Laboratory Experiment pubs.acs.org/jchemeduc
Synthesis and Metalation of a Ligand: An Interdisciplinary Laboratory Experiment for Second-Year Organic and Introductory Inorganic Chemistry Students Benjamin J. Kasting, Andrew K. Bowser, Amelia M. Anderson-Wile,* and Bradley M. Wile* Department of Chemistry and Biochemistry, Ohio Northern University, 525 South Main Street, Ada, Ohio 45810, United States S Supporting Information *
ABSTRACT: An interdisciplinary laboratory experiment involving second-year undergraduate organic chemistry and introductory inorganic chemistry undergraduate students is described. Organic chemistry students prepare a series of amine-bis(phenols) via a Mannich reaction, and characterize their products using melting point; FTIR; and 1H, 13C, DEPT-135, and HSQC NMR experiments. In the inorganic chemistry laboratory, students utilize these amine ligands to prepare a series of octahedral titanium complexes, and characterize the resultant complexes using FTIR, and 1H, 13C, DEPT-135, and HSQC NMR spectroscopy. Students are asked to revisit concepts such as the two- and three-dimensional representations of their target molecules and reaction mechanisms throughout both experiments. From these experiments, students gain an appreciation for the multidisciplinary nature of chemistry. KEYWORDS: Second-Year Undergraduate, Upper-Division Undergraduate, Organic Chemistry, Inorganic Chemistry, Interdisciplinary/Multidisciplinary, Laboratory Instruction, Hands-On Learning/Manipulatives, Coordination Compounds, NMR Spectroscopy, Spectroscopy
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he use of interlaboratory or interdisciplinary experiments in the undergraduate curriculum has been promoted as a way to increase communication between students and to mimic the research environment in a professional setting.1 Asking undergraduate students to return to the same class of molecules in two or more courses may lead to greater student engagement and interest in the laboratory session, as well as greater retention of material.2 Revisiting these same molecules also provides a unique opportunity to assess changes in a student’s perception of structure and representations of molecular shape at two defined points in the undergraduate curriculum. By repurposing student products from an organic chemistry laboratory as ligands for an inorganic chemistry laboratory, students are forced to view the species they produce or consume in lab as chemical entities with various uses or purposes, rather than fixed goals for a 3 h block of time. It is especially desirable to avoid the “make and discard” approach taken in some synthetic-based laboratory experiments. This interdisciplinary experiment is designed to provide undergraduate students with a deeper understanding of the connected nature of chemistry research. To date, there are no examples of organic/inorganic interdisciplinary experiments designed for undergraduate students. © 2015 American Chemical Society and Division of Chemical Education, Inc.
EXPERIMENTAL DESIGN AND OBJECTIVES
One issue facing many organic chemistry laboratory experiments is that compounds are synthesized, characterized and then discarded at the end of a course. For an organic chemistry majors laboratory course, it was important that students synthesize a compound that would be used in a subsequent inorganic chemistry laboratory course. The target reaction had several requirements: (1) an experiment that could be carried out by second-year students over the course of two, 3 h lab periods; (2) product formation occurs through familiar mechanisms; and (3) products may be characterized using a combination of 1D and 2D NMR techniques. At this point in their undergraduate program, students are still in the process of mastering the acquisition and interpretation of 1D NMR spectra, so extensive characterization of the ligands is carried out to assist students in their attempts to become proficient with NMR spectroscopy. Since full assignments cannot be made on the basis of 1H and 13C NMR spectra alone, this is an ideal place to illustrate the utility of 2D techniques in structural identification. By synthesizing and characterizing the ligands for use in an inorganic chemistry laboratory, students begin to gain an appreciation for the interdisciplinary nature of chemistry. The preparation of both type I and type II aminebis(phenols) (Scheme 1) proceeds via a Mannich reaction.3,4 Published: April 16, 2015 1103
DOI: 10.1021/ed500802t J. Chem. Educ. 2015, 92, 1103−1109
Journal of Chemical Education
Laboratory Experiment
Scheme 1. Preparation of Type I (Bridging Amines) and Type II (Pendant Amines) Amine-bis(phenols) via the Mannich Reaction
these amine-bis(phenolate) ligands are known to be active for the polymerization of olefins and cyclic esters.4,5 In addition to the group 4 complexes, aluminum,16 lanthanides,17 and group 3 metals18 have been shown to be competent catalysts for cyclic ester polymerization. Although amine-bis(phenolate) ligands may be complexed with a variety of transition metals, group 4 metals are targeted due to their ease of synthesis. The need to heat reactions involving zirconium precursors, as well as the generation of toluene instead of isopropanol, prompted a decision to focus on the readily prepared titanium K4-chelate complexes of these amine-bis(phenolate) ligands. The reaction of ligands 1−3 with 1 equiv of titanium(IV) isopropoxide generates complexes with a variety of cis/trans isomers possible (Figure 1). The trans(OiPr, OiPr) isomer A is commonly obtained for salentype ligands,3,19 and is considered less desirable as a polymerization catalyst.4b For these complexes, the C2symmetric isomer B is formed preferentially to the C1-
This multicomponent reaction is targeted due to its facile setup and isolation of product. All reaction components are combined in an appropriate solvent, heated, and the ligand typically precipitates from solution upon cooling, facilitating isolation of the product. Although the complexity of these products may appear daunting to a second-year undergraduate student, the mechanism may be broken down into reactions with which they are familiar, namely imine formation and electrophilic aromatic substitution. In addition to their facile synthesis, these ligands readily form group IV metal complexes.4,5 Desirable characteristics for a suitable metal complexation experiment for an inorganic chemistry lab curriculum are (1) the metalation reaction to be studied should be high-yielding, preferably with no further purification required; (2) the experiment should be capable of being completed entirely within one, 3 h laboratory meeting; (3) students should gain experience working with air- and moisture-sensitive compounds using inert-atmosphere techniques; and (4) students should gain experience characterizing the products of their reaction, with a focus on NMR spectroscopy. For these reasons, the preparation of a series of amine-bis(phenolate) titanium complexes (Scheme 2) was targeted.3,4 Scheme 2. Metallation of Amine-bis(phenols) via Reaction with Titanium(IV) Isopropoxide
The coordination chemistry of aminebis(phenolate) (or “salan”) ligands has been widely reported,6 especially iron complexes, which may serve as a useful model for the active site of a variety of nonheme metalloenzymes. 7 Aminebis(phenolate) complexes of Ni,8 Rh,9 Pd,10 Mn,11 Co,12 Cu,13 Mo,14 and V15 have been reported recently, with most papers reporting structural and spectroscopic parameters, and catalytic applications ranging from C−H activation to oxidation via oxotransfer. Complexes bearing aminebis(phenolate) ligands have been widely reported for the polymerization of a number of different monomers. Titanium and zirconium complexes of
Figure 1. Possible isomers for the metal complex 2−Ti(OiPr)2. 1104
DOI: 10.1021/ed500802t J. Chem. Educ. 2015, 92, 1103−1109
Journal of Chemical Education
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symmetric isomer C. Similar isomerism is observed for the pendant amines 4−9.
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Laboratory Experiment
RESULTS AND DISCUSSION
Organic Chemistry Laboratory
In the first laboratory meeting, the organic students were introduced to the idea of 2D NMR spectroscopy. Students were given a basic overview of 2D NMR spectroscopic theory, followed by an introduction to COSY, HSQC, and HMBC experiments. Having a foundational background in 2D NMR spectroscopy, students analyzed their ligands by considering the 1 H, 13C, DEPT135, and HSQC spectra (see Supporting Information for representative student spectra) acquired in the second meeting.20 For all ligands, analysis of the HSQC data allowed students to assign more carbons in the NMR spectrum definitively than they would have been able to assign with just 1D spectra. For an additional challenge, students utilized the HMBC data to assign completely the 1H and 13C NMR spectra. Ligands bearing methyl (1, 4) and tert-butyl (2, 5, 7) groups exhibited more straightforward NMR spectra than the ligands containing cumyl (3, 6, 8) moieties, which had complex aromatic regions. Upon completing the characterization of the pure ligands, students submitted an experimental section along with clean copies of their spectral data. This information was shared with the inorganic students the following semester. In this double Mannich reaction, five components were heated in the presence of a solvent and a single product was obtained. Upon cooling the reaction mixture, the product precipitated, making this an easy experiment for second-year undergraduate organic chemistry students to carry out. Traditionally, these ligands have been synthesized by refluxing the reaction components in methanol for 24 h.2−4 Attempts to shorten the reflux period in order to fit into a 3 h laboratory period resulted in moderate yield for ligands 1, 3, and 4; however, no product was observed for ligands 2, 5, 6, 7, and 8. Many smaller institutions have limited fume hood space to devote to extended reactions conducted using a traditional reflux setup, making synthesis following literature procedures difficult in a teaching laboratory. Using poly(ethylene glycol) (PEG-400) as the solvent,21 and scintillation vials (20 mL) as the reaction vessels allowed up to 17 reactions to be heated at 75 °C in an aluminum reactor block. After 24 h, students obtained reasonable yields (Table 1, 33.9−90.2%) for all eight
EXPERIMENT
Organic Chemistry Laboratory
Because the mechanism for the Mannich reaction can be broken down into imine formation and electrophilic aromatic substitution, the ligand synthesis experiment is typically carried out toward the end of a second-year organic chemistry course. Students work individually. In the first laboratory period, the reaction components (Scheme 1) are combined in a scintillation vial (20 mL) fitted with a PTFE-lined cap and heated to 75 °C using an aluminum reactor block for 24 h. Upon cooling, the solid product is dissolved in CH2Cl2 and subsequently reprecipitated in copious (approx 200 mL) methanol to remove excess impurities. While synthesis is completed in one laboratory meeting, characterization of the resultant product requires a second laboratory period. In the second laboratory period, students complete the purification and characterize their products using NMR spectroscopy and melting point. Inorganic Chemistry Laboratory
Students in the inorganic chemistry laboratory work in groups of two for this experiment. Titanium complexes of these aminebis(phenolate) ligands are readily prepared by reaction of the corresponding amine-bis(phenol) with one equivalent of titanium(IV) isopropoxide in ethereal solution, resulting in the release of 2 equiv of 2-propanol (Scheme 2). The reaction is conducted in an inert atmosphere glovebox in a scintillation vial (20 mL) fitted with a PTFE-lined cap containing a magnetic stir bar. Addition of the liquid titanium(IV) isopropoxide and diethyl ether solvent is facilitated using an adjustable volume pipettor. Laboratories without an inert atmosphere glovebox may accomplish the same complexation reaction by dropwise addition of liquid titanium(IV) isopropoxide to a Schlenk tube containing an ethereal solution of the chosen ligand under a positive pressure of nitrogen gas. The complexation reaction is rapid at room temperature, as evidenced by a change in solution color (colorless to yellow) within minutes of the addition of the titanium reagent. After 1.5 h, diethyl ether, 2-propanol, and other volatiles are removed in vacuo by connecting the reaction vessel to a vacuum source fitted with a liquid-nitrogen cooled coldfinger apparatus. NMR and FT-IR spectra of the product are collected.
Table 1. Student Yield Ranges for the Preparation of Ligands
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HAZARDS Gloves and goggles should be worn at all times during this experiment. All organic solvents, reagents, and products should be treated as flammable and harmful if inhaled, swallowed, or absorbed through the skin. Students should treat the aminebis(phenols) like other aromatic amines or phenols; these compounds should be prepared and handled in a ventilated fumehood. CH2Cl2, CDCl3, and C6D6 are carcinogens, and should only be handled in a ventilated fume hood. Metal complexes may be harmful if inhaled, swallowed, or absorbed through the skin. Mannich reactions are conducted at 75 °C, and should be allowed to cool to room temperature before handling. PEG-400 has a vapor pressure of
