Process of preparing diaminopyridine compounds

Abstract

A process for preparing diaminopyridines of the formula ##STR1## where one of the two radicals X.sup.1 and X.sup.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen or nitro and the other is cyano,R.sup.1 is hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,R.sup.2 and R.sup.3 are each hydrogen, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy,R.sup.4 is hydrogen or C.sub.1 -C.sub.4 -alkyl, andR.sup.5 is optionally substituted C.sub.1 -C.sub.10 -alkyl, C.sub.3 -C.sub.4 -alkenyl or C.sub.5 -C.sub.7 -cycloalkyl,by reacting dichloropyridines of the formula ##STR2## in a first step with an amine of the formula R.sup.5 -NH.sub.2 at from 10.degree. to 80.degree. C. in the presence of a base and of an inert organic diluent and/or water, then removing the diluent and thereafter, with or without prior intermediate isolation of the reaction product, comprises carrying out the second step in a melt at from 90.degree. to 165.degree. C. and at a pH from 3.5 to 6.5 using from 1.3 to 3 mol of aniline IV are used per mole of dichloropyridine II.

Description

This application is a 371 of PCT/EP93/00538, filed Mar. 10, 1993.

The present invention relates to a novel process for preparing 2,6-diaminocyanopyridines by reacting the 2,6-dichloro compounds with amines.

U.S. Pat. No. 3,853,895 discloses the preparation of 2,6-diaminopyridines. However, the manner of preparation described therein is unsatisfactory, since large amounts of amine are required and, what is more, the target products are obtained only in a low yield.

Furthermore, DE-A-2 260 827, DE-A-2 916 319 and U.S. application Ser. No. 3,980,659 describe the preparation of 2,6-diaminocyanopyridines using the corresponding dichloro or aminomonochloro compounds as starting materials.

It is an object of the present invention to provide a novel process for preparing 2,6-diaminocyanopyridines which likewise starts from the 2,6-dichloro compounds and gives the target products in a simple manner and in high yield and purity.

We have found that this object is achieved in an advantageous manner by a process for preparing diaminopyridines of the formula I ##STR3## where

one of the two radicals X.sup.1 and X.sup.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen or nitro and the other is cyano,

R.sup.1 is hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,

R.sup.2 and R.sup.3 are each independently of one another hydrogen, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy,

R.sup.4 is hydrogen or C.sub.1 -C.sub.4 -alkyl, and

R.sup.5 is C.sub.1 -C.sub.10 -alkyl which may be interrupted by from 1 to 3 oxygen atoms in ether function and is optionally hydroxyl-, C.sub.1 -C.sub.4 -alkanoyloxy-, phenoxy-, phenyl-, tetrahydrofuranyl- or tetrahydropyranyl-substituted, C.sub.3 -C.sub.4 -alkenyl or C.sub.5 -C.sub.7 -cycloalkyl,

by reacting dichloropyridines of the formula II ##STR4## where R.sup.1 and X.sup.1 are each as defined above, with amines by reacting in a first step a dichloropyridine of the formula II with an amine of the formula III R.sup.5 --NH.sub.2 (III) where R.sup.5 is as defined above, at from 10.degree. to 80.degree. C. in the presence of a base and of an inert organic diluent and/or water, then removing the diluent and thereafter, with or without prior intermediate isolation of the reaction product, reacting it in a second step with an aniline of the formula IV ##STR5## where R.sup.2, R.sup.3 and R.sup.4 are each as defined above, which comprises carrying out the second step in a melt at from 90.degree. to 165.degree. C. and at a pH from 3.5 to 6.5 using 1.3 to 3 mol of aniline IV per mole of dichloropyridine II.

Any alkyl appearing in the abovementioned formulae may be not only straight-chain but also branched.

R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, X.sup.1 and X.sup.2 are each for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl or sec-butyl.

R.sup.4 may also be for example methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or sec-butoxy.

R.sup.5 may also be for example pentyl, isopentyl, neopentyl, tert-pentyl, hexyl, 2-methylpentyl, heptyl, octyl, 2-ethylhexyl, isooctyl, nonyl, isononyl, decyl, benzyl, 1- or 2-phenylethyl, 2- or 3-phenylpropyl, 3-phenylprop-2-yl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 3- hydroxyprop-2-yl, 2-hydroxybutyl, 4-hydroxybutyl, 5-hydroxypentyl, 6-hydroxyhexyl, 2-methoxyethyl, 2-ethoxyethyl, 2-propoxyethyl, 2-isopropoxyethyl, 2-butoxyethyl, 2- or 3-methoxypropyl, 2- or 3-ethoxypropyl, 2- or 3-propoxypropyl, 2- or 3-butoxypropyl, 2- or 4-methoxybutyl, 2- or 4-ethoxybutyl, 2- or 4-propoxybutyl, 2- or 4-butoxybutyl, 3,6-dioxaheptyl, 3,6-dioxaoctyl, 4,8-dioxanonly, 3,7-dioxaoctyl, 3,7-dioxanonyl, 4,7-dioxaoctyl, 4,7-dioxanonyl, 4,8-dioxadecyl, 3,6,9-trioxadecyl, 3,6,9-trioxaundecyl, 4,8,12-trioxatridecyl, 2-phenoxyethyl, 2-phenoxypropyl, 3-phenoxypropyl, 2-phenoxybutyl, 4-phenoxybutyl, 5-phenoxypentyl, 6-phenoxyhexyl, 5-hydroxy-3-oxapentyl, 8-hydroxy-4-oxaoctyl, 6 -phenoxy-4-oxahexyl, 2-formyloxyethyl, 2-acetyloxyethyl, 2-propionyloxyethyl, 2- or 3-formyloxypropyl, 2- or 3-acetyloxypropyl, 2- or 3-propionyloxypropyl, 2- or 4-formyloxybutyl, 2- or 4-acetyloxybutyl, 2- or 4-propionyloxybutyl, 2-(tetrahydropyran-4-yl)ethyl, 2- or 3-(tetrahydropyran-4-yl)-propyl, 2- or 4-(tetrahydropyran-4-yl)butyl, prop-2-en-1-yl, but-2-en-1-yl, 2-methylprop-2-en-1-yl, cyclo-pentyl, cyclohexyl or cycloheptyl.

X.sup.1 and X.sup.2 may each also be example fluorine, chlorine and bromine.

Preference is given to a process for preparing diaminopyridines of the formula I where X.sup.1 is hydrogen and X.sup.2 is cyano.

Further preference is given to a process for preparing diaminopyridines of the formula I where R.sup.1 is methyl.

Further preference is given to a process for preparing diaminopyridines of the formula I where R.sup.2, R.sup.3 and R.sup.4 are each hydrogen.

Further preference is given to a process for preparing diaminopyridines of the formula I where R.sup.2 is methyl or methoxy and R.sup.3 and R.sup.4 are each hydrogen or methyl or where R.sup.2 and R.sup.3 are each methyl and R.sup.4 is hydrogen.

Further preference is given to a process for preparing diaminopyridines of the formula I where R.sup.5 is C.sub.1 -C.sub.8 -alkyl which may be interrupted by 1 or 2 oxygen atoms in ether function and is optionally hydroxyl- or phenyl-substituted, or allyl.

In the process of the invention, the first step (step 1) is carried out in the presence of an inert organic diluent and/or water. Suitable diluents are in particular those which are either completely immiscible with water or which are miscible with water only to a limited extent. Examples are isobutanol, toluene, o-, m- or p-xylene, ethylbenzene and mixtures thereof. The use of isobutanol, toluene or xylene is preferred.

Suitable bases for use in the first step are for example alkali metal carbonates or bicarbonates, such as sodium or potassium carbonate or bicarbonate. The use of sodium carbonate is preferred.

The second step (step 2) of the novel process is carried out at a pH from 3.5 to 6.5, preferably from 4 to 5.5. Since it is difficult to determine the pH in a melt, it is advisable, every time the pH of the melt is to be determined, to add a sample of the melt to water and to determine the pH of the aqueous system. The above-mentioned pH can be set not only with organic but also with inorganic acids. Suitable acids are for example sulfuric acid, hydrochloric acid and p-toluenesulfonic acid. The use of p-toluenesulfonic acid is preferred.

In the process of the invention the molar ratio of dichloropyridine II:amine III is from 1:1.03 to 1:1.5, preferably from 1:1.05 to 1:1.25, and the molar ratio of dichloropyridine II:aniline IV is from 1:1.3 to 1:3, preferably from 1:1.5 to 1:3.

Per mole of dichloropyridine II it is customary to use in the first step from 1 to 2 mole equivalents, preferably from 1 to 1.3 mole equivalents, of a base.

Based on the weight of dichloropyridine II the amount of inert organic diluent used in the first step is in general from 10 to 150% by weight, preferably from 30 to 100% by weight.

To initiate the second-stage reaction it is in general sufficient to employ catalytic amounts of an acid.

The process of the invention is conveniently carried out by starting in the first step with an initial charge of dichloropyridine II and inert organic diluent and raising the temperature with stirring initially to 10.degree.-80.degree. C., preferably 45.degree.-70.degree. C., in particular 45.degree.-60.degree. C. To this mixture is added at the stated temperature the amine III and then the base. Thereafter the reaction is carried out at the stated temperature. When the reaction has ended, which in general takes from 12 to 24 hours, the reaction mixture can be acidified, diluted with water and then freed of the diluent-water mixture. This can be done for example by distillation. The diluent thus recovered can be recycled into the process.

In the first step the diaminopyridines of the formula I are obtained as isomer mixtures consisting predominantly of a product of the formula I where X.sup.1 is hydrogen and X.sup.2 is cyano and to a minor proportion of a product of the formula I where X.sup.1 is cyano and X.sup.2 is hydrogen when the reaction is carried out at up to 55.degree. C. for about 12 hours.

The predominant diaminopyridine I (X.sup.1 =H, X.sup.2 =CN) is preferably isolated in a practically isomer-free state before the diluent is separated off and the second step is started. This can be done for instance by filtering off since, for example if toluene is used as diluent, the product in question is in general in the form of a precipitate.

To prepare those diaminopyridines of the formula I where R.sup.5 is an alkyl radical with a hydroxyl group, it is advisable in some cases to start not from the corresponding hydroxyalkylamines III but from their esterified compounds (C.sub.1 -C.sub.4 -alkanoyloxyalkyl compounds). Afterwards the alkanoyl group can be re-eliminated by hydrolysis.

By adding acid and aniline IV to the melt resulting from the removal of the diluent it is then possible to form the diaminopyridines I in the second step. The second reaction step is in general carried out at from 90.degree. to 165.degree. C., preferably at from 125.degree. to 140.degree. C. After the reaction has ended, which in general takes from 8 to 20 hours, the product is worked up.

This can be done in a conventional manner. For example, the reaction mixture can be diluted with water and isobutanol and be neutralized with a base, for example sodium hydroxide solution. Thereafter the water, the isobutanol and the excess aniline IV are distilled off under atmospheric pressure. The remaining aniline IV can be removed from the reaction mixture by distillation under reduced pressure. It is possible to recycle the aniline IV back into the reaction.

The resulting diaminopyridine of the formula I can either be further used in that form or be subjected to a reprecipitation. For this it is dissolved in concentrated hydrochloric acid and then reprecipitated with sodium hydroxide solution.

The process of the invention gives the diaminopyridines of the formula I in a simple manner and in high purity, in particular high isomer purity, and yield.

The diaminopyridines of the formula I are useful intermediates, in particular coupling components (X.sup.1 /X.sup.2 =H, CN), for the synthesis of dyes.

The Examples which follow illustrate the invention.

EXAMPLE 1

900 ml of isobutanol were mixed at room temperature with a mixture of 935 g of 2,6-diaminopyridine and 180 ml of water. Then the temperature is raised to 40.degree. C. and a total of 479 g of 3-methoxypropylamine were added in the course of 1 hour with slight cooling. This was followed by stirring at from 40.degree. to 45.degree. C. for 2 hours, at which point 300 g of sodium carbonate were added. The mixture was stirred at from 40.degree. to 45.degree. C. for a further 2 hours and then the temperature was gradually raised to a maximum of 80.degree. C. until the reaction has ended. The inorganic salts were then dissolved by adding 1000 ml of water, the mixture was acidified with sulfuric acid to pH 1, and the lower, aqueous layer, which contained the excess of amine, was separated off. The organic phase was then adjusted to pH 4-5 and then the isobutanol was removed by distillation. At 125.degree. C. 1400 g of o-anisidine and 20 g of p-toluenesulfonic acid were added, and stirring was then continued at from 130.degree. to 135.degree. C. During the reaction the pH of a sample stirred into water/ methanol was monitored. The pH of the reaction mixture was maintained within the range from 4.5 to 5.5 by the regular addition of anhydrous sodium carbonate to the reaction mixture. A total of 216 g of sodium carbonate were required. Then the reaction mixture was heated at 155.degree. C. for 6 hours until the reaction has ended. The mixture was then cooled down to 110.degree.-115.degree. C., and 60 g of water were gradually added, as the result of which the reaction complex gave off carbon dioxide. After the evolution of carbon dioxide had ceased, the pH of the mixture was adjusted to 7-7.5 and the excess of o-anisidine was distilled off virtually quantitatively under reduced pressure. The residue was crystallized by adding a little ethylene diglycol monomethyl ether and, after precipitation with water, filtered off, washed and dried. Yield: 1460 g of product mixture of the formula ##STR6## in which the isomer ratio of product 1 (X.sup.1 =H/X.sup.2 =CN):product 2 (X.sup.1 =CN/X.sup.2 =H) was 75:25.

EXAMPLE 2

Step 1

374 g of 2,6-dichloro-3-cyano-4-methylpyridine were added to 1000 ml of 70% by weight aqueous ethylamine solution at not more than 30.degree. C. The mixture was stirred at from 15.degree. to 30.degree. C. for 3 hours, and then precipitated with ice, and the precipitate was filtered off, washed with water and dried. This gave a mixture of 2-chloro-3-cyano-4-methyl-6-ethylaminopyridine (about 290 g) and 2-ethylamino-3-cyano-4-methyl-6-chloropyridine (about 96 g), which had a melting point of from 90.degree. to 110.degree. C. This mixture was dissolved in 600 ml of hot toluene. Cooling brought down a grayish white product of formula ##STR7## It was isolated by filtering with suction. Yield: 220 g, melting point: 128.degree. C.

Step 2

Step 2 was carried out analogously to Example 1. The aniline derivative used was unsubstituted aniline.

This produced 270 g of a product of formula ##STR8## melting point: 96.degree. C.

EXAMPLE 3

Step 1

440 g of 2,6-dichloro-3-cyano-4-methylpyridine were suspended in a mixture of 1000 ml of toluene and 300 ml of water. 230 g of 3-methoxypropylamine were then added at from 36.degree. to 48.degree. C. with cooling over 1 hour and the mixture was subsequently stirred at from 45.degree. to 55.degree. C. for 2 hours. The 141 g of sodium carbonate were added over 20 min and the mixture was subsequently stirred at from 45.degree. to 55.degree. C. for 10 hours and at 75.degree. C. for a further 3 hours. It was then acidified with concentrated hydrochloric acid to about pH 1.5 and the bottom, aqueous layer was then separated off. This was followed by cooling to room temperature, followed by removal of the precipitated 2-chloro-3-cyano-4-methyl-6-(3-methoxypropylamino)-pyridine by filtration and isolation thereof as per Example 2.

This gave 370 g of a isomerically pure (3-cyano) product having a melting point of 106.degree. C.

Step 2

Step 2 was carried out analogously to Example 1. The aniline derivative used was o-anisidine.

This gave 507 g of a product of the formula ##STR9## melting point; 120.degree. C.

The same method gives the compounds of the formula ##STR10## listed in the following table:

__________________________________________________________________________Ex. No. L.sup.1 L.sup.2 L.sup.3 L.sup.4 L.sup.5 mp. [.degree.C.]__________________________________________________________________________4 H H H H C.sub.3 H.sub.6 OCH.sub.3 885 C.sub.3 H.sub.7 H H H C.sub.3 H.sub.6 OCH.sub.3 756 CH.sub.3 H H H C.sub.2 H.sub.4 OH 1407 CH.sub.3 H H H C.sub.4 H.sub.8 OH 688 CH.sub.3 H H H CH(CH.sub.3)CH.sub.2 OH9 CH.sub.3 H H H C.sub.2 H.sub.510 CH.sub.3 H H H C.sub.2 H.sub.4 OCH.sub.3 9811 CH.sub.3 H H H C.sub.3 H.sub.6 OC.sub.2 H.sub.512 CH.sub.3 H H H C.sub.3 H.sub.6 OCH(CH.sub.3).sub.213 CH.sub.3 H H H n-C.sub.3 H.sub.7 8514 CH.sub.3 H H H i-C.sub.3 H.sub.7 12515 CH.sub.3 H H H CH(CH.sub.3)C.sub.2 H.sub.516 CH.sub.3 H H H n-C.sub.4 H.sub.9 4517 CH.sub.3 H H H CH.sub.2 CHCH.sub.218 CH.sub.3 H H H C.sub.2 H.sub.4 OC.sub.2 H.sub.519 CH.sub.3 H H H C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH20 CH.sub.3 H H H n-C.sub.5 H.sub.1121 CH.sub.3 H H H ##STR11##22 CH.sub.3 H H H ##STR12##23 CH.sub.3 H H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin24 CH.sub.3 H H H CH.sub.2 C.sub.6 H.sub.525 CH.sub.3 H H H C.sub.2 H.sub.4 C.sub.6 H.sub.526 CH.sub.3 H H H CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.527 CH.sub.3 H H H ##STR13## 12028 CH.sub.3 H H H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH 4029 CH.sub.3 H H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.530 H H H OCH.sub.3 C.sub.3 H.sub.6 OCH.sub.3 7631 C.sub.3 H.sub.7 H H OCH.sub.3 C.sub.3 H.sub.6 OCH.sub.3 5532 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.4 OH33 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OH34 CH.sub.3 H H OCH.sub.3 CH(CH.sub.3)CH.sub.2 OH35 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.536 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.4 OCH.sub.337 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.5 8038 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OCH(CH.sub.3).sub.239 CH.sub.3 H H OCH.sub.3 n-C.sub.3 H.sub.7 8040 CH.sub.3 H H OCH.sub.3 i-C.sub.3 H.sub.7 15041 CH.sub.3 H H OCH.sub.3 CH(CH.sub.3)C.sub.2 H.sub.542 CH.sub.3 H H OCH.sub.3 n-C.sub.4 H.sub.943 CH.sub.3 H H OCH.sub.3 CH.sub.2 CHCH.sub.244 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.5 8645 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH46 CH.sub.3 H H OCH.sub.3 n-C.sub.5 H.sub.1147 CH.sub.3 H H OCH.sub.3 ##STR14##48 CH.sub.3 H H OCH.sub.3 ##STR15## 10149 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin50 CH.sub.3 H H OCH.sub.3 CH.sub.2 C.sub.6 H.sub.551 CH.sub.3 H H OCH.sub.3 C.sub.2 H.sub.4 C.sub.6 H.sub.552 CH.sub.3 H H OCH.sub.3 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.553 CH.sub.3 H H OCH.sub.3 ##STR16## 12054 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.8 OH55 CH.sub.3 H H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.556 H H OCH.sub.3 H C.sub.3 H.sub.6 OCH.sub.357 C.sub.3 H.sub.7 H OCH.sub.3 H C.sub.3 H.sub.6 OCH.sub.358 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.4 OH59 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OH60 CH.sub.3 H OCH.sub.3 H CH(CH.sub.3)CH.sub.2 OH61 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.562 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.4 OCH.sub.363 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OC.sub.2 H.sub.564 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OCH(CH.sub.3).sub.265 CH.sub.3 H OCH.sub.3 H n-C.sub.3 H.sub.766 CH.sub.3 H OCH.sub.3 H i-C.sub.3 H.sub.7 13567 CH.sub.3 H OCH.sub.3 H CH(CH.sub.3)C.sub.2 H.sub.568 CH.sub.3 H OCH.sub.3 H n-C.sub.4 H.sub.969 CH.sub.3 H OCH.sub.3 H CH.sub.2 CHCH.sub.270 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.4 OC.sub.2 H.sub.571 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH72 CH.sub.3 H OCH.sub.3 H n-C.sub.5 H.sub.1173 CH.sub.3 H OCH.sub.3 H ##STR17##74 CH.sub.3 H OCH.sub.3 H ##STR18##75 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin76 CH.sub.3 H OCH.sub.3 H CH.sub.2 C.sub.6 H.sub.577 CH.sub.3 H OCH.sub.3 H C.sub.2 H.sub.4 C.sub.6 H.sub.578 CH.sub.3 H OCH.sub.3 H CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.579 CH.sub.3 H OCH.sub.3 H ##STR19##80 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH81 CH.sub.3 H OCH.sub.3 H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.582 H OCH.sub.3 H H C.sub.3 H.sub.6 OCH.sub.383 C.sub.3 H.sub.7 OCH.sub.3 H H C.sub.3 H.sub.6 OCH.sub.384 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.4 OH85 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OH86 CH.sub.3 OCH.sub.3 H H CH(CH.sub.3)CH.sub.2 OH87 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.588 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.4 OCH.sub.389 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.590 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin91 CH.sub.3 OCH.sub.3 H H n-C.sub.3 H.sub.792 CH.sub.3 OCH.sub.3 H H i-C.sub.3 H.sub.793 CH.sub.3 OCH.sub.3 H H CH(CH.sub.3)C.sub.2 H.sub.594 CH.sub.3 OCH.sub.3 H H n-C.sub.4 H.sub.995 CH.sub.3 OCH.sub.3 H H CH.sub.2 CHCH.sub.296 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.4 OC.sub.2 H.sub.597 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.4L OC.sub.2 H.sub.4 OH98 CH.sub.3 OCH.sub.3 H H n-C.sub.5 H.sub.1199 CH.sub.3 OCH.sub.3 H H ##STR20##100 CH.sub.3 OCH.sub.3 H H ##STR21##101 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3102 CH.sub.3 OCH.sub.3 H H CH.sub.2 C.sub.6 H.sub.5103 CH.sub.3 OCH.sub.3 H H C.sub.2 H.sub.4L C.sub.6 H.sub.5104 CH.sub.3 OCH.sub.3 H H CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5105 CH.sub.3 O H CH.sub.3 ##STR22##106 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH107 CH.sub.3 OCH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5108 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OCH.sub.3 86109 C.sub.3 H.sub.7 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OCH.sub.3110 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub.4 OH111 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OH112 CH.sub.3 CH.sub.3 H OCH.sub.3 CH(CH.sub.3)CH.sub.2 OH113 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub.5114 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub. 4 OCH.sub.3115 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.5 75116 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin117 CH.sub.3 CH.sub.3 H OCH.sub.3 n-C.sub.3 H.sub.7 147118 CH.sub.3 CH.sub.3 H OCH.sub.3 i-C.sub.3 H.sub.7 150119 CH.sub.3 CH.sub.3 H OCH.sub.3 CH(CH.sub.3)C.sub.2 H.sub.5120 CH.sub.3 CH.sub.3 H OCH.sub.3 n-C.sub.4 H.sub.9121 CH.sub.3 CH.sub.3 H OCH.sub.3 CH.sub.2 CHCH.sub.2122 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.5 95123 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH124 CH.sub.3 CH.sub.3 H OCH.sub.3 n-C.sub.5 H.sub.11125 CH.sub.3 CH.sub.3 H OCH.sub.3 ##STR23##126 CH.sub.3 CH.sub.3 H OCH.sub.3 ##STR24##127 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3128 CH.sub.3 CH.sub.3 H OCH.sub.3 CH.sub.2 C.sub.6 H.sub.5129 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.2 H.sub.4 C.sub.6 H.sub.5130 CH.sub.3 CH.sub.3 H OCH.sub.3 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5131 CH.sub.3 CH.sub.3 H OCH.sub.3 ##STR25## 116132 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH133 CH.sub.3 CH.sub.3 H OCH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5134 H H H CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3135 C.sub.3 H.sub.7 H H CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3136 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.4 OH137 CH.sub.3 H H CH.sub.3 C.sub.3 H.sub.6 OH138 CH.sub.3 H H CH.sub.3 CH(CH.sub.3)CH.sub.2 OH139 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.5140 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.4 OCH.sub.3141 CH.sub. 3 H H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.5142 CH.sub.3 H H CH.sub.3 C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin143 CH.sub.3 H H CH.sub.3 n-C.sub.3 H.sub.7 92144 CH.sub.3 H H CH.sub.3 i-C.sub.3 H.sub.7145 CH.sub.3 H H CH.sub.3 CH(CH.sub.3)C.sub.2 H.sub.5146 CH.sub.3 H H CH.sub.3 n-C.sub.4 H.sub.9147 CH.sub.3 H H CH.sub.3 CH.sub.2 CHCH.sub.2148 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.5149 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH150 CH.sub.3 H H CH.sub.3 n-C.sub.5 H.sub.11151 CH.sub.3 H H CH.sub.3 ##STR26##152 CH.sub.3 H H CH.sub.3 ##STR27##153 CH.sub.3 H H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin154 CH.sub.3 H H CH.sub.3 CH.sub.2 C.sub.6 H.sub.5155 CH.sub.3 H H CH.sub.3 C.sub.2 H.sub.4 C.sub.6 H.sub.5156 CH.sub.3 H H CH.sub.3 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5157 CH.sub.3 H H CH.sub.3 ##STR28## 112158 CH.sub.3 H H CH.sub.3 C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH159 CH.sub.3 H H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5160 H H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3161 C.sub.3 H.sub.7 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3162 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.4 OH163 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OH164 CH.sub.3 H CH.sub.3 CH.sub.3 CH(CH.sub.3)CH.sub.2 OH165 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.5166 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.4 OCH.sub.3167 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.5168 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin169 CH.sub.3 H CH.sub.3 CH.sub.3 n-C.sub.3 H.sub.7170 CH.sub.3 H CH.sub.3 CH.sub.3 i-C.sub.3 H.sub.7171 CH.sub.3 H CH.sub.3 CH.sub.3 CH(CH.sub.3)C.sub.2 H.sub.5172 CH.sub.3 H CH.sub.3 CH.sub.3 n-C.sub.4 H.sub.9173 CH.sub.3 H CH.sub.3 CH.sub.3 CH.sub.2 CHCH.sub.2174 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.5175 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH176 CH.sub.3 H CH.sub.3 CH.sub.3 n-C.sub.5 H.sub.11177 CH.sub.3 H CH.sub.3 CH.sub.3 ##STR29##178 CH.sub.3 H CH.sub.3 CH.sub.3 ##STR30##179 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin180 CH.sub.3 H CH.sub.3 CH.sub.3 CH.sub.2 C.sub.6 H.sub.5181 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.2 H.sub.4 C.sub.6 H.sub.5182 CH.sub.3 H CH.sub.3 CH.sub.3 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5183 CH.sub.3 H CH.sub.3 CH.sub.3 ##STR31## 110184 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH185 CH.sub.3 H CH.sub.3 CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5186 H CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3187 C.sub.3 H.sub.7 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OCH.sub.3188 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.4 OH189 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OH190 CH.sub.3 CH.sub.3 H CH.sub.3 CH(CH.sub.3)CH.sub.2 OH191 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.5192 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.4 OCH.sub.3193 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.5194 CH.sub.3 CH.sub. 3 H CH.sub.3 C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2195 CH.sub.3 CH.sub.3 H CH.sub.3 n-C.sub.3 H.sub.7196 CH.sub.3 CH.sub.3 H CH.sub.3 i-C.sub.3 H.sub.7197 CH.sub.3 CH.sub.3 H CH.sub.3 CH(CH.sub.3)C.sub.2 H.sub.5198 CH.sub.3 CH.sub.3 H CH.sub.3 n-C.sub.4 H.sub.9199 CH.sub.3 CH.sub.3 H CH.sub.3 CH.sub.2 CHCH.sub.2200 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.5201 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH202 CH.sub.3 CH.sub.3 H CH.sub.3 n-C.sub.5 H.sub.11203 CH.sub.3 CH.sub.3 H CH.sub.3 ##STR32##204 CH.sub.3 CH.sub.3 H CH.sub.3 ##STR33##205 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3 Resin206 CH.sub.3 CH.sub.3 H CH.sub.3 CH.sub.2 C.sub.6 H.sub.5207 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.2 H.sub.4 C.sub.6 H.sub.5208 CH.sub.3 CH.sub.3 H CH.sub.3 CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5209 CH.sub.3 CH.sub.3 H CH.sub.3 ##STR34##210 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH 35211 CH.sub.3 CH.sub.3 H CH.sub.3 C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5212 H H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OCH.sub.3213 C.sub.3 H.sub.7 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OCH.sub.3214 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.4 OH215 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OH216 CH.sub.3 H C.sub.2 H.sub.5 H CH(CH.sub.3)CH.sub.2 OH217 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.5218 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.4 OCH.sub.3219 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OC.sub.2 H.sub.5220 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin221 CH.sub.3 H C.sub.2 H.sub.5 H n-C.sub.3 H.sub.7222 CH.sub.3 H C.sub.2 H.sub.5 H i-C.sub.3 H.sub.7223 CH.sub.3 H C.sub.2 H.sub.5 H CH(CH.sub.3)C.sub.2 H.sub.5224 CH.sub.3 H C.sub.2 H.sub.5 H n-C.sub.4 H.sub.9225 CH.sub.3 H C.sub.2 H.sub.5 H CH.sub.2 CHCH.sub.2226 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.4 OC.sub.2 H.sub.5227 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH228 CH.sub.3 H C.sub.2 H.sub.5 H n-C.sub.5 H.sub.11229 CH.sub.3 H C.sub.2 H.sub.5 H ##STR35##230 CH.sub.3 H CH.sub.3 H ##STR36## 130231 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OC.sub.2 H.sub.4L OCH.sub.3232 CH.sub.3 H C.sub.2 H.sub.5 H CH.sub.2 C.sub.6 H.sub.5233 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.2 H.sub.4 C.sub.6 H.sub.5234 CH.sub.3 H C.sub.2 H.sub.5 H CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5235 CH.sub.3 H C.sub.2 H.sub.5 H ##STR37## 108236 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH 36237 CH.sub.3 H C.sub.2 H.sub.5 H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5238 H CH.sub.3 H H C.sub.3 H.sub.6 OCH.sub.3239 C.sub.3 H.sub.7 CH.sub.3 H H C.sub.3 H.sub.6 OCH.sub.3240 CH.sub.3 CH.sub.3 H H C.sub.2 H.sub.4 OH241 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OH242 CH.sub.3 CH.sub.3 H H CH(CH.sub.3)CH.sub.2 OH243 CH.sub.3 CH.sub.3 H H C.sub.2 H.sub.5244 CH.sub.3 CH.sub.3 H H C.sub.2 H.sub.4 OCH.sub.3245 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.5246 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OCH(CH.sub.3).sub.2 Resin247 CH.sub.3 CH.sub.3 H H n-C.sub.3 H.sub.7248 CH.sub.3 CH.sub.3 H H i-C.sub.3 H.sub.7 105249 CH.sub.3 CH.sub.3 H H CH(CH.sub.3)C.sub.2 H.sub.5250 CH.sub.3 CH.sub.3 H H n-C.sub.4 H.sub.9251 CH.sub.3 CH.sub.3 H H CH.sub.2 CHCH.sub.2252 CH.sub.3 CH.sub.3 H H C.sub.2 H.sub.4 OC.sub.2 H.sub.5253 CH.sub.3 CH.sub.3 H H C.sub.2 H.sub.4 OC.sub.2 H.sub.4 OH254 CH.sub.3 CH.sub.3 H H n-C.sub.5 H.sub.11255 CH.sub.3 CH.sub.3 H H ##STR38##256 CH.sub.3 CH.sub.3 H H ##STR39## 110257 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OCH.sub.3258 CH.sub.3 CH.sub.3 H H CH.sub.2 C.sub.6 H.sub.5259 CH.sub.3 CH.sub.3 H H C.sub. 2 H.sub.4 C.sub.6 H.sub.5260 CH.sub.3 CH.sub.3 H H CH(CH.sub.3)CH.sub.2 C.sub.6 H.sub.5261 CH.sub.3 CH.sub.3 H H ##STR40## 127262 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH263 CH.sub.3 CH.sub.3 H H C.sub.3 H.sub.6 OC.sub.2 H.sub.4 OC.sub.6 H.sub.5264 CH.sub.3 H H H C.sub.3 H.sub.6 OC.sub.4 H.sub.8 OH265 CH.sub.3 H n-C.sub.4 H.sub.9 H i-C.sub.3 H.sub.7 92 (hydrochloride)266 CH.sub.3 H H OCH.sub.3 CH(C.sub.2 H.sub.5)CH.sub.2 OCH.sub.3 46267 CH.sub.3 H H OCH.sub.3 ##STR41## 105268 CH.sub.3 H H h CH(CH.sub.3)CH.sub.2 OCH.sub.3 120 (pure isomer)269 CH.sub.3 H H H CH(CH.sub.3)CH.sub.2 OCH.sub.3 114 (mixed isomers)270 CH.sub.3 H OCH.sub.3 H CH(CH.sub.3)CH.sub.2 OCH.sub.3 90271 CH.sub.3 H CH.sub.3 H CH(CH.sub.3)CH.sub.2 OCH.sub.3 110272 CH.sub.3 H H H CH(CH.sub.3)CH.sub.2 OCH.sub.3 114273 CH.sub.3 H H H CH(CH.sub.3)CH.sub.2 OCH.sub.3 80__________________________________________________________________________

Claims

1. A process for preparing diaminopyridines of the formula I ##STR42## where one of the two radicals X.sup.1 and X.sup.2 is hydrogen, C.sub.1 -C.sub.4 -alkyl, halogen or nitro and the other is cyano,

R.sup.1 is hydrogen, C.sub.1 -C.sub.4 -alkyl or phenyl,

R.sup.2 and R.sup.3 are each independently of one another hydrogen, C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -alkoxy,

R.sup.4 is hydrogen or C.sub.1 -C.sub.4 -alkyl, and

R.sup.5 is C.sub.1 -C.sub.10 -alkyl which may be interrupted by from 1 to 3 oxygen atoms in ether function and is optionally hydroxyl-, C.sub.1 -C.sub.4 -alkanoyloxy-, phenoxy-, phenyl-, tetrahydrofuranyl- or tetrahydropyranyl-substituted, C.sub.3 -C.sub.4 -alkenyl or C.sub.5 -C.sub.7 -cycloalkyl,

by reacting dichloropyridines of the formula II ##STR43## where R.sup.1 and X.sup.1 are each as defined above, with amines by reacting in a first step a dichloropyridine of the formula II with an amine of the formula III

R.sup.5 --NH.sub.2 (III)

where R.sup.5 is as defined above, at from 10.degree. to 80.degree. C. in the presence of a base and of an inert organic diluent and/or water, then removing the diluent and thereafter, with or without prior intermediate isolation of the reaction product, reacting it in a second step with an aniline of the formula IV ##STR44## where R.sup.2, R.sup.3 and R.sup.4 are each as defined above, which comprises carrying out the second step in a melt at from 90.degree. to 165.degree. C. and at a pH from 3.5 to 6.5 using from 1.3 to 3 mol of aniline IV are used per mole of dichloropyridine II.

2. A process as claimed in claim 1, wherein in the formula I, X.sup.1 is hydrogen and X.sup.2 is cyano.

3. A process as claimed in claim 1, wherein in the formula I, R.sup.1 is methyl.

4. A process as claimed in claim 1, wherein the diluent used in the first step is isobutanol, toluene, o-, m- or p-xylene, ethylbenzene or a mixture thereof.