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For energetic materials, stereo- and regioisomers matter

Study shows isomers exhibit different physical properties

by Bethany Halford
August 7, 2019 | A version of this story appeared in Volume 97, Issue 32


Six stereo- and regioisomers of a cyclobutane with four pendant nitrate esters

Unlike chemists who make drugs, fragrances, and agrochemicals, chemists who make energetic materials, like explosives and propellants, don’t spend much time worrying about stereo- and regiochemistry. Their thinking is that the precise arrangement of substituents on a compound doesn’t really matter if they’re going to blow it up or burn it. But that logic is all wrong, say researchers at CCDC US Army Research Laboratory and Scripps Research in California. They report that differences in stereo- and regiochemistry can result in energetic molecules with vastly different physical properties (J. Am. Chem. Soc. 2019, DOI: 10.1021/jacs.9b06961).

The group, led by the Army Research Lab’s Jesse J. Sabatini and Scripps’ Phil S. Baran, synthesized six stereo- and regioisomers of a cyclobutyl compound with four nitrate ester substituents (shown). Computations suggested that the compounds’ explosive properties would be similar to one another and just a little better than the explosive TNT. Based on that information alone, Sabatini says, some chemists in the energetic materials field would not have bothered to make any of them.

But Sabatini and Baran wanted to see if there were differences in the isomers’ physical properties. Their team found that the isomers have different melting points. Based on their melting points, two of the six compounds could be combined with other chemicals to make melt-castable explosives. Another isomer has a melting point of about 86 °C—a sweet spot that suggests it could be a standalone melt-castable explosive. And one of the regioisomers is liquid at temperatures as low as –40 °C, which makes it attractive as a propellant.

“Making and testing new explosives is a dangerous endeavor,” says Adam J. Matzger, who studies energetic materials at the University of Michigan. Consequently, chemists in this field often rely on computational methods to decide if a molecule is promising enough to synthesize. Sabatini and Baran’s work show that computations can fall short, he says. “The work highlights the importance of continued experimental work in the energetic materials field and the need for development of more robust theory.”

Karl O. Christe, an expert in energetic materials at the University of Southern California, says “although the principle is limited to structures exhibiting multiple isomers, it nevertheless should become a standard component in the toolbox of chemists working on the formulation of energetic materials.”

Lisa M. Barton, a graduate student in Baran’s lab who spearheaded the synthesis of the isomers, notes that all six synthetic routes the group used produce pure material on up to kg scale and at low cost. Sabatini says the Army is considering further study of some of the compounds to see if they could be used to replace TNT or for other practical purposes.


This story was updated on Aug. 19, 2019, to correct the description of the six isomers studied. These six are not all of the possible isomers of the cyclobutyl compound with four nitrate ester substituents.



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