Molecular structure of tris[(6-bromopyridin-2-yl)- methyl]amine

Coordination compounds of polydentate nitrogen ligands with metals are used extensively in research areas such as catalysis, and as models of complex active sites of enzymes in bioinorganic chemistry. Tris(2-pyridylmethyl)amine (TPA) is a tripodal tetradentate ligand that is known to form coordination compounds with metals, including copper, iron and zinc. The related compound, tris[(6-bromopyridin-2-yl)methyl]amine (TPABr3), C18H15Br3N4, which possesses a bromine atom on the 6-position of each of the three pyridyl moieties, is also known but has not been heavily investigated. The molecular structure of TPABr3 as determined by X-ray diffraction is reported here. The TPABr3 molecule belongs to the triclinic, P\overline{1} space group and displays interesting intermolecular Br...Br interactions that provide a stabilizing influence within the molecule.


Chemical context
Tris(2-pyridylmethyl)amine (TPA) was first reported in 1967 (Anderegg & Wenk, 1967), although more recent syntheses are known (Canary et al., 1998;Bazley et al., 2018).TPA is a very versatile ligand and has been used to coordinate metal ions that include, for instance, copper, iron and chromium, thereby forming five-or six-coordinate complexes (Tyeklar et al., 1993;Jang et al., 1991;Gafford & Holwerda, 1990).A more comprehensive review of metal binding to TPA can be found elsewhere (Bravin et al., 2021;Bazley et al., 2018).The TPA ligand has also been successfully employed in the construction of complexes for biological models, for example, coppercluster enzymes involved in oxygen activation (Maiti et al., 2009) and in iron dioxygenases (Costas et al., 2004).There is also an active interest in pursuing the synthesis of such ligands as biochemical sensors that can rapidly and selectively detect certain metals that are associated with the pathogenesis of diseases, such as Alzheimer's disease (Jomova et al., 2022;Tyczynska et al., 2024).In this regard, TPA has been used to prepare piperidine compounds that can differentially chelate trace metals such as zinc and copper (Dai et al., 2002).In addition to being used in biochemical sensor applications, other areas in which TPA has potential applications include anion sensors, molecular switches, chiral probes and as building blocks in the synthesis of supramolecular cages (Bravin et al., 2021).Despite the prolific use of this ligand, its X-ray structure has only become available within the last ten years and has been chosen as the candidate to introduce crystallography to undergraduate students (Bats & Lerner, 2016;Bazley et al., 2018).
TPA ligands containing various substituted moieties are also known.For instance, TPA containing mono-, bis-, and tris-�-methyl substitutions in the ligand complexed to FeCl 2 have been characterized (Benhamou et al., 2008).In addition, TPA ligands containing other alkyl or bromo substitutions that are also complexed to iron have been described as well as their ability to catalyze cyclohexane oxygenation by hydrogen peroxide (Guisado-Barrios et al., 2010).Unexpectedly, a high turnover rate and efficient incorporation of oxygen from H 2 O 2 into cyclohexane were reported for the iron complex of TPABr 3 , which was assumed to have the formula [Fe(TPABr 3 )(CH 3 CN) 2 ] 2+ .However, a crystal structure of the TPABr 3 ligand with or without the complexed metal has not been reported.Therefore, herein, we describe the molecular structure as determined by X-ray diffraction.The synthesis of TPABr 3 is depicted in the scheme and crystals were obtained from a solution in acetonitrile.

Supramolecular features
Fig. 2 shows the packing in the unit cell along the a-axis direction.There are no significant intermolecular hydrogenbonding interactions.However, there are intramolecular distances of 2.852, 2.765 and 2.793 A ˚for N4� � �H12A, N4� � �H22A and N4� � �H32A, respectively, which at best, may indicate a very weak interaction.
For comparison, the packing in the unit cell of the related tris(bromopyrazolylmethyl)amine ligand is arranged in a different fashion, displaying intermolecular pyrazolyl N� � �Br distances of 3.099 A ˚ (Haldo ´n et al., 2014).The N-C-N-N torsion angle (from the central nitrogen atom to the nitrogen

Database survey
Much effort has been expended synthesizing TPA ligands that contain novel substitutions on the pyridyl rings.For instance, TPA derivatives containing the following types of groups have been reported: (i) tripodal tetradentate ligands containing pyridyl-pivalamido groups have been prepared and complexed to copper and zinc ions (Harata et al., 1998;Rivas et al., 2003); (ii) TPA ligands containing pyridyl-trimethoxyphenyl groups have been synthesized (and complexed with copper and zinc ions) in an effort to enhance their solubility in aqueous and common organic solvents (Liang et al., 2009); (iii) TPA-related derivatives containing carboxylic acid functionalities on the pyridyl rings have been synthesized and their complexation to gadolinium investigated (Bretonnie `re et al., 2001); (iv) a TPA derivative containing thiourea substitutions has been prepared and coordinated with different transition metal ions, forming seven co-ordinate Mn II and Cd II , six coordinate Ni II and five co-ordinate Co II , Cu II and Zn II complexes (Saad et al., 2012); (v) sulfonyl subunits have been attached to the pyridyl rings in order to make TPA highly water compatible, which allows for broader applicability to the biomedical arena (Salaam et al., 2020); (vi) isoquinolinederivatized TPAs have been prepared for use as fluorescent zinc sensors (Mikata et al., 2014(Mikata et al., , 2015)), and (vii) other TPAbased ligands that have been prepared include those possessing phenylethynyl units and their copper(II) complexes investigated (Lim et al., 2016).Furthermore, TPA ligands containing one and two chiral substituents on the tripodal skeleton have been synthesized using lipase enzyme and lanthanide complexation investigated (Yamada et al., 2003).
Tripod ligands containing pyrazolyl rather than pyridyl rings are also known.In this regard, novel tris-(pyrazolylmethyl)amine ligands that contain methyl and bromo substituents on the pyrazolyl moiety have been synthesized and structurally characterized (Haldo ´n et al., 2014).The catalytic activities of the copper(I) complexes of these ligands were explored in carbene-and nitrene-transfer studies.In this case, the crystal structure for the tris(bromopyrazolylmethyl)amine ligand is known (Haldo ´n et al., 2014).
Mesylate 3 was reacted with NaN 3 in an S N 2 reaction to afford the organic azide (compound 4), which was subsequently reduced by PPh 3 to a primary amine (compound 5).Reacting compound 5 with two equivalents of mesylate compound 3 resulted in the target compound TPABr 3 6, with an overall yield of 49%.
The resulting compound, TPABr 3 (0.0133 g; 0.024 mmol), was dissolved in acetonitrile (CH 3 CN; 2 mL) and allowed to evaporate.After 4 days at ambient temperature, colorless needles of TPABr 3 , suitable for X-ray diffraction, were crystallized from the solution.

Figure 1
Figure 1Crystal structure of TPABr 3 .Displacement ellipsoids are drawn at the 30% probability level.

Table 1
Experimental details.
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