Benzochromene derivatives

Abstract

The present invention relates to benzochromene derivatives of the formula I

Description

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 bondand 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 S_A 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 optionallyc) 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 whichR²¹, 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 C_7-1E-alkenyl, C₄- to C_7-3E-alkenyl, C₅- to C_7-4-alkenyl, C₆- to C_7-5-alkenyl and C_7-6-alkenyl, in particular C₂- to C_7-1 E-alkenyl, C₄- to C_7-3E-alkenyl and C₅- to C_7-4-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 C_nH_2n+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 C_nH_2n+1 and C_mH_2m+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.

T_g=−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

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

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

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

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

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

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

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

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