Question

Reaction of acid chlorides with sodium azide, \(\mathrm{NaN}_{3}\), yields acyl azides, RCON \(_{3}\). When heated, these undergo the Curtius rearrangement to amines, \(\mathrm{RNH}_{2}\), or, in a non-hydroxylie solvent, to isocyanates, RNCO. Using the structure for the azide, suggest a mechanism for the rearrangement.

Short answer

The mechanism for the Curtius rearrangement involves the following steps: 1. Acid chlorides (R-COCl) react with sodium azide (NaN3) through nucleophilic acyl substitution to form acyl azides (RCON3). 2. Upon heating, acyl azides undergo Curtius rearrangement through cyclic intermediate rearrangement, resulting in the formation of isocyanates (RNCO). 3. If water is present, isocyanates can further react with it to form amines (RNH2) and carbon dioxide (CO2) via carbamic acid intermediate.

Step-by-step solution

Structure of azide

The azide ion, N3-, has the structure: \[\hspace{1cm} \overset{-}{N} = \overset{+}{N} - \overset{}{N} \hspace{1cm} (1)\] To react with the acid chlorides, the azide will act as a nucleophile in the reaction.

Formation of acyl azides

Acid chlorides (R-COCl) react with sodium azide to form acyl azides (RCON3). The reaction occurs through nucleophilic acyl substitution, as shown below: 1. The negative end of azide ion \((1)\) acts as a nucleophile, attacking the carbonyl carbon of the acid chloride, forming a tetrahedral intermediate. 2. The chloride ion, being a good leaving group, leaves and acyl azide is formed. This reaction is favored since the azide ion is a strong nucleophile while the chloride ion is a good leaving group. The reaction is as follows: \[ RCOCl + \mathrm{NaN}_{3} \rightarrow RCON_{3} + \mathrm{NaCl} \]

Curtius rearrangement

When acyl azides are heated, they undergo Curtius rearrangement. The reaction proceeds through the following steps: 1. The nitrogen-nitrogen double bond in the acyl azide (RCON3) attacks the carbonyl carbon, forming a cyclic intermediate. 2. The cyclic intermediate rearranges by breaking the N-N single bond and migrating the R group to the central nitrogen atom. 3. The resulting isocyanate (RNCO) is formed. In a non-hydroxylic solvent, the rearrangement ends at this step. The reaction is as follows: \[ \mathrm{RCON}_{3} \xrightarrow[\mathrm{Heating}]{} \mathrm{RNCO}+ \mathrm{N}_{2} \]

Formation of amines (Optional step)

If water is present, isocyanates can react with water to form amines (RNH2) and carbon dioxide (CO2). The reaction proceeds through the following steps: 1. Water molecule acts as a nucleophile and attacks the carbon of the isocyanate, forming a carbamic acid intermediate. 2. The carbamic acid intermediate breaks down, losing a carbon dioxide molecule, and forming an amine (RNH2). The reaction is as follows: \[ \mathrm{RNCO} + \mathrm{H}_{2}\mathrm{O} \rightarrow \mathrm{RNH}_{2} + \mathrm{CO}_{2} \]

Summary of Curtius rearrangement mechanism

1. Acid chlorides react with sodium azide to form acyl azides through nucleophilic acyl substitution. 2. Acyl azides undergo Curtius rearrangement upon heating, forming isocyanates through migration of the R group to the central nitrogen atom. 3. If water is present, isocyanates can react with it to form amines and carbon dioxide through carbamic acid intermediate.

Key concepts

Nucleophilic Acyl Substitution

The process of nucleophilic acyl substitution involves a nucleophile attacking the acyl carbon of a carbonyl compound. This reaction type is crucial for forming new bonds in organic synthesis. In the context of our exercise, sodium azide (\( \mathrm{NaN}_3 \)) acts as the nucleophile. It attacks the carbon atom bonded to the chlorine in acid chlorides (\( R-COCl \)).

• This attack leads to the formation of a tetrahedral intermediate.
• The intermediate is unstable and collapses to expel a good leaving group, which in this case is the chloride ion.
• The result is the substitution of the chloride ion by an azide to form an acyl azide (\( RCON_3 \)).

Nucleophilic acyl substitution is a versatile transformation in organic chemistry and occurs under various conditions, depending on the nucleophile and the leaving group. Here, the azide ion plays a pivotal role by efficiently replacing the chloride ion due to its nucleophilic nature.

Acyl Azides

Acyl azides (\( RCON_3 \)) are unique compounds derived from acid chlorides by replacing the chlorine atom with an azide group. Their formation from acid chlorides via nucleophilic acyl substitution is a key step in the Curtius rearrangement.

• The azide group consists of three nitrogen atoms, arranged as -N=N=N-.
• Within this structure, the central nitrogen holds a positive charge, while the terminal nitrogen is negatively charged.
• These structural features facilitate the subsequent rearrangement process.

Acyl azides are highly reactive, especially upon heating, which triggers the Curtius rearrangement. Their ability to rearrange into other functional groups, like isocyanates, makes them valuable intermediates in organic synthesis.

Isocyanates

Isocyanates (\( RNCO \)) are formed during the Curtius rearrangement of acyl azides when heated in non-hydroxylic solvents. They are characterized by the functional group -N=C=O.

• The rearrangement proceeds via the migration of the R group from the carbonyl carbon to a nitrogen atom, releasing nitrogen gas (\( N_2 \)).
• Isocyanates are reactive, facilitating further transformation depending on the conditions and reactants present.
• They are often intermediates leading to the formation of amines, especially when they react with nucleophiles like water.

This transformation highlights the rearrangement's utility, as isocyanates serve as pivotal intermediates in synthesizing various important organic compounds. Their production marks a crucial step in converting acyl azides to more reactive and versatile species.

Amines Formation

Amines (\( RNH_2 \)) can be formed from isocyanates when water is present, highlighting the versatility of the Curtius rearrangement. This reaction occurs through the hydrolysis of the isocyanate functional group.

• Water acts as a nucleophile, attacking the electrophilic carbon atom in the -N=C=O group.
• This attack leads to the formation of a carbamic acid intermediate.
• The intermediate is unstable, which causes it to decompose, releasing carbon dioxide (\( CO_2 \)) and forming an amine.

This transformation demonstrates the rearrangement pathway's ability to produce amines directly from acyl azides. Amines have significant importance as they constitute an essential class of compounds in pharmaceuticals and other chemical industries.