NZ203467A

NZ203467A - 2-aminomethylphenol derivatives

Info

Publication number: NZ203467A
Application number: NZ203467A
Authority: NZ
Inventors: H C Englert; H-J Lang; M Hropot; J Kaiser
Original assignee: Hoechst Ag
Priority date: 1982-03-06
Filing date: 1983-03-04
Publication date: 1985-11-08
Also published as: ES8401457A1; FI75558C; HU192792B; MA19737A1; FI830727A0; GR77952B; CA1238908A; ES520313A0; ATE13665T1; ZA831499B; JPS58162571A; EP0088346B1; EP0088346A2; PT76347A; FI75558B; IL68044A0; DE3360236D1; FI830727L; NO156047C; PT76347B

Abstract

1. Claims for the Contracting States : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE 2-Aminomethylphenols of the formula I see diagramm : EP0088346,P33,F2 in which R represents hydrogen or alkyl having 1 or 2 C atoms, R**1 represents alkyl having 1 to 8 C atoms, cycloalkyl having 3 to 12 C atoms and up to 8 ring members, alkenyl having 2 to 8 C atoms or cycloalkenyl having 5 to 12 C atoms and up to 8 ring members, it being possible for each of the aforementioned radicals to be substituted with 1 to 5 identical or different halogen atoms, R**2 and R**4 are identical or different and denote hydrogen, halogen, alkyl having 1 or 2 C atoms or alkoxy having 1 or 2 C atoms, R**3 denotes halogen, alkyl having 1 to 12 C atoms or cycloalkyl having 3 to 12 C atoms and up to 8 ring members, R**5 and R**6 are identical or different and represent hydrogen, alkyl having 1 to 6 C atoms, cycloalkyl having 3 to 10 C atoms and up to 8 ring members or the radical -[CH2 ]o -Ar, wherein o = 1 or 2, the -[CH2 ]o - chain can be substituted by 1 or 2 (C1 or C2 )-alkyl groups and Ar is a 5- or 6- membered aromatic or heteroaromatic system, which is optionally substituted by 1 to 3 identical or different radicals (C1 or C2 )-alkyl, (C1 or C2 )-alkoxy or halogen, and n is 1 or 2, it being possible for the radicals R**5 and R**6 and/or two of the radicals R**2 , R**3 and R**4 also to form a -[CH2 ]m - chain having m = 3 to 6, which can optionally be substituted by 1 or 2 methyl groups and, in the case of R**5 and R**6 , can also be interrupted by 1 or 2 oxygen atoms, sulfur atoms and/or imino groups, and their physiologically tolerated salts. 1. Claims for the Contracting State : AT A process for the preparation of the 2-aminomethylphenols of the formula I see diagramm : EP0088346,P35,F4 in which R represents hydrogen or alkyl having 1 or 2 C atoms, R**1 represents alkyl having 1 to 8 C atoms, cycloalkyl having 3 to 12 C atoms and up to 8 ring members, alkenyl having 2 to 8 C atoms or cycloalkenyl having 5 to 12 C atoms and up to 8 ring members, it being possible for each of the aforementioned radicals to be substituted with 1 to 5 identical or different halogen atoms, R**2 and R**4 are identical or different and denote hydrogen, halogen, alkyl having 1 or 2 C atoms or alkoxy having 1 or 2 C atoms, R**3 denotes halogen, alkyl having 1 to 12 C atoms or cycloalkyl having 3 to 12 C atoms and up to 8 ring members, R**5 and R**6 are identical or different and represent hydrogen, alkyl having 1 to 6 C atoms, cycloalkyl having 3 to 10 C atoms and up to 8 ring members or the radical -[CH2 ]o -Ar, wherein o = 1 or 2, the -[CH2 ]o - chain can be substituted by 1 or 2 (C1 or C2 )-alkyl groups and Ar is a 5- or 6-membered aromatic or heteroaromatic system, which is optionally substituted by 1 to 3 identical or different radicals (C1 or C2 )-alkyl, (C1 or C2 )-alkoxy or halogen, and n is 1 or 2, it being possible for the radicals R**5 and R**6 and/or two of the radicals R**2 , R**3 and R**4 also to form a -[CH2 ]m - chain having m = 3 to 6, which can optionally be substituted by 1 or 2 methyl groups and, in the case of R**5 and R**6 , can also be interrupted by 1 or 2 oxygen atoms, sulfur atoms and/or imino groups, and their physiologically tolerated salts, which comprises a) reacting a compound of the formula II see diagramm : EP0088346,P36,F1 wherein n, R**1 , R**2 , R**3 and R**4 have the abovementioned meanings, with an N-hydroxymethylcarboxamide of the general formula III see diagramm : EP0088346,P36,F2 in which R has the abovementioned meaning, R**5 denotes hydrogen or alkyl having 1 to 4 C atoms and R**7 represents hydrogen, optionally halogen-substituted alkyl having 1 to 4 C atoms or aryl having 6 to 10 C atoms, or in which R**5 and the radical COR**7 together represent the o-phthaloyl radical, to give a compound of the general formula IV see diagramm : EP0088346,P36,F3 and removing the acyl radical R**7 -CO by hydrolysis, b) reacting a compound of the formula II, in which the radicals R**1 to R**4 and n have the abovementioned meanings, in the presence of formaldehyde, with an amine of the general formula V see diagramm : EP0088346,P36,F4 in which R**5 and R**6 have the meanings mentioned in claim 1 with the exception of hydrogen, c) reacting a compound of the general formula VI see diagramm : EP0088346,P36,F5 in which n and R to R**4 have the abovementioned meanings and Z represents a leaving group, with an amine of the general formula H-N = Y, wherein Y represents an amine-protective group or the radicals R**5 and R**6 defined in claim 1, it being possible for R**6 also to be an amine-protective group, to give a compound of the general formula VII see diagramm : EP0088346,P37,F1 and, if appropriate, removing the amine-protective group by hydrolysis or hydrogenolysis, or d) reacting compounds of the general formula XIV see diagramm : EP0088346,P37,F2 in which n and R to R**4 have the abovementioned meanings, with an amine of the formula R**5 -NH2 , with R**5 having the abovementioned meaning, to give Schiff's bases of the formula XV see diagramm : EP0088346,P37,F3 in which n and R to R**5 have the abovementioned meanings, and reducing the latter to give a compound of the formula I, and optionally converting the compound of the formula I obtained according to one of the variants a) - d) into its physiologically tolerated salts.

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £03467 203 /f Priority Date(s): . .£>^ ; Complete Specification Filed: .4 >' Class: .C&7S!t*?j.. 977..^; ! g&~7 £>2.1,1] CO~7£>3.(+l- I j Publication Data ... .■ ■?? .'p®' •n-0. Journal, No: /*?.7.7... no mmims N.Z. No. NEW ZEALAND Patents Act 1953 COMPLETE SPECIFICATION 112-AMINOMETHYLPHENOL DERIVATIVES, A PROCESS FOR THEIR , PREPARATION, THEIR USE, AND PHARMACEUTICAL FORMULATIONS BASED ON THESE COMPOUNDS. i. We, HOECHST AKTIENGESELLSCHAFT, a corporation organized under the laws of the Federal Republic of Germany, of D-6230 Frankfurt/Main 80, Federal Republic of Germany, do hereby declare the invention, for which we pray that a Patent may be granted to us, and the ;method by which it is to be performed,to be particularly described in and by the following statement -1- 2 034 >5 - 2 - The invention relates to 2-aminomethylphenoIs of the formula I (!) in whi ch 5 R represents hydrogen or alkyl having 1 or 2 C atoms, R represents alkyl having 1 to 8 C atoms, cycloalkyl having 3 to 12 C atoms and up to 8 ring members, alkenyl having 2 to 8 C atoms or cycloalkenyl having 5 to 12 C atoms and up to 8 ring members, it being possible for each 10 of the aforementioned radicals to be substituted with 1 to 5 identical or different halogen atoms, 0 A R and R are identical or different and denote hydrogen, halogen, alkyl having 1 or 2 C atoms or alkoxy having 1 or 2 C atoms, 15 R^ denotes halogen, alkyl having 1 to 12 C atoms or cycloalkyl having 3 to 12 C atoms and up to 8 ring members, Rand R^1 are identical or different and represent hydrogen, alkyl having 1 to 6 C atoms, cycloalkyl having 3 to 10 C atoms and up to 8 ring members or the radical 20 -CCH-,3 -Ar, wherein o = 1 or 2, the -CCH.,3 chain can 2 o to 2 - 3 - be substituted by 1 or 2 (C<j or C2)"*alkyl groups and Ar is a 5- or 6-membered aromatic or heteroaromatic system, which is optionally substituted by 1 to 3 identical or different radicals (C^ or C2>-alkyl, (C^ or C2>-alkoxy 5 or halogen/, and n is 1 or 2 , it being possible for the radicals R-* and and/or two of the radicals R^, R^ and R ^ also to.form a -CCH23m~ chain having m = 3 to 6 , which can optionally be substituted by 1 or 2 methyl groups and, in the case of R"* and R^, can also be interrupted 10 by 1 or 2 oxygen atoms, sulfur atoms and/or imino groups, and their physiologically tolerated salts. The aromatic system Ar is preferably understood to be phenyl. A 5- or 6-membered heteroaromatic system Ar is preferably a radical of a 5- or 6-membered 0-, N- and/ 15 or S-heterocyc I ic ring, in particular furyl, thienyl, pyrrolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl or triazinyl. The halogen as substituent on Ar is understood to be F, CI, Br and/or I, preferably F 20 and/or CI. If one of the cycloalkyl or cycloalkenyl groups defined above has a C number which exceeds the number of ring members, it is understood to include a cycloalkyl or cycloalkenyl group which is substituted by one or more 25 alkyl groups, or an optionally a Ikyl-substituted cyclo-alkylalkyl or cycIoa I keny I a I ky I group. If compounds of the formula I have chiral C and/or S atoms, then the invention relates to compounds both of the S configuration and of the R configuration at the 34w - 4 - particular center. The compounds can then exist as optical isomers, as diastereomers, as racemates or as mixtures of these. 2-Aminomethylphenols, substituted in the 6-position, 5 are known from J.med.Chem. Z3_ C1980D, pages 1,414-1,427. The 4-a Iky l-6-ha logeno derivatives have saluretic properties of a type and strength shown by diuretics having a short and intensive action, such as, for example, furose-mi de. 10 In the particular case,of a 6-iodo derivative, an additional antihypertensive effect is observed. Thus it was extremely surprising that the compounds of the formula I according to the invention exert a saluretic effect on the dog or the rat, which effect can reach 15 the order of magnitude of activity of the halogen derivatives described above, in particular the iodo compound. However, they differ advantageously from the latter in that they exhibit a significantly lower acute toxicity, as can be shown in rats. 20 Furthermore, it was surprising that some of the compounds according to the invention exhibit not only a very good saluretic effect, but also have a strong hypotensive effect on spontaneously hypertensive rats in doses be low 20 mg /kg. 25 Compounds of the formula I are preferred in which R represents hydrogen, R represents alkyl having 1 to 4 C atoms, cycloalkyl having 3 to 7 C atoms and up to 6 ring members, alkenyl having 2 to 6 C atoms or halogeno- alkyl having 1 to 4 C atoms and 1 to 3 identical or differ- n % A \ „ M ■< k cJ* - 5 - ent halogen atoms, R^ denotes halogen, alkyl having 1 to 8 C atoms or cycloalkyl having 3 to 10 C atoms and up to 7 ring members, R and R ^ have the meanings defined C Z previously, with the exception that RJ and/or R° represents 5 alkyl having 1 or 2 C atoms, n is 1 or 2, it being possible for the radicals R-* and R^ and/or two of the radicals R , R° and RH to form a po I ymethy lene chain as defined previ ous ly. In particular, those compounds of the formula I. 10 are suitable in which R denotes hydrogen, R^ denotes methyl, chloromethyl, iodomethyl or ethyl, R^ and R^ denote hydrogen, R^ denotes isopropyl, tert.-butyl, tert.-amyl or sec.-butyl, R^ and R^ denote hydrogen and n denotes 1 or 2, those compounds being emphasized as particularly 15 preferred in which R represents hydrogen, R represents n / methyl or chloromethyl, R and R represent hydrogen, R"* represents tert.-butyl, R-5 and R^ represent hydrogen and n represents 2. Furthermore, the invention relates to a process 20 for the preparation of 2-aminomethy IphenoIs of the formula I, which comprises a) reacting compounds of the formula II OH (II) 4 n t / wherein n, R, R , R and R have the abovementioned meanings, with an N-hydroxymethylcarboxamide of the - 6 - general formula III, R- R5 O I I II 7 HO-HC-N-C-R (III) in which R denotes hydrogen or alkyl having 1 or 2 C atoms, R-* denotes hydrogen or alkyl having 1 to 4 C atoms and R^ represents hydrogen, optionally halogen-substituted alkyl having 1 to 4 C atoms or aryl having 6 to 10 C atoms, or in which R"5 and the radical C 0 R ^ together represent the o-phthaloyl radical, to give compounds of the general formula IV 10 p n <iv) 7 and removing the acyl radical R -CO by hydrolysis or b) reacting compounds of the formula II, in which A f the radicals R to R 4 and n have the abovementioned meanings, in the presence of formaldehyde, with amines of 15 the general formula V, ■ R6 H - N (V) in which R^ and R^ have the abovementioned meanings with the exception of hydrogen, c) reacting compounds of the general formula VI, n & ' T £ f ' X- - 7 - (VI) I t in which n, R to RH have the abovementioned meanings, and Z represents a leaving group, with amines of the general formula H-N=Y, wherein Y represents an amine-protective group or the radicals R and R ^ defined in claim 1, it being possible for R^ also to be an amine-protective group, to give compounds of the general formula VII, OH (VII) and, if appropriate, removing the amine-protective group by hydrolysis or hydrogenolysis, or d) reacting compounds of the general formula XIV O OH 1 r: R ' c s(0)n" R n -R2 K3 (XIV) in which n and R to R^ have the abovementioned meanings, with amines of the formula R^-NI^, with R"5 having the abovementioned meaning, to give Schiff's bases of the formula XV - 8 - 2 OH 20 (XV) in which n and R to R^ have the abovementioned meanings, and reducing the latter to give compounds of the formula I, and optionally converting the compounds of the formula 5 I obtained according to one of the variants a) - d) into their physiologically tolerated salts. Suitable leaving groups Z in process variant c are all groups which can easily be displaced by nucleophiles, such as, for example, halogen, tosyl, dimethylamino or 10 trimethyIammonium. Y, as the amino-protective group, denotes, for example, the diazo radical or thephthaloyl radical. R^, as the amino-protective group, represents the monovalent radicals known from peptide synthesis, such 7 7 as the benzyl radical or other acyl radicals -C0-R , R 15 assuming the meaning mentioned previously. The invention also relates to compounds of the 1 / general formula II in which n and R to R have the meaning mentioned previously. They are precursors in the preparation of compounds of the general formula I. 0 ,7. » The removal of the radical R -C from compounds of the general formula IV according to procedure a) is carried out in general with the aid of an acid or a base in the presence of water. If the removal is carried out under 25 acid conditions, preferably a strong mineral acid, such V ^ - 9 - as hydrochloric acid, hydrobromic acid or hydriodic acid or sulfuric acid is used. On the other hand, if a base is used, advantageously alkali metal bases, such as sodium hydroxide or potassium hydroxide are employed. Virtually 5 every solvent which is inert towards the reactants, such as, for example, alkanols, preferably ethanol or, when using acid conditions of hydrolysis, alkanoic acid, such as, for example, acetic acid, can be used as the solvent. In general, at least 1 equivalent of water must be added 10 to the reaction mixture, but in most cases a larger excess is used or water alone serves as the solvent, which is advantageous for alkaline hydrolyses in particular. The reaction temperature can be between 20 and 150°C, the reaction advantageously being carried out at the boiling 15 point of the solvent used. With acid hydrolysis, the product results either immediately, or after removing the solvent, as crystals in the form of an acid addition salt. If necessary, it is purified in a customary manner by re-crystallization from a suitable solvent. 20 On the other hand, with alkaline hydrolyses, the free benzylamine of the general formula I is obtained in general directly after neutralization of excess base. The preparation of the compounds of the general formula IV is carried out in a manner known per se by 25 reacting the phenols of the general formula II with N- hydroxymethyIcarboxamides III, preferably with 2-halogeno-N-hydroxymethylacetamides, such as, for example, 2-chloro-N-hydroxymethylacetamide by the method of the Tscherniac-Einhorn reaction with acid catalysis. Particularly suit- ' 2 03 4^ - 10 - able as efficient catalytic acids are strong mineral acids, such as, for example, hydrochloric acid or sulfuric acid. All solvents customary for reactions of this type serve as the solvent, and alkanoic acids, such as acetic 5 acid or propionic acid have been found to be particularly suitable, but excess mineral acid can also be advantageous as the solvent, such as, for example, pure concentrated sulfuric acid. The reactions are carried out between 0 and 100°C, advantageously in a range from 0 to 30°C in 10 order to prevent by-products. In certain circumstances, it can be reasonable to produce the N-hydroxymethylcarboxamide of the formula III in situ, for example by reacting, in the abovementioned manner, phenols of the formula II with a mixture of car- 0 15 boxamide R^-Jl-NHg and a carbonyl compound of the formula R-CKO, in which R has the abovementioned meaning, in order to obtain compounds of the formula IV. It has emerged, in particular, that amidomethy la-tions of this type can still be carried out satisfactorily 20 if a reaction time is strictly observed, which can be between 10 minutes and several hours, depending on the compound and reaction temperature, even when more severe reaction conditions (such as, for example, concentrated sulfuric acid as the solvent) are used, and this can prove 25 to be necessary, in certain circumstances, for rapid and complete reaction. Side reactions which may be expected, such as, for example, deaIky I ation, in particular de-tert.- butylation, can be reduced to a minimum by exactly con ^ 1; -1 .C v ^ - 11 - trolled reaction conditions. The isolation of the reaction products is carried out most advantageously by adding a non-solvent, such as, for example, water to the reaction mixture, and, as a 5 rule, they are then immediately obtained as crystals and can be further processed, after recrystallization from a suitable solvent or, in many cases, without further purification. The starting compounds of the general formula II 10 used for the procedures a and b can be prepared by various processes. An example of a method comprises oxidizing thioethers of the general formula VIII: VIII II 15 wherein the radicals R <| to R^ and n have the abovementioned meanings. Oxidations of this type are known from the literature. It is known, furthermore, that either sulfoxides (n=1) or sulfones (n=2) can be obtained by choice of the reaction conditions. 20 The thioethers of the general formula VIII can be prepared in a manner known per se from the phenols of the formula IX, in which R to R have the abovementioned 1 1 meaning; for example by the action of a sulfoxide R -S0-R in the presence of perchloric acid and phosphorus oxy- ' ' ^ A 4 - 12 - A chloride or by reaction with a sulfenyl chloride R 1 — S — CI in a manner known per se, having the abovementioned meaning in each case. OH IX 5 The phenols IX can be easily prepared by standard methods (cf. Houben-Weyl, Methoden der org. Chem. -Phenole CMethods of Organic Chemistry - Phenols] Part 2, pages 925 et seq., 6. Thieme Verlag, Stuttgart 1976). Another method for the preparation of phenols of 1 L. 10 the general formula II, in which R' to R have the above-mentioned meanings and n is 2, comprises the ether cleavage of anisoles of the general formula X, with the approp- 1 A riate meanings for R to R and n. OCH. i .1 X I „2 R 15 It is carried out in a manner known per se by the action of mineral acids, such as hydriodic acid, or of Lewis acids, such as aluminum chloride or boron tribromide, in inert solvents, such as, for example, methylene chloride or chloroform. The commonly used cleavage with pyri- 20 dinium hydrochloride at temperatures above 180°C can also be carried out successfully. S(0)n-R] 2 03 4 " - 13 - Compounds of the general formula X having n=2 are prepared from the anisoles XI by a sequence of standard methods known per se: Su Ifoch lorides XII are obtained in a manner known per se by the action of chlorosulfuric acid on anisoles XI. This reaction is advantageously carried out in an 10 inert solvent, such as chloroform or methylene chloride. When in XI represents a higher alkyl, a temperature range of 0 - 20°C should be maintained and a relatively large excess of more than 3 equivalents of chlorosulfonic acid, which is customary per se, should be avoided. 15 The reduction to give the sulfinic acids XIII can be carried out by a wide variety of processes (cf. Houben- Weyl, Methoden der org. Chemie CMethods of Organic Chemis- 2 A A " - 14 - try], Volume X, pages 563 et seq., 6. Thieme Ver lag, Stuttgart, 1955). Reduction with sodium sulfite in the presence of sodium hydroxide in solutions in aqueous acetone has been found to be a simple and efficient method. 5 The alkylation of sulfinic acids to give sulfones is a reaction known per se, which is preferably carried out under base catalysis. In the case of the sulfinic acids XIII,. alkyl iodides have been found to be particularly 1 1 suitable alkylating agents R -X, where R has the 10 abovementioned meaning and X represents halogen, preferably iodine. Advantageously employed bases are organic bases, such as, for example, triethylamine in solution in acetone but also inorganic bases, such as LiOH, NaOH, KOH etc. in aqueous solution or in solution in aqueous acetone. 15 If R represents an oL-balogenoaIkyI radical, a number of variants of this alkylation reaction can be advantageously used, such as, for example, the reaction of sulfinic acids wi th 0(^-di ha logenoca rboxy I i c acids in the presence of l<2C03' the J^-su I f ony l-o(rha logeno-20 carboxylic acid, which is formed as an intermediate, splitting off CO2 in a manner known per se with the formation of the oC.-ha logenomethylsulfonyl radi ca I. The anisoles XI are prepared from the phenols IX by standard methods (Organikum, VEB Deutscher Verlag der 25 Wissenschaften, Berlin 1971, page 222). Compounds of the general formula I, in which R-* and R^ are both alkyl radicals or are bonded together to form a ring, as defined in the introduction, are advantageously prepared by process b, by reacting the phenols II. 2 0 3 4 - 15 - in a manner known per se, by the method of the Mannich reaction with amines of the general formula V. In this reaction, formaldehyde is preferably employed in the form of an aqueous solution, but all other commonly used 5 variants of the Mannich reaction can also be used, such as, for example, the use of paraformaldehyde. The solvent can also be varied within wide limits, particularly suitable solvents are alkanols, such as, for example, methanol or ethanol. The reaction is carried 10 out in a temperature range from 40 to 150°C, preferably in a range from 60 to 100°C. The reaction time is critically dependent on the temperature; in general, the reactions are complete after a few hours. The products are preferably isolated by evaporating off the solvent and excess 15 reagents and they are obtained usually as highly viscous oils which are purified by crystallization from a suitable solvent or are immediately further processed according to process variant c. The process variant c is particularly suitable 20 for the preparation of benzylamines I, particularly of those in which R and R ^ represent hydrogen or those which additionally carry a radical sensitive to acid, such as, for example, the sulfinylalkyl radical. In this case, the procedure is such that the compounds VI are reacted with 25 the amines H-N=Y, with or without base catalysis. The method of carrying out the reaction depends on the meaning . of Y and on the nature of the leaving group Z in the compounds VI. For example, if Y represents the diazo radical, - 16 - which is particularly suitable as an amine-protective group, this means that the compounds XII are obtained from the compounds VI, preferably from those in which Z represents the tria Ikylammonium radical, for example the 5 trimethylammonium radical, with halide, preferably iodide, as the counterion, by the action of hydrazoic acid, with base catalysis. Suitable bases are organic bases, such as tertiary amines, for example triethylamine, or quaternary nitrogen bases, such as tetraethyLammonium hydroxide, 10 but inorganic bases, such as, for example, alkali metal or alkaline earth metal hydroxides, can also be used. It is also possible and particularly advantageous for the salts of hydrazoic acid to be employed directly, for example the alkali metal salts, such as, for example, 15 sodi um az i de. Polar aprotic solvents principally serve as the solvent, such as dimethyl sulfoxide, dimethylformamide or sulfolane, but protic polar solvents, such as alkanols, for example ethanol, can also be used, with or without 20 the addition of water. The reaction is carried out in a temperature range from 40 - 150°C, preferably at temperatures between 60 and 120°C. Depending on the type of solvent and the temperature, the reaction is usually complete after a few 25 hours; as a rule, heating at 100°C for one hour suffices. The azide of the general formula VII (Y is =^5 is easily obtained in an adequately pure form by the addition of a non-solvent, such as, for example, water, and is immediately subjected to reduction to give the amines I. - 17 - In principle, all the methods known for reactions of this type are suitable for this purpose, such as are referred to in, for example, H. Bayley, D.N. Standring, J.R. Knowles, Tetrahedron Letters 3_9, 3,633 (1978). It 5 is advantageous to carry out the process by subjecting the azide to catalytic hydrogenation. Virtually all solvents customary for hydrogenations are suitable, but alkanols, such as, for example, methanol, are preferred. The hydrogenation catalyst, too, can be varied within 10 wide limits; it is possible, advantageously, to use, for example, all noble metal catalysts, with or without support, for example platinum dioxide, rhodium, palladium or Raney nickel, the reaction preferably being carried out with palladium on animal charcoal. 15 The hydrogenation can be carried out at tempera tures between 0 and 100°C and under pressures of 1 to 100 atm, but it is preferably carried out under normal pressure and at temperatures between 20 and 40°C. The product obtained generally requires further 20 purification after it has been isolated by filtration and removal of the solvent by evaporation. Chromatography is very suitable, amongst other methods, preferably on silica gel and using polar eluting agents, such as, for example, acetone or methanol. 25 Compounds of the general formula VI with Z having the meaning of tria IkyIammonium can easily be obtained in the form of their halides, for example, in the form of their iodides, when the Mannich bases obtained by process variant b are quaternized in a manner known per se with 2 034 5 - 18 - Q O alkylating agents, such as R -X, R representing alkyl having 1 to 4 C atoms, benzyl or alkenyl having 3 to 6 C atoms, and X" preferably denoting the anion of a leaving group, such as halogen, but other leaving groups, such as, 5 for example, the tosyl radical, the mesyl radical or the methyl sulfate radical are also suitable. In this reaction, methylating agents, such as iodomethane, are preferred. Every solvent which is inert to the reactants can be used in the reaction, for example, ketones, such as 10 acetone, esters, such as ethyl acetate or chlorinated hydrocarbons, such as methylene chloride. Preferably excess alkylating agent is used as the solvent. In general, the reaction can be carried out in the temperature range between 0 and 150°C, but for reactive alkyl-15 ating agents, such as iodomethane, room temperature generally suffices to permit the reaction to run its course in relatively short times of a few minutes to a fewhours. If compounds of the formula I are prepared by 20 process variant d), then the reaction of the carbonyl compounds of the formula XIV with amines of the formula R5-NH2 takes place under conditions which favor the production of a Schiff's base (cf., for example, Chem. Reviews 63 C19633 489-510). In the simplest case, this takes place 25 by mixing the starting components in a suitable solvent, for example in a lower alcohol such as methanol. The reaction usually takes place at room temperature, higher reaction temperatures only being necessary in a few cases. If necessary, water-removing agents must be ^ ,1 * ' --V ' ^ - 19 - added, for example TiCl^ or molecular sieves, or the water of reaction is removed by azeotropic distillation. It is generally not necessary to isolate the Schiff's base for the subsequent reduction, on the con-5 trary, the resulting solutions of these compounds are immediately reduced further, all the methods known for reactions of this type being suitable, for example catalytic hydrogenation or reduction with complex hydrides, such as, for example, NaBH^, LiBH^, LiAlH^ or MaBHjCN 10 (cf., for example, Houben-Weyl, Methoden der organischen Chemie CMethods of Organic Chemistry!!, Volume 11/1, Stuttgart 1957, page 341). NaBH^ in alcoholic solution is preferably used, room temperature generally being sufficient. The carbonyl compounds of the formula XIV can be 15 prepared from the compounds of the formula I with R, R"*, R^ = H by standard methods, for example by oxidation with dimethyl sulfoxide or with urotropine. The compounds of the general formula I prepared by the various process variants are obtained either as 20 the free bases or as acid addition salts. In order to produce the free base from an acid addition salt, it is necessary to treat the salt with at least one equivalent of a base. For this purpose, both organic and also inorganic bases are suitable, for example, triethylamine, 25 tetraethylammonium hydroxide or pi peri dine, or lithium, sodium or potassium hydroxide, sodium bicarbonate or sodium carbonate. In this reaction, the acid addition salt is advantageously employed in a dissolved form, for example in alkanols, such as methanol or ethanol, or, as 2 034' - 20 - has been found to be particularly favorable, in the form of aqueous solutions, in which the addition of an inorganic base, such as, for example, sodium hydroxide, brings about precipitation of crystalline free base I. 5 Conversely, acid addition products with a desired acid HA are prepared by treating solutions of the free base I with at least one equivalent of the acid HA, either alcoholic solutions, such as, for example, a methanolic solution, or aqueous solutions are preferred. The acid 10 addition salt either crystallizes out in a pure form immediately or after removal of the solvent, if necessary, after recrystallization from a suitable solvent. Examples of suitable acids HA for pharmaceutical^ preferred acid additions are: organic acids, such as 15 tartaric acid, malic acid, lactic acid, acetic acid, citric acid, methanesu Ifonic acid, benzenesu Ifonic acid and the like, inorganic acids, such as hydrochloric, hydro-bromic or hydriodic acid, sulfuric acid, nitric acid, phosphoric acid or amidosu I fonic acid etc. 20 Apart from the compounds described in the exem plary embodiments, the compounds of the general formula I listed in the fo I lowing tab le can also be obtained according to the invention: Am = amyl Bu - 21 - = but y I a R1 R2 R3 R4 R5 6 R n ' "R c2h5 h t-Am - h h H . 2 h c3h7 h t-Am K h h 2 K iso-c^h^ h t-Am h h h 2 h ch2~ch=ch2 h t-Am h h h 2 h ch3-och- h t-Am h h h 2 h ch2c1 h t-Am h h h 2 H ch2f H t-Bu h h h 2 H CHF 2 H t-Bu h h h 2 h cf3 h t-Bu h h h 2 h ch2~cf3 H t-Bu h h H 2 h cyclo-C5H9 h t-Bu h h h 2 H cyclo-CgH^1 h' t-Bu H h h 2 h C2H5 h t-Bu H h h 1 H C3H7 H t-Bu h h h 1 H iso-C^H^ h t-Bu h h h 1 H ch2-hc=ck2 1 ch2~c=ch h t-Bu h H h 1 h h t-Bu h h h 1 h ch2c1 II t-Bu h h h 1 h ch2f "h t-Bu h h h 1 H chf2 h t-Bu . . h h h 1 H cp3 h t-Bu h h h 1 H CH2cf3 h t-Bu H h h 1 k cyclo-C5Hg h t-Bu . h h h 1 H ch2=ch- _H t-Bu H k n 2 H ch2=ch- H t-Bu h h h 1 H ch3-c=ch h t-Bu h h ' h 2 H 2^3 4 - 22 - R1 R2 R3 R4 • R5 R6 n r CH3 H t-Bu h C2H5 C2H5 2 h CH3 h t-Bu h ch3 C2H5 2 H CH3 h t-Bu h h C2H5 2 IT CK3 h t-Bu h C2H3 C2H5 1 h CH3 h t-Bu h CH3 C2H5 1 k CH3 h t-Bu h h CH3 1 H CH3 h t-Bu h H C2H5 1 H CH3 H t-Bu H — c 4h8~ 1 H ch3 H t-Bu H c 5h10— 1 H ch3 H sec.-Bu H H H 1 H ch3 H cch3(c2h5>2 H H H 1 9 H ch3 H n-Bu H H H 1 H CH3 H n-Bu H H H 2 H ch3 H cyclo-C-H j y H H H 1 H CH3 H cyclo-cgh^ 1 H H H 1 H ch3 H cyclo-C,H,. d 1 1 H H H 2 K CH3 H cyclo-C7H13 H H H 1 H ch3 H cyclo-C^H^3 H H H 2 K ch3 H t^Bu - (a?2) 2-^7(^2) 2-- 2 H CH3 H t-Bu H - (CH2) 2-NH- (CH2) - 1 H ch3 h t-Bu H h I CH3 1 H • i - 23 - 2 R1 R2 R3 R4 R5 R6 n R C,I3 H iso-C3H7 H H H 1 h CH3 CI CI Cl H H 1 h ch3 CH3 CI CH3 H H 1 h CH3 CH3 Br CH3 H H 2 h CH3 ch3 Br CH3 H H 1 h CH3 c2h5 CI C2H5 H H 1 h CH3 och3 CI och3 h H 1 h CH3 och3 t-Bu och3 •H H 2 h CH. oc,hc CH _ oc_hc H H 2 h 3 2 5 3 2 5 CH0 0cohc CH_ oc_h_ H H 1 h 3 2 5 3 2 5 CH3 CH3 CH3 CH3 H H 1 h CH3 CK3 CK3 CK3 H H 2 h ch3 ch3 ch3 H . H H 2 h CH3 H CH3 CH3 H H 2 h CH3 H CH3 CH3 H h 1 h CH3 CH3 CH3 H H h 1 h ch3 - c4h£ H H H 1 h ch3 h ~CA} 4 8~ H H 1 n CH3 " C4K8 " h H H 2 h CH3 " C3H< - H H H 2 h ch3 " C3H6 H H H , 1 h ch3 h — c h ^36 H H 1 h ch3 H t-Am H h H 2 ch. ch3 h iso-c3h^ h H H 2 ch. ch3 • H t-Bu H H H 1 ch- CH3 H t-Bu H h H 2 CH3 h t-Bu H H H 1 £ :j 3 4 '5 - 24 - R1 ' R2 R3 R4- I R5 R6 n R CH2-Br H t-Bu h h H 1 h CH2-Br ' h t-Bu h h H 1 h CH3 f ci h H H 2 h C,,3 ci ci H h H 2 h ch3 CH3 ci h h h 2 h CH3 f ci H h H 1 h CH3 ci ci H H H 1 H CH3 CH3 CI H H H 1 h ch3 och3 ci H H H 2 H CH3 och3 ci H K H 1 H CH3 H ci f H H 2 H CH3 H CI CI H H 2 h CH3 H ci CH3 h h 2 h CH3 H CI f H H 1 h ch3 H ci CI h H 1 H CH3 H ci CH3 h h 1 h CH3 H CI och3 H H 1 h ch=ch? H t-Bu h H H '1 K ch=ch2 H t-Bu h H H 2 H Cyclo-C^H^ h " t-Eu h H K ' 2 h Cyclo-C^H^ h t-Bu H H K 1 H - 25 - The compounds of the formula I according to the invention and their pharmaceutica I ly tolerated salts are diuretics, saluretics and antihypertensive agents, which can be employed as drugs in human and veterinary medicine. 5 They are administered enterally, for example, orally with a tube or the like, or parenterally (injection into the vascular system, for example, intravenously or injection into a muscle or under the skin and the like) in dosages of 6 - 4,000 yuug/kg per day, preferably 60 - 1,300 y/g/kg 10 per day and especially 60 - 700g/kg per day in capsules, coated tablets, tablets or solutions with various additives. They are suitable both for the treatment of hypertension and also for the treatment of edematous disorders, such as cardiac, renal or hepatic edema and other manifes-15 tations which may be attributed to disturbance of the water and electrolyte balance. The compounds can be used alone or combined with other substances having a saluretic action, even when the type of action differs. The following are particularly 20 mentioned: spironolactone, triamterene, amiloride and other K+-retaining compounds or long-acting saluretics of the type of chlortalidone. However, other, purely hypotensive, compounds are suitable for possible combination, for example, hydralazine, clonidine, reserpine and, 25 in particular, beta-blocking substances, such as, for example, metoprolol or penbutolol. ^ ™-"y * a / ' 5 -t, S ,4w*<3 - y ^ ' - 26 - Example 1 2-Aminomethyl-4-(1,1-dimethylethyl)-6-methylsulfonyl-phenol hydrochloride a) 3-(1,1-Dimethylethyl)-6-methoxybenzenesulfonyl 5 chloride 12.3 g (0.075 mole) of 4-(1/1-dimethyIethyI) -anisole in 30 ml of methylene chloride are added dropwise, with cooling in ice, to 16.5 ml of chlorosulfonic acid dissolved in 20 ml of methylene chloride. The mixture is 10 stirred for 40 minutes and poured onto ice-water. The organic phase is separated off, washed with water, dried with MgSO^. and evaporated. The recrystallization is carried out from toluene/petroleum ether. Crystals of melting point: 75 - 77°C 15 b) 3-(1,1-Dimethylethyl)-6-methoxybenzenesulfini c acid 10.7 g (0.04 mole) of 3-(1,1-dimethyIethyI)-6-methoxybenzenesulfonyl chloride are introduced into a solution of 15 g of Na2S0j and 4 g of NaOH in 100 ml of water. After adding a little acetone, the mixture is 20 heated on a steam bath for 30 minutes, filtered and the filtrate is adjusted to pH 2 - 3 with concentrated hydrochloric acid. Colorless crystals of melting point: 105 - 107°C c) 4-(1,1-Dimethylethyl)-2-methylsulfonylanisole 25 17.4 g (0.076 mole) of 3-(1,1-dimethyIethyI)-6- methoxybenzenesu I finic acid are suspended in 120 ml of acetone, and 13.3 ml (0.095 mole) of triethylamine and 8.5 ml (0.12 mole) of iodomethane are added. The mixture is stirred at room temperature for 2 hours and then poured ■ 2 034 - 27 - onto ice-water. The precipitate which separates out is filtered off with suction and recrysta11ized from n-but ano I. White crystals of melting point: 111 - 112°C 5 d) 4-(1,1-Dimethylethyl)-2-methylsulfonylphenol 23.1 g (0.095 mole) of 4-(1,1-dimethy I ethy I )-2-methylsulfonylanisole are mixed with 60 g of pyridinium hydrochloride arid heated at 210 - 220°C for 2 hours. The cooled mass is suspended in water and the solid 10 material which separates out is filtered off with suction and extracted by boiling with petroleum ether. The solution is evaporated until crystallization starts. White needles of melting point: 103 - 104°C e) 2-Chloro-N-C5-(1/1-dimethylethyl)-2-hydroxy-3-methyl-15 sulfonylbenzylDacetamide 13.5 g (0.06 mole) of 4-(1,1-dimethyIethyI)-2-methyIsuIfony Ipheno I are dissolved in 100 ml of concentrated sulfuric acid. 6.63 g (0.054 mole) of 2-chloro-N-hydroxymethylacetamide are added and the mixture is 20 stirred at room temperature for 10 minutes. The mixture is poured onto ice-water and the crude product is filtered off with suction and recrysta 11ized from toluene. Colorless crystals of melting point: 134 - 135°C f) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-methylsulfonyl-2 5 phenol hydrochloride 6.3 g (0.028 mole) of ?.-chloro-N-C5-(1/1-dimethyl-ethyI)-2-hydroxy-3-methy Isu Ifony Ibenzy13acetamide in a mixture of 20 ml of concentrated hydrochloric acid and 40 ml of ethanol are boiled under reflux for 16 hours. 2 034': - 28 - The precipitated product is filtered off with suction and recrysta 11ized from ethanol. Colorless needles of melting point: 242 - 243°C (decomposition) 5 Example 2 2-Aminomethyl-4-isopropyl-6-methylsulfonylphenol hydrochloride a) 3-Isopropyl-6-methoxybenzenesulfonyl chlor. ide 3-1 sopropyl-6-methoxybenzenesuIfonyI chloride, of 10 melting point: 60 - 61°C, is obtained from 15 g (0.1 mole) of 4-isopropylanisole and 20 ml of chlorosulfuric acid in analogy to Example 1a). b) 3-Isopropyl-6-methoxybenzenesulfinic acid 3-Isopropyl-6-methoxybenzenesulfinic acid, of 15 melting point 98 - 99°C, is obtained from 21.6 g (0.09 mole) of 3-isopropyl-6-methoxybenzenesu I fony I chloride, 32.6 g of Na2S(>3 and 100 ml of 2N sodium hydroxide solution in analogy to Example 1b). c) 4-Isopropyl-2-methylsulfonylanisole 20 21.4 g (0.1 mole) of 3-isopropyl-6-methoxybenzene- sulfinic acid, 17.32 ml (0.125 mole) of triethylamine and 10.6 ml (0.17 mole) of iodomethane give, in analogy to Example 1c), 4-isop ropy l-2-methy Isu I fonylaniso le of melting point 50 - 52°C. 25 d) 4-Isopropyl-2-methylsulfonylphenol 10.0 g (0.044 mole) of 4-isop ropy I-2-methyIsul-fonylanisole are cleaved with 36 g of pyridinium hydrochloride in analogy to Example 1d) to give 4-isopropy1-2- methylsulfonylphenol. 2^. /* P 1 ^ / i .-*v - 29 - Melting point: 74 - 76°C e) 2-Chloro-N-(2-hydroxy-5-isopropyl-3-methylsulfonyl-benzyl)acetamide 6.8 g <0.032 mole) of 4-isop ropyl-2-methyIsuIfon-5 ylphenol are dissolved in a mixture of 40 ml of glacial acetic acid and 40 ml of concentrated sulfuric acid, and 4.73 g (0.038 mole) of 2-chloro-N-hydroxymethyI acetamide are added. The mixture is stirred at room temperature for 15 minutes, poured onto ice-water and filtered off 10 with suction. The 2-chloro-N-(2-hydroxy-5~isopropyl-3-methylsulfonylbenzyDacetamide, which is obtained as a white powder of melting point: 97 - 98°C, is still slightly contaminated with starting material. It is employed in the next reaction without further purification. 15 f) 2-Aminomethyl-4-isopropyl-6-methylsulfonylphenol hydrochloride The 2-chloro-N-(2-hydroxy-5-isopropyl-3-methylsuLfonylbenzyDacetamide produced in reaction 3e) is treated with concentrated hydrochloric acid in ethanol in 20 analogy to Example 1f). The 2-aminomethy1-4-isopropy1-6-methy I suLfonyLpheno I hydrochloride, of melting point: 246 - 247°C (decomposition), is obtained after re-crystallization from ethanol. Examp le 3 25 2-Aminomethyl-4-(1,1-dimethylethyl)-6-isopropylsulfonyl-phenol hydrochloride a) 4-(1,1-Dimethylethyl)-2-isopropylsulfonylanisole 22.7 g (0.1 mole) of 3-(1,1-dimethylethyI)-6- methoxybenzenesuIfinic acid are suspended in 160 ml of - 30 - acetone, and 19.35 ml <0.125 mole) of triethylamine and 16.9 ml of isopropyl iodide are added. The mixture is stirred at room temperature for 1 hour and is then poured onto ice-water. This water is extracted three times with 5 ethyl acetate, the organic phase is evaporated to a small volume and the residue is chromatographed on silica gel, eluting with to luenelethy I acetate. White crystals of melting point: 75 - 76°C b) 4-(1,1-Dimethylethyl)-2-isopropylsulfonylphenol 10 4.6 g <0.017 mole) of 4-(1,1-dimethylethyl)-2- isopropylsulfonylanisole are dissolved in 50 ml of methylene chloride, and 2.5 ml of boron tribromide (0.027 mole) are added. The mixture is stirred at room temperature for 1 hour, excess BBr^ is destroyed with methanol and 15 the solvent is removed in vacuo. The residue is triturated with water and filtered off with suction. White crystals of melting point: 54 - 55°C c) 2-Chloro-N-C5-(1,1-dimethylethyl)-2-hydroxy-3-iso-propylsulfonylbenzylPacetamide 20 4.1 g <0.016 mole) of 4-(1,1-dimethy I ethy I)-2- isopropylsulfonylphenol are dissolved in 36 ml of concentrated sulfuric acid, and 3.65 g (0.03 mole) of 2-chloro-N-hydroxymethylacetamide are added. After stirring at room temperature for 10 minutes, ice-water is added, and 25 the mass of crystals which separates out is filtered off with suction and recrystallized with methanol/ether. Crystals of melting point: 94 - 95°C 2 934- - 31 - d) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-isopropyl-su Ifony Ipheno I hydrochloride 4.0 g (0.011 mole) of 2-chloro-N-C5-(1,1-dimethy l-et hyI)-2-hydro xy-3-isopropylsulfonylbenzylDacetamide in 5 30 ml of ethanol and 10 ml of concentrated hydrochloric acid are boiled under reflux for 8 hours. The mixture is evaporated, the residue is dissolved in 2N hydrochloric acid, extracted several times by shaking with ethyl acetate and the solvent is removed in vacuo. The residue is 10 crystallized with ether. White crystals of melting point: 209 - 212°C (decomposition) Examp le 4 2-Aminomethyl-4-ethyl-6-methylsulfony I phenol hydrochloride 15 a) 3-Ethyl-6-methoxybenzenesulfonyl chloride 3-Ethyl-6-methoxybenzenesu IfonyI chloride, of melting point: 61 - 62°C, is obtained from 91 g (0.67 mole) of 4-ethyI aniso I e and 148 ml (1.5 moles) of chlorosulfuric acid in analogy to Example 1a). 20 b) 3-Ethyl-6-methoxybenzenesulfinic acid 68.5 g (0.29 mole) of 3-ethy l-6-methoxybenzene-sulfonyl chloride are reduced with 108 g of sodium sulfite and 360 ml of 2N sodium hydroxide solution in analogy to Example 1b) to give 3-ethy l-6-methoxybenzenesu I finic 25 acid. Melting point: 57 - 58°C c) 4-Ethyl-2-methylsulfonylanisole 2.0 g (0.01 mole) of 3-ethy l-6-methoxybenzene- sulfinic acid are reacted with 1.73 ml (0.0125 mole) of - 32 - triethylamine and 1.06 ml of methyl iodide to give 4-ethyl-2-methyIsuIfonyI anisoIe. The crude product is purified by column chromatography on silica gel eluting with toluene/ethyl acetate 4:1. The substance is obtained as 5 a light yellow oil. d) 4-Ethyl-2-methylsulfonylphenol 6.0 g (0.028 mole) of 4-ethy l-2-methy I suIfony l-anisole are cleaved with 18 g of pyridinium hydrochloride in analogy to Example 1d) to give 4-ethyl-2-methylsulfon-10 ylphenol. Melting point: 101 - 102°C e) 2-Chloro-N-(2-hydroxy-5-ethyl-3-methylsulfonyl-benzy Dacetamide 2.5 g (0.012 mole) of 4-ethyl-2-methylsulfonyl-15 phenol are dissolved in 30 ml of concentrated sulfuric acid, and 1.77 g (0.014 mole) of 2-ch loro-N-hydroxymethy l-acetamide are added. The mixture is stirred at room temperature for 10 minutes, poured onto ice-water and extracted with ether. The ether extracts are dried with mag-20 nesium sulfate and evaporated until 2-ch loro-N-(2-hydroxy-5-ethy1-3-methyIsuIfony Ibenzy I )acetamide crystallizes out. Colorless crystals of melting point: 78 - 79°C f) 2-Aminomethyl-4-ethyl-6-methylsulfonylphenol hydro-ch loride 25 2.4 g (0.008 mole) of 2-chloro-N-(2-hydroxy-5- ethyl-3-methyIsuIfonyIbenzy I )acetamide are hydrolyzed in analogy to Example 1f) to give 6-arrii nomethy l-4-ethyl-2-methylsulfonylphenol hydrochloride. Recrystallization from methanoI/ether provides colorless crystals of melting - 33 - point: 210 - 211°C (decomposition) Example 5 2-Aminomethyl-4-(1.,1-dimethylethyl)-6-ethylsulfonylphenol hydroch loride 5 a) 2-Ethylsulfonyl-4-(1,1-dimethylethyl)anisole 15.3 g (0.067 mole) of 3-(1,1-dimethyIethy I)-6-methoxybenzenesulfinic acid are suspended in 100 ml of acetone, 12 ml of triethylamine and 8.6 ml (0.11 mole) of ethyl bromide are added and the mixture is stirred at room 10 temperature for 1 hour. The working up is in analogy to Examp le 1c). Melting point: 104 - 105°C b) 2-Ethylsulfonyl-4-(1,1-dimethylethyl)phenol 6.0 g (0.038 mole) of 2-ethyIsuIfony1-4-(1,1-15 dimethylethyl)anisole are reacted with 18 g of pyridinium hydrochloride in analogy to Example 1d) to give 2-ethyl-sulfonyl-4-(1,1-dimethylethyl)phenol. Melting point: 74 - 75°C c) 2-Chloro-N-r5-(1,1-dimethylethyl)-3-ethylsulfonyl-2-20 hydroxybenzylHacetamide 5.7 g (0.026 mole) of 2-ethy I suIfony1-4-(1,1 -dimethy I ethy I)pheno I and 3.92 g (0.032 mole) of N-hydroxy-methylchloroacetamide are reacted in analogy to Example 1e) to give 2-chloro-N-C5-(1,1-dimethylethyl)-3-ethyl-25 sulfonyl-2-hydroxybenzylDacetamide. White crystals of melting point: 116 - 117°C d) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-ethylsulfonyl-phenol hydrochloride 2.4 g of 2-chloro-N-C5-(1,1-dimethylethyl)-3- ' !v> 7 ^ 4. ^ - 34 - ethylsulfonyl-2-hydroxybenzylDacetamide in 25 ml of EtOH and 2.5 ml of concentrated hydrochloric acid are boiled under reflux for 8 hours. Working up as under Example 3d) provides crystals of melting point: 203 - 204°C (decont-5 position) Example 6 2-Aminomethyl-6-chloromethylsulfonyl-4-(1,1-dimethylethyl)-phenol hydrochloride a) 2-Chloromethylsulfonyl-4-(1,1-dimethylethyl)anisole-10 22.8 g (0.1 mole) of 5-(1,1-dimethyIethy1)-2- methoxybenzenesulfinic acid are dissolved in 150 ml of H2O with 23 g of ^2^03 and 15 g (0.117 mole) of dichloro-acetic acid. The solution is slowly evaporated to dryness at a bath temperature of 160°C. The residue is again 15 taken up with H2O, neutralized with a little dilute hydrochloric acid and extracted several times by shaking with ethyl acetate. After the solvent has been removed, the product is obtained as crystals. Melting point: 114 - 116°C 20 b) 2-Chloromethylsulfonyl-4-(1,1-dimethylethyl)-phenol 13 .4 g (0.049 mole) of 2-ch loromethyIsuIfony1-4-(1,1-dimethy lethy I)aniso le are cleaved in analogy to Example 3b) to give 2-ch loromethy I suIfony1-4-(1,1-dimethyl-ethyOphenol. 25 Melting point: 94 - 95°C c) 2-Chloro-N-C3-chloromethylsulfonyl-5-(1,1-dimethyl-•ethyl)-2-hydroxybenzyl3acetamide This compound is prepared in analogy to Example 1e), and the crude product is recrystallized from toluene/ petroleum ether. Melting point: 139 - 140°C d) 2-Aminomethyl-6-chloromethylsulfonyl-4-(1,1-dimethyl-ethy Dphenol hydrochloride 5 This compound is prepared in analogy to Example 1 d) . Recrysta 11 ization from methanoI/ether provides white crystals of melting point: 218 - 219°C (decomposition) Example 7 2-Aminomethyl-4-methyl-6-methylsulfonylphenol hydrochloride 10 a) 2-Chloro-N-(2-hydroxy-5-methy 1-3-methylsulfonyl-benzyl)acetamide 7.4 g (0.04 mole) of 4-methyl-2-methylsulfonyl-phenol are dissolved in 70 ml of concentrated sulfuric acid. 4.4 g (0.03 6 mole) of 2-chloro-N-hydroxymethyl-15 acetamide are added and the mixture is stirred at room temperature for 10 minutes. The mixture is poured onto ice-water, the precipitate is filtered off with suction and recrysta 11ized from methanol. White crystals of melting point: 115 - 116°C. 20 b) 2-Aminomethyl-4-methyl-6-methylsulfonylphenol hydrochloride 7.4 g (0.026 mole) of 2-ch loro-N-(2-hydroxy-5-methyl-3-methyIsuIfonyIbenzy I)acetamide are dissolved in 25 ml of ethanol and 3 ml of concentrated hydrochloric 25 acid and heated under reflux for 10 hours. The product is filtered off with suction and recrysta 11ized from methano l/ether. White crystals of melting point: 227 - 228°C - 36 - c) Preparation of the starting compound: 4-Methyl-2-methy I su I fony IphenoI from Example 7a) is prepared from 4-methyLaniso I e in analogy to the reaction sequence 1a) - d). It has a melting point of 84 -85°C . Example 8 2-Aminomethyl-4-(1/1-dimethylpropyl)-6-methylbenzene-su Ifony I ch lori de a) 3-(1,1-Dimethylpropyl)-6-methoxybenzenesulfonyl chloride SuIfochlorination is carried out in analogy to Example 1a) using 4-(1,1-dimethy IpropyI)aniso Ie as the starting material. White crystals of melting point: 40 -42°C . b) 3-(1,1-Dimethylpropyl)-6-methoxybenzenesulfinic acid This compound is prepared from 3-(1,1-dimethyl-propyI)-6-methoxybenzenesu I fony I chloride in analogy to Example 1b). White crystals of melting point: 91 - 92°C. c) 4-(1,1-Dimethylpropyl)-2-methylsulfonylanisole The compound is prepared from 3 - (1,1-dimethy l-propy I)-6-methoxybenzenesu I finic acid and iodomethane in analogy to Example 1c). Crystals of melting point: 64 - 65°C d) 4-(1,1-Dimethylpropyl)-2-methylsulfonylphenol The compound is obtained from 4-(1/1-dimethyl-propyI)-2-methyIsuIfony I aniso I e by the action of boron tribromide in analogy to Example 3b) and is produced as a pale ye I low oil. ^ 4 ° ihm ? S K-i/ ' " i y - 37 - e) 2-Chloro-N-C5-(1,1-dimethylpropyl)-2-hydroxy-3-methylsulfonylbenzyllacetamide 8.5 g (0.035 mole) of 4-(1,1-dimethyLpropy I)-2-methyIsu I fonyLphenoL are dissolved in 80 ml of concentra-5 ted sulfuric acid, 8 g (0.065 mole) of 2-ch loro-N-hydroxy-methyI acetamide are added and the mixture is stirred at room temperature for 10 minutes. The mixture is poured onto ice-water, the solid is filtered off with suction and recrysta11ized from toluene/petroleum ether. 10 White crystals of melting point: 119 - 120°C f) 2-Aminomethyl-4-(1,1-dimethylpropyl)-6-methylsulfonyl-phenol hydrochloride The compound is prepared in analogy to Example 1f) but using 2-chloro-N-C5-(1,1-dimethy IpropyI)-2-hydroxy-3-15 methyIsuIfonyIbenzyID acetamide as the starting material. White needles of melting point: 187 - 188°C (decomposition) Example 9 2-AminomethyL-4-chloro-3,5-dimethyl-6-roethylsulfonylphenol hydroch lo r i de 20 a) 4-Chloro-3,5-dimethyl-2-methylsulfonylanisole This compound is prepared in analogy to the reaction sequence 1a) - 1c), but with 4-chloro-3,5-dimethyl-anisole as the starting material. The final product melts at 129 - 130°C. 2 5 b) 4-Chloro-3,5-dimethyl-2-methylsulfonylphenol 16.5 g of 4-chIoro-3,5-dimethyl-2-methyIsu I fony l-anisole (0.066 mole) are reacted with 50 g of pyridinium hydrochloride at 190 - 210°C. The reaction mass is triturated with water and the precipitate produced is fil- tered off with suction. Colorless crystals of melting point: 119 - 120°C. c) 2-Chloro-N-C5-chloro-4,6-dimethyl-2-hydroxy-3-methyl-sulfonylbenzylDacetamide 5 14.0 g (0.059 mole) of 4-ch loro-3,5-dimethy1-2- methylsulfonylphenol are dissolved in 150 ml of concentrated sulfuric acid, 8.7 g (0.07 mole) of 2-chloro-N-hydroxymethy lacetamide are added and the mixture is stirred at room temperature for 10 minutes. The solution 10 is stirred into ice-water iand the solid is filtered off with suction. White crystals of melting point: 204 - 205°C d) 2-Aminomethyl-4-chloro-3,5-dimethyl-6-methylsulfonyl-phenol hydrochloride 15 16.0 g (0.048 mole) of 2-ch loro-N-C5-chloro-4,6- dimethyl-2-hydroxy-3-methylsulfonylbenzyl3acetamide in 120 ml of ethanol and 40 ml of concentrated hydrochloric acid are boiled under reflux for 8 hours. Aft^er cooling down in an ice bath, the solid is filtered off with 20 suction and recrysta11 ized from methanoI/ether. Colorless needles of melting point: 259 - 260°C (decompos i t i on) Example 10 2-Aminomethyl-4-(1,1-dimethylethyl)-6-propyl9ulfonylphenol 25 hydrochlori de a) 4-(1,1-Dimethylethyl)-2-propylsulfonylanisole 22.8 g (0.1 mole) of 3-(1,1-dimethylethyl)-6-methoxybenzenesulfinic acid are reacted with n-propyl iodide in the presence of triethylamine in analogy to 2 034 67 - 39 - Example 1c) to give 4-(1,1-dimethylethyI)-2-propy I aniso Ie. White crystals of melting point: 65 - 66°C. b) 4-(1,1-Dimethylethyl)-2-propylsulfonylphenol 7 g (0.026 mole) of 4-(1,1-dimethyIethyI)-2-5 propylsulfonylanisole are cleaved to give the phenol in analogy to Example 1d).The substance is obtained as a pale yellow oil which is employed in the next reaction without further purification. c) 2-Chloro-N-C5-(1,1-dimethylethyL)-2-hydroxy-3-propyl-10 sulfonylbenzylHacetamide 5.1 g (0.02 mole) of 4-(1,1-dimethylethyl)-2-propylsulfonylphenol are dissolved in 45 ml of concentrated sulfuric acid, 4.56 g (0.037 mole) of 2-chloro-N-hydroxymethylacetamide are added and the mixture is 15 stirred at room temperature for 10 minutes. The mixture is poured onto ice-water and the solid is filtered off with suction and crystallized with ether. White crystals of melting point: 108 - 110°C. d) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-propylsulfonyl-20 phenol hydrochloride 2.35 g (0.007 mole) of 2-ch loro-N-E5-(1,1-dimethy l-ethy l)-2-hydroxy-3-propy Isulfony Ibenzyllacetamide in a mixture of 20 ml of ethanol and 5 ml of concentrated hydrochloric acid are boiled under reflux for 8 hours. 25 The mixture of solvents is removed in a rotary evaporator and the residue is recrystallized from methanol/ether. White needles of melting point: 189 - 190°C (decomposition) - 40 - Example 11 2-N,N-Dimethylaminomethyl-4-(1,1-dimethylethyl)-6-methyl-sulfonylphenol hydrochloride 4.56 g (0.02 mole) of 4-(1,1-dimethylethyl)-2- 5 methy I su I fony Ipheno I are dissolved in 30 ml of ethanol, / and 5.6 ml (0.04 mole) of 40% strength aqueous dirnethyl-amine solution and 4 ml (0.04 mole) of 35% strength aqueous formaldehyde solution are added. The mixture is boiled under reflux for 1 hour, the solution is evaporated 10 to dryness in a rotary evaporator and the residue is taken up in 2N hydrochloric acid. The aqueous phase is extracted several times by shaking with ethyl acetate and then evaporated to dryness. The residue is recrystallized from isopropanol/ether. 15 White crystals of melting point: 218 - 220°C Examp le 12 Methyl 3-aminomethyl-5-(1,1-dimethylethyl)-2-hydroxy-phenyl sulfoxide hydrochloride dihydrate a) Methyl 5-(1,1-dimethy lethy I)-2-hydroxyphenyI sulfoxide 20 52 g (0.27 mole) of 4-(1,1-dimethyIethy I )-2- hydroxythioaniso I e are dissolved in 300 ml of glacial / acetic acid. 30 ml of 30% H2O2 are added dropwise while cooling in ice. The mixture is stirred at room temperature for 2 hours, poured onto ice-water and the solid is 25 filtered off with suction and recrystallized from toluene. White crystals of melting point: 149 - 150°C. b) C5-(1,1-Dimethylethyl)-2-hydroxy-3-methylsulfoxy-benzy l]trimethy I ammonium iodide 11 g (0.052 mole) of methyl 5-(1,1-dimethy I ethy I)- 2f* T> /! ^ - y C 'J ' - 41 - 2-hydroxyphenyI sulfoxide, together with 14 ml (0.1 mole) of 40% strength aqueous dimethy I amine solution and 10 ml of 35% strength aqueous formaldehyde solution (0.1 mole) in 100 ml of ethanol, are boiled under reflux for 1 hour. 5 The solvent is removed in a rotary evaporator, the residue is taken up in 2N hydrochloric acid and extracted with ethyl acetate. The aqueous phase is again evaporated to dryness, the residue is taken up in acetone and 30 ml of iodomethane are added. The mixture is left at room tem-10 perature for about 1 hour and then evaporated until crystallization begins. White crystals of melting point: 183 - 185°C c) Methyl 3-azidomethyl-5-(1,1-dimethylethyl)-2-hydroxy-pheny I su Ifoxi de 15 8.9 g (0.022 mole) of the ammonium iodide obtained under 11b) are dissolved in 80 ml of dimethyLformamide, 5 g (0.08 mole) of sodium azide are added and the mixture is stirred at 100°C for 30 minutes. The mixture is then poured onto ice-water and the solid is filtered off with 20 suction. The yellowish product, which is still slightly moist, is dissolved in 80 ml of methanol without further purification. d) Methyl 3-aminomethyl-5-(1,1-dimethylethyl)-2-hydroxy-phenyl sulfoxide hydrochloride dihydrate 25 The methanol ic solution of methyl 3-azidomethyl- 5-(1,1-dimethy lethy I)-2-hydroxypheny I sulfoxide obtained under 11c) is mixed with a suspension of 1 g of 10% palladium on charcoal and hydrogenated at room temperature and under normal pressure for 2 hours. The mixture is Z W ^ / - 42 - filtered, the filtrate is evaporated and the residue is chromatographed on silica gel, eluting with a mixture of ethyl acetate and methanol (2:1). The free amine is initially obtained (melting point: 192 - 193°C), which is 5 converted into the title compound by recrysta 11 ization from 2N hydrochloric acid. White crystals of melting point: 84 - 86°C. Example 13 4-Aminomethyl-5-hydroxy-6-methylsulfonylindan hydro-10 chloride a) 6-Chlorosulfonyl-5-methoxyindan 50 g (0.34 mole) of 5-methoxyindan are reacted with 75 ml of chlorosulfonic acid in analogy to Example 1a) to give 6-chlorosuIfonyl-5-methoxyindan. 15 White crystals of melting point: 75 - 77° C . b) 5-Methoxy-6-sulfinoindan The sulfinic acid is obtained from 6-chloro-su I fony 1-5-methoxyindan in analogy to Example 1b). White crystals of melting point: 105 - 106°C 20 c) 5-Methoxy-6-methylsulfonylindan 5-Methoxy-6-methy I su I fony I indan, of melting point: 108 - 110°C, is obtained from 5-methoxy-6-sulfinoindan in analogy to Example 1c). d) 5-Hydroxy-6-methylsulfonylindan 25 The compound is obtained from 5-methoxy-6-methyl- su I fony I indan by the action of boron tribromide in analogy to Examp le 3b) . White crystals of melting point: 149 - 151°C . ? cr - 43 - e) 4-(N-Chloroacetylaminomethyl)-5-hydroxy-6-methyl su Ifony Li ndan 13.5 g (0.064 mole) of 5-hydroxy-6-methyIsu I fony l-indan are dissolved in 100 ml of sulfuric acid, and 6 g 5 of 2-chloro-N-hydroxymethylacetamide (0.048 mole) are added. The mixture is stirred at room temperature for 10 minutes and then poured onto ice-water. The solid is filtered off with suction and re c ry s t'a 11 i zed from ethanol. White crystals of melting point: 152 - 153°C 10 f) 4-Aminomethyl-5-hydroxy-6-methylsulfonylindan hydrochloride The compound is prepared from 4-(N-ch loroacety l-aminonethyI)-5-hydroxy-6-methy I su I fonyIindan in analogy to Example 1f). \ 15 White crystals of melting point: 244 - 248°C (decomposition) Examp I e 14 2-Aminomethyl-4-bromo-6-methylsulfonylphenol hydrochloride a) 2-Ch loro-N-(2-hydroxy-5-bromo-3-methylsulfonyl-20 benzy Dacetamide 8.2 g (0.035 mole) of 4-bromo-2-methylsulfonyl-phenol are dissolved in 82.5 ml of concentrated sulfuric acid, and 4.86 g (0.039 mole) of 2-ch loro-N-hydroxymethyl-acetamide are added. The mixture is stirred at room tem-25 perature for about 30 minutes and then poured onto ice-water. The precipitate is filtered off with suction and recrystallized from ethanol. Melting point: 124 - 125°C *7 f\ 1 r - -\^v .* ....- ^ c y • - 44 - b) 2-Aminomethyl-4-bromo-6-methylsulfonylphenol hydroch to r i de This compound is prepared from 2-ch loro-N-(2-hydroxy-5-bromo-3-methyIsu I fonyLbenzy I)acetamide in 5 analogy to Example 1f). Melting point: 228 - 229°C (decomposition) c) Preparation of the starting compound 4-Bromo-2-methylsulfonylphenol from Example 15a) is prepared from 4-bromoaniso le in analogy to the reaction 10 sequence 1a) - d). It has a melting point of 63 - 65°C. Example 15 2-Aminomethyl-4-(1-methylpropyl)-6-methylsulfonylphenol hydrochlori de 15 a) 2-Chloro-N-C2-hydroxy-5-(1-methylpropyl)-3-roethyl-sulfonylbenzylDacetamide The compound is prepared in analogy to Example 1e but with 4-(1 -met hy Ip r opy I )-2-met hy I s.u I f ony Iph eno I as the starting material. The crude product is recrystallized 20 from ether'/petroleum ether. Melting point: 61 - 62°C b) 2-Aminomethyl-4-(1-methylpropyl)-6-methylsulfonyl-phenol hydrochloride The preparation is in analogy to Example 1d). 25 White crystals of melting point: 236 - 238°C. c) Preparation of the starting compound The 4-(1-methyIpropy I )-2-methyIsuIfonyIphenoI is prepared in analogy to the reaction sequence 1a) - 1d) from 4-(1-methyIpropyI)aniso Ie. 2r* / v ./ CV - 45 - Heltingpoint: 58-59°C Examp Le 16 2-Aminomethyl-3,4,5-trichloro-2-roethylsulfonylphenol methanesuLfonate 5 a) 2-Chloro-N-(2-hydroxy-4,5,6-trichloro-3-methyLsulfon-ylbenzyl)acetamide This compound is prepared in analogy to Example 1e, but with 3,4,5-trichlorophenol as the starting material. 10 Melting point: 224 - 225°C b) 2-Aminomethyl-3,4,5-trichloro-2-methyLsulfonylphenol methanesu lfonate The preparation is carried out in analogy to Example 1d) but using 20% aqueous rnethanesulfonic acid 15 instead of concentrated hydrochloric acid. Melting point: 253 - 254°C c) Preparation of the starting compound The 3,4,5-trich loro-2-methy Isu1fony IphenoI necessary for 16a is prepared in analogy to the reaction 20 sequence 1a) - 1d). Melting point: 146 - 147°C Examp Le 17 2-(1-Pyrrolidinyl)methyL-4-(1,1-dimethylethyl)-6-methyl-su Ifony Ipheno I hydrochloride 25 This compound is prepared in analogy to Example 11. However, instead of a dimethylamine solution, pyrrol dine is used. Recrysta 11 ization from isopropano I/ether . White crystals of melting point: 230 - 231°C L ^ •" ■ ■ " ■ - 46 - Example 18 2-(3-Thiazolidinyl)methyl-4-(1,1-dimethylethyl)-6-methyl-suIfony Ipheno I hydrochloride Preparation in analogy to Example 11 using 5 thiazolidine instead of dimethylamine. White crystals of melting point: 207 - 208°C. Example 19 2-(4-Thiorr.orpholinyl)methyl-4-(1,1-dimethyLethyl)-6-methylsulfonylphenol hydrochloride 10 In analogy to Example 11 using thiomorpho I ine instead of dimethylamine. White crystals of melting point: 249 - 250°C. Example 20 2-(4~Morpholinyl)niethyl-4-(1,1-dimethylethyl)-6-methyl-15 suIfony Ipheno I hydrochloride In analogy to Example 11 using morpholine instead of dimethylamine. White crystals of melting point: 246 -247°C. Example 21 20 2-(4-Piperidinyl)methyl-4-(1/.1-dimethylethyl)-6-methyl-su Ifony Ipheno I hydrochloride In analogy to Example 11 using piperidine instead of dimethylamine. White crystals of melting point: 233 - 234°C. 25 Example 22 2-Hexamethyleneiminomethyl-4-(1/1-dimethylethyl)-6-methyl-su I fony Ipheno I hydrochloride In analogy to Example 11 using hexamethy I eneimine instead of dimethylamine. r*."% < . - 47 - Melting point: 174 - 175°C Example 23 2-Aminomethyl-4-(1-methylcyclohexyl)-6-methylsulfonyl-phenol hydrochloride 5 a) 2-Chloro-N-C2-hydroxy-5-(1-methylcyclohexyl)-3-methyl-sulfonylbenzylDacetamide This compound is prepared in analogy to 1e but with 4-(1-methyIcyclohexy I)-2-methy IsuIfony Ipheno I as starting material. The crude product is brought to 10 crystallization by trituration with ether. Melting point: 146 - 148°C. b) 2-Aminomethyl-4-(1-methylcyclohexyl)-6-methylsulfonyl-phenol hydrochloride In analogy to Example 1d). 15 White crystals of melting point: 226 - 227°C. c) Preparation of the starting compound The 4-(1-methyIcycI ohexyI)-2-methyIsuIfonyIphenoI necessary under 23a) is prepared in analogy to Example 1a) - 1d). 20 Melting point: 67 - 68°C Examp le 24 2-Aminomethyl-4-(1/.1-diethylethyl)-6-methylsulfonylphenol hydrochlori de a) 2-Chloro-N-C2-hydroxy-5-(1,1-diethylethyl)-3-methyl-25 sulfonylbenzylDphenol hydrochloride In analogy to Example 1e but using 4-(1/.1-diethyl-ethyl)-2-methylsulfonylphenol hydrochloride as starting material. Recrystallization from ether. Melting point: 117 - 118oC 2^ y*. <?. vy' C^' •' ..J > - 48 - b) 2-Aminomethyl-4-(1,1-diethylethyl)-6-methylsulfonyl-phenol hydrochloride In analogy to Example 1f. White crystals of melting point: 179 - 181°C 5 c) Preparation of the starting compound The 4-(1,1-diethy lethy I)-2-methyIsuIfonyIphenoI necessary under 24a) is prepared in anatogy to Example 1a) - 1d). Melting point: 84 - 86°C 10 Example 25 2-AminomethyL-3,5-dimethoxy-4-chloro-6-methylsulfonyl-phenol hydrochloride a) 2-Chloro-N-(2-hydroxy-4/6-dimethoxy-5-chloro-3-rnethyl-sulfonylbenzyOacetamide 15 In analogy to Example 1e) but using 3,5-dimethoxy- 4-chloro-2-methylsulfony Iphenol as starting material. In addition, the reaction mixture is heated at 60°C for about 15 minutes. The crude product is purified by extraction by boiling with n-butanol. 20 Melting point: 181 - 182°C b) 2-Aminomethyl-3,5-dimethoxy-4-chloro-6-methylsulfonyl-phenol hydrochloride In analogy to Example 1f). Recrysta11ization from methano I/ether provides crystals of melting point: 159 -25 160°C . c). Preparation of the starting compound The 3,5-dimet hoxy-4-ch loro-2-methyIsuIfonyIphenoI necessary under 25a) is prepared in analogy to Example 12a) but using 2-hydroxy-4,6-dimethoxy-5-chlorothioanisole - 49 - as starting material and using trif luoroacetic acid instead of acetic acid as the solvent. Melting point: 170 - 172°C Example 26 5 2-Aminomethyl-4-(1,1-dimethylethyl)-6-iodomethylsulfonyl~ phenol hydrochloride a) 2-Chloro-N-C2-hydroxy-5-(1,1-dimethylethyl)-5-iodo-methylsulfonylbenzylJacetamide In analogy to Example 1e) but using 4-(1/1-di-10 methylethyl)-2-iodomethylsulfonylphenol. The crude product is recrystallized from isopropanot. Melting point: 118 - 119°C b) 2-Aminomethyl-4-(1/1-dimethylethyl)-6-iodomethyl-su Ifony Ipheno I hydrochloride 15 In analogy to Example 1f). White crystals of melting point: 220 - 223°C. c) Preparation of the starting compound 4-(1/.1-Dimethylethyl)-2-iodomethylsulfonylphenol is prepared in analogy to Example 1d) from 4-(1/1-dimethyl-20 ethyl)-2-iodomethylsulfonylanisole and melts at 82 - 84°C. The 4-(1,1-dimethyIethyI)-2-iodomethyIsuIfony I aniso Ie is prepared in a manner known from the literature from the sulfinic acid described under 1b) and methylene iodide. Melting point:. 98- 102°C 25 Example 27 2-Atninornethyl-4-(1/.1-dimethylethyl)-6-(2-methylpropyl)-su Ifony Ipheno I hydrochloride a) 2-Chloro-N-C2-hydroxy-5-(1,1-dimethyLethyl)-3-(2-methylpropyDsulfonylbenzyllacetamide 2^ "X * v .> - 50 - In analogy to Example 1e) but using 4-(1,1-dimethy I -ethyl)-2-(2-methylpropyl)sulfonylphenol as starting material. Melting point: 97 - 98°C b) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-(2-methylpropyl)-sulfonylphenol hydrochloride In analogy to Example 1f). Melting point: 216 - 21 7°C c) Preparation of the starting compound 4-(1,1-Dimethylethyl)-2-(2-methylpropyl)sulfonyl-phenol from 27a) is prepared in analogy to Example 1c) and 1d) from 2-methoxy-5-(1,1-dimethy lethyI)benzenesuIfinic acid and 1-iodo-2-methy Ipropane instead of iodomethane. Meltingpoint: 52-53°C Example 28 2-Aminomethyl-4-(1/.1-dimethyLethyl)-6-allylsulfonylphenol hydrochloride a) 2-Chloro-N-C2-hydroxy-5-(1/.1-dimethylethyl)-3~aLlyl-sulfonylbenzyUacetamide In analogy to Example 1e) but using 4-(1,1-dimethyIethyI)-2-aI lyIsu I fony Ipheno I as starting material. Meltingpoint: 119-120°C b) 2-Aminomethyl-4-(1,1-dimethylethyl)-6-aL lylsulfonyl-phenot hydrochloride In analogy to Example 1f). Melting point: 242 - 245°C c) Preparation of the starting compound 4-(1,1-Dimethylethyl)-2-a I lylsulfonytphenol from Example 28a) is prepared in analogy to Example 1c) and 2 4**. *%, & / , / <■- > ' / - 51 - 1 d) . Melting point: 63 - 64°C Examp le 29 2-Aminomethyl-4-<1,1-dimethylethyl)-6-cyclopropyLsulfonyl 5 phenol hydrochloride a) 2-Chloro-N-C2-hydroxy-5-(1/.1-dimethylethyl)-3-cyclo-propylsulfonylbenzyl3acetamide In analogy to Example 1e) but using 4 - <1 ,1 -dimethy1ethyI)-2-cycI opropy Isu I fony IphenoI as starting 10 material. The crude product is recrystallized from ether. Melting point: 96 - 97°C b) 2-Aminomethyl-4-C1,1-dimethylethyl)-6-cyclopropyl-su Ifony Ipheno I hydrochloride In analogy to Example 1f), recrysta I lization of 15 the crude product from isopropano I/ether. Melting point: 159 - 160°C c) Preparation of the starting compound 26.5 g of the sulfinic acid <0.115 mole) obtained under 1b), 87.5 g <0.1175 mole) of 20% aqueous tetraethyl- \ 20 ammonium hydroxide solution and 55.5 g <0.275 mole) of di-bromopropane in 100 ml of dich loroethane are heated to reflux for 4 hours. The organic phase is separated off and chromatographed on silica gel with toluene/ethyl acetate 4:1. 25 The 4-<1,1-dimethy I ethy I )-2-<3-bromopropyI)- su Ifony laniso le is obtained and is reacted with 1.1 equivalents of potassium tert.-buty I ate in boiling tert.-butanol to give 4-<1/,1-dimethylethyl)-2-cyclopropylanisole. The 4-<1,1-dimethyIethyI)-2-cyc lopropyIsuIfony IphenoI, of i, j j - 52 - melting point: 85 - 86°C, necessary in Example 29a) is obtained from the latter in analogy to Example 1d). Examp le 30 1-Aminomethyl--3-methylsulfonyl-5,6,7,8-tetrahydro-2-5 naphthol hydroch loride a) 1-Chloroacetylaminomethyl-3-methylsulfonyl-5,6,7,8-tetrahydro-2-naphthol This compound is prepared in analogy to Example 1e). The crude product is recrystallized from ethanol. 10 Melting point: 173 - 175°C b) 1-Aminomethyl-3-methylsulfonyl-5,6,7,8-tetrahydro-2-naphthol hydrochloride In analogy to Example 1f). The crude product is purified by boiling with acetone. 15 Melting point: 238 - 242°C c) Preparation of the starting compound The starting material 3-methy I suIfony1-5,6,7,8-tetrahydro-2-naphthoI necessary in Example 30a) is prepared in analogy to the reaction sequence 1a) to 1d) from 2-20 methoxy-5,6,7,8-tetrahydronaphthalene and melts at 132 -135°C . Example 31 2-(1-Aminoethyl)-4-(1,1-dirnethylethyl)-6-methylsulfonyl-phenol hydrochloride 25 a) 2-(1-ChloroacetyLaminoethyl)-4-(1,1-dimethylethyl)-6-methylsulfonylphenol 5.7 g (0.025 mole) of 4-(1,1-dimethyIethyI)-2-methy I su I fony Ipheno I , 2.25 g (0.025 mole) of chloroacet- amide and 1.1 g (0.025 mole) of acetaldehyde are dissolved 2 - 53 - A in 30 ml of concentrated sulfuric acid and stirred at 0°C for 1 hour. The mixture is poured onto ice-water, extracted with ethyl acetate, dried with MgSO^ and evaporated. By column chromatography on silica gel, using the eluting 5 agent petroleum ether/ethyl acetate 4:1, initially 2.3 g of starting material are obtained followed by the desired product. Melting point: 137 - 139°C b) 2-(1-Aminomethyl)-4-(1,1-dimethylethyl)-6-methyl-10 su I fonyIphenoI hydrochloride In analogy to Example 1f). The crude product is recrystallized from isopropanol. Melting point: 205 - 206°C Example 32 15 2-Aminomethyl-4-(1,1-dimethylpropyl)-6-butylsulfonyl-phenol hydrochloride The preparation takes place in analogy to reaction sequence 1a) to 1f) but butyl iodide, instead of methyl iodide, is employed in step 3 (analogous to 1c) and 4-(1-20 methylpropyDphenol is employed, instead of 4 - (1 ,1 - dimethyLethyDphenol, in step 1 (analogous to 1a). All intermediate products were obtained as oils. The final product melts at 148 - 151°C. Example 33 25 Methyl 3-dimethylaminomethyl-5-(1,1-dimethylethyl)-2-hydroxyphenyl sulfoxide 4.24 g (0.02 mote) of methyl 5-(1,1-dimethylethyl)-2-hydroxyphenyt sulfoxide are dissolved in 30 ml of ethanol, and 2.2 g of dimethylamine solution (40% in Hjq) 1 ^ r~' - 54 - and 2 ml (0.02 mole) of formaldehyde solution (35% in H2O) are added. The mixture is boiled under reflux for 2 hours, evaporated and the residue is crystallized with petroleum ether. 5 Melting point: 105 - 106°C Example 34 Methyl 3-(1-pyrrplidinyl)methyl-5-(1>1-dimethylethyl)-2-. hydroxypheny1 sulfoxide In analogy to Example 33 using pyrrolidine instead 10 of dimethylamine. Melting point: 83 - 84°C Examp le 35 Methyl 3-(4-morpholinyl)methyl-5-(1,1-dimethylethyl)-2-hydroxyphenyL sulfoxide 15 In analogy to Example 33 using morpholine instead of dimethylamine. Melting point: 110 - 111°C Example 36 Methyl 3-(3-thiazolidinyl)methyl-5-(1,1-dimethylethyl)-2-20 hydroxypheny1 sulfoxide In analogy to Example 33 using thiazolidine instead of dimethylamine. Melting point: 164 - 165°C Example 37 25 2-Benzylaminomethyl-4-(1,1-dimethylethyl)-6-methylsulfonyl-phenol hydrochloride a) C2-Hydroxy-3-methylsulfonyl-5-(1,1-dimethylethyl)-benzyUdimethylmethoxycarbonylammonium chloride 29.1 g (102 mmoles) of 2-dimethyI aminomethy1-4- 2tr>. A ; c ■>' ' ■ ' - 55 - (1,1-dimethylethyl)-6-methylsulfonylphenol are dissolved in 250 ml of acetone and, cooling in ice, 13.3 ml (108 mmoles) of methyl ch loroformate are added. The mixture is allowed to stand at room temperature for 24 hours and 5 the precipitate formed is filtered off with suction. Melting point: 152 - 153°C b) 2-Benzylaminomethyl-4-(1,1-dimethylethyl)-6-methyl-sulfonylphenol hydrochloride 9.85 g (25 mmoles) of the ammonium salt obtained 10 under 36a) are dissolved in 50 ml of methanol, 5.35 g (50 mmoles) of benzylamine are added and the mixture is boiled under reflux for 2 hours. The solvent is removed, the residue is triturated with ether and the crystals are filtered off with suction and stirred with 2N hydrochloric 15 acid. The oil, which separates out, crystallizes. White crystals of melting point: 213 - 215°C Example 38 2-(2-Phenylethylaminomethyl)-4-(1,1-dimethylethyl)-6-methylsulfonyIphenoI hydrochloride 20 In analogy to Example 37b) but with 2-phenylethyl- amine instead of benzylamine. The crude product is recrystallized from isopropanol. Melting point: 195 - 197°C Example 39 25 2-Homoveratrylaminomethyl-4-(1,1-dimethylethyl)-6-methyl-sulfonylphenol hydrochloride In analogy to Example 37b) but with homoveratry l-amine instead of benzylamine. Melting point: 216 - 218oC - 56 - Example 40 2-Butylaminomethyl-4-(1,1-dimethylethyl)-6-methylsulfonyl-phenol hydrochloride In analogy to Example 37b) but with n-butylamine 5 instead of benzylamine. Melting point: 140 - 141°C Example 41 2-Ethylaminomethyl-4-(1,1-dimethyLethyl)-6-methylsulfonyl-phenol hydrochloride 10 In analogy to Example 37b) but with ethylamine instead of benzylamine. Melting point: 187 - 189°C Example 42 2-Methylaminomethyl-4-(1,1-dimethylethyL)-6-methylsuLfon-15 ylphenol hydrochloride In analogy to Example 37b) with methylamine instead of benzylamine. The reaction mixture is kept at 150°C in a closed apparatus for 4 hours. Melting point: 164 - 165°C 20 Example 43 2-Cyclohexylaminomethyl-4-(1,1-dimethylethyL)-6-methyL-suIfonyIphenoI hydrochloride In analogy to Example 37b) with eye lohexy lamine instead of benzylamine. 25 Melting point: 210 - 211°C Example 44 2-(1/.1-Dimethylethyl)aminomethyl-4-(1,1-dimethylethyl)-6-methylsulfonylphenol hydroch loride In analogy to Example 42 but with tert.-buty lamine "3 A ^ - 57 - instead of methylamine. Melting point: 229 - 230°C Example 45 2-(4-MethylbenzylaminomethyL)-4-(1,.1-dimethyLethyl)-6-5 tnethylsulfonylphenol hydrochloride In analogy to Example 37b) but with 4-methyl-benzylamine instead of benzylamine. Melting point: 185 - 186°C Example 46 10 2-(4-Methoxybenzylaroinomethyl)-4-(1/.1-dimethylethyL)-6-methylsulfonylphenol hydroch loride In analogy to Example 37b) but with 4-methoxy-benzylamine instead of benzylamine. Meltingpoint: 160-161°C x 15 Example 47 2-(2-ChlorobenzylaminomethyL)-4-(1r1-dimethylethyL)-6-methylsulfonylphenol hydrochloride In analogy to Example 37b) but with 2-chloro-benzylamine instead of benzylamine. 20 Melting point: 187 - 188°C Example 48 2-(1-Phenylethylaminomethyl)-4-(1/1-dimethylethyl)-6-methylsulfonylphenol hydrochloride In analogy to Example 37b) but with 1-pheny I ethy l-25 amine instead of benzylamine. Melting point: 217 -21 9°C Example 49 2-r2-(4-Chlorophenyl)ethylaminomethylU-4-(1,1-dimethyl- ethyl)-6-methylsulfony Ipheno I hydroch Loride « "7 A' 2 0 - - 58 - In analogy to Example 37b) but with 2-(4-chloro-pheny I)ethyI amine instead of benzylamine. Melting point: 172 - 173°C Example 50 5 2-C2-(4-Methylphenyl)ethylaminomethylI]-4-(1,1-dimethyt-ethyl)-6-methylsulfonylphenol hydrochloride In analogy to Example 37b) but with 2-(4-methyl-phenyl)ethylamine instead of benzylamine. Melting point: 157 - 158°C 10 Example 51 2-Furfurylaminomethyl-4-(1,1-dimethylethyl)-6-methyl-su IfonyIphenoI hydrochloride In analogy to Example 37b) but with 2-furfuryl-amine instead of benzylamine. 15 Melting point: 161 - 162°C Example 52 4-Aminomethyl-1,1-dimethyl-5-hydroxy-6-methylsulfonylindan hydrochloride a) 1,1-Dimethyl-5-methoxyindan 20 100 g of 1,1-dimethy l-5-hydroxyindan are alkylated by methods known from the literature (see "Reaktion und Synthesen" CReaction and Syntheses}, L.F. Tieze, Th. Eicher, Thieme V e r I a g , Stuttgart 1981, page 56). Boiling point: 80 - 85°C / 2 mm Hg 25 b) 6-Chlorosulfonyl-1,1-dimethyl-5-methoxyindan In analogy to Example 1a) but with 1,1-dimethy l- 5-methoxyindan as starting material. The product is recrystallized from diisopropyl ether. Crystals of melting point: 142 - 143oC v _ <- £ " > - 59 - c) 1,1-Dimethyl-5-methoxy-6-methylsulfonylindan ,In analogy to Example 1b) and 1c) but with 6-chlorosuIfony1-1,1-dimethy l-5-methoxyindan as starting material. The product is recrystallized from diisopropyl 5 ether. Crystals of melting point: 174 - 175°C d) 1,1-Dimethyl-5-hydroxy-6-methyLsulfonylindan 10 ml (0.1 mole) of boron tribromide are added dropwise at 0°C to a solution of 12.7 g (0.05 mole) of 1,1-dimethyl-5-methoxy-6-methylsulfonylindan in 120 ml of 10 methylene chloride. After stirring at RT for 4 hours, the excess boron tribromide is destroyed with methanol in the cold, the solution is evaporated in vacuo and introduced into ice-water. The precipitate is dried and recrystallized from diisopropyl ether. 1 15 Crystals of melting point: 111-112°C e) 4-Chloroacetamidomethyl-1,1-dimethyl-5-hydroxy-6-methylsulfonylindan 7.4 g (0.06 mole) of chloroacietamidotnethylol are introduced at RT into a solution of 9.6 g 20 (0.04 mole) of 1,1-dimethy l-5-hydroxy-6-methyIsuIfonyl-indan in a mixture of 60 ml of glacial acetic acid and 30 ml of concentrated H2SO4, stirred for 1 hour and introduced into ice-water. The precipitate is dried and recrystallized from ethyl acetate. Crystals of melting 25 point: 190 - 191°C f) 4-Aminomethyl-1,1-dimethyl-5-hydroxy-6-methylsulfonyl-indan hydrochloride 3.1 g (0.01 mole) of 4-ch loroacetamidomethy1-1,1 - dimethyl-5-hydroxy-6~methylsulfonylindan are hydrolyzed </div>

Claims

<div class="application article clearfix printTableText" id="claims"> 2 ^ - 60 - in 50 ml of a mixture of ethanol/concentrated HCl (4:1) at reflux temperature for 20 hours. The mixture is then evaporated and the res i due is recrystallized from ethanol. Crystals of melting point: 246 - 248°C. WHATJ/WE CLAIM IS: ,f*\ ^ /] £L ■- ; - 61 - 5. ^ 1. 2-AminomethyIpheno Is of the formula I (I) R~ in which R represents hydrogen or alkyl having 1 or 2 C atoms, R represents alkyl having 1 to 8 C atoms, cycloalkyl having 3 to 12 C atoms and up to 8 ring members, alkenyl having 2 to S C atoms or cycloalkenyl having 5 to 12 C atoms and up to 8 ring members, it being possible for each of the aforementioned radicals to be substituted with 1 to 5 identical or different halogen atoms, p / R and R are identical or different and denote hydrogen, halogen, alkyl having 1 or 2 C atoms or alkoxy having 1 or 2 C atoms, R3 denotes halogen, alkyl having 1 to 12 C atoms or cycloalkyl having 3 to 12 C atoms and up to 8 ring members, R-* and are identical or different and represent hydrogen, alkyl having 1 to 6 C atoms, cycloalkyl having 3 to 10 C atoms and up to 8 ring members or the radical -CCH23Q-Ar, wherein o = 1 or 2, the -CC^Uq- chain can be substituted by 1 or 2 (C-j or C2)-alkyl groups and Ar is a 5- or 6-membered aromatic or heteroaromatic system, which is optionally substituted by 1 to 3 identical or different radicals < C -j or C2)-alkyl, (C-j or C2>-alkoxy or halogen, and n is 1 or 2, it being possible for the 203467 - 62 - radicals R^ and and/or two of the radicals R^, R3 and R^ also to form a -CCHgDn,- chain having m = 3 to 6, which can optionally be substituted by 1 or 2 methyl groups and, in the case of R^ and R^, can also be interrupted by 1 or 2 oxygen atoms, sulfur atoms and/or imino groups, and their physiologically tolerated salts. 2. A compound of the formula I as claimed in claim 1, in wh i ch R denotes hydrogen, R^ represents alkyl having 1 to 4 C atoms, cycloalkyl having 3 to 7 C atoms and up to 6 ring members, alkenyl having 2 to 6 C atoms or ha logenoaIky I having 1 to 4 C and l^to 3 identical or different halogen atoms, - R and R have the meanings defined in claim 1, / R denotes halogen, alkyl having i to 8 C atoms or cycloalkyl having 3 to 10 C atoms and up to 7 ring members, R^ and R^ have the meanings defined in claim 1 with the exception that R5 and/or R6 represents alkyl having 1 or 2 C atoms, and n is 1 or 2, it being possible for the radicals R^ and R^ and/or two ^ ^ A of the radicals R , R° and R to form a polymethyle.ne chain as defined in claim 1. 3. 2-Aminomethy 1-4-<1,1-dimethylethyl)-6-methyl-suIfonyIpheno I and its physiologically tolerated acid addition salts. 4. 2-Aminomethyl-4-(1,1-dimethylethyl)-6-chloro-methylsulfonylphenol and its physiologically tolerated;' acid addition salts. 5' '' 5. 2-Aminomethyl-4-(1,1-dimethylpropyl)-6-methyl- 203467 - 63 - sulfonyIphenol and its physiologically tolerated acid addition salts. 6. Methyl 3-aminomethyl-5-(1,1-dimethylethyl)-2- hydroxyphenyl sulfoxide and its physiologically tolerated acid addition salts. 7. 2-Aminomethyl-4-isopropyl-6-methylsulfonylphenol and its physiologically tolerated acid addition salts. 8. 2-Aminomethyl-4-(1,1-dimethylpropyl)-6-ethylsul-fonylphenol and its physiologically tolerated acid addition salts. 9. 2-Aminomethyl~4-(1,1-dimethylpropyl)-6-iodomethyl-su Ifony Ipheno I and its physiologically tolerated acid addition salts. 10. A process for the preparation of the 2-aminomethylpheno Is as claimed in claim 1, which comprises a) reacting a compound of the formula II oh .1 j£. s(o> -R n (id R r3 wherein n, R^, R^, R3 and R^ have the abovementioned meanings, with an N-hydroxymethylearboxamide of the formula III r5o - ho- hc-n-c-r7 t _ fe <ui|'"7^g;sbs3 in which R has the abovementioned meaning, R^ denotes hydrogen or alkyl having 1 to 4 C atoms and R^ represents hydrogen, optionally halogen-substituted alkyl having 1 to 203467 - 64 - 4 C atoms or aryl having 6 to 10 C atoms, or in which R! 7 and the radical COR together represent the o-phthaloyl radical, to give a compound of the formula IV S(O) -R n (IV) and removing the acyl radical R7-C0 by hydrolysis thus obtaining compounds of formula I in which R5 is hydrogen or C^C^alkyl, and R is hydrogen, b) reacting a compound of the formula II, in which the 1 4 radicals R to R and n have the abovementioned meanings, in the presence of formaldehyde, with an amine of the formula V E6 H - R° (V) 5 6 in which R and R have the meanings mentioned in claim 1 with the exception of hydrogen thus obtaining compounds of 5 6 ... formula I in which R and R have the meanings given in claim 1 with the exception of hydrogen, c) reacting a compound of the formula VI S(O) -R1 n in which n and R to R have the abovementioned meanings. and Z represents a leaving group, with an amine of the formula H - N = Y, wherein Y represents an amine-protective 5 6 group or the radicals R and R defined in claim 1, it being possible for R6 also to be an amine-protective group, fw' 203467 - 65 - to give a compound of the formula VII (VII) and/ if appropriate, removing the amine-protective group by hydrolysis or hydrogenolysis, or d) reacting.a compound of the formula XIV OH ^ s tn\ (XIV) s(0) r.R*' R in which n and R to R^ have the abovementioned meanings, with an amine of the formula R^-Nl^, with R^ having the abovementioned meaning, to give a Schiff's base of the formula XV (XV) in which n and R to R^ have the abovementioned meanings, .and reducing the latter to give a compound of the formula I, /fl("Wherein R ^ is hydrogen /yP ~7 and opt i ona I ly converting Jt+rTT a compound of the formula 4— I obtained according to one of the variants a) - d) into •203467 / - 66 - any one of /its physiologically tolerated salts. 11. A pharmaceutical formulation based on a compound as claimed in claim 1. 12. A process for the preparation of a pharmaceutical formulation as claimed in claim 11, which comprises converting a compound as claimed in claim 1, optionally with pharmacologically tolerated vehicles and/or stabilizers, Into a suitable form for administration. . 1*3- A compound of the formula II and in which n /R to R have the meanings mentioned in claim 1. It}. A compound according to claim 1 substantially as hereinbefore described with reference to the Examples and Table. HOECHST AKTIENGESELLSCHAFT By Their Attorneys </div>