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Journal of Chemistry
Volume 2015 (2015), Article ID 268306, 5 pages
Research Article

Synthesis and Crystal Structure of N-Dichloroacetyl-3,4-dihydro-3-methyl-6-chloro-2H-1,4-benzoxazine

College of Science, Northeast Agricultural University, Harbin, Heilongjiang 150030, China

Received 5 June 2015; Accepted 21 July 2015

Academic Editor: Bartolo Gabriele

Copyright © 2015 Shuang Gao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


A new compound, N-dichloroacetyl-3,4-dihydro-3-methyl-6-chloro-2H-1,4-benzoxazine, was synthesized and characterized. The crystal structure of the title compound (C11H10Cl3NO2, ) has been determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group , with , ,  Å, , , ,  Å3, ,  Mg/cm3,  Å, ,  mm−1, , and for 2217 reflections with .

1. Introduction

Heterocyclic compounds are used, for instance, as antifungal, herbicide, and growth accelerator for plants; the biological properties of heterocycles generally make them play a vital role in human life [1, 2]. In view of the significant biological properties of 1,4-benzoxazine and its derivatives, they usually exhibit safener activity on some crops [3]. In particular, N-dichloroacetyl-3,4-dihydro-3-methyl-2H-1,4-benzoxazine known as herbicide safeners can effectively protect maize against the injury of chloroacetanilides and thiolcarbamates herbicides [4].

Due to the importance of 1,4-benzoxazine and its derivatives, several synthetic methods have been reported over the past few decades. Most of the reported methods were about the synthesis of specific benzoxazines by O-alkylation, cyclization, and reduction with catalyst to give the target compounds [5, 6]. But most of these methods employ harsh reaction conditions, expensive catalysts, or poor yields. As part of our efforts to develop an efficient and synthetic procedure for bioactive molecules [7, 8], here we described the synthesis and crystal structure of N-dichloroacetyl-3,4-dihydro-3-methyl-6-chloro-2H-1,4-benzoxazine, which provided useful molecular information in explaining the detoxified mechanism of structure and activity.

2. Materials and Methods

2.1. Instruments

All reagents were of analytical grade. The infrared (IR) spectra were recorded in KBr on a KJ-IN-27G infrared spectrophotometer. Melting points were determined on Beijing Taike melting point apparatus (X-4) and uncorrected. The 1H-NMR and 13C-NMR spectra were recorded on Bruker AVANCE 300 MHz, with CDCl3 as the solvent and TMS as the internal standard. MS was recorded on a Waters Xevo TQ mass spectrometer. Elemental analysis was taken on a FLASH EA1112 Elemental Analysis Instrument. The X-ray data were collected on a Bruker AXS II CCD area-detector diffractometer using graphite-monochromated Mo Ka radiation ( Å) at 293(2) K.

2.2. Synthesis

The N-dichloroacetyl-3,4-dihydro-3-methyl-6-chloro-2H-1,4-benzoxazine(3) was prepared; see Scheme 1.

Scheme 1: Procedure of preparing the title compound.

The solution of compound 1 (50 nmol), in mixture of toluene (200 mL) and isopropanol (100 mL), was stirred under hydrogen atmosphere (1.5 Mpa) at 55–60°C for 10 h with Pt/C (2 g) as catalyst. Then the resulting mixture was filtered, separated, and dried over anhydrous magnesium sulfate, and the volatiles were removed under vacuum. The crude product was purified by column chromatography using silica gel, eluting with EtOAc : light petroleum (1 : 4 V/V) with the benzoxazine 2 being collected in 87% yield, white solid, m.p. 80-81°C, IR (KBr, cm−1): ν 3365 (N-H), 2975–2871 (C-H), 1596–1442 (C=C). 1H-NMR (CDCl3, 300 MHz): δ 6.56–6.72 (m, 3H, Ar-H), 4.16–4.21 (m, 1H, N-H), 3.72–3.78 (m, 2H, O-CH2), 3.51–3.57 (m, 1H, N-CH), 1.18–1.21 (m, 3H, CH3); 13C-NMR (CDCl3, 75 MHz): δ 142.17, 134.46, 125.95, 118.18, 117.35, 114.69, 70.56, 44.98, 17.72. Anal. Calcd for C9H10ClNO: C 59.00, H 5.51, N 7.65. Found: C 59.06, H 5.46, N 7.62.

Dichloroacetyl chloride (17.6 nmol) was added slowly in the mixture containing compound 2 (14 nmol), Na2CO3 (15.2 nmol), and benzene (25 mL). The system was stirred at room temperature for 2 h. Then the mixture was rinsed, and the organic phase was dried over anhydrous magnesium sulfate. Benzene was removed under vacuum. The crude product 3 was obtained and recrystallized from ethanol and light petroleum. Yield: 80%, white solid. m.p. 136-137°C. IR (KBr, cm−1): ν 3029–2893 (C-H), 1675 (C=O), 1600–1415 (C=C). 1H-NMR (CDCl3, 300 MHz): δ 7.16–7.90 (m, 3H, Ar-H), 6.99 (s, 1H, Cl2CH), 4.62 (m, 1H, N-CH), 4.20–4.32 (m, 2H, O-CH2), 1.17–1.19 (m, 3H, CH3); 13C-NMR (CDCl3, 75 MHz): δ 162.21, 145.21, 127.43, 125.51, 124.43, 122.94, 118.42, 69.74, 66.20, 47.74, 15.31. Anal. Calcd for C11H10Cl3NO2: C 45.05, H 3.44, N 4.78. Found: C 45.12, H 3.38, N 4.71. ESI-MS m/z: 293 [M−H+].

2.3. Crystal Structure Determination

The crystal with dimensions of 0.33 mm × 0.30 mm × 0.22 mm was mounted on a Bruker AXS II CCD area-detector diffractometer equipped with a graphite-monochromator Mo Ka radiation ( Å) by using an ω scan mode at 293(2) K. The total of 11955 reflections was collected in the range of , of which 2840 were independent () and 2217 were observed with .

The structure was solved by direct methods using the SHELXS-97 program and refined by full-matrix least-squares methods on using SHELXL-97 crystallographic software package [9]. The nonhydrogen atoms were refined anisotropically. All hydrogen atoms were located in the geometrically calculated positions and refined isotropically and fixed isotropic thermal parameters. The final full-matrix least-squares refinement gave , , , where , , , , and  eÅ−3. Crystallographic data for the structural analysis of title compound has been deposited with the Cambridge Crystallographic Data Centre (CCDC 1007753). The details of the crystal data, intensity data collection, and structure refinements are summarized in Table 1.

Table 1: Crystal and structure refinement for the title compound.

3. Results and Discussion

3.1. Synthesis and Structure Identification

The synthesis of compound 3 was carried out in two separate steps. Compound 2 was prepared by reduction and cyclization at 55–60°C with the pressures of 1.5 MPa, and Pt/C was used as catalyst. Isopropanol was used as cosolvent and dehydrating agent. Isopropanol increased the solubility of the reactants in toluene. And it made the system homogeneous. A homogeneous phase reaction system was more conductive to the reaction.

Low temperature should be employed because of N-acylation reaction being by exothermic. For the steric hindrance effect of 3-methyl made the N-acylation go smoothly at room temperature instead of low temperature.

In the infrared spectrum, a characteristic carbonyl band at around 1675 cm−1 was assigned to the presence of C=O. However, for the steric hindrance effect of 3-methyl, the N-acylation went smoothly at room temperature instead of low temperature. The three hydrogen atoms of oxazine signals were observed at δ 4.22–4.92 ppm. In the 13C NMR spectra, the signals observed at δ 162.21 ppm were for the carbon of C=O, at δ 66.20 ppm for the carbon of –CHCl2, and at δ 47.74 and 69.74 ppm for the two carbons of the oxazine ring.

3.2. Crystal Structure

The structure of title compound is confirmed by X-ray crystallographic analysis. Selected bond lengths and angles are given in Table 2. The atomic coordinates and equivalent isotropic displacement parameters for the non-H atoms in the title compound are given in Table 3. The molecular structure and the packing view are shown in Figures 1 and 2, respectively.

Table 2: Selected bond lengths () and angles (°) for the title compound.
Table 3: Atomic coordinates (×104) and equivalent isotropic displacement parameter (×103) for nonhydrogen atoms.
Figure 1: Molecular structure for title compound at 30% probability level.
Figure 2: Packing view of the title compound.

According to the data from X-ray analysis of the structure, the bond lengths of C8-N1 and C7-O1 conformed to the value for normal single bond. The C10-O2 (1.212 Å) was similar for C=O double bond (1.19–1.23 Å) found in 1,4-benzoxazine ring. The title compound crystallized in the monoclinic, P21/c space group. The two six-member rings were almost coplanar with a dihedral angle of 7.703 (63)°. The oxazine ring was in a half-chair conformation. However, compared with the normal aliphatic bond value, the bond lengths of C10-N1, C6-O1, and C5-N1 were shorter than typical lengths because of the strong p-π-p-π conjugation between O1, benzene ring [C1, C3, C4, C5, C6, and C2], N1, and C10-O2 [C=O] (Figure 1 and Table 2). The molecular packing in the unit cell showed that no significant π-π stacking was found in the title compound. The title compound had an extensive network of hydrogen bonding. The crystal structure was stabilized by the combination of C-H⋯O and C-H⋯Cl intermolecular interactions (Figure 2 and Table 4).

Table 4: Hydrogen-bond distance (, °) of the title compound.

4. Conclusion

Good quality single crystals of N-dichloroacetyl-3,4-dihydro-3-methyl-6-chloro-2H-1,4-benzoxazine were grown by slow evaporation technique at room temperature. The molecular structure and crystal packing are stabilized by C-H⋯Cl and C-H⋯O intermolecular interactions with the generation of an infinite network.

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.


This work was supported by the National Nature Science Foundation of China (no. 31101473), the project funded by China Postdoctoral Science Foundation (2014M551208), and the Science and Technology Research Project of Heilongjiang Education Department (12531027).


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