Reactions of Grignard Reagents

Transcription

1 Magnesium The Song For alkyl halides' majesty Magnesium is meant, Assisted by completely dry E-ther-e-al sol-vent. Magnesium, Magnesium, A Grignard has M-g, It's understood, its bonds are good From C to shining C. A carbonyl is polarized, Its carbon end is plus. A nucleophile will thus attack The carbon nucleus. Magnesium, Magnesium, A Grignard has M-g, Each one is fond of making bonds From C to shining C. Plus 4 more verses! Reactions of Grignard Reagents Synthesis of an Unknown Alcohol 1

2 Grignard reagents - Structure Grignard reagents are defined as compounds containing an organic group bonded to magnesium monohalide by a carbon-magnesium bond. The C-Mg bond is polarized so that the carbon atom is nucleophilic - the opposite to the polarization for carbon atoms bonded to electronegative atoms. Grignard reagents - Preparation Organomagnesium halides were first prepared by Victor Grignard. He found that these reagents could be prepared from reaction of magnesium metal with alkyl halides provided that the solvent used was an ether solvent. Mg R-Br R'-O-R' R'-O-R' is diethyl ether, tetrahydrofuran, or other ether 2

3 Grignard reagents - Utility Grignard reagents are important in organic chemistry, because they provide a reagent containing a nucleophilic carbon. Reaction of Grignard reagents with compounds containing a carbonyl group (with an electrophilic carbon) provides a very general synthesis of alcohols with a more complex carbon skelton than the starting materials. Grignard reagents - Utility H 2 C O ether H 3 O + workup RCH 2 OH 1 o 3

4 Grignard reagents - Utility H 2 C O ether R'CH O ether H 3 O + workup H 3 O + workup RCH 2 OH R'CH OH R 1 o 2 o Grignard reagents - Utility H 2 C O ether R'CH ether R'C R" ether O O H 3 O + workup H 3 O + workup H 3 O + workup RCH 2 OH R'CH OH R R R'C R'' 1 o 2 o OH 3 o 4

5 Grignard reagents - Utility R'C R" O R' MgBr R" MgBr RC O R R" R'C OH R'' 3 o RC O R' Grignard reagents - Difficulties The major difficulty in conducting Grignard reactions in a student lab is getting the reaction of the alkyl halide with magnesium started. Magnesium metal reacts with atmospheric oxygen to form an unreactive magnesium oxide coating on the surface of the metal. Any moisture present makes initiation even more difficult. 5

6 Grignard reagents - Ultrasound We are going to use a method to help abrade the oxide coating while the magnesium is shielded from air and alkyl halide is present to react immediately with the fresh magnesium metal surface. The method we will use is ultrasound sonication. We will use simple ultrasonic baths of the type that are used to clean very dirty glassware and jewelry. Grignard reagents - Ultrasound Ultrasound refers to sound waves with frequencies above human hearing; i.e. > 18,000 Hz. Ultrasonic irradiation of a liquid results in acoustic cavitation - the formation, growth and implosive collapse of bubbles in a liquid. The cavitational collapse causes intense localized high pressure and localized heating of the bubbles. 6

7 Grignard reagents - Ultrasound The effect of sonication on magnesium turnings is the abrasion of the oxide surface and localized heating of the metal. These effects produce clean, warm magnesium metal that will react with the alkyl halide. Although ultrasonic baths produce relatively low intensity ultrasound, they are sufficient to make a big difference in our ability to initiate the Grignard reaction. Grignard Reaction - Objective You will prepare a 3 o alcohol by reaction of one of three possible primary alkyl halides with one of four possible ketones (12 possible products). You will use IR spectra to identify your alcohol product. This will allow you to determine which starting materials you were given to conduct the reaction. 7

8 Grignard Reaction - Procedures This experiment is a 2-week experiment. Today, you will prepare the Grignard reagent and allow the ketone to react with it. After aqueous work-up of the reaction, you will store your product solution in a sample vial containing drying agent until next week. Next week, you will distill the solvent, and then distill your product and use infrared spectroscopy to identify your product. Grignard Reaction - Procedures Starting Materials - Two vial racks in the lab room contain THF solutions of the starting materials. The vial numbers correspond to Bin numbers. Therefore, the student with Bin #1 will use the vial labeled 1H (H=halide) and the vial labeled 1K (K=ketone). Empty reagent vials (with caps) should be returned to the vial racks before the end of the lab! 8

9 Drying Apparatus Use one of the heat guns to heat your flask, Claisen head, air condenser, and stir bar BEFORE you begin the procedure described in the handout. Get them warm enough that they are hot to the touch. We want to make sure all moisture has been driven from the interior walls of the glassware. DO NOT heat your plastic disposable pipette with the heat gun! Grignard Reaction - Apparatus Set the 25-mL round-bottomed flask on a cork ring. Then add the stir bar, a measured amount of magnesium metal, and a small amount of THF solvent. You will then assemble the apparatus shown on the next slide by attaching a Claisen head and air condenser. Securely clamp this apparatus to your rack when you add the alkyl halide. 9

10 Grignard Reaction - Apparatus open to atmosphere.. air condenser additions can be made through septum with syringe Claisen head use a Keck clamp to secure this joint You will add your reagents with a plastic disposable pipette through the open top of the air condenser as described in the lab manual. One pipette can be used for both reagents. Grignard Reaction BE SURE you use the halide solution to prepare the Grignard reagent. The reaction will NOT work if you add ketone to the magnesium. The disposable plastic pipette in your bin has a mark that shows the 1-mL fill level for your first addition of halide to the reaction flask. 10

11 Grignard Reaction 1-mL mark You may leave your disposable pipette standing in your open vial of alkyl halide or ketone between additions. Do not lay the pipette on the counter-top. Grignard Reaction - Safety READ everything in this procedure up to the point labeled Second Week BEFORE you start the procedure. Make sure you note and use the revisions given in this presentation. THF (tetrahydrofuran) is flammable, but less so than diethyl ether. NO heat guns are to be used after THF as been added to any flasks. 11

12 Grignard Reaction - Safety You want the reaction to warm while you are adding the alkyl halide, but not boil so vigorously that solvent vapors escape through the air condenser. The liquid in the original mixture of magnesium, THF and a small amount of alkyl halide solution will be clear. After the reaction initiates, the stirred mixture will become cloudy because of suspended magnesium oxides. Grignard Reaction - Safety IF you cannot feel the reaction warming as you add alkyl halide, STOP the addition and return to the ultrasonic bath for additional sonication. Have an ice bath ready to moderate the reaction ONLY if solvent vapor starts to rise to the top of the condenser. If the reaction still has not begun at this time, talk to your TA about adding a small crystal of iodine to your reaction flask. 12

13 Grignard Reaction - Safety The reaction of the Grignard reagent with the ketone will also be exothermic. Add the ketone solution slowly to avoid overheating. Storage Procedures Your product solution from the extraction procedure will be stored until next week, when you will remove solvent and distill the product. Transfer the product solution to a sample vial. Add magnesium sulfate to dry the solution. Cap the vial tightly, label it with your name and section number, and have your TA store it in the appropriate section drawer until next week. 13

14 Cleanup Procedures Your 25-mL round-bottomed flask needs to be meticulously cleaned before you return your bin at the end of the lab period. Use soapy water AND the test tube brush in your drawer to clean the flask. Rinse the flask with acetone and then use a gentle stream of pressurized air to evaporate the acetone. Rinse other glassware with acetone. Cleanup Procedures (Cont.) Dispose of the disposable pipette in the labeled beaker in the Chem 238 hood. DO NOT return this pipette with your glassware bin. Empty reagent vials (with caps) should be returned to the vial racks before the end of the lab! TAs should place these racks in the section drawer with the sample vials (in racks) containing today s products. 14

15 Aggie Honor Code An Aggie does not lie, cheat or steal, or tolerate those who do. 15