Process for the preparation of nitro diphenyl amine derivatives

A process for the preparation of nitro-diphenyl amines is disclosed by decarboxylation of a urethane in the presence of a base at an elevated temperature using tetramethylene sulphone as reaction medium is disclosed. The urethane can be one formed by the reaction of a nitrophenol with an aromatic isocyanate.

The invention relates to a process for the preparation of nitro-diphenyl 
amine derivatives. 
4-nitro-diphenyl amine can be obtained by reacting 4-nitro-chloro benzene 
with aniline (DE-OS (German Offenlegungsschrift No.) 10 30 834) or by 
reacting 4-nitro-chloro benzene with formanilide (DE-OS 1056 615). 
Furthermore it is known (U.S. Pat. No. 3,847,990) to obtain 
4-nitro-diphenyl amine by reacting 4-nitro-phenol with phenol isocyanate 
in the presence of alkaline catalysts and nitrobenzene as the solvent at 
temperatures in the region of 200.degree. C. This process has a decisive 
disadvantage from the point of view of safety: alkali metal 
4-nitro-phenolates can be formed from the 4-nitro-phenol used and from the 
alkali metal acetates, hydroxides and carbonates particularly suitable as 
alkaline catalysts, these alkali metal 4-nitrophenolates being 
precipitated in solid form from the nitrobenzene solution, particularly 
towards the end of the reaction. These alkali metal 4-nitro-phenolates 
are, as is known, liable to explode at high temperatures when in solid 
form. 
A process has been found for the preparation of nitro-diphenyl amine 
derivatives by the reaction of a nitrophenol of the formula 
##STR1## 
in which R.sup.1 represents hydrogen, alkyl, cycloalkyl, aryl, alkoxy, 
aryloxy, acyl, halogen, nitro or cyano, 
with an aromatic isocyanate of the formula 
##STR2## 
in which R.sup.2 represents hydrogen, alkyl, cycloalkyl, aryl, alkoxy, 
aryloxy, acyl, halogen, nitro or cyano 
in the presence of a base within a temperature range of 100.degree. to 
250.degree. C., the urethane forming intermediately being decarboxylated, 
characterised in that the process is conducted in tetramethylene sulphone 
as the reaction medium. 
In the process according to the invention nitrophenols of formula (I) are 
preferably used, in which R.sup.1 denotes hydrogen, alkyl, phenyl, alkoxy, 
phenyloxy or halogen. 
Particularly preferred in the process according to the invention is the use 
of nitrophenols of formula (I), in which R.sup.1 denotes hydrogen, methyl, 
methoxy, phenyloxy or chlorine. 
Preferably an aromatic isocyanate of formula (II), in which R.sup.2 denotes 
hydrogen, alkyl, phenyl, alkoxy, phenyloxy or halogen, is used in the 
process according to the invention. 
The use of an aromatic isocyanate of formula (II), in which R.sup.2 denotes 
hydrogen, methyl, methoxy, phenyloxy or chlorine, is particularly 
preferred in the process according to the invention. 
Straight chained or branched hydrocarbon radicals with 1 to 6 carbon atoms 
may be mentioned as the alkyl, such as for example, methyl, ethyl, propyl, 
isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl or isohexyl. 
Preferred as the alkyl are hydrocarbon radicals with 1 to 4 carbon atoms, 
such as for example methyl, ethyl, propyl, isopropyl, butyl or isobutyl. 
The particularly preferred alkyl is the methyl radical. 
Cyclic hydrocarbon radicals with 5 to 7 carbon atoms, which can optionally 
be substituted by low alkyl, may be mentioned as the cycloalkyl, such as 
for example cyclopentyl, methyl-cyclopentyl, cyclohexyl, 
methyl-cyclohexyl, cycloheptyl or methyl-cyclo-heptyl. 
Aromatic hydrocarbon radicals with 6 to 14 carbon atoms, for example, 
phenyl naphthyl or anthryl, may be mentioned as the aryl. The preferred 
aryl is the phenyl radical. 
As the alkoxy radicals may be mentioned which are derived from a low 
alcohol with 1 to 4 carbon atoms, for example, methoxy, ethoxy, propoxy, 
isopropoxy, butoxy or isobutyloxy. The preferred alkoxy is the methoxy 
radical. 
As the aryloxy, radicals may be mentioned which are derived from an 
aromatic hydroxyl compound, such as for example phenoxy, naphthyloxy or 
anthryloxy. The preferred aryloxy is the phenoxy radical. 
As the acyl, alkylcarbonyl radicals with 2 to 5 carbon atoms may be 
mentioned, such as for example acetyl, propionyl, butyryl or valeroyl. The 
preferred acyl is the acetyl radical. 
Fluorine, chlorine or bromine, preferably chlorine may be mentioned as the 
halogen. 
The following may be mentioned as examples of the nitrophenols to be used 
according to the invention: p-nitrophenol, o-nitrophenol, 
2,4-dinitrophenol, 4-nitro-2-chlorophenol, 4-nitro-3-chlorphenol, 
3-chloro-2-nitrophenol, 4-chloro-2-nitrophenol, 5-chloro-2-nitrophenol, 
6-chloro-2-nitrophenol, 2,6-dichloro-4-nitrophenol, 4-nitroorthocresol, 
4-nitro-metacresol, 6-nitro-orthocresol, 6nitro-metacresol, 
4-nitro-2-isoproplylphenol, 4-nitro-2-isobutylphenol, 
4-nitro-2-cyclohexylphenol. 
Examples which may be mentioned of aromatic isocyanates able to be used 
according to the invention are: phenyl isocyanate, m-methylphenyl 
isocyanate, p-methylphenyl isocyanate, m-isobutylphenyl isocyanate, 
m-2-ethylhexylphenyl isocyanate, m-cyclohexylphenyl isocyanate, 
m-chlorophenyl isocyanate, p-chlorophenyl isocyanate, m-nitrophenyl 
isocyanate, p-nitrophenyl isocyanate. 
A urethane of the formula 
##STR3## 
in which R.sup.1 and R.sup.2 have the above mentioned meaning, can, of 
course, also be used instead of an optionally substituted nitrophenol and 
an optionally substituted aromatic isocyanate, which react in the reaction 
mixture accompanied by the formation of a urethane, the above urethane 
then being heated in the presence of a base to a temperature of 
approximately 100.degree.-250.degree. C. in tetramethylene sulphone as the 
reaction medium. 
Urethanes of the formula (III) are able to be prepared according to known 
processes, for example by the reaction of optionally substituted 
nitrophenols with isocyanates (Ind. Eng. Chem., Anal. Ed. 16, 304 (1944)) 
or by the reaction of optionally substituted nitrophenyl-chlorocarbonic 
acid esters with optionally substituted amines (Liebigs Ann. Chem. 562, 
205 (1949)). 
The starting products in the process according to the invention can be used 
in the ratio of 0.5 to 5 mol of aromatic isocyanate to 1 mol of 
nitrophenol, preferably in the ratio of 1 to 2 mols of aromatic isocyanate 
to 1 mol of nitrophenol. 
Basic inorganic or organic compounds may be mentioned as bases for the 
process according to the invention. 
As basic inorganic compounds, basically reacting compounds of alkali metals 
and alkaline earth metals may be mentioned, for example their hydroxides, 
carbonates or basically reacting salts of organic acids, such as the 
acetates, formates, benzoates or phthalates. 
As basic organic compounds, phenolates or substituted phenolates, such as 
nitrophenolates, of alkali metals, may be mentioned. In addition tertiary 
high-boiling amines and phosphines may be mentioned as basic organic 
compounds. Examples of the latter are 
N-methyl-bis(.beta.-hydroxyethyl-phenyl ether)-amine and 
tri-n-butyl-phosphine. 
Preferred bases for the process according to the invention are the 
carbonates or hydroxides of sodium or potassium. 
The base can be used in amounts of 0.5 to 50 mol %, preferably in amounts 
of 1 to 10 mol %, relative to the nitrophenol or nitrophenyl-N-phenyl 
urethane used. 
As reaction temperature for the process according to the invention a range 
of 100.degree. to 250.degree. C., preferably a range of 150.degree. to 
220.degree. C., may be mentioned. 
The nitro-diphenyl amine derivatives which can be prepared in the process 
according to the invention can be represented by the formula 
##STR4## 
in which R.sup.1 and R.sup.2 can be identical or different and denote 
hydrogen, alkyl, cycloalkyl, aryl, alkoxy, aryloxy, acyl, halogen, nitro 
or cyano. 
Examples which may be mentioned of compounds of formula (IV) are: 
2-nitro-diphenyl amine, 3-nitro-diphenyl amine, 4-nitro-diphenyl amine, 
2-nitro-4-methyl-diphenyl amine, 4-nitro-2-methyl-diphenyl amine, 
4-nitro-2-phenyl-diphenyl amine, 4-nitro-2-cyclohexyl-diphenyl amine, 
4-nitro-2-methoxy-diphenyl amine, 2-nitro-4-acetyl-diphenyl amine, 
2-nitro-4-acetyl-diphenyl amine, 2-nitro-4-chloro-diphenyl amine, 
4-nitro-2-cyano-diphenyl amine, 2,4-dinitro-diphenyl amine, 
2-nitro-4'-methyl-diphenyl amine, 4-nitro-4'-phenyl-diphenyl amine, 
4-nitro-2'-methoxy-diphenyl amine, 2-nitro-4'-acetyl-diphenyle amine, 
4-nitro-3'-methyl-diphenyl amine, 2,4'-dinitro-diphenyl amine, 
2-nitro-2',4-dimethyl-diphenyl amine, 4-nitro-2,4'-dichloro-diphenyl 
amine, 3-nitro-2,4'-dimethyl-diphenyl amine, 4-nitro-3'-chloro-diphenyl 
amine. 
The process according to the invention can be conducted in the following 
way: 
The optionally substituted nitrophenol is dissolved in tetramethylene 
sulphone (Sulfolan) and the basic compound is added. If the basic compound 
is added in the form of an aqueous solution, this water is subsequently 
removed by distillation. Then the mixture is heated to the desired 
temperature and the optionally substituted aromatic isocyanate is added 
dropwise whilst stirring vigorously. 
Carbon dioxide evolution begins which can end after half and hour or up to 
4 hours, depending on the amount of the starting mixture. Then the basic 
compound is neutralized by adding mineral acid. After filtering off any 
salts precipitated the majority of the Sulfolan is removed by 
distillation. The solid residue, which can still contain 1% to 5% by 
weight of Sulfolan, is purified further by means of conventional 
processing methods, for example by means of recrystallization from xylene. 
It is possible to free the mother liquor of the recrystallization step 
from solvent and to incorporate the residue obtained from this in a new 
starting mixture for the process according to the invention. 
If, in the variant of the process, according to the invention, the starting 
compound is an optionally substituted nitrophenyl-N-phenyl urethane of 
formula (III), this can be dissolved in the Sulfolan and the alkaline 
compound is added. Then this reaction mixture is heated to the desired 
reaction temperature and the same procedure is followed as above. 
The purified products thus obtained are of a purity of more than 96%. The 
process according to the invention has the following advantages: 
1. No solid alkali metal 4-nitrophenolate is precipitated from the reaction 
mixture. Thus the process according to the invention is not dangerous, in 
contrast to the process of U.S. Pat. No. 3,847,990. 
2. The triphenyl isocyanurate to be expected in small quantities as 
secondary product, which can be formed from the aromatic isocyanate, 
remains, as opposed to the nitrophenol process, in solution, so that 
incrustation of the reaction apparatus is avoided. 
3. The yield of worked-up, pure nitrodiphenyl amine is approximately up to 
10% higher in the process according to the invention than in the process 
of the named U.S. Pat. No. 
4. The reaction speed is approx. 3 times' greater in the Sulfolan used 
according to the invention than in nitrobenzene, although the conditions 
are otherwise the same. At the same time higher concentrations of the 
reaction components can be used in the process when using Sulfolan than 
when using nitrobenzene. This produces a considerable increase in the 
space/time yield. 
It is surprising that by the use, according to the invention, of 
tetramethylene sulphone as the reaction medium, a process was able to be 
achieved which is satisfactory as far as safety of operation is concerned 
and which, in addition, produces a higher yield than that of the prior 
art. This is all the more surprising because of the high boiling point of 
tetramethylene sulphone and its high polarity caused one to expect 
difficult separation from the reaction product. 
Nitrodiphenyl amine and its derivatives are important intermediate products 
for the synthesis of p-alkylamino-diphenyl amine and 
p-dialkylamino-diphenyl amine, which, as stabilizers, almost completely 
prevent the oxidation (by oxygen) of natural and synthetic rubbers. 
Thus, for example, p-nitrodiphenylamine is partly reduced by electrolysis 
in a nearly neutral reaction medium consisting of acetic acid, sodium 
acetate, ethanol and ethyl acetate to p-nitroso diphenylamine 
(Houben-Weyl, Methoden der Organischen Chemie [methods in organic 
chemistry], 4th ed., Vol. X/1, part 1, page 1064, Georg Thieme Verlag, 
Stuttgart (1971)) which itself is reacted with 2-octanone and hydrogen in 
one step at elevated temperatures (50.degree. to 150.degree. C.) in the 
presence of catalysts such as platinum, Raney nickel or copper 
oxide-chromium oxide combinations to yield 
N-phenyl-N'-2-octyl-p-phenylenediamine as a valuable stabilizer for 
natural and synthetic rubbers (U.S. Pat. No. 3,163,616).

EXAMPLE 1 
150.2 g (1.08 mol) p-nitrophenol are dissolved in 750 ml Sulfolan and 5.52 
g (0.04 mol) potassium carbonate in 10 ml water are added. The water is 
distilled off in vacuo and at 250.degree. C. 129.7 g (1.09 mol) phenyl 
isocyanate are added dropwise over a period of 1 hour while stirring 
vigorously. After a further 1.5 hours approximately 24 l of CO.sub.2 have 
evolved. At 150.degree. C. the reaction mixture is reacted with 2.2 ml of 
concentrated H.sub.2 SO.sub.4, stirred again briefly and filtered over a 
glass-sintering suction filter. The Sulfolan is almost completely 
distilled off in a film evaporator at 1 to 2 mm Hg. 
234 g crude product remain, which are recrystallized from 620 ml xylene. 
185 g (86.5% of the theoretical yield) 4-nitro-diphenyl amine are 
obtained. M.P.: 129.degree. to 130.degree. C. 
EXAMPLE 2 
The same method is followed as in Example 1, but using: 
270.4 g (1.94 mol) p-nitrophenol, 
750 ml Sulfolan, 9.94 g (0.072 mol) potassium carbonate, 214 g (189 mol) 
phenyl isocyanate, 
4 ml concentrated sulphuric acid. 
182.8 g=85.4% of the theoretical yield of 4-nitro-diphenyl amine were 
obtained; m.p.:130.degree. to 131.degree. C. 
EXAMPLE 3 
Same procedure as in Example 2, but with 8.1 g (0.14 mol) potassium 
hydroxide. 188.1 g=87.9% of the theoretical yield of 4-nitro-diphenyl 
amine were able to be isolated: m.p.: 129.degree. to 130.degree. C. 
EXAMPLE 4 
The same method is followed as described in Example 1, except that the 
process is conducted using 167.4 g (1.09 mol) m-chlorophenyl isocyanate. 
165.3 g (66.5% of the theoretical yeild) of 4-nitro-3'-chloro-diphenyl 
amine are obtained. M.p.: 127.degree. to 128.degree. C. 
EXAMPLE 5 
The same method is followed as described in Example 1, except that the 
process is conducted using 167.4 g (1.09 mol)p-chlorophenyl isocyanate. 
159 g (64% of the theoretical yield) of 4-nitro-4'-chloro-diphenyl amine 
are obtained. M.p.: 179.degree. to 180.degree. C. 
EXAMPLE 6 
The same method is followed as described in Example 1, except that the 
process is conducted using 145.1 g (1.09 mol) m-methyl phenyl isocyanate. 
182.6 g (80.1% of the theoretical yield) of 4-nitro-3'-methyl-diphenyl 
amine are obtained M.p.: 129.degree. to 130.degree. C.