WO2023233129A1 - Macrocyclic compounds comprising tetrafluorophenyl moieties - Google Patents

Abstract

The invention provides a macrocyclic compound of Formula (I): wherein each R1 is independently an aromatic ring system that is optionally substituted, and wherein n is an integer of from 2 to 50.

Description

MACROCYCLIC COMPOUNDS COMPRISING TETRAFLUOROPHENYL MOIETIES

The present invention relates to macrocyclic compounds, and in particular to fluorinated cyclic corona[n] arenes.

Background to the Invention

Macrocyclic compounds have many uses. For example, they can be used to provide a cavity for receiving molecules and they can be used in guest-host chemistry, polymerization chemistry, catalysis, and the like.

Non-fluorinated cyclic corona[n] arenes are known in the art. These materials are valuable precursors for both synthetic and materials chemistry.

J. Franke, F. Vogtle, Tetrahedron Lett. 1984, 25, 3445-3448 describes cyclic compounds of the following formula, where n=4-9, as products of 1,4-C₆H₄Br(SCu) oligomerisation, with n = 6 being major.

JP 2012 072222 A describes a cyclic polyphenylene sulfide mixture, having the same general formula as shown above, but where the degree of polymerization is from 4-20. Further, it is required that the sum of the content of cyclic polyphenylene sulfide monomers with a degree of polymerization of 4, 6 and 8, respectively, is less than 15 wt.% relative to the sum of the total monomers. In addition, the content of cyclic polyphenylene sulfide monomer with a degree of polymerization of 5 must be not less than 15 wt.%, relative to the sum of the total monomers.

I. Baxter, A. Ben-Haida, H. M. Colquhoun, P. Hodge, F. H. Kohnke, D. J. Williams, Chem. Eur. J. 2000, 6, 4285-4296 and A. Ben-Haida, H. M. Colquhoun, P. Hodge, J. Raftery, A. J. P. White, D. J. Williams, Org. Biomol. Chem. 2009, 7, 5229-5235 reported sulfone macrocycles as shown below, where n=4-6, 8, 12, in 0.7-26% yields, often isolated from complex mixtures.

Q.-H. Guo, L. Zhao, M.-X. Wang, Chem. Eur. J. 2016, 22, 6947-6955, and M.-Y. Zhao, D.-X. Wang, M.-X. Wang, J. Org. Chem.2018, 83, 1502-1509 and Z.-C. Wu, Q.-H. Guo, M.-X. Wang, Angew. Chem. Int. Ed. 2015, 54, 8386-8389 describe the preparation of heterocycle-based macrocycles derived from 3,6-dichloro-1,2,4,5-tetrazine, such as those set out below:

n=2, R=CO₂Me JPH05-301962 A describes a cyclic arylene sulfide oligomer expressed by the following formula:

where Ar is 6-24 C arylene; R is 1-12 C alkyl, 1-12 C alkoxy, 6-24 C arylene or primary, secondary or tertiary amino; n is 2-50; and m is 0-15. Alternative options for the R substituent are mentioned as being a carboxyl group or its ester, a cyano group, a sulfonic acid group, or a halogen atom; however no synthetic route to successfully obtain a fluorinated product is provided. The compounds of JPH05-301962 A are macrocycles with a single R-substituted Ar group present as the monomer. The monomer backbone that forms the macrocycle ring structure therefore only includes one type of aromatic group. The polymerisation of fluorine-containing arylthio ethers is also known, providing polymers such as:

See, for example, WO2007/006300 A1; N. S. J. Christopher, J. L. Cotter, G. J. Knight, W. W. Wright, J. Appl. Poly. Sci. 1968, 12, 863-870; R. Kellman, J. C. McPheeters, D. J. Gerbi, R. F. Williams, R. B. Bates, Polymer Preprints (American Chemical Society, Division of Polymer Chemistry) 1981, 22, 383- 384 [Chem. Abs.1983, 99, 6080]; R. Kellman, M. T. Henry, R. F. Williams, R. G. Dimotsis, D. J. Gerbi, J. C. Williams, Preprints - American Chemical Society, Division of Petroleum Chemistry 1985, 30, 408- 14 [Chem. Abs. 1985, 103, 178727]; R. Kellman, R. F. Williams, G. Dimotsis, D. J. Gerbi, J. C. Williams, ACS Symposium Series 1987, 326 (Phase Transfer Catalysis), 128-42; and N. H. Park, G. dos Passos Gomes, M. Fevre, G. O. Jones, I. V. Alabugin, J. L. Hedrick, Nat. Commun.2017, 8, 166. US2018/0290952 describes halogenated macrocyclic “nanohoop” compounds such as:

US2019/025315, US2020/010419, US2021/095069 and US2021/095070 also describe similar “nanohoop” compounds. However, there remains a need in the art for new macrocyclic ring systems. Summary of the Invention The present invention provides, in a first aspect, a macrocyclic compound of Formula (I):

wherein each R¹ is independently an aromatic ring system that is optionally substituted, and wherein n is an integer of from 2 to 50. The compounds of the invention are therefore macrocycles with two aromatic ring systems present in each monomer. One characterising feature of the invention is the inclusion of two different aryls. Both the R¹ aromatic ring system and the fluorinated phenylene aromatic ring system are within the backbone of the monomer that forms the macrocycle (rather than being pendant therefrom). Therefore the monomer backbone that in turn forms the macrocycle ring structure includes both of these aromatic groups. The skilled reader will appreciate that the macrocyclic nature of the compound is represented by the solid curved line. In the above formula this solid curved line represents a bond formed between an R¹ group and a sulphur atom attached to a para-positioned carbon atom of a fluorinated aromatic ring, to thereby form the macrocyclic structure. In general, the macrocyclic compounds of the invention can be used in a variety of different applications. For example, they could be used as transport facilitators, synthetic templates (e.g., nanoreactors), or as electrically conductive materials. As such, the macrocyclic compounds of the invention can be used in different biological and/or chemical systems and even in energy storage devices. These compounds of the invention are valuable synthetic intermediates, e.g. for manipulation into other macrocyclic species. In this regard, the displaceable fluorine substituents within the macrocyclic compounds of Formula (I) afford further valuable macrocyclic compounds by their (SNAr) displacement with suitable nucleophiles and other carbon-based and heteroatom nucleophiles. These compounds of the invention may be used as precursors for electronics molecules. The compounds can stack in a barrel-like arrays, giving the ability to create a 2D conductor. These compounds are also useful due to the cavity provided within the macrocyclic structure. For example, they may be used as sequestering agents, or they may be used as sensors whereby an agent to be detected binds inside the cavity. Thus, the macrocyclic compounds of the invention may further comprise an interlocked compound constrained within the cavity defined by the macrocycle. These compounds are also useful due to the reactive C-F bonds and their overall size, which is greater than 1nm. This provides potential utility as scaffolds for use in pharmaceutical applications, in sensing apparatus and in membrane reactors. Detailed Description of the Invention In the compound of Formula (I), each R¹ is independently an aromatic ring system that is optionally substituted. In one embodiment each R¹ is the same. However, it will be recognised that Formula (I) also allows for the preparation of mixed systems, where the R¹ groups are different. The synthesis of the macrocyclic compounds of the invention from monomers, as described below, facilitates the incorporation of different R¹ aromatic ring systems, in particular when the pre- organised macrocyclization route is used. Therefore, in one embodiment the macrocyclic compound of the invention includes two or more different R¹ groups, such as two, three or four different R¹ groups. For example, there may be two different R¹ groups, which can therefore be represented as follows:

wherein R¹´ and R¹´´ are each an aromatic ring system that is optionally substituted, and wherein n´ is an integer of from 1 to 49 and wherein n´´ is an integer of from 1 to 49 and where n´+n´´ is an integer of from 2 to 50. Thus, each of R¹´ and R¹´´ is an R¹ aromatic ring system and these groups can each independently follow the definitions and preferred embodiments as disclosed herein for the R¹ aromatic ring system. It will also be appreciated that n´ plus n´´ equals n, and that the definitions and preferred embodiments as disclosed herein for the values of n apply. In one embodiment the R¹ aromatic ring system has from 5 to 18 ring members, such as from 5 to 12 ring members. The R¹ aromatic ring system may be a monocyclic ring (e.g. phenylene) or may be a fused ring, e.g. resulting from the condensation of multiple benzene rings or resulting from the condensation of benzene and other rings. In one embodiment the fused ring is formed from two or three rings. In one embodiment it is formed from a five-membered ring fused with a six-membered ring, or from two fused six-membered rings, or from two fused five-membered rings. Examples of fused rings include a pentalene ring, indene ring, naphthalene ring, anthracene ring, azulene ring, biphenylene ring, indacene ring, acenaphthylene ring, fluorene ring, phenalene ring, and a phenanthrene ring. Heterocyclic aromatic rings could be contemplated, e.g. where the aromatic ring system includes one or more S, N or O atom within the ring system. The skilled person will appreciate that the heteroatom(s) replace one or more of the carbon atoms within the ring. In general, in the heterocyclic aromatic ring there may suitably be up to four heteroatoms which replace a carbon in the ring, e.g. one, two or three heteroatoms which replace a carbon in the ring. Examples of heterocyclic rings include a pyridine ring, pyrimidine ring, pyrazine ring, pyridazine ring, carbazole ring, indole ring, isoindole ring, indolizine ring, quinoline ring, isoquinoline ring and a purine ring. The R¹ aromatic ring system preferably contains a bivalent 6-membered aromatic ring or a bivalent 6-membered heterocyclic aromatic ring. In one embodiment, it has binding sites at the para-positions. The R¹ aromatic ring system is preferably selected from phenylene, biphenylene and naphthylene ring systems, each of which may optionally be substituted. Thus, in one preferred embodiment, R¹ is selected from:

wherein each Y is a substituent group (which may be as further defined below) and wherein m is an integer from 0 to 8, e.g. from 0 to 4, such as 0, 1 or 2. It will be appreciated that if m is zero then the R¹ aromatic ring system is unsubstituted. In one preferred embodiment, R¹ is selected from a phenylene group (in particular, a 1,4- phenylene group) and a naphthylene group (in particular, a 1,5-naphthylene group or 2,6- naphthylene group), each of which may optionally be substituted. In one such embodiment, R¹ is a phenylene group, which may optionally be substituted. In one embodiment, R¹ is not

. It is desirable that R¹ is not C₆F_4. In one embodiment, R¹ is unsubstituted. In another embodiment, R¹ is substituted. When R¹ is substituted, there may be one or more substituent groups, e.g. one or two or three substituent groups. It may be that each substituent group is independently selected from an electron-donating group or an electron-accepting group. Electron-donating groups can be any functional groups capable of donating at least a portion of its electron density into the ring to which it is directly attached, such as by resonance. Exemplary electron-donating groups can be selected from, but not limited to, one or more of the following groups: alkoxy, thioether, amide, amine, hydroxyl, thiol, acyloxy, aliphatic (e.g., alkyl, alkenyl, alkynyl), aryl, or combinations thereof. Electron-accepting groups can be any functional groups capable of accepting electron density from the ring to which it is directly attached, such as by inductive electron withdrawal. Exemplary electron-accepting groups can be selected from, but not limited to, one or more of the following: aldehyde, ketone, ester, carboxylic acid, acyl, acyl halide, cyano, sulfonate, nitro, nitroso, quaternary amine, pyridinyl (or pyridinyl wherein the nitrogen atom is functionalized with an aliphatic or aryl group), alkyl halide, or combinations thereof. In one embodiment, each substituent group is independently selected from: halo, C1-12 alkyl, C1-12 alkylhalo, CN, NO₂, OR^x, NR^xRy, OC(O)R^x, C(O)R^x, C(O)NR^xR¹², C(O)OR¹¹, OS(O) ^{x x x x} 2R , SR , and R ; wherein R and Ry are each independently selected from hydrogen, C1-12 alkyl, C1-12 alkylhalo, C5-12 aryl, and C5-12 heteroaryl (e.g., in one embodiment, R^x and Ry are each independently selected from hydrogen and C1-6 alkyl). In one embodiment, each substituent group is independently selected from: halo, C1-12 alkyl, C1-12 alkylhalo, OR^x, NR^xR^y, SR^x, and R^x; wherein R^x and R^y are each independently selected from hydrogen, C1-12 alkyl, C1-12 alkylhalo, C5-12 aryl, C5-12 heteroaryl (e.g. in one embodiment, R^x and R^y are each independently selected from hydrogen and C1-6 alkyl). In one embodiment, each substituent group is independently selected from: C1-6 alkyl (e.g. methyl or ethyl), halo (e.g. Br), OR^x (e.g. OH or OMe) and NR^xR^y (e.g. NH₂ or NMe₂). In one embodiment, where a substituent group on the R¹ is halo, it is not F. In one embodiment, therefore, where there is halo substitution on the R¹ group, it is selected from Cl and Br and I, such as Br. When the alkyl group has three or more carbon atoms, it may be straight chain or branched. The aryl group is a carbocyclic group having aromatic character, examples of which include phenyl and naphthyl. The aryl or heteroaryl group can, for example, have from 5 to 10 ring members. The aryl or heteroaryl group can, for example, be a five-membered or six-membered monocyclic ring or a bicyclic structure formed from a five-membered ring fused with a six- membered ring, or from two fused six-membered rings, or from two fused five-membered rings. In the heteroaryl group there may suitably be up to four heteroatoms which replace a carbon in the ring; these are typically selected from nitrogen, sulphur and oxygen. Typically, the heteroaryl ring will contain up to 3 heteroatoms, more usually up to 2, for example a single heteroatom. In one embodiment, there are up to three substituent groups on the R¹ aromatic ring system. In one embodiment, there are zero, one, or two substituent groups on the R¹ aromatic ring system. In one embodiment, n is an integer from 2 to 48, such as from 2 to 36, or from 2 to 24 or from 4 to 24; in certain embodiments n is an integer from 2 to 20 or from 2 to 18, such as from 4 to 16 or from 4 to 12, e.g. 4, or 6, or 8, or 10, or 12. In one embodiment, n is an integer from 4 to 10. In one embodiment, n is 4 or 6. In one preferred embodiment, the macrocyclic compound of the invention is of Formula (I-i):

wherein each Y is independently selected from hydrogen or a substituent group as defined above, and where n is an integer as defined above. For example, each Y may independently be selected from: hydrogen, C1-6 alkyl (e.g. methyl or ethyl), halo (e.g. Br), OR^x (e.g. OH or OMe) and NR^xR^y (e.g. NH₂ or NMe₂), and n may be an integer from 2 to 20 or from 2 to 18, such as from 4 to 16 or from 4 to 12, e.g. 4, or 6, or 8, or 10, or 12. In one embodiment, the compound is of Formula (I-a), where n=4, or Formula (I-b), where n=6:

The skilled reader will recognise that the definitions provided above are not intended to include impermissible substitution patterns (e.g., methyl substituted with 5 different groups, and the like). In formulae and specific compounds disclosed herein, a hydrogen atom is present and completes any formal valency requirements (but may not necessarily be illustrated) wherever a functional group or other atom is not illustrated. The compounds of Formula (I) can be obtained by use of known monomers together with an ammonium salt templating agent. Surprisingly, it has been found that by using these specific templating agents the macrocyclic ring structure is formed, rather than a linear polymer chain. The ammonium salt templating agent is of Formula (II): [N R^a R^b R^c R^d]+X- (II) wherein each of R^a, R^b, R^c, and R^d are independently selected from hydrogen, C1-C12 alkyl, C5-12 aryl and C6-C22 alkaryl, and wherein X is a counterion. When the alkyl group has three or more carbon atoms, it may be straight chain or branched. The aryl group is a carbocyclic group having aromatic character, examples of which include phenyl and naphthyl. The aryl group can, for example, be a five-membered or six-membered monocyclic ring or may be a bicyclic structure from a five-membered ring fused with a six- membered ring, or from two fused six-membered rings, or from two fused five-membered rings. The aryl group can, for example, have from 5 to 10 ring members. Alkaryl refers to - alkylene-aryl groups, preferably having from 1 to 10 carbon atoms in the alkylene moiety and preferably having from 6 to 10 carbon atoms in the aryl moiety. Such alkaryl groups are exemplified by benzyl, phenethyl and the like. For example, each of R^a, R^b, R^c, and R^d may be independently selected from hydrogen, methyl, ethyl, n-propyl, n-butyl, Ph, -CH₂-aryl and -CH₂CH₂-aryl. The aryl group can, for example, have from 5 to 10 ring members. In one preferred embodiment, each of R^a, R^b, R^c, and R^d may be independently selected from hydrogen, methyl, ethyl, n-butyl, and Ph. In particular, each of R^a, R^b, R^c, and R^d may be independently selected from hydrogen, methyl, ethyl and n-butyl. In one embodiment, R^a R^b R^c and R^d are all the same. In one embodiment, each of R^a, R^b, R^c, and R^d is the same and each is H, or each is methyl, or each is ethyl, or each is n-butyl. In one such embodiment, each of R^a, R^b, R^c, and R^d is the same and each is methyl. X may be any suitable counterion. In one embodiment, X is selected from a halogen (F, Cl, Br, I) or a pseudohalogen (for example: OH, CN, OCN, SCN, N₃). In one preferred embodiment, X is a halogen, such as F.

In one preferred embodiment, the ammonium salt templating agent is NMe₄ ⁺F-, or NH₄ ⁺F- or NBU₄ ⁺F-. In one such embodiment, the ammonium salt templating agent is NMe₄ ⁺F-.

Advantageously, it has been found that there is a kinetic effect associated with the use of the ammonium salt templating agent of Formula (II), as well as a templating effect. The ammonium salt templating agent of Formula (II) allows the reaction to proceed at room temperature and with a reaction time of about 0.5 hours.

Although templating is known for other molecules, it has not been described for use in relation to forming macrocyclic rings according to the present invention. Unexpectedly, the ammonium salt templating agent of Formula (II) works without any apparent size limitation; a range of different sized macrocycles have been obtained successfully. Additionally, the ammonium salt templating agent of Formula (II) provides significant rate accelerations over traditional templating approaches.

The compounds of Formula (I) can be obtained by use of the above -noted ammonium salt templating agent in a one-pot macrocyclization or in a pre-organised macrocyclization.

A one-pot macrocyclization can be illustrated by the following exemplary reaction scheme:

Thus, in this exemplary scheme (a) benzenedithiol is reacted with (b) a fluorine-substituted six-membered aromatic ring. In general, it will be appreciated that (a) a dithiol form of the R¹ aromatic ring system is reacted with (b) a fluorine -substituted six-membered aromatic ring, e.g. C₆F₆. For monomer (a), the dithiol form of the R¹ aromatic ring system is preferably a para dithiol form, e.g. a 1,4-dithiol.

The monomers (a) and (b) may suitably be provided in molar ratios of 1: 10 to 10: 1, e.g. 1:5 to 5: 1, and most commonly about 1: 1.

In one embodiment the reaction is between the dithiol 1,4-HSC₆H₄SH and C₆F₆.

A pre-organised macrocyclization can be illustrated by the following exemplary reaction scheme:

Thus, in this exemplary scheme (a) benzenedithiol is reacted with (b) a triaryl monomer formed from two units of fluorine-substituted six-membered aromatic ring and one unit of benzenedithiol.

In general, it will be appreciated that (a) a dithiol form of the R¹ aromatic ring system is reacted with (b) a multi -aryl monomer formed from alternating units of (i) fluorine-substituted six-membered aromatic ring and (ii) a dithiol form of the R¹ aromatic ring system. The multi- aryl monomer formed from alternating units may, for example, be (i)-(ii)-(i), or (i)-(ii)-(i)- (ii)-(i), or (i)-(ii)-(i)-(ii)-(i)-(ii)-(i).

For monomer (a), the dithiol form of the R¹ aromatic ring system is preferably a para dithiol form, e.g. a 1,4-dithiol.

For monomer (b), the units (ii) are preferably linked to the units (i) at the para position. In one embodiment, for monomer (b) a triaryl monomer (i)-(ii)-(i) is used and thus it will be appreciated that (a) a dithiol form of the R¹ aromatic ring system is reacted with (b) a triaryl monomer formed from two units of fluorine-substituted six-membered aromatic ring and one unit of a dithiol form of the R¹ aromatic ring system. The monomers (a) and (b) may suitably be provided in molar ratios of 1:10 to 10:1, e.g. 1:5 to 5:1, and most commonly about 1:1. In both the one-pot macrocyclization and the pre-organised macrocyclization, an ammonium salt templating agent of Formula (II) is used, e.g. NMe₄+F- , together with a suitable solvent, e.g. pyridine. The skilled person will appreciate that a range of alternative solvents could be used. For example, triethylamine and N-methylmorpholine could be contemplated. In both the one-pot macrocyclization and the pre-organised macrocyclization, the reaction can be carried out at room temperature. A suitable reaction time may be about 0.5 hours. The ammonium salt templating agent is suitably employed in an amount of 1.0 equivalents or more (with respect to dithiol monomer (a)), e.g. from 1.0 to 2.0 equivalents. The skilled person can control the ring size for the macrocyclic compound by the choice of ammonium salt templating agent of Formula (II) and/or by the choice of monomers used in the pre-organised macrocyclization. In general, the use of a larger template for the reaction (e.g. a large tetra-substituted ammonium fluoride salt) leads to a larger macrocycle (greater n value). Thus R^a, R^b, R^c, and R^d can be selected to be sterically bulkier groups if a large n value is desired. Likewise, the use of a larger monomers in the pre-organised macrocyclization route would leads to a larger macrocycle (greater n value). For example, a multi-aryl monomer (b) formed from alternating units (i)-(ii)-(i)-(ii)-(i) or (i)-(ii)-(i)-(ii)-(i)-(ii)-(i) may be selected if a large n value is desired. This pre-organised macrocyclization route also beneficially provides greater control over ring size. Thus, although the following examples illustrate the preparation of the macrocyclic compounds according to the invention where n is 4 or 6, it is readily within the ability of the skilled person to use larger templates and/or to use larger monomers in order to obtain further macrocyclic compounds according to the invention where n is higher. Examples The invention will be further illustrated by the following non-limiting examples. Example 1a: Reagent 1

CuSC₆F₅: To a 100 mL flask fitted with a dropping funnel was added CuSO₄·5H₂O (2.49 g, 10 mmol) in H₂O (35 mL) and vigorously stirred at rt. A solution of pentafluorothiophenol (1.88 g, 9.4 mmol) in H₂O (5 mL) was added to the dropping funnel and added dropwise over 20 min. A yellow precipitate immediately forms. Upon complete addition, the reaction mixture was further stirred for 30 min at rt. The resulting yellow precipitate was isolated by vacuum filtration and washed with H₂O (20 mL), MeOH (5 mL) and Et₂O (5 mL). The yellow solid was then dried under vacuum at 40 °C overnight. The title product was isolated as a yellow solid (2.04 g, 7.8 mmol, 83%). M.P. 270 – 271 °C. Example 1b: Monomer 2

Triaryl monomer: To a small oven-dried Schlenk tube was added CuSC₆F₅ as made in Example 1a (11.7 g, 45 mmol), 1,4-diiodobenzene (5.3 g, 16 mmol) and anhydrous DMF (30 mL). The Schlenk tube was capped, and the mixture deoxygenated (3 × freeze-pump- thaw cycles under N₂) then stirred for 2.5 h at 145 °C. Upon cooling to rt, a 10% aqueous solution of HCl (25 mL) was added. The mixture was extracted with Et₂O (5 × 25 mL) and the organic layers were combined and dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The crude yellow solid was purified by column chromatography (SiO₂, Hexane-CH₂Cl₂, 5%) and recrystalised from pentane at 20 °C. The title product was isolated as fine colourless crystals (6.10 g, 12.90 mmol, 81%). M.P. 153 – 154 °C. ¹H NMR (500 MHz, CDCl₃) δ 7.24 (s, 4H, H1). ¹³C NMR (126 MHz, CDCl₃) δ 148.7 – 146.7 (CX, ¹J_CF = 248.5 Hz), 143.5 – 141.5 (CX, app. dtt, ¹J_CF = 255.9, ²J_CF = 13.4, ³J_CF = 5.0 Hz), 139.0 – 137.0 (CX, ¹J_CF = 255.9 Hz), 133.3 (C₂), 131.2 (C¹), 108.2 (C₃, dt, ⁴J_CF = 4.5, ²J_CF = 20.9 Hz (Not all J-CF apparent in AA’MXX’ system). ¹⁹F NMR (376 MHz, CDCl₃) δ -131.36 (m, 4F), -150.28 (t, J = 21.0 Hz, 2F), -159.86 (m, 4F). HR-ESI MS m/z = 496.9501 [M+Na]+ (calculated for C₁₈H₄F₁₀S₂Na = 496.9492). Example 1c: Monomer 3

E-Triaryl monomer: To a quartz vessel was added triaryl monomer as made in Example 1b (24 mg, 0.05 mmol), K₂CO₃ (21 mg, 0.15 mmol), MeCN (5 mL) and H₂O (1 mL). The mixture was then deoxygenated (3 × freeze-pump-thaw cycles under N₂) and irradiated for 6 h (4 × 9W 254 nm). Upon complete consumption of the starting material, the mixture was poured onto H₂O (5 mL) and extracted with EtOAc (3 ×10 mL) and the organic layers were combined and dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The crude solid was purified by column chromatography (SiO₂, Pentane). The title product was isolated as fine colourless crystals (20 mg, 0.042 mmol, 83%). ¹H NMR (500 MHz, CDCl₃) δ 7.98 (s, 2H, H₁) δ ¹⁹F NMR (376 MHz, CDCl₃) δ - 131.36 (m, 4F), -150.28 (t, J = 21.0 Hz, 2F), -159.86 (m, 4F). HR-ESI MS m/z = 456.9355 [M+Na]+ (calculated for C₁₈H₂F₈S₂Na = 456.93678). Example 1d: Reagent 4

O,O'-(1,4-phenylene) bis(dimethylcarbamothioate): To an dried oven-dried Schlenk tube was added hydroquinone (2.0 g, 18 mmol), DABCO (5.04 g, 45 mmol) and anhydrous N-Methyl-2-pyrrolidone (30 mL) and heated to 50 °C. A solution of dimethyl thiocarbonyl chloride (4.74 g, 38 mmol) in anhydrous N-Methyl-2-pyrrolidone (8 mL) was added dropwise to the heated mixture over 30 min. The mixture was then stirred at 55 °C for 20 hours. H₂O (100 mL) was added dropwise over 1 h at 55 °C, yielding a light brown precipitate. The precipitate was isolated by vacuum filtration and washed with H₂O (3 x 25 mL), then dried at 50 °C under reduced pressure. The title product was isolated as a beige powder (2.6 g, 9.15 mmol, 51%). ¹H NMR (500 MHz, CDCl₃) δ 7.08 (s, 4H, H¹), 3.46 (s, 6H, H ), 3.34 (s, 6H, H ). HR-ESI-MS m/z = 307.0548 [M+ + 4 4 Na] (calculated for C₁₂H₁₆N₂O₂S₂Na = 307.0551). Example 1e: Reagent 5

S,S'-(1,4-phenylene) bis(dimethylcarbamothioate): To an oven dried Schlenk tube was added, O,O'-(1,4-phenylene) bis(dimethylcarbamothioate) as made in Example 1d (0.92 g, 3.24 mmol) and sulfolane (2 mL). The mixture was heated to 280 °C for 1 hour under vigorous stirring with no precautions taken to maintain an inert atmosphere. The hot mixture was slowly added dropwise to H₂O (5 mL), to form a light brown precipitate. The precipitate was isolated by vacuum filtration and washed with H₂O (3 x 25 mL), then dried at 50 °C under reduced pressure. The title product was isolated as a beige powder (0.85 g, 3.0 mmol, 93%)^{. 1}H NMR (500 MHz, CDCl₃) δ 7.50 (s, 4H, H₁), 3.03 (bs, 12H, H₄). ¹³C NMR (126 MHz, CDCl₃) δ 166.5 (C₃), 135.9 (C₁), 130.3 (C₂), 37.1 (C₄). HR-ESI-MS m/z = 285.0748 [M+H]+ (calculated for C₁₂H₁₇N₂O₂S₂ = 285.0731). Example 1f: Monomer 6

Benzene-1,4-dithiol: To an oven dried round bottom flask was added, S,S'-(1,4- phenylene) bis(dimethylcarbamothioate) (0.85 g, 3.0 mmol), KOH (3.36 g, 60 mmol, 20 equiv) and MeOH (17 mL). The reaction mixture was heated to reflux for 4 hours under an N₂ atmosphere. Upon cooling to rt, H₂O (30 mL) and CH₂Cl₂ (15 mL) was added, and the organic layer removed. The aqueous fraction was carefully acidified through dropwise addition of concentrated HCl and then extracted with EtOAc (3 × 25 mL). The organic layers were combined and dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The crude solid was passed through a short silica gel (SiO₂) plug, eluting with pentane (150 mL) and evaporated to dryness under reduced pressure. The title product was isolated as a colourless solid (0.4 g, 2.8 mmol, 93%). M.P. 96 – 98 °C. ¹H NMR (500 MHz, CDCl₃) δ 7.16 (s, 4H, H1), 3.33 (s, 2H, H₃). ¹³C NMR (126 MHz, CDCl₃) δ ESI-MS m/z = 142.9973 [M+H]⁺ (calculated for C₆H₇S₂ = 142.9989). Example 2a: Macrocyclic compound of Formula (I-a) - pre-organised macrocyclization to obtain S₈-corona[4]phenylene[4]tetrafluorophenylene

To an oven dried Schlenk tube was added benzene-1,4-dithiol as made in Example 1f (1.42 g, 10 mmol, 1 equiv) and tetramethyl ammonium fluoride tetrahydrate as templating agent (1.70 g, 10 mmol, 1 equiv) and this was deoxygenated through 3 × vacuum-N₂ cycles. Deoxygenated pyridine (70 mL) as solvent was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. A solution of triaryl monomer as made in Example 1b (3.78 g, 8 mmol, 0.8 equiv) in pyridine (70 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 0.5 hr at room temperature. Upon complete addition the reaction was stirred for a further 0.5 h before the solvent was removed under reduced pressure (water bath temp <35 °C) to yield a crude yellow solid. The crude material was sonicated in CHCl₃ (400 mL) and filtered to remove polymeric insoluble material. The organic soluble mixture was successively washed with H₂O (5 × 100 mL), brine (100 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was washed with hot pentane (3 × 50 mL) to give a mixture of [8] macrocycle (compound of Formula (I-a)) and [12] macrocycle (ratio 1: 0.06) (1.3 g, 1.13 mmol, 28% yield). An analytical sample of the compound of Formula (I-a) was isolated via sublimation (1 mbar, 300 °C) to yield a colourless crystalline solid.¹H NMR (500 MHz, CDCl₃) δ 7.31 (s, 16H, H1). ¹³C-¹⁹F decoupled NMR (126 MHz, CDCl₃) δ 146.4 (C₄), 132.6 (C₂), 131.4 (C₁), 115.5 (C₃). ¹⁹F NMR (376 MHz, CDCl₃) δ -134.5 (s, 16F). MALDI-MS m/z = 1152.0 [M]⁺ (calculated for C₄8H16F16S8 = 1151.88). Example 2b: Macrocyclic compound of Formula (I-a) – one-pot macrocyclization to obtain S₈-corona[4]phenylene[4]tetrafluorophenylene

To an oven dried Schlenk tube was added, benzene-1,4-dithiol as made in Example 1f (0.55 g, 3.9 mmol), tetramethyl ammonium fluoride tetrahydrate as templating agent (0.68 g, 4.1 mmol mmol, 1.05 equiv) and deoxygenated through 3 × vacuum-N₂ cycles. Deoxygenated pyridine (35 mL) as solvent was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. A solution of C₆F₆ (0.47 mL, 4.1 mmol) in pyridine (35 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 0.5 h at rt. Upon complete addition the mixture was allowed to stir at rt, under an N₂ atmosphere for 0.5 h. The solvent was removed under reduced pressure to yield a crude yellow solid. The crude material was dissolved in CHCl₃ (20 mL) and filtered to remove polymeric insoluble material. The organic mixture was successively washed with H₂O (5 × 25 mL), brine (25 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was washed with hot pentane (3 × 10 mL) to give a mixture of [8] macrocycle (compound of Formula (I-a)) and minor amounts of [12] macrocycle (isolated mass yield: 0.35 g, 27% mass yield). Pure compound of Formula (I-a) was purified via sublimation (1 mbar, 250 °C). The title product was isolated as a colourless solid. ¹H NMR (500 MHz, CDCl₃) δ 7.31 (s, 16H, H1). ¹³C-¹⁹F decoupled NMR (126 MHz, CDCl₃) δ 146.4 (C₄), 132.6 (C2), 131.4 (C1), 115.5 (C3). ¹⁹F NMR (376 MHz, CDCl₃) δ -134.5 (s, 16F). Solid-probe MALDI-MS m/z = 1152.0 [M]⁺ (calculated for C₄8H16F16S8 = 1151.88). Example 2c: Macrocyclic compound of Formula (I-a) - pre-organised macrocyclization to obtain S₈-corona[4]phenylene[4]tetrafluorophenylene

To an oven dried Schlenk tube was added, benzene-1,4-dithiol (0.23 g, 1.6 mmol), tetramethyl ammonium fluoride tetrahydrate (0.33 g, 2 mmol, 1.25 equiv) and deoxygenated through 3 × vacuum-N₂ cycles. Deoxygenated pyridine (16 mL) was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. A solution of triaryl monomer as made in Example 1b (0.77 g, 1.6 mmol) in pyridine (16 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 0.5 h at rt. Upon complete addition the mixture was allowed to stir at rt, under an N₂ atmosphere for 24 hours. The solvent was removed under reduced pressure to yield a crude yellow solid. The crude material was dissolved in CH₂Cl₂ (50 mL) and filtered to remove polymeric insoluble material. The organic mixture was successively washed with 1 M HCl (3 x 15 mL), water (15 mL), brine (15 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting yellow solid was washed with hot pentane (3 × 10 mL) to give a mixture of I-a and I-b (crude 19F NMR ratio 10:1) as a colourless solid 0.18 g, (comprising 0.17 g of I-a, 0.15 mmol, 18% and 0.009 g I-b, 5 μmol, ca. 1%). A pure analytical sample of I-a was attained via sublimation (1 mbar, 300 °C) to yield a colourless solid. 1H NMR (500 MHz, CDCl₃) δ 7.31 (s, 16H). 13C{19F} decoupled NMR (126 MHz, CDCl₃) δ 146.4 (C₄), 132.6 (C₂), 131.4 (C1), 115.5 (C3). 19F NMR (376 MHz, CDCl₃) δ - 131.3 (s, 16F). MALDI-MS m/z 1152.0 [M]+ (calculated for C₄₈H₁₆F₁₆S₈1151.88). Example 2d: Macrocyclic compound of Formula (I-b) – one-pot macrocyclization to obtain S12-corona[6]phenylene[6]tetrafluorophenylene

To an oven dried Schlenk tube was added, benzene-1,4-dithiol (0.1 g, 0.7 mmol), and deoxygenated through 3 × vacuum-N₂ cycles. Deoxygenated pyridine (4 mL) was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. Tetramethyl ammonium fluoride tetrahydrate (0.16 g, 0.85 mmol, 1.2 equiv) was added under N₂ and stirred at rt. A solution of C₆F₆ (0.1 mL, 0.87 mmol) in pyridine (3 mL) was deoxygenated (3 × freeze- pump- thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 1 h at rt. Upon complete addition the mixture was allowed to stir at rt, under an N₂ atmosphere for 24 hours. The solvent was removed under reduced pressure to yield a crude yellow solid. The crude material was dissolved in CHCl₃ (20 mL) and filtered to remove polymeric insoluble material. The organic mixture was successively washed with 1 M HCl (2 x 15 mL), water (15 mL), brine (15 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was washed with hot pentane (3 × 10 mL) to give a mixture of I-a and I-b (crude 19F NMR signal ratio 1:1) 8 mg (comprising 5.5 mg of I-a, 5 μmol, ca. 2.7% and 2.5 mg I-b, 1.4 μmol, ca. 1.2%). 1H NMR (500 MHz,

(376 MHz, CDCl₃) δ -131.3 (s, 16F, I-a); -131.2 (s, 24F, I-b). MALDI-MS for (I-a) m/z 1152.0 [M]+ (calculated for C₄₈H₁₆F₁₆S₈ 1151.88); for (I-b) m/z 1727.91 [M]+ (calculated for C₇₂H₂₄F₂₄S₁₂1727.81). Example 3a: Monomer 7

2,5-dibromohydroquinone: To an oven dried round bottom flask was added hydroquinone (2.0 g, 18.2 mmol) and acetic acid (15 mL) and cooled to 10 °C in a cold- water bath. Bromine (5.92 g, 1.9 mL, 37.0 mmol) was added dropwise over 0.5 h. The reaction mixture was stirred for 20 h, while the temperature was allowed to slow warm from 10 °C to rt. Upon complete consumption of hydroquinone, a small amount of Na2S2O3 was added, turning the reaction mixture from brown to off white. H₂O (100 mL) was added dropwise over 0.5 h, forming an off-white precipitate. The precipitate was isolated by vacuum filtration and washed with H₂O (3 x 25 mL), then dried at 50 °C under reduced pressure. The title product was isolated as a colourless crystalline solid (3.48 g, 13.1 mmol, 72%). ¹H NMR (500 MHz, DMSO-d⁶) δ 9.76 (s, 2H, H¹), 6.95 (s, 2H, H⁴). ¹³C NMR (126 MHz, DMSO-d6) δ 147.4 (C₂), 119.5 (C4), 108.3 (C3). ESI-MS m/z = 264.8508 [M-H]⁺ (calculated for C6H3Br2O₂ = 264.8499). Example 3b: Reagent 8

O,O'-(2,5-dibromo-1,4-phenylene) bis(dimethylcarbamothioate): To an oven dried two-neck round bottom flask fitted with a condenser and a dropping funnel, was added 2,5-dibromohydroquinone as made in Example 3a (2.7 g, 10.1 mmol), 1,4- Diazabicyclo[2.2.2]octane (2.1 g, 18.8 mmol, 2.5 equiv.) and anhydrous NMP (8 mL). The reaction mixture was heated to 50 °C and a solution of dimethylthiocarbonyl chloride (2.80 g, 22.7 mmol, 2.25 equiv.) in anhydrous NMP (4 mL), was slowly added dropwise to the heating mixture over 30 mins. Upon complete addition, the reaction mixture was stirred at 50 °C for 6 hours. H₂O (30 mL) was added dropwise over 30 mins to the heated mixture to induce precipitation, before being cooled slowly to 20 °C. The precipitate was isolated by vacuum filtration and washed with H₂O (3 x 25 mL). The crude solid was purified by column chromatography (Al2O3, Pentane-CH₂Cl₂, 30%). The title product was isolated as a colourless crystalline solid (3.90 g, 8.9 mmol, 88%). ¹H NMR (500 MHz, CDCl₃) δ 7.40 (s, 2H, H6), 3.46 (s, 6H, H2), 3.38 (s, 6H, H1). ¹³C NMR (126 MHz, CDCl₃) δ 185.8 (C3), 149.2 (C4), 128.8 (C6), 116.02 (C5), 43.7 (C2), 39.1 (C1). ESI-MS m/z = 462.8758 [M+Na]⁺ (calculated for C12H14Br2O2S2Na = 462.8761). Example 3c: Reagent 9

S,S'-(2,5-dibromo-1,4-phenylene) bis(dimethylcarbamothioate): To an oven dried microwave vial was added O,O'-(2,5-dibromo-1,4-phenylene) bis(dimethylcarbamothioate) as made in Example 3b (1.0 g, 2.3 mmol) and anhydrous NMP (4 mL). The reaction mixture was sparged with N₂ and sealed before being heated in a microwave reactor at 230 °C for 20 min. Once cooled, the solution was added dropwise to H₂O (30 mL) and the crude brown precipitate was isolated by vacuum filtration and washed with H₂O (3 x 25 mL). The crude mixture was recrystallized from hot EtOH and cooled to -20 °C to further induce crystallisation. The title product was isolated via vacuum filtration as fine colourless needles (0.87 g, 2.00 mmol, 87%). ¹H NMR (500 MHz, CDCl₃) δ 7.93 (s, 2H, H5), 3.11–3.05 (m, 12H, H1). ¹³C NMR (126 MHz, CDCl₃) δ 165.3 (C2), 141.2 (C5), 133.7 (C3), 128.7 (C₄), 37.2 (C1). ESI-MS m/z = 462.8753 [M+Na]⁺ (calculated for C12H14Br2N2O2S2Na = 462.8761). Example 3d: Monomer 10

2,5-dibromobenzene-1,4-dithiol: To a small oven dried round bottom flask was added S,S'-(2,5-dibromo-1,4-phenylene) bis(dimethylcarbamothioate) as made in Example 3c (265 mg, 0.6 mmol) and KOH (0.7 g, 12.4 mmol) and MeOH (5 mL) was added and heated to reflux under a N₂ atmosphere for 3 h. Upon cooling to rt, H₂O (10 mL) and CH₂Cl₂ (15 mL) was added, and the organic layer removed. The aqueous fraction was carefully acidified through dropwise addition of concentrated HCl and then extracted with EtOAc (3 × 25 mL). The organic layers were combined and dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The crude solid was passed through a short silica gel (SiO₂) plug, eluting with pentane (150 mL) and evaporated to dryness under reduced pressure. The title product was isolated as a colourless solid (0.14 g, 0.47 mmol, 78%). ¹H NMR (500 MHz, CDCl₃) δ 7.73 (s, 2H, H4), 3.94 (m, 2H, H1). ESI-MS m/z = 296.8055 [M-H]- (calculated for C6H3Br2S2 = 296.8043). Example 3e: Monomer 11

Brominated triaryl monomer: To a dried Schlenk flask was added triaryl monomer as ^{made in Example 1b} (0.5, 1.05 mmol), trifluoroacetic acid (8 mL) and conc. H₂SO₄ (2.5 mL) and heated to 60 °C. N-bromosuccinimide (0.56 g, 3.15 mmol, 3 equiv.) was added portion wise over 6 hours to the heated reaction mixture. Upon complete addition, the reaction was further heated at 60 °C for 48 h. Upon cooling to rt, the mixture was added to ice cold H₂O (75 mL) and the resulting colourless precipitate was isolated via vacuum filtration and washed with H₂O (3 x 20 mL). The crude colourless solid was recrystalised from a supersaturated solution in EtOH. The title compound was isolated as a colourless crystalline solid (0.60 g, 0.95 mmol, 90%). ¹H NMR (500 MHz, CDCl₃) δ 7.12 (s, 2H, H2). ¹³C NMR (126 MHz, CDCl₃) δ 148.7 (C₂), 146.8 (C5), 144.1 (C3), 142.0 (C), 139.3 137.2 135.4, 133.2, 122.8, 106.2 ESI-MS m/z = 628.7751[M-H]- (calculated for C18HBr2F10S2 = 628.7726). Example 4: Macrocyclic compound

To an oven dried Schlenk tube was added, 2,5-dibromobenzene-1,4-dithiol as made in Example 3d (0.18 g, 0.6 mmol, 1 equiv), and tetramethyl ammonium fluoride tetrahydrate as templating agent (0.1 g, 0.6 mmol, 1 equiv) and deoxygenated through 3 × vacuum-N₂ cycles. Deoxygenated anhydrous pyridine (6 mL) as solvent was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. A solution of brominated triaryl monomer as made in Example 3e (0.35 g, 0.5 mmol, 0.8 equiv) in anhydrous pyridine (6 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 0.5 h at rt under N₂. Upon complete addition, the solvent was removed under reduced pressure (water bath temp <35 °C) to yield a crude yellow solid. The crude material was dissolved in CHCl₃ (50 mL) and filtered to remove polymeric insoluble material. The organic soluble mixture was successively washed with H₂O (5 × 15 mL), brine (15 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was washed with hot pentane (3 × 10 mL) to give [8] Br-macrocycle as a single product (20 mg, 0.011 mmol, 4.5 %)^{. 1}H NMR (500 MHz, CDCl₃) δ 7.40 (s, 8H, H1). ¹³C NMR (126 MHz, CDCl₃) δ 146.8 (C5), 135.5 (C4), 135.0 (C1), 124.3 (C3), 114.02 (C₂). ¹⁹F NMR (376 MHz, CDCl₃) δ -130.5 (s, 16F). MALDI MS m/z = 1783.89 [M]⁺ (calculated for C48H8Br8F16S8 = 1783.15 (most abundant isotope peak). Example 5a: Reagent 12

(2,5-dimethyl-1,4-phenylene)bis(isopropylsulfane): To a flame dried Schlenk flask was added, sodium isopropylthiolate (2.15 g, 21.9 mmol, 4 equiv.) and 1,4-dibromo-2,5- dimethylbenzene (1.40 g, 5.47 mmol) and evacuated through 3 × vaccum-N₂ cycles. Anhydrous DMA (12 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) and added to the reaction mixture then stirred at 110 °C for 20 h under N₂. The reaction mixture was allowed to cool to rt, poured onto brine (30 mL) and extracted with Et2O (5 x 25 mL). The combined organic extracts were washed extensively with H₂O (5 x 30 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure to yield a colourless oil that crystalised on standing. The title product was isolated as a colourless crystalline solid (1.30 g, 5.12 mmol, 94%). ¹H NMR (500 MHz, CDCl₃) δ 7.19 (s, 2H, H3), 3.33 (d, J = 6.9 Hz, 2H, H5), 2.35 (s, 6H, H1) 1.29 (d, J = 6.7 Hz, 12H, H6). ¹³C NMR (126 MHz, CDCl₃) δ 137.3 (C₂), 133.3 (C4), 133.3 (C3), 37.9 (C5), 23.3 (C6), 20.4 (C1). ESI-MS m/z = 255.1227 [M+H]⁺ (calculated for C14H23S2 = 255.1241). Example 5b: Monomer 13

2,5-dimethylbenzene-1,4-dithiol: To a flame dried Schlenk flask was added, anhydrous DMA (12 mL) that had been deoxygenated (3 × freeze-pump-thaw cycles under N₂) and sodium metal (X mg, x mmol, 4 equiv.) then stirred at rt for 5 min under N₂. (2,5-dimethyl- 1,4-phenylene)bis(isopropylsulfane) as made in Example 5a was added to the reaction mixture and stirred at 110 °C for 2.5 h under N₂. The reaction mixture was allowed to cool to rt before being poured onto 2 M HCl in an ice bath under N₂ and stirred for 15 min. The resulting suspension was extracted with Et2O (3 x 25 mL) and the combined organic extracts were washed extensively with H₂O (5 x 30 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The title product was isolated, without the need for further purification, as fine colourless crystals (0.15 g, 0.88 mmol, 97%). ¹H NMR (400 MHz, CDCl₃) δ 7.09 (s, 2H, H3), 3.20 (s, 2H, H5), 2.25 (s, 6H, H1). ¹³C NMR (126 MHz, CDCl₃) δ 134.7 (C2), 132.0 (C3), 128.1 (C₄), 20.51 (C1). ESI-MS m/z = 171.0262 [M+H]⁺ (calculated for C8H11S2 = 171.0302). Example 5c: Monomer 14

Dimethyl triaryl monomer: To a flame dried Schlenk flask was added, 1,4-diiodobenzene (0.40 g, 1.12 mmol) and CuSC6F5 (1.0 g, 3.82 mmol, 3.5 equiv.) and evacuated through 3 × vacuum-N₂ cycles. Anhydrous DMF (2 mL) that had been deoxygenated (3 × freeze- pump-thaw cycles under N₂) was added to the reaction mixture and heated to 145 °C for 3 h under N₂. Upon complete consumption of 1,4-diiodobenzene, the reaction mixture was allowed to cool to rt before being poured onto 1M HCl (5 mL) and extracted with Et₂O (3 x 20 mL). The combined organic extracts were washed extensively with H₂O (5 x 30 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The crude off white solid was recrystallised from a supersaturated solution in hexane and cooled to 20 °C. The title product was isolated as colourless solid (0.52 g, 1.04 mmol, 93%). ¹H NMR (400 MHz, CDCl₃) δ 6.97 (s, 2H, H4), 2.35 (s, 6H, H₁). ¹³C NMR (126 MHz, CDCl₃) δ 151.23, 148.6, 146.2, 137.4, 132.8, 132.0, 110.1, 20.00. ¹⁹F NMR (376 MHz, CDCl₃) δ -131.55, -151.04, -160.07. HR-ESI-MS m/z = 501.9886 [M]⁺ (calculated for C20H8F10S2 = 501.9908). Example 5d: Monomer 15

To a small quartz vessel was added dimethyl triaryl monomer as made in Example 5c (25 mg, 0.05 mmol), benzophenone (1.5 mg, 7.5 μmol, 0.15 equiv) and MeCN (3.4 mL) and deoxygenated (3 × freeze-pump-thaw cycles under N₂). A solution of K2CO3 (15 mg, 0.11 mmol, 2.2 equiv) in H₂O (0.6 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) and added slowly to the quartz vessel. The vessel is capped under Ar and irradiated (4 x 9W bulbs (λ = 254 nm)) for 3 hours. Upon complete consumption of the starting material, the reaction mixture was dried under reduced pressure. The resulting crude solid was dissolved in CH₂Cl₂ (10 mL) and washed with 1M HCl (10 mL), H₂O (2 × 10 mL), and brine (10 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was passed through a short pad of silica and eluted with pentane. The filtrate was collected and evaporated to dryness to yield the title compound as a colourless solid (20 mg, 0.04 mmol, 80%). ¹H NMR (400 MHz, C₆D₆) δ 2.81 (s, 3H, H₁), 2.79 (s, 3H, H₁). ¹⁹F NMR (376 MHz, C6D6) δ -128.93 (m,2F), -140.45 (dd, 2F), -156.01 (td, 2F), -159.04 (t, 2F). HR-ESI-MS m/z = 484.9772 [M+Na]⁺ (calculated for C₂₀H₆F₈S₂Na = 484.9681). Example 6: Macrocyclic compound

To an oven dried Schlenk tube was added, 2,5-dimethylbenzene-1,4-dithiol as made in Example 5b (0.04 g, 0.24 mmol, 1 equiv) and tetramethyl ammonium fluoride tetrahydrate as templating agent (0.04 g, 0.24 mmol, 1 equiv) and deoxygenated through 3 × vacuum- N₂ cycles. Deoxygenated anhydrous pyridine (2.5 mL) as solvent was added to the reaction mixture and stirred for 10 min under an N₂ atmosphere. A solution of dimethyl triaryl monomer as made in Example 5c (0.24 g, 0.48 mmol, 1 equiv) in anhydrous pyridine (2.5 mL) was deoxygenated (3 × freeze-pump-thaw cycles under N₂) before being added dropwise to the stirring mixture using a syringe pump over 0.5 h at rt under N₂. Upon complete addition, the solvent was removed under reduced pressure (water bath temp <35 °C) to yield a crude yellow solid. The crude material was sonicated in CHCl₃ (50 mL) and filtered to remove polymeric insoluble material. The organic soluble mixture was successively washed with H₂O (5 × 25 mL), brine (25 mL), dried over anhydrous MgSO₄, filtered and the solvent was removed under reduced pressure. The resulting solid was washed with hot pentane (3 × 20 mL) to give the title compound as a single product (35 mg, 0.028 mmol, 23% yield). ¹H NMR (500 MHz, CDCl₃) δ 7.08 (s, 16H, H2), 2.32 (s, 24H, H₁). ¹³C NMR (126 MHz, CDCl3) δ 146.9 (C₆) 138.1 (C₃), 133.9 (C₂), 131.9 (C₄), 114.7 (C₅), 20.2 (C₁). ¹⁹F NMR (376 MHz, CDCl₃) δ -130.5 (s, 16F, F⁶). MALDI MS m/z = 1264.01 [M]⁺ (calculated for C₅₆H₃₂F₁₆S₈ = 1264.00; most abundant isotope peak). One-pot macrocyclization process – analysis Figure 1 shows the 19F NMR shifts in the crude product obtained from the one-pot process of Example 2b. Based on this analysis, the following products were present: n=4, n=6, n=8 and n=10, as well as some linear oligomers. The products were present in the following amounts:

Claims

CLAIMS 1. A macrocyclic compound of Formula (I):

wherein each R¹ is independently an aromatic ring system that is optionally substituted, and wherein n is an integer of from 2 to 50.

2. The compound of claim 1, wherein the R¹ aromatic ring system has from 5 to 18 ring members.

3. The compound of claim 1 or claim 2, wherein the R¹ aromatic ring system is selected from phenylene, biphenylene and naphthylene ring systems, each of which may optionally be substituted.

4. The compound of any one of claims 1 to 3, wherein the R¹ aromatic ring system is substituted, and each substituent group is independently selected from: halo, C1-12 alkyl, C1-12 alkylhalo, CN, NO₂, OR^x, NR^xR^y, OC(O)R^x, C(O)R^x, C(O)NR^xR¹², C(O)OR¹¹, OS(O)2R^x, SR^x, and R^x; wherein R^x and R^y are each independently selected from hydrogen, C1-12 alkyl, C1-12 alkylhalo, C5-12 aryl, C5-12 heteroaryl.

5. The compound of claim 4, wherein each substituent group is independently selected from: C1-6 alkyl (e.g. methyl), halo (e.g. Br), OR^x (e.g. OH) and NR^xR^y (e.g. NH2).

6. The compound of any one of claims 1 to 5, wherein the R¹ aromatic ring system is substituted with up to three substituent groups.

7. The compound of claim 6, wherein the R¹ aromatic ring system is substituted with one or two substituent groups.

8. The compound of any one of claims 1 to 3, wherein the R¹ aromatic ring system is unsubstituted.

9. The compound of any one of claims 1 to 8, wherein n is an integer of from 2 to 20.

10. The compound of claim 9, wherein n is an integer of from 4 to 16, such as from 4 to 10.

11. The compound of any one of claims 1 to 10, wherein R¹ is not C₆F_4. 12. The compound of any one of claims 1 to 11, wherein the macrocyclic compound is of Formula (I-i):

wherein each Y is independently selected from hydrogen or a substituent group and where n is an integer of from 2 to 50. 13. The compound of claim 12, wherein each Y is independently selected from: hydrogen, C1-6 alkyl, halo, OR^x and NR^xR^y, wherein R^x and R^y are each independently selected from hydrogen, C1-12 alkyl, C1-12 alkylhalo, C5-12 aryl, and C5-12 heteroaryl. 14. The compound of claim 13, wherein each Y is independently selected from: hydrogen, methyl, Br, OH and NH₂. 15. The compound of any one of claims 12 to 14, wherein n is an integer from 2 to 20. 16. The compound of claim 15, wherein n is an integer of from 4 to 16, such as from 4 to 10. 17. The use of an ammonium salt templating agent of Formula (II): [NR^aR^bR^cR^d]+X- (II) wherein each of R^a, R^b, R^c, and R^d is independently selected from hydrogen, C1-C12 alkyl, C5-12 aryl and C6-C22 alkaryl, and wherein X is a counterion, to manufacture a compound as defined in any one of claims 1 to 13. 18. The use of claim 17, wherein each of R^a, R^b, R^c, and R^d is independently selected from hydrogen, methyl, ethyl, n-propyl and n-butyl. 19. The use of claim 18, wherein each of R^a, R^b, R^c, and R^d is the same and each is hydrogen or each is methyl or each is n-butyl. 20. The use of any one of claims 17 to 19, wherein X is selected from a halogen or a pseudohalogen. 21. The use of claim 20, wherein X is F.