EP0912160A2

EP0912160A2 - Oxidation dyes

Info

Publication number: EP0912160A2
Application number: EP97931764A
Authority: EP
Inventors: Andreas Joachim Bittner; Astrid Kleen
Original assignee: Hans Schwarzkopf and Henkel GmbH
Current assignee: Hans Schwarzkopf and Henkel GmbH
Priority date: 1996-07-03
Filing date: 1997-07-03
Publication date: 1999-05-06
Also published as: JP2000514073A; WO1998001106A2; WO1998001106A3; US20010005914A1

Abstract

The invention relates to oxidation dyes which are particularly suitable for dyeing keratin fibres. Said dyes contain as the preliminary oxidation dye at least one diamino aniline of the general formula (I), in which R1 to R6 independently of each other are hydrogen, a (C1-C4) alkyl group, a hydroxy-(C2-C3)-alkyl group, a (C1-C4)-alkoxy-(C2-C3)-alkyl group, an amino-(C2-C3)-alkyl group in which the amino group can also have one or two (C1-C4)-alkyl radicals, or a 2,3-dihydroxypropyl group provided that not all substituents R1 to R6 are simultaneously hydrogen, and R1 and R2 and/or R3 and R4 and/or R5 and R6 along with the nitrogen atom to which they are attached are also an aziridine ring, an azetidine ring, a pyrrolidine ring, a piperidine ring, an azepane ring, an azocine ring or a morpholino group, thiomorpholino group or piperazino group which has another substituent R7 on the nitrogen atom which is selected from hydrogen, a (C1-C4) alkyl group, a hydroxy-(C2-C3)-alkyl group, a (C1-C4)-alkoxy-(C2-C3)-alkyl group, an amino-(C2-C3)-alkyl group or a 2,3-dihydroxypropyl group, and the three remaining hydrogen atoms on the benzol ring can also be replaced independently of each other by a halogen atom or a (C1-C4) alkyl group, or the physiologically tolerable salts thereof with inorganic and organic acids. Shades of colour are obtained which have a high level of brilliancy and colour fastness.

Description

.Oxidation Colorants' "

The invention relates to oxidation colorants with special diaminoaniols as oxidation dye precursors.

For dyeing keratin fibers, especially human hair, the so-called oxidation colorants play a preferred role because of their intense colors and good fastness properties. Such colorants contain oxidation dye precursors, so-called developer components and coupler components. The developer components form the actual dyes under the influence of oxidizing agents or atmospheric oxygen with one another or under coupling with one or more coupler components.

Good oxidation dyes (primary product) must first and foremost meet the following requirements: They must develop the desired color shades with sufficient intensity and authenticity in the oxidative coupling. They must also have a good ability to draw onto the fiber, whereby there must be no noticeable differences between stressed and freshly regrown hair, especially with human hair (leveling ability). They should be resistant to light, heat and the influence of chemical reducing agents, e.g. B. against perm fluids. After all, if they are used as a hair dye, they should not stain the scalp too much, and above all they should be harmless from a toxicological and dermatological point of view.

Primary aromatic amines with a further free or substituted hydroxy or amino group in the para or ortho position, diaminopyridine derivatives, heterocyclic hydrazones, 4-amino-pyrazolone derivatives and 2,4,5,6-tetraaminopyrimidine and its derivatives are examples of developer components used.

Usually m-phenylenediamine derivatives, naphthols, resorcinol and resorcinol derivatives, pyrazolones, m-aminophenols and pyridine derivatives are used as coupler components used. With regard to the individual dye components that can be used, reference is expressly made to the Colipa list, published by the Köφeφflege und Waschmittel industry association in Frankfurt.

As a rule, it is not possible to achieve natural color nuances with the help of a single Kuppier developer combination. In practice, therefore, a combination of different developer components and coupler components is usually required in order to obtain a natural-looking color.

Many of the intense blue colors available with the known coupler-developer combinations contain a clear red component. The red component is disadvantageous, in particular in the case of lighter shades, but also in order to achieve natural shades which are to have a sufficient depth of color and adequate gray coverage.

There is therefore still a need for coupler-developer combinations which result in an intense coloration in the clear blue area and in particular a pure black shade which is neither blue nor red.

Furthermore, as the number of oxidation dye products used increases, so too does the risk of a non-uniform coloring result, poorer leveling capacity and less good fastness properties.

There is therefore still a need for new oxidation dye precursors which, in particular, also allow natural dyeings to be obtained on the basis of a smaller number of dye precursors used.

It was therefore the object of the present invention to find new compounds which meet the requirements for oxidation dye precursors to a particular degree.

Surprisingly, it has now been found that the compounds of the general formula (I) described in the present invention fulfill these requirements particularly well on account of their particular electronic structure. In particular, they can be used to achieve "pure black" colorations, as well as very natural shades of blonde and in particular brown. 98/01106. 3rd ^{rL 1}

Furthermore, these compounds surprisingly have both pronounced coupler and developer properties. As a result, a large number of color tones are accessible even with a small number of further oxidation dye void products of the coupler and / or developer type, without the leveling and authenticity problems frequently observed when a larger number of oxidation dye void products are used at the same time.

A first subject of the present invention are therefore oxidation colorants for dyeing keratin fibers, which as oxidation dye product have at least one diaminoaniline of the general formula (I),

in the R until R «stand independently for

- hydrogen,

a (C ₁ -C ₄ ) alkyl group,

a hydroxy (C ₂ -C ₃ ) alkyl group,

a (C _r C ₄ ) alkoxy (C ₂ -C ₃ ) alkyl group,

- An amino (C ₂ -C ₃ ) alkyl group in which the amino group can also carry one or two (C, -C ₄ ) alkyl radicals or

- A 2,3-dihydroxypropyl group with the proviso that not all of the substituents R to R simultaneously represent hydrogen, and

R, and R ₂ and / or R ₃ and R ₄ and / or K _$ and R "together with the nitrogen atom to which they are attached can also represent an aziridine, azetidine, pyrrolidine, piperidine, azepane -, Azocin ring or a Moφholino-, Thiomoφholino- or Piperazinogruppe, which carries on the nitrogen atom another substituent R ₇ , which is selected from hydrogen, a (C, -C ₄ ) alkyl, a hydroxy (C ₂ - C ₃ ) alkyl, a (C, -C ₄ ) alkoxy (C ₂ -C ₃ ) alkyl, an amino (C ₂ -C ₃ ) alkyl or a 2,3-dihydroxypropyl group O 98/01106

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and the three remaining hydrogen atoms on the benzene ring can also be replaced independently of one another by a halogen atom or a (C, -C ₄ ) -alkyl group, or their physiologically tolerable salts with inorganic and organic acids.

These compounds can be prepared by known processes. For this purpose, express reference is made to the explanations in the example section.

Agents which contain a compound of the formula (I) in which at least two of the groups R to R do not represent hydrogen have particularly excellent coloring properties.

Also preferred are those compounds according to formula (I) in which at least one of the groups -NR, R ₂ , -NR ₃ R ₄ or for an aziridine, azetidine, pyrrolidine, piperidine, azepane, azocin ring or a Moφholino, Thiomoφholino or Piperazinogruppe, which carries a further substituent R ₇ on the nitrogen atom, which is selected from hydrogen, a (C, -C ₄ ) - alkyl-, a hydroxy- (C ₂ -C ₃ ) -alkyl-, a (C, -C ₄ ) -alkoxy- (C ₂ -C ₃ ) -alkyl-, an amino- (C ₂ -C ₃ ) alkyl or a 2,3-dihydroxypropyl group.

Preferred groups R to R ^ are hydrogen, methyl, ethyl, 2-hydroxyethyl and 3-hydroxypropyl.

Preferred groups -NR, R ₂ , -NR ₃ R, and -NR-jR _« are pyrrolidine, piperidine, azepane, Moφholin and piperazine, the latter bearing hydrogen on the other nitrogen atom.

The compounds of formula (I) can be used both as free bases and in the form of their physiologically tolerable salts with inorganic or organic acids, e.g. the hydrochloride, the sulfate and hydrobromide. Other acids suitable for salt formation are phosphoric acid and acetic acid, propionic acid, lactic acid and citric acid. The statements made below on the compounds of the formula (I) therefore always include these salts.

Keratin fibers are to be understood as furs, wool, feathers and in particular human hair. Although the oxidation colorants of the invention primarily for 98/011

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Dyeing keratin fibers are suitable, in principle there is nothing to prevent them from being used in other areas, particularly in color photography.

The hair colorants according to the invention preferably contain the compounds of the formula (I) in an amount of 0.001 to 10% by weight, preferably 0.1 to 5% by weight, in each case based on the total oxidation colorant. The “total oxidation colorant” or “total colorant” here and in the following means the means that is made available to the user. Depending on the formulation form, this agent can either be directly or after mixing with water or e.g. an aqueous solution of an oxidizing agent can be applied to the hair.

The compounds of the formula (I) can act both as developer and as coupler components in the oxidation colorants according to the invention.

According to a first embodiment, the agents according to the invention only contain the compounds of the formula (I) as oxidation dye precursors.

The number of available color shades is significantly increased, however, if the agent contains at least one further oxidation dye product in addition to the compounds of the formula (I).

According to a second preferred embodiment, the agents according to the invention therefore contain at least one further oxidation dye product of the coupler type.

Coupler components preferred according to the invention are 1-naphthol, pyrogallol, 1,5-, 2,7- and 1,7-dihydroxynaphthalene, o-aminophenol, 5-amino-2-methylphenol, m-aminophenol, resorcinol, resorcinol monomethyl ether, m-phenylenediamine, l-phenyl-3-methyl-pyrazolon-5, 2,4-dichloro-3-aminophenol, 1,3-bis (2,4-diaminophenoxy) propane, 4-chlororesorcinol, 2-chloro-6- methyl-3-aminophenol, 2-methylresorcinol, 5-methylresorcinol, 2,5-dimethylresorcinol, 2,6-dihydroxypyridine, 2,6-diaminopyridine, 2-amino-3-hydroxypyridine, 2,6-dihydroxy-3, 4-diaminopyridine, 3-amino-2-methylamino-6-methoxypyridine, 4-amino-2-hydroxytoluene, 2,6-bis (2-hydroxyethylamino) toluene, 2,4-diaminophenoxyethanol, 2-amino-4- hydroxyethylamino anisole. 98/01106

According to the invention, 1,7-dihydroxynaphthalene, m-aminophenol, 2-methylresorcinol, 4-amino-2-hydroxytoluene, 2-amino-4-hydroxyethylamino-anisole and 2,4-diaminophenoxyethanol are particularly preferred.

Of course, this embodiment also includes the use of several additional coupler components. Coupler combinations preferred according to the invention are

• resorcinol, m-phenylenediamine, 4-chlororesorcinol, 2-amino-4-hydroxyethylamino anisole

• 2-methylresorcinol, 4-chlororesorcinol, 2-amino-3-hydroxypyridine

• resorcinol, m-aminoaniline, 2-hydroxy-4-aminotoluene

• 3-methyl-4-aminoaniline, m-aminoaniline, 2-hydroxy-4-aminotoluene, 2-amino-3-hydroxypyridine

• 2-methylresorcinol, m-aminoaniline, 2-hydroxy-4-aminotoluene, 2-amino-3-hydroxy-pyridine

According to a second, preferred embodiment, the agents according to the invention therefore contain, if desired, at least one further oxidation dye pre-product of the coupler type, if desired, at least one further oxidation dye pre-product of the developer type.

Preferred developer components according to the invention are p-phenylenediamine, p-toluenediamine, p-aminophenol, 3-methyl-1,4-diaminobenzene, 1- (2'-hydroxyethyl) -2,5-diaminobenzene, N, N-bis- ( 2-hydroxy-ethyl) -p-phenylenediamine, 2- (2,5-diaminophenoxy) ethanol, 1-phenyl-3-carboxyamido-4-amino-pyrazolone-5, 4-amino-3-methylphenol , 2-methylamino-4-aminophenol, 2,4,5,6-tetraaminopyrimidine, 2-hydroxy-4,5,6-triaminopyrimidine, 4-hydroxy-2,5,6, -triaminopyrimidine, 2,4-dihydroxy- 5,6-diaminopyrimidine, 2-dimethylamino-4,5,6-triaminopyrimidine and 2-hydroxyethylaminomethyl 1-4-aminophenol.

According to the invention, p-toluenediamine, p-aminophenol, 1- (2'-hydroxyethyl) -2,5-diaminobenzene, 4-amino-3-methylphenol, 2-methylamino-4-aminophenol and 2,4,5, 6-tetraaminopyrimidine.

Of course, this embodiment also includes the use of several additional 98/01106

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additional developer components. Coupler combinations preferred according to the invention are

P-toluenediamine, p-phenylenediamine

• 3-methyl-4-aminoaniline, p-toluenediamine

P-toluenediamine, 4-amino-3-methylphenol

P-toluenediamine, 2-methylamino-4-aminophenoI

• 2,4,5,6-tetraaminopyrimidine, l- (2'-hydroxyethyl) -2,5-diaminobenzene

• 2,4,5,6-tetraaminopyrimidine, p-toluenediamine

Developer components and coupler components are usually used in approximately molar amounts to one another. If the molar use has also proven to be expedient, a certain excess of individual oxidation dye precursors is not disadvantageous, so that developer components and coupler components can preferably be present in the colorant in a molar ratio of 1: 0.5 to 1: 2. The total amount of oxidation dye products is generally at most 20% by weight, based on the total agent.

According to a fourth, likewise preferred embodiment, the colorants according to the invention, optionally in addition to further oxidation dye products, additionally contain direct dyes, for example for further modification of the color shades, e.g. from the group of nitrophenylenediamines, nitroaminophenols, anthraquinones or indophenols. Preferred direct dyes are those with the international names or trade names HC Yellow 2, HC Yellow 4, Basic Yellow 57, Disperse Orange 3, HC Red 3, HC Red BN, Basic Red 76, HC Blue 2, Disperse Blue 3, Basic Blue 99, HC Violet 1, Disperse Violet 1, Disperse Violet 4, Disperse Black 9, Basic Brown 16, Basic Brown 17, Picramic Acid and Rodol 9 R known compounds as well as 4-amino-2-nitrodiphenylamine-2'-carboxylic acid, 6-nitro -l, 2,3,4-tetrahydroquinoxaline, (N-2,3-dihydroxypropyl-2-nitro-4-trifluoromethyl) amino-benzene and 4-N-ethyl 1 - 1, 4-bis (2 '- hydroxyethylamino) -2-nitrobenzene hydrochloride. The agents according to the invention in accordance with this embodiment preferably contain the substantive dyes in an amount of 0.01 to 20% by weight, based on the total colorant.

Furthermore, the colorants according to the invention can also include naturally occurring dyes such as, for example, henna red, henna neutral, henna black, chamomile flowers, 98/01106

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Sandalwood, black tea, sapwood, sage, blue wood, madder root. Contain catechu, sedre and alkanna root.

It is not necessary that the mandatory or optional oxidation dyes or the optional direct dyes each represent uniform compounds. Rather, in the hair colorants according to the invention, due to the production processes for the individual dyes, further components may also be present in minor amounts, provided that these do not adversely affect the coloring result or for other reasons, e.g. toxicological, must be excluded.

Usual formulations for the oxidation coloring agents according to the invention are agents based on water or non-aqueous solvents as well as powders.

According to a preferred embodiment for producing the colorants according to the invention, the oxidation dye pre-products are incorporated into a suitable water-containing carrier. For the purpose of hair coloring, such carriers are e.g. Creams, emulsions, gels or also surfactant-containing foaming solutions, e.g. Shampoos, aerosols or other preparations that are suitable for use on the hair. The colorants according to the invention are preferably adjusted to a pH of 6.5 to 11.5, in particular 9 to 10.

Furthermore, the colorants according to the invention can contain all active ingredients, additives and auxiliaries known in such preparations. In many cases, the colorants contain at least one surfactant, both anionic and zwitterionic, ampholytic, nonionic and cationic surfactants being suitable in principle. In many cases, however, it has proven advantageous to select the surfactants from anionic, zwitterionic or nonionic surfactants. Anionic surfactants can be very particularly preferred.

Suitable anionic surfactants in preparations according to the invention are all anionic surface-active substances suitable for use on the human body. These are characterized by a water-solubilizing, anionic group such as. B. a carboxylate, sulfate, sulfonate or phosphate group and a lipophilic alkyl group with about 10 to 22 carbon atoms. In addition, in the molecule 98/01106

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Glycol or polyglycol ether groups, ether, amide and hydroxyl groups and usually also ester groups may be included. Examples of suitable anionic surfactants are, in each case in the form of the sodium, potassium and ammonium as well as the mono-, di- and trialkanolammonium salts with 2 or 3 carbon atoms in the alkanol group,

linear and branched fatty acids with 8 to 22 carbon atoms (soaps),

Ether carboxylic acids of the formula RO- (CH ₂ -CH2θ) _χ -CH ₂ -COOH, in which R is a linear alkyl group with 10 to 22 C atoms and x = 0 or 1 to 16,

Acyl sarcosides with 10 to 18 carbon atoms in the acyl group,

Acyl taurides with 10 to 18 carbon atoms in the acyl group,

Acyl isethionates with 10 to 18 carbon atoms in the acyl group,

Monosulfonic succinate and dialkyl esters with 8 to 18 carbon atoms in the

Alkyl group and sulfosuccinic acid mono-alkyl polyoxyethyl ester with 8 to 18 C-

Atoms in the alkyl group and 1 to 6 oxyethyl groups, linear alkanesulfonates with 12 to 18 C atoms, linear alpha-olefin sulfonates with 12 to 18 C atoms,

Alpha-sulfofatty acid methyl esters of fatty acids with 12 to 18 carbon atoms,

Alkyl sulfates and alkyl polyglycol ether sulfates of the formula

RO (-CH2-CH2θ) _χ -Sθ3H, in which R is a preferably linear alkyl group with 10 to

18 C atoms and x = 0 or 1 to 12,

Mixtures of surface-active hydroxysulfonates according to DE-A-3725 030, sulfated hydroxyalkyl polyethylene and / or hydroxyalkylene propylene glycol ethers according to DE-A-37 23 354,

Sulfonates of unsaturated fatty acids with 12 to 24 carbon atoms and 1 to 6

Double bonds according to DE-A-3926 344,

Esters of tartaric acid and citric acid with alcohols, the additive

Products of about 2-15 molecules of ethylene oxide and / or propylene oxide

Represent fatty alcohols with 8 to 22 carbon atoms. 98/01106

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Preferred anionic surfactants are alkyl sulfates, alkyl polyglycol ether sulfates and ether carboxylic acids with 10 to 18 carbon atoms in the alkyl group and up to 12 glycol ether groups in the molecule, and in particular salts of saturated and in particular unsaturated C8-C22 carboxylic acids, such as oleic acid, stearic acid, isostearic acid and palmitic acid.

Zwitterionic surfactants are those surface-active compounds which contain at least one quaternary ammonium group and at least one -COθ ( ^" ) - or wear. Particularly suitable zwitterionic surfactants are the so-called betaines such as the N-alkyl-N, N-dimethylammonium glycinate, for example the coconut alkyl dimethylammonium glycinate, N-acylaminopropyl-N, N-dimethylammonium glycinate, for example the cocoacylaminopropyl dimethyl-onium-glycinate, and 2-alkyl-3-carboxymethyl-3-hydroxyethyl-imidazolines each having 8 to 18 carbon atoms in the alkyl or acyl group and the cocoacyl-aminoethyl-hydroxyethylcarboxymethylglycinate. A preferred zwitterionic surfactant is the fatty acid amide derivative known under the CTFA name Cocamidopropyl Betaine.

Ampholytic surfactants are surface-active compounds which, in addition to a C8-C18-alkyl or -acyl group, contain at least one free amino group and at least one -COOH or -SO ₃ H group in the molecule and are capable of forming internal salts. Examples of suitable ampholytic surfactants are N-alkylglycines, N-alkylpropionic acids, N-alkylaminobutyric acids, N-alkylimino dipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids each with about 8 to 18 carbon atoms in the alkyl group. Particularly preferred ampholytic surfactants are N-cocoalkylaminopropionate, cocoacylaminoethylaminopropionate and C12-18 acylsarcosine.

Nonionic surfactants contain z as a hydrophilic group. B. a polyol group, a polyalkylene glycol ether group or a combination of polyol and polyglycol ether group. Such connections are, for example

Addition products of 2 to 30 moles of ethylene oxide and / or 0 to 5 moles 98/01106

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Propylene oxide to linear fatty alcohols with 8 to 22 carbon atoms, to fatty acids with 12 to 22 carbon atoms and to alkylphenols with 8 to 15 carbon atoms in the alkyl group,

C12-C22 fatty acid monoesters and diesters of addition products from 1 to 30

Mole of ethylene oxide to glycerol,

C8-C22 alkyl mono- and oligoglycosides and their ethoxylated analogues,

Addition products of 5 to 60 moles of ethylene oxide with castor oil and hardened castor oil,

Adducts of ethylene oxide with sorbitan fatty acid esters,

Addition products of ethylene oxide with fatty acid alkanolamides.

Examples of the cationic surfactants which can be used in the hair treatment compositions according to the invention are, in particular, quaternary ammonium compounds. Ammonium halides such as alkyltrimethylammonium chlorides, dialkyldimethylammonium chlorides and trialkylmethylammonium chlorides, for. B. cetyltrimethylammonium chloride, stearyltrimethylammonium chloride, distearyldimethylammonium chloride, lauryldimethylammonium chloride, lauryldimethylbenzylammonium chloride and tricetylmethylammonium chloride. The quaternized protein hydrolyzates are further cationic surfactants which can be used according to the invention.

Also suitable according to the invention are cationic silicone oils such as, for example, the commercially available products Q2-7224 (manufacturer: Dow Corning; a stabilized trimethylsilylamodimethicone), Dow ^Corning® 929 emulsion (containing a hydroxylamino-modified silicone, which is also referred to as amodimethicone), SM-2059 (manufacturer: General Electric), SLM-55067 (manufacturer: Wacker) and Abil ^® -Quat 3270 and 3272 (manufacturer: Th. Goldschmidt; diquaternary polydimethylsiloxanes, Quatemium-80).

In addition to a good conditioning effect, alkylamidoamines, especially fatty acid amidoamines such as the ^{stearylamidopropyldimethylamine} available under the name Tego Amid ^® S 18, are notable for their good biodegradability.

Quaternary ester compounds, so-called "esterquats", such as the dialkylammo- sold under the trademark Stepantex ^® , are also readily biodegradable. 98/01106

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nium methosulfates and methyl-hydroxyalkyl-dialkoyloxyalkyl-ammonium-methosulfates and the corresponding products of the Dehyquart ^® series.

An example of a suitable cationic surfactant quaternary sugar derivative is the commercial product Glucquat ^® 100, according to CTFA nomenclature a "lauryl methyl Gluceth-10 Hydroxypropyl Dimonium Chloride".

The compounds with alkyl groups used as surfactants can each be uniform substances. However, it is generally preferred to start from natural vegetable or animal raw materials in the production of these substances, so that substance mixtures with different alkyl chain lengths depending on the respective raw material are obtained.

In the case of the surfactants, which are addition products of ethylene and / or propylene oxide onto fatty alcohols or derivatives of these addition products, both products with a "normal" homolog distribution and those with a narrowed homolog distribution can be used. “Normal” homolog distribution is understood to mean mixtures of homologues which are obtained as catalysts when fatty alcohol and alkylene oxide are reacted using alkali metals, alkali metal hydroxides or alkali metal alcoholates. In contrast, narrow homolog distributions are obtained if, for example, hydrotalcites, alkaline earth metal salts of ether carboxylic acids, alkaline earth metal oxides, hydroxides or alcoholates are used as catalysts. The use of products with a narrow homolog distribution can be preferred.

Other active ingredients, auxiliaries and additives are, for example

non-ionic polymers such as, for example, vinyl pyrrolidone / vinyl acrylate copolymers, polyvinyl pyrrolidone and vinyl pyrrolidone / vinyl acetate copolymers and polysiloxanes, cationic polymers such as quaternized cellulose ethers, polysiloxanes with quaternary groups, dimethyl amidolamethylamethylamidylamethylamidylamethylamidylamethylamidylamethylamidylamethylamidylamethylamidylamidylamethylamidylamethylpolymer Imidazolinium methochloride copolymers and quaternized polyvinyl alcohol, 1106

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zwitterionic and amphoteric polymers such as, for example, acrylamidopropyltrimethylammonium chloride / acrylate copolymers and octylacrylamide / methyl methacrylate tert.butylaminoethyl methacrylate / 2-hydroxypropyl methacrylate

Copolymers, anionic polymers such as polyacrylic acids, cross-linked polyacrylic acids, vinyl acetate / crotonic acid copolymers, vinyl pyrrolidone / vinyl acrylate copolymers, vinyl acetate / butyl maleate / isobomylacrylate copolymers, methyl vinyl ether / maleic anhydride tert-copolymers and acrylic acid / acrylic acid / acrylic acid copolymers. Butylacrylamide polymers,

Thickeners such as agar agar, guar gum, alginates, xanthan gum, gum arabic, karaya gum, locust bean gum, linseed gums, dextrans,

Cellulose derivatives, e.g. B. methyl cellulose, hydroxyalkyl cellulose and

Carboxymethyl cellulose, starch fractions and derivatives such as amylose,

Amylopectin and dextrins, clays such as e.g. B. bentonite or fully synthetic

Hydrocolloids such as Polyvinyl alcohol,

Structurants such as glucose, maleic acid and lactic acid, hair-conditioning compounds such as phospholipids, for example

Soy lecithin, egg lecithin and cephaline, as well as silicone oils,

Protein hydrolyzates, especially elastin, collagen, keratin, milk protein,

Soy protein and wheat protein hydrolyzates, their condensation products with

Fatty acids and quaternized protein hydrolyzates,

Perfume oils, dimethyl isosorbide and cyclodextrins,

Solubilizers such as ethanol, isopropanol, ethylene glycol, propylene glycol,

Glycerin and diethylene glycol,

Anti-dandruff agents such as piroctone olamine and zinc omadine,

Alkalizing agents such as ammonia, monoethanolamine, 2-amino

2-methylpropanol and 2-amino-2-methyl-propanediol-1,3. other substances for adjusting the pH value,

Active ingredients such as panthenol, pantothenic acid, allantoin, pyrrolidone carboxylic acids and their salts, plant extracts and vitamins,

Cholesterol,

Light stabilizers,

Consistency enhancers such as sugar esters, polyol esters or polyol alkyl ethers,

Fats and waxes such as whale, beeswax, montan wax, paraffins, fatty alcohols and fatty acid esters, 98/01106

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Fatty acid alkanolamides,

Complexing agents such as EDTA, NTA and phosphonic acids,

Swelling and penetration substances such as glycerol, propylene glycol monoethyl ether,

Carbonates, hydrogen carbonates, guanidines, ureas and primary, secondary and tertiary phosphates,

Opacifiers like latex,

Pearlescent agents such as ethylene glycol mono- and distearate,

Blowing agents such as propane-butane mixtures, N ₂ O, dimethyl ether, CO ₂ and

Air,

Antioxidants.

The constituents of the water-containing carrier are used to produce the colorants according to the invention in amounts customary for this purpose; e.g. emulsifiers are used in concentrations of 0.5 to 30% by weight and thickeners in concentrations of 0.1 to 25% by weight of the total colorant.

The oxidative development of the coloring can in principle take place with atmospheric oxygen or an oxidizing agent contained in the agent or added to it immediately before use.

According to a first, preferred embodiment, a chemical oxidizing agent is used. This is particularly advantageous in cases where, in addition to the coloring, a lightening effect on human hair is desired. Particularly suitable oxidizing agents are hydrogen peroxide or its adducts with urea, melamine or alkali borate. According to a particularly preferred variant of this embodiment, the colorant according to the invention is mixed with the preparation of the oxidizing agent, in particular an aqueous H ₂ O ₂ solution, immediately before use. The resulting ready-to-use hair dye preparation should preferably have a pH in the range from 6 to 10. It is particularly preferred to use the hair dye in a weakly alkaline environment. The application temperatures can range between 15 and 40 ° C. After an exposure time of approx. 30 minutes, the hair dye is removed from the hair to be colored by rinsing. The night 98/01106

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washing with a shampoo is not necessary if a strong surfactant carrier, e.g. a coloring shampoo was used.

In particular in the case of hair that is difficult to dye, the preparation with the oxidation dye pre-products can be applied to the hair without prior mixing with the oxidation component. After an exposure time of 20 to 30 minutes, the oxidation component is then applied, if necessary after an intermediate rinse. After a further exposure time of 10 to 20 minutes, rinsing is then carried out and, if desired, re-shampooing.

According to a second embodiment, the coloring takes place with atmospheric oxygen. It is advantageous to add an oxidation catalyst to the colorant according to the invention. Suitable oxidation catalysts are metal salts or metal complexes, with transition metals being preferred. Copper, manganese, cobalt, selenium, molybdenum, bismuth and ruthenium compounds are preferred. Copper (II) chloride, sulfate and acetate can be preferred oxidation catalysts. The complexes with ammonia, ethylenediamine, phenanthroline, triphenylphosphine, 1,2-diphenylphosphinoethane, 1,3-diphenylphosphinopropane or amino acids can be preferred as metal complexes. The metal salts or metal complexes are preferably present in the agents according to the invention in amounts of 0.0001 to 1% by weight, based on the total agent. Of course, it is also possible to use several oxidation catalysts in one agent. With regard to the production of suitable catalysts, reference is made to the corresponding disclosure in EP 0 709 365 AI (page 4, lines 19 to 42), to which reference is expressly made.

It is also possible to carry out the oxidation with the aid of enzymes. The enzymes can be used both to produce oxidizing per compounds and to enhance the effect of a small amount of oxidizing agents present. An example of an enzymatic process is the procedure to increase the effect of small amounts (e.g. 1% and less, based on the total agent) of hydrogen peroxide by peroxidases.

Another object of the invention is the use of diaminoanilines of the general formula (I) according to claim 1 for dyeing keratin fibers. The following examples are intended to explain the subject of the invention in more detail

98/01106

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B e i s p i e l e

1. Manufacturing process. 1.1. General manufacturing processes

1.1.1. General production process starting from 2,4-dinitrohalobenzenes According to a first process, the compounds of the general formula (I) according to the invention are prepared by 2,4-dinitrohalobenzenes of the general formula (II), in which X = fluorine, chlorine, bromine or iodine , with A inen of the general formula (III), wherein R, and R _{2 have} the meaning given in claim 1, in an alkaline reaction medium, optionally with the addition of phase transfer catalysts, to give 2,4-dinitro-anilines of the general formula (IV). Suitable phase transfer catalysts are, for example, methyl or benzyl tri (C ₆ - C ₈ ) alkylammonium chloride. This reaction can optionally be carried out in an autoclave under pressure if the boiling point of the amine is lower than the reaction temperature or the conversion is not complete. The compounds of the general formula (IV) are reduced to the compounds of the general formula (V), optionally alkylated or oxyalkylated to the compounds of the general formula (I) according to the invention and optionally converted into their salts with inorganic or organic acids.

The compounds of the general formula (III) are common chemical raw materials and can be purchased.

(II) 98/01106

- 18th

Reduction N

(V) (I)

1.1.2. General manufacturing process starting from 4-amino-2-nitrohalobenzenes

According to a second process, the compounds of the general formula (I) according to the invention can be obtained by first substituting substituted 4-amino-2-nitrohalobenzenes of the general formula (VI) with amines of the general formula (III) to give compounds of the general formula (VII) be implemented.

(VI) (III) (VII)

The compounds of the general formula (VII) are converted into the compounds of the general formula (I) by reduction and, if appropriate, subsequent alkylation or oxalkylation.

1.1.3 General manufacturing process based on 2-amino-4-nitrohalobenzenes

According to a third process, the compounds of the general formula (I) according to the invention can be obtained by substituting substituted 2-amino-4-nitrohalobenzenes of the general formula (Via) with amines of the general formula

(III) are first converted into compounds of the general formula (VIIa). 98/01106

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(Via) (III) (Vlla)

The compounds of the general formula (VIIa) are converted into the compounds of the general formula (I) by reduction and, if appropriate, subsequent alkylation or oxalkylation.

1.1.4. General manufacturing process starting from 3-amino-4-nitrohalobenzenes

According to a fourth process, the compounds of the general formula (I) according to the invention can be obtained by substituting 3-amino-4-nitrohalobenzenes of the general formula (VIb) with amines of the general formula

(Illb) are first converted into compounds of the general formula (VHb).

(VIb) (Illb) (VHb)

After reduction and optionally further alkylation or oxalkylation, the compounds of the general formula (I) according to the invention are then obtained and these are optionally converted into their salt with an inorganic or organic acid. 98/01106

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1.1.5. General manufacturing process starting from 2-nitro-5-acetylaminohalogenbenzenes

The compounds of the general formula (I) according to the invention are prepared by 2-nitro-5-acetylaminohalogenbenzenes of the general formula (II) ', in which X = fluorine, chlorine, bromine or iodine, with amines of the general formula (purple), in which R ₃ and R _{4 have} the meaning given above, in an alkaline reaction medium, optionally with the addition of phase transfer catalysts, to give 2-nitro-5-acetylaminoanilines of the general formula (IV) '. These are hydrolyzed to the compounds of the general formula (V) 'and optionally alkylated or oxalkylated and then further reduced and optionally alkylated or oxalkylated to the compounds of the general formula (I) according to the invention. Suitable phase transfer catalysts are, for example, methyl or benzyl tri (C ₆ -C _g ) alkylammonium chloride. This reaction can optionally be carried out in an autoclave under pressure if the boiling point of the amine is lower than the reaction temperature or the conversion is not complete.

(II) '(purple) (IV)'

The compounds of the general formula (purple) are common chemical raw materials and can be purchased. The compounds of the general formula (IV) 'are converted into the compounds of the general formula (I) and, if appropriate, with acids in their salts by hydrolysis and, if appropriate, alkylation or oxyalkylation, reduction and, if appropriate, further alkylation or oxyalkylation. 98/01106

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(V) '(I)

1.1.6. General manufacturing process starting from 2-nitro-5-aminohalobenzenes

In a further process, the compounds of the general formula (I) according to the invention can be obtained by substituting 2-nitro-5-aminohalobenzenes of the general formula (VI) ', where R ₅ and R ^ have the meaning given in claim 1 Amines of the general formula (III) initially

Compounds of the general formula (Villa) are implemented.

(VI) '(iπ> (VHb)

The compounds of the general formula (VHb) are then converted into the compounds of the general formula (I) by reduction and, if appropriate, subsequent alkylation or oxalkylation.

1.1.7. General manufacturing process starting from 4-nitro-3-acetaminohalogenbenzenes

The compounds of the general formula (I) according to the invention are prepared by 4-nitro-3-acetaminohalogenbenzenes of the general formula (II) ", in which X =

Is fluorine, chlorine, bromine or iodine, with amines of the general formula (IIIb), in which R ₅ and Rn- have the meaning given above, in an alkaline reaction medium 98/01106

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optionally with the addition of phase transfer catalysts to substituted 4-nitro-3-acetaminoanilines of the general formula (IV) ". Suitable phase transfer catalysts are, for example, methyl- or benzyl-tri (C ₆ -C ₈ ) alkylammonium chloride. This reaction can optionally be carried out in an autoclave under pressure if the boiling point of the amine is lower than the reaction temperature or the conversion is not complete. The compounds of the general formula (IV) "are hydrolyzed to the compounds of the general formula (VHb) and, if appropriate, reduced and reduced after alkylation or oxalkylation the compounds of general formula (I) according to the invention are further alkylated or oxyalkylated and optionally converted into their salts with inorganic or organic acids. The compounds of the general formula (IIIb) are customary chemical raw materials and can be purchased.

(II) "(Illb) (IV)"

98/01

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1.2. General comments on the manufacturing process

The first stage of these processes consists in principle of replacing a halogen substituent with an amine substituent on the phenyl ring. In the known processes, an amine excess of about 40-80% is usually used; the products are obtained in yields of approx. 90% and with a purity of 95-96%. Surprisingly, it has now been found that higher yields with the same or better purity and faster conversion can be achieved if the amine excess is 30% and less, in particular 5 to 10 mol%, based on the amounts of the compound of the formula (II), (VI ), (Via), (VIb), (II) ', (VI)' and (II) ". The reaction of the amines (III), (purple) or (Illb) with compounds of the formula (II), ( VI), (Via), (VIb), (II) ', (VI)' and (II) "is preferably carried out in the presence of alkali carbonates as acid-binding agents. It is also preferred to carry out the reaction in an organic solvent. The use of one or more phase transfer catalysts, for example methyl- or benzyl-tri (C ₆ -Cg) alkylammonium chloride, is also preferred in this reaction. Finally, the reaction is preferably carried out under a pressure of from 1 to 15 bar, in particular from 1 to 8 bar and very particularly preferably from 1 to 2.5 bar.

The compounds, for example of the general formula (VI), (Via), (VIb), (V) 'and (VHb), can be obtained by compounds of the formula (VI), (Via), (VIb) (V)' and ( VHb), for which R ₃ and R ₄ or R ₅ and R.- = hydrogen, are alkylated or oxalkylated; this is achieved by reacting these compounds in an inert solvent with dialkyl sulfate, alkyl halide or alkylene oxides or by rearrangement of carbamates prepared therefrom and subsequent treatment with the aforementioned alkylating agents.

The reaction of, for example, the compounds of the formula (V) ', (VII), (VIIa) or (VHb) [R ₃ and R ₄ = hydrogen or R ₅ and 1 ^ = hydrogen] with 2-chloroethyl chloroformate or chloroformate - 3-chloro-propyl ester can be based on the known selective hydroxyalkylation of an amine with chloroformic acid chloroalkyl ester with subsequent basic treatment of the chloroalkyl carbamates. According to this process, for example a compound of the formula (VII), (VIIa) or (VHb) in which R ₃ , R ₄ , R ₅ and R * are hydrogen, 98/01106

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reacted in an inert solvent with 2-chloroethyl chloroformate or 3-chloroformate chloroformate to give the compounds of the general formula (VIII), (Villa) or (VIIIb), in which R ₇ = CH ₂ CH ₂ C1 or CH ₂ CH _{2 is} CH ₂ C1,

(VIII) (Villa) (VHIb)

which are reacted in a solvent with bases to give the compounds of the general formula (IX), (IXa) or (IXb), in which R _g = CH ₂ CH ₂ OH or CH ₂ CH ₂ CH ₂ OH

are, which are reacted with known alkylating agents or oxalkylating agents to give the compounds of the general formula (VII), (VIIIa) or (VIIb), where R to R * have the meanings already given, which after reduction and optionally after further alkylation or Oxalkylation of the compounds of 98/01106

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general formula (I).

The compounds of the general formula (I) can be prepared by reducing the compounds of the general formula (V) ', (IV), (VII), (VIIa) or (VHb), optionally after alkylation or oxalkylation, with base metals or by catalytic reduction take place.

In the catalytic reduction, conventional catalysts, e.g. B. Raney nickel, palladium on activated carbon or platinum on activated carbon. The reaction temperature is between room temperature and 120 ° C, preferably between 35 and 100 ° C, the pressure is between normal pressure and 20 bar, preferably between 2 and 7 bar. Common solvents such as water, toluene, glacial acetic acid, lower alcohols or ethers are used as solvents. After the reduction and separation of the catalyst has taken place, the product of the general formula (I), if appropriate after alkylation or oxalkylation, can be isolated in free form by stripping off the solvent under a protective gas. The known compounds dimethyl and diethyl sulfate have proven to be suitable as alkylating agents and the known compounds ethylene oxide and propylene oxide have proven useful as oxyalkylating agents. The product of the general formula (I) is preferably converted under a protective gas by adding a 1.0 to 1.1 equivalent amount of an acid into a salt which either precipitates directly or is obtained after removal of the solvent.

As inorganic acids such. B. hydrochloric acid, sulfuric acid, phosphoric acid and as organic acids acetic acid, propionic acid, lactic acid or citric acid suitable for salt formation.

O 98/01106

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1.3. Preparation of special compounds according to formula (I)

The compounds prepared have been characterized by IR or IR (KBr compact) and 'H-NMR spectra (in D ₆ -DMSO). Only the very strong and strong bands are listed in the IR spectra. In the case of the 'H-NMR spectra, s singlet, d doublet, dd doublet from the doublet, t triplet, q quartet, qi quintet, m multiple «, ³ J or ⁴ J mean the coupling via three or four bonds , as well as H \ H \ H ⁴ , H ⁵ and H ⁶ the hydrogen atoms in position 2, 3, 4, 5 and 6 of the benzene ring.

1.3.1. Preparation of N, N-dimethyl-2,4-diaminoanüin sulfate

Step a) N, N-dimethyl-2,4-dinitroaniline

97.3 g (0.5 mol) of 2,4-dinitroaniline were dissolved in 500 ml of dimethyl sulfoxide and 141.9 g (1.0 mol) of methyl iodide were added dropwise with stirring. The mixture was stirred until everything had dissolved and 112.2 g (1.0 mol) of 50% strength potassium hydroxide solution were then slowly added dropwise.

The mixture was allowed to cool to room temperature while stirring and then to 10 ° C. in an ice bath, the product precipitating out. The precipitated product was filtered off, washed twice with about 100 ml of water and dried at 40 ° C in a vacuum.

Yield: 92.1 g (87.2% of theory)

Melting point: 90 ° C (decomp.)

IR: 3356 cm ^"1 (v CH, 3115, 2928 cm ^{" 1} (v CH), 1622 cm ^"1 (v C = C), 1587,

1523 cm ^'1 (v "NO ₂ ), 1337, 1311 a ¹ (v _s NO ₂ ). 'H NMR: 8.83 ppm (H \ d, ⁴ J _{H, H} = 2.68 Hz); 8.27 ppm (H ⁵ , dd, M ^ = 9.58 Hz,

⁴ J _{H, H} = 2.59 Hz); 7.27 ppm (H ⁶ , d, ³ J _HH = 9.59 Hz); 3.07 ppm (3H, s, syn-NCH ₃ ) 3.05 ppm (3H, s, anti-NCH ₃ ). Step b) N, N-dimethyl-2,4-diaτninoaniline sulfate

150 ml of methanol were placed in a 0.3 l autoclave, 42.2 g (0.2 mol) of NN-dimethyl-2,4-dinitroaniline (stage a; alternatively also the compound according to Example 1.3.8 stage a) were dissolved and 2 g of palladium on activated carbon 10% (Degussa) were added. After sealing and inerting with nitrogen, the mixture was hydrogenated at a pressure of 3 bar and a temperature of 35-40 ° C. until no more hydrogen was taken up. 1.3 g of activated carbon were added to the warm solution under nitrogen and the catalyst was filtered off. 37 g of 80% sulfuric acid (alternatively 32 ml of concentrated hydrochloric acid per 0.2 mol) were added dropwise to the solution with ice cooling at 5 ° C. The precipitated product was filtered off, washed with methanol and dried. Yield: 39.9 g (80% of theory) 9

27 -

Melting point:> 250 ° C

IR: 3397 cm ^' ' (v OH), 3234 cm ^"1 (v CH, 2920 cm ^{" 1} (v CH ^,), 1661.

1630, 1515 cm ^"1 (vNH ₃ ⁺ ), 1596 cm ^'1 (vC = C).' H NMR: 7.65 - 4.75 ppm (6H, NH ₃ ⁺ ); 6.65 ppm (H ⁶ , d, ^ = 8.34 Hz); 6.51 ppm (H ⁵ , dd, ³ J _aH = 8.48 Hz, ⁴ J _aH = 2.34 Hz); 6.46 ppm (H ³ , d, ⁴ J _HH =

2.29 Hz); 2.77 ppm (6H, s, N (CH ₃₎ _2).

1.3.2. Preparation of N, N-diethyl-2,4-diaminoaniline trihydrochloride

Step a) N, N-diethyl-2,4-dinitroaniline

In 150 ml of di sulfoxide ^{'* 1} 20.26 g (0.1 mol) were dissolved 2,4-dinitrochlorobenzene,

8.3 g (0.06 mol) of potassium carbonate were added and 10.5 g (0.14 mol) of diethylamine were added

Stir added dropwise. The mixture was stirred at 80 ° C. until the reaction was complete. The mixture was poured onto 800 ml of ice-water mixture and stirred, the product precipitating. The precipitated product was filtered off, twice with about 100 ml

Washed water and dried at 40 ° C in a vacuum.

[*] This reaction can also be carried out very advantageously in 1,2-dimethoxyethane.

Yield: 21.9 g (90.8% of theory)

Melting point: 75 - 77 ° C

IR: 3117 cm ^" '(v O, 2983, 2930 cm ^{" 1} (v CH), 1607 cm ^"1 (v C = C), 1576,

1528 cm ^'1 (v _B N0 ₂ ), 1321 cm ^" ' (v _s NO ₂ ). 'H-NMR: 8.55 ppm (H ³ , d, ⁴ J _{H> H} = 2.80 Hz); 8 , 22 ppm (H ⁵ , dd, ³ J _{H, H} = 9.58 Hz, J _RH = 2.81 Hz); 7.36 ppm (H ⁶ , d, ^ = 9.58 Hz); 3.35 ppm (4H, q,

NCH ₂ ) 1.16 ppm (6H, t, NCH ₂ CH ₃ ). Step b) N, N-diethyl-2,4-diaminoaniline trihydrochloride

The product obtained in stage a) was reacted analogously to Example 1.3.1. Step b) by catalytic reduction and subsequent precipitation with hydrochloric acid. Yield: 8 g (34.6% of theory).

1.3.3. Preparation of N- (2,4-diaminophenyl) morpholine sulfaf

Step a) N- (2,4-dinitrophenyl) morpholine

Stage a) was carried out analogously to Example 1.3.1. Stage a) through

Implementation of 2,4-dinitrochlorobenzene with Moφholin.

Yield: 24.0 g (94.0% of theory) 98/01106

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Melting point: 104-105 ° C

IR: 3093 cm ^'1 (v CH *,), 2988, 2919, 2865 cm ^{' 1} (v CH), 1606 cm ^"1 (v C = C),

1532, 1504 cm ^'1 (v ^ NO,), 1327 cm ^{' 1} (v _s NO ₂ ). 'H NMR: 8.63 ppm (H ³ , d, ^A i _w = 2.74 Hz); 8.31 ppm (H ⁵ , dd, ³ J _HH = 9.37 Hz.

⁴ J _{H, H} = 2.75 Hz); 7.45 ppm (H ⁶ , d, ³ J _H. _H = 9.46 Hz); 3.74 ppm (4H. T, ³ J _HH

= 4.68 Hz, OCH ₂ ) 3.31 ppm (4H, q, NCH ₂ ). Step b) N- (2,4-diaminophenyl) morpholine sulfate

The preparation was carried out analogously to Example 1.3.1. Step b) by catalytic reduction of the product obtained in step a) above and precipitation with sulfuric acid. Yield: 18.0 g (74.3% of theory)

Melting point: 176 - 178 ° C

IR: 3351 cm ^'1 (v CH, 2860, 2567 cm ^{' 1} (v CH), 1560 cm ^'1 (v C = C).

'H NMR: 8.35 ppm (H ⁶ , d, ³ J _aH = 8.54 Hz); 7.22 ppm (H ³ , d, ³ J _HH = 2.29 Hz); 7.08 ppm (H ⁵ , dd, 'Jam = 8.47 Hz,% _M = 2.31 Hz); 3.81 ppm (4H, t, \ _M =

4.29 Hz, NCH ₂ ); 2.93 ppm (4H, t,% _M = 4.21 Hz, NCH ₂ CH ₂ ).

1.3.4. Preparation of N- (2,4-diaminophenyl) piperidine sulfate

Step a) N- (2,4-dinitrophenyl) piperidine

Stage a) was carried out analogously to Example 1.3.1. Stage a) through

Reaction of 2,4-dinitrochlorobenzene with piperidine.

Yield: 24.8 g (98.0% of theory)

Melting point: 88 - 91 ° C

IR: 3110 cm ^" '(v CH, 2949, 2927, 2861 cm ^{' 1} (v CH), 1604 cm ^'1 (v C = C),

1525, 1505 cm ^'1 (v ,, NO ₂ ), 1325 cm ^' '(v _s NO ₂ ). 'H NMR: 8.60 ppm (H ³ , d, "J ^ = 2.82 Hz); 8.25 ppm (H ⁵ , dd, ³ J _HH = 9.42 Hz,

⁴ J _HJ1 = 2.76 Hz); 7.41 ppm (H ⁶ , d, ³ J _H = 9.49 Hz); 3.27 ppm (4H, s,

NCH ₂ ) 1.65 ppm (6H, m, NCH ₂ Α. CH ^ CH _j ). Step b) N- (2,4-diaminophenyl) piperidine sulfate

The preparation was carried out analogously to Example 1.3.1. Step b) by catalytic reduction of the product obtained in step a) above and subsequent precipitation with sulfuric acid. Yield: 28.3 g (94.1% of theory) 98/01106

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1.3.5. Preparation of N- (2,4-diaminophenyl) pyrrolidine sulfate stage a) N- (2,4-dinitrophenyl) pyrrolidine

Stage a) was carried out analogously to Example 1.3.5. Step a) by reacting 2,4-dinitrochlorobenzene with pyrrolidine.

Yield: 21.5 g (89.9% of theory)

Melting point: 79 - 81 ° C

IR: 3122 cm ^'1 (v CH, 2990, 2956 cm ^{' 1} (v CH), 1612 cm ^'1 (v C = C), 1527,

1506 cm ^'1 (v "NO ₂ ), 1327 cm ^{' 1} (v _s NO ₂ ). 'H NMR: 8.58 ppm (H \ d, "J ^ = 2.72 Hz); 8.21 ppm (H ⁵ , dd, ³ J _RH = 9.58 Hz,

\ _M = 2.67 Hz); 7.17 ppm (H ⁶ , d, \ _M = 9.59 Hz); 3.31 ppm (4H, s,

NCH ₂ ) 2.57 ppm (4H, s, NCH ₂ CH ₂ ). Step b) N- (2,4-diaminophenyl) pyrrolidine sulfate

The preparation was carried out analogously to Example 1.3.1. Step b) by catalytic reduction of the product obtained in step a) above and subsequent precipitation with sulfuric acid. Yield: 11.8 g (37.8% of theory)

1.3.6. Preparation of 2,4-diamino-N, N-di- (2-hydroxyethyl) aniline sulfate stage a) 2,4-Dinitro-N, N-di- (2-hydroxyethyl) aniline

The reaction in stage a) was carried out analogously to example 1.3.1. Stage a) below

Use of 2,4-dinitrochlorobenzene and diethanolamine.

Yield: 22.0 g (80.5% of theory)

Melting point: 90 - 92 ° C

IR: 3076 cm ^'1 (v CH, 2927 cm ^{' 1} (v CH), 1606 cm ^'1 (v C = C), 1527, 1505 cm ^{' 1} (v _M NO ₂ ), 1328 cm ^'1 (v _p NO ₂ ). 'H NMR: 8.55 ppm (H ³ , d, "J ^ = 2.84 Hz); 8.22 ppm (H ⁵ , dd, = 9.57 Hz,

⁴ J _aH = 2.85 Hz); 7.50 ppm (H ⁶ , d, ³ J _aH = 9.59 Hz); 4.82 ppm (2H, t, ³ J _HJ1

= 5.27 Hz, OH); 3.60 ppm (4H, q, ³ J _HH = 5.56 Hz, CH ^ OH); 3.54 ppm

(4H, t, ³ J _RH = 5.76 Hz, NCH ^). Step b) 2,4-diamino-N, N-di- (2-hydroxyethyl) aniline sulfate

The preparation was carried out analogously to Example 1.3.1. Step b) by catalytic reduction of the product obtained in step a) above and subsequent precipitation with sulfuric acid. Yield: 10.3 g (32.1% of theory). 98/01106

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1.3. 7. Preparation of 2,4-diamino-N- (2-hydroxyethyl) -N-ethylaniline sulfate

Step a) 2, 4-Dinitro-N- (2-hydroxyethyl) -N-ethylaniline

Stage a) was analogous to Example 1.3.1. Stage a) by implementing 2.4-

Run dinitrochlorobenzene with N-methylethanolamine.

Yield: 20.9 g (81.2% of theory)

Melting point: 105-108 ° C

IR: 3096 cm ^'1 (v CH, 2932, 2818 cm ^{' 1} (v CH), 1621 cm ^'1 (v C = C), 1582,

1523 cm ^'1 (v ,, NO ₂ ), 1342 cm ^{' 1} (v _s NO ₂ ).

'H NMR: 8.86 ppm (H ³ , d, ⁴ J _aH = 2.74 Hz); 8.26 ppm (H ⁵ , dd, ³ J _H = 9.58 Hz,

⁴ J _aH = 2.73 Hz); 7.26 ppm (H ⁶ , d, M ^ = 9.66 Hz); 4.54 ppm (1H, s, OH); 3.53 ppm (2H, t, "J ^ = 5.02 Hz, CH ₂ OH); 3.51 ppm (2H, q, ³ J _H = 6.05 Hz, NCH ₂ CH ₃ ); 2.87 ppm (4H, t, ³ J _aH = 6.1 1 Hz, NCH ₂ CH ₂ OH); 2.65 ppm (3H, t, ³ J _H = 5.75 Hz, NCH, CH ₃ ).

Step b) 2,4-diamino-N- (2-hydroxyethyl) -N-ethylaniline sulfate

The preparation from stage a) was carried out analogously to Example 1.3.1. Step b) by catalytic reduction of the product obtained in step a) above and subsequent precipitation with sulfuric acid.

Yield: 8 g (34.6% of theory)

1.3.8. Preparation of N- (2,4-diaminophenyl) azepane sulfate

Step a) N- (4-amino-2-nitrophenyl) azepane

By reaction of 4-amino-2-nitrochlorobenzene with azepane analogously to Example 1.3.1.

Stage a).

Yield: 37.2 g (39.5% of theory)

Melting point: 72 - 73.5 ° C

IR: 3467, 3380 cm ^'1 (v CHJ, 2926, 2853 cm ^{' 1} (v CH), 1631 cm ^'1 (v C = C),

1520 (v _β NO ₂ ), 1360 cm ^'1 (v _s NO ₂ ). 'H NMR: 7.07 ppm (H ⁶ , d, ³ J _aH = 8.64 Hz); 6.79 ppm (H ⁵ , dd, ³ J _aH = 6.96 Hz,

⁴ J _aH = 2.59 Hz); 6.75 ppm (H ³ , d, J _aH = 2.68 Hz); 5.24 ppm (2H, s,

NΪ; 3.00 ppm (4H, t, ^ = 5.49 Hz, NCH ₂ ); 1.62 ... 1.56 ppm (8H, m,

NCH ^ CH.CK .CHz). Step b) N- (2,4-diaminophenyl) azepane sulfate

The product was prepared by catalytic reduction of the product obtained in step a) above and subsequent precipitation with sulfuric acid. Yield: 19.5 g (64.5% of theory) 98/01106

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1.3.9. Preparation of 4- (2-hydroxyethylamino) -2-amino-N, N-dimethylaniline sulfate

Step a) 4-amino-2-nitro-N, N-dimethylaniline

In 250 ml of 1,2-dimethoxyethane, 62.5 g (0.4 mol) of 4-fluoro-3-nitraniline, 45.1 g (0.4

Mol, 40% solution.) Dimethylamine and 21.2 g (0.2 mol) of sodium carbonate.

The mixture was heated under reflux until the conversion was complete and each set

1 g of activated carbon and Celite, stirred for about 30 minutes and filtered. The product was freed from solvent using a rotary evaporator and the oil obtained was processed further.

Yield: 62.8 g (86.6% of theory)

Melting point: (oil)

IR: 3373 cm ^'1 (v CH *,), 3227, 2946, 2870, 2792 cm ^{' 1} (v CH), 1631 cm ^'1 (v

C = C), 1564, 1525 cm ^"1 (v" NO ₂ ), 1353, 1293 cm ^'1 (v _s NO ₂ ). "H-NMR: 7.10 ppm (H ⁶ , d, M ^ = 8 , 77 Hz); 6.94 ppm (H ³ , d, ⁴ J _aH = 2.64 Hz);

6.83 ppm (H ⁵ , dd, ³ J _aH = 8.77 Hz, ⁴ J _aH = 2.70 Hz); 5.29 ppm (2H, s,

NH ₂ ); 2.59 ppm (6H, s, N (CH ₃₎ _2). Step b) 4- (2-chloroethoxycarbonylamino) -2-nitro-N, N-dimethylaniline 28.5 g (160 mmol) of 4-amino-2-nitro-N, N-dime were added to 100 ml of 1,2-dimethoxyethane - Thylaniline and 9 g (80 mmol) calcium carbonate presented. 22.5 g (160 mmol) of 2-chloroethyl chloroformate were added dropwise to this solution at room temperature and the mixture was stirred until the conversion was complete. The pH was then adjusted to 3-4 using concentrated hydrochloric acid and 100 g of ice / water mixture were added. The precipitated product was filtered off and washed twice with 100 ml of water.

Yield: 25.5 g (59.1% of theory)

Melting point: 178-180 ° C IR: 3424 cm ^'1 (v CH, 3177, 3032 cm ^' '(v CH), 1727 cm ^{' 1} (v C = O), 1607 cm ^'1 (C = C), 1544 cm ^'1 (v ,, NO ₂ ), 1322 cm ^{' 1} (v _s NO ₂ ), 1227 cm ^'1 (v O-

C). 'H NMR: 8.03 ppm (H \ d, "J ^ = 2.15 Hz); 7.62 ppm (H ⁵ , dd,' J ^ = 9.06 Hz, J _aH = 2.55 Hz ); 7.35 ppm (H ⁶ , d, ³ J _aH = 9.11 Hz); 4.36 ppm (2H, q,

C (O) OCH ₂ ); 3.89 ppm (2H, q, CH ₂ C1); 2.83 ppm (6H, s, N (CH ₃₎ _2). Step c) 4- (2-hydroxyethylamino) -2-nitro-N, N-dimethylaniline

23.0 g (80 mmol) of 4- (2-chloroethoxycarbonylamino) -2-nitro-N, N-dimethylaniline were placed in 100 ml of ethanol. 33 g were added dropwise to this solution at room temperature 98/01106

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(412 mmol) 50% sodium hydroxide solution and stirred the mixture until the conversion was complete. The mixture was then heated to approximately 80 ° C. and the solution was filtered. The pH of the filtrate was adjusted to 8 with acetic acid. Then 75 ml of water were added and ethanol was distilled off until the boiling temperature was 99.degree. After the solution had cooled, it was extracted with ethyl acetate, the ester phase was dried over sodium sulfate and the solution was concentrated in vacuo. After rubbing with a glass rod, the product crystallized. It was suctioned off and dried. Yield: 12.1 g (67.2% of theory)

Melting point: 110 ° C IR: 3285 cm ^'1 (v CH, 3178 cm ^{' 1} (v CH), 1640 cm ^'1 (v C = O), 1559 cm ^' '

( _Vas NO ₂ ), 1413 cm ^'1 (v, NO ₂ ), 810 cm ^{' 1} (v CH ^). 'H NMR: 7.19 ppm (H ⁶ , d,' J ^ = 9.60 Hz); 6.855 ppm (H ⁵ , dd, ³ J _{H> H} = 9.64 Hz,

⁴ J _{H, H} = 2.87 Hz); 6.854 ppm (H ³ , d, "J ^ = 2.50 Hz); 6.01 ppm (1H, t,

\ _M = 1 1 Hz, CH ₂ OH); 3.54 ppm (2H, t, 'J ^ = 5.81 Hz, NCH ₂ ); 3.07 ppm (2H, q, ³ J _a0H = 11.35 Hz, ³ J _aH = 5.65 Hz, CH ₂ OH); 2.59 ppm (6H, s, N (CH ₃₎ _2). Stage d) 4- (2-Hydroxyethylarnino) -2-amino-N, N-dimethylaniline sulfate 100 ml of methanol were placed in a 0.3 l autoclave, 12.0 g (53 mmol) of 4- (2-hydroxyethylamino) ) -2-nitro-N, N-dimethylaniline (from stage c) dissolved and 2 g of palladium on activated carbon 10% (Degussa) added. After sealing and inerting with nitrogen, the mixture was hydrogenated at a pressure of 4 bar and a temperature of 35-40 ° C. until no more hydrogen was taken up. 1.3 g of activated carbon were added to the warm solution under nitrogen and the catalyst was filtered off. 7 g of 80% sulfuric acid (alternatively: 16 ml of 35% hydrochloric acid per 0.1 mol) were added dropwise to the solution while cooling with ice at 5 ° C. The precipitated product was filtered off, washed with methanol and dried. Yield: 12.2 g (78.8% of theory)

Melting point:> 250 ° C IR: 3397 cm ^'1 (v OH), 3234 cm ^' '(v CH, 2920 cm ^{' 1} (v CH ^,), 1661,

1630, 1515 cm ^'1 (v NH ₃ ⁺ ), 1596 cm ^{' 1} (v C = C). 'H NMR: 7.65-4.75 ppm (6H, NH ₃ ⁺ ); 6.65 ppm (H ⁶ , d, 'J ^ = 8.34 Hz); 6.51 ppm (H ⁵ , dd, ^ = 8.48 Hz, "J ^ = 2.34 Hz); 6.46 ppm (H \ d, ⁴ J _aH =

2.29 Hz); 2.77 ppm (6H, s, N (CH ₃₎ _2).

1.3.10. Preparation of N- [4- (2-hydroxyethylamino) -2-aminophenyl] morpholine sulfate - 33 -

Step a) N- (4-amino-2-nitrophenyl) morpholine

Stage a) was carried out analogously to Example 1.3.9. Stage a) through

Reaction of 4-fluoro-3-nitraniline with Moφholin.

Yield: 61.9 g (69.3% of theory)

Melting point: 131 - 132 ° C

IR: 3479 cm ^'1 (v CH, 3042, 2958, 2857, 2830 cm ^{' 1} (v CH), 1626 cm ^'1 (v

C = C), 1515 (v ^ NO ₂ ), 1343 cm ^'1 (v _s NO ₂ ). 'H NMR: 7.18 ppm (H ⁶ , d, ³ J _aH = 8.66 Hz); 6.88 ppm (H ³ , d, ⁴ J _HH = 2.44 Hz);

6.80 ppm (H ⁵ , dd, ³ J _HιH = 8.59 Hz, "J ^ = 2.43 Hz); 5.46 ppm (2H, s,

NH ₂ ); 3.63 ppm (4H, t, ³ _W = 4.66 Hz, OCH ₂ ); 2.79 ppm (4H, t, ³ J _H =

4.43 Hz, NCH ₂ ). Stage b) N- [4- (2-chloroethoxycarbonylamino) -2-nitrophenyl] morpholine The preparation in stage b) was carried out analogously to Example 1.3.9. Step b) by reaction of N- (4-amino-2-nitrophenyl) moφholin with 2-chloroethyl chloroformate.

Yield: 32.7 g (95.1% of theory)

Melting point: 121 - 122 ° C IR: 3304 cm ^'1 (v CH, 3177, 3102 cm ^{' 1} (v CH), 1732 cm ^'1 (v C = O), 1596 cm ^{' 1} (C = C), 1537 cm ^'1 (v „NO ₂ ), 1342 cm ^{' 1} (v _s NO ₂ ), 1224 cm ^' ' (v O-

C). 'H NMR: 10.1 ppm (1H, s, NH); 8.01 ppm (H ⁶ , d, 'J ^ = 2.21 Hz); 7.64 ppm (H ⁵ , dd, ³ J _H = 8.89 Hz, J _aH = 2.46 Hz); 7.85 ppm (H ³ , d, M ^ = 8.94 Hz);

4.38 ppm (2H, t, ^ = 5.16 Hz, C (O) OCH ₂ ); 3.89 ppm (2H, t, ³ J _H =

5.16 Hz, CH ₂ C1); 3.69 ppm (4H, t, 'J ^ = 4.48 Hz, CH ₂ OCH ₂ ); 2.92 ppm (4H, t, ³ J _aH = 4.50 Hz, CH ₂ NCH ₂ ). Step c) N- [4- (2-Hydroxyethylamino) -2-nitrophenyl] morpholine

Stage c) was analogous to Example 1.3.9. Stage c) by converting N- [4- (2-chloroethoxycarbonylamino) -2-nitrophenyl] moφholin with potassium hydroxide solution. Yield: 20 g (93.5% of theory)

Melting point: (oil) IR: 3282 cm ^'1 (v CH, 2941 cm ^{' 1} (v CH), 1632 cm ^'1 (v C = O), 1567 cm ^' '

(v ^ NO,), 1368 cm '(v _s NO ₂ ). 'H NMR: 8.6 ppm (4H, s, NH / OH); 7.36 ppm (H ⁶ , d, M ^ = 8.63 Hz); 7.21 ppm

(H ³ , d, ⁴ J _aH = 2.19 Hz); 7.10 ppm (H ⁵ , dd, ³ J _aH = 8.59 Hz, ⁴ J _aH = 2.19

Hz); 3.84 ppm (4H, t, ³ J _H = 4.22 Hz, CH ₂ OCH ₂ ); 3.67 ppm (2H, t, ^ 98/01106

- 34 -

= 5.47 Hz, CHjOH); 3.23 ppm (2H, t, ^ = 5.48 Hz, NCH, CH, OH);

2.97 ppm (4H, t, ^ = 4.06 Hz, CH ₂ NCH ₂ ). Stage ά) N- [4- (2-hydroxyethylamino) -2-aminophenyl] morpholine sulfate The reaction in stage d) was carried out analogously to Example 1.3.9 stage d) by catalytic reduction of the product obtained in stage c) and subsequent Precipitation with sulfuric acid. Yield: 7.4 g (28.3% of theory)

1.3.11. Preparation of N- [4- (2-hydroxyethylamino) -2-aminophenyl] piperidine sulfate

Step a) N- (4-amino-2-nitrophenyl) piperidine

Stage a) was carried out analogously to Example 1.3.9. Step a) by reaction of 4-fluoro-3-nitraniline with piperidine.

Yield: 80.6 g (91.1% of theory)

Melting point: 112-113 ° C

IR: 3486, 3389 cm ^'1 (v CH, 2950, 2934, 2848 cm ^{' 1} (v CH), 1629 cm ^'1 (v

C = C), 1511 (v ^ NO,), 1361 cm ^'1 (v _s NO ₂ ). 'H NMR: 7.12 ppm (H ⁶ , d, M ^ = 8.68 Hz); 6.86 ppm (H \ d, "J ^ = 2.51 Hz);

6.78 ppm (H ⁵ , dd, ^ = 8.60 Hz, M ^ = 2.52 Hz); 5.38 ppm (2H, s,

NH _j ); 2.75 ppm (4H, t, 'J ^ = 4.66 Hz, NCH ₂ ) 1.54..1.45 ppm (6H, m,

NCH, CH _; CH _; CH ₂ ). Stage b) N- [4- (2-chloroethoxycarbonylamino) -2-nitrophenyl] piperidine stage b) was carried out analogously to Example 1.3.9. Step b) was carried out by reacting N- (4-amino-2-nitrophenyl) piperidine with 2-chloroethyl chloroformate. Yield: 31.1 g (94.8% of theory)

Melting point: 74 - 76 ° C IR: 3373 cm ^" '(v CH *,), 2936, 2853 cm ^{' 1} (v CH), 1730 cm ^'1 (v C = O), 1588 cm' (C = C) , 1532 cm ^'1 (v „NO ₂ ), 1307 cm ^{' 1} (v _s NO ₂ ), 1224 cm ^'1 (v O-

C). 'H NMR: 10.0 ppm (1 H, s, NH); 7.96 ppm (H ⁶ , d, 'J ^ = 2.35 Hz); 7.59 ppm (H ⁵ , dd, ³ J _aH = 8.95 Hz, "J ^ = 2.00 Hz); 7.31 ppm (H ³ , d, ³ J _W = 8.97 Hz);

4.36 ppm (2H, t, ^ = 5.19 Hz, C (0) OCH ^); 3.88 ppm (2H, t, ^ =

5.19 Hz, CH ₂ C1); 2.87 ppm (4H, t, ^ = 5.03 Hz, CH ₂ NCH ₂ );

1.59..1.50 ppm (6H, m, CH ₂ CH ₂ CH ₂ ). Step c) N- [4- (2-Hydroxyethylamino) -2-nitrophenyl] piperidine 98/01106

- 35 -

The reaction in stage c) was carried out analogously to example 1.3.9. Step c) by conversion of N- [4- (2-chloroethoxycarbonylamino) -2-nitrophenyI] piperidine with sodium hydroxide solution.

Yield: 19 g (90% of theory)

Melting point: (oil)

Step d) N- [4- (2-Hydroxyethylamino) -2-aminophenylpiperidine sulfate

The reaction in stage d) was carried out analogously to example 1.3.9. Stage d) by catalytic reduction of the product obtained in stage c) and subsequent precipitation with sulfuric acid.

Yield: 11.4 g (83.5% of theory)

Melting point: 200 - 202 ° C

IR: 3413 cm ^'1 (v OH), 3197 cm ^{' 1} (v CH, 2946 cm ^'1 (v CH), 1628 cm ^{' 1} (v

C = C), 1516 cm ^'1 (v _β NO ₂ ), 1451 cm ^{' 1} (v _s NO ₂ ).

'H NMR: 7.6 ppm (6H, s, NH ₃ 7 NH ₂ 7OH); 7.48 ppm (H ⁶ , d, _M = 8.89 Hz);

6.87 ppm (H ³ , d, "J ^ = 2.09 Hz); 6.75 ppm (H ⁵ , dd, ³ J _aH = 8.83 Hz, ⁴ J _H = 2.09 Hz) 3, 64 ppm (2H, t,% _M = 5.55 Hz, CH ₂ OH); 3.46 ppm (4H, t, tm = 4.58 Hz, CH ₂ NCH ₂ ); 3.20 ppm (2H, t , ³ J _aH = 5.54 Hz, NCH ₂ CH ₂ OH); 2.06 ppm (4H, s, 1.65 ppm (4H, s, CH ₂ CH ₂ CH ₂ CH ₂ CH).

1.3.12. Preparation of Η- [4- (3-hydroxypropylamino) -2-aminophenyl] morpholine-dihydrochlo d

Step a) N- (4-amino-2-nitrophenyl) morpholine

Stage a) was carried out by reacting 4-fluoro-3-nitraniline with

Moφholin, as in Example 1.3.10. Stage a) specified.

Step b) N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyl] morpholine

The compound was formed by conversion of N- (4-amino-2-nitrophenyl) moφholin with

3-chloroformate chloroformate in analogy to example 1.3.10. Stage b) made.

Yield: 32.7 g (95.1% of theory)

Melting point: 122-124 ° C

IR: 3245 cm ^'1 (v CH, 2964 cm ^{' 1} (v CH), 1737 cm ^'1 (v C = O), 1596 cm ^{' 1}

(C = C), 1537 cm ^'1 (v "NO ₂ ), 1373 cm ^" ' (v _s NO ₂ ), 1221 cm ^'1 (v OC).

'H NMR: 9.95 ppm (1H, s, NH); 7.99 ppm (H ³ , s); 7.62 (H ⁵ , dd, ^ = 8.81 Hz,

* 2 _W = 1.81 Hz); 7.38 ppm (H ⁶ , d, »J ^ = 8.93 Hz); 4.23 ppm (2H, t, \ _M = 6.18 Hz, C (O) OCHj); 3.75 ppm (2H, t, \ _M = 6.43 Hz, CH ₂ C1); 3.69 98/01106

- 36 -

ppm (4H, t, ³ J _aH = 4.08 Hz, CH ₂ OCH ₂ ); 2.93 ppm (4H, t, ³ J _aH = 4.06 Hz, CH ₂ NCH ₂ ); 2.10 ppm (2H, q, ³ J _aH = 6.27 Hz, CH ₂ CH ₂ CH ₂ ).

Step c) N- [4- (3-hydroxypropylamino) -2-nitrophenyl] morpholine

The compound was obtained by converting N- [4- (3-chloropropoxycarbonylarnino) -2-nitrophenyljmoφholin with sodium hydroxide solution in analogy to Example 1.3.10. Stage c) made.

Yield: 20.4 g (90.5% of theory)

Melting point: 93 - 95 ° C

IR: 3433, 3347 cm ^"1 (v CH, 2964, 2867 cm ^" '(v CH), 1622 cm ^{' 1} (v C = C),

1543 cm ^'1 (v ^ NO ^, 1371 cm ^' '(v _s NO ₂ ).

'H NMR: 7.24 ppm (H ⁶ , d, ³ J _HJ1 = 8.55 Hz); 6.84 ppm (H ³ , d, \ _M = 2.52 Hz);

6.81 ppm (H ⁵ , dd, ³ J _aH = 8.59 Hz, "J ^ = 2.72 Hz); 6.03 ppm (1H, t, ³ J _aH = 5.46 Hz, OH); 3.63 ppm (4H, t, ³ J _aH = 4.49 Hz, CH ₂ OCH ₂ ); 3.49 ppm (2H, t, ³ J _aH = 6.21 Hz, CH, OH); 3.06 ppm (2H, q, ³ J _aH = 6.75 Hz, ³ J _aNH = 12.53 Hz, NCH ₂ CH ₂ CH ₂ OH); 2.81 ppm (4H, t, ³ J _aH = 4.49 Hz , CH ₂ NCH ₂ ); 1.67 ppm (2H, qi, ³ J _aH = 6.56 Hz, NCH _j CH _j CH.OH).

Step d) N- [4- (3-hydroxypropylamino) -2-aminophenyl] morpholine dihydrochloride

The product was obtained by catalytic reduction of the product obtained in step c) above and salt formation with hydrochloric acid.

Yield: 11.4 g (83.5% of theory)

Melting point: 139 - 141 ° C

IR: 3365, 3196 cm ^'1 (v CHJ, 2614, 2436 cm ^{' 1} (v NH ₃ ⁺ , NH ₂ ⁺ ), 1628 cm ^'1 (v

C = C), 1123 cm ^'1 (v COC).

'H NMR: 7.39 ppm (H ⁶ , d, ^ = 8.62 Hz); 7.33 ppm (H ³ , d, _M = 2.14 Hz);

7.21 ppm (H ⁵ , dd, M ^ = 8.54 Hz, ⁴ J _aH = 2.09 Hz); 3.83 ppm (4H, t, ³ J _aH = 4.15 Hz, CH ₂ OCH ₂ ); 3.48 ppm (2H, t, ³ J _a "= 6.04 Hz, CH ^ OH);

3.22 ppm (2H, q, ^ = 7.68 Hz, NCH-, CH ₂ CH ₂ OH); 2.97 ppm (4H, s, CH ₂ NCH ₂ ); 1.83 ppm (2H, qi, *} _w = 6.84 Hz, NCH ^ H _j CH.OH).

1.3.13. Preparation of N- [4- (3-hydroxypropylamino) -2-aminophenyl] piperidine sulfate

Step a) N- (4-amino-2-nitrophenyl) piperidine

Step b) N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyl] piperidine - 37 -

Stage b) was analogous to Example 1.3.9. Step b) was carried out by reacting N- (4-amino-2-nitrophenyl) piperidine with 3-chloroformate chloroformate.

Yield: 20.6 g (60.4% of theory)

Melting point: (oil)

IR: 3331 cm ^'1 (v CHJ, 2938, 2854 cm ^{' 1} (v CH), 1708 cm ^'1 (v C = O), 1587 cm ^{' 1} (C = C), 1532 a ¹ (v _B NO ₂ ), 1305 cm ^'1 (v _s NO ₂ ), 1224 cm' ¹ (v O-C).

'H NMR: 9.95 ppm (1H, s, NH); 7.95 ppm (H ⁶ , d, \ _M = 1.71 Hz); 7.57 ppm (H ⁵ , dd, ^ = 8.87 Hz, 'J _HJ , = 2.05 Hz); 7.28 ppm (H \ d, ³ J _HΛ = 8.89 Hz); 4.21 ppm (2H, t, ^ = 6.19 Hz, C (O) OCH ₂ ); 3.73 ppm (2H, t, ³ J _aH = 6.44 Hz, CH ₂ C1); 2.85 ppm (4H, t, ^ = 4.83 Hz, CH ₂ NCH ₂ ); 1.57 ppm (4H, m, CH ^ CH,); 1.49 ppm (2H, m, CH ₂ CH ₂ CH ₂ ).

Step c) N- [4- (3-hydroxypropylamino) -2-nitrophenyl] piperidine

The reaction in stage c) was carried out analogously to example 1.3.9. Step c) by conversion of N- [4- (3-chloroformoxycarbonylamino) -2-nitrophenyl] piperidine with sodium hydroxide solution.

Yield: 20.6 g (60.4% of theory)

Step ά) N- [4- (3-hydroxypropylamino) -2-aminophenyl] piperidine sulfate

Yield: 20.6 g (60.4% of theory)

1.3.14. Preparation of N- [4- (3-hydroxypropylamino) -2-a inophenylpyrrolidine sulfate

Step a) N- (4-amino-2-nitrophenyl) pyrrolidine

Stage a) was carried out analogously to Example 1.3.9. Step a) by reaction of 4-fluoro-3-nitraniline with pyrrolidine.

Yield: 61.0 g (73.6% of theory)

Melting point: 84 - 86 ° C

IR: 3486, 3389 cm ^' ' (v CHJ, 2950, 2934, 2848 cm ^'1 (v CH), 1624 cm ^{' 1} (v

C = C), 1521 (v ^ NO _j ), 1364 cm- '(v ₅ NO ₂ ). 'H NMR: 6.98 ppm (H ³ , d, ⁴ J _a "= 2.28 Hz); 6.87 ppm (H ⁵ , H ⁶ , m); 4.92 ppm (2H, s, NH _j ); 3.00 ppm (4H, t, ³ J _aH = 6.49 Hz, NCH ₂ ); 1.85 ppm (6H, m,

NCH _? CH _Z CH ₂ ). Step b) N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyl] pyrrolidine 98/01106

- 38 -

Stage b) was analogous to Example 1.3.9. Step b) was carried out by reacting N- (4-amino-2-nitrophenyl) pyrrolidine with 3-chloroformate chloroformate.

Yield: 23.7 g (72.2% of theory)

Melting point: (oil)

IR: 3331 cm- '(v CHJ, 2967, 2873 cm ^{' 1} (v CH), 1703 cm '(v C = O), 1578 cm ^{' 1} (C = C), 1533 cm ^' ' (v ,, NO ₂ ), 1365 cm ^'1 (v _s NO ₂ ), 1226 cm ^{' 1} (v O-C).

'H NMR: 9.7 ppm (1H, s, NH); 7.96 ppm (H ⁶ , s); 7.49 ppm (H ⁵ , dd, ³ J _HH = 9.07

Hz, ⁴ J _aH = 2.04 Hz); 6.98 ppm (H ³ , d, ³ J _aH = 9.24 Hz); 4.20 ppm (2H, t, ³ J _H = 6.22 Hz, C (O) OCH ₂ ); 3.73 ppm (2H, t, ^ = 6.46 Hz, CH ₂ C1); 3.09 ppm (4H, t, ³ J _HJ1 = 6.05 Hz, CH ₂ NCH ₂ ); 2.08 ppm (2H, q, ³ J _HH = 6.35 Hz, CH ₂ CH ₂ CH ₂ C1); 1.88 ppm (4H, m, ^ = 6.27 Hz, CH ₂ CH ₂ ).

Step c) N- [4- (3-hydroxypropylamino) -2-nitrophenyl] pyrrolidine

The reaction in stage c) was carried out analogously to example 1.3.9. Step c) by conversion of N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyI] pyrrolidine with sodium hydroxide solution.

Yield: 1.2 g (81.8% of theory)

Step d) N- [4- (3-hydroxypropylamino) -2-aminophenyl] pyrrolidine sulfate

Yield: 16.6 g (86.9% of theory)

/.3.15. Preparation of N- [2-amino-4- (3-hydroxypropylamino) phenyl] azepane sulfate

Step a) N- (4-amino-2-nitrophenyl) azepane

Stage a) was carried out analogously to Example 1.3.9. Step a) by reaction of 4-fluoro-3-nitraniline with azepane.

Yield: 37.2 g (39.5% of theory)

Melting point: 72-73.5 ° C

IR: 3467, 3380 cm ^'1 (v CHJ, 2926, 2853 cm ^" ' (v CH), 1631 cm ^" '(v C = C),

1520 (v "NO ₂ ), 1360 cm ^" '(v _s NO ₂ ).' H NMR: 7.07 ppm (H ⁶ , d, ³ J _H = 8.64 Hz); 6.79 ppm (H ⁵ , dd, ³ J _aH = 6.96 Hz,

'JH _H = 2.59 Hz); 6.75 ppm (H \ d, "J ^ = 2.68 Hz); 5.24 ppm (2H, s,

NO.); 3.00 ppm (4H, t, ^ = 5.49 Hz, NCH ₂ ); 1.62 ... 1.56 ppm (8H, m,

NCH ^ CH _j CH ^ CI J. Step b) N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyl] azepane O 98/011

- 39 -

Stage b) was analogous to Example 1.3.9. Step b) carried out by reacting N- (4-amino-2-nitrophenyl) azepane with 3-chloroformate chloroformate.

Yield: 13.6 g (63.7% of theory)

Melting point: 61 - 63 ° C

IR: 3395, 3098 cm ^" '(v CHJ, 2928, 2856 cm ^{' 1} (v CH), 1726 cm ^'1 (v C = O),

1574 cm ^' ' (v C = C), 1533 ( _Vas NO ₂ ), 1354 cm ^'1 (v _s NO ₂ ), 1226 cm' ¹ (v OC).

'H NMR: 9.75 ppm (1H, s, NH); 7.90 ppm (H ³ , s); 7.48 ppm (H ⁵ , dd, ³ J _H = 9.08

Hz,% _M = 1.89 Hz); 7.15 ppm (H ⁶ , d, "J ^ = 9.17 Hz); 4.20 ppm, 4.23 ppm (2H, t, ^ = 6.17 Hz, C (O) OCH ₂ ); 3 , 72 ppm (2H, t, ³ J _aH = 6.44 Hz, CH ₂ C1); 3.13 ppm (4H, t, ^ = 5.44 Hz, CH ₂ NCH ₂ ); 2.08 ppm (2H m 1.67 ppm (4H, s, NCH ₂ CH ₂ ); 1.49 ppm (4H, s, NCH _J CH _J CI.

Step c) N- [4- (3-hydroxypropylamino) -2-nitrophenyl] azepane

The reaction in stage c) was carried out analogously to example 1.3.9. Step c) by converting N- [4- (3-chloropropoxycarbonylamino) -2-nitrophenyl] azepane with sodium hydroxide solution.

Yield: 12.8 g (34.3% of theory)

Step d) N- [2-amino-4- (3-hydroxypropylamino) phenyl] azepane sulfate

The reaction in stage d) was carried out analogously to example 1.3.9 stage d) by catalytic reduction of the product obtained in stage c) and subsequent precipitation with sulfuric acid.

Yield: 12.9 g (81.8% of theory)

1.3.16. Preparation of N- {2-amino-4- [di- (2-hydroxyethyl) amino] phenyl} pyrrolidine sulfate

Step -) N- {2-nitro-4- [di- (2-hydroxyethyl) amino] phenyl} pyrrolidine 24.4 g (0.1 mol) of 4-fluoro-3- nitro-N, N-di- (2-hydroxyethyl) aniline, 7.8 g (0.11 mol) pyrrolidine, 5.3 g (0.05 mol) potassium carbonate and 0.25 g methyl-tri (C ₆ -C,) alkylammonium chloride (70% in wo-propanol) dissolved and heated under reflux until the reaction was complete. The undissolved salts were filtered off while hot and the mother liquor was cooled. The precipitated product was filtered off and dried. Yield: 23.8 g (80.6% of theory)

IR: 3401 cm ^'1 (v CHJ, 2965, 2870 cm ^{' 1} (v CH), 1630 cm ^'1 (v C = C), 1547 ( _Vas

NO ₂ ), 1358 cm ^' ' ( _vs NO ₂ ). 98/01106

- 40 -

'H NMR: 7.02 ppm (H ³ H ⁵ H ⁶ , m); 4.73 (2H, t, ³ J _a0H = 5.38 Hz, CH ₂ OH); 3.53 ppm (4H, q, ³ J _aH = 6.34 Hz, CH ₂ OH); 3.36 ppm (4H, t, ³ J _H = 5.74 Hz, NCH CH ₂ OH); 3.04 ppm (4H, t, ^ = 6.39 Hz, NCH ₂ ); 1.88 ppm (4H. T, ³ J _HH = 6.42 Hz, NCH ₂ CH ₂ CH ₂ ).

Step b) N- {2-amino-4- [di- (2-hydroxyethyl) amino] phenyl} pyrrolidine sulfate

The reaction in stage b) was carried out analogously to example 1.3.9. Stage d) by catalytic reduction of the product obtained in stage a) and subsequent precipitation with sulfuric acid.

Yield: 1 1.5 g (45.3% of theory)

NOj) 1358 cm- '(v _s NO _2).

'H NMR: 7.02 ppm (H ³ H ⁵ H ⁶ , m); 4.73 (2H, t, ³ J _a0H = 5.38 Hz, CH ₂ OH); 3.53 ppm (4H, q, ³ J _aH = 6.34 Hz, CH ₂ OH); 3.36 ppm (4H, t, ³ J _aH = 5.74 Hz, NCH _j - CH ₂ OH); 3.04 ppm (4H, t, ³ J _aH = 6.39 Hz, NCH ₂ ); 1.88 ppm (4H, t, ³ J _H = 6.42 Hz, NCH ₇ CH, CH _Z ).

1.3.17. Preparation of N-methyl-2,5-diaminoaniline sulfate

Step a) N-methyl-2-nitro-5-acetaminoaniline

100 ml of 1,2-dimethoxyethane, 21.5 g (0.1 mol) of 2-nitro-5-acetylaminochlorobenzene, 15.1 g (0.11 mol) of potassium carbonate and 12.4 g (0.11 Mole) 40

% methylamine solution submitted. This mixture was heated for eight hours

Stir to 120 ° C. The inorganic salts were filtered hot and the product was drawn off

Solvent in a vacuum. The precipitated yellow powder was recrystallized from ethanol.

Yield: 17 g (100% of theory)

IR: 3351 cm ^'1 (v CHJ, 3303, 3183, 2808 cm ^" ' (v CH), 1694 cm ^' ' (v C = O),

1639 cm ^'1 (v C = C), 1582, 1562 cm ^{' 1} (v., NO ₂ ), 1366, 1325 cm ^" '(v,

NO ₂ ). 'H NMR: 10.2 ppm (1H, s, NHAc); 8.43 ppm (1H, m, NHCH ₃ ); 8.19 ppm (H ³ , d,, = 9.34 Hz); 7.56 ppm (H ⁶ , d, ^ = 2.95 Hz); 6.97 ppm (H ⁴ , dd,

³ J _aH = 9.42 Hz,% _M = 2.14 Hz); 3.08 ppm (3H, t, M ^ = 4.93 Hz,

NCH ₃ ); 2.27 ppm (3H, s, C (= O) CH ₃ ). Step b) N-methyl-2-nitro-5-aminoaniline

15.9 g (0.095 mol) of N-methyl-5-acetamino-2-nitroaniline (from stage a) were placed in a mixture of 78 ml of water and 26 ml of methanol and concentrated with 25.8 ml 98/01106

- 41 -

Hydrochloric acid heated under reflux for one hour. After conversion was complete, the pH of the mixture was adjusted to 7 with ammonia and the product was stirred.

The product was filtered off and washed with water.

Yield: 12.4 g (78.1% of theory)

IR: 3425 cm ^'1 (v CHJ, 3336, 3227, 2926 cm ^{' 1} (v CH), 1636 cm ^'1 (v C = C),

1577 ^{cm -1} NOj), 1331 ^{cm -1} (v _s NO _2). 'H NMR: 8.33 ppm (1H, m, NHCH ₃ ); 7.82 ppm (H ³ , d,, = 9.37 Hz); 6.59 ppm

(2H, s, NH ₂ ); 6.0 ppm (H ⁴ , dd, M ^ = 9.36 Hz, ⁴ J _aH = 2.12 Hz); 5.8 ppm (H ⁶ , d, "J _H J _J = 2.11 Hz); 2.86 ppm (3H, t, ³ J _aH = 4.96 Hz, NCH ₃ ). Step c) N-methyl -2,5-diaminoaniline sulfate

15.9 g (0.064 mol) of N-methyl-2-nitro-5-aminoaniline (from stage b) with 1 g of palladium on activated carbon 10% (Degussa) in 180 ml of methanol were placed in a 0.3 l autoclave. After sealing and inerting with nitrogen, the mixture was hydrogenated at a pressure of 3 bar and a temperature of 35-40 ° C. until no more hydrogen was taken up. 1.3 g of activated carbon were added to the warm solution under nitrogen and the catalyst was filtered off. 8.4 g of 80% sulfuric acid were added dropwise to the solution while cooling with ice at 5 ° C. The precipitated product was filtered off, washed with methanol and dried. Yield: 14.4 g (90% of theory)

Melting point:> 200 ° C

IR: 3384 cm '(v OH), 2878 cm ^{' 1} (v CHJ, 1602 cm ^'1 (v C = C).

'H NMR: 8.2-7.2 ppm (6H, NH ₃ ⁺ ); 6.69 ppm (H \ d, = 7.82 Hz); 6.19 ppm

(H ⁴ , s); 6.16 ppm (H ⁶ , s); 2.71 ppm (3H, s, NCH ₃ ).

1 3.18. Preparation of N-ethyl-2,5-diaminoaniline sulfate

Step a) N-ethyl-2-nitro-5-acetaminoaniline

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with ethylamine.

Yield: 19.7 g (88.2% of theory) of yellow crystals

IR: 3343 cm ^'1 (v CHJ, 3225, 2971, 2873 cm ^"1 (v CH), 1702 cm ^{' 1} (v C = O),

1621 cm ^'1 (v C = C), 1582 cm ^{' 1} (v _B NO ₂ ), 1367 cm ^'1 (v _s NO ₂ ). 'H NMR: 10.31 ppm (1H, s, NHAc); 8.19 ppm (1H, t, NHEt, M ^ = 5.22 Hz);

8.02 ppm (H ³ , d, ³ J _aH = 9.42 Hz); 7.46 ppm (H ⁶ , d, ⁴ J _aH = 1.97 Hz);

6.79 ppm (H ⁴ , dd, 'J ^ = 9.39 Hz, M ^ = 2.01 Hz); 3.08 ppm (2H, m, 98/01106

42 -

rc = 5.71 Hz, M _C ∞. _CH , = 6.99 Hz, NCH ₂ ); 1.25 ppm (3H, t, ³ J _aH =

7.1 Hz, NCH ₂ CH ₃ ). Step b) N-ethyl-2-nitro-5-aminoaniline

The preparation in stage b) was carried out analogously to Example 1.3.17. Step b) by reaction of N-ethyl-2-nitro-5-acetaminoaniline with hydrochloric acid. Yield: 15.3 g (84.4% of theory)

IR: 3438 cm ^'1 (v CHJ, 3339, 3232, 2979 cm ^{' 1} (v CH), 1619 cm ^'1 (v C = C),

1564 cm ^'1 (v _B NO ₂ ), 1354 cm ^{' 1} (v, NO ₂ ). 'H NMR: 8.29 ppm (1H, s, NH); 7.82 ppm (H ³ d, ³ J _aH = 9.22 Hz); 6.59 ppm (2H, s, NH ₂ ); 6.0 ppm (H \ dd,% _M = 9.48 Hz, ⁴ J _aH = 2.0 Hz); 5.84 ppm (H ⁶ d, * J _HJ1 = 2.03 Hz); 3.2 ppm (2H, m, ³ J _acH3 = 5.45 Hz, ³ J _CH2 . _CH3 = 7.08

Hz, NCH ₂ ); 1.24 ppm (3H, t, ³ J _CH2 . _CH3 = 7.12 Hz, NCH ₂ CH ₃ ). Step c) N-ethyl-2,5-diaminoaniline sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N-ethyl-2-nitro-5-aminoaniline. Yield: 15.4 g (85.8% of theory)

Melting point:> 200 ° C

IR: 3369 cm ^'1 (v OH), 2883 cm ^{' 1} (v CHJ, 1618 cm '(v C = C).

'H NMR: 8.2-7.2 ppm (6H, NH ₃ ⁺ ); 6.81 ppm (H ³ , s); 6.71 ppm (HH ⁶ , s); 3.03 ppm (2H, q, J ^ = 7.11 Hz, NCH ₂ ); 2.71 ppm (3H, t, J _aH = 7.11 Hz,

NCH ₂ CH ₃ ).

1.3.19. Preparation of N-n-propyl-2,5-diaminoaniline sulfate

Step a) N-n-propyl-2-nitro-5-acetylaminoaniline

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with «-propylamine.

Yield: 15.5 g (65.3% of theory) of yellow crystals

IR: 3349 cm ^'1 (v CHJ, 3235, 2964, 2934 cm ^" ' (v CH), 1694 cm ^'1 (v C = O),

1623 cm ^'1 (v C = C), 1582 cm ^" ' (v _M NO ₂ ), 1326 cm ^'1 (v, NO ₂ ).

'H NMR: 10.30 ppm (1H, s, NHAc); 8.25 ppm (1H, t, NHPr, \ _M = 5.40 Hz);

8.02 ppm (H \ d, \ _M = 9.35 Hz); 7.46 ppm (H ⁶ , d, ⁴ J _aH = 2.08 Hz); 6.78 ppm (H ⁴ , dd, 'J ^ = 9.39 Hz, ⁴ J _aH = 2.14 Hz); 3.22 ppm (2H, m, NCH ₂ ); 2.09 ppm (3H, s, C (= O) CH _3); 1.65 ppm (2H, m, NCH _J CH _J CH,); 0.96 ppm (3H, t, ^ = 7.40 Hz, NCH ₂ CH ₂ CH ₃ ).

Step b) Nn-propyl-2-nitro-5-aminoaniline 98/01106

- 43 -

The preparation in stage b) was carried out analogously to Example 1.3.17. Step b) by reaction of N - «- propyl-2-nitro-5-acetaminoaniline with hydrochloric acid.

Yield: 11.7 g (98.3% of theory) IR: 3444 cm ^'1 (v CHJ, 3343, 3232, 2964 cm ^{' 1} (v CH), 1631 cm ^'1 (v C = C),

1570 cm ^'1 (v ,, NO ₂ ), 1364 cm ^{' 1} (v _s NO ₂ ).

'H NMR: 8.38 ppm (1H, t, ^ = 4.67 Hz, NH); 7.84 ppm (H ³ d, ³ J _aH = 9.36 Hz);

6.59 ppm (2H, s, NH ₂ ); 6.02 ppm (H ⁴ , dd, ³ J _aH = 9.38 Hz, ⁴ J _aH = 1.81

Hz); 5.86 ppm (H ⁶ s); 3.16 ppm (2H, m, ³ J _aH = 7.21 Hz, NCH ₂ ); 1.64 ppm (2H, t, 'J _HJ , = 7.37 Hz, NCH ₂ CH ₂ CH ₃ ); 0.97 ppm (3H, t, ³ J _HH =

7.37 Hz, NCH ₂ CH ₂ CH ₃ ). Step c) Nn-propyl-2,5-diaminoanüin sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N - «- propyl-2-nitro-5-aminoaniline. Yield: 12.1 g (83.5% of theory)

Melting point:> 200 ° C

IR: 3370 cm ^'1 (v OH), 2932 cm ^{' 1} (v CHJ, 1608 cm ^"1 (v C = C). 'H-NMR: 7.8 - 5.4 ppm (6H, NH ₃ ⁺ ) ; 6.78 ppm (H ³ , d, ³ J _aH = 8.06 Hz); 6.71 ppm

(H ⁴ H ⁶ , m); 2.95 ppm (2H, t, J ^ = 7.08 Hz, NCH ₂ ); 1.62 ppm (2H, q,

J _HM = 7.16 Hz, NCH ₂ CH ₃ ); 0.96 ppm (3H, t, ³ J _aH = 7.34 Hz,

NCH ₂ CH ₂ CH ₃ ).

1.3.20. Preparation of N-iso-butyl-2,5-diaminoaniline sulfate

Step a) N- \ so-butyl-2-nitro-5-acetylaminoaniline

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with wo-butylamine.

Yield: 14.5 g (57.7% of theory) of yellow crystals

IR: 3347 cm ^"1 (v CHJ, 3083, 2969, 2936 cm ^{" 1} (v CH), 1704, 1680 cm ^'1 (v

C = O), 1621 cm ^"1 (v C = C), 1581 cm ¹ (v ^ NOj), 1325 cm ^{" 1} (v _s NO ₂ ).

'H NMR: 10.31 ppm (1H, s, NHAc); 8.09 ppm (1H, t, NHBu, ³ J _aH = 7.51 Hz);

8.08 ppm (H \ d,] "= 9.38 Hz); 7.53 ppm (H ⁶ , d, ⁴ J _aH = 2.01 Hz); 6.78 ppm (H ⁴ , dd, ^ = 9.38 Hz, J _W = 2.09 Hz); 3.53 ppm (1H, q, CH (CH ₃₎ _2); 2.1 ppm (3H, s, C (= O) CH _3); 1.61 ppm (2H, m, ^ = 7.09 Hz, NCH ^ CH,) -,); 1.24 ppm (3H, d, ^ = 6.34 Hz, syn-CH (CH ₃ ) ₂ ); 0.94 ppm (3H, t, 'J ^ = 7.42 Hz, anti-CH (CH ₃ ) ₂ ). 98/01106

- 44 -

Step b) N-iso-butyl-2-nitro-5-aminoaniline

The preparation in stage b) was carried out analogously to Example 1.3.17. Stage b) through

Reaction of N-wo-butyl-2-nitro-5-acetaminoaniIin with hydrochloric acid.

Yield: 11.5 g (55.2% of theory)

Melting point: (red oil)

IR: 3467, 3350, 3234 cm ^'1 (v CHJ, 2967, 2932, 2876 cm ^{' 1} (v CH), 1631 cm ^' ' (v C = C), 1568 cm ^'1 (v _B NO ₂ ), 1355 cm ^'1 (v, NO ₂ ).

'H NMR: 8.33 ppm (1H, d, M ^ = 7.56 Hz, NH); 7.82 ppm (H ³ d, ³ J _aH = 9.46 Hz);

6.00 ppm (H ⁴ , dd, ^ = 9.48 Hz, M ^ = 2.18 Hz); 5.87 ppm (H ⁶ d, * 3 _HM = 2.1 1 Hz); 3.49 ppm (1H, m, ³ J _aH = 6.56 Hz, NCH ₂ CH); 1.59 ppm (2H, m, ³ J _aH = 9.21 Hz, NCH ₂ CH (CH ₃ ) ₂ ); 1.21 ppm (3H, d, ³ J _HH = 6.33 Hz, anti-NCH ₂ CH (CH ₃ ) ₂ ); 0.93 ppm (3H, t, ^ = 7.44 Hz, syn-NCH ₂ CH (CH ₃ ) ₂ ).

Step c) 3- \ so-Butylamino-4-aminoanüin sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N-wo-butyl-2-nitro-5-aminoaniline.

Yield: 8 g (55.5% of theory)

Melting point:> 200 ° C

IR: 3393 cm ^' ' (v OH), 2968 cm ^'1 (v CHJ, 1608 cm ^{' 1} (v C = C).

'H NMR: 7.8-7.0 ppm (6H, NH ₃ ⁺ ); 6.69 ppm (H ³ , d, M "^ = 8.15 Hz); 6.19 ppm

(H ⁶ , s); 6.13 ppm (H ⁴ , d, *} "= 8.10 Hz); 3.27 ppm (1H, m, NHCH ₂ CH (CH ₃ ) ₂ ); 1.59 ppm (1H, m, ^ = 6.77 Hz, anti-NCH ₂ ); 1.46 ppm (1H, m, J ^ = 6.91 Hz, syn-NCH ₂ ); 1.14 ppm (3H, m, ³ J _HH = 6.22 Hz, anti-NCH2CH (CH ₃ )); 0.93 ppm (3H, m, J _HH = 7.33 Hz, syn-NCH ₂ ) ;.

1.3.21 Preparation of N, N-dimethyl-2,5-diaminoaniline sulfate stage a) N, N-dimethyl-2-nitro-5-acetylaτninoaniline

Stage a) was carried out analogously to Example 1.3.17. Step a) by reacting 2-nitro-5-acetylaminochlorobenzene with dimethylamine. Yield: 16.8 g (75.5% of theory) of yellow crystals

IR: 3552, 3363 cm ^'1 (v CHJ, 2928, 2801 cm ^{' 1} (v CH), 1678 cm ^'1 (v C = O),

1613 cm ' ¹ (v C = C), 1554 cm ^{' 1} (v ,, NO ₂ ), 1337 cm ^"1 (v _s NO ₂ ). 98/01106

45 -

'H NMR: 10.2 ppm (1H, s, NHAc); 7.8 ppm (H \ d, J _aH = 9.02 Hz); 7.48 ppm

(H ⁶ , d,, = 1.83 Hz); 7.05 ppm (H \ dd, ³ J _aH = 9.03 Hz, ⁴ J _aH = 1.98 Hz); 2.08 ppm (3H, s, C (= O) CH _3); 2.78 ppm (6H, s, N (CH ₃₎ _2).

Step b) N, N-dimethyl-2-nitro-5-aminoaniline

Reaction of N, N-dimethyl-2-nitro-5-acetaminoaniline with hydrochloric acid.

Yield: 18.9 g (100% of theory) of yellow crystals

IR: 3449, 3337 cm ^'1 (v CHJ, 2971, 2872 cm ^{' 1} (v CH), 1619 cm ^'1 (v C = C),

1562 cm ^'1 (v "NO ₂ ), 1320 cm ^{' 1} (v _s NO ₂ ).

'H NMR: 7.83 ppm (H ³ , d, ^ = 9.70 Hz); 7.29 ppm (2H, s, NH ₂ ); 6.38 ppm (H \ dd, _M = 9.76 Hz, ^ = 2.60 Hz); 6.23 ppm (H ⁶ , d, J _aH = 2.60 Hz); 3.71 ppm (3H, t, 'J ^ = 4.88 Hz, syn-NCH ₃ ); 3.27 ppm (3H, t,% _M = 4.90 Hz, anti-NCH ₃ ).

Step c) N, N-dimethyl-2,5-diaminoaniline sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N, N-dimethyl-2-nitro-5-aminoaniline.

Yield: 19.6 g (81.1% of theory)

Melting point:> 200 ° C

IR: 3368, 3224 cm ^'1 (v OH), 2851 cm ^" ' (v CHJ, 1630 cm ^'1 (v C = C).

'H NMR: 8.0-7.0 ppm (6H, NH ₃ ⁺ ); 7.0 ppm (H ³ , d, ^ = 8.65 Hz); 6.43 ppm

(H ⁶ , d, ³ J _H = 2.46 Hz); 6.31 ppm (H \ dd,% _M = 8.73 Hz, ⁴ J _aH = 2.46 Hz); 3.72 ppm (3H, t,% _M = 4.69 Hz, syn-NCH ₃ ); 3.03 ppm (3H, t, ³ J _H = 4.71 Hz, anti-NCH ₃ ).

1.3.22. Preparation of N, N-diethyl-2,5-diaminoaniline sulfate

Step a) N, N-diethyl-2-nitro-5-acetylaminoaniline

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with diethylamine.

Yield: 20.1 g (79.9% of theory) of yellow crystals

IR: 3437, 3294 cm ^'1 (v CHJ, 2979, 2934 cm ^" ' (v CH), 1671 cm ¹ (v C = O),

1613 cm ^'1 (v C = C), 1558 cm ^" ' (v ^ NO ₂ ), 1347 cm ^'1 (v _s NO ₂ ).

'H NMR: 10.43 ppm (1H, s, NHAc); 7.92 ppm (H ³ , d, ⁱ i _w = 9.24 Hz); 7.75 ppm

(H ⁶ , d, ⁴ J _aH = 2.06 Hz); 7.35 ppm (H ⁴ , dd, ³ J _aH = 8.97 Hz, ^« J ^ = 2.06 Hz); 3.26 ppm (4H, q, ³ J _aH = 7.04 Hz, N ^ H ^ CH,),); 2.26 ppm (3H, s, C (= O) CH ₃ ); 1-20 ppm (6H, t, ³ J _W = 7.04 Hz, ^ (CH ₂ C ^. 98/01106

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Step b) N, N-diethyl-2-nitro-5-aminoaniline

Reaction of N, N-diethyl-2-nitro-5-acetaminoaniline with hydrochloric acid.

Yield: 12.6 g (60.2% of theory)

Melting point: (red oil)

IR: 3469, 3367, 3233 cm ^'1 (v CHJ, 2974, 2923, 2872 cm ^{' 1} (v CH), 1631 cm ^'1 (v C = C), 1567 cm ^{' 1} (v ^ NO ₂ ), 1344 cm ^'1 (v, NO ₂ ).' H-NMR: 7.91 ppm (H ³ , d, ³ J _aH = 8.99 Hz); 6.45 ppm (2H, s, NH ₂ ); 6, 41 ppm (H ⁶ , d, J _aH = 2.23 Hz); 6.32 ppm (H ⁴ , dd, ³ J _aH = 9.08 Hz, ⁴ J _aH = 2.23 Hz);

3.23 ppm (3H, t, \ _M = 7.04 Hz, N (CH ₂ CH ₃ ) ₂ ); 1.21 ppm (3H, t, ³ J _H =

7.03 Hz, N (CH ₂ CH ₃ ) ₂ ). Step c) N, N-diethyl-2,5-diaminoaniline sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N, N-diethyI-2-nitro-5-aminoaniline. Yield: 10.1 g (64.3% of theory)

Melting point:> 200 ° C IR: 3379 cm ^'1 (v OH), 3233 cm ^{' 1} (v CHJ, 2901 cm ^'1 (v CH, 1630 cm ^{' 1} (v

C = C). 'H NMR: 8.4-7.0 ppm (6H, NH ₃ ^* ); 6.84 ppm (H ³ , d, ^ = 8.51 Hz); 6.81 ppm

(H ⁶ , d, \ _M = 2.41 Hz); 6.7 ppm (H \ dd,% _M = 8.41 Hz, ⁴ J _aH = 2.13

Hz); 2.91 ppm (3H, t, ^ = 7.04 Hz, N CH ^ CH ^); 0.93 ppm (3H, t,

³ J _a "= 7.05 Hz, N (CH ₂ CH ₃ ) ₂ ).

1.3.23. Preparation of N- (2,5-diaminophenyl) pyrrolidine sulfate

Step a) N- (5-acetylamino-2-nitrophenyl) pyrrolidine

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with pyrrolidine.

Yield: 24.3 g (97.5% of theory) of yellow crystals

IR: 3262 cm ^* '(v CHJ, 2969, 2873 cm ^{' 1} (v CH), 1667 cm ^'1 (v C = O), 1614 cm ^{' 1} (v C = C), 1548 cm ^'1 (v, , NO ₂ ), 1358 cm ^"1 ( _vs NO ₂ ).

'H NMR: 10.38 ppm (1H, s, NHAc); 7.91 ppm (H ³ , d, ³ J _HJ1 = 9.05 Hz); 7.61 ppm

(H ⁶ , d, "J ^ = 1.95 Hz); 7.11 ppm (H ⁴ , dd, ³ J _aH = 9.06 Hz,% = 2.01 Hz); 3.27 ppm (4H, t, ³ J _a "= 6.25 Hz, N (CH ₂ ) ₂ ); 2.25 ppm (3H, s, C (= O) CH ₃ ); 2.09 ppm (4H, t, ^ = 6 , 25 Hz, N (CH ₂ CH ₂ ) ₂ ) ;.

Step b) N- (5-amino-2-nitrophenyl) pyrrolidine 98/0110

- 47 -

Reaction of N- (5-acetylamino-2-nitrophenyl) pyrrolidine with hydrochloric acid.

Yield: 18.3 g (98.1% of theory)

Melting point: (red oil)

IR: 3468, 3366, 3231 cm ^" '(v CHJ, 2970, 2874 cm ^{' 1} (v CH), 1608 cm ^" '(v

C = C), 1560 cm ^" '(v. NO _2), 1360 ^{cm" 1} (v _s NO _2). 'H NMR: 7.81 ppm (H \ d, ^ = 9.35 Hz); 6.32 ppm (2H, s, NH ₂ ); 6.18 ppm

(H ⁴ H ⁶ , m); 3.25 ppm (4H, t,% _M = 6.34 Hz, N (CH ₂ CH ₂ ) ₂ ); 2.05 ppm

(4H, t, ^3. ^ = 6.35 Hz, N (CH ₂ CH ₂ ) ₂ ). Step c) N- (2,5-diaminophenyl) pyrrolidine sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N- (5-amino-2-nitrophenyl) pyrrolidine. Yield: 13.5 g (59.5% of theory)

Melting point:> 200 ° C IR: 3382 cm ^'1 (v OH), 3231 cm ^"1 (v CHJ, 2882 cm ^{" 1} (v CH, 1625 cm ^{' 1} (v

C = C). 'H NMR: 8.0-6.4 ppm (6H, NH ₃ ⁺ ); 6.82 ppm (H ³ , d, ³ J _HιH = 8.35 Hz); 6.57 ppm

(H ⁶ , d, ³ J _aH = 2.06 Hz); 6.45 ppm (H ⁴ , dd, ³ J _H = 8.33 Hz, ⁴ J _aH = 2.06

Hz); 3.03 ppm (4H, t, M ^ = 5.86 Hz, N (CH ₂ CH ₂ ) ₂ ); 1.88 ppm (4H, t,

% _M = 5.98 Hz, NC ^ CH ^).

1.3.24 Preparation of N- (2,5-diaminophenyl) piperidine sulfate

Step a) N- (5-acetylamino-2-nitrophenyl) piperidine

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with piperidine.

Yield: 22.1 g (84.1% of theory) of yellow crystals

Step b) N- (5-amino-2-nitrophenyl) pipehdin

Reaction of N- (5-acetylamino-2-nitrophenyl) piperidine with hydrochloric acid.

Yield: 17.8 g (81.5% of theory)

Melting point: (red oil)

IR: 3449, 3358, 3245 cm ^'1 (v CHJ, 2990, 2938 cm ^" ' (v CH), 1604 cm ^'1 (v

C = C), 1563 cm ^" '(v _B N0 ₂ ), 1341 cm ^{' 1} (v _s NO ₂ ). 'H-NMR: 7.83 ppm (H ³ , d, ³ J _aH = 8.91 Hz ); 6.40 ppm (2H, s, NH ₂ ); 6.19 ppm (H \ dd, ³ J _aH = 4.36 Hz, _H = 2.19 Hz); 6.15 ppm (H ⁶ , d , "J ^ = 2.29 Hz); 98/01106

- 48 -

2.88 ppm (4H, t, ³ J _aH = 5.37 Hz, N (CH ₂ CH ₂ ) ₂ CH ₂ ); 1.63 ppm (4H, m, N (CH ₂ CH ₂₎ ₂ CH _2); 1.54 ppm (2H, m, N (CH ₂ CH ₂ ) ₂ CH ₂ ).

Step c) N- (2,5-diaminophenyl) piperidine sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N- (5-amino-2-nitrophenyl) piperidine.

Yield: 13.3 g (57.5% of theory)

Melting point:> 200 ^C C

1.3.25. Preparation of N- (2,5-diaminophenyl) azepane sulfate

Step a) N- (5-acetylamino-2-nitrophenyl) azepane

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with azepan.

Yield: 25.3 g (91.3% of theory) of yellow crystals

IR: 3331, 3285 cm ^'1 (v CHJ, 2934, 2856 cm ^{' 1} (v CH), 1700, 1681 cm ^'1 (v

C = O), 1613 cm ^'1 (v C = C), 1549 cm ^"1 (v" NO ₂ ), 1338 cm ^"1 (v ₅ NO ₂ ).

'H NMR: 10.2 ppm (1H, s, NHAc); 7.70 ppm (H ³ , d,>] "= 9.02 Hz); 7.62 ppm

(H ⁶ , d, "= 1.85 Hz); 6.97 ppm (H ⁴ , dd, ^ = 8.98 Hz, ⁴ J _W = 1.83 Hz); 3.20 ppm (4H, t, ³ J _aH = 5.57 Hz, N (CH ₂ ) ₂ ); 2.08 ppm (3H, s, C (= O) CH _3); 1.76 ppm (4H, s, N (CH ₂ CH ₂₎ _2); 1.52 ppm (4H, s, N (CH ₂ CH ₂ CH ₂ ) ₂ ) ;.

Step b) N- (5-amino-2-nitrophenyl) azepane

Reaction of N- (5-acetylamino-2-nitrophenyI) azepan with hydrochloric acid.

Yield: 19.8 g (95.6% of theory) of yellow crystals

IR: 3460, 3353 cm ^'1 (v CHJ, 3230, 2926, 2855 cm ^"1 (v CH), 1607 cm ^{" 1} (v

C = C), 1550 cm ^"1 (v" NO ₂ ), 1362 cm ^"1 (v _s NO ₂ ).

'H NMR: 7.65 ppm (H ³ , d, ^ = 9.08 Hz); 6.19 ppm (H ⁶ , d, ⁴ J _aH = 1.95 Hz);

6.16 ppm (2H, s, NH ₂ ); 6.05 ppm (H ⁴ , dd,> J _W = 9.02 Hz,% _M = 1.85 Hz); 3.18 ppm (4H, t, ^ = 5.48 Hz, N (CH ₂ ) ₂ ); 1.72 ppm (4H, s, N (CH ₂ CH ₂₎ _2); 1.53 ppm (4H, s, N (CH ₂ CH ₂ CH ₂ ) ₂ ) ;.

Step c) N- (2,5-diaminophenyl) azepane sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N- (5-amino-2-nitrophenyl) azepane.

Melting point:> 200 ° C 98/01106

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IR: 3368 cm ^'1 (v OH), 3214 cm ^"1 (v CHJ, 2926 cm ^{" 1} (v CHJ, 1618 cm ^" ' (v

C = C).

'H NMR: 8.4-6.4 ppm (6H, NU); 6.82 ppm (H ³ H ⁶ , m); 6.65 ppm (H \ dd, ³ J _H

= 8.41 Hz,% _M = 2.27 Hz); 2.95 ppm (4H, t, ³ J _HH = 5.41 Hz, N (CH ₂ CH ₂ ) ₂ ); 1.70 ppm (8H, m, N (CH ₂ CH ₂ CH ₂ ) ₂ ).

2.3.26 Preparation of N- (2,5-diaminophenyl) morpholine sulfate

Step a) N- (5-acetylamino-2-nitrophenyl) morpholine

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Implementation of 2-nitro-5-acetylaminochlorobenzene with Moφholin.

Yield: 25.6 g (96.5% of theory) of yellow crystals

IR: 3291 cm ^"1 (v CHJ, 2968, 2836 cm ^{" 1} (v CH), 1698 cm ^'1 (v C = O), 1612 cm ^{' 1} (v C = C), 1550 cm ^"1 (v, , NO ₂ ), 1331 cm ^'1 (v _s NO ₂ ).' H-NMR: 10.54 ppm (1H, s, NHAc); 8.1 ppm (H ³ , d, ³ J _aH = 9.02 Hz); 7.71 ppm

(H ⁶ , d, ⁴ J _aH = 2.08 Hz); 7.48 ppm (H ⁴ , dd, M ^ = 8.97 Hz, ⁴ J _aH = 2.08

Hz); 3.9 ppm (4H, t, ³ J _aH = 4.54 Hz, N (CH ₂ CH ₂ O) ₂ ); 3.13 ppm (4H, t,

³ J _HΛ = 4.56 Hz, N (CH ₂ CH ₂ O) ₂ ); 2.27 ppm (3H, s, C (= O) CH ₃ ) ;. Step b) N- (5-amino-2-nitrophenyl) morpholine

The preparation in stage b) was carried out analogously to Example 1.3.17. Step b) by reaction of N- (5-acetylamino-2-nitrophenyl) moφholin with hydrochloric acid. Yield: 19.2 g (95.6% of theory) of yellow crystals

Melting point: (red oil) IR: 3466, 3320, 3220 cm ^"1 (v CHJ, 2970, 2867 cm ^{" 1} (v CH), 1606 cm ^"1 (v

C = C), 1572 cm ^" '(v ,, NO ₂ ), 1344 cm ^" ' (v _s NO ₂ ). 'H NMR: 7.88 ppm (H \ d, ³ J _aH = 8.63 Hz); 6.51 ppm (2H, s, NH ₂ ); 6.22 ppm

(HH ⁶ , m); 3.73 ppm (4H, t, ³ J _aH = 4.44 Hz, NfCH.CH ^ O),); 2.92 ppm

(4H, t, \ _M = 4.47 Hz, N (CH ₂ CH ₂ O) ₂ ). Step c) N- (2,5-diaminophenyl) morpholine sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N- (5-amino-2-nitrophenyl) moφholin. Yield: 22.3 g (95.7% of theory)

Melting point:> 200 ° C

IR: 3411 cm ^" '(v CHJ, 2873 cm ^{' 1} (v CH, 1613 cm ^'1 (v C = C).

'H NMR: 8.4-6.6 ppm (6H, NH ₃ ⁺ ); 6.83 ppm (H ³ , d, ^ = 8.44 Hz); 6.81 ppm

(H ⁶ , d, ³ J _aH = 2.02 Hz); 6.72 ppm (H ⁴ , dd, ^ = 8.34 Hz, "J ^ = 1.84 98/01106

- 50 -

Hz); 3.76 ppm (4H, t, ³ J _HJi = 4.33 Hz, N (CH ₂ CH ₂ O) ₂ ); 2.78 ppm (4H, t, ³ J _aH = 4.31 Hz, N (CH ₂ CH ₂ O) ₂ ).

1.3.27. Preparation of N- (2,5-diaminophenyl) piperazine sulfate stage a) N- (5-acetylamino-2-nitrophenyl) piperazine

Stage a) was carried out analogously to Example 1.3.17. Stage a) through

Reaction of 2-nitro-5-acetylaminochlorobenzene with piperazine.

Yield: 21.5 g (81% of theory) of yellow crystals

IR: 3435 cm ^" '(v CHJ, 3039, 2920, 2853 cm ^{' 1} (v CH), 1695 cm ^{" 1} (v C = O),

1615 cm ^"1 (v C = C), 1558 cm ^{" 1} (v _ω NO ₂ ), 1366 cm ^"1 (v _s NO ₂ ). 'H-NMR: 10.32 ppm (1H, s, NHAc); 7.86 ppm (H ³ , d, X _M = 9.01 Hz); 7.51 ppm

(H ⁶ , d, * 3 _ιw = 1.93 Hz); 7.25 ppm (H ⁴ , dd, X _M = 8.99 Hz, ⁴ J " _{, H} = 1.97

Hz); 2.86 ppm (4H, t, ³ J _aH = 5.65 Hz, NfCH _j CH ^ NH),); 2.82 ppm (4H, t, Step b) N- (5-amino-2-nitrophenyl) piperazine

The preparation in stage b) was carried out analogously to Example 1.3.17. Step b) by reaction of N- (5-acetylamino-2-mtrophenyl) piperazine with hydrochloric acid. Yield: 14.6 g (93.8% of theory) of yellow crystals

IR: 3411, 3317, 3217 cm ^'1 (v CHJ, 2962, 2837 cm ^"1 (v CH), 1608 cm ^{' 1} (v

C = C), 1567 cm ^'1 (v "NO ₂ ), 1349 cm"' (v _s NO ₂ ). 'H-NMR: 7.88 ppm (H ³ , d, ³ J _aH = 9.66 Hz ); 6.59 ppm (2H, s, NH ₂ ); 6.26 ppm (H ⁴ , dd, ³ J _aH = 9.56 Hz, ⁴ J _aH = 2.18 Hz,); 6.25 ppm ( H ⁶ , d,, = 2.07 Hz,);

5.2 ppm (1H, s, NH); 3.02 ppm (8H, s, N CB _j CH _j NH).,). Step c) N- (2,5-diaminophenyl) piperazine sulfate

The preparation in stage c) was carried out analogously to Example 1.3.17. Step c) by catalytic reduction of N- (5-amino-2-nitrophenyl) piperazine. Yield: 13.2 g (75.8% of theory)

Melting point:> 200 ° C

IR: 3436 cm ^"1 (v CHJ, 2848 cm ^'1 (v CHJ, 1616 cm ^" ' (v C = C).

'H NMR: 8.8-6.8 ppm (6H, NH ₃ ⁺ ); 6.66 ppm (H ³ , s); 6.58 ppm (H ⁴ H ⁶ , d); 3.28 ppm (4H, s, N (CH ₂ CH ₂ NH ⁺ ₂₎ _2); 2.97 ppm (4H, s, N (CH ₂ CH ₂ NH ⁺ ₂₎ _2);

2.51 ppm (2H, s, N (CH ₂ CH ₂ NH ⁺ ₂₎ _2).

1.3.28. Preparation of N, N-dimethyl-3,4-diaminoaniline sulfate stage a) N, N-dimethyl-4-nitro-3-acetaminoaniline O 98/01106

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100 ml of 1,2-dimethoxyethane, 21.5 g (0.1 mol) of 4-nitro-3-acetaminochlorobenzene, 20.7 g (0.15 mol) of potassium carbonate and 16.9 g (0.15 mol) were placed in an autoclave. 40

% Dimethylamine solution submitted. This mixture was heated to 120 ° C. with stirring for eight hours. The inorganic salts were then filtered off hot and the solvent was removed in vacuo. The precipitated yellow powder was recrystallized from ethanol.

Yield: 21.3 g (95.4% of theory)

IR: 3313 cm ^'1 (v CHJ, 3313, 3143, 2927 cm ^"1 (v CH), 1702 cm ^{' 1} (v C = O),

1622 cm ^"1 (v C = C), 1575, 1548 cm ^{" 1} (v ,, NO ₂ ), 1344, 1310 cm ^'1 (v _p

NO ₂ ). 'H NMR: 10.59 ppm (1H, s, NHAc); 8.02 ppm (H ⁵ , d, ³ J _aH = 9.70 Hz); 7.63 ppm

(H ² , d, ⁴ J _aH = 2.71 Hz); 6.54 ppm (H ⁶ , dd, ³ J _H = 9.57 Hz, ⁴ J _aH = 2.55

Hz); 3.07 ppm (6H, s, N CH ^); 2.17 ppm (3H, s, C (= O) CH ₃ ). Step b) N, N-dimethyl-2-nitro-5-aminoaniline

20.3 g (0.091 mol) of NN-dimethyl-4-nitro-3-acetaminoaniline (from stage a) were placed in a mixture of 75 ml of water and 21 ml of methanol and refluxed for one hour with 20.7 ml of concentrated hydrochloric acid . After conversion was complete, the pH of the mixture was adjusted to 7 with ammonia and the product was stirred. The product was filtered off and washed with water. Yield: 15.9 g (96.4% of theory)

IR: 3468, 3348 cm ^"1 (v CHJ, 2922 cm ^{" 1} (v CH), 1619 cm ^"1 (v C = C), 1557 cm ^'1 (v ,, NO ₂ ), 1312 cm ^{' 1} (v _$ NO ₂ ). 'H NMR: 7.82 ppm (H ⁵ , d, ³ J _W = 9.75 Hz); 7.25 ppm (2H, s, NH ₂ ); 6.20 ppm (H ⁶ , dd, ³ J _W = 9.81 Hz, * 3 _flii = 2.68 Hz); 5.96 ppm (H ² , d, X = 2.67 Hz);

3.00 ppm (6H, s, N (CH ₃₎ _2). Step c) N, N-dimethyl-3,4-diaminoaniline sulfate

14.9 g (0.082 mol) of N, N-dimethyl-2-nitro-5-aminoaniline (from stage b) with 1 g of palladium on activated carbon 10% (Degussa) in 180 ml of methanol were placed in a 0.3-1 autoclave. After sealing and inerting with nitrogen, the mixture was hydrogenated at a pressure of 3 bar and a temperature of 35-40 ° C. until no more hydrogen was taken up. 1.3 g of activated carbon were added to the warm solution under nitrogen and the catalyst was filtered off. 8.4 g of 80% sulfuric acid were added dropwise to the solution while cooling with ice at 5 ° C. The precipitated product was filtered off, washed with methanol and dried. Yield: 10.1 g (49.4% of theory) 98/01106

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Melting point:> 200 ° C

IR: 3399 cm ^'1 (v OH), 3222, 2856 cm ^{' 1} (v CHJ, 1641 cm ^'1 (v C = C).

'H NMR: 7.6-6.4 ppm (6H, NH ₃ ⁺ ); 6.94 ppm (H ⁵ , d, ³ J " _H = 8.68 Hz); 6.30 ppm

(H ² , d, V, = 2.47 Hz); 6.18 ppm (H ⁶ , dd, ³ J _H = 8.70 Hz, ⁴ J _HH = 2.47

Hz); 2.88 ppm (6H, s, N (CH ₃₎ _2).

1.3.29. Preparation of N- (3,4-diaminophenyl) morpholine sulfate

Step a) N- (4-nitro-3-acetaminophenyl) morpholine

Stage a) was carried out analogously to Example 1.3.28. Stage a) through

Implementation of 4-nitro-3-acetaminochlorobenzene with Moφholin.

Yield: 24.1 g (90.8% of theory) of yellow crystals

IR: 3438 cm ^'1 (v CHJ, 3312, 3140, 2973, 2855 cm ^{' 1} (v CH), 1698 cm " ¹ (v

C = O), 1617 cm ^"1 (v C = C), 1580 cm ^'1 (v _M NO ₂ ), 1312 cm ^{" 1} (v, NO ₂ ).

'H NMR: 10.43 ppm (1H, s, NHAc); 7.98 ppm (H ⁵ , d, ³ } _w = 9.55 Hz); 7.70 ppm

(H ² , d, ⁴ J _H = 2.69 Hz); 6.78 ppm (H ⁶ , dd, ³ J _aH = 9.59 Hz, ⁴ J _aH = 2.72 Hz); 3.73 ppm (4H, t, ³ i _w = 4.85 Hz, 3.35 ppm (4H, t, ³ J _HJI = 4.91 Hz, NCCHjCHjfcO); 2.15 ppm (3H, s, C (= O) CH ₃ ).

Step b) N- (4-nitro-3-aminophenyl) morpholine

The preparation in stage b) was carried out analogously to Example 1.3.28. Stage b) through

Reaction of N- (4-nitro-3-acetaminophenyl) -moφholin with hydrochloric acid.

Yield: 15.3 g (84.4% of theory)

Step c) N- (3,4-diaminophenyl) morpholine sulfate

The preparation in stage c) was carried out analogously to example 1.3.28. Step c) by catalytic reduction of N- (4-nitro-3-aminophenyl) -mθφholin.

Yield: 15.4 g (85.8% of theory)

Melting point:> 200 ° C

2. Discolorations

2.1. Coloring agent: based on cream Cl

Sodium lauryl sulfate (70%) 2.5 g

Oleic acid 1.0 g

Sodium sulfite, anhydrous 0.6 g

Cetyl stearyl alcohol 12.0 g 98/01

- 53 -

Myristyl alcohol 6.0 g

Propylene glycol 1.0 g

Ammonia, 25% 10.0 g

Oxidationsfarbstoffvoφrodukte x, x g water ad 100 g

based on cream C2

Oleic acid 1.2 g

Sodium dithionite 0.5 g lauryl alcohol diglycol ether sulfate,

Sodium salt (28% solution) 6.2 g

Cetyl stearyl alcohol 18.0 g

Ammonia, 25% 7.5 g

Oxidationsfarbstoffvoφrodukte x, x g water to 100 g

on gel basis Gl

Oleic acid 12.0 g

Isopropanol 12.0 g

Nonoxynol-4 5.0 g

Ammonia, 25% 10.0 g

Sodium sulfite, anhydrous 0.5 g

Oxidationsfarbstoffvoφrodukte x, x g water ad 100 g

2.2. Oxidation dye products

- according to formula (I)

(I-1) N- (2,4-diaminophenyl) ethanolamine sulfate

(1-2) 2,4-diamino-N, N-diethylaniline sulfate

(1-3) N- (2,4-diaminophenyI) pyrrolidine sulfate

(1-4) N, N-dimethyl-2,4-diamine aniline sulfate

(1-5) N- (2,4-Diaminophenyl) MoφhoIin sulfate

(1-6) N- [4- (2-Hydroxyethylamino) -2-aminophenyl] piperidine sulfate 98/01106

- 54 -

(1-7) N- {2-amino-4- [di- (2-hydroxyethyl) amino} phenyl} pyrrolidine sulfate

(1-8) N- [N, N-Diethylaminoethyl] -2-amino-4- (3-hydroxypropylamino) aniIin sulfate

(1-9) N- [2-amino-4- (3-hydroxypropylamino) phenyl] azepane sulfate

(I-10) N, N-dimethyl-2,5-diaminoaniline sulfate

(1-1 1) N- (2,5-diaminophenyl) moφholin sulfate

(I-12) N- (2,5-diaminophenyl) pyrrolidine sulfate

(1-13) N, N-diethyl-2,5-diaminoaniline

(1-14) N- (2,5-diaminophenyl) piperazine

(1-15) N-methyl-2,5-diaminoaniine sulfate

(I-16) N, N-Dime yl-3,4-diaminoaniine sulfate

- Developer components (E-1) p-aminophenol

(E-2) 2- (2 '-hydroxyethyl) -p-phenylenediamine sulfate (E-3) p-phenylenediamine dihydrochloride (E-4) 2,5-diaminotoluene sulfate (E-5) 4-amino- m-cresol

- Coupler components

(K-1) resorcinol

(K-2) m-aminophenol

(K-3) 4-amino-2-hydroxytoluene

(K-4) 2 - Amino-4-hydroxyethyl lamino anisole sulfate

2.3. method

50 g of the colorant were mixed shortly before use with 50 g H ₂ O ₂ solution (6% in water) and applied to 100% gray hair (4 g colorant per g hair) using a brush. After a contact time of 30 minutes at room temperature, the cream-based dye was rinsed off and the hair was dried. In the case of the gel base, the hair was shampooed after rinsing out the coloring material and the hair was dried. 98/01106

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2.4. Results

The results of the colorations are summarized in the following table:

Basis Oxidationsfarbstoffvoφrodukte shade

Cl 2.65 g l-I + 1.09 g E-1 evenly light brown-red

Cl 2.65 g l-l + 1.52 g E-2 evenly medium brown

Cl 2.65 g l-l + 1.08 g E-4 evenly dark brown

Cl 2.65 g l-l + 1.23 g E-5 evenly light brown-red

Cl 2.65 g 1-4 + 1.10 g K-l uniform olive orange

Cl 2.65 g 1-4 + 1.09 g K-2 uniform green-blue

Cl 2.65 g 1-4 + 1.23 g K-3 evenly azure

Cl 2.65 g 1-4 + 2.80 g K-4 even navy blue

Gl 2.66 g 1-2 + 1.10 g K-l brown violet

Gl 2.66 g 1-2 + 1.09 g E-l light golden blonde

Gl 2.66 g 1-2 + 1.52 g E-2 light ash blonde

Gl 2.66 g 1-2 + 1.08 g E-3 light ash violet

Gl 2.66 g 1-2 + 1.22 g E-4 light ash blonde

Gl 2.66 g 1-2 + 1.23 g E-5 light golden blonde

Cl 2.75 g 1-3 + 1.09 g E-l medium gold blonde

C 1 2.49 g I- 10 + 1, 10 g K- 1 even olive orange

C 1 2.49 g I-10 + 1, 09 g K-2 uniform green-blue

C 1 2.49 g I- 10 + 1, 23 g K-3 evenly azure

C 1 2.49 g 1-10 + 2.80 g K-4 even navy blue

Gl 2.91 g 1-11 + 1.10 g K-l brown violet

G 1 2.91 g I-11 + 1, 09 g K-2 blue-gray

Gl 2.91 g 1-11 + 1.23 g K-3 ash violet

Gl 2.91 g 1-11 + 2.80 g K-4 blue-gray

Gl 2.49 g 1-15 + 1.09 g E-l light violet red

C 1 2.49 g I- 15 + 1, 09 g E-2 light violet red

Gl 2.49 g 1-15 + 1.38 g E-3 dark purple red

C2 2.49 g 1-15 + 1.09 g E-4 dark purple brown

Cl 2.49 g 1-16 + 1.09 g E-l evenly light golden brown

C 1 2.49 g I- 16 + 1, 52 g E-2 evenly light brown

C 1 2.49 g 1-16 + 1, 38 g E-3 evenly medium brown 98/01106 - 56 -

Cl 2.49 g 1-16 + 1.22 g E-4 evenly light brown

Gl 2.91 g 1-16 + 1.23 g E-5 light brown orange

Gl 2.49 g 1-16 + 1.10 g K-1 light brown-red

C2 2.49 g 1-16 + 1.09 g K-2 dark green

Gl 2.49 g 1-16 + 1.23 g K-3 blue-green

C2 2.49 g 1-16 + 2.80 g K-4 dark blue violet

Furthermore, by combining the following

Oxidationsfarbstoffvoφrodukte get the listed colors:

1-3 + E-2 ash violet

1-3 + E-4 light brown-red

1-3 + E-5 light blonde copper

1-4 + E-l light brown

1-4 + E-2 dark gray

1-4 + E-3 deep blue black

1-4 + E-4 dark gray black

1-4 + E-5 light ash brown

1-5 + E-l light brown violet

1-5 + E-2 ash gray blue

1-5 + E-3 deep blue black

1-5 + E-4 ash gray blue

1-5 + E-5 light golden blonde

1-6 + E-l brown red

1-6 + E-2 dark purple

1-6 + E-4 ash violet

1-6 + E-5 ash red violet

1-7 + E-l light golden blonde

1-7 + E-2 ash gray brown

1-7 + E-4 dark ash blonde

1-7 + E-5 light golden blonde

1-8 + E-l light golden blonde

1-8 + E-2 light ash gray

1-8 + E-3 dark blonde

1-8 + E-4 light ash blonde 1-8 + E-5 light blonde

1-9 + E-l light blonde copper

1-9 + E-2 medium ash gray

1-9 + E-3 medium brown violet

1-9 + E-4 dark ash blonde

1-9 + E-5 light blonde copper -12 + Kl silver-gray cendre -12 + K-2 ash gray-cendre -12 + K-3 green-gray -12 + K-4 violet gray -13 + Kl cendre -13 + K- 2 olive-violet -13 + K-3 violet-gray -13 + K-4 blue-violet -14 + Kl brown-violet -14 + K-2 gray-green -14 + K-3 violet-brown -14 + K-4 blue-gray -15 + Kl light violet - 15 + K-2 light violet -15 + K-3 light violet -15 + K-4 dark violet -11 + El medium gold blonde -1 1 + E-2 dark blonde -11 + E-3 light brown -11 + E-4 medium gold blonde -11 + E-5 light gold blonde -12 + El medium gold blonde -12 + E-2 light ash blonde -12 + E-3 light brown -12 + E-4 medium gold blonde -12 + E-5 light ash blonde -13 + El medium gold blonde -13 + E-2 light ash violet - 13 + E-3 light brown 1-13 + E-4 medium blonde

1-13 + E-5 light ash blonde

1-14 + E-l medium gold blonde

1-14 + E-2 light ash blonde

1-14 + E-3 light brown

1-34 + E-4 medium gold blonde -14+ E-5 light ash blonde -10+ E-l light blonde copper -10+ E-2 light gold blonde -10+ E-3 medium brown -10+ E-4 light gold blonde -10+ E-5 orange-red

Claims

98/01106 - 59 - P atent claims

1. Oxidation dye for dyeing keratin fibers, characterized in that it contains at least one diaminoaniline of the general form as the oxidation dye product

in which R, to R^ independently stand for

- hydrogen,

- a (C,-C ₄ )alkyl group,

- a hydroxy (C ₂ -C ₃ )alkyl group,

- a (C,-C ₄ )-alkoxy-(C ₂ -C ₃ )-alkyl group,

- an amino-(C ₂ -C ₃ )alkyl group, in which the amino group can also carry one or two (C,-C ₄ -alkyl radicals, or

- a 2,3-dihydroxypropyl group with the proviso that not all substituents R to R^ are used at the same time

Hydrogen stand, and

R, and R ₂ and/or R ₃ and R ₄ and/or R ₅ and R _< , together with that

The nitrogen atom to which they are bound can also represent an aziridine,

Azetidine, pyrrolidine, piperidine, azepane, azocine ring or a Moφholino,

Thiomoφholino or piperazino group, which has another on the nitrogen atom

Substituent R ₇ carries, which is selected from hydrogen, a (C,-C ₄ )-alkyl, a hydroxy-(C ₂ -C ₃ )-alkyl, a (C,-C ₄ )-alkoxy-(C ₂ -C ₃ )-alkyl-, an amino-

(C ₂ -C ₃ )-alkyl or a 2,3-dihydroxypropyl group and the three remaining hydrogen atoms on the benzene ring can also be independently replaced by a halogen atom or a (C,-C ₄ )-

Alkyl group, or their physiologically compatible salts with inorganic and organic

Contain acids. 98/01106

- 60 -

? Agent according to claim 1, characterized in that at least two of the groups R to R^ do not represent hydrogen

3. Agent according to one of claims 1 or 2, characterized in that at least one of the groups -NR, R ₂ , -NR ₃ R ₄ or -NR _j R _fc stands for an aziridine, azetidine, pyrrolidine, piperidine. , azepane, azocine ring or a moφholino, thiomoφholino or piperazino group, which carries another substituent R ₇ on the nitrogen atom, which is selected from hydrogen, a (C,-C ₄ )-alkyl, a hydroxy-(C ₂ -C ₃ )-alkyl-, a (C,-C ₄ )-alkoxy-(C ₂ -C ₃ )-alkyl-, an amino-(C ₂ -C ₃ )-alkyl- or a 2,3- Dihydroxypropyl group.

4. Composition according to one of claims 1 to 3, characterized in that the compound according to formula (I) in amounts of 0.001 to 10% by weight, in particular from 0.1 to 5% by weight, based on the entire agent , is included.

5. Composition according to one of claims 1 to 4, characterized in that it further contains an oxidation dye product of the coupler type.

6. Composition according to one of claims 1 to 5, characterized in that it further contains an oxidation dye product of the developer type.

7. Composition according to one of claims 1 to 6, characterized in that it further contains a substantive dye.

8. Composition according to one of claims 3 to 7, characterized in that it further contains a metal salt or a metal complex.

9. Composition according to claim 8, characterized in that the metal is selected from copper, manganese, cobalt, selenium, molybdenum, bismuth and ruthenium.

10. Use of diaminoalkanes of the general formula (I) according to claim 1 for coloring keratin fibers.