from 4 (64 mg, 0.20 mmol) and CuTC (114 mg,
0.60 mmol) in dry DMF (5 mL). After quenching with a saturated
solution of NH4Cl (15 mL) and ammonia (2 mL), flash chromatog-
raphy (EtOAc/MeOH, 9:1) gave 2,2Ј-dimer 5 (33 mg, 87%) as a
1
yellow solid. M.p. 172–176 °C. H NMR (300 MHz, CDCl3): δ =
1.68 (d, J = 6.7 Hz, 12 H, CH3), 4.36 (s, 6 H, OCH3), 5.14 [m, 2 H,
CH(CH3)2], 8.11 (s, 2 H, 8-H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 23.0, 46.9, 54.2, 121.5, 140.8, 152.5, 156.7, 161.0 ppm. IR
(CHCl ): ν = 2987, 1597, 1575, 1464, 1392, 1380, 1327, 1244 cm–1.
˜
3
HRMS (EI): calcd. for C18H22N8O2 382.1866; found 382.1851.
IR (CHCl ): ν = 2935, 2853, 1601, 1575, 1484, 1470, 1394, 1363,
˜
3
9,9Ј-Diisopropyl-6,6Ј-dimethoxy-9H,9ЈH-[8,8Ј]bipurinyl (7): General
procedure starting from 6 (50 mg, 0.16 mmol) and CuTC (90 mg,
0.47 mmol) in dry DMF (3 mL). After quenching with a saturated
solution of NH4Cl (15 mL) and ammonia (2 mL), flash chromatog-
raphy (EtOAc/MeOH, 9:1) gave dimer 7 (29 mg, 95%) as a white
1331, 1299, 1266, 1239 cm–1. HRMS (EI): calcd. for C18H22N8O2
382.1866, found 382.1870.
X-ray Crystallography: Crystals suitable for single-crystal X-ray
diffraction analysis were selected directly from the reaction batch
([1aH2]Br2: yellow needle, 0.03ϫ0.05ϫ0.28 mm3) or grown by
1
solid. M.p. 223–225 °C. H NMR (300 MHz, CDCl3): δ = 1.78 (d,
recrystallization
from
toluene
(1c:
yellowish
needle,
J = 7.1 Hz, 12 H, CH3), 4.24 (s, 6 H, OCH3), 5.48 [m, 2 H,
CH(CH3)2], 8.62 (s, 2 H, 2-H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 21.3, 50.4, 54.3, 121.8, 141.6, 152.1, 153.0, 161.5 ppm. IR
0.12ϫ0.20ϫ0.35 mm3). Crystals of 1a were obtained from at-
tempted preparation of a zinc–halide adduct by crystallization of
(CDCl ): ν = 2947, 1598, 1573, 1485, 1422, 1325, 1294, 1266 cm–1.
a
1a–ZnCl2 mixture from aqueous ethanol (colorless bar,
˜
3
0.10ϫ0.12ϫ0.40 mm3). Full-set diffraction data (ϮhϮkϮl; 1c:
θՅ27.5°, 1a: θՅ27.1°, and [1aH2]Br2: θՅ26.0°) were collected
with a Nonius KappaCCD diffractometer equipped with a Cryo-
stream Cooler (Oxford Cryosystems) by using graphite monochro-
matized Mo-Kα radiation (λ = 0.71073 Å) and analyzed with the
HKL program package.[21] The data were corrected for absorption
by a Gaussian routine incorporated in the diffractometer software
([1aH2]Br2); the range of the transmission factors is given in
Table 2.
HRMS (EI): calcd. for C18H22N8O2 382.1866; found 382.1862.
By following the same procedure and by using CuMeSal (129 mg,
0.60 mmol) and 6 (64 mg, 0.20 mmol) in dry DMF (3 mL) gave,
after quenching with a saturated solution of NH4Cl (15 mL) and
ammonia (2 mL) and flash chromatography (EtOAc/MeOH, 9:1)
dimer 7 (11 mg, 29%) as a white solid.
9,9Ј-Diisopropyl-6-methoxy-9H,9ЈH-[2,6Ј]bipurinyl (8): General
procedure starting from
4 (92 mg, 0.29 mmol), 2c (83 mg,
0.29 mmol), and CuTC (343 mg, 1.8 mmol) in dry DMF (5 mL).
After quenching with a saturated solution of NH4Cl (15 mL) and
ammonia (2 mL), flash chromatography (EtOAc/MeOH, 9:1) gave
successively 2,2Ј-dimer 5 (10 mg, 18%) and 2,6Ј-dimer 8 (27 mg,
26%) as yellow amorphous solids. Subsequent elution (EtOAc/
Table 2. Crystallographic data, data collection, and structure re-
finement parameters for 1c, 1a, and [1aH2]Br2.
1c
1a
[1aH2]Br2
1
Formula
C8H9N4
506.27
C24H18N8
418.46
C24H20Br2N8
580.30
MeOH, 3:2) afforded 6,6Ј-dimer 1c (65 mg, 69%). Data for 8: H
M [gmol–1
]
NMR (300 MHz, CDCl3): δ = 1.65 (m, 12 H, CH3), 4.36 (s, 3 H,
OCH3), 5.01 [m, 1 H, CH(CH3)2], 5.17 [m, 1 H, CH(CH3)2], 8.12
(s, 2 H, 8-H), 8.28 (s, 2 H, 8-H), 9.18 (s, 2 H, 2-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 22.5, 23.1, 46.9, 47.5, 54.6, 121.5, 132.3,
Crystal system
Space group
a [Å]
b [Å]
c [Å]
monoclinic
monoclinic
tetragonal
C2/c (no. 15) P21/c (No. 14) I41/a (no. 88)
20.2888(6)
5.4443(2)
13.8576(5)
96.313(2)
8
1521.41(9)
1.407
150(2)
10.0120(5)
6.6310(2)
14.8380(8)
99.054(2)
2
972.81(8)
1.429
150(2)
0.091
12399
4.9
2146/1577
4.16
28.6321(6)
28.6321(6)
5.9260(2)
–
152.2, 152.3, 153.0, 153.4, 155.4, 161.1 ppm. IR (CDCl ): ν = 2987,
˜
3
2935, 1707, 1599, 1578, 1493, 1467, 1395, 1376, 1332, 1262 cm–1.
β [°]
Z
8
HRMS (EI): calcd. for C17H20N8O 352.1760; found 352.1764.
V [Å3]
4858.1(2)
1.578
9,9Ј-Diisopropyl-6Ј-methoxy-9H,9ЈH-[6,8Ј]bipurinyl (9): General
Dcalcd. [gmL–1
T [K]
]
procedure starting from 2c (58 mg, 0.20 mmol),
6 (64 mg,
150(2)
µ(Mo-Kα) [mm–1
Diffrns. total
Rint [%][a]
]
0.093
12248
3.3
3.367[d]
23866
0.20 mmol), and CuTC (229 mg, 1.20 mmol) in dry DMF (3 mL).
After quenching with a saturated solution of NH4Cl (15 mL) and
ammonia (2 mL), flash chromatography (EtOAc/Hexane, 2:1) gave
8,8Ј-dimer 7 (19 mg, 50%). Subsequent elution (EtOAc/MeOH,
9:1) afforded 6,8Ј-dimer 9 (21 mg, 30%) as a colorless oil. Subse-
quent elution (EtOAc/MeOH, 3:2) gave 6,6Ј-dimer 1c (21 mg,
9.5
2388/1718
4.80
7.80, 15.1
0.93, –0.43
Unique/obsd.[b] diffrns. 1737/1456
R (obsd. data) [%][c]
R, wR (all data) [%][c]
3.96
4.96, 10.0
0.21, –0.23
6.77, 9.89
0.15, –0.20
∆ρ [eÅ–3
]
1
65%). Data for 9: H NMR (300 MHz, CDCl3): δ = 1.69 (d, J =
2
[a] Rint = Σ|Fo – Fo2(mean)|/ΣFo2, where Fo2(mean) is the average inten-
6.9 Hz, 6 H, CH3), 1.79 (d, J = 6.9 Hz, 6 H, CH3), 4.17 (s, 3 H,
OCH3), 5.01 [m, 1 H, CH(CH3)2], 5.64 [m, 1 H, CH(CH3)2], 8.29
(s, 2 H, 8-H), 8.58 (s, 2 H, 2-H), 9.08 (s, 2 H, 2-H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 21.3, 22.5, 47.6, 50.3, 53.8, 122.8, 133.1,
144.3, 146.1, 147.3, 151.3, 151.9, 152.6, 153.2, 161.8 ppm. IR
sity of symmetry equivalent diffractions. [b] Diffractions with Io Ͼ 2σ(Io).
2
[c] R = Σ||Fo| – |Fc||/Σ|Fo|, wR = [Σ{w(Fo – Fc2)2}/Σ w(Fo2)2]1/2. [d] Cor-
rected for absorption; the range of transmission coefficients: 0.378–0.937.
(CDCl ): ν = 3053, 2946, 1610, 1580, 1486, 1459, 1449, 1350, 1334, The structures were solved by direct methods (SIR97[22]) and re-
˜
3
1266 cm–1. HRMS (EI): calcd. for C17H20N8O 352.1760; found
fined by weighted full-matrix least-squares procedure on F2
352.1766.
(SHELXL97[23]). All non-hydrogen atoms were refined with aniso-
Eur. J. Org. Chem. 2008, 2167–2174
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2173

ˇ
T. Tobrman, P. Steˇpnicˇka, I. Císarˇová, D. Dvorˇák
FULL PAPER
[11] Additional interactions of the bromide ions with the H(8)
atom: C(8)–H(8)···Br, C(8)···Br 3.604(5) Å, angle at H(8) 143°;
were not considered, as the C(8)···Br distance exceeds the sum
of the contact radii (ca. 3.55 Å).
[12] A search in Cambridge Structural Database (version 5.24 of
November 2004 with updates of February, May and August
2005) revealed a rather low ability of bromide ions to attract
water molecules into the “organic” crystals. Among 3923 struc-
tures of bromide salts with organic cations, only about 8% fea-
ture water molecules in distances suitable for O–H···Br hydro-
gen bond formation.
[13] The corresponding hydrogensulfate salt, which was obtained as
described for the bromide except that 1 mL of 96% H2SO4 was
used, crystallizes with one water molecule per diprotonated
bis(purine) unit. However, in regard to the arrangement of the
organic part and distribution of the anions, the structures of
both salts can be considered isostructural. Crystallographic
tropic thermal motion parameters. The H(7) atom in the structure
of [1aH2]Br2 was identified from the difference electron density
maps and refined as a riding atom. All other hydrogen atoms were
included in the calculated positions and refined by using the riding
model. Relevant crystallographic data are given in Table 2. Geo-
metric parameters and structural drawing were obtained by using a
recent version of the Platon program.[24] Values involving hydrogen
atoms in the calculated positions are given without estimated stan-
dard deviations.
CCDC-672184 (for 1c), -672185 (for 1a), and -672186 (for [1aH2]-
Br2) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic
data_request/cif.
Data
Centre
via
www.ccdc.cam.ac.uk/
data for [1aH2](HSO4)2·H2O
ϵ (C24H20N8)(HSO4)2·H2O:
Acknowledgments
tetragonal, I41/a (no. 88), a = b = 30.364(1) Å, c = 5.9130(1) Å;
V = 5451.6(3) Å3, Z = 8. CCDC-672187.
[14] L.-L. Gundersen, A. K. Bakkestuen, A. J. Aasen, H. Øverås,
F. Rise, Tetrahedron 1994, 50, 9743–9756.
This project was supported by the Research Centre of the Ministry
of Education, Youth and Sports of the Czech Republic
(MSM6046137301 and MSM0026120857) and by the Grant Ag-
ency of the Czech Republic (grant no. 203/06/0888).
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Published Online: March 3, 2008
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