Grignard - Introduction to Organic Chemistry - Lecture Notes, Study notes of Organic Chemistry

Download Grignard - Introduction to Organic Chemistry - Lecture Notes and more Study notes Organic Chemistry in PDF only on Docsity! Figure 1: Grignard apparatus EXPERIMENT SEVEN SYNTHESIS OF 2-METHYL-2-HEXANOL: A GRIGNARD REACTION DISCUSSION A standard Grignard synthesis is carried out in three steps: (1) preparation of RMgX; (2) the reaction of RMgX with the carbonyl compound or other reactant; and (3) the acidic hydrolysis. The first two steps (and often all three steps) are generally carried out in the same reaction vessel. The intermediate products (the Grignard reagent,and the alkoxide) are rarely isolated. PREPARATION OF THE GRIGNARD REAGENT (STEP 1) In this experiment, the Grignard reagent is prepared by slowly adding a solution of 1-bromobutane in anhydrous diethyl ether (not solvent ether, which is wet) to Mg turnings. Unfortunately, the reaction leading to the formation of a Grignard reagent is often difficult to initiate. Difficulties can usually be traced to contaminants, primarily water. Therefore, scrupulous care must be taken to dry all glassware and to use only dry reagents and solvents. The techniques used to start the reaction are discussed in Experimental Note 3. Once started, the formation of a Grignard reagent is exothermic; therefore, excess 1-bromobutane should not be added to initiate the reaction. If a large excess of 1- bromobutane is present in the reaction vessel, the reaction may be difficult to control. Once the reaction has begun, the 1-bromobutane is added at a rate that will maintain a gentle reflux of the ether in the reaction flask. At the end of the reaction, some of the magnesium may remain unconsumed. The reason for this is that some 1- bromobutane is destroyed by undergoing a coupling reaction with the Grignard reagent to yield octane. Other than providing a mechanical inconvenience in the extraction steps, the residual magnesium metal does not interfere with the remainder of the experiment. An ether solution of a Grignard reagent has a translucent gray-to-black tint. The color arises from impurities in the magnesium metal, rather than from the Grignard reagent itself. Once formed, the Grignard reagent must be carried on to Step 2 (the reaction with acetone) immediately. It cannot be saved until the next laboratory period because it reacts with oxygen and moisture from the air. REACTION WITH ACETONE (STEP 2) Docsity.com The reaction of n-butylmagnesium bromide with acetone is extremely vigorous. The acetone must be added very slowly; otherwise, the reaction mixture will boil over. The product is a magnesium alkoxide of an alcohol and thus insoluble in diethyl ether. This alkoxide sometimes forms a crusty precipitate that must be broken up by swirling the flask so that the unreacted acetone can become mixed with the Grignard reagent. After the reaction of acetone and the Grignard reagent is completed, it is no longer necessary to protect the reaction mixture from air or moisture. This mixture can be stored until the next laboratory period. HYDROLYSIS OF THE ALKOXIDE (STEP 3) The alkoxide product of the Grignard reaction is converted to 2-methyl-2-hexanol by treatment with aqueous NH4Cl instead of with a dilute mineral acid. The reason is that the final product is a tertiary alcohol (R3COH) and is easily dehydrated to an alkene by a strong acid. When the magnesium alkoxide is poured into aqueous NH4Cl, the alkoxide ion (a strong base) reacts with water or NH4 + to extract a proton. Water alone is not used as a hydrolyzing agent for two reasons. First, the product hydroxide ion is only a slightly weaker base than the alkoxide ion. The addition of an acid results in a more favorable equilibrium. Second, in alkaline solution, the magnesium ions are converted to a gelatinous precipitate of Mg(OH)2, which is difficult to remove from the product. In a neutral or acidic medium, the magnesium ions remain in solution. The product alcohol is extracted from the aqueous layer with diethyl ether (solvent grade). The aqueous layer, which contains the magnesium salts, is discarded. The ether solution is washed with sodium carbonate solution to ensure alkalinity prior to distillation. (Any acid remaining in the ether layer would cause dehydration of the alcohol during the distillation.) Because diethyl ether can dissolve a considerable amount of water (1.2 g H2O in 100 g of ether), the ether extract is partially dried by extraction with saturated NaCl solution before an inorganic drying agent is used. The final drying is accomplished by allowing the ether solution to stand over anhydrous MgSO4. The bulk of the ether is removed by simple distillation. Before the alcohol is distilled, the residue is transferred to a smaller distillation flask; otherwise, a considerable amount of product would be lost as vapor filling the large flask. EQUIPMENT: 400-mL beaker calcium chloride drying tube Claisen head condenser disposable pipet 25-mL or 50-mL tared distillation receiving flask 125-mL dropping funnel 50-mL, 125-mL, and two 250-mL Erlenmeyer flasks heating mantle and rheostat (or steam bath) ice bath 50-mL (or 100-mL) and 250-mL round-bottom flasks 250-mL or 400-mL separatory funnel simple distillation apparatus stirring rod warm water bath Docsity.com Add fresh boiling chips and distil the product, collecting the fraction boiling at 135-143EC in a tared receiver. A typical yield is 5.0 g (43%). (The yield may vary considerably, depending on the degree of dryness of the anhydrous ether used in Step 1.) Determine the refractive index of the product. Place the distilled product in a correctly labeled vial, and hand it in to your instructor. EXPERIMENTAL NOTES 1) The purpose of the drying tube is to prevent atmospheric moisture from entering the reaction vessel via the condenser and yet allow the reaction vessel to be open to the atmosphere so that gas pressure does not build up. There are two types of drying tubes: curved (better) and straight (less expensive). A straight drying tube must not be connected directly to the top of the condenser because the dessicant can liquefy and drain into the condenser. Connect the straight tube to the condenser by a short length of heavy-walled rubber tubing, as shown in Figure 10. In either type of drying tube, the dessicant is held in place with loose plugs of glass wool. A one-hole rubber stopper may be used as a secondary plug at the wide end of the drying tube. 2) Solvent ether contains an appreciable amount of water (up to 1-2%) and is totally unsuitable as a Grignard solvent. Anesthesia ether contains ethanol, which makes it also unsuitable. Commercial anhydrous ether is adequate only if a freshly opened can is used. Anhydrous ether must not be left open to the air because it absorbs both oxygen and moisture. (Oxygen and ethers yield peroxides, which can explode if the ether is distilled. Absorbed moisture will ruin a Grignard reagent.) Your instructor will probably provide anhydrous ether for this experiment. In many laboratories, storeroom personnel prepare anhydrous ether by passing solvent ether through a column containing molecular sieves, which are adsorbents with pores that trap molecules of a certain size (in this case, H2O molecules). Another procedure for the preparation of anhydrous ether from solvent ether and a procedure for the testing of peroxides in anhydrous ether follow. If you find it necessary to prepare your own anhydrous ether, allot an additional laboratory period. Preparation of Anhydrous Diethyl Ether. With cooling, mix a 2: ! ratio of solvent ether and conc. H2SO4 in a large round-bottom flask, and distill about two-thirds of the ether. (Do not distill all the ether.) Any water and ethanol contaminating the ether will remain with the sulfuric acid. To discard the residue, pour it onto cracked ice, allow the residual ether to evaporate in the hood, then dilute the aqueous acid with water and pour it down the hood drain with additional water. Add freshly prepared sodium wire or ribbon to the distilled ether, then allow the ether to stand at least overnight in the fume hood with the fan on. Stopper the container with a very loose- fitting cork or drying tube to allow the hydrogen gas to escape. Sodium wire or ribbon is prepared by pressing sodium metal through a die, using a press. If a sodium press is not available, the ether can be dried with finely diced sodium; however, diced sodium is inferior to wire or ribbon. Another method is to add a few grams of CaCl2 to the ether and allow the mixture to stand until hydrogen has ceased to be evolved. The dried ether can then be decanted or (better) pipetted, using a rubber bulb, as needed. Commercial anhydrous ether can be further dried with sodium wire without the sulfuric acid purification step. Peroxide Test. Shake 5 mL of ether with a solution of 1 mg of sodium dichromate and one drop of dilute H2SO4 in 1 mL of water in a corked test tube. If the ether layer turns blue (from perchromate ion), peroxides are present and must be removed. Peroxide Removal. Shake the peroxide-contaminated ether with 5% aqueous ferrous sulfate (FeSO4) solution acidified with H2SO4. The iron(II) ions are oxidized with concurrent reduction Docsity.com of the peroxide. Aqueous sodium sulfite (Na2SO3) can be substituted for the ferrous sulfate solution. 3) The most common cause of failure of initiation of the reaction leading to the Grignard reagent is moisture (in the apparatus, in the ether, or on the magnesium turnings). In addition, in a humid atmosphere, water will collect on the sides of a cold condenser. If the initial cloudiness becomes a white precipitate, then the Mg is being converted to Mg(OH)2 by the water, and not to RMgX. If excessive moisture is present, it is best to begin anew with dry equipment and reagents. Sometimes, Grignard reagents are reluctant to form because of a magnesium oxide coating on the metal turnings. The following procedure can often overcome this difficulty. First, warm the reaction flask with a pan of warm water (about 50-60EC). This warming will cause the ether to boil (not a sign of initiation, in this case). Remove the warm water bath and watch for the signs of initiation (spontaneous boiling of the ether). This warming may be repeated if initiation does not occur. If repeated warming does not initiate Grignard-reagent formation, add an additional 5 mL of the 1- bromobutane solution from the dropping funnel and warm the flask again. As a last resort, another reagent may be added to activate the surface of the magnesium and/or indirectly complex with any water present. A number of reagents are useful: a crystal of I2, a few drops of Br2, 1.0 mL of iodomethane (methyl iodide) or dibromomethane (methylene bromide). (Only one, not all, of these should be added.) Add the reagent directly to the reaction mixture without swirling, then warm the flask in the water bath. The two inorganic halogen compounds function by reacting with the magnesium to yield an anhydrous magnesium halide, which complexes with any water present. Iodomethane and dibromomethane are reactive organohalogen compounds that react with the magnesium in slightly different ways. For example, iodomethane first forms a Grignard reagent (even when a less reactive alkyl halide does not react), which then reacts with any water present and thus removes it from solution. 4) The reaction mixture may contain small pieces of unreacted magnesium metal. If possible, avoid transferring these bits of metal to the ice mixture. However, a tiny piece of magnesium that cannot be removed easily from the ice mixture will do no harm. Docsity.com PROBLEMS 1) Write equations for the three standard steps in a Grignard synthesis in which the principal reactants are cyclohexanone and ethylmagnesium bromide. 2) A student oven-dries the glassware needed for a Grignard reaction, then stores them in a locker until the next laboratory period. Will the glassware still be dry when the Grignard reaction is begun? Explain. 3) Suggest a reason for using magnesium turnings instead of magnesium powder or chunks in a Grignard reaction. 4) In which of the following steps in a Grignard synthesis is anhydrous ether (instead of solvent ether) necessary? Explain. (a) Preparation of the Grignard reagent. (b) Addition of an ether solution of a ketone (instead of pure ketone, as in this experiment). (c) Extracting the product from the hydrolysis mixture. (d) Washing the dried product into a distillation flask. 5) Are diethyl ether vapors lighter or heavier than air? What are the safety implications of your answer? Docsity.com