Malaysian Journal of Analytical Sciences Vol 23 No 4 (2019): 690 - 702

DOI: 10.17576/mjas-2019-2304-16

 

 

 

SYNTHESIS AND BINDING PROPERTIES OF TERT-BUTYL AMIDE MACROCYCLES FOR PSEUDOROTAXANES FORMATION

 

(Sintesis dan Sifat Pengikatan Makrosiklik Tetrabutil-Amida bagi Penghasilan Pseudorotazen)

 

Nurul Izzaty Hassan¹* and Douglas Philp²

 

¹Center for Advanced Material & Renewable Resources,

Faculty of Science and Technology

Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

²Department of Chemistry,

Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, USA

 

*Corresponding author:  drizz@ukm.edu.my

 

 

Received: 31 March 2018; Accepted: 17 April 2019

 

 

Abstract

The  tert-butyl  amide  macrocycle  containing ethylene glycol moiety  (cMDG)  was constructed starting from 5-tert-butylisophthalic acid 1 which was activated to acid chloride derivative 2 using thionyl  chloride in toluene. Further, the synthesis of the second macrocycle based on pyridine framework (cMP) was achieved in similar way before coupled to the diamine derivative 4. Following that, the compound’s electronic structure was calculated using simple molecular mechanics calculation to represent the preferable conformation of these macrocycles. In order to evaluate the influence of the benzene ring in the framework of both macrocycles to complex the guests, the following binding experiments were carried out with the synthesized maleimide 5 and CF₃ maleimide 6. An equimolar mixture of macrocycle cMDG and maleimide 5 or 6 in CdCl₃ was prepared and analysed by ¹H and ¹⁹F NMR spectroscopy, respectively. The similar binding experiments were then carried out with macrocycle cMP. The association constant, K_a for the complexation of pseudorotaxane [cMDG·5] and [cMP·5] were estimated to be 190 ± 20 M^-1 and 160 ± 20 M^-1, respectively. On contrary, the association constant for the complexation of pseudorotaxane [cMDG·6] and [cMP·6] complexes were enhanced with a K_a value of 1000 ± 100 M^-1 and 460 ± 50 M^-1 at 25 °C in CdCl₃. In addition, the ¹H and ¹⁹F NMR spectra of these macrocycles and maleimides showed complexes are in slow exchange on the ¹H NMR chemical shift timescale. This can be attributed to significant binding events of pseudorotaxane complexes, compare to the free species observed in isolation. In the case of slow exchange, the K_a was determined using the single-point method.

 

Keywords:  macrocylic, ethylene glycol, pyridine, pseudorotaxane

 

Abstrak

Makrosiklik  tetra-butil  amida  yang  mengandungi  moieti  etilena  glikol  (cMDG)  disintesis  bermula  dari  pengaktifan asid 5-tetrabutilisoftalik 1 kepada sebatian asid klorida 2 menggunakan tionil klorida dalam pelarut toluena. Sebatian perantara ini kemudiannya ditambah kepada sebatian bis amina 3 untuk menghasilkan makrosiklik cMDG melalui sintesis pencairan tinggi. Selain itu, sintesis makrosiklik kedua berasaskan kerangka pyridina (cMP) turut dicapai melalui cara yang sama sebelum ditambah kepada sebatian terbitan diamina 4. Berikutan itu, struktur elektronik makrosiklik dikira menggunakan pengiraan molekular mekanik asas bagi mendapatkan gambaran konformasi yang sesuai. Untuk menilai pengaruh gelang benzena dalam moeiti makrosiklik untuk pengkompleksan dengan tetamu, kajian pengikatan telah dijalankan menggunakan sebatian maleimida 5 dan CF₃ maleimida 6 yang telah disintesis terlebih dahulu. Satu campuran dengan kemolaran yang sama di antara makrosiklik cMDG dan maleimida 5 atau 6 dalam pelarut CdCl₃ disediakan dan dianalisa menggunakan ¹H dan ¹⁹F RMN spektroskopi. Kajian pengikatan yang sama turut dijalankan menggunakan makrosiklik cMP. Nilai pemalar pengikatan, K_a bagi kompleks pseudorotazen [cMDG·5] dan [cMP·5] telah dianggarkan sebanyak 190 ± 20 M^-1 dan 160 ± 20 M^-1, masing-masing. Sebaliknya, kekuatan pengikatan semakin meningkat bagi perkompleksan pseudorotazen [cMDG·6] dan [cMP·6] di mana nilai K_a yang diperolehi ialah 1000 ± 100 M^-1 dan 460 ± 50 M^-1 pada 25 ° C dalam pelarut CdCl₃. Di samping itu, ¹H dan ¹⁹F RMN spektra bagi sebatian makrosiklik dan maleimida menunjukkan kompleks dalam pertukaran lambat pada 1H NMR anjakan kimia. Ini boleh dikaitkan dengan proses pengikatan signifikan pada kompleks pseudorotazen berbanding sebatian yang tidak berikatan. Nilai K_a ditentukan menggunakan kaedah titik tunggal bagi kes pertukaran lambat.

 

Kata kunci:  makrosikilik, etilena glikol, piridina, pseudorotazen

 

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