Macrocyclic receptor molecules for guanidinium cations. 2. Synthesis and x-ray structures of 2,6-pyrido crown ethers and their guanidinium complexes

Abstract

A series of 2,6-pyrido crown ethers with ring sizes of 15-33 ring atoms has been synthesized. Their complexation with guanidinium salts has been studied by using two phase extraction experiments. The crystal and molecular structures of 2,6-pyrido-27-crown-9-guanidinium perchlorate (l:l), 2,6-pyrido-30-crown-lGguanidinium perchlorate (l:l), 2,6-pyrido-27-crown-9-guanidinium thiocyanate-ethanol (2:3:1), 2,6-pyrido-27-crown-9-picric acid (l:l), and the free 2,6-pyrido-24-crown-8 have been determined by X-ray crystallography. In the free and protonated crown ethers, the cavity is occupied by the aromatic ring of the crown ether. In the complexes with guanidinium salts the guest molecule is encapsulated within the cavity, using all its hydrogen atoms for H-bonding between host and guest. The best fit for the guanidinium ion is found for the 27-membered macrocycle with a complementary host-guest H-bonding scheme. Crown ethers with 18 ring atoms form perching complexes.

Application of Flow Chemistry to Macrocyclization of Crown Ethers

“…Macrocyclization reactions resulting pyridino-18-crown-6 ethers in batch mode Scheme 2. Preparation of diiodide derivatives is in accordance with our earlier results from our group [16,17,[21][22][23]25] and also those of others [20,24]. We presume that the solubility of the appropriate alkali iodide in tetrahydrofuran plays an important role in this type of macrocyclization reaction.…”

“…Adjusting the flow rate to 150 μL/min, the residence time was approximately 30 min. (20)(21)(22)(23). In a dry two-necked round-bottomed flask equipped with a reflux condenser and argon inlet, a solution of the starting tosylate 16 or 17 or 18 or 19 (1.8 mmol, 0.018 M) was stirred in anhydrous acetone (100 mL).…”

“…This macrocyclization is a Williamsontype ether formation reaction, where alkylation of primary or secondary alcohols is carried out with alkyl tosylates after a deprotonation step applying NaH [16,17,[20][21][22][23][24][25]. Using batch conditions this reaction takes place up to 120 hours and usually provides poor yields.…”

“…Preparation of crown ethers 2-12 (Scheme 1) in batch mode is already published [16,17,[20][21][22][23][24][25]. Here, we describe a new continuous-flow method applying a column which contained a solid base for their synthesis, which provides better yields in shorter reaction times.…”

Structure of 2,6-pyrido-18-crown-6–guanidinium perchlorate–deuterochloroform

“…Only 0.32 mmol of guanidinium perchlorate proved to be transferred. Upon addition of 0.5 ml of * IUPAC name: 3,6,9,12, (Uiterwijk, van Staveren, Reinhoudt, den Hertog, Kruise & Harkema, 1986).…”