DE102007002410A1 - Synthesis of chroman derivatives - Google Patents

Abstract

The present invention relates to a process for the preparation of compounds of the formula (I) starting from compounds of the formula (II) and (III), where the reaction medium contains at least one ionic liquid.

Description

The The present invention relates to a process for the preparation of Compounds of the formula (I), starting from compounds of the formula (II) and (III), wherein the reaction medium is at least one ionic liquid contains.

chroman are naturally occurring compounds in nature that assume a number of biological functions. The most well-known representatives of this class are those in 2-position with a 4,8,12-trimethyltridecyl radical substituted chroman-6-ols (also referred to as 3,4-dihydro-2H-1-benzopyran-6-ols), generally be referred to as tocopherols.

tocopherols are pale yellowish-reddish, oily liquids, insoluble in water, soluble in fats and oils as well as in the usual solvents for Fats. A distinction is made inter alia α-, β-, γ-, δ-, ζ and η-tocopherols, α-, β- and γ-tocotrienols, which are still beyond the original unsaturated prenyl side chain, as well as α-tocopherol quinone and α-tocopherol hydroquinone, in which the pyran ring system is open. Especially α-tocopherol in the (2R, 4'R, 8'R) form (Trivial name: RRR-α-tocopherol), but also β-, γ- and δ-tocopherol, α-, β- and γ-tocotrienol and various tocopherol acetates and tocopherol succinates Vitamin E activity.

tocopherols occur in many vegetable oils. Are particularly rich the seed oils of soya, wheat, corn, rice, cotton, alfalfa and nuts, but with oil refining a part is lost. Also some fruits and vegetables, z. Raspberries, beans, peas, fennel, peppers, salsify and celery contain tocopherols. Worldwide, about 7000 t / a Tocopherols produced and preferably by synthesis of the racemic α-tocopherol (all-rac-α-tocopherol) from trimethylhydroquinone and from acetone via linalool accessible isophytol.

This process is catalyzed by numerous Lewis or Brönsted acids, for example by zinc chloride with mineral acids, SF ₃ or AlCl ₃ . The industrial synthesis is carried out in a number of different solvents, for example ethyl acetate, acetic acid or halogenated hydrocarbons. The use of volatile organic solvents and the use of catalysts makes the process very complicated and causes a large amount of waste, such as contaminated solvents or residues of AlCl ₃ . Overall, the process of making tocopherols becomes very uneconomical and less environmentally friendly.

It So is the object of the present invention, alternative manufacturing methods Chromium derivatives ready to steep, which have the disadvantages mentioned above do not have.

Surprisingly can accomplish the above complex task through the use of ionic liquids be solved.

umfassend die Umsetzung von Verbindungen der Formel (II)

mit Verbindungen der Formel (III),

worin R1-R4
H, F, Cl, Br, I, -OH, -CN, -C(O)OH, -C(O)NR'₂, -SO₂NR'₂, -SO₂OH, -SO₂X, -OR', -NO₂, -NR'₂
geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen,
geradkettiges oder verzweigtes Alkenyl mit 2-40 C-Atomen und einer oder mehreren nicht konjugierten Doppelbindungen,
geradkettiges oder verzweigtes Alkinyl mit 2-40 C-Atomen und einer oder mehreren nicht konjugierten Dreifachbindungen,
gesättigtes, teilweise oder vollständig ungesättigtes Cycloalkyl mit 3-7 C-Atomen, das mit Alkylgruppen mit 1-20 C-Atomen substituiert sein kann, bedeutet, wobei ein oder mehrere R1-R4 teilweise oder vollständig mit Halogenen, insbesondere -F und/oder -Cl, oder teilweise mit -OR', -CN, -C(O)OH, -C(O)NR'₂, -SO₂NR'₂, -SO₂OH, -SO₂X, -NO₂, substituiert sein können, und wobei ein oder zwei nicht benachbarte und nicht α-ständige Kohlenstoffatome von R1-R4 durch Atome und/oder Atomgruppierungen ausgewählt aus der Gruppe -O-, -S-, -S(O)-, -SO₂-, -N⁺R'₂-, -C(O)NR'-, -SO₂NR'-, oder -P(O)R'- ersetzt sein können mit R' = H, nicht, teilweise oder perfluoriertes C₁- bis C₆-Alkyl, C₃- bis C₇-Cycloalkyl, unsubstituiertes oder substituiertes Phenyl, X = Halogen und R'' = H oder C₁- bis C₆-Alkyl,
und wobei zwei oder mehrere Reste R1 bis R4 miteinander verbunden sein können,
worin R5-R6 H,
OAlkyl mit 1-6 C-Atomen,
geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen,
geradkettiges oder verzweigtes Alkenyl mit 2-40 C-Atomen und einer oder mehreren nicht konjugierten Doppelbindungen, bedeutet oder R5 und R6 gemeinsam eine C=O Gruppe bilden,
worin R7 H oder geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen bedeutet,
worin R5, R6 und/oder R7 miteinander verbunden sein können,
wobei die Umsetzung in einem Reaktionsmedium enthaltend mindestens eine Ionische Flüssigkeit der allgemeinen Formel K⁺A^– erfolgt.Accordingly, an object of the present invention is a process for the preparation of compounds of the formula (I)

comprising the reaction of compounds of the formula (II)

with compounds of the formula (III),

wherein R1-R4
H, F, Cl, Br, I, -OH, -CN, -C (O) OH, -C (O) NR ' ₂ , -SO ₂ NR' ₂ , -SO ₂ OH, -SO ₂ X, - OR ', -NO ₂ , -NR' ₂
straight-chain or branched alkyl having 1-40 C atoms,
straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-40 C atoms and one or more non-conjugated triple bonds,
saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-20 C atoms, wherein one or more R1-R4 partially or completely with halogens, in particular -F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two non-adjacent and non-α-carbon atoms of R1-R4 are substituted by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, -SO ₂ - , -N ⁺ R ' ₂ -, -C (O) NR'-, -SO ₂ NR'-, or -P (O) R'- may be replaced with R' = H, not, partially or perfluorinated C ₁ C ₁ to C ₆ alkyl, C ₃ to C ₇ cycloalkyl, unsubstituted or substituted phenyl, X is halogen and R is H or C ₁ to C ₆ alkyl,
and where two or more radicals R1 to R4 can be connected to one another,
wherein R5-R6 is H,
Oalkyl with 1-6 C atoms,
straight-chain or branched alkyl having 1-40 C atoms,
straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds, or R5 and R6 together form a C =O group,
where R 7 is H or straight-chain or branched alkyl having 1-40 carbon atoms,
wherein R5, R6 and / or R7 may be linked together,
wherein the reaction in a reaction medium containing at least one ionic liquid of the general formula K ⁺ A ^- takes place.

The Radicals R1-R4 as well as R5, R6 and / or R7 can together be connected, that is, the radicals together form ring systems out. These ring systems can be mononuclear or polynuclear, both saturated and unsaturated or aromatic be. The chroman ring system of the formula (I) can therefore be used in the sense of present invention itself part of a ring system, for example with finned rings, his. Preferably, the radicals R2 and R3 or the radicals R5, R6 and / or R7 connected to each other. All the radicals R 2 and R 3 and the radicals R 7 and are particularly preferred R5 and R6 connected together.

Preferably R5-R6 is selected from the group comprising H, Oalkyl with 1-6 C atoms and straight-chain or branched alkyl with 1-40 C atoms or straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds.

R1-R4 are preferably selected from the group comprising H, F, Cl, Br, -OH, -OR ', straight-chain or branched alkenyl with 2-40 C atoms and one or more non-conjugated double bonds and straight-chain or branched alkyl having 1-40 C atoms, in particular 1-20 C atoms and most preferably 1-5 C atoms. Especially R1, R3 and R4 are preferably selected from the group comprising H and straight-chain alkyl having 1-5 C atoms, with methyl being very particular is preferred, while R2 is OH.

R7 is preferably H.

R5 and R6 are preferably selected from the group comprising H, straight-chain or branched alkyl having 1-40 C atoms, or straight-chain or branched alkynyl having 2-40 C atoms and a or more non-conjugated triple bonds. Especially preferably R5 and R6 are selected from the group comprising straight-chain or branched alkyl having 1-40 C atoms, in particular 1-20 C-atoms or straight-chain or branched alkenyl with 2-40 C atoms, in particular 1-20 C atoms, and one or more not conjugated double bonds. Very particularly preferred is one the radicals R5 and R6 straight-chain alkyl having 1-5 C atoms, in particular Methyl, while the other is branched alkyl of 1-16 C atoms and R''H means.

The Subcombination of the above preferred ranges for R1-R7 is particularly preferred.

Preferably, compound (I) is tocopherols, in particular vitamin E, of the following basic structure:

mit der Verbindung der Formel (IIIa) umgesetzt.For the preparation of the above-mentioned tocopherol of the formula (Ia), in the process according to the invention the compound of the formula (IIa)

reacted with the compound of formula (IIIa).

R1, R3 and R4 in formula (Ia) and (IIa) are preferably selected from H and straight-chain alkyl having 1-5 C atoms, in particular methyl.

About that In addition, with the inventive Method also tocotrienols of the general formula (Ib) prepared become.

The compounds of the formula (Ib) are prepared starting from compounds of the formula (IIa) by reaction with compounds of the formula (IIIb)

R1, R3 and R4 in formula (Ib) or (IIa) are preferably selected from H and straight-chain alkyl having 1-5 C atoms, in particular methyl.

Accordingly acts it is the most preferred compounds of the formula (I) to α, β, γ, δ, ζ and η-tocopherols and α-, β- and γ-tocotrienols.

Essential for the process according to the invention is the use of a reaction medium containing at least ionic liquid of the general formula K ⁺ A ^- . The selection of the anion A ^- the ionic liquid plays a special role. Preferably, the anion A ^- is an anion of a corresponding strong acid. In particular, the anion A ^{- of} the ionic liquid is selected from the group comprising [HSO ₄ ] ^- , [SO ₄ ] ^2- , [NO ₃ ] ^- , [BF 4] ^- , [(R _F ) BF ₃ ] ^- , [( R _F ) ₂ BF ₂ ] ^- , [(R _F ) ₃ BF] ^- , [(R _F ) ₄ B] ^- , [B (CN) ₄ ] ^- , [PO ₄ ] ^3- , [HPO ₄ ] ^{2 -} , [H ₂ PO ₄ ] ^- , [alkyl-OPO ₃ ] ^2- , [(alkyl-O) ₂ PO ₂ ] ^- , [alkyl-PO ₃ ] ^2- , [R _F PO ₃ ] ^2- , [ (Alkyl) ₂ PO ₂ ] ^- , [(R _F ) ₂ PO ₂ ] ^- , [R _F SO ₃ ] ^- , [HOSO ₂ (CF ₂ ) _n SO ₂ O] ^- , [OSO ₂ (CF ₂ ) _n SO ₂ O] ^2- , [alkyl-SO ₃ ] ^- , [HOSO ₂ (CH ₂ ) _n SO ₂ O] ^- , [OSO ₂ (CH ₂ ) _n SO ₂ O] ^2- , [alkyl-OSO ₃ ] ^- , [alkylC (O) O] ^- , [HO (O) C (CH ₂ ) _n C (O) O] ^- , [R _F C (O) O] ^- , [HO (O) C ( CF ₂ ) _n C (O) O] ^- , [O (O) C (CF ₂ ) _n C (O) O] ^2- , [(R _F SO ₂ ) ₂ N] ^- , [(FSO ₂ ) ₂ N] ^- , [((R _F ) ₂ P (O)) ₂ N] ^- , [(R _F SO ₂ ) ₃ C] ^- , [(FSO ₂ ) ₃ C], Cl ^- and / or Br
in which
n = 1 to 8 means
R _{F is} fluorinated alkyl (C _m F _{2m-x + 1} H _x ) with m = 1-12 and x = 0-7, where for m = 1 x = 0 to 2, and / or fluorinated (also perfused) aryl or alkyl-aryl.

The Alkyl group in the above-mentioned anions can be selected from straight-chain or branched alkyl groups having 1 to 20 C atoms, preferably having 1 to 14 carbon atoms, and particularly preferred with 1 to 4 carbon atoms.

Preferably R _{F is} CF ₃ , C ₂ F ₅ , C ₃ F ₇ or C ₄ F ₉ .

There are no restrictions per se on the choice of cation K ^{+ of} the ionic liquid. Preferably, however, they are organic cations, with particular preference being given to ammonium, phosphonium, thiouronium, guanidinium cations or heterocyclic cations.

Ammonium cations can be exemplified by the formula (1) [HR ₄ ] ⁺ (1), be described, wherein
R each independently
H, where not all substituents R may be H at the same time,
straight-chain or branched alkyl having 1-20 C atoms,
straight-chain or branched alkenyl having 2-20 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-20 C atoms and one or more non-conjugated triple bonds,
saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-6 C atoms, wherein one or more R partially or completely with halogens, in particular -F and / or -Cl , or partially substituted by -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ and one or two non-adjacent and non-α-carbon atoms of the R may be substituted by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR'-, -SO ₂ NR'-, or -P (O) R'- may be replaced by R' = H, not, partially or perfluorinated C ₁ - to C ₆ alkyl, C ₃ - to C ₇ cycloalkyl, unsubstituted or substituted phenyl and X = halogen may be.

Phosphonium cations can be exemplified by the formula (2) [PR ² ₄ ] ⁺ (2), be described, wherein
R ² each independently
H, NR ' ₂
straight-chain or branched alkyl having 1-20 C atoms,
straight-chain or branched alkenyl having 2-20 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-20 C atoms and one or more non-conjugated triple bonds,
saturated, partially or completely unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-6 C atoms, wherein one or more R ² partially or completely with halogens, in particular -F and / or Cl, or partially substituted by -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ and wherein one or two non-adjacent and non-α-carbon atoms of R ² , by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR'-, -SO ₂ NR'-, or -P (O) R'- may be replaced by R' = H, not, partially or perfluorinated C ₁ - to C ₆ alkyl, C ₃ - to C ₇ cycloalkyl, unsubstituted or substituted phenyl and X = halogen.

Excluded, however, are cations of the formulas (1) and (2) in which all four or three substituents R and R ^{2 are} completely substituted by halogens, for example the tris (trifluoromethyl) methylammonium cation, the tetra (trifluoromethyl) ammonium cation or the tetra (nonafluorobutyl ) ammonium cation.

Suitable thiouronium cations can be represented by the formula (3) [(R ³ R ⁴ N) -C (= SR ⁵ ) (NR ⁶ R ⁷ )] ⁺ (3), be described, wherein
R ³ to R ^{7 are} each independently
Hydrogen,
straight-chain or branched alkyl having 1 to 20 C atoms,
straight-chain or branched alkenyl having 2-20 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-20 C atoms and one or more non-conjugated triple bonds,
saturated, partially or completely unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-6 C atoms, wherein one or more of the substituents R ³ to R ⁷ partially or completely with halogens, in particular F and / or -Cl, or partially with -OH, -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two non-adjacent and non-α-carbon atoms of R ³ to R ^{7 are} substituted by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR', -SO ₂ NR ', or -P (O) R' - may be replaced with R '= H, not, partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl and X = halogen.

Guanidinium cations can be represented by the formula (4) [C (NR ⁸ R ⁹ ) (NR ¹⁰ R ¹¹ ) (NR ¹² R ¹³ )] ⁺ (4) be described, wherein
R ⁸ to R ^{13 are} each independently
Hydrogen, -CN, NR ' ₂ ,
straight-chain or branched alkyl having 1 to 20 C atoms,
straight-chain or branched alkenyl having 2-20 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-20 C atoms and one or more non-conjugated triple bonds,
saturated, partially or completely unsaturated cycloalkyl having 3-7 C atoms which may be substituted by alkyl groups having 1-6 C atoms, where one or more of the substituents R ⁸ to R ^{13 are} partially or completely halogenated, in particular F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two non-adjacent and non-α-carbon atoms of R ⁸ to R ^{13 are} substituted by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR', -SO ₂ NR ', or -P (O) R' - may be replaced with R '= H, not , partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl and X = halogen.

bedeutet, wobei die Substituenten
R^1' bis R^4' jeweils unabhängig voneinander
Wasserstoff, -CN,
geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen,
geradkettiges oder verzweigtes Alkenyl mit 2-20 C-Atomen und einer oder mehreren nicht konjugierten Doppelbindungen,
geradkettiges oder verzweigtes Alkinyl mit 2-20 C-Atomen und einer oder mehreren nicht konjugierten Dreifachbindungen,
gesättigtes, teilweise oder vollständig ungesättigtes Cycloalkyl mit 3-7 C-Atomen, das mit Alkylgruppen mit 1-6 C-Atomen substituiert sein kann, gesättigtes, teilweise oder vollständig ungesättigtes Heteroaryl, Heteroaryl-C₁-C₆-alkyl oder Aryl-C₁-C₆-alkyl bedeutet,
wobei die Substituenten R^1', R^2', R^3' _und/oder R^4' zusammen auch ein Ringsystem bilden können,
wobei ein oder mehrere Substituenten R^1' bis R^4' teilweise oder vollständig mit Halogenen, insbesondere -F und/oder -Cl, oder -OR', -CN, -C(O)OH, -C(O)NR'₂, -SO₂NR'₂, -C(O)X, -SO₂OH, -SO₂X, -NO₂, substituiert sein können, wobei jedoch nicht gleichzeitig R^1' und R^4' vollständig mit Halogenen substituiert sein dürfen, und wobei ein oder zwei nicht benachbarte und nicht am Heteroatom gebundene Kohlenstoffatome der Substituenten R^1' bis R^4', durch Atome und/oder Atomgruppierungen ausgewählt aus der -O-, -S-, -S(O)-, -SO₂-, -N⁺R'₂-, -C(O)NR'-, -SO₂NR'-, oder -P(O)R'- ersetzt sein können mit R' = H, nicht, teilweise oder perfluoriertes C₁- bis C₆-Alkyl, C₃- bis C₇-Cycloalkyl, unsubstituiertes oder substituiertes Phenyl und X = Halogen.In addition, cations of the general formula (5) [HetN] ⁺ (5) be used, where
HetN ⁺ a heterocyclic cation selected from the group

means, wherein the substituents
R ^{1 '} to R ^{4' are} each independently
Hydrogen, -CN,
straight-chain or branched alkyl having 1-20 C atoms,
straight-chain or branched alkenyl having 2-20 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-20 C atoms and one or more non-conjugated triple bonds,
saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-6 C atoms, saturated, partially or fully unsaturated heteroaryl, heteroaryl-C ₁ -C ₆ alkyl or aryl-C C ₁ -C ₆ -alkyl,
where the substituents R ^{1 '} , R ^2' , R ^{3 '} _{and / or} R ^4' together can also form a ring system,
wherein one or more substituents R ^{1 '} to R ^4' partially or completely with halogens, in particular -F and / or -Cl, or -OR ', -CN, -C (O) OH, -C (O) NR' _2nd , -SO ₂ NR ' ₂ , -C (O) X, -SO ₂ OH, -SO ₂ X, -NO ₂ , may be substituted, but not simultaneously R ^1' and R ^{4 '} may be completely substituted with halogens and wherein one or two non-adjacent and non-heteroatom-bonded carbon atoms of the substituents R ^{1 '} to R ^4' , by atoms and / or atomic groups selected from the -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR'-, -SO ₂ NR'-, or -P (O) R'- may be replaced by R' = H, not, partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl and X = halogen.

As substituent R ^{2 '} are in particular also atom groups selected from -OR', -NR ' ₂ , -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, - SO ₂ X or -NO ₂ .

Under become fully unsaturated substituents in the context of the present invention also aromatic substituents Understood.

Suitable substituents R and R ² to R ^{13 of} the compounds of the formulas (1) to (4) according to the invention are preferably hydrogen in addition to hydrogen: C ₁ - to C ₂₀ -, in particular C ₁ - to C ₁₄ -alkyl groups, and saturated or unsaturated, that is also aromatic, C ₃ - to C ₇ -cycloalkyl groups which may be substituted by C ₁ - to C ₆ -alkyl groups, in particular phenyl.

The substituents R and R ² in the compounds of formula (1) or (2) may be the same or different. Preferably, the substituents R and R ^{2 are} different.

The substituents R and R ² are particularly preferably methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, pentyl, hexyl, octyl, decyl or tetradecyl.

Up to four substituents of the guanidinium cation [C (NR ⁸ R ⁹ ) (NR ¹⁰ R ¹¹ ) (NR ¹² R ¹³ )] ⁺ may also be linked in pairs to form mono-, bi-, or polycyclic cations.

wobei die Substituenten R⁸ bis R¹⁰ und R¹³ eine zuvor angegebene oder besonders bevorzugte Bedeutung haben können.Without restriction of generality, examples of such guanidinium cations are:

where the substituents R ⁸ to R ¹⁰ and R ^{13 may have} a previously given or particularly preferred meaning.

Optionally, the carbocycles or heterocycles of the guanidinium cations previously indicated by C ₁ - to C ₆ alkyl, C ₁ - to C ₆ alkenyl, NO ₂ , CN, NR ' ₂ , F, Cl, Br, I, C C ₁ -C ₆ alkoxy, SCF ₃ , SO ₂ CF ₃ , COOH, SO ₂ NR ' ₂ , SO ₂ X' or SO ₃ H be substituted, where X and R 'have the meaning given above, substituted or unsubstituted phenyl or unsubstituted or substituted heterocycle be substituted.

Up to four substituents of the thiouronium cation [(R ³ R ⁴ N) -C (= SR ⁵ ) (NR ⁶ R ⁷ )] ⁺ may also be linked in pairs in such a way that mono-, bi- or polycyclic cations are formed.

wobei die Substituenten R³, R⁵ und R⁶ eine zuvor angegebene oder besonders bevorzugte Bedeutung haben können.Without restricting generality, examples of such cations are given below, where Y = S:

where the substituents R ³ , R ⁵ and R ^{6 may have} a previously stated or particularly preferred meaning.

Optionally, the carbocycles or heterocycles of the abovementioned cations can also be replaced by C ₁ - to C ₆ -alkyl, C ₁ - to C ₆ -alkenyl, NO ₂ , CN, NR ' ₂ , F, Cl, Br, I, C ₁ - C ₆ alkoxy, SCF ₃ , SO ₂ CF ₃ , COOH, SO ₂ NR ' ₂ , SO ₂ X or SO ₃ H or substituted or unsubstituted phenyl or unsubstituted or substituted heterocycle may be substituted, wherein X and R' is as defined above to have.

The substituents R ³ to R ¹³ are each, independently of one another, preferably a straight-chain or branched alkyl group having 1 to 10 C atoms. The substituents R ³ and R ⁴ , R ⁶ and R ⁷ , R ⁸ and R ⁹ , R ¹⁰ and R ¹¹ and R ¹² and R ¹³ in compounds of the formulas (3) to (4) may be identical or different. R ³ to R ^{13 are} each particularly preferably, independently of one another, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, sec-butyl, phenyl or cyclohexyl, very particularly preferably methyl, ethyl, n-propyl, Isopropyl or n-butyl.

Suitable substituents R ^{1 '} to R ^4' of compounds of the formula (5) according to the invention are preferably hydrogen in addition to hydrogen: C ₁ - to C ₂₀ , in particular C ₁ - to C ₁₂ -alkyl groups, and saturated or unsaturated, ie also aromatic , C ₃ - to C ₇ -cycloalkyl groups which may be substituted by C ₁ - to C ₆ -alkyl groups, in particular phenyl.

The substituents R ^{1 '} and R ^4' are each, in each case independently of one another, particularly preferably methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, pentyl, hexyl, octyl, decyl, cyclohexyl, phenyl or benzyl. They are very particularly preferably methyl, ethyl, n-butyl or hexyl. In pyrrolidinium, piperidinium or indolinium compounds, the two substituents R ^{1 '} and R ^{4' are} preferably different.

The substituent R ^{2 '} or R ^3' is, in each case independently of one another, in particular hydrogen, methyl, ethyl, isopropyl, propyl, butyl, sec-butyl, tert-butyl, cyclohexyl, phenyl or benzyl. Particularly preferred is R2. Hydrogen, methyl, ethyl, isopropyl, propyl, butyl or sec-butyl. Most preferably, R ^{2 '} and R ^{3' are} hydrogen.

The C ₁ -C ₁₂ -alkyl group is, for example, methyl, ethyl, isopropyl, propyl, butyl, sec-butyl or tert-butyl, and also pentyl, 1-, 2- or 3-methylbutyl, 1,1-, 1 , 2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl. Optionally, difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoropropyl or nonafluorobutyl.

A straight-chain or branched alkenyl having 2 to 20 C atoms, wherein several double bonds may also be present, is for example allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, furthermore 4-pentenyl, iso-pentenyl, hexenyl, Heptenyl, octenyl, -C ₉ H ₁₇ , -C ₁₀ H ₁₉ to -C ₂₀ H ₃₉ ; preferably allyl, 2- or 3-butenyl, isobutenyl, sec-butenyl, furthermore preferred is 4-pentenyl, iso-pentenyl or hexenyl.

A straight-chain or branched alkynyl having 2 to 20 C atoms, wherein a plurality of triple bonds may also be present, is, for example, ethynyl, 1- or 2-propynyl, 2- or 3-butynyl, furthermore 4-pentynyl, 3-pentynyl, hexynyl, Heptynyl, octynyl, -C ₉ H ₁₅ , -C ₁₀ H ₁₇ to -C ₂₀ H ₃₇ , preferably ethynyl, 1- or 2-propynyl, 2- or 3-butynyl, 4-pentynyl, 3-pentynyl or hexynyl.

Aryl-C ₁ -C ₆ -alkyl is, for example, benzyl, phenylethyl, phenylpropyl, phenylbutyl, phenylpentyl or phenylhexyl, where both the phenyl ring and the alkylene chain, as described above, partially or completely with halogens, in particular -F and / or -Cl, or partially with -OR ', -NR' ₂ , -CN, -C (O) OH, -C (O) NR ' ₂ , -SO ₂ NR' ₂ , -C (O) X, -SO ₂ OH, -SO ₂ X, -NO ₂ may be substituted.

Unsubstituted saturated or partially or fully unsaturated cycloalkyl groups having 3-7 C atoms are therefore cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexenyl, phenyl, cycloheptenyl, which may be substituted by C ₁ - to C ₆ -alkyl groups, wherein in turn, the cycloalkyl group or substituted with C ₁ - to C ₆ alkyl cycloalkyl group with halogen atoms such as F, Cl, Br or I, in particular F or Cl or -OR ', -CN, -C (O) OH, -C (O) NR ' ₂ , -SO ₂ NR' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ may be substituted.

In the substituents R, R ² to R ¹³ or R ^{1 '} to R ^4' can also one or two non-adjacent and not α-bonded to the heteroatom carbon atoms, by atoms and / or atomic groups selected from the group -O-, - S, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR', -SO ₂ NR ', or -P (O) R' - be replaced , where R '= not, partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl.

Without restriction of generality, examples of such modified substituents R, R ² to R ¹³ and R ^{1 '} to R ^{4' are} :
-OCH ₃ , -OCH (CH ₃ ) ₂ , -CH ₂ OCH ₃ , -CH ₂ -CH ₂ -O-CH ₃ , -C ₂ H ₄ OCH (CH ₃ ) ₂ , -C ₂ H ₄ SC ₂ H ₅ , -C ₂ H ₄ SCH (CH ₃ ) ₂ , -S (O) CH ₃ , -SO ₂ CH ₃ , -SO ₂ C ₆ H ₅ , -SO ₂ C ₃ H ₇ , -SO ₂ CH (CH ₃ ) ₂ , -SO ₂ CH ₂ CF ₃ , -CH ₂ SO ₂ CH ₃ , -OC ₄ H ₈ -OC ₄ H ₉ , -CF ₃ , -C ₂ F ₅ , -C ₃ F ₇ , -C ₄ F ₉ , -C (CF ₃ ) ₃ , -CF ₂ SO ₂ CF ₃ , -C ₂ F ₄ N (C ₂ F ₅ ) C ₂ F ₅ , -CHF ₂ , -CH ₂ CF ₃ , -C ₂ F ₂ H ₃ , -C ₃ FH ₆ , -CH ₂ C ₃ F ₇ , -C (CFH ₂ ) ₃ , -CH ₂ C (O) OH, -CH ₂ C ₆ H ₅ or P (O) (C ₂ H ₅ ) ₂ .

In R ', C ₃ - to C ₇ -cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

In R 'is substituted phenyl, by C ₁ - to C ₆ alkyl, C ₁ - to C ₆ alkenyl, NO ₂ , CN, NR' ₂ , F, Cl, Br, I, C ₁ -C ₆ alkoxy , SCF ₃ , SO ₂ CF ₃ , COOH, SO ₂ X ', SO ₂ NR'' ₂ or SO ₃ H substituted phenyl, where X' is F, Cl or Br and R '' is a non, partially or perfluorinated C ₁ - to C ₆ -alkyl or C ₃ - to C ₇ -cycloalkyl as defined for R ', for example, o-, m- or p-methylphenyl, o-, m- or p-ethylphenyl, o-, m- or p -Propylphenyl, o-, m- or p-isopropylphenyl, o-, m- or p-tert-butylphenyl, o-, m- or p-nitrophenyl, o-, m- or p-methoxyphenyl, o-, m - or p-ethoxyphenyl, o-, m-, p- (trifluoromethyl) phenyl, o-, m-, p- (trifluoromethoxy) phenyl, o-, m-, p- (trifluoromethylsulfonyl) phenyl, o-, m- or p-fluorophenyl, o-, m- or p-chlorophenyl, o-, m- or p-bromophenyl, o-, m- or p-iodophenyl, more preferably 2,3-, 2,4-, 2,5 -, 2,6-, 3,4- or 3,5-dimethylphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dihydroxyphenyl, 2 , 3-, 2,4-, 2,5-, 2,6-, 3,4- or r is 3,5-difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dichlorophenyl, 2,3-, 2,4-, 2, 5-, 2,6-, 3,4- or 3,5-dibromophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dimethoxyphenyl, 5-fluoro-2-methylphenyl, 3,4,5-trimethoxyphenyl or 2,4,5-trimethylphenyl.

In R ^{1 '} to R ^4' is understood as a heteroaryl saturated or unsaturated mono- or bicyclic heterocyclic radical having 5 to 13 ring members, where 1, 2 or 3 N and / or 1 or 2 S or O atoms may be present and the heterocyclic radical is mono- or polysubstituted by C ₁ - to C ₆ -alkyl, C ₁ - to C ₆ -alkenyl, NO ₂ , CN, NR ' ₂ , F, Cl, Br, I, C ₁ -C ₆ - Alkoxy, SCF ₃ , SO ₂ CF ₃ , COOH, SO ₂ X ', SO ₂ NR' ₂ or SO ₃ H may be substituted, wherein X 'and R' have the meaning given above.

The heterocyclic radical is preferably substituted or unsubstituted 2- or 3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2-, 4- or 5-imidazolyl, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, more preferably 1,2,3-triazole-1, -4- or -5-yl, 1,2,4-triazole-1 , -4- or -5-yl, 1- or 5-tetrazo lyl, 1,2,3-oxadiazol-4 or -5-yl 1,2,4-oxadiazol-3 or -5-yl, 1,3,4-thiadiazol-2 or -5-yl, 1 , 2,4-thiadiazol-3 or -5-yl, 1,2,3-thiadiazol-4 or -5-yl, 2-, 3-, 4-, 5- or 6-2H-thiopyranyl, 2 , 3- or 4-4H-thiopyranyl, 3- or 4-pyridazinyl, pyrazinyl, 2-, 3-, 4-, 5-, 6- or 7-benzofuryl, 2-, 3-, 4-, 5- , 6- or 7-benzothienyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-1H-indolyl, 1-, 2-, 4- or 5-benzimidazolyl, 1-, 3- , 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzisoxazolyl, 2-, 4 -, 5-, 6- or 7-benzthiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benz-2,1,3-oxadiazolyl, 1 -, 2-, 3-, 4-, 5-, 6-, 7- or 8-quinolinyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolinyl, 1-, 2 -, 3-, 4- or 9-carbazolyl, 1-, 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-acridinyl, 3-, 4-, 5-, 6 -, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl or 1-, 2- or 3-pyrrolidinyl.

By heteroaryl-C ₁ -C ₆ -alkyl is now understood analogously to aryl-C ₁ -C ₆ -alkyl, for example pyridinyl-methyl, pyridinyl-ethyl, pyridinyl-propyl, pyridinyl-butyl, pyridinyl-pentyl, pyridinyl-hexyl, wherein furthermore the previously described heterocycles can be linked in this way with the alkylene chain.

wobei die Substituenten R^1' bis R^4' jeweils unabhängig voneinander eine zuvor beschriebene Bedeutung haben.HetN ⁺ is preferred

wherein the substituents R ^{1 '} to R ^4' each independently have a meaning as described above.

Preferably it is the cations of the invention ionic liquid to ammonium, phosphonium, imidazolium, Pyridinium or pyrrolidinium cations.

Especially preferred ionic liquids are ammonium, phosphonium, Imidazolium or pyrrolidinium hydrogen sulfates, alkyl sulfates, Alkyl sulfonates, perfluoroalkyl sulfonates, phosphates, hydrogen phosphates, Alkyl phosphates, alkyl and perfluoroalkyl phosphinates, alkyl and Perfluoroalkyl-phosphonates or perfluoroalkylcarboxylates. All particularly preferred ionic liquids are imidazolium or pyrrolidinium hydrogensulfates, alkylsulfonates, perfluoroalkylsulfonates, Hydrogen phosphates, perfluoroalkyl phosphinates, perfluoroalkyl phosphonates or perfluoroalkylcarboxylates.

The reaction according to the invention can be summarized in the following reaction scheme:

The inventive method has the advantage that the two reaction steps directly behind each other, that is without isolation of the intermediate can. The present method thus provides a simple one-pot synthesis for chroman derivatives to be carried out, in particular for tocopherols.

Preferably, the method is the following method:

In a further preferred embodiment of the process according to the invention, the reaction medium containing at least one ionic liquid additionally contains at least one acid, preferably one corresponding to the anion A ^- corresponding acid. In general, any acid is suitable for mixing with the ionic liquid. Examples of preferred mixtures which prove to be particularly suitable in the process according to the invention are, for. B. mixtures of ionic liquids with [HSO ₄ ] ^- anions and H ₂ SO ₄ . Alternative examples are mixtures of ionic liquids with [CF ₃ SO ₃ ] ^- anions and CF ₃ SO ₃ H or mixtures of ionic liquids with [(C ₂ F ₅ ) ₂ P (O) O] ^- anions and (C ₂ F ₅ ) ₂ P (O) OH. The mixtures mentioned are to be regarded as exemplary without representing a limitation of the possibilities of the present invention.

Of the Proportion of the acid in the ionic liquid may be 0 to 90 wt .-%, based on the mixture, preferably it is in the range of 0 to 50 wt .-%.

The Process temperature is not critical per se and is usually -30 ° C. to 200 ° C, preferably 20 ° C to 120 ° C.

The above-mentioned mixtures of ionic liquids and at least one acid are particularly suitable in the process according to the invention, since the presence of the acid makes the ring closure in the second step of the process faster than with the ionic liquid alone. In addition, it has been found that in particular mixtures of ionic liquids and acids corresponding to the anion A ^- the ionic liquid, characterized in that the acid in the mixture is low volatile, that is in the mixture in a constant concentration even at higher Temperatures, is present. Thus, for example, trifluoroacetic acid in the mixture with an ionic liquid with a trifluoroacetate anion proves to be virtually non-volatile and has only a low vapor pressure.

Another object of the present invention is the use of ionic liquids of the general formula K ⁺ A ^- for the preparation of chroman derivatives. With respect to the chroman derivatives, there are no limitations in the case of the present invention, that is, all compounds having a chroman ring system as shown in formula (I) can be prepared by using ionic liquids according to the present invention. The chroman system itself may be part of a larger, for example fused, ring system. In particular, the chroman derivatives are those of the general formula (I), and very particularly preferably those from the group comprising α-, β-, γ-, δ-, ζ- and η-tocopherols and α-, β- and γ-tocotrienols. In a very particularly preferred embodiment of the use according to the invention, the ionic liquid of the formula K ⁺ A ^- in combination with an acid corresponding to the anion A ^{- is} present.

worin R7 H oder geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen, R5-R6 geradkettiges oder verzweigtes Alkyl mit 1-12 C-Atomen und R1-R4 geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen bedeuten und wobei R2 und R3 nicht gleichzeitig CH₃, oder gleichzeitig CH₃ und H sind. Vorzugsweise ist R7 H.Likewise provided by the present invention are compounds of the formula (I)

wherein R7 is H or straight-chain or branched alkyl having 1-20 C atoms, R5-R6 straight-chain or branched tes alkyl having 1-12 C atoms, and R1-R4 is straight-chain or branched alkyl having 1-20 C atoms and wherein R2 and R3 are not simultaneously CH _3, or CH ₃ and H at the same time are. Preferably, R7 is H.

worin R7 H oder geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen, R2 Br ist und R5-R6 H und/oder geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen bedeuten und R1, R3, R4 H und/oder geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen bedeuten, wobei nicht alle R1, R3, R4 gleichzeitig CH₃ oder H sind und wobei 6-Brom-5-isopropyl-2,8-dimethylchroman ausgenommen ist. Vorzugsweise ist R7 H.Another object of the present invention are compounds of the formula (I)

wherein R7 is H or straight-chain or branched alkyl having 1-20 C atoms, R2 is Br and R5-R6 is H and / or straight-chain or branched alkyl having 1-40 C atoms and R1, R3, R4 is H and / or straight-chain or branched alkyl having 1-20 C atoms, wherein not all R ₁ , R ₃ , R 4 are simultaneously CH ₃ or H and wherein 6-bromo-5-isopropyl-2,8-dimethylchroman is excluded. Preferably, R7 is H.

worin R7 H oder geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen, R5-R6 geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen bedeuten, und R1-R4 geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen, das vollständig mit F substituiert ist und/oder F bedeuten, mit der Maßgabe, dass mindestens einer der Reste R1-R4 ein geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen ist und R1 oder R3 nicht CF₃ sind, ebenfalls Gegenstand der vorliegenden Erfindung. Vorzugsweise ist dabei R7 H.In addition, compounds of the formula (I)

in which R 7 is H or straight-chain or branched alkyl having 1-20 C atoms, R 5 -R 6 is straight-chain or branched alkyl having 1-40 C atoms, and R 1 -R 4 is straight-chain or branched alkyl having 1-40 C atoms, which is complete is substituted with F and / or F, with the proviso that at least one of the radicals R1-R4 is a straight-chain or branched alkyl having 1-20 C atoms, and R1 or R3 are not CF _3, also subject of the present invention. Preferably, R7 is H.

worin R7 H oder geradkettiges oder verzweigtes Alkyl mit 1-20 C-Atomen, R5-R6 geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen bedeuten, und wobei mindestens einer der Reste R1-R4 CN bedeutet und mindestens einer der Reste R1-R4 geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen bedeutet und worin die übrigen Reste R1-R4 ausgewählt sein können aus F, Cl, Br, I, -C(O)OH, -C(O)NR'₂, -SO₂NR'₂, -SO₂OH, -SO₂X, -NO₂, -NR'₂,
geradkettiges oder verzweigtes Alkyl mit 1-40 C-Atomen,
geradkettiges oder verzweigtes Alkenyl mit 2-40 C-Atomen und einer oder mehreren nicht konjugierten Doppelbindungen,
geradkettiges oder verzweigtes Alkinyl mit 2-40 C-Atomen und einer oder mehreren nicht konjugierten Dreifachbindungen,
gesättigtes, teilweise oder vollständig ungesättigtes Cycloalkyl mit 3-7 C-Atomen, das mit Alkylgruppen mit 1-20 C-Atomen substituiert sein kann, bedeutet, wobei ein oder mehrere der genannten Reste teilweise oder vollständig mit Halogenen, insbesondere -F und/oder -Cl, oder teilweise mit -OR', -CN, -C(O)OH, -C(O)NR'₂, -SO₂NR'₂, -SO₂OH, -SO₂X, -NO₂, substituiert sein können, und wobei ein oder zwei nicht benachbarte und nicht α-ständige Kohlenstoffatome von R1-R4 durch Atome und/oder Atomgruppierungen ausgewählt aus der Gruppe -O-, -S-, -S(O)-, -SO₂-, -N⁺R'₂-, -C(O)NR'-, -SO₂NR'-, oder -P(O)R'- ersetzt sein können mit R' = H, nicht, teilweise oder perfluoriertes C₁- bis C₆-Alkyl, C₃- bis C₇-Cycloalkyl, unsubstituiertes oder substituiertes Phenyl, X = Halogen und R'' = H oder C₁- bis C₆-Alkyl, sind ein weiterer Gegenstand der vorliegenden Erfindung. Vorzugsweise ist dabei R7 H.Compounds of the formula (I)

in which R 7 denotes H or straight-chain or branched alkyl having 1-20 C atoms, R 5 -R 6 denotes straight-chain or branched alkyl having 1-40 C atoms, and where at least one of the radicals R 1 -R 4 denotes CN and at least one of the radicals R 1 R4 is straight-chain or branched alkyl having 1-40 C atoms and wherein the remaining residues R1-R4 may be selected from F, Cl, Br, I, -C (O) OH, -C (O) NR _'2, - SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , -NR' ₂ ,
straight-chain or branched alkyl having 1-40 C atoms,
straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds,
straight-chain or branched alkynyl having 2-40 C atoms and one or more non-conjugated triple bonds,
saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms, which may be substituted by alkyl groups having 1-20 C atoms, wherein one or more of said radicals partially or completely with halogens, in particular -F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two non-adjacent and non-α-carbon atoms of R1-R4 are substituted by atoms and / or atomic groups selected from Grup pe is -O-, -S-, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR' -, -SO ₂ NR '-, or -P (O ) R 'can be replaced with R' = H, not, partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl, X = halogen and R "= H or C ₁ - to C ₆ -alkyl, are a further subject of the present invention. Preferably, R7 is H.

The mentioned compounds are suitable for the preparation of chromium derivatives and / or chroman-2-one and / or chroman-4-one derivatives and in cosmetic and / or pharmaceutical formulations. cosmetic and / or pharmaceutical formulations containing at least one the compounds of the invention are thus Another object of the present invention.

It is understood by the skilled person that in the mentioned ionic liquids or compounds of Formula (I), (II) or (III) substituents such as H, N, O, Cl, F may be replaced by the corresponding isotopes.

The following embodiments are intended to illustrate the invention without limiting it. Above and below, percentages are by weight. All temperatures are in degrees Celsius. Examples: Example 1: Production of Vitamin E in Ionic Liquids with Hydrogen Sulfate Anions

To 28.3 g (136 mmol) of 1-ethyl-3-methyl hydrogen sulfate (EMIM hydrogen sulfate) in a 100 ml round bottom flask are added 13.1 g (127 mmol) of 95-97% H ₂ SO ₄ . After the mixture has cooled to room temperature, 2.84 g (18.7 mmol) of 2,3,6-trimethylhydroquinone and 6.05 g (20.4 mmol) of isophytol are added and the reaction mixture is heated to 76 ° C. (temperature of the bath) with stirring for 6 hours. The transparent colored mixture is extracted with 170 ml of toluene. The toluene phase is decanted and all volatiles removed in vacuo (20 mbar) at 40 ° C. There are obtained 5.16 g of a viscous brown crude product. After purification, a lightly colored oily material is obtained which has identical ¹ H and ¹³ C NMR data compared to commercially available vitamin E. The yield of vitamin E is 64%, based on the amount of 2,3,6-trimethylhydroquinone used. Example 2: Production of vitamin E in ionic liquids with triflate anions

• ¹H NMR (300.14 MHz) in CDCl₃ by 24°C, Standard – TMS; Vitamin E: δ, ppm = 1.05 pseudo-t (4CH₃ ^a, 12H), 1.2–1.7 m (8CH₂ ^b + 2CH^b, 18H), 1.40 s (CH₃ ^c), 1.73 sep (CH^d, ³J_H,H = 6.6 Hz,), 1.93 pseudo-oct (CH₂ ^e), 2.28 s (3CH₃ ^f, 9H), 2.74 s (2CH^g, 2H), 4.57 s (OH^h, 1H)
• ¹³C{1H} NMR (75.47 MHz) in CD₃CN bei 24°C, Standard – TMS; Vitamin E: δ, ppm = 11.3 s (C²³), 11.9 s (C²⁵), 12.3 s (C²⁴), 19.8–19.9 s (C^27-29), 20.9 s (C²²), 21.3 s (C²⁶), 22.8 s (C⁹), 22.9 s (C⁸), 23.9 s (C¹⁰), 25.0 s (C²¹), 25.0 s (C¹⁷), 28.2 s (C¹³), 31.7 s (C¹⁵), 32.8–33.0 s (C¹⁹), 37.5–37.8 s (C^{12,14,16,18,20}), 39.6 s (C¹¹), 74.5 s (C¹), 117.3 s (C⁴), 119.0 s (C⁶), 121.6 s (C⁷), 122.6 s (C⁵), 144.7 s (C³), 145.7 s (C²)

Beispiel 3: Herstellung von Vitamin E in einem Zwei-Phasensystem [BMIM]⁺[HSO₄]^–, H₂SO₄ und n-Hexan

To 37.6 g (145 mmol) of 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMIM triflate) in a 100 ml round bottom flask is added 5.28 g (35 mmol) of CF ₃ SO ₃ H. After the mixture has cooled to room temperature, 4.79 g (31.5 mmol) of 2,3,6-trimethylhydroquinone and 9.34 g (31.5 mmol) of isophytol are added, and the reaction mixture is stirred at room temperature for 1.5 hours. The transparent colored mixture is extracted with 250 ml of hexene. The hexane phase is decanted and all volatiles removed in vacuo (20 mbar) at 40 ° C. There are obtained 9.84 g of a viscous brown crude product. After purification, a lightly colored oily material is obtained which has identical ¹ H and ¹³ C NMR data compared to commercially available vitamin E. The yield of vitamin E is 73%. MR data: α-tocopherol (vitamin E)

• ¹ H NMR (300.14 MHz) in CDCl ₃ by 24 ° C, standard TMS; Vitamin E: δ, ppm = 1:05 pseudo-t (4CH ₃ ^a, 12H), 1.2-1.7 m (8CH ₂ ^b + 2CH ^b, 18H), 1:40 s (CH ₃ ^c), 1.73 sep (CH ^{d, 3} J _{H, H} = 6.6 Hz,), 1.93 pseudo-oct (CH ₂ ^e ), 2.28 s (3CH ₃ ^f , 9H), 2.74 s (2CH ^g , 2H), 4.57 s (OH ^h , 1H)
• ¹³ C {1H} NMR (75.47 MHz) in CD ₃ CN at 24 ° C, standard TMS; Vitamin E: δ, ppm = 11.3 s (C ²³ ), 11.9 s (C ²⁵ ), 12.3 s (C ²⁴ ), 19.8-19.9 s (C ^27-29 ), 20.9 s (C ²² ), 21.3 s (C ²⁶ ), 22.8 s (C ⁹ ), 22.9 s (C ⁸ ), 23.9 s (C ¹⁰ ), 25.0 s (C ²¹ ), 25.0 s (C ¹⁷ ), 28.2 s (C ¹³ ), 31.7 s (C ¹⁵ ), 32.8-33.0 s (C ¹⁹ ), 37.5-37.8 s (C ^{12,14,16,18,20} ), 39.6 s (C ¹¹ ), 74.5 s (C ¹ ), 117.3 s (C ⁴ ), 119.0 s (C ⁶ ), 121.6 s (C ⁷ ), 122.6 s (C ⁵ ), 144.7 s (C ³ ), 145.7 s (C ² )

Example 3: Production of vitamin E in a two-phase system [BMIM] ⁺ [HSO ₄ ] ^- , H ₂ SO ₄ and n-hexane

In a 100 ml round bottom flask 14.58 g (61.7 mmol) of 1-butyl-3-methylimidazoliumhydrogensulfat, [BMIM] ⁺ [HSO ₄ ] ^- presented and 6.14 g (62.6 mmol) of 100% H ₂ SO ₄ , was added (strongly exothermic !). After the ionic liquid is cooled (RT), n-hexane (20 ml) is added. 2.10 g (13.8 mmol) of 2,3,6-trimethylhydroquinone and 4.09 g (13.9 mmol) of isophytol are added rapidly to the existing two-phase system ionic liquid / n-hexane and stirred at RT for about 10 min. The reaction mixture is stirred for 2.5 hours at 75 ° C (temperature of the bath), both phases are dark brown colored. The n-hexane phase is decanted and distilled in vacuo (100 mbar) at 40-50 ° C and then distilled in vacuo (10 ^-2 mbar) at 60 ° C. The viscous, slightly brown vitamin E crude product (5.80 g, 13.4 mmol, yield 97%) is isolated and characterized by ¹ H and ¹³ C NMR spectra. Example 4: Multiple production of vitamin E in a two-phase system [EMIM] ⁺ [HSO ₄ ] ^- , H ₂ SO ₄ and n-hexane

14.24 g (68.4 mmol) of 1-ethyl-3-methylimidazolium hydrogensulfate, [EMIM] ⁺ [HSO ₄ ] ^- , and 6.71 g (68.4 mmol) of 100% H ₂ SO ₄ are placed in a 100 mL round bottom flask (strongly exothermic! ) and n-hexane (20 mL) were added. Pre-weighed 2,3,6-trimethylhydroquinone and isophytol are added quickly and stirred at RT for about 10 min. Both the ionic liquid phase and the n-hexane phase turn brown. The reaction mixtures are stirred for 2-3 hours at 55-66 ° C (temperature of the bath), both phases are deep brown to black colored. The upper n-hexane phase is decanted and the ionic liquid extracted again with n-hexane (20 mL). The decanted mother liquors are first distilled in vacuo (40 mbar) at 40 ° C and finally at 10 ^-2 mbar and 60 ° C. The crude product, vitamin E, is stored until clean. The ionic liquid is again treated with trimethylhydroquinone and isophytol. Every second time, the ionic liquid is regenerated by pumping out all volatiles at 50-143 ° C over a period of 2-5 hours in vacuo (10 ^-2 mbar). Subsequently, trimethylhydroquinone and isophytol are added again.

Batch 1

• 2,3,6-trimethylhydroquinone 2.584 g (17.0 mmol)
• Isophytol 5.050 g (17.0 mmol)
• Yield Vitamin E 6.243 g (14.5 mmol, 85.3%)

Batch 2

• 2,3,6-trimethylhydroquinone 2.678 g (17.6 mmol)
• Isophytol 5.263 g (17.7 mmol)
• Yield Vitamin E 6,426 g (14.9 mmol, 84.7%)

Regeneration 1 of the ionic liquid

Batch 3

• 2,3,6-Trimethylhydroquinone 3.029 g (19.9 mmol)
• Isophytol 5.932 g (20.0 mmol)
• Yield Vitamin E 7.827 g (18.2 mmol, 91.5%)

Batch 4

• 2,3,6-trimethylhydroquinone 2.673 g (17.6 mmol)
• Isophytol 5.328 g (18.0 mmol)
• Yield Vitamin E 7.623 g (17.7 mmol, 100.7%)

Regeneration 2 of the ionic liquid

Lot 5

• 2,3,6-trimethylhydroquinone 2.906 g (19.1 mmol)
• Isophytol 5.675 g (19.1 mmol)
• Yield Vitamin E 7.906 g (18.4 mmol, 96.3%)
• Total yield of vitamin E 91.6%

After purification by distillation (bath temperature: 300 ° C., head temperature: 180 ° C., vacuum: 1 × 10 ^-7 mbar), a lightly colored oily material is obtained which has identical ¹ H and ¹³ C NMR data, compared with commercially available Vitamin E, has. Example 5: Preparation of vitamin E in two-phase system [BMPL] ⁺ [CF ₃ SO ₃ ] ^- + 0.1 mol CF ₃ SO ₃ H and n-hexane

16,250 g (55.9 mmol) of clear and colorless 1-butyl-1-methylpyrrolidinium triflate, [BMPL] ⁺ [CF ₃ SO ₃ ] ^- and 0.846 g (5.5 mmol) of triflouretic acid, CF ₃ SO ₃ H, are placed in a 100 mL round bottom flask. added (exothermic). After cooling (RT), n-hexane (20 mL) is added. 2.42 g (15.9 mmol) of 2,3,6-trimethylhydroquinone and 4.75 g (16.0 mmol) of isophytol are rapidly added to the existing two-phase system, ionic liquid / n-hexane, and stirred at RT for about 10 min. The reaction mixture is stirred for 18 hours at RT and 2 hours at 46 ° C (temperature of the bath), the n-hexane phase decanted and distilled in vacuo (100 mbar) at 40-50 ° C and then in vacuo (10 ^-2 mbar) and distilled at 60 ° C. The viscous light brown vitamin E crude product (5.00 g, 11.6 mmol, yield: 73.0%) was isolated and characterized by ¹ H and ¹³ C NMR spectroscopy. Example 6 Production of Vitamin E in Two-Phase System [EMIM] ⁺ [(C ₂ F ₅ ) ₂ P (O) O] ^- , (C ₂ F ₅ ) ₂ P (O) OH and n-hexane

In a 100 ml round bottom flask are charged 10.52 g (25.5 mmol) of 1-ethyl-3-methylimidazolium bis (pentafluoroethyl) phosphinate, [EMIM] ⁺ [(C ₂ F ₅ ) ₂ PO ₂ ] ^- and 3.87 g (12.8 mmol) of bis ( pentafluoroethyl) phosphinic acid, (C ₂ F ₅ ) ₂ P (O) OH. Then n-hexane (20 ml) is added. 2.15 g (14.1 mmol) of 2,3,6-trimethylhydroquinone and 4.19 g (14.1 mmol) of isophytol are rapidly added to the existing two-phase system, ionic liquid / n-hexane, and stirred at RT for about 10 min. The reaction mixture is stirred for 2 hours at 71 ° C (temperature of the bath), whereby both phases are dark brown colored. The reaction mixture is stirred for a further 3 days at RT, n-hexane is decanted, the IL extracted again with n-hexane (20 ml), then distilled off in vacuo (100 mbar) at 40-50 ° C and obtained vitamin E crude product ( 3.53 g; 8.2 mmol; Yield: 57.8%) were isolated and characterized by ¹ H and ¹³ C NMR spectroscopy. Example 7: Preparation of 2,2,5,8-tetramethylchroman in two-phase system [BMIM] ⁺ [HSO ₄ ] ^- , H ₂ SO ₄ and n-hexane

• ¹H NMR Spektrum (300,14 MHz) in CDCl₃ bei 24°C, Standard – TMS; δ, ppm: 1.36 s (2 CH₃ ^g), 1.88 t (CH₂ ^a, ³J_H,H = 7.3 Hz), 2.09 s (CH₃ ^c), 2.20 s (CH₃ ^f), 2,73 t (CH₂ ^b, ³J_H,H = 7.3 Hz), 6.57 d (CH^d, ³J_H,H = 7.6 Hz), 6.84 d (CH^e, ³J_H,H = 7,4 Hz).

Beispiel 8: Herstellung von 2,2,5,7,8-Pentamethylchroman-6-ol in Zwei-Phasensystem [BMIM]⁺[HSO₄]^–, H₂SO₄ und n-Hexan

[EMIM] ⁺ [HSO ₄ ] ^- H ₂ SO ₄ (23.747 g, 77.5 mmol) is placed in a 100 mL round bottom flask and n-hexane (20 mL) is added. 2.76 g (22.6 mmol) of 2,5-dimethylphenol and 1.96 g (22.7 mmol) of 2-methyl-3-buten-2-ol were added rapidly to the existing two-phase system, ionic liquid / n-hexane, and 2 hours at RT touched. In this case, the IL and n-hexane phase immediately turn brown. The n-hexane phase is decanted and first distilled off in vacuo (100 mbar) at 40-50 ° C (temperature of the bath) and finally in vacuo (10 ^-2 mbar) at 50 ° C. What remains is brown, clear and viscous 2,2,5,8-tetramethylchroman crude product (2.56 g, 13.4 mmol, yield: 59%). The ionic liquid is further extracted with toluene (20 mL), whereby further 2,2,5,8-tetramethylchroman crude product (0.51 g, 2.7 mmol, 12%) can be isolated. The crude product is characterized by ¹ H NMR spectroscopy. NMR 2,2,5,8-tetramethylchroman

• ¹ H NMR spectrum (300.14 MHz) in CDCl ₃ at 24 ° C, standard TMS; δ, ppm: 1.36 s (2 CH ₃ ^g ), 1.88 t (CH ₂ ^a , ³ J _{H, H} = 7.3 Hz), 2.09 s (CH ₃ ^c ), 2.20 s (CH ₃ ^f ), 2.73 t (CH ₂ ^b , ³ J _{H, H} = 7.3 Hz), 6.57 d (CH ^d , ³ J _{H, H} = 7.6 Hz), 6.84 d (CH ^e , ³ J _{H, H} = 7.4 Hz).

Example 8: Preparation of 2,2,5,7,8-pentamethylchroman-6-ol in two-phase system [BMIM] ⁺ [HSO ₄ ] ^- , H ₂ SO ₄ and n-hexane

• ¹H NMR (300,14 MHz) in CDCl₃ bei 24°C, Standard – TMS; δ, ppm: 1.37 s (2CH₃ ^g), 1.86 t (2CH^a, ³J_H-H = 7.1 Hz), 2.18 s (CH₃ ^c), 2.20 s(CH₃ ^e), 2.22 s (CH₃ ^f), 2.69 t (2CH^b, ³J_H-H = 6.6 Hz), 4.23 s (OH^e).
• ¹³C{1H} NMR (75,47 MHz) in CDCl₃ bei 24°C δ, ppm = 11.41 s (1C¹¹), 11.92 s (1C¹³), 12.35 s (1C¹²), 21.21 s (1C³), 26.82 s, (2C¹⁰), 33.20 s (1C²), 72.55 s (1C¹), 117.17 s (1C⁹), 118.95 s (1C⁴), 121.48 s (1C⁶), 122.63 s (1C⁷), 144.73 s (1C⁵), 145.83 s (1C⁸)

In a 100 mL round bottom flask is charged 28.93 g (94.4 mmol) of [EMIM] ⁺ [HSO ₄ ] ^- . H ₂ SO ₄ and n-hexane (20 mL) is added. 4.53 g (29.8 mmol) of trimethylhydroquinone and 2.57 g (29.9 mmol) of 2-methyl-3-buten-2-ol are rapidly added to the existing two-phase system, ionic liquid / n-hexane (exothermic). The IL-phase immediately turns brown. The reaction mixture is stirred for 17 hours at RT. The brown n-hexane phase is decanted, the ionic liquid is extracted three more times with n-hexane (20 mL each) and all n-hexane phases are combined. The n-hexane mother liquor is distilled off only at 100 mbar at 50 ° C. and finally in vacuo at 10 ^-2 mbar at 50 ° C. 2,2,5,7,8-pentamethylchroman-6-ol (2.39 g, 10.8 mmol, yield: 36.2%) of crude product can be isolated as a brown oil. Pure product can be obtained by distilling the brown oil in vacuo (10 ^-2 mbar) at 195 ° C (bath temperature). The remaining reaction mixture (ionic liquid) is treated with more n-hexane (20 mL) and stirred for a further 4 hours at 61 ° C (temperature of the bath). The yellow n-hexane phase is decanted and distilled off in vacuo (100 mbar) at 50 ° C. What remains is a golden, viscous oil. After cooling (RT), white 2,2,5,7,8-pentamethylchroman-6-ol (0.57 g, 2.6 mmol, 8.7%) crystallized out. Pure product is characterized by ¹ H and ¹³ C NMR spectroscopy. NMR 2,2,5,7,8-pentamethylchroman-6-ol

• ¹ H NMR (300.14 MHz) in CDCl ₃ at 24 ° C, standard TMS; δ, ppm: 1.37 s (2CH ₃ ^g ), 1.86 t (2CH ^a , ³ J _HH = 7.1 Hz), 2.18 s (CH ₃ ^c ), 2.20 s (CH ₃ ^e ), 2.22 s (CH ₃ ^f ), 2.69 t (2CH ^b , ³ J _HH = 6.6 Hz), 4.23 s (OH ^e ).
• ¹³ C {1H} NMR (75.47 MHz) in CDCl ₃ at 24 ° C δ, ppm = 11.41 s (1C ¹¹ ), 11.92 s (1C ¹³ ), 12.35 s (1C ¹² ), 21.21 s (1C ³ ) , 26.82 s, (2C ¹⁰ ), 33.20 s (1C ² ), 72.55 s (1C ¹ ), 117.17 s (1C ⁹ ), 118.95 s (1C ⁴ ), 121.48 s (1C ⁶ ), 122.63 s (1C ⁷ ), 144.73 s (1C ⁵ ), 145.83 s (1C ⁸ )

The values mentioned are in line with those in the literature [ S. Witkowski, D. Maciejewska and J. Wawer, J. Chem. Soc., Perkin Trans. 2, 2000, p. 1471-1476 ] agree. Example 9: Preparation of 6-bromo-2,2,5,7-tetramethylchroman in two-phase system [BMIM] ⁺ [HSO ₄ ] ^- , H ₂ SO ₄ and n-hexane

• ¹H NMR (300,14 MHz) in CDCl₃ bei 24°C, Standard – TMS; δ, ppm: 1.32 s (2CH₃ ^a), 1.82 t (2CH^b, ³J_H-H = 6.8 Hz), 2.36 s (2CH₃d), 2.67 t (2CH^c, ³J_H-H = 6.8 Hz), 6.63 s (CH^e).
• ¹³C {1H} NMR (75,47 MHz) in CDCl₃ bei 24°C δ, ppm = 19.6 s (1C¹²), 21.8 s (1C³), 24.1 s (1C¹³), 26.7 s (2C^10,11), 33.1 s (1C²), 73.4 s (1C¹), 117.4 s (1C⁷), 118.3 s (1C⁴), 118.8 s (1C⁶), 136.6 s (1C⁹), 136.8 s (1C⁸), 152.8 s (1C⁵)

21.77 g (71.1 mmol) of [EMIM] ⁺ [HSO ₄ ] ^- . H ₂ SO ₄ are initially charged in a 100 ml round-bottom flask and n-hexane (20 ml) is added. 2.63 g (13.1 mmol) of 4-bromo-3,5-dimethylphenol are completely dissolved in the ionic liquid / H ₂ SO ₄ complex at 55-60 ° C. At 55-60 ° C (temperature of the bath) 1.34 g (15.9 mmol) of 2-methyl-3-buten-2-ol are added in portions to this reaction mixture. The ionic liquid and n-hexane phase immediately stain deep purple. The reaction mixture is stirred for another 15 minutes at 55-60 ° C (temperature of the bath). The dark purple (near-black) upper n-hexane phase is decanted, the ionic liquid extracted 2 more times with n-hexane (20 ml) and the mother liquor combined. The entire n-hexane mother liquor is distilled off in vacuo (100 mbar) at 50 ° C. It can be isolated deep violet crude product, 6-bromo-2,2,5,7-tetramethylchroman, (3.13 g, 11.7 mmol, yield: 89.4%). The remaining violet liquid is then distilled in vacuo 2 mbar at ~ 240 ° C (temperature of the bath) (head temperature: 165 ° C). Pure, gold-colored, slightly viscous 6-bromo-2,2,5,7-tetramethylchroman are isolated and characterized by ¹ H and ¹³ C NMR spectroscopy. NMR 6-bromo-2,2,5,7-tetramethylchroman

• ¹ H NMR (300.14 MHz) in CDCl ₃ at 24 ° C, standard TMS; δ, ppm: 1.32 s (2CH ₃ ^a ), 1.82 t (2CH ^b , ³ J _HH = 6.8 Hz), 2.36 s (2CH ₃ d), 2.67 t (2CH ^c , ³ J _HH = 6.8 Hz), 6.63 s (CH ^e ).
• ¹³ C {1 H} NMR (75.47 MHz) in CDCl ₃ at 24 ° C δ, ppm = 19.6 s (1C ¹² ), 21.8 s (1C ³ ), 24.1 s (1C ¹³ ), 26.7 s (2C ^{10, 11} ), 33.1 s (1C ² ), 73.4 s (1C ¹ ), 117.4 s (1C ⁷ ), 118.3 s (1C ⁴ ), 118.8 s (1C ⁶ ), 136.6 s (1C ⁹ ), 136.8 s (1C ⁸ ), 152.8 s (1C ⁵ )

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited non-patent literature

• S. Witkowski, D. Maciejewska and J. Wawer, J. Chem. Soc., Perkin Trans. 2, 2000, p. 1471-1476 [0086]

Claims (21)

Process for the preparation of compounds of the formula (I)

comprising the reaction of compounds of the formula (II)

with compounds of the formula (III),

wherein R 1 -R 4 H, F, Cl, Br, I, -OH, -CN, -C (O) OH, -C (O) NR ' ₂ , -SO ₂ NR' ₂ , -SO ₂ OH, -SO ₂ X, -OR ', -NO ₂ , -NR' ₂ straight-chain or branched alkyl having 1-40 C atoms, straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds, straight-chain or branched alkynyl having 2-40 carbon atoms and one or more non-conjugated triple bonds, saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms which may be substituted with alkyl groups having 1-20 C atoms, wherein one or more R1-R4 partially or completely with halogens, in particular -F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two nonadjacent and non-α-carbon atoms of R1-R4 are substituted by atoms and / or atomic groups selected from the group -O-, -S, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR' -, -SO ₂ NR'-, or -P (O) R'- may be replaced with R '= H, not, partially or perfluorinated C ₁ - to C ₆ alkyl, C ₃ - to C ₇ cycloalkyl, unsubstituted or substituted phenyl , X = halogen and R '' = H or C ₁ - to C ₆ -alkyl, and wherein two or more radicals R ₁ to R ₄ may be linked together, wherein R 5 -R 6 is H, Oalkyl having 1-6 C atoms, straight-chain or branched alkyl having 1-40 C atoms, straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds, or R5 and R6 together form a C = O group, wherein R7 is H or straight-chain or branched Alkyl having 1-40 carbon atoms, wherein R5, R6 and / or R7 may be bonded together, characterized in that the reaction in a reaction medium containing at least one ionic liquid of the general formula K ⁺ A ^- takes place. A process according to claim 1, characterized in that R 1 -R 4 are selected from the group comprising H, F, Cl, Br, -OH, -OR ', straight-chain or branched alkenyl having 2-40 carbon atoms and one or more non-conjugated Double bonds and straight-chain or branched alkyl having 1-40 carbon atoms and R5-R6 are selected from the group consisting of H, and straight-chain or branched alkyl having 1-40 C atoms or straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds. A method according to claim 1 or 2, characterized in that R1, R3 and R4 are selected from the group comprising H and straight-chain alkyl having 1-5 C atoms, and that R2 means OH. Method according to one or more of claims 1 to 3, characterized in that R5 and R6 are selected from the group comprising straight-chain or branched alkyl having 1-40 C atoms, or straight chain or branched alkynyl having 2-40 carbon atoms and one or more not conjugated triple bonds. Method according to one or more of claims 1 to 4, characterized in that R7 H is. Method according to one or more of claims 1 to 5, characterized in that the compound according to formula (I) is a compound of formula (Ia)

or a compound of formula (Ib)

wherein R1, R3 and R4 are selected from H and straight-chain alkyl having 1-5 C atoms. Method according to one or more of claims 1 to 6, characterized in that the anion K of the ionic liquid is selected from the group comprising [HSO ₄ ] ^- , [SO ₄ ] ^-2 , [NO ₃ ] ^- , [BF ₄ ] ^- , [(R _F ) BF ₃ ] ^- , [(R _F ) ₂ BF ₂ ] ^- , [(R _F ) ₃ BF] ^- , [(R _F ) ₄ B] ^- , [B (CN) ₄ ] ^- , [PO ₄ ] ^-3 , [HPO ₄ ] ^-2 , [H ₂ PO ₄ ] ^- , [alkyl-OPO ₃ ] ^-2 , [(alkyl-O) ₂ PO ₂ ] ^- , [alkyl-PO ₃ ] ^- , [R _F PO ₃ ] ^- , [(alkyl) ₂ PO ₂ ] ^- , [(R _F ) ₂ PO ₂ ] ^- , [R _F SO ₃ ] ^- , [alkyl-SO ₃ ] ^- , [aryl -SO ₃ ] ^- , [alkyl-OSO ₃ ] ^- , [R _F C (O) O] ^- , [(R _F SO ₂ ) ₂ N] ^- , {[(R _F ) ₂ P (O)] ₂ N} ^- , Cl ^- and / or Br ^- , where R _{F is} fluorinated alkyl (C _n F _{2n-x + 1} H _x ) with n = 1-12 and x = 0-7, where for n = 1 x = 0 to 2, and / or has fluorinated aryl or alkyl-aryl. Method according to one or more of claims 1 to 7, characterized in that the cations K ^{+ of} the ionic liquid are selected from the group of ammonium, phosphonium, thiouronium, guanidinium cations or heterocyclic cations. Method according to one or more of claims 1 to 8, characterized in that the ionic liquid additionally contains an acid corresponding to the anion A ^- . Method according to claim 9, that the proportion of acid in the ionic liquid 0 to 90 wt .-%, based on the mixture. Method according to one or more of claims 1 to 10, characterized in that the process temperature -30 up to 200 ° C. Use of ionic liquids of the general formula K ⁺ A ^- for the preparation of chroman derivatives. Use according to claim 12, characterized in that the chroman derivatives are selected from compounds of the formula (I)

wherein R 1 -R 4 H, F, Cl, Br, I, -OH, -CN, -C (O) OH, -C (O) NR ' ₂ , -SO ₂ NR' ₂ , -SO ₂ OH, -SO ₂ X, -OR ', -NO ₂ , -NR'2 straight-chain or branched alkyl having 1-40 C atoms, straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds, straight-chain or branched alkynyl having 2-40 carbon atoms and one or more non-conjugated triple bonds, saturated, partially or fully unsaturated cycloalkyl having 3-7 C atoms which may be substituted with alkyl groups having 1-20 C atoms, wherein one or more R1-R4 partially or completely with halogens, in particular -F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , and wherein one or two nonadjacent and non-α-carbon atoms of R1-R4 are substituted by atoms and / or atomic groups selected from the group -O-, -S, -S (O) -, -SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR' -, -SO ₂ NR'-, or -P (O) R'- may be replaced with R '= H, not, partially or perfluorinated C ₁ - to C ₆ alkyl, C ₃ - to C ₇ cycloalkyl, unsubstituted or substituted phenyl , X = halogen and R '' = H or C ₁ - to C ₆ -alkyl, and wherein two or more radicals R ₁ to R ₄ may be linked together, wherein R 5 -R 6 is H, Oalkyl having 1-6 C atoms, straight-chain or branched alkyl having 1-40 C atoms, straight-chain or branched alkenyl having 2-40 C atoms and one or more non-conjugated double bonds, or R5 and R6 together form a C = O group, wherein R7 is H or straight-chain or branched Alkyl having 1-40 carbon atoms, and wherein R5, R6 and / or R7 may be joined together. Use according to claim 12 or 13, characterized in that the chroman derivatives selected are from the group comprising α-, β-, γ-, δ-, ζ and η-tocopherols and α-, β- and γ-tocotrienols. Use according to one or more of claims 12 to 14, characterized in that the ionic liquid of the formula K ⁺ A ^- in combination with an acid corresponding to the anion A ^- is present. Compounds of the formula (I)

wherein R7 is H or straight-chain or branched alkyl having 1-20 C atoms, R5-R6 straight-chain or branched alkyl having 1-12 C atoms and R1-R4 straight-chain or branched alkyl having 1-20 C atoms and wherein R2 and R3 are not simultaneously CH CH _3, or ₃ and at the same time H. Compounds of the formula (I)

wherein R7 is H or straight-chain or branched alkyl having 1-20 C atoms, R2 is Br and R5-R6 is H and / or straight-chain or branched alkyl having 1-40 C atoms and R1, R3, R4 is H and / or straight-chain or branched alkyl having 1-20 C atoms, wherein not all R ₁ , R ₃ , R 4 are simultaneously CH ₃ or H and wherein 6-bromo-5-isopropyl-2,8-dimethylchroman is excluded. Compounds of the formula (I)

in which R 7 is H or straight-chain or branched alkyl having 1-20 C atoms, R 5 -R 6 is straight-chain or branched alkyl having 1-40 C atoms, and R 1 -R 4 is straight-chain or branched alkyl having 1-40 C atoms, which is complete is substituted with F and / or F, with the proviso that at least one of the radicals R1-R4 is a straight-chain or branched alkyl having 1-20 C atoms, and R1 or R3 are not CF _3. Compounds of the formula (I)

in which R 7 denotes H or straight-chain or branched alkyl having 1-20 C atoms, R 5 -R 6 denotes straight-chain or branched alkyl having 1-40 C atoms, and where at least one of the radicals R 1 -R 4 denotes CN and at least one of the radicals R 1 R4 is straight-chain or branched alkyl having 1-40 C atoms and wherein the remaining residues R1-R4 may be selected from F, Cl, Br, I, -C (O) OH, -C (O) NR _'2, - SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, -NO ₂ , -NR' ₂ straight-chain or branched alkyl having 1-40 C atoms, straight-chain or branched alkenyl having 2-40 C atoms and one or a plurality of non-conjugated double bonds, straight-chain or branched alkynyl having 2-40 carbon atoms and one or more non-conjugated triple bonds, saturated, partially or fully unsaturated cycloalkyl having 3-7 carbon atoms substituted with alkyl groups having 1-20 carbon atoms where one or more of the radicals mentioned is partially or completely halogenated, in particular -F and / or -Cl, or partially with -OR ', -CN, -C (O) OH, -C (O) NR' ₂ , -SO ₂ NR ' ₂ , -SO ₂ OH, -SO ₂ X, - NO ₂ , and wherein one or two non-adjacent and non-α-carbon atoms of R 1 -R 4 are substituted by atoms and / or atomic groups selected from the group -O-, -S-, -S (O) -, - SO ₂ -, -N ⁺ R ' ₂ -, -C (O) NR', -SO ₂ NR ', or -P (O) R' - may be replaced by R '= H, not, partially or perfluorinated C ₁ - to C ₆ -alkyl, C ₃ - to C ₇ -cycloalkyl, unsubstituted or substituted phenyl, X = halogen and R "= H or C ₁ - to C ₆ -alkyl. Use of compounds according to one or more of claims 16 to 19 for the Preparation of Chromium Derivatives and / or Chroman-2-on and / or Chroman-4-one derivatives as well as in cosmetic and / or pharmaceutical Formulations. Cosmetic and / or pharmaceutical formulations containing at least one of the compounds according to one or more of claims 16 to 19.