Related Experiment Video
Updated: Jun 28, 2026
09:26
Synthesis and Characterization of Supramolecular Colloids
Published on: April 22, 2016
A theoretical study on nBuLi/lithium aminoalkoxide aggregation in hexane and THF
Hassan K Khartabil1, Philippe C Gros, Yves Fort
1Equipe Chimie et Biochimie Théoriques, SRSMC, Nancy-University, CNRS, BP 239, 54506 Vandoeuvre-lès-Nancy, France.
The Journal of Organic Chemistry
|October 29, 2008
Summary
Theoretical calculations reveal that lithium aminoalkoxide superbases, like n-butyllithium/lithium N-methyl-2-pyrrolidine methoxide (nBuLi/LiPM), exhibit distinct aggregation behaviors and reactivity in different solvents, clarifying their complex mechanisms.
Area of Science:
- Organometallic Chemistry
- Computational Chemistry
- Physical Chemistry
Background:
- The aggregation of n-butyllithium (nBuLi) and lithium aminoalkoxide superbases, such as nBuLi/LiPM, in solution leads to unique reactivity that is not fully understood.
- Elucidating the reaction mechanisms requires detailed knowledge of aggregation energetics and solvent effects on equilibrium constants.
Purpose of the Study:
- To compute and compare the stability of nBuLi, LiPM, and mixed nBuLi/LiPM aggregates in the gas phase, hexane, and THF.
- To investigate the influence of solvent environments (hexane and THF) on the aggregation behavior and energetics.
Main Methods:
- Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d) level were employed.
- Continuum and discrete continuum solvation models were used to simulate the solvent effects.
- Higher-level calculations (MP2/aug-ccpVQZ) were performed for validation.
Main Results:
- Enthalpic and entropic contributions to aggregation stability were found to vary significantly between gas/hexane and THF.
- LiPM and mixed nBuLi/LiPM solutions showed distinct characteristics compared to nBuLi solutions.
- Calculated results were consistent with experimental data in both hexane and THF.
Conclusions:
- The study provides crucial insights into the aggregation behavior of organolithium compounds in solution.
- Computational findings align with experimental observations, validating the theoretical approach.
- A proposed value for the entropy of THF solvent molecule release (ΔS ≈ 23 eu) aids in understanding computational errors for entropic contributions.
Related Concept Videos
01:19Acid Halides to Alcohols: LiAlH4 Reduction
Acid halides are reduced to alcohols in the presence of a strong reducing agent like lithium aluminum hydride.
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
The mechanism proceeds in three steps. First, the nucleophilic hydride ion attacks the carbonyl carbon of the acid halide to form a tetrahedral intermediate. Next, the carbonyl group is re-formed, and the halide ion departs as a leaving group, generating an aldehyde. A second nucleophilic attack by the hydride yields an alkoxide ion, which, upon protonation, gives a primary alcohol as...
01:26Radical Substitution: Hydrogenolysis of Alkyl Halides with Tributyltin Hydride
Radical substitution reactions can be used to remove functional groups from molecules. The hydrogenolysis of alkyl halides is one such reaction, where the weak Sn–H bond in tributyltin hydride reacts with alkyl halides to form alkanes. Here, the reagent Bu3SnH yields tributyltin halide as a byproduct.
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
The bonds formed in this reaction are stronger than the bonds broken, making it energetically favorable. The reaction follows a radical chain mechanism similar to radical halogenation reactions,...
02:38Electrophilic Addition to Alkynes: Halogenation
Introduction
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
00:55Nitriles to Amines: LiAlH4 Reduction
Nitriles are reduced to amines in the presence of strong reducing agents like lithium aluminum hydride through a typical nucleophilic acyl substitution. The reaction requires two equivalents of the reducing agent. The reducing agent acts as a source of hydride ions.
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
As shown below, the mechanism involves three steps. Firstly, the hydride ion acting as a nucleophile attacks the nitrile carbon to form an anion. In the second step, a second equivalent of the hydride ion attacks the anion to...
02:26Preparation and Reactions of Sulfides
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
01:20Amides to Amines: LiAlH4 Reduction
Amide reduction with strong reducing agents like lithium aluminum hydride proceeds through a nucleophilic acyl substitution to form amines. Primary, secondary, and tertiary amides yield primary, secondary, and tertiary amines, respectively.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.
Amide reduction requires two equivalents of the reducing agent, acting as a source of hydride ions. As shown in the figure, the reaction is initiated with a nucleophilic attack by the hydride ion at the carbonyl carbon to form a tetrahedral intermediate.