Experiments of Microscale Organic Chemistry 1 Workshop for Secondary School Teachers Dr. W M TSUI Department of Chemistry, HKUST Department of Chemistry Outline 2 Introduction of Microscale Organic Chemistry Introduction of designing experimental procedures Microscale Organic Glassware Techniques in Microscale Organic Experiments: Solvent /Reagent Dispensing, Reaction Setup Liquid-Liquid Extraction, Filtration Purification methods Characterization Method of Organic Compounds Experiment highlights Department of Chemistry Organic synthesis & natural products synthesis 3 Complex and fascinating molecular structures can be assembled from simple starting materials. Designed molecular frameworks containing carbon atoms in combination with H, O, N, S, and halogens, can be synthesized on demand and tested for various applications. Department of Chemistry Organic synthesis & natural products synthesis 4 These useful compounds range from biological tools and medicines to high-value materials for cosmetics, computers and useful devices O OH NaOH C O OH OH C OH (CH3CO)2O O CO2 C O CH3 aspirin Department of Chemistry Introduction of Microscale Organic Chemistry 5 Had been gradually recognized and adopted at secondary school level Handle with small quantities of chemical substances Department of Chemistry Macroscale vs. Microscale 6 Quantities of chemicals Glasswares Cost per experiment Macroscale Microscale 5-100 g 0.005-0.5 g 25 - 500 mL Microscale kit (<5mL) $10-100 $100-1000 Department of Chemistry Advantages 7 1. 2. 3. 4. 5. 6. 7. 8. Require smaller storage area Save laboratory space Reduce amount of chemical waste Improve laboratory safety (smaller amount of …) Shorter reaction time (efficient heat transfer…) Save time for preparation and work up More time for evaluation and communication …………. Department of Chemistry Microscale Organic Glassware 8 Various designs http://www.sigmaaldrich.com/labware/glassware-catalog/glassware-kits-microscale.html Department of Chemistry Microscale Organic Glassware All-purpose kit: 9 Department of Chemistry Designing experimental procedures 10 Stage 1: Setup reaction Experimental Stage 2: Isolation of crude product Solvent extraction, Filtration, Precipitation Stage 3: Purification of crude product Distillation, setup, Temperature, Time, Catalyst, Solvent Recrystallization, Sublimation Stage 4: Characterization Melting point, Boiling point, IR, MS Technique: Department of Chemistry Transfer of reagent/dispensing of solvent 11 Macroscale: Measuring cylinder Beaker Conical flask Dropping funnel Microscale: Syringe Needle Septum 1.0 mL Syringe Department of Chemistry Technique: Setup for Organic Synthesis 12 Organic Synthesis: Formation and breaking of C-C bond, C-O bond, C-H bond, C-X bond, etc. Reflux: for long reaction time Macroscale reflux setup Department of Chemistry Technique: Microscale Experiment Setup 13 Microscale Organic Synthesis: Water condenser Microscale Condenser, Threaded Water out Reagents (+ catalyst) Anti-bumping granules Microscale Round-Bottom Flasks, Threaded Sand bath Microscale reflux setup Water in Department of Chemistry Technique: Microscale Experiment Setup 14 Microscale Organic Synthesis: Air condenser Reagents (+ catalyst) Anti-bumping granules Microscale RoundBottom Flasks, Threaded Microscale reflux setup Department of Chemistry Isolation Technique: Filtration 15 Vacuum filtration: Probably the most common type of filtration used by chemists. The funnel used for this method is called Hirsch funnel. This funnel has a flat disc inside which is made from porous ceramic materials Department of Chemistry Isolation Technique: Filtration 16 Pipette filtration: For small quantity of crystals Department of Chemistry Isolation Technique: Liquid-liquid Extraction 17 Partition coefficient Solubility in solvents Screw cap Test tube Separatory funnel Department of Chemistry Purification Technique: Distillation 18 For liquids with various volatilities Macroscale distillation setup Microscale distillation setup Department of Chemistry Purification Technique: Sublimation 19 For solids Macroscale sublimation setup Microscale sublimation setup Department of Chemistry Purification Technique: Recrystallization 20 For solids Various Solubility Temperature controlled by depth in sand Microscale 5mL Reaction tube Macroscale 250mL Conical flask Microscale 5mL Conical flask Department of Chemistry Purification Technique: Recrystallization 21 1. 2. 3. 4. 5. Steps in Recrystallization: Dissolution (various choice of Solvent) Hot Filtration Decolorization Crystallization Collection Department of Chemistry Purification Technique: Recrystallization 22 The general idea is to follow the “like dissolves like” principle, e.g. compounds containing hydroxyl groups are best recrystallized from hydroxy-containing solvents Class of compound Suggested solvents Hydrocarbons Light petroleum, pentane, cyclohexane and toluene Ethers Diethyl ether and dichloromethane Halides Dichloromethane Carbonyl compounds Ethyl acetate and acetone Alcohols, acids Salts Ethanol Water Department of Chemistry Methods for crystallization 23 2 Ice bath Department of Chemistry Purification Technique: Recrystallization 24 Crystallization Slow cooling: the easiest method and works for most cases Scratching: induced crystallization by scratching the inside of the beaker or flask with a glass stirring rod. This will produce microscopic fragments of glass that may act as surfaces on which crystal growth can begin Seeding: taking a small crystal from the original solid or the other groups and dropping them into the solution Department of Chemistry Characterization of organic compound 25 Melting point / melting point apparatus Simplest and most common characterization method for solid organic compounds Purity check Affordable Department of Chemistry Characterization of organic compound 26 Boiling point / distillation apparatus Simplest and most common characterization method for liquid organic compounds Purity check Affordable Department of Chemistry Characterization of organic compound 27 Infrared spectrum Infrared spectrophotometer Absorption of infrared electromagnetic radiation Information of functional groups Department of Chemistry Characterization of organic compound • • To allow passage of IR, most sample cuvettes have mineral salt windows [Caution! Avoid high humidity.] Transmission limit: – NaCl 650cm-1 – KBr 350cm-1 – CsI 56 μm (200cm-1) Department of Chemistry Characterization of organic compound 29 Bond Base Value Strength / Shape Comments 1 C=O 1715 s, "finger" Exact position depends on type of carbonyl 2 O-H 3600 s, broad Broad due to hydrogen bonding 3 N-H 3500 m Can tell primary from secondary 4 C-O 1100 s Also check for O–H and C=O 5 C=C 1650 w alkene m-s aromatic Alkene w due to low polarity Aromatic usually in pairs 6 CΞC 2150 w, sharp Most obvious in terminal alkynes 7 C-H 3000 s As hybridisation of C changes sp3-sp2-sp, the frequency increases 8 CΞN 2250 m, sharp Characteristic since little else around this value Department of Chemistry Characterization of organic compound 30 Functional groups can be identified Infrared spectrum of acetone Department of Chemistry Characterization of organic compound 31 Mass spectrum / mass spectrometer mass-to-charge ratio of molecular ion Picture from http://www.mhhe.com/physsci/chemistry/carey/student/olc/ch13ms.html Department of Chemistry Characterization of organic compound 32 Mass-to-charge ratio: Molecular ion Fragmentation pattern of molecular ion Molecular ion The ion obtained by the loss of an electron from the molecule M+ Symbol often given to the molecular ion Radical cation +ve charged species with an odd number of electrons Fragment ions Lighter cations formed by the decomposition of the molecular ion. These often correspond to stable carbcations. Department of Chemistry Characterization of organic compound 33 Decane (C10H22) Molecular ion at m/z = 142 142-29 = 113 113-14 = 99 etc Department of Chemistry Characterization of organic compound 34 Acetone (C3H6O) Molecular ion at m/z = 58 O H3C C 43 CH3 –15 –28 15 58 Department of Chemistry Experiment 1: Microscale separation of components in a mixture 35 3 components caffeine p-dimethoxybenzene acetaminophen Separation based on their different physical and chemical properties Department of Chemistry Experiment 1: Microscale separation of components in a mixture 36 Step 1: Solubility test Technique: Solid-liquid extraction (Filtration) Step 2: Acid-base chemistry Technique: Liquid-liquid extraction, Pipette filtration, Evaporation Step 3: Purity check Technique: TLC analysis Department of Chemistry Experiment 1: Microscale separation of components in a mixture 37 Step 1: Solubility test water, dichloromethane, hexane soluble Insoluble Powder Slightly soluble Department of Chemistry Experiment 1: Microscale separation of components in a mixture 38 Solid-liquid extraction (Filtration) Department of Chemistry Experiment 1: Microscale separation of components in a mixture 39 Step 2: Acid-base chemistry basic neutral HCl org NaOH aq org Department of Chemistry Experiment 1: Microscale separation of components in a mixture 40 Liquid-liquid extraction Release pressure Which layer on the top? Test by adding water Department of Chemistry Experiment 1: Microscale separation of components in a mixture Some water will be transferred into the organic phase because of the partial miscibility of the organic phase and water Organic solution contaminated with traces of water. pdimethoxybenzene aqueous organic 41 Sodium chloride Diethyl ether Water brine works to pull the water from the organic layer to the water layer Department of Chemistry Experiment 1: Microscale separation of components in a mixture 42 Dry by anhydrous Na2SO4 (Preliminary purification) Pipette filtration Department of Chemistry Experiment 1: Microscale separation of components in a mixture 43 Evaporation Needle Compressed air Department of Chemistry Experiment 1: Microscale separation of components in a mixture 44 Step 3: Purity check Thin layer chromatography (TLC) Department of Chemistry Experiment 1: Microscale separation of components in a mixture 45 Thin layer chromatography (TLC) Chromatography: Separation of compounds by the distribution between two phases – Mobile phase & Stationary phase Department of Chemistry Experiment 1: Microscale separation of components in a mixture 46 stationary phase (TLC plate: Silica gel) Sample mixture mobile phase (solvent) Department of Chemistry Experiment 1: Microscale separation of components in a mixture 47 Department of Chemistry Experiment 2: Catalytic Hydrogenation of Methyl Oleate 48 Organic Synthesis by Hydrogenation Microscale Experiment Setup methyl oleate H2(g) Catalyst: Pd/C methyl stearate Reagents: Methyl oleate, H2, Palladium on charcoal, Methanol Department of Chemistry Catalytic Hydrogenation of Methyl Oleate 49 Syringe instead of dropping funnel Setup: Generation of hydrogen gas as reagent H2(g) of septum Use of needles Use of syringe HCl(aq) Use Zn metal in 5mL flask 5mL flask Department of Chemistry Catalytic Hydrogenation of Methyl Oleate 50 Collect H2 into a inverted measuring cylinder H2(g) Syringe instead of dropping funnel HCl(aq) Zn metal in 5mL flask 5mL flask Department of Chemistry Catalytic Hydrogenation of Methyl Oleate 51 Beginning of synthetic reaction Use of syringe + needle H2(g) Methyl oleate + methanol Department of Chemistry Catalytic Hydrogenation of Methyl Oleate 52 Use of parafilm to prevent leakage Department of Chemistry Catalytic Hydrogenation of Methyl Oleate 53 Workup: Filter off Pd/C Evaporate excess CH3OH Purification of methyl stearate Isolation of second crop of product (by adding H2O to filtrate) Characterization Melting point determination