WO2008074653A1

WO2008074653A1 - Method for producing menthyl derivatives

Info

Publication number: WO2008074653A1
Application number: PCT/EP2007/063473
Authority: WO
Inventors: Andreas Job; Uwe Westeppe; Lars Rodefeld
Original assignee: Saltigo Gmbh
Priority date: 2006-12-20
Filing date: 2007-12-06
Publication date: 2008-06-26
Also published as: DE102006060949A1

Abstract

The invention provides an improved method for producing menthyl derivatives through the reaction of menthyl halides with magnesium and the subsequent reaction with electrophiles in the presence of additives.

Description

Process for the preparation of mentliyl derivatives

The present invention relates to an improved process for the preparation of Menthy 1 derivatives.

Menthol is known for its physiological cooling effect on the skin and mucous membrane of the mouth and is widely used as a flavor in foods, drinks, toothpaste, mouthwash, as well as a component in a variety of toiletries, ointments and lotions for topical application. The Ktihleffekt is a physiological effect due to the direct effect of menthol on the nerve endings of the human body, which are responsible for the perception of heat or cold, and is not based on the latent heat of vaporization. It is believed that menthol has a direct stimulating effect on the cold receptors on the nerve endings, which in turn stimulate the central nervous system.

However, the use of menthol is limited because of its strong peppermint odor and its relatively high volatility.

In DE-A-24 136 39 and DE-A-22 052 55 special menthylamides have been described for the first time, which likewise have a strong physiological cooling effect on the skin and on the mucosal membranes of the body, in particular of the nose, mouth, throat and gastrointestinal tract , In many cases, this cooling effect is much more durable than that obtained with menthol without the strong odor at the same time. The compounds also have a lower volatility than menthol and are used as so-called cooling agents in the food industry. Their economic production is thus of great interest.

From DE-A-24 136 39 and DE-A-22 052 55 a process for the preparation of menthyl amides is known in which starting from menthyl chloride first forms a Grignard reagent, which is reacted in a subsequent step with carbon dioxide to Menthylcarbonsäure. This intermediate is then reacted with a chlorinating agent such as thionyl chloride to give the corresponding menthyl chloride, which reacts with a suitable mono- or disubstituted amine in a further step in the presence of a hydrogen chloride acceptor such as sodium hydroxide to give the desired menthylamide. This procedure is disadvantageous in that, starting from menthyl chloride, it requires four chemical synthesis steps up to the target molecule. From US-A-4,350,832 and US-A-4,366,317 a method is known, according to which the reaction of menthyl magnesium chloride (in a 0.5% excess based on isocyanate) with tert-butyl isocyanate to the corresponding N-tert-butyl-p -menthyl-3-carboxamide. According to US-A-4,350,832, a reaction temperature in the range between -1O ⁰ C and + 100 ⁰ C is selected. Yields of more than 50% are obtained, but this yield relates to the total yield of both epimers, ie, your menthyl and neomenthyl epimer. If a reaction temperature of O ⁰ C to 30 ⁰ C, ie selected in the lower part of this temperature range, the proportion of the menthyl epimer is 57-80 wt.% Based on the sum of menthyl and Neomenthyl epimer. Since the menthyl epimer has a greater physiological cooling effect than the neomenthyl epimer, US Pat. No. 4,366,317 seeks to provide an improved process in which the product obtained contains at least 90% by weight of the menthyl epimer and at most 10% by weight. % consists of the neomenthyl epimer. For this purpose, the reaction with tert-butyl isocyanate at a temperature in the range between -20 ⁰ C and -70 ⁰ C performed. However, this leads to a very low reaction rate, so that the reaction time is 20 to 80 hours. Simultaneously, the total yield of both epimers% decreases clearly, for example, 24.2 wt. At a reaction temperature of -7O ⁰ C.

From Angew. Chem., Int. Ed. 2006, 45, 6509 it is known that a mixture (ratio 1: 1) of menthyl magnesium chloride and its epimer Neomenthylmagnesiumchlorid forms from menthyl chloride and Magnesiuni. In a subsequent reaction with electrophiles, the menthylmagnesium chloride very preferably first reacts from this mixture to give the desired menthyl derivative. Thus, if an equimolar amount of menthyl chloride is first reacted with magnesium and then with the corresponding electrophile, a maximum yield of 50% is obtained. This is particularly disadvantageous because in these reactions usually the menthyl chloride is the more valuable reaction component (in comparison to the respective electrophile).

Due to the widespread use of menthylamides and their derivatives in the food industry, there was thus a need for an improved, technically simple and economical production process.

Surprisingly, it has been found that the reaction of a menthyl halide with magnesium and subsequently with electrophiles in the presence of additives with respect to the desired epimer of the respective menthyl derivative leads to significantly higher yields than 50%. This process therefore represents a significant economic improvement of the previous Synthesevvegs. The invention relates to a process for the preparation of compounds of the general formula (1)

in which

ZC (= O) NR'R ² or CH ₂ NR ¹ R ² means where

R ¹ Ci-C ₃₀ alkyl, C ₂ -C ₂₀ alkenyl, C ₂ -C _2fl alkynyl, C ₇ -C ₂ o-alkylaryl, C ₆ -C ₀ -AIyI, Cs-C | o-heteroaryl, or substituted by Cs-Cjo-heteroaryl, phenyl, C ₃ - C ₂ o-cycloalkyl, Cj-Cio-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, C ₁ -C ₂₀ - hydroxyalkyl, C ₃ -C _2O - acyloxyalkyl C | -C ₂ -alkoxy, Ca-C ₂₀ - alkoxyalkyl, C ₂ - C ₂₀ alkylthioalkyl, C2-C2o-aminoalkyl, Ca-C jo-acylaminoalkyl, C ₂ -C ₂₀ - carboxyalkyl, a radical -C _n H ₂ "C (= O) R ^' or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, Q C 1 -C ₈ -alkyl, C 1 -C ₈ -hydroxyalkyl, C 1 -C ₅ -alkoxyalkyl or C 1 -C ₆ -cycloxyalkyl, R ^{2 has} the same meanings as R ¹ , furthermore may denote hydrogen or a radical --X-OH, where X is represents a straight-chain or branched C _r C ₂ o-alkylene group, optionally substituted by one or more heteroatoms, preferably oxygen or sulfur, under is skate, or in which

R ^! and R ² together form an alkylene chain optionally interrupted by one or more heteroatoms, preferably oxygen or sulfur, taken together with the nitrogen atom to which R ¹ and R ^{2 are} bonded, forming a maximum 10-membered ring, or ZC (OH) R ⁴ R ⁵ means in which

R ⁴ and R ^{3 are the} same or different and those previously indicated for R ¹

Own meanings and

Alternatively, R ⁵ may be hydrogen, or Z is C (= O) R ⁶ , where

R ^{ά has} the meanings given for R ¹ , or Z is CR ⁷ R ⁸ R ⁹ , in which

R ^{7 has} the meanings given for R ¹ and

R ⁸ and R ^{9 are the} same or different and are 0-Ci-C ₃ o-alkyl, or wherein alternatively

R ⁷ and R ^{8 are the} same or different and have the meanings given for R ¹ and

R ^{9 is} 0-Ci-C ₃ o-alkyl, or Z is CHR ¹⁰ CHR "OH, wherein

R ¹⁰ and R ^{11 are the} same or different and those previously indicated for R ¹

Have meanings, or Z represents SO ₂ R ¹² , in which

R ^{12 is} an optionally substituted Cβ-Cis-aryl radical.

by first preparing a compound of general formula (II)

wherein

Hal is chlorine, bromine or iodine, reacted with magnesium and optionally elemental iodine or an alkyl halide, and then in the presence of an additive with an electrophile, which is selected from the group consisting of

Isocyanates of the general formula (III),

O = C = NR ¹ (I II) where R ^{1 has} the meanings given for the general formula (J),

Heterocycles of the general formula (IV),

wherein R ¹ and X have the meanings given for the general formula (I),

Carbamoyl chlorides of the general formula (V),

wherein R ¹ and R ^{2 have} the meanings given for the general formula (I),

Aminoethers of the general formula (VI),

wherein R ¹ and R ^{2 have} the meanings given for the general formula (I) and R ^{13 is} a C ₁ -C 20 -alkyl radical,

Aldehydes of the general formula (VII),

wherein R ⁴ above for formula (I) esitzt g <date set out meaning ^(e ^v n ⁱ ^ι ^b)

Ketones of the general formula (VIII),

O

R ₅ ⁵ J ^ k R 4 ^{4 (Vll ()} wherein R ⁴ and R ⁵ are identical or different and have the meanings given above for R ^1,

Nitriles of the general formula (IX),

N≡CR ⁶ (IX) in which R ^{s has} the meanings given above for formula (1),

Acetals of the general formula (X),

wherein R ⁷ and R ^{8 are the} same or different and have the meanings given for R ¹ in the general formula (I) and R ⁹ and R ^{14 are} identical or different and represent O-Ci- C ₃ o-alkyl,

Orthoestheses of general formula (XI),

in which R ^{7 has} the meanings given for R ¹ in the general formula (I), and R ⁸ , R ⁹ and R ^{14 are} identical or different and represent 0-C 1 -C ₃₀ -alkyl, Epoxides of the general formula (XB),

wherein R ¹⁰ and R ^{11 have} the meanings given for the general formula (1), and • sulfonyl chlorides of the general formula (XIII)

wherein R ^{12 has} the meanings given for formula (I).

If the term "substituted" is used in the context of this application, this means that a hydrogen atom on a given radical or atom is replaced by one of the specified groups, with the proviso that the valency of the atom given is not exceeded and the Substitution leads to a stable compound.

For all the radicals mentioned in the context of this application, which may be in branched or unbranched form, such as. Alkyl, alkoxy, alkenyl and alkynyl radicals, the mention of these radicals includes both the unbranched and the branched forms.

In the context of this application and invention, all of the definitions of residues, parameters or explanations mentioned above, general or in preferred ranges mentioned above and also mentioned below, ie also between the respective ranges and preferred ranges, can be combined in any desired manner and are thus disclosed.

A Cjj-Cio-heteroaryl radical is an aromatic radical in which at least one skeletal carbon atom in the rest is replaced by a heteroatom selected from the group of nitrogen, sulfur or oxygen. Preferably, one, two, three or four skeletal carbon atoms in the entire radical are replaced by heteroatoms selected from the group of nitrogen, sulfur or oxygen.

All the compounds of the above general formulas (III) to (XIII) have in common that they are electrophiles. The implementation of the invention succeeds by using the entire width of these electrophiles according to the same inventive principle.

It is essential to the invention that this reaction is carried out in the presence of an additive. Examples of such additives are LiCl, LiBr, ZnCl ₂ , ZnBr ₂ , SnCl ₂ , SnCU, MgCl ₂ , MgBr ₂ , AlCl ₃ , TiCl ₄ , Al (OiPr) ₃ , Ti (OiPr) ₄ , CeCl ₃ , ZnEt, CuBr, LiClO ₄ , BCl ₃ , BF ₃ and their etherate, boric acid, unsubstituted and substituted phenylboronic acids and other Lewis acids used.

By adding such an additive, a significant increase in the yield with respect to the desired epimer can be observed in all types of reactions.

The additive may be added at all times in the course of the process, i. before, during or after addition of the electrophile of the general formulas (III) to (XIII). Preferably, the addition of the additive is carried out before the addition of the electrophile, wherein the addition can be done either to the finished Grignard compound or before the preparation of the Grignard compound to magnesium.

In the latter case, the additive is introduced together with magnesium under inert gas, mixed with the solvent and then optionally elemental iodine or the alkyl halide is added. In the former case, the additive is added to the solution containing the Grignard compound simultaneously, before or after the electrophile.

It has proven useful to use the additive in an amount of 1-100 mol%, preferably 10-50 mol%, based on the forming Grignard compound.

For the sake of simplicity, in the context of this application, the compounds of the general formula (I) are also referred to as "menthyl derivatives".

The preparation of the educts of the general formula (II) is possible by methods known to the person skilled in the art. The preparation of the menthyl chloride from menthol is comprehensively described, for example, in the literature, e.g. in J. Org. Chem. 2000, 65, 2337.

The reaction of the starting materials of the general formula (II) with the Grignard compound can be carried out in various solvents (see, for example, J. Org. Chem. 2000, 65, 2337 with regard to possible solvents for the preparation of the Grignard compound). Suitable solvents are THF, dioxane, methyl THF, cyclopentyl methyl ether, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether or mixtures of the abovementioned solvents with aromatic solvents such as toluene or xylene. Isocyanates of the general formula (IU):

As electrophiles can in the reaction of the invention isocyanates of the general

Formula (III) can be used, in which

R ^{1 is} CpCso-alkyl, C ₂ -C ₂ -o [kenyl, C ₂ -C ₂₀ -alkyl, C _r C ₂₀ -alkylaryl, C ₆ -C ₁₀ -aryl, C ₅ -C ₁₀ -heteroaryl or by Cs-Cio heteroaryl substituted phenyl], C ₃ -C ₂ o-cycloalkyl, C ₃ - C ₂ o-cycloalkenyl, C ₃ -C ₂₀ cycloalkynyl, C _r C ₂₀ hydroxyalkyl, C ₃ -C ₂ o-acyloxyalkyl, C ₁ -C ₂₀ -alkoxy, C ₂ -C ₂₀ alkoxyalkyl, C ₂ -C ₂ o-alkylthioalkyl, C ₂ -C ₂ o-aminoalkyl, C ₃ - C ₂ o-acylaminoalkyl, C ₂ -C ₂ o-carboxyalkyl, a radical -C "H _2n C (= O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched Alkylengrupppc in which n is an integer from 1 to 10 and R Represents hydrogen, C 1 -C 6 -alkyl, C 1 -C 9 -hydroxyalkyl, C 1 -C ₈ -alkoxyalkyl or C 1 -C -cycloxyalkyl,

Preferably, R ¹ in the general formula (III) is

C ₁ -C ₄ -AIkVi, C ₂ -Cio-alkenyl, C ₂ -C ₀ - alkynyl, C ₃ -Cι ₀ cycloalkyl, C ₅ -C ₀ cycloalkenyl, _C5 - Cio-cycloalkynyl, Ci-CIO hydroxyalkyl, d-Cio-Acyloxyalky-, C D _C alkoxy, C ₂ -CiQ- alkoxyalkyl, C ₂ -C ₀ alkylthioalkyl, C ₂ -C ₁₀ aminoalkyl, C ₃ -C ₁₀ -Acylaminoalkyl, C ₂ - Ci ₀ - carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or an oxazolyl, triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR, wherein -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 6 and R is hydrogen, C ₁ -C 6 -alkyl, C ₁ -C 8 -hydroxyalkyl, Cj -Cβ-alkoxyalkyl or Ci-C ₈ acyloxyalkyl.

Particularly preferably, R ¹ in the general formula (III) is a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert. Butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1- Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1, 2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n- Octyl, 11-nonyl or n-decyl, for a Cs-Cβ-cycloalkyl radical, in particular a cyclopentyl or a cyclohexyl radical, for a benzoxazolyl, benzo-l, 3-dioxolanyl or an oxazolyl radical, Triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical.

Obtained therewith compounds of the general formula (1), wherein Z is a radical Cf = O) NR ¹ R ² , where R ^{1 is} as above for the compounds of general formula (HI) has the general, preferred or particularly preferred meanings mentioned, and in which R ^{2 is} hydrogen.

Hetrocycles of the general formula (IV):

As further electrophiles, heterocycles of the general formula (IV) can also be used in the reaction according to the invention.

be used, where ^(ιv)

R ¹ can assume all general, preferred or particularly preferred meanings which R ^{1 has} in the general formula (III), and

X is a straight or branched C | -C ₂ o-alkylene, preferably a straight or branched C | -C ₈ alkylene group, particularly preferably a methylene, ethylene, n-propylene, n-pentylene or n-Burylen- Group, wherein these general, preferred or particularly preferred alkylene groups are optionally interrupted by one or more heteroatoms, preferably oxygen or sulfur.

Here are compounds of general formula (I) obtained wherein Z is a radical - C (^ = O) NR ¹ R ² , R ^{1 has} the abovementioned general, preferred or particularly preferred meanings, R ^{2 is} an X-OH radical and X has the general, preferred and particularly preferred meanings mentioned above for the general formula (IV). The compounds of general formula (I) thus obtained are hydroxy-functionalized amides.

Carbamoyl chlorides of the general formula (V):

As further electrophiles, carbamoyl chlorides of the general formula (V) can also be used in the reaction according to the invention,

wherein R ¹ and R ^{2 are the} same or different and may have all the general, preferred and particularly preferred meanings given above for the general formula (III). Compounds of the general formula (I) are obtained, where Z is a radical C (K)) NR ¹ R ² , in which R ¹ and R ^{2 are} identical or different and have all the general meanings given above for the general formula (HI), have preferred and particularly preferred meanings.

Aminoethers of general formula (VI):

As further electrophiles, aminoethers of the general formula (VI) can also be used in the reaction according to the invention,

wherein

R ¹ Ci-Cao-alkyl, C ₂ -C rAlkenyl _2t, C ₂ -C ₂₀ alkynyl, C ₇ -C _2O -AUCyIaIyI, C ₆ -C ₀ aryl, C ₅ -C ₀ - heteroaryl, by C ₅ -Cio-heteroaryl-substituted phenyl, C ₃ -C ₂ o-cycloalkyl, Cs-C ₂₀ - cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, C ₁ -C ₂₀ -hydroxyalkyl, C ₃ -C ₂ o-acyloxyalkyl, C ₁ - C ₂₀ alkoxy, C ₂ -C ₂₀ alkoxyalkyl, C ₂ -C ₂ o-alkylrhioalkyl, C ₂ -C ₂₀ -AmInOaIkVl, Cj-C ₂₀ - acylaminoalkyl, C ₂ -C ₂₀ carboxyalkyl, a radical -C _{7I is} H ₂ -C (= O) R or a radical - C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, CpClio Alkyl, Ci-C ₈ - represents hydroxyalkyl, Ci-Cg-Alkoxyalkyl or Ci-Cβ-Acyloxyalkyl,

R ^{2 has} the same meaning as R ', further hydrogen or a radical -X-OH, wherein X represents a straight-chain or branched Ci-Cjn-alkylene group, which is optionally interrupted by one or more heteroatoms, or wherein

R ¹ and R ² together form an alkylene chain optionally interrupted by one or more heteroatoms, taken together with the nitrogen atom to which R ¹ and R ^{2 are} bonded, forming a maximum 10-membered ring, and

R ^{13 is} a C 1 -C ₂₀ -alkyl radical.

Amino ethers of the general formula (VI) are preferably used, wherein R ¹ is C ₁ -C] ₄ -alkyl, C ₂ -C ₀ alkenyl, C ₂ -C ₀ alkynyl, Cj-Cjo-cycloalkyl, _C5 -C ₀ -Cycloalkenyl, C ₅ -Cin _. -Cycloalkinyl, Ci-Cio-hydroxyalkyl, C ₃ -Ci ₀ -Acyloxyalky-, Ci -C ₀ -alkoxy, C ₂ - Ciβ-alkoxyalkyl, C ₂ -Cio-alkylthioalkyl, C ₂ -C ₀ aminoalkyl, Cs-Cio -Acylaminoalkyl, C ₂ -Ci ₀ -Carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or an oxazolyl, triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (= O) R ^' or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 6 and R Hydrogen C _r Cio-alkyl, Ci-C ₈ -Hydroxya alkyl, C |! -C ₈ alkoxyalkyl or C ₈ -

Acyloxyalkyl, and R ^{2 has} the same meanings as R ¹ , may mean fine hydrogen or a radical -X-OH, wherein X represents a straight-chain or branched Ci-Cπ-alkylene group, which is optionally interrupted by one or more heteroatoms, or wherein R ¹ and R ² together represent an optionally interrupted by one or more heteroatoms

Alkylene chain taken together with the nitrogen atom, to the R ¹ and

R ^{2 are} bonded, forms a maximum 8-membered ring, and R ^{13 is} a Ci-Ci ₄ -alkyl radical.

Particular preference is given to using aminoethers of the general formula (VI) in which

R ^{1 is} a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2 Methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl. 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1 Ethyl butyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n-octyl, represents n-nonyl or n-decyl, for a C ₅ -C ₈ -cycloalkyl radical, in particular a cyciopentyl or a cyclohexyl radical, or for a benzoxazolyl, benzo-l, 3-dioxolanyl or an oxazolyl radical Triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical,

R ^{2 has} the same meanings as R ¹ , furthermore hydrogen or a radical -X-OH, where X represents a straight-chain or branched Ci-Cn-alkylene group, which is optionally interrupted by one or more sulfur or oxygen atoms, or wherein

R ¹ and R ² together form an alkylene chain optionally interrupted by one or more sulfur or oxygen atoms, taken together with the nitrogen atom to which R ¹ and R ^{2 are} bonded, forming a maximum 8-membered ring, and

R ^{13 is} a Ci-Cio-alkyl radical, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-Metliylbutyl , 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl , 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-di-, methylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl], n -Hexyl, n-hptyl, n-octyl, n-nonyl or n-decyl.

In each case, compounds of the general formula (I) are obtained in which Z represents a radical -CH ₂ NR ¹ R ² and R ¹ and R ^{2 have} the meanings given above.

Aldehydes of the general formula (VII):

As further electrophiles aldehydes of the general formula (VII) can also be used in the reaction according to the invention,

wherein

R ⁴ _Ci-C30 alkyl, _{C2-C2o-alkenyl,} CrQo alkynyl, C ₇ -C ₂₀ - alkylaryl, C ₆ -C ₀ -ATyI, C ₅ -C ₀ - heteroaryl, by Cs-CIO Heteroaryl-substituted phenyl, C ₅ -C ₂ o-cycloalkyl, C ₃ -C _2O -cycloalkenyl, C ₃ -C ₂₀ -cycloalkynyl, C ₁ -C ₂₀ -hydroxyalkyl, C ₃ -C ₂ o-acyloxyalkyl, Q-C ₂₀ - alkoxy, C ₂ -C _2ß alkoxyalkyl, C ₂ -C ₂ o-alkylthioalkyl, C ₂ -C ₂₀ aminoalkyl, C ₃ -C ₂₀ - acylaminoalkyl, C ₂ -C ₂₀ carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical - C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched Alkylengrupppe, in which n is an integer from 1 to 10 and R is hydrogen, Ci-C] ₀ alkyl Ci-Cg hydroxyalkyl Ci-C represents, ₈ alkoxyalkyl or Ci-Cβ-acyloxyalkyl or a heterocycle.

In the reaction according to the invention, aldehydes of the general formula are preferred

(VIl) used in which

R ⁴ Ci-Cw-alkyl, C ₂ -C ₀ -Aikenyl, C ₂ -C ₀ alkynyl, C ₅ -C -Cyc1oalkyl _0, Cj-C ₁₀ cycloalkenyl, C ₅ -Cio-cycloalkynyl, CRDO hydroxyalkyl, C ₃ -C | _0- acyloxyalky-, C _r C | ₀ -alkoxy, C ₂ -C 10 -alkoxyalkyl, C ₁ -C 10 -alkylthioalkyl, C ₂ -C 10 -aminoalkyl, C ₁ -C 10 -acylaminoalkyl, C ₂ -C 10 -carboxyalkyl, a benzoxazolyl, benzo-1,3-dioxolanyl-, or an oxazolyl -, triazolyl, Moipholinyl- or pyrazolyl-substituted phenyl radical, a radical -C "H _2n C (= O) R ^' or a radical -C _n H _2n COOR, wherein -C _n H _{2n is} a straight-chain or branched Alkylengruppe is in which n is an integer from 1 to 6 and R is hydrogen C _r Ci ₀ alkyl, Ci-Cg-hydroxyalkyl, Ci-C ₈ alkoxyalkyl or C ₈ - represents acyloxyalkyl or heterocycle. In the reaction according to the invention, particular preference is given to using aldehydes of the general formula (VII) in which

R ⁴ a straight-chain or branched Ci-Cjo-alkyl radical, in particular methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1 -Methylbυtyl, 2 Methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4 Methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1.1 , 2-trimethylphenyl, 1, 2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl , or represents a Cs-Cg-cycloalkyl radical, in particular a cyclopentyl or a cyclohexyl radical, or a furanyl radical.

Here, compounds of the general formula (I) are obtained, wherein Z is a radical - C (OH) R ⁴ R ⁵ , R ^{4 has} the abovementioned general, preferred and particularly preferred meanings and R ^{5 is} hydrogen.

Ketones of the general formula (VIII):

As further electrophiles, ketones of the general formula (VIII) can also be used in the reaction according to the invention,

wherein

R ⁴ and R ⁵ are identical or different and are Ci-Cjo alkyl, C ₂ -C ₂ -alkenyl, C ₂ -C ₂ o-alkynyl, Cv-C ₂ o-alkylaryl, Ce-Cio-aryl, Cs Cio-heteroaryl, substituted by Cs-Cio-heteroaryl, phenyl, C ₃ -C _2O -Cy cloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, Ci-Cio-hydroxyalkyl, C ₃ -C2o -Acyloxyalkyl ₎ Ci-C ₂₀ -alkoxy, C ₂ -C ₂ o-Alkoxyalkyl, C ₂ - C ₂ o-Alkylthioalkyl, C ₂ -C ₂₀ -Ammoalkyl, C3-C ₂ o-Acylaminoalkyl, C ₂ -C ₂ o -Carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR ', where -C _n H _{2n is} a straight-chain or branched Alkylengrupppe in which n is an integer from 1 to Is 10 and R ^"is hydrogen, C 1 -C 10 -alkyl, C 1 -C ₈ -hydroxyalkyl, C 1 -C ₆ -alkoxyalkyl or C 1 -C 6 -acyloxyalkyl.

In the reaction according to the invention, preference is given to using ketones of the general formula (VIII) in which R ⁴ and R ^{5 are the} same or different and Ci-Cw-alkyl, C ₂ -C | ₀ -Allcenyl, C ₂ -Cιo alkynyl, C ₅ - Cio-cycloalkyl, C ₅ -Cio-Cycloalkeny1, Cs-Cio-cycloalkynyl, C | -C ₁₀ hydroxyalkyl, C ₃ - Cio-Acyloxyalky-, C _r Cio alkoxy, C ₂ -C ₀ alkoxyalkyl, C2-Ciα _{alkylthioalkyl)} C ₂ -C ₀ - aminoalkyl, Cs-Cio-acylaminoalkyl, C _Σ -Cio-carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl or an oxazolyl, triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (O) R ^' or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 6 and R is hydrogen, C ₁ -C ₁₀ -alkyl, C ₁ -C ₈ -hydroxyalkyl, C ₁ -C ₈ -alkoxyalkyl or C ₁ -C ₈ -acyloxyalkyl,

In the reaction according to the invention, particular preference is given to using aldehydes of the general formula (VI) in which

R ⁴ and R ⁵ are identical or different and are a straight-chain or branched C _I -C _JO - alkyl radical, especially methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl , n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-diniethylpropyl, 1,2-dimethylpropyl, I- Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl , 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n -Octyl, n-nonyl or n-Dccyl or and fllr a Cs-Cg-cycloalkyl radical, in particular a cyclopentyl or a cyclohexyl radical.

Here, compounds of the general formula (1) are obtained, wherein Z is a radical - C (OH) R ⁴ R ⁵ and R ⁴ and R ^{5 have} the meanings given above.

Nitriles of the general formula (IX):

As further electrophiles, nitriles of the general formula (IX) can also be used in the reaction according to the invention,

N≡CR ⁶ (IX) where

R ⁶ can assume all general, preferred or particularly preferred meanings which R ^{1 has} in the general formula (III).

Here, compounds of the general formula (I) are obtained, wherein Z is a radical - C (= O) R ⁶ and R ^{6 has} the meanings of R ¹ mentioned above in the general formula (I). Acetals of the general formula (X):

As further electrophiles, acetals of the general formula (X) can also be used in the reaction according to the invention,

wherein

R ⁷ and R ⁸ are identical or different and are Ci-C ₃₀ - alkyl, C ₂ -C ₂ -alkenyl, C ₂ -C ₂₀ -AIkJ nyl, C ₇ - C ₂₀ alkylaryl, C ₆ -C ₀ -aryl , C ₅ -Cio-heteroaryl, substituted by Cs-Cio-heteroaryl, phenyl, C ₃ -C ₂ o-cycloalkyl, C ₃ -C ₂₀ cycloalkenyl, C ₃ -C ₂₀ cycloalkynyl, C ₁ -C ₂₀ - hydroxyalkyl, C ₃ -C ₂₀ -Acyloxyalkyl, C ₂₀ alkoxy, C ₂ -C ₂₀ -AIkOXyBIlCyI, C ₂ -C ₂₀ - alkylthioalkyl, C ₂ -C ₂₀ aminoalkyl, CrCΣo-Acylarninoalkyl, C ₂ -C ₂₀ -Carboxyalkyl, a radical -C _n H _2n C (O) R or a radical -C _n H _2n COOR mean, wherein -C _n H _{2n is} a straight-chain or branched Alkylengruppe in which n is an integer from 1 to 10 and R ^'is hydrogen, C 1 -C 10 -alkyl, C 1 -C ₈ -hydroxyalkyl, C 1 -C ₈ -alkoxyalkyl or C 1 -C ₈ -cycloxyalkyl,

R ⁹ and R ^{14 are the} same or different and are -O-Ci-C ₃ α-alkyl.

In the reaction according to the invention, acetals of the general formula are preferred

(X) used in which

R ⁷ and R ⁸ are identical or different and d-Cμ alkyl, C ₂ -Cιo alkenyl, C ₂ -C ₀ alkynyl, C ₅ _- Cio-cycloalkyl, C ₅ -Cio-cycloalkenyl, Cs-q O- cycloalkynyl, Ci-Cio-hydroxyalkyl, C ₃ - Cio-Acyloxyalky-, Ci-Cio-alkoxy, C ₂ -Cio-AIkoxyalkyl, C ₂ -C ₁₀ - Al kylthioalkyl, C ₂ -C ₀ - aminoalkyl, C ₃ -C ₁₀ -Acylaminoalkyl, C ₂ -Ci ₀ -Carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or an oxazolyl, triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (^ O) R or a radical -C _n H _2n COOR ^' , wherein -C _n H _{2n is} a straight-chain or branched Alkylengrupppe, in which n is an integer from 1 to 6 and R ^{' is} hydrogen Ci-Cio-alkyl , C 1 -C ₈ -hydroxyalkyl, C 1 -C ₈ -alkoxyalkyl or C 1 -C ₈ -acyloxyalkyl,

R ⁹ and R ^{14 are the} same or different and are -OC | -C ₂₀ -alkyl.

Particular preference is given in the reaction according to the invention to acetals of the general formula

Formula (X) used in which

R ⁷ and R ^{8 are the} same or different and a straight-chain or branched C _r C | ₀ -alkyl radical, especially methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo Pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1, 2-dimethylpropyl, 1, 2-dimethylpropyl, 1 Methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n- Represent octyl, n-nonyl or n-decyl or and represent a Cs-Cβ-cycloalkyl radical, in particular a cyclopentyl or a cyclohexyl radical, and R ⁹ and R ^{14 are} identical or different and are -O-Ci -Cn-alkyl, in particular O-methyl, O-ethyl, on-propyl, O-iso-propyl, on-butyl, O-sec-butyl, O-tert-butyl, O-n-pentyl, O-1-methylbutyl, O-2-methylbutyl, O-3-methylbutyl, O-neo-pentyl, 0-1-ethylpropyl, on-hexyl, 0-1,1-dimethylpropyl, 0-1,2-dimethylpropyl, 0-1,2-dimethylpropyl, 0-1-methylpentyl, O-2-methyl-pentyl, O-3-methylpentyl, 0-4-methylpentyl, O-1,1-dimethylbutyl, O-1,2-dimethylbutyl, O- 1,3-dimethylbutyl, O-2,2-dimethylbutyl, O-2,3-dimeth ylbutyl, 0-3,3-dimethylbutyl, O-1-ethylbutyl, 0-2-ethylburyl, oleic, 1,2-trimethylpropyl, 0-1,2,2-trimethylpiopyl, oleoethyl-1-methylpropyl, oleoyl Ethyl 2-methylpropyl, on-hexyl, on-heptyl, on-octyl, 0-n-nonyl or O-n-decyl.

Here, compounds of the general formula (I) are obtained, wherein Z is a radical - CR ⁷ R ⁸ R ⁹ , and R ⁷ , R ⁸ and R ^{9 have} the abovementioned general, preferred and particularly preferred meanings.

Ortho-radical of the general formula (XI):

As further electrophiles it is also possible to use orthoers of the general formula (XI) in the reaction according to the invention,

wherein

R ⁷ C-Cso alkyl, C _Σ -C _ϊ o alkenyl, -C ₂ o-alkynyl, C ₇ -C ₂₀ -A] kylary1, C ₆ -C ₀ -ATyI, C ₃ -C ₀ - heteroaryl, by Cs-Cio-heteroaryl substituted phenyl, _{C3-C2o-cycloalkyl,} C ₃ -C ₂₀ - cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, -C ₂ o-hydroxyalkyl, Cs-Cao-Acyioxyalkyl, Ci- _C2o Alkoxy, C ₂ -C ₂ o -alkoxyalkyl, C ₂ -C ₂₀ -alkylthioalkyl, C ₂ -C ₂ t> -aminoalkyl, Cj-C _2O - acylaminoalkyl, C ₂ -C ₂ o-carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical - C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, C 1 -C 4 alkyl, C 1 -C 6 hydroxyalkyl, C 1 -C ₈ alkoxyalkyl or C 1 -C ₈ acyloxyalkyl,

R ⁸ , R ⁹ and R ^{14 are the} same or different and are -O-C 1 -C 30 -alkyl. Orthoester of the general formula (XI) are preferably employed, wherein, R ⁷ CRCI ₄ alkyl, C ₂ -C, o-alkenyl, C ₂ -Cio-alkynyl, C ₅ -C ₀ cycloalkyl, C ₅ -C | ₀ -Cycloalkenyl, C5-C] o-cycloalkynyl, Ci-Cio-hydroxyalkyl, C ₃ -Cio-Acyloxyalky-, CpCio-alkoxy, C ₂ - Cio-alkoxyalkyl, C ₂ -Cιo-alkylthioalkyl, C ₂ -Ci <rAminoalkyl , C ₃ -Cio-Acylaminoalkyl, C ₂ -Cio-Catboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or an oxazolyl, triazolyl, morpholinyl or pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 6 and R is hydrogen C _r C, ₀ alkyl, C, -C ₈ -hydroxyalkyl, d-Cg alkoxyalkyl or C ₈ - represents acyloxyalkyl, and R ^8, R ⁹ and R ¹⁴ are identical or different and represent -0-Ci-C ₂ o alkyl ,

Orthoesters of the general formula (XI) are particularly preferably used in the reaction according to the invention, in which

R ⁷ denotes a straight-chain or branched C 1 -C 10 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl], tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyi, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylibutyl, 1, 1, 2-trimethylpropyl, 1, 2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, n-octyl, n-nonyl or n-decyl represent or and represent a CrCβ-cycloalkyl radical, in particular a cyclopentyl or a cyclohexyl radical, and

R ^8, R ⁹ and R ¹⁴ are identical or different and are -O-C | -C ₄ -alkyl, in particular O-methyl, O-ethyl, on-propyl, O-iso-propyl, On-butyl, O scc-butyl, O-tert-butyl, on-pentyl, O-1-methylbutyl, O-2-methylbutyl, O-3-methylbutyl, O-neo-pentyl, 0-1-ethylpropyl, on-hexyl, Ol, 1-dimethylpropyl, O-1,2-dimethylpropyl, 0-1,2-dimethylpropyl, O-1-methylpentyl, O-2-methylpentyl, O-3-methylpentyl, 0-4-methylpentyl, Ol, l Dimethylbutyl, O-1,2-dimethylbutyl, O-1,3-dimethylbutyl, O-2,2-dimethylbutyl, O-2,3-dimethylbutyl, O-3,3-dimethylbutyl, O-1-ethylbutyl, O- 2-ethylbutyl, 0-1,1,2-trimethylpropyl, 0-1,2,2-trimethylpropyl, Ol-ethyl-1-methylpropyl, Ol-ethyl-2-methylpropyl, on-hexyl, on-heptyl, on- Octyl, 0-n-nonyl or O-n-decyl. In this case, compounds of the general formula (I) are obtained, in which Z represents a radical -CR ⁷ R ⁸ R ⁹ , in which R ⁷ , R ⁸ and R ^{9 have} the abovementioned meanings,

Epoxides of the general formula (XII):

As further electrophiles, it is also possible to use epoxides of the general formula (XII) in the reaction according to the invention,

wherein

R ¹⁰ and R "are the same or different and are -C ₃₀ -AUCyI, C _r C ₂₀ alkenyl, C ₂ -C ₂ o-alkynyl, C ₇ -C ₂ o-Alkylaiyl, Cβ-Cio-aryl, Cs-CIO heteroaryl, by CrCio-heteroaryl substituted phenyl, C ₃ -C ₂ o-cycloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, Ci-C ₂ o-hydroxyalkyl, C ₃ -C ₂₀ - acyloxyalkyl, C ₂₀ alkoxy, C ₂ -C ₂₀ - alkoxyalkyl, C ₂ - C ₂₀ alkylthioalkyl, C ₂ -C ₂₀ aminoalkyl, C ₃ -C ₂₀ -Acylaminoalkyl, C ₂ -C ₂ o-carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched Alkylengrupppe in which n is an integer from 1 to 10 and R Is hydrogen, C ₁ -C ₄ -alkyl, C ₁ -C ₈ -hydroxyalkyl, C 1 -C ₈ -alkoxyalkyl or C 1 -C ₈ -cycloxyalkyl,

Epoxides of the general formula (XII) are preferably used, wherein R ¹⁰ and R ^{1 1} are the same or different and are Ci-C ₄ alkyl _(C ₂ -Cio-alkenyl, C ₂ -C ₀ alkynyl, C ₅ -C ₀ cycloalkyl, C ₅ -C ₀ _{cycloalkenyl;} C ₅ -C | ₀ cycloalkynyl, Ci-Cio-hydroxyalkyl, Cϊ-Cio-Acyloxyalky-, Ci-Cio-alkoxy, C ₂ -C ₀ - alkoxyalkyl, C ₂ - Ci ₀ alkylthioalkyl, C ₂ - C _fl aminoalkyl, Cj-Cio-acylaminoalkyl, C ₂ -C ₀ carboxyalkyl, a benzoxazolyl, benzo-l, 3-dioxolanyl, or oxazolyl, triazolyl, morpholinyl or a pyrazolyl-substituted phenyl radical, a radical -C _n H _2n C (O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 6 and R is hydrogen C, -d _o -alkyl, Ci-Cg-hydroxyalkyl, Cj-Cg-alkoxyalkyl or Ci-Cg-acyloxyalkyl.

Particular preference is given to using epoxides of the general formula (XII) in which R ¹⁰ and R ^{11 are} identical or different and represent a straight-chain or branched C 1 -C 20 -alkyl radical, in particular methyl, ethyl, n-propyl, isopropyl, n- Butyl, sec-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, neo-pentyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2- Dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbenzyl, 2,2-dimethylbutyl, 2, 3-dimethylbutyl, 3,3- Dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, 1-ethyl-2-methylpropyl, n-hexyl, n-heptyl, represent n-octyl, n-nonyl or n-decyl or and represent a Cs-Cg-cycloalkyl radical, in particular a cyclopentyl or a cycloliexyl radical.

In this case, compounds of the general formula (I) are obtained, wherein Z is a residue - CHR ¹⁰ CHR ¹¹ OH, wherein R ¹⁰ and R ^{11 have} the abovementioned general, preferred and particularly preferred meanings.

Sulfonyl chlorides of the general formula (XIII):

As further electrophiles, it is also possible to use sulfonyl chlorides of the general formula (XHI) in the reaction according to the invention,

O O

^N V (XIIi)

Cl ^ R ¹² in which

R ^{12 represents} an optionally substituted Cβ-Cu-aryl radical.

In the reaction according to the invention, preference is given to using sulfonyl chlorides of the general formula (XIII) in which R ^{12 is} phenyl, naphthyl, phenanthryl.

In this case, compounds of the general formula (I) are obtained, wherein Z is a radical -SChR ¹² , wherein R ^{12 has} the abovementioned meanings.

The fiction, contemporary method is usually carried out so that under inert gas magnesium is vo voiced and is mixed with a solvent. Subsequently, optionally elemental iodine or an alkyl halide such as ethyl bromide, 1,2-dichloroethane or 1,2-dibromoethane, preferably ethylbroraid added. The addition of elemental iodine or an alkyl halide has proven especially in the use of magnesium. The temperature is maintained in a range of 20 ⁰ C to 8O ⁰ C and adjusted depending on the solvent used. Subsequently, the compound of general formula (II) is added. It has been found useful to solve this compound of the general formula (II) in the same solvent as that presented. Usually, the molar ratio of magnesium to the compound of the general formula (II) is (0.9-1.6): 1, preferably (1.0-1.4): 1. The addition is made in such a manner that the Temperature of the reaction mixture in a range of 2O ⁰ C to 8O ⁰ C moves. Again, an adaptation to the solvent used can be done. Subsequently, will Usually stirred for a while, the reaction mixture was cooled to a temperature of 20 ⁰ C to 5O ⁰ C and filtered off or decanted.

The addition of the additive is then usually followed by the reaction with the electrophile in the form of the isocyanate of the general formula (III), the heterocycle of the general formula (IV), the carbamoyl chloride of the general formula (V), of the amino ether of the general formula ( VI), the aldehyde of the general formula (VII), the ketone of the general formula (VIH), the nitrile of the general formula (IX), the acetal of the general formula (X), the orthoester of the general formula (XI), the epoxide the general formula (XII) or the sulfonyl chloride of the general formula (XIII). These compounds may be either as such, i. be used in substance or diluted in an organic solvent.

A variant of the procedure is to add the electrophile to the reaction mixture, which is obtained in the reaction of the compound of general formula (II) with magnesium. It is also possible, however, to reverse the order of addition, i. the reaction mixture from the reaction of the compound of the general formula (II) with magnesium is added to the respective electrophiles of the formulas (III) to (XIII).

Usually, the molar ratio of the compound of the general formulas (III) to (XIII) to the compound of the general formula (II) is (0.95-1.4): 1, preferably (1.0-1.2): 1. It is also possible to partially distill off the solvent used for the reaction with magnesium before adding these reagents. In this case, the reagent to be added is then advantageously used dissolved in an organic solvent, for example toluene or xylene. After the reaction, the still present, originally used for the reaction with magnesium and lower boiling solvent can be further distilled off and optionally recycled.

After the reaction, the reaction mixture is treated with aqueous acid and the mixture is worked up, for example by phase separation or extraction with an organic solvent. The desired compound of general formula (I) is removed via the organic phases, dried and isolated.

The above-mentioned steps of the reaction and the work-up can be carried out not only batchwise but also continuously. If a continuous operation is used, the solution obtained after the reaction of the compound of the general formula (II) with magnesium is advantageously transferred via an overflow device into the next reaction vessel, thus separating off the excess magnesium.

Examples:

Example 1: (comparison: no addition of an additive)

Magnesium turnings (0.87 g) introduced under nitrogen were placed in a heated flask and treated with 7.6 ml of THF. At 5O ⁰ C to start the reaction about 92 mg of ethyl bromide were added. Thereafter, a solution of 5 g of menthyl chloride in 10.2 ml of THF at 55 ⁰ C in 3.5 h was added to the mixture. Subsequently, stirring was continued at 70 ^° C. for a further 1.3 hours. After cooling the mixture to 22 ⁰ C, this was filtered and transferred to another flask. To the filtered reaction solution was added 3.05 g of butyl isocyanate and stirring was continued for one hour. While cooling and stirring, this mixture was added to 127 g of 2% hydrochloric acid igc. The mixture was extracted three times with 20 ml dichloromethane each. The combined organic phases were dried over magnesium sulfate and concentrated.

Was obtained 5.70 g of pale yellow oil, which contains 53% product according to gas chromatographic analysis. This corresponds to a yield of 45% of theory.

Example 2: (comparison: no addition of an additive)

Magnesium turnings (0.87 g) introduced under nitrogen were placed in a heated flask and treated with 7.6 ml of THF. At 50 ^° C., about 92 mg of ethyl bromide were added to start the reaction. Then a solution of 5 g of menthyl chloride in 10.2 mL of THF was added to the mixture 55 h at ⁰ C in 3.5. The mixture was then stirred at 7O ⁰ C for a further 1.3 hours. After cooling the mixture to 22 ⁰ C, this was filtered and transferred to another flask. To the filtered reaction solution was added 2.23 g of ethyl isocyanate and stirring was continued for one hour. While cooling and stirring, this mixture was added to 127 g of 2% hydrochloric acid. The mixture was extracted three times with 20 ml dichloromethane each. The combined organic phases were dried over magnesium sulfate and concentrated.

Obtained were 5.30 g pale yellow oil, which according to gas chromatographic analysis contains 43% product. This corresponds to a yield of 39% of theory.

Example 3:

Preparation of a menthyl magnesium chloride solution

Magnesium (8.0 g) initially introduced under nitrogen was placed in a heated flask and treated with 31.3 ml of THF. At 60 ^° C., 1.5 ml of dibromomethane was added to start the reaction. Then, a solution of 47.5 g of menthyl chloride in 49 ml of THF was added to the mixture at 55-65 ° C in 3 hours. It was then under 3 hours Reflux, and stirred at 50 ⁰ C for 15 hours. After cooling to 22 ⁰ C 123.7 g of menthyl magnesium solution were obtained.

Example 4: (comparison, no addition of an additive)

Reaction of the menthyl magnesium chloride solution with ethyl isocyanate

In a flame-dried flask 6.16 g of ethyl isocyanate were placed in 5 ml THF under nitrogen and at 25-30 ⁰ C in 15 prepared in Example 3 solution of Menthylmagnesiumchlorid min mixed with 37.0 g. This solution was stirred for 17 hours at 23 ° C and then for 20 hours at 5O ⁰ C. After cooling to 23 ° C, the solution was added dropwise to 350 g of a cooled to 1O ⁰ C 2% hydrochloric acid solution. This mixture was stirred for 16 hours at 23 ⁰ C, before being extracted twice with 50 ml of dichloromethane. The combined dichloromethane phases were dried with 5 g of sodium sulfate and then concentrated.

There were obtained 14.2 g of yellow oil, which crystallized during storage. According to gas chromatographic analysis, the mixture contains 61% of the desired N-ethyl-p-menthyl-3-carboxamide, this corresponds to a yield of 53% of theory. Only one epimer could be observed.

Example 5 (Inventive Addition of Lithium Chloride) Reaction of the menthyl magnesium chloride solution with ethyl isocyanate

0.72 g of lithium chloride together with 7.17 g of ethyl isocyanate in 5 ml of THF were placed under nitrogen in a heated flask and 43.1 g of the solution of menthylmagnesium chloride prepared in Example 3 were added at 25-3O ⁰ C in 15 minutes. This solution was stirred for 17 hours at 23 ⁰ C and then at 50 ⁰ C for 20 hours. After cooling to 23 ° C, the solution was added dropwise to 410 g of a cooled to 10 ⁰ C 2% hydrochloric acid solution. This mixture was stirred for 16 hours at 23 ⁰ C, before being extracted twice with 50 ml of dichloromethane. The combined dichloromethane phases were dried with 5 g of sodium sulfate and then concentrated.

There were obtained 17.85 g of yellow oil, which crystallized during storage. According to gas chromatographic analysis, the mixture contains 71% of the desired N-ethyl-p-menthyl-3-carboxamide, this corresponds to a yield of 67% of theory. Only one epimer could be observed.

Claims

claims:

1. Process for the preparation of compounds of the general formula (I)

in which

Z is Ct = O) NR ¹ R ² or CH ₂ NR ¹ R ² , in which

R ¹ is C-Cjo alkyl, C ₂ -C _2R alkenyl, C ₂ -C ₂₀ -AUdHyI,

C ₆ -Cn> aryl, C ₅ -Cio -hetcroaryl or C ₅ -C ₂₀ -heteroaryl-substituted phenyl, C ₃ -C _2O -cycloalkyl, C ₃ -C ₂₀ -cycloalkenyl, C ₃ -C ₂₀ -cycloalkynyl , Ci-C ₂ o-hydroxyalkyl, C ₃ -C ₂₀ -Acyloxyalkyl, C | -C _{2 ()} -alkoxy, C ₂ -C ₂₀ alkoxyalkyl, C ₂ -C ₂₀ - alkylthioalkyl, C ₂ -C aminoalkyl _2ß , C ₃ -C ₂ o-acylaminoalkyl, C ₂ -C ₂₀ -carboxyalkyl, a radical -C _n H _2n Cf = O) R or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, Ci-C | ₀ -alkyl, Ci-Cs-hydroxyalkyl, Cj-Cg-alkoxyalkyl or C | -C ₈ -acyloxyalkyl, R ^{2 has} the same meanings as R ¹ , furthermore hydrogen or a radical - X-OH, where X is a represents alkylene, optionally substituted by one or more hetero atoms, preferably oxygen or sulfur, is interrupted, or wherein - straight or branched C ₁ -C _2O

R ¹ and R ² together form an alkylene chain optionally interrupted by one or more heteroatoms, preferably oxygen or sulfur, taken together with the nitrogen atom to which R ¹ and R ^{2 are} bonded, forming a maximum 10-membered Ritig, or ZC ( OH) R ⁴ R ⁵ , in which

R ⁴ and R ^{5 are the} same or different and those previously indicated for R ¹

Own meanings and

Alternatively, R ⁵ may be hydrogen, or Z is C (= O) R ⁶ , where

R ^{6 has} the meanings given in R ¹ , or Z is CR ⁷ R ⁸ R ⁹ , in which

R ^{7 has} the meanings given for R 'and

R ⁸ and R ^{9 are the} same or different and represent O-C 12 -alkyl, or alternatively

R ^{9 is} O-C, -C ₃ o-alkyl, or Z is CHR ¹⁰ CHR ¹¹ OH, in which

R ^{! 0} and R ^{11 are the} same or different and those previously indicated for R ¹

Have meanings, or Z represents SO ₂ R ¹² , in which

R ^{12 is} an optionally substituted

stands.

by first preparing a compound of general formula (II)

wherein

Isocyanates of the general formula (III),

O = C = NR ¹ (III) where R ^{1 has} the meanings given for the general formula (I),

Heterocycles of the general formula (IV),

wherein R ¹ and X have the meanings given for the general formula (I),

Carbamoyl chlorides of the general formula (V),

wherein R ¹ and R ² have genaiinten meanings for the general formula (I),

Ainoethers of general formula (VI),

in which R ¹ and R ^{2 have} the meanings given for the general formula (I) and R ^{13 is} a C ₁ -C ₂ 0-alkyl radical,

Aldehydes of the general formula (VII),

in which R ^{4 has} the meanings given above for the general formula (I) ⁽ t ^v en ^{iι> has} meanings,

Ketones of the general formula (VEiI),

wherein R ⁴ and R ^{5 are} identical or different and have the meanings given above for R ¹ ,

Nitriles of the general formula (IX),

N≡CR ⁶ (IX) in which R ^{6 has} the meanings given above for the general formula (I),

Acetals of the general formula (X),

wherein R ⁷ and R ^{8 are} identical or different and have the meanings given for R ¹ in the general formula (I) and R ⁹ and R ^{14 are} identical or different and are O-C ¹ -C ₃₀ -alkyl,

Orthoesters of general formula (XI),

in which R ^{7 has} the meanings given for R ¹ in the general formula (I), and R ⁸ , R ⁹ and R ^{14 are} identical or different and represent 0-C 1 -C ₃₀ -alkyl, Epoxides of general formula (XII) ₁

O

_R 10x ^ \ _R 11 ( ^X ")

wherein R ¹⁰ and R ¹ 'have the meanings given for the general formula (1), and • sulfonyl chlorides of the general formula (XIII)

O. .0

V (XII) he R J'2

wherein R ^{12 has} the meanings given for formula (II).

2. The method of claim 1, wherein the additive is selected from the group consisting of LiCl, LiBr, ZnCl _2, ZnBr _2, SnCl _2, SnCl _4, MgCl _2, MgBr _2, AlCl _3, TiCl _4, Al (OiPr) ₃ , Ti (OiPr) ₄ , CeCl ₃ , ZnEt, CuBr, LiClO ₄ , BCl ₃ , BF ₃ and their etherate, boric acid, unsubstituted and substituted phenylboronic acids.

3. The method of claim 1 or 2, v / obei the additive is added before, during or after addition of the electrophile of the general formulas (III) to (XIU), preferably before the addition of the electrophile.

4. The method according to one or more of claims 1 to 3, wherein the additive in an amount of 1 -100 mol%, preferably 10-50 mol%, based on by the reaction of the compound of general formula (I) with magnesium forming Grignard compound is used.

5. The method according to one or more of claims 1 to 4 using an isocyanate of the general formula (III), wherein

R ¹ Ci-C _3O -AikVl, C ₂ -C _{2 (r} alkenyl, C ₂ -C ₂₀ alkynyl, C ₇ -C ₂₀ alkylaryl, C ₆ -C ₁₀ aryl, C ₅ -Cio heteroaryl or by C ₅ -Cio-heteroaryl-substituted phenyl, C ₃ -C ₂₀ -cycloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, Ci-co-hydroxyalkyl, C ₃ - C ₂ o-acyloxyalkyl , C ₂₀ alkoxy, C ₂ -C ₂₀ alkoxyalkyl, C ₂ - C ₂₀ - alkylthioalkyl, C ₂ -C ₂₀ aminoalkyl, Cs-C ^ -Acylaminoalkyl, C ₂ -C ₂ o-carboxyalkyl, a group - C _n H _2n Q = O) R ^' or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, Ci-Ci ₀ - alkyl, CHVHydroxyalkyl, Cr-C ₈ - alkoxyalkyl or Ci-Cβ-acyloxyalkyl group, wherein compounds of the general formula (I) are obtained in which Z is a radical -C (= O) is NR'H and R ^{1 has} the meanings given above.

6. The method according to one or more of claims 1 to 4 using a heterocycle of the general formula (FV)

in which ^(IV)

R ^{1 has} the meanings, the R ¹ in the general formula (III) according to claim

5, and X is a straight-chain or branched C _r C ₂ o-alkylene group _} preferably a straight-chain or branched C 1 -C ₈ -alkylene group, more preferably a methylene, ethylene, n-propylene, n-butylene or n- pentylene

Represents group, these general, preferred or particularly preferred alkylene groups optionally by one or more

Heteroatoms, preferably oxygen or sulfur, are interrupted, whereby a compound of the general formula (I) is obtained, in which Z is a radical

- C (= O) NR'R ² , wherein R ^{1 has} the abovementioned meanings given for the general formula (IV), R ^{2 is} a radical X-OH and X are those previously mentioned for the general formula (IV) Has meanings.

7. The method according to one or more of claims 1 to 4 using a carbamoyl chloride of the general formula (V)

wherein R ¹ and R ^{2 are the} same or different and have all the meanings given above for the general formula (III), whereby compounds of the general formula (I) are obtained, in which Z is a radical -CX = O) NR ¹ R ² wherein R ¹ and R ^{2 are the} same or different and have all the meanings given above for the general formula (HI).

8. The method according to one or more of claims 1 to 4 using an amino ether of the general formula (VI)

(Vi)

wherein

R 'is Ci-Cjo-alkyl, Ca-Cjo-alkenyl, G-Czo-alkynyl, C ₇ -C ₂₀ -alkylaryl, C ₆ -C ₁₀ -ATyI, Cs-Cio-heteroaryl or by Cs-Cio-heteroaryl-substituted phenyl, C ₃ - C ₂ o-cycloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ -C ₂₀ -Cyc1oalkinyl, C ₁ -C ₂ Q- hydroxyalkyl, C ₃ -C ₂₀ -Acyloxyalkyl, C ₂ O -Akoxy, C ₂ -C ₂ <ralkoxyalkyl, C ₂ -C ₂₀ -alkylthioalkyl, C ₂ -C ₂₀ -aminoalkyl, C ₃ -C ₂₀ -alkylaminoalkyl, C ₂ -C ₂₀ -carboxyalkyl, a radical -C _n H _2n C (= O) R ^' or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched Alkylengmpppe in which n is an integer from 1 to 10 and R is hydrogen, Q-Cio Alkyl, C 1 -C ₈ hydroxyalkyl, C 1 -C 12 alkoxyalkyl or C 1 -C ₈ acyloxyalkyl,

R ^{2 has} the same meaning as R ¹ , further hydrogen or a radical - X-OH, where X represents a straight-chain or branched Ci-C _2O - alkylene group, which is optionally interrupted by one or more heteroatoms, or wherein

R ^{13 is} a C ¹ -C ₂₀ -alkyl radical, compounds of the general formula (I) are obtained in which Z is a -

Rest -CH ₂ NR ¹ R ² and R ¹ and R ^{2 have} the meanings given above.

9. The method according to one or more of claims 1 to 4 using an aldehyde of the general formula (VIl)

wherein

R ¹ * Cj-Cao-alkyl, C ₂ -C ₂₀ -alkenyl, C ₂ -C ₂ o-alkynyl, C ₇ -C ₂ o-alkylaryl, C ₆ -C | _0- aryl, Cs-Cio-heteroaryl or by Cs-C _t o-heteroaryl-substituted phenyl, C ₃ -C _2O - cycloalkyl, Ca ^ o-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, -CC ₂ o -Hydroxyalkyl, C ₃ -C ₂₀ -acyloxyalkyl, C ₁ -C ₂₀ -alkoxy, C ₂ -C ₂₀ -alkoxyalkyl, C ₂ -C _2O -alkylthioalkyl, C ₂ -C ₂ o-aminoalkyl, C ₃ -C ₂₀ - Acylaminoalkyl, C ₂ -C ₂₀ carboxyalkyl, a radical -C "H _2n C (= O) R ^' or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group, in n is an integer of 1 to IO and R is hydrogen, Ci-Ci _o alkyl, Ci-Cg-Hydroxyallcyl, Ci-Cg-Alkoxyalkyl or Ci-Cg-Acyloxyalkyl or a Heterocyclus represents. wherein compounds of the general formula (I) are obtained in which Z is a radical -C (OH) R ⁴ R ⁵ , R ^{4 are} the abovementioned general; preferred and particularly preferred B edeutiingen and R ^{5 is} hydrogen.

10. The method according to one or more of claims 1 to 4 using a ketone of the general formula (VlII)

wherein

R ⁴ and R ⁵ are the same or different and Ci-C ₃ -alkyl, C ₂ -C ₂ -alkenyl, C ₂ -C ₂₀ - alkynyl, C ₇ -C ₂ o-alkylaryl, C ₆ -C ₁₀ - ATyI, C ₃ -C ₀ -heteroaryl or C ₅ -C ₁₀ - heteroaryl substiruiertes phenyl, C ₃ -C ₂ o-cycloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ - Cao-cycloalkynyl. Ci-C ₂₀ -HydiOxyalkyl, C ₃ -C ₂₀ acyloxyalkyl, Ci-C ₂ Q-AIkOXy. C ₂ -C ₂ o-alkoxyalkyl, C ₂ -C ₂ o-alkylthioalkyl, _J C ₂ -C ₂₀ -aminoalkyl, C ₃ -C ₂₀ -acylaminoalkyl, C ₂ -C ₂ o-carboxyalkyl, a radical -C "H _2n C (= O) R or a radical -C _n H _2n COOR ', where -C _n H _{2n is} a straight-chain or branched alkylene group in which n is an integer from 1 to 10 and R is hydrogen, Ci-C | ₀ alkyl, Ci- <: ₈ hydroxyalkyl, Ci-Cs-Cg alkoxyalkyl or Q represents-acyloxyalkyl. wherein compounds of the general formula (I) are obtained in which Z is a radical -C (OH) R ⁴ R ⁵ and R ⁴ and R ^{5 have} the meanings given above.

1 1. The method according to one or more of claims 1 to 4 using a nitrile of the general formula (IX)

N≡CR ⁶ (IX) in which R ^{6 has} the meanings that R ^{1 has} in the general formula (III), giving compounds of the general formula (I) in which Z represents a -COR ⁶ radical and R ^{6 represents} the Has meanings which R ^{1 has} in the general formula (III).

12. The method according to one or more of claims 1 to 4 using an acetal of the general formula (X) R ¹⁴ \ R ⁹

Y (X)

R ⁷ ^ R ⁸ wherein

R ⁷ and R ^{8 are} identical or different and C 1 -C ₃₀ -alkyl, C ₂ -C ₂ o-alkenyl, C ₂ -C _2Ü -alkynyl, C ₇ -C ₂ o-alkylaryl, C ₆ -Cιo-aryl , C ₅ -C ₀ -heteroaryl or Cs-C ₁₀ - substituted heteroaryl, phenyl, C ₃ -C ₂₀ cycloalkyl, C ₃ -C ₂ o-Cycloalkeny1, C ₃ - C ₂ o-cycloalkynyl, Ci-C ₂ o hydroxyalkyl, C ₃ -C ₂ o-acyloxyalkyl, Ci-C _2O -alkoxy, C ₂ -C ₂ o-alkoxyalkyl, C ₂ -C2o-alkylthioalkyl, C ₂ -C ₂₀ -Atninoalkyl, C ₃ -C ₂₀ - Acylarainoalkyl , C ₂ -C ₂ o-carboxyalkyl, a radical -C _n H ₂ "C (= O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched Alkylengrupppe, in which n is an integer from 1 to 10 and R is hydrogen, C _r C, ₀ -Alky], Ci-Q-hydroxyalkyl, C, -C ₈ -AIkoxyalkyl or C -C acyloxyalkyl, and

R ⁹ and R ^{14 are the} same or different and are -O-C ₃ -C ₃ -alkyl, to give compounds of general formula (I) in which Z is a radical - CR ⁷ R ⁸ R ⁹ , and R ⁷ , R ⁸ and R ^{9 have} the meanings mentioned above.

13. The method according to one or more of claims 1 to 4 using an orthoester of the general formula (XI)

wherein

R ⁷ is C, -C ₃ -alkyl, C _r C ₂ o-alkenyl, C ₂ -C ₂₀ -AIkJiIyI, C ₇ -C ₂₀ alkylaryl, C ₆ -C ₀ aryl,

C ₅ -C] ₀ -HeteiOaryl or by Cs-Cio-heteroaryl substituted phenyl, C ₃ - C ₂₀ cycloalkyl, C ₃ -C ₂ o-cycloalkenyl, C ₃ -C ₂ o-cycloalkynyl, C ₂₀ - hydroxyalkyl, C ₃ -C ₂ o-acyloxyalkyl, C -C ₂₀ -A lkoxy, C ₂ -C ₂ o-alkoxyalkyl, C ₂ - C ₂₀ alkylthioalkyl, C ₂ -C ₂₀ - Aminoalkyi, C ₃ -C ₂₀ - Acylaminoalkyl, C ₂ -C ₂₀ carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR ^' , where -C _n H _{2n is} a straight-chain or branched alkylene group, in which n is an integer from 1 to 10 and R is hydrogen, C 1 -C 10 -alkyl, C 1 -C ₈ -hydroxyalkyl, C 1 -C 6 -alkoxyalkyl or C 1 -C ₈ -acyloxyalkyl, and

R ⁸ , R ⁹ and R ^{14 are the} same or different and are -O-C 1 -C ₃₀ -alkyl, to give compounds of general formula (1) wherein Z is a radical - CR ⁷ R ⁸ R ⁹ , wherein R ⁷ , R ⁸ and R ^{9 have} the meanings given above.

14. The method according to one or more of claims 1 to 4 using an epoxide of the general formula (XIl)

O

_R 10 ^ \ 11 (XU)

wherein

R ¹⁰ and R ¹¹ are identical or different and are C | -C ₃₀ alkyl, C ₂ -C ₂ O- alkenyl, C ₂ -C ₂₀ - alkynyl, C ₁ -C _O - alkylaryl, Cβ-Cio-aryl, C ₀ ₅ -C -heteroaryl or C $ -C \ o- heteroaryl-substituted phenyl, C ₃ -C ₂₀ cycloalkyl, Cj-do-cycloalkenyl, C ₃ - C _{2 (r} cycloalkynyl, C _r C ₂₀ hydroxyalkyl, Ca-C ₂ o-acyloxyalkyl, C ₂ -alkoxy, C ₂ -C ₂₀ alkoxyalkyl, C ₂ -C ₂₀ - alkylthioalkyl "C ₂ -C ₂ _{o-aminoalkyl)} C ₃ -C ₂₀ - acylaminoalkyl, C C ₂ -C ₂₀ carboxyalkyl, a radical -C _n H _2n C (= O) R or a radical -C _n H _2n COOR, where -C _n H _{2n is} a straight-chain or branched alkylene group, in which n is an integer is from 1 to 10 and R is hydrogen, Ci-Cio-alkyl, C, -C _R hydroxyalkyl, C | -C ₈ -Alkoxyaikyl or C, - Cβ-acyloxyalkyl represent. wherein compounds of the general formula (I) are obtained, in which Z represents a residue -CHR ¹⁰ CHR ¹¹ OH, wherein R ¹⁰ and R ^{11 are} those mentioned above

Own meanings.

15. The method according to one or more of claims 1 to 4 using a sulfonyl chloride of the general formula (XIII)

wherein

R ^{12 is} an optionally substituted Cβ-Cig-aryl radical, preferably

Phenyl, naphthyl or phenanthryl, wherein compounds of the general formula (I) are obtained, in which Z is a radical - SO ₂ R ¹² , wherein R ^{12 has} the abovementioned meanings.

16. The method according to one or more of claims 1 to 15, wherein the molar ratio of the compound of general formulas (III) to (XIII) to the compound of general formula (II) (0.95 - 1.4): 1, preferred (1.0-1.2): 1.

17. The method according to one or more of claims 1 to 16, wherein the method is carried out either batchwise or continuously.