Molecular and crystal structures of dialkylated adenines (N6,N9-Me2Ade, N3,N6-MeBnAde) and cytosines (N1,N4-Me2Cyt)

Article abstract of DOI:10.1016/j.molstruc.2008.03.008

N⁶,N⁹-Dimethyladenine (N⁶,N⁹-Me₂Ade, 1) and N¹,N⁴-dimethylcytosine (N¹,N⁴-Me₂Cyt, 3) were obtained by conventional methods, whereas the reaction of N⁶-benzyladenine with MeI/NaOH resulted in the formation of N³,N⁶-MeBnAde (2a) and N⁶,N⁹-BnMeAde (2b). All compounds were fully characterized by microanalysis, NMR spectroscopy (¹H, ¹³C) and 1, 2a·2MeOH and 3 also by single-crystal X-ray diffraction analyses. In single-crystals of 1, obtained from THF solutions, twofold N6-H···N7′ hydrogen-bonded dimeric units (N⁶,N⁹-Me₂Ade)₂ (AA1² type according to Jeffrey and Saenger, 1991) were found. This proved to be another modification than that obtained by crystallization N⁶,N⁹-Me₂Ade from MeOH/PhCl (Sternglanz, 1978). Crystals of 2a·2MeOH exhibited an analogous hydrogen bond pattern as found in 1. The shorter N6···N7′ distance in 2a·2MeOH (2.932(2) A?) indicates slightly stronger hydrogen bonds than in 1 (3.078(3) A?). Crystals of 3 are built up from centrosymmetric dimers (N¹,N⁴-Me₂Cyt)₂ having a twofold N4-H···N3′ hydrogen bond, thus exhibiting the CC3² hydrogen bond pattern. The hydrogen bonding patterns in the dialkylated nucleobase derivatives are discussed in terms of those found in crystals of the less substituted nucleobases N⁹-MeAde and Cyt/N¹-MeCyt, respectively.

Full text of DOI:10.1016/j.molstruc.2008.03.008

Journal of Molecular Structure 891 (2008) 110–114
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: www.elsevier.com/locate/molstruc
Molecular and crystal structures of dialkylated adenines (N6,N9-Me2Ade,
N3,N6-MeBnAde) and cytosines (N1,N4-Me2Cyt)
Thomas Krüger a, Christoph Wagner a, Clemens Bruhn b, Tadeusz Lis c, Dirk Steinborn a,
*
a Institut für Chemie – Anorganische Chemie, Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle, Kurt-Mothes-Straße 2, Germany
b Institut für Chemie, Universität Kassel, D-34132 Kassel, Heinrich-Plett Straße 40, Germany
c Faculty of Chemistry, Wroclaw University, 14, F. Joliot-Curie, 50-383 Wroclaw, Poland
a r t i c l e i n f o
a b s t r a c t
N6,N9-Dimethyladenine (N6,N9-Me2Ade, 1) and N1,N4-dimethylcytosine (N1,N4-Me2Cyt, 3) were obtained
by conventional methods, whereas the reaction of N6-benzyladenine with MeI/NaOH resulted in the for-
mation of N3,N6-MeBnAde (2a) and N6,N9-BnMeAde (2b). All compounds were fully characterized by
microanalysis, NMR spectroscopy (1H, 13C) and 1, 2aꢀ2MeOH and 3 also by single-crystal X-ray diffraction
analyses. In single-crystals of 1, obtained from THF solutions, twofold N6–HꢀꢀꢀN70 hydrogen-bonded
dimeric units (N6,N9-Me2Ade)2 (AA12 type according to Jeffrey and Saenger, 1991) were found. This
proved to be another modification than that obtained by crystallization N6,N9-Me2Ade from MeOH/PhCl
(Sternglanz, 1978). Crystals of 2aꢀ2MeOH exhibited an analogous hydrogen bond pattern as found in 1.
The shorter N6ꢀꢀꢀN70 distance in 2aꢀ2MeOH (2.932(2) Å) indicates slightly stronger hydrogen bonds than
in 1 (3.078(3) Å). Crystals of 3 are built up from centrosymmetric dimers (N1,N4-Me2Cyt)2 having a two-
fold N4–HꢀꢀꢀN30 hydrogen bond, thus exhibiting the CC32 hydrogen bond pattern. The hydrogen bonding
patterns in the dialkylated nucleobase derivatives are discussed in terms of those found in crystals of the
less substituted nucleobases N9-MeAde and Cyt/N1-MeCyt, respectively.
Article history:
Received 22 February 2008
Received in revised form 11 March 2008
Accepted 11 March 2008
Available online 20 March 2008
Keywords:
Nucleobases
Adenine
Cytosine
Single-crystal X-ray diffraction analysis
Hydrogen bonding
Ó 2008 Elsevier B.V. All rights reserved.
1. Introduction
stituents and environmental conditions. Blocking the N9 and N1 po-
sition in adenines and cytosines, respectively, by an alkyl group
Although hydrogen bonds belong to the weaker forces in chem-
istry, they play a major role for understanding the chemistry of life.
Thus hydrogen bonds between nucleobases are fundamental to
understanding their structures, reactivities and intermolecular
associations, both between different (hetero-base pairing) and
identical nucleobases (homo-base pairing) [1,2]. Due to the mani-
fold hydrogen donor and acceptor sites and the existence in differ-
ent tautomeric forms, a large number of hydrogen bond patterns
exists between nucleobases, even in homo-base pairs. Overall six
homo-base pairs of adenine and three of cytosine were described.
All these types were denoted in a four-character code (e.g., AA12)
whereas the first two letters stand for the involved bases (A,
Ade; C, Cyt; G, Gua; U, Ura) followed by a sequential number and
an exponent describing twofold (2) and threefold (3) hydrogen
bonds, respectively, see Scheme 2 for examples [1]. Besides the
‘‘parent” nucleobases, a multitude of N-alkylated nucleobases are
known. These derivatives, found in mutant organisms [3], may give
rise to base mispairing under biological conditions [4]. This may be
caused, at least in part, by different hydrogen bond patterns that
proved to be highly sensitive even against small variations in sub-
leads to model compounds for nucleosides that are frequently used
in coordination chemistry [5]. Here we report the crystal structures
of the dialkylated nucleobases N6,N9-dimethyladenine (1), N3-
methyl-N6-benzyladenine (2aꢀ2MeOH) and N1,N4-dimethylcyto-
sine (3) and discuss their hydrogen bonding patterns in crystals.
2. Results and discussion
2.1. Synthesis and characterization
As described in Ref. [6] N6,N9-dimethyladenine (1, Scheme 1)
was synthesised by the reaction of N9-methyladenine and methyl
iodide resulting in the N1 methylated product that underwent in
alkaline medium a Dimroth rearrangement yielding 1 [7]. The
cytosine derivative N1,N4-dimethylcytosine (3, Scheme 1) was ob-
tained by the reaction of 1-methyl-4-methoxypyrimidin-2-one
with methyl amine according to Ref. [8]. Own experiments exhib-
ited that the reaction of the commercially available N6-benzylade-
nine with methyl iodide and sodium hydroxide resulted in a
mixture of N3-methyl-N6-benzyladenine (2a) and N6-benzyl-N9-
methyladenine (2b). The isomers were separated by preparative
centrifugal thin-layer chromatography and obtained as white
microcrystalline products in 25% and 30% yield, respectively
* Corresponding author.
E-mail address: steinborn@chemie.uni-halle.de (D. Steinborn).
0022-2860/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.molstruc.2008.03.008

T. Krüger et al. / Journal of Molecular Structure 891 (2008) 110–114
111
Me
Me
N
NH
NH
N
N
N
N
Me
O
N
Me
1
3
NH
NH
N
NH
N
N
N
N
NaOH, MeI
+
N
N
N
N
N
H
N
Me
N
Me
2a
2b
Scheme 1. Formulae and synthesis of nucleobase derivatives 1–3.
(Scheme 1). The identities of all substances were characterized by
microanalysis and by 1H and 13C NMR spectroscopy. The 1H NMR
data of 1 [6], 2b [9] and 3 [10] proved to be identical with those
given in the literature. Furthermore, the crystal structures of 1,
2aꢀ2MeOH and 3 could be obtained by single-crystal X-ray diffrac-
tion analyses.
Table 1
Geometrical parameters of hydrogen bonds of AA12 type [1] in adenine derivatives
and of CC32 type [1] in cytosine derivatives
b
1a
10
2a 2MeOHa
(AdeH)Clꢀ1/2H2Oc
N6ꢀꢀꢀN70
N6–H
3.078(3)
0.90
2.33
3.020
0.89
2.17
159
2.932(2)
0.98
2.01
2.901(1)
0.95
2.00
HꢀꢀꢀN70
N6–HꢀꢀꢀN70
159
157
159
2.2. Crystal structure of N6,N9-dimethyladenine (1)
3a
N1-MeCytd
5-MeCytꢀ1/2H2Oe
Crystals of 1 for X-ray diffraction measurements were obtained
from THF solution. 1 crystallized in the monoclinic space group
P21/c in dimeric (N6,N9-Me2Ade)2 units between them no unusual
contacts were found (shortest contact between non-hydrogen
atoms: 3.355(7) Å for N1ꢀꢀꢀC800). The structure of the dimers is
shown in Fig. 1, selected bond lengths and angles are listed in
the Figure caption. The monomers are planar in good approxima-
tion (greatest deviation from the mean plane: 0.075(3) Å for C9).
N4ꢀꢀꢀN30
N4–H
3.024(3)
0.90
2.13
3.038(2)
0.91
2.14
3.064(3)
0.89
2.18
HꢀꢀꢀN30
N4–HꢀꢀꢀN30
176
167
177
a
This work.
b
c
Taken from Refs. [11,24].
Taken from Refs. [16,24].
Taken from Refs. [15,24].
Taken from Refs. [18,24].
d
e
The centrosymmetric dimers represent
a twofold hydrogen-
bonded homo-base pair of the type AA12 [1], the geometric param-
eters of the N6–HꢀꢀꢀN70 hydrogen bonds are given in Table 1. By
recrystallization from MeOH/PhCl Sternglanz [11] obtained an-
other modification of N6,N9-dimethyladenine (10; monoclinic,
space group P21/c). Although the two modifications crystallize in
the same space group, the hydrogen bond patterns in crystals of
1 and 10 are different. As for 1, the central units in 10 are dimers
of the AA12 type. Additionally, the N1 atoms act as H acceptors
yielding N6–HꢀꢀꢀN1 hydrogen bonds. Thus, the crystals of 10 consist
of tetrameric units (Scheme 2).
2.3. Crystal structure of N3-methyl-N6-benzyladenine (2aꢀ2MeOH)
Well shaped crystals of 2aꢀ2MeOH suitable for single-crystal X-
ray diffraction measurements were obtained from methanol solu-
tion at 6 °C. 2aꢀ2MeOH crystallized in the monoclinic space group
C2/c in isolated centrosymmetric dimeric (N3,N6-MeBn-
Adeꢀ2MeOH)2 units that are shown in Fig. 2 along with selected
bond lengths and angles in the Figure caption. Between these units
no unusual contacts were found (shortest distance between non-
hydrogen atoms: 3.311(8) Å for N9ꢀꢀꢀC200). Analogous to 1, the pla-
nar nucleobases (greatest deviation from the mean plane is
0.031(2) Å for C5) are twofold N6–HꢀꢀꢀN70 hydrogen-bonded (Table
1; type: AA12). Furthermore, the N9 atoms act as hydrogen accep-
tor for solvate MeOH molecules (N9ꢀꢀꢀO1 2.748(2) Å, O1–H 0.93 Å,
HꢀꢀꢀN9 1.82 Å, N9–H–O1 176°). Additionally, the O1 atoms act as
hydrogen acceptors for another solvate molecules forming O2–
HꢀꢀꢀO1 hydrogen bonds (O2ꢀꢀꢀO1 2.748(3) Å, O2–H 0.96 Å, HꢀꢀꢀO1
1.80 Å, O2–H–O1 169°).
N7'
C7
N6
N6'
C6
N1
C5
N7
C2
C4
C8
N9
N3
2.4. Crystal structure of N1,N4-dimethylcytosine (3)
C9
Fig. 1. The dimeric unit (N6,N9-Me2Ade)2 in crystals of 1. The displacement ellips-
oids are drawn at the 30% probability level. Selected bond lengths (in Å) and angles
(in °): N1–C6 1.361(3), N6–C6 1.334(3), N6–C7 1.449(3), N9–C8 1.368(3), N9–C9
1.449(3), C2–N1–C6 118.2(2), C2–N3–C4 110.7(2), C5–N7–C8 103.9(2).
Recrystallization from boiling ethanol resulted in monoclinic
single-crystals of 3 (space group P21/c). The crystals are built up
from centrosymmetric (N1,N4-Me2Cyt)2 dimers shown in Fig. 3.

112
T. Krüger et al. / Journal of Molecular Structure 891 (2008) 110–114
Me
N
Me
N
N
N
N
AA22
N1' H N6''
Me
N
N1''
N7'
7'
N
N
N6''
6
N6'
6
N
Me
N
H
Me
1N
H
H
H
N
N6'
N
N
Me
H
H
H
H
7
H
N
6'''H
1
7
N
N
N
N
AA12
AA12
N
Me
N
Me
N
Me
N
N
9-MeAde
1'
N
1
N3'
O'''
N3'
O'
O'''
4
4
N
H
H
4
N
Me
H
H
N1'
N4'
N
N4'
H
3
N
H
3
N
3
N
H
CC32
CC32
CC22
1
N
1
N
1
N
Me
IV
O
N4
O
H
O
H
N4''
Me
H
H
N3''
N4''
1-MeCyt
3
Cyt
N
Scheme 2. Hydrogen bond patterns in crystals of cytosine and in mono- and dimethylated adenines and cytosines.
C7
N7'
C11
N3'
N6'
C10
N6
C6
N4
C4
N4'
N7
N1
C2
C5
N3
C2
C5
C8
N9
C4
N3
C3
O
C6
N1
C1''
O1
O2
C1
Fig. 2. The dimeric unit (N3,N6-MeBnAdeꢀ2MeOH)2 in crystals of 2aꢀ2MeOH. The
displacement ellipsoids are drawn at the 30% probability level. Selected bond len-
gths (in Å) and angles (in °): N1–C6 1.376(2), N6–C6 1.334(2), N3–C3 1.471(2), N6–
C10 1.455(2), N9–C8 1.363(2), C2–N1–C6 119.5(2), C2–N3–C4 116.4(2), C5–N7–C8
102.2(1).
Fig. 3. The dimeric unit (N1,N4-Me2Cyt)2 in crystals of 3. The displacement ellips-
oids are drawn at the 30% probability level. Selected bond lengths (in Å) and angles
(in °): N1–C1 1.468(3), N1–C2 1.401(3), N4–C4 1.341(3), N4–C7 1.456(3), C2–O
1.237(3), C2–N1–C6 120.5(2), N1–C2–N3 119.1(2), C2–N3–C4 120.0(2).
Selected bond lengths and angles are given in the Figure caption.
The molecules are planar in good approximation (greatest devia-
tion from the mean plane: 0.036(3) Å for N4). Two cytosine mole-
cules were found to be twofold hydrogen-bonded (N4–HꢀꢀꢀN30,
Table 1), thus exhibiting a hydrogen bond pattern of the CC32 type
[1]. Furthermore, these dimers are connected by additional C100–
HꢀꢀꢀO hydrogen bonds resulting in a two dimensional structure.
The C100ꢀꢀꢀO distance (3.197(3) Å) is in the typical range for C–HꢀꢀꢀO
hydrogen bonds of this type [12].
as a consequence, also the variety of hydrogen bond patterns. To
verify this, only nucleobases crystallizing without additional sol-
vent molecules should be considered. Because the crystal structure
of solvate-free non-methylated adenine is not described yet, in
Scheme 2 the hydrogen bonding patterns in crystals of the
monomethylated adenine N9-MeAde [13] and dimethylated ade-
nine N6,N9-Me2Ade 1/10 are shown. In crystals of N9-MeAde the
molecules are linked via hydrogen bonds of AA22 type (N6–HꢀꢀꢀN70,
N1ꢀꢀꢀH–N60) in ribbons. For N6,N9-Me2Ade dimeric (1) and tetra-
meric units (10), respectively, resulting from the hydrogen bonds
of AA12 type were found.
2.5. Discussion
In crystals of solvate-free cytosine (Cyt) [14] homo-base pairs of
the CC22 types (N4–HꢀꢀꢀO0, N3ꢀꢀꢀH–N10) were found as shown in
Scheme 2. Further N–HꢀꢀꢀO hydrogen bonds give rise to a three
In general, stepwise alkylation of the ‘‘parent” nucleobases
(adenine, cytosine) limits the number of possible tautomers and,

T. Krüger et al. / Journal of Molecular Structure 891 (2008) 110–114
113
Table 2
Crystal data, data collection and refinement parameters of 1 and 2aꢀ2MeOH and 3
1
2aꢀ2MeOH
3
Empirical formula
Formula weight
C7H9N5
163.19
C15H21N5O2
303.37
C6H9N3O
139.16
T/K
220(2)
100(2)
153(2)
Crystal system/space group
a/Å
b/Å
c/Å
Monoclinic/P21/c
6.448(2)
8.007(2)
15.300(5)
100.14(4)
777.6(4)
Monoclinic/C2/c
30.951(4)
4.963(2)
21.335(3)
103.34(3)
3189(2)
8
1.264
0.711
Monoclinic/P21/c
9.581(2)
10.209(1)
6.846(1)
96.04(2)
665.9(2)
4
b/°
V/Å3
Z
4
q/g cmꢁ3
1.394
0.095
1.388
0.100
l/mmꢁ1
F(000)
344
1296
296
Scan range/°
2.70 < h < 25.97
ꢁ7 ? 7, ꢁ9 ? 9, ꢁ18 ? 18
5533
1428 (Rint = 0.1390)
1428/0/145
0.958
0.0547, 0.1292
0.0811, 0.1446
0.247/ꢁ0.279
4.26 < h < 69.99
ꢁ18 ? 37, ꢁ5 ? 6, ꢁ26 ? 25
13358
2903 (Rint = 0.0886)
2903/0/284
1.082
0.0702, 0.1989
0.0752, 0.2087
0.452/ꢁ0.353
2.14 < h < 25.00
Reciprocal lattice segments h,k,l
Reflections collected
Reflections independent
Data/restraints/parameters
Goodness-of-fit on F2
R1, wR2 [I > 2r(I)]
R1, wR2 (all data)
Largest diff. peak and hole/e Åꢁ3
ꢁ11 ? 11, ꢁ12 ? 10, ꢁ8 ? 8
4177
1173 (Rint = 0.0754)
1173/0/97
0.981
0.0441, 0.1109
0.0738, 0.1178
0.164/ꢁ0.197
dimensional cross linking of the cytosine molecules. In N1-methyl-
cytosine (N1-MeCyt) [15] and N1,N4-dimethylcytosine (3) homo-
base pairs of the CC32 type are the central building blocks. Only
in the monomethylated cytosine N1-MeCyt these units are con-
nected further via N4–HꢀꢀꢀO0 hydrogen bonds (Scheme 2).
lized from acetonitrile (30 ml) and finally dried in vacuo. Yield:
1.0 g (30%). Fp: 182–184 °C (Ref. [21] 181.5–182.5 °C). Anal. Calc.
for C7H9N5: C, 51.52; H, 5.56; N, 42.92. Found: C, 51.47; H, 5.60;
N, 42.82%. 1H NMR (DMSO-d6, 400 MHz): d 2.95 (s, br, 3H, N6–
CH3); 3.71 (s, 3H, N9–CH3); 7.59 (s, br, 1H, NH); 8.05 (s, 1H, H8);
8.21 (s, 1H, H2). 13C NMR (DMSO-d6, 100 MHz): d 27.3 (s, N6–
CH3); 29.3 (s, N9–CH3); 120.8 (s, C5); 140.9 (s, C8); 150.4 (s, C2);
153.6 (s, C4); 156.5 (s, C6).
In Table 1 geometrical parameters of the N6–HꢀꢀꢀN70 hydrogen
bonds in adenine derivatives of the AA12 type (N6,N9-Me2Ade, 1/
1
10; N3,N6-MeBnAdeꢀ2MeOH, 2aꢀ2MeOH; (AdeH)Clꢀ /2H2O) [16])
are given. The N6ꢀꢀꢀN70 distances indicate a much stronger hydro-
gen bond in the latter one, most likely, due to the positive charge
in (AdeH)22+. Furthermore, the quite strong hydrogen bond in the
benzylated derivative 2aꢀ2MeOH can be interpreted in terms of
the electron withdraw of the benzyl group [17]. The geometrical
data of the N4–HꢀꢀꢀN30 hydrogen bonds in CC32 type derivatives
3.3. Synthesis of N3-methyl-N6-benzyladenine (2a) and N6-benzyl-N9-
methyladenine (2b)
To a solution of N6-benzyladenine (3.0 g, 13.3 mmol) and so-
dium hydroxide (560 mg, 14.0 mmol) in ethanol (100 ml) methyl
iodide (1.99 g, 14.0 mmol) was added dropwise with stirring at
ꢁ5 °C. After 2 h the solution was refluxed for 1 h. Then the solvent
was removed in vacuo and the residue was extracted with methy-
lene chloride (2 ꢂ 25 ml). The combined extracts were dried
(Na2SO4) and the solvent was removed under reduced pressure.
The both formed isomers were separated by preparative centrifu-
gal thin layer chromatography using at first diethyl ether/methanol
(8/1) and then chloroform/methanol (4/1) as eluent to elute at
first 2b and then 2a. The solvents of both fractions were removed
in vacuo and the obtained products were dried under reduced
pressure.
2a: Yield: 800 mg (25%). Fp.: 194–195 °C (Ref. [22] 203–204 °C).
Anal. Calc. for C13H13N5: C, 65.25; H, 5.48; N, 29.27. Found: C,
65.69; H, 5.67; N, 29.16%. 1H NMR (DMSO-d6, 500 MHz): d 3.87
(s, N3–CH3); 4.70 (s, br, 2H, N–CH2); 7.18–7.33 (m, 5H, Phenyl);
7.74 (s, 1H, H8); 8.33 (s, 1H, H2), 8.85 (s, br, NH). 13C NMR
(DMSO-d6, 125 MHz): d 35.8 (s, N3–CH3), 43.3 (s, N–CH2); 109.5
(s, C5); 126.7 (s, p-CH); 127.1 (s, m-CH); 128.2 (s, o-CH); 139.6 (s,
C2); 139.9 (s, i-C); 149.7 (s, C4); 153.1 (s, C8); 154.0 (s, C6).
2b: Yield: 950 mg (30%). Fp.: 124 °C (Ref. [9] 127–128 °C). Anal.
Calc. for C13H13N5: C, 65.25; H, 5.48; N, 29.27. Found: C, 65.22; H,
5.53; N, 28.92%. 1H NMR (DMSO-d6, 500 MHz): d 3.71 (s, N9–CH3);
4.71 (s, 2H, N–CH2); 7.17–7.33 (m, 5H, Phenyl); 8.09 (s, 1H, H8);
8.24 (s, 1H, H2), 8.30 (s, 1H, NH). 13C NMR (DMSO-d6, 125 MHz):
d 29.5 (s, N3–CH3), 43.0 (s, N–CH2); 119.1 (s, C5); 126.7 (s, p-CH);
127.2 (s, m-CH); 128.3 (s, o-CH), 139.8 (s, i-C); 140.4 (s, C8);
148.7 (s, C4); 152.5 (s, C2); 154.5 (s, C6).
1
(N1,N4-Me2Cyt, 3; N1-MeCyt [15], 5-MeCytꢀ /2H2O [18]) given in
Table 1 are very similar in all three derivatives. The slightly longer
1
N4ꢀꢀꢀN30 distance in 5-MeCytꢀ /2H2O might indicate a slightly
weaker hydrogen bond.
3. Experimental part
3.1. General information
NMR spectra were recorded on Varian Gemini 2000 and Unity
500 spectrometers operating at 400 and 500 MHz for 1H, respec-
tively. Solvent signals (1H, 13C) were used as internal references.
When necessary assignments were verified by gHMQC experi-
ments and by running 13C NMR spectra in APT mode, respectively.
Microanalyses (C, H, N) were performed by the microanalytical
laboratory of the University of Halle using CHNS-932 (LECO) ele-
mental analyzer. Starting materials were commercially available.
N9-Methyladenine [19] and 1-methyl-4-methoxypyrimidin-2-one
[20] were prepared according to the literature. The preparative
thin layer chromatography was made by using a Chromatotron
(Harrison Research).
3.2. Synthesis of N6,N9-dimethyladenine (1)
Compound 1 was synthesized from N9-methyladenine (3.0 g,
20.1 mmol) and methyl iodide (4.3 g, 30.0 mmol) in dimethylacet-
amide (100 ml) according to Ref. [6]. The product was recrystal-

114
T. Krüger et al. / Journal of Molecular Structure 891 (2008) 110–114
3.4. Synthesis of N1,N4-dimethylcytosine (3)
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge, CB2, IEZ, UK [Fax: +44(0)1223/336 033; E-mail:
deposit@ccdc.cam.ac.uk].
Compound 3 was synthesized according to Ref. [8] from 1-
methyl-4-methoxypyrimidin-2-one (1.00 g, 7.1 mmol) and methyl
amine (4 ml) in methanol whereas in Ref. [8] methyl amine in
water was used. The product was recrystallized from boiling etha-
nol and finally dried in vacuo. Yield: 420 mg (43%). Fp.: 177 °C (Ref.
[8] 179 °C). Anal. Calc. for C6H9N3O: C, 51.79; H, 6.52; N, 30.20.
Found: C, 52.10; H, 6.52; N, 29.81%. 1H NMR (DMSO-d6,
Acknowledgements
Financial support from the Deutsche Forschungsgemeinschaft
and gifts of chemicals by Merck (Darmstadt) are gratefully
acknowledged.
3
400 MHz): d 2.73 (d, JH,H = 4.7 Hz, 3H, N4–CH3); 3.19 (s, 3H, N1–
3
CH3); 5.61 (d, JH,H = 7.2 Hz, 1H, H5); 7.44 (1H, br, NH); 7.48 (d,
References
3JH,H = 7.2 Hz, 1H, H6). 13C NMR (DMSO-d6, 100 MHz): d 26.7 (s,
N4–CH3); 36.4 (s, N1–CH3); 93.5 (s, C5); 145.2 (s, C6); 156.3 (s,
C2); 164.3 (s, C4).
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4. Supplemental materials
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