# Patent

## Title
Benzochromene derivatives

## Abstract

The present invention relates to benzochromene derivatives of the formula I




where the various parameters have the meaning indicated in the text, and to liquid-crystal media which comprise these compounds, and to the use of the media in electro-optical displays, in particular in VAN-LCDs, and to the use of the compounds and physiologically acceptable derivatives thereof as therapeutic active ingredients.

## Background
The present invention relates to benzochromene derivatives, preferably mesogenic benzochromene derivatives, in particular liquid-crystalline benzochromene derivatives, and to liquid-crystalline media comprising these benzochromene derivatives. The present invention furthermore relates to liquid-crystal displays, in particular active matrix addressed liquid-crystal displays (AMDs or AM LCDs) and very particularly so-called VAN (“vertically aligned nematic”) liquid-crystal displays, an embodiment of ECB (“electrically controlled birefringence”) liquid-crystal displays, in which nematic liquid crystals of negative dielectric anisotropy (Δ∈) are used.
In liquid-crystal displays of this type, the liquid crystals are used as dielectrics, whose optical properties change reversibly on application of an electric voltage. Electro-optical displays which use liquid crystals as media are known to the person skilled in the art. These liquid-crystal displays use various electro-optical effects. The commonest thereof are the TN (“twisted nematic”) effect, with a homogeneous, virtually planar initial alignment of the liquid-crystal director and a nematic structure which is twisted by about 90°, the STN (“super-twisted nematic”) effect and the SBE (“supertwisted birefringence effect”) with a nematic structure which is twisted by 180° or more. In these and similar electro-optical effects, liquid-crystalline media of positive dielectric anisotropy (Δ∈) are used.
Besides the said electro-optical effects, which require liquid-crystal media of positive dielectric anisotropy, there are other electro-optical effects which use liquid-crystal media of negative dielectric anisotropy, such as, for example, the ECB effect and its sub-forms DAP (“deformation of aligned phases”), VAN and CSH (“colour super homeotropics”).
An electro-optical effect having excellent, low viewing-angle dependence of the contrast uses axially symmetrical micropixels (ASMs). In this effect, the liquid crystal of each pixel is surrounded in a cylindrical manner by a polymer material. This mode is particularly suitable for combination with addressing through plasma channels. Thus, in particular, large-area PA (“plasma addressed”) LCDs having good viewing-angle dependence of the contrast can be achieved.
The IPS (“in plane switching”) effect employed to an increased extent recently can use both dielectrically positive and also dielectrically negative liquid-crystal media, in a similar manner to “guest/host” displays, which can employ dyes either in dielectrically positive or dielectrically negative media, depending on the display mode used.
Since the operating voltage in liquid-crystal displays in general, i.e. also in displays utilising these effects, should be as low as possible, use is made of liquid-crystal media having a large absolute value of the dielectric anisotropy which generally predominantly and in most cases even essentially consist of liquid-crystal compounds having a dielectric anisotropy having the corresponding sign, i.e. of compounds of positive dielectric anisotropy in the case of dielectrically positive media and of compounds of negative dielectric anisotropy in the case of dielectrically negative media. In the respective types of media (dielectrically positive or dielectrically negative), at most significant amounts of dielectrically neutral liquid-crystal compounds are typically employed. Liquid-crystal compounds having the opposite sign of the dielectric anisotropy to that of the dielectric anisotropy of the medium are generally employed extremely sparingly or not at all.
An exception is formed here by liquid-crystalline media for MIM (“metal-insulator-metal”) displays (Simmons, J. G., Phys. Rev. 155 No. 3, pp. 657-660 and Niwa, J. G. et al., SID 84 Digest, pp. 304-307, June 1984), in which the liquid-crystal media are addressed by means of an active matrix of thin-film transistors. In this type of addressing, which utilises the non-linear characteristic line of diode switching, a storage capacitor cannot be charged together with the electrodes of the liquid-crystal display elements (pixels), in contrast to TFT displays. In order to reduce the effect of the drop in voltage during the addressing cycle, the largest possible base value of the dielectric constant is thus necessary. In the case of dielectrically positive media, as employed, for example, in MIM-TN displays, the dielectric constant perpendicular to the molecular axis (∈⊥) must thus be as large as possible since it determines the basic capacitance of the pixel. To this end, as described, for example, in WO 93/01253, EP 0 663 502 and DE 195 21 483, compounds of negative dielectric anisotropy are simultaneously also employed besides dielectrically positive compounds in the dielectrically positive liquid-crystal media.
A further exception is formed by STN displays, in which, for example, dielectrically positive liquid-crystal media comprising dielectrically negative liquid-crystal compounds in accordance with DE 41 00 287 are employed in order to increase the steepness of the electro-optical characteristic line.
The pixels of the liquid-crystal displays can be addressed directly, time-sequentially, i.e. in time multiplex mode, or by means of a matrix of active elements having nonlinear electrical characteristic lines.
The commonest AMDs to date use discrete active electronic switching elements, such as, for example, three-pole switching elements, such as MOS (“metal oxide silicon”) transistors or thin film transistors (TFTs) or varistors, or 2-pole switching elements, such as, for example, MIM (“metal-insulator-metal”) diodes, ring diodes or “back-to-back” diodes. Various semiconductor materials, predominantly silicon, but also cadmium selenide, are used in the TFTs. In particular, amorphous silicon or polycrystalline silicon is used.
In accordance with the present application, preference is given to liquid-crystal displays having an electric field perpendicular to the liquid-crystal layer and liquid-crystal media of negative dielectric anisotropy (Δ∈<0). In these displays, the edge alignment of the liquid crystals is homeotropic. In the fully switched-on state, i.e. on application of an electric voltage of appropriate magnitude, the liquid-crystal director is aligned parallel to the layer plane.
Benzochromene derivatives, for example of the following three formulae




    
    
        in which
        R1 and R2 denote, for example, alkyl,

are disclosed in DE 10 2002 004 228.4 and JP2005120073. These compounds are characterised by very high absolute values of the dielectric anisotropy and, as a consequence of the biphenyl partial structure, have very high birefringence. Owing to the different requirements of the physical properties of liquid-crystal mixtures, it is necessary also to provide substances having lower birefringence, in particular, for example, for reflective displays. This applies, in particular, to the VA mode, since the lateral substitution by polar groups generally takes place on aromatic rings. It can thus be seen that there is both a demand for further mesogenic compounds and also, in particular, a demand for liquid-crystal media of negative dielectric anisotropy, a large absolute value of the dielectric anisotropy, a value of the optical anisotropy (Δn) corresponding to the particular application, a broad nematic phase, good stability to UV, heat and electric voltage, and low rotational viscosity.

    
    


This is achieved through the use of the mesogenic compounds of the formula I according to the invention




    
    
        in which
        Y denotes —CO—, CS, —CH2— or —CF2—, preferably CH2 or CF2,
        L denotes H, halogen or CF3, preferably H, F or Cl, particularly preferably H or F and very particularly preferably F,
    
    






    
    
         each, independently of one another and, if present more than once, also these independently of one another, denote
        (a) a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—,
        (b) a 1,4-cyclohexenylene radical,
        (c) a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
        (d) naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
        (e) a radical selected from the group 1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene and spiro[3.3]heptane-2,6-diyl, where in
        
            (a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
            (c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group, preferably a —CF═ group, and preferably denote
        
        
    
    










    
    
         denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, and one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group, preferably a —CF═ group,
        R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least mono-substituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,
    
    










    
    
         —CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
        preferably one of
        R1 and R2 denotes alkyl or alkoxy having 1 to 12 C atoms, alkoxyalkyl, alkenyl or alkenyloxy having 2 to 12 C atoms and the other, independently of the first, likewise denotes alkyl and alkoxy having 1 to 12 C atoms, alkoxyalkyl, alkenyl or alkenyloxy having 2 to 12 C atoms or also F, Cl, Br, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3 or —OCHF2 
        Z1 and Z2 each, independently of one another and, if present more than once, also these independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another,
        preferably —(CH2)4—, —CH2—CH2—, —CF2—CF2—, —CH═CH—, —CF═CF—, —C≡C—, —CH2O—, —CF2O— or a single bond,
        particularly preferably —CH2O—, —CH2—CH2—, —CF2—CF2—, —CF═CF—, —CF2O— or a single bond, and
        n and m each denote 0, 1 or 2, where
        n+m denotes 0, 1, 2 or 3, preferably 0, 1 or 2, particularly preferably 0 or 1.
    
    


Particular preference is given to liquid-crystal compounds of the formula I of the sub-formulae I-1 to I-3




in which the parameters have the meanings given above under formula I, and

    
    
        L preferably denotes F.
    
    


Preference is given to compounds of the formula I, preferably selected from the group of the compounds of the formulae I-1 to I-3, in which

    the sum n+m is 0 or 1, preferably 0.


A preferred embodiment is represented by the compounds of the formula I in which the sum n+m is 1 and preferably

    m or n denotes 1,






    Z2 preferably denotes —(CH2)4—, —CH2—CH2—, —CF2—CF2—, —CH═CH—, —CF═CF—, —C≡C—, —O—CH2—, —O—CF2— or a single bond,
    
        particularly preferably —O—CH2—, —CH2—CH2—, —CF2—CF2—, —CF═CF—, —O—CF2— or a single bond

and L, R1 and R2 have the meaning given above for formula I, and L preferably denotes F.

    
    


Particular preference is given to compounds of the formula I, preferably selected from the group of the compounds of the formulae I-1 to 1-3, in which

    n and m both denote 0, and
    L, R1 and R2 have the meaning given above for the corresponding formula and L preferably denotes F.


Compounds of the formula I containing branched wing groups R1 and/or R2 may occasionally be of importance owing to better solubility in the usual liquid-crystalline base materials, but in particular as chiral dopants if they are optically active. Smectic compounds of this type are suitable as components of ferroelectric materials. Compounds of the formula I having SA phases are suitable, for example, for thermally addressed displays.
If R1 and/or R2 denote an alkyl radical and/or an alkoxy radical, this may be straight-chain or branched. It is preferably straight-chain, has 2, 3, 4, 5, 6 or 7 C atoms and accordingly preferably denotes ethyl, propyl, butyl, pentyl, hexyl, heptyl, ethoxy, propoxy, butoxy, pentoxy, hexyloxy or heptyloxy, furthermore methyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, methoxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy or tetradecyloxy.
Oxaalkyl or alkoxyalkyl preferably denotes straight-chain 2-oxapropyl (=methoxymethyl), 2-(=ethoxymethyl) or 3-oxabutyl (=2-methoxyethyl), 2-, 3- or 4-oxapentyl, 2-, 3-, 4- or 5-oxahexyl, 2-, 3-, 4-, 5- or 6-oxaheptyl, 2-, 3-, 4-, 5-, 6- or 7-oxaoctyl, 2-, 3-, 4-, 5-, 6-, 7- or 8-oxanonyl, or 2-, 3-, 4-, 5-, 6-, 7-, 8- or 9-oxadecyl.
If R1 and/or R2 denote an alkyl radical in which one CH2 group has been replaced by —CH═CH—, this may be straight-chain or branched. It is preferably straight-chain and has 2 to 10 C atoms. Accordingly, it denotes, in particular, vinyl, prop-1- or -2-enyl, but-1-, -2- or -3-enyl, pent-1-, -2-, -3- or -4-enyl, hex-1-, -2-, -3-, -4- or -5-enyl, hept-1-, -2-, -3-, -4-, -5- or -6-enyl, oct-1-, -2-, -3-, -4-, -5-, -6- or -7-enyl, non-1-, -2-, -3-, -4-, -5-, -6-, -7- or -8-enyl, or dec-1-, -2-, -3-, -4-, -5-, -6-, -7-, -8- or -9-enyl.
If R1 and/or R2 denote an alkyl radical in which one CH2 group has been replaced by —O— and one has been replaced by —CO—, these are preferably adjacent. These thus contain an acyloxy group —CO—O— or an oxycarbonyl group —O—CO—. These are preferably straight-chain and have 2 to 6 C atoms. Accordingly, they denote, in particular, acetoxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, acetoxymethyl, propionyloxymethyl, butyryloxymethyl, pentanoyloxymethyl, 2-acetoxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 3-acetoxypropyl, 3-propionyloxypropyl, 4-acetoxybutyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, pentoxycarbonyl, methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, butoxycarbonylmethyl, 2-(methoxycarbonyl)ethyl, 2-(ethoxycarbonyl)ethyl, 2-(propoxycarbonyl)ethyl, 3-(methoxycarbonyl)propyl, 3-(ethoxycarbonyl)propyl or 4-(methoxycarbonyl)butyl.
If R1 and/or R2 denote an alkyl radical in which one CH2 group has been replaced by unsubstituted or substituted —CH═CH— and an adjacent CH2 group has been replaced by CO or CO—O or O—CO, this may be straight-chain or branched. It is preferably straight-chain and has 4 to 13 C atoms. Accordingly, it denotes, in particular, acryloyloxymethyl, 2-acryloyloxyethyl, 3-acryloyloxypropyl, 4-acryloyloxybutyl, 5-acryloyloxypentyl, 6-acryloyloxyhexyl, 7-acryloyloxyheptyl, 8-acryloyloxyoctyl, 9-acryloyloxynonyl, 10-acryloyloxydecyl, methacryloyloxymethyl, 2-methacryloyloxyethyl, 3-methacryloyloxypropyl, 4-methacryloyloxybutyl, 5-methacryloyloxypentyl, 6-methacryloyloxyhexyl, 7-methacryloyloxyheptyl, 8-methacryloyloxyoctyl or 9-methacryloyloxynonyl.
If R1 and/or R2 denote an alkyl or alkenyl radical which is monosubstituted by CN or CF3, this radical is preferably straight-chain. The substitution by CN or CF3 is in any desired position.
If R1 and/or R2 denote an alkyl or alkenyl radical which is at least mono-substituted by halogen, this radical is preferably straight-chain, and halogen is preferably F or Cl. In the case of polysubstitution, halogen is preferably F. The resultant radicals also include perfluorinated radicals. In the case of monosubstitution, the fluorine or chlorine substituent may be in any desired position, but is preferably in the ω-position.
Branched groups generally contain not more than one chain branch. Preferred branched radicals R are isopropyl, 2-butyl (=1-methylpropyl), isobutyl (=2-methylpropyl), 2-methylbutyl, isopentyl (=3-methylbutyl), 2-methylpentyl, 3-methylpentyl, 2-ethylhexyl, 2-propylpentyl, isopropoxy, 2-methylpropoxy, 2-methylbutoxy, 3-methylbutoxy, 2-methylpentoxy, 3-methylpentoxy, 2-ethylhexyloxy, 1-methylhexyloxy and 1-methylheptyloxy.
If R1 and/or R2 represent an alkyl radical in which two or more CH2 groups have been replaced by —O— and/or —CO—O—, this may be straight-chain or branched. It is preferably branched and has 3 to 12 C atoms. Accordingly, it denotes, in particular, biscarboxymethyl, 2,2-biscarboxyethyl, 3,3-biscarboxypropyl, 4,4-biscarboxybutyl, 5,5-biscarboxypentyl, 6,6-biscarboxyhexyl, 7,7-biscarboxyheptyl, 8,8-biscarboxyoctyl, 9,9-biscarboxynonyl, 10,10-biscarboxydecyl, bis(methoxycarbonyl)methyl, 2,2-bis(methoxycarbonyl)ethyl, 3,3-bis(methoxycarbonyl)propyl, 4,4-bis(methoxycarbonyl)butyl, 5,5-bis(methoxycarbonyl)pentyl, 6,6-bis(methoxycarbonyl)hexyl, 7,7-bis(methoxycarbonyl)heptyl, 8,8-bis(methoxycarbonyl)octyl, bis(ethoxycarbonyl)methyl, 2,2-bis(ethoxycarbonyl)ethyl, 3,3-bis(ethoxycarbonyl)propyl, 4,4-bis(ethoxycarbonyl)butyl or 5,5-bis(ethoxycarbonyl)penyl.
Particular preference is given to compounds of the formula I in which n=0 or 1 and m=0 and R1 denotes methyl, ethyl, propyl, butyl, pentyl, vinyl, 1E-propenyl, 1E-butenyl or 1E-pentenyl, and to media comprising these compounds. Of these compounds, the alkyl-substituted compounds are particularly preferably employed.
The compounds of the formula I may be in the form of stereoisomers owing to asymmetrically substituted carbon atoms in ring B. The invention relates to all isomers, both in pure form, as a racemate and also as a mixture of diastereomers or enantiomers. Optically active compounds of the formula I can also be used as dopants in liquid-crystal mixtures.
The compounds of the formula I are synthesised (see Schemes I to V) by the processes described in the literature (Houben Weyl, Methoden der organischen Chemie [Methods of Organic Chemistry], Georg Thieme Verlag, Stuttgart, N.Y., 4th Edn. 1993. Regarding Scheme II, see also DE 10 2004 004 228 (A) and Taugerbeck, M. Klasen-Memmer, Application Number 10 2004 036831.7).
In the following schemes, the compounds of the formula I are abbreviated to compounds 1. Compounds 1b and 1c here are accessible from the lactones 1a. Thus, 1b is obtained either directly by reduction of 1a using sodium borohydride in the presence of boron trifluoride or in two steps by reduction of 1a to the diol 2 and subsequent etherification, for example by treatment with acids or by Mitsunobu reaction with triphenylphosphine and diethyl azodicarboxylate (see Scheme I).




in which, as in the following schemes, unless explicitly indicated otherwise,

    R1 and R2 each, independently of one another, have the meanings indicated above for R1 and R2 respectively in the case of formula I and the other parameters each have the corresponding meanings indicated above in the case of formula I.


The difluoroether 1c is obtained, for example, either by reaction of the lactones 1a with Lawesson's reagent and subsequent treatment with DAST or NBS in the presence of Ohla's reagent (W. H. Bunnelle, B. R. McKinnis, B. A. Narayanan, J. Org. Chem. 1990, 55, pp. 768-770) or analogously to the process described in A. Taugerbeck, M. Klasen-Memmer, Application Number 10 2004 036831.7 by fluorodesulfuration of dithioorthoesters of type 4 using an oxidant, such as, for example, bromine, NBS, DBH, inter alia, in the presence of a fluoride ion source, such as HF/pyridine complex, triethylamine trishydrogenfluoride, etc. (see Scheme II).




in which n=0 or 1.

The lactones 1a can be prepared as described by S. Sethna, R. Phadke, Org. React. 1953, 7, p. 1 by Pechmann condensation of phenol derivatives or resorcinols with β-ketoesters of type 6 (V. H. Wallingford, A. H. Homeyer, D. M. Jones, J. Am. Chem. Soc. 1941, 63, pp. 2252-2254) and subsequent hydrogenation (Scheme III).
An alternative reduction of the compounds 7 using lithium in ammonia is described in D. J. Collins, A. G. Ghingran, S. B. Rutschmann, Aust. J. Chem. 1989, 42, pp. 1769-1784.




The compounds 7 are also obtainable by the method of P. Sellès, U. Mueller, Org. Lett. 2004, 6, pp. 277-279 by Suzuki coupling from enol triflates 8 (see Scheme IV). The compounds 8 can be obtained from the ketoesters 5 described above by treatment with trifluoromethanesulfonic anhydride in the presence of a base, such as, for example, collidine (E. Piers, H. L. A. Tse, Tetrahedron Lett. 1984, 25, 3155-3158). The boronic acids 9 are accessible, for example, from the corresponding alkyl bromides described in A. Taugerbeck, M. Klasen-Memmer, DE102004004228 by bromine/lithium exchange and subsequent reaction with trimethyl borate.




The compounds 1a are obtained after hydrogenation as an isomer mixture, which can be separated by conventional methods, crystallisation and/or chromatography. Compounds having the 6aR*,8R*,10aS* configuration can be obtained as shown in Scheme V in two additional synthesis steps and by the method of D. J. Collins, A. G. Ghingran, S. B. Rutschmann, Aust. J. Chem. 1989, 42, pp. 1769-1784 by base-catalysed isomerisation, where it may be advantageous firstly to open the lactone ring by saponification analogously to J. M. Fevig et al., Bioorg. Med. Chem. Lett. 1996, 6, pp. 295-300 and to close it again after base-catalysed isomerisation is complete.




Examples of structures of preferred compounds of the formula I, in which R and R′ have the respective meaning given for R1 and R2 respectively under formula I, are given below.
















Compounds of the formula I according to the invention may be chiral owing to their molecular structure and can accordingly occur in various enantiomeric forms. They can therefore be in racemic or optically active form.
Since the pharmaceutical efficacy of the racemates or stereoisomers of the compounds according to the invention may differ, it may be desirable to use the enantiomers. In these cases, the end product or alternatively even the intermediates can be separated into enantiomeric compounds by chemical or physical measures known to the person skilled in the art or even employed as such in the synthesis.
In the case of racemic amines, diastereomers are formed from the mixture by reaction with an optically active resolving agent. Suitable resolving agents are, for example, optically active acids, such as the R and S forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid, suitably N-protected amino acids (for example N-benzoylproline or N-benzenesulfonylproline) or the various optically active camphorsulfonic acids. Also advantageous is chromatographic enantiomer separation with the aid of an optically active resolving agent (for example dinitrobenzoylphenylglycine, cellulose triacetate or other derivatives of carbohydrates or chirally derivatised methacrylate polymers immobilised on silica gel). Suitable eluents for this purpose are aqueous or alcoholic solvent mixtures, such as, for example, hexane/isopropanol/acetonitrile, for example in the ratio 82:15:3.
The invention encompasses not only the said compounds, but also mixtures and compositions which, besides these compounds according to the invention, also comprise other pharmacological active ingredients or adjuvants which are able to influence the primary pharmacological action of the compounds according to the invention in the desired manner.
The compounds according to the invention can be employed as medicament active ingredients in human or veterinary medicine, in particular for the prophylaxis or therapy of diseases which can be influenced by the central-nervous action of the compounds.
The compounds according to the invention can particularly preferably be employed for treating sexual disorders or increasing sexual performance, diarrhoea, nicotine dependence, inflammatory CNS diseases (demyelination, viral meningitis, multiple sclerosis, Guillain-Barré syndome) and accident-induced brain injuries or head injuries, appetence disorders, i.e. dependences of various types (drugs, alcohol, sugar), bulimia and any consequences thereof (obesity, diabetes).
They are furthermore active against hypertension or act against anxiety states and/or depression, as sedative, tranquilliser, analgesic, antiemetic or they have an inflammation-inhibiting action.
The central-nervous action can be demonstrated by administration to rats in doses of 0.1-1000 mg/kg, preferably of 1-100 mg/kg. Effects such as reduced spontaneous motor activity are observed, where the requisite dose depends both on the efficacy of the compound and also on the body weight of the experimental animal.
The invention accordingly relates to compounds of the formulae defined above and below and in the claims, including physiologically acceptable salts thereof, as medicaments, diagnostic agents or reagents.
The invention also relates to corresponding pharmaceutical compositions which comprise at least one medicament of the formula I and optionally excipients and/or adjuvants. Suitable excipients are organic or inorganic substances which are suitable for enteral (for example oral), parenteral or topical administration or for administration in the form of an inhalation spray and do not react with the novel compounds, for example water, vegetable oils, benzyl alcohols, alkylene glycols, polyethylene glycols, glycerol triacetate, gelatine, carbohydrates, such as lactose or starch, magnesium stearate, talc and Vaseline. Suitable for oral use are, in particular, tablets, pills, dragees, capsules, powders, granules, syrups, juices or drops, suitable for rectal use are suppositories, suitable for parenteral use are solutions, preferably oily or aqueous solutions, furthermore suspensions, emulsions or implants, and suitable for topical use are ointments, creams or powders. The novel compounds may also be lyophilised and the resultant lyophilisates used, for example, for the preparation of injection preparations. The compositions indicated may have been sterilised and/or comprise adjuvants, such as lubricants, preservatives, stabilisers and/or wetting agents, emulsifiers, salts for modifying the osmotic pressure, buffer substances, colorants, flavours and/or a plurality of further active ingredients, for example one or more vitamins.
For administration as inhalation spray, it is possible to use sprays which comprise the active ingredient either dissolved or suspended in a propellant gas or propellant-gas mixture (for example CO2). The active ingredient here is advantageously used in micronised form, where one or more additional physiologically tolerated solvents may be present, for example ethanol. Inhalation solutions can be administered with the aid of conventional inhalers.
The substances according to the invention can generally be administered analogously to other, commercially available THC analogues, preferably in doses of between about 0.05 and 500 mg, in particular between 0.5 and 100 mg, per dosage unit. The daily dose is preferably between about 0.01 and 20 mg/kg of body weight. However, the specific dose for each patient depends on a very wide variety of factors, for example on the efficacy of the specific compound employed, on the age, body weight, general state of health, sex, on the diet, on the administration time and method, on the excretion rate, medicament combination and severity of the particular disease to which the therapy applies.
Furthermore, the novel compounds of the formula I can be used in analytical biology and molecular biology.
Specific ligand binding to the receptors is defined as the difference between complete binding and non-specific binding, which is determined in the presence of an excess of unlabelled ligands (see, for example, MUNRO, S., THOMAS, K. L. and ABU-SHAAR, M. (1993), Molecular characterisation of a peripheral receptor for cannabinoids. Nature, 365: 61-65. RINALDI-CARMONA, M., CALANDRA, B., SHIRE, D., BOUABOULA, M., OUSTRIC, D., BARTH, F., CASELLAS, P., FERRARA, P. and LE FUR, G. (1996), Characterisation of two cloned human CB1 cannabinoid receptors isoform; J. Pharmacol. Exp. Ther., 278:871-878).
The present invention also relates to liquid-crystal media which comprise one or more compound(s) of the formula I.
In a preferred embodiment, the liquid-crystal media in accordance with the present invention comprise
a) one or more dielectrically negative compound(s) of the formula I




    
    
        in which
        Y denotes —CO—, CS, —CH2— or —CF2—, preferably CH2 or CF2,
        L denotes H, halogen or CF3, preferably H, F or Cl, particularly preferably H or F and very particularly preferably F,
    
    






    
    
         each, independently of one another and, if present more than once, also these independently of one another, denote
        (f) a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—,
        (g) a 1,4-cyclohexenylene radical,
        (h) a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
        (i) naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
        (j) a radical selected from the group 1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene and spiro[3.3]heptane-2,6-diyl, where in
        
            (a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
            (c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group, preferably a —CF═ group, and preferably denote
        
        
    
    










    
    
         denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, and one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group, preferably a —CF═ group,
        R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least mono-substituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,
    
    










    
    
         —CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
        preferably one of
        R1 and R2 denotes alkyl or alkoxy having 1 to 12 C atoms, alkoxyalkyl, alkenyl or alkenyloxy having 2 to 12 C atoms and the other, independently of the first, likewise denotes alkyl and alkoxy having 1 to 12 C atoms, alkoxyalkyl, alkenyl or alkenyloxy having 2 to 12 C atoms or also F, Cl, Br, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3 or —OCHF2 
        Z1 and Z2 each, independently of one another and, if present more than once, also these independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another,
        preferably —(CH2)4—, —CH2—CH2—, —CF2—CF2—, —CH═CH—, —CF═CF—, —C≡C—, —CH2O—, —CF2O— or a single bond,
        particularly preferably —CH2O—, —CH2—CH2—, —CF2—CF2—, —CF═CF—, —CF2O— or a single bond, and
        n and m each denote 0, 1 or 2, where
        n+m denotes 0, 1, 2 or 3, preferably 0, 1 or 2, particularly preferably 0 or 1.

b) one or more dielectrically positive compound(s) of the formula II

    
    






    
    
        in which
        R21 and R22 each, independently of one another, have the meaning given above for R1 in the case of formula I,
        Z21 and Z22 each, independently of one another, have the meaning given above for Z1 in the case of formula I,
        at least one of the rings present
    
    






    
    
        preferably
    
    






    
    
         denote(s)
    
    






    
    
         and the others, in each case independently of one another, denote
    
    






    
    
        particularly preferably
    
    






    
    
         if present, denotes
    
    






    
    
        L21 and L22 both denote C—F or one of the two denotes N and the other denotes C—F, preferably both denote C—F, and
        I denotes 0, 1 or 2, preferably 0 or 1;

and optionally

c) one or more dielectrically neutral compounds of the formula III

    
    






    
    
        in which
        R31 and R32 each, independently of one another, have the meaning given above for R1 in the case of formula I, and
        Z31, Z32 and Z33 each, independently of one another, denote —CH2CH2—, —CH═CH—, —COO— or a single bond,
    
    






    
    
         each, independently of one another, denote
    
    






    
    
        o and p, independently of one another, denote 0 or 1,
        but preferably
        R31 and R32 each, independently of one another, denote alkyl or alkoxy having 1-5 C atoms or alkenyl having 2-5 C atoms,
    
    






    
    
         each, independently of one another, denote
    
    






    
    
        and very particularly preferably at least two of these rings denote
    
    






    
    
        where very particularly preferably two adjacent rings are linked directly, to be precise preferably
    
    






where in the case of the phenylene ring, one or more H atoms, independently of one another, may be replaced by F or CN, preferably by F, and one or two non-adjacent CH2 groups of the cyclohexylene ring or of one of the cyclohexylene rings may be replaced by O atoms.

The liquid-crystal media preferably comprise one or more compounds of the formula I which contain no biphenyl unit.
The liquid-crystal media particularly preferably comprise one or more compounds of the formula I
in which two adjacent rings are linked directly, to be precise preferably




where in the case of the phenylene ring, one or more H atoms, independently of one another, may be replaced by F or CN, preferably by F, and one or two non-adjacent CH2 groups of the cyclohexylene ring or of one of the cyclohexylene rings may be replaced by O atoms.

In a preferred embodiment, which may be identical with the embodiments just described, the liquid-crystal media comprise one or more compounds selected from the group of the compounds of the formula I-3.
The liquid-crystal medium preferably comprises one or more compounds selected from the group of the compounds of the formulae II-1 to II-3




in which

R21, R22, Z12, Z22,





and I each have the meaning given above in the case of formula II. Preferably, R21 is alkyl, preferably having 1-5 C atoms, R21 is alkyl or alkoxy, preferably each having 1 to 5 C atoms, and Z22 and Z21, if present, denote a single bond.

The liquid-crystal medium particularly preferably comprises one or more compounds selected from the group of the compounds of the formulae III-1 to III-3:




in which R31, R32, Z31, Z32,





each have the meaning given above in the case of formula III.

The liquid-crystal medium particularly preferably comprises one or more compounds selected from the group of the compounds of the formulae III-1a to III-1d, III-1e, III-2a to III-2g, III-3a to III-3d and III-4-a:




in which n and m each, independently of one another, denote 1 to 5, and o and p each, independently both thereof and of one another, denote 0 to 3,





in which R31 and R33 each have the meaning indicated above under formula III, preferably that under formula III-1, and the phenyl rings, in particular in the case of compounds III-2g and III-3c, may optionally be fluorinated, but not in such a way that the compounds are identical with those of the formula II and its sub-formulae. Preferably, R31 is n-alkyl having 1 to 5 C atoms, particularly preferably having 1 to 3 C atoms, and R32 is n-alkyl or n-alkoxy having 1 to 5 C atoms or alkenyl having 2 to 5 C atoms. Of these, particular preference is given to compounds of the formulae III-1a to III-1d.

Preferred fluorinated compounds of the formulae III-2g and III-3c are the compounds of the formulae III-2g′ and III-3c′




in which R31 and R33 each have the meaning indicated above under formula III, preferably the meaning indicated under formula III-2g or III-3c.

In the present application, the term compounds is taken to mean both one compound and a plurality of compounds, unless expressly stated otherwise.
The liquid-crystal media according to the invention preferably have nematic phases of in each case from at least −20° C. to 80° C., preferably from −30° C. to 85° C. and very particularly preferably from −40° C. to 100° C. The term “have a nematic phase” here is taken to mean firstly that no smectic phase and no crystallisation are observed at low temperatures at the corresponding temperature and secondly also that no clearing occurs on heating from the nematic phase. The investigation at low temperatures is carried out in a flow viscometer at the corresponding temperature and checked by storage in test cells having a layer thickness corresponding to the electro-optical application for at least 100 hours. At high temperatures, the clearing point is measured in capillaries by conventional methods.
Furthermore, the liquid-crystal media according to the invention are characterised by low optical anisotropy values.
The term “alkyl” preferably encompasses straight-chain and branched alkyl groups having 1 to 7 carbon atoms, in particular the straight-chain groups methyl, ethyl, propyl, butyl, pentyl, hexyl and heptyl. Groups having 2 to 5 carbon atoms are generally preferred.
The term “alkenyl” preferably encompasses straight-chain and branched alkenyl groups having 2 to 7 carbon atoms, in particular the straight-chain groups. Particularly preferred alkenyl groups are C2- to C7-1E-alkenyl, C4- to C7-3E-alkenyl, C5- to C7-4-alkenyl, C6- to C7-5-alkenyl and C7-6-alkenyl, in particular C2- to C7-1 E-alkenyl, C4- to C7-3E-alkenyl and C5- to C7-4-alkenyl. Examples of further preferred alkenyl groups are vinyl, 1E-propenyl, 1E-butenyl, 1E-pentenyl, 1E-hexenyl, 1E-heptenyl, 3-butenyl, 3E-pentenyl, 3E-hexenyl, 3E-heptenyl, 4-pentenyl, 4Z-hexenyl, 4E-hexenyl, 4Z-heptenyl, 5-hexenyl, 6-heptenyl and the like. Groups having up to 5 carbon atoms are generally preferred.
The term “fluoroalkyl” preferably encompasses straight-chain groups having a terminal fluorine, i.e. fluoromethyl, 2-fluoroethyl, 3-fluoropropyl, 4-fluorobutyl, 5-fluoropentyl, 6-fluorohexyl and 7-fluoroheptyl. However, other positions of the fluorine are not excluded.
The term “oxaalkyl” or “alkoxyalkyl” preferably encompasses straight-chain radicals of the formula CnH2n+1—O—(CH2)m, in which n and m each, independently of one another, denote 1 to 6. Preferably, n is 1 and m is 1 to 6.
Compounds containing a vinyl end group and compounds containing a methyl end group have low rotational viscosity.
In the present application, the term dielectrically positive compounds denotes compounds having a Δ∈ of >1.5, the term dielectrically neutral compounds denotes those in which −1.5≦Δ∈≦1.5, and the term dielectrically negative compounds denotes those having a Δ∈ of <−1.5. The dielectric anisotropy of the compounds is determined here by dissolving 10% of the compounds in a liquid-crystalline host and determining the capacitance of this mixture at 1 kHz in at least one test cell with a layer thickness of about 20 μm having a homeotropic surface alignment and at least one test cell with a layer thickness of about 20 μm having a homogeneous surface alignment. The measurement voltage is typically 0.5 V to 1.0 V, but is always less than the capacitive threshold of the respective liquid-crystal mixture.
The host mixture used for determining the applicationally relevant physical parameters is ZLI-4792 from Merck KGaA, Germany. As an exception, the determination of the dielectric anisotropy of dielectrically negative compounds is carried out using ZLI-2857, likewise from Merck KGaA, Germany. The values for the respective compound to be investigated are obtained from the change in the properties, for example the dielectric constants, of the host mixture after addition of the compound to be investigated and extrapolation to 100% of the compound employed.
The concentration employed for the compound to be investigated is 10%. If the solubility of the compound to be investigated is inadequate for this purpose, the concentration employed is, by way of exception, halved, i.e. reduced to 5%, 2.5%, etc., until the concentration is below the solubility limit.
The term threshold voltage usually relates to the optical threshold for 10% relative contrast (V10). In relation to the liquid-crystal mixtures of negative dielectric anisotropy, however, the term threshold voltage is used in the present application for the capacitive threshold voltage (V0), also known as the Freedericksz threshold, unless explicitly stated otherwise.
All concentrations in this application, unless explicitly stated otherwise, are indicated in percent by weight and relate to the corresponding mixture as a whole. All physical properties are and have been determined in accordance with “Merck Liquid Crystals, Physical Properties of Liquid Crystals”, status November 1997, Merck KGaA, Germany, and apply to a temperature of 20° C., unless explicitly stated otherwise. An is determined at 589 nm and Δ∈ at 1 kHz.
In the case of the liquid-crystal media of negative dielectric anisotropy, the threshold voltage was determined as the capacitive threshold V0 in cells with a liquid-crystal layer aligned homeotropically by means of lecithin.
The liquid-crystal media according to the invention may, if necessary, also comprise further additives and optionally also chiral dopants in the conventional amounts. The amount of these additives employed is in total from 0% to 10%, based on the amount of the mixture as a whole, preferably from 0.1% to 6%. The concentrations of the individual compounds employed are in each case preferably from 0.1 to 3%. The concentration of these and similar additives is not taken into account when indicating the concentrations and the concentration ranges of the liquid-crystal compounds in the liquid-crystal media.
The compositions consist of a plurality of compounds, preferably 3 to 30, particularly preferably 6 to 20 and very particularly preferably 10 to 16 compounds, which are mixed in a conventional manner. In general, the desired amount of the components used in lesser amount is dissolved in the components making up the principal constituent, advantageously at elevated temperature. If the selected temperature is above the clearing point of the principal constituent, the completion of the dissolution process is particularly easy to observe. However, it is also possible to prepare the liquid-crystal mixtures in other conventional ways, for example using pre-mixes or from so-called “multibottle” systems.
By means of suitable additives, the liquid-crystal phases according to the invention can be modified in such a way that they can be employed in any type of display and in particular of ECB displays and IPS displays that has been disclosed hitherto.
The examples below serve to illustrate the invention without representing a restriction. In the examples, the melting point T(C,N), the transition from the smectic (S) phase to the nematic (N) phase T(S,N) and the clearing point T(N,I) of a liquid-crystal substance are indicated in degrees Celsius. The various smectic phases are characterised by corresponding suffixes.
The percentages above and below are, unless explicitly stated otherwise, percent by weight, and the physical properties are the values at 20° C., unless explicitly stated otherwise.
All the temperature values indicated in this application are ° C. and all temperature differences are correspondingly differential degrees, unless explicitly stated otherwise.
In the synthesis examples and schemes, the abbreviations have the following meanings:

    DAST diethylaminosulfur trifluoride,
    DBH dibromodimethylhydantoin,
    DEAD diethyl azodicarboxylate,
    MTB ether methyl tert-butyl ether,
    NBS N-bromosuccinimide,
    THF tetrahydrofuran.


In the present application and in the examples below, the structures of the liquid-crystal compounds are indicated by means of acronyms, the trans-formation into chemical formulae taking place in accordance with Tables A and B below. All radicals CnH2n+1 and CmH2m+1 are straight-chain alkyl radicals having n and m C atoms respectively. The coding in Table B is self-evident. In Table A, only the acronym for the parent structure is indicated. In individual cases, the acronym for the parent structure is followed, separated by a dash, by a code for the substituents R1, R2, L1, L2 and L3:















Code for R1, R2, L1, L2, L3
R1
R2
L1
L2
L3







nm
CnH2n+1 
CmH2m+1
H
H
H


nOm
CnH2n+1
OCmH2m+1
H
H
H


nO.m
OCnH2n+1
CmH2m+1
H
H
H


nmFF
CnH2n+1
CmH2m+1
F
H
F


nOmFF
CnH2n+1
OCmH2m+1
F
H
F


nO.mFF
OCnH2n+1
CmH2m+1
F
H
F


nO.OmFF
OCnH2n+1
OCmH2m+1
F
H
F


n
CnH2n+1
CN
H
H
H


nN.F
CnH2n+1
CN
F
H
H


nN.F.F
CnH2n+1
CN
F
F
H


nF
CnH2n+1
F
H
H
H


nF.F
CnH2n+1
F
F
H
H


nF.F.F
CnH2n+1
F
F
F
H


nCl
CnH2n+1
Cl
H
H
H


nCl.F
CnH2n+1
Cl
F
H
H


nCl.F.F
CnH2n+1
Cl
F
F
H


nmF
CnH2n+1
CmH2m+1
F
H
H


nCF3
CnH2n+1
CF3
H
H
H


nOCF3
CnH2n+1
OCF3
H
H
H


nOCF3.F
CnH2n+1
OCF3
F
H
H


nOCF3.F.F
CnH2n+1
OCF3
F
F
H


nOCF2
CnH2n+1
OCHF2
H
H
H


nOCF2.F.F
CnH2n+1
OCHF2
F
F
H


nS
CnH2n+1
NCS
H
H
H


rVsN
CrH2r+1—CH═CH—CsH2s—
CN
H
H
H


nEsN
CrH2r+1—O—CsH2s—
CN
H
H
H


nAm
CnH2n+1
COOCmH2m+1
H
H
H


nF.Cl
CnH2n+1
F
Cl
H
H

















TABLE A








PYP








 









PYRP








 









BCH








 



CBC








 



CCH








 



CCP








 









CP








 









CPTP








 









CEPTP








 









D








 









ECCP








 



CECP








 



EPCH








 









HP








 









ME








 



PCH








 



PDX








 



PTP








 









BECH








 



EBCH








 









CPC








 



EHP








 



BEP








 









ET























TABLE B








CCZU-n-X








 









CDU-n-X








 









T3n








 



K3n








 



M3n








 









CGP-n-X








 



CGU-n-X








 



CGG-n-X








 









Inm








 









CGU-n-X








 









C-nm








 



C15








 



CB15








 









CBC-nmF








 



CCN-nm








 









G3n








 









CCEPC-nm








 









CCPC-nm








 









CH-nm








 



HD-nm








 



HH-nm








 









NCB-nm








 









OS-nm








 









CHE








 









CBC-nmF








 



ECBC-nm








 



ECCH-nm








 









CCH-n1EM








 









T-nFN








 









GP-nO-X








 









CVCC-n-m








 



CVCP-n-m








 



CVCVC-n-m








 









CP-V-N








 



CC-n-V








 









CCG-V-F








 









CPP-nV2-m








 









CCP-V-m








 









CCP-V2-m








 









CPP-V-m








 









CPP-nV-m








 



CPP-V2-m








 









CC-V-V








 



CC-1V-V








 









CC-1V-V1








 









CC-2V-V








 









CC-2V-V2








 



CC-2V-V1








 









CC-V1-V








 









CC-V1-1V








 



CC-V2-1V








 









PCH-n(O)mFF








 



CCP-n(O)mFF








 









CPTP-n(O)mFF








 









Ph-n-(0)mFF








 









Ph-n0-(0)mFF








 









BHHO-n-(0)mFF








 









BHHO-n0-(0)mFF








 









BFFO-n-(0)mFF








 









BFFO-n0-(0)mFF








 









BFO-n-(0)mFF








 









BFO-n0-(0)mFF








 



BCOO-n-(0)mFF








 









BCOO-n0-(0)mFF








 









BHHO-O1P-n(O)-HFF








 









BHHO-O1P-n(O)-(O)mFF








 



BHHO-O1C-n(O)-(O)mFF

















EXAMPLES
The following examples are intended to explain the invention without limiting it. Above and below, percentages are percent by weight. All temperatures are indicated in degrees Celsius. Δn denotes the optical anisotropy (589 nm, 20° C.), Δ∈ the dielectric anisotropy (1 kHz, 20° C.), H.R. the voltage holding ratio (at 100° C., after 5 minutes in the oven, 1 V). V10, V50 and V90 (the threshold voltage, mid-grey voltage and saturation voltage respectively) and V0 (the capacitive threshold voltage) were each determined at 20° C.
Substance Examples
Example 1
(3-Ethoxy-6,6-difluoro-8-propyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene)
1.1. Preparation of 3-ethoxy-8-propyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one




16.6 g (78.5 mmol) of methyl 2-oxo-5-propylcyclohexanecarboxylate, 7.65 g (69.5 mmol) of resorcinol and 5.6 ml (6.1 mmol) of phosphoryl chloride are dissolved in 55 ml of toluene, and the mixture is heated under reflux for 3 h. After hydrolysis using water, the deposited precipitate is filtered off with suction, washed with toluene and dried. The product is dissolved in 200 ml of acetone, 20 g (145 mmol) of potassium carbonate and 9.00 g (57.7 mmol) of ethyl iodide are added, and the mixture is heated under reflux for 5 h. The majority of the solvent is removed under reduced pressure, and the residue is taken up in MTB ether/water. The aqueous phase is separated off and extracted with MTB ether. The combined organic phases are washed with water and dried over sodium sulfate. The solvent is removed under reduced pressure, and the crude product is recrystallised from ethanol, giving 3-ethoxy-8-propyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one as colourless crystals. The melting point is 108° C. The other physical properties are:

Δ∈=−7.5 (extrapolated from 5% solution in ZLI-2857), Δn=0.1302 (5% in ZLI-4792).

1.2. Preparation of 3-ethoxy-8-propyl-6a,7,8,9,10,10a-hexahydrobenzo[c]-chromen-6-one




8.60 g (30 mmol) of 3-ethoxy-8-propyl-7,8,9,10-tetrahydrobenzo[c]-chromen-6-one are dissolved in THF and hydrogenated to cessation on palladium/active carbon. The solution is filtered and evaporated, giving 3-ethoxy-8-propyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-6-one as colourless oil.
1.3. Preparation of 10-ethoxy-7-oxa-17-propyl-1,5-dithia-14,15,16,17,18,19-hexahydrodibenzospiro[5.5]nonadecane




29 ml (58 mmol) of a 2M solution of trimethylaluminium in heptane are initially introduced in 35 ml of dichloromethane under nitrogen and cooled to −75° C., and a solution of 2.9 ml (28.5 mmol) of 1,3-propanedithiol in 15 ml of dichloromethane is then added dropwise. The batch is allowed to thaw and cooled to −20° C., and a solution of 8.20 g (26.0 mmol) of 3-ethoxy-8-propyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-6-one in 10 ml of dichloromethane is added dropwise. The batch is left to stir overnight at room temp., added to ice-water and extracted with dichloromethane. The combined organic phases are washed with water and dried over sodium sulfate. The solvent is removed under reduced pressure, and the residue is filtered through silica gel with heptane/MTB (8:2), giving 10.9 g of dithioorthoester as yellow oil, which is employed in the next step without further purification.
1.4. Preparation of 3-ethoxy-6,6-difluoro-6a,7,8,9,10,10a-hexahydro-8-propyl-6H-benzo[c]chromene




4.14 g (10.9 mmol) of dithioorthoester are initially introduced in 300 ml of dichloromethane at −70° C., and 8.9 ml (55 mmol) of triethylamine trishydrofluoride are added. A suspension of 15.7 g (55 mmol) of dibromodimethylhydantoin in 200 ml of dichloromethane is subsequently added in portions, and the batch is left to stir for 2 h. The cooling is then removed, and the solution is added to an ice-cold mixture of 400 ml of 1M sodium hydroxide solution and 20 ml of 39% sodium hydrogensulfite soln. The aqueous phase is separated off and extracted three times with dichloromethane. The combined organic phases are washed with water and dried over sodium sulfate. Removal of the solvent under reduced pressure gives a yellow oil. The latter is taken up in THF and hydrogenated to cessation on a palladium/active carbon catalyst. After filtration, the resultant solution is evaporated under reduced pressure, and the residue is purified by chromatography, giving 3-ethoxy-6,6-difluoro-6a,7,8,9,10,10a-hexahydro-8-propyl-6H-benzo[c]chromene as colourless oil having the following properties.
Tg=−39° C.
19F-NMR (235 MHz, CDCl3)
δ=−66.8 ppm (d, 2J=155 Hz, 1F, CF2O), −81.8 (d, 2J=155 Hz, 1F, CF2O).
MS (EI)
m/e (%)=310 (98) [M+], 225 (100).
Example 2
(3-Ethoxy-4,6,6-trifluoro-8-propyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene)
2.1. Preparation of 3-ethoxy-4-fluoro-8-propyl-7,8,9,10-tetrahydrobenzo[c]-chromen-6-one




18.2 g (56.6 mmol) of methyl 5-propyl-2-trifluoromethanesulfonyloxycyclohex-1-enecarboxylate, 21.5 g (74.6 mmol) of 4-ethoxy-3-fluoro-2-(2-methoxyethoxymethoxy)benzeneboronic acid, 1.5 ml of water, 33 g (120 mmol) of sodium metaborate, 1.12 g (1.6 mmol) of bis(triphenylphosphine)palladium(II) chloride and 0.1 ml (1.6 mmol) of hydrazinium hydroxide are heated under reflux overnight in 300 ml of tetrahydrofuran. After addition of water, the aqueous phase is separated off and extracted twice with MTB ether. The combined organic phases are washed with saturated sodium chloride soln. and dried over sodium sulfate. The solvent is removed under reduced pressure, and the residue is filtered through silica gel with n-heptane/MTB ether (6:4), giving 3-ethoxy-4-fluoro-8-propyl-7,8,9,10-tetrahydrobenzo[c]chromen-6-one as colourless crystals.
13C-NMR (CDCl3, 75 MHz)
δ=14.2 ppm (CH3), 14.8 (CH3), 19.9 (CH2), 25.4 (CH2), 27.5 (CH2), 30.4 (CH2), 32.6 (CH), 32.7 (CH2), 38.3 (CH2), 65.6 (OCH2CH3), 109.8 (CH), 114.870 (C), 117.7 (d, J=4.4 Hz, CH), 121.184 (C), 139.7 (d, J=250 Hz, CF), 146.860 (C), 148.384 (C), 148.485 (C), 160.755 (C═O).
2.2. Preparation of 3-ethoxy-4,6,6-trifluoro-8-propyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene




3-Ethoxy-4,6,6-trifluoro-8-propyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]-chromene is obtained analogously to the synthesis described under 1.
Examples 3 to 120
The following are prepared analogously to Example 1.2.:


















 















Phase sequence

T*(N,I)/


No.
R1
R2
T/° C.
Δε*
° C.















3
CH3
CH3





4
CH3
C2H5


5
CH3
n-C3H7


6
CH3
n-C4H9


7
CH3
n-C5H11


8
CH3
n-C6H13


9
CH3
n-C7H15


10
CH3
CH3O


11
CH3
C2H5O


12
CH3
n-C3H7O


13
CH3
n-C4H9O


14
CH3
CH2═CH


15
CH3
E-CH3—CH═CH


16
CH3
CH2═CH—O


17
CH3
CH2═CH—CH2O


18
C2H5
CH3


19
C2H5
C2H5


20
C2H5
n-C3H7


21
C2H5
n-C4H9


22
C2H5
n-C5H11


23
C2H5
n-C6H13


24
C2H5
n-C7H15


25
C2H5
CH3O


26
C2H5
C2H5O


27
C2H5
n-C3H7O


28
C2H5
n-C4H9O


29
C2H5
CH2═CH


30
C2H5
E-CH3—CH═CH


31
C2H5
CH2═CH—O


32
C2H5
CH2═CH—CH2O


33
n-C3H7
CH3


34
n-C3H7
C2H5


35
n-C3H7
n-C3H7


36
n-C3H7
n-C4H9


37
n-C3H7
n-C5H11


38
n-C3H7
n-C6H13


39
n-C3H7
n-C7H15


40
n-C3H7
CH3O


1.2
n-C3H7
C2H5O


41
n-C3H7
n-C3H7O


42
n-C3H7
n-C4H9O


43
n-C3H7
CH2═CH


44
n-C3H7
E-CH3—CH═CH


45
n-C3H7
CH2═CH—O


46
n-C3H7
CH2═CH—CH2O


47
n-C4H9
CH3


48
n-C4H9
C2H5


49
n-C4H9
n-C3H7


50
n-C4H9
n-C4H9


51
n-C4H9
n-C5H11


52
n-C4H9
n-C6H13


53
n-C4H9
n-C7H15


54
n-C4H9
CH3O


55
n-C4H9
C2H5O


56
n-C4H9
n-C3H7O


57
n-C4H9
n-C4H9O


58
n-C4H9
CH2═CH


59
n-C4H9
E-CH3—CH═CH


60
n-C4H9
CH2═CH—O


61
n-C4H9
CH2═CH—CH2O

















Phase sequence



No.
R1
R2
T/° C.
Δε*














62
CH3O
CH3




63
CH3O
C2H5


64
CH3O
n-C3H7


65
CH3O
n-C4H9


66
CH3O
n-C5H11


67
CH3O
n-C6H13


68
CH3O
n-C7H15


69
CH3O
CH3O


70
CH3O
C2H5O


71
CH3O
n-C3H7O


72
CH3O
n-C4H9O


73
CH3O
CH2═CH


74
CH3O
E-CH3—CH═CH


75
CH3O
CH2═CH—O


76
CH3O
CH2═CH—CH2O


77
C2H5O
CH3


78
C2H5O
C2H5


79
C2H5O
n-C3H7


80
C2H5O
n-C4H9


81
C2H5O
n-C5H11
C 137 I


82
C2H5O
n-C6H13


83
C2H5O
n-C7H15


84
C2H5O
CH3O


85
C2H5O
C2H5O


86
C2H5O
n-C3H7O


87
C2H5O
n-C4H9O


88
C2H5O
CH2═CH


89
C2H5O
E-CH3—CH═CH


90
C2H5O
CH2═CH—O


91
C2H5O
CH2═CH—CH2O


92
CH2═CH
CH3


93
CH2═CH
C2H5


94
CH2═CH
n-C3H7


95
CH2═CH
n-C4H9


96
CH2═CH
n-C5H11


97
CH2═CH
n-C6H13


98
CH2═CH
n-C7H15


99
CH2═CH
CH3O


100
CH2═CH
C2H5O


101
CH2═CH
n-C3H7O


102
CH2═CH
n-C4H9O


103
CH2═CH
CH2═CH


104
CH2═CH
E-CH3—CH═CH


105
CH2═CH
CH2═CH—O


106
CH2═CH
CH2═CH—CH2O


107
CH2═CH—O
CH3


108
CH2═CH—O
C2H5


109
CH2═CH—O
n-C3H7


110
CH2═CH—O
n-C4H9


111
CH2═CH—O
n-C5H11


112
CH2═CH—O
n-C6H13


113
CH2═CH—O
n-C7H15


114
CH2═CH—O
CH3O


115
CH2═CH—O
C2H5O


116
CH2═CH—O
n-C3H7O


117
CH2═CH—O
n-C4H9O


118
CH2═CH—O
CH2═CH


119
CH2═CH—O
E-CH3—CH═CH


120
CH2═CH—O
CH2═CH—O


121
CH2═CH—O
CH2═CH—CH2O





Note:


*values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 122 to 240
The following are prepared analogously to Example 1.4.:


















 















Phase sequence

T*(N,I)/


No.
R1
R2
T/° C.
Δε*
° C.















122
CH3
CH3





123
CH3
C2H5


124
CH3
n-C3H7


125
CH3
n-C4H9


121
CH3
n-C5H11


126
CH3
n-C6H13


127
CH3
n-C7H15


128
CH3
CH3O


129
CH3
C2H5O


130
CH3
n-C3H7O


131
CH3
n-C4H9O


132
CH3
CH2═CH


133
CH3
E-CH3—CH═CH


134
CH3
CH2═CH—O


135
CH3
CH2═CH—CH2O


136
C2H5
CH3


137
C2H5
C2H5


138
C2H5
n-C3H7


139
C2H5
n-C4H9


140
C2H5
n-C5H11


141
C2H5
n-C6H13


142
C2H5
n-C7H15


143
C2H5
CH3O


144
C2H5
C2H5O


145
C2H5
n-C3H7O


146
C2H5
n-C4H9O


147
C2H5
CH2═CH


148
C2H5
E-CH3—CH═CH


149
C2H5
CH2═CH—O


150
C2H5
CH2═CH—CH2O


151
n-C3H7
CH3


152
n-C3H7
C2H5


153
n-C3H7
n-C3H7


154
n-C3H7
n-C4H9


155
n-C3H7
n-C5H11


156
n-C3H7
n-C6H13


157
n-C3H7
n-C7H15


158
n-C3H7
CH3O


159
n-C3H7
C2H5O


1.4
n-C3H7
n-C3H7O
Tg = −39° C.


160
n-C3H7
n-C4H9O


161
n-C3H7
CH2═CH


162
n-C3H7
E-CH3—CH═CH


163
n-C3H7
CH2═CH—O


164
n-C3H7
CH2═CH—CH2O


165
n-C4H9
CH3


166
n-C4H9
C2H5


167
n-C4H9
n-C3H7


168
n-C4H9
n-C4H9


169
n-C4H9
n-C5H11


170
n-C4H9
n-C6H13


171
n-C4H9
n-C7H15


172
n-C4H9
CH3O


173
n-C4H9
C2H5O


174
n-C4H9
n-C3H7O


175
n-C4H9
n-C4H9O


176
n-C4H9
CH2═CH


177
n-C4H9
E-CH3—CH═CH


178
n-C4H9
CH2═CH—O


179
n-C4H9
CH2═CH—CH2O


180
CH3O
CH3


181
CH3O
C2H5


182
CH3O
n-C3H7


183
CH3O
n-C4H9


184
CH3O
n-C5H11


185
CH3O
n-C6H13


186
CH3O
n-C7H15


187
CH3O
CH3O


188
CH3O
C2H5O


189
CH3O
n-C3H7O


190
CH3O
n-C4H9O


191
CH3O
CH2═CH


192
CH3O
E-CH3—CH═CH


193
CH3O
CH2═CH—O


194
CH3O
CH2═CH—CH2O


195
C2H5O
CH3


196
C2H5O
C2H5


197
C2H5O
n-C3H7


198
C2H5O
n-C4H9


199
C2H5O
n-C5H11


201
C2H5O
n-C6H13


202
C2H5O
n-C7H15


203
C2H5O
CH3O


204
C2H5O
C2H5O


205
C2H5O
n-C3H7O


206
C2H5O
n-C4H9O


207
C2H5O
CH2═CH


208
C2H5O
E-CH3—CH═CH


209
C2H5O
CH2═CH—O


210
C2H5O
CH2═CH—CH2O

















Phase sequence



No.
R1
R2
T/° C.
Δε*





211
CH2═CH
CH3


212
CH2═CH
C2H5


213
CH2═CH
n-C3H7


214
CH2═CH
n-C4H9


215
CH2═CH
n-C5H11


216
CH2═CH
n-C6H13


217
CH2═CH
n-C7H15


218
CH2═CH
CH3O


219
CH2═CH
C2H5O


220
CH2═CH
n-C3H7O


221
CH2═CH
n-C4H9O


222
CH2═CH
CH2═CH


223
CH2═CH
E-CH3—CH═CH


224
CH2═CH
CH2═CH—O


225
CH2═CH
CH2═CH—CH2O


226
CH2═CH—O
CH3


227
CH2═CH—O
C2H5


228
CH2═CH—O
n-C3H7


229
CH2═CH—O
n-C4H9


230
CH2═CH—O
n-C5H11


231
CH2═CH—O
n-C6H13


232
CH2═CH—O
n-C7H15


233
CH2═CH—O
CH3O


234
CH2═CH—O
C2H5O


235
CH2═CH—O
n-C3H7O


236
CH2═CH—O
n-C4H9O


237
CH2═CH—O
CH2═CH


238
CH2═CH—O
E-CH3—CH═CH


239
CH2═CH—O
CH2═CH—O


240
CH2═CH—O
CH2═CH—CH2O





Note:


*values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 241 to 359
The following are prepared analogously to Example 1.2.:




























Phase sequence



No.
R1
R2
T/° C.
Δε*





241
CH3
CH3




242
CH3
C2H5


243
CH3
n-C3H7


244
CH3
n-C4H9


245
CH3
n-C5H11


246
CH3
n-C6H13


247
CH3
n-C7H15


248
CH3
CH3O


249
CH3
C2H5O


250
CH3
n-C3H7O


251
CH3
n-C4H9O


252
CH3
CH2═CH


253
CH3
E-CH3—CH═CH


254
CH3
CH2═CH—O


255
CH3
CH2═CH—CH2O


256
C2H5
CH3


257
C2H5
C2H5


258
C2H5
n-C3H7


259
C2H5
n-C4H9


260
C2H5
n-C5H11


261
C2H5
n-C6H13


262
C2H5
n-C7H15


263
C2H5
CH3O


264
C2H5
C2H5O


265
C2H5
n-C3H7O


266
C2H5
n-C4H9O


267
C2H5
CH2═CH


268
C2H5
E-CH3—CH═CH


269
C2H5
CH2═CH—O


270
C2H5
CH2═CH—CH2O


271
n-C3H7
CH3


272
n-C3H7
C2H5


273
n-C3H7
n-C3H7


274
n-C3H7
n-C4H9


275
n-C3H7
n-C5H11


276
n-C3H7
n-C6H13


277
n-C3H7
n-C7H15


278
n-C3H7
CH3O


279
n-C3H7
C2H5O


280
n-C3H7
n-C3H7O


281
n-C3H7
n-C4H9O


282
n-C3H7
CH2═CH


283
n-C3H7
E-CH3—CH═CH


284
n-C3H7
CH2═CH—O


285
n-C3H7
CH2═CH—CH2O


286
n-C4H9
CH3


287
n-C4H9
C2H5


288
n-C4H9
n-C3H7


289
n-C4H9
n-C4H9


290
n-C4H9
n-C5H11


291
n-C4H9
n-C6H13


292
n-C4H9
n-C7H15


293
n-C4H9
CH3O


294
n-C4H9
C2H5O


295
n-C4H9
n-C3H7O


296
n-C4H9
n-C4H9O


297
n-C4H9
CH2═CH


298
n-C4H9
E-CH3—CH═CH


299
n-C4H9
CH2═CH—O


300
n-C4H9
CH2═CH—CH2O


300
CH3O
CH3


302
CH3O
C2H5


303
CH3O
n-C3H7


304
CH3O
n-C4H9


305
CH3O
n-C5H11


306
CH3O
n-C6H13


307
CH3O
n-C7H15


308
CH3O
CH3O


309
CH3O
C2H5O


310
CH3O
n-C3H7O


311
CH3O
n-C4H9O


312
CH3O
CH2═CH


313
CH3O
E-CH3—CH═CH


314
CH3O
CH2═CH—O


315
CH3O
CH2═CH—CH2O


316
C2H5O
CH3


317
C2H5O
C2H5


318
C2H5O
n-C3H7


319
C2H5O
n-C4H9


320
C2H5O
n-C5H11


241
C2H5O
n-C6H13


321
C2H5O
n-C7H15


322
C2H5O
CH3O


323
C2H5O
C2H5O


324
C2H5O
n-C3H7O


325
C2H5O
n-C4H9O


326
C2H5O
CH2═CH


327
C2H5O
E-CH3—CH═CH


328
C2H5O
CH2═CH—O


329
C2H5O
CH2═CH—CH2O


330
CH2═CH
CH3


331
CH2═CH
C2H5


332
CH2═CH
n-C3H7


333
CH2═CH
n-C4H9


334
CH2═CH
n-C5H11


335
CH2═CH
n-C6H13


336
CH2═CH
n-C7H15


337
CH2═CH
CH3O


338
CH2═CH
C2H5O


339
CH2═CH
n-C3H7O


340
CH2═CH
n-C4H9O


341
CH2═CH
CH2═CH


342
CH2═CH
E-CH3—CH═CH


343
CH2═CH
CH2═CH—O


344
CH2═CH
CH2═CH—CH2O


345
CH2═CH—O
CH3


346
CH2═CH—O
C2H5


347
CH2═CH—O
n-C3H7


348
CH2═CH—O
n-C4H9


349
CH2═CH—O
n-C5H11


350
CH2═CH—O
n-C6H13


351
CH2═CH—O
n-C7H15


352
CH2═CH—O
CH3O


353
CH2═CH—O
C2H5O


354
CH2═CH—O
n-C3H7O


355
CH2═CH—O
n-C4H9O


356
CH2═CH—O
CH2═CH


357
CH2═CH—O
E-CH3—CH═CH


358
CH2═CH—O
CH2═CH—O


359
CH2═CH—O
CH2═CH—CH2O





Note:


*values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 360 to 479
The following are prepared analogously to Example 2.2.:
















 














Phase sequence



No.
R1
R2
T/° C.
Δε*





360
CH3
CH3




361
CH3
C2H5


362
CH3
n-C3H7


363
CH3
n-C4H9


364
CH3
n-C5H11


365
CH3
n-C6H13


366
CH3
n-C7H15


367
CH3
CH3O


368
CH3
C2H5O


369
CH3
n-C3H7O


370
CH3
n-C4H9O


371
CH3
CH2═CH


372
CH3
E-CH3—CH═CH


373
CH3
CH2═CH—O


374
CH3
CH2═CH—CH2O


375
C2H5
CH3


376
C2H5
C2H5


377
C2H5
n-C3H7


378
C2H5
n-C4H9


379
C2H5
n-C5H11


380
C2H5
n-C6H13


381
C2H5
n-C7H15


382
C2H5
CH3O


383
C2H5
C2H5O


384
C2H5
n-C3H7O


385
C2H5
n-C4H9O


386
C2H5
CH2═CH


387
C2H5
E-CH3—CH═CH


388
C2H5
CH2═CH—O


389
C2H5
CH2═CH—CH2O


390
n-C3H7
CH3


391
n-C3H7
C2H5


392
n-C3H7
n-C3H7


393
n-C3H7
n-C4H9


394
n-C3H7
n-C5H11


395
n-C3H7
n-C6H13


396
n-C3H7
n-C7H15


397
n-C3H7
CH3O


398
n-C3H7
C2H5O

−12.6


399
n-C3H7
n-C3H7O


400
n-C3H7
n-C4H90


401
n-C3H7
CH2═CH


402
n-C3H7
E-CH3—CH═CH


403
n-C3H7
CH2═CH—O


404
n-C3H7
CH2═CH—CH2O


405
n-C4H9
CH3


406
n-C4H9
C2H5


407
n-C4H9
n-C3H7


408
n-C4H9
n-C4H9


409
n-C4H9
n-C5H11


410
n-C4H9
n-C6H13


411
n-C4H9
n-C7H15


412
n-C4H9
CH3O


413
n-C4H9
C2H5O


414
n-C4H9
n-C3H7O


415
n-C4H9
n-C4H9O


416
n-C4H9
CH2═CH


417
n-C4H9
E-CH3—CH═CH


418
n-C4H9
CH2═CH—O


419
n-C4H9
CH2═CH—CH2O


420
CH3O
CH3


421
CH3O
C2H5


422
CH3O
n-C3H7


423
CH3O
n-C4H9


424
CH3O
n-C5H11


425
CH3O
n-C6H13


426
CH3O
n-C7H15


427
CH3O
CH3O


428
CH3O
C2H5O


429
CH3O
n-C3H7O


430
CH3O
n-C4H9O


431
CH3O
CH2═CH


432
CH3O
E-CH3—CH═CH


453
CH3O
CH2═CH—O


434
CH3O
CH2═CH—CH2O


435
C2H5O
CH3


436
C2H5O
C2H5


437
C2H5O
n-C3H7


438
C2H5O
n-C4H9


439
C2H5O
n-C5H11


440
C2H5O
n-C6H13


441
C2H5O
n-C7H15


442
C2H5O
CH3O


443
C2H5O
C2H5O


444
C2H5O
n-C3H7O


445
C2H5O
n-C4H9O


446
C2H5O
CH2═CH


447
C2H5O
E-CH3—CH═CH


448
C2H5O
CH2═CH—O


449
C2H5O
CH2═CH—CH2O


450
CH2═CH
CH3


451
CH2═CH
C2H5


452
CH2═CH
n-C3H7


453
CH2═CH
n-C4H9


454
CH2═CH
n-C5H11


455
CH2═CH
n-C6H13


456
CH2═CH
n-C7H15


457
CH2═CH
CH3O


458
CH2═CH
C2H5O


459
CH2═CH
n-C3H7O


460
CH2═CH
n-C4H9O


461
CH2═CH
CH2═CH


462
CH2═CH
E-CH3—CH═CH


463
CH2═CH
CH2═CH—O


464
CH2═CH
CH2═CH—CH2O


465
CH2═CH—O
CH3


466
CH2═CH—O
C2H5


467
CH2═CH—O
n-C3H7


468
CH2═CH—O
n-C4H9


469
CH2═CH—O
n-C5H11


470
CH2═CH—O
n-C6H13


471
CH2═CH—O
n-C7H15


472
CH2═CH—O
CH3O


473
CH2═CH—O
C2H5O


474
CH2═CH—O
n-C3H7O


475
CH2═CH—O
n-C4H9O


476
CH2═CH—O
CH2═CH


477
CH2═CH—O
E-CH3—CH═CH


478
CH2═CH—O
CH2═CH—O


479
CH2═CH—O
CH2═CH—CH2O





Note:


*values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 480 to 509
The following are prepared analogously to Example 1.4.:
















 


in which


 








 








 


Z1 denotes a single bond.














Phase sequence



No.
R1
R2
T/° C.
Δε*





480
CH3
CH3




481
CH3
C2H5


482
CH3
n-C3H7


483
C2H5
CH3


484
C2H5
C2H5


485
C2H5
n-C3H7


486
n-C3H7
CH3


487
n-C3H7
C2H5


488
n-C3H7
n-C3H7


489
n-C3H7
n-C5H11


490
n-C5H11
n-C3H7


491
n-C5H11
n-C5H11


492
CH2═CH
CH3


493
CH2═CH
C2H5


494
CH2═CH
n-C3H7


495
CH2═CH
CH2═CH


496
CH3
CH2═CH


497
C2H5
CH2═CH


498
n-C3H7
CH2═CH


499
E-CH3—CH═CH
CH2═CH


500
E-CH3—CH═CH
E-CH3—CH═CH


501
CH3
CH3O


502
CH3
C2H5O


503
CH3
n-C3H7O


504
n-C3H7
CH3O


505
n-C3H7
C2H5O


586
n-C3H7
n-C3H7O


507
CH3O
CH3O


508
C2H5O
C2H5O


509
n-C3H7O
n-C3H7O





Note:


*values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 510 to 539
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





510
CH3
CH3



511
CH3
C2H5


512
CH3
n-C3H7


513
C2H5
CH3


514
C2H5
C2H5


515
C2H5
n-C3H7


516
n-C3H7
CH3


517
n-C3H7
C2H5


518
n-C3H7
n-C3H7


519
n-C3H7
n-C5H11


520
n-C5H11
n-C3H7


521
n-C5H11
n-C5H11


522
CH2═CH
CH3


523
CH2═CH
C2H5


524
CH2═CH
n-C3H7


525
CH2═CH
CH2═CH


526
CH3
CH2═CH


527
C2H5
CH2═CH


528
n-C3H7
CH2═CH


529
E-CH3—CH═CH
CH2═CH


530
E-CH3—CH═CH
E-CH3—CH═CH


531
CH3
CH3O


532
CH3
C2H5O


533
CH3
n-C3H7O


534
n-C3H7
CH3O


535
n-C3H7
C2H5O


536
n-C3H7
n-C3H7O


537
CH3O
CH3O


538
C2H5O
C2H5O


539
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 540 to 569
The following are prepared analogously to Example 2.2.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





540
CH3
CH3



541
CH3
C2H5


542
CH3
n-C3H7


543
C2H5
CH3


544
C2H5
C2H5


545
C2H5
n-C3H7


546
n-C3H7
CH3


547
n-C3H7
C2H5


548
n-C3H7
n-C3H7


549
n-C3H7
n-C5H11


550
n-C5H11
n-C3H7


551
n-C5H11
n-C5H11


552
CH2═CH
CH3


553
CH2═CH
C2H5


554
CH2═CH
n-C3H7


555
CH2═CH
CH2═CH


556
CH3
CH2═CH


557
C2H5
CH2═CH


558
n-C3H7
CH2═CH


559
E-CH3—CH═CH
CH2═CH


560
E-CH3—CH═CH
E-CH3—CH═CH


561
CH3
CH3O


562
CH3
C2H5O


563
CH3
n-C3H7O


564
n-C3H7
CH3O


565
n-C3H7
C2H5O


566
n-C3H7
n-C3H7O


567
CH3O
CH3O


568
C2H5O
C2H5O


569
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 570 to 599
The following are prepared analogously to Example 2.2.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





570
CH3
CH3



571
CH3
C2H5


572
CH3
n-C3H7


573
C2H5
CH3


574
C2H5
C2H5


575
C2H5
n-C3H7


576
n-C3H7
CH3


577
n-C3H7
C2H5


578
n-C3H7
n-C3H7


579
n-C3H7
n-C5H11


580
n-C5H11
n-C3H7


581
n-C5H11
n-C5H11


582
CH2═CH
CH3


583
CH2═CH
C2H5


584
CH2═CH
n-C3H7


585
CH2═CH
CH2═CH


586
CH3
CH2═CH


587
C2H5
CH2═CH


588
n-C3H7
CH2═CH


589
E-CH3—CH═CH
CH2═CH


590
E-CH3—CH═CH
E-CH3—CH═CH


591
CH3
CH3O


592
CH3
C2H5O


593
CH3
n-C3H7O


594
n-C3H7
CH3O


595
n-C3H7
C2H5O


596
n-C3H7
n-C3H7O


597
CH3O
CH3O


598
C2H5O
C2H5O


599
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 600 to 629
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





600
CH3
CH3



601
CH3
C2H5


602
CH3
n-C3H7


603
C2H5
CH3


604
C2H5
C2H5


605
C2H5
n-C3H7


606
n-C3H7
CH3


607
n-C3H7
C2H5


608
n-C3H7
n-C3H7


609
n-C3H7
n-C5H11


610
n-C5H11
n-C3H7


611
n-C5H11
n-C5H11


612
CH2═CH
CH3


613
CH2═CH
C2H5


614
CH2═CH
n-C3H7


615
CH2═CH
CH2═CH


616
CH3
CH2═CH


617
C2H5
CH2═CH


618
n-C3H7
CH2═CH


619
E-CH3-CH═CH
CH2═CH


620
E-CH3-CH═CH
E-CH3-CH═CH


621
CH3
CH3O


622
CH3
C2H5O


623
CH3
n-C3H7O


624
n-C3H7
CH3O


625
n-C3H7
C2H5O


626
n-C3H7
n-C3H7O


627
CH3O
CH3O


628
C2H5O
C2H5O


629
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 630 to 659
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





630
CH3
CH3



631
CH3
C2H5


632
CH3
n-C3H7


633
C2H5
CH3


634
C2H5
C2H5


635
C2H5
n-C3H7


636
n-C3H7
CH3


637
n-C3H7
C2H5


638
n-C3H7
n-C3H7


639
n-C3H7
n-C5H11


640
n-C5H11
n-C3H7


641
n-C5H11
n-C5H11


642
CH2═CH
CH3


643
CH2═CH
C2H5


644
CH2═CH
n-C3H7


645
CH2═CH
CH2═CH


646
CH3
CH2═CH


677
C2H5
CH2═CH


648
n-C3H7
CH2═CH


649
E-CH3—CH═CH
CH2═CH


650
E-CH3—CH═CH
E-CH3—CH═CH


651
CH3
CH3O


652
CH3
C2H5O


653
CH3
n-C3H7O


654
n-C3H7
CH3O


655
n-C3H7
C2H5O


656
n-C3H7
n-C3H7O


657
CH3O
CH3O


658
C2H5O
C2H5O


659
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 660 to 689
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





660
CH3
CH3



661
CH3
C2H5


662
CH3
n-C3H7


663
C2H5
CH3


664
C2H5
C2H5


665
C2H5
n-C3H7


666
n-C3H7
CH3


667
n-C3H7
C2H5


668
n-C3H7
n-C3H7


669
n-C3H7
n-C5H11


670
n-C5H11
n-C3H7


671
n-C5H11
n-C5H11


672
CH2═CH
CH3


673
CH2═CH
C2H5


674
CH2═CH
n-C3H7


675
CH2═CH
CH2═CH


676
CH3
CH2═CH


677
C2H5
CH2═CH


678
n-C3H7
CH2═CH


679
E-CH3—CH═CH
CH2═CH


680
E-CH3—CH═CH
E-CH3—CH═CH


681
CH3
CH3O


682
CH3
C2H5O


683
CH3
n-C3H7O


684
n-C3H7
CH3O


685
n-C3H7
C2H5O


686
n-C3H7
n-C3H7O


687
CH3O
CH3O


688
C2H5O
C2H5O


689
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 690 to 719
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





690
CH3
CH3



691
CH3
C2H5


692
CH3
n-C3H7


693
C2H5
CH3


694
C2H5
C2H5


695
C2H5
n-C3H7


696
n-C3H7
CH3


697
n-C3H7
C2H5


698
n-C3H7
n-C3H7


699
n-C3H7
n-C5H11


700
n-C5H11
n-C3H7


701
n-C5H11
n-C5H11


702
CH2═CH
CH3


703
CH2═CH
C2H5


704
CH2═CH
n-C3H7


705
CH2═CH
CH2═CH


706
CH3
CH2═CH


707
C2H5
CH2═CH


708
n-C3H7
CH2═CH


709
E-CH3—CH═CH
CH2═CH


710
E-CH3—CH═CH
E-CH3—CH═CH


711
CH3
CH3O


712
CH3
C2H5O


713
CH3
n-C3H7O


714
n-C3H7
CH3O


715
n-C3H7
C2H5O


716
n-C3H7
n-C3H7O


717
CH3O
CH3O


718
C2H5O
C2H5O


719
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 720 to 749
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





720
CH3
CH3



721
CH3
C2H5


722
CH3
n-C3H7


723
C2H5
CH3


724
C2H5
C2H5


725
C2H5
n-C3H7


726
n-C3H7
CH3


727
n-C3H7
C2H5


728
n-C3H7
n-C3H7


729
n-C3H7
n-C5H11


730
n-C5H11
n-C3H7


731
n-C5H11
n-C5H11


732
CH2═CH
CH3


733
CH2═CH
C2H5


734
CH2═CH
n-C3H7


735
CH2═CH
CH2═CH


736
CH3
CH2═CH


737
C2H5
CH2═CH


738
n-C3H7
CH2═CH


739
E-CH3—CH═CH
CH2═CH


740
E-CH3—CH═CH
E-CH3—CH═CH


741
CH3
CH3O


742
CH3
C2H5O


743
CH3
n-C3H7O


744
n-C3H7
CH3O


745
n-C3H7
C2H5O


746
n-C3H7
n-C3H7O


747
CH3O
CH3O


748
C2H5O
C2H5O


749
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 750 to 779
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





750
CH3
CH3



751
CH3
C2H5


752
CH3
n-C3H7


753
C2H5
CH3


754
C2H5
C2H5


755
C2H5
n-C3H7


756
n-C3H7
CH3


757
n-C3H7
C2H5


758
n-C3H7
n-C3H7


759
n-C3H7
n-C5H11


760
n-C5H11
n-C3H7


761
n-C5H11
n-C5H11


762
CH2═CH
CH3


763
CH2═CH
C2H5


764
CH2═CH
n-C3H7


765
CH2═CH
CH2═CH


766
CH3
CH2═CH


767
C2H5
CH2═CH


768
n-C3H7
CH2═CH


769
E-CH3—CH═CH
CH2═CH


770
E-CH3—CH═CH
E-CH3—CH═CH


771
CH3
CH3O


772
CH3
C2H5O


773
CH3
n-C3H7O


774
n-C3H7
CH3O


775
n-C3H7
C2H5O


776
n-C3H7
n-C3H7O


777
CH3O
CH3O


778
C2H5O
C2H5O


779
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 780 to 809
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





780
CH3
CH3



781
CH3
C2H5


782
CH3
n-C3H7


783
C2H5
CH3


784
C2H5
C2H5


785
C2H5
n-C3H7


786
n-C3H7
CH3


787
n-C3H7
C2H5


788
n-C3H7
n-C3H7


789
n-C3H7
n-C5H11


790
n-C5H11
n-C3H7


791
n-C5H11
n-C5H11


792
CH2═CH
CH3


793
CH2═CH
C2H5


794
CH2═CH
n-C3H7


795
CH2═CH
CH2═CH


796
CH3
CH2═CH


797
C2H5
CH2═CH


798
n-C3H7
CH2═CH


799
E-CH3—CH═CH
CH2═CH


800
E-CH3—CH═CH
E-CH3—CH═CH


801
CH3
CH3O


802
CH3
C2H5O


803
CH3
n-C3H7O


804
n-C3H7
CH3O


805
n-C3H7
C2H5O


806
n-C3H7
n-C3H7O


807
CH3O
CH3O


808
C2H5O
C2H5O


809
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Examples 810 to 839
The following are prepared analogously to Example 1.4.:
















 








 








 













Phase sequence Δε*


No.
R1
R2
T/° C.





810
CH3
CH3



811
CH3
C2H5


812
CH3
n-C3H7


813
C2H5
CH3


814
C2H5
C2H5


815
C2H5
n-C3H7


816
n-C3H7
CH3


817
n-C3H7
C2H5


818
n-C3H7
n-C3H7


819
n-C3H7
n-C5H11


820
n-C5H11
n-C3H7


821
n-C5H11
n-C5H11


822
CH2═CH
CH3


823
CH2═CH
C2H5


824
CH2═CH
n-C3H7


825
CH2═CH
CH2═CH


826
CH3
CH2═CH


827
C2H5
CH2═CH


828
n-C3H7
CH2═CH


829
E-CH3—CH═CH
CH2═CH


830
E-CH3—CH═CH
E-CH3—CH═CH


831
CH3
CH3O


832
CH3
C2H5O


833
CH3
n-C3H7O


834
n-C3H7
CH3O


835
n-C3H7
C2H5O


836
n-C3H7
n-C3H7O


837
CH3O
CH3O


838
C2H5O
C2H5O


839
n-C3H7O
n-C3H7O





Note:


* values extrapolated from 10% solution in ZLI-4792 or ZLI-2857 (Δε).






Mixture Examples
Liquid-crystalline mixtures are prepared and investigated for their applicational properties.
Example M 1
A liquid-crystal mixture having the composition indicated in the following table was prepared and investigated. It has the properties likewise shown in the table.












Composition









Compound

Conc./


#
Abbreviation
% by wt.












1
CY-3-O4
7


2
CY-5-O2
5


3
CCY-3-O2
7


4
CCY-4-O2
8


5
CCY-3-O3
7


6
CPY-2-O2
9


7
CPY-3-O2
9


8
PYP-2-3
8


9
PYP-2-4
8


10
CC-5-V
9


11
CC-4-V
6


12
CC-3-V1
6


13
CCH-301
6


14
Comp. 398
5


Σ

100.0










Physical properties













T(N,I) =
86° C.



ne (20° C., 589 nm) =
1.6161



Δn (20° C., 589 nm) =
0.1207



ε⊥ (20° C., 1 kHz) =
7.3



Δε (20° C., 1 kHz) =
−4.2










The liquid-crystal medium has very good applicational properties and can be employed for various VA technologies, such as MVA, PVA, ASV and also for IPS.

## Claims

1. A compound of formula I



in which
Y denotes CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or more —CH2—groups, in each case independently of one another, may each be replaced by a —CHF—or —CF2—group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,





—CO—,—CO—O—,—O—CO— or —O—CO—O—in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where
n +m denotes 0, 1, 2 or 3.

2. The compound according to claim 1, of the formulae I-3

3. The compound according to claim 1, wherein L denotes F.

4. The compound according to claim 1, wherein Z1 and Z2 both denote a single bond.

5. A liquid-crystalline medium, comprising one or more compounds of formula I as



in which
Y denotes —CO—, —CS—, —CH2— or —CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3 —CHF2 —CH2F —OCF3 —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,





—CO—, —CO—O—, —O—CO—or —O13 CO—O—in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where n +m denotes 0, 1, 2 or 3.

6. A liquid-crystalline medium, comprising a nematic phase and having one or more compounds of formula I as defined in claim 5.

7. The liquid-crystalline medium according to claim 5, comprising
one or more dielectrically negative compound(s) of formula II




in which
R21 and R22 each, independently of one another, have the meaning given for R1 in the case of formula I,
Z21 and Z22 each, independently of one another, have the meaning given for Z1 in the case of formula I,





each, independently of one another, denote





L1 and L2 both denote C—F or one of the two denotes N and the other denotes C—F, and 1 denotes 0 or 1.

8. The liquid-crystalline medium according to claim 7, comprising one or more compound(s) of formula II-1




in which R21, R22, Z12, Z22,




and 1 have the meaning given in claim 7.

9. An electro-optical display comprising a liquid-crystal medium according to claim 5.

10. The display according to claim 9, which is a VAN LCD.

11. A method for the inhibition of cannabinoid receptor, comprising administering to a host in need thereof an effective amount of a compound



in which
Y denotes —CO—, —CS—, —CH2— or —CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4- tetrahydronaphthalene -2,6-diyl,
1,4-bicyclo[2.2.21]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3,—CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,





—CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2——CH2—,—CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where
n +m denotes 0, 1, 2 or 3. or a salt or solvate thereof.

12. A pharmaceutical composition, comprising at least one compound of formula I according to claim 1 and/or a physiologically acceptable salt or solvate thereof.

13. A method for the treatment or prophylaxis of diseases or symptoms which can be influenced by inhibition of cannabinoid receptors comprising administering a compound of formula I



in which
Y denotes —CO—, —CS—, —CH2— or —CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4- tetrahydronaphthalene -2,6-diyl,
1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2 , —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,





—CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where
n +m denotes 0, 1, 2 or 3. and/or a physiologically acceptable salt or solvate thereof.

14. A method of claim 13 comprising treatment or prophylaxis of psychoses, anxiety disorders, depression, aprosexia, memory disorders, cognitive disorders, loss of appetite, obesity, addiction, drug dependence and neurological disorders, such as neurodegenerative processes, dementia, dystonia, muscle spasms, tremor, epilepsy, multiple sclerosis, traumatic brain injuries, strokes, Parkinson's, Alzheimer's, Huntington's disease, Tourette's syndrome, cerebral ischaemia, cerebral apoplexy, craniocerebral trauma, spinal cord injuries, neuroinflammatory diseases, cerebral arteriosclerosis, viral encephalitis, diseases associated with demyelination, for the treatment of pain, neuropathic pain diseases, diseases in which cannabinoid neurotransmission plays a role, septic shock, glaucoma, cancer, diabetes, vomiting, nausea, asthma, respiratory tract diseases, gastrointestinal diseases, gastric ulcers, diarrhoea or cardiovascular diseases.

15. A compound according to claim 1, wherein




is

16. A method for the treatment or prophylaxis of diseases or symptoms which can be influenced by inhibition of cannabinoid receptors comprising administering a compound of formula I



in which
Y denotes —CO—, —CS—, —CH2— or —CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, and one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—,





—CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —COO—, —O—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where
n +m denotes 0, 1, 2 or 3.

17. A method for the treatment or prophylaxis of psychoses, anxiety disorders, depression, aprosexia, memory disorders, cognitive disorders, loss of appetite, obesity, addiction, drug dependence and neurological disorders, such as neurodegenerative processes, dementia, dystonia, muscle spasms, tremor, epilepsy, multiple sclerosis, traumatic brain injuries, strokes, Parkinson's, Alzheimer's, Huntington's disease, Tourette's syndrome, cerebral ischaemia, cerebral apoplexy, craniocerebral trauma, spinal cord injuries, neuroinflammatory diseases, cerebral arteriosclerosis, viral encephalitis, diseases associated with demyelination, for the treatment of pain, neuropathic pain diseases, diseases in which cannabinoid neurotransmission plays a role, septic shock, glaucoma, cancer, diabetes, vomiting, nausea, asthma, respiratory tract diseases, gastrointestinal diseases, gastric ulcers, diar-rhoea or cardiovascular diseases, comprising administering to a host in need thereof a compound of formula I and



in which
Y denotes —CO—, —CS—, —CH2— or —CF2—,
L denotes H, halogen or —CF3,





each, independently of one another and, if present more than once, also these independently of one another, denote a trans-1,4-cyclohexylene radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, a 1,4-cyclohexenylene radical,
a 1,4-phenylene radical, in which, in addition, one or two non-adjacent CH groups may be replaced by N, or
naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetrahydronaphthalene-2,6-diyl,
1,4-bicyclo[2.2.2]octylene, 1,3-bicyclo[1.1.1]pentylene or spiro-[3.3]heptane-2,6-diyl,
wherein
(a) and (b), one or more —CH2— groups, independently of one another, may each be replaced by a —CHF— or —CF2— group, and in
(c) and (d), one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group,





denotes a 1,4-trans-cyclohexane-1,2,4-triyl radical, in which, in addition, one or two non-adjacent CH2 groups may be replaced by —O— and/or —S—, and one or more —CH2— groups, in each case independently of one another, may each be replaced by a —CHF— or —CF2— group, and the —CH< group may be replaced by a —CF< group, and which may optionally contain one or two C—C double bonds, where, in this case, one or more —CH═ groups, independently of one another, may each be replaced by a —CF═, —C(CN)═, —C(CH3)═, —C(CH2F)═, —C(CHF2)═, —C(O—CH3)═, —C(O—CHF2)═ or —C(O—CF3)═ group, preferably a —CF═ group,
R1 and R2 each, independently of one another, denote H, halogen, —CN, —SCN, —SF5, —CF3, —CHF2, —CH2F, —OCF3, —OCHF2, an alkyl group having 1 to 15 C atoms which is monosubstituted by CN or CF3 or at least monosubstituted by halogen, where, in addition, one or more CH2 groups, in each case independently of one another, may be replaced by —O—, —S—, —CH═CH—, —C0F═CF—, —CF═CH—, —CH═CF—,





—CO—, —CO—O—, —O—CO— or —O—CO—O— in such a way that neither O nor S atoms are linked directly to one another,
Z1 and Z2 each, independently of one another, denote —CH2—CH2—, —CF2—CF2—, —CF2—CH2—, —CH2—CF2—, —CH═CH—, —CF═CF—, —CF═CH—, —CH═CF—, —C≡C—, —COO—, —OCO—, —CH2O—, —OCH2—, —CF2O—, —OCF2—, or a combination of two of these groups, where no two O atoms are bonded to one another, and
n and m each denote 0, 1 or 2, where
n +m denotes 0, 1, 2 or 3.