Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons

Multidentate ligands involving tethered pyridyl groups coordinated to transition metal ions have been frequently used to mimic the 3-histidine (3H), 2-histidine-1-carboxylate (2H1C) brace motifs or other combinations of histidine and carboxylate endogenous ligating residues found in bioinorganic met...

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Main Authors: Troy T. Handlovic, Tyler Moreira, Anoshia Khan, Haroon Saeed, Yousuf Khan, Mohammed R. Elshaer, Justin A. Bogart
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:C
Subjects:
Online Access:https://www.mdpi.com/2311-5629/7/3/54
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spelling doaj-88f236954e64444aa9238d9b9a2a8ca22021-09-25T23:50:45ZengMDPI AGC2311-56292021-07-017545410.3390/c7030054Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized CarbonsTroy T. Handlovic0Tyler Moreira1Anoshia Khan2Haroon Saeed3Yousuf Khan4Mohammed R. Elshaer5Justin A. Bogart6Department of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USADepartment of Chemistry, Biochemistry and Physics, Becton College of Arts and Sciences, Fairleigh Dickinson University, Madison, NJ 07940, USAMultidentate ligands involving tethered pyridyl groups coordinated to transition metal ions have been frequently used to mimic the 3-histidine (3H), 2-histidine-1-carboxylate (2H1C) brace motifs or other combinations of histidine and carboxylate endogenous ligating residues found in bioinorganic metalloenzymes. It is of interest to immobilize these ligand chelates onto heterogeneous supports. This, however, requires the use of bromine-substituted (chloromethyl)pyridines, whose current synthetic routes involve the use of extremely pyrophoric chemicals, such as <i>n</i>-butyllithium that require cryogenic reaction conditions, and toxic chemicals, such as thionyl chloride, that are challenging to handle and require extensive hazard controls. Herein, we report alternative methodologies towards the syntheses of 2-bromo-6-hydroxymethylpyridine and 2-bromo-6-chloromethylpyridine from inexpensive commercially available 2,6-dibromopyridine using isopropylmagnesium chloride lithium chloride complex (Turbo Grignard) and cyanuric chloride which are easier to handle and require milder reaction conditions than the conventional reagents. Gas chromatography-mass spectrometry (GC-MS) methods were developed and simple <sup>1</sup>H- and <sup>13</sup>C- nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopies were also used to monitor the conversion of both reaction steps and showed that products could be obtained and isolated through simple workups without the presence of unreacted starting material or undesired overchlorinated 2-chloro-6-chloromethylpyridine side product.https://www.mdpi.com/2311-5629/7/3/54substituted pyridinesmetal halogen exchangechlorine transferalternative synthesisgas chromatography mass spectrometry
collection DOAJ
language English
format Article
sources DOAJ
author Troy T. Handlovic
Tyler Moreira
Anoshia Khan
Haroon Saeed
Yousuf Khan
Mohammed R. Elshaer
Justin A. Bogart
spellingShingle Troy T. Handlovic
Tyler Moreira
Anoshia Khan
Haroon Saeed
Yousuf Khan
Mohammed R. Elshaer
Justin A. Bogart
Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
C
substituted pyridines
metal halogen exchange
chlorine transfer
alternative synthesis
gas chromatography mass spectrometry
author_facet Troy T. Handlovic
Tyler Moreira
Anoshia Khan
Haroon Saeed
Yousuf Khan
Mohammed R. Elshaer
Justin A. Bogart
author_sort Troy T. Handlovic
title Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
title_short Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
title_full Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
title_fullStr Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
title_full_unstemmed Facile Synthesis and Characterization of a Bromine-Substituted (Chloromethyl)Pyridine Precursor towards the Immobilization of Biomimetic Metal Ion Chelates on Functionalized Carbons
title_sort facile synthesis and characterization of a bromine-substituted (chloromethyl)pyridine precursor towards the immobilization of biomimetic metal ion chelates on functionalized carbons
publisher MDPI AG
series C
issn 2311-5629
publishDate 2021-07-01
description Multidentate ligands involving tethered pyridyl groups coordinated to transition metal ions have been frequently used to mimic the 3-histidine (3H), 2-histidine-1-carboxylate (2H1C) brace motifs or other combinations of histidine and carboxylate endogenous ligating residues found in bioinorganic metalloenzymes. It is of interest to immobilize these ligand chelates onto heterogeneous supports. This, however, requires the use of bromine-substituted (chloromethyl)pyridines, whose current synthetic routes involve the use of extremely pyrophoric chemicals, such as <i>n</i>-butyllithium that require cryogenic reaction conditions, and toxic chemicals, such as thionyl chloride, that are challenging to handle and require extensive hazard controls. Herein, we report alternative methodologies towards the syntheses of 2-bromo-6-hydroxymethylpyridine and 2-bromo-6-chloromethylpyridine from inexpensive commercially available 2,6-dibromopyridine using isopropylmagnesium chloride lithium chloride complex (Turbo Grignard) and cyanuric chloride which are easier to handle and require milder reaction conditions than the conventional reagents. Gas chromatography-mass spectrometry (GC-MS) methods were developed and simple <sup>1</sup>H- and <sup>13</sup>C- nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopies were also used to monitor the conversion of both reaction steps and showed that products could be obtained and isolated through simple workups without the presence of unreacted starting material or undesired overchlorinated 2-chloro-6-chloromethylpyridine side product.
topic substituted pyridines
metal halogen exchange
chlorine transfer
alternative synthesis
gas chromatography mass spectrometry
url https://www.mdpi.com/2311-5629/7/3/54
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