Mixed acid nitrolysis with

The high performance nitramine explosive known as CL-20 (5) has been synthesized via a two-stage nitrolysis starting from the key intermediate (83). The first stage uses dinitrogen tetroxide or nitrosonium tetrafluoroborate for nitrosolysis. The second step, involving nitrolysis of the acetamide and nitrosamine bonds, is achieved with nitronium tetrafluoroborate (>90 %) or mixed acid at 75 °C to 80 °C (93 %). The synthesis of CL-20 is discussed in more detail in Chapter 6. 

Inductive effects can have very pronounced effects on the reactivity of amides and similar substrates towards nitrolysis. Chemists at the Naval Air Warfare Center (NAWC) have reported an extreme case encountered during the synthesis of the energetic 1,5-diazocine known as HNFX (86). A key step in this synthesis involves a very difficult nitrolysis of the electron deficient N-nosyl (4-nitrobenzenesulfonyl) bonds of (85). Nitrolysis with strong mixed acid requires a temperature of 70 °C for 6 weeks to achieve a yield of 16 %. The same reaction with nitric acid-triflic acid requires a temperature of 55 °C for 40 hours to achieve a 65 % yield of HNFX. The same chemists reported a similar case of N-nosyl bond nitrolysis which needed a nitrating agent composed of nitric acid-triflic acid-antimony pentafluoride. ... 

Adolph and Cichra prepared a number of cyclic nitramines from the nitrolysis of tert-butyl protected Mannich products (Table 5.5). Nitrolysis of the fert-butyl groups was achieved with mixed acid, pure nitric acid or a mixture of nitric acid in acetic anhydride depending on the substrate. Pure nitric acid was found to affect the nitrolysis of both the ferr-butyl groups of (97), (Table 5.5, Entry 4) whereas the use of mixed acid led to the isolation of the product where only one of the ferf-butyl groups had undergone nitrolysis. Some of the cyclic nitramine products... 

The above synthesis has a few noteworthy points. The nitrolysis of bicyclic amides like (67) are frequently problematic in terms of inertness towards nitrolysis and the ease with which ring decomposition occurs. This synthesis is an interesting balancing act. Ring decomposition results when the bicycle (67) is treated with absolute nitric acid, mixed acid or nitronium salts. When the diacetyl equivalent of the bicycle (67) is treated with dinitrogen pentoxide-absolute nitric acid-TFAA reagent, the yield drops to 10 %. 

Pentanitropiperidine (91) is prepared from the condensation of 2,2-dinitro-l,3-propanediol (89) with formaldehyde and f-butylamine under slightly acidic conditions, followed by nitrolysis of the f-butyl group of the resulting piperidine (90) with mixed acid or absolute nitric acid. ... 

The synthesis of HMX from the nitrolysis of hexamine with conventional reagents is far more problematic. However, HMX (25) is synthesized in high yield from the nitrolysis of l,3,5,7-tetraacetyl-l,3,5,7-tetraazacyclooctane (TAT) (23) and l,5-diacetyl-3,7-dinitro-1,3,5,7-tetraazacyclooctane (DADN) (24) with dinitrogen pentoxide in nitric acid. DADN (24) is readily synthesized from the acetolysis of hexamine followed by mild nitration with mixed acid. The synthesis of HMX (25) via the nitrolysis of DADN (24) is now a pilot plant... 

---