XU Di DAI Li LI Lan ZHOU Zhi-Ming ZHANG Jun

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Synthesis, Crystal Structure and Analysis of 6-Methoxycarbonylmethyl-7-methyl-6-dibenzopyran①

XU Di DAI Li LI Lan ZHOU Zhi-Ming ZHANG Jun②

(100081)

The compound 6-methoxycarbonylmethyl-7-methyl-6-dibenzopyran has been synthesized by one-pot tandem reaction catalyzed by palladium and norbornene, which was initially structurally characterized by X-ray diffraction. The DSC spectra and chiral HPLC chromatography are reported. Crystal data of the title compound: C17H16O3, orthorhombic system, space group,= 14.507(3),= 9.3993(16),= 19.562(3) ?,= 2667.4(8) ?3,M= 268.30,D= 1.336 g/cm3,= 0.091 mm-1,= 8,(000) = 1136,= 0.0653 and= 0.1447.

dibenzopyran, palladium catalysis, crystal structure, chiral center;

1 INTRODUCTION

Exploring the synthetic methods to construct benzopyran and dibenzopyran derivatives has attracted increasing attention in the field of orga- nometallic chemistry and pharmaceutical scien- ces[1-4]because the derivatives are widely present in natural substances and pharmaceuticals[3-6], belon- ging to an important class of biologically active compounds, such as sonepiprazole and canna- binols[7-9](Fig. 1). Herein, we report the synthesis, crystal structure, DSC data and chiral separation chromatography of the title compound 4 (Scheme 1).

Scheme 1. Synthesis of 6-methoxycarbonylmethyl-7-methyl-6-dibenzopyran

Fig. 1. Bioactive and pharmacologically active molecules containing benzopyran and dibenzopyran moieties

The compound is prepared by palladium- and norbornene-catalyzed cascade reaction[10-12]. Its structure was characterized by IR,1H NMR,13C- NMR, elemental analyses, DSC, chiral HPLC and X-ray diffraction.

2 EXPERIMENTAL

2. 1 Apparatus and materials

All starting materials were commercially available and used without further purification. All reactions were carried out under nitrogen using standard Schlenk techniques. DMF was dried and stored over 4 ? molecular sieves under nitrogen. Gas chromatography analyses were performed with an Agilent Technologies 7820A GC System using a 30 m SE-30 capillary column. Flash column chro- matography was carried out on Merck Kieselgel 60 and TLC on Merck 60F254 plates.1H and13C NMR spectra were recorded in CDCl3on a 400 MHz nuclear magnetic resonance spectrometer operating at 400 and 100 MHz, respectively. Electron impact mass spectra (m/z, relative intensity (%)) were determined with an Agilent Technologies instrument working at 70 eV ionization energy (6890 GC system and 5973 Mass selective detector). Infrared spectra were recorded using a Bruker Alpha spectrophotometer with an ATR-Ge device. Elemen- tal analyses were obtained on an Elementar Vario MICRO CUBE (Germany) elemental analyzer. The melting point was recorded on a differential scanning calorimeter (DSC) at a scan rate of 5oC·min-1in a dynamic nitrogen atmosphere (flow rate = 50 mL·min-1). The enantiomeric separation of the product was performed by chiral HPLC using a Daicel Chiralcel OD-H column with 2-propanol/he- xane as the eluent.

2. 2 Synthesis of compound 4: reaction of 1-iodo-2-methylbenzene with 2-bromo-phenol in the presence of norbornene, Pd(OAc)2and K2CO3in DMF

To a Schlenck-type flask containing Pd(OAc)2(4 mg, 0.018 mmol) and K2CO3(196 mg, 1.428 mmol) was added a DMF solution (8 mL) of 1-iodo-2- methylbenzene 1 (0.446 mmol), 2-bromophenol 2 (77 mg, 0.446 mmol), methyl acrylate 3 (123 mg, 1.428 mmol) and norbornene (34 mg, 0.357 mmol). The reaction mixture was allowed to stir under nitrogen for 24 h at 80 °C. After cooling to room temperature, the mixture was diluted with EtOAc (30 mL), washed with a saturated solution of NaCl (3 × 25 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the resulting residue was purified by flash chroma- tography on silica gel using mixtures of petrol ether-EtOAc as eluent. Yield: 83%. m.p. (petroleum ether): 82～83 ℃. Eluent:hexane-ethyl acetate is 95:5. Anal. Calcd. for C17H16O3: C, 76.10; H, 6.01%. Found: C, 75.97; H, 6.06%. IR (KBr, cm-1):1722, 1567, 1432.1H NMR:7.73 (1H, dd,= 7.7, 1.6 Hz), 7.58 (1H, br d,= 7.8 Hz), 7.29 and 7.24 (2H, t,= 7.7 Hz and td,= 7.7, 1.6 Hz), 7.14 (1H, br d,= 7.6 Hz), 7.05 (1H, td,= 7.6, 1.2 Hz), 6.96 (1H, dd,= 8.0, 1.2 Hz), 5.93 (1H, dd,= 10.7, 2.8 Hz), 3.75 (3H, s, CO2CH3), 2.90 (1H, dd,= 15.2, 10.7 Hz), 2.39 and 2.35 (4H, dd,= 15.2, 2.8 Hz and s);13C NMR:170.74 (CO2CH3), 151.07, 132.93, 131.46, 129.95, 129.65, 128.79, 128.27, 123.17, 122.23, 122.22, 120.26, 118.52, 71.39, 51.87 (CO2CH3), 38.08, 18.19. MS (EI, 70 eV): M+268(8),/195(100), 165(12), 152(8).

2. 3 Crystal structure determination

The colourless single crystal with dimensions of 0.40mm × 0.19mm × 0.11mm was selected for X-ray diffraction analysis. It was obtained by the diffusion of petroleum ether when the compound was dissolved in ethyl acetate for a few days. The diffraction data were collected with a Bruker SMART CCD diffractometer using a graphite-mo- nochromated Moradiation (= 0.71070 ?) at 153(2) K. The structure was solved by direct methods with SHELXS-97 program and refine- ments on2were performed with SHELXL-97 pro- gram by full-matrix least-squares techniques[13, 14]. A total of 22672 reflections (3581 independent ones withint= 0.0411) were collected in the range of 2.78<<29.14o by using anscan mode,of which 3409 were observed with> 2(). The structure was solved by direct methods and refined by full- matrix least-squares calculations for 183 parame- ters. All the calculations were carried out and re- fined with SHELXL-97 program package. All non- hydrogen atoms were refined with anisotropic thermal parameters. H atoms were placed in the calculated positions and refined isotropically using a riding model. The final full-matrix least-squares refinement gave= 0.0653,= 0.1447, (Δ/)max= 0.001,= 1.001, (Δ)max= 0.237 and (Δ)min= –0.211 e/?3.

3 RESULTS AND DISCUSSION

The selected bond lengths and bond angles are presented in Table 1. The molecular structure and crystal packing scheme of compound 4 are shown in Figs. 2 and 3, respectively. Single-crystal X-ray dif- fraction analysis reveals that the title compound is made up of three six-membered sings, which exist in two configurations. In the middle six-membered ring, atoms O(1), C(1), C(12) and C(13) are not in one plane. In the molecule, all bond distances are normal. The C(1)–O(1) bond length is 11.380(2) ? and the O(1)–C(13) bond length is 1.446(2). The C(1)–O(1)–C(13), O(1)–C(1)–C(6), C(1)–C(6)– C(7), C(12)–C(7)–C(6), C(7)–C(12)–C(13) and O(1)–C(13)–C(12) bond angles are 114.41(12)°, 120.48(15)°, 118.10(15)°, 117.92(15)°, 117.53(15)° and 111.07(13)°, respectively. Compared with the molecular structures of compounds 5[15], 6[16], 7[17]and 8[12](Fig. 4), we can infer that the structure of the compound is quite stable.

Table 1. Selected Bond Lengths (?) and Bond Angles (°)

Fig. 2. Molecular structure of 6-methoxy-carbonylmethyl-7-methyl-6-dibenzopyran

Fig. 3. Packing diagram of 6-methoxy-carbonylmethyl-7-methyl-6-dibenzopyran

Fig. 4. Molecular structures of compounds 5, 6, 7 and 8

In the crystal lattice, two molecules with the same configuration are linked through intermolecu- lar interactions C–H···O, C(16)–H(16A)···π (cen- troid of C(1)–C(6)) and C(17)–H(17A)···π (centroid of C(7)–C(12)) interaction[18-20]with the distances of 3.815 and 5.001 ?.

The DCS result shows that 6-methoxycarbonyl- methyl-7-methyl-6-dibenzopyran melts appro- ximately at 83oC. And it is stable at least up to 200oC (Fig. 5).

Fig. 5. DSC (differential scanning calorimeter) spectra of the title compound

As 6-methoxycarbonylmethyl-7-methyl-6-dibenzopyran owns a chiral center at atom C(13), the chromatographic separation of two enantiomers was executed on chiral HPLC. Satisfactory reso- lution was achieved under the following condition: daicel OD-H column:hexane/i-propane = 95:5, detection wavelengths = 215 and 254 nm, flow rate = 1.0 mL/min, 25oC (Fig. 6).

Fig. 6. HPLC spectra of the title compound

4 CONCLUSION

In summary, we have synthesized a useful com- pound 6-methoxycarbonylmethyl-7-methyl-6-di- benzopyran. Its structure was characterized by IR,1H NMR,13C NMR and X-ray crystal analysis and its properties were studied by DSC and chiral chromatography for the first time. Further study can be carried out according to these data.

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① This work was supported by the National Natural Science Foundation of China for financial support (No. KZ200610011006)

. Born in 1958, PhD, lecturer, majoring in anti-high blood pressure medicine and energetic materials. E-mail: zhangjun603@bit.edu.cn

10.14102/j.cnki.0254-5861.2011-0667

4 February 2015; accepted19 June 2015 (CCDC 1024787)