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One-Pot Synthesis of Monofunctionalized Oligoethylene Glycols through Ring-Opening and Heterogeneous Hydrolysis of Macrocyclic Sulfates.

ABSTRACT: The one-pot nucleophilic ring-opening reaction of oligoethylene glycol macrocyclic sulfates provides an efficient strategy for the monofunctionalization of oligoethylene glycols without protecting or activating group manipulation. In this strategy, the hydrolysis process is generally promoted by sulfuric acid, which is hazardous, difficult to handle, environmentally unfriendly, and unfit for industrial operation. Here, we explored a convenient handling solid acid, Amberlyst-15, as a replacement for sulfuric acid to accomplish the hydrolysis of sulfate salt intermediates. With this method, 18 valuable oligoethylene glycol derivatives were prepared with high efficiency, and gram-scale applicability of this method has been successfully demonstrated to afford a clickable oligoethylene glycol derivative 1b and a valuable building block 1g for F-19 magnetic resonance imaging traceable biomaterial construction.

SUBMITTER: Yang L

PROVIDER: S-EPMC9979223 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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One-Pot Synthesis of Monofunctionalized Oligoethylene Glycols through Ring-Opening and Heterogeneous Hydrolysis of Macrocyclic Sulfates.

Yang Lan L Li Yu Y Ke Changsheng C Zheng Yujie Y Long Hanxiong H Ouyang Zhen Z Lin Ruoyun R Zhou Xin X Chen Shizhen S Jiang Zhong-Xing ZX

ACS omega 20230216 8

The one-pot nucleophilic ring-opening reaction of oligoethylene glycol macrocyclic sulfates provides an efficient strategy for the monofunctionalization of oligoethylene glycols without protecting or activating group manipulation. In this strategy, the hydrolysis process is generally promoted by sulfuric acid, which is hazardous, difficult to handle, environmentally unfriendly, and unfit for industrial operation. Here, we explored a convenient handling solid acid, Amberlyst-15, as a replacement ...[more]

PMID: 36873021

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Project description:A facile post-synthetic modification of a tetracationic tetraimidazolium macrocycle, 14+ (i.e., the "Texas-sized" molecular box (cyclo[2](2,6-di(1H-imidazol-1-yl)pyridine)[2](1,4-dimethylenebenzene)), is described. Under mild basic conditions, ring-opening of the imidazolium moieties occurs. This results in two new isomeric dicationic macrocycles. This simple yet efficient modification serves to alter the size of the molecular cavity, the charge of the macromolecular receptor, and the manner whereby it interacts with dianionic guest molecules. The isomeric mixture of imidazolium ring opened macrocycles can be synthesized in relatively high overall yield (86-93%). The reaction shows regioselectivity and the ratio of major to minor (i.e., trans : cis ring-opened products) was determined to be ca. 3 : 1 via1H NMR spectroscopy. The major isomer, trans-cyclo[2]((Z)-N-(2-((6-(1H-imidazol-1-yl)pyridin-2-yl)amino)vinyl)formamide)[2](1,4-bismethylbenzene) hexafluorophosphate (22+·2PF6-), was isolated in its pure form in 42% yield via recrystallization. The molecular recognition properties of 22+ were investigated using a series of dianionic guests (i.e., 2,6-naphthalenedicarboxylate (4), 2,6-naphthalenedisulfonate (5), and 1,5-naphthalenedisulfonate (6)) whose binding interactions with 14+ have been previously reported. This allowed us to evaluate how imidazolium ring-opening affects the inherent host/guest interactions of 14+. On the basis of solution spectroscopic studies (e.g., 1H NMR, 1H-1H COSY NMR, DOSY NMR, and NOESY NMR), in tandem with mass spectrometric analyses (ESI-MS) and single-crystal X-ray diffraction studies, we conclude that opening up the macrocyclic structure (i.e., converting 14+ to 22+) leads to considerable changes in the recognition behavior, with so-called outside binding or weak ion pair interactions, rather than pseudorotaxane formation, being favored both in solution and the solid-state. We postulate that methodologies such as those described herein could provide a means to control the molecular interactions of both free-standing macrocycles and those used to construct mechanically-interlocked molecules. Indeed, the application of hydroxide anion under the present conditions not only serves to effect the ring-opening of 14+, but also pseudorotaxane structures, such as, e.g., [14+·4] or [14+·5] derived there from.

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Dataset Information

One-Pot Synthesis of Monofunctionalized Oligoethylene Glycols through Ring-Opening and Heterogeneous Hydrolysis of Macrocyclic Sulfates.

Publications

One-Pot Synthesis of Monofunctionalized Oligoethylene Glycols through Ring-Opening and Heterogeneous Hydrolysis of Macrocyclic Sulfates.

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