CHEM 231: Organic Form and Function
CHEM 231: Organic Form and Function
Laboratory 5 Multi-step Synthesis: Part A Specific Practical Goals
to prepare an ether using the Williamson Ether Synthesis to synthesize an intermediate for subsequent use in a multi-step procedure to heat a reaction using the reflux technique to isolate a product using aqueous extraction and rotary evaporation to determine the yield of a reaction based on the limiting reagent to characterize a product using TLC and IR spectroscopy
Background Alkoxybenzaldehydes are a class of aromatic compounds commonly found in nature which have very interesting properties. For example, anisaldehyde (Figure 1) is one of the components found in the essential oils of Star Anise 1 (Illicium verum) used for obtaining the characteristic flavor of the black jelly bean. The homologous 4-ethoxybenz2 aldehyde has shown promise in reducing the facial inflammation associated with rosacea. And the disubstituted benzaldehyde vanillin is responsible for the delectable flavor in hot cocoa and crème brûlée.
Figure 1. Some examples of alkoxybenzaldehydes One convenient route to alkoxybenzaldehydes is via the Williamson Ether Synthesis. For example, the readily available and inexpensive (10¢/g) 4-hydroxybenzaldehyde (1) is heated with 1-iodopropane and potassium carbonate in acetonitrile to give 4-propoxybenzaldehyde (2). Note that there are two reactive functionalities in the starting material (alcohol and aldehyde), and this reaction modifies only one. In the next lab you will modify the aldehyde functional group selectively. Since the product is a liquid, it cannot be isolated by filtration. Instead, the reaction mixture is subjected to aqueous extraction with dichloromethane. The product is then characterized by TLC (vs. the starting material) and infrared (IR) analysis, which should demonstrate the loss of the OH stretch.
Scheme 1. Synthesis of 2-propoxynaphthalene
Pre-lab Reading Technique Primers 1,3,5,6, & 8: TLC, Separatory Funnel, Reflux, Infrared Spectroscopy, and Yields 1 2
Gholivand, M.B.; Rahimi-Nasrabadiab, M.; Chalabib, H., Analyt. Lett. 2009, 42, 1382. Dralos, Z.D.; Fuller, B.B., Dermatol. Surg. 2005, 7, 881.
Safety Considerations You must abide by all laboratory safety rules. Acetonitrile [75-05-8]. Highly flammable liquid and vapour. Harmful if swallowed or in contact with skin Causes mild skin irritation. Causes serious eye damage. Harmful if inhaled. Dichloromethane [75-09-2]. Harmful if swallowed. Causes skin and eye irritation. Suspected of causing cancer. May be harmful if inhaled. Causes respiratory tract irritation. Harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. Harmful if swallowed. 4-Hydroxybenzaldehyde [123-08-0]. May be harmful if swallowed. Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. 1-Iodopropane [107-08-4]. Flammable liquid and vapour. Harmful if swallowed or if inhaled Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. Toxic to aquatic life. Harmful to aquatic life with long lasting effects.. Potassium carbonate [584-08-7]. Harmful if swallowed. Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. 4-Propoxybenzaldehyde [5736-85-6]. Harmful if swallowed or in contact with skin Causes skin irritation. Causes serious eye irritation. Harmful if inhaled. May cause respiratory irritation. Procedural Overview This reaction will be run by each person. Important Note: The product you synthesize in this lab will be used as the starting material for the next lab. Make sure the product is properly labeled and stored. Do not discard! In a 100 mL round-bottom flask, combine 610 mg of 4-hydroxybenzaldehyde and 3.50 g of potassium carbonate. Add 5 mL acetonitrile and swirl to dissolve the organic material. Using an Eppendorf pipet, add 390 L of 1-iodopropane and swirl briefly to mix. Add 2-3 boiling chips (IMPORTANT!) and set up the flask for reflux. Heat at reflux for 1h, then remove the
heat. After letting the flask cool briefly, transfer the contents to a separatory funnel using 40 mL of dichloromethane and 75 mL of deionized water. Vigorously shake the funnel and let the phases separate. Collect the organic layer, dry over sodium sulfate, and remove the solvent using rotary evaporation. Weigh the isolated material to determine the yield of the reaction (note: to determine the theoretical yield, you must first identify the limiting reagent!). Prepare a TLC sample using a small amount of product, spot on a TLC plate alongside the TLC standard for the starting material, and develop the plate in a mobile phase of ethyl acetate/hexane 1:3. Prepare a salt plate for IR analysis using a single small drop of neat (undiluted) product and collect an IR spectrum. Both samples can be washed back into the rotavap flask using dichloromethane, so that all the product can be recovered for the next reaction. Remove the residual solvent by placing on the rotavap. Label and store your product until next lab. Make sure the flask is tightly stoppered with a yellow plastic cap (not the glass stopper!).
revision 10-24-13
Laboratory 5 Multi-step Synthesis: Part A Specific Practical Goals
to prepare an ether using the Williamson Ether Synthesis to synthesize an intermediate for subsequent use in a multi-step procedure to heat a reaction using the reflux technique to isolate a product using aqueous extraction and rotary evaporation to determine the yield of a reaction based on the limiting reagent to characterize a product using TLC and IR spectroscopy
Background Alkoxybenzaldehydes are a class of aromatic compounds commonly found in nature which have very interesting properties. For example, anisaldehyde (Figure 1) is one of the components found in the essential oils of Star Anise 1 (Illicium verum) used for obtaining the characteristic flavor of the black jelly bean. The homologous 4-ethoxybenz2 aldehyde has shown promise in reducing the facial inflammation associated with rosacea. And the disubstituted benzaldehyde vanillin is responsible for the delectable flavor in hot cocoa and crème brûlée.
Figure 1. Some examples of alkoxybenzaldehydes One convenient route to alkoxybenzaldehydes is via the Williamson Ether Synthesis. For example, the readily available and inexpensive (10¢/g) 4-hydroxybenzaldehyde (1) is heated with 1-iodopropane and potassium carbonate in acetonitrile to give 4-propoxybenzaldehyde (2). Note that there are two reactive functionalities in the starting material (alcohol and aldehyde), and this reaction modifies only one. In the next lab you will modify the aldehyde functional group selectively. Since the product is a liquid, it cannot be isolated by filtration. Instead, the reaction mixture is subjected to aqueous extraction with dichloromethane. The product is then characterized by TLC (vs. the starting material) and infrared (IR) analysis, which should demonstrate the loss of the OH stretch.
Scheme 1. Synthesis of 2-propoxynaphthalene
Pre-lab Reading Technique Primers 1,3,5,6, & 8: TLC, Separatory Funnel, Reflux, Infrared Spectroscopy, and Yields 1 2
Gholivand, M.B.; Rahimi-Nasrabadiab, M.; Chalabib, H., Analyt. Lett. 2009, 42, 1382. Dralos, Z.D.; Fuller, B.B., Dermatol. Surg. 2005, 7, 881.
Safety Considerations You must abide by all laboratory safety rules. Acetonitrile [75-05-8]. Highly flammable liquid and vapour. Harmful if swallowed or in contact with skin Causes mild skin irritation. Causes serious eye damage. Harmful if inhaled. Dichloromethane [75-09-2]. Harmful if swallowed. Causes skin and eye irritation. Suspected of causing cancer. May be harmful if inhaled. Causes respiratory tract irritation. Harmful if absorbed through skin. Causes skin irritation. Causes eye irritation. Harmful if swallowed. 4-Hydroxybenzaldehyde [123-08-0]. May be harmful if swallowed. Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. 1-Iodopropane [107-08-4]. Flammable liquid and vapour. Harmful if swallowed or if inhaled Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. Toxic to aquatic life. Harmful to aquatic life with long lasting effects.. Potassium carbonate [584-08-7]. Harmful if swallowed. Causes skin irritation. Causes serious eye irritation. May cause respiratory irritation. 4-Propoxybenzaldehyde [5736-85-6]. Harmful if swallowed or in contact with skin Causes skin irritation. Causes serious eye irritation. Harmful if inhaled. May cause respiratory irritation. Procedural Overview This reaction will be run by each person. Important Note: The product you synthesize in this lab will be used as the starting material for the next lab. Make sure the product is properly labeled and stored. Do not discard! In a 100 mL round-bottom flask, combine 610 mg of 4-hydroxybenzaldehyde and 3.50 g of potassium carbonate. Add 5 mL acetonitrile and swirl to dissolve the organic material. Using an Eppendorf pipet, add 390 L of 1-iodopropane and swirl briefly to mix. Add 2-3 boiling chips (IMPORTANT!) and set up the flask for reflux. Heat at reflux for 1h, then remove the
heat. After letting the flask cool briefly, transfer the contents to a separatory funnel using 40 mL of dichloromethane and 75 mL of deionized water. Vigorously shake the funnel and let the phases separate. Collect the organic layer, dry over sodium sulfate, and remove the solvent using rotary evaporation. Weigh the isolated material to determine the yield of the reaction (note: to determine the theoretical yield, you must first identify the limiting reagent!). Prepare a TLC sample using a small amount of product, spot on a TLC plate alongside the TLC standard for the starting material, and develop the plate in a mobile phase of ethyl acetate/hexane 1:3. Prepare a salt plate for IR analysis using a single small drop of neat (undiluted) product and collect an IR spectrum. Both samples can be washed back into the rotavap flask using dichloromethane, so that all the product can be recovered for the next reaction. Remove the residual solvent by placing on the rotavap. Label and store your product until next lab. Make sure the flask is tightly stoppered with a yellow plastic cap (not the glass stopper!).
revision 10-24-13
