Chemical Communications Blog

The synthesis of quaternary amino acids is an important challenge facing researchers in bioorganic and medicinal chemistry. While there are a number of ways to transform tertiary amino acids into their quaternary counterparts, α-arylation of amino acids and their derivatives remains limited.

Now, in this HOT ChemComm article, Professor Jonathan Clayden and co-workers at the University of Manchester have revealed an elegant intramolecular arylation of tertiary amino acid derivates, which exploits the use of a urea linkage to connect the amino acid derivative—a nitrile or acid—and the aryl “electrophile”. During the course of the reaction, this N-aryl substituent migrates to the α-carbon of the amino acid moiety. This is followed by a cyclisation, leading to a heterocyclic hydantoin derivative. The reaction is mediated by strong base, and is thought to proceed via the metallated enolate.

Interestingly, the researchers found that the migration of the aryl ring was not influenced by its electronic properties, and that the transition-metal–free reaction could be applied successfully to a range of natural and unnatural tertiary amino acid substrates. If the tertiary amino acid nitrogen is protected with a PMB (p-methoxybenzyl) group, the resulting hydantoin product can subsequently be hydrolysed, affording the acyclic quaternary amino acid.

The reaction was monitored by in situ infrared spectroscopy (ReactIR) to identify the reaction intermediates and cast light on the mechanism of the arylation. Further details of the ReactIR analysis can be found in the electronic supplementary information. Ultimately, Clayden and his group hope to further develop this useful methodology to allow the enantioselective arylation of amino acids.

For more, check out this HOT ChemComm article in full:

Ruth E. Gilligan is a guest web-writer for ChemComm.  She has recently completed her PhD in the group of Prof. Matthew J. Gaunt at the University of Cambridge, focusing on the development and application of C–H functionalisation methodology.

The improvement of high energy density materials (HEDM) is an ongoing challenge. These materials are widely used in propellants, explosives, and pyrotechnics, and researchers face the difficult task of optimising their explosive potential while ensuring their safety and ease of handling. Nitro-substituted methanide compounds are an important class of HEDM, but often suffer from thermal instability and impact sensitivity. This HOT ChemComm article addresses this challenge by highlighting the preparation and analysis of impact insensitive dinitromethanide salts.

Jean’ne Shreeve at the University of Idaho, working with Ling He at Sichuan University and co-workers at the US Naval Research Laboratory, proposed that by combining an oxygen-rich polynitromethanide anion (either a nitroform anion TNM, or a dinitromethanide anion DNM) with nitrogen-rich cations such as guanidinium, triazolium and tetrazolium anions, the resulting salt would exhibit high energetic properties as well as improved stability.

Using a range of guanidinium, triazolium and tetrazolium halides, the researchers prepared nine DNM salts and analysed their physicochemical properties. All of the salts displayed good thermal and detonation properties while being significantly less sensitive to impact than common explosives such as 2,4,6-trinitrotoluene (TNT) and cyclotrimethylenetrinitramine (RDX).

Molecular structure and Packing diagram of DNM salt 3

Guanidinium–DNM salt 3, decomposing at 187 °C, displayed the best thermal stability among all other known DNM salts. X-ray crystallography revealed that this increased stability is due to its strongly hydrogen-bonded structure. Each guanidinium cation forms six hydrogen bonds with the NO₂ groups of four surrounding anions, creating a planar, layered packing structure.

Insights such as these will allow researchers to design HEDM with better thermal stability and less impact sensitivity, controlling their energetic potential yet ensuring greater safety and utility.

For more, check out the ChemComm article in full:
Impact insensitive dinitromethanide salts
Ling He, Guo-Hong Tao, Damon A. Parrish, and Jean’ne M. Shreeve
Chem. Commun., 2013, Accepted Manuscript
DOI: 10.1039/C3CC46518G

Ruth E. Gilligan is a guest web-writer for ChemComm.  She has recently completed her PhD in the group of Prof. Matthew J. Gaunt at the University of Cambridge, focusing on the development and application of C–H functionalisation methodology.