WO2018054877A1

WO2018054877A1 - Method for producing substituted bistolanes

Info

Publication number: WO2018054877A1
Application number: PCT/EP2017/073578
Authority: WO
Inventors: Andreas Lohr; Juergen Schemel; Mansoor D'lavari
Original assignee: Merck Patent Gmbh
Priority date: 2016-09-21
Filing date: 2017-09-19
Publication date: 2018-03-29
Also published as: CN109715590B; TW201819346A; DE112017004727A5; CN109715590A

Abstract

The invention relates to a method for producing bistolanes which are substituted in the 1,1 '-position with halogen and to products from said compounds. The C-C-triple bonds of the bistolanes are produced by elimination reactions.

Description

Process for the preparation of substituted bistolanes

The present invention relates to a process for the preparation of

Bistolanes which are substituted in the 1, 1 'position with halogen and products of these compounds. The C-C triple bonds of the bistolanes are generated by elimination reactions.

Bistolanverbindungen are among others as performance chemicals such. As liquid crystals or organic (semi-) conductors or their

Known precursors. Among others, their anisotropic optical properties are of interest in the application as a liquid crystal. The optoelectronic properties of corresponding polymers are also of interest. 1, 1 'dihalo-bis-olane derivatives are important as useful intermediates for the construction of highly conjugated aromatic compounds, e.g. B. oligo- (p-phenyleneethynylene) s. In EP 3053909 A1, bisiodebistolane is prepared from 1,4-diiodobenzene and 1,4-bisethynylbenzene.

The synthesis of 1, 1 '-dihalo-bistolic derivatives by double

Sonogashira coupling of 1, 4-dihalobenzene to 1, 4-bisethynylbenzene is basically possible, but the yields are lowered by the possible subsequent reaction of the 1-halo radical on the product

(Oligomerization) and the synthesis is not safe from a safety point of view. Alternatively, mixed halogenated benzenes such. B. 1 -lod-4-bromo-benzene compounds used, which react to dibromo-bistolanes. For further derivatization is therefore usually z. B. a bromine-iodine exchange as a further reaction step is necessary (see Xue et al., Tetrahedron 60 (2004), 6285-6249). The synthesis of 1, 1 '- Dihalogen-Bistolanderivaten is insufficiently developed on an industrial scale.

The present invention therefore has for its object to provide a process for the preparation of halogenated bistolanes, which gives the desired product in high yield and purity and is safe and inexpensive to carry out on an industrial scale. Surprisingly, it has been found that these as well as other tasks not explicitly mentioned, however, are based on the introductory ones

discussed contexts are readily derivable or disclosed, be solved by methods for the preparation of substituted bistolanes with all features of claim 1. Advantageous modifications of the methods according to the invention are set forth in the dependent claims appended to claim 1.

In particular, it has been found that bistolanes which are substituted in the 1,1 'position with halogen (Cl, Br, I) are efficiently and in high yield in a multi-step process of benzylphenylsulfone and

Terephthalaldehyd or their derivatives can be produced.

The subject of the present invention is accordingly a

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

I (iodine) or Br or Cl,

each independently of one another straight-chain or branched alkyl, alkenyl, alkoxy, alkylcarbonyl, alkoxycarbonyl,

Alkylcarbonyloxy or alkoxycarbonyloxy having 1 to 25 C atoms, in which also one or more H atoms may be replaced by F or Cl, F, Cl, Br, I, -CN, -NO ₂ , -C (= O) N ( R °) ₂ , -C (= O) R ° or cycloalkyl having 3 to 6 C atoms,

where two ortho-permanent groups L are also a radical of the formula

N / TisN or mean

Each R ° is independently H or alkyl of 1 to 12 C atoms,

and

r1, r2 are each independently 0, 1, 2, 3 or 4, preferably 0, 1 or 2,

mean, which is characterized in that the process comprises the reaction steps a), b) and c): a) the double addition of an educt of the formula (II)

wherein X, L and r1 have the abovementioned meaning,

and

Ar represents an optionally substituted phenyl radical, to the carbonyl functions of a bis-aldehyde of the formula

wherein L and r 2 are as defined for formula (I) in the presence of a base, b) after step a) conversion to a compound of formula (IV)

wherein Ar, X, L, r1 and r2 are independently as defined above, by means of an acid chloride R- (CO) Cl or an equivalent reagent, wherein Cyclohexyl or straight-chain or branched alkyl having 2 to 15 carbon atoms, wherein the alkyl radical is preferably a

secondary or tertiary alkyl radical

double double elimination on the compound of formula (IV) to the bistolan of formula (I) in the presence of an alkali metal base e.g. Example of alcohols, amines or CH-acidic compounds, preferably and exemplarily KOtBu (potassium tert-butylate), LiHMDS (lithium-1,1,3,3,3,3-hexamethyldisilazane), NaHMDS (sodium-1, 1, 1, 3,3,3-hexamethyldisilazane), KHMDS (potassium 1, 1, 1, 3,3,3-hexamethyldisilazane), LiTMP (lithium 2,2,6,6-tetramethylpiperidine), NaOtBu (sodium tert-butoxide), Na-amylate (sodium tert-pentoxide), K-amylate (potassium tert-pentoxide), LDA (lithium diisopropylamide), sec-butyl lithium and other organometallic reagents.

Preferred meanings of the substituents in formula (I) or their sub-formulas and starting materials are independent of one another:

r1 0,

r2 0,

L is alkyl having 1 to 4 C atoms,

X is iodine or bromine, preferably iodine,

and

Ar is phenyl or p-tolyl.

The bistolans obtained can advantageously be converted into more highly refined derivatives, for example by exchanging the halogen groups. A further process according to the invention therefore comprises the preparation of bistolan derivatives of the formula (VI)

(VI)

which is characterized in that a compound of formula (I) is prepared according to the process of the invention described above, and then reacted in one or more subsequent steps to give a compound of formula (VI), wherein in one of said subsequent steps a compound of the formula (I) is reacted with a substituted ethyne. For this purpose, for example, the compound of formula (I) is reacted by metal-catalyzed coupling at the position of the substituent X in the presence of a palladium complex (Sonogashira coupling).

In the formula (VI), the radicals are:

Alkylcarbonyloxy or alkoxycarbonyloxy having 1 to 25 C atoms, in which also one or more H atoms may be replaced by F or Cl, F, Cl, Br, I, -CN, -NO ₂ , -C (= O) N ( R °) ₂ , -C (= O) R ° or cycloalkyl having 3 to 6 C atoms, each independently 0, 1, 2, 3 or 4, preferably 0, 1 or 2,

including their mirror images, wherein the rings U ¹ and U ^{2 are} each bound via the axial bond to the central bistol group,

A ^{1 "4} are each independently a radical selected from the following groups a) the group consisting of trans-1, 4-cyclohexylene, 1, 4-cyclohexenylene and 4,4 ^{'-Bicyclohexylen,} in which one or more non-adjacent CH ₂ groups may be replaced by -O- and / or -S- and in which also one or more H atoms may be replaced by a group L,

b) the group consisting of 1, 4-phenylene and 1, 3-phenylene, wherein also one or two CH groups may be replaced by N and wherein also one or more H atoms replaced by a group L or -Sp-P could be,

Z ^{1 "4} each independently a single bond,

-O-, -S-, -CO-, -COO-, -OCO-, -O-COO-, -CO-NR ⁰ -, -NR ° -CO-, -NR ° -CO- NR ° -, -OCH 2, -CH 2 O, -SCH 2, -CH ₂ S, -CF ₂ O, -OCF 2, -CF ₂ S, -SCF 2, -CH ₂ CH ₂ -, - (CH ₂ ) ₃ -, - (CH ₂ ) ₄ -, -CF2CH2-, -CH2CF2-, -CF2CF2-, -CH = CH-, -CY ¹ = CY ² -, -CH = N-, -N = CH-, -N = N-, -CH = CR ° -, -C = C-, -CH = CH-COO-, -OCO-CH = CH-, CR ° R ⁰⁰ , preferably in each case independently of one another -CO-O-, -O-CO-, -CH 2 O-, -OCH 2, -CF 2 O, -OCF 2, -O-, -CO-, -C (R ^c R ^d ) -, -CH ₂ CF ₂ -, -CF 2 CF 2 - or a single bond, more preferably a single bond, -CH ₂ CH ₂ -, - (CH ₂ ) ₄ -, -COO- or -OCO-,

Y ¹ ' ^{2 are} each independently H, F, Cl, CN or R °,

R °, R ^{00 are} each independently H or alkyl of 1 to 12 C atoms, m and n are independently 0, 1, 2, 3 or 4, o and p are independently 0, 1, 2, 3 or 4,

R ^{1 "is} H, F, Cl, -OH, CN or straight-chain or branched alkyl having 1 to 25 C atoms, in which one or more non-adjacent CH ₂ groups are each independently denoted by C (R °) = C ( R ⁰⁰ ) -, -C = C-, -O-, -S-, -CO-, -CO-O-, -O-CO-, -O-CO-O- may be replaced so that and / or S atoms are not directly linked to one another and in which also one or more H atoms can be replaced by F, Cl, CN or P-Sp-, preferably straight-chain or branched, optionally mono- or polyfluorinated, alkyl, Alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl or alkylcarbonyloxy having 1 to 12 carbon atoms (where the alkenyl and

Alkynyl radicals at least two and the branched radicals at least three Having C atoms),

wherein the compounds preferably at least one group R ^{1 "4}

having P or P-Sp-, P is a polymerizable group, preferably

W ^{1 is} H, F, Cl, CN, CF ₃ , phenyl or alkyl having 1 to 5 C atoms, in particular H, Cl or CH ₃ , in particular CH ₂ = CH-CO-O-, CH ₂ = C ( CH ₃ ) -CO-O- and CH ₂ = CF-CO-O-, Sp on each occurrence identically or differently a spacer group or a single bond, preferably a single bond or selected from the formula Sp "-X", so that the rest P ¹ -Sp- of the formula P ¹ - Sp "-X" -, where Sp "denotes alkylene having 1 to 20, preferably 1 to 12 C atoms, which is optionally substituted by F, Cl, Br, I or CN. or polysubstituted, and wherein also one or more non-adjacent CH ₂ groups are each independently selected from -O-, -S-, -Si (R ⁰⁰ R ⁰⁰⁰ ) -, -CO-, -CO-O-, -O-CO-, -O-CO-O-, -S-CO-, -CO-S-, -N (R ⁰⁰ ) -CO-O-,

-O-CO-N (R ⁰⁰ ) -, -N (R ⁰⁰ ) -CO-N (R ⁰⁰ ) -, -CH = CH- or -C = C- may be replaced by O- and / or S Atoms are not directly linked, preferably - (CH ₂ ) i- with i = 2, 4 or 6,

X "-O-, -S-, -CO-, -CO-O-, -O-CO-, -O-CO-O-, -CO-N (R ⁰⁰ ) -, -N (R ⁰⁰ ) -CO-, -N (R ⁰⁰ ) -CO-N (R ⁰⁰ ) -, -OCH ₂ -, -CH ₂ O-, -SCH ₂ -, -CH ₂ S-, -CF ₂ O-,

-OCF ₂ -, -CF ₂ S-, -SCF ₂ -, -CF ₂ CH ₂ -, -CH ₂ CF ₂ -, -CF ₂ CF ₂ -, -CH = N-,

-N = CH-, -N = N-, -CH = CR ° -, -CY ² = CY ³ -, -C = C-, -CH = CH-CO-O-,

Represents -O-CO-CH = CH- or a single bond, preferably -CO-O- or -O-CO-,

R ⁰⁰ is independently alkyl having 1 to 12 C atoms,

Each R ⁰⁰⁰ is independently H or alkyl of 1 to 12 carbon atoms, and

Y ² and Y ^{3 are} each independently H, F, Cl or CN. The required alkyne is a compound of the formula

wherein the radicals are independently defined as for formula (I).

The alkyne may already be substituted as the end compound of the formula (I), or it may correspond to an intermediate compound which is converted into a compound of the formula (VI) in a further reaction step (cf., Example 2.2)

The compound of the formula (VI) is in particular a compound selected from the compounds of the formulas (VI-1), (VI-2) and (VI-3):

(VI-2)

wherein R ¹ and R ^{2 are} as defined in formula (VI), and

q is 1, 2, 3, 4, 5 or 6, preferably 4.

The process according to the invention for the preparation of compounds of the formula (I) in the form of a one-pot reaction enables shortened, very efficient and general approaches to bistolanes of the formula (I). The general synthetic methodology makes it possible to convert substrates of the formula (III) with reactive bromine or iodine substituents into the corresponding structures of the formula (I).

The bistolane compounds obtainable by the process according to the invention are obtained in high purities and high yields of pure product. Furthermore, the products can be obtained overall cost-effective and without serious threat to humans and the environment. The use of very toxic chlorophosphates as in conventional alkyne syntheses can likewise be dispensed with by the process according to the invention.

The reaction is also suitable for additionally substituted dihalo-bistolanes of the formula (I) which are accessible by appropriately substituted starting materials of the formulas (II) and (III). Corresponding derivatives are generally known or obtainable by conventional methods in analogy.

The ring system Ar contained in the intermediates of the formula (II) and (IV) is optionally substituted by one or more radicals, preferably radicals L ² , which are independently defined when occurring repeatedly. The radical L ² mentioned as substituent of the ring system Ar preferably denotes, in each case independently of one another, F, Cl, Br, I, -CN, -NO 2, straight-chain or branched alkyl, alkenyl, alkynyl, alkoxy,

Alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or alkoxycarbonyloxy having 1 to 25 carbon atoms, wherein one or more H atoms may be replaced by F, Cl or -OSi (R °) 3, wherein R ° each independently of one another with 1 to alkyl 12 carbon atoms means.

In the context of the present invention, the term "alkyl" means a straight-chain or branched, saturated or

unsaturated, preferably saturated, aliphatic hydrocarbon radical of 1 to 15 (i.e., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15)

Carbon atoms. By 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 any of these radicals can also be substituted, preferably with one or more fluorine atoms. Particular preference is given to alkoxy -OCH ₃ , -OC ₂ H 5, -OnC ₃ H ₇ , -OnC ₄ H ₉ , -OtC ₄ H ₉ , -OCF ₃ ,

-OCHF2, -OCHF or -OCHFCHF ₂ . In the context of the present invention, the term "alkenyl" means an alkyl radical as defined above in which one or more -CH = CH groups are present. If two -CH = CH groups are present in the radical, this may also be referred to as "alkadienyl". An alkenyl radical may contain from 2 to 15 (ie 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15) carbon atoms and is branched chain or preferably straight chain. The rest is unsubstituted or monosubstituted or polysubstituted or differently substituted in particular with F, Cl, Br, I and / or CN. Furthermore, one or more CH ₂ groups may each be independently replaced by -O-, -S-, -C = C-, -CO-O-, -OC-O- such that heteroatoms (O, S) are not are directly connected. If the CH = CH group on both carbon atoms another When R Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest Rest etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa etwa In general, the E isomer (trans) is preferred. Preferably, the alkenyl radical contains 2, 3, 4, 5, 6 or 7

Carbon atoms and is vinyl, 1 E-propenyl, 1 E-butenyl, 1 E

Pentenyl, 1E-hexenyl, 1E-heptenyl, 2-propenyl, 2E-butenyl, 2E-pentenyl, 2E-hexenyl, 2E-heptenyl, 3-butenyl, 3E-pentenyl, 3E-hexenyl, 3E-heptenyl, 4- Pentenyl, 4Z-hexenyl, 4E-hexenyl, 4Z-heptenyl, 5-hexenyl and 6-heptenyl. Particularly preferred alkenyl radicals are vinyl, 1E-propenyl and 3E-butenyl.

If one or more CH ₂ groups in an alkyl radical have been replaced by -C = C-, an alkynyl radical is present. The replacement of one or more CH ₂ groups by -CO-O- or -O-CO- is possible. The following of these radicals are preferred: acetyloxy, propionyloxy, butyryloxy, pentanoyloxy, hexanoyloxy, acetyloxymethyl, propionyloxymethyl,

Butyryloxymethyl, pentanoyloxymethyl, 2-acetyloxyethyl, 2-propionyloxyethyl, 2-butyryloxyethyl, 2-acetyloxypropyl, 3-propionyloxypropyl, 4-acetyloxybutyl, 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.

In the context of the present invention, the term "cycloalkyl" means a cyclic aliphatic (alicyclic) radical having 3 to 16 carbon atoms which is saturated or partially unsaturated and unsubstituted or mono- or polysubstituted by halogen, carboxy, nitro, alkanyl, alkoxy, -NH ₂ and / or is substituted with -N (alkanyl) ₂ , wherein the multiple substitution with the same or different

Substituents can be made. Preferably, the cycloalkyl radical is unsubstituted and has 5, 6 or 7 carbon atoms. In particular, cycloalkyl is a cyclohexyl radical. In the context of the present invention, "alkylene" means a divalent aliphatic hydrocarbon radical having 1, 2, 3, 4, 5, 6, 7 or 8 carbon atoms in the chain, optionally also mono- or polysubstituted by halogen, CN, carboxy, nitro , Alkanyl, alkoxy, -NH ₂ or substituted with -N (alkanyl) ₂ , which multiple substitution can be made with the same or different substituents. Preferably, "alkylene" is a straight-chain, unsubstituted or mono- or disubstituted by methyl, saturated aliphatic radical having 1, 2, 3, 4, 5 or 6 carbon atoms, in particular -CH ₂ CH ₂ CH ₂ - and -CH ₂ C. (CH ₃ ) ₂ CH ₂ -.

The radical X in the formulas (I), (II) and (IV) is preferably iodine or bromine, more preferably iodine. The iodine compounds of the formula (I) can advantageously be easily derivatized. For the reaction of terminal alkynes by Sonogashira coupling are iodaryl compounds

to bromarylene in general advantageous. Due to the higher price of iodine compounds over bromine derivatives, it is important to apply an economical production process with high yields. By the method according to the invention this object is achieved.

Particularly preferred compounds of formula (I) obtainable by the present process are selected from the following preferred structures:

Particularly preferred is a process product of the formula 1-1.

Particular preference is given to educts of the formula (II) selected from the following structures:

The aldehydes of the formula (III) are preferably selected from the following sub-formulas:

wherein "alkyl" means a linear or branched alkyl radical having 2 to 15 carbon atoms.

The inventive method is characterized by the fact that the compound of formula (IV) in reaction step b) from a

Intermediate of the reaction step a) according to the formula (IVa)

or another salt of the anionic organic group in formula (IVa). In reaction step a) is preferably a

Compound of formula (IVa) obtained as an intermediate, or a corresponding organic radical with another cation, for. Li ⁺ , Na ⁺ . The cation, here potassium ⁽⁺⁾ , is determined by the base used.

A preferred method according to the invention is characterized

in that the product obtained in reaction step a)

Intermediate is reacted with a carboxylic acid chloride of the formula R- (CO) CI. Other activated carboxylic acid derivatives (e.g., anhydrides) are also possible. The preferred carboxylic acid derivatives have a radical R selected from cyclohexane and alkyl having 3 to 15 C atoms.

Preferred radicals are cyclohexane and alkyl radicals having 3 to 15 carbon atoms, wherein the alkyl radical is preferably a secondary or tertiary alkyl radical, that is, the α-C atom is a secondary or tertiary carbon atom for steric shielding. Particular preference is given to cyclohexane, radicals having 3-5 C atoms, such as isopropyl, tert-butyl, isobutyl, tert-pentyl and sec-pentyl. The reaction in step b) is preferably carried out between -70 ° C and 25 ° C. The reaction time should be chosen so that the reaction has progressed sufficiently, but side reactions do not or only to a small extent occur. The reaction time is typically less than 120 minutes, preferably less than 80 minutes.

The double elimination (step c) on the compounds of formula (IV) towards the bistolanes of formula (I) is carried out in the presence of an alkali metal base. Alkali in this context means Li, Na, K, etc. The base is preferably not nucleophilic. Strong bases are also preferred. The alkali metal bases are preferably bases of alcohols, N-H compounds (eg, amines, silazanes) and CH compounds. Suitable bases are KOtBu, LiHMDS, NaHMDS, KHMDS, LiTMP (lithium 2,2,6,6-tetramethylpiperidine), NaOtBu, Na-amylate (sodium tert-pentoxide), K-amylate (Potassium tert-pentoxide), LDA (lithium diisopropylamide), sec-butyl lithium and other organometallic reagents.

It is advantageous to use bases of the HMDS (1,1,1,3,3,3-hexamethyldisilazane). In a further preferred case, the less expensive base KOtBu (potassium tert-butylate) is used. Due to the nature of the leaving group R- (CO) -O- produced from the carboxylic acid derivative, it is possible according to this invention to resort to the preferred base KOtBu. This variant has a considerable savings potential compared to lithium-based bases. The preferred reaction temperature is between -30 ° C and 5 ° C.

The process according to the invention is preferably carried out using a solvent. This means that the starting materials are preferably dissolved in a homogeneous phase or present as a suspension and react. The solvents to be used include polar and hydrophobic solvents.

The sulfone of the formula (II) used is relatively sparingly soluble, especially in cold solvent. It is preferably initially charged in tetrahydrofuran (THF). The sulfone goes in a preferred

Embodiment slowly in solution and is immediately quantitatively deprotonated while the temperature of the reaction mixture of sulfone and base (eg KOtBu) is continuously increased. This implementation prevents the formation of stilbene derivatives. In the preferred

In the process variant, the base used is an alkali metal base (preferably soluble, for example KOtBu) instead of NaH. The dosage is much easier compared to solid NaH on an industrial scale. The compounds of the formula (I) prepared according to the invention can be excellently further derivatized, in particular by the known transition metal-catalyzed couplings of aryl halides.

Catalysts for carrying out Sonogashira, Heck or Suzuki coupling on the products of formula (I) are well known, preferably containing palladium compounds. The preferred catalysts to be used can be made from common palladium (II) salts such as palladium chloride, bromide, iodide, acetate, acetylacetonate optionally substituted by further ligands, such as. B. alkylnitriles may be stabilized, or from Pd (0) species such as palladium on activated carbon or tris (dibenzylideneacetone) dipalladium and phosphine ligands are generated in situ. Alternatively, it is also possible to use defined palladium complexes which have been previously produced from the abovementioned ligands in one or more process steps. Particular preference is given in particular to bis (triphenylphosphine) palladium (II) chloride

be used.

For Sonogashira couplings, a substoichiometric amount of Cul is additionally added as cocatalyst.

A quantity of catalyst of from 0.01 mol% to 20 mol%, based on the aromatic or heteroaromatic starting material of the formula (II), is preferably used.

The base to be used in the Sonogashira coupling is preferably a nitrogen base, e.g. As pyridine or secondary amine, which can also serve as a solvent. The Suzuki coupling base to be used is preferably selected from bases such as sodium hydroxide, sodium methoxide, sodium acetate, potassium fluoride, potassium phosphate or potassium carbonate (see Zysman-Colman, E., Science of Synthesis (2010) 45, 175, Chapter 45.4.2.1. 4 Method 4: Alkylation of Arenes via Suzuki Reaction of Alkylboranes and Related Alkylboron Reagents with Aryl Halides, DOI: 10.1055 / sos-SD-045-00123).

The process according to the invention and the subsequent work-up of the reaction mixture and / or the further reaction can in principle be carried out as a batch reaction or in a continuous reaction mode. The continuous reaction includes z. As the reaction in a continuous stirred tank reactor, a stirred tank cascade, a loop or cross-flow reactor, a flow tube or in a microreactor. The work-up of the reaction mixtures is optionally carried out, as required, by filtration over solid phases,

Chromatography, separation between immiscible phases (eg. Extraction), adsorption on solid supports, distilling off

Solvents and / or azeotropic mixtures, selective distillation, sublimation, crystallization, cocrystallization or by nanofiltration on membranes.

Further combinations of the embodiments and variants of

Invention will be apparent from the claims.

Further preferred process variants can be taken from the examples whose details - also generalized according to more general

Expertise - representative of preferred embodiments of the process and its products of the invention.

The invention will be explained in more detail below with reference to exemplary embodiments, without, however, being limited thereby.

Examples

Example 1. Preparation of 1,1'-diiodobistolane

Example 1.1. 4-lodbenzylphenylsulphon

Iodobenzyl bromide (45.0 kg, 152 mol), sodium benzenesulfinate (26.2 kg, 160 mol) and ethanol (270 kg) are refluxed for 3 h. After cooling to 20 ° C., water (270 kg) is metered in over the course of 15 minutes, and the mixture is stirred further for 1 h. The product is isolated by filtration and the filter cake washed with water (180 kg) and ethanol (120 kg). The product is dried at 80 ° C in a vacuum.

Yield: 50.8 kg (142 mol, 93%). Purity: 99.9 area% (GC). The

Product is used in the next reaction step without further purification.

Example 1.2. 1, 1 'diiodobistolane

4-iodobenzylphenylsulfone (18.0 kg, 50.3 mol) is dissolved in tetrahydrofuran

(140 kg) and the mixture was cooled to -55 ° C with stirring.

A solution of potassium tert-butylate (6.6 kg, 58.8 mol) in

Tetrahydrofuran (60 kg) is added. The mixture is warmed to -25 ° C and stirred at this temperature for a further 90 min. The solution is cooled to -70 ° C and a solution of terephthalaldehyde (3.15 kg, 23.5 mol) in tetrahydrofuran (75 kg) is metered in so that the temperature is maintained in the range of -65 ° C ± 5K. The mixture is stirred for a further 30 min. Cyclohexanecarboxylic acid chloride (9.3 kg, 63.4 mol) is metered in over the course of 15 minutes and the metering line is rinsed with 20 kg of tetrahydrofuran. The mixture is heated at a rate of 3K / min to 20 ° C and stirred at this temperature for 1 h. The mixture is again cooled to -20 ° C and LiHMDS in THF (20%, 157 kg, 188 mol) added so that the temperature remains below 0 ° C. The mixture is stirred for a further 40 min at 0 ° C and then heated for 40 min at reflux. After cooling to 20 ° C hydrochloric acid (2 mol / L, 130 kg, 250 mol) is added slowly and stirred for a further 30 min. The solid is isolated by filtration and washed with water (180 kg) and tetrahydrofuran (160 kg). The product is dried at 50 ° C in a vacuum. Yield: 1 1, 4 kg (21, 5 mol, 91%). Purity: 99.6% (HPLC).

Example 2. Use of the bistolane for the synthesis of compounds with special optical properties

Example 2.1. Sonogashira clutch of the Bistolane

1, 1 'Diiodobistolan, copper iodide and bis (triphenylphosphine) - palladium dichloride are suspended in a mixture of THF and diisopropylam and the mixture is heated to 60 ° C. Subsequently, a solution of the alkyne in tetrahydrofuran is added slowly. The

Reaction mixture is cooled to room temperature and stirred overnight. After work-up, crystallization, filtration of the solid and drying, the product is obtained in 80% yield.

Example 2.2. Preparation of polymerizable compounds for optical films

Diiodobistolan (Example 1 .2) is suspended at 20 ° C in toluene. The corresponding cyclohexylcarboxylic acid acrylate compound, DMAP and stabilizer are added. A solution of DCC in toluene is metered in and the mixture stirred for a further 5 h at 20 ° C. The resulting N.N'-dicyclohexylurea is filtered off and the filtrate is worked up further. After crystallization, filtration of the solid and drying, the product is obtained in 75% yield.

The exemplary compound and the compounds of formula (VI) generally have a negative optical dispersion and impart special retardation properties to optical films (see WO 2016/020035 A1).

Claims

P16187 ST.doc

WO 2018/054877 PCT / EP2017 / 073578

- 22 -

claims

1 . Process for the preparation of dihalobistolanes of the formula (I)

10 I or Br or Cl, in each case independently of one another straight-chain or branched alkyl, alkenyl, alkoxy, alkylcarbonyl,

Alkoxycarbonyl, alkylcarbonyloxy or alkoxycarbonyloxy with

15 1 to 25 C atoms, in which also one or more H atoms can be replaced by F or Cl, F, Cl, Br, I, -CN, -NO 2, -C (= O) N (R °) ₂ , -C (= O) R ⁰ or cycloalkyl having 3 to 6 C atoms,

where two ortho groups L also contain a remainder of

20 formula

can mean

25

Each R ° independently is H or alkyl of 1 to 12 carbon atoms, and each of r1, r2 is independently 0, 1, 2, 3 or 4, characterized in that the process comprises the reaction steps

30

a), b) and c) comprises: a) the double addition of an educt of the formula (II)

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wherein X, L and r1 have the abovementioned meaning, and

Ar is an optionally substituted phenyl radical

5

to the carbonyl functions of a bisaldehyde of the formula (III)

wherein the substituents are as defined above, by means of an acid chloride R- (CO) Cl or an equivalent

reagent

wherein

R is cyclohexyl or straight-chain or branched alkyl having 2 to 15 C atoms, and

c) double elimination on the compound of formula (IV) to the bistolane of formula (I) in the presence of alkali metal bases.

2. The method according to claim 1, characterized in that

X I means.

35 P16187 ST.doc

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3. The method according to claim 1 or 2, characterized in that R is cyclohexane or an alkyl radical having 3 to 15 carbon atoms

means.

Method according to one or more of claims 1 to 3, characterized in that in formula (I)

r1 is 0.

Method according to one or more of claims 1 to 4, characterized in that in formula (I)

r2 is 0.

Method according to one or more of claims 1 to 5, characterized in that in formula (I) the radical

Ar represents a phenyl radical which is optionally substituted by L ² ,

wherein each independently of one another, F, Cl, Br, I, -CN, -NO2, straight-chain or branched alkyl, alkenyl, alkynyl, alkoxy, alkylcarbonyl, alkoxycarbonyl, alkylcarbonyloxy or

Alkoxycarbonyloxy having 1 to 25 carbon atoms, wherein also one or more H atoms may be replaced by F, Cl or -OSi (R °) 3, wherein R ° each independently represents alkyl having 1 to 12 carbon atoms.

7. The method according to one or more of claims 1 to 6, characterized ekennzeichnet that a Bisiodobistolan of formula 1-1

will be produced.

35 P16187 ST.doc

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Method according to one or more of claims 1 to 7, characterized in that the reaction step a) is carried out in the presence of KOtBu as the base.

Method according to one or more of claims 1 to 8, characterized in that the reaction step c) in the presence of the base Li-1, 1, 1, 3,3,3-hexamethyldisilazane or KOtBu is performed.

Method according to one or more of claims 1 to 9, characterized in that the compound of formula (IV) in reaction step b) from an intermediate of

Reaction step a) according to the formula (IVa)

or another salt of the anionic organic group in formula (IVa),

20

will be produced.

1 1. Process for the preparation of compounds of the formula (VI),

(VI), characterized in that a compound of formula (I) according to claim 1 by a process according to one or more of claims 1 to 10 is prepared, and then the compound of formula (I) in one or more subsequent steps to a compound of the formula (VI) is reacted, wherein in one of said subsequent reaction steps a

Compound of formula (I) is reacted with an ethyne, wherein in formula (VI) P16187 ST.doc

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L, r1, r2 and r3 are as defined in claim 1, and

U ¹ , U ² are independently selected from the radicals of the formulas

10 including their mirror images, wherein the rings U ¹ and U ^{2 are} each bound via the axial bond to the central bistol group,

A ^{1 "4} are each independently a radical selected from the following groups 15 a) the group consisting of trans-1, 4-cyclohexylene, 1, 4-cyclohexenylene and 4,4 ^{'-Bicyclohexylen,} wherein one or more non-adjacent CH ₂ Groups by -O- and / or -S-

20 and in which also one or more H atoms can be replaced by a group L,

b) the group consisting of 1, 4-phenylene and 1, 3-phenylene, wherein also one or two CH groups may be replaced by N and wherein also one or more H atoms by a group L or

25 SP-P can be replaced,

Z ^{1 "4} each independently means one

Single bond, -O-, -S-, -CO-, -COO-, -OCO-, -O-COO-, -CO-NR ⁰ -, -NR ° -CO-, -NR ° -CO-NR ° -, -OCH ₂ -, -CH ₂ O-, -SCH ₂ -, -CH ₂ S-, -CF ₂ O-, 30 -OCF ₂ -, -CF ₂ S-, -SCF ₂ -, -CH ₂ CH ₂ -, - (CH ₂ ) ₃ -, - (CH ₂ ) ₄ -, -CF ₂ CH ₂ -,

-CH ₂ CF ₂ -, -CF ₂ CF ₂ -, -CH = CH-, -CY ¹ = CY ² -, -CH = N-, -N = CH-, -N = N-, -CH = CR ° -, -C = C-, -CH = CH-COO-, -OCO-CH = CH-, CR ° R ⁰⁰ ,

_Y 1, 2 are each independently H, F, Cl, CN or R °,

35

ηθ D00 are each independently H or alkyl of 1 to 12 C atoms, P16187 ST.doc

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m and n are independently 0, 1, 2, 3 or 4, o and p are independently 0, 1, 2, 3 or 4,

R ^{1 "is} H, F, Cl, -OH, CN or straight-chain or branched alkyl having 1 to 25 C atoms, in which one or more non-adjacent CH ₂ groups are each independently denoted by C (R °) = C ( R ⁰⁰ ) -, -C = C-, -O-, -S-, -CO-, -CO-O-, -O-CO-, -O-CO-O- may be replaced so that and / or S atoms are not directly linked to one another, and in which also one or more H atoms may be replaced by F, Cl, CN or P-Sp-, preferably straight-chain or branched, optionally mono- or polyfluorinated, alkyl, Alkoxy, alkenyl, alkynyl, alkylcarbonyl, alkoxycarbonyl or alkylcarbonyloxy having 1 to 12 C atoms,

P is a polymerizable group, and

Sp on each occurrence the same or different one

Spacer group or a single bond,

mean.

A method according to claim 1 1, characterized in that the compound of formula (I) is carried out with an ethyne by metal-catalyzed coupling in the presence of a palladium complex

The method of claim 1 1 or 12, characterized in that a compound of formula

35 will be produced.