2. Experiment 18: THE GRIGNARD REACTION

3. Objectives:  To synthesize a 3 o alcohol from an alkyl halide and a ketone using a Grignard reaction.  To purify product using a liquid extraction method.  To identify compounds and determine purity of product sample using GC analysis.  To characterize reactants and product using IR, 1 H-NMR, and 13 C-NMR spectra.

4. Before coming to lab…  Review the following techniques: Extraction Drying organic solvents with MgSO 4 Preparing GC samples  You will be expected to perform these will little review, as you learned these techniques in the first semester lab.

5. CHEMICAL EQUATION

6. MAKING THE GRIGNARD REAGENT  Organic halides react with magnesium metal in diethyl ether or THF to yield an organomagnesium halide: RMgX DIETHYL ETHER R-X + Mg -------------> R-Mg-X or THF Where R= 1 o, 2 o, or 3 o alkyl, aryl or alkenyl X= Cl, Br, I  The C-Mg bond is a highly polar covalent bond. The carbon atom is both nucleophilic and basic making it very reactive with a wide variety of E +.

7. MECHANISM 2. Nucleophilic addition of butyl group to acetone produces a tetrahedral intermediate… 3….which reacts with water when aqueous HCl is added, undergoing hydrolysis to form the product alcohol. 1. The Lewis acid Mg 2+ forms an acid-base complex with the basic oxygen atom of the ketone, making the carbonyl group a better acceptor.

8. WHEN THE GRIGNARD REAGENT MEETS WATER…  Since the carbon atom of a Grignard reagent is so nucleophilic and basic, it reacts with proton donors (Brönsted acids) such as H 2 O, ROH, RCOOH, RNH 2 to yield hydrocarbons.  This makes it extremely important to keep the reaction flask and solvent completely dry of water.

9. OVERVIEW  Heat alkyl halide, magnesium turnings, and ketone in diethyl ether under reflux to synthesize intermediate.  Hydrolyze intermediate with HCl to produce neutral product.  Purify product by extraction.  Prepare GC sample.  Analyze product using GC to identify and determine purity.

10. EXPERIMENTAL PROCEDURE (Synthesis of Grignard reagent…)  Place Mg turnings in 50mL flask and place a CaSO 4 tube in the top IMMEDIATELY!  Clamp flask to ring stand and set up remainder of reflux with addition apparatus.  Start reaction with a small amount of n- butylbromide and ether by scratching Mg surface and stirring with glass rod.  Add remaining n-butylbromide and ether to sep funnel.  Add to reaction mixture dropwise. Keck clips CaSO 4 drying tube in adapter

11. EXPERIMENTAL PROCEDURE (Synthesis of alcohol product…)  Add acetone/ether to sep funnel.  Add to reaction mixture dropwise.  Cool reaction flask in water bath.  Transfer cooled liquid to 125 mL Erlenmeyer flask.  Add an ice cube and NH 4 Cl.

12. EXPERIMENTAL PROCEDURE (Purification…)  Set up an extraction apparatus.  Transfer the liquid from the flask to the funnel.  Extract with 5%HCl, 10% NaHCO 3, and Sat. NaCl.  Transfer organic layer to a 50 mL flask and dry over MgSO 4.  Transfer dried organic liquid to a beaker.  Submit a GC sample.

13. Table 18.1: GC Results Record retention times for ALL peaks in standard chromatogram! Record retention times and area % for ALL peaks present in sample chromatogram! Calculate AA% for REACTANTS AND PRODUCT only! Compound GC Retention Times (min) Area Percent Adjusted Area Percent Standard Sample methanol --- acetone n-butyl bromide 2-methyl-2- hexanol octane ---

14. Product Analysis (IR Spectroscopy)

15. Table 18.2: IR Analysis Functional Group Base Valuesn-butyl bromide 2-methyl-2- hexanol Frequency (cm -1 ) Frequency (cm -1 ) Frequency (cm -1 ) OH stretch2500-3300 sp 3 CH stretch2850-3000 C-O stretch1000-1200 C-Br stretch500-700 IR spectra available on p. 157, 158 of the lab manual! In discussion, only refer to frequencies which indicate a CONVERSION to product!

16. Product Analysis ( 1 H-NMR Spectroscopy)

17. Product Analysis ( 13 C-NMR Spectroscopy) NMR solvent C 1 29 

18. Table 18.3: NMR Analysis n-butylbromide (reactant) 2-methyl-2-hexanol (product) Enter chemical shifts ONLY based on the spectra on page 157, 158. In discussion, only refer to signals which indicate a CONVERSION to product!

19. SAFETY CONCERNS Diethyl Ether is EXTREMELY flammable. Use extreme caution at all times! Be sure to wear goggles at ALL times during this experiment! GLOVES are available upon request!

20. WASTE MANAGEMENT  RECOVERED MAGNESIUM WASTE: Unreacted magnesium & water rinse.  LIQUID WASTE: Aqueous extracts and washes, crude alcohol product.  SOLID WASTE: Magnesium sulfate.

21. CLEANING  Rinse condenser and Claisen adapter with wash acetone only.  Clean all other glassware with soap, water, brush, and rinse with wash acetone.  Leave all ground glass jointware in lab hood for inspection. DO NOT place any in lab drawer.  DO NOT return any glassware to lab drawer dirty or wet.

22. In-lab Question (The following question should be answered in laboratory notebook.)  Draw the product, and a complete mechanism for its formation, of the reaction between propyl magnesium bromide with acetophenone.

23. In-lab Question (The following question should be answered in laboratory notebook.)  During the experiment a student neglected to completely dry the glassware prior to assembling the apparatus. Write the chemical equation that occurs between propyl magnesium bromide and water, and explain how this would affect the Grignard synthesis.