Organic Chemistry of Explosives

Azetidines – 1,3,3-trinitroazetidine 267

Br Br

NH 3 Br

25

N

26

N

NO

27

NaOH (aq), 80 °C H

remove via

azeotropic

distillation

NaNO 2 , HCl (aq), 0 °C

1 % from 25

NO 2

Figure 6.6

The synthesis of TNAZ (18) via the electrophilic addition of NO+NO− 2 across the C(3)–

N bond of 1-azabicyclo[1.1.0]butane (26) was found to be very low yielding (∼1 %) and

impractical.^5 Nagao and workers^6 reported a similar synthesis of TNAZ via this route but the

overall yield was low.

OH

NH 2

28

OH

OTs

NHTs

29

OH

OTs

NHTs

30

OTBS

N

NO 2

18

O 2 N NO 2

N

NOH

Ts

34

N

O

Ts

33

N

OH

Ts

32

N

OTBS

Ts

31

TsCl, pyr THF, LiH

66 %

Imidazole,

DMF, TBSCl

88 %

AcOH,

reflux

83 %

CrO 3 , AcOH

95 %

91 %

100 %

HNO 3 , CH 2 Cl 2

40–50 %

NH 2 OH.HCl,

NaOAc (aq)

Figure 6.7 Axenrod and co-workers route to TNAZ^7 ,^8

Axenrod and co-workers^7 ,^8 reported a synthesis of TNAZ (18) starting from 3-amino-1,2-

propanediol (28). Treatment of (28) with two equivalents ofp-toluenesulfonyl chloride in the

presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative,

followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31)

in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated

temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the

ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime

(34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric

acid in methylene chloride, a reaction leading to oxidation–nitration of the oxime group to

gem-dinitro functionality and nitrolysis of theN-tosyl bond. This synthesis provides TNAZ

in yields of 17–21 % over the seven steps.

Archibald, Coburn, and Hiskey^9 at Los Alamos National Laboratory (LANL) have reported

a synthesis of TNAZ (18) that gives an overall yield of 57 % and is suitable for large scale

manufacture. Morton Thiokol in the US now manufactures TNAZ on a pilot plant scale via

this route. This synthesis starts from readily available formaldehyde and nitromethane, which

under base catalysis form tris(hydroxymethyl)nitromethane (35), and without isolation from