Multi-Step Synthesis

Question

Convert acetylene to hexanoic acid justifying why each step is taken. 

 

Answer 1

A simpler approach would be:

 

Step 1:  React acetylene with 1 equivalent of sodium amide to generate the acetylide anion.

 

HC≡CH  +  1 eq NaNH₂  -->  HC≡C‾

 

Step 2:  The acetylide anion is nucleophilic.  Therefore, you can react it with 1-bromopentane via an S_N2 reaction to form hept-1-yne (a 7-carbon alkyne).

 

HC≡C‾  +  CH₃CH₂CH₂CH₂CH₂-Br   -->   CH₃CH₂CH₂CH₂CH₂-C≡CH

 

Step 3:  Since hept-1-yne is a terminal alkyne, you can perform an ozonolysis reaction where the triple bond breaks to form hexanoic acid and carbon dioxide gas

 

CH₃CH₂CH₂CH₂CH₂-C≡CH  +  O₃   --> INTERMEDIATE + H₂O -->  CH₃CH₂CH₂CH₂CH₂COOH  +  CO₂ 

Answer 2

Although a bit lengthy, this is a route I came up to prepare hexanoic acid:

 

Step 1: Making ethyl chloride

H2C2 + 2 Na + NH3(l) + EtOH --> H2C=CH2

H2C=CH2 + HCl --> CH3CH2Cl

 

Step 2: Making 1-butyne

H2C2 + NaH --> NaC2H

CH3CH2Cl + NaC2H --> CH3CH2C2H

 

Step 3: Preparing acetaldehyde

C2H2 + H2O + HgSO4 + H2SO4 --> CH3C(O)H

 

Step 4: Preparation of hexanoic acid by alcohol formation, followed by hydrogenation, bromide substitution, anti-Markovnikov alcohol addition and oxidation

CH3C(O)H + CH3CH2C2Na --> CH3CH(O)C2CH2CH3 + HCl --> CH3CH(OH)C2CH2CH3

 

CH3CH(OH)C2CH2CH3 + 2 H2 --> CH3CH(OH)(CH2)3CH3

 

CH3CH(OH)(CH2)3CH3 + PBr3 --> CH3CH(Br)(CH2)3CH3

 

CH3CH(Br)(CH2)3CH3 + NaN(SiMe3)2 (low T) --> CH2=CH(CH2)3CH3

 

CH2=CH(CH2)3CH3 + H2O + H2O2 + Hg(OAc)2 --> HO(CH2)5CH3

 

HO(CH2)5CH3 + KMnO4 --> CH3(CH2)4CO2H

 

 

Answer 3

The question clearly states: Synthesize hexanoic acid using [only] acetylene as the carbon source .

 

Where does pentyl bromide appear from? If you can add whatever intermediate you want, this is not multistep synthesis nor solves the problem.

 

Ishwar, while simpler, your answer violates the only rule in the question.

The point of the question is to use the alkyne to concatenate 2C pieces into a 6-C chain leaving enough functionality with the proper regiochem to create the acid. There are dozens of possible ways to do this.

Here is one:

Acetylene + H2/Lindlar's cat. --> ethene + Br2 --> 1,2-dibromoethane (A)

Acetylene + NaNH2 (acetylide), then (A) --> 4-bromo-1-butyne (B)

(B) + H2/Pd/C --> 4-bromobutane (C) --> (C) added to Acetylide --> 1-hexyne (D)

1- hexyne + 1) HB(sia)2 or 9-BBN 2) H2O2 --> hexanal (E) --> Jones oxidation (HCrO4) of E

= product (hexanoic acid).

A = BrCH2CH2Br

B = BrCH2CH2CCH

C = Br-CH2CH2CH2CH3

D = CH3CH2CH2CH2CCH

E = CH3CH2CH2CH2CH2CHO

Product = CH3CH2CH2CH2CH2CO2H

There is no almost no doubt who the thumbs down came from, Ishwar...all you answers contain flaws but I refrained from giving you thumbs down because that is adolescent behavior. This is not YouTube.