DE10220549A1 - New Grignard, organomanganese, organozinc and organic halogen compounds are used in the preparation of decalin, diphenyl, diphenylethane and diphenylethene compounds, used in liquid crystal displays - Google Patents

Abstract

New Grignard, organo-manganese and organic halogen compounds with the metal or halogen bound directly to decalin-2,6-diyl, diphenyl-4,4'-diyl, diphenylethane-4,4'-diyl or diphenylethene-4,4'-diyl; corresponding organic di-magnesium, -Mn and -zinc compounds; and organo-Zn and halogen compounds with the metal or halogen bound directly to decalin-2,6-diyl. The compounds are used in the synthesis of decalin, diphenyl, diphenylethane and diphenylethene derivatives. New compounds are claimed, comprising: (1) Grignard compounds of formula R<1>(A<0>)k(Z<1>)mA<1>M<1> (IIA); (2) organo-manganese (Mn) compounds of formula R<1>(A<0>)k(Z<1>)mA<1>M<2> (IIB); (3) organo-zinc (Zn) compounds of formula (IIC); (4) organic bimetal compounds of formula M(A<0>)k(Z<1>)mA<1>M<4> (IID); and (5) halogen compounds of formulae (IVA) and X(A<0>)k(Z<1>)mA<1>X (IVB). M<1> = MgCl, MgBr or MgI; R<1> = hydrogen (H), halogen or 1-18 carbon (C) alkyl, in which 1 or 2 non-adjacent CH2 groups may be replaced by -O-, -S-, -CHR<3>-CHR<4>-, -CR<3>=CR<4>- and/or -CC- and/or one or more H atoms may be replaced by halogen; R<3>, R<4> = H, 1-6 C alkyl, F, Cl, Br, CF3 or CN; A<0> = 1,4-cyclohexylene (optionally with 1 or 2 non-adjacent CH2 groups replaced by -O- and/or -S- and/or 1-substituted by R<3>), 1,4-cyclohexenylene, 1,4-bicyclo-2,2,2)octylene or 1,4-phenylene (optionally mono- or di-substituted by R<3> and optionally with CH group(s) replaced by N); Z<1> = -CH2-CH2, -CH2CHF-, -CHFCH2-, -CHFCHF-, -CF2CH2-, -CH2CF2-, -CF2CHF-, -CHFCF2-, -CF2CF2-, -CH=CH-, -CF=CH-, -CH=CF-, -CF=CF-, -OCH2-, -CH2O-, -CF2O-, -OCF2-, a single bond, -C(O)O-, -O-CO-, -CHCN-CH2- or -CH2-CHCN-; A<1> = group of formula (VA)-(VD); L<0>, L<1>, L<2>, L<3> = H or F; k = 0 or 1; m = 0, 1 or 2. In (IIA), R<1>, Z<1> are not -CN, -NCS, Cl, Br, -O-C(O)-, -C(O)O- or -CO-. M<2> = MnCl, MnBr or MnI; M<3> = ZnCl, ZnBr, ZnI or formula (i); M<4> = MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI, ZnA<1>(Z<1>)m(A<0>)kM<4> or Zn(A<0>)k(Z<1>)mA<1>M<4>; X = Cl, Br or I. Independent claims are also included for: (1) preparation of decalin, diphenyl, diphenylethane and diphenylethene derivatives; (2) preparation of Grignard compounds of formula (IIA) and organo-Mg compounds of formula (IID) (where M<4> = Mg); (3) preparation of Zn compounds of formula (IID) (where M<4> = Zn); (4) preparation of Mn compounds of formula (IID) (where M<4> = Mn).

Description

The invention relates to a process for the preparation of ring-linked compounds, in particular compounds of the formula I.

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I

in the
R ^{1 is} H, halogen or alkyl having 1-18 C atoms, in which one or two non-adjacent CH ₂ groups are also represented by -O-, -S-, -CHR ³ -CHR ⁴ -, -CR ³ = CR ⁴ - and / or -C∼C- can be replaced and / or in which one or more H atoms can also be replaced by halogen,
R ² H, halogen, -CN, -NCS, -SF ₅ , alkyl with 1-18 C atoms, in which also one or two non-adjacent CH ₂ groups by -O-, -S-, -CO-, - O-CO-, -CO-O-, -CHR ³ -CHR ⁴ -, -CR ³ = CR ⁴ - and / or -C∼C- can be replaced and / or in which one or more H atoms can also be replaced by halogen -NR'R "or -CO ₂ R ', where R' and R" independently of one another are optionally substituted benzyl or allyl,
A ^{0 is} a 1,4-cyclohexylene group, in which one or two non-adjacent CH ₂ groups can also be replaced by -O- and / or -S- and / or which can be substituted in the 1-position by R ³ , a 1 , 4-cyclohexenylene or 1,4-bicyclo [2,2,2] octylene group, an unsubstituted or once or twice substituted by R ³ 1,4-phenylene group, in which also one or more CH groups are replaced by N. could be,
A ^{2 has} one of the meanings given for A ⁰ or one of the meanings given for A ¹ ,
E -CR ³ = CR ⁴ -,
R ³ , R ⁴ each independently of one another H, alkyl having 1-6 C atoms, F, Cl, Br, CF ₃ or CN,
Z ¹ , Z ² each independently of one another -CH ₂ -CH ₂ -, -CH ₂ CHF-, -CHFCH ₂ -, -CHFCHF-, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CF ₂ CHF- , -CHFCF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF-, -OCH ₂ -, -CH ₂ O-, -CF ₂ O-, -OCF ₂ -, a single bond, -CO-O-, -O-CO-, -CHCN-CH ₂ - or -CH ₂ -CHCN-,

L ⁰ , L ¹ , L ² , L ³ each independently of one another H or F,
Q is an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene, in which one or more CH groups may be replaced by N, or a 1,4-cyclohexylene group, wherein one or two non-adjacent CH ₂ - Groups can be replaced by -O- and / or -S- and / or which can be substituted in the 1-position by R ³ , a 1,4-cyclohexenylene or 1,4-bicyclo [2,2,2] - octylene group,
m, p each independently of one another 0, 1 or 2 and
n, o, k each independently represent 0 or 1,
using organometallic compounds.

The invention also relates to a process for the preparation of compounds of the formula I '

R ^'2 - (A ^{' 2} -Z ^'2 ) _p' - (Q ') _o' - (E ') _n' - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I '

in the
R ² , R ^'2 each independently of one another have one of the meanings given for R ² in formula I,
A ^{0 has} one of the meanings given for A ⁰ in formula I,
A ² , A ^'2 each independently of one another has one of the meanings given for A ⁰ or one of the meanings given for A ¹ ,
E, E '-CR ³ = CR ⁴ -,
R ³ , R ⁴ each independently of one another H, alkyl having 1-6 C atoms, F, Cl, Br, CF ₃ or CN,
Z ¹ , Z ² , Z ^'2 each independently of one another -CH ₂ -CH ₂ -, -CH ₂ CHF-, -CHFCH ₂ -, -CHFCHF-, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, - CF ₂ CHF-, -CHFCF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF-, -OCH ₂ -, -CH ₂ O -, -CF ₂ O-, -OCF ₂ -, a single bond, -CO-O-, -O-CO-, -CHCN-CH ₂ - or -CH ₂ -OHCN-,

L ⁰ , L ¹ , L ² , L ³ each independently of one another H or F,
Q, Q 'each independently of one another have one of the meanings given for formula I for Q,
m, p, p 'each independently of one another 0, 1 or 2,
n, n ', o, o', k each independently represent 0 or 1,
using organometallic compounds.

The invention also encompasses a process for the preparation of Grignard compounds of the formula IIa as starting material in the first-mentioned process

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIa

and of Grignard compounds of the formula II'a as starting material in the second process according to the invention

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'a

in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for formula I and
M means MgCl, MgBr or MgI.

The invention further relates to a process for the preparation of zinc compounds of the formula IIb as starting material in the process mentioned first

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIb,

in which M denotes ZnCl, ZnBr, ZnI or Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -R ¹ ,
and of zinc compounds of the formula II'b as starting material in the second process according to the invention

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'b,

in which M denotes ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M,
wherein in formula IIb and II'b R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for formula I.

The invention further relates to a process for the preparation of manganese compounds of the formula IIc as starting material in the process mentioned first

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIc,

in which M means MnCl, MnBr or MnI,
and of manganese compounds of the formula II'c as starting material in the second process according to the invention

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'c,

in which M means MnCl, MnBr or MnI,
where in formula IIc and II'c R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for formula I.

The invention also relates to Grignard compounds of the formula IIIa, Manganese compounds of formula IIc and organometallic compounds Formula IIw and formula II 'according to the claims as Starting compounds in the aforementioned processes.

The invention also includes halogen compounds of the formula IVw and of formula IV 'according to the claims as starting compounds in  Process according to the invention for producing the Grignard Links.

In general, there is an increasing need for liquid crystalline compounds different physical and chemical properties. The aim is to use suitable mixtures of such compounds different and rapidly changing requirements of different To comply with display technologies. For example, Vorga ben the temperature range of a mesophase, the viscosities, esp in particular the rotational viscosity, the optical anisotropy, the dielek tric anisotropy, polarity and resistivity to be fulfilled as optimally as possible. There are usually several representatives for this to provide a structure class. The aim is therefore one economic synthesis of a diversity in the basic structure of similar compounds in just a few synthetic steps accessible output connections.

WO 88/02357 describes a process for the preparation of alkylene- or ring-linked compounds, in particular of the formula R ¹ - (A ⁰ ) _k - (Z ¹ -A ¹ ) _m - Z ⁰ - (E) _n - (Q ) _o - (Z ² -A ² ) _p -R ² . Here R and R ^{2 have} the meaning of optionally substituted alkyl radicals. A ⁰ , A ¹ and A ² include cyclohexylene groups. Z ¹ and Z ² can be single bonds or ethylene bridges. For Z ⁰ single bonds and C ₁ - to C ₄ alkylene are mentioned. Q can mean 1,4-phenylene. According to this process, a corresponding organozinc compound of the formula II 'R ¹ - (A ⁰ ) _k - (Z ¹ -A ¹ ) _m -Z ⁰ -ZnY with Y = Cl, Br, I or R ¹ - (A ⁰ ) _k - (Z ¹ -A ¹ ) _m -Z ⁰ - with a halogen compound of the formula X- (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² , where X is Br, I, OSO ₂ - (CF ₂ ) _0-10 -CF ₃ means reacted in the presence of a Pd or Ni compound catalyzing the reaction.

Cahiez et al., J. Organomet. Chem. 624 (2001) 376-379, describe the Palladium-catalyzed arylation of organomanganese chlorides Aryl bromides, predominantly the asymmetrical coupling of deactivated or sterically hindered aryl groups was considered. A important cross-coupling of 1,4- for the synthesis of liquid crystals  disubstituted cyclohexane derivatives or decalines with aryl or Ethenyl compounds are not shown here.

The synthesis of calamitic liquid crystal compounds by means of a transition metal-catalyzed cross-coupling reaction was described by E. Poetsch in Contacts (Darmstadt) 1988 (2) pages 15 to 28. The underlying reaction scheme is

where MLn is a Ni, Pd, Rh or Ru complex, m among others Metals Mg or Zn means and R, R ', X the meaning given have. Depending on the type of groups R and R 'to be linked together and their functional groups become different variants this principle with regard to a convergent synthesis if possible high chemo-, regio- and stereoselectivity described. It had however, alkyl biscyclohexyl bromides were shown to undergo a Grignard reaction are not accessible. As an alternative to the one not accessible afterwards Transmetallation of an alkyl biscyclohexyl grignard, for example in the corresponding zinc compound, the method was applied according to J.L. Luche suggested. Then the corresponding dialkyl zinc Compound from an alkyl biscyclohexyl bromide by reaction with Lithium under the influence of ultrasound and transmetallation using a Get zinc halide. The alkyl biscyclohexyl zinc Connections are made according to the scheme above, for example with an aryl halide compound in the presence of a Pd compound implemented liquid crystalline biscyclohexylphenyl compound.

The object of the present invention is to provide one the known variants of the transition metal catalyzed cross coupling reaction alternative process for the preparation of the Invention related and initially mentioned compounds of the formula I and the formula I ', the desired products in good yields are obtained with sufficient stereo and regioselectivity.  

Furthermore, it is an object of the invention to the above Starting compounds required according to the method of the invention and to show advantageous processes for their production.

The object of the invention is achieved with a process for the preparation of the compounds of the formula I.

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I

according to claim 1, wherein R ¹ , A ⁰ , Z ¹ , A ¹ , E, Q, Z ² , A ² , R ² , k, m, n, o and p have the meanings given in the introduction and in claim 1.

Thereafter, an organometallic compound of formula II

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II

in which M means MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI or Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -R ¹ and R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for the formula I, with a compound of the formula III

X- (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² III,

in which X denotes Cl, Br, I or -O-SO ₂ - (CF ₂ ) _0-10 CF ₃ and E, Q, Z ² , A ² , n, o and p have the meaning given for the formula I, in the presence of at least one metal compound catalyzing the reaction, in particular a compound containing Pd and / or Ni.

The object of the invention is also achieved with a process for the preparation of the compounds of the formula I '

R ^'2 - (A ^{' 2} -Z ^'2 ) _p' - (Q ') _o' - (E ') _n' - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I '

according to claim 2, wherein A ⁰ , Z ¹ , A ¹ , E, E ', Q, Q', Z ² , Z ^'2 , A ² , A ^{' 2} , R ² , R ^'2 , k, m, n , n ', o, o', p and p 'have the meanings given in the introduction and in claim 2.

Thereafter, an organometallic compound of the formula II '

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II '

in the
M MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _{m means} -A ¹ -M and
A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for the formula I ',
with a compound of formula III

X- (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² III,

and with a compound of formula III '

X '- (E') _{n '} - (Q') _{o '} - (Z ^{' 2} -A ^'2 ) _p' -R ^'2 III',

in which
X, X 'each independently mean Cl, Br, I or -O-SO ₂ - (CF ₂ ) _0-10 CF ₃ and
E, E ', Q, Q', Z ² , Z ^'2 , A ² , A ^{' 2} , R ² , R ^'2 , n, n', o, o ', p and p' those for the formula I. 'have the meaning given,
in the presence of at least one metal compound catalyzing the reaction, in particular a compound containing Pd and / or Ni.

Starting from the bimetallic compound of the formula II ', it is then possible to couple two identical or different compounds of the formulas III and III' by means of a double cross-coupling reaction and thus to specifically synthesize liquid-crystalline compounds of the formula I '. This is illustrated by the following scheme:

wherein the substituents and indices are those specified in claim 2 Importance.

The methods according to the invention have compared to known methods the decisive advantage that they are more economical in synthesis individual compounds with a view to a shorter synthetic route than also with several connections with regard to a high convergence are. Furthermore, the processes according to the invention are good to very good good yields and regio- and stereoselectivities achieved.

The method of claim 2 is advantageously in one synthesis step carried out. However, it is also conceivable for the two cross couplings Compound of formula II 'with the two compounds of formula III and of formula III 'one after the other, if necessary after separation and purification of the intermediate products.

In principle, all known cross-coupling catalysts are known Catalysts or precatalysts can be used. These are preferred Transition metals or their compounds, in particular Ni, Pd, Rh and / or Ru and their compounds. The ligands of the catalyzing Metal complexes are preferably N, P, As, O, S or carbon as carbenes containing compounds, such as triphenylphosphine. in the With a view to suppressing unwanted β-elimination and  In terms of high regioselectivity, the choice of ligands is important. Suitable catalysts are described for example in E. Poetsch, contacts (Darmstadt), 1988 (2), 15; S. P. Stan Forth, Tetrahderon 54, 263 (1988); Merck GmbH, DE 43 40 490 A1 dated 11/26/93; A.F. Indolese, Tetrahedron Letters 38, 3513 (1997); N. E. Leadbeater, S.M. Resouly, Tetrahedron 55, 11889 (1999); P. Kocovsky, S. Vyskocil et al., J. Amer. Chem. Soc. 121: 7714 (1999); C. Zhang, J. Huang, M.L. Trudell, S.P. Nolan, J. Org. Chem. 64, 3804 (1999).

The metal atom is preferably in the zero-valent state, in particular Ni or Pd as Ni ⁰ or Pd ⁰ . If the precatalyst has a metal cation, such as Ni (II) or Pd (II), this can be converted into the zero-valent state by reduction in situ with the metal compound of the formula II or the formula II 'to be reacted or by an additional reducing agent ( A. Jutand et al., Acc. Chem. Res. 33 (2000) 314). The reaction with the Pd ⁰ -14 electron complex, which can be derived from the precatalyst 1,1'-bisdiphenylphosphino-ferrocene-palladium (II) dichloride (PdCl ₂ .dppf), is most advantageously achieved using Pd ⁰ catalysts. The 1,2-bis (diphenylphosphino) -ethane nickel (II) dichloride (NiCl ₂ .dppe) and the 1,1'-bisdiphenylphosphino-ferrocene-nickel (II) dichloride ( NiCl ₂ .dppf) was found to be very advantageous. As a rule, the corresponding catalysts are generated in situ from the metal derivatives, but can also be prepared by means of reduction using complex hydrides, such as LiAlH ₄ , NaBH ₄ or diisobutylaluminum hydride. In addition to the chlorides, the corresponding acetates are also advantageously suitable as precatalyst compounds. The catalysts or precatalysts are usually used in an amount of 0.1 to 10 mol%, preferably 0.5 to 5 mol%, based on the organometallic compound.

The inventive implementation of the metal compound of formula II or of formula II 'with the compound of formula III and / or the formula III 'is preferably carried out in an inert solvent or solution medium mixture, for example ethers, such as diethyl ether, dimethoxyethane, Tetrahydrofuran or dioxane, hydrocarbons such as hexane, cyclo  hexane, benzene or toluene or mixtures of these solvents Temperatures in the range of -100 ° C to + 100 ° C, especially from -20 ° C to + 50 ° C. The required response times are between about 1 and 50 hours. The processing of the raw product and its Purification takes place in the specialist for such and comparable Implementations and products in a known manner.

The inventive implementation with manganese organic compounds is particularly advantageous with the addition of one or more Cosolvents such as dimethoxyethane, tetramethylethylene diamine, N-methylpyrrolidone and / or sulfolane. The cosolvents will usually 0.1 to 10 times, preferably 0.5 to 5 times, molar amount based on the organometallic compound used.

Those obtainable using the method according to the invention liquid crystalline compounds can be used in Liquid crystal mixtures or in the synthesis of polymers as mesogenic component. Such compounds, mixtures or Polymers are used in liquid crystal display elements (displays), like STN, TN, AMD-TN, temperature compensation, so-called guest host, phase change or surface stabilized or polymer stabilized cholesteric texture (SSCT, PSCT) displays, in active or passive optical elements such as polarizers, compensators, so-called alignment layers, color filters or holographic elements, liquid crystal pigments, for decorative or security applications, in non-linear optics or optical information storage.

The following are preferred meanings of each group and substituents of the compounds of the invention and the Starting compounds, intermediates and products accordingly of the method according to the invention.

R ¹ , R ² , R ^'2 each independently have the following preferred meaning: H, fluorine, alkyl having 1-12 C atoms, in which also one or two non-adjacent CH ₂ groups by -O-, -E- and / or -C∼C- can be replaced and / or in which one or more H atoms can also be replaced by fluorine.

If organic manganese or zinc compounds are used and M and M 'are not MgCl, MgBr or MgI, R ² and R ^{' 2} additionally have the preferred meanings —CN, —NCS and alkyl with 1-12 C atoms, wherein one or two non-adjacent CH ₂ groups can be replaced by -O-, -CHR ³ -CHR ⁴ -, -CR ³ = CR ⁴ -, -COO-, -OOC- and / or -C∼C- and / or in which one or more H atoms can also be replaced by fluorine.

Particularly preferred meanings of R ¹ , R ² and R ^'2 are H, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, vinyl, 1-propenyl, Allyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-pentenyl, 4-pentenyl, 1,5-hexadienyl, methoxy, ethoxy, n-propoxy, n-butoxy, n-pentoxy, n-hexoxy, vinyloxy, 1-propenyloxy, 2-propenyloxy, 2-butenyloxy, methoxy-methylene, 2-methoxy-ethylene, 3-methoxy-propylene, 4-methoxy-butylene, 5-methoxy-pentylene, ethoxy-methylene, 2-ethoxy-ethylene, ethenoxy -Methylene, 2-ethenoxyethylene, in which one or more H atoms can also be substituted by fluorine. Preferred fluorinated groups are -CF ₃ , -CH ₂ CF ₃ , -CF ₂ CF ₃ , -OCHF ₂ , -OCF ₃ , -OCF ₂ CHF ₂ , -OCHFCF ₃ , -OCF ₂ CF ₃ .

A ⁰ preferably denotes a 1,4-cyclohexylene group.

A ² , A ^'2 independently of one another preferably denote a 1,4-cyclohexylene group, an unsubstituted or once or twice substituted by R ³ 1,4-phenylene group, in which one or more CH groups can also be replaced by N, or one of the meanings of A ¹ .

E, E 'are preferably -CH = CH- and / or -CF = CF-.

Preferred meanings of R ³ and R ⁴ are each independently of the other H, alkyl having 1-6 C atoms or F.

Z ¹ , Z ² and Z ^'2 each independently have the preferred meaning -CH ₂ -CH ₂ -, -CH ₂ CHF-, -CHFCH ₂ -, -CHFCHF-, -CF ₂ CH ₂ -, -CH ₂ CF. ₂ -, -CF ₂ CHF-, -CHFCF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF-, -OCH ₂ -, -CH ₂ O-, -CF ₂ O-, -OCF ₂ - or a single bond.

Preference is given to Q, Q 'independently represent an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene, in which one or more CH groups may be replaced by N, or a 1,4-cyclohexylene, in which one or two non-adjacent CH ₂ groups can be replaced by -O- and / or -S- and / or which can be substituted in the 1-position by R ³ , a 1,4-cyclohexenylene or 1,4-bicyclo [ 2,2,2] -octylengruppe. Q, Q 'are particularly preferably an 1,4-phenylene group which is unsubstituted or substituted one to four times by R ³ , in particular F.

Since a coupling is pure according to the method according to the invention aliphatic groups cannot be carried out among themselves, Q means 1,4-phenylene, which can be substituted as indicated, and o = 1 for the Case that n = 0. The same applies to Q 'and o' if n '= 0.

The leaving groups X, X 'have the following preferred meaning independently of one another: Cl, Br, I, -O-SO ₂ -CF ₃ or -O-SO ₂ -CF ₂ -CF ₃ .

K = 1 and m = 0 or both k = 0 and m = 0 are preferred.

Also preferred are n = 0, o = 1 and p = 0, so that Q is optionally substituted 1,4-phenylene.

Also preferred is n '= 1, o' = 0 and p '= 0 and n = 0, o = 1 and p = 0, see above that Q represents optionally substituted 1,4-phenylene.

M and / or M 'MgCl, MgBr or MgI and A ¹ are preferred at the same time

the first two meanings of A ^{1 being} particularly preferred.

A ¹ are also preferred at the same time

and M and / or M 'is one of the Mg, Mn or Zn compounds given above, where M MgCl, MgBr or MgI is very particularly preferred.

Cyclohexyl groups are preferred in process product I or I ' and / or the decalin groups are substituted in the trans position, where as Dekalin the trans-decalin is preferred. The configuration is corresponding the educts to be chosen, with a possible configuration reversal in the individual synthesis steps must be taken into account.

The synthetic economic advantages of a shorter synthesis route the synthesis of a single compound I or I 'and high convergence in the synthesis of several representatives I and I 'are shown below illustrated.

The known synthesis of some representatives of structure I with k = m = 0 and

and n = p = 0, o = 1 and Q = 1,4-phenylene, requires 6 to 7 steps for the synthesis of the central key step A (Helv. Chim. Acta 65, 1242 (1982)).

Two to three further steps are necessary to introduce substituents R ² , such as CN, alkyl, CO ₂ alkyl or fluorine. Derivatives B with a di- or trifluorine substitution, an OCF ₃ , CF ₃ - or double, for example F, OCF ₃ substitution must be prepared in a 6- to 7-step new synthesis analogously to A, with the four synthesis steps for the corresponding arylcyclohexanones being added Need to become. After that, 10 to 11 steps are necessary for these substituted derivatives.

As a preliminary stage for the synthesis according to the invention, the halogen compounds C, which are used, for example, as starting materials IV for the Grignard synthesis according to claim 3, can be obtained from the corresponding, easily accessible alkylcyclohexanones in only 5 stages.

Via a metalation step to the corresponding Grignard Connection, possibly subsequent re-metalation to the corresponding Manganese or zinc compound and subsequent cross coupling with the Compound (III) in the presence of a catalyst according to the invention are all derivatives corresponding to compound B in one stage accessible.

For a single connection B, this means 6 instead of the previous 10 to 11 steps, for three different derivatives B in 5 + 3 = 8 instead of 30 to 33 levels, if, which is largely the case, the educt III without further ado is commercially available.

Coupling partner III with CN, ester and other carbonyl Functions can be used to advantage if the precursor C derivable manganese or zinc compounds are used because  these chemoselectively only enter into the coupling reaction and the Leave the carbon-heteroatom multiple bond intact.

The advantages of the process according to the invention when using bi-functional metal compounds of the formula II 'can also be easily demonstrated using an example according to the following reaction scheme for the preparation of a liquid-crystalline compound H falling under the general formula I':

Starting from the usually commercially available diols and easily accessible dihalogen compounds IV '(here 4,4'- Dibromobiscyclohexane in all-cis configuration) are after the here described methods the bimetallic compounds II ', the in one step with the two coupling reactants III 'and III according to the inventive method can be linked. As an example of that Coupling educt III 'became a vinyl halide F and for III a 1-halogen 3,4-difluorobenzene G selected. However, it is also possible to have two of the same To couple educts III 'or III to the bimetal compound II'. outgoing The desired product of the diols is I ', here 1- [4' - (4 "-ethenyl-trans- Cyclohexyl) trans-cyclohexyl) -3,4-difluorobenzene according to formula H, Available in only two stages according to the diagram above.

Although this short synthesis route is statistically determined Implementation of the two halides is subject to its overall yield higher than in known linear syntheses.  

The starting compounds of the formula II required for the processes according to the invention

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II

with the meanings given in claim 1 for R ¹ , A ⁰ , Z ¹ , A ¹ , k, m and M were previously unknown.

In particular the Grignard compounds of the formula IIa

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIa

and the formula II'a

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'a

in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have one of the meanings given in Claim 3, and M denotes MgCl, MgBr or MgI, were previously not accessible to a satisfactory synthesis.

So far, the alkyl biscyclohexyl bromides have been shown to be Grignard reaction as essentially inert so that others Synthesis routes to obtain liquid crystalline biscyclohexylaryl Connections were made (Poetsch, op. Cit., Page 22).

Contrary to this experience, which has existed for a long time, it was found, completely surprisingly, that the Grignard compounds of the formula IIa and II'a given above consist of a corresponding halogen compound of the formula IV

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV,

and Formula IV '

X '- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV',

in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meanings given for formulas IIa and II'a and X, X 'independently of one another are Cl, Br or I, but are obtainable in good yields. For this purpose, according to the invention, the halogen compound of the formula IV or the formula IV 'is reacted with magnesium in a solvent mixture which has at least one non-polar solvent and at least one polar solvent, with the supply of external heat.

It is particularly advantageous that the desired Grignard reaction according to the invention without or only with a small proportion β-elimination, which leads, for example, to HBr or HMgBr formation, runs.

Examples of suitable non-polar solvents are aliphatic and aromatic hydrocarbons without polar groups, such as hexane, Cyclohexane, benzene, toluene or xylenes or mixtures thereof Solvent.

Suitable polar solvents are, for example, ethers, such as diethyl ether, methyl tert-butyl ether, dimethoxyethane, tetrahydrofuran or Dioxane.

The mixing ratio (based on volume) of the non-polar Solvent or mixture to the polar solvent or mixture is generally 10: 1 to 1: 2, preferably from 8: 1 to 1: 1, particularly preferably 6: 1 to 2: 1.

A particularly preferred solvent mixture is benzene and / or Toluene with tetrahydrofuran. A mixing ratio is advantageous here selected from 5: 1 to 3: 1.

In addition to solvent mixtures with 2 components, there are also those with 3, 4, 5 or more components can be used, provided that at least one each sufficiently polar and at least one essentially each non-polar solvent is present.  

The reaction is advantageously carried out at the boiling point of the solvent mixture at normal pressure. A preferred temperature range is 40 ° C up to 100 ° C, in particular from 50 ° C to 80 ° C.

According to an advantageous embodiment, magnesium is more suitable Shape, for example as chips, advantageously in a protective gas atmosphere, such as nitrogen, and part of the solution containing the Halogen compound of formula IV or formula IV 'in the solution medium mixture, let run. The amount submitted is fiction according to heated with the magnesium and a suitable starter, such as for example iodine granules or a small amount of dibromoethane, added to start the Grignard reaction. After starting the The reaction takes place over a period of a few to 120 minutes Allow the majority of the solution to run in and the reaction mixture further heated for another 5 to 360 minutes, preferably under Reflux conditions. Only after the addition has been completed and continued most of the magnesium reacts, the time required for the external heat supply as a rule is longer than the previous addition time of the solution. The exothermic of Grignardization is not enough to keep the reaction going, which is why an external heat supply is provided according to the invention.

After cooling, the Grignard connection is made according to the expert known methods separated and purified or the successor reaction is carried out using the reaction solution.

Starting from the Grignard compounds of the formulas IIa and II'a obtainable by the process according to claim 3, the corresponding zinc organyl compounds of the formula IIb and the formula II can be obtained by re-metalization using zinc dihalides, in particular ZnCl ₂ and / or ZnBr ₂ 'b can be obtained in a simple manner according to claim 4. In addition, the zinc organyls which can be used for the production processes according to the invention as claimed in claims 1 and 2 can also be synthesized by known processes (Poetsch, contacts (Darmstadt) 1988 (2), 15).

The corresponding manganese compounds of the formulas IIc and II'c can be obtained by the process according to claim 5 from the Grignard compounds of the formulas IIa and II'a by transmetallation using manganese dihalides or alkali metal manganese halide compounds. Preferred manganese dihalides are MnCl ₂ and MnBr ₂ , a preferred alkali metal manganese halide is Li ₂ MnCl ₄ . In principle, the synthesis of manganese organyls from the corresponding Grignard compounds is known (G. Cahiez, M. Alami, Tetrahedron 45 (1989), 4163) and can be used in an analogous application for the preparation of the starting compounds according to the invention.

The process parameters to be selected here are general, such as Temperature, pressure, solvent and reaction time, the expert known analogous implementations, especially taking into account existing functional groups, known or easily accessible. The so Manganese and zinc organyls obtained can be prepared as the corresponding ones Grignard compounds as starting materials in the process according to the invention be used according to claim 1 and claim 2.

The Grignard reaction to be used for the above invention Halogen compounds of formula IV and formula IV 'can for example, starting from the corresponding alcohols below Use of known halogenating agents can be obtained. Please note both in the halogenation and in the later synthesis of the Grignard connection configuration reversal taking place on the concerned C atom, however, the cross-coupling reaction according to the invention takes place while maintaining the configuration.

The halogen compounds corresponding to the metal compounds of the formulas II and II 'can be synthesized from the corresponding alcohols, which in turn can be prepared from the corresponding ketones by reduction, for example using complex metal hydrides such as LiAlH ₄ .

The underlying ketones for

can be synthesized on the basis of known methods (Sucrow et al., J. Chem. Soc. Chem. Commun. 1982, 308 and Chimia 36, 460 (1982)). What is important here is the result that the hydrogenated trans-decalin configuration in the decalinones can only be generated in a satisfactory manner from the corresponding α, β-unsaturated decalinenone accessible by Stork annulation by Birch reduction. Hydrogenation of the decalinenone in polar solvents leads almost quantitatively to the less suitable cis-decalin system, which is also predominantly formed using non-polar solvents. This result differs from that on bicyclo [4.4.0] dec-1 (2) en-3,8-dione

results obtained (JB Jones and DR Dodds, Can. J. Chem. 65, 2397 (1987)) and is important for the synthesis of the bis-metal compounds of trans-decalin

The Grignard compounds according to the invention have the formula IIa

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIa

in which M denotes MgCl, MgBr or MgI and R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given in claim 7. As stated as a boundary condition, R ¹ , A ⁰ and Z ¹ do not have the functional groups -CN, -NCS, -NCO, Cl, Br, -O-CO-, -CO-O- or -CO-, otherwise a reaction of the Grignard compound formed with the functional groups mentioned would lead to undesirable by-product formation.

The manganese compounds according to the invention according to claim 8 correspond to formula IIc

R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIc

in which M is MnCl, MnBr or MnI and R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given in claim 8.

The meanings for R ¹ , A ⁰ , Z ¹ , A ¹ , k and m given as preferred or particularly preferred for the process according to the invention for the preparation of the compounds of the formula I and the formula I 'also apply with regard to the Grignard and manganese Compounds as preferred.

In particular for A ¹

prefers.

Carrying out the process according to the invention with metal organyls of formula II and formula II ', in which M is a manganese or zinc Represents connection has a use of the previously Grignard connections mentioned the advantage of a higher Chemoselectivity, according to which even in the presence of the functional Groups -CN, -NCS, -NCO, Cl, Br, -O-CO-, -CO-O- or -CO- via the Cross-coupling reaction the desired C-C linkage in high Yield takes place.

Conversely, the use of the Grignard Compounds have the advantage of higher reactivity. Furthermore allows the synthesis of the Grignard compounds according to the invention advantageous commercial production. A direct synthesis of the zinc Connections, on the other hand, require the use of ultrasound (according to Luche, a. a. O.) or iodides (after Knochel, op. Cit.), Which is in production technically complex and is only partially possible.

Therefore lies in the manufacturing method according to the invention Zinkorganyle according to claim 4, the particular advantage that this without Use of ultrasound in a simple manner from the invention accessible Grignard connections are available.  

According to the invention, both the manganese and zinc organyls and the Grignard compounds can be present as a bimetallic compound which allow cross-coupling according to the invention of two identical or different compounds of the formulas III and III 'to the organometallic compound. The organometallic compound according to the invention has the formula II '

M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II '

in the M MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _m denotes -A ¹ -M and A ⁰ , Z ¹ , A ¹ , k and m have the meanings given in claim 10. Here, too, the meanings given above as preferred for A ⁰ , Z ¹ , A ¹ , k and m are preferred according to the invention.

The dimetal compounds of the formula II 'can be synthesized from the corresponding dihalogen compounds of the formula IV',

X- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV '

in which A ⁰ , Z ¹ , A ¹ , k and m have the meanings given in Claim 12 and X denotes Cl, Br or I. The dihalogen compounds are in turn obtainable from the corresponding diols using known halogenating agents with configuration reversal.

The bimetallic compounds of formula II ', in which M MgCl, MgBr or MgI means, that is, the Grignard connections, are the same as before described method according to the invention from an implementation of a Dihalogen compound of formula IV 'with magnesium under configuration reversal available.

The corresponding dizinc and dimanganese compounds of the formula II ' are according to claim 4 or claim 5 on the corresponding Grignard connections available.  

In general, such dizink compounds are also known via others Process accessible, such as the re-metalation from corresponding Organolithium compounds or the Luche method using Ultrasound over the lithium compound in the presence of Zinc dihalides (Luche et al., Tetrahedron Letters 25, 3463 (1984); J. Org. Chem. 50, 5761 (1985)), in which also a configuration reversal takes place. The Knochel method (P. Knochel et al., Tetrahedron 50 (1994) 2415-2432), according to which the corresponding Diiodides can be reacted with metallic zinc, however under Configuration receipt. The dihalogen necessary for the latter method Connections with a suitable configuration are from the corresponding ones Ketones by hydrogenation instead of reduction over those obtained in this way Alcohols accessible.

Using the example of a compound of the formula II ', in which k = m = 0, the desired trans-substituted metal compound with configuration reversal is obtainable via the dihalo compound of the formula IV' according to the following scheme:

The bicyclohexyl-4,4'-dione can be according to Hoffmann et al. (J. Amer. Chem. Soc. 76, 1733 (1954), Trost et al. (ibid, 99, 3101 (1977)) or the DE 44 15 803 A1 can be obtained. The trans-bicyclo [4.4.0] decane-3,8-dione is accessible according to Jones and Dodds (loc. cit.).

In addition, the previously unknown starting compounds of the process according to the invention according to formula IIw belong to the present invention,

in which R ¹ , A ⁰ , Z ¹ , k and m have the meanings given in claim 9, and M ZnCl, ZnBr, ZnI or

means. The corresponding Grignard and Manganese compounds are according to the invention from claims 7 and 8.

The invention also relates to the starting compounds of the formula IVw for the preparation of the metal organyls of the formula IIw described above by one of the processes mentioned above, in particular for the preparation of the Grignard compounds according to the invention,

in which R ¹ , A ⁰ , Z ¹ , k and m have the meanings given in Claim 11, and X denotes Cl, Br or I.

In the compounds according to the invention, in particular IIw and IVw, with a decalin group, the trans configuration is

prefers.

The following examples are intended to illustrate the invention without limiting it limit. Percentages above and below mean percentages by weight percent. All temperatures are given in degrees Celsius.

"Normal work-up" means: if necessary, water is added, if necessary, adjusts to pH values depending on the constitution of the end product between 2 and 10, extracted with dichloromethane, diethyl ether, methyl tert-butyl ether or toluene, separates, dries the organic phase, evaporates and purifies the product by distillation under reduced Pressure or crystallization and / or chromatography.

1st embodiment

Grignard reaction of a biscyclohexylhalogen compound and cross coupling with an arylhalogen compound using a palladium catalyst

0.100 mol of magnesium chips are placed in a round bottom flask, heated to 80 ° C. and about 25 ml of a solution of 0.100 mol of 1-bromo-4- (4'-n-propylcyclohexl) cyclohexane (IV.1) in a solvent mixture 160 ml of benzene and 40 ml of tetrahydrofuran were added. At the boiling point on a reflux apparatus, a grain of iodine is added as a starter for the Grignard reaction and the remaining solution of IV.1 in the solvent mixture is allowed to run in in about 10 minutes. After heating for a further 30 minutes under reflux conditions, the mixture is cooled to 50 ° C. and then 1.463 g of the PdCl ₂ .dppf catalyst are added.

Then about 0.130 mol of 1-bromo-3,4,5-trifluorobenzene (III.1) Added dropwise for 15 minutes, the in a very strongly exothermic reaction Temperature rises briefly to 70 ° C. Then 1.5 Stirred hours at 50 ° C and then cooled to about 20 ° C.

This batch is poured into 250 ml of water and acidified with hydrochloric acid and diluted with 250 ml of methyl tert-butyl ether. The organic phase will separated, the aqueous phase extracted again with the ether and the combined organic phases on the rotary evaporator from the Free solvents. The crude product thus obtained becomes as usual worked up.  

2nd embodiment

Grignard reaction of a biscyclohexylhalogen compound and cross-coupling with a vinylhalogen compound using a nickel catalyst

0.100 mol of magnesium shavings were placed under nitrogen and about 20 ml of a solution of 0.100 mol of 1-bromo-4- (4'-n-propylcyclohexyl) cyclohexane (IV.2) in a solvent mixture of 160 ml of benzene and 40 ml of tetrahydrofuran added. At the boiling point on a reflux apparatus, a grain of iodine was added as a starter for the Grignard reaction and the remaining solution of IV.2 in the solvent mixture was run in in about 10 minutes. After heating for a further 30 minutes under reflux conditions, the mixture was cooled to about 20 ° C. At 5 ° C 0.100 mol of vinyl bromide (III.2) and 1.056 g of NiCl ₂ .dppe were added and the mixture was stirred at 20 ° C overnight. Then water was added and acidified with hydrochloric acid and the organic phase was diluted with 500 ml of hexane for better separation and worked up as usual.

3rd embodiment

Grignard reaction of a biscyclohexylhalogen compound, transmetalation and cross coupling with an arylhalogen compound using a palladium catalyst

0.100 mol of magnesium shavings are introduced, heated to 80 ° C. and about 25 ml of a solution of 0.100 mol of 1-bromo-4- (4'-n-propylcyclohexl) cyclohexane (IV.3) in a solvent mixture of 160 ml of benzene and 40 ml of tetrahydrofuran added. In the boiling heat on a reflux apparatus, a grain of iodine is added as a starter for the Grignard reaction and the remaining solution of IV.3 in the solvent mixture is run in in about 10 minutes. After heating for a further 30 minutes under reflux conditions, the mixture is cooled to about 50 ° C. Then 3.658 g of PdCl ₂ .dppf and 0.681 g of ZnCl _{2 were} added and then 0.100 mol of 1-bromo-3,4,5-trifluorobenzene (III.3) was added dropwise in about 15 minutes, a very strongly exothermic reaction with a rise in temperature up to 70 ° C is observed. The mixture is stirred for a further 1.5 hours at 50 ° C and then cooled to about 20 ° C. The mixture, which was added to 250 ml of water, was acidified with hydrochloric acid and diluted with 250 ml of methyl tert-butyl ether. The processing is carried out analogously to the 1st embodiment.

This process has a zinc organyl corresponding to the Grignard such as the use of manganese organylene (see Example 9) Advantage that the coupling educt (III) functional groups, such as -CN or Carbonyl-containing groups, to which the zinc Connection does not couple, whereas a Grignard connection in the Usually shows insufficient chemoselectivity.

4th embodiment

4.1 Synthesis of a trans-decalin halogen compound

4.1.1 Enamine synthesis

4.00 mol of 4-n-propylhexanone and 5.952 mol of morpholine are mixed with 7.61 g Toluene-4-sulfonic acid monohydrate combined in 3000 ml of toluene and refluxed on a water separator for over 8 hours. Finally  the solvent is removed on a rotary evaporator in order to To obtain enamine formed above reaction equation.

4.1.2 Addition of methyl vinyl ketone

3.699 mol of the enamine according to the above equation and 4.690 mol Methyl vinyl ketone are in 2665 ml of toluene at 100 ° C for 2 hours Nitrogen stirred. Then the batch is cooled and that Removed solvent on the rotary evaporator. The backlog is in 2000 ml of toluene dissolved, mixed with 1142 ml of 15% hydrochloric acid and that Mixture refluxed for 15 minutes. The reaction solution becomes as usual worked up.

4.1.3 Ring closure through water elimination and isomerization

1.712 mol of the starting material according to the above equation are added under nitrogen 3200 ml of methanol dissolved and 2.141 mol of sodium methylate (397 ml of a 30% solution in methanol) added. After that, the approach 2.5 hours refluxed. The reaction solution is worked up as usual.

4.1.4 Hydrogenation of the decalinone and reduction of the decalinone

0.140 mol of the decalinenone obtained from the above synthesis according to the above equation are hydrogenated in 300 ml of 1,4-dioxane using 3.14 l of hydrogen and 3.00 g of 10% palladium-activated carbon until no more olefin is present. Then 0.103 mol of the decalinone obtained is taken up in 21 ml of tetrahydrofuran and this solution is added dropwise to a batch of 0.030 mol of LiAlH ₄ and 100 ml of tetrahydrofuran and refluxed for a further 30 minutes. The reaction solution is worked up as usual.

4.1.5 Bromination of decalinol to bromine decalin

0.102 mol triphenylphosphine is suspended in 130 ml acetonitrile and at 10 to 15 ° C 0.102 mol bromine was added dropwise. After stirring for 1 hour white suspension are 0.102 mol of decalinol according to the above Added the equation and stirred overnight at room temperature. The The reaction solution is worked up as usual.

4.2 Grignard reaction of a trans-decalin halide compound and cross-coupling with an aryl halogen compound using a nickel catalyst

0.160 mol of magnesium shavings are presented and a solution of 0.150 mol of trans-2-bromo-6-propy-decalin (IV.4), obtainable according to the above  Synthesis steps 4.1.1 to 4.1.5, in a solvent mixture 240 ml of benzene and 60 ml of tetrahydrofuran were added at the boil. As a starter for the Grignard reaction, a grain of iodine is added, the reaction started, but was only slightly exothermic. To the addition is completed under reflux conditions for 30 minutes warmed, then cooled to about 50 ° C. The cross coupling with 0.150 mol of an aryl halogen compound (III.4) is analogous to the 1st Embodiment performed.

Analogously to one of the exemplary embodiments 1 to 4, the trans-decalin-halogen compounds of the formula can be used according to the invention

with the starting materials of the general formula III, in particular with optionally substituted halogen aromatics according to Formula III, implement the Grignard, manganese or zinc compounds.

5th embodiment

Conversion of a trans-decalin halogen compound to the corresponding zinc compound according to Luche and cross coupling with an aryl halogen compound

0.010 mol of all-trans-2-bromo-6-propyl-decalin (IV.5) are dissolved in a mixed solution of 11.538 ml of toluene and 2.885 ml of tetrahydrofuran and 0.005 mol of anhydrous zinc bromide is added. After cooling to 10 ° C., 0.020 mol of lithium granules are added and, after the reaction has started, the mixture is stirred under ultrasound at 5 to 15 ° C. for 2 hours. Then 0.146 g of PdCl ₂ .dppf and 0.010 mol of 4-bromobenzonitrile (IV.5) are added and the mixture is stirred at about 20 ° C. for 48 hours. Finally, the reaction solution is mixed with an ammonium chloride solution and worked up as usual.

The zinc organyl compound formed in the first stage can also analogous to embodiment 3 by metal remodeling corresponding Grignard connection, obtainable in an analogous manner Example 4 above.

6th embodiment

6.1 Synthesis of a biscyclohexyl halide compound

20.17 mol triphenylphosphine are at room temperature in 28.00 l Acetonitrile suspended. Then, under strong ice cooling 20.15 mol of bromine were added dropwise within 2 hours. Into the created one finely crystalline white suspension becomes 10.08 mol after removal of the cooling Bicyclohexane-4,4'-diol was added within 15 minutes and 1 more Stirred for one hour at room temperature. It is then heated and 1 Hour under reflux conditions. At 70 ° C it becomes clear Obtain solution that is kept boiling for a further 4 hours. It is then cooled to 40 ° C and the reaction solution in a Solvent mixture of 20 l petroleum spirit and 10 l toluene stirred. After 1 hour of stirring, the precipitated Filtered triphenylphosphine oxide and discarded. From the lower phase of the filtrate, triphenylphosphine oxide is removed twice. After a further purification, both phases are combined.

If the all-trans bicyclohexane-4,4'-diol, which can be obtained directly by reduction from the corresponding diketone using NaBH ₄ or LiAlH ₄ , is used as the starting material, then virtually isomer-pure all-cis-bicyclohexane-4,4 'is obtained. dihalide.

6.2 Grignard reaction of a dihalogen compound and cross-coupling with two different starting materials

0.150 mol of magnesium shavings are placed under nitrogen and 50 ml of a solution of 0.075 mol of trans-trans-1-bromo-4- (4'-bromo-cyclohexyl) cyclohexane (IV.6), obtainable according to synthesis 6.1 above, in a solvent mixture of 240 ml of benzene and 60 ml of tetrahydrofuran was added and heated to boiling. As a starter for the Grignard reaction, a grain of iodine is added and the remaining dibromide solution is run in at the boil and heated under reflux for a further 30 minutes. After the external heat supply has ended, 1.098 g of PdCl ₂ .dppf are added and 0.075 mol of 1-bromo-3,4-difluorobenzene (III.6) is added dropwise over the course of 10 minutes, with a strongly exothermic reaction causing the reaction mixture to boil without external heat holds. The mixture is then heated under reflux for a further 40 minutes and then 0.075 mol of vinyl bromide (III.6) is added dropwise under reflux conditions. After the addition has ended, the mixture is refluxed for a further hour and then cooled somewhat. The processing of the raw product is carried out analogously to the first embodiment.

7th embodiment

Grignard reaction of a dihalogen compound, transmetalation to the corresponding zinc compound and cross-coupling with two different starting materials

40 mmol trans-trans-1-bromo-4- (4'-bromo-cyclohexyl) -cyclohexane (IV'.7) in 70 ml benzene-tetrahydrofuran mixture (4: 1) are in a Grignard Column with 52 g magnesium shavings to the corresponding Grignard Connection implemented. This is the one with the solvent mixture charged column kept at around 65 ° C by external heating.

The solution thus obtained is cooled to 5 ° C. and 40 mmol of anhydrous zinc bromide dissolved in 35 ml of tetrahydrofuran are added dropwise, the temperature rise caused by the exothermic reaction being limited to 20 to 25 ° C. by cooling. After stirring for 15 minutes at 20 ° C. and adding 0.585 g of PdCl ₂ .dppf, a solution of 40 mmol of 4-bromo-2-fluorobenzonitrile (III.7) in 20 ml of tetrahydrofuran is added, the temperature rise being limited to 40 ° C. becomes. 40 mmol bromethylene (III'.7) are added at 10 ° C. The mixture is stirred at 20 ° C. overnight.

Then a saturated ammonium chloride solution added and worked up as usual.  

8th embodiment

Synthesis of the corresponding zinc compound from a dihalogen compound according to Luche and cross-coupling with two different starting materials

40 mmol of trans-trans-1-bromo-4- (4'-bromo-cyclohexyl) -cyclohexane (IV'.8) in 70 ml of a 4: 1 mixture of toluene with tetrahydrofuran are mixed with 40 mmol of zinc bromide and at a maximum of 25 ° C stirred until dissolved. Then 160 mmol of lithium granules are added and sonicated in an ultrasonic bath at 15 to 20 ° C. for 5 hours with stirring. 0.585 g of PdCl ₂ .dppf and then 20 mmol of bromethylene (III'.8) and 40 mmol of 3,4-difluorobromobenzene (III.8) are added at 10 ° C. Cooling prevents a temperature rise above 40 ° C. The mixture is then stirred for a further 48 hours at 20 ° C. The reaction solution is worked up analogously to embodiment 7.

9. Embodiment

Ummetallation of a cyclohexylcyclohexane-Grignard compound to the corresponding manganese compound and cross-coupling with an aryl compound

0.100 mol of the 4- (4'-n-propylcyclohexyl) cyclohexane-Grignard compound IIa.9 (advantageously available as an intermediate according to one of Examples 1 to 3) in 200 ml of a benzene-tetrahydrofuran mixture (4: 1) added with stirring between -10 ° C and 0 ° C to a suspension of 0.104 mol of anhydrous MnCl ₂ in 200 ml of tetrahydrofuran. The reaction mixture is stirred at about 20 ° C for three hours. Then 0.002 mol of PdCl ₂ .dppf and 0.100 mol of 1-bromo-3,5-difluoro-4-nitro benzene III.9 are added over the course of 15 minutes and the mixture is stirred for about 12 hours. The processing takes place as usual.

10th embodiment

Ummetallation of a cyclohexylcyclohexane-Digrignard compound to the corresponding manganese compound and double cross-coupling

0.100 mol of the 4- (4'-n-propylcyclohexyl) cyclohexane-Digrignard compound II'.10 (advantageously obtainable as an intermediate according to one of Examples 6.2 or 7) in 400 ml of a benzene-tetrahydrofuran mixture (4: 1) are added with stirring between -10 ° C and 0 ° C to a suspension of 1.04 mol of anhydrous Li ₂ MnCl ₄ in 200 ml of tetrahydrofuran. The reaction mixture is stirred at about 20 ° C for one hour. Then 0.002 mol of PdCl ₂ .dppf and 0.100 mol of 1-bromo-3,5-difluoro-4-nitro benzene III.10 are added over the course of 15 minutes. Then 0.100 mol of vinyl bromide III'.10 are added and the mixture is stirred for about 72 hours. The processing takes place as usual.

The tables below contain connections that are according to using one or more of the above embodiments of the corresponding starting compounds are available. About that in addition to those listed for those skilled in the art homologous compounds in analogous application above Examples accessible.

Claims (12)

1. Process for the preparation of compounds of formula I.
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I
in the
R ^{1 is} H, halogen or alkyl having 1-18 C atoms, in which one or two non-adjacent CH ₂ groups are also represented by -O-, -S-, -CHR ³ -CHR ⁴ -, -CR ³ = CR ⁴ - and / or -C∼C- can be replaced and / or in which one or more H atoms can also be replaced by halogen,
R ² H, halogen, -CN, -NCS, -SF ₅ , alkyl with 1-18 C atoms, in which also one or two non-adjacent CH ₂ groups by -O-, -S-, -CO-, - O-CO-, -CO-O-, -CHR ³ -CHR ⁴ -, -CR ³ = CR ⁴ - and / or -C∼C- can be replaced and / or in which one or more H atoms can also be replaced by halogen -NR'R "or -CO ₂ R ', where R' and R" independently of one another are optionally substituted benzyl or allyl,
A ^{0 is} a 1,4-cyclohexylene group, in which one or two non-adjacent CH ₂ groups can also be replaced by -O- and / or -S- and / or which can be substituted in the 1-position by R ³ , a 1 , 4-cyclohexenylene or a 1,4-bicyclo [2,2,2] octylene group, an unsubstituted or once or twice substituted by R ³ 1,4-phenylene group, in which also one or more CH groups by N can be replaced
A ^{2 has} one of the meanings given for A ⁰ or one of the meanings given for A ¹ ,
E -CR ³ = CR ⁴ -,
R ³ , R ⁴ each independently of one another H, alkyl having 1-6 C atoms, F, Cl, Br, CF ₃ or CN,
Z ¹ , Z ² each independently of one another -CH ₂ -CH ₂ -, -CH ₂ CHF-, -CHFCH ₂ -, -CHFCHF-, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CF ₂ CHF- , -CHFCF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF-, -OCH ₂ -, -CH ₂ O-, -CF ₂ O-, -OCF ₂ -, a single bond, -CO-O-, -O-CO-, -CHCN-CH ₂ - or -CH ₂ -CHCN-,
L ⁰ , L ¹ , L ² , L ³ each independently of one another H or F,
Q is an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene, in which one or more CH groups may be replaced by N, or a 1,4-cyclohexylene group, wherein one or two non-adjacent CH ₂ - Groups can be replaced by -O- and / or -S- and / or which can be substituted in the 1-position by R ³ , a 1,4-cyclohexenylene or 1,4-bicyclo [2,2,2] - octylene group,
m, p each independently 0, 1 or 2,
n, o, k each independently represent 0 or 1,
in which an organometallic compound of the formula II
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II
in the
M denotes MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI or Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -R ¹ and
R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for the formula I,
with a compound of formula III
X- (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² III,
in the
X denotes Cl, Br, I or -O-SO ₂ - (CF ₂ ) _0-10 CF ₃ and
E, Q, Z ² , A ² , R ² , n, o and p have the meaning given for the formula I,
is reacted in the presence of at least one metal compound which catalyzes the reaction,
with the proviso that

• a) the sum of n, o and p is 1, 2, 3 or 4,
• b) Q is an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene, in which one or more CH groups may be replaced by N, and o = 1, if n = 0,
• c) M is MgCl, MgBr, MgI, MnCl, MnBr or MnI if A ¹
  means and
• d) R ¹ , R ² , R ³ , R ⁴ , A ⁰ , A ² , E, Q, Z ¹ and Z ² not -CN, -NCS, Cl, Br, -O-CO-, -CO-O - or -CO- if M is MgCl, MgBr or MgI.

2. Process for the preparation of compounds of the formula I '
R ^'2 - (A ^{' 2} -Z ^'2 ) _p' - (Q ') _o' - (E ') _n' - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ - (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² I '
in the
R ² , R ^'2 each independently of one another have one of the meanings given in Claim 1 for R ² ,
A ^{0 has} one of the meanings given in Claim 1 for A ⁰ ,
A ² , A ^'2 each independently of one another have one of the meanings given for A ⁰ or one of the meanings given for A ¹ ,
E, E 'CR ³ = CR ⁴ ,
R ³ , R ⁴ each independently of one another H, alkyl having 1-6 C atoms, F, Cl, Br, CF ₃ or CN,
Z ¹ , Z ² , Z ^'2 each independently of one another -CH ₂ -CH ₂ -, -CH ₂ CHF-, -CHFCH ₂ -, -CHFCHF-, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, - CF ₂ CHF-, -CHFCF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CF = CH-, -CH = CF-, -CF = CF-, -OCH ₂ -, -CH ₂ O -, -CF ₂ O-, -OCF ₂ -, a single bond, -CO-O-, -O-CO-, -CHCN-CH ₂ - or -CH ₂ -CHCN-,
L ⁰ , L ¹ , L ² , L ³ each independently of one another H or F,
Q, Q 'each independently of one another have one of the meanings given in Claim 1 for Q,
m, p, p 'each independently of one another 0, 1 or 2,
n, n ', o, o', k each independently represent 0 or 1,
in which an organometallic compound of the formula II '
M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II '
in the
M MgCl, MgBr, Mgl, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _{m means} -A ¹ -M and
A ⁰ , Z ¹ , A ¹ , k and m have the meaning given for the formula I ',
with a compound of formula III
X- (E) _n - (Q) _o - (Z ² -A ² ) _p -R ² III,
and with a compound of formula III '
X '- (E') _{n '} - (Q') _{o '} - (Z ^{' 2} -A ^'2 ) _p' -R ^'2 III',
in which
X, X 'each independently mean Cl, Br, I or -O-SO ₂ - (CF ₂ ) _0-10 CF ₃ and
E, E ', Q, Q', Z ² , Z ^'2 , A ² , A ^{' 2} , R ² , R ^'2 n, n', o, o ', p and p' those for the formula I ' have the specified meaning,
is reacted in the presence of at least one metal compound which catalyzes the reaction,
with the proviso that

• a) the sum of n, o and p and the sum of n ', o' and p 'are each independently 1, 2, 3 or 4,
• b) Q is an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene, in which one or more CH groups may be replaced by N, and o = 1, if n = 0,
• c) Q 'is an unsubstituted or mono- to tetrasubstituted by R ³ substituted 1,4-phenylene group in which may also be replaced one or more CH groups are replaced by N, and o' = 1, if n '= 0,
• d) R ² , R ^'2 , R ³ , R ⁴ , A ⁰ , A ² , A ^{' 2} , E, E ', Q, Q', Z ¹ , Z ² and Z ^'2 not -CN, -NCS , Cl, Br, -O-CO-, -CO-O- or -CO- if M is MgCl, MgBr or MgI.

3. Process for the preparation of Grignard compounds of the formula IIa
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIa
or of Grignard compounds of the formula II'a
M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'a
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given in claim 1 and
M denotes MgCl, MgBr or MgI,
in which a halogen compound of formula IV
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV
or a halogen compound of the formula IV '
X '- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV'
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meanings given for formula IIa or II'a and
X, X 'each independently mean Cl, Br or I,
is reacted with magnesium in a solvent mixture which has at least one non-polar solvent and at least one polar solvent with external heat supply,
with the proviso that R ¹ and Z ¹ do not have -CN, -NCS, Cl, Br, -O-CO-, -CO-O- or -CO-. 4. Process for the preparation of zinc compounds of formula IIb
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIb,
in which M denotes ZnCl, ZnBr, ZnI or Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -R ¹ ,
or of zinc compounds of the formula II'b
M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'b,
in which M denotes ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M,
where in formulas IIb and II'b R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given in claim 1,
in which a Grignard compound of the formula IIa
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M 'IIa
or a Grignard compound of the formula II'a
M '- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M'II'a
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meanings given for formula IIb or II'b and
M 'means MgCl, MgBr or MgI,
is reacted with at least one zinc dihalide in at least one organic solvent,
with the proviso that R ¹ and Z ¹ do not have -CN, -NCS, Cl, Br, -O-CO-, -CO-O- or -CO-. 5. Process for the preparation of manganese compounds of formula IIc
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIc,
in which M means MnCl, MnBr or MnI,
or of manganese compounds of the formula II'c
M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II'c,
in which M means MnCl, MnBr or MnI,
where in formula IIc and II'c R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meaning given in claim 1,
in which a Grignard compound of the formula IIa
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M 'IIa
or a Grignard compound of the formula II'a
M '- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M'II'a
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have the meanings given for formula IIc or II'c and
M 'means MgCl, MgBr or MgI,
is reacted with at least one manganese dihalide or an alkali metal manganese halide compound in at least one organic solvent,
with the proviso that R ¹ and Z ¹ do not have -CN, -NCS, Cl, Br, -O-CO-, -CO-O- or -CO-. 6. The method according to any one of claims 1 to 5, characterized in that A ¹
means. 7. Grignard compounds of the formula IIa
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIa
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have one of the meanings given in Claim 1, and
M denotes MgCl, MgBr or MgI,
with the proviso that
R ¹ and Z ¹ do not have -CN, -NCS, Cl, Br, -O-CO-, -CO-O- or -CO-. 8. Manganese compounds of the formula IIc
R ¹ - (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M IIc
in which R ¹ , A ⁰ , Z ¹ , A ¹ , k and m have one of the meanings given in Claim 1, and
M means MnCl, MnBr or MnI. 9. Organometallic compounds of the formula IIw
in which R ¹ , A ⁰ , Z ¹ , k and m have one of the meanings given in Claim 1, and
M ZnCl, ZnBr, ZnI or
means. 10. Organometallic compounds of the formula II '
M- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -M II '
in the
M MgCl, MgBr, MgI, MnCl, MnBr, MnI, ZnCl, ZnBr, ZnI, Zn-A ¹ - (Z ¹ ) _m - (A ⁰ ) _k -M or Zn- (A ⁰ ) _k - (Z ¹ ) _{m means} -A ¹ -M and
A ⁰ , Z ¹ , A ¹ , k and m have one of the meanings given in claim 1. 11. Halogen compounds of the formula IVw
in which R ¹ , A ⁰ , Z ¹ , k and m have one of the meanings given in Claim 1, and
X means Cl, Br or I. 12. Halogen compounds of the formula IV '
X- (A ⁰ ) _k - (Z ¹ ) _m -A ¹ -X IV '
in the
A ⁰ , Z ¹ , A ¹ , k and m have one of the meanings given in Claim 1 and
X means Cl, Br or I.