Question

We know that for substitution reactions in any cyclic compound which involves ortho and para directing groups, the one which gets substituted in the para group is the major product because of high stability. But, it is not so in the case of nitration of phenols.Why is it different?

Answer 1

Nitrophenols are important intermediates for the manufacture of drugs and

pharmaceuticals. Catalytic hydrogenation of 2-nitrophenol gives 2-aminophenol,

which is used as a photographic developer and as a versatile intermediate for dyes and

fine chemicals. Para-nitrophenol is an important starting material used in multiple step

synthesis of valuable compounds [1].

Among the aromatic compounds phenol is very active and is nitrated with

nitric acid to various nitro derivatives, which makes it difficult to isolate [2]. Nitration

of phenol using mixture of nitric acid and sulfuric acid gives 2-nitrophenol and 4-

nitrophenol in a ratio of 1.42 [3]. Nitration of phenol as a special case has been studied

by several researchers using various nitrating agents under different conditions [4].

Recently Zolfigol et al. [5] reported a use of solid inorganic acid salts (NaHS04.H20,

Mg(HS04)2) with sodium nitrate, which gave in situ generation of HNO3 and

nitrophenols in high yields.

Phenols are easily mononitrated at room temperature by NaNC«3 in a two phase

system (water-ether) in presence of HC1 and a catalytic amount of La (NC>3)3 with o/p

ratio 2:1 [6]. Lazslo demonstrated that phenol can be nitrated in a system called

claycop (trihydrated cupric nitrate supported on montmorillonite/acetic

anhydride/CCU) in 92 % yield with an o/p ratio 13.3 [7]. Very high regioselective

nitration of phenol was achieved with a surfactant suspended in acetonitrile treated

with nitronium tetrafluoroborate, which gave an o/p ratio of 19.0 [8].

Nitration of phenol has been performed by ACONO2 /HNO3/ and aromatic

solvents [9], N-nitropyrazole/BF3.Et20/CH2Cl2 [10], via nitroso compounds and their

subsequent oxidation to nitrocompounds with HNO3 [11], metal nitrates [12], clay