92 Synthetic Routes to Nitrate Esters
the nitrating agent of choice. Solid polyols like pentaerythritol, erythritol and mannitol (13)
are commonlyO-nitrated with fuming or anhydrous nitric acid. In a typical procedure, dry air
is bubbled through anhydrous nitric acid to remove any oxides of nitrogen present, followed
by the addition of a trace of urea to remove any nitrous acid present. The so-called ‘white nitric
acid’ is then cooled to 0◦C and the substrate, either as a liquid or finely powdered solid, added
slowly to an excess of the acid and stirred for a short time. The solution is poured into a large
excess of water and after extraction or filtration the nitrate ester is usually procured in excellent
yield. In these cases the use of excess nitric acid is essential to ensure completeO-nitration of
the substrate. Pentaerythritol tetranitrate, erythritol tetranitrate and mannitol hexanitrate (14)
can be prepared in∼95 % yield using this simple method.^11 Many nitrated sugars have been
prepared using either fuming nitric acid^12 or mixed acid^13 at 0–10◦C.
Commercial 70 % nitric acid can be used for theO-nitration of low molecular weight
alcohols like ethanol and 2-propanol. The nitrate ester products are isolated from the cautious
distillation of a mixture of the alcohol and excess 70 % nitric acid.^14 The presence of urea in
these reactions is very important for the destruction of nitrous acid and its omission can lead
to very violent fume-off. However, this method is not recommended on safety grounds. Using
temperatures above ambient for theO-nitration of alcohols, with either nitric acid or mixed
acid, is dangerous and greatly increases the risk of explosion.
A mixture of fuming nitric acid in acetic anhydride is a common nitrating agent for the
synthesis of nitrate esters from alcohols and polyols.^15 The reaction of fuming nitric acid with
acetic anhydride can be violent, and as such, the components are usually mixed between 0
and 5◦C. It is generally accepted that these mixtures contain acetyl nitrate. Acetyl nitrate is
a weak nitrating agent but in the presence of a strong acid like nitric acid this can ionize to
nitronium and acetate ions. Acetyl nitrate reagent has been extensively used for the nitration
of sugars.^16 The nitration of unsaturated alcohols with nitric acid in acetic anhydride has been
studied.^17 In most cases yields are low (10–30 %) because acetyl nitrate can add to the double
bond to formβ-nitroacetates (Section 1.3.1). The reaction of the corresponding unsaturated
halide derivatives with silver nitrate in acetonitrile is a more useful method for the synthesis
of unsaturated nitrate esters (Section 1.4.1).^18
More obscure reagents used forO-nitration include mixtures of phosphoric and nitric acids,
and anhydrous nitric acid in which phosphorous pentoxide has been dissolved.^19 The latter
mixture contains dissolved dinitrogen pentoxide and is a powerful nitrating agent. A mixture
of anhydrous nitric acid containing catalytic amounts of boron trifluoride has been reported to
lead to the rapidO-nitration of alcohols.^20
OHOHHOHONO 2 NO 2NO 2OHHONO 2NO 2 NO 2ONO 2 ONO 2ONO 2O 2 NOO 2 NO O 2 NO90 % HNO 3 ,
Ac 2 O70 %HNO 3 , H 2 SO 4
or
HNO 3 , CHCl 3or
HNO 3 , Ac 2 O(LLM-101)16 15 17Figure 3.7An interesting example of the effectiveness of different reagents forO-nitration can be
seen during the synthesis ofneo-inositol-based nitrate ester explosives. 1,4-Dideoxy-1,4-
dinitro-neo-inositol (15), a compound readily prepared from the condensation of nitromethane
and glyoxal in the presence of base,^21 undergoes conversion to the tetranitrate ester (16) on