Question

Show the mechanism for formation of a Boc derivative by reaction of an amino acid with di-tert-butyl dicarbonate.

Short answer

The amino acid reacts with di-tert-butyl dicarbonate to form a Boc-protected amino acid.

Step-by-step solution

Understanding the Reactants

We begin by identifying the reactants involved in the formation of a Boc derivative. The two reactants are an amino acid and di-tert-butyl dicarbonate (Boc anhydride). An amino acid has an amino group (-NH2) that will react with Boc anhydride to form the Boc-protected compound.

Nucleophilic Attack on Boc Anhydride

The amino group of the amino acid acts as a nucleophile and attacks the carbonyl carbon of one of the esters in di-tert-butyl dicarbonate. This forms a tetrahedral intermediate. This step leads to the addition of the amino group to the Boc anhydride.

Formation of the Boc-Protected Intermediate

The tetrahedral intermediate collapses, and one of the t-butyl groups of the Boc anhydride leaves as t-butanol (t-BuOH). This step creates an acyl substitution product, where the carbonyl carbon is now bonded to the nitrogen, forming the Boc-protected amino acid.

Product Formation and Final Adjustment

The newly formed Boc-protected amino acid may equilibrate any tautomeric forms, but the significant result is the addition of the Boc group to the amino acid. The final product is a Boc-protected amino acid, ready for use in further peptide synthesis or other applications.

Key concepts

Amino Acid Protection

For chemists working with amino acids, protecting the functional groups is a crucial step in many synthetic processes. Amino acids have both an amino group and a carboxyl group, making them susceptible to reactions. In peptide synthesis, we often need to "protect" one group to avoid unwanted reactions while the other is being modified.
- Boc (tert-butoxycarbonyl) protection is a popular method to shield the amino group during synthesis. - The use of Boc is advantageous due to its stability under mildly acidic conditions and its easy removal under acidic conditions.
This way, reactions can be carried out on other parts of the molecule without disturbing the protected amino group.

Nucleophilic Attack

The concept of nucleophilic attack is central to understanding chemical reaction mechanisms. A nucleophile is an atom or molecule with an excess of electrons, making it attracted to positively charged, electron-deficient centers. In our Boc amino acid protection example, the amino group (-NH2) acts as a nucleophile.
- It attacks the electrophilic carbon in the carbonyl group of di-tert-butyl dicarbonate. - This crucial first step leads to the formation of a new covalent bond, setting the stage for subsequent reaction steps. Understanding nucleophilic attack helps demystify how molecules interact and transform during chemical reactions.

Tetrahedral Intermediate

During the process of forming a Boc-protected amino acid, the reaction passes through a tetrahedral intermediate stage. This form is a transient structure that appears right after the nucleophilic attack.
- As the amino group attacks the carbonyl carbon of Boc anhydride, the carbon atom temporarily has four bonds instead of the typical three. - This intermediate is called "tetrahedral" because the central carbon has a geometry resembling a tetrahedron. As short-lived as it is, this intermediate plays a pivotal role in the rearrangement of bonds needed for the final product formation.

Acyl Substitution

Acyl substitution is a type of reaction that occurs after the tetrahedral intermediate is formed. This involves the replacement of one group (leaving group) attached to an acyl carbon with another group. In our context: - The tetrahedral intermediate formed after the nucleophilic attack on Boc anhydride collapses. - One of the t-butyl groups leaves as t-butanol, a process that results in the formation of a carbon-nitrogen bond.
This transformation results in the stabilization of the reaction's final product, the Boc-protected amino acid, ready for further synthetic steps in peptide chain creation.