Supporting Information for Visualizing molecular chirality in the organic chemistry laboratory using cholesteric liquid crystals

Transcription

1 Supporting Information for Visualizing molecular chirality in the organic chemistry laboratory using cholesteric liquid crystals Maia Popova, Stacey Lowery Bretz, and C. Scott Hartley* Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio Student Lab Manual... S2 Instructor s Notes... S8 Characterization... S16 S1

2 Objectives Student Lab Manual To investigate chirality by observing its macroscopic manifestations To synthesize an imine To determine the absolute stereochemistry of a product mixture To examine liquid crystals and their phase behavior To identify a structure-property relationship between chiral dopants and liquid crystals The Assignment Complete Part 1 individually. Complete Part 2 in groups of three. All notebook entries and answers to questions should be prepared individually. Turn in the notebook pages for this experiment with answers to questions as a summary report. Safety 1-phenylethylamine is corrosive. The toxicity of the synthesized chiral imine is unknown. Many imines are carcinogenic. Biphenyl-4-carboxaldehyde, ethanol, MBBA, and EBBA are irritants to the skin, eyes, and respiratory system. Wear gloves during all operations involving the chiral dopant. The synthesis should be conducted in a fume hood. Introduction Substances can change from one state of matter to another. For example, water can exist as a solid (ice), liquid, or gas (water vapor). Some substances can exist in states in addition to these conventional ones. 1 For example, N-(4-methoxybenzylidene)-4-butylaniline (MBBA) is a crystalline solid below 21 C. When heated above 21 C (its melting temperature), it turns into a cloudy fluid. When the cloudy fluid is further heated to 45 C (its clearing temperature), it becomes a clear liquid (Fig. 1). Thus, an additional intermediate state exits between the crystalline solid state and the isotropic liquid state, called a liquid crystal (LC) state. 2 Figure 1. Transition temperatures of liquid crystal N-(4-methoxybenzylidene)-4- butylaniline (MBBA). As suggested by the name, liquid crystals combine some properties of conventional liquids with those of crystals. Molecules in the liquid state are randomly oriented, whereas molecules in crystalline phases are arranged in a lattice with orientational order. Liquid crystals can be defined S2

3 as ordered fluids because their molecules have some elements of orientational and/or positional order. Hence, they exhibit some properties characteristic of the crystalline state, but the molecules are free to diffuse and flow (Fig. 2). 2 Figure 2. Transitions between solid, liquid crystalline, and liquid states of matter. Figure 3. Cholesteric liquid crystal obtained by addition of a chiral molecule to an achiral nematic host; p is the pitch of the helix. Chart 1. The chiral dopant N-(4-phenylbenzylidene)-1-phenylethanamine will be mixed with the mixture of two nematic liquid crystals N-(4-methoxybenzylidene)-4-butylaniline (MBBA) and 4- (ethoxybenzylidene)-4-butylanline (EBBA). Cholesteric LCs can be obtained by dissolving a chiral compound, the dopant, in an achiral nematic LC host. Addition of the chiral dopant induces the helical structure of the chiral nematic liquid crystalline phase, defined by its pitch p, where p is the length of the helical axis over a full 360 rotation of the rod-like molecules. 3 As helices are inherently chiral, the configuration of the constituent molecules is manifested in the structure of the bulk phase. The two enantiomers of a chiral compound give helices that twist in opposite directions (i.e., left- or right-handed helices). The compounds to be used in this experiment are given in Chart 1. A useful property of cholesteric phases is the selective reflection of polarized light (not the same as the optical rotation of linearly polarized light taught in lecture). Incident light with a S3

4 wavelength similar to the pitch (p) of the helix is reflected when it strikes a film of a cholesteric liquid crystal. The observed color therefore depends on the pitch of the helix. The reflected light has another important property: it is circularly polarized, with the polarization dependent on the twist sense of the cholesteric helix. The material reflects only circular polarized light with the same handedness as the handedness of the helix. The opposite handedness is transmitted through the material. In other words, a left-handed helix will selectively reflect left-handed circularly polarized light. 3 This combination of properties has found broad application in the production of liquid crystal thermometers. 4 This method can also be used for enantiomeric excess (ee) determination by visual color inspection. The method makes use of the sensitivity of the pitch towards the strength of the chiral perturbation. A chiral analyte of interest is doped into the liquid crystal, and, based on its enantiomeric excess, a whole spectrum of different colors can be obtained, allowing the ee to be rapidly estimated. 5 Figure 4. Selective reflection of the circularly polarized light Chirality plays a very important role in the pharmaceutical industry. For example, amino acids are the building blocks of proteins and enzymes in our body. All standard amino acids, except glycine, are chiral. Therefore, the chemistry of our bodies is controlled by chiral molecules. This plays a very important role in drug design and development as proteins are often selective towards one stereoisomer. Although one enantiomer of the drug may be therapeutic, the other can cause irreparable harm. 6 The drug thalidomide is a perfect example of how chirality impacts differing selectivity. It was designed as a treatment for morning sickness for pregnant women (Chart 2). Although enantiomerically pure (R)-thalidomide possesses a sedative effect and helps calm down the nervousness of pregnant women who ingest it, (S)-thalidomide causes a specific birth defect known as phocomelia (deformed limbs). 7 Presently, the government closely monitors chirality in drug development to minimize side effects. Chart 2. (R)-Thalidomide (left) and (S)-thalidomide (right) S4

5 In the experiment that follows, you will observe the interaction between chiral dopants and nematic liquid crystalline hosts as indicated by light reflection. The absolute stereochemistry of the dopant will be also determined. Part 1: Synthesis of the Chiral Dopant Chart 3. Starting materials to synthesize the chiral dopant: (R)-1-phenylethylamine (left), (S)-1- phenylethylamine (center), biphenyl-4-carboxaldehyde (right) Reflux Obtain 0.26 ml of an amine of unknown configuration from the teaching assistant. Weigh 0.25 g of biphenyl-4-carboxaldehyde in a weigh boat. Measure 6.0 ml of 95% ethanol. Transfer the materials into a 50 ml round-bottom flask that will serve as a reflux flask; make sure to perform a quantitative transfer of the amine by rinsing the vial with ethanol. Add a stir bar to the reflux flask. Heat at reflux for 15 minutes once the mixture starts boiling. While reaction mixture is boiling, measure about 7.0 ml of 95% ethanol into a graduated cylinder. Place the graduated cylinder in a beaker filled with ice. Also while the reaction mixture is boiling, determine the melting and clearing temperatures of liquid crystal EBBA. After refluxing, disconnect the heating supply and allow the solution to cool. Place the room temperature flask in a beaker filled with ice. Vacuum filtration Collect the crystals from the reaction mixture by vacuum filtration through a Büchner funnel. Wash the crystals with small amounts (no more than 7 ml total) of ice-cold ethanol. Leave the crystals on the Büchner funnel to dry. When the crystals are fully dried, collect them into a previously tared weigh boat and determine the mass of the sample. Characterization Obtain a melting point and the IR spectrum of the synthesized chiral dopant. Part 2: Mixing LCs with Dopant Prepare a 13% by mass mixture of synthesized chiral dopant and liquid crystals MBBA and EBBA as follows: in order to keep the liquid crystals in 1:1 ratio to each other, weigh 0.10 ± 0.01 g of EBBA and measure 0.10 ± 0.01 ml of MBBA. Weigh ± g of synthesized chiral dopant. Vigorously grind these substances in a mortar with a pestle for about 2 minutes until you get a slightly opalescent mixture. Let it sit for 2 more minutes. Place a drop of the LC-chiral dopant mixture on a glass slide. Cover with a cover slip. S5

6 Characterization For this part of experiment, students will work in groups of three. Each group of students will share one pair of 3D glasses. Using the LC/chiral dopant mixture prepared earlier, shear the cover slip on your and your partners mixtures. Observe what happens while shearing the cover slip for each member of the group, alternating between different lenses of the 3D glasses. Record your observations. Slightly heat your glass slides. Once mixtures on the glass slides are no longer in the liquid crystal phase, shear the cover slip. Observe what happens while shearing cover slips again alternating between different lenses of the 3D glasses. Record your observations. Let your glass slides cool down to room temperature. Observe your glass slides with and without shearing of the cover slips, alternating between different lenses of the 3D glasses. Record your observations. Obtain two glass slides from the teaching assistant, one with known (R)-dopant in the mixture and one with the (S)-dopant. Shear the glass slides in the same way as you did for the glass slides with your LC/dopant mixtures and with the racemic mixture. Record your observations for each lens of the 3D glasses. Calibrate the lenses of the 3D glasses. Determine which enantiomer you were assigned. Make a 13% racemic dopant liquid crystals mixture. Place a drop of this mixture on a glass slide. Cover with a cover slip. Shear, heat, and cool down the glass slide in the same way as you did for the glass slides with your LC/chiral dopant mixtures. The Report Answer each of the following questions in your notebook. 1. Write the reaction mechanism for the dopant synthesis. 2. Calculate the percent yield of the chiral dopant. 3. Interpret the IR spectrum of the synthesized chiral dopant. 4. Report the melting point of the synthesized dopant. 5. At what temperatures is EBBA a crystalline solid? A liquid crystal? A liquid? 6. 3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was used to identify which enantiomer of the dopant? How can you explain your observations? 7. Which enantiomer of 1-phenylethylamine were you assigned? Explain your answer. 8. What did you notice once the glass slide had been heated? What did you observe once the slide had cooled down to room temperature? Explain your observations. 9. Explain your observations of the racemic mixture using the glasses. 10. Draw the R and S enantiomers of the amine used for the synthesis, show the chirality center and rank group priorities to demonstrate the configuration of each enantiomer. 11. List some properties that you would expect the enantiomers prepared by your group to share. What properties are not shared by the enantiomers? References 1. Chemical of the week Liquid Crystals. (accessed March 16, 2015). 2. Verbit, L. Liquid Crystals Synthesis and Properties. J. Chem. Educ. 1972, 49 (1), S6

7 3. Mulder, D. J.; Schenning, A. P. H. J.; Bastiaansen, C. W. M. Chiral-nematic liquid crystals as one dimensional photonic materials in optical sensors. J. Mater. Chem. C, 2014, 2, Li, Y.; Wang, M.; Urbas, A.; Li, Q. A photoswitchable and thermally stable axially chiral dithienylperfluorocyclopentene dopant with high helical twisting power. J. Mater. Chem. C, 2013, 1, van Delden, R. A.; Feringa, B. L. Colour indicator for enantiomeric excess and assignment of the configuration of the major enantiomer of an amino acid ester. Chem. Commun. 2002, Brooks, W. H.; Guida, W. C.; Daniel, K. G. The significance of chirality in drug design and development. Curr. Top. Med. Chem. 2011, 11 (7), Eriksson, T.; Bjorkman, S.; Hoglund, P. Clinical pharmacology of thalidomide. Eur. J. Clin. Pharmacol. 2001, 57, S7

8 Pre-Lab Instructor s Notes In order for students to calibrate the lenses of the 3D glasses, prepare (R)- and (S)-mixtures for the known glass slides by following the same procedure as given in the part 1 of the Student Lab Manual. It might be more convenient to double the amount of the reactant to obtain a bigger amount of the chiral dopant N-(4-phenylbenzylidene)-1-phenylethanamine. For each prepared glass slide, one or two drops of the chiral dopant LCs mixture is needed. In order to avoid pre-lab preparation of the chiral dopant, students can be told which lens of 3D glasses is responsible for which enantiomer: the (R)-chiral dopant LCs mixture is seen through the right lens of the 3D glasses (right circular polarizer in a standard pair of glasses) and the (S)-chiral dopant LCs mixture is observable through the left lens of the 3D glasses (left circular polarizer). Note that 3D glasses produced by another manufacturer might differ from the ones used by our students. Reflux Students perform synthesis individually. For the characterization in part 2, students will work in groups of three. Prepare and label vials with 0.26 of (R)- and (S)-1-phenylethylamine that will be given to students in the beginning of lab as the reactant of unknown configuration. In order to achieve a decent purity of the final product, it is very important for the students to measure the right amount of biphenyl-4-carboxaldehide. Mixing LCs with dopant In order to achieve color generation, students need to grind the mixture of N-(4- methoxybenzylidene)-4-butylaniline (MBBA) and 4-(ethoxybenzylidene)-4-butylanline (EBBA) liquid crystals with the synthesized chiral dopant very vigorously for not less than 2 minutes (Fig. 1). Before placing a drop of the mixture on a glass slide, students should let it sit for 2 more minutes. * N N O MBBA N O Chiral dopant EBBA Figure 1. Mixing nematic liquid crystals N-(4-methoxybenzylidene)-4-butylaniline (MBBA) and 4-(ethoxybenzylidene)-4-butylanline (EBBA) with the chiral dopant of unknown configuration. S8

9 Characterization For this part of the experiment, students will work in groups of three. We suggest to make groups of three instead of groups of two in order to make it more difficult for students to guess which amine configuration they were assigned. This will also make it more difficult for students to find out the stereochemistry of their chiral dopants by process of elimination. Two types of groups of three can be formed: Type 1 Type 2 Two students that made (R)-chiral dopant LCs mixture Two student that prepared prepared (S)-chiral dopant LCs mixture One student that prepared prepared (S)- chiral dopant LCs mixture One students that made (R)-chiral dopant LCs mixture When shearing the glass cover slips on the glass slide before heating, students should observe multicolored shimmering or sparkling of their mixtures. Shearing promotes a planar alignment of the molecules with the long molecular axis being oriented in the plane of the glass slide (Fig. 2). Depending on the configuration of the chiral dopant used, the students will be able to see the color generation in the (R)-chiral dopant LC mixtures through the right lens of the 3D glasses (right circular polarizer) and through the left lens of the 3D glasses for the (S)-chiral dopant LC mixtures. TAs should guide students through their observations. An easy way to switch between the lenses of the 3D glasses is to simply cover one of the lenses with palm and then switch and cover the other lens with a palm. Figure 2. Observation of the nematic LCs chiral dopant mixture without 3D glasses at room temperature under shearing. On the left mixture before touching, on the right the same mixture during shearing. While heating the glass slides, the mixtures will melt (transition from LC state of matter to isotropic liquid) and will look transparent. Shearing will not promote any color generation. After cooling and shearing, in some cases, students will obtain permanent color of their mixtures without subsequent shearing. The mixtures obtained might vary in color from red-orange to green (Fig. 3). Students might also see a combination of colors. This may be a result of small variations in the concentration of the LCs-chiral dopant mixtures or because planar alignment of molecules was only partially achieved (Fig. 4). S9

10 (S)-Mixture (R)-Mixture left right left right Without polarizers Under circular polarizers Without polarizers Under circular polarizers Figure 3. Observation of the students nematic LCs chiral dopant mixtures with and without right and left circular polarizers after heating and cooling. In order to calibrate the lenses of the 3D glasses, students will make similar observations of the glass slides with mixtures of known stereochemistry. Label the corresponding glass slides either R or S (Fig. 4). Figure 4. Observation of the students nematic LCs (S)-chiral dopant mixture through different lenses of 3D glasses. In order to prepare a 13% by mass racemic mixture of synthesized dopant and liquid crystals MBBA and EBBA, the students need to figure out which dopant enantiomer each member of the group has. Groups have to grind in the mortar ± g of synthesized (R)-chiral dopant, ± g (S)-chiral dopant, 0.10 ± 0.01 g of EBBA, and 0.10 ± 0.01 ml of MBBA. When observing the glass slide alternating between different lenses of 3D glasses while shearing the cover slip, students will not observe any color generation. The color is sufficiently sensitive to enantiomeric excess that the students should not observe it even if they are not all that close to a perfect 1:1 mixture. Incorporation of the Lab in the Teaching Curriculum The laboratory activity can be combined with polarimetry and resolution of racemic 1- phenylethylamine by crystallization with tartaric acid experiments. The chiral dopant has a 1.4 specific rotation value. Required Materials Name CAS Amount Available Catalog Price S10

11 per from Number Student 1. (R)-(+)-1-Phenylethylamine ml AK Scientific $50 for 100 ml 2. (S)-(-)-1-Phenylethylamine ml AK Scientific $50 for 100 ml 3. 4-Biphenylcarboxaldehyde g AK Scientific $150 for 100 g 4. N-(4-Methoxybenzylidene)- 4-butylaniline ml VWR TCM G 25 g for $ Ethoxybenzylidene-4- butylaniline g VWR TCE G 25 g for $ Ethanol 95% ml The 3D glasses were purchased from Amazon.com as a 4 pack for $19.95 (B00GTVV3NM). One can also purchase a set of left/right circular polarizers from Polarization.com for $20 for a pair of cm 2 films that can be cut (PFC-EC Economy Circular Polarizer Pair (left and right hand)). S11

12 Answers to Student Lab Report Questions 1. Write the reaction mechanism for the dopant synthesis. 2. Calculate the percent yield of the chiral dopant. Assuming that actual yield is g: 1-phenylethylamine s mass: =0.244 Reagent Molar Weight (g/mol) Mass (g) Moles 1-phenylethylamine biphenyl-4-carboxaldehyde N-(4-phenylbenzylidene)-1- phenylethanamine Theoretical yield: % yield: %=82.9 % =0.391 (limiting reagent) 3. Interpret the IR spectrum of the synthesized chiral dopant. Type of bond Wavenumber (cm -1 ) C=C ~ 3050 C H ~ 2970 C=N ~ Report the melting point of the synthesized dopant C 5. At what temperatures is EBBA a crystalline solid? A liquid crystal? A liquid? Crystalline solid: under 36 C. Liquid crystal: C. S12

13 Liquid: above 78 C. 6. 3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was used to identify which enantiomer of the dopant? How can you explain your observations? The (R)-enantiomer and (S)-enantiomer show colors through different lenses of the 3D glasses. When shearing the sample mixtures, color is observed through the right lens when looking at the (R)-dopant LCs mixture and through the left lens for the (S)-dopant LCs mixture. The light reflected by the (R)-mixture has the same handedness as the right circular filter in the 3D glasses. The color is transmitted only through this lens. The light reflected by the (S)-mixture has the same handedness as the left circular filter in the 3D glasses. The color is transmitted only through the left lens. 7. Which enantiomer of 1-phenylethylamine were you assigned? Explain your answer. R if the color is observed through the right lens of 3D glasses. S if the color is observed through the left lens of 3D glasses. 8. What did you notice once the glass slide had been heated? What did you observe once the slide had cooled down to room temperature? Explain your observations. When heating the glass slide, the colored cholesteric liquid crystal mixture transforms into a transparent, colorless isotropic liquid. The color disappears because the structure is no longer helical and does not possess the property of selective reflection of light. Once the glass slide cools down, the mixture again reaches the cholesteric liquid crystalline state of matter. A cholesteric twist is regenerated and the material again selectively reflects circularly polarized light. 9. Explain your observations of the racemic mixture using the glasses. When mixing equal amounts of R- and S-chiral dopants with non-chiral MBBA and EBBA liquid crystals, the mixtures remain white in color because no chiral twist is generated in the structure of nematic liquid crystals. 10. Draw the R- and S-enantiomers of the amine used for the synthesis, show the chirality center and rank group priorities to demonstrate the configuration of each enantiomer. 11. List some properties that you would expect the enantiomers prepared by your group to share. What properties are not shared by the enantiomers? Share: physical properties. Do not share: interaction with polarized light as well as interaction with other chiral compounds. S13

14 Grading Rubric 1. Write the reaction mechanism for the dopant synthesis. Correct Some incorrect mechanism steps, or wrong arrow directions, or missing charges All wrong 2. Calculate the percent yield of the chiral dopant. Correct (not grading on students % yield values, only correctness of calculations) All wrong 3. Interpret the IR spectrum of the synthesized chiral dopant. C=N, C-H, C=C C-H, C=C, not including C=N OR only C=N peak One out of three not including C=N 4. Report the melting point of the synthesized dopant. In range of o C Differ significantly from the range 5. At what temperatures EBBA is solid? Liquid crystal? Liquid? Solid below 29 o C, liquid crystal between o C, liquid above 80 o C Differ significantly from the range 2 pts. 2 pts. 6. 3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was used to identify which enantiomer of the dopant? How can you explain your observations? Right lens R, left lens S. Explanation based on the specific reflection of circularly polarized light Correct observations with lenses but wrong explanation Both wrong 3 pts. 2 pts. 7. Which enantiomer of 1-phenylethylamine you were assigned? Explain your answer. Correct enantiomer (check with the unknown key) and correct explanation 2 pts. Correct enantiomer, but wrong explanation All wrong 8. What did you notice once the glass slide had been heated? What did you observe once the slide cooled down to room temperature? Explain your observations. All correct Partial credit: Answer for the first question Answer for the second question 3 pts. S14

15 Explanation All wrong 9. Explain your observations of the racemic mixture using the glasses. Correct observation AND explanation (LC is no longer helical) Correct observations, but incomplete reasoning (interaction of two enantiomers with the polarized light), or wrong explanation All wrong 2 pts. 10. Draw the R- and S-enantiomers of the amine used for synthesis, show the chirality center and rank group priorities to demonstrate the configuration of each enantiomer. Both structures correct One or both wrong 11. List some properties that you would expect the enantiomers prepared by your group to share. What properties are not shared by the enantiomers? Both correct Share: physical properties Not share: interaction with polarized light AND interaction with other chiral compounds One correct Both wrong Total number of points: 20 2 pts. S15

16 Characterization The values for the melting range obtained by students vary from 64 to 90 C. However, some students obtain well over 100%, typically because they did not allow sufficient time for the solid product to dry. When analyzing the IR spectra, students are expected to note the absence of the carbonyl peak and presence of imine peak at ~1645 cm -1. Nuclear magnetic resonance spectrum of the chiral dopant N-(4-phenylbenzylidene)-1- phenylethanamine S16

17 Representative student infrared spectrum of the chiral dopant N-(4-phenylbenzylidene)-1- phenylethanamine: S17