Catalyst-free decarboxylation of 4-hydroxycinnamic acids: efficient synthesis of 4-vinylphenols

We report herein an efficient protocol for the synthesis of 4-vinylphenols by a catalyst-free decarboxylation of trans-4-hydroxycinnamic acids. A variety of 4-vinylphenols has been synthesized in moderate to excellent yields. This protocol also features no polymerization.


Results and discussion
Our initial studies were carried out with readily available 4-hydroxycinnamic acid 1a as a test substrate. 1a in DMF was stirred at 200°C for 60 min under an air atmosphere to give the desired product 2a in 15% yield anti-oxidant/cancer/mutagenic anti-fungal phenylalanine hydrolase inhibitor  Under the optimized conditions, the scope of this decarboxylation was then examined by varying 4-hydroxycinnamic acids 1 (table 2). It is apparent from table 2 that 4-vinylphenols bearing electrondonating/withdrawing groups were prepared in excellent yields (86-96%) and no polymers were detected under the given conditions. Specifically, we investigated the decarboxylation of some natural products such as p-coumaric acid (1a), caffeic acid (1b), ferulic acid (1c) and sinapinic acid (1d), achieving corresponding 4-vinylphenols in excellent yields (2a-2d). Meanwhile, employing methyl-or ethoxy-substituted 4-hydroxycinnamic acids (1e-1g) also afforded the products in high yields (2e-2g). However, electron-withdrawing group (NO 2 , F, Cl or Br) gave lower yields (2 h-2l). Moreover, 4-hydroxycinnamic acids containing methyl on the double bond (1p and 1q) were also compatible with the current conditions, providing the corresponding products 2p and 2q in moderate yields (68% and 63%). The products 2p and 2q exist in the E forms, based on their NMR spectra and in accordance with literature report [35]. Next, we tested several cinnamic acids without 4-hydroxyl substituent under the optimized reaction conditions. Unfortunately, no corresponding vinylbenzenes were detected (scheme 2).
In addition, we found that the polymerization product 2aa was isolated in 48% yield when the reaction time and temperature were increased (table 3, 2aa). Subsequently, we tested another two substrates bearing electron-donating/withdrawing group (table 3, 1f and 1l). Moderate yields were obtained. Obviously, for electron-withdrawing group (Br) substituted substrate, related polymer was got in higher yield (table 3, 2ff versus 2ll).
Plausible mechanisms for the decarboxylation and polymerization of 4-hydroxycinnamic acids are depicted in scheme 3. Species 3 is formed under elevated reaction temperature. Finally, hydrogen

Conclusion
In summary, we have developed an efficient method for the preparation of 4-vinylphenols via a catalystfree decarboxylation of 4-hydroxycinnamic acids. This method features good functional group tolerance and no polymerization. However, corresponding polymers were obtained in moderate yields when under harsher reaction conditions.

Experimental section 4.1. General information
Unless otherwise noted, all reagents, catalysts and solvents were purchased from commercial suppliers and used without further purification. Column chromatography was performed with silica gel (200-300 mesh). Melting points were determined using a X-4 melting point apparatus with microscope. The IR spectra were recorded with Mattson FTIR spectrometer 5000. Absorption maxima were measured in cm −1 . 1 H and 13