A green synthesis of 2-phenyl/2-styrylchromones under solvent-free conditions using grinding technique

Abstract

An efficient eco-friendly synthesis of flavones and 2-styrylchromones via cyclodehydration of corresponding 1-(2-hydroxyaryl)-3-aryl/styryl-1,3-propanediones is described under solvent-free conditions using grinding technique.

Keywords:

• flavones
• 2-styrylchromones
• cyclodehydration
• grinding technique
• eco-friendly reaction

Introduction

Flavones (2-phenylchromones) and 2-styrylchromones constitute an important class of naturally occurring compounds belonging to flavonoid group 1–4. These compounds have been reported to exhibit a variety of pharmacological properties 5–10 including anticancer 1 and anti HIV 11.

There are a number of methods available for the synthesis of chromone derivatives including the Allan–Robinson synthesis 12 and the oxidative cyclization of 2′-hydroxychalcones/2-hydroxycinnamylideneacetophenones 13. However, the cyclodehydration of 1-(2-hydroxyaryl)-3-aryl/styryl-1,3-propanediones obtained by the Baker–Venkataraman rearrangement of 2-aryloxy/cinammoyloxy acetophenones remains the most practical method for their preparation 14. The cyclodehydration of the ensuing 1,3-propanediones requires heating under strongly acidic conditions using acetic acid 15, hydrochloric acid 16, sulfuric acid 17, and p-toulenesulphonic acid 18. Recently, the cyclodehydration of these 1,3-propanediones has been reported with CuCl₂ in ethanol 19 under microwave irradiation.

Today much emphasis is on the development of synthetic procedures which avoid toxic and hazardous chemicals and solvents 20. In continuation of our work to develop simple and eco-friendly procedures for the synthesis of organic compounds, we wish to report a high yield synthesis of flavones and 2-styrylchromones which involves the grinding of the intermediate 1,3-propanediones with phosphorous pentoxide in a mortar and pestle at room temperature in the absence of any solvent (Scheme 1). The moisture absorbed by the reaction mixture during the grinding seems to be sufficient for the formation of a homogeneous mixture and the product is isolated by diluting the reaction mixture with ice cold water.

short-legendScheme 1. Synthesis of flavone and 2-styrylchromone.

The possibility of the cyclodehydration of 1,3-propanediones occurring by phosphoric acid which could have formed during the grinding by absorption of water by phosphorous pentoxide, was investigated by grinding the 1,3-propanediones with phosphoric acid alone. No reaction was found to have taken place even after grinding for 30 minutes.

The validity of the procedure was checked by preparing differently substituted flavones and 2-styrylchromones. The identity of the compounds (Table 1) was confirmed from their IR, H¹-NMR spectra and melting point comparison with literature value.

Table 1. Physical data of the compounds synthesized.

Compound	R1	R2	R3	Time (min)^a	Melting point (°C)	Literature melting point (°C)	Yield (%)^b
Ia	H	H	H	10	98–100	97 (21)	80
Ib	H	CH3	H	10	121	122 (21)	85
Ic	H	H	OCH3	10	160	157–158 (22)	90
Id	H	CH3	OCH3	10	166–168	170 (23)	95
Ie	OCH3	H	OCH3	10	147	145 (24)	90
If	OCH3	H	H	10	103	103–105 (25)	80
IIa	H	H	H	15	130	131 (26)	75
IIb	H	CH3	H	15	135	137 (27)	80
IIc	H	H	OCH3	15	170	167 (27)	95
IId	H	CH3	OCH3	15	157	160 (27)	85
IIe	OCH3	H	H	15	187	189–190 (28)	90
^aGrinding time.
^bYield after crystallization.

Experimental

All the chemicals were purchased from Aldrich and Fluka. Melting points were determined in open capillary tubes. IR (KBr) spectra were recorded in a Perkin–Elmer spectrum BX series FT-IR spectrophotometer and ¹H NMR on Bruker Avance II 400 MHz instrument using tetramethyl-silane as an internal standard.

General procedure

Synthesis of flavones/2-styrylchromones

The substituted 1-(2-hydroxyphenyl)-3-phenyl/styryl-1,3-propanedione (2.1 mmol) was ground with phosphorous pentoxide (2.1 mmol) by a pestle in a mortar for 10–15 minutes. The completion of the reaction was checked by thin layer chromatography (benzene). The reaction mixture was diluted with ice-cold water and the solid that separated out was filtered at vacuum, washed with water, and recrystallized from methanol to afford flavones/2-styrylchromones.

4′-Methoxyflavone (Table 1, Compound Ic)

IR (KBr) 1646 (C = O); ¹H NMR (CDCl₃) δ 3.90 (s, 3H, OCH₃); 6.75 (s, 1H, H-3); 7.0 (d, J=9.0 Hz, 2H, H-3′, H-5′); 7.25–7.55 (m, 3H, H-6, H-7, H-8); 7.80 (d, J=9.0 Hz, 2H, H-2′, H-6′); 8.20 (d, J=9.0Hz, 1H, H-5).

4′-Methoxy-6-methylflavone (Table 1, Compound Id)

IR (KBr) 1640 (C = O); ¹H NMR (CDCl₃) δ 2.30 (s, 3H, CH₃); 3.75 (s, 3H, OCH₃); 6.60 (s, 1H, H-3); 6.70 (d, J=9.0 Hz, 2H, H-3′, H-5′); 7.30 (s, 2H, H-7, H-8); 7.75 (d, J=9.0 Hz, 2H, H-2′, H-6′); 7.90 (s, 1H, H-5).

6-Methyl-2-styrylchromone (Table 1, Compound IIb)

IR (KBr) 1629 (C = O); ¹H NMR (CDCl₃) δ 2.45 (s, 3H, CH₃); 6.30 (s, 1H, H-3); 6.78 (d, J=16.0 Hz, 1H, H-α); 6.82–7.42 (m, 8H, C₆H₅, H-β, H-7, H-8); 7.90 (s, 1H, H-5).

6-Methyl-2-(4-methoxystyryl)chromone (Table 1, Compound IId)

IR (KBr) 1640 (C = O); ¹H NMR (CDCl₃) δ 2.40 (s, 3H, CH₃); 3.80 (s, 3H, OCH₃); 6.20 (s, 1H, H-3); 6.50 (d, J=16.0 Hz, 1H, H-α); 6.70–7.80 (m, 8H, C₆H₅, H-β, H-7, H-8); 7.90 (s, 1H, H-5).

Conclusion

In conclusion, it can be said that the present method developed for the synthesis of flavones and 2-styrylchromones is simple, highly efficient and eco-friendly, and avoids the use of organic solvent during the reaction and working up of the reaction mixture.

Acknowledgements

The authors are grateful to M.D. University, Rohtak for financial assistance to provide research fellowship to Dinesh Sharma.