Question

Show how to synthesize the following compounds using either the malonic ester synthesis or the acetoacetic ester synthesis. (a) 4-Phenyl-2-butanone (b) 2-Methylhexanoic acid (c) 3-Ethyl-2-pentanone (d) 2-Propyl-1,3-propanediol (e) 4-Oxopentanoic acid (f) 3-Benzyl-5-hexene-2-one (g) Cyclopropanecarboxylic acid (h) Cyclobutyl methyl ketone

Short answer

Question: Determine the appropriate method (malonic ester synthesis or acetoacetic ester synthesis) for synthesizing each of the following compounds: (a) 4-Phenyl-2-butanone, (b) 2-Methylhexanoic acid, (c) 3-Ethyl-2-pentanone, (d) 2-Propyl-1,3-propanediol, (e) 4-Oxopentanoic acid, (f) 3-Benzyl-5-hexene-2-one, (g) Cyclopropanecarboxylic acid, (h) Cyclobutyl methyl ketone. Answer: (a) Acetoacetic ester synthesis, (b) Malonic ester synthesis, (c) Acetoacetic ester synthesis, (d) Malonic ester synthesis followed by reduction, (e) Acetoacetic ester synthesis followed by hydrolysis, (f) Acetoacetic ester synthesis, (g) Malonic ester synthesis, (h) Acetoacetic ester synthesis.

Step-by-step solution

(a) 4-Phenyl-2-butanone

For synthesizing 4-Phenyl-2-butanone, we will use the acetoacetic ester synthesis, as we target a ketone functionality. 1. Formation of acetoacetic ester: Ethyl acetate is treated with ethoxide (\ce{EtO^-}) to form ethyl acetoacetate (acetoacetic ester). 2. Alkylation: Ethyl acetoacetate reacts with phenyl bromide (\ce{C6H5Br}) in the presence of a strong base like sodium ethoxide (\ce{NaOEt}) for an S_N2 reaction to form the substituted ester. 3. Hydrolysis and decarboxylation: The substituted ester is hydrolyzed in acidic conditions and then heated to cause decarboxylation, yielding 4-Phenyl-2-butanone.

(b) 2-Methylhexanoic acid

For synthesizing 2-Methylhexanoic acid, we will use the malonic ester synthesis, as we target a carboxylic acid functionality. 1. Formation of diethyl malonate: Same as step 1 in the synthesis of 4-Phenyl-2-butanone. 2. Alkylation: Diethyl malonate reacts with 1-bromobutane in the presence of a strong base like sodium ethoxide to form the substituted ester. 3. Hydrolysis and decarboxylation: Same as step 3 in the synthesis of 4-Phenyl-2-butanone, yielding 2-Methylhexanoic acid.

(c) 3-Ethyl-2-pentanone

For synthesizing 3-Ethyl-2-pentanone, we will use the acetoacetic ester synthesis. 1.-3. Follow the same steps 1-3 as in the synthesis of 4-Phenyl-2-butanone using ethyl bromide instead of phenyl bromide, yielding 3-Ethyl-2-pentanone.

(d) 2-Propyl-1,3-propanediol

For synthesizing 2-Propyl-1,3-propanediol, we will use the malonic ester synthesis followed by reduction. 1.-3. Follow the same steps 1-3 as in the synthesis of 2-Methylhexanoic acid using propyl bromide instead of 1-bromobutane, yielding 2-Propylpropanoic acid. 4. Reduction: Treat 2-Propylpropanoic acid with lithium aluminum hydride (\ce{LiAlH4}) to reduce the carbonyl group to an alcohol, yielding 2-Propyl-1,3-propanediol.

(e) 4-Oxopentanoic acid

For synthesizing 4-Oxopentanoic acid, we will use the acetoacetic ester synthesis followed by hydrolysis. 1.-2. Follow the same steps 1-2 as in the synthesis of 4-Phenyl-2-butanone using ethyl bromide instead of phenyl bromide. 3. Hydrolysis: Treat the alkylated ester with an acid or base to hydrolyze the ester group, yielding 4-Oxopentanoic acid.

(f) 3-Benzyl-5-hexene-2-one

For synthesizing 3-Benzyl-5-hexene-2-one, we will use the acetoacetic ester synthesis. 1.-3. Follow the same steps 1-3 as in the synthesis of 4-Phenyl-2-butanone using benzyl bromide and the conjugate base of the alkene instead of phenyl bromide, yielding 3-Benzyl-5-hexene-2-one.

(g) Cyclopropanecarboxylic acid

For synthesizing Cyclopropanecarboxylic acid, we will use the malonic ester synthesis. 1.-3. Follow the same steps 1-3 as in the synthesis of 2-Methylhexanoic acid using bromocyclopropane instead of 1-bromobutane, yielding Cyclopropanecarboxylic acid.

(h) Cyclobutyl methyl ketone

For synthesizing Cyclobutyl methyl ketone, we will use the acetoacetic ester synthesis. 1.-3. Follow the same steps 1-3 as in the synthesis of 4-Phenyl-2-butanone using bromocyclobutane instead of phenyl bromide, yielding Cyclobutyl methyl ketone.