Slicing open a phenol ring with a simple nitrite reagent allows chemists to create a variety of nitrogen-containing products. The new method adds to the toolbox of skeletal editing strategies that tweak the structures of complex molecules – something that has previously been difficult to do with phenols. The researchers behind the reaction demonstrated its use in making an additive that drastically enhances the mechanical properties of rubber.
Aromatic rings form the backbone of many feedstock and pharmaceutical chemicals, due to their stability and the many ways in which they can be functionalised. In recent years, chemists have developed several new methods to edit the shape and structure of such rings, but it remains challenging due to the low reactivity of aromatic carbon–carbon bonds.
Arene ring opening (ARO) reactions, which use strong oxidants or enzymes to break apart aromatic rings into linear structures, offer a potential solution to this issue. For example, these reactions have previously been used to convert anilines into alkenyl nitriles.
Now, researchers in China have extended these ring opening reactions to work on phenols. To do this, the team use a simple and inexpensive alkyl nitrite reagent, in the presence of base, to add a nitro group on to the carbon next to the phenol group. This molecule then tautomerises to give an oxime and a ketone, breaking the ring’s aromaticity. This allows a nucleophile to react with the ketone, causing the carbon–carbon bond in the ring to break.
Depending on the nucleophile, this reaction forms linear dialkenyl chains with amide, ester or carboxylic acid end groups at one end, and cyano groups at the other. Introducing these linear intermediates could, for example, help chemists convert a flat, rigid aromatic ring into a flexible chain. Equally, further reactions allowed Jiao’s team to reconfigure the linear chains back into five-, six- and seven-membered nitrogen-containing rings.
‘Our main challenge centred on the key nitrosophenol intermediate,’ says Ning Jiao at Peking University in China, who led the work. He explains that the team eventually isolated the compound by altering the reaction conditions so that there were no nucleophiles present. X-ray crystallography then confirmed the nitrosophenol’s structure, before the team reacted the intermediate with a nucleophile to generate the same product as starting with the original phenol.
‘Such strategies for the opening of arenes combine the virtues of the increased reactivity by a dearomatisation with the ability to entirely remodel aromatic rings,’ says Christof Sparr at the University of Basel in Switzerland, who was not involved in the work. He describes the cleavage of phenols used by Jiao and his team as a ‘striking and thought-provoking masterclass of this new realm of synthesis ’.
Practical application
To demonstrate the practical power of the new reaction, Jiao’s team used it to produce rubber with improved mechanical properties. ‘Our ARO products feature conjugated double bonds analogous to 1,3-butadiene,’ says Jiao, adding that butadiene is a common monomer for rubber.
To do this, Jiao’s team first carried out an ARO reaction using a phenol and an alkylated amine. Reacting a small amount of the linear compound with butadiene, along with a neodymium catalyst, created a cross-linked polymer, with the polar amide and cyano groups from different polymer strands forming complexes with neodymium ions . Compared to butadiene rubber, the cross-linked polymer had a smoother surface and was able to withstand more than five million strength-testing cycles without failure. This was around 20 times more than for butadiene rubber, which broke after 260,000 cycles.
Jiao says that he now hopes to use ARO with ‘more challenging molecular skeletons’ , such as unactivated benzene rings, as well as finding new practical applications of these reactions.
