The difluoromethylene (CF2) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF2 groups

Yi Wang,Alexandra M Z Slawin,Ricardo Callejo,David O’Hagan

doi:10.3762/bjoc.10.4

Abstract

The syntheses of palmitic acids and a nonadecane are reported with CF2 groups located 1,3 or 1,4 to each other along the aliphatic chain. Specifically 8,8,10,10- and 8,8,11,11-tetrafluorohexadecanoic acids (6b and 6c) are prepared as well as the singly modified analogue 8,8-difluorohexadecanoic acid (6a). Also 8,8,11,11-tetrafluorononadecane (27) is prepared as a pure hydrocarbon containing a 1,4-di-CF2 motif. The modified palmitic acids are characterized by differential scanning calorimetry (DSC) to determine melting points and phase behaviour relative to palmitic acid (62.5 °C). It emerges that 6c, with the CF2 groups placed 1,4- to each other, has a significantly higher melting point (89.9 °C) when compared to the other analogues and palmitic acid itself. It is a crystalline compound and the structure reveals an extended anti-zig-zag chain. Similarly 8,8,11,11-tetrafluorononadecane (27) adopts an extended anti-zig-zag structure. This is rationalized by dipolar relaxation between the two CF2 groups placed 1,4 to each other in the extended anti-zig-zag chain and suggests a design modification for long chain aliphatics which can introduce conformational stability.

Highlights

The selective replacement of hydrogen by fluorine is widely practised in bio-organic and medicinal chemistry [1,2,3,4]
As part of an on-going interest in the behaviour and influence of the CF2 group we have explored the effect of locating two CF2 groups along an extended aliphatic chain
The synthesis of palmitic acid 6a is illustrated in Scheme 1

Summary

Introduction

The selective replacement of hydrogen by fluorine is widely practised in bio-organic and medicinal chemistry [1,2,3,4]. In this study we selected the three palmitic acid analogues 6a–c shown, as targets for synthesis and comparative analysis. As a general strategy palmitic acids 6a–c were prepared by aryl oxidation of long chain pentadecabenzenes [10,11]. The synthesis of palmitic acid 6a is illustrated in Scheme 1.

Results

Conclusion