Synthesis of 2-Methyl-2-Hexanol-The Grignard Reaction-Lu Le Laboratory

The Grignard reaction is an organometallic chemical reaction in which alkyl- or aryl-magnesium halides (Grignard reagents) add to a carbonyl group in an aldehyde or ketone. This reaction is an important tool for the formation of carbon–carbon bonds. The reaction of an organic halide with magnesium is not a Grignard reaction, but provides a Grignard reagent.

Grignard reactions and reagents were discovered by and are named after the French chemist François Auguste Victor Grignard (University of Nancy, France), who was awarded the 1912 Nobel Prize in Chemistry for this work. Grignard reagents are similar to organolithium reagents because both are strong nucleophiles that can form new carbon-carbon bonds.  (Wikipedia)

An organometallic compound is an organic compound that contains carbon bonded to a metal. Some organometallic compounds are highly reactive, while others are relatively stable.

The degree of reactivity of an organometallic compound depends on the degree of ionic character of the carbon-metal covalent bond. Because carbon is more electronegative than metals, a carbon atom bonded to a metallic atom withdraws electrons towards itself. Thus, the carbon atom attains a partial negative charge and the organic group can behave as a carbanion (R3C:-).

A more negative carbon is more reactive than a less negative carbon; therefore, the most reactive organometallic compounds are those containing the most electropositive metals (the alkali metals). An organometallic compound containing a less electropositive metal is less reactive.

CH₃CdCH₃ < CH₃MgI < CH₃Li

increasing ionic character; increasing reactivity

In 1901, the French mathematician-chemist Victor Grignard reported organomagnesium halides (RMgX), now called Grignard reagent, in his doctoral dissertation. He received the 1912 Nobel prize in chemistry for his discovery and Subsequent development of the reactions of these reagents.

One useful reaction of a Grignard reagent is its reaction with a ketone to yield the magnesium salt of a tertiary alcohol, which can be converted to the alcohol by hydrolysis.

Preparation of a Grignard Reagent

A Grignard reagent is prepared by the reaction of magnesium metal with an organohalogen compound in an ether solvent.

 An ether solvent is necessary for the formation of the Grignard reagent. It is thought that the unshared electrons of the oxygen coordinate with the Mg to stabilize the organometallic compound. Also, the alkyl portion of the ether provides a hydrocarbon=like solvent for organic part of the Grignard reagent. Both these factors result in Grignard reagents being soluble in ether.

 Diethyl ether is the usual solvent because it is inexpensive. Other ethers, such as THF(tetrahydrofuran), can also be used.

Mechanism

Ionic mechanism:

Radical mechanism:

Chemicals

1.      Ammonium chloride: 8.333g

2.      Anhydrous acetone: 1.933g

3.      Anhydrous diethyl ether: 17.0mL

4.      Anhydrous magnesium sulfate: 1.70g

5.      10% aqueous sodium carbonate: 8.333mL

6.      1-bromobutane: 4.567g

7.      Diethyl ether: 25mL

8.      Magnesium turnings: 0.800g

9.      Saturated aqueous NaCl: 8.333mL

Procedure

Step1: Preparation of n-Butylmagnesium Bromide

1.      Dry a two-neck, round-bottom flask, a condenser and a dropping funnel with a hair dryer. Then assemble them as shown below the picture.

2.      Place 0.800g magnesium turnings in the round-bottom flask.

Shiny Magnesium Turnings

3.      To the dropping funnel, add a well-mixed solution of 4.567g of 1-bromobutane and 17.0mL of anhydrous diethyl ether.

4.      To initiate the reaction, add ~5mL (sufficient to sink all magnesium turnings under the ether solution) of the ether solution from the dropping funnel to the reaction flask. Start stirring with a magnetic stir bar and use a hair dryer as a heater to heat the reaction flask. After it can produce bubble spontaneously, stop heating it.

 

Use hair dryers to heat the round-bottom flask

 

The reaction mixture start react spontaneously

5.      Reflux the reacting mixture for 15 minutes. As the magnesium is consumed, the mixture will become gray. At the end of the reflux period, proceed immediately to Step 2.

 The Grignard reagent looks gray

Refluxing apparatus

Drying Tube

Step 2: Reaction of n-Butylmagnesium Bromide with Acetone

1.      Chill the flask containing the Grignard reagent with an ice bath.

2.      Pour 1.933g of anhydrous acetone in the dropping funnel, and add it a few drops at a time to the reaction mixture.

3.      When the addition of acetone is completed, allow the reaction mixture to stand at room temperature for 30 minutes.

 Before hydrolysis, all the reacting system should be very dry

Step 3: Hydrolysis and Pruification

1.      Prepare 33mL of 25% aqueous ammonium chloride. Mix 25mL of this solution with 17g ice in a beaker. Transfer the remaining 8.33mL oh the ammonium chloride solution to a 50-mL conic flask, and chill it in an ice bath.

2.      Slowly pour the Grignard reaction mixture into the ice mixture in the beaker, stirring vigorously. Rinse the reaction vessel into the ice mixture, first with 8.33mL of chilled NH₄Cl solution, then with 10mL of solvent ether.

Use a dropper to transfer the Grignard reaction 

mixture into another place chilled NH₄Cl solution

 

 Magnesium bromide hydroxide forms immediately

 

As soon as, magnesium bromide hydroxide

 dissolved into the acidic solution

 

3.      Transfer the mixture into a separator funnel. Add solvent ether to bring the upper ether layer to about 10mL, shake the funnel, and allow the layer to separate.

4.      Drain the lower aqueous layer into a flask, and use another part of 10mL ether to extract it again.

5.      Wash the combined ether with 10mL water, then with 10mL 10% sodium carbonate solution.

6.      Finally, wash the ether solution with 10~15mL of saturated sodium chloride solution.

7.      Pour the ether solution into a clean, dry conic flask, add some anhydrous magnesium sulfate, cork the flask tightly and stand it for a while.

8.      Pour the ether into a round-bottom flask and set it on a rotary to evaporate all the solvent ether.

9.      Calculate the yield and figure the index of refraction.

Experimental Record

Weight of 1-bromobutane	4.567g
Weight of Acetone	1.933g
Weight of Magnesium Turnings	0.800g
Theoretical Weight of 2-methyl-2-hexanol	3.867g
Weight of 2-methyl-2-hexanol	2.358g
Theoretical nD20 of 2-methyl-2-hexanol	1.4175
nD20 of 2-methyl-2-hexanol	1.4109
Yield	61.0%