New 2-aminonitropyridine derivatives are disclosed of the formula: ##STR1## wherein the nitro group is in the 3- or 5-position and X represents hydrogen, an alkoxy group with 1 to 3 C atoms or an unsubstituted or alkyl- or hydroxyalkyl substituted amino group, the alkyl portion of which has 1 to 3 C atoms PA1 R.sub.1 and R.sub.2 may be the same or different and represent hydrogen, divalent alkyl- with 1 to 3 C atoms, divalent cyclopropyl- or divalent alkenyl with 1 to 3 C atoms, phenylene- or divalent pyrrol and PA1 Y and Z may be the same or different and represent hydrogen, hydroxyl- or amino group of the formula II: ##STR2## wherein R.sub.3 and R.sub.4 may be the same or different and represent hydrogen, an unsubstituted alkyl or alkyl with 1 to 3 C atoms, substituted at any position by hydroxy or amino with 1 to 3 C atoms, with the proviso that whenever X represents hydrogen, then R.sub.1 and R.sub.2 cannot both be hydrogen, and R.sub.1 is not hydrogen, R.sub.2 is not divalent alkyl-, pheneylene-, divalent cycloalkyl- or divalent heterocyclic group and R.sub.3 and R.sub.4 do not both signify hydrogen. The compounds are produced by conversion of halogen-, alkoxy- or sulfonic acid substituted nitropyridines with the corresponding amines. These compounds are pharmaceutical intermediates and nontoxic coupler components in oxidation hair dyes.

The invention relates to new nitropyridine derivatives which in the 
2-position have a primary, secondary or tertiary amino group. On the one 
hand, these compounds represent important pharmaceutical intermediate 
products, and unexpectedly, on the other hand they may be used as nontoxic 
coupler components in oxidation hair dyes and when so used they result in 
brilliant shades of color. 
The nitropyridine derivatives of the invention are represented by the 
structural formula I: 
##STR3## 
wherein 
the nitro group is in the 3- or 5-position and X represents hydrogen, 
alkoxy of 1 to 3 C atoms or unsubstituted amino or alkyl- or hydroxyalkyl 
substituted amino, the alkyl portion thereof having from 1 to 3 C atoms, 
and 
R.sub.1 and R.sub.2 may be the same or different and represent hydrogen, 
divalent alkyl-, divalent cyclopropyl- or divalent alkenyl of 1 to 3 C 
atoms, divalent phenyl- or divalent pyrrol which is in turn substituted by 
Y and Z, and 
Y and Z may be the same or different and represent hydrogen, hydroxyl- or 
amino of the formula II: 
##STR4## 
wherein 
R.sub.3 and R.sub.4 may be the same or different and represent hydrogen, 
unsubstituted alkyl, alkyl or substituted at any position with a hydroxyl- 
or amino, the alkyl containing 1 to 3 C atoms, 
with the proviso that whenever X represents hydrogen; then R.sub.1 and 
R.sub.2 do not both signify hydrogen, R.sub.1 does not signify hydrogen, 
and R.sub.2 does not signify the residue of phenyl-, cyclopropyl- or 
pyrrolo; and R.sub.3 and R.sub.4 do not both signify hydrogen. 
By the expression "divalent alkyl, divalent cyclopropyl or divalent alkenyl 
of 1 to 3 C atoms, divalent phenyl or divalent pyrrolo which in turn is 
substituted by Y and Z" is meant the divalent organic group which is 
obtained as a result of the stated monovalent organic group having lost an 
additional hydrogen and which, as a result, has an additional valence 
available for bonding to another substituent, viz. to Y and Z, 
respectively. 
For example, when R.sub.1 or R.sub.2 is the divalent group --CH.sub.2 
--(methylene), it may be considered to be a residue of the methyl group 
--CH.sub.3 ; that is, a methyl group which has lost an additional hydrogen 
to become a divalent organic group and which is capable of substitution by 
Y and Z. 
The nitropyridine derivatives of the invention are largely stable at 
ambient temperature against oxidation by the oxygen present in the air. 
They are soluble in water or in a mixture composed of water and a 
solvating agent such as, for example, ethyl alcohol. 
In the compounds according to the invention, the nitro group may be present 
in either the 3- or 5-position. 
X may represent hydrogen, a methoxy-, ethoxy-, propoxy-, i-propoxy group or 
an unsubstituted or alkyl- or hydroxyalkyl substituted amino group. 
The amino group in the 2-position may be primary, secondary or tertiary 
amino. Whenever this amino group is secondary or tertiary, then the 
substituents R.sub.1 and R.sub.2 may be the same or different and may 
signify hydrogen, the residues of alkyl such as, for example, methylene-, 
ethylene-, propylene-, i-propylene, or phenylene- or heterocyclic group 
such as, for example, a pyrrolo group bonded to a C atom and, in turn 
substituted by Y and Z. These substituents on their part are substituted 
by the Y and Z substituents. Y and Z may be the same or different and may 
be either hydrogen, hydroxyl- or amino. Examples of such substituents are 
the following groups: hydroxymethyl-, hydroxyethyl- or hydroxypropyl-. The 
amino group is represented by the structural formula: 
##STR5## 
in which R.sub.3 and R.sub.4 are the same or different and represent 
hydrogen, an unsubstituted alkyl with 1 to 3 C atoms or alkyl which is 
hydroxyl- or amine substituted at any given position. 
Examples of this amino group are the unsubstituted amino group itself as 
well as methyl-, dimethyl-, ethyl-, diethyl-, methylethyl-, propyl-, 
i-propyl-, dipropyl-, diisopropyl-, aminomethyl-, aminoethyl-, 
aminopropyl-, bis-aminomethyl-, bis-aminoethyl-, bis-amino-propyl-, 
hydroxymethyl-, dihydroxymethyl-, hydroxyethyl-, dihydroxyethyl-, 
hydroxypropyl-, dihydroxypropylamino-, or pyrrol- or methylpyrrol. 
However, whenever X is hydrogen, then the further limitation applies that 
R.sub.1 and R.sub.2 are not both hydrogen, R.sub.3 and R.sub.4 are not 
both hydrogen, and further that R.sub.1 is not hydrogen and R.sub.2 is not 
alkyl-, alkoxy-, phenyl-, cyclopropyl- or heterocyclic. 
The nitropyridine derivatives of the invention are produced by conversion 
of the corresponding nitropyridine which in the 2-position has a group 
substitutable by amines with the designated amines. Such substitutable 
groups are alkoxy or sulfonic acid groups or halogens. The conversion 
reaction is carried out at 20.degree.-100.degree. C. 
These starting nitropyridines are obtained in a preferred manner by 
nitration of the corresponding alkoxy or halogen alkoxy pyridines as 
described, for example, in the German patent application P No. 33 08 449.1 
and the European application EP No. 0 102 652 Al. The conversion of these 
nitropyridines with the amines takes place in the course of a reaction 
requiring several hours of contacting the reactants with each other at 
ambient pressure and temperatures in the range of 20.degree. to 
100.degree. C. At the same time, the reactants are intensively mixed with 
one another in a polar solvent such as, for example, water or in an 
alcohol. They are either dissolved in this reaction medium or are entirely 
or partially suspended or emulsified. 
In general, the nitropyridine starting materials are prepared by nitration 
of halo-, alkoxy-, or haloalkoxy-pyridines. These reactions are described 
in "Pyridine And Its Derivatives" Part Two, pages 470-478 by E. 
Klingsberg, 1961, Interscience Publishers, Inc., N.Y.C., the disclosure of 
which is relied on and incorporated herein by reference. 
The reactants may be used in equimolar quantities. For achieving a better 
yield however, it is advisable to use the less expensive aminocomponent in 
excess. 
The end products obtained are insoluble in cold water and thus they may be 
separated in a cooled, aqueous reaction medium or in a reaction medium 
mixed with water.

The following examples serve to illustrate the invention without limiting 
it in any way. 
EXAMPLE 1 
2-(Dimethylaminoethyleneamino)-5-nitropyridine 
A mixture of 154 g (1 mole) of 2-methoxy-5-nitropyridine, 105.8 g (1.2 
mole) or 110 g of 95% N,N-dimethylethylenediamine as well as 200 ml of 
water is heated to reflux in the course of hours with stirring. 
Subsequently, an additional 100 ml of water are added and after cooling 
the crystallized product is filtered off with suction, washed with water 
and then dried. The yellow colored substance has a melting point of 
94.degree.-5.degree. C. and is obtained in a yield of 89% of theory. 
EXAMPLE 2 2-(N-hydroxyethyl-N-methylamino)-5-nitropyridine 
A mixture of 154 g (1 mole) of 2-methoxy-5-nitropyridine, 90 g (1.2 mole) 
of N-methylethanolamine and 200 ml of water is heated to reflux for 8 
hours with stirring. After cooling, the solid substance is filtered off 
with suction, washed with water and is then dried in the vacuum. An 
intensively yellow dyed product is obtained with a melting point of 
83.degree.-4.degree. C. and in a yield of 78% of theory. 
EXAMPLE 3 
2-(dimethylaminotrimethyleneamino)-5-nitropyridine 
A mixture of 154 g (1 mole) of 2-methoxy-5-nitropyridine, 132.8 (1.3 mole) 
of N,N-dimethyltrimethylenediamine as well as 200 ml of water is heated to 
reflux for 6 hours with stirring. After cooling off, the crystallized 
product is filtered off with suction. It is washed 3 times with 100 ml of 
water and dried. An intensively yellow colored powder with a melting point 
of 73.degree.-4.degree. C. is obtained in a yield of 83% of theory. 
EXAMPLE 4 
2-(hydroxyethylaminoethyleneamino)-5-nitropyridine 
A mixture of 154 g (1 mole) of 2-methoxy-5-nitropyridine, 125 g (1.2 mole) 
of N-hydroxyethylethylenediamine and 200 ml of water is heated to reflux 
for 6 hours with stirring. After that, an additional 100 ml of water are 
added and the crystallized product is filtered off with suction, washed 
with water and then dried. An intensively yellow colored compound is 
obtained with a melting point of 146.degree.-7.degree. C., in a yield of 
76% of theory. 
EXAMPLE 5 
2-(1-methyl-1H-pyrrol-2-yl-ethaneamino)-5-nitropyridine 
To a stirred mixture of 158.6 (1 mole) of 2-chloro-5-nitropyridine and 200 
ml of methanol, a mixture of 136.6 g (1.1 mole) of 
1-methyl-1H-pyrrol-2-yl-ethaneamine and 121.4 g (1.2 mole) of 
triethylamine is added drop by drop in the course of 1 hour. After 6 
hours, 300 ml of water are added, the crystallized product is filtered off 
by suction, washed with water and dried. A yellow colored substance with a 
melting point of 141.degree.-2.degree. C. is obtained in a yield of 98% of 
theory. 
EXAMPLE 6 
2-(1,5-dimethyl-1H-pyrrol-2-yl-methaneamino)-5-nitropyridine 
To a stirred mixture of 158.6 g (1 mole) of 2-chloro-5-nitropyridine and 
200 ml of methanol, a mixture of 136.6 g (1.1 mole) 
1,5-dimethyl-1H-pyrrol-2-yl-methaneamine and 121.4 g (1.2 mole) of 
triethylamine are added drop by drop in the course of 2 hours, at the 
same time, the temperature is kept at 45.degree.-50.degree. C. by cooling. 
After 8 hours, 300 ml of water are added, the precipitated product is 
filtered off by suction, the suction cake is washed with ample water and 
is dried at 50.degree. C. A yellow colored compound with a melting point 
of 163.degree.-5.degree. C. is obtained in a yield of 96% of theory. 
EXAMPLE 7 
2-(2-hydroxyphenylamino)-6-methoxy-3-nitropyridine 
A mixture of 188.6 (1 mole) of 2-chloro-6-methoxy-3-nitropyridine and 262 g 
(2.4 mole) of o-aminophenol is heated in 500 ml of methanol gradually up 
to reflux. After heating for a period of 2 hours, the mixture is filtered 
off hot by suction; the suction cake is washed with enough methanol until 
the filtrate runs off practically colorless and is dried. Bright red 
crystals with a melting point of 206.degree.-7.degree. C. are obtained in 
a yield of 94.6% of theory. 
EXAMPLE 8 
2-(dimethylaminopropylamino)-6-methoxy-3-nitropyridine hydrochloride 
To a suspension of 188.6 g (1 mole) of 2-chloro-6-methoxy-3-nitropyridine 
in 300 ml of methanol, 265.2 g (2.6 mole) of N,N-dimethylaminopropylene 
amine are added drop by drop while stirring and cooling. The mixture is 
stirred once more for another 2 hours after the addition of amine and then 
is poured into 300 ml of water, whereby the substance is obtained as a 
yellow oil. The oil is separated and is mixed twice more with water until 
the wash water layer appears only weakly yellow in color. It is then 
absorbed in isopropanol and is precipitated as the HCl salt by the 
introduction of HCl-gas. The salt is filtered off by suction and is washed 
with isopropanol and dried. The product is obtained in the form of 
luminously yellow colored crystalls with a melting point of 186.degree. C. 
and in a yield of 76% of theory. 
EXAMPLE 9 
6-methoxy-3-nitro-2-n-propylaminopyridine 
Into a stirred and cooled (water bath) mixture of 188.6 g (1 mole) of 
2-chloro-6-methoxy-3-nitropyridine and 200 ml of isopropanol, 141.9 g (2.4 
mole) of n-propylamine are added drop by drop in the course of about 3 
hours at a maximum temperature of 25.degree. C. Stirring is continued 
overnight and then 1000 ml of water are added; the precipitated product is 
filtered off by suction, washed with water and then dried. The product 
obtained thereby is intensively yellow colored with a melting point of 
69.degree.-70.degree. C. in a yield of 98% of theory. 
EXAMPLE 10 
2-(2-hydroxyethylamino)-6-methoxy-3-nitropyridine 
To a mixture of 188.6 g (1 mole) of 2-chloro-6-methoxy-3-nitropyridine with 
350 ml of isopropanol, 83.5 g (1.4 mole) of aminoethanol are added drop by 
drop with cooling while stirring and maintaining a temperature of 
25.degree.-30.degree. C. After the addition, the reaction mixture is 
continued to be stirred for another hour at a maximum of 30.degree. and 
then 47.5 ml of 50% caustic soda solution are added drop by drop over the 
course of about 2 hours at a maximum temperature of 30.degree. C. After 6 
hours of stirring, 500 ml of water are stirred in and the product is 
filtered off with suction, is then washed sufficiently with water and is 
then dried. The compound is obtained in the form of a yellow powder with a 
melting point of 121.degree.-2.degree. C. and in a yield of 95.5% of 
theory. 
EXAMPLE 11 
2-(3-hydroxyphenylamino)-6-methoxy-3-nitropyridine 
A mixture of 188.6 g (1 mole) of 2-chloro-6-methoxy-3-nitropyridine and 262 
g (2.4 mole) of m-aminophenol is heated in 500 ml of methanol gradually up 
to the reflux. After 2 hours of heating time, the mixture is cooled down, 
1000 ml of water are stirred in, the crystals formed are filtered off by 
suction and are thoroughly washed with water. The compound is obtained in 
the form of orange colored crystals with a melting point of 
156.degree.-8.degree. C. and in a yield of 97.7% of theory. 
EXAMPLE 12 
2,6-bis-(2-hydroxyethylamino)-3-nitro-pyridine 
To a mixture of 188.5 g (1 mole) of 2-chloro-6-methoxy-3-nitropyridine and 
500 ml of isopropanol, 220 g (3.6 mole) of monoethanolamine are added drop 
by drop during approximately 60 minutes. After the exothermal reaction has 
subsided, 200 ml of water are added and the resulting mixture is then 
heated for 10 hours under reflux. Then the isopropanol is distilled off, 
the excess base is neutralized by the addition of dry ice. During the 
cooling off to 5.degree. C., the compound is precipitated, it is filtered 
off by suction, washed again with ice water and dried. The yield of 
intensively yellow colored product with a melting point of 
130.degree.-1.degree. C. amounts to 94% of theory. 
EXAMPLE 13 
6-ethoxy-2-methylamino-3-nitropyridine 
In a stirred mixture consisting of 202.6 g (1 mole) of 
2-chlor-6-ethoxy-3-nitropyridine and 500 ml of methanol, 202 g (2.6 mole) 
of a 40% monomethylamine solution is added drop by drop while stirring in 
the course of 90 minutes and at 25.degree.-30.degree. C. sump temperature. 
Subsequently, the mixture is again stirred for yet another 5 hours, is 
reacted with 650 ml of water, and then the product is filtered off by 
suction, is washed again with ample water and dried. Melting point 
106.degree.-7.degree. C., Yield: 183.2 g (92.9% of theory). 
The compounds of the present invention can be used as nontoxic coupler 
components for human hair dyeing. When used in this way, they are combined 
with conventional developer compounds, such as a primary aromatic amine 
(e.g. p-phenylene diamine, p-aminophenol) which are known for this purpose 
in the hair dyeing art. Usually, the coupler compounds are used in the 
amount of 1-2% by weight in a hair dyeing composition, although the exact 
amount may vary. Methods and techniques for hair dyeing that are known in 
the art may be used in connection with the 2-aminopyridine derivatives of 
this invention. 
Further variations and modifications of the present invention will become 
apparent to those skilled in the art from a reading of the foregoing and 
are intended to be encompassed by the claims appended hereto. 
The German priority application P. No. 33 34 029.3 is relied on and 
incorporated herein by reference.