Question

Following is a retrosynthetic analysis for an intermediate in the industrial synthesis of vitamin \(A\). (a) Addition of one mole of \(\mathrm{HCl}\) to isoprene gives 4 -chloro-2-methyl-2-butene as the major product. Propose a mechanism for this addition and account for its regioselectivity. (b) Propose a synthesis of the vitamin A precursor from this allylic chloride and ethyl acetoacetate.

Short answer

Question: Propose a mechanism for the addition of one mole of HCl to isoprene to form 4-chloro-2-methyl-2-butene and explain its regioselectivity. Then, propose a synthesis of the vitamin A precursor from the allylic chloride and ethyl acetoacetate. Answer: The addition of HCl to isoprene follows a hydrohalogenation mechanism. The steps involve the nucleophilic attack of the alkene, forming a carbocation intermediate, and the subsequent nucleophilic attack of the chloride ion. The regioselectivity can be explained by Markovnikov's rule, which leads to the formation of the observed major product. To synthesize the vitamin A precursor, an enolate ion is formed from ethyl acetoacetate, which reacts with the allylic chloride through a nucleophilic substitution reaction, creating a new carbon-carbon bond. An acid-base workup then yields the vitamin A precursor.

Step-by-step solution

(a) Part (a): Mechanism for the addition of HCl to isoprene

The addition of HCl to isoprene follows a hydrohalogenation mechanism. The steps are as follows: Step 1: Nucleophilic attack of the alkene The nucleophilic double bond of isoprene attacks the hydrogen atom in the HCl molecule. The electron pair in the H-Cl bond shifts to the chlorine atom, forming a carbocation intermediate and a chloride ion. \[\ce{H2C=C(CH3)CH=CH2 + HCl -> H2C^+-C(CH3)=CH-CH3 + Cl^-}\] Step 2: Nucleophilic attack of the chloride ion The chloride ion, which is a nucleophile, attacks the positively charged carbon atom in the carbocation intermediate, forming the final product, 4-chloro-2-methyl-2-butene. \[\ce{H2C^+-C(CH3)=CH-CH3 + Cl^- -> Cl-CH2-C(CH3)=CH-CH3}\] Regioselectivity can be explained by the Markovnikov's rule, which states that in the addition of a proton and a halide to an alkene, the halide will attach to the more substituted carbon. In this case, the carbocation intermediate is more stable when the positive charge is on the secondary carbon (which is more substituted) than when it is on the primary carbon. This leads to the formation of the observed major product.

(b) Part (b): Synthesis of the vitamin A precursor from the allylic chloride and ethyl acetoacetate

We can use a substitution reaction between the allylic chloride and ethyl acetoacetate to form the vitamin A precursor. The steps are as follows: Step 1: Formation of enolate ion The ethyl acetoacetate reacts with a base to lose a proton, forming an enolate ion. This enolate ion will act as a nucleophile in the reaction. \[\ce{CH3COCH2COOCH2CH3 + B^- -> CH3COCH=C(O^-)COOCH2CH3 + BH}\] Step 2: Nucleophilic substitution reaction The nucleophilic enolate ion attacks the allylic halide (4-chloro-2-methyl-2-butene), replacing the chlorine atom and forming a new carbon-carbon bond. The chloride ion is released as a leaving group. \[\ce{CH3COCH=C(O^-)COOCH2CH3 + Cl-CH2-C(CH3)=CH-CH3 -> CH3COCH=C(O)COOCH2CH3-C(CH3)=CH-CH2CH3 + Cl^-}\] Step 3: Acid-base workup To remove the negative charge on the oxygen atom, an acid-base reaction takes place. \[\ce{CH3COCH=C(O^-)COOCH2CH3-C(CH3)=CH-CH2CH3 + H3O^+ -> CH3COCH=C(OH)COOCH2CH3-C(CH3)=CH-CH2CH3 + H2O}\] The resulting product is a vitamin A precursor, which can be further converted into vitamin A through subsequent reactions.