*2.1. Preparation of the Functionalized Calix[4]arenes*

For a better understanding of the complexation ability, two sets of calix[4]arene derivatives either with open-chain or bridged oligoethers were evaluated. The first set of chelators containing the open-chain oligo ether functions was prepared to start from the basic compound **1**, which contains the same number of oxygen donor atoms as calix[4]crown-6 **14a**. The complete synthesis path is described in Scheme 1. Calix **1** is proposed to form complexes with Na<sup>+</sup> and K<sup>+</sup> [56]. For the introduction of proton-ionizable groups to improve the complexation behavior, the two remaining free OH groups were modified by alkylation with ethyl bromoacetate to yield calix **2**. In the next step, calix **2** was saponified under basic conditions to yield diacid **3** in quantitative yield without further purification after precipitation with HCl. To introduce the amide functions, compound **3** was then treated with oxalyl chloride to form the dichloride **4**, which was instantly reacted with morpholine or 1,4,7-trioxa-10-azacyclododecane to yield amides **5** and **6**, respectively. Both amines

were used for modification to raise the number of donors for complexation and the steric demand. The introduction of proton-ionizable sulfonamides to yield **7a**–**c** follows the same procedure by using trifluoromethyl sulfonamide, perfluoroisopropyl sulfonamide, and perfluorophenyl sulfonamide, respectively, which were deprotonated prior to the reaction with dichloride **4**.

**Scheme 1.** Synthesis of the amide functionalized open-chain calix[4] derivatives **5**, **6**, and **7a**–**c**.

To check the influence of the resulting cavity, the flexibility of the functionalized crown ether bridge on the association constant and the possibility to introduce further functional groups at the crown, the second set of chelators is prepared based on the bridging moiety like a simple crown, benzocrown or aza crown. For this purpose, the respective bridging compounds 3,6,10,13-tetraoxapentadecane-1,15-diyl ditosylate (**8b**) [57] and the catechol derivatives **12a** and **12b** [58] were prepared according to literature procedures. Additionally, ditosylates **12c**,**d** resulting from functionalized catecholes **9b**,**c** were prepared to allow a later functionalisation of the calix-bridge using conventional ligation reactions. The preparation procedure is outlined in Scheme 2.

**Scheme 2.** Structure of alkyl ditosylates **8a**,**b** and synthesis of the benzo ditosylates **12a**–**d**.

For the connection of the functionalized crown ethers with the calix[4]arene skeleton, the resulting ditosylates **8a**,**b** and **12a**–**d** of the oligo ethers were reacted with <sup>t</sup>Bu-calix[4]arene (**13**) under basic conditions using K2CO<sup>3</sup> in dichloromethane (DCM) to prepare the calix-crown-6 derivatives **14a**,**b** and the calix-benzocrown-6 derivatives **14c**–**f** in yields of 36–81%. The complete synthesis path is described in Scheme 3. The two remaining free OH groups of the calix-crowns **14a**–**f** were alkylated with ethyl bromoacetate to yield **15a**–**f**. In the next step, they were saponified under basic conditions to yield the respective diacid derivatives **16a**–**f** in mostly quantitative yields without further purification after precipitation with HCl. To introduce the proton-ionizable fluorinated sulfonamide functions, an amide coupling strategy using EDC and (Cl-)HOBt was applied. Thus, compounds **16a**–**f** were dissolved in anhydrous acetonitrile and reacted with the respective perfluorinated sulfonamides **17**–**19** at ambient temperature using the aforementioned coupling agents to form calix-crowns **20**–**22** and the modified calix-benzocrowns **23**–**27** in yields of 27–97%.

**Scheme 3.** Preparation of the proton-ionizable calix[4]crown derivatives **20**–**27** with perfluorosulfonamide functions.
