Exp t 111 Structure Determination of a Natural Product

Transcription

1 Exp t 111 Adapted by R. Minard, K. Smereczniak and Jon Landis (Penn State Univ.) from a microscale procedure used by the University of California, Irvine, in its undergraduate labs. The procedure is based on an experiment by John Lehman in perational rganic Chemistry, A Laboratory Course, (Allyn and Bacon, 1981). Revised4/9/01 Introduction: Step 1 C 3 C 3 + KMn Mn 2 + C 2 C 3 5 Compound "X" C - K + C 3 C 3 Step 2 C - K S 4 + KS 4 Compound X has a molecular formula of C and contains a benzene ring, a methoxy group (- C 3 ), and an unsaturated side-chain (-C 3 5 ). The position of the side chain on the benzene ring (ortho, para, or meta) with respect to the methoxy group on the benzene ring can be determined by oxidation of the side chain to a carboxylic acid group (see your organic chemistry textbook for a discussion of "side chain" oxidation). KMn 4, a strong oxidizing agent, oxidizes the side-chain in Compound X: C A comparison of the melting point of the carboxylic acid product with the melting point of o-methoxybenzoic acid, m-methoxybenzoic acid, and p-methoxybenzoic acid, will establish the identity of the oxidation product and therefore the position of the unsaturated side chain in Compound X. IR analysis is used to confirm this positional assignment (see Table II). The unsaturated side chain (-C 3 5 ) can have four possible structures depending on the location of the benzene ring with respect to the double bond. Each of these structures (see Table I) has characteristic pattern of infrared peaks caused by C- out-of-plane bending vibrations. Analysis of the infrared spectrum of Compound X should enable the experimentalist to identify the structure of the side chain. owever, this analysis is complicated by the fact that C- out-of-plane bending vibrations for substituted alkenes occur in the same region as C- out-of-plane bending vibrations for the various isomers of disubstituted aromatic compounds (see Table II). Therefore the aromatic bands must be assigned before bands in the same general region can be used to establish the structure of the unsaturated side chain. Table I -C 2 Structure Frequency Range (cm -1 ) and Table II Structure ortho Frequency Range (cm -1 ) cis trans C 3 C 3 C meta para and

2 Prelaboratory Exercises: (Remember you don't need to worry about chrom behavior etc. for starting material) 1. When KMn 4 oxidizes a compound, it is reduced to a brown Mn 2 precipitate. Write a balanced redox equation for the oxidation of benzaldehyde to benzoic acid using potassium permanganate. 2. Write the balanced redox equation for the reaction of sulfurous acid ( 2 S 3, formed from sodium bisulfite, NaS 3, in sulfuric acid, 2 S 4 ) with Mn 2 that dissolves the brown precipitate to give a clear solution of the soluble MnS 4. Precautions: Potassium permanganate and solutions thereof are strong oxidizing agents. Since this reaction has shown a tendency to "bump", you are encouraged to wear gloves and to keep the opening of the reaction container pointed toward the back of the hood. Experimental: Infrared Analysis: btain your sample of Compound X from the hooded shelf and run an infrared spectrum of it using salt plates (see the Lab Guide). Expand and annotate the critical absorptions in the region of interest, 650 to 1000 cm -1. Remember that you cannot successfully interpret this spectrum until after you have determined the location of the side chain on the benzene ring with respect to the methoxy group! xidation Reaction: Using a disposable pasture pipet, add 8 drops of Compound X to a tared 10 ml Erlenmeyer flask. Reweigh to determine the weight of Compound X in the flask. For every 10 mg of X, weigh out 30 mg of potassium permanganate (KMn 4 ). Place the KMn 4 in a separate 10 ml flask and add 4.0 ml of distilled water to it. Warm the solution in a beaker of gently boiling water (hot water bath; do not use a sand bath!) until all the solid KMn 4 has dissolved. Transfer this solution, via a pipet, to the flask containing Compound X. For every 20 mg of X, add one drop of 1M aqueous sodium hydroxide (Na) using the dropper attached to the reagent bottle. Stir the mixture and let it stand at room temperature for minutes. (When the reaction has started, some brown color will develop.) At the end of this time, secure the flask in the hot water bath. eat the mixture until all the purple of the permanganate has disappeared (about 1 hr). The solution will appear to be totally brown, but this is really a finely divided brown precipitate. Isolation and Purification: Let the mixture cool to room temperature and then add a few drops of 6M sulfuric acid ( 2 S 4 ) to acidify the mixture. Check for acidity with p paper, and when acidified, heat in the hot water bath for about 10 minutes. In the hood, using a microscale metal spatula, very carefully, stir a few crystals of solid sodium bisulfite into the hot solution to destroy any excess manganese dioxide (Mn 2 ). Add just enough to turn the mixture from a brown color into a creamy off-white color... this should be no more than a quarter of a teaspoon. Be sure to keep the solution acidic during this treatment, check with p paper, and add 6M sulfuric acid dropwise as needed. Allow the mixture to cool and then filter off the product * on a irsch funnel. Transfer the weighed compound that you collected from the funnel into a tared reaction tube. To the solid, add about 1 ml of the mixed 50:50 ethanol-water solution. Place a boiling stick in the tube and heat to reflux in the sand bath. If the solid has not completely dissolved after a minute of boiling, add additional solvent drop-wise. After all the solid has dissolved, set the tube into a test tube rack and allow the solution to cool slowly. After 5 minutes of slow cooling, crystals should have formed. When the solution is close to room temperature, cool it further by placing the tube in a small beaker of ice. Remove the solvent using the pipet filtration method. Let the sample dry until the next lab period. Then very carefully determine the melting point of the purified and well-dried product. Compare with listed values. * If you don't get crystals, but a sticky glob, follow this procedure: Put everything into a 125- ml separatory funnel (including the glob and what was just filtered off). Wash three times with 3- ml portions of dichloromethane. Wash Expt 111

3 the C 2 Cl 2 extracts with 1 ml of distilled water, dry over anhydrous sodium sulfate, and decant from the sodium sulfate into a clean dry flask. Let the extracts slowly evaporate until the next lab. Crystals should appear. Take some out to use as seed crystals. Recrystallize the remainder as directed above. Cleaning Up: The filtrate from the reaction can be disposed of in the eavy Metals Waste container. The filtrate from the recrystallization can be flushed down the drain. Final Report: Present the spectroscopic and chemical evidence, give the structure of Compound X using the results from the sidechain oxidation experiment and the infrared analysis, and explain your reasoning. Answer the following questions at the end of your report: (1) What product would result if the side chain had the composition C 2 3 instead of C 3 5? (2) Predict the product from the oxidation of p-chlorotoluene.

4 Synthetic Experiment PreLab Grading Sheet Name(s): TA: Date: PreLab For Exp't #:111 Date, Name, Desk #, Experiment # & Title(abbreviated after 1 st pg), Section & TA Name Possible 4 Missed Summary 10 Goals 8 Generic reactions, possible structures, conditions 16 Completeness of Chemical Data Table(s) Information for starting material is not yet determined so enter N.A. 14 Chromatographic Behavior Comparison for different possible products 18 Spectral Features Comparison for different possible products. 8 Work-up - Explanation of the product isolation and purification process 8 PreLab Exercises 14 TTAL FR PRELAB 100 Date anded in: General Comments: Total :

5 Synthetic Experiment Final Report Grading Sheet Name: TA: Date: Final Report For Exp't #:111 Name, Date, Experiment Title (abbreviated after 1st page) and every page numbered Possible 4 Missed BSERVATIN and DATA - verall organization, readability, completeness 8 Data: Weighing data, molecular weights, volumes, melting points, analysis conditions. (Examples: IR - analysis method; NMR - solvent and field strength) Yield: Show % yield calculations with limiting reagent clearly stated. Purity: Give melting point or other indicators of purity, such as TLC RESULTS AND DISCUSSIN - verall organization, readability, completeness 12 Results; Achievement of goals 16 Product Analysis Data: Quality and Interpretation Structure(s) drawn on each Spectrum or Chromatogram Assignment and discussion of all important IR peaks. Unknown Determination, Correctness and Rationale See Lab Guide Chapter 3, Section 3.4 for guidelines in annotating spectra and Ch 11 for help with interpretation. 24 PSTLAB QUESTINS 16 TTAL PINTS 100 Date anded in: General Comments: Total :