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WO2006125530A1 - Derives de tetrahydropyranne pourvus de plusieurs cycles contenant de l'oxygene et procede de production desdits derives - Google Patents

Derives de tetrahydropyranne pourvus de plusieurs cycles contenant de l'oxygene et procede de production desdits derives Download PDF

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Publication number
WO2006125530A1
WO2006125530A1 PCT/EP2006/004425 EP2006004425W WO2006125530A1 WO 2006125530 A1 WO2006125530 A1 WO 2006125530A1 EP 2006004425 W EP2006004425 W EP 2006004425W WO 2006125530 A1 WO2006125530 A1 WO 2006125530A1
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formula
compounds
aldehyde
ocf
ring
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PCT/EP2006/004425
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German (de)
English (en)
Inventor
Eike Poetsch
Lars Lietzau
Volker Meyer
Werner Binder
Kai Jaehrling
Melanie Klasen-Memmer
Atsutaka Manabe
Michael Wittek
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Merck Patent Gmbh
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Priority to CN2006800179759A priority Critical patent/CN101180295B/zh
Priority to JP2008512723A priority patent/JP5484724B2/ja
Priority to KR1020077030219A priority patent/KR101311569B1/ko
Priority to DE112006000955T priority patent/DE112006000955A5/de
Publication of WO2006125530A1 publication Critical patent/WO2006125530A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D309/06—Radicals substituted by oxygen atoms

Definitions

  • the invention relates to processes for the preparation of tetrahydropyran derivatives with at least one further oxygen-containing ring.
  • compounds are prepared with two tetrahydropyran rings or with at least one tetrahydropyran ring and one dioxane ring each. Condensations with aldehydes and / or ring-closing reactions are used.
  • the preparation processes give rise to novel tetrahydropyran compounds having at least two O-heterocyclic rings.
  • Liquid-crystalline substances often have 1, 4-substituted cyclohexane rings within a rod-shaped structure. If these cyclohexane rings are replaced by arbitrarily oriented 2,5-substituted tetrahydropyran units, then, depending on the orientation of the electronegative oxygen atom, advantageous changes in the overall physical properties of the molecule can result. In particular, an increase in the anisotropy of the electrical constants ( ⁇ ) can be achieved, both for positive ( ⁇ > 0) and for negative dielectric compounds ( ⁇ ⁇ 0). Examples of positive values of ⁇ are disclosed in EP 1482019 A1, likewise one finds an amplification of negative ⁇ values in
  • Amplification of the positive ⁇ is e.g. For use in IPS-type liquid crystal displays (IPS 4 in pjain switching), amplification of the negative ⁇ in VA-type (VA) liquid-crystal displays is advantageous.
  • B stands for or stands a, b, c, d, e, f are independently 0 or 1, where a + b
  • + c + d + e + f is 1, 2, 3, 4, 5 or 6 and c + d is not 0;
  • a 1 , A 2 , A 3 , A 4 , A 5 , A 6 are independently, the same or different, also rotated or mirrored, for
  • a 6 is C or B; in which
  • Y 1, Y 2 and Y 3 are independently H, halogen, CN, Ci- 6 alkanyl, C 2 - 6 - alkenyl, C 2 - 6 alkynyl, -OCR 6 alkanyl, -OC 2 - 6 alkenyl, and -OC 2 - 6 alkynyl, wherein the aliphatic radicals are unsubstituted or mono- or polysubstituted by halogen;
  • W 1 is -CH 2 -, -CF 2 - or -O-;
  • a main aspect of the invention are simple processes for the preparation of the compounds of the formula I.
  • the processes according to the invention are summarized in Scheme 1 and are described in detail below.
  • MES ' R 2 - (A 6 - Z 6 ), - (A 5 -Z 5 ) e - (A 4 -Z 4 ) d -, wherein Z 1'6 , A 1 "6 , af, R 1 and R 2 are as defined for formula I.
  • MES and MES ' may also represent a group of molecules that can be derivatized in a few reaction steps to a final structure, that is to say a synthetic precursor to the desired end compounds, for example, MES can be a 1, 3-diol group as a precursor for the production of a At least one of the molecular moieties MES and MES 'contains a further O-heterocyclic ring (1,3-dioxane-2,5-diyl, tetrahydropyran-2,5-diyl), so that a total of at least one pyran ring
  • the reactions in Scheme 1 lead either directly or via intermediates from the educts to the product of formula I. Die Ring-closing metathesis is z. B. usually followed by a catalytic hydrogenation of the resulting double bond in the resulting dihydropyran ring.
  • X 1 is chlorine, bromine or iodine
  • R -> 3 3 u. , n_d, JR n 4 4 is a protecting group for alcohols
  • variants a) to e) of the process according to the invention have in common that they open up a simple and variably substitutable access to tetrahydropyran compounds having a plurality of O-heterocyclic rings.
  • Formula I are particularly characterized by a) that a diol of the formula II and an aldehyde of the formula
  • X 1 is chlorine, bromine or iodine
  • R 3 and R 4 is a protecting group for alcohols
  • R 1 , R 2 , B, A 1 -A 6 , af and Z 1 -Z 6 have the meanings given for I.
  • B in aldehyde compounds of the formula III is a group of the formula
  • oxygen-containing rings and O-heterocycles particularly pyran and dioxane rings are addressed, especially the 2,5-substituted pyran derivatives (B) and the 2,5-substituted 1,3-dioxane derivatives (C).
  • Preferred are the saturated variants, ie tetrahydropyrans and 1, 3-dioxanes, and the monounsaturated dihydropyrans.
  • the heterocycles are unsubstituted except in the 2,5-position or carry one to two halogen substituents.
  • the compounds of the formula I which emerge from a process according to the invention contain at least one pyran ring.
  • the compounds of the formula I also contain at least one further O-heterocyclic ring within the defined ring positions A 1 -A 6 . From methods according to variant a), compounds are apparent which a Include dioxane next to a pyran ring in a predetermined orientation to each other. According to the other process variants b) -e), further chain members Z and A can also be present between the O-heterocycles.
  • a bond between two O-heterocycles is a bond, an ethylene bridge, a vinylene bridge, a cyclohexane-1, 4-diyl ring, a 1, 3-cyclobutane-1, 3-diyl ring or a spiro [3.3] heptane-2 , 6-diyl ring.
  • a bond or an ethylene bridge between the rings most preferably a single bond.
  • compounds of the formula I are prepared via a condensation reaction of an aldehyde group with a 1, 3-propane-diol compound which, as shown in Scheme 2, is substituted in position 2.
  • the aldehyde function depends directly or via a link Z 3 on a tetrahydropyran ring B.
  • the position of the oxygen atom in the tetrahydropyran ring can vary by the choice of suitable aldehyde compounds.
  • the acid used is preferably a sulfonic acid, more preferably p-toluenesulfonic acid or trifluoromethanesulfonic acid.
  • the resulting water by azeotropic distillation from the
  • Preferred methods for forming dioxanes are also Lewis acid catalyzed variants of acetal formation.
  • Particular preference is also given to particularly mild processes with the aid of catalytic amounts of ruthenium or indium halides, in particular RuCl 3 and InCl 3 (cf Literature: BC Janu et al., Adv. Synth. Catal. (2004), 346, 446-50 J.-Y.Qi et al., Tetr. Lett. (2004), 45, 7719-21; SK De, RA Gibbs, Tetr. Lett. (2004), 45, 8141-4).
  • the mild reaction conditions are particularly suitable for compounds with structural parts of the ether type and for acid-sensitive groups.
  • compounds of the formula I are obtained by a ring-closing metathesis on diene compounds, so that, as explained in Scheme 3, a new pyran ring is formed as ring B.
  • dienes By appropriate choice of dienes, pyran rings with different oxygen atom position in the ring can generally be generated.
  • the resulting after the ring closure unsaturated dihydropyrans are converted into the saturated tetrahydropyrans, z. B. by catalytic hydrogenation.
  • the hydrogenation is achieved by literature methods on suitable homogeneous or heterogeneous metal catalysts, in particular on transition metal catalysts.
  • the dienes required as starting material for the ring-closing metathesis are preferably prepared by the process shown in Scheme 3a.
  • At least one further tetrahydropyran or dioxane ring is in Scheme 3a in the formulas instead of the rings A 1 -A 6 , preferably at the site of A 3 and / or A 4 .
  • the compounds Ib represented by this embodiment have at least two tetrahydropyran rings.
  • an allyl halide and a homoallyl alcohol according to the formulas XIV or XV are connected by an ether bond.
  • the etherification takes place in principle by literature methods for the formation of dialkyl ethers.
  • the possibilities for the preparation of the allyl halides XIV and the etherification are described in principle in EP 1482018 A1 in particular and are hereby disclosed by way of example.
  • the illustration of homoallylic alcohols XV will be described later.
  • a 3 represents the tetrahydropyran ring
  • the following synthesis is preferred for allyl halides of formula XIV wherein X 2 is a halogen or a substituent -OSO 2 CF 3 (Scheme 3b).
  • compounds of the formula I are prepared by forming a pyran ring from a homoallyl alcohol and an aldehyde. At least one further tetrahydropyran or dioxane ring is present in Scheme 5 in the formulas in place of the rings A 1 -A 6 , preferably at the site of A 3 and / or A 4 . In this embodiment of the process, at least one of the reactive groups preferably hangs on another tetrahydropyran ring B, on a dioxane ring or on a molecule group which serves to form an O-heterocyclic ring.
  • Such a group may particularly be a 1, 3-diol for the construction of dioxanes, a homoallyl alcohol for the construction of (hydro) pyran rings or they may be derivatives of these groups bearing protecting groups on the OH functions.
  • Preferred protecting groups are benzyl ethers, acetals, acyl derivatives or silyl groups.
  • the reactants are a formyl tetrahydropyran and a substituted homoallyl alcohol.
  • the reaction of the aldehyde with the homoallyl alcohol is carried out with the aid of a halogen-containing acid, preferably a halogenated Lewis acid, in an organic solvent such. For example, dichloromethane.
  • a similar reaction of an aldehyde with an alkenol is described in JO Metzger et al. and the references cited therein (Bull. Soc. Chem. BeIg. (1994), 103, 393-7).
  • the process can be carried out in the presence of a Lewis acid of the formulas M (X 1 ) n or R 5 M (X 1 ) n -i, where
  • M is B, Al, In, Sn, Ti, Fe, Zn, Zr, Au or Bi;
  • X 1 represents Cl, Br or I
  • R 5 represents a straight-chain or branched alkyl radical having 1 to 10 carbon atoms; and n is an integer 2, 3 or 4 and is selected to be equal to the formal oxidation number of M.
  • Lewis acids for reactions according to the invention are halides of the elements boron, aluminum, iron, zinc or bismuth. Especially suitable for. AICI 3 or BiBr 3 .
  • Lewis acid and Bronsted acids such as hydrogen bromide (HBr) can be used.
  • the intermediate of formula VIII is reacted (in situ or after isolation) either by elimination to the dihydropyran of formula IX or reacted directly by a reductive elimination to the final product of formula I (or here Id).
  • the elimination of the halide substituent X 1 can be effected by base action. Preference is given to using strong, nonionic Nitrogen bases, such as.
  • the most preferred commercially available bases such as 1, 5-diazabicyclo [4.3.0] non-5-ene (DBN), 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU) or 1, 1 , 3,3-Tetramethylguanidine, which are heated together with the Bromtetrahydropyranen in bulk or in a solvent for 2 to 6 hours.
  • Preferred solvents for this are, for. As toluene or dioxane.
  • the intermediate of the formula IX is hydrogenated to the product of the formula Id by literature methods, preferably with a catalyst in the form of a transition metal complex of the metals rhodium, ruthenium or iridium with at least one phosphorus ligand, more preferably with a rhodium-phosphine complex such as [Rh (Rh). PPh 3 ) 3 CI] or a corresponding mixture of a commercially available rhodium complex precursor with a phosphine ligand.
  • a catalyst in the form of a transition metal complex of the metals rhodium, ruthenium or iridium with at least one phosphorus ligand more preferably with a rhodium-phosphine complex such as [Rh (Rh). PPh 3 ) 3 CI] or a corresponding mixture of a commercially available rhodium complex precursor with a phosphine ligand.
  • the reductive elimination of VIII to Id via a radical chain reaction in the course - formally abstracted - the halogen atom X 1 is abstracted in the tetrahydropyran derivative of the formula VIII and replaced by a hydrogen atom. It is particularly preferred that X 1 in the reacted compound of the formula II is bromine or chlorine, in particular bromine.
  • this variant of the reductive elimination is carried out in the presence of an organotin hydride or an organosilicon hydride.
  • organotin hydrides are trialkyl and dialkyl tin hydrides Monoaralkyl, most preferably trialkyltin hydrides, in particular tri-n-butyltin hydride (BU ß SnH).
  • BU ß SnH tri-n-butyltin hydride
  • 1 to 10 equivalents and preferably 2 to 4 equivalents of the tin hydride, based on the compound of formula II to be reduced, are used.
  • organotin hydrides bound to solid, preferably solid, organic carriers is preferred;
  • the solid support-bound organotin hydride is usually used in amounts of from 2 to 4 equivalents based on the compound of formula II.
  • Preferred organosilicon hydrides are substituted silanes, particularly preferably tris (trialkylsilyl) silanes, in particular tris (trimethylsilyl) silane (TTMSS) (see, for example, M. Ballestri et al., J. Org. Chem. 1991, 56, 678-683).
  • the organosilicon hydride is usually used in an amount of 1 to 3 equivalents, preferably 1, 1 to 1, 5 equivalents, based on the compound of formula II to be reduced.
  • a further reducing agent such as a complex metal hydride, for.
  • Sodium borohydride, NaBH 4 see, for example, M.
  • This preferred variant of the reductive elimination using an organotin hydride or an organosilicon hydride is usually carried out in the presence of at least one free-radical chain initiator ("radical initiator") such as a suitable azo or peroxy compound, for example AIBN (2,2'-azobisisobutyronitrile) or tert. Butyl hydroperoxide in the presence of UV light.
  • radical initiator such as a suitable azo or peroxy compound, for example AIBN (2,2'-azobisisobutyronitrile) or tert.
  • Butyl hydroperoxide in the presence of UV light.
  • the radical initiator is used in amounts customary for this type of reaction, preferably in one Amount of 1 to 20 mol%.
  • the reaction can also be initiated by the action of UV radiation.
  • the invention relates to hydrocarbons such as heptane, benzene, xylenes and ethers such as dimethoxyethane or methoxyethanol.
  • the reaction is usually carried out at 20 to 140 0 C.
  • the reaction time is usually 2 to 24 h.
  • X 1 in formula VIII is bromine and the reaction with hydrogen takes place in the presence of a hydrogenation catalyst and an amine.
  • the hydrogenation catalyst is a homogeneous catalyst (eg, a Pd (O) or Pd (II) or a Ni (O) or Ni (II) complex with alkyl- and / or aryl-substituted phosphine or phosphite ligands ) or preferably a heterogeneous transition metal catalyst.
  • the hydrogenation catalyst is particularly preferably a heterogeneous palladium or nickel catalyst, in particular palladium-on-carbon or palladium on aluminum oxide.
  • the amine is preferably a trialkylamine, more preferably diisopropylethylamine or triethylamine, especially triethylamine.
  • a fifth embodiment of the preparation process of compounds of the formula II is carried out according to Scheme 6 from a 2-substituted homoallyl alcohol of the formula VI and an aldehyde of the formula X which contains as a substitution of a 1, 3-diol synthon.
  • R 3 and R 4 are protective groups for the diol. Suitable protecting groups are known from the literature
  • Protecting groups of the type of selectively cleavable ethers or esters preferably benzyl ethers and trialkylsilyl ethers (eg trimethylsilyl ether). After deprotection, the two OH groups serve to form a dioxane ring by condensation with another aldehyde OHC- (Z 5 -A 5 ) e - (Z 6 -A 6 ) f -R 2 .
  • the formation of the pyran ring proceeds analogously to the reaction in Scheme 5. The reaction conditions given for this can be transferred to this embodiment.
  • preparation process for compounds of formula I 1 which are characterized by reacting compounds of formula VI with aldehydes of the formula VII or X in the presence of at least one (Lewis) acid containing at least one halide of the series I, Br or Cl.
  • the reaction regime under the action of a Lewis acid such as BiBr 3 is particularly preferred.
  • the halogenated tetrahydropyran derivative can be further reacted by various means as described above for compounds of formula VIII.
  • a preferred variant is the elimination of hydrogen halide under the action of a base.
  • a preferred method is the treatment of the 4-bromo-tetrahydropyran derivatives with DBN to give a compound of formula XI.
  • Compound XI leads to the corresponding tetrahydropyran derivatives.
  • the hydrogenation is carried out by literature methods of catalytic hydrogenation, eg. Example by means of hydrogenation of rhodium (l) complexes such as rhodium (l) tristriphenylphosphinchlorid.
  • Another preferred method is the reductive elimination of the group X 1 by hydrogenation in the presence of a base, such as thethylamine, on a transition metal catalyst.
  • X 1 is a bromine.
  • the deprotection of the OH groups is again carried out by hydrogenation, following or combined with the preceding hydrogenation of the double bond.
  • Preferred for the hydrogenation of the double bond are rhodium catalysts, especially rhodium phosphine catalysts.
  • Preferred for the deprotection of the benzyl ethers are supported noble metal catalysts, in particular palladium or platinum on carbon or on inert metal oxides, very particularly preferably palladium on carbon.
  • the further derivatization of the compounds of the formula XI toward the End products of the formula Ie is carried out by at least one further condensation of the diol with an aldehyde compound which carries the remaining moiety - [Z 5 -A 5 ] e - [Z 6 -A 6 ] rR 2 in a manner analogous to the condensation of compounds of the Formula II with compounds of formula III.
  • the sequence of the method steps described can in principle also be meaningfully changed in order to arrive at the same product Ie.
  • the preceding embodiments of the preparation of compounds of the formula I can also be used for the preparation of particularly suitable compounds with negative or reduced Use ⁇ , in which the heterocyclic pyran moiety makes a (negative) contribution to the dielectric anisotropy.
  • the particularly suitable compounds are characterized by a left-side oriented tetrahydropyran ring, based on the representation in Schemes 3a, 4, 5 and 6.
  • the particularly suitable compounds with negative or reduced ⁇ can be achieved by interchanging the radicals R 1 and R 2 and by reversing the numbering of 1 to 6 of the structural members Z 'and A'; that is, the index number 6 becomes 1, 5 to 2, 4 to 3, and conversely, the index numbers 1 to 6, 2 to 5 and 3 to 4.
  • the thus constituted embodiments of the partially mirrored structures of the formula correspond approximately to the right part of Schemes 1.
  • the preparation of the required allyl alcohols can also be formulated and carried out by a similar modification of Schemes 7, 8 and 9.
  • Preferred embodiments of the said production processes according to the variants a) to e) include processes for the preparation of compounds of the formula I, which are characterized in that
  • a 3 stands for or B.
  • Particularly preferred embodiments of the said production processes include processes for the preparation of compounds of the formula I, which are characterized in that, in the formula I, the central part of the molecule
  • Q is a single bond, -CF 2 O- or -OCF 2 -,
  • L 1 , L 2 , L 3 , L 4 are independently, the same or different, H or F, a, m, n is 0 or 1,
  • B 1 , B 2 are independently, same or different, B or 1,3-dioxane-2,5-diyl, so that at least B 1 or B 2 is B, and
  • alkyl is as defined below.
  • Alkyl in the formulas a to F preferably denotes a straight-chain alkoxy, alkanyl or alkenyl radical having up to 8 C atoms.
  • alkyl unless otherwise defined in this specification or the claims, means in its most general meaning a straight-chain or branched, saturated or unsaturated one aliphatic hydrocarbon radical containing from 1 to 15 (ie 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms; this radical is unsubstituted or monosubstituted or polysubstituted by fluorine, chlorine, bromine, iodine, carboxy, nitro, NH 2 , N (alkanyl) 2 and / or cyano, the multiple substitution being carried out with the same or different substituents can.
  • the alkyl radical in the aliphatic hydrocarbon chain itself may be functionalized.
  • alkyl is a straight-chain or branched, unsubstituted or substituted alkanyl, alkenyl or alkoxy radical having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms.
  • alkyl is an alkanyl radical, this is preferably methyl, ethyl, n-propyl, i-propyl, n-butyl, isobutyl, t-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl , CF 3 , CHF 2 , CH 2 F or CF 2 CF 3 .
  • the alkanyl radical is particularly preferably straight-chain and unsubstituted or substituted by F.
  • alkyl also includes "alkoxy" or "oxaalkyl” radicals.
  • alkoxy is meant an O-alkyl radical in which the oxygen atom is bonded directly to the group or substituted ring substituted by the alkoxy radical and alkyl is as defined above; preferably, alkyl is then alkanyl or alkenyl.
  • Preferred alkoxy radicals are methoxy, ethoxy, propoxy, butoxy, pentoxy, hexoxy, heptoxy and octoxy, where each of these radicals may also be substituted, and preferably with one or more fluorine atoms.
  • Alkoxy is particularly preferably OCH 3 , OC 2 H 5 , OnC 3 H 7 , OnC 4 H 9 , OtC 4 H 9 , OCF 3 , OCHF 2 , OCH 2 F or OCHFCHF 2 .
  • oxaalkyl means alkyl radicals in which at least one non-terminal CH 2 group has been replaced by -O- such that there are no adjacent heteroatoms (O, S).
  • oxaalkyl includes straight-chain radicals of the formula C a H 2a + rO- (CH 2 ) b - wherein a and b are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10; more preferably a is an integer from 1 to 6 and b is 1 or 2.
  • the homoallylic alcohols of the formulas VI and XV are either known in the art, are commercially available or can be readily prepared by synthesis methods which are known per se from the literature.
  • Scheme 7 represents the synthesis of a 1-substituted homoallylic alcohol from aldehydes.
  • an AIIyI Grignard reagent is reacted with an aldehyde.
  • the aldehydes are again known compounds, can be prepared by standard methods or can be obtained by a method similar to those in the Examples.
  • halide XX is - according to the procedure in Scheme 8 - transferred with a suitable reagent in the organometallic derivative of formula XXI, which is then reacted with a compound of formula XXII to Homoallylacetat of formula XXIII. From XXIII then the desired homoallyl alcohol of the formula III is obtainable by saponification.
  • homoallylic alcohols of the formula III in which R 1 - [A 1 -Z 1 ] a - [A 2 -Z 2 ] b - is an alkyl radical are also prepared by appropriate alkylation with an alkyl halide R 1 - [A 1 -Z 1 ] a - [A 2 -Z 2 ] b -Hal the dianion of crotonic acid and subsequent reduction with LiAlH 4 accessible.
  • This dianion is from crotonic acid z. B. obtained by reaction with 2 equivalents of lithium diisopropylamide (LDA) (see, PE Pepper, LS Silbert, J. Org. Chem. 36 (1971), 3290; RH van der Veen, H. Cerfountain, J. Org. Chem. 50 (1985), 342).
  • LDA lithium diisopropylamide
  • Another major aspect of the present invention are compounds obtainable by the methods of the invention.
  • compounds in addition to a tetrahydropyran ring, compounds have at least one further O-heterocyclic ring.
  • the proper combination of multiple O-heterocyclic rings can produce compounds with improved properties, particularly with high absolute values of dielectric anisotropies, while maintaining other critical values such as viscosity, solubility in liquid crystalline mixtures, and optical anisotropy.
  • the substances can be produced easily and on an industrial scale by the synthesis routes shown, which additionally increases their value in practice in addition to the excellent physical properties.
  • the common methodology of the synthesis does not necessarily require use in only one type of liquid crystal displays. On the contrary, depending on the characteristics of their dipolar properties (eg the value of ⁇ ), the compounds according to the invention can be used in very different types of liquid crystal display devices (IPS, VA, TN, STN, etc.)
  • R 1 , A 1 , A 4 , A 5 , Z 1 , Z 4 , a, e are as defined in formula I,
  • Z 6 is -CF 2 O-, -OCF 2 -, -CF 2 CF 2 -, -CH 2 CH 2 CF 2 O-,
  • X 1 is F, CN 1 SF 5 , NCS, OCF 3 , CF 3 ,
  • L 1 , L 2 are H, Cl or F, and p is O or 1.
  • Preferred compounds of formulas XXVI, XXVII and XXVIII are characterized in that L 1 is F and L 2 is H or F; L 1 and L 2 are particularly preferably F.
  • Particularly preferred compounds according to the invention are the compounds of the following formulas C and D.
  • stereoisomers unless specific spatially emphasized binding forms are specified.
  • the formulas generally stand for all stereoisomers, in any desired mixture or as pure substances. Particularly preferred are the equatorial, all-transient stereoisomers which, when linked together, give a molecular structure which is as linear as possible. Even with chiral compounds, both enantiomers are generally addressed in any mixture or as pure substance.
  • ⁇ n and ⁇ values of the compounds according to the invention are obtained by extrapolation from liquid-crystalline mixtures which consist of 10% of the particular compound according to the invention and 90% of the commercially available liquid crystal ZLI 4792 (Merck, Darmstadt). The following abbreviations are used above and below:
  • Tetrahydrofuran with 1, 8 ml of 20% aqueous sodium hydroxide solution and stirred at room temperature for one hour. It is then neutralized with hydrochloric acid and the solution is concentrated to the residue. The evaporation residue is mixed with 1 l MTB ether and washed twice with 300 ml of water. After drying, the organic extract is evaporated, yielding 33 g of an 88% aldehyde mixture which, in addition to the trans-5-formyltetrahydropyran (3), still contains some 4-formyltetrahydropyran.
  • 0.2 mol (48.8 g) (3) are dissolved in 200 ml of tetrahydrofuran and mixed between 15 to 25 0 C with 100 ml of 2-molar allyl magnesium chloride solution in tetrahydrofuran within 30 min dropwise. After completion of the addition is stirred for 2 h at RT, then poured into 200 ml of 0.5 N hydrochloric acid, the organic phase separated and the aqueous phase extracted twice with MTB ether. The combined organic extracts are washed with water, dried and evaporated. The evaporation residue is filtered through silica gel with toluene / ethyl acetate (98: 2 to 9: 1).
  • the filtrates give 38.7 g (67.6% of theory) of an isomer mixture of Homoallylalkohole (5).
  • 0.135 mole (38.7 g) of (5) and 0.135 mole (16.1 g) of propargyl bromide are dissolved in 80 ml of tetrahydrofuran and made into a vigorously stirred emulsion of sodium hydroxide pellets (0.27 mole, 10.8 g), 0.5 ml of water, 40 ml of tetrahydrofuran and 6.75 mmol (2.46 g) of N-cetyl-NNN-trimethyl ammonium bromide, heated to 45 ° C and 16 h in this
  • 0.2 g (7) are hydrogenated in 5 ml of methanol and 1 ml of toluene with 0.1 g of tris (triphenylphosphine) rhodium (l) chloride at 10 bar hydrogen pressure and 90 0 C for 6 h. After cooling, the reaction mixture is evaporated in vacuo and filtered through silica gel with toluene / heptane (3: 7). After evaporation, 0.15 g (8) of oil is obtained.
  • Compound (9) is prepared from the corresponding homoallylic alcohol precursor by O-alkylation with ethyl 2- (bromomethyl) acrylate.
  • 0.2 mol (8.0 g) of sodium hydride are added dropwise as a 60% suspension in 80 ml of tetrahydrofuran with stirring and external cooling with ice water with 0.2 mol (76.1 g) Homoallylalkohol in 80 ml of tetrahydrofuran under a nitrogen blanket, wherein the temperature is maintained at 20 0 C. After about two hours, the hydrogen evolution is completed.
  • Dihydropyranester (10) are hydrogenated in 300 ml of methanol and 60 ml of toluene at 10 bar hydrogen pressure and 100 ° C for 12 h with 2 g of tris (triphenylphosphine) rhodium (l) chloride.
  • the aldehyde (12) is then reacted with 2-ethyl-1, 3-propanediol to dioxane (4c). To this are dissolved 44.5 g (110 mmol) of the aldehyde (12) and 12.0 g (115 mmol) of the diol 2-ethyl-1,3-propanediol in 250 ml of toluene, 400 mg of p-toluenesulfonic acid monohydrate and until for complete conversion of the aldehyde (DC) on a water under
  • the dihydropyran (32) generated by metathesis is converted by analogy to Example 1 by hydroformylation to the aldehyde (33) and first reacted with the homoallylic alcohol (34) in an ene-carbonyl reaction to the bromotetrahydropyran (35).
  • the homoallylic alcohol is synthesized via the acetate of the zinc alcohol (38) which can be prepared by conventional methods by reaction with gaseous formaldehyde in the presence of zinc dust and CoBr 2 .
  • the hydrogenation of the isomer mixture (36) (15.7 g) is carried out by dissolving in 300 ml of methanol and 75 ml of toluene and 20 hours of hydrogenation at 10 bar, 90 ° C by means of 0.48 mmol (448 mg) of tris (triphenylphosphine) rhodium (I) chloride as a catalyst. After evaporation of the solvent, the residue is filtered through silica gel with toluene. Multiple fractionated crystallizations from ethanol and heptane give 0.5 g (37).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyrane Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Liquid Crystal Substances (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

La présente invention concerne des procédés de production de dérivés de tétrahydropyranne pourvus d'au moins un autre cycle contenant de l'oxygène. Elle concerne en particulier des composés ayant deux cycles de tétrahydropyranne ou ayant chacun au moins un cycle de tétrahydropyranne et un cycle de dioxanne. Les procédés utilisés sont des condensations avec des aldéhydes et / ou des réactions de fermeture de cycles. Les procédés de production selon la présente invention permettent d'obtenir de nouveaux composés de tétrahydropyranne ayant au moins deux cycles O-hétérocycliques.
PCT/EP2006/004425 2005-05-25 2006-05-11 Derives de tetrahydropyranne pourvus de plusieurs cycles contenant de l'oxygene et procede de production desdits derives WO2006125530A1 (fr)

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CN2006800179759A CN101180295B (zh) 2005-05-25 2006-05-11 包含多个含氧环的四氢吡喃衍生物及其制备方法
JP2008512723A JP5484724B2 (ja) 2005-05-25 2006-05-11 酸素を含む環を複数含むテトラヒドロピラン誘導体類、およびそれの調製方法
KR1020077030219A KR101311569B1 (ko) 2005-05-25 2006-05-11 다수의 산소-함유 고리를 포함하는 테트라하이드로피란유도체 및 그 제조방법
DE112006000955T DE112006000955A5 (de) 2005-05-25 2006-05-11 Tetrahydropyranderivate mit mehreren sauerstoffhaltigen Ringen und Verfahren zu ihrer Herstellung

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WO2010047260A1 (fr) 2008-10-21 2010-04-29 チッソ株式会社 Composé de cristal liquide pentacyclique présentant un hétérocycle contenant de l’azote, composition de cristaux liquides, et élément d’affichage à cristaux liquides
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WO2008105286A1 (fr) 2007-02-28 2008-09-04 Chisso Corporation Composé pentacyclique de cristaux liquides ayant un groupe de liaison cf2o, composition de cristaux liquides et affichage à cristaux liquides
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US10174252B2 (en) 2015-02-24 2019-01-08 Jnc Corporation Liquid crystal composition and liquid crystal display device

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KR101311569B1 (ko) 2013-09-26
CN101180295A (zh) 2008-05-14
CN101180295B (zh) 2011-08-10

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