30 Synthetic Routes to AliphaticC-Nitro
carbanions such as malonate arises from the perturbation of a side-reaction observed with alkyl
nitrates, namely, the carbanion attacking the carbon atom of alkyl nitrate instead of nitrogen,
and thus giving alkylation instead of nitration. Alkaline nitrations with acetone cyanohydrin
nitrate compliment reactions using alkoxide base and nitrate esters; the latter are generally not
applicable to substrates with proton acidities below pKa16.
1.8.1.3 Alkaline nitration with tetranitromethane
CH 3
O 2 N NO 2NO 2CH 2 NO 2
O 2 N NO 2NO 2+ FC(NO 2 ) 3NaOH (aq)THF, MeOH
89 %979899+ FC(NO 2 ) 2Figure 1.40The carbon–nitrogen bonds of tetranitromethane are very electron deficient and prone to
attack by nucleophiles. Consequently, tetranitromethane and its derivatives behave like nitrating
agents in alkaline solution.^179 Fluorotrinitromethane (98) behaves in a similar way and has been
used for the nitration of the acidic methyl group of 2,4,6-trinitrotoluene (97) (TNT) to give
α,2,4,6-tetranitrotoluene (99) in 89 % yield.^225
1.8.1.4 Alkaline nitration with nitrogen oxides and related compounds
O 2 NO 2 N
O 2 NO 2 N
O 2 NNO 2 NO 2NO 2
NO 2 NO 2O 2 N
100
101O 2 N
O 2 NO 2 N
O 2 NNO 2
NO 2NO 2
NO 2
102- LiN(TMS) 2 ,
CH 2 Cl 2 , -78 °C - NOCl, -78 °C
- O 3 , -78 °C
45–55 % (3 steps) - 4 eq NaN(TMS) 2 ,
THF, -78 °C - N 2 O 4 (excess),
pentane, -125 °C - HNO 3 , Et 2 O, -30 °C
74 % (3 steps)
Figure 1.41Eaton and co-workers^226 synthesis of octanitrocubane (102) (ONC) is a milestone in high-
energy materials synthesis. The explosive performance of octanitrocubane is predicted to be
very high with a detonation velocity of 9900 m/s.^227 This pioneering synthesis involves, as
a key step, the alkaline nitration of 1,3,5,7-tetranitrocubane (100). In this reaction hexam-
ethyldisilazide anion is used to deprotonate positionsβto three nitro groups and the resulting
tetra-anion is quenched/nitrated with excess dinitrogen tetroxide in pentane to give a 74 %
yield of a mixture containing 95 % heptanitrocubane (101) and 5 % hexanitrocubane. This re-
action involves nitration of the sodium anion of 1,3,5,7-tetranitrocubane at the melting interface
(∼ 105 ◦C) between frozen THF and dinitrogen tetroxide in pentane. This is a new nitration
technique known as ‘interfacial nitration’ and probably proceeds via a radical process.^226
Heptanitrocubane (101) is converted to octanitrocubane (102) by further reaction with hex-
amethyldisilazide anion, followed by quenching with nitrosyl chloride and oxidation with
ozone.^226 This example ofβ-deprotonation-nitration is only feasible because of the combined