Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 The Cannizzaro Reaction Synthesis of p-chlorobenzylalcohol and p-chlorobenzoic acd Supplementary Material This experiment is an interesting transformation since one can obtain two different compounds from a single reagent. The reaction is named after Stanislao Cannizzaro (1826-1910) who was an Italian chemist. He was first studying medicine, but soon turned to the study of organic chemistry. He discovered that aromatic aldehydes are decomposed by an alcoholic solution of potassium hydroxide into a mixture of the corresponding acid and alcohol. One typical example is the decomposition of benzaldehyde into benzoic acid and benzyl alcohol.1 This reaction seems to be very popular among the different universities because of it character. It can done in macro- or microscale and can be found from many organic synthesis articles and books. The Cannizzaro reaction is the disproportionation of an aldehyde to on equimolar mixture of primary alcohol and carboxylic acid. The first step in the mechanism is the nucleophilic attack of the hydroxide anion on the carbonyl group of the aldehyde to give a tetrahedral intermediate, which expels hydride ion as a leaving group and is thereby oxidized. A second aldehyde molecule accepts the hydride ion in another nucleophilic step and is thereby reduced. The detailed mechanism for the Cannizzaro reaction can be found from the books and article which are listed below.1-4 It is advisable to weight the p-chlorobenzaldehyde into a small beaker since it takes 5-10 minutes to be dissolved in methanol by stirring the mixture with a glass rod. The solution is then added to disstillation flask containing the 11 M potassium hydroxide solution. At this point of the experiment there is some precipitate (figure SM 17.1.2). While refluxing, the solid does not go completely into solution, starts to get stuck to the round bottom flask walls and occasional shaking is needed (Figure SM 17.1.3). After cooling the reaction mixture, students separate products by extracting mixture with dichloromethane. The newly formed alcohol will move to the organic layer while the carboxylic acid is left behind in the water layer in form of carboxylate. Students don’t always realize which layer is the upper one and which layer the lower one (figure SM 17.1.4), and so they are advised to look to the dichloromethane density (1,326620g/cm3). The dichloromethane layers are washed with the saturated sodium bicarbonate solution in order to remove the acid residue (the students are usually challenged at this point to explain why this is done). After drying over anhydrous sodium sulfate, the dichloromethane layers are filtered to the distillation flask and the dichloromethane is evaporated in the rotary evaporator. The crude alcohol is purified by recrystallizing it using a solution of acetone in hexane (1:9) (usually 5-10 ml). 1 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 When acidifying the water layer with hydrochloric acid the mixture will warm up (figure SM 17.1.5). In order to avoid losses by dissolution of the carboxylic acid in the medium, the mixture should be cooled in an ice bath. About 20 mL of methanol are needed to perform the crystallization of the carboxylic acids. This synthesis is one of the four syntheses for 2nd year Chemistry M. Sc. Students in the Technical university of Tampere who are doing their first organic chemistry laboratories. The experiment has been run by 60 students for two year, working individually in up 12 students per class. The reaction time mentioned in the experimental part is 1 h in order to fit the lab sessions into the planned schedule. Longer reaction times have not been tested. This experiment yields and melting points were measured by seven students and ranges of those are listed in the table below. 1 5 6 H NMR spectra of p-chlorobenzoic acid and p-chlorobenzyl alcohol in CDCl3 can be found online in Sigma-Aldrich or Spectral Database for Organic Compounds websites. Table SM 17.1.1 – Yields and melting points of the products Product Yield [%] Melting point [˚C] p-chlorobenzyl alcohol 16-66 70-73 p-chlorobenzoic acid 31-56 239-243 If the students don’t have time to be in the laboratory 7 hours at a time, it would be better to split the overall experiment in 3 sessions. The session 1 (3h) would consist of reaction and products isolation. During the next session (2h) the students can purify the crude products by recrystallizing and leave to dry overnight. During the last session (2h) they weight the products, determine the melting points and obtain IR and NMR spectra if it is possible. Answers to the question in the experimental part 1. The mechanism for the reaction can be found from the literature mentioned below.1-4 2. The basis for separation of the compounds from the reaction mixture can be found from the background section of the main document 2 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 3. The reaction rate order for benzaldehyde, p-nitrobenzaldehyde, p-chlorobenzaldehyde and p- methoxybenzaldehyde in Cannizzaro reaction would be following: MeO− < H− < Cl− < NO2−. The aromatic aldehydes may be divided into two classes: those that react faster than unsubstituted benzaldehyde and those that react more slowly. Those that go slower have electron donating substituents on the 4-position of the aromatic ring, whilst the electron withdrawing substituted benzaldehydes react faster due to their increased electrophilicity. See more details from the literature mentioned below.2 4. The melting points for the products can be found for example from the Handbook of Chemistry and Physics. In the edition 93th the melting point for the p-chlorobenzyl alcohol is 75°C and for the p- chlorobenzoic acid 243°C. 5. Interprepation of the main bands for the IR spectra can be found from the books dealing with principles of instrumental analysis. The IR spectra shown below (Figures SM 17.1.8 and SM 17.1.9) have been measured using the Fourier transform infrared spectrometer with attenuated total reflectance (diamond-ATR) and can differ from those where samples are powdered in KBr. Photos of the experiment Cooling water out Condenser Cooling water in Disstillation flask (100 ml) Heating device 3 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 Figure SM 17.1.1 – The reaction setup. Used to reaction and recrystallizing. Figure SM 17.1.2 - Reaction mixture before refluxing, just after the heat is turned off and after the set up is cooled. Figure SM 17.1.3 - Shaking off the precipitate from the walls of distillation flask. 4 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 Water layer Dichloromethane layer Figure SM 17.1.4 – Reaction mixture dissolved in water and after extraction with first 15 ml portion of dichloromethane. Figure SM 17.1.5 – The water layer after acidification with hydrochloric acid. Figure SM 17.1.6 – The filtration instrumentation. 5 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 Figure SM 17.1.7 – The final products after recrystallization. IR spectra of products Figure SM 17.1.8 – IR spectra of p-chlorobenzoic acid 6 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 Figure SM 17.1.9 – IR spectra of p-chlorobenzyl alcohol _______________________________ 1 McMurry, J., Organic Chemistry, Thomson Learning, Inc., USA, 7th ed, 2008, 724-725 2 Clayden, J., Greeves, N., Warren, S., Wothers, P., Organic Chemistry, Oxford University Press, UK, first published 2001, 2008, 1081-1084 3 Swain, C. G., Powell, A. L., Sheppard, W. A. and Morgan, C. R., J. Am. Chem. Soc. 1979, 101(13), 3576 4 Vogel, A. I., A Textbook of Practical Organic Chemistry, Longman Scientific and Technical, London, 5th ed, 1989, 1028-1031 5 http://www.sigmaaldrich.com/spectra/fnmr/FNMR001008.PDF ; http://sdbs.db.aist.go.jp (SDBS no. 1976) – accessed March 2015 6 http://www.sigmaaldrich.com/spectra/fnmr/FNMR009685.PDF ; http://sdbs.db.aist.go.jp (SDBS no. 5668) – accessed March 2015 7 Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 The Kemp Elimination in Water: A Laboratory Experiment for Introductory Organic Chemistry Supplementary Material 1. Material Provided to Students a. Pre-Lab Assignment b. Green Chemistry. An Introduction 2. Instructor Notes a. Description of the Experiment b. Answer key for Pre-Lab Questions c. Answer key for Post-lab Questions d. TA Notes 3. Representative 1H NMR and IR Spectra 4. Summary of Student Results 5. CAS Registry Numbers Supplementary information for Comprehensive Organic Chemistry Experiments for the Laboratory Classroom © The Royal Society of Chemistry 2017 1a. Pre-Lab Assignment The Kemp Elimination in Water: A Laboratory Experiment for Introductory Organic Chemistry Note: The six questions found in the “Results interpretation and additional questions” section of the experiment document were modified from the pre- and post-lab assignments questions included here. PRE-LAB ASSIGNMENT In this experiment, you will conduct an elimination reaction, using NaOH as base, to convert benzisoxazole to salicylonitrile. The product will be isolated and its melting point will be determined. 1. Given the following information, state whether the reaction will follow an E1 or E2 mechanism and explain how you arrived at your answer. Experiment Result concentration of benzisoxazole doubled reaction rate doubles concentration of NaOH doubled reaction rate doubles concentration of both SM and NaOH reaction rate quadruples doubled 2.