2-Cyano-6-(trifluoromethyl)-4H-pyran-4-one: A novel versatile CF3-containing building block

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Abstract

A highly electrophilic pyrone, 2-cyano-6-(trifluoromethyl)-4H-pyran-4-one, was synthesized. The reactions of this cyanopyrone with N-nucleophiles can proceed with or without substitution of the cyano group to give a wide range of novel trifluoromethylated compounds. An oxindole derivative was synthesized from a phenylhydrazide using unusual (acidic) conditions.

Highlights

► 2-Cyano-6-(trifluoromethyl)-4H-pyran-4-one was synthesized. ► Various trifluoromethylated compounds were prepared on the base of 2-cyano-6-(trifluoromethyl)-4H-pyran-4-one. ► An oxindole derivative was synthesized from a phenylhydrazide using unusual (acidic) conditions.

Introduction

Trifluoromethylated and other fluoroalkylated pyrones [1] are still poorly investigated compounds. The pyrone ring activated by the trifluoromethyl group easily reacts with some nucleophilic reagents, resulting in CF3-bearing heterocycles [1a,c–h,j,m,n]. However, the scope of nucleophiles, which are known to give preparatively useful results in the reactions with CF3-pyrones, is currently very limited.

2-Cyano-4-pyrones described in the literature [2] can be prepared from the corresponding 4-pyrone-2-carboxamides [2a–d], -carbaldehyde oximes [2e], -carbaldehyde dimethylhydrazones [2f], and from kojic acid derivatives [2g–i]. Chemical properties of 2-cyanopyrones practically were not investigated. It is known that azide anion reacts with 6- [2a–c] and 5-aryl-substituted [2c] 2-cyano-4-pyrones on the cyano group without affecting the pyrone ring to produce 2-tetrazolyl-4-pyrones. Alcoholysis of 2-cyano-5-methoxy-4-pyrone also proceeds at the cyano group to give the corresponding esters [2g]. Reactions of the 2-cyano-4-pyrones with other nucleophiles are unknown so far.

In this paper, we report the synthesis and some properties of 2-cyano-6-(trifluoromethyl)-4-pyrone, the first representative of trifluoromethylated cyano-4-pyrones.

Section snippets

Results and discussion

We have shown that dehydration of pyronecarboxamide 1 [1g] with trifluoroacetic anhydride in the presence of pyridine [2a] leads to the formation of 2-cyano-6-(trifluoromethyl)-4-pyrone 2 (through intermediate A) in 61% yield (Scheme 1). It was found that pyrone 2 due to the activation of the conjugated system by two electron-withdrawing groups (CF3 and CN) is a highly electrophilic substrate, which is able to react with different nucleophiles with or without affecting the pyrone ring.

These

Conclusion

Thus, we have synthesized the first representative of trifluoromethylated cyano-4-pyrones, 2-cyano-6-(trifluoromethyl)-4-pyrone, shown its high reactivity towards N-nucleophiles and revealed its rich chemistry. It was found that this highly electrophilic pyrone can be used as a novel CF3-containing building block for the regioselective syntheses of various trifluoromethylated heterocycles. These results will be very useful for development of chemistry of other functionalized CF3(RF)-bearing

General

1H, 19F and 13C NMR spectra were recorded on Bruker AVANCE DRX-400 spectrometer. Chemical shifts for 1H NMR spectra are reported in parts per million (ppm) downfield from TMS. 19F NMR spectra were externally referenced against C6F6 (δ = −163 relative to CFCl3). Coupling constants (J) are given in hertz (Hz). Infrared spectra (IR) were recorded on Nicolet 6700 spectrometer, equipped with attenuated total reflection accessory (ATR), absorbance frequencies are given at maximum of intensity in cm−1.

2-Cyano-6-(trifluoromethyl)-4H-pyran-4-one (2)

Acknowledgments

The authors thank Ural Federal University and the Deutsche Forschungsgemeinschaft for financial support (grant No. RO 362/45-1).

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