DE102005004055B4 - synthesis method - Google Patents

Abstract

A process in which a bis (alkylthio) carbenium salt is first reacted in the presence of a base with at least one compound having at least one hydroxy group and then reacted with a fluorinating agent and an oxidizing agent to give a crude product containing a compound having at least one difluoroxymethylene bridge, characterized in that the crude product of the reaction is taken up in a strongly polar alcohol or a mixture of strongly polar alcohols.

Description

The present invention relates to a process for the preparation of compounds having a difluoroxymethylene bridge starting from bis (alkylthio) carbenium salts.

Bis (alkylthio) carbenium salts (or dithianylium salts, both of which are used synonymously in the present specification and claims) are organic compounds which have been shown to be useful in the preparation of many more complex compounds. Thus, in the prior art bis (alkylthio) carbenium salts as important starting compounds or intermediates, inter alia, for the preparation of cyclic carboxylic acid orthoester fluorides ( WO 02/34740 A1 ), of α, α-difluoroalkyl peroxides ( DE 102 60 474 A1 ) and in particular of liquid-crystalline compounds having at least one difluoroxymethylene bridge ( WO 01/64667 A1 . WO 01/27221 A1 . WO 02/48073 A1 . WO 03/033619 A1 ). Such liquid-crystalline substances with at least one CF ₂ O bridge between two ring systems have meanwhile become of great importance for versatile liquid-crystal mixtures (see, for example, K. Kirsch, M. Bremer, Angew Chem 2000, 112, 4384, P. Kirsch et al., Angew Chem. 2001, 113, 1528). Bis (alkylthio) carbenium salts can be prepared by various synthetic methods. Commonly used are, inter alia, processes in which a carboxylic acid or an activated carboxylic acid derivative, such as a carboxylic acid halide, a carboxylic acid ester, a carboxylic acid sulfonate or a carboxylic acid anhydride, with at least one thiol and / or a dithiol compound or a Ketendithioketal, which preferably beforehand from a ketone and at least one thiol or dithiol, in the presence of an acid, preferably a Brönsted acid with a non-coordinating or weakly coordinating anion, is converted to a desired bis (alkylthio) carbenium salt (see, for example, US Pat. WO 01/64667 A1 . WO 01/27221 A1 . WO 02/48073 A1 . WO 03/033619 A1 and P. Kirsch et al., Angew. Chem. 2001, 113, 1528). These processes are suitable in principle and in particular on a "laboratory scale" for the preparation of bis (alkylthio) carbenium salts, which can be used as precursors for the synthesis of liquid-crystalline compounds with Difluoroxymethylenbrücke. When carrying out these processes on a commercial or industrial scale, however, there are often difficulties, for example, to reduce the conversion or the yield, unwanted side reactions and by-products, which in turn require costly purification measures lead to increased consumption of reagents, etc., which increased Production costs result.

• – eine Carbonsäure oder ein aktiviertes Carbonsäurederivat und mindestens eine Thiol- und/oder eine Dithiolverbindung mit einer Säure; oder
• – ein Ketendithioketal mit einer Säure

zu einem Bis(alkylthio)carbeniumsalz umgesetzt werden, und das dadurch gekennzeichnet ist, dass die Umsetzung in einem Lösungsmittelsystem erfolgt, welches eine Hauptkomponente aufweist, die mindestens einen aliphatischen Kohlenwasserstoff mit einem Siedepunkt von größer als 90°C (bei Normaldruck, d. h. 1013 mbar) umfasst.Previously, a synthesis method is disclosed in which

• A carboxylic acid or an activated carboxylic acid derivative and at least one thiol and / or dithiol compound with an acid; or
• - a ketene dithioketal with an acid

to a bis (alkylthio) carbenium salt, and which is characterized in that the reaction takes place in a solvent system having a main component containing at least one aliphatic hydrocarbon having a boiling point greater than 90 ° C (at normal pressure, ie 1013 mbar ).

The synthetic method allows the preparation of bis (alkylthio) carbenium salts in excellent yields, which are generally better than those which can be achieved by conventional methods. Furthermore, less by-products are formed than is the case in conventional processes, so that the isolation and purification of the desired bis (alkylthio) carbenium salts is considerably simplified. The process is particularly suitable for the preparation of bis (alkylthio) carbenium salts on a (large) industrial scale.

This method of synthesis is also particularly suitable for the preparation of bis (alkylthio) carbenium salts from carboxylic acids and carboxylic acid derivatives by reaction with thiols or dithiols in the presence of an acid, in particular a Brönsted acid with a non or weakly coordinating anion.

It is preferred that the boiling point of the solvent system at normal pressure is between about 95 ° C and about 130 ° C. It is particularly preferred that the boiling point of the at least one aliphatic hydrocarbon contained in the main component of the solvent system at normal pressure (1013 mbar) is between about 95 ° C and about 130 ° C; more preferably, the boiling point is from 99 ° C to about 110 ° C.

In this case, the at least one aliphatic hydrocarbon of the solvent system is preferably selected from the group consisting of chain and cyclic aliphatic hydrocarbons, particularly preferably heptane, isooctane (2,2,4-trimethylpentane), methylcyclohexane and mixtures of two or three of these aliphatic hydrocarbons. Very particular preference is given to using only one of the aliphatic hydrocarbons in the solvent system of the process according to the invention. In particular, the aliphatic hydrocarbon is isooctane.

The term "main component" in the context of the present invention means that this component has a proportion of the solvent system of more than 50% by volume, based on the total volume of the solvent system. The proportion of the main component which comprises the at least one aliphatic hydrocarbon in the solvent system is preferably at least 75% by volume and more preferably at least 90% by volume and in particular at least 95% by volume, based in each case on the volume of the solvent system.

Surprisingly, it has also been found in a particular embodiment that particularly good results can be achieved and it is therefore particularly preferred if the solvent system consists essentially of only the at least one aliphatic hydrocarbon, d. H. not more than about 5% by volume, and in particular no more than traces of another solvent component (or another solvent or another solvent constituent) are included in the solvent system except for the major component. Under certain circumstances, this can mean that the acid used dissolves only poorly (or not at all) in the aliphatic solvent, which can lead to an increase in the reaction time. Nevertheless, in this embodiment of the invention, the best yields are achieved in comparison, even if the acid dissolves poorly or not at all in the solvent system. In addition, so does the formation of by-products from the reaction of the acid with a different solvent (or solvent component) than the main component, when using a larger proportion of the further solvent (or the other solvent component) than about 5 vol .-% in a mixture with the main component of the at least one aliphatic hydrocarbon can not always be completely suppressed avoided. This further simplifies the work-up of the reaction. Furthermore, when using only a single solvent this can be easily recovered from the reaction mixture in the workup, for example by distillation and recycled to the synthesis process - which is usually too expensive when using a solvent mixture and therefore usually omitted.

In a further embodiment of the invention, the solvent system in addition to the main component of the at least one aliphatic hydrocarbon, another solvent component having a boiling point greater than 90 ° C, wherein the further component one or more solvents selected from the group consisting of aromatic Hydrocarbons and halogenated hydrocarbons. This variant of the method according to the invention makes it possible to bring the acid used in the reaction mixture almost completely or completely into solution. As a rule, this shortens the reaction time compared with the previously known methods or with the embodiment described above, in which the solvent system consists essentially only of the main component.

Preferably, the further solvent component (or its constituents) has a boiling point of not more than about 130 ° C, in particular a boiling point in the range between about 100 ° C and about 120 ° C.

Preference is given to the aromatic hydrocarbons of the further solvent component selected from o-, m- and p-xylene and mixtures of xylenes, chlorobenzene and toluene and mixtures of one or more xylenes with toluene. Preferably, the aromatic hydrocarbon of the further solvent component is toluene.

The halogenated hydrocarbons of the further solvent component are preferably selected from aliphatic hydrocarbons, which are multiply substituted with fluorine and / or chlorine, d. H. aliphatic perchloric, perfluoro and perchlorofluorocarbons, especially 1,1,2,2-tetrachloroethane and tetrachlorethylene.

The proportion of the further solvent component in the solvent system of the process according to the invention is in this embodiment preferably not more than about 25% by volume, in particular not more than about 10% by volume, in each case based on the volume of the solvent system.

The use of the solvent system in the process according to the invention offers significant advantages over the conventional processes, especially in the variant in which a carboxylic acid or a carboxylic acid derivative and a thiol or dithiol are reacted with an acid. If you carry out the reaction, as in WO 01/64667 described without solvent, so the carboxylic acid used or the carboxylic acid chloride used are apparently not fully implemented and obtained the desired bis (alkylthio) carbenium in best moderate yields and with a number of by-products. If, instead, the acid is not used in equimolar amounts but in large excess, the conversion of the starting materials and the yield of the bis (alkylthio) carbenium salt can be improved, but the unreacted acid remains in the reaction mixture and can not or only by consuming purification of the desired Product to be separated. Even an economically and ecologically desirable recovery of the acid is then not possible.

In contrast, the use of the solvent system in the synthesis method according to the invention already by use of a slight excess of the acid, preferably about 1.1 to about 1.8 equivalents, more preferably about 1.3 to about 1.7 equivalents (based on the carboxylic acid or the carboxylic acid derivative), the desired bis (alkylthio) carbenium salt in high yields - usually greater than 90% - to obtain without significant by-products in high purity. By using the solvent system, it is possible and preferred to remove the water formed during the reaction by azeotropic distillation on the water from the reaction mixture and thus to realize a substantial or complete reaction of the starting materials. In this case, the reaction is preferably carried out at at least 90 ° C., more preferably at least about 100 ° C.

On the other hand, unlike the use of, for example, an aromatic hydrocarbon such as toluene as the sole solvent, the use of the solvent system of the present invention offers the advantage of being able to carry out the process of the invention at lower temperatures than with the aromatic alone (e.g. Toluene, boiling point 110 ° C) would be possible.

The acid used in the synthesis process may in principle be any inorganic or organic acid capable of producing the desired formation of the bis (alkylthio) carbenium salt according to the process of the invention. Preferably, the acid is a Bronsted acid of formula VI H ⁺ Y ^- VI,

In this case, Y ^- in formula VI is preferably a non-coordinating or weakly coordinating anion. Hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, tetrafluoroboric acid, hexafluorophosphoric acid, perchloric acid, alkylcarboxylic acid, arylcarboxylic acid, alkylsulfonic acid or arylsulfonic acid is particularly preferably used as the acid of formula VI, one or more hydrogen atoms in the alkyl or aryl groups being substituted by fluorine and / or chlorine can. Optionally, these acids may also be released from one of their salts by the addition of another acid. The non-coordinating or weakly coordinating anion Y ^- is therefore particularly preferably a fluoride, chloride, bromide, iodide, tetrafluoroborate, hexafluorophosphate, perchlorate or alkyl or Arylcarboxylat- or alkyl or arylsulfonate anion, wherein in Alkyl or aryl groups one or more hydrogen atoms may be substituted by fluorine and / or chlorine. The acid of the formula VI is very particularly preferably tetrafluoroboric acid or trifluoromethanesulfonic acid, in particular trifluoromethanesulfonic acid.

The carboxylic acid which can be converted to a desired bis (alkylthio) carbenium salt in the synthesis process is an organic compound having an organic radical bearing at least one -C (= O) -OH group as a functional group. The organic radical may in general be any organic molecule group, for example an aliphatic, alicyclic, aromatic, heterocyclic radical or also a radical composed of aliphatic and / or alicyclic and / or aromatic and / or heterocyclic radicals. Each of these radicals may carry further substituents and functional groups. Preferably, the organic radical of the carboxylic acid is a so-called mesogenic radical, d. H. a radical which may be part of a mesogenic or liquid-crystalline compound. Typical mesogenic radicals or parts of such radicals include unsubstituted and substituted 1,4-cyclohexylene, 1,4-phenylene, 2,6-naphthalenylene, 2,5-dioxanediyl and 2,5-tetrahydropyranediyl rings.

The activated carboxylic acid derivative which can be used in the synthesis process are derivatives of a carboxylic acid as defined above which are activated by modification at the functional carboxyl group for the desired reaction with a thiol or dithiol. Examples such activated carboxylic acid derivatives are carboxylic acid halides, carboxylic acid esters, carboxylic acid sulfonates and carboxylic acid anhydrides.

wobei
a 0, 1 oder 2 ist;
R¹ H, einen unsubstituierten oder einfach mit CN oder einfach oder mehrfach mit F, Cl, Br und/oder I substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen bedeutet, wobei in dem Alkylrest auch eine oder mehrere CH₂-Gruppen durch -C≡C-, -CH=CH-, -O-, -S-, -SO₂-, -C(O)-O- oder -O-C(O)- so ersetzt sein können, dass Heteroatome in der Kette nicht direkt miteinander verknüpft sind;
A¹

A²

b unabhängig für A¹ und A² 0, 1, 2, 3 oder 4 ist;
c und d unabhängig voneinander und unabhängig für A¹ und A² 0, 1, 2 oder 3 sind;
Z¹ eine Einfachbindung, -CH₂CH₂-, -CF₂CH₂-, -CH₂CF₂-, -CF₂CF₂-, -CH₂O-, -OCH₂-, -CF₂O-, -OCF₂-, -C(O)-O-, -O-C(O)-, -CH=CH-, -CF=CH-, -CH=CF-, -CF=CF- oder -C≡C- bedeutet;
X¹ OH, F, Cl, Br, OR², OSO₂R³, OC(=O)R⁴ bedeutet;
R², R³ und R⁴ unabhängig voneinander einen geradkettigen oder verzweigten, unsubstituierten oder einfach oder mehrfach mit dem gleichen oder verschiedenen Substituenten substituierten Alkylrest mit 1 bis 20 Kohlenstoffatomen, in dem eine oder mehrere CH₂-Gruppen unabhängig voneinander so durch -CH=CH-, -C≡C-, -O-, -S-, -CO-O, -O-CO- oder -O-CO-O- ersetzt sein können, dass Heteroatome nicht direkt miteinander verknüpft sind, einen unsubstituierten oder einfach oder mehrfach mit dem gleichen oder verschiedenen Substituenten substituierten Cycloalkyl-, Aryl-, Heterocyclyl- oder Aralkylrest mit bis zu 20 Kohlenstoffatomen bedeuten;
wobei A¹, Z¹, b, c und d jeweils auch verschiedene Bedeutungen annehmen können, wenn a 2 ist.The carboxylic acid or the carboxylic acid derivative preferably has the formula II:

in which
a is 0, 1 or 2;
R ^{1 is} H, an unsubstituted or mono- or polysubstituted with F, Cl, Br and / or I substituted alkyl radical having 1 to 15 carbon atoms, wherein in the alkyl radical and one or more CH ₂ groups by -C≡C -, -CH = CH-, -O-, -S-, -SO ₂ -, -C (O) -O- or -OC (O) - may be replaced so that heteroatoms in the chain are not directly linked are;
A ¹

A ²

b is independently A ¹ and A ^{2 is} 0, 1, 2, 3 or 4;
c and d are independently and independently for A ¹ and A ^{2 are} 0, 1, 2 or 3;
Z ^{1 is} a single bond, -CH ₂ CH ₂ -, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CF ₂ CF ₂ -, -CH ₂ O-, -OCH ₂ -, -CF ₂ O-, -OCF ₂ -, -C (O) -O-, -OC (O) -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF- or -C≡C- means;
X ^{1 is} OH, F, Cl, Br, OR ² , OSO ₂ R ³ , OC (= O) R ⁴ ;
R ² , R ³ and R ⁴ are each independently a straight-chain or branched, unsubstituted or mono- or polysubstituted by identical or different substituent alkyl radical having 1 to 20 carbon atoms, in which one or more CH ₂ groups independently of one another by -CH = CH, -C≡C, -O-, -S-, -CO-O, -O-CO- or -O-CO-O- may be replaced, that heteroatoms are not directly linked to each other, an unsubstituted or mono- or polysubstituted by the same or different substituents substituted cycloalkyl, aryl, heterocyclyl or aralkyl radical having up to 20 carbon atoms;
where A ¹ , Z ¹ , b, c and d may each also assume different meanings when a is 2.

steht und insbesondere einen 1,4-Cyclohexylenring oder einen 1,4-Phenylenring, der gegebenenfalls in 3- und/oder 5-Stellung mit Fluor substituiert ist, bedeutet;
A² für

steht und insbesondere einen 1,4-Cyclohexylenring oder einen 1,4-Phenylenring, der gegebenenfalls in 3- und/oder 5-Stellung mit Fluor substituiert ist, bedeutet;
b unabhängig voneinander für A¹ und A² 0, 1 oder 2 bedeutet;
Z¹ eine Einfachbindung oder -CF₂CF₂- bedeutet; und
X¹ OH, Chlor oder Brom bedeutet.Particular preference is given to carboxylic acids or carboxylic acid derivatives of the formula II in which
a is 0 or 1;
R ^{1 is} a straight-chain or branched, unsubstituted or mono- or polysubstituted with fluorine, chlorine, bromine and / or iodine substituted alkanyl or alkenyl radical and in particular a straight-chain and unsubstituted alkanyl radical having 1 to 8 carbon atoms;
A ¹

and in particular a 1,4-cyclohexylene ring or a 1,4-phenylene ring, which is optionally substituted in the 3- and / or 5-position by fluorine, means;
A ² for

and in particular a 1,4-cyclohexylene ring or a 1,4-phenylene ring, which is optionally substituted in the 3- and / or 5-position by fluorine, means;
b is independently A ¹ and A ^{2 is} 0, 1 or 2;
Z ^{1 represents} a single bond or -CF ₂ CF ₂ -; and
X ^{1 is} OH, chlorine or bromine.

The carboxylic acid or the activated carboxylic acid derivative, in particular of the formula II, is preferably reacted in the synthesis process with at least one thiol of the formula III and / or IV or a dithiol of the formula III-IV: R ³¹ -SH III R ⁴¹ -SH IV HS-R ³¹ R ⁴¹ -SH III-IV in which
R ³¹ and R ⁴¹ in the formulas III and IV are each independently a straight-chain or branched, unsubstituted or mono- or polysubstituted by the same or different substituents alkyl radical having 1 to 20 carbon atoms, in which one or more CH ₂ groups independently so by -CH = CH-, -C≡C-, -O-, -S-, -CO-O-, -O-CO- or -O-CO-O- may be replaced, that heteroatoms are not directly linked an unsubstituted or mono- or polysubstituted by the same or different substituents cycloalkyl, heterocyclylalkyl or aralkyl radical having up to 20 carbon atoms; and
R ³¹ and R ⁴¹ in the formula III-IV together represent a straight or branched, saturated or unsaturated hydrocarbon bridge having 1 to 6 carbon atoms in the bridge, wherein one or more of the hydrocarbon bridge carbon atoms independently of each other with the same or different alkyl, cycloalkyl -, aryl, heterocyclyl or aralkyl / en substituted or bridged by another hydrocarbon chain or may be part of a saturated or unsaturated carbocyclic or heterocyclic ring system.

It is in principle possible that the carboxylic acid or the activated carboxylic acid derivative in particular of the formula II with a single thiol of the formula III or IV in an amount sufficient (formally two molar equivalents) or with two different thiols of the formula III or IV or with a dithiol of Formula III-IV is converted to the desired bis (alkylthio) carbenium salt. If at least one thiol of the formula III or IV is used, it is particularly preferred that only a single thiol be used. In this case, R ³¹ and R ^{41 are} identical and are preferably a straight-chain or branched, unsubstituted alkanyl radical having 1, 2, 3, 4, 5 or 6 carbon atoms; R ³¹ = R ⁴¹ = methyl, ethyl, n-propyl, n-butyl is particularly preferred.

In a particularly preferred embodiment of the synthesis process, the carboxylic acid or the carboxylic acid derivative, in particular of the formula II, is reacted with a dithiol of the formula III-IV. It is particularly preferred that R ³¹ and R ⁴¹ together represent a straight-chain or branched, unsaturated hydrocarbon bridge having 2, 3, 4, 5 or 6 carbon atoms in the bridge, wherein one or two of the hydrocarbon bridge carbon atoms each having an alkanyl radical with each up to four Carbon atoms can be substituted. In particular, R ³¹ and R ⁴¹ together form a -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH ₂ - or -CH ₂ C (CH ₃ ) ₂ CH ₂ -bridge.

wobei
R¹, a, A¹, Z¹, R³¹ und R⁴¹ wie oben für die Formeln II, III, IV beziehungsweise III-IV definiert sind und auch deren bevorzugte Bedeutungen annehmen; und
A^2a für

steht.In a further embodiment of the synthesis process, a ketene dithioketal of the formula V is reacted with an acid to a desired bis (alkylthio) carbenium salt:

in which
R ¹ , a, A ¹ , Z ¹ , R ³¹ and R ^{41 are} as defined above for the formulas II, III, IV and III-IV, respectively, and also assume their preferred meanings; and
A ^2a for

stands.

The representation of Ketendithioketals of formula V required for carrying out this process variant, for example, according to the in the WO 02/48073 disclosed methods; In this case, for example, in a 4-position with R ¹ - [- A ¹ -Z ¹ -] _a - substituted cyclohexanone with 2-trimethylsilyl-1,3-dithiane in the presence of butyllithium to the corresponding Ketendithioketal the formula V implemented.

wobei
R¹, A¹, Z¹, a, A², R³¹ und R⁴¹ wie für die Formeln II, III, IV und III-IV definiert sind; und Y^– wie oben für Formel VI definiert ist. Die Formeln VIIa, VIIb und VIIc geben verschiedene mögliche isomere Formen des nach dem erfindungsgemäßen Syntheseverfahren hergestellten Bis(alkylthio)carbeniumsalz wieder, in welchem Verhältnis die durch die Formeln VIIa, VIIb und VIIc dargestellten isomeren Formen jeweils vorliegen, hängt u. a. von der Wahl der Reste R³¹ und R³², der Bedeutung von A², R¹ und gegebenenfalls A¹ und Z¹ sowie von der Bedeutung von Y^– ab. Im allgemeinen können die Formeln VIIa, VIIb und VIIc als Schreibweise für ein und dasselbe Bis(alkylthio)carbeniumsalz aufgefasst werden.The bis (alkylthio) carbenium salt prepared by the synthesis process is preferably a dithianylium salt which is represented by the formulas VIIa, VIIb and / or VIIc:

in which
R ¹ , A ¹ , Z ¹ , a, A ² , R ³¹ and R ^{41 are} as defined for formulas II, III, IV and III-IV; and Y ^- as defined above for formula VI. The formulas VIIa, VIIb and VIIc represent various possible isomeric forms of the bis (alkylthio) carbenium salt prepared by the synthesis process according to the invention, in which ratio the isomeric forms represented by the formulas VIIa, VIIb and VIIc are present depends inter alia on the choice of the radicals R ³¹ and R ³² , the meaning of A ² , R ¹ and optionally A ¹ and Z ¹ and the meaning of Y ^- from. In general, formulas VIIa, VIIb and VIIc may be construed as notation for one and the same bis (alkylthio) carbenium salt.

steht und insbesondere einen 1,4-Cyclohexylenring oder einen 1,4-Phenylenring, der gegebenenfalls in 3- und/oder 5-Stellung mit Fluor substituiert ist, bedeutet;
A² für

steht und insbesondere einen 1,4-Cyclohexylenring oder einen 1,4-Phenylenring, der gegebenenfalls in 3- und/oder 5-Stellung mit Fluor substituiert ist, bedeutet;
b unabhängig voneinander für A¹ und A² 0, 1 oder 2 bedeutet;
Z¹ eine Einfachbindung oder -CF₂CF₂- bedeutet;
R³¹ und R⁴¹ zusammen für -CH₂CH₂CH₂-, -CH₂CH₂- oder -CH₂C(CH₃)₂CH₂- stehen; und
Y^– ein Trifluormethansulfonat-Anion ist.It is particularly preferred that in the formulas VIIa, VIIb or VIIc
R ^{1 is} a straight-chain or branched, unsubstituted or mono- or polysubstituted with fluorine, chlorine, bromine and / or iodine substituted alkanyl or alkenyl radical and in particular a straight-chain and unsubstituted alkanyl radical having 1 to 8 carbon atoms;
a is 0 or 1;
A ¹ for

and in particular a 1,4-cyclohexylene ring or a 1,4-phenylene ring, which is optionally substituted in the 3- and / or 5-position by fluorine, means;
A ² for

and in particular a 1,4-cyclohexylene ring or a 1,4-phenylene ring, which is optionally substituted in the 3- and / or 5-position by fluorine, means;
b is independently A ¹ and A ^{2 is} 0, 1 or 2;
Z ^{1 represents} a single bond or -CF ₂ CF ₂ -;
R ³¹ and R ⁴¹ together represent -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH ₂ - or -CH ₂ C (CH ₃ ) ₂ CH ₂ -; and
Y ^{- is} a trifluoromethanesulfonate anion.

The synthesis process is generally carried out at ambient pressure and boiling temperature of the solvent system used. Due to the choice of components of the solvent system, the reaction temperature is more than 90 ° C, preferably at least about 95 ° C and not more than 130 ° C, and more preferably between about 99 ° C and about 110 ° C, when the reaction at ambient pressure in the Normally normal pressure (1013 mbar), executed.

The reaction time is not critical per se and can be chosen so that the reaction of the carboxylic acid or the activated carboxylic acid derivative and the at least one thiol compound or dithiol compound with an acid or ketene dithioketals with an acid completely or almost completely to the desired bis (alkylthio) carbenium salt expires. Typical reaction times are between 60 minutes and 48 hours, preferably between 2 hours and 12 hours. If the synthesis process is carried out in an apparatus with a water separator, the progress of the reaction to the desired product can be monitored on the basis of the water formed and separated, and the duration of the exposure set accordingly.

As already stated above, it is preferred that the acid be present in a slight excess of from 1.1 to about 1.8 equivalents, more preferably from about 1.3 to about 1.7 equivalents (based on the carboxylic acid, the carboxylic acid derivative or the ketene dithioketal, respectively). use. In the reaction of a carboxylic acid or a carboxylic acid derivative, the at least one thiol or dithiol is also preferably used in a slight molar excess, based on the carboxylic acid or the carboxylic acid derivative, wherein it is particularly preferred that per 1 equivalent of the carboxylic acid about 2.6 Equivalent thiol or about 1.3 equivalents of dithiol can be used. Acid and thiol are preferably used in a molar ratio of about 1: 2, while acid and dithiol are preferably used in a molar ratio of about 1: 1.

The absolute amount of the solvent system used is likewise not critical per se and is generally chosen so that the carboxylic acid to be reacted or the carboxylic acid derivative to be reacted or the ketene dithioketal to be reacted solves in the solvent at least to the extent that a sufficiently high reaction rate is ensured.

In a particularly preferred embodiment of the present invention, the crude reaction mixture initially obtained by the process described above, which contains the desired bis (alkylthio) carbenium salt, subjected to a further process step, wherein the crude reaction mixture with at least one Diethylenglykoldialkylether of formula I. R ^b - (- OCH ₂ CH ₂ -) ₂ -OR ^a I wherein
R ^{a represents} an unsubstituted, straight-chain or branched alkanyl radical;
R ^{b represents} an unsubstituted and straight-chain alkanyl radical; is offset. In the method step according to the invention, a specific diethylene glycol dialkyl ether of the formula I or a mixture of two or more diethylene glycol dialkyl ethers of the formula I can be used. It is preferred to use only one particular diethylene glycol dialkyl ether of the formula I. Further preferably R ^a and R ^b independently of one another straight-chain C ₁ -C ₁₀ alkanyls, and more preferably selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, n-pentyl, n-hexyl. R ^a and R ^b are in particular n-butyl. By using a diethylene glycol dialkyl ether of the formula I, precipitation or crystallization of the bis (alkylthio) carbenium salt formed from the crude reaction mixture is effected. After separation of the precipitated or crystallized product, for example by filtration and optionally subsequent washing and drying of the solid, the desired bis (alkylthio) carbenium salt is generally obtained in such a purity that makes a further purification before subsequent use superfluous.

The use of a diethylene glycol dialkyl ether of the formula I for separating the bis (alkylthio) carbenium salt from the tubular reaction mixture of the process according to the invention avoids some difficulties which may arise when other ethereal solvents are used, in particular on a (large) industrial scale. Thus, the use of lower dialkyl ethers is undesirable because of their low boiling and flash points on an industrial scale. However, it has also been shown that the use of higher dialkyl ethers or cyclic ethers can sometimes lead to poor yields of reaction product and / or to the formation of by-products.

The displacement of the crude reaction mixture of the synthesis process according to the invention with an ether of the formula I is preferably carried out at about room temperature. Insofar as this is desirable or necessary in individual cases, the addition of the ether of the formula I to the crude reaction mixture of the synthesis process according to the invention can also be carried out at relatively high temperatures; Thus, the hot crude reaction mixture can be mixed with the ether. The desired precipitation or crystallization of the bis (alkylthio) carbenium salt brought about by the addition of the ether of the formula I can, if appropriate, also be accelerated by cooling the ethereal reaction mixture under room temperature, for example at 10 ° C. or 5 ° C.

It should be noted at this point that the precipitation or crystallization of a bis (alkylthio) carbenium salt in particular of the formulas VIIa, VIIb, VIIc by addition of at least one Diethylenglykoldialkylether of formula I and independently of carrying out the synthesis method of the invention in which a carboxylic acid or an activated carboxylic acid derivative and at least one thiol and / or one dithiol compound can be reacted with an acid or a ketene dithioketal with an acid. A further aspect of the present invention is therefore the precipitation and / or crystallization of a bis (alkylthio) carbenium salt in particular of the formulas VIIa, VIIb, VIIc from a solvent or solvent mixture by addition of at least one diethylene glycol dialkyl ether of the formula I as defined above.

The present invention now relates to a process in which a bis (alkylthio) carbenium salt is first reacted in the presence of a base having at least one compound having at least one hydroxyl group and then containing a fluorinating agent and an oxidizing agent to a compound containing at least one Difluoroxymethylenbrücke Is reacted crude product, this process being characterized in that the crude product of the reaction is taken up in a strongly polar alcohol or a mixture of strongly polar alcohols, preferably a strongly polar alcohol. The term "strongly polar alcohol" means an alcohol which is miscible with water and immiscible with alkanes. Preferred strongly polar alcohols for the purposes of this invention include trifluoroethanol, 2-cyanoethanol, hexafluoroisopropanol, di-, tri- and polyols such as glycol, propane-1,2-diol and glycerol and in particular methanol.

This process offers various advantages over the hitherto known processes for preparing compounds having at least one difluorooxymethylene bridge WO 01/64667 A1 known processes for the preparation of compounds having at least one Difluoroxymethylenbrücke by oxidative fluorination usually good yields (up to 90%) of crude product. However, the crude products are usually heavily contaminated, more or less strongly colored and often afflicted with an unpleasant odor. This is particularly disadvantageous in the enlargement from laboratory to production scale. A series of purification procedures are required to obtain a product of the purity necessary for many applications of these compounds, particularly as liquid crystals. Thus, first an extraction of the crude product with a non-polar solvent or a first recrystallization, then a column chromatography using large Quantities of silica gel and finally usually two more recrystallization steps are performed. Furthermore, it is necessary to concentrate the solution obtained after the respective purification step with distillation, if appropriate under reduced pressure. Naturally, the multiplicity of these steps means that the yield of pure product is significantly lower than the crude yield and, at best, between 50 and 60%. Particularly troublesome is the content of sulfur-containing impurities, which are responsible not only for the odor, but also for the formation of polymeric deposits and regularly for complications in the workup and in the subsequent cleaning of equipment and chromatography columns.

In contrast, the treatment according to the invention of the crude product containing the compound having at least one difluorooxymethylene bridge with a strongly polar alcohol, in particular methanol, surprisingly offers numerous advantages. The treatment may consist in that the crude product obtained mostly after simple aqueous workup is stirred with hot, strongly polar alcohol or boiled with strongly polar alcohol, in particular methanol and then the mixture is cooled again with stirring or stirred at or below room temperature, shaken or extracted. Most byproducts, especially the troublesome sulfur compounds, are removed from the product to a degree sufficient for further use of the desired product. If the product which mostly precipitates or crystallizes out of the strongly polar alcohol, in particular methanol in the cold, must or must be further purified, a normally dimensioned column chromatography over silica gel, to which optionally a crystallization step can follow, is sufficient. By this procedure, the necessary number of process steps and the equipment and material costs for the workup of the crude product is significantly reduced. At the same time, a significantly higher pure yield of the desired product is achieved, which deviates only insignificantly from the crude yield.

A process for the preparation of compounds having at least one difluoroxymethylene bridge by reacting a bis (alkylthio) carbenium salt in the presence of a base having at least one compound having at least one hydroxy group and subsequent reaction with a fluorinating agent and an oxidizing agent are known in the art and described inter alia in WO 01/64667 A1 . WO 02/48073 A1 and WO 03/033619 A1 , which are incorporated by reference into the disclosure of the present invention.

The process for preparing a compound having at least one difluorooxymethylene bridge with a bis (alkylthio) carbenium salt of the above-defined formulas VIIa, VIIb, VIIc is preferably carried out. R ¹ , A ¹ , Z ¹ , a, A ² , R ³¹ , R ³² and Y ^- in the formulas VIIa, VIIb, VIIc have the same preferred meanings as mentioned above. The bis (alkylthio) carbenium salt used in the process according to the invention for preparing a compound having at least one difluoroxymethylene bridge can be used as such, ie in isolated form or, for example, in situ from a corresponding ketene dithioketal, in particular of the formula V, with the aid of a suitable acid, in particular of the formula I. be formed and implemented.

stehen; f unabhängig für A³ und A⁴ 0, 1, 2, 3 oder 4 bedeutet;
g und h unabhängig voneinander und unabhängig für A³ und A⁴ 0, 1, 2 oder 3 bedeuten;
Z⁴ eine Einfachbindung, -CF₂O- oder -CO-O- bedeutet; und
X² F, Cl, CN, NCS, SF₅ oder einen unsubstituierten oder einfach mit CN oder einfach oder mehrfach mit F, Cl, Br und/oder I substituierten Alkylrest mit 1 bis 15 Kohlenstoffatomen bedeutet, wobei in dem Alkylrest auch eine oder mehrere CH₂-Gruppen durch -C≡C-, -CH=CH-, -O-, -S-, -SO₂-, -C(O)-O- oder -O-C(O)- so ersetzt sein können, dass Heteroatome in der Kette nicht direkt miteinander verknüpft sind;
wobei A⁴, Z⁴, f, g und h jeweils auch verschiedene Bedeutungen annehmen können, wenn e 2 ist.It is further preferred that the compound having at least one hydroxyl group has the formula VIII: HO-A ³ - [- Z ⁴ -A ⁴ -] _e -X ² VIII in which
e is 0, 1 or 2; A ³ and A ^{4 are} independently for

stand; f is independently A ³ and A ^{4 is} 0, 1, 2, 3 or 4;
g and h independently of one another and independently for A ³ and A ^{4 are} 0, 1, 2 or 3;
Z ^{4 represents} a single bond, -CF ₂ O- or -CO-O-; and
X ^{2 is} F, Cl, CN, NCS, SF ₅ or an unsubstituted or mono- or polysubstituted with F, Cl, Br and / or I substituted alkyl radical having 1 to 15 carbon atoms, wherein in the alkyl radical also one or more CH ₂ groups can be replaced by -C≡C-, -CH = CH-, -O-, -S-, -SO ₂ -, -C (O) -O- or -OC (O) -, that heteroatoms in the chain are not directly linked to each other;
where A ⁴ , Z ⁴ , f, g and h can each also assume different meanings when e is 2.

wobei
L¹, L², L³ und L⁴ unabhängig voneinander H oder F bedeuten; und
X² F, Cl, CN, NCS, SF₅, CF₃, OCF₃, SCF₃ oder SO₂CF₃ bedeutet.The compound of the formula VIII is particularly preferably selected from a compound of the formula VIII-A and of the formula VIII-B:

in which
L ¹ , L ² , L ³ and L ^{4 are} independently H or F; and
X ^{2 is} F, Cl, CN, NCS, SF ₅ , CF ₃ , OCF ₃ , SCF ₃ or SO ₂ CF ₃ .

The compound of the formula VIII which has at least one hydroxyl group is very particularly preferably a compound of the formula VIII-A, in particular where X ² is fluorine, chlorine, cyano, CF ₃ or OCF ₃ .

The base used in the process for preparing a compound having at least one difluorooxymethylene bridge may generally be any basic compound which is capable of at least partially deprotonating the hydroxy group-containing compound having at least one hydroxy group. The preferred base is a tertiary amine, more preferably a tertiary aliphatic amine such as triethylamine or ethyldiisopropylamine.

The fluorinating agent used is preferably selected from the group consisting of aliphatic and aromatic amine-hydrogen fluoride complexes, which particularly preferably comprise: pyridine-hydrogen fluoride complexes, NEt ₃ · 3HF, melamine · HF, polyvinylpyridine · HF. Very particularly preferred are pyridine-hydrogen fluoride complexes and NEt ₃ .3HF.

The oxidizing agent used is preferably a compound which releases halonium equivalents. The halonium equivalents releasing compound selected from the group consisting of dimethyldibromohydanthoin, N-bromosuccinimide, N-iodosuccinimide, bromine, SOCl ₂ , SO ₂ ClF, nitrosonium salts, nitronium salts and chloramine T is particularly preferred. Dimethyldibromohydanthoin, N-bromosuccinimide and bromine are very particularly preferred ,

The synthesis process for the preparation of a compound having at least one difluorooxymethylene bridge is carried out under the conditions customary for this reaction, as described, for example, in US Pat WO 01/64667 A1 disclosed executed.

In a preferred embodiment of the invention, the bis (alkylthio) carbenium salt used in the process according to the invention for preparing a compound with at least one difluoroxymethylene bridge is prepared by the synthesis process described above.

In the context of the present invention, the term "alkyl", unless otherwise defined in this specification or claims, means a straight or branched chain aliphatic hydrocarbon radical of 1 to 15 (ie 1, 2, 3, 4, 5 , 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms; this radical is unsubstituted or singly or multiply with fluorine, chlorine, Substituted bromine, iodine, carboxy, nitro, -NH ₂ , -N (alkanyl) ₂ or cyano, wherein the multiple substitution can be made with the same or different substituents.

If this alkyl radical is a saturated radical, it is also referred to as "alkanyl". Furthermore, the term "alkyl" also includes unsubstituted or correspondingly in particular with F, Cl, Br, I and / or -CN mono- or polysubstituted or differently substituted hydrocarbon radicals in which one or more CH ₂ groups are substituted by -O- ( "Alkoxy", "oxaalkyl"), -S- ("thioalkyl"), -SO ₂ -, -CH = CH- ("alkenyl"), C≡C- ("alkynyl"), -CO-O- or -O-CO- may be replaced, that heteroatoms (O, S) in the chain are not directly linked. Preferably, alkyl is a straight-chain or branched, unsubstituted or substituted alkanyl, alkenyl or alkoxy radical having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms. If alkyl is an alkanyl radical, this is preferably methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl ; CF ₃ , CHF ₂ , CH ₂ F; CF ₂ CF ₃ . The alkanyl radical is particularly preferably straight-chain and unsubstituted or substituted by F.

Since one or more CH ₂ groups in an alkyl radical may be replaced by -O-, the term "alkyl" also includes "alkoxy" or "oxaalkyl" radicals. By alkoxy is meant an O-alkyl radical in which the oxygen atom is bonded directly to the group or substituted ring substituted by the alkoxy radical and alkyl is as defined above; preferably, alkyl is then alkanyl or alkenyl. Preferred alkoxy radicals are methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy and octoxy, where any of these radicals can also be substituted, preferably with one or more fluorine atoms. Particularly preferred is alkoxy-OCH ₃ , -OC ₂ H ₅ , -OnC ₃ H ₇ , -OnC ₄ H ₉ , -OtC ₄ H ₉ , -OCF ₃ , -OCHF ₂ , -OCHF or -OCHFCHF ₂ . In the context of the present invention, the term "oxaalkyl" means alkyl radicals in which at least one non-terminal CH ₂ group has been replaced by -O- such that there are no adjacent heteroatoms (O, S). Oxaalkyl preferably comprises straight-chain radicals of the formula C _a H _{2a + 1} -O- (CH ₂ ) _b -, where a and b are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 ; more preferably a is an integer from 1 to 6 and b is 1 or 2.

If one or more CH ₂ groups have been replaced by sulfur in an alkyl radical as defined above, a "thioalkyl" radical is present. Preferably, "thioalkyl" includes a straight chain radical of the formula C _a H _{2a + 1} -S- (CH ₂ ) _b - wherein a is 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 and b 0, 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; more preferably a is an integer from 1 to 6 and b is 0, 1 or 2. The thioalkyl radical may also be substituted with F, Cl, Br, I and / or -CN and is preferably unsubstituted.

In the context of the present invention, the term "alkenyl" means an alkyl radical as defined above in which one or more -CH = CH groups are present. If two -CH = CH groups are present in the radical, this may also be referred to as "alkadienyl". An alkenyl radical may contain 2 to 15 (ie 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms and is branched chain or preferably straight chain. The rest is unsubstituted or monosubstituted or polysubstituted or differently substituted in particular with F, Cl, Br, I and / or CN. Furthermore, one or more CH ₂ groups may each be independently replaced by -O-, -S-, -C≡C-, -CO-O-, -OC-O- such that heteroatoms (O, S) are not are directly connected. If the CH = CH group on each carbon atom carries a radical other than hydrogen, for example, if it is a nonterminal group, the CH = CH group can exist in two configurations, namely as the E isomer and as the Z isomer. In general, the E-isomer (trans) is preferred. Preferably, the alkenyl radical contains 2, 3, 4, 5, 6 or 7 carbon atoms and is vinyl, 1E-propenyl, 1E-butenyl, 1E-pentenyl, 1E-hexenyl, 1E-heptenyl, 2-propenyl, 2E-butenyl, 2E- Pentenyl, 2E-hexenyl, 2E-heptenyl, 3-butenyl, 3E-pentenyl, 3E-hexenyl, 3E-heptenyl, 4-pentenyl, 4Z-hexenyl, 4E-hexenyl, 4Z-heptenyl, 5-hexenyl and 6-heptenyl. Particularly preferred alkenyl radicals are vinyl, 1E-propenyl and 3E-butenyl.

If one or more CH ₂ groups in an alkyl radical have been replaced by -C≡C-, an alkynyl radical is present. The replacement of one or more CH ₂ groups by -CO-O- or -O-CO- is possible. The following of these radicals are preferred: acetyloxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, acetyloxymethyl, propionyloxymethyl, butyryloxymethyl, pentanoyloxymethyl, 2-acetyloxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 2-acetyloxypropyl, 3-propionyloxypropyl, 4-acetyloxybutyl, Methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, 2- (methoxycarbonyl) ethyl, 2- (ethoxycarbonyl) ethyl, 2- (propoxycarbonyl) ethyl, 3- (methoxycarbonyl) propyl, 3- (ethoxycarbonyl ) propyl or 4- (methoxycarbonyl) butyl.

In the context of the present invention, the term "cycloalkyl" means a cyclic aliphatic (alicyclic) radical having 3 to 16 carbon atoms which is saturated or partially unsaturated and unsubstituted or mono- or poly-halogen, carboxy, nitro, alkanyl, alkoxy, -NH ₂ or with -N ( Alkanyl) ₂ , which multiple substitution can occur with the same or different substituents. Preferably, the cycloalkyl radical is unsubstituted and has 5, 6 or 7 carbon atoms. In particular, cycloalkyl is a cyclohexyl radical.

In the context of the present invention, "alkylene" is a divalent aliphatic hydrocarbon radical having 1, 2, 3, 4, 5, 6, 7, 8 carbon atoms in the chain, which may also be mono- or polysubstituted by halogen, CN, carboxy, nitro, Alkanyl, alkoxy, -NH ₂ or substituted with -N (alkanyl) ₂ , wherein the multiple substitution can be made with the same or different substituents. Preferably, "alkylene" is a straight-chain, unsubstituted or mono- or disubstituted by methyl, saturated aliphatic radical having 1, 2, 3, 4, 5, 6 carbon atoms, in particular -CH ₂ CH ₂ CH ₂ -, -CH ₂ CH ₂ - and -CH ₂ C (CH ₃ ) ₂ CH ₂ -.

"Halogen" in the context of the present invention for fluorine, chlorine, bromine or iodine.

In the context of the present invention, the term "aryl", unless otherwise defined elsewhere in the specification or in the claims, means an aromatic hydrocarbon having from 6 to 14 carbon atoms optionally substituted by halogen, nitro, alkanyl, alkoxy, -NH ₂ or with -N (alkanyl) ₂ monosubstituted or polysubstituted, wherein the multiple substitution can be made with the same or different substituents. The term also includes aromatic hydrocarbons having more than one ring, ie, fused ring systems and ring systems having single or double bond linked rings. In particular, "aryl" is an unsubstituted or substituted phenyl, naphthyl or 4,4'-biphenyl radical.

In the context of the present invention, the term "aralkyl" is an aryl-alkyl radical, ie a radical in which an aryl substituent via an alkyl bridge with an atom, a chain, another ring, another radical or a functional group is linked. The alkyl bridge is preferably a saturated bivalent hydrocarbon radical ("alkylene"), in particular methylene (-CH ₂ -) and ethylene (-CH ₂ -CH ₂ -). Preferred examples of an aralkyl group are benzyl and phenethyl. An "aralkyl-O-radical" for the purposes of the present invention is an aralkyl radical which is linked via an oxygen atom bound to the alkyl bridge with another atom, a chain, another radical or a functional group. Preferred examples of an aralkyl O radical are O-benzyl and O-CH ₂ CH ₂ phenyl.

For the purposes of the present invention, a "heteroaryl radical" is understood as meaning a cyclic, (hetero) aromatic organic radical having 5 to 18 ring atoms which contains, in addition to carbon atoms, one or more identical or different heteroatoms in its ring, these heteroatoms preferably being composed of nitrogen , Oxygen and sulfur are selected. The heterocycle has at least one ring and may also have two, three or more rings, which are optionally fused together, wherein at least one of the plurality of rings has at least one heteroatom. The heteroaryl radical may be unsubstituted in the same way as the above-defined aryl radical or may be monosubstituted or polysubstituted by identical or different substituents with halogen, nitro, alkanyl, alkoxy, -NH ₂ or with -N (alkanyl) ₂ . The heteroaryl radical may be bonded via each of its ring atoms. Preferably, the heteroaryl radical is selected from the group consisting of pyrrolyl, pyrazolyl, imidazolyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolyl, furanyl, thienyl, oxazolyl, isoxazolyl, pyranyl, benzofuranyl, benzothienyl.

For the purposes of the present invention, a "heterocyclyl radical" means a cyclic organic radical having 5 to 18 ring atoms which has at least one saturated (endocyclic) bond between two ring atoms in its ring and contains one or more identical or different heteroatoms, which are preferred selected from nitrogen, oxygen and sulfur. The heterocycle has at least one ring and may also have two, three or more rings, which are optionally fused together, wherein at least one of the plurality of rings has at least one heteroatom. The heterocyclyl radical can be unsubstituted in the same way as the above-defined aryl radical or monosubstituted or polysubstituted by identical or different substituents with halogen, nitro, alkanyl, alkoxy, -NH ₂ or with -N (alkanyl) ₂ . The heterocyclyl radical may be bonded via each of its ring atoms. Preferably, the heterocyclyl radical is selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, tetrahydrofuran, dioxane, dihydropyrazole, dihydroimidazole, dihydrooxazole, tetrahydrooxazole, dihydroisoxazole and tetrahydroisoxazole. By a "heterocyclylalkyl" is meant a radical in which a heterocyclyl radical is linked via an alkyl bridge with an atom, a chain, another ring, another radical or a functional group.

The compounds used in the process of the invention are - as far as a synthesis in the present description is not expressly stated - as well as the reagents and solvents used known from the literature and mostly commercially available. Alternatively, they can be prepared by methods known per se, as described in the literature (for example in standard works of synthetic organic chemistry, such as Houben-Weyl, Methods of Organic Chemistry, Georg Thieme Verlag, Stuttgart), namely under reaction conditions which are known and suitable for the said reactions. But you can also make use of known per se, not mentioned here variants.

The present invention will be further illustrated by way of examples which, however, are not intended to limit the scope of the invention or the scope of the claims. Examples Example 1

The acid A (50.0 g, 0.178 mol) was taken up in 150 ml of isooctane and treated with 25.0 g (0.231 mol) of 1,3-propanedithiol. The white suspension was heated to 60 ° C. Then, trifluoromethanesulfonic acid (34.7 g, 0.231 mol) was added dropwise to the suspension within five minutes. The resulting cloudy yellow solution was heated to boiling for five hours on a water. After distilling off 5.4 g of water, the biphasic reaction mixture was treated within 15 minutes with diethylene glycol dibutyl ether at 80-90 ° C. The orange suspension was slowly cooled to 0-5 ° C. The crystals were filtered off, washed with 50 ml of isooctane and dried overnight at 35 ° C. under reduced pressure. Yield: 85.9 g (96%). Example 2

3,4,5-Trifluorophenol (162.9 g, 1.10 mol) and triethylamine (116.4 g, 1.15 mol) were dissolved in dichloromethane. The solution was cooled to -70 ° C and then treated dropwise with a solution of the bis (alkylthio) carbenium salt C (498.6 g, 1.00 mol) at this temperature. After about 2 hours, triethylamine trishydrofluoride (483.7 g, 3.0 mol) was added dropwise over 30 minutes. After allowing to react for fifteen minutes, bromine (799.1 g, 5.0 mol) in dichloromethane was added over two hours. After stirring for fifteen minutes, the batch was warmed to 0 ° C. The batch was added to an ice / potassium hydroxide mixture and stirred for three hours. After phase separation, the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with water and then concentrated in vacuo. The residue was taken up in methanol, boiled and filtered hot, the filtrate was then slowly cooled with stirring to first 20 ° C and then to -10 ° C. The precipitated crystals were filtered off, washed with methanol in the cold and dried in vacuo. By concentration of the mother liquor further material was obtained. Total yield: 330.5 g (76%). Example 3

To a mixture of 111 g of 3,4,5-trifluorophenol, 76 g of triethylamine and 1250 ml of dichloromethane at about -75 ° C with stirring, a solution of 355 g of propyl cyclohexyl-cyclohexyl-dithianylium trifluoromethanesulfonate E in 1.1 l Dichloromethane added dropwise. Subsequently, 363 g of triethylamine trishydrofluoride and then 540 g of bromine are added dropwise. It is slowly warmed to 0 ° C; the reaction mixture is metered in with cooling to about 0 ° C and with vigorous stirring in 5 l of 10% potassium hydroxide solution. After phase separation, the organic phase is evaporated to dryness.

The residue is taken up in 1 liter of methanol and the mixture is stirred at 45 ° C. for one hour. Then the mixture is cooled to 0 ° C and filtered. The filter residue is washed with a little methanol, dried in vacuo and dissolved in 1 l of heptane. This solution is applied to a silica gel column; the column is eluted with heptane. The eluates are evaporated in vacuo, the residue is dried for a further 2 days in vacuo. This gives 261 g of propyl-cyclo-hexyl-cyclohexyl-difluoro-methoxy-trifluorobenzene F (yield: 86%) in a purity of 99.8% (GC). If desired, this material is recrystallized from heptane; after obtaining secondary crystals gives 236 g of product F (yield: 78%) in a purity of 99.9%.

(After the usual work-up procedure, however, the residue is taken up in 1.5 l of heptane and the mixture is stirred vigorously.The oily phase, which settles upon completion of the stirring, is separated off.The supernatant solution is filtered through a little silica gel and then in vacuo The concentrate is applied to a silica gel column, the column is eluted with heptane until no product is found in the eluate after TLC, the combined eluates are evaporated to dryness in vacuo, the residue is recrystallized from ethanol, after concentrating the The first and second crystals are combined, dried in vacuo and recrystallized from heptane, here again after concentration of the mother liquor, a secondary crystallizate is obtained, the first and second crystals of the heptane recrystallization are combined and dried in vacuo. 185 g of propylcyclohexylcyclohexyl-dif Luoro-methoxy-trifluorobenzene F (yield: 61%) in a purity of 99.8% (GC).)

Claims (9)

A process in which a bis (alkylthio) carbenium salt is first reacted in the presence of a base with at least one compound having at least one hydroxy group and then reacted with a fluorinating agent and an oxidizing agent to give a crude product containing a compound having at least one difluoroxymethylene bridge, characterized in that the crude product of the reaction is taken up in a strongly polar alcohol or a mixture of strongly polar alcohols. Process according to claim 1, characterized in that the alcohol (s) used are not miscible with alkanes. A method according to claim 1 or 2, characterized in that the one or more strongly polar alcohols trifluoroethanol, 2-cyanoethanol, hexafluoroisopropanol, a di-, tri- or polyol and / or methanol is / are. Process according to at least one of claims 1 to 3, characterized in that the bis (alkylthio) carbenium salt is represented by the formulas VIIa, VIIb, VIIc:

where a is 0, 1 or 2; R ^{1 is} H, an unsubstituted or mono- or polysubstituted with F, Cl, Br and / or I substituted alkyl radical having 1 to 15 carbon atoms, wherein in the alkyl radical and one or more CH ₂ groups by -C≡C -, -CH = CH-, -O-, -S-, -SO ₂ -, -C (O) -O- or -OC (O) - may be replaced so that heteroatoms in the chain are not directly linked are, means; A ¹ for

A ² for

b is independently A ¹ and A ^{2 is} 0, 1, 2, 3 or 4; c and d are independently and independently for A ¹ and A ^{2 are} 0, 1, 2 or 3; Z ¹ is a single bond, -CH ₂ CH ₂ -, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CF ₂ CF ₂ -, -CH ₂ O-, -OCH ₂ -, -CF ₂ O-, -OCF ₂ -, -C (O) -O-, -OC (O) -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF- or -C≡C- means; R ³¹ and R ⁴¹ independently of one another denote a straight-chain or branched, unsubstituted or mono- or polysubstituted or substituted by the same or different substituent alkyl radical having 1 to 20 carbon atoms, in which one or more CH ₂ groups independently of one another by -CH = CH-, -C≡C, -O-, -S-, -CO-O-, -O-CO- or -O-CO-O- may be replaced, that heteroatoms are not directly linked, an unsubstituted or mono- or multiply substituted by the same or different substituents cycloalkyl, heterocyclylalkyl or aralkyl radical having up to 20 carbon atoms; or R ³¹ and R ⁴¹ together represent a straight-chain or branched, saturated or unsaturated hydrocarbon bridge having 1 to 6 carbon atoms in the bridge, wherein one or more of the hydrocarbon bridge carbon atoms independently of each other with the same or different alkyl, cycloalkyl, aryl, Heterocyclyl or aralkyl / en substituted or bridged by another hydrocarbon chain or part of a saturated or unsaturated carbocyclic or heterocyclic ring system; and Y ^{- is} a non or weakly coordinating anion; where A ¹ , Z ¹ , b, c and d may each also assume different meanings when a is 2. Method according to one of the preceding claims, characterized in that Y ^{- is} a tetrafluoroborate or Trifluormethansulfonat anion. Process according to at least one of Claims 1 to 3, characterized in that the compound having at least one hydroxyl group has the formula VIII: HO-A ³ - [- Z ⁴ -A ⁴ -] _e -X ² VIII where e is 0, 1 or 2; A ³ and A ^{4 are} independently for

stand; f is independently A ³ and A ^{4 is} 0, 1, 2, 3 or 4; g and h independently of one another and independently for A ³ and A ^{4 are} 0, 1, 2 or 3; Z ^{4 represents} a single bond, -CF ₂ O- or -CO-O-; and X ^{2 is} F, Cl, CN, NCS, SF ₅ or an unsubstituted or mono- or polysubstituted with F, Cl, Br and / or I substituted alkyl radical having 1 to 15 carbon atoms, wherein in the alkyl radical and an or several CH ₂ groups can be replaced by -C≡C-, -CH = CH-, -O-, -S-, -SO ₂ -, -C (O) -O- or -OC (O) - in that heteroatoms in the chain are not directly linked to one another; where A ⁴ , Z ⁴ , f, g and h can each also assume different meanings when e is 2. Process according to the preceding claim, characterized in that the compound of formula VIII is selected from a compound of formula VIII-A or VIII-B:

wherein L ¹ , L ² , L ³ and L ^{4 are} independently H or F; and X ^{2 is} F, Cl, CN, NCS, SF ₅ , CF ₃ , OCF ₃ , SCF ₃ or SO ₂ CF ₃ . A method according to any one of claims 1 to 3, characterized in that the fluorinating agent is selected from the group consisting of aliphatic and aromatic amine-hydrogen fluoride complexes. A method according to any one of claims 1 to 3, characterized in that the oxidizing agent is a compound which releases Haloniumequivalente.