Organic Chemistry of Explosives

266 Nitramines and Their Derivatives

Archibald and co-workers^4 reported the first synthesis of TNAZ (18) in 1989. This route

uses the reaction betweentert-butylamine and epichlorohydrin to form the required azeti-

dine ring. TheN-tert-butyl-3-hydroxyazetidine (14) formed from this reaction is treated with

methanesulfonyl chloride and the resulting mesylate (15) reacted with sodium nitrite in the

presence of phloroglucinol to yieldN-tert-butyl-3-nitroazetidine (16), the phloroglucinol used

in this reaction preventing the formation of nitrite ester by-product. Oxidative nitration ofN-

tert-butyl-3-nitroazetidine (16) toN-tert-butyl-3,3-dinitroazetidine (17) is achieved in 39 %

yield with a mixture of sodium nitrite and silver nitrate, and in 60 % yield with sodium nitrite

and sodium persulfate in the presence of potassium ferricyanide. The synthesis of TNAZ (18)

is completed by nitrolysis of thetert-butyl group of (17) with nitric acid in acetic anhydride.

Unfortunately, this synthesis provides TNAZ in less than 20 % overall yield, a consequence of

the low yields observed for both the initial azetidine ring-forming reaction and the reaction of

(15) with nitrite ion.

HO OH

OH

NH 2

Br Br

Br

NH 3 Br

N

21

Br

N

NO

22

2 N CH 2 BrO

N

NO 2

23

2 N CH 2 BrO

N

NO 2

24

2 N CH 2 OHO

N

NO 2

18

O 2 NNO 2

NaHCO 3 , NaI

1. AcOH, CHCl 3 , Et 2 O


2. HBr-AcOH, 160 °C,
   sealed tube, 72 %

NaOH, 80 °C

60 mmHg

1. NaNO 2 (aq)


2. HCl (aq)
   10 %

HNO 3 , TFAA

DMSO, 100 °C 0 °C, 81%

78 %

NaNO 2 , NaOH

K 3 Fe(CN) 6 ,

K 2 S 2 O 8 , 37 %

19 20

Figure 6.5 Marchand and co-workers route to TNAZ^5

Marchand and co-workers^5 reported a synthetic route to TNAZ (18) involving a novel elec-

trophilic addition of NO+NO− 2 across the highly strained C(3)–N bond of 3-(bromomethyl)-

1-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the

reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium

hydroxide under reduced pressure. The product of this reaction,N-nitroso-3-bromomethyl-

3-nitroazetidine (22), is formed in 10 % yield but is also accompanied by N-nitroso-3-

bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed

by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the

tert-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide

in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis

of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both pro-

cesses achieved in ‘one pot’ with an alkaline solution of sodium nitrite, potassium ferricyanide

and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large

scale manufacture.