Fluorinated molecules

I thoroughly enjoyed the article by Ann Thayer on the use of fluorinated building blocks to synthesize new biologically active molecules (C&EN, June 5, page 27). It was interesting to learn that fluorine-containing compounds are now being investigated for these and other applications. The article did not mention the difluoramino (NF₂) group as a possible building block.

In the early 1960s, a considerable amount of classified research, funded by the Office of Naval Research, was conducted on compounds that contained the difluoramino group for use in solid rocket propellant formulations. At that time, I worked at the Reaction Motors Division of Thiokol Chemical where we performed synthesis and studied the chemistry of organic compounds containing these groups. The work was declassified many years ago, but unfortunately some of it went unpublished as many of us moved on to other industries after government funding ceased later in the 1960s.

Most of our work involved the use of tetrafluorohydrazine and difluoramine. These are hazardous materials to be sure, but with proper handling using vacuum line techniques, we were very successful in safely preparing many compounds that had multiple difluoramino groups. While compounds that contained one or two difluoramino groups per carbon atom were certainly shock sensitive, we prepared many other compounds that were quite stable.

The strong electron-withdrawing nature of the difluoramino group might make it a candidate for use in biologically active molecules. Starting with tetrafluorohydrazine, a colorless gas that readily dissociates into free radicals, many types of difluoramino-containing compounds can be synthesized. Coupling with other free radicals can lead to molecules that have one difluoramino group. The reaction between tetrafluorohydrazine and tert-butyl iodide, for example, yields tert-butyldifluoramine. Vicinal bis-difluoramines can be prepared by the addition of tetrafluorohydrazine to olefins. Difluoramines undergo facile dehydrofluorination with a variety of bases to form N-fluorimines. These are just some examples of the interesting chemistry that was done some 40 years ago.

If there are any adventurous chemists who might be interested in resurrecting this fascinating field, a good starting point would be "Advanced Propellant Chemistry," an ACS Advances in Chemistry Series Publication, Number 54 (1966).

Joseph A. Castellano
San Jose, Calif.