Question

Show how to convert benzoic acid to 3 -methyl-1-phenyl-1-butanone (isobutyl phenyl ketone) by the following synthetic strategies, each of which uses a different type of reaction to form the new carbon-carbon bond to the carbonyl group of benzoic acid. O=C(O)c1ccccc1 CC(C)CC(=O)c1ccccc1 Benzoic acid 3-Methyl-1-phenyl-1-butanone (a) A lithium diorganocopper (Gilman) reagent (b) A Claisen condensation

Short answer

Question: Describe two synthetic strategies for converting benzoic acid to 3-methyl-1-phenyl-1-butanone: (a) using a lithium diorganocopper (Gilman) reagent, and (b) performing a Claisen condensation. Answer: (a) The first strategy involves converting benzoic acid to its acid chloride using thionyl chloride. Then, prepare a Gilman reagent by reacting methyl iodide with magnesium to form a Grignard reagent, and then add copper(I) iodide. Finally, react the acid chloride with the Gilman reagent to form 3-methyl-1-phenyl-1-butanone. (b) The second strategy involves converting benzoic acid to its ethyl ester using ethanol and catalytic sulfuric acid. Next, perform Claisen condensation by reacting the ethyl ester with ethyl butanoate and sodium ethoxide to form an ester enolate, which then reacts with another ester molecule to form 3-methyl-1-phenyl-1-butanone.

Step-by-step solution

(a) Lithium diorganocopper (Gilman) reagent

For this strategy, we will follow these steps: 1. Convert benzoic acid to its acid chloride 2. Prepare the Gilman reagent 3. Perform the reaction with the prepared Gilman reagent and follow with hydrolysis #Step 2: Benzoic acid to acid chloride#

(a.1) Conversion to acid chloride

To convert the carboxylic acid (benzoic acid) into an acid chloride, we will use thionyl chloride (SOCl2) as the reagent. The reaction proceeds as follows: \[ O=C(O)c1ccccc1 + SOCl2 \rightarrow O=C(Cl)c1ccccc1 + SO_2 + HCl \] #Step 3: Preparation of the Gilman reagent#

(a.2) Preparation of the Gilman reagent

We will now prepare the lithium diorganocopper (Gilman) reagent using the following steps: 1. Perform a Grignard reaction on methyl iodide (CH3I) with magnesium (Mg) to form the Grignard reagent (CH3MgI) 2. Add the Grignard reagent to a solution containing copper(I) iodide (CuI) \[ CH3I + Mg \rightarrow CH3MgI \] \[ CH3MgI + CuI \rightarrow CH3CuLi + MgI_2 \] #Step 4: Reaction of acid chloride with Gilman reagent#

(a.3) Perform the reaction

React the acid chloride (prepared in Step 2) with the lithium diorganocopper (Gilman) reagent (prepared in Step 3) to form the desired product, 3-methyl-1-phenyl-1-butanone. \[ O=C(Cl)c1ccccc1 + CH3CuLi \rightarrow 3-Methyl-1-phenyl-1-butanone + LiCl \] #Step 5: Claisen condensation#

(b) Claisen condensation

For this strategy, we will follow these steps: 1. Convert benzoic acid to its ethyl ester 2. Perform the Claisen condensation with an ester enolate #Step 6: Benzoic acid to ethyl ester#

(b.1) Conversion to ethyl ester

To convert the carboxylic acid (benzoic acid) into an ethyl ester, we will use ethanol (EtOH) and catalytic sulfuric acid (H2SO4) as reagents. The reaction proceeds as follows: \[ O=C(O)c1ccccc1 + HOCH_2CH_3\rightarrow O=C(OCH_2CH_3)c1ccccc1 + H_2O \] #Step 7: Formation of ester enolate and Claisen condensation#

(b.2) Claisen condensation

Finally, we will perform Claisen condensation by reacting the ethyl ester with ethyl butanoate (ethyl butyrate) and sodium ethoxide (NaOEt) to form the desired product: \[ O=C(OCH_2CH_3)c1ccccc1 + EtO^-(Na^+) \rightarrow Ester\,Enolate \] \[ Ester\,Enolate + O=C(OCH_2CH_3)CH_2CH_2CH_3 \rightarrow 3-Methyl-1-phenyl-1-butanone \] In summary, we have demonstrated two synthetic strategies for converting benzoic acid to 3-methyl-1-phenyl-1-butanone, namely (a) using a lithium diorganocopper (Gilman) reagent and (b) performing a Claisen condensation.