Question

2,6-Di-tert-butyl- 4 - methylphenol, alternatively known as butylated hydroxytoluene (BHT), is used as an antioxidant in foods to "retard spoilage" (Section 8.7). BIIT is synthesized industrially from 4 -methylphenol by reaction with 2 -methylpropene in the presence of phosphoric acid. Propose a mechanism for this reaction.

Short answer

Question: Propose a mechanism for the synthesis of 2,6-Di-tert-butyl-4-methylphenol (BHT) from 4-methylphenol and 2-methylpropene in the presence of phosphoric acid. Answer: The synthesis of BHT involves six steps: 1) Protonation of 4-methylphenol by phosphoric acid; 2) Electrophilic aromatic substitution on 4-methylphenol with 2-methylpropene; 3) Deprotonation of the phenolic intermediate; 4) Protonation and second alkylation of the phenolic product; 5) Second electrophilic aromatic substitution with 2-methylpropene; and 6) Final deprotonation of BHT.

Step-by-step solution

Protonation of 4-methylphenol by phosphoric acid

In the presence of the phosphoric acid, the oxygen atom in the hydroxyl group on 4-methylphenol will be protonated, making it more electrophilic. $$\mathrm{4{-}methylphenol}\;+\;\mathrm{H_3PO_4}\;\rightarrow\;[\mathrm{4{-}methylphenol\;OH^+}]$$

Electrophilic aromatic substitution on 4-methylphenol

The electrophilic aromatic substitution will occur between the positively charged 4-methylphenol and the 2-methylpropene. The 4-methylphenol will act as a nucleophile, attacking the electrophilic pi bond of 2-methylpropene. $$[\mathrm{4{-}methylphenol\;OH^+}]\;+\;\mathrm{2{-}methylpropene}\;\rightarrow\;[\mathrm{4{-}methylphenol{-}O\;tert{-}butyl}]$$

Deprotonation of the phenolic intermediate

The newly formed 4-methylphenol-O-tert-butyl intermediate is a strong acid and will donate a proton in the presence of phosphoric acid. $$[\mathrm{4{-}methylphenol{-}O\;tert{-}butyl}]\;+\;\mathrm{H_2PO_4^{-}}\;\rightarrow\;\mathrm{2{-}tert{-}butyl{-}4{-}methylphenol}$$

Protonation and second alkylation of the phenolic product

We need to alkylate the phenolic product one more time, so the oxygen atom in the hydroxyl group of the 2-tert-butyl-4-methylphenol is protonated by phosphoric acid. $$\mathrm{2{-}tert{-}butyl{-}4{-}methylphenol}\;+\;\mathrm{H_3PO_4}\;\rightarrow\;[\mathrm{2{-}tert{-}butyl{-}4{-}methylphenol\;OH^+}]$$

Second electrophilic aromatic substitution

The positively charged 2-tert-butyl-4-methylphenol will undergo another electrophilic aromatic substitution, adding another tert-butyl from 2-methylpropene. $$[\mathrm{2{-}tert{-}butyl{-}4{-}methylphenol\;OH^+}]\;+\;\mathrm{2{-}methylpropene}\;\rightarrow\;[\mathrm{2,6{-}Di{-}tert{-}butyl{-}4{-}methylphenol{-}O]$$

Final deprotonation of BHT

Finally, the last intermediate will lose a proton, forming the stable 2,6-Di-tert-butyl-4-methylphenol (BHT) product. $$[\mathrm{2,6{-}Di{-}tert{-}butyl{-}4{-}methylphenol{-}O}]\;+\;\mathrm{H_2PO_4^{-}}\;\rightarrow\;\mathrm{2,6{-}Di{-}tert{-}butyl{-}4{-}methylphenol\;(BHT)}$$