Preparation of substituted aromatic amines

A process for the preparation of substituted aromatic amines comprising (1) contacting a primary aromatic amine with an oxidizing agent in a homogeneous solution containing water, an oxidizable water-miscible organic solvent and a base, and (2) reducing the solution with a reducing agent to produce the substituted aromatic amine.

FIELD OF THE INVENTION 
The invention relates to a process for the preparation of substituted 
aromatic amines. More specifically, the invention relates to the 
preparation of aminodiphenylamines. 
DESCRIPTION OF RELATED ART 
British Pat. No. 1,440,767 describes the direct synthesis of 
4-aminodiphenylamine (4-ADPA) by the head-to-tail coupling of aniline by 
oxidation with ferricyanide followed by hydrogenation. This process has 
numerous disadvantages. The oxidation step occurs in a two-phase system 
containing an oxidation-resistant organic solvent, typically a chlorinated 
solvent. Environmental concerns require the reduction or elimination of 
the use of such chlorinated solvents. Additionally, intense mixing is 
required to keep the two-phase in contact. Finally, the overall 
selectivities to 4-ADPA are relatively low, in the range of about 9 to 37% 
based on aniline consumed after the hydrogenation step. 
SUMMARY OF THE INVENTION 
A process for the preparation of substituted aromatic amines of the formula 
##STR1## 
wherein n equals from 2 to 5, R.sub.1 and R.sub.2 are either the same or 
different aliphatic radicals or hydrogen, which comprises (1) contacting a 
primary aromatic amine with an oxidizing agent in a homogeneous solution 
containing water, an oxidizable water-miscible organic solvent and a base, 
and (2) reducing the solution with a reducing agent to form the 
substituted aromatic amine. 
The present invention is an improvement over BP 1,440,767, in that it 
allows the use of oxidizable organic solvents in the oxidation step, 
thereby eliminating the use of environmentally hazardous chlorinated 
organic compounds. In addition, the oxidation occurs in a homogeneous 
solution, which eliminates the need for intense mixing and special reactor 
design. Finally, the process provides a method of preparing quantities of 
substituted aromatic amines in much higher selectivities than produced by 
the methods taught in BP 1,440,767, e.g. in the range of about 25 to 71% 
based on aniline consumed after the hydrogenation step. 
DETAILED DESCRIPTION OF THE INVENTION 
The improved process involves two steps: the oxidation of a primary 
aromatic amine and its reduction to form substituted aromatic amines. The 
substituted amines are oligomers of the primary aromatic amines where n 
equals from 2 to 5 and R.sub.1 and/or R.sub.2 are hydrogen or the same or 
different aliphatic radicals. 
In the first step, a primary aromatic amine is oxidized to form a mixture 
of oxidation products which includes some products where benzene rings are 
bound by azo linkages. The oxidation step is carried out by mixing the 
amine or a solution of the amine in a homogeneous solution containing 
water, an oxidizable water-miscible organic solvent, an oxidizing agent 
and a strong base. 
Suitable primary aromatic amines are of the structure 
##STR2## 
where R.sub.1 and R.sub.2 are either the same or different aliphatic 
radicals or hydrogen. Examples of such primary aromatic amines include 
2-methyl aniline, 2-ethyl aniline and 2,6-dimethyl aniline. The preferred 
amine is aniline, a readily available commodity chemical. 
The oxidation step is carried out with an oxidizing agent and a base in a 
homogeneous solution containing water and an oxidizable water-miscible 
organic solvent. The organic solvent can be any of a number of 
water-miscible organic solvents such as alcohols, e.g. methanol, ethanol, 
propanol, isopropanol, butanol, 2-butanol; nitriles such as acetonitrile; 
ethers such as polyethylene glycols; ketones such as methylethyl ketone 
and acetone; and other solvents such as tetrahydrofuran. If the desired 
product is the para-position polymer exclusive of other isomers, e.g. 
4-ADPA, then the preferred solvent is methanol, which produces the almost 
pure para-isomer. If it is desired to maximize selectivity to the 
para-isomer and produce a mixture of isomers, e.g. a mixture of ortho- and 
para-isomers, the 1-propanol solvent is preferred. 
The ratio of solvent to water in the oxidation step can be varied widely, 
in the range of about 5:95 to 95:5 volume ratio, with the preferred volume 
ratios being in the range of 40:60 to 60:40, which improves the 
selectivity to the para-position isomer, the most preferred being 50:50. 
The amount of primary aromatic amine reactant present in the solvent-water 
solution is very dilute to discourage side reactions, such as 
polymerization of the substituted amine where n is greater than 5. 
Typically, the weight ratio of amine to homogeneous solvent solution is in 
the range of about 0.001 to about 1.20, and the preferred range is about 
0.01 to about 0.1, to provide a dilute enough solution to discourage 
excessive polymerization but high enough concentration to produce an 
appreciable amount of substituted amine. 
The oxidizing agent is an alkali metal ferricyanide, such as potassium 
ferricyanide or sodium ferricyanide. The preferred alkali metal 
ferricyanide is potassium ferricyanide. The amount of oxidizing agent used 
can vary widely. The smaller the amount used, the greater the selectivity 
to the substituted aromatic amines and the lower the conversion. The 
greater the amount used, the higher the conversion of the primary aromatic 
amine but low selectivity to substituted aromatic amine. Typically, the 
mole ratio of oxidizing agent to primary amine is in the range of about 
4:1 to about 1:4, with the preferred ratio being about 1:1 to achieve the 
desired balance of selectivity and conversion. 
The base which is used in the oxidation step can be any of a number of 
bases, such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, 
tetramethyl hydroxide, ammonium sodium carbonate and lithium hydroxide, or 
a mixture of such bases. The minimum amount of base required for the 
oxidation step is equal molar amounts with the oxidizing agent. Typically, 
there is some excess of base used, to guarantee that a sufficient amount 
is present in the reaction system. Therefore, the mole ratio of base to 
oxidizing agent is in the range of about 1:1 to about 6:1, the preferred 
range being from about 1:1 to about 2:1. 
The oxidation step reaction occurs quickly and the reaction time, 
therefore, can be very short. If the reaction is allowed to continue for a 
long period of time, a slow reaction of the substituted amine continues, 
resulting in polymers where n is greater than 5 and a subsequent loss of 
selectivity. The reaction time is typically in the range of about 1 to 
about 60 minutes, with the preferred range being about 15 to about 45 
minutes. 
The oxidation step reaction can be run at relatively low temperatures, with 
the best results occurring below about 35.degree. C. At higher 
temperatures the substituted amines react further to form polymers with n 
greater than 5 and tars, resulting in a loss of selectivity. The preferred 
reaction temperature range is about 20.degree. C. to 30.degree. C. The 
most preferred reaction temperature, because of ease of operation, is room 
temperature, around 23.degree. C. 
Although the oxidation step occurs as a homogeneous system, some mixing is 
required, because ferrocyanide salts will settle out of the solution. 
Adequate mixing can be achieved with a magnetic stirrer or a paddle 
stirrer in the bottom of a round bottom flask. 
The second step of the process to make substituted aromatic amines is to 
reduce the oxidation product. This results in two reactions. One produces 
the substituted amines from an unidentified intermediate. The second 
reduces the azobenzene compound to the primary aromatic amine, which can 
be recovered and recycled. The reduction can be carried out by any of many 
known reductive processes, such as using a hydride such as sodium 
borohydride or sodium borohydride in conjunction with palladium- or 
platinum-on-carbon calatyst. The preferred process is catalytic reduction 
wherein hydrogenation can be effected under pressure in the presence of 
platinum-or palladium-on-carbon as catalyst. This process is described in 
detail in "Catalytic Hydro-genation in Organic Synthesis", P. N. Rylander, 
Academic Press, N.Y. 1979, p 299, which is hereby incorporated by 
reference.