21.4 Chemistry of Acid Halides
2 min read•may 7, 2024
are versatile compounds formed by replacing the hydroxyl group of with a halogen. They're highly reactive due to their and excellent halogen , making them key players in organic synthesis.
undergo reactions with various nucleophiles, forming carboxylic acids, , , and . They can also be reduced to primary alcohols or react with to form tertiary alcohols, showcasing their diverse reactivity.
Preparation and Reactions of Acid Halides
Preparation of acid halides
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- Convert hydroxyl group of carboxylic acids to halogen (chlorine or bromine) to prepare acid halides
- Use () to prepare acid chlorides
- Oxygen of carboxyl group attacks sulfur in displacing chloride ion which then attacks carbon of carboxyl group forming acid chloride and releasing and as byproducts
- Use () to prepare acid bromides
- Similar mechanism to thionyl chloride where oxygen attacks phosphorus displacing bromide ion which then attacks carboxyl carbon forming acid bromide and releasing and phosphorous acid () as byproducts
Structure and Reactivity
- Acid halides contain an (R-CO-) bonded to a halogen
- The carbonyl group makes the molecule highly reactive
- Halogen acts as an excellent , enhancing reactivity
- Carbonyl carbon serves as an in reactions
- Nucleophiles readily attack the electron-deficient carbonyl carbon
Nucleophilic acyl substitution reactions
- Acid halides highly reactive due to electron-withdrawing nature of halogen making carbonyl carbon more electrophilic and susceptible to nucleophilic attack
- Reaction with water yields carboxylic acids
- Water acts as attacking carbonyl carbon and displacing halide ion
- Reaction with carboxylate ions (from another carboxylic acid) yields anhydrides
- Carboxylate ion acts as nucleophile attacking carbonyl carbon and displacing halide ion
- Reaction with alcohols yields esters
- Alcohol acts as nucleophile attacking carbonyl carbon and displacing halide ion
- Reaction with amines yields amides
- Amine acts as nucleophile attacking carbonyl carbon and displacing halide ion followed by proton transfer to form amide
Reduction vs Grignard reactions
- Reduction with () yields primary alcohols
- Hydride () from acts as nucleophile attacking carbonyl carbon and displacing halide ion followed by protonation to form primary alcohol
- Reaction with Grignard reagents () yields tertiary alcohols
- Alkyl group () of Grignard reagent acts as nucleophile attacking carbonyl carbon and displacing halide ion
- Forms ketone intermediate which can be further attacked by two more equivalents of Grignard reagent ultimately forming tertiary alcohol upon aqueous workup
- Alkyl group () of Grignard reagent acts as nucleophile attacking carbonyl carbon and displacing halide ion
Key Terms to Review (26)
$H_3PO_3$: $H_3PO_3$, also known as phosphorous acid, is a chemical compound composed of one phosphorus atom and three hydrogen atoms bonded to three oxygen atoms. It is an important intermediate in the chemistry of acid halides, specifically in the context of 21.4 Chemistry of Acid Halides.
$LiAlH_4$: $LiAlH_4$, also known as lithium aluminum hydride, is a powerful reducing agent used in organic chemistry. It is particularly relevant in the context of comparing biological reactions to laboratory reactions, as well as understanding the chemistry of acid halides.
$PBr_3$: $PBr_3$, or phosphorus tribromide, is a covalent compound composed of one phosphorus atom and three bromine atoms. It is an important reagent in organic chemistry, particularly in the context of acid halide reactions.
$RMgX$: $RMgX$ is a Grignard reagent, which is an important class of organometallic compounds used extensively in organic synthesis. These reagents are formed by the reaction of an alkyl or aryl halide with magnesium metal, and they exhibit high nucleophilicity and reactivity, making them versatile tools for carbon-carbon bond formation.
$SOCl_2$: $SOCl_2$, or thionyl chloride, is a highly reactive acid chloride compound commonly used in organic synthesis reactions. It serves as a versatile reagent for the conversion of alcohols, carboxylic acids, and other functional groups into more reactive derivatives.
Acid anhydrides: Acid anhydrides are organic compounds formed by the removal of water between two carboxylic acid molecules. They play a significant role in nucleophilic acyl substitution reactions, where they act as electrophiles ready to react with nucleophiles.
Acid halides: Acid halides are a type of carboxylic acid derivative where the hydroxyl group (OH) of the carboxylic acid is replaced by a halogen (e.g., chlorine, bromine). They are highly reactive compounds that participate in nucleophilic acyl substitution reactions.
Acid Halides: Acid halides, also known as acyl halides, are a class of organic compounds that contain a carbonyl group (C=O) bonded to a halogen atom (F, Cl, Br, or I). These compounds are highly reactive and serve as important intermediates in various organic reactions, particularly in the synthesis of carboxylic acid derivatives.
Acyl group: An acyl group is a functional group derived from a carboxylic acid by removal of a hydroxyl group (OH), represented as RCO-, where R can be any alkyl or aryl group. It plays a crucial role in the acylation reactions, including the synthesis of ketones and aldehydes through electrophilic aromatic substitution.
Acyl Group: An acyl group is a functional group with the general formula R-C(=O)-, where R represents an alkyl or aryl group. It is a key structural component in many organic compounds, particularly those involved in nucleophilic acyl substitution reactions and the chemistry of acid halides.
Amides: Amides are a class of organic compounds that contain a carbonyl group (C=O) bonded to a nitrogen atom. They are derived from carboxylic acids and can be considered the result of replacing the hydroxyl group (-OH) of a carboxylic acid with an amino group (-NH2). Amides are important functional groups in many organic molecules, including proteins, and play a crucial role in various chemical reactions and processes.
Anhydrides: Anhydrides are organic compounds derived from carboxylic acids, characterized by a carbonyl-oxygen-carbonyl functional group. They play a crucial role in various reactions and transformations involving carboxylic acid derivatives, including naming, nucleophilic acyl substitution, and the chemistry of acid halides.
Carbonyl group: A carbonyl group is a functional group characterized by a carbon atom double-bonded to an oxygen atom, represented as C=O. This group is pivotal in organic chemistry as it forms the backbone of various important classes of compounds, influencing their chemical properties and reactivity.
Carboxylic Acids: Carboxylic acids are a class of organic compounds containing a carboxyl functional group (-COOH) attached to an alkyl or aryl group. They are characterized by their acidic properties and play a crucial role in various chemical reactions and biological processes.
Carboxylic acids, RCO2H: Carboxylic acids are organic compounds characterized by the presence of a carboxyl group (-COOH), where "R" represents an alkyl or aryl group attached to the carbon atom of the carboxyl group. They are known for being acidic due to the ability of the hydroxyl (OH) part of the carboxyl group to release a proton (H+).
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.
Esters: Esters are a class of organic compounds formed by the reaction between a carboxylic acid and an alcohol, resulting in the replacement of the hydroxyl group (-OH) of the acid with an alkoxy group (-OR). Esters are ubiquitous in nature and play a crucial role in various chemical processes and applications.
Grignard Reagents: Grignard reagents are a class of highly reactive organometallic compounds that are widely used in organic synthesis. They are formed by the reaction of an alkyl or aryl halide with magnesium metal and play a crucial role in various organic transformations.
Leaving group: A leaving group in organic chemistry is an atom or group that detaches from the parent molecule during a nucleophilic substitution (SN2) reaction, forming a lone pair or negative ion. The ease with which a leaving group departs affects the rate and success of the reaction.
Leaving Group: A leaving group is a functional group or atom that is displaced or removed from a molecule during a chemical reaction. It is a key component in many organic reactions, particularly substitution and elimination reactions, as it facilitates the formation of a new bond or the creation of a new product.
Lithium Aluminum Hydride: Lithium aluminum hydride (LiAlH4) is a powerful reducing agent used in organic chemistry for the selective reduction of various functional groups. It is a white, crystalline solid that reacts violently with water and other protic solvents, making it an important reagent in many synthetic transformations.
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 Acyl Substitution: Nucleophilic acyl substitution is a type of organic reaction where a nucleophile attacks the carbonyl carbon of a carboxylic acid derivative, such as an acid chloride, anhydride, or ester, leading to the replacement of the leaving group with the nucleophile. This process is central to the reactivity and transformations of carboxylic acid derivatives.
Nucleophilic acyl substitution reaction: A nucleophilic acyl substitution reaction is a type of chemical reaction where a nucleophile replaces the leaving group in an acyl compound. This reaction is fundamental in organic chemistry for modifying carboxylic acid derivatives into other functional groups.
Phosphorus Tribromide: Phosphorus tribromide is a colorless, fuming liquid compound with the chemical formula PBr3. It is an important reagent in organic chemistry, particularly in the context of preparing alkyl halides from alcohols, the chemistry of acid halides, and the alpha bromination of carboxylic acids.
Thionyl Chloride: Thionyl chloride (SOCl2) is a highly reactive organic compound commonly used as a reagent in various chemical reactions, particularly in the context of preparing alkyl halides from alcohols, as well as in the reactions and chemistry of carboxylic acids and their derivatives.