Q65E - Organic Chemistry (Mcmurry)

Question

How would you synthesize the following compounds from cyclohexanone?

1. 1-Methylcyclohexene
2. 2-Phenylcyclohexanone
3. cis-1,2-Cyclohexanediol
4. 1-Cyclohexylcyclohexanol

Step-by-Step Solution

Answer

a) 

b) 

c) 

d)

Step-by-Step Solution Step 1: Synthesis of compounds from ketones

When ketones are treated with Grignard reagents, an alcohol formation occurs, and an alkene product is formed by further dehydrating the alcohol. A diol compound is formed when alkene is treated with ${\text{OsO}}_{\text{4}}$ and then with ${\text{NaHSO}}_{\text{3}},{\text{H}}_{\text{2}}\text{O}$ .

Step 2: The synthesis of 1-Methylcyclohexene from cyclohexanone

a) When cyclohexanone is treated with methylmagnesium bromide (Grignard reagent), a methyl group is introduced, and tertiary alcohol is obtained. Further, on dehydration of tertiary alcohol by ${\text{H}}_{\text{3}}{\text{O}}^{\text{+}}$generates 1-methylcyclohexene. The synthesis for this compound is shown below.

                                      Synthesis of 1-Methylcyclohexene

Step 3: The synthesis of 2-Phenylcyclohexanone from cyclohexanone

b)  When cyclohexanone is treated with phenylmagnesium bromide (Grignard reagent), tertiary alcohol is formed. This further dehydrates to form 1-phenylcyclohexene.

Now, 1-phenylcyclohexene is treated with ${\text{BH}}_{\text{3}}$- , and alcohol is obtained along with its enantiomer. Further, on oxidation with ${\text{CrO}}_{\text{3}}{\text{/H}}_{\text{3}}{\text{O}}^{\text{+}}$- , the desired ketone is produced. The synthesis of 2-phenylcyclohexanone is show below

                                         Synthesis of 2-Phenylcyclohexanone

Step 4 : The synthesis of cis-1,2-Cyclohexanediol from cyclohexanone

c)  When cyclohexanone is treated with ${\text{NaBH}}_{\text{4}}$ (a reducing agent), and then ${\text{H}}_{\text{3}}{\text{O}}^{\text{+}}$, secondary alcohol is formed. Further reaction of secondary alcohol with ${\text{POCl}}_{\text{3}}\text{/pyridine}$ gives cyclohexene compound. 

When cyclohexene is treated with ${\text{OsO}}_{\text{4}}\text{-}$, and then with ${\text{NaHSO}}_{\text{3}},{\text{H}}_{\text{2}}\text{O}$ , the product yielded is cis-1,2-cyclohexandiol compound

                       Synthesis of cis-1,2-Cyclohexanediol

Step 5 : The synthesis of 1-Cyclohexylcyclohexanol from cyclohexanone

d)  Secondary alcohol is formed when cyclohexanone is treated with ${\text{NaBH}}_{\text{4}}$ (a reducing agent) and then ${\text{H}}_{\text{3}}{\text{O}}^{\text{+}}$.

On the treatment of cyclohexanol with ${\text{PBr}}_{\text{3}}$ and then with Mg and ether, a Grignard compound is formed (${\text{C}}_{\text{6}}{\text{H}}_{\text{11}}\text{MgBr}$). This Grignard reagent on reacting with cyclohexanone and then with ${\text{H}}_{\text{3}}{\text{O}}^{\text{+}}$gives 1-Cyclohexylcyclohexanol product.

                               Synthesis of 1-Cyclohexylcyclohexanol