3.1 Aldehydes and ketones
7 min read•august 21, 2024
Aldehydes and ketones are vital organic compounds containing a . Their unique structure and reactivity make them crucial in organic synthesis, biological processes, and industrial applications. Understanding their properties is key to predicting their behavior in various chemical reactions.
This topic explores the structure, nomenclature, and physical properties of aldehydes and ketones. It delves into their reactivity, synthesis methods, and important reactions like and aldol condensation. Spectroscopic analysis and biological significance of these compounds are also covered.
Structure of aldehydes vs ketones
- Aldehydes and ketones contain a carbonyl group, playing a crucial role in organic chemistry reactions
- Understanding their structural differences helps predict reactivity and properties in various chemical processes
Carbonyl group characteristics
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- Consists of a carbon atom double-bonded to an oxygen atom (C=O)
- Forms a planar trigonal structure with 120° bond angles
- Exhibits high polarity due to electronegativity difference between carbon and oxygen
- Resonance stabilization occurs through electron delocalization
Aldehyde vs ketone nomenclature
- Aldehydes named with suffix "-al" (propanal)
- Ketones named with suffix "-one" (propanone)
- Aldehydes always have the carbonyl group at the end of the carbon chain
- Ketones have the carbonyl group between carbon atoms
- prioritizes aldehyde group over ketone when both are present
Physical properties comparison
- Aldehydes generally have lower boiling points than ketones of similar molecular weight
- Both form hydrogen bonds with water, leading to increased solubility
- Dipole moments of aldehydes slightly higher than ketones due to less shielding of carbonyl group
- Aldehydes more prone to than ketones
- Ketones typically have a more pleasant odor compared to the often pungent smell of aldehydes
Reactivity of carbonyl compounds
- Carbonyl compounds are highly versatile in organic synthesis due to their electrophilic nature
- Understanding their reactivity patterns essential for predicting outcomes in complex organic reactions
Nucleophilic addition mechanism
- Nucleophile attacks the electrophilic carbonyl carbon
- Forms tetrahedral intermediate with negatively charged oxygen
- Proton transfer occurs to generate final product
- Reversible process in many cases, leading to equilibrium mixtures
- Stereochemistry of product determined by direction of nucleophilic attack
Factors affecting reactivity
- Steric hindrance around carbonyl group decreases reactivity
- Electron-withdrawing groups increase electrophilicity of carbonyl carbon
- Resonance stabilization in conjugated systems can decrease reactivity
- Solvent polarity affects stabilization of charged intermediates
- Catalysts (acids or bases) can enhance reaction rates
Comparison to other functional groups
- More reactive than ethers or esters towards nucleophilic addition
- Less reactive than acyl halides or anhydrides
- Similar reactivity to carboxylic acids in some reactions
- More electrophilic than alkenes or alkynes
- Can undergo both addition and condensation reactions unlike many other functional groups
Synthesis of aldehydes and ketones
- Multiple synthetic routes available for preparing aldehydes and ketones
- Choice of method depends on starting materials and desired selectivity
Oxidation of alcohols
- Primary alcohols oxidized to aldehydes using mild oxidants (PCC, Swern oxidation)
- Secondary alcohols oxidized to ketones with various oxidizing agents (CrO3, Jones reagent)
- Over-oxidation of aldehydes to carboxylic acids must be avoided
- Chemoselective oxidations possible using enzyme-catalyzed reactions
- Green chemistry approaches utilize oxygen as oxidant with metal catalysts
Ozonolysis of alkenes
- Alkenes cleaved by ozone to form carbonyl compounds
- Reductive workup with zinc dust yields aldehydes or ketones
- Oxidative workup with hydrogen peroxide produces carboxylic acids
- Mechanism involves formation of molozonide and ozonide intermediates
- Useful for determining structure of unknown alkenes
Friedel-Crafts acylation
- Aromatic compounds react with acyl chlorides to form aromatic ketones
- Requires Lewis acid catalyst (AlCl3)
- Cannot be used to synthesize aldehydes directly
- Regioselectivity governed by directing effects of substituents
- Limited to electron-rich aromatic systems
Reactions of aldehydes and ketones
- Aldehydes and ketones undergo a wide range of transformations
- Understanding these reactions crucial for synthetic planning and analysis
Nucleophilic addition reactions
- Grignard reagents add to form alcohols after workup
- Cyanide ion forms cyanohydrins
- Hydride reagents (NaBH4, LiAlH4) reduce to alcohols
- Amines form imines or enamines
- Water adds reversibly to form geminal diols (hydrates)
Reduction to alcohols
- (NaBH4) reduces to primary or secondary alcohols
- Lithium aluminum hydride (LiAlH4) provides stronger
- Catalytic hydrogenation uses H2 gas with metal catalysts
- Meerwein-Ponndorf-Verley reduction employs aluminum isopropoxide
- Stereochemistry of reduction can be controlled with chiral reducing agents
Oxidation of aldehydes
- Aldehydes easily oxidized to carboxylic acids
- Tollens' reagent (silver mirror test) used for aldehyde detection
- Fehling's solution and Benedict's reagent also oxidize aldehydes
- Jones oxidation employs in acetone
- Ketones generally resistant to further oxidation under mild conditions
Aldol condensation
- Important carbon-carbon bond forming reaction in organic synthesis
- Involves reaction between two carbonyl compounds, one acting as nucleophile
Mechanism and stereochemistry
- Base-catalyzed formation of enolate ion
- Nucleophilic addition of enolate to second carbonyl compound
- Dehydration step forms α,β-unsaturated carbonyl product
- E-alkene typically favored due to thermodynamic stability
- Zimmerman-Traxler model explains stereochemical outcomes
Crossed aldol reactions
- Involves two different carbonyl compounds
- Can lead to mixture of products if both reactants enolizable
- Controlled by using one non-enolizable partner or kinetic enolate formation
- Useful for synthesizing more complex structures
- Mukaiyama aldol reaction uses silyl enol ethers for better control
Intramolecular aldol condensation
- Occurs when molecule contains both aldehyde/ketone and enolizable hydrogen
- Forms cyclic products, often five- or six-membered rings
- Entropy-driven, often more favorable than intermolecular reactions
- Key step in many natural product syntheses
- Can lead to formation of bridged or fused ring systems
Imine and enamine formation
- Important reactions for introducing nitrogen functionality
- Serve as intermediates in many organic transformations
Mechanism of imine formation
- Nucleophilic addition of primary amine to carbonyl compound
- Formation of tetrahedral intermediate
- Loss of water to form C=N double bond
- Acid-catalyzed process, often requires dehydrating agent
- Reversible reaction, equilibrium can be shifted by removing water
Enamine synthesis and reactivity
- Secondary amines react with aldehydes or ketones to form enamines
- Tautomerization occurs between imine and enamine forms
- Enamines act as nucleophiles due to electron-rich double bond
- Can undergo alkylation reactions at α-carbon
- Hydrolysis of product regenerates carbonyl compound
Applications in organic synthesis
- Imines used in reductive amination to form secondary amines
- Chiral imines serve as substrates for asymmetric synthesis
- Enamine catalysis employed in organocatalytic transformations
- Stork enamine alkylation allows α-functionalization of ketones
- Gabriel synthesis uses phthalimide to prepare primary amines
Wittig reaction
- Powerful method for converting carbonyl compounds to alkenes
- Named after Georg Wittig, who received Nobel Prize for this discovery
Mechanism and stereoselectivity
- Phosphorus ylide (phosphorane) attacks carbonyl carbon
- Forms oxaphosphetane intermediate in reversible step
- Decomposition of oxaphosphetane yields alkene and phosphine oxide
- Stereochemistry determined by stability of oxaphosphetane intermediate
- Unstabilized ylides favor Z-alkenes, stabilized ylides favor E-alkenes
Preparation of phosphorus ylides
- Alkyl halides react with triphenylphosphine to form phosphonium salts
- Strong base (NaH, n-BuLi) deprotonates to generate ylide
- Stabilized ylides contain electron-withdrawing groups adjacent to carbanion
- Unstabilized ylides highly reactive, often prepared and used in situ
- Betaines can be isolated for some stabilized ylides
Synthetic applications
- Widely used in total synthesis of natural products
- Allows precise control of double bond position
- Horner-Wadsworth-Emmons reaction uses phosphonate esters for improved E-selectivity
- Schlosser modification achieves high Z-selectivity with unstabilized ylides
- One-pot Wittig reactions combine ylide formation and carbonyl addition
Spectroscopic analysis
- Spectroscopic techniques crucial for structure determination of carbonyl compounds
- Combination of methods provides comprehensive structural information
IR spectroscopy of carbonyls
- Strong absorption band for C=O stretch (1650-1750 cm⁻¹)
- Aldehydes show additional weak C-H stretch (2720-2820 cm⁻¹)
- Conjugation lowers C=O frequency due to resonance
- Hydrogen bonding affects peak position and shape
- Useful for distinguishing between aldehydes and ketones
NMR characteristics
- Aldehyde proton appears as downfield singlet (9-10 ppm) in ¹H NMR
- α-Hydrogens to carbonyl show increased chemical shift
- ¹³C NMR shows carbonyl carbon peak at 190-205 ppm
- Coupling patterns help determine substitution patterns
- 2D NMR techniques (COSY, HMQC) aid in structure elucidation
Mass spectrometry fragmentation patterns
- Molecular ion peak often visible for aldehydes and ketones
- Common loss of 28 (CO) or 29 (CHO) mass units
- α-Cleavage characteristic fragmentation mode
- McLafferty rearrangement occurs in molecules with γ-hydrogen
- High-resolution MS provides accurate mass for molecular formula determination
Biological significance
- Aldehydes and ketones play crucial roles in biological systems
- Understanding their reactivity important for biochemistry and medicinal chemistry
Aldehydes and ketones in metabolism
- Glucose exists in equilibrium with open-chain aldehyde form
- Pyruvate, a key metabolic intermediate, is an α-keto acid
- Acetone produced as byproduct in diabetic ketoacidosis
- Aldehydes formed during lipid peroxidation (malondialdehyde)
- Acetaldehyde, toxic intermediate in ethanol metabolism
Carbonyl compounds in natural products
- Vanillin, principal component of vanilla flavor, is an aromatic aldehyde
- Carvone, found in caraway seeds, contains a cyclic α,β-unsaturated ketone
- Camphor, a bicyclic ketone, used in traditional medicine
- Retinal, aldehyde form of vitamin A, crucial for vision
- Steroid hormones (testosterone, progesterone) contain ketone groups
Pharmaceutical applications
- Corticosteroids (prednisone) contain multiple ketone functionalities
- Local anesthetics (lidocaine) often include amide linkages derived from ketones
- Propofol, an intravenous anesthetic, is a substituted phenol with isopropyl groups
- Paclitaxel (Taxol), anticancer drug, contains both ketone and ester carbonyl groups
- Norethindrone, oral contraceptive, features an α,β-unsaturated ketone
Key Terms to Review (21)
2,4-dinitrophenylhydrazine: 2,4-dinitrophenylhydrazine (DNPH) is a chemical compound used primarily as a reagent to detect aldehydes and ketones through the formation of hydrazones. This reaction is significant in organic chemistry because it provides a method for identifying carbonyl compounds, which are key functional groups in many organic molecules.
Acetylation: Acetylation is a chemical modification process that involves the addition of an acetyl group (C2H3O) to a molecule, often affecting its reactivity and properties. This modification is significant in organic chemistry, particularly in transforming carboxylic acids, acid anhydrides, aldehydes, and ketones into their respective acetyl derivatives. Acetylation plays a critical role in various reactions and mechanisms, influencing the synthesis and functionality of organic compounds.
Aldehyde functional group: An aldehyde functional group is characterized by a carbon atom double-bonded to an oxygen atom and single-bonded to a hydrogen atom (–CHO). This distinctive structure defines aldehydes, making them a vital class of organic compounds that are important in various chemical reactions, including oxidation and reduction processes. Aldehydes are known for their reactivity, particularly in nucleophilic addition reactions, and their presence in biological molecules and industrial applications enhances their significance in organic chemistry.
Boiling point: The boiling point is the temperature at which a liquid's vapor pressure equals the external pressure surrounding it, causing the liquid to transition into a gas. This phenomenon is influenced by intermolecular forces, molecular weight, and the presence of functional groups in organic compounds, which can vary greatly among different classes of compounds.
Cannizzaro Reaction: The Cannizzaro reaction is a chemical reaction that involves the disproportionation of an aldehyde that lacks alpha-hydrogens in the presence of a strong base, resulting in the formation of a carboxylic acid and an alcohol. This reaction is significant for aldehydes that cannot undergo aldol condensation due to the absence of reactive alpha-hydrogens, providing a pathway to convert them into useful functional groups.
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 structure is crucial in organic chemistry as it forms the backbone of many important compounds, including aldehydes, ketones, and carboxylic acids, and plays a significant role in various chemical reactions and spectroscopic analyses.
Chirality: Chirality refers to the geometric property of a molecule having a non-superimposable mirror image, much like left and right hands. This characteristic is essential in organic chemistry as it impacts molecular interactions, physical properties, and biological activity. The presence of chiral centers, typically carbon atoms bonded to four different substituents, leads to the existence of enantiomers, which can have vastly different effects in biological systems.
Chromic Acid: Chromic acid is a powerful oxidizing agent commonly used in organic chemistry for the oxidation of alcohols and aldehydes to their corresponding carbonyl compounds. It is often represented by the chemical formula H2CrO4, and its strong oxidative properties make it essential in transforming primary and secondary alcohols into aldehydes and ketones respectively.
Common names: Common names are informal or widely recognized names given to chemical compounds, which often reflect their structure, origin, or function rather than adhering strictly to IUPAC nomenclature. These names provide a simpler way for people to refer to complex molecules and are commonly used in everyday language, scientific literature, and industries such as pharmaceuticals and food.
Fragrance production: Fragrance production is the process of creating aromatic compounds that are used in perfumes, cosmetics, and other products to provide a pleasant scent. This process often involves the extraction and synthesis of natural and synthetic ingredients, particularly aldehydes and ketones, which are essential for crafting distinctive fragrances.
Grignard reaction: The Grignard reaction is a powerful organic reaction that involves the formation of carbon-carbon bonds through the reaction of Grignard reagents with electrophiles. This reaction is crucial for synthesizing various organic compounds and allows for functional group interconversions, particularly involving aldehydes and ketones, by forming new carbon chains.
Hydration: Hydration refers to the addition of water to a substance, typically leading to the formation of alcohols from aldehydes and ketones through nucleophilic addition. In organic chemistry, this process plays a significant role in the transformation of carbonyl compounds, impacting their reactivity and the structure of resulting products.
Iupac naming: IUPAC naming is a systematic method for naming organic chemical compounds established by the International Union of Pure and Applied Chemistry. This naming convention provides a unique and unambiguous name for each compound, reflecting its structure and functional groups, ensuring clarity in communication among chemists. It's essential for identifying compounds such as aldehydes, ketones, and fatty acids, where specific rules dictate how to construct the names based on the molecular structure and functional groups present.
Ketone functional group: A ketone functional group is characterized by a carbonyl group (C=O) bonded to two carbon atoms. This structure gives ketones distinct properties and reactivity compared to other carbonyl-containing compounds. Ketones are crucial in various chemical reactions, including nucleophilic additions, and they play significant roles in both organic synthesis and biological processes.
Nucleophilic Addition: Nucleophilic addition is a chemical reaction where a nucleophile forms a bond with an electrophilic center, typically in carbonyl compounds like aldehydes and ketones. This process is central to many organic reactions, leading to the formation of alcohols and larger molecules through the addition of various nucleophiles to carbonyl carbons.
Optical Activity: Optical activity refers to the ability of chiral molecules to rotate the plane of polarized light as it passes through them. This phenomenon is crucial for understanding the behavior of various organic compounds, especially those that are asymmetric and possess at least one chiral center. The extent and direction of this rotation can provide insights into the compound's molecular structure and its interactions with light.
Oxidation: Oxidation is a chemical process that involves the loss of electrons or an increase in oxidation state by a molecule, atom, or ion. This concept is fundamental in understanding various organic reactions, where the transformation of compounds often includes the introduction of oxygen or the removal of hydrogen. In many biological and chemical processes, oxidation plays a crucial role, such as in the metabolism of carbohydrates and the conversion of functional groups in organic molecules.
Pharmaceuticals: Pharmaceuticals are substances used in the diagnosis, treatment, or prevention of disease and are often derived from natural or synthetic compounds. These compounds play a crucial role in healthcare by providing therapeutic benefits, alleviating symptoms, and improving overall patient outcomes. They can be classified into various categories based on their chemical structure and biological activity, including esters, amides, aldehydes, and ketones, which contribute significantly to their efficacy and functionality in medical applications.
Reduction: Reduction is a chemical process that involves the gain of electrons or the decrease in oxidation state of a molecule, often resulting in the addition of hydrogen or the removal of oxygen. This transformation is essential for synthesizing various organic compounds, including amines, carbohydrates, and other functional groups, making it a cornerstone of organic chemistry reactions.
Sodium Borohydride: Sodium borohydride is a chemical compound with the formula NaBH4, widely recognized as a powerful reducing agent. It is commonly used in organic synthesis to reduce carbonyl compounds such as aldehydes and ketones into their corresponding alcohols, highlighting its importance in nucleophilic addition reactions. The ability of sodium borohydride to selectively reduce carbonyl groups while leaving other functional groups intact makes it a valuable tool in organic chemistry.
Solubility in water: Solubility in water refers to the ability of a substance to dissolve in water to form a homogeneous solution. This property is influenced by the molecular structure of the substance, particularly the presence of polar functional groups that can interact favorably with water molecules. In the context of aldehydes and ketones, their solubility often depends on the length of the carbon chain and the presence of functional groups like carbonyls, which can engage in hydrogen bonding with water.