Question

Suggest a reasonable series of synthetic transformations (i.e. a series of reagents and reaction conditions) to prepare cis-2-methylcyclohexyl acetate (a) from trans-2-methylcyclohexano.

a) HCl, heat
b) NaOH, reflux
c) H2, Pd/C
d) H2SO4, heat

Answer 1

The synthesis of cis-2-methylcyclohexyl acetate from trans-2-methylcyclohexanol involves hydrochlorination, base-promoted E2 elimination, hydrogenation, and acid-catalyzed esterification using HCl, NaOH, H2 and Pd/C, and H2SO4 respectively.

Step-by-step explanation:

The question asks for a synthetic pathway to convert trans-2-methylcyclohexanol to cis-2-methylcyclohexyl acetate. Here's a step-by-step process using the provided reagents:

• Hydrochlorination: Treat trans-2-methylcyclohexanol with HCl and heat. This step will protonate the hydroxyl group, making it a better leaving group and allowing the formation of the corresponding methylcyclohexyl chloride.
• Base-promoted E2 elimination: Use NaOH under reflux conditions to induce an E2 elimination, converting the methylcyclohexyl chloride into the less substituted alkene, thus forming trans-2-methylcyclohexene.
• Hydrogenation: Subject the alkene to hydrogenation using H2 gas and a Pd/C catalyst. This step will result in a non-stereospecific addition of hydrogen, leading to a mix of cis and trans methylcyclohexane, but the former is typically favored due to reduced steric hindrance.
• Acid-catalyzed esterification: Finally, the cis-2-methylcyclohexanol can be esterified using H2SO4 and heat with acetic acid to form the target molecule, cis-2-methylcyclohexyl acetate.

The reagents provided in the sequence are designed to first create a good leaving group, induce formation of an alkene, selectively reduce the alkene to favor the cis isomer, and then transform the alcohol into the desired ester.