Synthesis of the novel bicyclic oxepinopyrimidine and fluorinated pyrrolidinopyrimidines

Article abstract of DOI:10.3987/com-04-10176

The new 5,6-disubstituted pyrimidine nucleoside analogues (5-8) were synthesized by addition of the C-6 lithiated pyrimidine derivative to oxirane as key reaction step. The bicyclic tetrahydrooxepinopyrimidine (9) and fluorinated pyrrolidinopyrimidines (12 and 15) were obtained by intramolecular linkage of acyclic chain to the CH₂-5 and N-1 of the pyrimidine ring. The structure of compound (9) containing pyrimidine and tetrahydrooxepine skeleton was determined unequivocally by its X-Ray crystal structure analysis.

Full text of DOI:10.3987/com-04-10176

HETEROCYCLES, Vol. 63, No. 11, 2004, pp. 2523 - 2536
Received, 16th July, 2004, Accepted, 16th September, 2004, Published online, 17th September, 2004
SYNTHESIS OF THE NOVEL BICYCLIC OXEPINOPYRIMIDINE
AND FLUORINATED PYRROLIDINOPYRIMIDINES
Sanja Batinac,a Draginja Mrvoš Sermek,b Mario Cetina,c Krešimir Pavelić,d
Mladen Mintas,a and Silvana Raić-Malića*
aDepartment of Organic Chemistry, Faculty of Chemical Engineering and
Technology, Marulićev trg 20, HR-10000 Zagreb, Croatia
bLaboratory of General and Inorganic Chemistry, Faculty of Science,
Zvonimirova 8, HR-10000 Zagreb, Croatia
cFaculty of Textile Technology, Pierottijeva 6, HR-10000 Zagreb, Croatia
dDivision of Molecular Medicine, Ruđer Bošković Institute, Bijenička 54, HR-
10000 Zagreb, Croatia
* Corresponding author. Tel.: +385-1-4597-214; fax: +385-1-4597-224; e-mail:
silvana.raic@fkit.hr
Abstract – The new 5,6-disubstituted pyrimidine nucleoside analogues (5-8) were
synthesized by addition of the C-6 lithiated pyrimidine derivative to oxirane as
key reaction step. The bicyclic tetrahydrooxepinopyrimidine (9) and fluorinated
pyrrolidinopyrimidines (12 and 15) were obtained by intramolecular linkage of
acyclic chain to the CH2-5 and N-1 of the pyrimidine ring. The structure of
compound (9) containing pyrimidine and tetrahydrooxepine skeleton was
determined unequivocally by its X-Ray crystal structure analysis.
INTRODUCTION
Uracil derivatives substituted either at C-5 or C-6 position and their nucleosides have considerable
importance in the field of chemotherapy. Among the important 6-substituted uracil, 1-[(2-
hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT)1 and its derivatives have emerged as new anti-HIV-
1 agents. Another group of 6-substituted uracils, viz. 3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines
(DABOs)2 behave as non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis and
biological activity of variously 6-substituted uracils and their derivatives have also been reported.3 Our

previous studies have shown that C-6 alkylated pyrimidine nucleoside analogues have good binding
affinities to herpes simplex virus type 1 thymidine kinase (HSV-1 TK) and no cytotoxic effect.4
Furthermore, radiolabelled pyrimidine nucleosides were evaluated as a tracers for non-invasive positron
emission tomography (PET) imaging of HSV-1 TK gene expression.5 Labelled thymidine is preferred
radiopharmaceutical for indicating cellular proliferation, because its specific incorporation into DNA is
linked to the S phase of the cell cycle.6 Additionally, the tissue distribution of 5-[18F]fluorouracil showed
that this compound indeed accumulates in different animal7 and human tumors.8 Excellent biological
activities exhibited by both 5- and 6-substituted uracil derivatives provided the impetus to explore
chemistry and biological activites of 5,6-disubstituted uracils.9
In this connection and related to our studies on acyclic pyrimidine nucleoside analogues,4, 10 our interest
was enhanced on C-6 alkylated pyrimidine derivatives and fluorinated pyrrolidinopyrimidine derivatives.
In this paper we report the synthesis of new 5,6-disubstituted pyrimidines (5-8) and bicyclic pyrimidine
derivatives (9, 12 and 15) formed by linkage of acyclic chain to the CH2-5 and N-1 (Figure 1).
O
O
O
CH
OCH
3
3
HN
O
CH OCH
CH OCH
2 3
2
3
HN
N
HN
O
N
OR
OR
O
N
H
CH O
O
3
N
N
H
R = Ac, H
R = CH2F, F
12 and 15
R
5 and 8
6 and 7
9
Figure 1. The novel 5,6-dialkylated pyrimidines (5-8) and bicyclic tetrahydrooxepinopyrimidine (9) and
fluorinated pyrrolidinopyrimidines (12 and 15).
RESULTS AND DISCUSSION
CHEMISTRY
Introduction of hydroxymethyl side chain at C-5 of the pyrimidine ring was performed by addition of
formaldehyde to 6-methyluracil (Scheme 1) according to the procedure analogous to that for the
preparation of 5-hydroxymethyluracil.11 5-Hydroxymethyl-6-methyluracil (2) has been shown to
decompose when subjected to hydrolysis forming 6-methyluracil and formaldehyde.12 On the contrary to
this, we found that the synthesis of 2 proceeded successfully and in good yield. Chlorination of 2 with
phosphoryl chloride and subsequent methoxylation of 3 with sodium methoxide in methanol gave 2,4-
dimethoxy-5-methoxymethyl-6-methylpyrimidine (4, Scheme 1). Alkylation at C-6 position of the
pyrimidine moiety was performed via an addition reaction of the lithiated pyrimidine derivative of 4 to
oxirane as electrophile.

Cl
O
O
OCH
3
CH Cl
2
CH OH
2
CH OCH
2
3
N
HN
HN
i
iii
N
ii
Cl
O
CH
3
O
N
CH
3
N
H
N
H
CH
3
CH O
3
N
CH
3
1
2
3
4
iv
OCH
OCH
3
3
CH OCH
CH OCH
2
3
2
3
N
N
2
4
v
5
6
Li
1'
OH
3'
CH O
3
CH O
N
N
3
2'
5
vi
O
OCH
3
CH OCH
CH OCH
2
3
2
3
HN
N
+
OAc
OAc
O
CH O
3
N
H
N
7
6
vii
O
O
CH OCH
2
3
O
HN
HN
+
OH
O
N
H
O
N
H
8
9
Scheme 1. Reagents and conditions: (i) paraformaldehyde, KOH, 50 oC; (ii) POCl3, reflux; (iii) NaOCH3,
CH3OH, rt; (iv) n-C4H9Li, THF; (v) oxirane, -50 oC, NH4Cl; (vi) AcCl, H2O; (vii) conc. HCl, 60 oC.
Ring opening reaction afforded pyrimidine containing 3-hydroxypropyl side-chain at C-6. Compound (5)
was then treated with acetyl chloride, containing several drops of water. Hydrolysis of 2- and 4- methoxy
groups of 5 gave acetylated pyrimidine-2,4-dione (6) and acetylated 2,4-dimethoxypyrimidine (7)
derivatives. Hydrolysis of 6 in concentrated hydrochloric acid afforded deacetylated pyrimidine-2,4-dione
derivative (8) and bicyclic tetrahydrooxepinopyrimidine (9) as predominant product (Scheme 1). When a
reaction of 5 with acetyl chloride and water was preformed during 7 days a mixture of all compounds (6-
9) was obtained. By monitoring of hydrolysis by TLC, we found that acetylation of hydroxy group
occurred first, following demethoxylation together with deacetylation and finally cyclization. Depending

on reaction time, ratio of thus obtained products (6-9) varied. Thus, bicyclic product (9) was obtained as
major product with prolonged time.
Conformationally constrained carbon-bridged pyrimidine acyclic nucleosides containing fluoromethyl
(12) or fluoro group (15) attached to the pyrrolidine moiety were also obtained (Scheme 2).
O
O
4
O
CH3
CH3
1'
OH
OH
OH
4'
CH3
HN
HN
5
6
HN
(ii)
(i)
2
OTrM
3'
O
O
N
H
N
H
2'
O
N
1013
11
F
12
O
O
O
N
CH3
OH
CH3
CH3
HN
HN
HN
OH
(ii)
(i)
OH
OTrM
O
O
N
H
N
H
O
134
14
F
15
Scheme 2. Reagents and conditions: (i) 4-methoxytrityl chloride, DMAP, TEA, DMF, 50 oC; (ii) DAST,
CH2Cl2, rt.
A primary hydroxy group in 6-[3-hydroxy-2-(hydroxymethyl)propyl]thymine (10)13 and 6-(2,3-
dihydroxypropyl)thymine (13)4 was protected with 4-methoxytrityl chloride using the method which has
been previously applied for the preparation of tritylated ganciclovir.14 The 11 and 14 were then subjected
to fluorination using DAST (Scheme 2).
These reactions proceeded by ring closure and formation of the bicyclic products (12) and (15). This
reaction most likely occurs through an initial proton abstraction from N-1 by fluoride and subsequent
nucleophilic attack at the methylene position by the N-1 of the pyrimidine ring.
1H AND 13C NMR SPECTRA
1
13
The structures of the new compounds were deduced by analysis of their H and C NMR spectra (see
1
13
EXPERIMENTAL). Assignment of H and C NMR spectra was performed on the basis of chemical
1
shifts, signal intensities, magnitude and multiplicity of H-H coupling constants. The H NMR
spectroscopic data of 2-9, 11, 12, 14 and 15 are displayed in Table 1. The chemical shifts and H-H
coupling constants are consistent with the proposed structures. The chemical shift assignments agree with
the corresponding ones of the related compounds.3, 4

X- RAY CRYSTAL STRUCTURE STUDY
The structure of the bicyclic compound (9) was determined by X-Ray crystal structure analysis. The
molecular structure with the atom numbering is displayed in Figure 2.
Figure 2. The molecular structure and labelling of 9. Displacement ellipsoids are drawn at the 30 %
probability level.
In the compound (9), a pyrimidine ring is fused with a seven-membered oxepine ring via common carbon
atoms C10 and C11. The pyrimidine ring is planar, because the largest observed deviation of the ring
atoms from the mean plane of the ring is 0.018(2) Å for the C2 atom. The carbonyl oxygen atoms O21
and O41 lie almost in the ring plane; the dihedral angles between the O21-C2 and O41-C4 bond lines and
the mean plane of the pyrimidine ring amount to 2.2(1) and 1.2(1)o. The oxepine ring adopts a chair
conformation. The C10, C11 and C7 atoms deviate from the mean plane of the atoms C5/C8/C9/O6 by
+0.979(1), +1.013(1) Å and -0.692(3) Å, respectively.
Both N-H donor atoms participate in the hydrogen-bonding, so generating two N-H···O hydrogen bonds
(Figure 3). Thus, two N1···O21i intermolecular hydrogen bonds connect the neighbouring molecules of 9
2
into a centrosymmetric
dimer [symmetry code: (i) -x, -y+1, -z+2]. The N1···O21 distance and N1-
8
( )
R2
H···O21 angle amount to 2.792(2)Å and 176(2)o, respectively. Furthermore, the N3 atom acts as a donor
to O6ii atom of the oxepine ring [symmetry code: (ii) –x+1, +y+1/2, -z+3/2], so producing infinite C(6)
chain motif along b axis [N3···O6 = 2.869(2) Å; N3-H···O6 = 165(2)o]. The combination of these two
motifs generates (1 0 2) sheets (Figure 3). The action of these two hydrogen bonds are reinforced by that
of a C8···O41iii hydrogen bond [symmetry code: (iii) x, -y+1/2, +z+1/2], which forms infinite C(7) chains
[C8···O41 = 3.502(3) Å; C8-H···O41 = 150(2)o]. This third motif is perpendicular to the first two
hydrogen-bonding motifs and links (1 0 2) sheets into a three-dimensional network (Figure 4).

Figure 3. Crystal packing diagram of 9 along a axis, showing N-H···O hydrogen bonds that generate (1 0
2) sheets. Hydrogen bonds are indicated by dashed lines.
Figure 4. Crystal packing diagram of 9 along b axis, showing C8···O41 hydrogen bond which links (1 0 2)
sheets into a three-dimensional network. Hydrogen bonds are indicated by dashed lines.
CONCLUSIONS
The 5,6-disubstituted (5-8) pyrimidine nucleoside analogues were prepared by hydroxymethylation at C-5
position and subsequent addition of the lithiated pyrimidine at C-6 with oxirane as electrophile. Ring
closure of C-5 and C-6 side chains in 6 by acid hydrolysis gave bicyclic compound (9) containing
tetrahydrooxepine and pyrimidine rings. The exact stereostructure of this compound was determined by

X-Ray structural analysis. Fluorinated pyrrolidinopyrimidine derivatives (12 and 15) were formed by N-1
linkage to the acyclic moiety at C-6 position.
EXPERIMENTAL
General. Melting points (uncorrected) were determined with Kofler micro hot-stage (Reichert, Wien).
Precoated Merck silica gel 60F-254 plates were used for thin layer chromatography (TLC) and the spots
were detected under UV light (254 nm). Column chromatography was performed using silica gel (0.063-
0.2 mm) Kemika; glass column was slurry-packed under gravity. The EIMS spectra were recorded with an
EXTREL FT MS 2001 instrument with ionising energy 70 eV. Elemental analyses were performed in the
Central Analytic Service, Ruđer Bošković Institute, Zagreb. 1H and 13C NMR spectra were recorded on a
Varian Gemini 300 spectrometer, operating at 75.46 MHz for the 13C resonance. The samples were
1
13
dissolved in DMSO-d6 and measured in 5 mm NMR tubes. The H and C NMR chemical shift values
(δ) are expressed in ppm referred to TMS and coupling constants (J) in Hz.
5-Hydroxymethyl-6-methylpyrimidine-2,4-dione (2)
A solution of 6-methyluracil (20 g; 0.159 mol), paraformaldehyde (5.95 g; 0.198 mol) and KOH (277.8
mL, 0.42 M) was stirred for 73 h at 50 °C. After dilution with water, reaction mixture was stirred with
freshly washed DOWEX (H+ form, strongly acidic, 100-200 mesh) (60 g) and filtrated to remove resin
and a little insoluble product. The filtrate was concentrated by evaporation on small volume, refrigerated
and filtered. Recrystalization from acetone and water (2:1) gave white crystals of 2 (18.92 g; 76.4 %; mp
13
> 308 °C). C NMR δ 164.26 (C-2), 151.52 (C-4), 109.37 (C-5), 151.01 (C-6), 53.31 (CH2-5), 15.94
(CH3-6); MS (70 eV) m/z: 156 [M+.].
2,4-Dichloro-5-chloromethyl-6-methylpyrimidine (3)
The mixture of 5-hydroxymethyl-6-methylpyrimidine-2,4-dione (2) (10 g; 64.045 mmol) and POCl3 (100
mL; 1.092 mol) was heated under reflux for 1 h. Excess of POCl3 was then removed under reduced
pressure and the residue was added to ice. Cold mixture was filtrated to give yellow crystals of 3 (8.14 g,
60.1 %; mp 38 °C). 13C NMR δ 181.82 (C-2), 170.99 (C-4), 137.02 (C-5), 167.27 (C-6), 49.00 (CH2-5),
31.55 (CH3-6); MS (70 eV) m/z: 212 [M+.].
2,4-Dimethoxy-5-methoxymethyl-6-methylpyrimidine (4)
To a solution of sodium (1.49 g; 64.944 mmol) in methanol (36.6 mL) was added compound (3) (4.358 g;
20.607 mmol). The reaction mixture was refluxed for 3 h. The solvent was evaporated and water was
added to dissolve NaCl. The oily layer was extracted with dichloromethane, dried over sodium sulfate and

concentrated under reduced pressure. The residue was kept in refrigerator and then applied to column
chromatography (CH2Cl2:MeOH = 40:1) to give 4 (2.52 g; 61.74 %; mp 40 °C). 13C NMR δ 169.36 (C-2),
168.95 (C-4), 108.42 (C-5), 163.55 (C-6), 63.69 (CH2-5), 57.39, 54.24 (OCH3-2, OCH3-4), 53.91 (OCH3-
5), 21.0 (CH3-6); MS (70 eV) m/z: 198 [M+.].
6-(3-Hydroxypropyl)-2,4-dimethoxy-5-methoxymethylpyrimidine (5)
Lithium diisopropylamide (LDA) (4.34 mL; 8.42 mmol) in hexane was added dropwise to a solution of 4
o
(1.015 g; 5.12 mmol) in anhydrous tetrahydrofuran (14.21 mL) at -70 C under argon atmosphere. The
o
temperature was warmed to -55 C and the solution was stirred for 30 min. Oxirane in excess (1.5 mL;
30.645 mmol) was added dropwise to the solution, temperature was raised to -10 oC and the stirring was
continued for 3 h. The reaction mixture was neutralized by the addition of saturated ammonium chloride
solution and the temperature was raised to rt. The solvent was removed under reduced pressure and the
residue was partitioned between dichloromethane and water. Organic layer was dried over sodium sulfate
and the solvent was removed by evaporation. The crude product was purified by column chromatography
13
(CH2Cl2:MeOH = 20:1) providing oily compound (5) (0.773 g; 67.92 %). C NMR δ 172.27 (C-2),
169.58 (C-4), 108.29 (C-5), 163.70 (C-6), 63.40 (CH2-5), 54.23, 53.96 (OCH3-2, OCH3-4), 31.51 (C-1’),
30.15 (C-2’), 60.38 (C-3’), 57.43 (OCH3-5); MS (70 eV) m/z: 242 [M+.]; Anal. Calcd for C11H18N2O4: C,
54.53; H, 7.49; N, 11.56. Found: C, 54.69; H, 7.47; N, 11.59.
6-(3-Acetoxypropyl)-5-methoxymethylpyrimidine-2,4-dione (6) and 6-(3-acetoxypropyl)-2,4-
dimethoxy-5-methoxymethylpyrimidine (7)
A solution of 5 (560 mg, 2.31 mmol) in acetyl chloride (8 mL) was refluxed for 5.5 h. Water (1 mL) was
added and the mixture was stirred at rt overnight. The solution was evaporated under reduced pressure.
The residue was applied to column chromatography (CH2Cl2:MeOH = 15:1) to give white crystals of 6
(137.9 mg, 23.30%, mp 140-142 °C) and oily compound (7) (81 mg, 0.12%).
13
6: C NMR δ 170.28 (CO), 164.26 (C-2), 155.54 (C-4), 106.01 (C-5), 150.94 (C-6), 63.39 (CH2-5),
27.20 (C-1’), 26.45 (C-2’), 57.14 (C-3’), 63.05 (OCH3-5), 20.69 (CH3CO); MS (70 eV) m/z: 256 [M+.];
Anal. Calcd for C11H16N2O3: C, 51.56; H, 6.29; N, 10.93. Found: C, 51.42; H, 6.30; N, 10.95.
13
7: C NMR δ 170.81 (CO), 171.65 (C-2), 170.01 (C-4), 108.85 (C-5), 164.12 (C-6), 63.74 (CH2-5),
30.08 (C-1’), 27.30 (C-2’), 63.82 (C-3’), 57.87 (OCH3-5), 54.70, 54.46 (OCH3-2, OCH3-4), 21.12
(CH3CO); MS (70 eV) m/z: 284 [M+.]; Anal. Calcd for C13H20N2O5: C, 54.92; H, 7.09; N, 9.85. Found: C,
54.83; H, 7.10; N, 9.88.

6-(3-Hydroxypropyl)-5-methoxymethylpyrimidine-2,4-dione (8) and 5,7,8,9-tetrahydrooxepino[4,3-
d]pyrimidine-2,4-dione (9)
A solution of 6 (294 mg, 1.148 mmol) in concentrated hydrochloric acid (1.38 mL) was heated at 65 °C
for 3 h. The solution was evaporated under reduced pressure. The residue was applied to column
chromatography (CH2Cl2:MeOH = 5:1) to give 8 (9 mg, 4 %, mp 110-112 °C) and 9 (42 mg, 20 %, mp
243-245 °C).
8: 13C NMR δ 164.34 (C-2), 156.41 (C-4), 105.75 (C-5), 151.0 (C-6), 63.43 (CH2-5), 31.38 (C-1’), 26.52
(C-2’), 57.15 (C-3’), 60.03 (OCH3-5); MS (70 eV) m/z: 214 [M+.]; Anal. Calcd for C9H14N2O4: C, 50.46;
H, 6.59; N, 13.08. Found: C, 50.61; H, 6.58; N, 13.11.
13
9: C NMR δ 163.36 (C-2), 156.16 (C-4), 109.02 (C-5), 150.65 (C-6), 63.01 (CH2-5), 30.30 (C-1’),
26.56 (C-2’), 72.58 (C-3’); MS (70 eV) m/z: 182 [M+.].
6-[2-Hydroxymethyl-3-(4-methoxytrityloxy)propyl]thymine (11)
6-[3-Hydroxy-2-(hydroxymethyl)propyl)]thymine (10)13 (13.23 mg, 0.062 mmol), 4-methoxytrityl
chloride (46.3 mg, 0.15 mmol), DMAP (0.76 mg, cat. amount, 0.007 mmol) and triethylamine (0.05 mL)
o
were dessolved in dimethylformamide (1 mL). The reaction mixture was heated at 50 C for 2 h, then
diluted with ethyl acetate and washed with water. The combined organic phase was dried (MgSO4),
evaporated and purified by column chromatography (CH2Cl2:MeOH = 20:1) to yield 11 (16.6 mg, 55 %,
mp 180-183 °C); MS (70 eV) m/z: 487 [M+.].
6-Fluoromethyl-4-methylpyrrolido[1,2-c]pyrimidine-1,3-dione (12)
Dimethylaminosulfur trifluoride (DAST) (6 µL, 0.046 mmol) was added into solution of compound (11)
(16.6 mg, 0.034 mmol) in dichloromethane (1.5 mL) under argon atmosphere. The reaction mixture was
then stirred at rt for 1.5 h and the solvent was removed under reduced pressure and the residue was
chromatographed (CH2Cl2:MeOH = 20:1) to give 12 (3.5 mg, 53 %, 160-163 °C); MS (70 eV) m/z: 198
[M+.]; Anal. Calcd for C9H11N2O2F: C, 54.54; H, 5.59; N, 14.13. Found: C, 54.67; H, 5.58; N, 14.18.
6-[2-Hydroxy-3-(4-methoxytrityloxy)propyl]thymine (14)
Compound (13)4 (160 mg, 0.8 mmol), 4-methoxytrityl chloride (494 mg, 1.6 mmol), DMAP (12 mg, cat.
amount), triethylamine (0.72 mL) were treated according to the procedure that is analogous to that for the
preparation of 11. Purification of crude product by column chromatography (CH2Cl2:MeOH = 12:1) gave
14 (160 mg, 43 %, 195-198 °C); MS (70 eV) m/z: 472 [M+.].
6-Fluoro-4-methylpyrrolido[1,2-c]pyrimidine-1,3-dione (15)

Compound (14) (80 mg, 0.169 mmol) was dissolved in dry dichloromethane (7 mL). DAST (31.2 µL,
0.236 mmol) was then added with stirring at rt under argon atmosphere. After 1 h the reaction mixture
was poured into saturated sodium hydrogen carbonate solution and extracted with dichloromethane. The
organic layer was concentrated and purified by column chromatography (CH2Cl2:MeOH = 15:1) to afford
15 (13.6 mg, 44 %, 170-172 °C); MS (70 eV) m/z: 184 [M+.]; Anal. Calcd for C8H9N2O2F: C, 52.17; H,
4.93; N, 15.21. Found: C, 52.03; H, 4.94; N, 15.24.
X-Ray crystal structure determination
Single crystal of the compound (9) suitable for X-Ray single crystal analysis was obtained at room
temperature by partial evaporation from ethanol solution (96 %). Crystal data, data collection and
refinement are summarized in Table 2.
Table 2. Crystal data and summary of data collection and refinement for 9.
Formula
C8H10N2O3
182.18
Formula weight
Temperature [K]
Crystal size [mm]
Crystal colour
Crystal system
Space group
a [Å]
295(2)
0.30x0.40x0.58
colourless
monoclinic
P 21/c
4.869(1)
14.013(2)
12.115(2)
92.68(2)
825.6(3)
4
1.466
0.114
384
b [Å]
c [Å]
β [o]
V [Å3]
Z
D
calc. [gcm-3]
µ [mm-1]
F(000)
scan-mode
ω and φ
4.45 to 28.99
-6 ≤ h ≤ 6
θ range for data collection [°]
Index ranges
-19 ≤ k ≤ 19
-16 ≤ l ≤ 16
25930 / 2182
1792 / 0.0773
2182 / 0 / 158
0.1095; 0.0544
1.172
Collected / Independent reflections
Reflections [I ≥2σ(I)] / Rint.
Data / restrains / parameters
Weighting parameters a;ba
Goodness-of-fit on F2
R [I ≥2σ(I)] / R [all data]
0.0581 / 0.0692

wR [I ≥2σ(I)] / Rw [all data]
0.1710 / 0.1825
0.345 / -0.222
Max. / min. electron density [eÅ-3]
2
2
aw = 1/[σ2(Fo ) + (aP)2+ bP], where P = (Fo + 2Fc2)/3
The intensities were collected at 295(2) K on a Oxford Diffraction Xcalibur2 diffractometer with
graphite-monochromated MoKα radiation (λ = 0.71073 Å). The data collection and reduction were carried
out with the CrysAlis programs.15 The intensities were corrected for Lorentz and polarization effects. The
crystal structure was solved by direct methods. All non-hydrogen atoms were refined anisotropically by
full-matrix least-squares calculations based on F2. All hydrogen atoms were found in a difference Fourier
map and their coordinates and isotropic thermal parameters have been refined freely. Programes used for
structure solution, refinement and analysis include SHELXS97,16 SHELXL9717 and PARST96.18 The
molecular and crystal structure drawings were prepared by PLATON program.19
Supplementary Material
CCDC 244691 contains the supplementary crystallographic data for this paper. These data can be
obtained
free
of
charge
via
www.ccdc.cam.ac.uk/data_request/cif,
by
emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
ACKNOWLEDGEMENTS
Support for this study was provided by the Ministry of Science of the Republic of Croatia (Projects
0125003 and 0098093).
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