Spring 2015 CH421 Independent Project 1 Synthesis of Chalcones via Aldol Condensation I: A Closer Look at Substituent Effects of the Aldehyde Number of students in project group: 4 or 5 Project Overview For the final four weeks of CH421 laboratory, students will be split into a total of four groups, and each group will work on one of four different independent projects. For Independent Project 1, the main goal is to ascertain whether or not the Hammett Sigma Constant values (these are known numerical values that describe aromatic substituent electron‐
donating or electron‐withdrawing effects – you will need to look these up!) correlate with the substituent effects of the R group in a series of substituted chalcone products (see Scheme 1 below). The chalcone substituent effects will be assessed in two ways: 1) by measuring the effect on IR C=O stretching frequency; and 2) by measuring the effect on the chemical shift of the distal methyl group of the ketone component. Scheme 1 The group will synthesize five different chalcone products using the aldol condensation reaction, whereby the para substituent of the aldehyde condensation partner is varied for each reaction, as shown in Scheme 1. Once all five chalcones are prepared and purified, they will be characterized by IR and 1H NMR. In theory, the substituent R group should have some sort of effect on both the IR C=O stretching frequency and the methyl chemical shift of the chalcone. However, given that the R group is somewhat far from the ketone, and it’s also very far from the methyl group, the effect may be diminished or even non‐existent. Thus, the Hammett Sigma Constants will be plotted versus the IR C=O stretch frequencies and versus the methyl chemical shifts (in a separate plot) in order to determine the extent of this effect. While one would expect a correlation in both cases, it’s possible that the substituent R is in fact too distant to have a measured effect on IR C=O frequency and/or on the methyl chemical shift. Let’s find out! Project Components and Point Distribution 1.
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SciFinder literature search (20 points) Lab work – cleanliness and acumen (20 points) PowerPoint presentation of results (80 points) Final lab write‐up (80 points) 1. SciFinder Literature Search (20 points): due with final lab report on Wednesday April 29 by 5:00 pm In groups of two or three, conduct a search on SciFinder to see whether or not each exact chalcone has been prepared previously and is referenced in the literature (there are 5 products – please divide up the searches). If so, write down the full reference(s) and try to download the paper(s) with the procedure. NOTE: if there are a lot of references, only use the two most recently published journal articles (not patents!) and note how many total journal articles that you found. Save the PDF file(s) to your H drive and email a copy to your instructor. Look through the procedure and note any differences from the conditions that we used in Experiment 6 (i.e. different solvent, base, etc.). Your findings should be typed up using an appropriate word processing program (i.e. MS Word) and emailed to your instructor. Be sure to include your lab section, project number, and “SciFinder search” in the file name. Spring 2015 CH421 Independent Project 1 2. Lab Work – cleanliness and acumen (20 points) NOTE: all laboratory work should be recorded in your laboratory notebook. A group of four to five students will share the lab work to synthesize, purify, and characterize (IR, and 1H NMR) each of the five chalcones. The chemistry portion will be completed in the first three weeks of lab. NOTE: there is no procedure to follow! You will perform the reactions starting with 1.0 g of the 4’‐methylacetophenone, and you should decide the appropriate amounts of the other chemicals, what solvent(s) to use, appropriate glassware, how to purify your final product, etc. You may ask your instructor for guidance. For IR and NMR data of your starting materials, the following website is very helpful: http://sdbs.db.aist.go.jp/sdbs/cgi‐bin/cre_index.cgi. Suggested division of lab and SciFinder work:  Week 1 o SciFinder Search (all group members – 1 hour) o Lab work: two pairs (or group of 3 and group of 2) synthesize, purify, and characterize (IR and 1H NMR) the chalcones with R = NO2 and R = Cl (one group for each R). Run a TLC of the crude vs. purified product. 
Week 2 o Two pairs synthesize, purify, and characterize (IR and 1H NMR) the chalcones with R = H and R = OMe (one group for each R). Run a TLC of the crude vs. purified product. o Fifth group member will synthesize, purify, and characterize (IR and 1H NMR) the chalcone with R = NMe2. Run a TLC of the crude vs. purified product. 
Week 3: Finish any remaining lab work and clean‐up. Afterwards, start work on the SciFinder results, the PowerPoint presentation, and the final lab write‐up, as described below: o Type up the SciFinder results. o Generate a data table in a graphing program (i.e. Excel) showing the substituents, the IR C=O stretch observed for o
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each substituent, and the corresponding Hammett Sigma Constant for each substituent. Pay special attention to how the table is organized – there is a proper order for the data that would show the trend most clearly when the data are plotted. Next, plot using scatter plot (ask your instructor if you are unfamiliar with Excel) the Hammett Sigma Constant (y‐axis) versus the IR C=O stretch frequency for the corresponding substituent (x‐axis). Label the plot with an appropriate title, label all axes (including units if appropriate), and label each data point with the corresponding R group (i.e. NO2, Cl, etc.). Then, generate the linear regression equation and display this on the plot with the R2 value. You will use this plot in your PowerPoint presentation, as well as in your final lab write‐up, so save the Excel file to your H drive! Generate another data table in Excel showing all substituents, the chemical shift of the aromatic methyl group on the ketone side of the molecule, and the corresponding Hammett Sigma Constant for each substituent. Again, pay special attention to how the table is organized – there is a proper order for the data that would show the trend most clearly when the data are plotted. Next, plot using scatter plot (ask your instructor if you are unfamiliar with Excel) the Hammett Sigma Constant (y‐axis) versus the methyl chemical shift for the corresponding substituent (x‐
axis). Label the plot with an appropriate title, label all axes (including units if appropriate), and label each data point with the corresponding R group (i.e. NO2, Cl, etc.). Then, generate the linear regression equation and display this on the plot with the R2 value. You will use this plot in your PowerPoint presentation, as well as in your final lab write‐up, so save the Excel file to your H drive! Start your PowerPoint presentation Start typing up procedures for the final lab report. Week 4: PowerPoint presentation to be given in lab during the last week of class. See details in Section 3 below. Spring 2015 CH421 Independent Project 1 3. PowerPoint Presentation of Results During the Final Lab Period (80 points): due Tues 4/21 or Thurs 4/23 Each project group will present their results to the class using PowerPoint (or some equivalent program). Each group member should give a portion of the presentation so that it is split up more or less evenly. Each slide should have an appropriate title. The PowerPoint presentation should include a slide for each of the following:  Title slide with all group members listed  Statement of the scientific purpose of the project  Brief explanation of chalcone structure and why they are interesting (give any reference(s) on the slide).  A slide showing a general scheme of the chemistry that was performed (i.e. just show “R” on the aldehyde), including the reaction conditions used. NOTE: each hallway computer has the drawing program ChemDraw installed, which is the appropriate software with which to draw your structures and paste into PowerPoint and into your final write‐up. As such, you should be sure to save your ChemDraw files to your H drive.  A slide showing the results of your chemistry in table format, including the R group, yield, a column on purity of each final product and how that was determined (i.e. TLC, NMR, etc.), and a comment column to discuss how well the different aldehyde substrates worked in the reactions or any other relevant comments (if any).  A slide showing the plot of the Hammett Sigma Constants versus the IR C=O stretch frequencies, with bullet point comments below the plot describing the results.  A slide showing the plot of the Hammett Sigma Constants versus the 1H NMR aromatic methyl chemical shift, with bullet point comments below the plot describing the results.  Conclusions slide with bullet point conclusions. The final PowerPoint presentation file should be emailed to your instructor for calculation of this part of your project grade. Be sure to include lab section and project number in the file name. Spring 2015 CH421 Independent Project 1 4. Final Lab Write‐Up (80 points): due on Wednesday April 29 by 5:00 pm Instead of grading individual lab notebooks (all of which should be kept perfectly at this point in the semester!), part of the independent project grade will come from a formal lab report (format discussed below). The report should be typed up using an appropriate word processing program (i.e. MS Word) and emailed to your instructor when complete. Be sure to include your lab section, project number, and “Lab Report” in the file name. The work should be divided evenly and compiled and edited together. The final report should be organized into several sections, in a similar same way that a chemistry journal article is organized. For an example, go to the Journal of Organic Chemistry website from a Regis computer, open a recent article, and refer to this for organization and style. The final report should be organized as follows:  Title: Project name and number. Include names of all group members below title.  Abstract: this is a succinct paragraph that starts with a general statement about the purpose of the experiment, and then proceeds to briefly describe the chemistry and methods used, and the results of the project.  Introduction: this should have relatively brief paragraphs discussing chalcones, the chemistry that you will be using to prepare them, and a paragraph explaining what the Hammett Sigma Constants mean (you should cite the source for your explanation).  Results and Discussion: First, discuss the success of the chemistry. Draw the general reaction with the R substituent for the aldehyde component, and include a table with separate entries for each R group and the % yield for each product. You should then present the plots that you generated and discuss whether or not you in fact observed a correlation or trend with the Hammett Sigma Constants versus the other parameters that you plotted. Be sure to include and refer to the two plots you will generate from the Hammett Sigma Constants vs. IR C=O stretch frequency and vs. methyl chemical shift.  Conclusion: start with a brief statement of the overall success of the project. Then, recount the chemistry results, and explain whether or not you were successful in showing the expected trends with the Hammett Sigma Constants. If you were not successful, provide a hypothesis as to why no correlation was observed.  Experimental (for each compound prepared; each group member should write at least one): first, draw the reaction performed, and below this put in a reaction table just like the ones you put in your notebook to organize reactants, mmol amounts, equivalents, etc. Below this, type up the experimental procedure for the preparation of each chalcone in the same way that you record it in your notebook. Please also include the printouts for the IR and 1H NMR spectra that you generate for each compound (please make sure these are properly labelled!). Be sure to assign all major peaks in the IR and all peaks in the NMR. For TLC, you may hand‐
draw the TLC plate at the end of each procedure, write in the mobile phase used, and show Rf’s. Be sure to include in the procedure that you ran a TLC, what mobile phase you used, and comment on what you observed. Final Note on Overall Grade Please note that the overall grade for each individual on the team is solely based on the team’s overall grade for this project. As such, it is VITAL that each and every team member participates and shares in ALL ASPECTS of the work for this project. All team members should perform the searches, do the lab work, help compile and edit the in‐class PowerPoint presentation, as well as contribute to and edit the final lab write‐up. If there is a problem with a particular group member (and this is not anticipated), please bring this up with your instructor immediately.