Synthesis and crystal structure of 4-dichloroacetyl-3-phenyl-3,4-dihyro-2H- 1,4-benzoxazine

Article abstract of DOI:10.14233/ajchem.2014.15959A

A new compound 4-dichloroacetyl-3-phenyl-3,4-dihyro-2H-1,4-benzoxazine with m.f. C₁₆H₁₃NO₂Cl₂ was synthesized and characterized. The crystal structure of the compound has been determined by single-crystal X-ray

Full text of DOI:10.14233/ajchem.2014.15959A

Asian Journal of Chemistry; Vol. 26, No. 10 (2014), 2913-2915
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.15959A
Synthesis and Crystal Structure of 4-Dichloroacetyl-3-phenyl-3,4-dihyro-2H-1,4-benzoxazine
*
YING FU, ZHAO-ZHENG XU and FEI YE
College of Science, Northeast Agricultural University, Harbin 150030, HeilongJiang Province, P.R. China
*Corresponding author: Fax: +86 451 55191844; Tel: +86 451 55191854; E-mail: yefei@neau.edu.cn
Received: 26 June 2013;
Accepted: 4 September 2013;
Published online: 10 May 2014;
AJC-15147
A new compound 4-dichloroacetyl-3-phenyl-3,4-dihyro-2H-1,4-benzoxazine with m.f. C16H13NO2Cl2 was synthesized and characterized.
The crystal structure of the compound has been determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group
P21/c with a = 15.105(3), b = 6.2685(13), c = 16.084(3) Å, α = 90°, β = 103.79(3)°, γ = 90°, V = 1479.1(5)Å3, Z = 4, F(000) = 664, Dc =
1.447 g/cm3, µ = 0.442 mm-1, the final R1 = 0.0507 and wR2 = 0.1435 for 2417 observed reflections with I > 2σ(I). A total of 13533
reflections were collected, of which 3362 were independent (Rint = 0.0307). Benzoxazine ring and the benzene plane were almost
perpendicular with the dihedral angle of 91.7º with each other.
Keywords: Benzoxazine, Synthesis, X-ray crystallography.
recorded on FTIR-8400S spectrometer. The 1H NMR and 13C
INTRODUCTION
NMR spectrum was recorded on a BrukerAV-300 spectrometer
Benzoxazines are promising agents as a starting material
in DMSO-d6, internal standard TMS. The mass spectrum was
for the synthesis of large structures that have properties such
recorded on a Xevo TQ spectrometer. The elemental analysis
as potassium channel activator or antibacterial agents1,2. They
was performed on FLASH EA1112 elemental analyzer.All the
were also been employed as the synthon of chiral compounds,
reagents were analytical reagent grade.
pharmaceutical intermediates and polymer3-5. N-Dichloroacetyl
Synthesis and characterization: 4-Dichloroacetyl-3-
benzoxazine is a significant safener for chlorinated amide
phenyl-3,4-dihyro-2H-1,4-benzoxazine (3) was prepared
herbicides and thiocarbamate herbicides. These aspects
following Scheme-I.
prompted us to synthesis, characteristics and biological activity
Preparation of compound 2: Pt/C (2g) was added to a
of novel N-dichloroacetyl benzoxazine derivatives with better
solution of 2-(o-nitrophenoxy)-phenylethanone (1) (0.05 mol,
safety and efficacy, we introduced different groups substitution
12.9 g) in toluene (200 mL) and isopropanol (100 mL). The
on the oxazine6,7.As part of our search for bioactive compounds,
reaction mixture was stirred under H2 at 60 °C at 1.5 Mpa for
here we report the synthesis and crystal structure of 4-dichloro-
10 h. Then the mixture was filtered. The toluene was removed
acetyl-3-phenyl-3,4-dihyro-2H-1,4-benzoxazine.
under vacuum. The 3-phenyl-3,4-dihyro-2H-1,4-benzoxazine
(2) was obtained as yellow oil with the yield of 93.3 %. Anal.
calcd. for C14H13NO (%): C, 79.58; H, 6.21; N, 6.63. Found:
C, 79.52; H, 6.28; N, 6.59. IR (KBr, νmax, cm-1): 3363 (NH),
3060 (C-H), 1608, 1427 (C=C). 1H NMR (300 M, DMSO-d6):
EXPERIMENTAL
The melting point was measured on a Beijing Taike point
apparatus (X-4) and uncorrected. The IR of KBr discs were
O
O
O
O
Pt/C, H2
1.5 MPa
Cl2CHCOCl
N
Cl
N
H
Na2CO3,C6H6, r.t.
NO2
O
Cl
3
1
2
Scheme-I: Synthetic route to the title compound

2914 Fu et al.
Asian J. Chem.
TABLE-1
CRYSTAL STRUCTURE AND DATA
REFINEMENT PARAMETERS
3.88-3.94, 4.20-4.24 (2H, m, O-CH2); 4.46-4.48 (1H, t, J =
2.7 Hz, NCH); 6.25 (1H, s, NH); 6.50-6.55 (1H, m, H Ar);
6.69-6.71 (3H, m, H Ar); 7.22-7.46 (5H, m, H Ar); 13C NMR
(75M, DMSO-d6): 53.3, 70.4, 115.4, 116.2, 117.4, 121.7,
127.6, 127.6, 128.1, 128.9, 128.9, 135.4, 140.7, 143.2.
Empirical formula
Formula weight
Crystal system, space group
C16H13Cl2NO2
322.17
Monoclinic, P21/c
Preparation of compound 3: Dichloroacetyl chloride
(17.6 nmol, 2.59 g) was added in a mixture containing 3-phenyl-
3,4-dihydro-2H-1,4-benzoxazine (2) (14 nmol, 2.95 g), K2CO3
(15.2 nmol, 2.08 g) and benzene (25 mL). The reaction mixture
was stirred at room temperature for 2 h. The organic phase
was dried over anhydrous magnesium sulfate and the benzene
was removed under vacuum, the 4-dichloroacetyl-3-phenyl-
3,4-dihyro-2H-1,4-benzoxazine (3) was recrystallized from
ethanol and light petroleum. The yield was 74.2 % (3.34 g);
m.p. 136-138 °C.Anal. calcd. for C16H13NO2Cl2 (%): C, 59.81;
H, 4.08; N, 4.36. Found, %: C, 59.78; H, 4.16; N, 4.32. IR
(KBr, ν,max, cm-1): 3045 (C-H), 1689 (C=O), 1591, 1492 (C=C).
1H NMR (300 M, DMSO-d6): 4.47-4.52, 4.99-5.03 (2H, m,
O-CH2-C); 5.82 (1H, s, N-CH-); 6.79-7.75 (9H, m HAr), 7.24
(1H, s, Cl2CH); 13C NMR (75 M, DMSO-d6): 66.8, 68.2, 117.4,
121.2, 124.0, 124.9, 127.0, 127.9, 127.9, 128.9, 128.9, 129.2,
129.2, 136.4, 147.1, 163.1. Mass spectrum: [M-1]+ = 321.
Crystal data and structure determination: The block-
shaped single crystal of the title compound was grown by slow
cooling from a hot saturated solution in ethanol. The crystal
with dimensions of 0.62 × 0.23 × 0.20 mm was mounted on a
BrukerAXSII CCD area-detector diffractometer using graphite
monochromated M Ka radiation (λ = 0.71073 Å) at 293 (2) K.
A total of 13533 reflections were collected in the range of
3.48 < θ < 27.48°, of which 3362 were independent and 2417
were observed with I > 2σ(I). The structure was solved by
direct methods using SHELXS-97 program8 and the semi-
empirical from equivalents absorption corrections were applied
to all intensity data. All nonhydrogen atoms were refined an
isotropically by the full-matrix least square method on F2 using
SHELXL-979. The hydrogen atoms were determined with
theoretical calculations and refined isotropically. A summary
of the key crystallographic information is given in Table-1.
The final full-matrix least squares refinement gave R = 0.0507
and wR = 0.1435 (w = 1/[σ2(Fo2) + (0.0912P)2 + 0.1416 P])
a (Å)
b (Å)
c (Å)
α (°)
15.105(3)
6.2685(13)
16.084(3)
90
103.79(3)
90
1479.1(5)
4
β (°)
γ (°)
V (Å3)
Z
Dc (g/cm3)
1.447
0.442
664
µ (mm–1)
F (000)
Crystal size (mm)
Color/shape
0.62 × 0.23 × 0.20
Colorless/block
293(2)
3.48 - 27.48
13533
3362
3362 / 0 / 190
1.122
Temp (K)
Theta range for collection
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2σ(I)]
R indices (all data)
Largest difference peak/hole (eÅ-3)
R1 = 0.0507, wR2 = 0.1435
R1 = 0.0691, wR2 = 0.1604
0.598 and -0.445
single sharp peak at 7.24 ppm for the Cl2CH of the title comp-
ound. With regard to the mass spectra, the title compound show
M-1 signals. The measured data of elemental analytical results
is in accord with the theoretical values.
Crystal structure: The molecular structure with atom-
numbering scheme and the packing diagram of the title comp-
ound are shown in Figs. 1 and 2, respectively. The selected
bond lengths and bond angles are shown in Table 2.
According to X-ray analysis of the structure, the bond
lengths of C(8)-N(1), C(1)-N(1) and C(7)-O(1) were close to
the typical C-N and C-O bond length. The C(15)-O(2) (1.206
Å) indicated a double bond C=O (1.19-1.23 Å). However,
compared with the normal aliphatic bond value, bond length
C(15)-N(1) (1.359 Å) and C(6)-O(1) (1.370 Å) were shorter
than normal.
where P = (Fo2 + 2Fc2)/3, S = 1.122, (∆/σmax = 0.000, ∆ρmax
=
0.598 and ∆ρmin = -0.445 eÅ-1. CIF file containing complete
information on the studied structure was deposited with
CCDC, deposition number 928571 and is freely available upon
request from the following web site: www.ccdc.cam.ac.uk/
data_request/cif.
RESULTS AND DISCUSSION
The structures of compound 2 and the title compound 3
were confirmed by elemental analysis, IR, 1H NMR, 13C NMR,
MS and X-ray diffraction analysis. The IR spectrum of the
title compound shows absorption band at 1689 cm-1 originated
from the stretching vibration of C=O stretching vibration. The
proton magnetic resonance spectra of compounds 2 and 3 have
1
been recorded in DMSO-d6. In the H NMR spectrum the
singlet at 3.8-5.8 ppm corresponds to the O-CH2-CH-N proton
indicating the formation of benzoxazine. The signals at 6.25
ppm range are N-H of compound 2. And it is replaced by a
Fig. 1. Molecular structure of 4-dichloroacetyl-3-phenyl-3,4-dihyro-2H-
1,4- benzoxazine, showing displacement ellipsoids drawn at the 30
% probability level

Vol. 26, No. 10 (2014)
Synthesis and Crystal Structure of 4-Dichloroacetyl-3-phenyl-3,4-dihyro-2H-1,4-benzoxazine 2915
It was obvious that there was pπ-pπ large conjunctive effect
between O(1), benzene ring [C(1), C(3), C(4), C(5), C(6) and
C(2)], N(1), C(15)-O(2) [C=O], which resulting in shorter bond
length than the typical C-N bond length and C-O bond length.
The title compound contained two benzene rings and an
oxazine ring. The torsion angle of O(1)-C(7)-C(8)-N(1) was
-59.0(2)°, forming 7,8-half-chair conformation. Benzene ring
plate I[C(1), C(3), C(4), C(5), C(6) and C(2)] made a dihedral
angle of 2.6º with oxazine plane II[O(1), C(6), C(1), N(1),
C(8), C(7)]. It means that they were almost coplanar because
of the conjunctive effect. Benzoxazine ring and plan III[C(9),
C(10), C(11), C(12), C(13) and C(14)] were almost perpendi-
cular with the dihedral angle being 91.7º.
Fig. 2. Packing of the title compound
ACKNOWLEDGEMENTS
TABLE-2
SELECTED BOND LENGTHS (Å) AND BOND ANGLES (º)
This work was supported by the National Nature Science
Foundation of China (31101473), the Natural Science Founda-
tion of Heilongjiang Province (B201212), the Science and
Technology Research Project of Heilongjiang Education
Department (12521015) and the Research Science Foundation
in Technology Innovation of Harbin (2012RFQXN015).
Atom
Distance
1.387(3)
1.394(3)
1.430(2)
1.372(3)
1.379(4)
1.383(4)
1.390(3)
1.370(3)
1.433(3)
1.523(3)
1.477(2)
1.518(3)
1.388(3)
1.393(3)
1.382(4)
1.357(5)
1.385(5)
1.388(3)
1.206(2)
1.359(3)
1.542(3)
1.756(2)
1.769(2)
Atom
Angle
C(1)-C(6)
C(1)-C(2)
C(1)-N(1)
C(2)-C(3)
C(3)-C(4)
C(4)-C(5)
C(5)-C(6)
C(6)-O(1)
C(7)-O(1)
C(7)-C(8)
C(8)-N(1)
C(8)-C(9)
C(9)-C(14)
C(9)-C(10)
C(10)-C(11)
C(11)-C(12)
C(12)-C(13)
C(13)-C(14)
C(15)-O(2)
C(15)-N(1)
C(15)-C(16)
C(16)-Cl(1)
C(16)-Cl(2)
C(6)-C(1)-C(2)
C(6)-C(1)-N(1)
C(2)-C(1)-N(1)
O(1)-C(6)-C(1)
O(1)-C(6)-C(5)
C(1)-C(6)-C(5)
O(1)-C(7)-C(8)
N(1)-C(8)-C(9)
N(1)-C(8)-C(7)
C(9)-C(8)-C(7)
C(14)-C(9)-C(10)
C(14)-C(9)-C(8)
C(10)-C(9)-C(8)
O(2)-C(15)-N(1)
O(2)-C(15)-C(16)
N(1)-C(15)-C(16)
C(15)-C(16)-Cl(1)
C(15)-C(16)-Cl(2)
Cl(1)-C(16)-Cl(2)
C(15)-N(1)-C(1)
C(15)-N(1)-C(8)
C(1)-N(1)-C(8)
C(6)-O(1)-C(7)
119.53(18)
118.30(17)
121.86(18)
122.98(18)
117.2(2)
119.8(2)
REFERENCES
112.73(17)
112.41(16)
105.24(17)
115.24(17)
118.6(2)
1. G. Caliendo, E. Perissutti, V. Santagada, F. Fiorino, B. Severino, D.
Cirillo, R. d'Emmanuele diVilla Bianca, L. Lippolis, A. Pinto and R.
Sorrentino, Eur. J. Med. Chem., 39, 815 (2004).
2. V.M. Ismailov, I.A. Mamedov and N.N. Yusubov, Russ. J. Org. Chem.,
40, 284 (2004).
3. T. Matola and I. Jablonkai, Crop Prot., 26, 278 (2007).
4. S. Silva, S. Tardy, S. Routier, F. Suzenet, A. Tatibouët, A.P. Rauter and
P. Rollin, Tetrahedron Lett., 49, 5583 (2008).
5. G.P. Cao, W.J. Chen and X.B. Liu, Polym. Degrad. Stab., 93, 739 (2008).
6. Y. Fu, L.H. Qu, S.S. Zhang, F. Ye, L.X. Zhao, S. Gao and Z.Y. Xing,
Heterocycl. Commun., 18, 143 (2012).
7. Y. Fu, S.S. Zhang and F. Ye, Indian J. Heterocycl. Chem., 20, 405
(2011).
8. G.M. Sheldrick, SHELXS-97, Program for X-Ray Crystal Structure
Solution, University of Göttingen, Göttingen, Germany (1997).
9. G.M. Sheldrick, SHELXS-97, Program for X-Ray Crystal Structure
Refinement, University of Göttingen, Göttingen, Germany (1997).
121.58(19)
119.7(2)
123.31(19)
120.01(18)
116.53(17)
110.06(15)
106.64(14)
110.83(12)
127.04(16)
118.52(16)
113.17(16)
117.11(17)