Question

The reagent diisobutylaluminum hydride (DIBALH) reduces esters to aldehydes. When nitriles are treated with DIBALH followed by mild acid hydrolysis, the product is also an aldehyde. Propose a mechanism for this reduction.

Short answer

Answer: The steps involved in this reaction are: 1) DIBALH reduces the nitrile to an imine intermediate, 2) the imine undergoes hydrolysis to form a tetrahedral intermediate, and 3) rearrangement and loss of ammonia lead to the formation of the desired aldehyde product.

Step-by-step solution

Understanding the chemical structures

In this step, it is essential to comprehend the structure and reactivity of diisobutylaluminum hydride, nitriles, and aldehydes. DIBALH is an organometallic compound with the formula i-Bu2AlH (i-Bu = isoteric butyl), which is a strong, bulky reducing agent. Nitriles have a triple bond between a carbon and nitrogen (R-C≡N), while aldehydes have a carbonyl group (R-CHO).

DIBALH reduces nitrile to imine

Initially, the nitrile reacts with DIBAL-H through nucleophilic attack by the aluminum hydride. The nucleophile attacks the electrophilic carbon of the C≡N triple bond, and a pair of electrons in the triple bond moves to nitrogen, forming a new C-Al bond and breaking the Al-H bond. The product of this step is a metalloiminium complex with one reduced carbon-nitrogen double bond, which is an intermediate imine species.

Hydrolysis of the imine

The next step involves the reaction of the imine intermediate with water in the presence of a mild acid to perform the hydrolysis. Acid will protonate the nitrogen of the imine, making it a good leaving group. Simultaneously, water molecule attacks the carbon in a nucleophilic fashion, leading to the generation of a tetrahedral intermediate with the nitrogen now having a positive charge.

Rearrangement and loss of ammonia

At this point, the nitrogen with a positive charge will eliminate as ammonia (NH3), and a pair of electrons moves back to the carbon-oxygen bond to generate the carbonyl group of the aldehyde. As a result, the aldehyde product forms. In summary, the reduction of nitriles to aldehydes using diisobutylaluminum hydride (DIBALH) followed by mild acid hydrolysis involves the following steps: DIBALH reduces the nitrile to an imine intermediate; the imine undergoes hydrolysis to form a tetrahedral intermediate; rearrangement and loss of ammonia lead to the formation of the desired aldehyde product.

Key concepts

DIBALH Mechanism

The reagent diisobutylaluminum hydride, commonly known as DIBALH, is a selective reducing agent particularly utilized for converting nitriles into aldehydes. It accomplishes this through a complex mechanism that starts with a nucleophilic attack. In the case of nitriles, the DIBALH donates a hydride ion, which is a hydrogen atom with an additional electron, to the electrophilic carbon atom of the nitrile group. This process effectively breaks the carbon-nitrogen triple bond, creating a metalloiminium complex.

The bulky nature of DIBALH is crucial as it impedes further reduction, preventing the process from going beyond the aldehyde stage to an alcohol. This selectivity is extremely valuable in synthetic organic chemistry, where controlling the degree of reduction is often necessary to achieve the desired compound.

After the initial attack, the metalloiminium complex is stabilized due to the electronic effects of the aluminum, and this intermediate is key to the controlled reduction carried out by DIBALH. The mechanism demonstrates the careful balance between reactivity and selectivity in chemical transformations, a cornerstone in synthetic strategies.

Organometallic Compound Reactivity

Organometallic compounds, such as diisobutylaluminum hydride, exhibit unique reactivities stemming from their metal-carbon bonds. The aluminum in DIBALH has vacant p-orbitals that synergize with the filled orbitals of carbon in the organometallic bond. This orbital interaction makes the hydride attached to aluminum highly nucleophilic and thus, capable of attacking electrophilic carbon centers, like those found in nitriles.

The reactivity of organometallic compounds is also significantly influenced by the nature of the metal and its ligands. With aluminum being less electronegative than carbon, there is a polarization in the Al-H bond leading to the hydride ion's high reactivity. The isobutyl groups attached to aluminum provide steric bulk and influence the selectivity of the reduction process.

Understanding the principles behind organometallic compound reactivity is essential when predicting the outcome of reactions. For example, in the DIBALH-nitrile reaction, knowing that DIBALH is a strong yet hindered reducing agent can help predict that the product will be an aldehyde rather than a primary alcohol.

Imine Hydrolysis

The final stage in the conversion of nitriles to aldehydes involves the hydrolysis of an imine intermediate. Hydrolysis, in general, is the chemical breakdown of a compound due to the reaction with water. When the intermediate imine complex produced by the reaction with DIBALH reacts with water, especially in the presence of a mild acid, the process is catalyzed, leading to the cleavage of the carbon-nitrogen double bond.

The presence of an acid during the hydrolysis is important because it protonates the imine, which increases the electrophilicity of the carbon, making it more reactive towards the nucleophilic attack by water. This results in a tetrahedral intermediate which eventually loses ammonia, regenerating a carbonyl group that characterizes the aldehyde.

The hydrolysis of imines to aldehydes is a delicate step that requires careful control of reaction conditions to ensure the purity and yield of the final aldehyde product. Only after properly aligning the correct sequence of reactivity and hydrolysis can the desired aldehyde be reliably obtained from a nitrile precursor.