EP1214306A1 - Liquid crystal compounds - Google Patents

Abstract

A liquid crystal compound of general formula (I) where X is O, S or Se, and R?1, R2, R3, R4¿, m, n, p and q are as specified in the application. Liquid crystal devices comprising said compounds are also claimed.

Description

LIQUID CRYSTAL COMPOUNDS

The present invention relates to novel compounds having a fused heterocyclic ring which have the properties of liquid crystals, together with processes for their preparation and liquid crystal devices incorporating them. The term "liquid crystals" is well known. It refers to compounds which, as a result of their structure, will align themselves in a similar orientation, preferably at working temperatures, for example of from -40 to 200°C. These materials are useful in various devices, in particular the liquid crystal display devices or LCDs.

Liquid crystals can exist in various phases. In essence there are three different classes of liquid crystalline material, each possessing a characteristic molecular arrangement. These classes are nematic, chiral nematic (cholesteric) and smectic.

Broadly speaking, the molecules of nematic compounds will align themselves in a particular orientation in a bulk material. Smectic materials, in addition to being orientated in a similar way, will align themselves closely in layers. A wide range of smectic phases exists, for example smectic A and smectic C. In the former, the molecules are aligned perpendicularly to a base or support, whilst in the latter, molecules may be inclined to the support. Some liquid crystal materials possess a number of liquid crystal phases on varying the temperature. Others have just one phase. For example, a liquid crystal material may show the following phases on being cooled from the isotropic phase:- isotropic - nematic - smectic A - smectic C - solid. If a material is described as being smectic A then it means that the material possesses a smectic A phase over a useful working temperature range.

Such materials are useful, in particular in display devices where their ability to align themselves and to change their alignment under the influence of voltage, is used to impact on the path of polarised light, thus giving rise to liquid crystal displays. These are widely used in devices such as watches, calculators, display boards or hoardings, computer screens, in particular laptop computer screens etc. The properties of the compounds which impact on the speed with which the compounds respond to voltage charges include molecule size, viscosity (Δn), dipole moments (Δε), conductivity etc. Some examples of bicyclic liquid crystal compounds are found in DE-A-

19900517 and WO 98/04544.

The applicants have found a new class of chemicals that have useful liquid crystal properties. In particular the invention provides a liquid crystal compound having a fused five and six-membered ring, at least one of said rings containing a heteroatom, and at least one of said rings carrying a substitutent. Preferably, each ring has at least one substitutent.

Suitable heteroatoms for use in the ring system of the invention include oxygen, sulphur, nitrogen and selenium. Where nitrogen is present, it may carry a hydrogen or a substituent group, depending upon the nature and the aromaticity of the ring system.

The ring system may be aromatic or non-aromatic, but is preferably aromatic. Specific examples of the ring system of the invention include benzofurans and benzopyrans.

The nature of the substituents on the ring will determine the particular liquid crystal properties of the compound. Large substituents will tend to increase the viscosity of the compound, thereby increasing the time taken for the molecules to adopt the appropriate orientation under the influence of a voltage. The number of free electrons which are contained within the substitutents influences optical properties of the compound. Aromatic rings will have relatively high conductivity whereas strongly electronegative groups such as cyano, will tend to reduce conductivity.

The nature of the substitutents on the ring can therefore be selected so as to impart the desired liquid crystal properties on the final compound. For example, some applications as outlined below require chiral molecules. For this purpose, the compounds of the invention suitably contain an asymmetric centre.

Typical substituents will comprise a functional group, optionally substituted hydrocarbyl, optionally substituted alkoxy, optionally substituted heterocyclyl or carboxy or a hydrocarbyl ester or amide thereof. As used herein, the term "hydrocarbyl" refers to any structure comprising carbon and hydrogen atoms. For example, these may be alkyl, alkenyl, alkynyl, aryl such as phenyl or napthyl, arylalkyl, cycloalkyl, cycloalkenyl or cycloalkynyl. Suitably they will contain up to 20 and preferably up to 10 carbon atoms. The term "heterocyclyl" includes aromatic or non-aromatic rings, for example containing from 4 to 20, suitably from 5 to 10 ring atoms, at least one of which is a heteroatom such as oxygen, sulphur or nitrogen. Examples of such groups include furyl, thienyl, pyrrolyl, pyrrolidinyl, imidazolyl, triazolyl, thiazolyl, tetrazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, quinolinyl, iosquinolinyl, quinoxalinyl, benzthiazolyl, benzoxazolyl, benzothienyl or benzofuryl.

As used herein, the term "alkyl" refers to straight or branched chain alkyl groups, suitably containing up to 20 and preferably up to 6 carbon atoms, and the term "alkoxy" relates to -O-alkyl groups. The term "alkenyl" and "alkynyl" refer to unsaturated straight or branched chains which include for example from 2-20 carbon atoms, for example from 2 to 6 carbon atoms. In addition, the term "aryl" refers to aromatic groups such as phenyl or naphthyl. The terms "cycloalkyl", "cycloalkenyl" and "cycloalkynyl" refer to such groups which are cyclic and have at least 3 and suitably from 5 to 20 ring atoms. These rings may be fused together to form bicyclic, tricyclic or even larger multiple ring systems.

Optionally subsituted hydrocarbyl groups will be may be substituted by functional groups, or by other types of hydrocarbyl group. For example, cyclic groups such as aryl, heterocyclic or cycloalkyl, cycloakenyl or cycloalkynyl may be substituted by hydrocarbyl chains such as alkyl, alkenyl or alkynyl groups as well as functional groups. Where the hydrocarbyl group itself an alkyl, alkenyl or alkynyl group, it may be substituted with cyclic groups such as heterocyclic groups, aryl groups, cycloalkyl, cycloalkenyl or cycloalkynyl groups, as described above, which may themselves be further substituted by hydrocarbyl or functional groups. The term "functional group" refers to reactive groups such as halo, cyano, nitro, oxo, C(O)OR^a, C(O)R^a, OC(O)R^a, OR^a, S(O R^a, NRV, OC^NR , C(O)NR^bR^c, -NR^bC(O)OR\ -NR^bC(O)R^a, -NR^aCONR^bR^c, =NOR^a, -N^R^, SCO^NR^or -NR^bS(O)tR^a where R^a , R^b and R^c are independently selected from hydrogen or optionally substituted hydrocarbyl, or R^b and R^c together form an optionally substituted ring which optionally contains further heteroatoms such as sulphur, S(O),S(O)₂, oxygen and nitrogen, t is 0 or an integer of from 1-3.

The term "heteroatom" as used herein refers to non-carbon atoms such as oxygen, nitrogen, selenium or sulphur atoms as mentioned above. Where the nitrogen atoms are present, they will generally be present as part of an amino residue so that they will be substituted for example by hydrogen or alkyl.

The term "amide" is generally understood to refer to a group of formula C(O)NR^bR° where R^b and R^c are hydrogen or an optionally substituted hydrocarbyl group. In particular, the compounds of the invention are liquid crystal compounds of general formula (I)

(I) where X is O, S or Se, each R¹ and R³ are independently selected from cyano, halo, optionally substituted hydrocarbyl, optionally substituted alkoxy, optionally substituted heterocyclyl, a group R¹³C(O)O- where R¹³ is optionally substituted hydrocarbyl or carboxy or a hydrocarbyl ester or amide thereof, provided that at least one or group R¹ or R³ is other than cyano or halo, each R² and R⁴is independently selected from halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁴C(O)O- where R¹⁴ is optionally substituted hydrocarbyl, n is 1 or 2, m is 0, 1, 2 or 3, p is 1 or 2 and q is 0 or 1, provided n + m does not exceed 4 and p + q does not exceed 2, and further provided the compounds are other than those described in DEI 990517 or WO 98/04544.

These compounds have useful liquid crystal properties. In some cases, they have wider nematic phase ranges than the equivalent biphenyl compounds. They have good solubility properties, being soluble in standard host mixtures and exhibit good mixture properties. For example, in formula (I), where X is O, S or Se, each R¹ and R³ are independently selected from cyano, halo, optionally substituted hydrocarbyl, optionally substituted alkoxy, optionally substituted heterocyclyl, or carboxy or a hydrocarbyl ester or amide thereof, provided that at least one or group R¹ or R³ is other than cyano or halo, each R² and R⁴ is independently selected from halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁴C(O)O- where R¹⁴ is optionally substituted hydrocarbyl, n is 1 or 2, m is 0, 1, 2 or 3, p is 1 or 2 and q is 0 or 1, provided n + m does not exceed 4 and p + q does not exceed 2, and further provided the compounds are other than those described in DEI 990517 or WO 98/04544.

Preferably, in the compound of formula (I), n is 1, and m is 0, 1 or 2, and more preferably 0 or 1 and most preferably 0.

Preferably p is 1 and q is 0.

Suitable lower alkyl groups for R² and R⁴ include methyl, fluoromethyl or trifluoromethyl.

Preferably, any group R² or R⁴ which are present are halo, especially fluoro. Suitably no more than two of the groups R¹ and R² are fluoro, and preferably no more than one of the groups R¹ and R² is fluoro. It has been found that Δε of the mixtures containing the fluorinated compounds of formula (I) are reduced compared to the mixutres which include non-fluorinated compounds of formula (I). Furthermore, the presence of fluorines at the position R² appears to impart more negative behaviour on the mixture.

The applicants have also found that where groups (R²)_m is/are fluorine, the compounds may show only nematic phases, and have no smectic phase, mixture and in all cases are much reduced on the cyano equivalent mixture PBS22.

Where R² or R⁴ is a group of formula R¹⁴C(O)O-, R¹⁴ is suitably alkyl, cycloalkyl or aryl, preferably alkyl or aryl.

Suitably at least one of R¹ or R³ is cyano, in particular where low Δε is required.

In a particularly preferred embodiment, one of R¹ or R³ is cyano or halo and the other is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof.

For example, one of R¹ or R³ is cyano or halo and the other is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof.

Suitably R¹ and R³, when they are other than cyano or halo, are selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl or optionally substituted cycloalkynyl.

Suitable optional substituents for alkyl, alkenyl, alkynyl, groups R¹ and R³ include functional groups as defined above, as well as aryl, cycloalkyl, heterocyclyl any of which may be substituted by alkyl, alkenyl or alkynyl as well as functional groups as defined above.

Suitable optional substituents for aryl, heterocyclyl, cycloalkyl, cycloalkenyl or cycloalkynyl groups R¹ and R³ include those listed above in respect of alkyl, alkyenyl and alkynyl groups, as well as alkyl, alkenyl or alkynyl, any of which may be optionally subsituted by a functional group, an aryl group, a heterocyclic group or a cycloalkyl, cycloalkenyl or cycloalkynyl group.

Preferably, R¹ and R³, where these are other than cyano or halo, are selected from optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof.

Where these are carboxy ester groups, they are preferably alkyl esters or aryl esters such as phenyl esters where the phenyl group may be optionally substituted for example with alkyl, alkoxy or cyano groups.

Suitable groups R¹ or R³ where these are other than cyano or halo are groups of formula (i), (ii), (iii), (iv), (v), (vi), (vii) or (viii)

where x is 0 or 1, R ° is an d^oalkyl group, and y and z are independently selected from 0, 1 or 2.

Preferably at least one R¹ or R³ group is a group of sub-formula (i) - (viii) as set out above.

A particularly preferred group for R¹ or R³ where these are other than cyano or halo are optionally substituted cycloalkyl or optionally substituted phenyl, and particularly optionally substituted phenyl.

Suitable substituents for the cycloalkyl or phenyl groups R¹ and R³ include halo, alkyl especially Cs^alkyl, alkoxy such as Cs^alkoxy, cyano or phenyl which may itself be substituted by alkyl or cyano. Particularly suitable substituents include alkyl especially C₃.9alkyl, alkoxy such as Cs^alkoxy, cyano or phenyl which may itself be substituted by alkyl or cyano.

When R¹ or R³ is a group is a group of formula R¹³C(O)O-₅ R¹³ is suitably alkyl, cycloalkyl or aryl, preferably cycloalkyl.

The selection of either R¹ or R³ as cyano can have significant effects on the properties of the compounds. For example, compounds where R¹ is cyano may have a significantly different dielectric anisotropy as compared to compounds where R³ is cyano. It has been found also that the birefringence of mixtures containing the compounds of the invention are lower when R³ is cyano in preference to R¹. Preferably X is oxygen or sulphur and most preferably oxygen. Suitably substituents are arranged on the ring so as to confer an advantageous dipole on the compound. For this purpose, the substituents are suitably arranged such that the overall shape of the molecule is either bent or wedge shaped. Thus substituents are suitably positioned at the 2 and 6 positions of the bicyclic ring where the group X is at position 1.

In particular, the invention provides a compound of general formula (IA)

_R2b (IA) where X is oxygen, sulphur or selenium, R^laand R^lb are independently selected from hydrogen, cyano, halo, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or carboxy or a hydrocarbyl ester or amide thereof, provided that at least one group R^la or R^1b is other than hydrogen; one of R¹⁷ or R¹⁸ is cyano, halo, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or carboxy or a hydrocarbyl ester or amide thereof, and the other is hydrogen, halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁵C(O)O- where R¹⁵ is an optionally substituted hydrocarbyl group; R^2a and R^2b are independently selected from hydrogen, halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁴C(O)O- where R¹⁴ is as defined above; subject to the provisos that:

(i) at least one group R^la or R^lb or R¹⁷ or R¹⁸ is other than cyano or halo; (ii) where X is S, R¹⁷ is carboxy or a hydrocarbyl ester or amide thereof, R¹⁸ is hydrogen, R^2a and R^2b are not both fluoro; (iii) where X is O, R¹ is an optionally substituted hydrocarbyl or carboxy or a hydrocarbyl ester or amide thereof, R^2a is hydrogen, and R^lb and R^2b are both fluorine, then R¹⁷ is other than Cι_-8 alkyl.

Where R¹⁷ is a group R¹⁵C(O)O-, R¹⁵ is suitably a group of formula R¹³ as defined above. Alternatively where R¹⁸ is a group of formula R¹⁵C(O)O-, R¹⁵ is suitably a group R¹⁴ as defined above.

Preferably in the compound of formula (IA) R^2a is hydrogen. Suitably at least one of R^Ib, R^2b or R¹⁸ in formula (IA) is fluoro. However, suitably no more than two of R^la, R^2a, R ^b or R^lb are fluoro, and preferably no more than one of these groups is fluoro.

Preferably one of R^lb or R^la or R¹⁷ or R¹⁸ in formula (IA) is cyano or halo and at least one of the said groups on the other ring of the bicyclic ring of formula (IA) is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof. Thus for example, where R^lb or R^,a is halo or cyano, at least one of R¹⁷ or R¹⁸ is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof. Conversely, where where R¹⁷ or R¹⁸ is halo or cyano, at least one of R^la or R^lb is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof

For instance, one of R^lb or R^la or R¹⁷ or R¹⁸ in formula (IA) is cyano or halo and at least one of the said groups on the other ring of the bicyclic ring of formula (I A) is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof.

Particular examples of said optionally substituted cycloalkyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof are groups of formula (i)-(viii) as set out above. A particularly preferred group of compounds of the invention are of formula

(II)

wherein R is a group R as defined above in relation to formula (I), one of R and R is a group R as defined in relation to formula (I) and the other is hydrogen or a group R¹ as defined in relation to formula (I); R⁶ is hydrogen, cyano or fluoro, preferably hydrogen or fluoro, and R⁹ is hydrogen, cyano or fluoro, provided that where R⁵ is cyano or fluoro, at least one of R⁷ or R⁸ is optionally substituted alkyl, optionally subsituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally subsituted alkoxy, optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof; and where one of R⁷ or R is cyano or fluoro and the other is hydrogen, R is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof.

Preferred groups R⁵ and R⁷ and/or R⁸ include cyano; fluoro; alkoxy; alkenyl; alkyl, aryl or alkylaryl esters of carboxy; arylalkyl, alkenylaryl wherein the aryl ring is optionally substituted with an alkyl group, a functional group such as fluoro or alkoxy, or further aryl groups which are themselves optionally substituted with alkyl; optionally substituted pyrimidinyl wherein the optional substituents are in particular alkyl or optionally substituted cycloalkyl where the cycloalkyl ring is optionally subsituted with an alkyl group.

Specific examples of compounds of formula (II) are compounds of formula (HA)

(IIA)

where R , 5' is cyano or fluoro, preferably fluoro, one of R and R⁸ is hydrogen and the other is an optionally substituted hydrocarbyl group or a heterocyclic group as described above. Particular examples of substituted hydrocarbyl groups for R⁷ or R⁸ are groups of sub-formula (i), (ii), (iii), (vi) or (viii) as defined above. Compounds of formula (IIA) may show advantageous properties in terms of their u.v. stability and a low susceptability to ion contamination, making them particularly suitable for use in thin film transmittor (TFT) devices.

Particular examples of the compounds of formula (H) are listed in Table 1.

Table 1

R⁹

In the above Table, * indicates the point of attachment to the ring structure. Particular examples of compounds of formula (I) where X is sulphur are listed able 2. Table 2

The compounds of the invention may be prepared by conventional methods which would be apparent to a skilled chemist.

In particular, compounds may be prepared by adding substituents to a bicyclic ring.

Thus, for example, a compound of formula (I) can be prepared by reacting a compound of formula (III)

(III) where R², R³, R⁴, X, n, m, p and q are as defined in relation to formula (I), and Z is either a leaving group or a group B(OH)₂, with a compound of formula (IV)

R'-Z' (IV) where R¹ is as defined in relation to formula (I) and Z' is a group B(OH)₂ where Z is a leaving group, or a leaving group where Z is a group B(OH)₂; and thereafter if desired or necessary, converting a group R², R³ or R⁴ to a different such group.

Suitable leaving groups for Z or Z' include halo such as bromo or iodo, mesylate, tosylate and triflate. The reaction is suitably effected in an inert organic solvent, such as 1,2-dimethoxyethane in the presence of a base such as sodium or potassium carbonate. The reaction is suitably effected in the presence of an inert atmosphere such as a nitrogen atmosphere. Optionally a catalyst such as a palladium catalyst for example tetrakis (triphenylphosphine) palladium is present. The reaction is suitably effected at elevated temperatures, for instance at the reflux temperature of the solvent.

Of course, other substituents may be introduced in an analogous way and the order in which this is done will depend to a large extent on the nature of the substituents and where they are positioned on the ring. In an alternative route, for example, compounds of formula (I), are prepared by reacting a compound of formula (V)

(V) where R¹, R²,R⁴, X, n, m, p and q are as defined in relation to formula (I), and Z is as defined in relation to formula (in), with a compound of formula (VI)

R³-Z'

(VI)

where R³ is as defined in relation to formula (I) and Z' is as defined in relation to formula (IV), and thereafter, if necessary, changing any groups R¹, R² and R⁴ to different such groups.

Suitable leaving groups Z or Z' and reaction conditions will be similar to those described above in relation to the reaction between compounds of formula (HI) and (TV). The conversion of groups R¹, R², R³ and R⁴ to different such groups could be carried out by conventional methods as would be apparent to a skilled chemist. A particularly useful reaction in this context is the conversion of a carboxylic ester group such as an alkyl ester, in particular an ethyl ester, to a cyano group. This reaction may be achieved by hydrolysis of the carboxylic ester group, followed by conversion of the resultant carboxylic acid to the corresponding acid chloride and thereafter to the amide. Dehydration of the amide gives the cyano compound. Each of the steps can be carried out using conventional chemistry and these are illustrated in the Examples given hereinafter. Compounds of formula (III) and (V) are suitably prepared by a cyclisation reaction as would be understood in the art. For example, a compound of formula (III) might be prepared by reacting a compound of formula (VTI)

(R²)r

(VII)

where X, n and m are as defined in relation to formula (I), and Z is as defined in relation to formula (ffl), with a compound of formula (VITI)

.CO₂R¹²

CH₂ ^R³

(VIM)

where R³ is as defined above in relation to formula (I) and R¹² is an alkyl group such as ethyl. Thereafter, groups R³ can be changed to different such groups on the compound of formula (III) in a similar manner to that outlined above.

A particular preferred compound of formula (VLTI) is a compound where R³ is a carboxylic ester group such as an alkyl ester group as this gives rise to the possibility of subsequent modification as outlined above. Thus a suitable compound of formula (VITI) is diethyl bromomalonate. The reaction is suitably effected in an organic solvent such as butanone in the presence of a base such as potassium carbonate.

Compounds of formulae (IV) and (VI) are either known compounds or they can be prepared by conventional methods. For example where Z or Z' are B(OH)₂ groups, these may be prepared by reacting the corresponding halo substituted compounds with magnesium in an organic solvent such as tetrahydrofuran, then with trimethyl borate, and finally acidifying the product using a mineral acid such as hydrochloric acid. Examples of such preparations are illustrated hereinafter.

Compounds of formula (XI) and (XII) are either known compounds or they can be prepared from known compounds by conventional methods.

In an alternative approach, compounds of formula (I) where q is 0 and p is 1 and R³ is a carboxy group may be prepared by introduction of a substituent R³ group to a compound of formula (IX)

(IX) were R², R⁴, X, m,n and q are as defined in relation to formula (I), and R¹ is a group R¹ as defined in relation to formula (I) or a precursor thereof; with a carboxylating agent such as Cardice in the presence of a base such as n-butyllithium and an organic solvent such as tetrahydrofuran, and thereafter acidifying the product with an acid such as glacial acetic acid. The carboxy group can subsequently be converted into different R³ groups as required.

Suitable precursor groups R¹ include groups which can be converted to the desired R¹ groups by conventional chemistry. Thus an example of such a group would be a group Z or Z' as defined above.

Compounds of formula (LX) where R¹ is a group R¹ (hereinafter referred to as compounds of formula (IXA) may have liquid crystal properties in their own right and therefore these form a further aspect of the invention. Compounds of formula (IX) where q is 0 may be prepared by cyclisation of an acetal compound of formula (X)

(X)

where R², R⁴ X, n and m are as defined in relation to formula (I), and R¹ is as defined in relation to formula (IX); in the presence of polyphosphoric acid. The reaction is suitably effected in an organic solvent such as chlorobenzene at elevated temperature, for example at the reflux temperature of the solvent.

Compounds of formula (X) are suitably prepared by reacting a compound of formula (XI)

(XI) where R¹ , R², X, m and n are as defined above, with a compound of formula (XII)

Z"-CH₂CR⁴(OCH₃)₂

(XH)

where R⁴ is as defined in relation to formula (I) and Z" is a leaving group. Suitable leaving groups Z" are defined above in relation to the group Z. The reaction is suitably effected in the presence of a base such as potassium carbonate in an organic solvent such as butanone. Compounds of formula (IX) may be converted to compounds of formula (V) where Z is a B(OH)2 group by reaction with trimethyl borate in the presence of a base such as n-butyl lithium. Subsequent acidification with an acid such as hydrochloric acid will yield the desired product. The reaction is suitably effected in an organic solvent such as tetrahydrofuran and reactions of this type are exemplified hereinafter.

An alternative cyclisation route which can lead directly to compounds of formula (I) where q is 0 involves reaction of a compound of formula (XHI)

(R²) m

(XΠD

where R , R , X, n and m are as defined above, with a compound of formula (XIV)

HO₂C-R^3' (MV)

where R³ is a group R³ as defined in relation to formula (I)or a precursor thereof. The reaction is suitably effected in an organic solvent such as dichloromethane in the presence of a base such as N,N'-dicyclocarbodiimide (DCC) and 4-N,N- dimethylaminopyridine (DMAP). The reaction is suitably carried out under an inert atmosphere for example of nitrogen.

Precursor groups R³ may be similar to those defined above in relation to R¹ . Compounds of formula (XIII) may be derived from compounds of formula

(XIV)

(XIV) where R¹ , R², X, n and m are as defined above with triphenylphosphine under conditions such as those illustrated hereinafter.

Variations and modifications to these routes would be apparent to the skilled person and these are all encompassed by the invention. The compounds of the invention can be selected such that their liquid crystal properties, in particular the nematic/smectic properties, suit the desired application. This may be achieved by varying the substituent groups on the central ring structure as outlined above, or it may be effected by mixing the compounds with other compounds of the invention or other different liquid crystal compounds. Mixtures are suitably eutectic mixtures. The compounds of the present invention may be in ed with each other to form useful liquid crystal mixtures, they may also be used with liquid crystal polymers or other low molar mass non-polymer liquid crystal materials.

As would be appreciated, the compounds of the invention can be used in a wide variety of devices, depending upon their particular properties. For applications where nematic compounds are required, compounds with low melting points, high transition temperatures (TN-I(°C)), low viscosity and high dipole moments giving for example high values of (Δε) are required. Compounds of the invention include those which have such properties and other properties such as flexoelectric properties. Where the melting point is not sufficiently low, this may be reduced by mixing the compound of the invention with other liquid crystal compounds, in particular a different compound of the invention, so as to form a mixture, preferably a eutectic mixture.

Transition temperatures may be increased by using or including in the mixture compounds of the invention which comprise at least three carbocyclic, heterocyclic or aryl ring systems, for example, compounds of formula (I) where both R¹ and R³ comprise a carbocyclic, heterocyclic or aryl group.

For trifluoroterphenyl (TFT) devices, compounds of the invention with TN twisted nematic values of the order of 90° are suitably selected. This is indicative of the degree of twist present in the alignment of the molecules. The viscosity of such compounds (Δn) is suitably low and for this reason, compounds with saturated substituent groups may be preferred. The compounds should have a positive Δε, which is a result of a longitudinal dipole moment. The value of the elastic constants ratio, K_H/K3₃, is preferably high, whilst the conductivity is preferably low. In order to achieve these latter requirements, halo substituents such as fluoro may be preferred to cyano substituents.

Compounds of the invention may have the properties of the so called "super- twist nematics" where the TN values are of the order of 240-270°. Such compounds generally have a high Δn value, and so may contain aromatic rings. They will have a positive Δε and the value of Kπ/K33 is high to provide a sharp threshold.

Liquid crystal devices comprising compounds of the invention of mixtures form a further aspect of the invention. Examples of such devices include optical and electro- optical devices, magneto-optical devices and devices providing responses to stimuli such as temperature changes and total or partial pressure changes. The compounds described above may also be included in a mixture, where the mixture comprises at least two compounds. Typical mixtures include mixtures consisting of compounds of the above- described compounds and also mixtures comprising at least one compound as described and at least one different liquid crystal compound. When a smectic A phase compound of the invention is composed of chiral molecules, it may exhibit an electroclinic effect, i.e. a direct coupling of molecular tilt to applied field. The origin of the electroclinic effect in a smectic A phase composed of chiral polar molecules has been described by Garoff and Meyer as follows. The application of an electric field parallel to the smectic layers of such a smectic A phase biases the free rotation of the transverse molecular dipoles and therefore produces a nonzero average of the transverse component of the molecular polarisation. When such a dipole moment is present and coupled to the molecular chirality, a tilt of the long molecular axis (the director) is induced in a plane perpendicular to the dipole moment. In thin samples, for example l-3μm, and with the smectic layers tilted or perpendicular with respect to the glass plates the electroclinic effect is detectable at low applied fields.

In an aligned smectic A sample a tilt of the director is directly related to a tilt of the optic axis. The electroclinic effect results in a linear electro-optic response. The electro-optic effect can manifest itself as a modulation of the effective birefringence of the device.

Electroclinic (EC) devices are useful, for example, in spatial light modulators having an output that varies linearly with applied voltage. A further advantage of EC devices is that they have high speed response times, much faster than twisted nematic type devices. One known type of ferroelectric device is bistable, in contrast the EC device is not bistable and has an output that varies linearly with applied voltage.

The electroclinic effect is sometimes referred to as the soft-mode effect see G Andersson et al in Appl. Phys. Lett., 51, 9, (1987). In general terms, regarding the electroclinic effect, it is advantageous if on applying a small voltage there results a large induced tilt. An increase in induced tilt may result in an increase in contrast ratio. It is also advantageous if a large induced tilt can be obtained at as low a voltage as possible.

It is also advantageous if the relationship between molecular induced tilt and applied voltage is temperature independent. When an increase in applied voltage results in little or no change in induced tilt then the material being tested is generally referred to as exhibiting a saturation voltage effect.

d = (2m+l)λ 4(Δn)

There are a variety of electroclinic devices in which the compounds of the present invention may be incorporated. For example, in a liquid crystal cell active black plane driving may be utilised. One of the walls forming the cell may be formed from a silicon substrate e.g. a wafer which possesses circuitry for driving pixels.

For many of these devices there exists an optimum thickness for the cell which is related to the birefringence (Δ n) given by:wherein λ = wavelength of operation

Δn = birefringence of liquid crystalline material m = integer.

Some suitable methods for driving electroclinic devices described by the present invention may be found in UK patent application GB-2247 972 A.

The mode of operation of these devices includes either amplitude modulation or phase modulation. Similarly devices may be used in reflectance or transmissive mode. By S_A* is meant a S_A phase which contains some proportion of chiral molecules, and therefore it is preferable that the compounds of the invention used in this way are chiral. Cholesteric or chiral nematic liquid crystals possess a twisted helical structure which is capable of responding to a temperature change through a change in the helical pitch length. Therefore as the temperature is changed, then the wavelength of the light reflected from the planar cholesteric structure will change and if the reflected light covers the visible range then distinct changes in colour occur as the temperature varies. This means that there are many possible applications including the areas of thermography and thermooptics.

The cholesteric mesophase differs from the nematic phase in that in the cholesteric phase the director is not constant in space but undergoes a helical distortion. The pitch length for the helix is a measure of the distance for the director to turn through 360°

By definition, a cholesteric material is chiral material. Chiral compounds of the invention may exhibit a helical mesophase and so may be used in thermographic or thermooptic applications. Chiral compounds of the invention may also be used in electro-optical displays as dopants, for example in twisted nematic displays where they may be used to remove reverse twist defects. They may also be used in cholesteric to nematic dyed phase change displays where they may be used to enhance contrast by preventing wave-guiding.

Thermochromic applications of cholesteric liquid crystal materials usually use thin film preparations of the materials which are then viewed against a black background. These temperature sensing devices may be placed into a number of applications involving thermometry, medical thermography, non-destructive testing, radiation sensing and for decorative purposes. Examples of these may be found in D G McDonnell in Thermotropic Liquid Crystals, Critical Reports on Applied Chemistry, Vol. 22, edited by G W Gray, 1987 pp 120-44; this reference also contains a general description of thermochromic cholesteric liquid crystals.

Generally, commercial thermochromic applications require the formulation of mixtures which possess low melting points, short pitch lengths and smectic transitions just below the required temperature-sensing region. Preferably the mixture or material should retain a low melting point and high smectic - cholesteric transition temperatures. In general, thermochromic liquid crystal devices have a thin film of cholesterogen sandwiched between a transparent supporting substrate and a black absorbing layer. One of the fabrication methods involves producing an 'ink' with the liquid crystal by encapsulating it in a polymer and using printing technologies to apply it to the supporting substrate. Methods of manufacturing the inks include gelatin microencapsulation, US patent 3,585,318 and polymer dispersion, US patents 1,161,039 and 3,872,050. One of the ways for preparing well-aligned thin film structures of cholesteric liquid crystals involves laminating the liquid crystal between two embossed plastic sheets. This technique is described in UK patent 2,143,323.

Other compounds of the present invention or mixtures of these may be used in ferroelectric mixtures and devices. In particular compounds of the invention may be used in many of the known forms of liquid crystal display devices, for example chiral smectic electro-optic devices. Such a device may comprise a layer of liquid crystal material contained between two spaced cell walls bearing electrode structures and surface treated to align liquid crystal material molecules.

Ferroelectric smectic liquid crystal materials, which can be produced by mixing an achiral host and a chiral dopant, use the ferroelectric properties of the tilted chiral smectic C, F, G, H, I, J and K phases. The chiral smectic C phase is denoted Sc* with the asterisk denoting chirality. The Sc phase is generally considered to be the most useful as it is the least viscous. Ferroelectric smectic liquid crystal materials should ideally possess the following characteristics: low viscosity, controllable spontaneous polarisation (Ps) and an Sc phase that persists over a broad temperature range which should include ambient temperature and exhibits chemical and photochemical stability. Materials which possess these characteristics offer the prospect of very fast switching liquid crystal containing devices. Some applications of ferroelectric liquid crystals are described by J S Patel and J W Goodby in Opt. Eng., 1987, 26, 273.

In ferroelectric liquid crystal devices the molecules switch between different alignment directions depending on the polarity of an applied electric field. These devices can be arranged to exhibit bi stability where the molecules tend to remain in one of two states until switched to the other switched state. Such devices are termed surface stabilised ferroelectric devices, e.g. as described in US 5061047 and US 4367924 and US 4563059. This bistability allows the multiplex addressing of quite large and complex devices.

One common multiplex display has display elements, i.e. pixels, arranged in an X, Y matrix format for the display of for example alpha numeric characters. The matrix format is provided by forming the electrodes on one side as a series of column electrodes, and the electrodes on the other slide as a series of row electrodes. The intersections between each column and row form addressable elements or pixels. Other matrix layouts are known, e.g. seven bar numeric displays.

There are many different multiplex addressing schemes. A common feature involves the application of a voltage, called a strobe voltage to each row or line in sequence. Coincidentally with the strobe applied at each row, appropriate voltages, called data voltages, are applied to all column electrodes. The differences between the different schemes lies in the shape of the strobe and data voltage waveforms.

Other addressing schemes are described in GB-2,146, 473-A; GB-2, 173, 336- A; GB-2,173, 337-A; GB-2, 173629-A; WO 89/05025; Harada et al 1985 S.I.D. Paper 8.4 pp 131-134; Lagerwall et al 1985 I.D.R.C. pp 213-221 and P Maltese et al in Proc 1988 I.D.R.C. pp 90-101 Fast Addressing for Ferroelectric LC Display Panels.

The material may be switched between its two states by two strobe pulses of opposite sign, in conjunction with a data waveform. Alternatively, a blanking pulse may be used to switch the material into one of its states. Periodically the sign of the blanking and the strobe pulses may be alternated to maintain a net d.c. value.

These blanking pulses are normally greater in amplitude and length of application than the strobe pulses so that the material switches irrespective of which of the two data waveforms is applied to any one intersection. Blanking pulses may be applied on a line by line basis ahead of the strobe, or the whole display may be blanked at one time, or a group of lines may be simultaneously blanked.

It is well known in the field of ferroelectric liquid crystal device technology that in order to achieve the highest performance from devices, it is important to use mixtures of compounds which give materials possessing the most suitable ferroelectric smectic characteristics for particular types of devices.

Devices can be assessed for speed by consideration of the response time vs pulse voltage curve. This relationship may show a minimum in the switching time (tmin) at a particular applied voltage (Vmm). At voltages higher or lower than Vπύn the switching time is longer than tπώ,. It is well understood that devices having such a minimum in their response time vs voltage curve can be multiplex driven at high duty ratio with higher contrast than other ferroelectric liquid crystal devices. It is preferred that the said minimum in the response time vs voltage curve should occur at low applied voltage and at short pulse length respectively to allow the device to be driven using a low voltage source and fast frame address refresh rate.

Typical known materials (where materials are a mixture of compounds having suitable liquid crystal characteristics) which do not allow such a minimum when included in a ferroelectric device include the commercially available materials known as SCE13 and ZLI-3654 (both supplied by Merck UK Ltd, Poole, Dorset). A device which does show such a minimum may be constructed according to PCT GB 88/01004 and utilising materials such as e.g. commercially available SCE8 (Merck UK Ltd). Other examples of prior art materials are exemplified by PCT/GB 86/00040, PCT GB 87/00441 and UK 2232416B.

Certain compounds of the invention may be useful in laser addressed applications in which laser beams are used to scan across the surface of the material or leave a written impression thereon. For various reasons many of these materials have consisted of organic materials which are at least partially transparent in the visible region. The technique relies upon localised absorption of laser energy which causes localised heating and in turn alters the optical properties of the otherwise transparent material in the region of contact with the laser beam. Thus as the beam traverses the material, a written impression of its path is left behind. One of the most important of these applications is in laser addressed optical storage devices, and in laser addressed projection displays in which light is directed through a cell containing the material and is projected onto a screen. Such devices have been described by Khan Appl. Phys. Lett. vol. 22, pi 11, 1973; and by Harold and Steele in Proceedings of Euro display 84, pages 29-31, September 1984, Paris, France, in which the material in the device was a smectic liquid crystal material. Devices which use a liquid crystal material as the optical storage medium are an important class of such devices. The use of semiconductor lasers, especially Ga_xAl_1-x As lasers where x is from 0 to 1, and is preferably 1, has proven popular in the above applications because they can provide laser energy at a range of wavelengths in the near infra-red which cannot be seen and thus cannot interfere with the visual display, and yet can provide a useful source of well-defined, intense heat energy. Gallium arsenide lasers provide laser light at wavelengths of about 850nm, and are useful for the above applications. With increasing Al content (x< 1), the laser wavelength may be reduced down to about 750nm. The storage density can be increased by using a laser of shorter wavelength. Thus some compounds of the present invention may be suitable as optical storage media and may be combined with dyes for use in laser addressed systems, for example in optical recording media.

The compounds of the present invention may also be used in pyroelectric devices for example detectors, steering arrays and vidicon cameras.

A pyroelectric detector consists of electrode plates at least one of which may be pixellated. In operation the detector is exposed to radiation R, for example infrared radiation, which is absorbed by an electrode. This results in a rise in temperature which is transmitted to a layer of pyroelectric material by conduction, The change in temperature results in a thermal expansion and a charge is generated. This change in charge is usually small when compared with the charge output due to the change in the spontaneous polarisation, Ps with a change in temperature; this constitutes the primary pyroelectric effect. A change in charge results in a change in potential difference between the electrodes. The charge on each pixel may be read out and the resulting signal is used to modulate scanning circuits in, for example, a video monitor and for a visual image of the infra red scans.

The selective reflective properties of the materials described by the current invention may also allow for materials of the current invention to be used in inks and paints and they may therefore be useful in anti-counterfeiting operation. They may also be used in so-called security inks. Other applications include thermal control management, for example the materials may be included in a coating which may be applied to one or more windows in order to reflect infra-red radiation.

Spatial light modulators comprises a liquid crystal cell formed by typically two glass walls and 0.1-10μm e.g. 2.5μm thick spacer. The inner faces of the walls carry thin transparent indium tin oxide electrodes connected to a variable voltage source. On top of the electrodes are surface alignment layers e.g. of rubbed polyimide described in detail later. Other alignment techniques are also suitable e.g. non-rubbing techniques such as evaporation of S1O2. A layer of liquid crystal material is contained between the walls and spacer. In front of the cell is a linear polariser; behind the cell is a quarter waveplate (this may be optional) and a mirror. An example of a linear polariser is a polarising beam splitter (not illustrated here). Suitable devices in which the materials of the current invention may be incorporated include beam steerers, shutters, modulators and pyroelectric and piezoelectric sensors.

The materials of the present invention may also be useful as dopants in ferroelectric liquid crystal devices, which may be multiplexed, or they may be used in active backplane ferroelectric liquid crystal systems. The materials of the present invention may also be useful as host materials. The materials of the present invention may be included in mixtures which also contain one or more dopants.

The invention will now be particularly described by way of example. Example 1

Preparation of Compound 3 in Table 1

Step l

Preparation of l-Bromo-4-heptylbenzene

Anhydrous aluminium chloride (19.8 g, 148 mmol) was added to a stirred solution of heptanoyl chloride (24.2 g, 163 mmol) in dry dichloromethane (135 ml). A solution of bromobenzene (21.2 g, 135 mmol) in dry dichloromethane (45 ml) was added, and the mixture was refluxed overnight with exclusion of moisture. The reaction was monitored by glc analysis. The mixture was cooled in an ice/water bath and poly(methylhydrosiloχane) (21.7 g, 360 mmol) was added dropwise with stirring. The mixture was refluxed overnight, glc analysis indicating complete conversion of the ketone. After removal of the solvent in vacuo the residue was poured into an ice/water mixture and sodium hydroxide solution (10%) was added to facilitate layer separation and to remove residual acid chloride. Ether was added and the separated aqueous layer was washed with ether (2 x 200 ml). The combined organic layers were washed with sodium hydroxide solution (10%), water and brine, and dried (MgSO4). Removal of the solvent in vacuo gave a residue which was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by distillation in vacuo. A colourless oil was obtained.

Yield 15.1 g (44%) bp 117 °C at 0.1 mm Hg *H NMR CDCl₃/δ 7.38 (2H, d), 7.04 (2H, d), 2.54 (2H, t),

1.57 (2H, qui) 1.28 (8H, m), 0.88 (3H, t) IR (KBr) V_jnax/cm"¹ 2930, 1490, 1073, 828, 799 MS m/z 256,254(M⁺), 199, 185, 171(100%), 90

Step 2

Preparation of 4-Heptylbenzeneboronic acid l-Bromo-4-heptylbenzene from step 1 (20.0 g, 78 mmol) in dry tetrahydrofuran(80 ml) was added in one portion to oven-dried magnesium (2.2 g, 90 mmol) in dry tetrahydrofuran (100 ml) with stirring under nitrogen. A crystal of iodine was added, and the mixture refluxed (2.5 h) and then allowed to return to room temperature. Dry tetrahydrofuran (80 ml) was added and the mixture cooled to -40 °C. Trimethyl borate (16.21 g, 156 mmol) was added dropwise, keeping the temperature below -10 °C. The mixture was allowed to return to room temperature and hydrochloric acid (5M, 36 ml) was added whilst stirring (45 min). The mixture was then poured into water and ether added. The separated aqueous layer was washed twice with ether (2 x 200 ml), and the product was extracted from the combined ethereal phases as the sodium salt by washing with potassium hydroxide (2M, 40 ml), The basic solution was then washed with ether, and the product released by acidification to pH3 by adding hydrochloric acid (cone.) to the aqueous solution. The product was then extracted with ether (2 x 200 ml), which was washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. A pale-brown solid was obtained. Yield 15.8 g (92%).

MS m/z 2200^), 192, 135, 122, 107(100%)

Step 3

Preparation of Ethyl 5-bromobenzo[blfuran-2-carbo ylate

A mixture of 5-bromosalicylaldehyde (2.0 g, 10 mmol), diethyl bromomalonate (2.0 g, 8.4 mmol), and potassium carbonate (2.5 g, 18 mmol) was refluxed in butanone (30 ml) (7 h). Glc analysis revealed no further reaction. When cool, the solvent was removed in vacuo, and water and dichloromethane added. The separated aqueous layer was washed twice with dichloromethane (2 x 100 ml) and the combined organic layers dried (MgSO4). After removal of the solvent in vacuo the residue was recrystallised (ethanol).

Pale yellow needle-like crystals were obtained. Yield 0.9 g (40%), mp 58-60 °C. ^XH NMR CDCl₃/δ 7.82 (1H, d), 7.54 (1H, dd), 7.47 (1H, d),

7.46 (1H, s), 4.46 (2H, q), 1.43 (3H, t) IR (KBr) Vmax/cm-¹ 1730, 1555, 1310, 1185, 855

MS m/z 268,270(TVr), 240, 225(100%), 196, 169 Step 4

Preparation of Ethyl 5-(4-heptylphenyl)benzo[blfuran-2-carboxylate

Ethyl 5-bromobenzo[b]furan-2-carboxylate (2.0 g, 7.4 mmol) from step 3, sodium carbonate (2.0 g, 18.5 mmol), 1,2-dimethoxyethane (10 ml) and water (30 ml), were stirred under nitrogen. Tetrakis(tιiphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) was added, followed by 4-heptylbenzeneboronic acid from step 2 (2.0 g, 8.9 mmol) in 1,2-dimethoxyethane (20 ml), and the mixture refluxed (4 h). Completion of the reaction was indicated by glc and tic analysis. After allowing to cool, the reaction mixture was poured into water and ether added. The separated aqueous layer was washed with ether (2 x 100 ml), and the combined ethereal layers washed with water and brine and dried (MgSO4). After removal of the solvent in vacuo the residue was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C) (impurity); petroleum fraction (bp 40-60 °C), dichloromethane 7:3 (product)]. The product was recrystallised (hexane). Colourless needles were obtained. Yield 1.3 g (48%), mp 46-8 °C.

^XH NMR CDCl₃/δ 7.84 (1H, dd), 7.67 (1H, dd), 7.63 (1H, d),

7.56 (1H, d), 7.52 (2H, d), 7.27 (2H, d), 4.46 (2H, q), 2.65 (2H, t), 1.65 (2H, qui), 1.44 (3H, t), 1.33 (8H, m), 0.89 (3H, t) IR (KBr) Vmax/cπr¹ 2930, 1725, 1560, 1160, 1095

MS m/z 364(M⁺)(100%), 279, 264, 251, 220

Step 5

Preparation of 5-(4-Heptylphenyl)benzo[blfuran-2-carboxylic acid

Potassium hydroxide (0.5 g, 6.8 mmol) in ethanol (30 ml) and water (3 ml) was added to ethyl 5-(4-heptylphenyl)benzo{b} furan-2-carboxylate from step 4 (1.2 g, 3.4 mmol). and the mixture was refluxed (5 min) with stirring. The solvent was then removed in vacuo and water added to the residue, which was then adjusted to pH 3 by adding hydrochloric acid (2M). The precipitated white solid was then filtered off and dried in vacuo (CaCfe), and recrystallised (acetic acid). White, fibrous needles were obtained. Yield 0.7 g (63%).

Transitions (°C) K 131 SmC 185 N 222 Iso.

*H NMR CDCl₃/δ 7.88 (1H, dd), 7.74 (1H, dd), 7.74 (1H, d),

7.67 (1H, d), 7.54 (2H, d), 7.28 (2H, d), 7.27 (1H, s), 2.66 (2H, t), 1.65 (2H, qui), 1.33 (8H, m), 0.89 (3H, m)

IR (KBr) Vmax/cm"¹ 2950, 2850, 1690, 1575, 1310, 1170, 805

MS m/z 336(M⁺), 292, 251(100%), 231, 207

Step 6

Preparation of 5-(4-heptylphenvDbenzofblfuran-2-carboxamide A mixture of 5-(4-heptylphenyl)benzo[b]furan-2-carboxylic acid from step 5

(0.70 g, 2.1 mmol) and thionyl chloride (0.75 g, 6.3 mmol) in dry benzene (25 ml) was refluxed (4 h) with exclusion of moisture. The solvent was then removed in vacuo, and the crude acid chloride dissolved in dry tetrahydrofuran (20 ml). Ammonia (d 0.880, 0.7 ml) was then added with stirring. After stirring for a further 30 min, water (40 ml) was added and the precipitate filtered off and washed with cold water. It was then recrystallised (ethanol), and dried in vacuo overnight (CaCk). White crystals were obtained.

Yield 0.55 g (78%), mp 201-2 °C.

*H NMR CDCl₃/δ 7.86 (1H, dd), 7.66 (1H, dd), 7.56 (1H, d), 7.56 (1H, d) 7.53 (2b, d), 7.27 (2H, d),

6.54 (1H, s), 5.65 (1H, s) 2.66 (2H, t), 1.66 (2H, qui), 1.31 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 3471, 3396, 3183, 2922, 2849, 1661, 1616,

1395, 801 MS m/z 3350VT), 250(100%), 191, 178, 165 Step 7

Preparation of 2-Cvano-5-(4-heptylphenv0benzofblfuran (Compound 3)

Thionyl chloride (1.8 g, 15 mmol) was added to a stirred solution of 5-(4- heptylphenyl)benzo[b]furan-2-carboxamide (0.5 g, 1.5 mmol) from step 6 in dry N,N- dimethylformamide (10 ml) under nitrogen. The mixture was stirred overnight, and then poured into an ice/water mixture. The product was extracted with ether (2 x 100 ml), and the combined extractions were washed with water and saturated sodium bicarbonate solution and dried (MgSO4). The solvent was removed in vacuo and the product purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), dichloromethane 1: 1], followed by recrystallization (ethanol). Colourless crystals were obtained.

Yield 0.3 g (63%). Purity (hplc) >99%.

Transitions (°C) K 31.1 Ν 60.5 Iso.

*H ΝMR CDCl₃/δ 7.83 (1H, d), 7.73 (1H, dd), 7.60 (1H, d), 7.51 (2H, d), 7.50 (1H, s), 7.28 (2H, d),

2.66 (2H, t), 1.65 (2H, qui), 1.33 (8H, m), 0.89 (3H, t) IR (KBr) Vmax/cm"¹ 2920, 2850, 2230, 1460, 1130, 885, 800

MS m/z 317(M⁺), 232(100%), 203, 190, 176 Example 2

Preparation of Compound No. 25 in Table 1

Step l

Preparation of 5-Bromobenzofblfuran-2-carboxylic acid

The title compound was prepared and purified in a similar manner to that described in Example 1 step 5 but using as starting material, ethyl 5- bromobenzo{b}furan-2-carboxylate (prepared as described in Example 1 step 3) (27.5 g, 102 mmol), potassium hydroxide (11.5 g, 204 mmol).

White crystals were obtained.

Yield 16.6 g (68%), mp >290 °C. *H NMR CD₂Cl₂/δ 7.80 (1H, dd), 7.49 (1H, dd), 7.44 (1H, d),

7.38 (1H, d) ER (KBr) Vmax/cm"¹ 3417, 1738, 1556, 1395, 1051, 946, 873, 803, 779

MS m/z 241 (Jvf), 223, 169, 89, 62(100%)

Step 2

Preparation of 5-Bromobenzolb|furan-2-carboxamide 5-Bromobenzo[b]furan-2-carboxylic acid from step 1 (16.5 g, 69 mmol), thionyl chloride (24.4 g, 205 mmol), ammonia (d 0.880, 46 ml) was converted to 5- bromobenzo[b]furan-2-carboxamide using a method analogous to that described in Example 1 step 6. White needles were obtained. Yield 9.9 g (60%), mp 212-215 °C.

*H NMR DMSO-d⁶/δ 7.80 (1H, d), 7.51 (1H, d), 7.40 (1H, dd),

7.32 (2H, s), 6.95 (1H, d)

IR (KBr) Vmax/cm"¹ 3024, 2860, 1591, 1563, 1473, 1318, 1179,

789, 422 MS m/z 240^), 223, 169, 89, 62(100%)

Step 3 Preparation of 2-Cyano-5-bromobenzo[blfuran

5-Bromobenzo[b]furan-2-carboxamide (9.8 g, 41 mmol) prepared as described in step 2, thionyl chloride (49.2 g, 410 mmol) were reacted using a method analogous to that described above in Example 1 step 7 to yield 2-Cyano-5-bromobenzo[b]furan. Off-white needles were obtained.

Yield 4.6 g (51%), mp 152.5-153.5 °C.

*H NMR CD₂Cl₂/δ 7.86 (1H, dd), 7.63 (1H, dd), 7.47 (1H, dd),

7.46 (1H, d) LR (KBr) Vmax/cm"¹ 2230, 1552, 1437, 1183, 949, 810, 571, 478

MS m/z 223,221(^(100%), 142, 114, 87, 58

Step 4

Preparation of l-Bromo-4-propylbenzene

Bromobenzene (31.4 g, 200 mmol), propionyl chloride (22.2 g, 240 mmol), aluminium chloride (29.5 g, 220 mmol), poly(methylhydrosiloxane) (32.1 g 533 mmol) were converted to l-bromo-4-propylbenzene using a method analogous to that described in Example 1 step 1 . A colourless liquid was obtained.

Yield 19.2 g (48%), bp 115 °C at 0.03 mm Hg. *H NMR CDCl₃/δ 7.38 (2H, d), 7.05 (2H, d), 2.51 (2H, t),

1.61 (2H, sxt), 0.92 (3H, t) IR (KBr) Vmax/cπr¹ 2965, 2871, 1489, 1077, 1011, 828, 796

MS m/z 200,198(M⁺), 169(100%), 119, 103, 90

Step 5 Preparation of 4-Propylbenzeneboronic acid l-Bromo-4-propylbenzene (11.0 g, 55 mmol) obtained in step 2, magnesium (1.5 g, 61 mmol), trimethyl borate (11.4 g, 110 mmol) were reacted using a method analogous to that described in Example 1 step 2. An off-white solid was obtained. Yield 7.5 g (83%). MS m/z 164(M⁺), 147, 135, 91, 43(100%)

Step 6

Preparation of 2-Cvano-5-(4-propylphenvπbenzo[blfuran (Compound 25 in Table 1)

2-Cyano-5-bromobenzo{b}furan obtained as described in step 3 above (1.0 g, 4.5 mmol), 4-propylbenzene boronic acid obtained as described in step 5 above (0.9 g, 5.4 mmol), sodium carbonate (1.2 g, 11.3 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) were reacted using a method analogous to that described in Example 1 step 4 to yield compound 25 in table 1 as white crystals. Yield 0.3 g (26%). Purity (hplc) >99%.

Transitions (°C) K 58.0 (48.9 N) Iso.

*H NMR CD₂Cl₂/δ 7.86 (1H, dd), 7.75 (1H, dd), 7.62 (1H, d),

7.55 (Hi d), 7.52 (2H, d), 7.29 (2H, d), 2.64 (2H, t), 1.67 (2H, sxt), 0.97 (3H, t) IR (KBr) Vmax/cπr¹ 2962, 2871, 2229, 1560, 1460, 1266, 1126,

885, 801, 612 MS m/z 261(M⁺), 232(100%), 203, 176, 151

Example 3

Preparation of Compound 26 in Table 1 Step l Preparation of l-Bromo-4-pentylbenzene

Bromobenzene (21.2 g, 135 mmol), valeryl chloride (19.7 g, 163 mmol), aluminium chloride (19.8 g, 148 mmol), poly(methylhydrosiloxane) (21.7 g, 360 mmol) were reacted using a method analogous to that described in Example 1 step 1 to yield l-bromo-4-pentylbenzene as a colourless liquid . Yield 11.6 g (38%) bp 100 °C at 0.2 mm Hg.

*H NMR CDCl₃/δ 7.38 (2H, d), 7.04 (2H, d), 2.54 (2H, t),

1.58 (2H, qui), 1.31 (4H, m), 0.88 (3H, t)

TR (KBr) Vmax/cπr¹ 2929, 2858, 1486, 1073, 830, 796

MS m/z 228,226(M⁺), 198, 183, 171(100%), 157 Step 2

Preparation of 4-Pentylbenzeneboronic acid

Using a method analogous to that described in Example 1 step 2, the title compound was obtained from l-bromo-4-penyltbenzene from Step 1 (15.2 g, 67 mmol), magnesium (1.9 g, 77 mmol), and trimethyl borate (13.9 g, 134 mmol). The product was obtained as a waxy white solid.

Yield 6.4 g (50%). MS m/z 522(3^-3^0), 465(100%), 409, 352, 175

Step 3

Preparation of 2-Cvano-5-(4-pentylphenvDbenzolblfuran (Compound 26 in Table 1}

2-Cyano-5-bromobenzo[b}furan obtained as described in Example 2 step 3 (0.6 g, 2.7 mmol), 4-pentylbenzeneboronic acid from step 2 above (0.6 g, 3.2 mmol), sodium carbonate (0.7 g, 6.8 mmol), tetrakis(tiiphenylphosphine)palladium(0) (0.2 g, 0.1 mmol) were reacted together in a method analogous to that described in Example 1 step 4 to give the desired compound as colourless plates. Yield 0.3 g (38%). Purity (hplc) >99%. Transitions (°C) K 51.1 N 56.4 Iso. ^LH NMR CD₂Cl₂/δ 7.87 (1H, dd), 7.75 (1H, dd), 7.61 (1H, ddd), 7.54 (1H, d), 7.52 (2H, d), 7.28 (2H, d), 2.66 (2H, t), 1.65 (2H, qui), 1.34 (4H, m), 0.91 (3H,t)

IR (KBr) v_maχ/cm ^■1 2965, 2861, 2232, 1558, 1439, 1187, 949,

819, 524

MS m/z 289QVT), 232(100%), 203, 189, 176

Example 4

Preparation of Compound 40 in Table 1

Step l

Preparation of l-Bromo-4-hexylbenzene l-Bromo-4-hexylbenzene was prepared and purified using a method analogous to that described in Example 1 step 1 but using as starting materials, bromobenzene (21.2 g, 135 mmol), hexanoyl chloride (20.0 g, 149 mmol), aluminium chloride (19.9 g, 149 mmol), and poly(methylhydrosiloxane) (21.7 g, 360 mmol). A colourless liquid was obtained.

Yield 10.4 g (32%), bp 110 °C at 0.01 mm Hg.

Η NMR CDCl₃/δ 7.38 (2H, d), 7.03 (2H, d), 2.54 (2H, t), 1.57 (2H, qui), 1.29 (6H, m), 0.88 (3H, t)

IR KB Vmax/cm- 2933, 2861, 1489, 1075, 807, 525

MS m/z 242,240^), 171(100%), 103, 91

Step 2

Preparation of 4-Hexylbenzeneboronic acid

4-Hexylbenzeneboronic acid was obtained from the product of step 1(8.0 g, 33 mmol), magnesium (1.0 g, 40 mmol), and trimethyl borate (6.9 g, 66 mmol) using a method analogous to that describedin Example 1 step 2. A light-brown solid was obtained.

Yield 4.8 g (71%). MS m/z 564(3M⁺-3H₂O), 535, 507, 493, 117(100%) Step 3

Preparation of 2-Cyano-5-(4-hexylphenyl)benzo[blfuran (Compound 40 in Table

1}

2-Cyano-5-bromobenzo[b]furan obtained as described in Example 2 step 3 (1.0 g, 4.5 mmol), 4-hexylbenzeneboronic acid (obtained as described in step 2 above) (1.0 g, 5 mmol), sodium carbonate (1.2 g, 11 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) were reacted together in a method analogous to that described in Example 1 step 4. Compound 40 in Table 1 was obtained as colourless crystals. Yield 0.3 g (22%).

Purity (hplc) 99%. Transitions (°C) K 25.4 N 45.2 Iso.

*H NMR CDCl₃/δ 7.83 (1H, d), 7.73 (1H, dd), 7.60 (1H, d),

7.51 (2H, d), 7.49 (1H, s), 7.28 (2H, d), 2.66 (2H, t), 1.66 (2H, qui), 1.39-1.31 (6H, m), 0.90 (3H,

IR (KBr) Vmax/cm"¹ 2933, 2861, 2235, 1561, 1271, 1128, 951, 808

MS m/z 303 ^), 274, 246, 232(100%), 219

Example 5 Preparation of Compound 36 in Table 1

Step 1

Preparation of l-Bromo-4-octylbenzene

The title was prepared and purified using a method analogous to that described in Example 1 step 1 but using the following starting materials: Bromobenzene (21.2 g, 135 mmol), nonanoyl chloride (24.2 g, 149 mmol), aluminium chloride (19.9 g, 149 mmol), poly(methylhydrosiloxane) (21.7 g, 360 mmol).

A colourless liquid was obtained.

Yield 16.4 g (45%), bp 158 °C at 0.9 mm Hg.

*H NMR CD₂Cl₂/δ 7.37 (2H, d), 7.06 (2H, d), 2.54 (2H, t), 1.56 (2H, qui), 1.26 (10H, m), 0.86 (3H, t)

IR (KBr) Vmax/cm"¹ 2932, 2859, 1489, 1074, 803, 519 MS m/z 270,268(M⁺), 211, 169(100%), 155, 89

Step 2

Preparation of 4-Octylbenzeneboronic acid

4-Octylbenzeneboronic acid was prepared and purified using a method analogous to that described in Example 1 step 2 using the following materials: l-Bromo-4-octylbenzene from step 1(6.0 g, 22 mmol), magnesium (0.7 g, 27 mmol), trimethyl borate (4.6 g, 44 mmol). A pale-yellow solid was obtained. Yield 4.2 g (82%). MS m/z 648(3M⁺-3H₂O), (100%), 551, 452, 353, 187

Step 3

Preparation of 2-Cvano-5-(4-octylphenyl)benzo[blfuran (Compound 36 in Table ii

Compound 36 was prepared and purified in a similar manner to that described in Example 1 step 4 from the following materials:

4-octylbenzeneboronic acid from step 2 (2.0 g, 8.5 mmol), 2-cyano-5- bromobenzo[b]furan (obtained as described in Example 2 step 3)(1.6 g, 7.1 mmol), sodium carbonate (1.9 g, 18 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol) A colourless liquid crystal was obtained. Yield 0.5 g (21%). Purity (hplc) 98.5%. Transitions (°C) K 28.2 SmA 34.3 N 48.8 Iso.

^XH NMR CD₂Cl₂/δ 7.87 (1H, dd), 7.45 (1H, dd), 7.62 (1H, d), 7.55 (1H, d), 7.53 (2H, d), 7.29 (2H, d),

2.66 (2H, t), 1.65 (2H, qui), 1.35-1.29 (10H, m), 0.89 (3H, t)

IR (KBr) Vmax cm"¹ 2932, 2859, 2235, 1561, 1464, 1184, 951, 807

MS m/z 33 l(W), 260, 232(100%), 203, 57 Example 6

Preparation of Compound 34 in Table 1

Step 1

Preparation of l-Bromo-4-nonylbenzene The title compound was prepared and purified in a similar manner to that described in Example 1 step 1 from the following reagents:

Bromobenzene (21.2 g, 135 mmol), nonanoyl chloride (26.3 g, 149 mmol), aluminium chloride (19.9 g, 149 mmol), poly(methylhydrosiloxane) (21.7 g, 360 mmol). A colourless liquid was obtained, which solidified to a waxy solid on standing. Yield 7.0 g (18%), bp 145 °C at 0.01 mm Hg.

^XH NMR CDCl₃/δ 7.38 (2H, d), 7.04 (2H, d), 2.54 (2H, t),

1.58 (2H, qui), 1.27 (12H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 2934, 2859, 1490, 1074, 825, 798, 634, 510

MS m/z 284,2820VT), 169, 91(100%), 71 Step 2

Preparation of 4-Nonylbenzeneboronic acid

The title compound was prepared and purified in a similar manner to that described in Example 1 step using the following reagents: l-Bromo-4-nonylbenzene from step 1(5.0 g, 18 mmol), magnesium (0.5 g, 22 mmol), trimethyl borate (3.7 g, 36 mmol). A waxy white solid was obtained.

Yield 3.7 g (83%). MS m/z 691(3M⁺-3H₂O), 578, 452, 354, 117(100%)

Step 3 Preparation of 2-Cvano-5-(4-nonylphenyl)benzofblfuran (Compound 34 in Table

1}

Compound 34 was prepared and purified in a similar manner to that described in Example 1 step 4 from the following reagents: 4-nonylbenzeneboronic acid from step 2 (1.2 g, 5 mmol), 2-cyano-5- bromobenzo[b]furan (obtained as described in Example 2 step 3) (1.0 g, 4.5 mmol), sodium carbonate (1.2 g, 11 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) Colourless needles were obtained. Yield 0.5 g (32%). Purity (hplc) 98.6%. Transitions (°C) K 28.1 SmA 49.6 N 60.0 Iso. *H NMR CD₂Cl₂/δ 7.86 (1H, dd), 7.75 (1H, dd), 7.61 (1H, d),

7.55 (1H, d), 7.52 (2H, d), 7.29 (2H, d),

2.66 (2H, t), 1.65 (2H, qui), 1.31 (12H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2929, 2858, 2333, 1464, 1127, 950, 887, 805

MS m/z 345^), 231(100%) 218, 190, 176 Example 7

Preparation of Compound 16 in Table 1

Step l

Preparation of 4-Nonyloxybenzeneboronic acid

The title compound was prepared and purified in a similar manner to that described in Example 1 step 2 using the following reagents:

4-Nonyloxybromobenzene (5.0 g, 17 mmol), magnesium (0.5 g, 22 mmol), trimethyl borate (3.5 g, 34 mmol).

A pale yellow solid was obtained. Yield 4.0 g (88%). MS m/z 264(M⁺), 238, 220, 151 , 94(100%)

Step 2

Preparation of Ethyl 5-(4'-nonyloxyphenyDbenzofblfuran-2-carboxylate

Ethyl 5-bromobenzo[b]furan-2-carboxylate (obtained as described in Example

1 step 3) (1.5 g, 14 mmol), 4-nonyloxybenzeneboronic acid (1.8 g, 7 mmol), sodium carbonate (1.5 g, 14 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol) were reacted together using a method analogous to that described in Example 1 step 4. Ethyl 5-(4'-nonyloxyphenyl)benzo[b]furan-2-carboxylate was obtained as a white solid.

Yield 0.7 g (31%). Transitions (°C) K 85.8 (84.6 SmA) Iso.

*H NMR CD₂Cl₂/δ 7.83 (1H, d), 7.66 (1H, dd), 7.62 (1H, d),

7.55 (1H, s), 7.54 (2H, d), 6.98 (2H, d), 4.41 (2H, q), 4.00 (2H, t), 1.80 (2H, qui), 1.41 (2H, t), 1.30 (12H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2923, 2852, 1722, 1607, 1574, 1517, 1164,

945, 839, 747 MS m/z 408(M⁺), 281, 227, 97, 57(100%)

Step 3 Preparation of 5-(4-Nonyloxyphenyl)benzolblfuran-2-carboxylic acid

5-(4-Nonyloxyphenyl)benzo[b]furan-2-carboxylic acid was prepared and purified in a similar manner to that described in Example 1 step 5 using the following reagents:

Ethyl 5-(4'-nonyloxyphenyl)benzo[b]furan-2-carboxylate from step 2(0.7 g, 1.7 mmol), potassium hydroxide (0.2 g, 3.4 mmol). A white crystalline solid was obtained. Yield 0.5 g (77%). Transitions (°C) K 212.2 SmC 223.0 Iso. H NMR CD₂Cl₂/δ 7.87 (1H, d), 7.72 (1H, dd), 7.69 (1H, s),

7.65 (1H, d), 7.54 (2H, d), 6.99 (2H, d), 4.01 (2H, t), 1.80 (2H, qui), 1.48 (2H, m), 1.30 (10H, m), 0.89 (3H, t) IR (KBr) Vmax/c " ¹ 3420, 2920, 2840, 2547, 1690, 1515, 1174,

942, 748 MS m/z 380(M⁺), 254(100%) 225, 210, 180

Step 4 Preparation of 5-(4-Nonyloxyphenyl)benzofb1furan-2-carboxamide The product of step 3 (0.9 g, 2.4 mmol), thionyl chloride (0.9 g, 7.2 mmol), and ammonia (d 0.880, 1.4 ml) were used in a method analogous to that described in Example 1 step 6 to yield the desired compound as a white crystalline solid. Yield 0.8 g (82%), mp 201-202 °C.

^XH NMR CD₂Cl₂/δ 7.83 (1H, dd), 7.65 (1H, dd), 7.57 (1H, d), 7.54 (2H, d), 7.49 (1H, d), 6.99 (2H, d),

6.53 (1H, s), 5.65 (1H, s), 4.00 (2H, t), 1.80 (2H, qui), 1.41 (12H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm'¹ 3462, 2919, 2851, 1678, 1601, 1518, 1166,

941, 812 MS m/z 379(M"), 253(100%) 225, 181, 152 Step 5

Preparation of 2-Cvano-5-(4-nonyloxyphenv0benzofblfuran (Compound 16 in Table 1)

Compound 16 was prepared and purified in a similar manner to that described in Example 1 step 7 using the quantities stated. The product of step 4 (0.7 g, 1.9 mmol), thionyl chloride (2.3 g, 19 mmol). Colourless plate-like crystals were obtained. Yield 0.1 g (15%). Purity (hplc) 99.9%. Transitions (°C) K 62 SmA 87 N 97 Iso *H NMR CD₂Cl₂/δ 7.80 (1H, d), 7.70 (1H, dd), 1.58 (1H, d),

7.52 (1H, s), 7.51 (2H, d), 6.97 (2H, d), 3.98 (2H, t), 1.78 (2H, qui), 1.46 (2H, mO, 1.28 (10H, m), 0.87 (3H, t) IR (KBr) Vmax/cm"¹ 2930, 2859, 2236, 1688, 1517, 1182, 1032, 842, 808

MS m/z 361^), 248, 235(100%), 206

Example 8

Preparation of Compound 41 in Table 1

Step l Preparation of 2-(4-Pentylcvclohexyl)phenoxy)acetaldehyde dimethyl acetal A mixture of 4-(4-pentylcyclohexyl)phenol (10.0 g, 41 mmol), bromoacetaldehyde dimethyl acetal (10.1 g, 60 mmol), potassium carbonate (11.1 g, 80 mmol) and potassium iodide (0.5 g, 3 mmol) in cyclopentanone (60 ml) was refluxed under nitrogen with stirring (48 h). The reaction was monitored by glc analysis. After allowing to cool, the mixture was poured into water and ether added. The separated aqueous phase was saturated with salt and washed with ether 2 x 200 ml). The combined organic layers were washed with sodium hydroxide solution (10%), water, dried (Na₂SO4), and the solvent removed in vacuo. The crude product was purified by flash chromatography [neutral alumina / petroleum fraction (bp 40-60 °C), dichloromethane 1: 1], A pale yellow liquid was obtained. Yield 10.1 g (75%), bp 195 °C at 0.01 mm Hg.

^XH NMR CD₂Cl₂/δ 7.11 (2H, d), 6.82 (2H, d), 4.66 (1H, t),

3.94 (2H, d), 3.41 (6H, s), 2.83-2.80 (1H, m), 1.73-1.66 (4H, m), 1.45-1.38 (1H, m), 1.35-1.20 (10H, m), 1.08-1.02 (2H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2928, 2860, 1709, 1644, 1514, 1139, 1081,

828 MS m/z 334(M⁺), 260, 176, 133, 75(100%)

Step 2 Preparation of 5-(4-PentylcycIohexyl)benzorb1furan

The product of step 1 (10.1 g, 31 mmol) was added dropwise to polyphosphoric acid (13 g) in chlorobenzene (130 ml) under reflux with stirring. The mixture was refluxed overnight (glc analysis indicated a complete reaction), and allowed to cool. The solvent was removed in vacuo and sodium hydroxide solution (10%) and ether were added. The separated aqueous layer was washed with ether (2 x 200 ml) and the combined organic layers washed with water and brine, and dried (MgSO4). The solvent was removed in vacuo and the crude product purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by distillation. A pale-yellow liquid was obtained. Yield 4.1 g (48%), bp 165 °C at 0.01 mm Hg.

*H NMR CD₂Cl₂/δ 7.76 (1H, d), 7.34 (1H, d), 7.31 (1H, d),

7.07 (1H, dd), 6.64 (1H, dd), 2.48 (1H, tt), 1.84-1.77 (4H, m), 1.44 (1H, dd), 1.38 (1H, dd), 1.26-1.14 (9H, m), 1.02 (1H, dd), 0.95 (lH, dd), 0.83 (3H, t)

IR (KBr) Vmax/cm"¹ 2927, 2856, 1514, 1455, 1197, 877, 809, 735 MS m/z 270(M⁺), 199, 171, 157(100%), 131

Step 3

Preparation of 5-(4-Pentylcvclohexyl)benzolblfuran-2-carboxylic acid

A flask containing the product of step 2 (1.7 g, 6.3 mmol) in dry tetrahydrofuran (70 ml) was flushed with nitrogen, degassed, flushed again with nitrogen and cooled (-70 °C). n-Butyllithium (2.5M in hexanes, 2.7 ml, 6.7 mmol) was then added dropwise with stirring, which was continued (0.5 h) at -70 °C. The mixture was then poured into a stirred slurry of 'Cardice' in dry tetrahydrofuran, and allowed to return to room temperature with continuous stirring. The solvent was removed in vacuo. The residue was dissolved in glacial acetic acid and the resulting solution was poured into water. The solid was filtered off, washed with water and dried in vacuo (KOH). A white solid was obtained.

Yield 0.2 g (10%). *H NMR CD₂Cl₂/δ 7.47 (1H, d), 7.44(1H, d), 7.39 (1H, s),

7.27 (1H, dd), 2.54 (1H, tt), 1.89-1.83 (4H, m), 1.49 (1H, dd), 1.42 (1H, dd), 1.31-1.19 (9H, m), 1.07 (1H, dd), 1.10 (1H, dd), 0.86 (3H, t) (acidic proton signal was not shown)

IR (KBr) Vmax/cm"¹ 3100, 2926, 2853, 1692, 1580, 1425, 943, 828

MS m/z 314(M⁺), 260, 201, 188(100%), 175

Step 4

Preparation of 5-(4-Pentylcvclohexyl)benzo[b1furan-2-carboxamide The title compound was prepared and purified in a similar manner to that described in Example 1 step 6 using the following reagents:

The product of step 3 (0.2 g, 0.6 mmol), thionyl chloride (0.2 g, 1.8 mmol), ammonia

(d 0.880, 0.4 ml).

Colourless needle-like crystals were obtained. Yield 0.08 g (50%), mp 214-215 °C

*H NMR CD₂Cl₂/δ 7.51 (1H, d), 7.43 (1H, d), 7.41 (1H, d),

7.31 (1H, dd), 6.51 (1H, s, br), 5.69 (1H, s, br), 2.59 (1H, tt), 1.93-1.88 (4H, m), 1.55-1.45 (2H, m), 1.33-1.21 (9H, m), 1.36- 1.03 (2H, m), 0.90 (3H, t) IR (KBr) Vmax/cm"¹ 3424, 3167, 2926, 2854, 1659, 1613, 1449, 1198, 939, 888

MS m/z 313(M⁺), 200, 187(100%), 187, 115

Step 5

Preparation of 2-Cvano-5-(4-pentylcvclohexy0benzofblfuran (Compound 41 in Table 1) Compound 41 was prepared and purified in a similar manner to that described in Example 1 step 7 using the following reagents:

5-(4-pentylcyclohexyl)benzo[b]furan-2-carboxamide from step 4(0.05 g, 0.2 mmol), thionyl chloride (0.2 g, 1.4 mmol). A white solid was obtained. Yield 0.03 g (60%).

Purity (hplc) >99%. Transitions (°C) K 77.6 (N 58.5) Iso.

*H NMR CD₂Cl₂/δ 7.51 (1H, dd), 7.47 (1H, ddd), 7.45 (1H, d),

7.39 (1H, dd), 2.60 (lH, tt), 1.93-1.87 (4H, m), 1.52-1.43 (2H, m), 1.33-1.21 (9H, m),

1.14-1.03 (2H, m), 0.90 (3H, t) IR (KBr) Vmax/cm"¹ 2924, 2852, 2230, 1557, 1465, 1198, 950,

874, 845, 815

MS m/z 295(M⁺), 252, 224, 182, 169(100%) Example 9

Preparation of Compound 42 in Table 1

Step l

Preparation of 2-(4-Bromophenoxy)acetaldehyde dimethyl acetal

A mixture of 4-bromophenol (87.2 g, 504 mmol), bromoacetaldehyde dimethyl acetal (85.2 g, 520 mmol), potassium carbonate (71.9 g, 520 mmol) and potassium iodide (4.2 g, 25 mmol) in butanone (500 ml) was refluxed under nitrogen with stirring

(48 h). The reaction was monitored by glc analysis. After allowing to cool, the mixture was poured into water and ether added. The separated aqueous phase was saturated with salt and washed with ether (3 x 300 ml). The combined organic layers were washed with sodium hydroxide solution (10%), and water, dried (Na₂SO4), and the solvent removed in vacuo. The crude product was then purified by flash chromatography [neutral alumina / dichloromethane], and distillation. Yield 52.6 g (40%), bp 105 °C at 0.25 mm Hg. H NMR CDCl₃/δ 7.37 (2H, d), 6.81 (2H, d), 4.70 (1H, t),

3.97 (2H, d), 3.45 (6H, s) IR (KBr) Vmax/cm"¹ 2940, 1555, 1485, 1070, 820, 645, 505 MS m/z 262,260(M⁺), 231, 199, 173, 75(100%)

Step 2 Preparation of 5-Bromobenzo[blfuran

5-Bromobenzo[b]furan was prepared and purified in a similar manner to that described in Example 8 step 2 using the following reagents: The product of step 1 (52.6 g, 202 mmol), polyphosphoric acid (85.0 g). A colourless liquid was obtained.

Yield 20.2 g (51%), bp 80 °C at 0.01 mm Hg (lit.² 15°C).

*H NMR CDCl₃/δ 7.72 (1H, dd), 7.61 (1H, d), 7.38 (1H, dd),

6.71 (1H, d), 7.37 (1H, d) IR (KBr) Vmax/cm-¹ 1440, 1165, 1030, 800, 760, 670, 420

MS m/z 198,196^), 168, 155, 117, 89(100%)

Step 3

Preparation of 5-Cvanobenzof blfuran

A mixture of the product of step 2 (20.0 g, 102 mmol) and cuprous cyanide monohydrate (22.0 g, 204 mmol) in N-methylpyrrolidin-2-one (700 ml) was refluxed (24 h) with stirring. Reaction completion was indicated by glc analysis. The reaction mixture was allowed to cool and filtered through a pad of Ηyflo SuperceF. It was then poured into water and ether added. The separated aqueous layer was extracted with ether (2 x 300 ml). The combined ethereal layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. The desired product was recrystallised from cyclohexane. Colourless needles were obtained.

Yield 6.6 g (45%), mp 82-83 °C.

*H NMR CD₂Cl₂/δ 7.98 (1H, dd), 7.78 (1H, d), 7.61 (1H, d),

7.60 (1H, dd), 6.89 (1H, dd) IR (KBr) Vmax/cm"¹ 3150, 2200, 1755, 1600, 1550, 1185, 1010,

885, 760, 610 MS m/z 143^), (100%), 88, 62, 50

Step 4 Preparation of 5-Cvanobenzolblfuran-2-boronic acid A solution of the product of step 3 (6.5 g, 45 mmol) in dry tetrahydrofuran (150 ml) was degassed and flushed with nitrogen. It was then cooled (-90°C) and n- butyllithium (2.5M in hexanes, 19.1 ml, 48 mmol) was added dropwise with stirring. Stirring was continued (0.5 h), and trimethyl borate (9.4 g, 90 mmol) was added at - 100 °C. After stirring (20 min), hydrochloric acid (2M, 137 ml) was added and the mixture stirred for a further 15 min. After allowing to return to room temperature, the mixture was poured into water and ether added. The separated aqueous layer was washed with ether (2 x 200 ml). The combined organic layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. An off-white solid was obtained. Yield 7.2 g (86%).

MS m/z 187(M⁺), 160, 145, 117, 43(100%)

Step 5

Preparation of 2-(4-PropylphenvO-5-cvanobenzolblfuran (Compound 42 in Table n Compound was prepared and purified in a similar manner to that described in

Example 1 step 4 using the following reagents: l-bromo-4-propylbenzene obtained as described in Example 2 step 4 (1.0 g, 5 mmol), the product of step 4 above (1.1 g, 6 mmol), sodium carbonate (1.3 g, 13 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol). Colourless crystals were obtained. Yield 0.1 g (8%). Purity (hplc) 98%. Transitions (°C) K 98.0 Iso. ^lΕL NMR CD₂Cl₂/δ 7.93 (1H, dd), 7.79 (2H, d), 7.61 (1H, d),

7.55 (1H, dd), 7.31 (2H, d), 7.06 (1H, d),

2.65 (2H, t), 1.68 (2H, sxt), 0.96 (3H, t) IR (KBr) Vmax/cm"¹ 2966, 2225, 1505, 1463, 1118, 818, 794, 738

MS m/z 261(M⁺), 232(100%), 202, 176, 58

Example 10

Preparation of 2-(4-PentylphenvP-5-cvanobenzolblfuran Compound 27 in Table

1 Compound 27 was prepared and purified in a similar manner to that described in Example 1 step 4 using the following reagents: l-bromo-4-pentylbenzene obtained as described in Example 3 step 1 (1.1 g, 5 mmol), 5-cycanobenzo[b] (1.1 g, 6 mmol), sodium carbonate (1.3 g, 13 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol). Colourless crystals were obtained. Yield 0.2 g (14%). Purity (hplc) >99%. Transitions (°C) K 99.7 (86.5 N) Iso.

^XH NMR CD₂Cl₂/δ 7.92 (1H, dd), 7.89 (2H, d), 7.61 (1H, d), 7.55 (1H, dd), 7.31 (2H, d), 7.05 (1H, d),

2.66 (2H, t), 1.65 (2H, qui), 1.35 (4H, m), 0.90 (3H, t)

TR (KBr) Vmax/cm"¹ 2933, 2865, 2224, 1504, 1461, 1185, 1115,

890, 800, 740 MS m/z 2890T), (100%), 245, 232, 202, 219, 203

Example 11

Preparation of Compound 13 in Table 1

Step l

Preparation of Methyl 3-chloromethyl-4-hvdroxybenzoate A suspension of methyl 4-hydroxybenzoate (15.2 g, 100 mmol) in hydrochloric acid (cone, 130 ml) was cooled (5 °C) with stirring. Paraformaldehyde (3.3 g, 11 mmol) was then added, and the mixture was heated (50-55 °C). The mixture was left to stand overnight. The solid was then filtered off and washed with water. The crude product was dried overnight in vacuo (CaCl₂), and recrystallised (CHCI3). A white solid was obtained. Yield 8.0 g (40%), mp 144-145 °C, (lit.³ 147-149 °C).

*H NMR CDCl₃/δ 8.03 (1H, d), 7.93 (1H, dd), 6.90 (1H, d),

6.18 (1H, s), 4.68 (2H, s), 3.90 (3H, s) IR (KBr) Vmax/cm"¹ 3241, 2958, 1688, 1605, 1287, 1152, 844,

754, 705 MS m/z 200(M⁺), 165(100%), 149, 133, 119

Step 2

Preparation of 2-Hvdroxy-5-(methoxycarbonyl)benzyltriphenylphosphonium chloride

A mixture of the product of step 1 (7.9 g, 39 mmol) and triphenylphosphine (9.8 g, 37 mmol) in chloroform (100 ml) was refluxed (1 h). The mixture was allowed to cool and the solvent was removed in vacuo. The residue was washed with toluene, whence it solidified. After filtering off the toluene the product heated in vacuo (100

°C, lh) and recrystallised (H₂O).

Colourless crystals were obtained. Yield 13.8 g (81%), mp 256-7 °C. H NMR CDCl₃/δ 11.37 (1H, s), 7.76 (3H, dt), 7.66 (1H, ddd), 7.59 (12H, m) 7.38 (1H, d), 7.38 (1H, d), 4.71 (2H, d), 3.76 (3H, s)

IR (KBr) Vmax/cm"¹ 3400, 1693, 1606, 1435, 1291, 1113, 770, 745, 690

MS m/z 4260T -Cl^"), 395, 349, 262(100%), 183

Step 3

Preparation of Methyl 2-(4-heptylphenv0benzo[blfuran-5-carboxylate

(Compound 11 in Table 1) N.N'-Dicyclohexylcarbodiimide (1.8 g, 9 mmol) in dry dichloromethane (20 ml) was added to a stirred mixture of 4-N,N-(dimethylamino)pyridine (0.2 g, 1.6 mmol), the product of step 2 (3.2 g, 6.8 mmol) and 4-heptylbenzoic acid (1.8 g, 8 mmol), in dry dichloromethane (80 ml). Stirring was continued (24 h), and dry toluene (350 ml) was added. The dichloromethane was distilled of in a stream of nitrogen. Dry triethylamine (2.0 g, 20 mmol) was added and the mixture was heated (85 °C) with stirring under nitrogen (14 h). Tic analysis indicated a complete reaction. After allowing to cool, the mixture was filtered and the solvent removed in vacuo. The residue was then flash chromatographed [silica gel / petroleum fraction (bp 40-60 °C), dichloromethane 6:4], and recrystallised (hexane). Colourless plate-like crystals were obtained. Yield 1.3 g (55%).

Transitions (°C) K 101 SmF 104.5 SmA 114.9 Iso.

*H NMR CD₂Cl₂/δ 8.30 (1H, dd), 7.98 (1H, dd), 7.79 (2H, d),

7.55 (1H, d), 7.30 (2H, d), 7.07 (1H, d), 3.92 (3H, s), 2.66 (2H, s), 1.62 (2H, qui), 1.32 (8H, m), 0.89 (3FL t)

IR (KBr) Vmax/c "¹ 2927, 2852, 1717, 1590, 1300, 1160, 1086,

838, 766 MS m/z 35001⁺), 319, 278, 265(100%), 206

Example 12 Preparation of 2-(4-HeptylphenvDbenzo[blfuran-5-carboxylic acid (Compound 43 in Table 1)

Compound 43 was prepared and purified in a similar manner to that described in Example 1 step 5 using the following reagents:

Compound 24 obtained as described in Example 40 step 3 (4.2 g, 12 mmol), potassium hydroxide (1.4 g, 24 mmol).

Colourless needle-like crystals were obtained. Yield 3.7 g (92%). Transitions (°C) K 200.3 SmC 255.8 Iso

^XH NMR DMSO-d⁶/δ 12.87 (1H, s), 8.25 (1H, s), 7.90 (1H, d), 7.83 (2H, d), 7.68 (1H, d), 7.47 (1H, s),

7.34 (2H, d), 2.61 (2H, t), 1.59 (2H, qui), 1.26 (8H, m), 0.85 (3H, t) IR (KBr) Vmax/c "¹ 3450, 2926, 2849, 2361, 1674, 1612, 1507,

1168, 912, 836 MS m/z 336dV ), 264, 251(100%), 206, 178

Example 13 Preparation of 2-(4-heptylphenyl)benzo[blfuran-5-carboxamide (Compound 44 in Table 1)

Compound 44 was prepared and purified in a similar manner to that described in Example 1 step 6 from the following reagents:

Compound 43 (Example 12) (1.0 g, 3 mmol), thionyl chloride (1.1 g, 9 mmol), ammonia, (d 0.880, 2.0 ml). A white solid was obtained.

Yield 0.6 g (60%), mp 242-243 °C.

*H NMR DMSO-d⁶/δ 8.10 (1H, d), 7.78 (2H, d), 7.77 (1H, d),

7.54 (1H, d), 7.28 (2H, d), 6.81 (1H, s), 5.85 (1H, s), 2.64 (2H, t), 1.63 (2H, qui),

1.25 (8H, m), 0.87 (3H, t)

IR (KBr) Vmax/cm"¹ 3419, 3192, 2922, 1646, 1608, 1391, 912,

801 MS m/z 3350VT), 250(100%), 217, 206, 178 Example 14

Preparation of Compound 54 in Table 1 (2-(4-Heptylphenyl)-5- cyanobenzofblfuran)

Compound 54 was prepared and purified in a similar manner to that described in Example 1 step 7 from the following reagents: Compound 44 (Example 13) (0.6 g, 1.6 mmol), thionyl chloride (1.9 g, 16 mmol). Colourless crystals were obtained. Yield 0.2 g (39%). Purity (hplc) >99.9%. Transitions (°C) K 86.5 N 87.5 Iso. ^XH NMR CD₂Cl₂/δ 7.92 (1H, d), 7.79 (2H, d), 7.61 (1H, d),

7.55 (1H, dd), 7.31 (2H, d), 7.05 (1H, s), 2.66 (2H, t), 1.65 (2H, qui), 1.30 (8H, m), 0.89 (3H, t) IR (KBr) Vmax/c "¹ 2920, 2840, 2229, 1616, 1504, 1119, 881,

741 MS m/z 317(M"), 245, 232(100%), 203, 176

Example 15

Preparation of Compound 45 in Table 1 (Methyl 2-(4- nonyloxyphenvObenzofblfuran-5-carboxylate)

A suspension of 4-nonyloxybenzoic acid (3.2 g, 12 mmol) in thionyl chloride (16.4 g, 138 mmol) was stirred overnight with exclusion of moisture. The solution was then refluxed (1 h), and allowed to cool. The excess thionyl chloride was removed in vacuo. Residual hydrogen chloride was removed by repeated addition of dry toluene, followed by removal in vacuo. The acid chloride was then added to 2-hydroxy-5- (methoxycarbonyl)benzyltriphenylphophonium chloride obtained as described in Example 11 step 2 (4.6 g, 10 mmol) and dry triethylamine (3.0 g, 30 mmol) in dry toluene (45 ml), and the mixture was refluxed (18 h) with stirring under nitrogen. The reaction was monitored by tic analysis. The mixture was allowed to cool, the precipitate of triethylammonium chloride was filtered off, and the solvent was removed in vacuo. The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), dichloromethane 7:3], followed by recrystallization (hexane).

A white solid was obtained. Yield 0.9 g (22%). Transitions (°C) K 151.5 SmA 152.0 Iso. *H NMR CD₂Cl₂/δ 8.19 (1H, d), 7.87 (1H, dd), 7.72 (2H, d),

7.45 (1H, d), 6.90 (2H, d), 6.89 (1H, s), 3.93 (2H, t), 3.83 (3H s), 1.72 (2H, qui), 1.39 (2H, qui), 1.22 (10H, m), 0.81 (3H, t) IR (KBr) Vma /cm"¹ 2920, 1722, 1612, 1506, 766 MS m/z 394(M⁺), 268(100%), 237, 210, 182 Example 16

Preparation of 2-(4-Nonyloxylphenyl)benzorblfuran-5-carboxylic acid

(Compound 46 in Table 1)

Compound 46 was prepared and purified in a similar manner to that described in Example 1 step 5 from the following reagents:

Compound 45 obtained as described in Example 15 (0.8 g, 1.9 mmol), potassium hydroxide (0.2 g, 4 mmol). A white crystalline solid was obtained. Yield 0.6 g (86%). Transitions (°C) K 172 SmC 193.2 N 253.7 Iso.

^XH NMR CD₂C1₂₅ DMSO-d⁶/δ 8.27 (1H, d), 7.97 (1H, dd), 7.81

(2H, d), 7.52 (lH, d), 7.00 (lH, d), 6.99 (2H, d), 4.02 (2H, t), 3.50 (1H, s), 1.80 (2H, t), 1.48 (2H, m), 1.27 (10H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 3450, 2920, 2857, 1679, 1615, 1504,

802, 769 MS m/z 380(M⁺), 363, 336, 254(100%), 225

Example 17 Preparation of 2-(4-Nonyloxylphenyl)benzo[blfuran-5-carboxamide (Compound 47 in Table 1)

Compound 47 was prepared and purified in a similar manner to that described in Example 1 step 6 using the following reagents:

Compound 46 obtained as described in Example 16 (0.5 g, 1.4 mmol), thionyl chloride (0.5 g, 4 mmol), ammonia, (d 0.880, 1.0 ml). A white solid was obtained. Yield 0.2 g (38%). Transitions (°C) K 225 N 235 Iso.

*H NMR CDCl₃/δ 8.15 (1H, s), 7.83 (1H, d), 7.80 (2H, d), 7.62 (1H, s), 7.51 (1H, d), 6.99 (2H, d),

6.98 (1H, s), 6.53 (1H, s), 4.02 (2H, t), 1.81 (2H, qui), 1.42 (2H, m), 1.28 (10H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 3440, 3200, 2919, 2850, 1645, 1611, 1504,

835, 807, 770 MS m/z 379(M⁺), 350, 336, 254(100%), 238 Example 18

Preparation of 2-(4-Nonyloxyphenyl)-5-cyanobenzoFblfuran (Compound 16 in Table 1)

Compound 16 was prepared and purified in a similar manner to that described in Example 1 step 7 using the following reagents. Compound 47 from Example 17 (0.2 g, 0.5 mmol), thionyl chloride (0.6 g, 5 mmol). A white solid was obtained. Yield 0.04 g (22%). Purity (hplc) 96.6%. Transitions (°C) K 103.0 SmA 119.7 Iso. ^lR NMR CD₂Cl₂/δ 7.90 (1H, dd), 7.80 (2H, d), 7.59 (1H, d),

7.53 (1H, dd), 7.00 (2H, d), 6.96 (1H, d), 4.02 2H, t), 1.80 (2H, qui), 1.47 (2H, m), 1.34-1.26 (10H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2921, 2850, 2225, 1609, 1504, 1175, 1010, 875, 802

MS m/z 36KM⁺), 235(100%), 206, 190, 164

Example 19

Preparation of Compound 48 in Table 1

Step l Preparation of Benzonitrile-4-boronic acid

Benzonitrile-4-boronic acid was prepared and purified in a similar manner to that described in Example 9 step 4 using the following reagents:

4-Bromobenzonitrile (25.0 g, 37 mmol), n-butyllithium (2.5M in hexanes, 57.5 ml, 44 mmol), trimethyl borate (28.5 g, 274 mmol). A white solid was obtained. Yield 16.6 g (82%).

MS m/z 147^), 119, 103, 91, 43(100%) Step 2

Preparation of 2-Heptyl-5-bromobenzo[blfuran n-Butyllithium (2.5M in hexanes, 3.3 ml, 8 mmol) was added to dry diisopropylamine (0.9 g, 8 mmol) with stirring under nitrogen at -70 °C. The system was degassed and flushed with nitrogen and 5-bromobenzo[b]furan (Example 9 step 2) (1.5 g, 7.6 mmol) in dry tetrahydrofuran (30 ml) was added dropwise with stirring. After stirring for a further 20 min, n-heptyl iodide (2.6 g, 11 mmol), was added dropwise. The mixture was allowed to return to room temperature with stirring under nitrogen. It was then poured into water and ether added. The separated aqueous phase was washed with ether (2 x 50 ml) and the combined organic layers washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. The residue was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by distillation. A colourless liquid was obtained. Yield 0.3 g (20%), bp 170 °C at 0.02 mm Hg.

*H NMR CD₂Cl₂/δ 7.60 (1H, dd), 7.29 (1H, s), 7.28 (1H, s),

6.36 (1H, s), 2.75 (2H, t), 1.73 (2H, qui), 1.32 (8H, m), 0.88 (3H, t)

IR (KBr) Vmax/c "¹ 2933, 2861, 1600, 1165, 1051, 949, 898, 731, 671, 582

MS m/z 296,294(M⁺), 239, 211(100%), 158, 109

Step 3

Preparation of 2-Heptyl-5-(4-cvanophenv0benzofblfuran (Compound 48 in Table

Ω Compound 48 was prepared and purified in a similar manner to that described in Example lstep 4 using the following reagents: Benzonitrile-4-boronic acid from step 1(0.2 g, 1.5 mmol), 2-heptyl-5- bromobenzo[b]furan from step 2 (0.4 g, 1.4 mmol), sodium carbonate (0.4 g, 3.5 mmol), tetrakis(triphenylphosphine)palladium(0) (0.05 g, 0.04 mmol). A white solid was obtained. Yield 0.03 g (7%). Purity (hplc) 90.5%. Transitions (°C) K 43.0 (30.9 N) Iso. *H NMR CD₂Cl₂/δ 7.71 (5H, m), 7.47 (1H, d), 7.43 (1H, dd),

6.45 (1H, d), 2.77 (2H, t), 1.74 (2H, qui), 1.33 (8H, m), 0.87 (3H, t) IR (KBr) Vmax/cm"¹ 2934, 2861, 2229, 1608, 1468, 844, 808

MS m/z 317(M⁺), 274, 260, 232( 100%), 190

Example 20

Preparation of Compound 28 in Table 1 Step l Preparation of l-Bromo-4'-pentylbiphenyl

4-Bromobiphenyl (35.0 g, 150 mmol), valeryl chloride (21.8 g, 181 mmol), aluminium chloride (22.0 g, 164 mmol), poly(methylhydrosiloxane) (24.0 g, 399 mmol) were reacted using a method analogous to that described in Example 1 step 1 except that dry 1,2-dichloroethane (600 ml) was used in place of dry dichloromethane. The title product was recrystallised from ethanol. A pale-brown solid was obtained.

Yield 21.1 g (46%), mp 94-96 °C (lit.[Jawdosiuk, 1977 #157] 95-96 °C).

^XH NMR CD₂Cl₂/δ 7.56 (2H, d), 7.49 (2H, d), 7.48 (2H, d),

7.27 (2H, d), 2.64 (2H, t), 2.64 (2H, t), 1.65 (2H, qui), 1.36 (4H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2931, 2865, 1690, 1137, 1079, 803, 502

MS m/z 304,302(M⁺), 247(100%)165, 152, 139

Step 2

Preparation of 4'-Pentylbiphenylboronic acid n-Butyllithium (2.5M in hexanes, 231 ml, 577 mmol) was added dropwise to a stirred solution of the product of step 1 in dry tetrahydrofuran (90 ml) at -70 °C under nitrogen. Stirring under nitrogen was continued (30 min) and trimethyl borate (6.9 g, 66 mmol) was added dropwise, maintaining the temperature below -10 °C. The system was allowed to return to room temperature with stirring under nitrogen. Hydrochloric acid (5M, 14 ml) was then added with stirring. The mixture was poured into water and ether added. The separated aqueous layer was washed with ether (2 x 200 ml) and the combined organic layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. A light-brown solid was obtained.

Yield 7.2 g (81%). MS m/z 2680VT), 224, 183(100%), 167, 152

Step 3 Preparation of 2-Cvano-5-(4^,-pentylbiphenv0benzolb|furan (Compound 28)

2-Cyano-5-bromobenzo[b]furan obtained as described in Example 2 step 3 (0.6 g, 2.7 mmol) and sodium carbonate (0.7 g, 6.8 mmol) in 1,2-dimethoxyethane (5 ml), were stirred under nitrogen. Tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) was added, followed by the product of step 2 (1.1 g, 4.1 mmol) in 1,2- dimethoxyethane (10 ml), and the mixture heated (80 °C) with stirring under nitrogen (4 h). Completion of the reaction was indicated by glc and tic analysis. After allowing to cool, the reaction mixture was poured into water and ether added. The separated aqueous layer was washed with ether (2 x 100 ml), and the combined ethereal layers washed with brine and dried (MgSO4). After removal of the solvent in vacuo the residue was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C) (impurity); petroleum fraction (bp 40-60 °C), dichloromethane 7:3 (product)]. The desired product was then recrystallised (hexane). Colourless needle-like crystals were obtained.

Yield 0.1 g (10%).

Purity (hplc) 99.9%.

Transitions (°C) K 134.0 B 147.3 N 255.6 Iso. ^l≡ NMR CD₂Cl₂/δ 7.94 (1H, dd), 7.82 (1H, dd), 7.71 (2H, d), 7.69 (2H, d), 7.66 (1H, ddd), 7.58 (2H, d),

7.57 (1H, d), 7.29 (2H, d), 2.66 (2H, t), 1.66 (2H, qui), 1.36 (4H, m), 0.92 (3H, t)

TR (KBr) Vmax/cm"¹ 2931, 2862, 2237, 1505, 1179, 949, 805

MS m/z 365(M⁺), (100%), 346, 308, 252, 58 Example 21

Preparation of Compound 29 in Table 1

Step l

Preparation of 2-(4'-PentylbiphenvD-5-cvanobenzo[blfuran Compound 29 was prepared and purified in a similar manner to that described in Example 1 step 4 using the following reagents: l-Bromo-4'-pentylbiphenyl (Example 20 step 1) (1.5 g, 5 mmol), 5- cyanobenzo[b]furan-2-boronic acid (Example 9 step 40 (1.5 g, 8 mmol), sodium carbonate (1.3 g, 13 mmol), tetrakis(triphenylphosphine)palladium(0) (0.6 g, 0.6 mmol)

The product was recrystallised from ethanol / dichloromethane 5: 1. A white crystalline solid was obtained. Yield 0.3 g (16%). Purity (hplc) >99%. Transitions (°C) K 187.1 N 284.2 Iso.

*H NMR CD₂Cl₂/δ 7.96 (1H, d), 7.95 (2H, d), 7.73 (2H, d),

7.63 (1H, d), 7.58 (2H, d), 7.56 (1H, dd), 7.30 (2H, d), 7.13 (1H, d), 2.66 (2H, t), 1.66 (2H, qui), 1.36 (4H, m), 0.91 (3H, t) IR (KBr) Vmax/cm'¹ 2933, 2859, 2229, 1497, 1122, 913, 803, 746

MS m/z 365(M⁺), 308, 277, 165, 43(100%)

Example 22

Preparation of Compound 49 in Table 1

Step l Preparation of 5-Bromobenzof blfuran-2-boronic acid

Dry diisopropylamine (2.0 g, 20 mmol) was added to n-butyllithium (2.5M in hexanes, 8 ml, 20 mmol) at -10 °C, and the mixture was stirred under nitrogen (20 min). 5-Bromobenzo[b]furan obtained as described in Example 9 step 2 (3.5 g, 18 mmol) in dry ether (35 ml) was added and the mixture stirred (2 h) at -10 °C under nitrogen. Trimethyl borate (3.7 g, 36 mmol) was added maintaining low temperature, and the mixture was allowed to return to room temperature with stirring under nitrogen. Hydrochloric acid (5M, 15 ml) was added with stirring. The mixture was then poured into water and ether added. The separated aqueous layer was washed with ether (2 x 50 ml) and the combined organic layers were washed with sodium hydroxide solution (10%, 30 ml). The separated aqueous layer was washed with light petroleum (40-60 °C fraction) and acidified to pH3 with hydrochloric acid (5M). It was then washed with ether (2 x 50 ml). The combined organic layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo.

A pale-orange solid was obtained. Yield 3.4 g (78%).

^XH NMR DMSO-d⁶/δ 8.62 (2H, s), 7.92 (1H, d), 7.56 (1H, d), 7.46 (1H, dd), 7.42 (1H, s)

MS m/z 196(M⁺-B(OH)₂), 165, 151 , 117, 89(100%),

Step 2

Preparation of l-Iodo-4-pentylbenzene l-Iodo-4-pentylbenzene was prepared and purified in a similar manner to that described in Example 1 step 1 using the following reagents:

Iodobenzene (20.4 g, 100 mmol), valeryl chloride (14.5 g, 120 mmol), aluminium chloride (14.7 g, 110 mmol), poly(methylhydrosiloxane) (16.0 g 267 mmol). A pale-yellow liquid was obtained.

Yield 14.4 g (53%), bp 105 °C at 0.01 mm Hg. ^XH NMR CDCl₃/δ 7.58 (2H, d), 6.93 (2H, d), 2.54 (2H, t),

1.58 (2H, m), 1.31 (4H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2962, 2862, 1486, 1118, 1065, 825, 795

MS m/z 274(M⁺), 217(100%), 203, 175, 89

Step 3 Preparation of 2-(4-pentylphenyl)-5-bromobenzofblfuran (Compound 49 in Table

U

Compound 49 was prepared and purified in a similar manner to that described in Example 1 step 4 using the following reagents: l-Iodo-4-pentylbenzene from step 2(3 g, 11 mmol), 5-bromobenzo[b]furan-2-boronic acid from step 1(1.3 g, 5 mmol), sodium carbonate (1.4 g, 13.5 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) The product was recrystallised from hexane. A white crystalline product was obtained. Yield 0.3 g (16%), mp 147-150 °C.

*H NMR CD₂Cl /δ 7.765 (2H, d), 7.71 (1H, dd), 7.41 (1H, d),

7.36 (1H, dd), 7.28 (2H, d), 6.96 (1H, d), 2.66 (2H, t), 1.65 (2H, qui), 1.34 (4H, m),

0.90 (3H, t) IR (KBr) Vmax/c "¹ 2932, 2860, 1610, 1583, 1162, 873, 795, 670,

508 MS m/z 344,342^), 287(100%), 274, 206, 152 Example 23 cvanophenvDbenzolblfuran)

Compound 50 was prepared in a similar manner to that described in Example 1 step 4 using the following reagents: d. Compound 49 (Example 22) (0.3 g, 0.9 mmol), benzonitrile-4-boronic acid (Example 19 step 1)(0.2 g, 1.0 mmol), sodium carbonate (0.2 g, 2 mmol), tetrakis(triphenylphosphine)palladium(0) (0.03 g, 0.03 mmol) The product was purified by flash chromatography [silica gel / hexane, propionitrile 40: 1], followed by recrystallisation (ethanol). A white solid was obtained. Yield 0.04 g (12%). Purity (hplc) 98%. Transitions (°C) K 133.8 N 230.5 Iso. ^l≡ NMR CD₂Cl₂/δ 7.74 1H, d), 7.73 (2H, d), 7.68 (4H, s), 7.53 (1H, d), 7.45 (1H, dd), 7.23 (2H, d),

6.99 (1H, d), 2.58 (2H, t), 1.58 (2H, qui), 1.27 (4H, m), 0.83 (3H, t)

IR (KBr) Vmax/cm"¹ 2927, 2854, 2226, 1607, 1463, 1153, 1125,

889, 841, 813 MS m/z 3650T^"), 308(100%), 264, 176, 154 Example 24

Preparation of Compound 35 in Table 1

Step l

Preparation of 5-(4-Pentylphenyl)benzofblfuran 5-(4-Pentylphenyl)benzo[b]furan was prepared in a similar manner to that described in Example 1 step 4 from the following reagents:

5-Bromobenzo[b]furan (Example 9 step 20 (2.5 g, 13 mmol), 4-pentylbenzeneboronic acid (Example 3 step 2) (2.9 g, 15 mmol), sodium carbonate (3.5 g, 33 mmol), tetrakis(triphenylphosphine)palladium(0) (0.5 g, 0.5 mmol) The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (hexane). Colourless plate-like crystals were obtained. Yield 1.2 g (35%), mp 62-64 °C.

*H NMR CD₂Cl₂/δ 7.54 (2H, d), 7.53 (1H, d), 7.52 (1H, dd), 7.27 (2H, d), 6.84 (1H, dd), 2.65 (2H, t),

1.66 (2H, qui), 1.36 (4H, m), 0.91 (3H, t)

IR (KBr) Vmax/cm"¹ 2958, 2931, 2858, 1516, 1131, 885, 845, 806, 771, 743

MS m/z 264(M⁺), 207(100%), 178, 165, 152

Step 2 Preparation of 5-(4-Pentylphenvπbenzofb1furan-2-boronic acid 5-(4-

Pentylphenyl)benzo[b]furan-2-boronic acid was prepared and purified in a similar manner to that described in Example 20 step 2 from the following reagents: 5-(4-Pentylphenyl)benzo[b]furan from step 1 (1.2 g, 5 mmol), n-butyllithium (2.5M in hexanes, 2 ml, 5 mmol), trimethyl borate (0.9 g, 9 mmol). A pale-pink solid was obtained.

Yield in g (84%). MS m/z 264(M⁺-B(OH)₂), 207(100%), 177, 151 , 127

Step 3

Preparation of 2-(4-CvanophenvD-5-(4^,-pentylphenyr)benzo[blfuran (Compound 35 in Table 1)

Compound 35 was prepared and purified in a similar manner to that described in Example 20 step 3 from the following reagents: Benzonitril-4-boronic acid (example 19 step 1) (0.7 g, 4 mmol), the product of step 2 above (1.1 g, 4 mmol), sodium carbonate (1.1 g, 10 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol). The product was recrystallised from carbon tetrachloride. Colourless, rhombic crystals were obtained.

Yield 0.4 g (30%).

Purity (hplc) 99.9%.

Transitions (°C) K 139.0 N 252.6 Iso

^JH NMR CD₂Cl₂/δ 7.99 (2H, d), 7.83 (1H, dd), 7.76 (2H, d), 7.62-7.57 (2H, m), 7.55 (2H, d), 7.29 (2H, d), 7.27 (2H, d), 2.66 (2H, t), 1.66 (2H, qui), 1.38-1.34 (4H, m), 0.92 (3H, t)

IR (KBr) Vmax/cm"¹ 2968, 2854, 2224, 1607, 1155, 842, 802

MS m/z 365(M⁺), 308(100%), 277, 252, 154 Example 25

Preparation of Compound 51 in Table 1

Step l

Preparation of 2-(4-Pentylphenoxy)acetaldehvde dimethyl acetal 2-(4-Pentylphenoxy)acetaldehyde dimethyl acetal was prepared and purified in a similar manner to that described in Example 8 step 1 using the following reagents;.

4-Pentylphenol (9.9 g, 60 mmol), bromoacetaldehyde dimethyl acetal (12.4 g, 73 mmol), potassium carbonate (20.8 g, 151 mmol), potassium iodide (0.6 g, 4 mmol).

A pale-yellow liquid was obtained. Yield 4.8 g (32%), bp 125 °C at 0.01 mm Hg.

*H NMR CD₂Cl₂/δ 7.08 (2H, d), 6.84 (2H, d), 4.72 (1H, t),

3.99 (2H, t), 3.46 (6H, s), 2.53 (2H, t), 1.57 (2H, qui), 1.31 (4H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 2936, 1616, 1514, 1247, 1139, 1081, 976, 827, 757

MS m/z 252(M⁺), 221, 149, 107, 75(100%) Step 2

Preparation of 5-Pentylbenzolblfuran

5-Pentylbenzo[b]furan was prepared and purified in a similar manner to that described in Example 8 step 2 from the following reagents; The product of step 1 above (4.8 g, 19 mmol), polyphosphoric acid (4.6 g). A colourless liquid was obtained.

Yield 2.2 g (62%), bp 125 °C at 0.1 mm Hg.

^XH NMR CD₂Cl₂/δ 7.61 (1H, d), 7.41 (1H, s), 7.40 (1H, d),

7.13 (1H, dd), 6.74 (1H, dd), 2.70 (2H, t), 1.65 (2H, qui), 1.35 (4H, m), 0.91 (3H, t)

IR (KBr) Vmax/c "¹ 2934, 2861, 1468, 1198, 1033, 881, 812, 764,

734 MS m/z 188(M⁺), 145, 131(100%), 115, 91

Step 3 Preparation of 5-Pentylbenzofblfuran-2-boronic acid

The product of step 2 (2.2 g, 12 mmol), n-butyllithium (2.5M in hexanes, 5.2 ml, 13 mmol), trimethyl borate (2.59 g, 24 mmol) were reacted using a method analogous to that described in Example 20 step 2 to yield the title compound.

A pale-orange solid was obtained. Yield 2.7 g (97%).

MS m/z 232(M⁺), 187, 174, 146, 130(100%),

Step 4

Preparation of 4-Cyano-4⁾-iodobiphenyl

4-Cyano-4'-iodobiphenyl was prepared and purified in a similar manner to that described in Example 1 step 4 from the following reagents: p-Diiodobenzene (14.7 g, 44 mmol), benzonitrile-4-boronic acid (Example 19 step

1)(5.0 g, 34 mmol), sodium carbonate (21.6 g, 204 mmol), tetrakis(triphenylphosphine)palladium(0) (3.0 g, 3 mmol).

The product was recrystallised from ethanol. A white crystalline product was obtained.

Yield 1.0 g (10%), mp 174-176 °C (lit.[Pummerer, 1931 #158] 166 °C). ^lΕL NMR CD₂Cl₂/δ 7.83 (2H, d), 7.74 (2H, d), 7.68 (2H, d), 7.37 (2H, d)

IR (KBr) Vmax/cm"¹ 2227, 1604, 1477, 997, 853, 813, 561

MS m/z 3O50VT), (100%), 178, 151, 127, 75

Step 5 Preparation of 2-(4^,-CvanobiphenvO-5-pentylbenzo[b1furan (Compound 51 in Table 1)

Compound 51 was prepared and purified from the product of step 4 above (1.0 g, 3 mmol), the product of step 3 above (0.8 g, 4 mmol), sodium carbonate (0.9 g, 8 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol) in method analogous to that described in Example 20 step 3. The product was recrystallised from ethanol. Colourless, plate-like crystals were obtained. Yield 36 mg (2%). Purity (hplc) 99.5%. Transitions (°C) K 150.8 B 167.0 N 280.3 Iso.

^XH NMR CD₂Cl₂/δ 7.97 (2H, d), 7.79-7.75 (4H, m), 7.72 (2H, d), 7.44 (1H, d), 7.42 (1H, d), 7.15 (1H, dd), 7.09 (1H, d), 2.71 (2H, t), 1.67 (2H, qui), 1.38-1.33 (4H, m), 0.91 (3H, t) IR (KBr) Vmax/c ^"1 2927, 2858, 2229, 1603, 1493, 1465, 1189,

825, 802

MS m/z 365^), 322, 308(100%), 264, 154

Example 26

Preparation of Compound 52 in Table 1 Step l

Preparation of 2-Pentyl-5-bromobenzo[blfuran

2-Pentyl-5-bromobenzo[b]furan was prepared and purified in a similar manner to that described in Example 19 step 2 using the following reagents;

5-Bromobenzo[b]furan (Example 9 step 2) (12.0 g, 61 mmol), dry diisopropylamine (6.8 g, 67 mmol), n-butyllithium (2.5M in hexanes, 26.8 ml, 67 mmol), n-pentyl iodide

(24.2 g, 122 mmol).

A colourless liquid was obtained. Yield 2.6 g (16%), bp 198 °C at 0.6 mm Hg. *H NMR CD₂Cl₂/δ 7.61 (1H, dd), 7.30 (1H, d), 7.28 (1H, d),

6.36 (1H, s), 2.76 (2H, dt), 1.74 (2H, d),

1.37 (4H, m), 0.91 (3H, t) IR (KBr) Vmax/cm"¹ 2935, 2868, 1599, 1450, 1117, 1050, 948,

867, 671, 579 MS m/z 268,266(M⁺), 251, 223, 208(100%), 116

Step 2 Preparation of 2-Pentylbenzo[blfuran-5-boronic acid The title compound was prepared and purified from the product of step 1 (2.5 g, 9 mmol), magnesium (0.3 g, 11 mmol) and trimethyl borate (2.09 g, 19 mmol) in a similar manner to that described in Example 1 step 2. A pale-yellow solid was obtained. Yield in g (78%). MS m/z 642(3M⁺-3H₂O), 585, 255, 188, 131(100%)

Step 3

Preparation of 2-Pentyl-5-(4-(4^,-cvano)biphenvπbenzofblfuran (Compound 52 in

Table 11

Compound 52 was prepared and purified in a similar manner to that described in Example 1 step 4 from the product of step 3 above (1.7 g, 7 mmol), 4-cyano-4'- iodobiphenyl (Example 25 step 2) (1.7 g, 6 mmol), sodium carbonate (1.5 g, 14 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol). The reaction was carried out with exclusion of light. A white crystalline solid was obtained. Yield 0.1 g (5%).

Purity (hplc) 97.6%.

Transitions (°C) K 94.8 N 236.7 Iso.

^XH NMR CD₂Cl₂/δ 7.77-7.68 (9H, m), 7.48 (1H, dd), 7.47 (1H, d), 6.45 (1H, s), 2.78 (2H, t), 1.76 (2H, qui), 1.40-1.34 (4H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2935, 2860, 2228, 1604, 1466, 1120, 948, 829, 802 MS m/z 365(M⁺), 350, 322, 308(100%), 278

Example 27

Preparation of Compound 53 in Table 1 Step l

Preparation of Benzolblfuran-5-boronic acid

Benzo[b]furan-5-boronic acid was prepared and purified from 5- bromobenzo[b]furan (Example 9 step 2) (2.0 g, 10 mmol), magnesium (0.3 g, 12 mmol) and trimethyl borate (2.1 g, 20 mmol)in a similar manner to that described in Example 1 step 2.

A light-brown solid was obtained.

Yield 0.7 g (43%) MS m/z 432(3M⁺-3H₂O), 144(100%), 117, 89, 63

Step 2 Preparation of 4-(4'-Pentylcvclohexyl)phenyl trifluoromethanesulphonate

Trifluoromethanesulphonic anhydride (6.5 g, 23 mmol) was added dropwise to a stirred, cooled (0 °C) solution of 4-(trø«s-n-yentylcyclohexyl)phenol (5.0 g, 20 mmol) in dry pyridine (80 ml) under dry nitrogen. The mixture was stirred at room temperature overnight. It was then poured into water and ether added. The separated aqueous layer was washed with ether (2 x 100 ml). The combined organic layers were washed with water, hydrochloric acid (10%) (twice), and brine, dried (MgSO4), and the solvent removed in vacuo. The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), dichloromethane 7:3] A pale yellow oil was obtained. Yield 5.2 g (69%).

^XH NMR CD₂Cl₂/δ 7.21 (2H, d), 7.10 (2H, d), 2.44 (1H, tt),

1.82-1.81 (2H, m), 1.78-1.77 (2H, m), 1.38- 1.36 (1H, m), 1.34-1.31 (1H, m), 1.26-1.12 (9H, m), 1.02-0.99 (1H, m), 0.96-0.93 (1H, m), 0.81 (3H, t)

IR (KBr) Vmax/cm"¹ 2929, 2858, 1503, 1427, 1143, 1018, 837,

740, 607 MS m/z 378(M⁺), 307, 252, 175, 69(100%)

Step 3

Preparation of 5-(4^,-Pentylcvclohexyl-4-phenyl)benzofblfuran

5-(4'-Pentylcyclohexyl-4-phenyl)benzo[b]furan, a compound of formula (IXA), was prepared and purified in a similar manner to that described in Example 1 step 4 from the following reagents: the product of step 2 above (3.4 g, 9 mmol), the product of step 1 above (1.6 g, 10 mmol), sodium carbonate (2.4 g, 23 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) Volatiles were removed by heating (95 °C) in vacuo (12 h). A white solid was obtained.

Yield in g (61%).

Transitions (°C) K 116.3 N 153.7 Iso. ^l≡ NMR CD₂Cl₂/δ 7.80-7.79 (1H, m), 7.67 (1H, d), 7.56-7.51 (4H, m), 7.30 (2H, d), 6.84 (1H, dd), 2.53

(1H, tt), 1.94-1.88 (4H, m), 1.48 (2H, ddd), 1.35-1.22 (9H, m), 1.08 (2H, ddd), 0.91 (3H, t) IR (KBr) Vmax/cm"¹ 3124, 2924, 2853, 1463, 1131, 1027, 883,

742, 697 MS m/z 346(M⁺), 331, 303, 275, 233(100%)

Step 4

Preparation of 5-(4^,-Pentylcvclohexyl-4-phenyl)benzo[blfuran2-carboxylic acid (Compound 53)

Compound 53 was prepared and purified from the product of step 3 (1.9 g, 5.5 mmol) and n-butyllithium (2.5M in hexanes, 2.4 ml, 6.1 mmol) in a similar manner to that described for in Example 8 step 3. A white solid was obtained. Yield 2.0 g (79%). Transitions (°C) K 183 N 299 Iso. *H NMR CD₂Cl₂/δ 7.79 (1H, dd), 7.59 (1H, dd), 7.54 (1H, d),

7.47 (2H, d), 7.45 (1H, d), 7.23 (2H, d), 2.45-2.42 (1H, m), 1.85-1.80 (4H, m), 1.43 (2H, ddd), 1.27-1.13 (9H, m), 1.00 (2H, ddd), 0.82 (3H, t)

IR (KBr) Vmax/cm"¹ 2929, 2853, 1691, 1566, 1173, 813

MS m/z 390(M⁺), (100%), 346, 333, 264, 189

Example 28 Preparation of Compound 54 in Table l(5-(4^,-Pentylcyclohexyl-4- phenyl)benzofblfuran2-carboxamide)

Compound 54 was prepared and purified in a similar manner to that described in Example 1 step 6 using the following reagents:

Compound 53 (Example 27) (2.0 g, 4.3 mmol), thionyl chloride (1.5 g, 13 mmol), ammonia, (d 0.880, 2.9 ml).

Fibrous white needle-like crystals were obtained.

Yield 1.1 g (66%).

Transitions (°C) K 275 N 296 Iso. H NMR CD₂Cl /δ, DMSO-d⁶/δ 7.83 (1H, d), 7.63 (1H, dd), 7.56 (1H, d), 7.53 (2H, d), 7.46 1H, d),

6.92 (1H, s), 6.54 (1H, s), 2.42- 2.35 (1H, m), 1.91-1.85 (4H, m), 1.47 (2H, ddd), 1.32-1.20 (9H, m), 1.05 (2H, ddd), 0.88 (3H, t) IR (KBr) Vmax/cm"¹ 3393, 3170, 2928, 2852, 1675, 1615,

1168, 817 MS m/z 389(M⁺), 316, 301, 250, 58(100%)

Example 29

Preparation of 2-Cvano-5-(4^,-trans-pentylcvclohexyl-4-phenyl)benzoIbIfuran (Compound 54 in Table 1)

Compound 54 was prepared and purified in a similar manner to that described in Example 1 step 7 from compound 54 (Example 28) (1.0 g, 2.6 mmol) and thionyl chloride (3.2 g, 26 mmol). The product was recrystallised from ethanol. Yield 0.5 g (52%).

Purity (hplc) >99%. Transitions (°C) K 113.0 N 240.7 Iso. 1 H NMR CD₂Cl₂/δ 7.86 (1H, dd), 7.75 (1H, dd), 7.61 (1H, dt), 7.55 (1H, d), 7.54 (2H, d), 7.32 (2H, d), 2.53 (1H, tt), 1.93-1.87 (4H, m), 1.56- 1.44 (4H, m), 1.35-1.19 (7H, m), 1.08 (2H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2925, 2854, 2234, 1558, 1515, 1462, 1178,

1128,950,887

MS m/z 371(M⁺)(100%), 300, 245, 232, 189

Example 30 Preparation of Compound 56 in Table 1

Step l

Preparation of Ethyl 5-methoxybenzo[blfuran-2-carboxylate Ethyl 5- methoxybenzo[b]furan-2-carboxylate was prepared and purified from 5- methoxysalicylaldehyde (20.0 g, 131 mmol), diethyl bromomalonate (26.3 g, 110 mmol), potassium carbonate (32.5 g, 236 mmol), potassium iodide (0.9 g,

6 mmol), in a similar manner to that described in Example 1 step 3.

Colourless cubic crystals were obtained.

Yield 14.5 g (50%), mp 58-59.5 °C, bp 150 °C at 0.02 mm Hg.

*H NMR CD₂Cl₂/δ 7.47 (1H, ddd), 7.45 (1H, d), 7.09 (1H, d), 7.06 (1H, dd), 4.39 (2H, q), 3.83 (3H, s),

1.40 (3H, t)

IR (KBr) Vmax/cm"¹ 2988, 1721, 1560, 1195, 940, 846, 822

MS m/z 220^), (100%), 205, 192, 175, 119

Step 2 Preparation of 5-Methoxybenzolblfuran-2-carboxylic acid

The title compound was prepared and purified from the product of step 1 (14.5 g, 66 mmol) and potassium hydroxide (7.3 g, 130 mmoι)in a similar manner to that described in Example 1 step 5. Colourless crystals were obtained. Yield 6.1 g (48%).

Transitions (°C) K 208 N 221 Iso. *H NMR CD₂C1₂, DMSO-d⁶/δ 11.5 (1H, s), 7.41 (1H, d), 7.38 (1H, d), 7.06 (lh, d), 7.00 (1H, dd), 3.78 (3H, s)

IR (KBr) Vmax/cm"¹ 2953, 1689, 1566, 1160, 943, 898, 850, 797

MS m/z 192(Tvf)(100%), 177, 162, 149, 107

Step 3

Preparation of 5-Methoxybenzof blfuran-2-carboxamide

The title compound was prepared and purified from the product of step 2 (6.0 g, 31 mmol), thionyl chloride (11.0 g, 93 mmol) and ammonia (d 0.880, 11.0 ml) in a similar manner to that described in Example 1 step 6. Colourless plate-like crystals were obtained.

Yield 4.6 g (78%).

^XH NMR CD₂Cl₂/δ 7.42 (2H, d), 7.40 (1H, s), 7.11, (1H, d), 7.04 (1H, dd), 6.53 (1H, s, br), 5.94 (1H, s, br), 3.84 (3H, s)

IR (KBr) Vmax/cm"¹ 3451, 3138, 1692, 1608, 1476, 1156, 854, 833

MS m/z 191(M⁺)(100%), 175, 159, 148, 133

Step 4 Preparation of 2-Cvano-5-methoxybenzofblfuran

The product of step 3 (4.8 g, 25 mmol) and thionyl chloride (14.3 g, 120 mmol) were converted to the title compound in a similar manner to that described in Example 1 step 7.

The product was recrystallised from methanol. White needle-like crystals were obtained.

Yield 1.5 g (36%), mp 79.5-80 °C.

*H NMR CD₂Cl₂/δ 7.46 (1H, ddd), 7.44 (1H, dd), 7.12 (1H, dd), 7.09 (1H, d), 3.84 (3H, s)

IR (KBr) Vmax/cm"¹ 2949, 2842, 2231, 1596, 1475, 1211, 1185, 949, 877, 750

MS m/z 173(M⁺), (100%), 158, 130, 102, 75 Step 5

Preparation of 2-Cvano-5-hvdroxybenzo[blfuran

A mixture of the product of step 4 (0.7 g, 4 mmol) and pyridinium chloride (4.6 g, 40 mmol) was refluxed (3 min). The reaction mixture was then poured into ice / water. The product was extracted into ether (2 x 200 ml), and the combined organic extracts were washed with water and brine and dried (MgSO4), and the solvent removed in vacuo. The product was recrystallised from ethanol. Colourless crystals were obtained. Yield 0.5 g (80%). Step 6

Preparation of 2-CvanobenzoFblfuran-5-trans-(oxycarbonyl-4-pentylcyclohexane) (Compound 56 in Table 1)

The product of step 5 (0.5 g, 3 mmol) and tra«s-4-pentylcyclohexylcarboxylic acid (0.6 g, 3 mmol) were dissolved in dry dichloromethane (30 ml) and (4-N,N- dimethylamino)pyridine (0.1 g, 1 mmol) was added, and the mixture stirred. N,N'- Dicyclohexylcarbodiimide (0.6 g, 3 mmol) was then added, and stirring was continued (24 h). The reaction was monitored by tic analysis. The precipitate of N,N'- dicyclohexylurea was filtered off, and the solvent removed in vacuo. The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), dichloromethane 7:3], followed by recrystallization (ethanol). A white crystalline solid was obtained. Example 31

Preparation of Compound 100 in Table 2 Step l Preparation of 4-Bromo(2_<2-dimethoxy)ethyl sulphanylbenzene

Sodium (13.8 g, 600 mmol) was added to superdry ethanol (400 ml) with stirring under nitrogen. 4-Bromothiophenol (compound 102) (103.3 g, 546 mmol) was added and stirring was continued (5 min). Bromoacetaldehyde dimethyl acetal (120.0 g, 709 mmol) was then added and the mixture refluxed overnight with stirring under nitrogen. The mixture was then washed with dichloromethane (3 x 100 ml). The combined washings were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. The residue was purified by distillation. A colourless oil was obtained. Yield 104.3 g (69%) bp 132 °C at 2 mm Hg. *H NMR CDCl₃/δ 7.39 (2H, d), 7.24 (2H, d), 4.5 (1H, t),

3.36 (6H, s), 3.08 (2H, d) IR (KBr) Vmax/cm"¹ 2930, 2830, 1470, 1120, 1090, 800, 480 MS m/z 278,276(M⁺), 247, 215, 201, 189, 75(100%)

Step 2 Preparation of 5-Bromobenzofblthiophene

The product of step 1, (104.3 g, 376 mmol) and polyphosphoric acid (156.2 g)were converted to 5-bromobenzo[b]thiophene in Example 8 step 2. A white crystalline solid was obtained.

Yield 12.0 g (15%), mp 46-47 °C (lit⁴ 47-48 °C). ^XH NMR CD₂Cl₂/δ 7.98 (1H, d), 7.77 (1H, d), 7.52 (1H, d),

7.44 (1H, dd), 7.30 (1H, dd) IR (KBr) Vmax/cm"¹ 3080, 1576,1399, 898, 807, 472 MS m/z 214,212(M⁺), 133(100%), 106, 89, 81

Step 3 Preparation of 5-(4-Heptylphenyl)benzo[blthiophene

The product of step 2 (4.6 g, 22 mmol), 4-heptylbenzeneboronic acid (Example 1 step 2) (5.7 g, 26 mmol), sodium carbonate (5.8 g, 55 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.8 g, 0.7mmol) were treated as described in Example 1 step 4 to give the title compound. A colourless was obtained, which solidified on cooling.

Yield 4.8 g (71%), bp 225 °C at 0.01 mm Hg. H NMR CD₂Cl /δ 7.95 (1H, d), 7.85 (1H, d), 7.51 (1H, dd), 7.50 (2H, d), 7.42 (1H, d), 7.31 (1H, dd),

7.20 (2H, d), 2.57 (2H, t), 1.57 (2H, qui), 1.28-1.20 (8H, m), 0.81 (3H, t)

IR (KBr) Vmax/c "¹ 2929, 2857, 1496, 1089, 899, 805, 757

MS m/z 308O , 252, 223(100%), 167, 58 Step 4

Preparation of 5-(4-Heptylphenyl)benzofblthiophene-2-carboxylic acid

(Compound 100 in Table 2)

Compound 100 was prepared and purified in a similar manner to that described in Example 8 step 3 using the following reagents: the product of step 3 above (2.5 g, 8 mmol) and n-butyllithium (2.5M in hexanes, 3.4 ml, 9 mmol).

A white solid was obtained.

Yield 1.1 g (39%), mp 164-170 °C. H NMR CD₂Cl₂,DMSO-d⁶/δ 8.05 (1H, d), 8.02 (1H, s), 7.90 (1H, d), 7.68 (1H, dd), 7.55 (2H, d), 7.26 (2H, d), 2.63 (2H, t), 1.62 (2H, qui), 1.32-1.23 (8H, m), 0.86 (3H, t) (acidic proton signal was not shown) IR (KBr) Vmax/cm"¹ 3010, 2931, 2855, 1690, 1547, 1514,

1165, 803, 757, 700

MS m/z 3520T^"), 281, 267(100%), 221, 208

Example 32

Preparation of 5- 4-Heptylphenyl)benzofblthiophene-2-carboxamide (Compound 101 in Table 2)

Compound 101 was prepared and purified in a similar manner to that described in Example 1 step 6 from compound 57 (Example 31)(1.1 g, 3 mmol), thionyl chloride

(1.1 g, 9 mmol) and ammonia (d 0.880, 1.1 ml).

A white crystalline solid was obtained. Yield 1.8 g (92%), mp 204-205 °C.

*H NMR CD₂Cl₂/δ 8.06 (1H, d,), 7.93 (1H, d), 7.81 (1H, s),

7.70 (1H, dd), 7.58 (2H, d), 7.30 (2H, d), 2.66 (2H, t), 1.65 (2H, qui), 1.36-1.26 (8H, m), 0.89 (3H, t) (H-bonded proton signals were not shown)

IR (KBr) Vmax/cm"¹ 3399, 3187, 2927, 2855, 1643, 1609, 1512, 1172, 800 MS m/z 351 (M⁺), 279, 266( 100%), 248, 221

Example 33

Preparation of 2-Cvano-5-(4-heptylphenyl)benzo[blthiophene (Compound 102 in Table 2)

Compound 102 was prepared and purified in a similar manner to that described in Example 1 step 7 from Compound 61 (Example 31) (1.0 g, 3 mmol), thionyl chloride (3.3 g, 28 mmol). A white crystalline solid was obtained. Yield 0.4 g (43%), mp 93.2 °C.

*H NMR CD₂Cl₂/δ 8.1 (1H, d), 7.97 (1H, d), 7.94 (1H, d),

7.80 (1H, dd), 7.57 (2H, d), 7.31 (2H, d), 2.66 (2H, t), 1.65 (2H, qui), 1.35-1.30 (8H, m), 0.89 (3H, t) Example 34

Preparation of 4-Heptylphenyl 5-(4-heptylphenyl)benzofblfuran-2-carboxylate

(Compound 5 in Table 1)

Step l

Preparation of 4-Heptylphenol Hydrogen peroxide (100 vol, 387 ml, 3.39 mol) was added slowly to a stirred solution of 4-heptyl benzeneboronic acid (15.8 g, 72.0 mmol) in dry diethyl ether (100 ml) and the mixture was refluxed (2 h). After allowing to cool, the mixture was washed with ether (3 x 150 ml). The combined ethereal layers were washed with saturated sodium sulphite solution and shaken with aqueous sodium hydroxide (2M). The white precipitate was filtered off and washed with petroleum fraction (bp 40-60 °C), and then adjusted to pH 3 with hydrochloric acid (cone). The product was extracted by washing with ether (3 x 150 ml). The combined organic layers were washed with brine and dried (MgSO4), and the solvent removed in vacuo. The residue was purified by distillation. A colourless liquid was obtained.

Yield 4.4 g (32 %) bp 115 °C at 0.03 mmHg (lit.¹ 65°C).

*H NMR CDCl₃/δ 7.02 (2H, d), 6.76 (2H, d), 5.10 (1H, s), 2.53 (2H, d) 1.56 (2H, m), 1.31 (8H, m), 0.87 (3H, t) IR (KBr) Vmax/cm"¹ 3340, 2925, 1615, 1515, 1175, 830, 760

MS m/z 192(M⁺) 120, 107, 91, 43(100%) Step 2

Preparation of Compound 5 in Table 1

5-(4-Heptylphenyl)benzo[b]furan-2-carboxylic acid (1.0 g, 3 mmol), prepared as described in Example 1 step 5 and the product of step 1 above (0.6 g, 3 mmol) were dissolved in dry DCM (100 ml) and DMAP (0.4 g, 3 mmol) was added, and the mixture stirred. DCC (0.6 g, 3 mmol) was then added, and stirring was continued (24 h). The reaction was monitored by tic analysis. The precipitate of dicyclohexylurea was then filtered off, and the solvent removed in vacuo. The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), DCM 7:3], followed by recrystallization (hexane).

A white solid was obtained.

Yield 0.8 g (52%). Purity (hplc) 99%. H NMR CD₂Cl₂/δ 7.91 (1H, dd), 7.75 (1H, d), 7.73 (1H, dd), 7.67 (1H, d), 7.54 (2H, d), 7.28 (2H, d), 7.25 (2H, d), 7.14 (2H, d), 2.65

(2h, t), 2.63 (2H, t), 1.64 (4H, m), 1.31 (16H, m), 0.88 (6H, t)

TR (KBr) Vmax/cm"¹ 2920, 1734, 1578, 802

MS m/z 510(M⁺), 481, 425, 319(100%), 191 Example 35

Preparation of 4-Butoxyphenyl 5-(4-heptylphenyl)benzof blfuran-2-carboxylate (Compound 7 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated. 5-(4-Heptylphenyl)benzo[b]furan-2-carboxylic acid (0.5 g, 1.5 mmol), 4-butoxyphenol (0.3 g, 1.5 mmol), DMAP (0.2 g, 1.5 mmol), DCC (0.3 g, 1.5 mmol). The product was obtained as a white, crystalline solid. Yield 0.4 g (52%). Purity (hplc) >98%. ^XH NMR CDCl₃/δ 7.89 (1H, dd), 7.75 (1H, s), 7.72 (1H, dd), 7.67 (1H, d), 7.54 (2H, d), 7.29 (2H, d), 7.17 (2H, d), 6.95 (2H, d), 3.98 (2H, t), 2.66 (2H, t), 1.79 (2H, qui),

1.66 (2H, qui) 1.49 (2H, qui), 1.32 (8H, m), 0.99 (3H, t), 0.89 (3H, t)

»

IR (KBr) Vmax/cm"¹ 2925, 1734, 1502, 1160, 948, 804

MS m/z 484(M ), 319, 264, 166, 69(100%) Example 36

Preparation of 4-Hexyloxyphenyl 5-(4-heptylphenyl)benzorblfuran-2-carboxylate (Compound 8 in Table 1)

The title compound was prepared and purified in a similar manner to that described in Example 34 using the quantities stated. 5-(4-Heptylphenyl)benzo[b]furan-2-carboxylic acid (0.5 g, 1.5 mmol), 4- hexyloxyphenol (0.3 g, 1.5 mmol), DMAP (0.2 g, 1.5 mmol), DCC (0.3 g, 1.5 mmol). A white, crystalline solid was obtained.

Yield 0.3 g (40%). Purity (hplc) >99.9%.

^XH NMR CD₂Cl₂/δ 7.93 (1H, dd), 7.77 (1H, d), 7.75 (1H, dd), 7.68 (1H, d) 7.56 (2H, d), 7.29 (2H, d), 7.16 (2H, d), 6.96 (2H, d) 3.98 (2H, t), 2.66 (2Ht), 1.79 (2H, qui), 1.64 (2H, qui), 1.48 (2H, qui), 1.34 (12H, m), 0.93 (3H, t), 0.89 (3H, t) IR (KBr) Vmax/cm"¹ 2933, 2858, 1733, 1502, 1310, 1199, 1160,

1072, 948, 803 MS m/z 512^), 482, 427, 398, 178(100%) Example 37

Preparation of 4-Pentylphenyl 5-(4-heptylphenyl)benzo[bIfuran-2-carboxylate

(Compound No. 66 in Table 1)

The title compound was prepared and purified in a similar manner to that described in Example 34 using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-carboxylic acid (0.5 g, 1.5 mmol), 4-pentylphenol (0.3 g, 1.5 mmol), DMAP (0.2 g, 1.5 mmol), DCC (0.3 g, 1.5 mmol). A white, crystalline solid was obtained.

Yield 0.2 g (30%). Purity (hplc) 97.6%. ^XH NMR CD₂Cl₂/δ 7.93 (1H, dd), 7.77 (1H, d), 7.75 (1H, dd), 7.69 (1H, d), 7.56 (2H, d), 7.30 (2H, d), 7.27 (2H, d), 7.15 (2H, d), 2.67 (2H, t), 2.64 (2H, t), 1.65 (4H, m), 1.33 (12H, m) 0.91 (3H, t), 0.89 (3H, t) IR (KBr) Vmax/cm"¹ 2958, 2921, 2852, 1732, 1303, 1221, 1161,

803, 741 MS m/z 482(M⁺), 397, 319(100%), 263, 178

Example 38

Preparation of (S)-(+)-4-(2-Methylbutyl)phenyl 5-(4-heptylphenyl)benzofblfuran- 2-carboxylate (Compound 11 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-carboxylic acid (0.5 g, 1.5 mmol), (S)-(+)-4-(2- methylbutyl)ρhenol (0.3 g, 1.5 mmol) DMAP (0.2 g, 1.5 mmol) , DCC (0.3 g, 1.5 mmol).

A white, crystalline solid was obtained.

Yield 0.5 g (75%). Purity (hplc) 99.1%. H NMR CD₂Cl₂/δ 7.93 (1H, dd), 7.77 (1H, d), 7.75 (1H, dd), 7.69 (1H, d),

7.56 (2H, d), 7.29 (2H, d), 7.24 (2H, d), 7.16 (2H, d), 2.68(1H, dd), 2.66 (2H, t), 2.41 (1H, dd), 1.66 (3H, m),

1.32 (10H, m), 0.93 (3H, t), 0.89(3H, t), 0.87 (3H, d) IR (KBr) Vmax/cm"¹ 2965, 2858, 1735, 1569, 1502, 1294, 1075,

950, 807, 745 MS m/z 4820VT), 397, 319(100%), 267, 178

[α]-f +5.0° (0.01947 g/ml) Example 39

Preparation of (S)-(+)-l-Methylheptyl 5-(4-heptylphenyl)benzofblfuran-2- carboxylate (Compound 62 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated. 5-(4-Heptylphenyl)benzo[b]ftιran-2-carboxylic acid (0.5 g, 1.5 mmol), (S)-(+)-octan-2- ol (0.2 g, 1.5 mmol), DMAP (0.2 g, 1.5 mmol), DCC (0.3 g, 1.5 mmol). A colourless oil was obtained.

Yield 0.5 g (74%). Purity (hplc) 99.7%.

^XH NMR CD₂Cl₂/δ 7.85 (1H, dd), 7.68 (1H, dd), 7.61 (1H, d), 7.53 (1H, d) 7.52 (2H, d), 7.27 (2H, d), 5.17 (1H, m),

2.64 (2H, t), 1.75(2H, m), 1.62 (2H, m), 1.33 (19H, m), 0.88 (3H, t), 0.87 (3H, t) IR (KBr) Vmax/cm"¹ 2929, 2856, 1719, 1539, 1461, 1245, 1165, 847, 803,

597 MS m/z 448(M⁺), 363, 336, 251, 57(100%)

\a\ +43.3° (0.01878 g/ml)

Example 40

Preparation of Preparation of Methyl 5-(4-heptylphenyl)benzo[b1furan-2- carboxylate (Compound 24 in Table 1) A mixture of compound Compound 43 in Table 1(0.1 g, 0.3 mmol) and sulphuric acid (cone.) (0.1 ml, 2.0 mmol) in methanol (5 ml) was refluxed (24 h) with exclusion of moisture. After allowing to cool, the mixture was poured into water (20 ml) and DCM added (20 ml) The separated aqueous layer was washed with DCM (2 x 20 ml). The combined organic layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo. The product was purified by recrystallization (hexane). A white crystalline solid was obtained.

Yield 0.1 g (95%). Purity (hplc) >99.5%.

^XH NMR CD₂Cl₂/δ 7.88 (1H, d), 7.70 (1H, dd), 7.64 (1H, d), 7.57 (1H, d), 7.53 (2H, d), 7.28 (2H, d), 3.95 (3H, s), 2.66 (2H, s), 1.65 (2H, qui), 1.32 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2930, 2856, 1736, 1565, 1438, 1164, 1099,

898, 847, 767 MS m/z 350(M⁺), 293, 265(100%), 177, 165

Example 41 Preparation of Ethyl 2-(4-heptylphenyl)benzofb1furan-5-carboxylate (Compound 64 in Table 1)

Compound 64 was prepared and purified in a similar manner to that described for the preparation of compound 24 using the quantities stated. Compound 63 in Table 1 (0.1 g, 0.3 mmol), sulphuric acid (cone.) (0.1 ml, 0.05 mmol), ethanol (5 ml).

Colourless needle-like crystals were obtained.

Yield 0.05 g (46%). Purity (hplc) >99%.

^XH NMR CD₂Cl₂/δ 8.30 (1H, d), 7.99 (1H, dd), 7.79 (2H, d), 7.55 (1H, d),

7.30 (2H, d), 7.06 (1H, d), 3.67 (2H, q), 2.66 (2H, t),1.65 (2H, qui), 1.14 (3H, t), 1.30 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2929, 2856, 1708, 1616, 1509, 1445, 1172,

1019, 817

MS m/z 364(M⁺), 279, 251, 203, 91(100%),

Example 42 Preparation of 4-Pentylphenyl 2-(4-heptylphenyl)benzo[blfuran-5-carboxylate

(Compound 65 in Table 1)

The title compound was prepared and purified in a similar manner to that described for the preparation of compound 5 in Table 1 in Example 34 using the quantities stated. Compound 63 in Table 1 (0.3 g, 0.9 mmol), 4-pentylphenol (0.2 g, 0.9 mmol), DCC

(0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). Colourless crystals were obtained.

Yield 0.3 g (67%). Purity (hplc) 97.1%.

*H NMR CD₂Cl₂/δ 8.46 (1H, d), 8.12 (1H, dd), 7.81 (2H, d), 7.62 1H, d), 7.31 2H, d), 7.26 (2H, d), 7.13 (2H, d), 7.11 (1H, d), 2.67 (2H, t), 2.65 (2H, t), 1.65 (4H, qui),

1.32 (14H, m), 0.91 (3H, t), 0.89 (3H, t) TR (KBr) Vmax/cm"¹ 2930, 2857, 1736, 1510, 1155, 1065, 913,

803, 761 MS m/z 4820 , 397, 369, 319(100%), 205 Example 43

Preparation of 4-Heptylphenyl 2-(4-heptylphenyl)benzo[blfuran-5-carboxylate (Compound 19 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated. Compound 63 in Table 1 (0.3 g, 0.9 mmol), 4-heptylphenol (0.2 g, 0.9 mmol), DCC (0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). A white solid was obtained.

Yield 0.3 g (65%). Purity (hplc) 99.1%.

*H NMR CD₂Cl₂/δ 8.46 (1H, dd), 8.13 (1H, dd), 7.81 (2H, d), 7.62 (1H, d), 7.31 (2H, d), 7.26 (2H, d), 7.13 (2H, d), 7.11 (1H, d),

2.66 (2H, t), 2.65 (2H, t), 1.65 (4H, m), 1.32 (16H, m), 0.90 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2929, 2857, 1737, 1510, 1465, 1156, 1065,

914, 838, 761 MS m/z 510(M⁺), 425, 318(100%), 220, 205

Example 44

Preparation of 4-Butoxyphenyl 2-(4-heptylphenyl)benzo[blfuran-5-carboxylate (Compound 20 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated. Compound 63 in Table 1 (0.3 g, 0.9 mmol), 4-butoxyphenol (0.2 g, 0.9 mmol), DCC (0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). A white solid was obtained.

Yield 0.3 g (69%). Purity (hplc) >99%. ^XH NMR CD₂Cl₂/δ 8.45 (1H, dd), 8.12 (1H, dd), 7.81 (2H, d), 7.62 (1H, d), 7.31 (2H, d), 7.13 (2H, d), 7.10 (1H, s), 6.94 (2H, d), 3.99 (2H, d), 2.67 (2H, t), 1.78 (2H, qui), 1.65 (2H, qui), 1.51 (2H, m), 1.30 (8H, m), 0.99 (3H, t), 0.86 (3H, t) IR (KBr) Vmax/cm"¹ 2930, 2858, 1742, 1616, 1510, 1468, 1156,

1068, 913, 803, 761 MS m/z 484(M⁺), 399, 319(100%), 206, 57

Example 45

Preparation of 4-Hexyloxyphenyl 2-(4-heptylphenyl)benzofb1furan-5-carboxylate (Compound 21 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated.

Compound 63 in Table 1 (0.3 g, 0.9 mmol), 4-hexyloxyphenol (0.2 g, 0.9 mmol), DCC (0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). A white solid was obtained.

Yield 0.3 g (65%). Purity (hplc) >99%. ^lR NMR CD₂Cl₂/δ 8.43 (1H, d), 8.10 (1H, dd), 7.79 (2H, d), 7.60 (1H, d),

7.29 (2H, d), 7.12 (2H, d), 7.08 (1H, s), 6.92 (2H, d), 3.96 (2H, t), 2.65 (2H, t), 1.77 (2H, qui), 1.63 (2H, qui), 1.46 (2H, qui), 1.30 (12H, m), 0.90 (3H, t), 0.87 (3H, t)

IR (KBr) Vmax/cm"¹ 2930, 2859, 1743, 1615, 1513, 1469, 1159,

1066, 916, 835, 803 MS m/z 512(M⁺), 483, 427, 319(100%), 291

Example 46 Preparation of (S)-(+)-4-(2-Methylbutyl)phenyl 2-(4-heptylphenyl)benzofblfuran- 5-carboxylate (Compound 22 in Table 1) The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated.

Compound 63 in Table 1 (0.3 g, 0.9 mmol), 4-(2-methyl-n-butyl)phenol (0.2 g, 0.9 mmol), DCC (0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). White, fibrous crystals were obtained.

Yield 0.3 g (69%). Purity (hplc) 98.9%.

^XH NMR CD₂Cl /δ 8.46 (1H, d), 8.13 (1H, dd), 7.81 (2H, d), 7.62 (1H, d), 7.31 (2H, d), 7.23 (2H, d), 7.13 (2H, h), 7.11 (1H, d), 2.69 (3H, m), 2.41 (1H, m), 1.66 (3H, m), 1.32 (10H, m), 0.93 (3H, t), 0.89 (3H, t), 0.88 (3H, d)

TR (KBr) Vmax/cm'¹ 2933, 2858, 1728, 1509, 1124, 1064, 1015,

911, 835, 798, 760 MS m/z 482^), 397, 319(100%), 206, 57

[α]²D^° +4.0° (0.01796 g/ml) Example 47

Preparation of (S)-(+)-l-Methylheptyl 2-(4-heptylphenyl)benzo[b1furan-5- carboxylate (Compound 23 in Table 1)

The title compound was prepared and purified in a similar manner to that described for in Example 34 using the quantities stated. Compound 63 in Table 1 (0.3 g, 0.9 mmol), octan-2-ol_.(0.1 g, 0.9 mmol), DCC (0.2 g, 0.9 mmol), DMAP (0.1 g, 0.9 mmol). A white crystalline solid was obtained.

Yield 0.2 g (50%). Purity (hplc) 98.7%.

*H NMR CD₂Cl₂/δ 8.27 (1H, dd), 7.96 (1H, dd), 7.77 (2H, d), 7.52 (1H, d), 7.28 (2H, d), 7.04 (1H, d), 5.13 (1H, sxt), 2.64 (2H, t),

1.74 (2H, m), 1.61 (2H, m), 1.30 (19H, m), 0.87 (6H, m)

IR (KBr) Vmax/cm"¹ 2933, 2861, 1715, 1595, 1507, 1163, 1087,

797, 765 MS m/z 448(M⁺), 336, 319, 251, 43(100%), Example 48

Preparation of 2,5-Bis-(4-heptylphenyl)benzo[blfuran (Compound 66 in Table 1)

Step 1:- Preparation of 5-(4-Heptylphenyl)benzo[blfuran

The title compound was prepared in a similar manner to that described for the preparation of ethyl 5-(4-heptylphenyl)benzo {b} furan-2carboxylate in Example 1 (4) using the quantities stated.

Compound 5-bromobenzofuran (10.0 g, 51 mmol), 4-heptylbenzene boronic acid (13.4 g, 61 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol), sodium carbonate (13.5 g, 128 mmol). The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (petroleum fraction (bp 40-60 °C)) Colourless plates were obtained. Yield 7.5 g (50%), mp 51-3 °C

*H NMR CDCl₃/δ 7.77 (1H, d), 7.64 (1H, d), 7.55 (1H, d), 7.53 (2H, d), 7.51 (1H, dd), 7.26 (2H, d), 6.81 (1H, d),

2.65 (2H, t), 1.65 (2H, q), 1.34 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2921, 1463, 1130, 804, 743

MS m/z 2920 , 220207(100%), 178, 165,

Step 2 Preparation of 5-(4-Heptylphenyl)benzo[b1furan-2-boronic acid

The title compound was prepared in a similar manner to that described for the preparation of 4'-pentylbiphenylboronic acid in Example 20(2) using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan from step 1 (4.0 g, 13.7 mmol), n-butyllithium (2.5M in hexanes, 4.5 ml, 11.3 mmol), trimethyl borate (2.9 g, 27.4 mmol). A pale-pink solid was obtained.

Yield 4.6 g (99%) H NMR CDCl₃/δ 7.82 (1H, d), 7.59 (1H, dd), 7.55 (1H, d), 7.53 (2H, d), 7.41 (1H, d), 7.26 (2H, d), 4.94 (2H, s), 2.65 (2H, t), 1.65 (2H, m), 1.33 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 3400, 2930, 2850, 1575, 1445, 1330, 1010, 805 MS m/z 336 VT), 292, 207(100%), 178, 107

Step 3 Preparation of 2,5-Bis-(4-heptylphenyl)benzo[blfuran (Compound 66) Compound 66 was prepared in a similar manner to that described in Example

1(4) using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-boronic acid (1.5 g, 4.5 mmol), l-bromo-4- heptylbenzene, (0.8 g, 3.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (1.0 g, 9.3 mmol). The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), DCM 9:1], followed by recrystallization (acetonitrile, toluene 5:1) A colourless crystalline solid was obtained

Yield 0.4 g (26%). Purity (hplc) 98.6%.

^XH NMR CD₂Cl₂/δ 7.78 (2H, d), 7.75 (1H, dd), 7.54 (2H, d), 7.53 (1H, d), 7.48 (1H, dd), 7.28(2H, d), 7.24 (2H, d),

7.03 (1H, d) 2.53 (4H, t), 1.52 (4H, m), 1.06 (16H, m), 0.57 (6H, t) TR (KBr) Vmax/cm"¹ 2920, 1465, 1160, 1015, 845, 800

MS m/z 466(M⁺), (100%), 381, 309, 296, 252 Example 49

Preparation of 5-(4-Heptylphenyl)-2-(4-pentylphenyl)-benzofblfuran (Compound 67 in Table 1)

The title compound was prepared and purified in a similar manner to that described for the preparation of compound 66 as described in Example 48 using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-boronic acid (1.5 g, 4.5 mmol), l-bromo-4- pentylbenzene, (0.8 g, 3.7 mmol), tetrakis(tiiphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (1.0 g, 9.3 mmol). A white crystalline solid was obtained. Yield 0.4 g (20%). Purity (hplc) 98.5%.

*H NMR CD₂Cl₂/δ 7.80 (2H, d), 7.77 (1H, dd), 7.55 (2H, d), 7.54 (1H, d), 7.50 (1H, dd), 7.29 (2H, d), 7.27 (2H, d), 7.05 (1H, d), 2.67 (2H, t), 2.66 (2H, t), 1.66 (4H, m), 1.33 (12H, m), 0.91 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/cm^"1 2961, 2857, 1465, 908, 801 MS m/z 438(M⁺), 381, 353, 296(100%), 283

Example 50

Preparation of 2-(5-Heptylpyrimidin-2-yl)-5-(4-heptylphenyl)benzorblfuran (Compound 68 in Table 1)

The title compound was prepared and purified in a similar manner to that described in Example 1(4) using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-boronic acid (1.5 g, 4.5 mmol), 2-chloro-5- heptylpyrimidine (0.8 g, 3.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (1.0 g, 9.3 mmol).

The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), DCM 1: 1], followed by recrystallization (hexane). Colourless needles-like crystals were obtained. Yield 0.8 g (46%). Purity (hplc) >99.9%.

^JH NMR CDCl₃/δ 8.67 (2H, s), 7.85 (1H, d), 7.69 (1H, d),

7.69 (1H, d), 7.60 (1H, dd), 7.55 (2H, d), 7.28 (2H, d), 2.68 (4H, t), 1.67 (4H, m), 1.34 (16H, m), 0.89 (6H, t)

IR (KBr) Vmax/c "¹ 2923, 2852, 1577, 1542, 1425, 1153, 804, 795

MS m/z 4680VT), 383(100%), 311, 298, 232

Example 51

Preparation of 2-(3,4-Difluorophenγl)-5-(4-heptylphenyl)benzo[blfuran (Compound 69 in Table 1)

The title compound was prepared and purified in a similar manner to that described in Example 1(4) using the quantities stated.

5-(4-Heptylphenyl)benzo[b]furan-2-boronic acid (0.4 g, 1.2 mmol), l-bromo-3,4- difluorobenzene, (0.2 g, 1.1 mmol), tetrakis(tiiphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (1.0 g, 9.3 mmol).

The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (ethanol). Colourless crystals were obtained.

Yield 0.1 g (12%). Purity (hplc) 98%. ^l≡ NMR CD₂Cl₂/δ 7.79 (1H, dd), 7.72 (1H, ddd), 7.65 (1H, m), 7.58 (2H, d), 7.57 (1H, d), 7.54 (1H, dd), 7.29 (1H, m), 7.28 (1H, m), 7.08 (1H, s), 2.66 (2H, t), 1.65 (2H. qui), 1.32 (8H, m), 0.89 (3H, t) IR (KBr) Vmax/c '¹ 2925, 2857, 1515, 1468, 1180, 874, 798,

772 MS m/z 707(M⁺), 319(100%), 305, 289, 159 Example 52

Preparation of 2-(2,3-Difluoro-4-heptylphenyl)-5-(4-heptylphenyl)benzofblfuran

(Compound 70 in Table 1)

Step l

Preparation of l-(2,3-Difluorophenyl)heptan-l-ol n-Butyllithium (2.5M in hexanes, 140.0 ml, 350.0 mmol) was added dropwise to a cooled (~78°C) solution of 0-difluorobenzene (40.0 g, 350.0 mmol) in dry THF (400 ml) with stirring under nitrogen. Stirring at low temperature was continued (P2 h) and n-heptanal (40.1 g, 333.0 mmol) was added dropwise. The mixture was allowed to return to room temperature overnight with stirring under nitrogen. 2M hydrochloric acid (225 ml) was added and stirring was continued (1 h). The mixture was then poured into water (400 ml) and ether added (200 ml). The separated aqueous layer was washed with ether (2 x 300 ml). The combined ethereal layers were washed with water and brine and dried (MgSO4), and the solvent removed in vacuo. The residue was then distilled. A pale-yellow oil was obtained.

Yield 63.1 g (83%) bp 140 °C at 0.001 mmHg.

*H NMR CD₂Cl₂/δ 7.24 (1H, m), 7.10 (2H, m), 5.00 (1H, t),

2.25 (1H, s), 1.75 (2H, m), 1.30 (8H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 3369, 2931, 1626, 1596, 1484, 1278, 1203, 1061, 786, 726

MS m/z 228(M⁺), 211, 199, 143(100%), 127 Step 2

Preparation of l-(2,3-Difluorophenyl)hept-l-ene

Phosphorus pentoxide (94.9 g, 669.0 mmol) was carefully added to a solution of l-(2,3-Difluorophenyl)heptan-l-ol (61.1 g, 267.0 mmol) from step 1 in pentane (90 ml) and the mixture was stirred overnight with exclusion of moisture. When glc analysis revealed a complete reaction, the mixture was poured into ice/water (300 ml) and ether added (200 ml). The separated aqueous layer was washed with ether (2 x 300 ml). The combined organic layers were washed with water and brine and dried (MgSO4), and the solvent removed in vacuo. The residue was then distilled. A colourless oil was obtained.

Yield 30.9 g (55%) bp 95 °C at 0.05 mmHg.

*H NMR CDCl₃/δ 7.16 (1H, m), 6.97 (2H, m), 6.51 (1H, d), 6.34 (1H, dt) 2.23 (2H, q), 1.48 (2H, qui), 1.34 (4H, m), 0.91 (3H, t)

IR (KBr) Vmax/cm'¹ 2929, 1621, 1589, 1482, 1205, 972, 773, 712

MS m/z 210(M⁺), 167, 153, 140(100%), 127

Step 3

Preparation of l,2-Difluoro-3-heptylbenzene

A mixture of the product of step 2 (30.5 g, 145 mmol) and palladium-on- charcoal (10% w/w, 1.0 g, 0.9 mmol) in ethanol (400 ml) was stirred in an atmosphere of hydrogen (glc analysis revealed a complete reaction). The mixture was then filtered through a pad of Ηyflo Supercef and the solvent was removed in vacuo. The product was purified by distillation.

A pale yellow liquid was obtained. Yield 26.4 g (86%) bp 95 °C at 0.003 mmHg.

*H NMR CDCl₃/δ 6.95 (3H, m), 2.65 (2H, t), 1.60 (2H, qui), 1.31 (8H, m),

0.88 (3H, t)

TR (KBr) Vmax/cm"¹ 2929, 2858, 1628, 1595, 1490, 1209, 822,

780, 725 MS m/z 212(M⁺), 141, 127(100%), 114, 83 Step 4

Preparation of 2,3-Difluoro-l-iodo-4-heptylbenzene n-Butyllithium (2.5M in hexanes, 14.4 ml, 36.0 mmol) was added dropwise to a cooled (-78°C) solution of the product of step 3 (7.0 g, 33.0 mmol) in dry THF (100 ml) with stirring under nitrogen. Stirring at low temperature was continued (1 h) and iodine (8.4 g, 33.0 mmol) in dry THF (100 ml) was added dropwise, maintaining low temperature. The mixture was allowed to return to room temperature overnight with stirring under nitrogen. It was then poured into water (50 ml) and ether added (50 ml). The separated aqueous layer was washed with ether (2 x 50 ml) and the combined organic layers were washed with saturated aqueous sodium sulphite, water and brine, and dried (MgSO4), and the solvent removed in vacuo. The product was purified by distillation. A pale-pink liquid was obtained.

Yield 5.0 g (45%) bp 125 °C at 0.005 mmHg. *H NMR CDCl₃/δ 7.37 (1H, ddd), 6.73 (1H, ddd), 2.63 (2H, dt), 1.58 (2H, t), 1.29 (8H, m), 0.88 (3H, t) IR (KBr) Vmax/cm"¹ 2927, 2856, 1457, 1285, 866, 806, 724,

612, 546 MS m/z 338(Jvf^"), 254, 139, 127(100%), 107 Step 5

Preparation of 2-(2,3-Difluoro-4-heptylphenyl)-5-(4-heptylphenyl)benzo [bl furan

Compound 70 in Table 1 was prepared in a similar manner to that described for the preparation of compound 66 in Example 48(3) using the quantities stated. 5-(4- Heptylphenyl)benzo[b]furan-2-boronic acid (0.6 g, 1.8 mmol), the product of step 4 (0.6 g, 1.6 mmol), tetrakis(tiiphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (0.4 g, 4.0 mmol). The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (hexane). A white crystalline solid was obtained.

Yield 0.3 g (37%). Purity (hplc) >99%. ^XH NMR CD₂Cl₂/δ 7.81 (1H, dd), 7.69 (1H, ddd), 7.57 (2H, m), 7.56 (2H, d), 7.28 (2H, d), 7.25 (1H, dd), 7.10 (1H, ddd), 2.72 (2H, t), 2.66 (2H, t), 1.65 (4H, qui), 1.33 (16H, m), 0.89 (6H, t)

IR (KBr) Vmax/cm"¹ 2927, 2856, 1498, 1123, 965, 878, 809, 726

MS m/z 502(M⁺)(100%), 417, 332, 166, 58

Example 53

Preparation of 2-(Hept-l-vnyl)-5-(4-heptylphenyl)benzofblfuran (Compound 17 in Table 1) Step 1

Preparation of 2-Iodo-5-(4-heptylphenyl)benzo[blfuran n-Butyllithium (2.5M in hexanes, 3.8 ml, 9.4 mmol) was added dropwise to a cooled (-10°C) solution of 5-(4-Heptylphenyl)benzo[b]furan_(2.5 g, 8.6 mmol) (prepared as described in Example 48(1) in dry THF (100 ml) with stirring under nitrogen. Stirring at low temperature was continued (2 h), and iodine (4.3 g, 17.2 mmol) in dry ether (30 ml) was added dropwise. After stirring at low temperature for a further 30 min the mixture was allowed to return to room temperature. It was then poured into water (50 ml) and ether added (50 ml). The separated aqueous layer was washed with ether (2 x 50 ml). The combined ethereal layers were washed with saturated aqueous sodium sulphite, water and brine, and dried (MgSO4). The solvent was removed in vacuo. The product was purified by recrystallization (hexane). Colourless plate-like crystals were obtained. Yield 2.5 g (70%), mp 94-95 °C

*H NMR CD₂Cl₂/δ 7.71 (1H, d), 7.52 (1H, d), 7.51 (2H, d), 7.46 (1H, dd), 7.04 (1H, d), 2.65 (2H, t), 1.64 (2H, qui), 1.31 (8H, m),

0.89 (3H, t)

IR (KBr) Vmax/c "¹ 2922, 2849, 1524, 1446, 1232, 1147, 1048,

918, 897, 884, 668 MS m/z 418(M⁺), 333, 207, 178, 43(100%), Step 2 Preparation of 2-(Hept-l-vnyl)-5-(4-heptylphenvI)benzofblfuran n-Butyllithium (2.5M in hexanes, 2.8 ml, 6.9 mmol) was added dropwise to a cooled (-40°C) solution of hept-1-yne (0.6 g, 6.3 mmol) in dry THF (17 ml) with stirring under nitrogen. Stirring at low temperature was continued (20 min), and a solution of anhydrous zinc chloride (1.1 g, 8.0 mmol) in dry THF (30 ml) was added dropwise, maintaining low temperature. Stirring under nitrogen was continued (4 h) and the mixture was allowed to return to room temperature. The product of step 1 (2.4 g, 5.7 mmol) and tetrakis(tiiphenylphosphine)palladium(0) (0.2 g, 0.2 mmol) were added, and the mixture was heated (70 °C) with stirring under nitrogen (12 h). When glc/tlc analysis revealed no further reaction the mixture was poured into water (50 ml) and ether added (50 ml). The separated aqueous layer was washed with ether (2 x 50 ml). The combined organic layers were washed with water and brine and dried (MgSO4), and the solvent removed in vacuo. The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)]. A yellow crystalline solid was obtained.

Yield 0.9 g (42%). Purity (hplc) 99.5%.

*H NMR CD₂Cl₂/δ 7.72 (1H, d), 7.54 (1H, dd), 7.53 (2H, d), 7.47 (1H, d),

7.27 (2H, d), 6.88 (1H, s), 2.65 (2H, t), 2.51 (2H, t), 1.67 (4H, m), 1.40 (12H, m), 0.95 (3H, t), 0.90 (3H, t) IR (KBr) Vmax/cm"¹ 2929, 2859, 2210, 1570, 1265, 992, 886,

842, 749, 727

MS m/z 386(M⁺), 371, 301(100%), 244, 207

Example 54

Preparation of 2-(4-heptylphenyl)-5-(hept-l-vnylphenyl)benzo[blfuran (Compound 71 in Table 1)

Step l

Preparation of 5-(Hept-l-ynylphenyl)benzo[b]furan )

The title compound was prepared and purified in a similar manner to that described for the preparation of compound 17 in Example 53 using the quantities stated, n- Butyllithium (2.5M in hexanes, 4.8 ml, 12.0 mmol), hept-1-yne (1.1 g, 11.0 mmol), zinc chloride (1.9 g, 14.0 mmol), 4-bromobenzofuran (2.0 g, 10.0 mmol).

A yellow liquid was obtained. Yield 1.2 g (57%) *H NMR CD₂Cl₂/δ 7.65 (2H, d), 7.42 (1H, d), 7.33 (1H, dd), 6.76 (1H, dd),

2.42 (2H, t), 1.63 (2H, qui), 1.41 (4H, m), 0.94 (3H, t) IR (KBr) Vmax/cm"¹ 2936, 2866, 1465, 1131, 1032, 883, 768, 735

MS m/z 212(M⁺), 197, 183, 169, 154(100%)

Step 2

Preparation of 5-(Hept-l-ynylphenyl)benzo[blfuran-2-boronic acid

The title compound was prepared in a similar manner to that described in Example 20(2) using the quantities stated.

5-(Hept-l-ynylphenyl)benzo[b]furan ) from step 1 (1.0 g, 5.2 mmol), n-butyllithium

(2.5M in hexanes, 2.3 ml, 5.7 mmol), trimethyl borate (1.2 g, 11.4 mmol).

An orange solid was obtained. Yield 1.0 g (83%) MS m/z 232QVT), 212, 183, 169, 155(100%)

Step 3

Preparation of 2-(4-heptylphenyl)-5-(hept-l-vnylphenyl)benzo[blfuran

(Compound 71 in Table 1)

The title compound was prepared and purified in a similar manner to that described for the preparation of compound 70 in Example 52 using the quantities stated. 5-(Hept-l-ynylphenyl)benzo[b]furan-2-boronic acid from step 2 (1.0 g, 4.3 mmol), l-bromo-4-heptylbenzene (Example 1(1)) (1.1 g, 4.3 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol), sodium carbonate (1.1 g,

11.0 mmol). Yield 0.3 g (18%). Purity (hplc) 85.1%.

*H NMR CD₂Cl₂/δ 7.76 (2H, d), 7.61 (1H, d), 7.42 (1H, d), 7.29 (1H, dd),

7.28 (2H, d), 6.96 (1H, s), 2.65 (2H, t), 2.42 (2H, t), 1.63 (4H, qui), 1.35 (12H, m), 0.94 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/c "¹ 2935, 2859, 1906, 1700, 1653, 1636, 1467, 1274, 878, 798

MS m/z 386 (M⁺)(100%), 343, 301, 244, 215 Example 55

Preparation of 2-(4-Heptylphenyl)-5-(4-pentylphenyl)benzo[blfuran (Compound 72 in Table 1) Step l Preparation of l-Heptyl-4-iodobenzene

The title compound was prepared and purified in a similar manner to that described in Example 1(1) using the quantities stated. Iodobenzene (20.4 g, 100 mmol), n-heptanoyl chloride (17.8 g, 120 mmol), aluminium chloride (14.7 g, 110 mmol), poly(methylhydrosiloxane) (16.1 g 267 mmol).

The compound was prepared and stored under exclusion of light. A pale-yellow liquid was obtained.

Yield 12.2 g (40%) bp 120 °C at 0.005 mmHg (lit.² 165°C at 10 mmHg). ^XH NMR CD₂Cl₂/δ 7.60 (2H, d), 6.96 (2H, d), 2.51 (2H, t), 1.60 (2H, m), 1.35-1.25 (8H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2926, 2854, 1466, 1062, 995, 794

MS m/z 302(M⁺)(100%), 259, 231, 217, 127

Step 2

Preparation of 2-(4-Heptylphenyl)-5-bromobenzo[bIfuran The title compound was prepared in a similar manner to that described in

Example 1(4) using the quantities stated. l-Heptyl-4-iodobenzene from step 1 (2.1 g, 7.0 mmol), 4-bromobenzo[b]furan-2- boronic acid (2.0 g, 8.0 mmol), sodium carbonate (1.9 g, 18.0 mmol), tetrakis(tiiphenylphosphine)palladium(0) (0.2 g, 0.2 mmol) The product was purified by flash chromatography [silica gel / petroleum fraction (bp

40-60 °C)], followed by recrystallisation (hexane).

A white solid was obtained.

Yield 0.5 g (20%), mp 144-149 °C

*H NMR CD₂Cl₂/δ 7.68 (2H, d), 7.62 (1H, d), 7.32 (1H, d), 7.28 (1H, dd), 7.20 (2H, d), 6.87 (1H, s), 2.57 (2H, t),

1.56 (2H, t), 1.23 (8H, m), 0.80 (3H, t) IR (KBr) Vmax/cm"¹ 2930, 2858, 1609, 1582, 1035, 922, 895,

670, 505 MS m/z 372,37O0v ), 285(100%), 205, 176, 152

Step 3 Preparation of 2-(4-Heptylphenyl)-5-(4-pentylphenyl)benzofblfuran (Compound 72 in Table 1)

The title compound was prepared in a similar manner to that described in Example 1(4) using the quantities stated.

2-(4-Heptylphenyl)-5-bromobenzo[b]furan (0.4 g, 1.1 mmol), 4-pentylbenzeneboronic acid (0.3 g, 1.3 mmol), sodium carbonate (0.3 g, 2.8 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol)

The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (hexane). A white crystalline solid was obtained. Yield 0.4 g (83%). Purity (hplc) 98.4%.

*H NMR CD₂Cl₂/δ 7.79 (2H, d), 7.77 (1H, d), 7.56 (1H, d), 7.55 (2H, d),

7.50 (1H, dd), 7.30 (2H, d), 7.28 (2H, d), 7.05 (1H, s), 2.66 (4H, t) 1.66 (4H, m), 1.33 (12H, m), 0.92 (3H, t), 0.89 (3H, t) IR (KBr) Vmax/cm"¹ 2963, 2928, 2858, 1589, 1121, 1034, 884,

799

MS m/z 438(Jvr), 381, 353, 296, 43(100%)

Example 56

Preparation of Compound 73 in Table 1 Step l

Preparation of l-Heptyl-2.3-difluorobenzene-4-boronic acid

The title compound was prepared in a similar manner to that described for the preparation of 4'-pentylbiphenylboronic acid in Example 20(2) using the quantities stated. l,2-Difluoro-3-heptylbenzene prepared as described in Example 52(3) (19.2 g, 90.0 mmol), n-butyllithium (2.5M in hexanes, 39.8 ml, 99.0 mmol), trimethyl borate (18.7 g, 180.0 mmol). A white solid was obtained. Yield 19.9 g (87%)

*H NMR DMSO-d⁶/δ 7.11 (1H, m), 7.10 (1H, m), 2.62 (2H, dt), 1.54 (2H, qui),

1.24 (8H, m), 0.84 (3H, t) (acidic proton was not shown) IR (KBr) Vmax/cm"¹ 3661, 3342, 2939, 2849, 1628, 1425, 1190,

929, 902, 835, 723 MS m/z 212(M⁺-B(OH)₂+H), 169, 140, 128(100%), 101

Step 2

Preparation of 5-(2,3-Difluoro-4-heptyIphenyl)benzo[blfuran The title compound was prepared in a similar manner to that described in

Example 1(4) using the quantities stated.

4-bromobenzofuran (1.8 g, 9.0 mmol), l-Heptyl-2,3-difluorobenzene-4-boronic acid from step 1 (2.8 g, 10.8 mmol), sodium carbonate (2.4 g, 23.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.3 g, 0.3 mmol) The product was purified by flash chromatography [silica gel / petroleum fraction (bp

40-60 °C)], followed by recrystallisation (hexane).

A pale-yellow liquid was obtained. Yield 1.4 g (47%)

^XH NMR CD Cl₂/δ 7.77 (1H, s), 7.70 (1H, d), 7.58 (1H, dd), 7.46 (1H, ddd), 7.16 (1H, ddd), 7.04 (1H, ddd), 6.85 (1H, d), 2.71 (2H, t), 1.66 (2H, qui), 1.38 (8H, m), 0.91 (3H, t)

IR (KBr) Vmax/cm"¹ 2933, 2861, 1468, 1113, 890, 808, 772,

739 MS m/z 328(M⁺), 243, 231, 194, 43(100%) Step 3

Preparation of 5-(2,3-Difluoro-4-heptylphenyl)benzofblfuran-2-boronic acid)

The title compound was prepared in a similar manner to that described for the preparation of 4'-pentylbiphenylboronic acid in Example 20(2) using the quantities stated. The product of step 2 (1.2 g, 3.7 mmol), n-butyllithium (2.5M in hexanes, 1.6 ml, 4.0 mmol), trimethyl borate (0.8 g, 7.4 mmol). A white solid was obtained.

Yield 1.1 g (80%) MS m/z 328(M⁺-B(OH)₂), 256, 243(100%), 201, 175

Step 4 Preparation of 5-(2.3-Difluoro-4-heptylphenyl)-2-(4-heptylphenyl)-benzofblfuran (Compound 73 in Table 1)

The title compound was prepared in a similar manner to that described for the preparation of in Example 1(4) using the quantities stated. l-bromo-4-heptylbenzene (0.8 g, 3.0 mmol), 5-(2,3-Difluoro-4- heptylphenyl)benzo[b]furan-2-boronic acid) from step 3 (1.1 g, 3.0 mmol), sodium carbonate (0.8 g, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol). A white, fibrous, crystalline solid was obtained.

Yield 0.4 g (27%). Purity (hplc) 98.4%. NMR CD₂Cl /δ 7.80 (2H, d), 7.73 (1H, m), 7.58 (1H, d), 7.43 (1H, ddd),

7.30 (2H, d), 7.18 (1H, m), 7.05 (1H, d), 7.04 (1H, m), 2.71 (2H, t), 2.66 (2H, t), 1.66 (4H, m), 1.33 (16H, m), 0.90 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/cm'¹ 2936, 2856, 1509, 1121, 1033, 916, 802, 754

MS m/z 502(M⁺), 417, 332, 224, 91(100%)

Example 57

Preparation of Compound 74 in Table 1

Step l Preparation of 5-(5-Heptylpyrimidin-2-yl)benzof blfuran

The title compound was prepared and purified in a similar manner to that described for the preparation of compound 68 in Table 1 using the quantities stated.

Benzo[b]furan-5-boronic acid (Example 22(1)) (0.7 g, 4.2 mmol), 2-chloro-5- heptylpyrimidine (0.8 g, 3.7 mmol) tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol), sodium carbonate (0.9 g, 8.8 mmol).

A pale-yellow, waxy solid was obtained Yield 0.9 g (83%) ^XH NMR CDCl₃/δ 8.69 (1H, d), 8.62 (2H, s), 8.42 (1H, dd), 7.65 (1H, d),

7.58 (1H, d), 6.84 (1H, dd), 2.61 (2H, t), 1.65 (2H, qui), 1.31 (8H, m), 0.87 (3H, t)

IR (KBr) Vmax/cm"¹ 2928, 2856, 1588, 1547, 1130, 1029, 796, 768, 737

MS m/z 294(M⁺), 265, 251, 223, 209(100%)

Step 2

Preparation of 5-(5-Heptylpyrimidin-2-yl)benzofblfuran-2-boronic acid n-Butyllithium (2.5M in hexanes, 2.0 ml, 5.1 mmol) was added dropwise to a cooled (-70 °C) solution of dry diisopropylamine (2.0 g, 20.0 mmol) in dry THF (15 ml) with stirring under nitrogen. Stirring was continued (10 min), and 5-(5- Heptylpyrimidin-2-yl)benzo[b]furan from step 1(1.5 g, 5.1 mmol) in dry THF (7 ml) was added dropwise at -70°C. After stirring under nitrogen (1 h) trimethyl borate (1.0 g, 10.0 mmol) was added dropwise at low temperature. The system was allowed to return to room temperature overnight whilst stirring under nitrogen. Hydrochloric acid (5M, 4.0 ml) was added with stirring. The mixture was then poured into water (100 ml) and ether added (50 ml). The separated aqueous layer was washed with ether (3 x 50 ml). The combined organic layers were washed with water and brine, and dried (MgSO4), and the solvent removed in vacuo. The residue was adsorbed onto silica and washed with petroleum fraction (bp 40-60 °C). The adsorbate was then washed with THF, and the solvent removed in vacuo. An orange solid was obtained.

Yield 1.4 g (78%) MS m/z 294(M⁺-B(OH₂), 223, 209(100%), 195, 181 Step 3

Preparation of 2-(2.3-Difluoro-4-heptyl)-5-(5-heptylpyrimidin-2-yl)benzo I blfuran (Compound 74)

The title compound was prepared in a similar manner to that described for the preparation of compound 68 in Table 1 using the quantities stated. 5-(5-Heptylpyrimidin-2-yl)benzo[b]furan-2-boronic acid from step 2 (1.3 g, 3.8 mmol), 2,3-Difluoro-l-iodo-4-heptylbenzene (Example 52 (4) (1.5 g, 4.6 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol), sodium carbonate (1.2 g, 12.0 mmol). The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C), DCM 7:3], followed by recrystallisation (ethanol, DCM 9: 1), and finally, by preparative hplc (acetonitrile, chloroform 4:1). Colourless needle-like crystals were obtained.

Yield 0.4 g (17%). Purity (hplc) >99.9%.

*H NMR CD₂Cl /δ 8.71 (1H, d), 8.62 (2H, s), 8.44 (1H, dd), 7.68 (1H, ddd),

7.59 (1H, d), 7.27 (1H, dd), 7.09 (1H, ddd), 2.70 (2H, t), 2.62 (2H, t), 1.66 (2H, qui), 1.64 (2H, t), 1.36-1.24 (16H, m),

0.87 (6H, t)

IR (KBr) Vmax/cm"¹ 2932, 2859, 1586, 1549, 1328, 1117, 964,

875, 797 MS m/z 504(M⁺)(100%), 462, 433, 419, 321 Example 58

Preparation of Compound 75 in Table 1

Ste l

Preparation of l,2-Difluorobenzene-3-boronic acid

The title compound was prepared in a similar manner to that described in Example 20(2) using the quantities stated.

O-difluorobenzene (65.8 g, 577.0 mmol), n-butyllithium (2.5M in hexanes, 231.0 ml, 577.0 mmol), trimethyl borate (71.9 g, 692.0 mmol).

The reaction mixture was poured into water (200 ml) and ether added (200 ml). The separated aqueous phase was washed with ether (3 x 200 ml). The product was extracted from the combined ethereal phases as the potassium salt by washing with potassium hydroxide (2M, 290 ml). The basic solution was then washed with ether, and the product released by acidification to pH3 by adding hydrochloric acid (cone.) to the aqueous solution. The product was then extracted with ether (3 x 200 ml). The combined organic layers were washed with water and brine, dried (MgSO4), and the solvent removed in vacuo.

A white solid was obtained. Yield 47.1 g (52%)

MS m/z 420 (3M⁺-3H₂O)(100%), 280, 140, 94, 75 Step 2

Preparation of 2,3-DifIuorophenol

Hydrogen peroxide (100 vol, 197.0 ml, 1.74 mol) was added slowly to a stirred solution of l,2-difluorobenzene-3 -boronic acid (458. g, 290.0 mmol) in dry diethyl ether (300 ml) and the mixmre was refluxed (2 h). After allowing to cool, the mixture was washed with ether (3 x 250 ml). The combined ethereal layers were washed with saturated aqueous sodium thiosulphate, water and brine and dried (MgSO4), and the solvent removed in vacuo. The product was purified by distillation. A colourless liquid was obtained, which solidified on cooling. Yield 24.2 g (64%) bp 150 °C at 760 mmHg.

*H NMR CDCl₃/δ 6.95 (1H, m), 6.75 (2H, m), 4.95 (1H, s)

IR (KBr) Vmax/cm"¹ 3187, 2986, 1623, 1534, 1196, 1023, 889,

773, 701 MS m/z 130(M⁺)(100%), 101, 82, 71, 56 Preparation of 4-Bromo-2,3-difluorophenol

Bromine (29.1 g, 182.0 mmol) in glacial acetic acid (45 ml) was carefully added dropwise, maintaining low temperature, to a vigorously stirred, cooled (10 °C) solution of 2,3-difluorophenol (21.4 g, 165.0 mmol) in glacial acetic acid / chloroform 4: 1 (55 ml) Stirring was continued (15 min) and the mixture was poured into water (200 ml) and DCM added (100 ml). The separated aqueous layer was washed with DCM (3 x 100 ml), and the combined organic layers were washed with saturated aqueous sodium bicarbonate, water and brine and dried (MgSO4). The solvent was then removed in vacuo. Hexane (100 ml) was added to the residue and the mixture was heated until homogeneous. It was then cooled (8 °C) and the solvent was removed by filtration. The product was then distilled. A colourless liquid was obtained.

Yield 26.7 g (77%) bp 135-160 °C at 20 mmHg.

*H NMR CDCl₃/δ 7.22 (1H, m), 6.71 (1H, m), 5.57 (1H, s)

IR (KBr) Vmax/cm"¹ 3395, 2970, 1622, 1187, 1032, 876, 798, 630, 535

MS m/z 210,208^), 179, 128, 101, 81(100%) NMR revealed approximately 33% impurity, consisting of starting material and dibromination product. Further purification was carried out after the next synthetic step.

Step 4

Preparation of 2-(4-Bromo-2.3-difluorophenoxy)acetaldehvde dimethyl acetal

The title compound was prepared in a similar manner to that described in

Example 9(1) using the quantities stated.

The product of step 3 (28.6 g, 137.0 mmol), bromoacetaldehyde dimethyl acetal (25.5 g, 151.0 mmol), potassium carbonate (37.9 g, 274.0 mmol) and potassium iodide (1.1 g, 7.0 mmol).

The crude product was purified by flash chromatography [neutral alumina / petroleum fraction (bp 40-60 °C), DCM 10:3], followed by distillation.

A colourless liquid was obtained. Yield 17.4 g (46%) bp 127 °C at 0.05 mmHg.

*H NMR CDCl₃/δ 7.21 (1H, m), 6.70 (1H, m), 4.71 (1H, t), 4.05 (2H, d),

3.47 (6H, s)

IR (KBr) Vmax/cm"¹ 2945, 2842, 1619, 1504, 1140, 880, 795,

593 MS m/z 298,296(M⁺), 265, 235, 207, 75(100%)

Step 5 Preparation of 5-Bromo-6,7-difluorobenzo[blfuran

The title compound was prepared and purified in a similar manner to that described for the preparation of 5-bromobenzo[b]furan in Example 9(2) using the quantities stated.

The product of step 4 (9.7 g, 33.0 mmol), polyphosphoric acid (13.9 g). The product was further purified by recrystallization (ethanol). White needle-like crystals were obtained.

Yield 1.9 g (25%), mp 96.5-98.0 °C *H NMR CD₂Cl₂/δ 7.73 (1H, d), 7.58 (1H, dd), 6.80 (1H, dd) IR (KBr) Vmax/cm"¹ 1603, 1485, 1125, 1084, 876, 814, 765,

730, 640, 531 MS m/z 234,232 (M⁺), 153, 125, 105(100%), 77

Step 6 Preparation of 5-Bromo-6,7-difluorobenzofblfuran-2-boronic acid

The title compound was prepared and purified in a similar manner to that described for the preparation of 5-(5-Heptylpyrimidin-2-yl)benzo[b]furan-2-boronic acid (Example 57(2) using the quantities stated. n-Butyllithium (2.5M in hexanes, 5.2 ml, 13.0 mmol) dry diisopropylamine (1.3 g, 13.0 mmol), the product of step 5 (3.0 g, 13.0 mmol), trimethyl borate (2.7 g, 26.0 mmol), hydrochloric acid (5M, 5.2 ml).

A cream-coloured solid was obtained. Yield 3.1 g (86%) MS m/z 777,775(3M⁺-3H₂O), 705(100%), 626, 231, 124

Step 7

Preparation of 5-Bromo-6,7-difluoro-2-(4-pentylphenyl)benzofblfuran

The title compound was prepared and purified in a similar manner to that described for the preparation of 5-(4-pentylphenyl)benzo[b]furan (Example 24 (1) using the quantities stated.

4-Iodo-4-pentylbenzene (Example 22(2) (1.8 g, 6.7 mmol), the product of step 6 (1.6 g, 5.6 mmol), sodium carbonate (1.8 g, 17.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol)

A white, crystalline solid was obtained. Yield 1.2 g (57%), mp 62-64 °C

*H NMR CD₂Cl₂/δ 7.76 (2H, d), 7.54 (1H, dd), 7.30 (2H, d), 6.96 (1H, d),

2.66 (2H, t), 1.65 (2H, qui), 1.34 (4H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2932, 2866, 1605, 1442, 1043, 909, 795,

548 MS m/z 380,378(lvf), 321(100%), 241, 213, 193 Step 8

Preparation of 6,7-Difluoro-5-(4-heptylphenyl)-2-(4-pentylphenyl)benzofb1furan

(Compound 75 in Table 1)

The title compound was prepared in a similar manner to that described in Example 1(4) using the quantities stated.

Product of step 7 (1.2 g, 3.2 mmol), 4-heptylbenzeneboronic acid (0.9 g, 3.8 mmol), sodium carbonate (0.9 g, 8.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g,

0.1 mmol)

The product was purified by flash chromatography [silica gel / petroleum fraction (bp 40-60 °C)], followed by recrystallisation (ethanol). It was then dissolved in carbon tetrachloride/chloroform 19: 1. The solution was triturated with methanol, the precipitate filtered, and washed with ethanol.

Colourless, needle-like crystals were obtained. Yield 0.4 g (23%). Purity (hplc) 99%. ^XH NMR CD₂Cl₂/δ 7.79 (2H, d), 7.47 (2H, d), 7.34 (1H, dd), 7.31 (2H, d),

7.30 (2H, d), 7.02 (1H, d), 2.67 (2H, t), 2.66 (2H, t), 1.66 (4H, qui), 1.37-1.26 (12H, m), 0.91 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2960, 2857, 1613, 1513, 1160, 1038, 910,

838, 807, 661 MS m/z 474(M⁺X100%), 417, 389, 331, 232

Example 59

Preparation of 6,7-Difluoro-2-(2.3-difluoro-4-heptylphenyl)-5-(4- heptylphenvDbenzofblfuran (Compound 76 in Table 1)

Step l Preparation of 5-Bromo-6,7-difluoro-2-(2,3-difluoro-4- heptylphenvDbenzofblfuran)

The title compound was prepared and purified in a similar manner to that described in Example 24(1) using the quantities stated.

2,3-Difluoro-l-iodo-4-heptylbenzene (Example 52 (4) (2.3 g, 6.7 mmol), 5-Bromo- 6,7-difluorobenzo[b]furan-2-boronic acid (Example 58(6))(1.6 g, 5.6 mmol), sodium carbonate (1.8 g, 17.0 mmol), tetrakis(triρhenylphosphine)palladium(0) (0.2 g, 0.2 mmol) A white, crystalline solid was obtained. Yield 0.6 g (24%), mp 62-65 °C

¹H NMR CD₂Cl₂/δ 7.69 (1H, ddd), 7.60 (1H, dd), 7.18 (1H, dd), 7.12 (1H, ddd), 2.72 (2H, dt), 1.65 (2H, qui), 1.31 (8H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2932, 2856, 1605, 1476, 1210, 1031, 932,

869, 731, 606

MS m/z 444,442(M⁺)(100%), 357, 277, 249, 230

Step 2 Preparation of 6,7-Difluoro-2-(2,3-dιfluoro-4-heptylphenyl)-5-(4- heptylphenyl)benzo[blfuran (Compound 76 in Table 1)

The title compound was prepared in a similar manner to that describedin

Example 24(1) using the quantities stated.

The product of step 1 (0.6 g, 1.2 mmol), 4-heptylbenzeneboronic acid (0.3 g, 1.5 mmol), sodium carbonate (0.3 g, 3.0 mmol), tetrakis(triphenylphosphine)palladium(0)

(0.1 g, 0.1 mmol)

The product was purified by flash chromatography [silica gel / petroleum fraction (bp

40-60 °C)], followed by recrystallisation (ethanol).

Colourless, plate-like crystals were obtained. Yield 0.1 g (17%). Purity (hplc) >99%.

*H NMR CD₂Cl₂/δ 7.72 (1H, ddd), 7.47 (2H, dd), 7.40 (1H, dd), 7.30 (2H, d), 7.25 (1H, dd), 7.12 (1H, ddd), 2.72 (2H, t), 2.67 (2H, t), 1.39-1.62 (4H, m), 1.37-1.28 (16H, m), 0.90 (3H, t), 0.89 (3H, t) IR (KBr) Vmax/cm"¹ 2928, 2857, 1616, 1475, 1164, 1093, 932,

879, 809, 719 MS m/z 538(^(100%), 467, 453, 368, 184 Example 60

Preparation of Compound 77 in Table 1

Ste l

Preparation of 5-(2,3-Difluoro-4-heptyl)-6.,7-difluorobenzo[b1furan The title compound was prepared and purified in a similar manner to that described in Example 24(1) using the quantities stated.

5-Bromo-6,7-difluorobenzo[b]furan (1.1 g, 4.7 mmol), l-heptyI-2,3-difluorobenzene- 4-boronic acid (1.4 g, 5.6 mmol), sodium carbonate (1.3 g, 12.0 mmol), tetrakis(triphenylphosphine)palladium(0) (0.2 g, 0.2 mmol) After refluxing (1 day) tic and glc analysis revealed some starting material still remained, so compound 161 (0.6 g, 2.3 mmol) and catalyst (0.1 g, 0.1 mmol) were added.

A white, crystalline solid was obtained. Yield 0.8 g (47%), mp 57-59.5 °C H NMR CD₂Cl₂/δ 7.75 (1H, d), 7.35 (1H, ddd), 7.08 (2H, m), 6.87 (1H, dd), 2.73 (2H, dt), 1.66 (2H, qui), 1.34 (8H, m), 0.90 (3H, t)

IR (KBr) Vmax/cm"¹ 2921, 2859, 1618, 1512, 1121, 1046, 963,

807, 738, 671 MS m/z 364(M⁺), 335, 279(100%), 250, 201

Step 2 Preparation of 5-(2,3-Difluoro-4-heptyl)-6.7-difluorobenzoIblfuran-2-boronic acid

The title compound was prepared and purified in a similar manner to that described for the preparation of 4'-pentylphenylboronic acid (Example 20(2)) using the quantities stated.

Product of step 1 (0.7 g, 1.9 mmol), n-butyllithium (2.5M in hexanes, 0.9 ml, 2.3 mmol), trimethyl borate (0.4 g, 3.8 mmol). A white solid was obtained. Yield 0.8 g (quant). MS m/z 364(M⁺-B(OH)₂), 292, 279(100%), 250, 121 Step 3

Preparation of 2-(4-Heptylphenyl)-5-(2,3-difluoro-4-heptyl)-6,7- difluorobenzoFblfuran (Compound 77)

The title compound was prepared and purified in a similar manner to that described in Example 24(1) using the quantities stated. l-Heptyl-4-iodobenzene (0.7 g, 2.4 mmol), the product of step 2 (0.8 g, 2.0 mmol), sodium carbonate (0.6 g, 5.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol)

Final purification was by preparative hplc (acetonitrile/chloroform 4:1). A white, crystalline solid was obtained.

Yield 0.1 g (5%). Purity (hplc) >99.9%.

^XH NMR CD₂Cl₂/δ 7.80 (2H, d), 7.32 (1H, m), 7.31 (2H, d), 7.13-7.07 (1H, m), 7.12-7.06 (1H, m), 7.04 (1H, d), 2.73 (2H, dt), 2.67 (2H, t), 1.69 (2H, qui), 1.67 (2H, qui), 1.38-1.26 (16H, m), 0.90 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax/cm'¹ 2929, 2859, 1618, 1279, 1053, 969, 908,

835, 811 MS m/z 538(M⁺)(100%), 453, 416, 368, 290

Example 61 Preparation of Compound 78 in Table 1 Step l Preparation of 2,3-Difluoro-4-heptylphenol

The title compound was prepared and purified in a similar manner to that described for in Example 58(2) using the quantities stated. Hydrogen peroxide (100 vol, 27.0 ml, 238.0 mmol), l-heptyl-2,3-difluorobenzene-4- boronic acid (10.0 g, 39.0 mmol). A colourless liquid was obtained.

Yield 5.9 g (66%), bp 205 °C at 20 mmHg.

*H NMR CD₂Cl₂/δ 6.82 (1H, ddd), 6.69 (1H, ddd), 5.25 (1H, s, br), 2.58 (2H, dt), 1.56 (2H, t), 1.31 (8H, m), 0.88 (3H, t) IR (KBr) Vmax/cm"¹ 3390, 2935, 2863, 1643, 1609, 1517, 1183, 1024, 961,

809, 676 MS m/z 228(M⁺), 169, 156, 143(100%), 95

Step 2 Preparation of 2-(2,3-Difluoro-4-heptylphenoxy)acetaldehde dimethyl acetal

The title compound was prepared and purified in a similar manner to that described for the preparation of 2-(4-pentylphenoxy)acetaldehyde dimethal acetal in Example 25(1) using the quantities stated.

2,3-Difluoro-4-heptylphenol (5.8 g, 25.0 mmol), bromoacetaldehyde dimethyl acetal (5.1 g, 30.0 mmol), potassium carbonate (6.9 g, 50.0 mmol), potassium iodide (0.2 g, 1.3 mmol). A colourless oil was obtained, which solidified on cooling to a waxy solid.

Yield 5.4 g (68%) bp 170 °C at 0.05 mmHg.

^XH NMR CDCl₃/δ 6.81 (1H, ddd), 6.67 (1H, ddd), 4.72 (1H, t), 4.05 (2H, d), 3.47 (6H, s), 2.57 (2H, dt), 1.57 (2H, m), 1.29 (8H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 2936, 2863, 1640, 1513, 1176, 1151, 1115,

1095 MS m/z 316(M⁺), 284, 253, 126, 75(100%) Step 3

Preparation of 6.7-Difluoro-5-heptylbenzo[blfuran

The title compound was prepared and purified in a similar manner to that described for the preparation of 5-bromobenzo[b]furan (Example 9(2)) using the quantities stated. The product of step 2 (5.4 g, 17.0 mmol), polyphosphoric acid (7.3 g). A pale yellow liquid was obtained.

Yield 0.5 g (12%) bp 135 °C at 0.1 mmHg.

^XH NMR CD₂Cl₂/δ 7.65 (1H, d), 7.16 (1H, m), 6.76 (1H, dd), 2.72 (2H, dt),

1.63 (2H, qui), 1.31 (8H, m), 0.88 (3H, t) IR (KBr) Vmax/cm"¹ 2933, 2867, 1616, 1131, 1077, 926, 871,

763, 733, 551 MS m/z 252(M⁺), 209, 167(100%), 153, 118

Step 4

Preparation of 6,7-Difluoro-5-heptylbenzolblfuran-2-boronic acid

The title compound was prepared and purified in a similar manner to that described in Example 20(2) using the quantities stated.

The product of step 3 (0.5 g, 1.8 mmol), n-butyllithium (2.5M in hexanes, 0.8 ml, 2.0 mmol), trimethyl borate (0.4 g, 3.6 mmol). An orange solid was obtained. Yield 0.3 g (66%) MS m/z 252^), 180, 167(100%), 119, 57

Step 5 Preparation of 4-Bromo-3-fluoro-4^,-pentylbiphenyl

The title compound was prepared and purified in a similar manner to that described in Example 24(1) using the quantities stated. l-Bromo-2-fluoro-4-iodobenzene (6.4 g, 21.0 mmol), 4-pentylbenzeneboronic acid (Example 3(2)) (4.5 g, 23.0 mmol), sodium carbonate (5.6 g, 53.0 mmol), tetrakis(triphenylphosphine)palladium(0) (1.2 g, 1.0 mmol) The product was further purified by distillation. A pale-yellow liquid was obtained. Yield 1.7 g (25%) (a quantity was lost through spillage) bp 190 °C at 0.04 mmHg.

*H NMR CD₂Cl₂/δ 7.60 (1H, dd), 7.49 (2H, d), 7.37 (1H, dd), 7.29 (1H, dd),

7.28 (2H, d), 2.65 (2H, t), 1.64 (2H, qui), 1.35 (4H, m), 0.91 (3H, t) IR (KBr) Vmax/cm"¹ 2933, 2861, 1560, 1195, 1057, 875, 805,

547 MS m/z 322,320(M⁺), 263, 250, 183(100%), 170

Step 6

Preparation of 2-(2-Fluoro-4^,-pentylbiphenyl)-6,7-difluoro-5-heptylbenzofb1furan (Compound 78)

The title compound was prepared and purified in a similar manner to that described for in Example 24(1) using the quantities stated. Product of step 5 (03.5 g, 1.4 mmol), product of step 4 (0.3 g, 1.2 mmol), sodium carbonate (0.4 g, 3.5 mmol), tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol)

Final purification was by preparative hplc (acetonitrile/chloroform 4: 1). A white solid was obtained.

Yield 0.04 g (7%). Purity (hplc) 99.2%.

^XH NMR CD₂Cl₂/δ 8.07 (1H, dd), 7.58 (2H, d), 7.55 (1H, dd), 7.45 (1H, dd),

7.30 (2H, d), 7.21-7.19 (1H, m), 7.19-7.17 (1H, m), 2.75 (2H, dt), 2.66 (2H, t), 1.68-1.64 (4H, m), 1.37-1.26 (12H, m), 0.91 (3H, t), 0.89 (3H, t)

IR (KBr) Vmax cm"¹ 2925, 2855, 1614, 1556, 1110, 1062, 915,

866, 800

MS m/z 492(M⁺)(100%), 435, 407, 350, 175

Example 62 Preparation of Compound 1 in Table 1

Step l

Preparation of l-Bromo-4-octyloxybenzene

A mixture of/?-bromophenol (40.0 g, 231 mmol), n-octyl bromide (50.2 g, 260 mmol), potassium carbonate (35.9 g, 260 mmol) and potassium iodide (2.2 g, 13 mmol) in butanone (500 ml) was refluxed under nitrogen (48 h) and the reaction monitored by glc analysis. The mixture was filtered, and the solid washed with ether (2 x 300 ml).

The filtrate was washed with sodium hydroxide (10%), followed by brine. The solvent was removed in vacuo, and the product purified by distillation. A colourless liquid was obtained.

Yield 61.0 g (93%) bp 145 °C at 0.02 mmHg (lit.³ 125°C).

*H NMR CDCl₃/δ 7.35 (2H, d), 6.76 (2H, d), 3.90 (2H, t), 1.76 (2H, qui),

1.35 (10H, m), 0.89 (3H, t)

IR (KBr) Vmax/cm"¹ 2900, 1580, 1475, 1240, 1170, 1070, 820, 640, 500

MS m/z 286,284(M⁺), 171(100%), 157, 143, 93 Step 2

Preparation of 2-methyl-4-(4-octyloχyphenyl) but-3-yn-2-ol

A mixture of compound the product of step 1 (61. Og, 214 mmol), tetrakis(triphenylphosphine)palladium(0) (2.4 g, 2.1 mmol), cuprous iodide (0.4 g, 2.1 mmol) and dry diisopropylamine (400 ml) was stirred under nitrogen (10 min).

2-Methyl-but-3-yn-2-ol (45.0 g, 535 mmol) in dry diisopropylamine (90 ml) was added dropwise, and the mixture was refluxed (4 h); the reaction progress was monitored by tic analysis. When cool, water was added, and the mixture was filtered through a pad of Ηyflo SuperceP, washing the pad with ether. The separated aqueous layer was washed with ether (2 x 300 ml), and the combined organic layers washed with brine and dried (MgSO4). After removal of the solvent in vacuo, the product was purified by flash chromatography [silica gel, petroleum fraction (bp 40-60 °C) (unreacted starting material), and DCM (product)]. A heavy brown oil was obtained Yield 33.2 g (54%).

*H NMR CDCl₃/δ 7.33 (2H, d), 6.81 (2H, d), 3.93 (2H, t),

1.76 (2H, qui), 1.60 (6H, s), 1.28 (12H, m), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 3440, 2880, 1600, 1505, 1465, 1370, 1245,

960, 835 MS m/z 288,286(M⁺), 273, 175, 159, 43(100%)

Step 3 Preparation of 4-Octyloxyphenylacetylene

The product of step 2 (33.0 g, 115 mmol) and potassium hydroxide (7.1 g, 126 mmol) in toluene (250 ml), were refluxed with stirring under nitrogen (3.5 h), using a Dean and Stark apparatus. Tic analysis indicated a complete reaction. The cooled reaction mixture was poured into water (150 ml) and the layers were separated. The aqueous phase was neutralised with hydrochloric acid (0.02 M) to pH 7, and washed with ether (3 x 100 ml). The combined organic layers were washed with brine and dried (MgSO4). After removal of the solvent in vacuo, the residue was flash chromatographed [silica gel / petroleum fraction (bp 40-60 °C), DCM 1:1]. The product was then distilled in vacuo. A pale-yellow liquid was obtained. Yield 6.4 g (68%) bp 122 °C at 2.7 mmHg *H NMR CDCl₃/δ 7.42 (2H, d), 6.82 (2H, d), 3.94 (2H, t), 3.00 (1H, s), 1.77

(2H, qui), 1.35 (10H, m), 0.88 (3, t) IR (KBr) Vmax/cm"¹ 3310, 3290, 2920, 2850, 2110, 1600, 1500, 830

MS m/z 230(M⁺), 187, 145, 118(100%), 101

Step 4

Preparation of 4,6-Diiodoresorcinol

To resorcinol (5.0 g, 45 mmol) in hydrochloric acid (cone.) / water 14: 11 v/v (185 ml), iodine monochloride (14.6 g, 90 mmol) was added with stirring under nitrogen. Stirring was continued (15 min), followed by addition of solid sodium sulphite until the iodine colouration was removed. The reaction mixture was filtered and the solid washed with cold water. The solid was then dried in vacuo (KOH) and recrystallized (CC1 ). Colourless needles were obtained.

Yield 8.6 g (53%) mp 139-145 °C (lit.⁴ 145°C).

^XH NMR DMSO-d⁶/δ 9.55 (2H, s), 7.57 (1H, s), 6.53 (1H, s)

IR (KBr) Vmax/c "¹ 3455, 1565, 1285, 1150, 1030, 875, 630,

460 MS m/z 362(M⁺), 235, 108, 79, 50(100%)

Step 5 Preparation of 4,6-Diiodoresorcinol dibenzoate ester

To a stirred mixture of compound the product of step 4 (15.0 g, 42 mmol) and benzoyl chloride (12.8 g, 91 mmol) in dry DCM (150 ml), dry triethylamine (9.2 g, 91 mmol) was added dropwise with exclusion of moisture, and the mixture was then refluxed (2 h). When cool, the mixture was poured into water and washed with DCM (2 x 200 ml). The combined organic phases were washed with hydrochloric acid (0.1M) and water, and dried (MgSO4). The solvent was removed in vacuo and the residue recrystallized (toluene). White, fibrous crystals were obtained.

Yield 20.6 g (86%), mp 185-7 °C (lit.⁴ 195-200°C (decomp.)). H NMR CDCl₃/δ 8.36 (1H, s), 8.26 (4H, d), 7.68 (2H, t),

7.54 (4H, t), 7.31 (1H, s) TR (KBr) Vmax/cm"¹ 1745, 1235, 1150, 1050, 700

MS m/z 570^), 443, 127(100%), 105, 77 Step 6

Preparation of2-(4-Octyloxyphenyl)-5-(4-octyloxyphenylethvnyl)benzofblfuran- 6-benzoate ester (Compound 1)

The product of step 3 (0.7g, 3 mmol) was placed in a three-necked flask fitted with septum, condenser, thermometer and addition funnel. The apparatus was heated, evacuated, and flushed with nitrogen. Dry THF (10 ml), was added and the system degassed at -40 °C. The flask was flushed with nitrogen and n-butyllithium (1.4 ml, 3.5 mmol, 2.5M in hexanes) was added dropwise with stirring, maintaining the temperature below 0 °C. The mixture was stirred at this temperature (15 min), the system was cooled (-40 °C) and anhydrous zinc chloride (0.5 g, 3.5 mmol) in dry THF (20 ml) was added dropwise with stirring. The mixture was allowed to return to room temperature whilst stirring. The product of step 5 (0.7 g, 1.2 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.1 g, 0.1 mmol) were added and the mixture refluxed with stirring under nitrogen. When tic analysis indicated no further reaction (3 days), the mixture was allowed to cool. The solvent was removed in vacuo and the residue triturated with ether, whence a white solid precipitated. The solid was then re-triturated with petroleum fraction (bp 40-60 °C) from solution in methanol, and finally recrystallized (ethanol). Pale yellow crystals were obtained.

Yield 0.1 g (14%). Purity (hplc) >98%. *H NMR CDCl₃/δ 8.34 (2H, d), 7.77 (2H, d), 7.74 (1H, s), 7.67 (1H, t), 7.53

(2H, t), 7.47 (1H, s), 7.09 (2H,d), 6.97 (2H, d),

6.86 (1H, d), 6.69 (2H, d), 4.20 (2H, t) 3.90 (2H, t), 1.78

(4H, m), 1.30 (20H, m), 0.89 (3H, t), 0.88 (3H, t)

IR (KBr) Vmax/cm"¹ 2920, 2850, 1735, 1500, 830 MS m/z 6710VT), 566, 446, 341, 105(100%) Example 63

Liquid Crystal Properties

The liquid crystal properties of the compounds of the invention were tested using conventional methods. Examples of transitions are provided above in the Examples. However, the results are summarised in Table 3.

Table 3

Example 64

Liquid crystal properties of mixtures including Compounds of the Invention

A number of mixtures were prepared by adding a given percentage of the compounds of the invention to general host mixture comprising ethyl linked phenyl cyclohexanes. The properties of the mixtures were analysed using conventional methods and the results are set out in the following Tables 4-7.

Table 4 Phase behaviour, mixture composition and structure

This data provides some indications regarding the structural effects on the properties. For example, the influence of fluorine substituents can be assessed by comparison of the properties of mixtures 7 and 8 and 9 and 16. When fluorines are present on the remote ring (mixtures 8 and 9 including compounds 82 and 31 respectively), smectic phases are observed, but when they are on the benzofiiran central ring (as in mixture 7 including compound 38), only a nematic phase is observed. The transition temperatures are signficantly lower in the fluorinated compounds as compared to the corresponding non-fluorinated compound.

Table 5 Permittivities (of mixtures at 20°C - not extrapolated)

It would appear, from a comparison of mixtures 1, 2 and 14, that εX is greater when the nitrile is a substituent on the phenyl rather than the furyl ring of the benzofiiran (i.e. where R¹ is cyano in preference to R³). This also appears to lead to an increase in Δε (from 7.8 to 8.7)

Table 6 Birefringence and refractive indices (of mixtures, not extrapolated)

* Base mixture of ethyl linked phenyl cyclohexanes without a compound of the invention.

Properties of ester containing compounds can be compared by comparing the results for mixtures 4, 5 and 12 and below.

Properties of three ring systems can be assessed relative to each other by comparing the results for example obtained with mixtures 1, 10 and 15. This indicates that the relative position of the benzofiiran ring to the phenyl rings in the system has quite a large effect on the dielectric anisotropy.

A comparison of the results for mixtures 1, 2, 11 and 14 indicates that the position of a cyano group on different rings of the benzofiiran ring does not appreciably affect the birefringence.

However a comparison of three ring systems 1, 10 and 15 indicates that the birefringence of the mixture is lower when the benzofiiran moiety in in the middle of the phenyl rings and remote from a cyano substitutent. The effects of other groups such as pyrimidines, triple bonds and chiral moities may be asssessed for example by the results obtained with mixtures 3, 6 and 13. Compound no. 37 in mixture 6 showed a tendency to precipitate out of solution and therefore, a 5% mixture was used in some of the tests. Compound 17 was less stable than some other compounds.

Each mixture was filled into a 6μm TN cell with rubbed polyimide alignment layers and the optical switching time at 25°C, 40°C and (T_N.ι-30) °C with the application of 5 V pk-pk 1 KHz square wavemeasured. The results are shown in Table 7, along with measurement of the mixture of ethyl linked phenyl cyclohexanes in the absence of compounds of the invention in a cell from the same batch.

Table 7

The switching speeds indicate that the compounds of the invention have a low switching viscosity.

Looking at the reduced temperature (T_N-_I-30) °C switching times (shown in bold in Table 7), these are generally significantly faster than in the pure compound. This appeared to be the case even when terphenyls and negative materials are added. Example 65

Comparison of Mixture of Compounds of the Invention with Cyanobiphenyl compounds

A comparison of the eutectic mixture (as calculated using the Schroeder van Laar equation) of the corresponding cyanobiphenyls of formula A

where R is propyl- (C3), pentyl- (C5) and heptyl (C7) and the equivalent eutectic mixture of the propyl- pentyl and heptyl phenyl benzofiirans was made and the results are as shown in Tables 8-10.

Table 8 Phase behaviour and composition of mixtures

The phase behaviour and composition of the mixtures is given in Table 8. The benzofiiran mixture has a higher clearing point than the cyanobiphenyl mixture by over 15°. Neither mixture recrystallised when held at -40 °C for 40 minutes, although it is likely that both would recrystallise at this temperature if held for a sufficiently long time. Table 9

Birefringence and refractive indices

These results show that the birefringence is higher for the compounds of the invention, as is the dielectric anisotropy.

Table 10 Dielectric permittivities

The liquid crystal properties of mixtures including compounds of the invention were compared with similar mixtures using the corresponding compounds where the benzofiiran ring had been substituted with a phenyl ring. The results are shown in Table 11

Table 11

These results indicate that, generally, the compounds of the invention have a wider nematic phase range than the equivalent biphenyl compounds. (The range is slightly reduced in the case of terphenyl equivalents).

Example 66

Liquid Crystal Properties of Mixtures of Fluoro vs Non-Fluoro Compounds of the

Invention

The phase behaviour and structure of mixtures of compounds of the invention including difluoro compounds some of the mixtures defined in Table 11 were measured

Table 11

Compounds of the invention have in some cases wider nematic phase ranges than the equivalent biphenyl compounds.

Claims

Claims

1. A liquid crystal compound of general formula (I)

(I) where X is O, S or Se, each R¹ and R³ are independently selected from cyano, halo, optionally substituted hydrocarbyl, optionally substituted alkoxy, optionally substituted heterocyclyl, a group R¹³C(O)O- where R¹³ is optionally substituted hydrocarbyl or carboxy or a hydrocarbyl ester or amide thereof, provided that at least one or group R¹ or R³ is other than cyano or halo, each R² and R⁴ is independently selected from halo, nitro, lower alkyl optionally substituted by halo, or a group R^I4C(O)O- where R¹⁴ is optionally substituted hydrocarbyl, n is 1 or 2, m is 0, 1, 2 or 3, p is 1 or 2 and q is 0 or 1, provided n + m does not exceed 4 and p + q does not exceed 2, and further provided the compounds are other than a compound of formula (A) or (B)

(A) where R¹¹ is a C_1-8 alkyl group;

R¹² is H, or a d-nalkyl or Cϊ-ϊ∑alkenyl group, either of which may be optionally substituted by one CN or CF₃ group or one or more halogen atoms; and wherein one or more -CH₂-groups in the alkyl or alkenyl groups is optionally replaced by -O-, -S-, - C(O)-, C(O)O-, -OC(O)- or -OC(O)O- provided that oxygen and sulphur atoms are not directly linked to each other; A' and A" are indepedently selected from: a) a trans- 1,4-cyclohexylene residue in which one or more non-adjacent CH₂ groups can be replaced by -O- and/or -S-; b) a 1,4-cyclohexenyl residue; c) a 1,4-phenylene residue in which one or two CH groups can be replaced by N; d) a residue from the group l,4-bicyclo(2,2,2)-octylene, piperidine-l,4-diyl, naphthalene-2,6-diyl, decahydronaphthalene-2,6-diyl and 1,2,3,4-tetra- hydronaphtahlene-2,6-diyl; whereby residues a), b) and c) can be substituted by CN, Cl, or F,

Z" and Z"' independently represent -C(O)O-, -OC(O)-, -CH₂O-, -OCH₂-, -CH₂CH₂-,

-CH=CH-, -C≡C- or a single bond and g is 0,1 or 2

(B)

where each Ar is a bond or a spacer group such as a C_2-3oalkylene or C_2-3oalkenylene group, optionally substituted with C_1- alkyl, fluoro, chloro, bromo, cyano, or hydroxy, and optionally interposed with one or more -O-, -S-, -NH-, -NR⁰-, -COO-, OCO, OCOO or

CO; each M is independently selected from optionally substituted aliphatic, aromatic, heteroaliphatic or a heteroaromatic ring system,

X' is O, S, COO, OCOO, CONH or CONR^c where R^c is e and fare independently selected from 0,1 or 2, each Y' group is independently selected from O, S, COO, OCO, OCOO, CONH,

NHCO, CONR^c, or NR^cCO where R^c is as defined above; each Z' group is independently selected from hydrogen, cyano or a polymerisable group.

2. A compound according to claim 1 wherein n is 1, and m is 0 or 1.

3. A compound according to claim 1 or claim 2 wherein no more than one of the groups R¹ and R² is fluoro.

4. A compound according to any one of the preceding claims where one of R¹ or R³ is cyano or halo and the other is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof.

5. A compound according to any one of the preceding claims wherein R¹ or R³ where these are other than cyano or halo are selected from groups of formula (i), (ii), (iii), (iv), (v), (vi), (vii) or (viii)

(iϋ) (iv) where x is 0 or 11, R¹⁰ is an C_1-2oalkyl group, and y and z are independently selected from 0, 1 or 2.

6. A liquid crystal compound according to claim 1 which is of general formula (IA)

_R2b

(IA) where X is oxygen, sulphur or selenium, R^la and R^lb are independently selected from hydrogen, cyano, halo, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or carboxy or a hydrocarbyl ester or amide thereof, provided that at least one group R^la or R^lb is other than hydrogen; one of R¹⁷ or R¹⁸ is cyano, halo, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or carboxy or a hydrocarbyl ester or amide thereof, and the other is hydrogen, halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁵C(O)O- where R¹⁵ is an optionally substituted hydrocarbyl group; R^2a and R ^b are independently selected from hydrogen, halo, nitro, lower alkyl optionally substituted by halo, or a group R¹⁴C(O)O- where R¹⁴ is as defined above; subject to the provisos that:

(i) at least one group R^la or R^lb or R¹⁷ or R¹⁸ is other than cyano or halo; (ii) where X is S, R¹⁷ is carboxy or a hydrocarbyl ester or amide thereof, R¹⁸ is hydrogen, R ^a and R^2b are not both fluoro; (iii) where X is O, R¹ is an optionally substituted hydrocarbyl or carboxy or a hydrocarbyl ester or amide thereof, R^2a is hydrogen, and R^lb and R^2b are both fluorine, then R¹⁷ is other than C_1-8 alkyl.

7. A compound according to claim 6 wherein one of R^lb or R^la or R¹⁷ or R¹⁸ in formula (IA) is cyano or halo and at least one of the said groups on the other ring of the bicyclic ring of formula (LA) is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, an optionally substituted aryl, optionally substituted heterocyclyl, carboxy or a hydrocarbyl ester thereof.

8. A compound according to claim 1 of formula (II)

wherein R⁵ is a group R³ as defined above in claim 1, one of R⁷ and R⁸ is a group R¹ as defined in claim 1 and the other is hydrogen or a group R¹ as defined in claim 1 ; R⁶ is hydrogen, cyano or fluoro, R⁹ is hydrogen, cyano or fluoro, provided that where R⁵ is cyano or fluoro, at least one of R⁷ or R⁸ is optionally substituted alkyl, optionally subsituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally subsituted alkoxy, optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof; and where one of R⁷ or R⁸ is cyano or fluoro and the other is hydrogen, R⁵ is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heterocyclyl, carboxy or an ester thereof.

9. A compound according to claim 8 of formula (HA)

(IIA)

where R⁵ is cyano or fluoro, preferably fluoro, one of R⁷ and R⁸ is hydrogen and the other is an optionally substituted hydrocarbyl group or a heterocyclic group as described above.

10. A compound according to claim 9 wherein at least one of R⁷ or R⁸ is a group of sub-formula (i), (ii), (iii), (vi) or (viii) as defined in claim 5.

11. A liquid crystal compound according to any one of claims 1 to 7 where X is oxygen.

12. A liquid crystal compound according to claim 8 which comprises a compound of formula (II) where R⁶ is hydrogen or fluoro, and R⁹ is hydrogen or fluoro.

13. A liquid crystal mixture comprising a compound according to any one of the preceding claims.

14. A liquid crystal mixture according to claim 13 which comprises at least two different compounds according to any one of claims 1 to 12.

15. A liquid crystal device such as a liquid crystal display device (LCD) comprising a compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14.

16. A liquid crystal compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14, which has electroclinic properties.

17. An electroclinic device comprising a liquid crystal compound or a mixture according to claim 16.

18. A liquid crystal compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14, which has cholesteric properties.

19. A device comprising a liquid crystal compound or a mixture according to claim 18, wherein said device is a thermoptic, thermographic or electro-optical device.

20. A liquid crystal compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14, which has ferroelectric properties.

21. A ferroelectric device comprising a liquid crystal compound or a mixture according to claim 20.

22. A liquid crystal compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14, which has flexo-electric properties.

23. A flexo-electric device comprising a liquid crystal compound or a mixture according to claim 22.

24. A liquid crystal compound according to any one of claims 1 to 12 or a mixture according to claim 13 or claim 14, which has pyro-electric properties.

25. A pyro-electric device comprising a liquid crystal compound or a mixture according to claim 24.

26. A method of preparing a compound of formula (I) according to claim 1 which comprises either (i) reacting a compound of formula (HI)

(III)

where R², R³, R⁴, X, n, m, p and q are as defined in claim 1, and Z is either a leaving group or a group B(OH)₂, with a compound of formula (TV)

R^J-Z'

(TV) where R¹ is as defined in relation to formula (I) and Z' is a group B(OH)₂ where Z is a leaving group, or a leaving group where Z is a group B(OH)₂; or (ii) reacting a compound of formula (V)

(V) where R¹, R²,R⁴, X, n, m, p and q are as defined in relation to formula (I), and Z is as defined in relation to formula (III), with a compound of formula (VI)

R³-Z'

(VI)

where R³ is as defined in relation to formula (I) and Z' is as defined in relation to formula (IV), or (iii) where q is 0 and p is 1 and R³ is a carboxy group, carboxylating a compound of formula (IX)

(IX) were R², R⁴, X, m,n and q are as defined in relation to formula (I), and R¹ is a group R¹ as defined in relation to formula (I) or a precursor thereof; with a carboxylating agent, and thereafter acidifying the product with an acid such as glacial acetic acid, or (IV) where q is 0, reacting a compound of formula (XHI)

where R , R , X, n and m are as defined above, with a compound of formula (XIV)

HO₂C-R³ (XIV) where R³ is a group R³ as defined in relation to formula (I)or a precursor thereof; and thereafter, if necessary, changing any groups R¹, R² R³ or R⁴ to different such groups.