Crystal structure of 2-butylamino-3-(4-fluorophenyl) benzofuro[3,2-d] pyrimidin-4(3H)-one

Article abstract of DOI:10.1134/S0022476611030280

The title compound (C₂₀H₁₈FN₃O ₂, Mr = 351.37) is prepared and its crystal structure is determined by single crystal X-ray diffraction. The crystal is tetragonal, the P-42(1)c space group with a = 11.0922(6) A,

Full text of DOI:10.1134/S0022476611030280

Journal of Structural Chemistry. Vol. 52, No. 3, pp. 635-638, 2011
Original Russian Text Copyright © 2011 by Ya.-G. Hu, X.-B. Chen, H.-T. Gao, and M.-W. Ding
CRYSTAL STRUCTURE OF 2-BUTYLAMINO-3-
(4-FLUOROPHENYL) BENZOFURO[3,2-d]PYRIMIDIN-4(3H)-ONE
1
Ya.-G. Hu, X.-B. Chen, H.-T. Gao, and M.-W. Ding
1
1
2
©
UDС 541.6:547.12
The title compound (C H FN O , Mr = 351.37) is prepared and its crystal structure is determined by
20 18 3 2
single crystal X-ray diffraction. The crystal is tetragonal, the P-42(1)c space group with a = 11.0922(6) Å,
3 3
b = 11.0922(6) Å, c = 28.6271(15) Å, V = 3522.2(3) Å , Z = 8, d = 1.325 g/cm , F(000) = 1472,
x
–1
μ = 0.095 mm , MoK radiation (λ = 0.71073), R = 0.0505, wR = 0.1090 for 2433 observed reflections
α
with I > 2σ(I ). The X-ray diffraction analysis reveals that all ring atoms in the benzo[4,5]furo[3,2-
d]pyrimidinone moieties are almost coplanar.
Keywords: crystal structure, benzo[4,5]furo[3,2-d]pyrimidin-4(3H)-one, aza-Wittig reaction.
Derivatives of benzofuropyrimidines are of great importance because of their remarkable biological properties, such
as the interesting analgesic, antihypertensive, antipyretic, antiviral, and anti-inflammatory activities. They are used in
agriculture as pesticides or plant growth regulators as well. The related furo[3,2-d]pyrimidine derivatives were reported as
antitumor, antibacterial and antiprotozoan agents as well as dihydrofolate reductase or thymidyates synthase inhibitors [1, 2].
In the recent years, we have been engaged in the preparation of derivatives of heterocycles via the aza-Wittig reaction [3, 4].
As a continuation of our previous studies on pyrimindine derivatives, the X-ray crystal structure determination of the title
compound has been undertaken in order to better understand the influence of structural modifications upon overall molecular
geometry and conformation and may be used as a new precursor for obtaining bioactive molecules.
Experimental. Synthesis. Melting point was uncorrected. MS was measured on a Finnigan Trace MS spectrometer.
–1
IR was recorded on a PE-983 infrared spectrometer as KBr pellet with absorption in cm . NMR was recorded in CDCl on a
3
Varian Mercury 400 spectrometer and resonance was given in ppm (δ) relative to TMS. Elementary analysis was taken on a
Vario EL III elementary analysis instrument.
Iminophosphorane 1 reacted with p-fluorophenyl isocyanate to give carbodiimides 2, which were allowed to react
with n-Butylamines to provide guanidine intermediates 3. In the presence of catalytic amount of sodium ethoxide, 3 were
converted easily to 2-dialkylamino-3-p-fluorophenyl-benzofuro[3,2-d]pyrimidin-4(3H)-ones 4 in satisfactory yields at room
1
temperature (Scheme 1). HNMR (400 MHz, CDCl ) δ = 0.89 (t, J = 7.2 Hz, 3H, CH ), 1.25-1.54 (m, 4H, 2CH ), 3.43-3.47
3
3
2
–1
(m, 2H, NCH ), 4.14 (s, 1H, NH), 7.29-8.01 (m, 8H, Ar–H); IR (KBr) cm 1704 (C=O), 1533, 1340, 1115; MS
2
+
m/z (%) = 351(78, M ), 334(41), 308(35), 294(100), 185(48), 130(70), 102(82), 95(52); Anal. Calcd for C H FN O
20 18 3 2
(351.4): C, 68.36; H, 5.16; N, 11.96. Found: C, 68.33; H, 5.20; N, 11.89.
Crystal data and structure determination. Suitable crystals were obtained by vapor diffusion of ethanol and
dichloromethane at room temperature. A colorless crystal of the title compound having approximate dimensions of
1
Institute of Medicinal Chemistry, Hubei University of Medicine, Shiyan 442000, China;
2
huyangg111@yahoo.com.cn. Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China
Normal University, Wuhan, 430079, P. R. China. The text was submitted by the authors in English. Zhurnal Strukturnoi
Khimii, Vol. 52, No. 3, pp. 649-652, May-June, 2011. Original article submitted April 11, 2009.
0022-4766/11/5203-0635
635

Scheme 1
TABLE 1. Selected Bond Lengths (Å), Bond Angles and Torsion Angles (deg)
Bond
Dist.
Bond Angle
deg
Torsion Angle
deg
C1–C6
C6–O1
1.386(4)
1.376(3)
1.353(4)
1.391(3)
1.343(4)
1.402(3)
1.455(4)
1.369(4)
1.231(3)
1.352(5)
1.355(3)
1.382(4)
C5–C4–C3
N1–C7–C8
N1–C7–C1
C8–C7–C1
121.4(3)
124.7(2)
129.2(2)
106.0(2)
109.9(2)
120.3(3)
123.0(2)
116.6(2)
113.5(2)
118.9(2)
118.5(3)
104.1(2)
C7–C1–C2–C3
N1–C7–C8–C9
178.4(3)
3.3 (4)
C7–N1
O1–C8–C9–O2
N2–C15–C20–C19
N3–C10–N1–C7
N2–C10–N1–C7
C8–C7–N1–C10
N1–C10–N2–C9
O2–C9–N2–C10
O2–C9–N2–C15
N1–C10–N3–C11
C12–C11–N3–C10
−2.0(5)
−177.7(3)
177.5(2)
−2.2(4)
0.5(4)
C8–O1
C10–N3
C10–N2
C11–N3
C15–C16
C9–O2
C8–C9–N2
N1–C10–N3
N1–C10–N2
N3–C10–N2
N3–C11–C12
C20–C15–N2
C17–C18–F1
C6–O1–C8
0.2(4)
−177.4(2)
4.1(4)
C18–C19
C18–F1
C19–C20
0.3(4)
76.8(3)
0.36×0.26×0.24 mm was mounted on a glass fiber in a random orientation at 295(2) K. The determination of unit cell and the
data collection were performed with MoK radiation (λ = 0.71073 Å) on a BRUKER SMART APEX-CCD diffractometer
α
with a ψ–ω scan mode. A total of 24418 reflections were collected in the range of 2.32 < θ < 21.6° at room temperature, and
2433 were independent (R = 0.0584), of which 2433 observed reflections with I > 2σ(I) were used in the structure
int
determination and refinements. The structure was solved by direct methods with SHELXS-97 program [5] and expanded by
Fourier technique. The non-hydrogen atoms were refined anisotropically, and the hydrogen atoms were determined with
theoretical calculation.
A
full-matrix least-squares refinement gave the final R = 0.0505, wR = 0.1090
2
(w = 1/[s (F ) + (0.0569P) + 0.3461P], where P = (F + 2F )/3), S = 1.080, (Δρ) = 0.184 e/ Å and (Δρ)
2
2
2
2
3
=
max
min
0
0
c
3
–0.145 e/ Å . All calculations were performed on a PC with SHELXS-97 program.
Results and discussion. We describe herein the structure of the title compound 4, prepared using an
iminophosphorane with p-F-phenyl isocyanate by a subsequent reaction with n-butylamine in the presence of catalytic
amount of sodium ethoxide.
636

Fig. 1. Molecular structure of the title compound.
Fig. 2. Packing diagram in a unit cell, hydrogen bonds are
shown as dashed lines.
Theoretically, the cyclization of guanidine intermediate 3 may produce two isomers, 4 and 5 respectively. Here,
however, we just got one of the isomers which have been identified as 4 by X-ray crystallographic analyses. The formation of
4 can be rationalized as the guanidine intermediate 3 cyclized across the arylamino group rather than the alkylamino one.
–
+
This is probably due to the preferential generation of –N–Ar from more acidic –NHAr under the catalysis of EtO Na .
The selected bond lengths and bond angles along with torsion angles are given in Table 1. Fig. 1 shows the
molecular structure of the title compound, and the packing diagram in a unit cell is shown in Fig. 2.
In the molecule, the bond lengths and angles present no unusual features. All ring atoms in the benzofuro[3,2-
d]pyrimidinone system are essentially coplanar, with maximum deviations being –0.019(1) Å and 0.022(1) Å for C5 and C2,
respectively; the C15–C20 phenyl ring is twisted with respect to it, with a dihedral angle of 87.35(3)°. Intermolecular C---
H…O and N---H…O hydrogen bonds link the molecules, helping to stabilize the crystal structure. The related bond lengths
and angles are listed in Table 2. Further stability the crystal structure is provided by offset π–π stacking interacttions
involving the fused benzofuro[3,2-d]pyrimidin system moieties. The interplanar distances are ca 3.4 Å and 3.7 Å, with
distances between adjacent ring centroids of 3.8(1)-3.9(1) Å (symmetry code relating the adjacent rings: –x, 1–y, z) (Fig. 2).
637

TABLE 2. Hydrogen-Bonding Geometry (Å, deg)
D–H…A
D–H
H…A
D…A
D–H…A
i
N3–H3A…O2
0.85
0.93
0.93
2.43
2.40
2.43
3.182(3)
3.227(3)
3.356(3)
149
148
173
ii
C17–H17…O1
iii
C20–H20…O2
Symmetry codes: i = x–1/2, –y+1/2, –z+1/2; ii = –x+1/2, y–1/2, –z+1/2; iii = –x, –y+1, z.
The structure has been deposited with the Cambridge Crystallographic Data Centre as supplementary publication
No. CCDC 671114. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ.
We gratefully acknowledge financial support of this work by the Key Science Research Project of Hubei Provincial
Department of Education (No. D200724001) and the Science Research Project of Yunyang Medical College
(No. 2006QDJ16, No. 2008CXG01).
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4. Y. G. Hu., M. G. Liu, and M. W. Ding, Helvetica Chimica Acta, 91, 862-872 (2008).
5. G. M. Sheldrick, SHELXL97, Program for the Refinement of Crystal Structure, Univ. Göttingen, Germany (1997).
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