There is a need for new “green chemistry” approaches to the preparation of precursors to important energetic ingredients, such as nitrogenous polycycles. One of the most important new ingredients for Department of Defense (DoD) applications is CL-20, but its production process suffers from several economic and environmental disadvantages, mostly related to requirements for benzylamine starting material and for heavy metal (typically, palladium) catalysts used in debenzylation steps. Besides its high material cost, benzylamine is an environmentally undesirable starting material.

The objective of this SERDP Exploratory Development (SEED) project was to demonstrate the feasibility of preparing the hexaazaisowurtzitane cage in a form that is directly nitrolyzable to CL-20 without a requirement for expensive benzylamine starting material or heavy metal catalysts, thereby introducing a new, preferably lower-cost, less wasteful, and environmentally cleaner process to produce CL-20.

Many attempts were made to achieve the transformation originally proposed for this project: the condensation of 1,4-diformyl-2,3,5,6-tetrahydroxypiperazine with any 1,1,2,2- tetraamidoethane to form a hexaacylhexaazaisowurtzitane suitable as a precursor to CL-20. All of the researchers’ attempts at this condensation, under many different conditions, were unsuccessful. The researchers next performed degradation chemistry on a known nitramine, HHTDD, in attempts to reorganize its degradation intermediates into a hexaazaisowurtzitane cage, but initial attempts were unsuccessful. The recent publication by French researchers of a new hexaazaisowurtzitane derivative, hexaallylhexaazaisowurtzitane (HAllylIW), presented a new opportunity to prepare a superior precursor to CL-20 without a requirement for benzylamine or heavy metal catalysts. The researchers applied a known transformation—base-catalyzed isomerization of allylamines into 1-propenylamines—to HAllylIW to prepare a new derivative, hexa(1-propenyl)hexaazaisowurtzitane (HPIW). The researchers next performed photooxygenation of this intermediate by singlet oxygen—using oxygen gas photolyzed by a quartz halogen headlamp in the presence of a tetraphenylporphine sensitizer—in order to oxidize the 1-propenyl substituents to formyl substituents. The resulting hexa- or polyformylhexaazaisowurtzitane was expected to be a new suitable precursor to CL-20. Although the oxidation reaction did not go to completion to produce hexaformylhexaazaisowurtzitane, the partially oxidized product formed did indeed undergo nitrolysis to form CL-20 in a clean reaction. Furthermore, the researchers demonstrated that the new intermediate, HPIW, underwent direct nitrolysis to form CL-20, though initial conditions did not do so as cleanly as with its oxidation product as a precursor for nitrolysis. This reactivity of the enamine HPIW is explained to be a mechanistically reasonable transformation.

By improving the efficiency of converting HAllylIW to CL-20 with one or two additional steps, a potentially practical benzylamine-free, heavy-metal-free synthesis of CL-20 has been successfully achieved. The overall process now avoids the preparation of benzyl chloride, which uses elemental chlorine, and catalytic hydrogenolysis steps—requiring palladium metal/compounds—are avoided. A heavy-metal-free sequence leading to CL-20, glycerol (available from biodiesel) is dehydrated in formic acid to make allyl alcohol; the alcohol is efficiently converted to allyl bromide or chloride by treatment with the corresponding hydrohalic acid; and the allyl halide is aminated to make allylamine. This commercially available reagent condenses with glyoxal, as recently reported, to make HAllylIW, leading to CL-20 with apparently high efficiency.

This SEED project constituted only a feasibility demonstration that new synthetic routes to CL-20 are available. Significant process development would be needed in order to demonstrate their overall superiority to the current production process.