Nitration of the parent alcohol 91including: remote handling, elaborate reactors and blast-proof buildings. Product separation is
a frequent problem with the mixed acid nitration of polyols. The mixed acid residue and the
aqueous washings often contain considerable amounts of dissolved nitrate ester, presenting
both a safety and a waste problem; ethylene glycol dinitrate is soluble in water to the extent of
0.5 g per 100 ml.^7 If the acid is to be recycled for other nitrations, additional plant is needed
to remove or destroy nitrate ester residue. Additionally, products need washing free from
occluded acid and may need additional purification steps for complete stabilization.
H 3 C OHOHH 3 C ONO 2ONO 2
H 2 SO 4 , HNO 3-5 °C(^1112)
Figure 3.5
However, given all these faults, the low cost and efficiency of mixed acid as anO-nitrating
agent is unparalleled on an industrial scale. Substrates containing both primary and secondary
hydroxy groups are usually nitrated efficiently with mixed acid; work-up and purification is
facile and the nitrate ester product is generally obtained in high yield. If nitration temperature
is controlled, by-product formation from oxidation is not usually a problem. Some substrates
are, however, much more susceptible to oxidation than others and this is the case for substrates
containing methylene groups next to a hydroxy group.^8 Accordingly, substrates like 1-propanol,
1,3-propanediol, and 1,3-butanediol (11) should be nitrated at temperatures below 0◦C. 2-
Nitro-1-propen-3-ol has beenO-nitrated with mixed acid at low temperature.^9 Mixed acid or
nitric acid cannot be used for theO-nitration of tertiary alcohols because the products, tertiary
nitrate esters, are unstable under the reaction conditions.
The presence of nitrous acid duringO-nitration is very undesirable, rendering the nitrate ester
product and the nitration reaction unstable through the formation of nitrite esters. The addition
of a trace amount of urea usually prevents nitrite ester formation. Marken and co-workers^10 used
mixed acid with methylene chloride as co-solvent for the nitration of polyols. A redox probe
was used to monitor the concentration of nitrite anion present in solution and hence regulate
the substrate addition so as to prevent the formation of significant amounts of unstable nitrite
esters. The procedure has been used to synthesize quantities of nitrate ester up to 450 g, both
in high yield and of analytical quality, without the need for potentially hazardous purification
procedures. 1,3-Propanediol dinitrate (89 %), diethylene glycol dinitrate (69 %), nitroglycerine
(90 %), erythritol tetranitrate (89 %), and mannitol hexanitrate (23 %) have been prepared from
the parent polyols via this method. Methylene chloride used in these reactions allows better
temperature control and the nitrate ester products can be isolated in solution which is safer.
HO
OH
OH
OH
OH
OH
O 2 NO
ONO 2
ONO 2
ONO 2
ONO 2
ONO 2
(^1314)
98 % HNO 3 , 0 °C
90–95 %
Figure 3.6
While nitric acid is a good solvent for many organic substrates, sulfuric acid is not, and its
presence often reduces the solubility of polyols in the mixed acid, leading to heterogeneous sus-
pensions. This is the case for many solid polyols, particularly sugars which form heterogeneous
‘pastey masses’ on addition to mixed acid. This has meant, for some substrates, nitric acid is