2-bromo-N-methylthiazolium bromide (BMTB) was developed as a peptide coupling agent that would be better at coupling...

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2-bromo-N-methylthiazolium bromide (BMTB) was developed as a peptide coupling agent that would be better at coupling sterically hindered amino acids better than the alternatives that existed at the time. It was made in three steps from chloropropanone (aka "chloroacetone"): H₂C *0* CI: chloroacetone NaSCN EtOH H₂C *0* HBr H₂O H₂C :Br: H₂C CH₂Br ;Br: BMTB The thiocyanate ion (SCN) has two nucleophilic sites. Draw both resonance structures for SCN and identify the two nucleophilic sites. Draw a mechanism for the reaction of SCN with chloroacetone and explain the regiochemistry of this reaction. In other words, why does SCN react using one nucleophilic site instead of the other one and why does chloroacetone react using one electrophilic site instead of the other one? (c) Propose a reasonable mechanism for the second step in the synthesis of BMTB. (shown below) 2-bromo-N-methylthiazolium bromide (BMTB) was developed as a peptide coupling agent that would be better at coupling sterically hindered amino acids better than the alternatives that existed at the time. It was made in three steps from chloropropanone (aka "chloroacetone"): H₂C *0* CI: chloroacetone NaSCN EtOH H₂C *0* HBr H₂O H₂C :Br: H₂C CH₂Br ;Br: BMTB The thiocyanate ion (SCN) has two nucleophilic sites. Draw both resonance structures for SCN and identify the two nucleophilic sites. Draw a mechanism for the reaction of SCN with chloroacetone and explain the regiochemistry of this reaction. In other words, why does SCN react using one nucleophilic site instead of the other one and why does chloroacetone react using one electrophilic site instead of the other one? (c) Propose a reasonable mechanism for the second step in the synthesis of BMTB. (shown below)

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