MX2008002330A

MX2008002330A - Preparation of thioalkylamines with high yields.

Info

Publication number: MX2008002330A
Application number: MX2008002330A
Authority: MX
Inventors: Sergiy Pazenok
Original assignee: Bayer Cropscience Ag
Priority date: 2005-08-24
Filing date: 2006-08-16
Publication date: 2008-03-18
Also published as: TW200800868A; EP1919860A1; CN101248040A; JP2009505997A; IL189297A0; KR20080036645A; WO2007022900A1; BRPI0615131A2

Abstract

The present invention relates to a novel process for the preparation of compounds of the formula (I) by mixing in a first step amino alcohols of the formula (II) with sulfuric acid to yield the salt, by then reacting them in a second step in a drying device to give sulfuric acid esters of the general formula (III) and by reacting these sulfuric acid esters in a third step with mercaptans or salts thereof of the general formula (IV): RSM in each formula, where applicable, R1, R2, R3, R4, R5, R6, R, n and M have the meanings given in the description, in the presence of a diluent and in the presence of a base.

Description

PREPARATION OF HIGH-PERFORMANCE THYOALKYLAMINES DESCRIPTION OF THE INVENTION The present invention relates to a new process for preparing known thioalkylamine derivatives. Due to their chemical structure, the thioalkylamines derivatives can be divided into two groups, thiols and sulfides. To prepare both classes, the procedures discussed below have been described. A first method for preparing thiols is based on the hydrolytic cleavage of thiazoline or thiazolidinone derivatives (see, for example, J. Med. Chem. 1965, 8, 762, JP 59-231064, Bull. Soc. Chim. Fr. 1967, 3637).

Since the thiazoline or thiazolidinone derivatives must first be prepared by several reaction steps, the overall yield of this process is very low. The thiols can also be obtained by a process comprising reacting sulfates of aminoalcohols with ammonium sulfide (see, for example, Nihon Kagaku Kaishi 1979, 149). This process requires long reaction times in a tightly closed reaction vessel, which produces high costs because the necessary production plants have low productivity. The reaction of oxazoline or oxazolidinone derivatives with thiols is a process for preparing sulphides (see, for example, J. Org. Chem. 1992. 57, 6257; J. Med. Chem. 1984, 27, REF .: 190071 1354). A hydrolytic process is necessary to obtain the reaction products in the form of amides according to this procedure. However, no reaction is observed if the oxazolidine ring of the starting compounds is substituted, for example with alkyl. Furthermore, using this process only aromatic sulfides can be prepared due to the acidity of the mercaptans. The hydrolytic cleavage of the amides, which can be obtained by reacting aminoalcohols with mercaptans in the presence of carboxylic acids, also produces sulphides (see, for example, DE-OS 1493534). This procedure must be carried out at high temperature and under pressure using long reaction times and is therefore restricted to the synthesis of sulfides. In addition, a hydrolytic step is necessary to obtain the reaction products from amides. The reaction of aziridines with sulfur compounds such as mercaptans represents a process for preparing sulfides and thiols (see, for example, Tetrahedron 1992, 48, 2359, Tetrahedron Lett, 1983, 24, 2131). High safety requirements for industrial scale production are very necessary using this procedure, because very toxic and possibly unstable aziridines have to be prepared and isolated. A procedure for the conversion of thioalkylalcohols in thioalkylamines is represented by the Ritter reaction with the subsequent hydrolytic cleavage (see, for example, DE-OS 2045905). This procedure uses excess hydrocyanic acid, which must be handled with extreme caution. In the case that nitriles that can be easily handled are used, the hydrolytic process causes problems. Another process for preparing thioalkylamine derivatives uses as starting material amino alcohols which are reacted with sulfuric acid to give the corresponding esters in a first step (see, WO 01/23350). After evaporating to dryness, these esters are further transformed by reaction with mercaptans. The evaporation necessary after the first reaction stage causes problems when this process is used in a large-scale production. Another method for preparing thioalkylamine derivatives from aminoalcohols was described in WO 03/099777 using fuming sulfuric acid as reagent. However, using the described procedure, the reaction mixture contains an excess of sulfuric acid which must be neutralized before carrying out the second step, thus increasing the formation of poorly soluble salts (Na2SO4). The performance of the second stage is also adversely affected by the additional dilution.

It has now been found that the compounds of formula (I) wherein R 1 and R 2 each independently represent hydrogen, C 1 -C 4 cycloalkyl, C 3 -C 4 cycloalkyl, (C 3 -C 8) cycloalkyl (C 1 -C 4) alkyl, C 1 -C 4 hydroxyalkyl; unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio C4, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, carboxyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxy-C 1 -C 4 alkyl, C 1 -C 4 alkylcarbonyl, haloalkyl C? -C, haloalkoxy C? -C, halogen-alkylthio C? -C4, halogen-alkylsulfinyl C? -C4, halogen-alkylsulfonyl C? -C4, halogen-alkyl (C? -C) -carbonyl, phenylcarbonyl, phenoxycarbonyl , amino, alkylamino C? ~ C and di- (C 1 -C 4 alkyl) -amino (where the alkyl group may be the same or different); phenyl, which is substituted on two adjacent carbon atoms with C3-C alkylene or C2-C2 alkylenedioxy; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 4 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C 4 halogen alkylthio, C 1 -C 4 halogeno alkylsulfinyl, and halogen-alkylsulfonyl C? -C4; R3 and R4 independently of each other represent hydrogen or C1-C4 alkyl, R5 and R6 independently of each other represent hydrogen, C1-C4 alkyl, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of group consisting of halogen, cyano, nitro, C? -C4 alkyl, C3-Cs cycloalkyl, C? -C4 alkoxy, C? -C4 alkylthio, C? -C4 alkylsulfinyl, C? -C4 alkylsulfonyl, C? -C4 haloalkyl, haloalkoxy C? ~ C4, halogen-C, -C4-alkylthio, halogen-C, -C-alkylsulfinyl and C, -C4-haloalkylsulfonyl; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 4 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C alkylsulfonyl, C 1 -C 4 haloalkyl, C 4 -C 4 haloalkoxy, C 4 -C 4 halogen alkylthio, C 1 -C 4 haloalkylsulfinyl C4 and halogen-alkylsulfonyl C? -C4; R represents unsubstituted or mono- or polysubstituted C? -C? 2 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, hydroxy, C-C4 alkoxy, haloalkoxy C? -C4, alkylthio C? -C4, alkylsulfinyl C? -C4 and alkylsulfonyl C? -C4; unsubstituted or mono- or polysubstituted C3-C8 cycloalkyl or (C3-C8) cycloalkyl-alkyl (C? -C4), in which the substituents are the same or different and are selected from the group consisting of halogen, C? -C4 alkyl and C4-C4 alkoxy; unsubstituted phenyl or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, C? -C6 alkyl, C3-Cs cycloalkyl, C? -C alkoxy, C? -C4 haloalkyl, haloalkoxy C? -C4; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 4 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen and C 1 -C 4 alkyl; naphthyl; unsubstituted or mono- or polysubstituted heteroaryl, wherein the substituents are the same or different and are selected from the group consisting of halogen, C? -C alkyl, C? -C4 alkoxy, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of halogen and C? -C alkyl; n represents 1, 2, 3, 4, 5, 6, 7 or 8, where the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together represent further C2-C5 alkylene, R1 together with R3 or R5 further represents C3-C5 alkylene, R3 and R4 together further represent C4-C6 alkylene, R3 and R5 together further represent C2-C4 alkylene, R5 and R6 together further represent C4-C6 alkylene, are obtained by mixing in a first step, amino alcohols of formula (II) wherein R1, R2, R3, R4, R5, R6 and n have the meanings given above, with sulfuric acid to give the corresponding salts in solution, then converting them, in a second step, into esters of sulfuric acid of the general formula (III ) wherein R1, R2, R3, R4, R5, R6 and n have the meanings given above, and reacting these sulfuric acid esters in a third step, with mercaptans or salts thereof of general formula (IV) RSM (IV ) in which R has the above meanings, and M represents hydrogen, ammonium or an alkali metal atom, in the presence of a base and preferably in the presence of a diluent. In contrast to the current state of the art, the second reaction stage according to the invention is not carried out in a reaction vessel but in a drying device. The very rapid removal of water from the reaction mixture drives the reaction. Using this procedure, the sulfuric acid does not have to be used in excess against the alcohol and therefore the pure product is obtained without residual acid. Furthermore, organic solvents are not used in the process according to the invention, making the process also advantageous from an ecological point of view compared to the process described in WO 01/23350 in which toluene is used to remove the water of the reaction mixture. Because aminoalcohol and sulfuric acid are used in equimolar amounts in the first stage, only a minor amount of base (approximately one mole per mole of alcohol) must be added in the second stage to keep the pH value high enough for avoid the decomposition of the mercaptan salt. This also makes it possible to carry out the third stage of the reaction in a very concentrated reaction mixture, which is also beneficial for the yield.

Surprisingly, using the process according to the invention, the thioalkylamines of formula (I) can be obtained in a simple way with a very good space-time yield. Therefore, the reaction according to the invention has the advantage of a higher reaction rate and higher yield. This leads to the technical advantage of a high space-time performance. Using 2-amino-2-methyl-1-propanol and the sodium salt of methylmercaptan as starting materials, the course of the reaction of the process according to the invention can be summarized by reaction scheme 1.

The formula (II) provides a general definition of the aminoalcohols necessary as starting materials for carrying out the first stage of the process according to the invention. As starting materials, the amino alcohols of the formula (II) are preferred, wherein R 1 and R 2 each independently represent hydrogen, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, (C 3 -C 6) cycloalkyl-alkyl (CC ), hydroxyalkyl C? -C4; unsubstituted phenyl or mono to pentasubstituted phenyl, wherein substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, alkylsulfinyl C 1. -C 4, C 1 -C 4 alkylsulfonyl, carboxyl, (C 1 -C 4) alkoxycarbonyl, C 1 -C 4 alkoxy-C 1 -C 4 alkyl, C 1 -C 4 alkylcarbonyl, C 1 haloalkyl -C4, haloalkoxy C? -C4, halogen-alkylthio C? -C4, halogen-alkylsulfinyl C? -C4, halogen-alkylsulfonyl C? -C4, halogen-alkyl (C? -C4) -carbonyl, each with 1 to 9 identical or different atoms of fluorine, chlorine and / or bromine, phenylcarbonyl, phenoxycarbonyl, amino, C 1 -C 4 alkylamino and di- (C 1 -C 4 alkyl) amino (where the alkyl group may be the same or different); phenyl, which is substituted on two adjacent carbon atoms with C3-C4 alkylene or C2-C2 alkylenedioxy; unsubstituted or mono-to-pentasubstituted phenyl-C 1 -C 2 -alkyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C alkyl C3-C6 cycloalkyl, C? -C4 alkoxy, C? -C4 alkylthio, C? -C4 alkylsulfinyl, C? -C4 alkylsulfonyl, C? -C haloalkyl, C? -C4 haloalkoxy, C? -C4 halogen alkylthio, halogen-alkylsulfinyl C? -C4 and halogen-alkylsulfonyl C? -C4, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; R3 and R4 independently of each other represent hydrogen or C? -C4 alkyl, R5 and R6 independently of one another represent hydrogen, C?-C4 alkyl, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 4 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, halogen -alkylthio C? -C4, halogen-alkylsulfinyl C? -C and halogen-alkylsulfonyl C-C4, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; unsubstituted or mono to pentasubstituted phenylalkyl (C? -C2), in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C? -C4alkyl, cycloalkyl C3-Cß, C?-C 4 alkoxy, C?-C 4 alkylthio, C?-C 4 alkylsulfinyl, C?-C 4 alkylsulfonyl, C?-C haloalkyl, C?-C4 haloalkoxy, halogen-Cilt-C 4 halogenyl, halogen C 1 -C 4 alkylsulfinyl and C 1 -C 4 alkylsulfonyl, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; n represents 1, 2, 3, 4, 5 or 6, where the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together also represent C2- alkylene Cs, R1 together with R3 or R5 further represents C3-Cs alkylene, R3 and R4 together also represent C4-C6 alkylene, R3 and R5 together also represent C-C4 alkylene, R5 and R6 together also represent C4-C6 alkylene. Particularly preferred starting materials are aminoalcohols of formula (II), in which R1 and R2 in each case independently represent hydrogen , methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, hydroxymethyl , hydroxyethyl; unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n-, i-propyl, n- , i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i- propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, difluorochloromethyl, fluorodichloromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodichloromethoxy, trifluoromethylthio, trichloromethylthio, difluoromethylthio, dichloromethylthio, difluorochloromethylthio, flúorodielorometiltio, trifluoromethylsulfinyl, triclorometilsulfinilo, difluorometilsulfinilo, diclorometilsulfinilo, difluoroclorómetilsulfinilo, fluorodiclorometilsulfinilo, trifluoromethylsulfonyl, trichloromethylsulfonyl, difluoromethylsulfonyl, diclorometilsulfonilo, difluoroclorometilsulfonilo, flúorodiclorometilsulfonilo, trifluoromethylcarbonyl, carboxyl, methoxycarbonyl, ethoxycarbonyl, methoxymethyl, ethoxyethyl, methoxyethyl, ethoxymethyl, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, phenoxycarbonyl, amino, methylamino, ethylamino, propylamino, dimethylamino, diethylamino; phenyl, which is substituted on two adjacent carbon atoms with - (CH2) 3-, - (CH2) 4-, -OCH20-, -0 (CH2) 20-; benzyl or phenylethyl in each case unsubstituted or mono to trisubstituted, in which in each case the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n -, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy , methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propyl-sulfinyl, n-, i-, s-, t-butylsulfinyl , methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, difluorochloromethyl, fluorodichloromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodiclorometoxi, trifluoromethylthio, trichloromethylthio, difluoromethylthio, dichloromethylthio, difluoroelorometiltio, fluorodichloromethylthio, trifluoromethylsulfinyl, triclorometilsulfinilo, difluorometilsulfinílo, diclorometilsulfInilo, difluoroclorometilsulfinilo, flúorodiclorometilsulfinilo, trifluoromethylsulfonyl, trichloromethylsulfonyl, difluoromethylsulfonyl, dichloromethylsulphonyl, difluorocloromethylsulfonyl, fluorodichloromethylsulfonyl; RJ and R4 independently from each other represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, R5 and R6 independently represent hydrogen, methyl, ethyl, n-, - i-propyl, n-, i-, s-, t-butyl, unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t- butylthio, methylsulphinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, difluorochloromethyl, fluorodichloromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodiclorometoxi, trifluoromethylthio, trichloromethylthio, difluoromethylthio, dichloromethylthio, difluorochloromethylthio, fluorodichloromethylthio, trifluoromethylsulfinyl, triclorometilsulfinilo, difluorometilsulfinilo, diclorometilsulfinilo, difluoroclorometilsulfinilo, flúorodiclorometilsulfinilo, trifluoromethylsulfonyl, trichloromethylsulfonyl, difluoromethyl-sulfonyl, dichloromethylsulfonyl, difluorochloromethylsulfonyl and fluorodichloromethylsulfonyl; benzyl or phenylethyl in each case unsubstituted or mono to trisubstituted, in which in each case the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n -, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy , methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, difluorochloromethyl, fluorodichloromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodichloromethoxy, trifluoromethylthio, trichloromethylthio, difluoromethylthio, dichloromethylthio, difluorochloromethylthio, fluorodichloromethylthio, trifluoromethylsulfinyl, triclorometilsulfinilo, difluorometilsulfinilo, diclorometilsulfinilo, difluoroclorometilsulfinilo, flúorodiclorometilsulfinilo, trifluoromethylsulfonyl, trichloromethylsulfonyl, difluoromethylsulfonyl, diclorometilsulfonilo, difluoroclorometilsulfonilo, flúorodiclorometilsulfonilo, n represents 1, 2, 3, 4, 5 or 6 wherein the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together also represent - (CH2) 2-, - (CH2) 3-, - (CH2) 4 -, - (CH2) s-, R1 together with R3 or R5 also represents - (CH2) 3-, - (CH2) 4- , - (CH2) 5-, R3 and R4 together also represent - (CH2) 4-, - (CH2) 5-, (CH2) 6-, R3 and R5 together also represent - (CH2) 2-, - (CH2 )3-, (CH2) 4-, R5 and R5 together also represent - (CH2) 4-, ~ (CH2) 5-, (CH2) 6-. Particularly preferred starting materials are aminoalcohols of formula (II), in which R1 and R2 in each case independently represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, hydroxymethyl, hydroxyethyl; unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n-, i-propyl, n- , i-, s-, t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i- propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylsulfinyl, trifluoromethylsulfonyl, trifluoromethylcarbonyl, carboxyl, methoxycarbonyl, methoxymethyl, ethoxyethyl, methoxyethyl, ethoxy ethyl, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, phenoxycarbonyl, amino, methylamino, ethylamino, propylamino, dimethylamino, diethylamino; phenyl, which is substituted in two adjacent carbon atoms with - (CH2) 3-, - (CH2) -, OCH20-, -0 (CH2) 20-; unsubstituted or mono to trisubstituted benzyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, methyl, ethyl, n-, i-propyl, n-, i-, s- , t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i-propylthio, n-, i -, s-, t-butylthio, methylsulphinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylsulfinyl, trifluoromethylsulfonyl; R3 and R4 independently of each other represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, R5 and R6 independently of each other represent hydrogen, methyl, ethyl, n-, i -propyl, n-, i-, s-, t-butyl, unsubstituted or mono to trisubstituted phenyl, in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano , nitro, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n- , i-propylsulfonyl, n-, i-, s-t-butylsulfonyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylsulfinyl, trifluoromethylsulfonyl; unsubstituted or mono to trisubstituted benzyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, methyl, ethyl, n-, i-propyl, n- , i-, s-, t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, methylthio, ethylthio, n-, i- propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulphinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl, trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylsulfinyl, trifluoromethylsulfonyl, n represents 1, 2, 3 or 4, where the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together also represent - (CH2) 2-, - (CH2) 3-, (CH2) 4-, "(CH2) 5-, R1 together with R3 or R5 further represents - (CH2) 3-, - (CH2) 4-, - (CH2) 5-, R3 and R4 together further represent - (CH2) 4-, ~ (CH2) 5-, (CH2) 6-, R3 and R5 together further represent - (CH2) 2-, - (CH2) 3 -, (CH 2 1 4 ~ r R5 and R6 together also represent - (CH2) 4-, - (CH2) 5-, (CH2) 6-. Most particularly preferred as starting materials are aminoalcohols of formula (II), in which R1 and R2 in each case independently represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s- , t-butyl, R3 and R4 independently represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, R5 and R6 independently represent hydrogen, methyl, ethyl , n-, i-propyl, n-, i-, s-, t-butyl, n represents 1 or 2, where the group C (R1) R2 can be the same or different, when n is greater than 1. They are marked as starting materials aminoalcohols of formula (II), in which R1 and R2 each independently represent hydrogen or methyl, R3 and R4 represent hydrogen, R5 and R6 independently represent hydrogen and n represents 1.

The aminoalcohols of formula (II) are widely known and / or can be prepared according to known procedures. The formula (IV) provides a general definition of the mercaptans or salts thereof, necessary as starting materials for carrying out the third stage of the process according to the invention. Preferred starting materials are mercaptans or salts thereof of formula (IV), in which R represents unsubstituted or mono- or polysubstituted C? -C? 2 alkyl, in which the substituents are the same or different and are selected from the group consisting of group consisting of fluorine, chlorine, bromine, iodine, hydroxy, C?-C4 alkoxy, C hal-C 4 halogenoalkoxy, having from 1 to 9 identical or different atoms of fluorine, chlorine and / or bromine, Cilt-C 4 alkylthio, C 1 -C 4 alkylsulfinyl and C 1 -C 4 alkylsulfonyl; unsubstituted or mono- or polysubstituted C3-C6 cycloalkyl or (C3-C6) cycloalkyl-alkyl (C? -C2), in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C? -C alkyl and C? -C4 alkoxy; unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C -C4 alkyl, C3-C6 cycloalkyl, C?-C4 alkoxy, haloalkyl C? -C4, haloalkoxy C? -C4, each with 1 to 9 atoms of the same or different fluorine, chlorine and / or bromine; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 2 alkyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, and C 1 -C 4 alkyl; naphthyl; unsubstituted or mono- or polysubstituted heteroaryl (preferably furyl, thienyl, pyrrolyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1, 2, 4 -thiadiazolyl, 1,3,4-thiadiazolyl, 1, 2, 3-thiadiazolyl, 1, 2, 5-thiadiazolyl, 1,2,3-triazolyl, 1, 2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl , pyrazinyl, triazinyl), in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, unsubstituted phenyl or mono to pentasubstituted phenyl , wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, and C 1 -C 4 alkyl; M represents hydrogen, ammonium or an alkali metal atom (preferably sodium, potassium, lithium and cesium). Particularly preferred as starting material are mercaptans or salts thereof of the formula (IV), in which R represents in each case methyl, ethyl, n-, i-propyl, n-, i-, s-, t -butyl unsubstituted or mono or polysubstituted, in each case the pentyls, hexyl, octyl, decyl and dodecyl isomers, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t -butoxy, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodichloromethoxy, methylthio, ethylthio, n-, i-propylthio, n-, i-, s-, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, n-, i-, s-, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, n-, i-, s-, t-butylsulfonyl; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl in each case unsubstituted or mono- or polysubstituted, in which the substituents are the same or different and are selected from the group consisting of fluorine , chlorine, bromine, iodine, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s- , t-butoxy; unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, trifluoromethyl, trichloromethyl, difluoromethyl, dichloromethyl, difluorochlor ethyl, fluorodichloromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, dichloromethoxy, difluorochloromethoxy, fluorodichloromethoxy; benzyl or phenylethyl in each case unsubstituted or mono to trisubstituted, in which in each case the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, and methyl, ethyl, n-, -propyl, n-, i-, s-, t-butyl; naphthyl; furyl, thienyl, pyrrolyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3, 4- thiadiazolyl, 1,2,3-thiadiazolyl, 1, 2, 5-thiadiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl in each case unsubstituted or mono- or polysubstituted, in which in each case the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, n-, i-propyl, n-, i-, s -, t-butyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, unsubstituted or mono to trisubstituted phenyl, in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine and methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, represents hydrogen, ammonium, sodium, potassium, lithium and cesium.

Particularly preferred as starting materials are mercaptans or salts thereof of formula (IV), in which R represents methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl in each unsubstituted or mono- or polysubstituted cases, in each case the pentyls, hexyl, octyl, decyl and dodecyl isomers, in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, methoxy , ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, trifluoromethoxy, trichloromethoxy, methylthio, ethylthio, n-, i-propylthio, t-butylthio, methylsulfinyl, ethylsulphinyl, n-, -propylsulfinyl, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, t-butylsulfonyl; cyclopropyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl in each case unsubstituted or mono- or polysubstituted, in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, n -, i-propyl, t-butyl, methoxy, ethoxy, n-, i-propoxy, t-butoxy; unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, cyclopropyl, cyclopentyl, cyclohexyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, trifluoromethyl, difluoromethyl, trifluoromethoxy; unsubstituted or mono to trisubstituted benzyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine and methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl; naphthyl; furyl, thienyl, pyrrolyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1, 2,4-thiadiazolyl, 1, 3, 4- thiadiazolyl, 1,2,3-thiadiazolyl, 1, 2, 5-thiadiazolyl, 1, 2, 3-triazolyl, 1,2,4-triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl in each case unsubstituted or mono- or polysubstituted, in which in each case the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, unsubstituted or mono to trisubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of group consisting of fluorine, chlorine, bromine and methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, M represents hydrogen, ammonium, sodium and potassium. Most particularly preferred as starting material are mercaptans or salts thereof of formula (IV), wherein R represents methyl, ethyl, n-, i-propyl or n-, i-, s-, t-butyl in each case unsubstituted or mono- or polysubstituted, in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, trifluoromethoxy, trichloromethoxy, methylthio, ethylthio, n-, i-propylthio, t-butylthio, methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl , n-, i-propylsulfonyl, t-butylsulfonyl. M represents sodium or potassium. The mercaptans or salts thereof of the formula (IV), in which R represents methyl and M represents sodium, are noted as starting material. The mercaptans or salts thereof of formula (IV) are widely known and / or can be prepared according to known procedures. The saturated or unsaturated hydrocarbon radicals, for example alkyl and alkenyl, can in each case be straight or branched chain whenever possible, including combinations with heteroatoms, for example, alkoxy. The optionally substituted radicals can be mono- or polysubstituted, and in the case of polysubstitution, the substituents can be the same or different. Radicals substituted with halogens, for example haloalkyl, are mono- or polysubstituted until perhalogenation. In the case of multiple halogenation, the halogen atoms may be the same or different. Halogen represents fluorine, chlorine, bromine or iodine. However, it is also possible to combine the definitions or illustrations of general or preferred radicals mentioned above with each other as appropriate, ie between the respective ranges and the preferred ranges. The definitions apply both to the final products and, correspondingly, to the precursors and intermediate products. The first stage of the reaction, the salt formation, according to the invention can be carried out by addition of the aminoalcohols of formula (II) in dilute sulfuric acid (50-70% (w / w)), for example .

Scheme 2 The addition of the aminoalcohol of formula (II) in sulfuric acid is preferably done in water by cooling to keep the temperature below 60 ° C, although a temperature range between 40 ° C and 50 ° C is particularly preferred. In general no carbonization will be observed even though more substituted amino alcohols are used. The amino alcohols are applied in liquid form. Solutions of up to 40-80% in water can also be used. The reaction temperatures used in the first step of the reaction according to the invention can vary over a wide range. In general, the reaction is carried out between 20 ° C and 70 ° C, preferably between 30-60 ° C, particularly preferably between 40 ° C and 50 ° C. The first stage of the reaction is conveniently carried out at atmospheric pressure, although it can also be worked under reduced or elevated pressure. It is particularly preferred to carry out the reaction at atmospheric pressure. The first step of the reaction is conveniently carried out using approximately equimolar amounts of aminoalcohol and sulfuric acid, ie, between 0.8 and 1.2, preferably between 0.9 and 1.1 moles of aminoalcohol per mole of sulfuric acid . The reaction time may be different depending on the scale of the reaction and may vary between 10 min and 4 hours, although normally the reaction is completed immediately after mixing the reagents.

The second stage of the reaction of the procedure (training of the sulfonate, see reaction scheme 3) is carried out in a drying device. In general, any drying device that can handle the chemicals used is suitable, for example, drying ovens, freeze dryers, spray dryers, combination dryers, rotary dryers, contact dryers, convection dryers, radiation dryers, dryers of infrared radiation, microwave radiation dryers, vacuum dryers, ultraviolet radiation dryers, fluid bed dryers, belt dryers or conveyor belt dryers. Preferred drying devices are drying ovens, spray dryers and conveyor dryers. Drying ovens are particularly preferred. The second stage of the reaction is conveniently carried out at atmospheric pressure and at elevated temperature (50-200 ° C, preferably 100-150 ° C), although it is also possible to work under reduced pressure in order to accelerate the removal of water. It is particularly preferred to carry out the reaction under reduced pressure (10-50 mbar) (lKPa-5KPa) at elevated temperature (80-120 ° C) to reduce the reaction time and increase the space-time yield.

The third step of the reaction according to the invention (see reaction scheme 4) can be carried out by addition of the sulfuric acid esters of formula (III) in the form of a solution or solid to the mercaptans or their salts of formula (IV) preferably in water. The pH of the reaction mixture should be maintained in the range of 10-12 while the ester is added. Preferably, the base in solid form is added directly to the mercaptide or its salt in water, followed by the addition of the sulfonate as a solid or concentrated solution. The addition of the sulfonate to the mixture of mercaptide and NaOH allows to increase the yield up to 92-95% (EP 1231698 yield 82%). Said method allows to avoid the formation of unstable, toxic and explosive ethylenimine which is formed immediately after adding the sulfonate to the base at pH 10-12 (see reaction scheme 5).

Scheme 5 In addition, it allows to maximize the concentration of reagents, improving the performance of the time and space of the reaction and decreasing the waste. The addition of the sulfuric acid ester of formula (III) is carried out between 10 min and up to 2 h depending on the scale of the reaction, preferably between 20 min and 1 h, in particular preferably between 30 min and 1 h. The third stage of the procedure is carried out in the presence of a base. Examples that may be mentioned are: alkali metal and alkaline earth metal hydroxides, such as NaOH, KOH, Ca (OH) 2, alkali metal carbonates or hydrogencarbonates, such as Na 2 CO 3, Li 2 CO 3, K 2 CO 3, Cs 2 CO 3 or NaHCO 3 and KHCO 3. Na 2 CO 3, KOH, NaOH and NaHCO 3 are preferred, in particular NaOH. The reaction temperatures used in the third step of the reaction according to the invention can vary over a wide range. In general, the reaction is carried out between 30 ° C and 150 ° C, preferably between 50 ° C and 120 ° C, particularly preferably between 60 ° C and 100 ° C. The third stage of the reaction is conveniently carried out at atmospheric pressure, although it can also be worked under reduced or elevated pressure. It is particularly preferred to carry out the reaction at atmospheric pressure. The third step of the reaction according to the invention can be carried out in the presence of another diluent, where all the usual inert organic solvents are applied. It is preferred to use aliphatic, alicyclic or aromatic optionally halogenated hydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; chlorobenzene, dichlorobenzene, dichloromethane, dichloroethane or trichloroethane; ethers such as diethyl ether, diisopropyl ether, methyl tert-butyl ether, methyl tert-amyl ether, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; nitriles, such as acetonitrile, propionitrile, n- or isobutyronitrile or benzonitrile; amides, such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone; esters such as methyl acetate or ethyl acetate, sulfoxides, such as dimethisulfoxide, or sulfones, such as sulfolane. Inert solvents are preferred which can be easily separated from the product by simple distillation. The third step of the process is carried out in practice, by reacting, for example, 1 mole of a sulfuric acid ester of formula (III) with between 1 and 5 moles, preferably between 1 and 3 moles, particularly preferably between 1 and 1.5 moles of a mercaptan or salt thereof of formula (IV) in the presence of a base, to maintain the pH value in general between pH 11 and 12. The reaction time can be reduced by using transfer catalysts of phase (PTC) such as tetraalkylammonium, tetraalkyl-, tetraarylphosphonium, guanidinium or pyridinium salts. At the same time the use of PTC allows to increase the yield, The preferred catalysts are tetramethylammonium bromide, hydroxide of tetrabutylammonium, tetrabutylammonium hydrogensulfate, tetrabutylammonium bromide, tetraphenylphosphonium bromide and 18-crown-6. The final product can be isolated using standard procedures, for example, crystallization, chromatography, extraction and distillation. The process according to the invention is illustrated by the preparation examples given below. The examples should not be understood as limiting in any way. Preparation examples Example 1 (2S) -1- (Methylthio) propan-2-amine 75 g (1 mol) of (2S) -2-aminopropanol (L-Alaninol) and 1 mol of H2SO4 were mixed together as an 80% aqueous solution (p / p) cooling to keep the temperature below 50 ° C. The formed solution was dried in the vacuum oven at 110 ° C for 2.5 h giving 155 g of a white solid, of (2S) -2-ammonium propylsulfate, which corresponds to a yield of 100%. P.f. 260-263 ° C. 1 H-NMR (d6-DMS0): d 1.2 (d, 3 H), 3.4 (m, H H), 3.6-3.8 (dm ABX system, 2 H), 7.8 (broad s, NH3) ppm.

Sodium mercaptide (1.2 mol) was placed as a 20% solution in water in a flask and 40 g (1 mol) of NaOH (solid) was added with stirring. The mixture was stirred vigorously and 155 g (1 mol) of crushed (2S) -2-ammonium propylsulfate was added in 30 min. The mixture was then stirred for 5-10 h at 90 ° C and cooled to 30 ° C. The upper organic phase was separated giving 159 g of the product (2S) -1- (methylthio) propane-2-amine with a purity of 62% (water content 38%). The product could be dried over MgSO4 or azeotropically distilled with hexane giving 102 g (94 * of theory) of the amine with a purity of 97%. P.e. 154 ° C. Comparative Preparation Examples Example 1: Preparation of 2-Methyl-1- (methylthio) propane-2-amine Preparation according to the invention 89 g (1 mol) of 2-amino-2-methyl-1-propanol and 1 mol of H2SO4 were mixed together as a 50% (w / w) aqueous solution cooling to maintain the temperature by below 50 ° C. The formed solution was kept in the vacuum oven at 120 ° C for 3 h to give a white solid. 169 g of 2-ammonium-2-methylpropyl sulfate could be isolated, which corresponds to a yield of 100%. Sodium mercaptide (1.2 mol) was added as a solution to the 20% in water in a flask and 40 g (1 mol) of NaOH (solid) were added with stirring. The mixture was stirred vigorously and 169 g (1 mol) of crushed 2-ammonium-2-methylpropyl sulfate were added in 30 min. The mixture was then stirred for 5-10 h at 90 ° C and cooled to 30 ° C. The upper organic phase was separated giving 169 g of the product 2-methyl-1- (methylthio) propane-2-amine with a purity of 53% (47% water content). The product could be dried over MgSO4 or distilled azeotropically with hexane giving 110 g (90% theory) of the amine with a purity of 97%. P.e. 55-58 ° C / 25 mbar (2.5 KPa) Preparation according to WO 03/099777 Fuming sulfuric acid (120.1 g of 20% S03 in H2SO4, ie 0.3 mol = 0.6 eq of S03) in a 1 liter flat bottom flask with flat flange gasket and 2-amino-2-methyl-l-propanol (46.9 g, 0.5 mol = 1 eq., 95%) with mechanical stirring directly in the fuming sulfuric acid so that the 2-amino-2-methyl-l-propanol touches the glass surface of the flask. The temperature is kept cool between 85 ° C and 90 ° C. The stirring of the reaction mixture is continued at 90 ° C for an additional 30 min. After cooling to room temperature, the mixture is first diluted with 200 ml of water and then 45% sodium hydroxide solution in water is added. In both procedures the temperature should not exceed 30 ° C. After After cooling, the sodium salt solution of methylmercaptan (183.6 g, 0.5 mol = 1 eq., 19.1% in water) is added and then stirring is continued at 60 to 65 ° C for 6 h. The mixture is cooled to 32 ° C and all other procedures are carried out at this temperature. 100 ml of methyl tert-butyl ether are added, the mixture is stirred and the organic phase is separated. The aqueous layer is extracted with two 100 ml portions of tert-butyl ether. The combined organic phases were dried over anhydrous sodium sulfate. After filtration, the solvent was removed at 20 ° C and at a reduced pressure of 150 mbar (15 kPa) Yield: 62.7 g (crude product, purity according to the internal standard: 68.8%, ie 72% of the theory) of 2-methyl-1-methylthio-2-propanamine. H-NMR (d6-DMSO): d 1.04 (s, 6H), 1.44 (broad, 2H), 2.10 (s, 3H), 2.48 (s, 2H) ppm. GC / MS-coupling: m / z (%) = 104 (3) [M-15] +, 58 (100), 42 (11), 41 (8), 31 (5). Preparation according to EP 1216988. Yield: 81%. It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Process for preparing compounds of formula (I) wherein R1 and R2 in each case independently represent hydrogen, C? -C4 alkyl, C3-C8 cycloalkyl, (C3-C8) cycloalkyl (C-C4) alkyl, C-C4 hydroxyalkyl; unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, alkylthio C C 4, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, carboxyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxy alkyl (C 4 -C 4), alkyl (C 1 -C 4) -carbonyl, haloalkyl C? -C4, haloalkoxy C? -C4, halogen-alkylthio C? -C4, halogen-alkylsulfinyl C? -C4, halogen-C1-C4 alkylsulfonyl, halogen-alkyl (C-C4) -carbonyl, phenylcarbonyl , phenoxycarbonyl, amino, C 1 -C 4 alkylamino and di- (C 1 -C 4 alkyl) amino (where the alkyl group may be the same or different); phenyl, which is substituted on two adjacent carbon atoms with C3-C4 alkylene or C2-C2 alkylenedioxy; unsubstituted or mono to pentasubstituted phenyl-C (-C) alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 1 -C halogen alkyl, halogen alkylsulfinyl C 1 C4 and halogen-alkylsulfonyl C? -C, -R3 and R4 independently of each other represent hydrogen or C? -C4 alkyl, R5 and R6 independently of each other represent hydrogen, C? -C4 alkyl, unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl , C 1 -C 4 alkylsulfonyl, C 1 -C 4 haloalkyl, C 1 -C 4 haloalkoxy, C 4 -C 4 halogen alkylthio, C 4 -C 4 halogeno alkylsulfinyl and halogen alkyl C 1 -C 4 -unsulfonyl; unsubstituted or mono-to-pentasubstituted phenyl-C 1 -C 4 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 8 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, haloalkyl
C? -C4, haloalkoxy C? -C4, halogen-alkylthio C? -C4, halogen-alkylsulfinyl C? -C4 and halogen-alkylsulfonyl C? -C4; R represents unsubstituted or mono- or polysubstituted C? -C? 2 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, hydroxy, C? -C4 alkoxy, halo? C4 alkanoxy, alkylthio C? C 4, C 1 -C 4 alkylsulfinyl and C 1 -C 4 alkylsulfonyl; unsubstituted or mono- or polysubstituted C3-C8 cycloalkyl or (C3-C8) cycloalkyl-alkyl (C? -C), in which the substituents are the same or different and are selected from the group consisting of halogen, C? -C4 alkyl and C4-C4 alkoxy; unsubstituted phenyl or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of halogen, C? -Ce alkyl, C3-C8 cycloalkyl, C? -C alkoxy, C? -C4 haloalkyl, haloalkoxy C? -C4; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 4 alkyl, wherein the substituents are the same or different and are selected from the group consisting of halogen and C 1 -C 4 alkyl; naphthyl; unsubstituted or mono- or polysubstituted heteroaryl, wherein the substituents are the same or different and are selected from the group consisting of halogen, C 1 -C 4 alkyl, C 1 -C alkoxy, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of halogen and C 1 -C 4 alkyl; n represents 1, 2, 3, 4, 5, 6, 7 or 8, where the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together represent further C2-C5 alkylene, R1 together with R3 or R5 further represents C3-C5 alkylene, R3 and R4 together further represent C4-C6 alkylene, R3 and R5 together further represent C2-C4 alkylene, R5 and R6 together further represent C4-alkylene C6, characterized in that in a first step, aminoalcohols of formula (II) are mixed wherein R1, R2, R3, R4, R5, R6 and n have the meanings given above, with sulfuric acid, because they are then reacted in a drying device giving esters of sulfuric acid of general formula (III) wherein R1, R2, R3, R4, R5, R6 and n have the meanings given before, and because these esters of sulfuric acid in a third stage are reacted with mercaptans or salts thereof of general formula (IV) RSM (IV) in which R has the meanings given above, and M represents hydrogen, ammonium or an alkali metal atom, in the presence of a base and preferably in the presence of a diluent. 2. Procedure in accordance with the claim 1, characterized in that a compound of formula (II) is used, in which R1 and R2 in each case independently represent hydrogen, C?-C4 alkyl, C3-C6 cycloalkyl, (C3-C6) cycloalkyl-alkyl (C ? -C2), hydroxyalkyl C? -C; unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C?-C4 alkyl, C3-C6 cycloalkyl, alkoxy C ? -C4, alkylthio C? ~
C4, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, carboxyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkoxy alkyl (C 1 -C 4), alkyl (C 2)
C4) -carbonyl, halogenalkyl C? -C4, halogenalkoxy C? -C4, halogen-alkylthio C? -C4, halogen-alkylsulfinyl C? -C4, halogen-C 1 -C 4 -alkylsulfonyl, halogen-C 1 -C 4 -alkylcarbonyl, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine, phenylcarbonyl, phenoxycarbonyl, amino, C 1 -C 4 alkylamino and di- (C 1 -C 4 alkyl) -amino (where the alkyl group may be the same or different); phenyl, which is substituted on two adjacent carbon atoms with C3-C4 alkylene or C2-C2 alkylenedioxy; unsubstituted or mono-to-pentasubstituted phenyl-C 1 -C 2 alkyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 4 alkyl , C3-C6 cycloalkyl, C? -C4 alkoxy, C? -C alkylthio, C? -C4 alkylsulfinyl, C? -C4 alkylsulfonyl, C? -C4 haloalkyl, C? -C4 haloalkoxy, C? -C4 halogen alkylthio, halogen-alkylsulfinyl C? -C4 and halogen-alkylsulfonyl C? -C4, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; R3 and R4 independently represent hydrogen or C? -C4 alkyl, R5 and R6 independently represent hydrogen, C? -C4 alkyl, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl C4, haloalkyl C? -C4, haloalkoxy C?
C4, halogen-C 1 -C 4 -alkylthio, halogen-C 1 -C 4 -alkylsulfinyl and halogen-C 1 -C 4 -alkylsulfonyl, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; unsubstituted or mono to pentasubstituted phenylalkyl (C? -C2), in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, cyano, nitro, C? -C4alkyl, cycloalkyl C 3 -C 8, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 1 -C 4 alkylsulfinyl, C 1 -C 4 alkylsulfonyl, C 4 -C 4 haloalkyl, C 4 -C 4 haloalkoxy, halogen C 1 -C 4 alkylthio, halogen C 1 -C 4 alkylsulfinyl and C 1 -C 4 alkylsulfonyl, each having 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; n represents 1, 2, 3, 4, 5 or 6, where the group C (R1) R2 can be the same or different, when n is greater than 1, and when n represents 1, R1 and R2 together also represent C2- alkylene C5, R1 together with R3 or R5 further represents C3-C5 alkylene, R3 and R4 together further represent C4-C6 alkylene, R3 and R5 together further represent C2-C4 alkylene, R5 and R6 together also represent C4-C6 alkylene. 3. Method according to claim 1 or claim 2, characterized in that a compound of formula (IV) is used, in which R represents unsubstituted or mono- or polysubstituted C? -C? 2 alkyl, in which the substituents are same or and are selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, C 1 -C 4 alkoxy, haloalkoxy C 1 -C 4, having from 1 to 9 atoms the same or different from fluorine, chlorine and / or bromine, alkylthio C? -C4, C? -C4 alkylsulfinyl and C? -C4 alkylsulfonyl; unsubstituted or mono- or polysubstituted C3-C6 cycloalkyl or (C3-C6) cycloalkyl-alkyl (C? -C2), in which the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C 1 -C 4 alkyl and C 1 -C 4 alkoxy; unsubstituted or mono to pentasubstituted phenyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C-C4 alkyl, Cs-Cg cycloalkyl, C?-C4 alkoxy, haloalkyl C? -C4, haloalkoxy C? -C4, each having from 1 to 9 same or different atoms of fluorine, chlorine and / or bromine; unsubstituted or mono to pentasubstituted phenyl-C 1 -C 2 alkyl, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, and C 1 -C 4 alkyl; naphthyl; unsubstituted or mono- or polysubstituted heteroaryl (preferably furyl, thienyl, pyrrolyl, oxazolyl, oxazolinyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, pyrazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1, 2, 4 -thiadiazolyl, 1,3,4-thiadiazolyl, 1, 2, 3-thiadiazolyl, 1, 2, 5-thiadiazolyl, 1,2,3-triazolyl, 1, 2, -triazolyl, tetrazolyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl), in the that the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, C -C 4 alkyl, C 1 -C 4 alkoxy, unsubstituted phenyl or mono to pentasubstituted, wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, and C 1 -C 4 alkyl; M represents hydrogen, ammonium or an alkali metal atom. 4. Method according to claim 1, characterized in that a compound of formula (II) is used, in which R1 and R2 in each case independently represent hydrogen, methyl, ethyl, n-, i-propyl, n- , i-, s-, t-butyl, R3 and R4 independently of each other represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, R5 and R6 independently of each other they represent hydrogen, methyl, ethyl, n-, i-propyl, n-, i-, s-, t-butyl, n represents 1 or 2, where the group C (R1) R2 can be the same or different, when n is greater than 1, and a compound of formula (IV), in which R represents methyl, ethyl, n-, i-propyl or n-, i-, s-, t-butyl in each case unsubstituted or mono- or polysubstituted , wherein the substituents are the same or different and are selected from the group consisting of fluorine, chlorine, bromine, iodine, hydroxy, methoxy, ethoxy, n-, i-propoxy, n-, i-, s-, t-butoxy, trifluoromethoxy, trichloromethoxy, methylthio, ethylthio, n-, i-propylthio, t-butylthio , methylsulfinyl, ethylsulfinyl, n-, i-propylsulfinyl, t-butylsulfinyl, methylsulfonyl, ethylsulfonyl, n-, i-propylsulfonyl, t-butylsulfonyl. M represents sodium or potassium. Method according to any of claims 1 to 4, characterized in that the second reaction step is carried out in a drying oven, a conveyor belt dryer or a spray dryer.
6. Process according to any of claims 1 to 5, characterized in that in the first reaction stage 0.8 to 1.2 moles of amino alcohol are used per mole of sulfuric acid.
7. Method according to any of claims 1 to 6, characterized in that the base used in the third stage of the process is selected from the group consisting of alkali metal and alkaline earth metal hydroxides, alkali metal carbonates or hydrogencarbonates.
8. Method according to any of claims 1 to 7, characterized in that an aqueous solution of a mercaptan or the salt thereof is used in the third reaction step.
9. Process according to any of claims 1 to 8, characterized in that the third step is carried out by first preparing a solution of the mercaptan or a salt thereof and the base, to which the sulfonate ester is then added.
10. Method according to any of claims 1 to 9, characterized in that the second stage of the process is carried out at a temperature between 50 ° C and 200 ° C.
11. Method according to any of claims 1 to 10, characterized in that the third step is carried out using a phase transfer catalyst.
12. Process according to any of claims 1 to 11, characterized in that between 1 and 5 moles of mercaptan or salt thereof are used per mole of sulfonate ester in the third reaction step.