Halide displacement 91.5.2 Modified Victor Meyer reaction
The synthesis of aliphatic nitro compounds from the reaction of alkyl halides with alkali metal
nitrites was discovered by Kornblum and co-workers^84 ,^85 and is known as the modified Victor
Meyer reaction or the Kornblum modification. The choice of solvent in these reactions is crucial
when sodium nitrite is used as the nitrite source. Both alkyl halide and nitrite anion must be
in solution to react, and the higher the concentration of nitrite anion, the faster the reaction.
For this reason, both DMF and DMSO are widely used as solvents, with both able to dissolve
appreciable amounts of sodium nitrite. Although sodium nitrite is more soluble in DMSO than
DMF the former can react with some halide substrates.^86 Urea is occasionally added to DMF
solutions of sodium nitrite to increase the solubility of this salt and hence increase reaction
rates. Other alkali metal nitrites can be used in these reactions, like lithium nitrite,^87 which is
more soluble in DMF than sodium nitrite but is also less widely available.
NO 2 −
RR'CHNO 2 + RR'CHONO 2 RR'CHOH + RR'C(NO)NO 2 (Eq. 1.1)Figure 1.8Reaction time is extremely important in avoiding the side reaction illustrated in Eq. (1.1),
where the nitroalkane product reacts with nitrite anion and any nitrite ester, formed as by-
product, to give a pseudonitrole.^88 The reaction of sodium nitrite with alkyl halides is much
faster than this competing nitrosation side reaction, even so, prompt work-up on reaction
completion is essential for obtaining good yields.
As a rule, the reaction of primary alkyl iodides with sodium nitrite in DMF takes about 2.5
hours for completion but this is raised to about 6 hours for primary alkyl bromides.^81 The addi-
tion of urea cuts these reaction times by approximately half.^80 The reaction of alkyl chlorides
with alkali metal nitrites is too slow to be synthetically useful. Secondary alkyl bromides and
alicyclic iodides require the addition of a nitrite ester scavenger such as phloroglucinol.^84 Under
these conditions secondary nitroalkanes and their derivatives are formed in good yield,^84 ,^85
an advantage over the use of silver nitrite which is generally limited to primary alkyl halides.
Nitroalkane products containing electron-withdrawing groups that significantly increase the
acidity of the nitro group, i.e.α-nitroesters, are particularly susceptible to nitrosation and also
require the addition of a nitrite ester scavenger.^89 ,^90 The reaction of tertiary alkyl halides with
sodium nitrite is not a feasible synthetic route to nitro compounds.^84
The modified Victor Meyer reaction has been used successfully for the synthesis of many
substituted and unsubstituted, primary and secondary, nitro compounds from the correspond-
ing alkyl iodides, bromides, sulfonate esters etc. (Table 1.3).^81 ,^84 Arylnitromethanes are
synthesized in good yield from benzylic halides if reactions are conducted at subambient
temperatures.^84 ,^92 α-Nitroesters^89 ,^90 andβ-nitroketones^91 are obtained from the corresponding
α-haloesters andβ-haloketones. Some substrates containing a strong electron-withdrawing
group on the same carbon as the halogen i.e.α-haloketones are destroyed under the modified
Victor Meyer conditions and so the use of silver nitrite is preferred.
Silver nitrite gives significantly higher yields of nitro compounds from primary alkyl halides,
and consequently, the synthesis ofα,ω-dinitroalkanes from the reaction ofα,ω-dihaloalkanes
with sodium nitrite^79 is inferior to the same reaction with silver nitrite^75 −^78 (Table 1.2). How-
ever, the use of a solvent system composed of DMSO and MEK is reported to considerably
improve the yields ofα,ω-dinitroalkane when using sodium nitrite.^93