19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation
2 min read•may 7, 2024
compounds are versatile players in organic chemistry. They readily undergo reactions, forming new carbon-carbon or carbon-hydrogen bonds. These transformations are key in synthesizing alcohols and other important molecules.
Nucleophilic additions to carbonyls involve donors like or carbon nucleophiles like Grignard reagents. Both form intermediates, which are then protonated to yield alcohol products. These reactions can create new and change the carbon's .
Nucleophilic Addition to Carbonyls
Mechanism of carbonyl reduction
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- Sodium borohydride () acts as a nucleophilic hydride source ()
- Nucleophilic hydride attacks the carbonyl carbon forming a tetrahedral alkoxide intermediate
- Protonation of the alkoxide intermediate during aqueous acid workup yields the final alcohol product
- Reduces aldehydes and ketones specifically (benzaldehyde, acetophenone)
- Does not reduce carboxylic acids or esters under these conditions (benzoic acid, ethyl benzoate)
- The of this process are typically second-order overall
Grignard reactions with carbonyls
- Grignard reagents have the formula ( = halogen) with a polarized carbon-magnesium bond
- group acts as a strongly nucleophilic () (phenyl, vinyl, alkyl)
- Nucleophilic Grignard carbon attacks the electrophilic carbonyl carbon forming a tetrahedral alkoxide intermediate with a bond
- Aqueous proton workup displaces magnesium and protonates the alkoxide yielding the alcohol product
- Aldehydes form secondary (2°) alcohols ( forms with )
- Ketones form tertiary (3°) alcohols ( forms with )
- Grignard reagents are examples of
Hydride vs Grignard nucleophilic additions
- Both react via nucleophilic addition to the electrophilic carbonyl carbon forming tetrahedral alkoxide intermediates
- Hydrides () from reagents like act as the nucleophile
- Grignard carbanions () from reagents like act as the nucleophile
- Alkoxide intermediates differ in their counter-ions
- Hydride reductions: typically counter-ion from the reagent
- Grignard additions: counter-ion where is the original Grignard halogen
- Aqueous workup protonates the alkoxide yielding the neutral alcohol product in both cases
- Hydrides reduce aldehydes to 1° alcohols ( to ) and ketones to 2° alcohols ( to )
- Grignards convert aldehydes to 2° alcohols (ethanal to with ) and ketones to 3° alcohols (propanone to with )
Stereochemistry and Oxidation State Considerations
- These reactions can create new chiral centers in the product molecules
- The oxidation state of the carbonyl carbon changes from +3 to +1 during these reactions
- of the product can be influenced by the approach of the nucleophile to the carbonyl
Key Terms to Review (39)
2-Butanol: 2-Butanol is a secondary alcohol with the chemical formula CH3CH2CHCH3. It is an isomer of 1-butanol, with the hydroxyl group (-OH) attached to the second carbon atom in the butane chain. This positioning of the hydroxyl group gives 2-butanol unique properties and reactivity compared to other butanol isomers.
2-methyl-2-butanol: 2-methyl-2-butanol is an organic compound with the chemical formula C5H12O. It is a secondary alcohol, meaning the hydroxyl group (-OH) is attached to a carbon atom that is bonded to two other carbon atoms. This term is particularly relevant in the context of the topics 8.4 Hydration of Alkenes: Addition of H2O by Oxymercuration and 19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation, as it represents a key product that can be formed through these reactions.
2-methyl-2-phenylpropanol: 2-methyl-2-phenylpropanol is an organic compound with the molecular formula C₁₀H₁₄O. It consists of a benzene ring (phenyl group) attached to a 2-methylpropanol group, forming a tertiary alcohol. This compound is relevant in the context of nucleophilic addition reactions and the formation of alcohols using hydride and Grignard reagents.
2-phenylethanol: 2-phenylethanol is an organic compound with the chemical formula C$_{6}$H$_{5}$CH$_{2}$CH$_{2}$OH. It is a colorless, viscous liquid with a rose-like odor and is used in the production of perfumes, flavorings, and pharmaceuticals.
2-propanol: 2-propanol, also known as isopropyl alcohol or isopropanol, is a colorless, flammable liquid with a characteristic odor. It is an important organic compound that is widely used in various applications, including as a solvent, disinfectant, and in the synthesis of other chemicals.
Acetone: Acetone is a simple organic compound with the chemical formula CH3COCH3. It is a colorless, volatile, flammable liquid that is widely used as a solvent and in various chemical processes. Acetone is a key term that is relevant in the context of several important organic chemistry topics.
Aldehyde: An aldehyde is a class of organic compounds containing a carbonyl group (C=O) where the carbon atom is bonded to one hydrogen atom and one alkyl or aryl group. Aldehydes are important functional groups in organic chemistry and are involved in various reactions and synthesis pathways.
Alkoxide: An alkoxide is a functional group consisting of an alkyl group (R-) bonded to an oxygen atom (O-). Alkoxides are important intermediates in many organic chemistry reactions, including Grignard reactions, elimination reactions, and carbonyl condensation reactions.
Anti stereochemistry: Anti stereochemistry describes the spatial arrangement in a chemical reaction where two substituents are positioned on opposite sides of a double bond or ring structure after the reaction. It is particularly relevant in the halogenation of alkenes, resulting in products where the added atoms are located across from each other.
Carbanion: A carbanion is a negatively charged species that contains a carbon atom with three bonds and a lone pair of electrons, giving it a formal negative charge. This species is crucial in various organic reactions, as it acts as a strong nucleophile and can participate in forming new bonds by attacking electrophiles.
Carbonyl: The carbonyl group is a functional group consisting of a carbon atom double-bonded to an oxygen atom. It is a key structural feature in many organic compounds, including aldehydes, ketones, carboxylic acids, and esters, and plays a crucial role in their chemical reactivity and properties.
Carboxylic Acid: Carboxylic acids are organic compounds characterized by the presence of a carboxyl functional group (-COOH), which consists of a carbonyl (C=O) and a hydroxyl (-OH) group. They are widely found in nature and play a crucial role in various organic chemistry topics.
Carboxylic acid derivative: Carboxylic acid derivatives are compounds that contain a functional group which is a modified form of the carboxylic acid group (–COOH), where the hydroxyl part (-OH) is replaced by another atom or group of atoms. These derivatives undergo nucleophilic acyl substitution reactions, where an electron-rich nucleophile attacks the carbonyl carbon, leading to the substitution of the leaving group.
Chiral Centers: Chiral centers are atoms within a molecule that have four different substituents attached, resulting in a non-superimposable mirror image. This asymmetry gives rise to the concept of chirality, which is essential in understanding optical activity, meso compounds, and the stereochemistry of various organic reactions and biomolecules.
Electrophilic: Electrophilic refers to a species or reagent that is attracted to or seeks out electron-rich regions, typically in organic chemistry reactions. These species are often positively charged or have a partial positive charge, and they interact with and form bonds with nucleophiles, which are electron-rich species.
Ester: An ester is a chemical compound formed by the reaction between an organic acid and an alcohol, resulting in the replacement of the hydrogen atom of the acid by an alkyl or aryl group. Esters are widely encountered in various topics in organic chemistry, including functional groups, oxidation-reduction reactions, alcohol formation, and spectroscopy.
Ethanal: Ethanal, also known as acetaldehyde, is the simplest aliphatic aldehyde with the chemical formula CH3CHO. It is a volatile, colorless liquid with a pungent, fruity odor. Ethanal is an important intermediate in organic chemistry, particularly in the context of naming aldehydes and ketones, nucleophilic addition reactions, and spectroscopic analysis.
Ethanol: Ethanol, also known as ethyl alcohol, is a colorless, volatile, and flammable liquid that is the principal type of alcohol found in alcoholic beverages. It is an important organic compound with diverse applications in various fields, including as a fuel, solvent, and chemical feedstock.
Grignard Reagent: A Grignard reagent is an organometallic compound consisting of an alkyl or aryl group bonded to a magnesium atom. These versatile reagents are widely used in organic synthesis to form new carbon-carbon bonds and introduce various functional groups, making them an essential tool in the preparation of alcohols from carbonyl compounds.
Grignard reagents (RMgX): Grignard reagents are organomagnesium compounds formed by the reaction of an alkyl or aryl halide with magnesium metal in dry ether. They act as nucleophiles that can form carbon-carbon bonds, making them valuable tools in organic synthesis.
Hydride: A hydride is a compound in which hydrogen is bonded to a more electropositive element, such as a metal or a metalloid. Hydrides play a crucial role in various organic chemistry reactions, including the hydration of alkenes, the oxidation of alcohols, the nucleophilic addition of hydrides and Grignard reagents, and the chemistry of esters.
Hydride shift: A hydride shift is a rearrangement process where a hydrogen atom with its pair of electrons moves from one carbon to an adjacent carbocation center, stabilizing the molecule during electrophilic additions. This mechanism is key in understanding how carbocations can rearrange to form more stable intermediates in reactions involving alkenes.
Ketone: A ketone is a functional group in organic chemistry that consists of a carbonyl group (a carbon-oxygen double bond) bonded to two alkyl or aryl groups. Ketones are widely encountered in various organic chemistry topics, including the hydration of alkynes, oxidative cleavage of alkynes, organic synthesis, oxidation and reduction reactions, and the chemistry of aldehydes and ketones.
NaBH4: NaBH4, or sodium borohydride, is a powerful reducing agent commonly used in organic chemistry reactions to reduce carbonyl compounds, such as aldehydes and ketones, to alcohols. This versatile reagent is particularly useful in the context of nucleophilic addition reactions, aldol condensations, and the synthesis of amines.
Nucleophilic Addition: Nucleophilic addition is a fundamental organic reaction in which a nucleophile, a species that donates electrons, adds to an electrophilic carbon center, typically a carbonyl carbon, to form a new product. This reaction is central to understanding many important topics in organic chemistry, including functional groups, polar reactions, carbocation stability, reaction stereochemistry, and the chemistry of aldehydes, ketones, alcohols, and other carbonyl-containing compounds.
Nucleophilic addition reaction: A nucleophilic addition reaction is a chemical process where a nucleophile forms a bond with an electrophilic carbon atom of a compound, typically found in aldehydes and ketones. This reaction results in the conversion of the carbonyl group into a more complex, often larger, molecule.
Organometallic Compounds: Organometallic compounds are a class of chemical compounds containing at least one covalent bond between a carbon atom and a metal atom. These compounds exhibit unique properties and reactivity patterns, making them valuable in various applications, including organic synthesis, catalysis, and materials science.
Oxidation State: Oxidation state is a measure of the degree of oxidation of an atom in a chemical compound. It is the hypothetical charge that an atom would have if all bonds to atoms of different elements were completely ionic, with the more electronegative atom(s) assigned the full negative charge(s).
Primary Alcohol: A primary alcohol is an organic compound containing a hydroxyl (-OH) functional group attached to a saturated carbon atom that is bonded to only one other carbon atom. Primary alcohols are an important class of organic compounds with diverse applications and are a key focus in the study of organic chemistry.
Propanal: Propanal is the simplest aliphatic aldehyde, with the molecular formula C$_{3}$H$_{6}$O. It is a colorless, volatile liquid with a pungent, fruity odor. Propanal is an important organic compound that is closely related to the topics of naming aldehydes and ketones, nucleophilic addition reactions, spectroscopy, and carbonyl condensation reactions.
Propanone: Propanone, also known as acetone, is a simple ketone compound with the chemical formula CH$_3$COCH$_3$. It is a colorless, volatile, and flammable liquid that is widely used in various industrial and commercial applications. Propanone is particularly relevant in the context of the topics 19.1 Naming Aldehydes and Ketones and 19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation.
Reaction Kinetics: Reaction kinetics is the study of the rates and mechanisms of chemical reactions. It examines the factors that influence the speed and efficiency of a reaction, such as temperature, pressure, and the presence of catalysts. This concept is crucial in understanding organic reactions, as the rate and pathway of a reaction can have a significant impact on the products formed and the overall efficiency of the process.
RMgX: RMgX, also known as a Grignard reagent, is an organometallic compound consisting of an alkyl or aryl group (R) bonded to a magnesium atom (Mg) and a halide (X). These versatile reagents are widely used in organic synthesis for the formation of new carbon-carbon bonds and the addition of nucleophiles to carbonyl groups, leading to the synthesis of alcohols.
Secondary Alcohol: A secondary alcohol is an organic compound in which a hydroxyl group (-OH) is attached to a carbon atom that is bonded to two other carbon atoms. This structural feature distinguishes secondary alcohols from primary alcohols, where the hydroxyl group is attached to a carbon atom bonded to only one other carbon, and tertiary alcohols, where the hydroxyl group is attached to a carbon atom bonded to three other carbons.
Sodium Borohydride: Sodium borohydride is a powerful reducing agent commonly used in organic chemistry reactions to reduce carbonyl compounds to alcohols. It is a versatile reagent that finds applications in various topics, including the reduction of aromatic compounds, the preparation of alcohols, the synthesis of ethers, and the nucleophilic addition of hydride to carbonyl groups.
Stereochemistry: Stereochemistry is the study of the three-dimensional arrangement of atoms in molecules and how this arrangement affects the chemical and physical properties of the substance. It examines the spatial orientation of atoms and their relationship to one another, which is crucial in understanding many organic chemistry concepts.
Tertiary Alcohol: A tertiary alcohol is an organic compound with a hydroxyl (-OH) group attached to a carbon atom that is bonded to three other carbon atoms. This unique structural feature distinguishes tertiary alcohols from primary and secondary alcohols, which have the hydroxyl group attached to carbon atoms with different environments.
Tetrahedral: Tetrahedral refers to a three-dimensional molecular geometry in which a central atom is bonded to four other atoms, forming a shape resembling a pyramid with a triangular base. This arrangement is a fundamental concept in chemistry, particularly in the context of chemical bonding theory, organic chemistry, and stereochemistry.
β Diketone: A β-diketone is an organic compound containing two ketone groups separated by a carbon atom, which is the beta (β) position relative to each ketone group. These molecules are characterized by the presence of hydrogen atoms on the carbon between the two carbonyl (C=O) groups, making them acidic and prone to enolate ion formation.