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Synthesis of Novel Phosphorylated Chrysin Derivatives

by 1, 3-Dipolar Cycloaddition Reaction

Shaohua Zhu,1 Yan Zhang,1 Peipei Li,1 Wenzhu Bi,1 Xiaolan Chen,1,* and Yufen Zhao1,2

1 College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450001, China

2 Department of Chemistry, Xiamen University, Xiamen, 361000, China

Email: chenxl@zzu.edu.cn

Supplemental Materials

Synthesis of 1-azido-3-chloropropane

1-bromine-3-chloropropane 6.0 g (40 mmol) was dissolved in 40 mL DMSO, then NaN3 3.0 g

(43 mmol) was added slowly. The reaction mixture was stirred at room temperature for about 2

days, diluted with water (30 mL) and extracted by Et2O (3 × 60 mL). The combined organic

phase were dried over Na2SO4. The solvent was removed in vacuum and the crude product was

obtained as light yellow liquid 4.1 g (90%). The product were directly used in the next step

without further purification.

Synthesis of 7-(3-azidopropoxy)-5-hydroxy-flavone

Chrysin (5.1 g, 20 mmol) were dissolved in DMF (40) mL in a 100 mL 3-neck round bottom

flask equipped with a Teflon coated magnetic stir bar and reflux condenser, then 1-azido-3-

chloropropane (2.4 g, 20 mmol) were added at 60 °C in an oil bath. After being completely

dissolved, potassium carbonate (4.2 g, 35 mmol) and potassium iodide (0.3 g, 2 mmol) were

slowly added into the mixture. After completion of the reaction, as indicated by TLC (thin layer

chromatography), the mixture was extracted by CH2Cl2 (3 × 20 mL). The combined organic layer

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was dried over anhydrous Na2SO4. The solvent was removed in vacuum and the crude product

was purified by column chromatography on silica gel (petroleum ether : ethyl acetate = 10 : 1, v :

v). Compound 1 was obtained as amorphous solid 5.5 g.

General procedure for the synthesis of dialkyl alkynylphosphonates1

Terminal alkynes (6 mmol), dialkyl H-phosphonates (5 mmol), CuSO4·5H2O (20 mmol%) and

Et3N (35 mmol%) were dissolved in DMF (60 mL) in a 250 mL 3-neck round bottom flask at 55

°C. The reaction was tracked by 31P NMR. After completion of the reaction, the mixture was

extracted by CH2Cl2 (3 × 30 mL). The combined organic layer was washed with saturated

ammonium chloride aqueous solution and dried over anhydrous Na2SO4. The solvent was

removed in vacuum and the brown oily crude product was purified by column chromatography

on silica gel (petroleum ether : ethyl acetate = 1 : 1, v : v).

[1] Qu, Z. B; Chen, X. L; Yuan, J. W; Qu, L. B; Li, X; Wang, F. J; Ding, X. L; Zhao, Y. F. Can.

J. Chem. 2012, 90, 747-52.

1D and 2D NMR copies of product 6a and 6b

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Figure S 1. 31P NMR of compound 6a

Figure S 2. 1H NMR of compound 6a

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Figure S 3. 13C NMR of compound 6aFigure S 4. DEPT-135 of compound 6a

Figure S 5. H-H COSY of compound 6a

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Figure S 6. HSQC of compound 6a

Figure S 7. 31P NMR of compound 6b

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Figure S 8. 1H NMR of compound 6b

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Figure S 9. 13C NMR of compound 6b

Figure S 10. DEPT-135 of compound 6b

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Figure S 11. H-H COSY of compound 6b

Figure S 12. HSQC of compound 6b1H NMR, 13C NMR，31P NMR copies of products 1-5 and 7

NN

NP O

OOO

O

OHO

NN

NP O

OOO

O

OHO

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Figure S 13. 1H NMR of compound 1a

Figure S 14. 13C NMR of compound 1a

NN

NP O

OOO

O

OHO

NN

N O

PO

OO

O

OH O

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Figure S 15. 31P NMR of the compound 1a

Figure S 16. 1H NMR of compound 1b

NN

N O

PO

OO

O

OH O

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Figure S 17. 13C NMR of compound 1b

Figure S 18. 31P NMR of the compound 1b

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Figure S 19. 1H NMR of compound 2a

Figure S 20. 13C NMR of compound 2a

Figure S 21. 31P NMR of compound 2a

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Figure S 22. 1H NMR of compound 2b

Figure S 23. 13C NMR of compound 2b

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Figure S 24. 31P NMR of compound 2b

Figure S 25. 1H NMR of compound 3a

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Figure S 26. 13C NMR of compound 3a

Figure S 27. 31P NMR of compound 3a

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Figure S 28. 1H NMR of compound 3b

Figure S 29. 13C NMR of compound 3b

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Figure S 30. 31P NMR of compound 3b

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Figure S 31. 1H NMR of compound 4a

Figure S 32. 13C NMR of compound 4a

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Figure S 33. 31P NMR of compound 4a

Figure S 34. 1H NMR of compound 4b

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Figure S 35. 13C NMR of compound 4b

Figure S 36. 31P NMR of compound 4b

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Figure S 37. 1H NMR of compound 5a

Figure S 38. 13C NMR of compound 5a

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Figure S 39. 31P NMR of compound 5a

Figure S 40. 1H NMR of compound 5b

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Figure S 41. 13C NMR of compound 5b

Figure S 42. 31P NMR of compound 5b

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Figure S 43. 1H NMR of compound 7a

Figure S 44. 13C NMR of compound 7a

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Figure S 45. 31P NMR of compound 7a

Figure S 46. 1H NMR of compound 7b

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Figure S 47. 13C NMR of compound 7bFigure S 48. 31P NMR of compound 7b