17.5 Alcohols from Carbonyl Compounds: Grignard Reaction
3 min read•may 7, 2024
Grignard reactions are powerful tools for making alcohols from . They involve forming a , then adding it to a carbonyl group. This process creates new carbon-carbon bonds, turning simple molecules into more complex ones.
These reactions work with different carbonyl compounds, producing various alcohols. However, they're sensitive to moisture and don't play well with certain functional groups. Understanding their limitations is key to using them effectively in organic synthesis.
Grignard Reaction: Synthesis of Alcohols from Carbonyl Compounds
Mechanism of Grignard reactions
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- formation:
- Alkyl or (methyl bromide) reacts with magnesium metal in solvent (diethyl ether)
- Electron transfer from Mg to the halide forms a carbon-magnesium bond (CH3-MgBr)
- :
- The nucleophilic carbon of the Grignard reagent attacks the electrophilic carbonyl carbon (acetone)
- The carbonyl oxygen forms a bond with the magnesium, creating a tetrahedral intermediate
- Protonation:
- An aqueous acid workup (HCl) protonates the alkoxide intermediate
- The carbon-magnesium and oxygen-magnesium bonds are cleaved, forming the final product (2-propanol)
Products of Grignard-carbonyl reactions
- Aldehydes (propanal):
- Yield primary alcohols (1-propanol)
- The Grignard reagent (ethylmagnesium bromide) adds a single alkyl or aryl group to the carbonyl carbon
- Ketones (cyclohexanone):
- Yield tertiary alcohols (1-phenyl-1-cyclohexanol)
- The Grignard reagent (phenylmagnesium bromide) adds a single alkyl or aryl group to the carbonyl carbon
- Esters (methyl benzoate):
- Yield tertiary alcohols (triphenylmethanol)
- Two equivalents of the Grignard reagent (phenylmagnesium bromide) are required
- The first equivalent adds to the carbonyl carbon, and the second equivalent displaces the alkoxide group (CH3O-)
- Carbon dioxide:
- Yields carboxylic acids (benzoic acid)
- The Grignard reagent (phenylmagnesium bromide) adds to the carbon atom of CO2, forming a intermediate
- Aqueous acid workup (HCl) protonates the carboxylate, yielding the
Limitations of Grignard reagents
- :
- Grignard reagents are highly reactive towards water and moisture
- Anhydrous conditions and dry, oxygen-free solvents (diethyl ether, THF) are essential to prevent decomposition
- :
- Grignard reagents are incompatible with acidic protons (alcohols, amines, carboxylic acids)
- These functional groups must be protected (silyl ethers, esters) or avoided in the substrate
- Grignard reagents also react with other electrophiles, such as nitriles and epoxides, limiting their selectivity
- :
- The reactivity of the alkyl or aryl halide decreases in the order: RI > RBr > RCl
- Alkyl iodides and bromides (ethyl bromide) are preferred for Grignard reagent formation
- Aryl chlorides and vinyl halides may require activation (metal catalysts, ultrasound) for Grignard formation
- :
- Bulky Grignard reagents (t-BuMgX) may exhibit reduced reactivity due to steric hindrance around the magnesium atom
- The carbonyl substrate (2,2-dimethylpropanal) may also experience steric effects, slowing down the
Organometallic Compounds and Reaction Characteristics
- Grignard reagents are , containing a carbon-metal bond
- They act as nucleophiles in reactions with carbonyl compounds (electrophiles)
- The is an addition reaction, forming a new carbon-carbon bond
- of the product depends on the structure of the reactants and reaction conditions
Key Terms to Review (34)
Addition Reaction: An addition reaction is a type of chemical reaction where two or more reactants combine to form a single product. In the context of organic chemistry, addition reactions typically involve the addition of atoms or molecules to an alkene or alkyne, resulting in the formation of a new compound with a different structure and properties.
Alcohol: In the context of organic chemistry, an alcohol is an organic compound in which a hydroxyl group (-OH) is bonded to a saturated carbon atom. The general formula for a simple alcohol can be represented as CnH2n+1OH, where n is the number of carbon atoms.
Alcohol: Alcohols are a class of organic compounds characterized by the presence of a hydroxyl (-OH) functional group attached to a saturated carbon atom. They are widely used in various chemical reactions and have diverse applications in organic synthesis, pharmaceutical industry, and everyday life.
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.
Alkyl halide: An alkyl halide is an organic compound in which one or more hydrogen atoms in an alkane (saturated hydrocarbon) have been replaced by a halogen atom (fluorine, chlorine, bromine, or iodine). This substitution results in a molecule with distinct chemical and physical properties compared to its alkane precursor.
Alkyl Halide: An alkyl halide is a type of organic compound that consists of an alkyl group (a hydrocarbon chain) bonded to a halogen atom (fluorine, chlorine, bromine, or iodine). These compounds are important intermediates in many organic reactions, including polar reactions, elimination reactions, and substitution reactions.
Anhydrous Ether: Anhydrous ether, also known as diethyl ether, is a colorless, highly flammable liquid ether that is widely used as a solvent and as a starting material in organic synthesis, particularly in the context of the Grignard reaction to produce alcohols from carbonyl compounds.
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.
Aryl Halide: An aryl halide is an organic compound that consists of a halogen atom (such as chlorine, bromine, or iodine) bonded directly to an aromatic ring. These compounds are widely used in organic synthesis and play a crucial role in various chemical reactions, including organometallic coupling reactions and the Grignard reaction.
Carbon-Magnesium Bond: The carbon-magnesium bond is a covalent bond formed between a carbon atom and a magnesium atom. This bond is a crucial component in the formation of Grignard reagents, which are important organometallic compounds used in organic synthesis.
Carbonyl Compounds: Carbonyl compounds are a class of organic compounds that contain a carbon-oxygen double bond (C=O), known as the carbonyl group. This functional group is found in a variety of important molecules, including aldehydes, ketones, carboxylic acids, esters, and amides, which are all integral to many organic chemistry topics and reactions.
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.
Electrophile: An electrophile is a species that is attracted to electron-rich regions and seeks to form new bonds by accepting electron density. Electrophiles play a crucial role in many organic reactions, including polar reactions, electrophilic aromatic substitution, and nucleophilic acyl substitution, among others.
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.
Functional Group Compatibility: Functional group compatibility refers to the ability of different functional groups to coexist and participate in chemical reactions without interfering with or reacting with one another. This concept is particularly important in the context of organic chemistry, especially in the Grignard reaction, which involves the formation of alcohols from carbonyl compounds.
Grignard reaction: A Grignard reaction involves the addition of an organomagnesium compound, known as a Grignard reagent, to a carbonyl group, leading to the formation of alcohols. It is a pivotal method in organic chemistry for creating carbon-carbon bonds.
Grignard Reaction: The Grignard reaction is a powerful organic synthesis technique that allows for the formation of new carbon-carbon bonds through the reaction of an organomagnesium compound, known as a Grignard reagent, with an electrophile such as a carbonyl compound. This reaction is widely used in the synthesis of alcohols and other organic compounds.
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.
Halide Reactivity: Halide reactivity refers to the chemical properties and behaviors of halogen-containing compounds, particularly their ability to participate in various reactions. This concept is crucial in understanding the Grignard reaction, a key method for synthesizing alcohols from carbonyl compounds.
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.
Magnesium Carboxylate: A magnesium carboxylate is a chemical compound formed by the reaction of a carboxylic acid and magnesium. These compounds are important intermediates in the Grignard reaction, a widely used method for forming alcohols from carbonyl compounds.
Moisture Sensitivity: Moisture sensitivity refers to the susceptibility of certain chemical compounds or materials to be adversely affected by the presence of water or moisture. This term is particularly relevant in the context of organic chemistry reactions, such as the Grignard reaction, where the presence of water can interfere with the desired outcome.
Nucleophile: A nucleophile is a species that donates a pair of electrons to form a covalent bond with another atom or molecule. Nucleophiles are central to understanding many organic reactions, including polar reactions, electrophilic addition reactions, and nucleophilic substitution reactions.
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.
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.
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.
Steric Hindrance: Steric hindrance, also known as steric strain or steric effect, refers to the repulsive forces that arise between atoms or groups of atoms in a molecule due to their physical size and spatial arrangement. This phenomenon can significantly impact the stability, reactivity, and conformations of organic compounds.
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 Intermediate: A tetrahedral intermediate is a key reaction step that occurs in many organic chemistry reactions, where a trigonal planar carbonyl carbon temporarily becomes a tetrahedral carbon with four bonded atoms. This transient intermediate is crucial for understanding the mechanisms of various nucleophilic addition and substitution reactions.
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.