Carbohydrates, aldehydes and ketones

Carbohydrates

Carbohydrates are essential biomolecules in living organisms. They mainly serve as energy sources and structural components. Carbohydrates range from monosaccharides (single sugar units) to polysaccharides (long chains of sugars).

Common examples include glucose, a major cellular fuel, and fructose, found in fruits and in table sugar.

Nomenclature and classification, common names

Monosaccharides: Single sugar units such as glucose ( $C_{6} H_{12} O_{6}$ ), galactose, and fructose.
Disaccharides: Two monosaccharides linked by a glycosidic bond (e.g., sucrose, lactose, maltose).
Polysaccharides: Long chains of monosaccharides (e.g., starch, glycogen, cellulose).
Prefixes:
- deoxy indicates removal of an $- O H$ group, replaced by $- H$ .
- D/L denotes the absolute configuration relative to D-glyceraldehyde or L-glyceraldehyde.
- $α$ / $β$ specifies the anomeric configuration in cyclic sugars, based on whether the anomeric $- O H$ group is on the opposite side or the same side as the $C H_{2} O H$ group.
All sugars end in -ose (e.g., glucose, fructose, galactose).

Absolute configuration

Monosaccharides often contain multiple chiral centers, but the D/L system uses one specific reference point. In the open-chain form, look at the chiral carbon farthest from the carbonyl group; its configuration determines whether the sugar is D or L.

D sugars have the -OH on this reference carbon aligned similarly to D-glyceraldehyde. L sugars have the mirror-image configuration. This system is independent of R/S designations, which use the Cahn-Ingold-Prelog priority rules.

Cyclic structure and conformations of hexoses

In water, many monosaccharides exist mainly in cyclic form. Cyclization occurs when an internal alcohol group reacts with the carbonyl group to form a cyclic hemiacetal (from an aldose) or a hemiketal (from a ketose).

For six-carbon aldoses (e.g., glucose), a six-membered pyranose ring is common. For ketoses (e.g., fructose), a five-membered furanose ring may form.

Chair and boat conformations can occur, with the chair form generally more stable because it minimizes steric hindrance.

Epimers and anomers

Epimers differ in configuration at one chiral center, excluding the newly formed anomeric center in the ring form.
Anomers differ specifically at the new chiral center (the anomeric carbon) created during cyclization.
- $α$ anomer: The anomeric $- O H$ is oriented opposite the $C H_{2} O H$ group.
- $β$ anomer: The anomeric $- O H$ is oriented on the same side as the $C H_{2} O H$ group.

Mutarotation is the interconversion between $α$ and $β$ forms in solution, which changes the observed optical rotation.

Hydrolysis of the glycoside linkage

Glycosidic bonds link monosaccharides to form disaccharides and polysaccharides. Under acidic or enzymatic conditions, these bonds can be hydrolyzed, splitting the carbohydrate into its constituent sugars. In biological systems, enzymes called glycosidases catalyze this process.

Keto-enol tautomerism of monosaccharides

Some monosaccharides (especially those that can adopt an open-chain form with an aldehyde or ketone) can undergo keto-enol tautomerism. In this process, the carbonyl group temporarily converts to an enediol intermediate. Under basic conditions, this can allow an aldose to rearrange into a ketose, or a ketose into an aldose.

This tautomerism is not always prominent at physiological pH, but it helps explain aspects of sugar reactivity and interconversion.

Disaccharides

Sucrose: Formed by $α -glucose$ and $β$ -fructose linked at their anomeric carbons.
Lactose: Consists of β-galactose joined to glucose ( $α$ or $β$ ) through a 1→4 glycosidic bond.
Maltose: Composed of two glucose units connected via a dehydration reaction, typically $α -1,4$ linkage.

Polysaccharides

Starch: Predominantly $α -1,4$ glycosidic bonds linking glucose; used by plants for energy storage.
Glycogen: Similar to starch but with more frequent $α -1,6$ branches, making it a highly branched energy reserve in animals.
Cellulose (not mentioned above but commonly noted): Features $β -1,4$ linked glucose units, providing structural support in plant cell walls.

Aldehydes and ketones

Aldehydes and ketones are defined by the carbonyl group ( $C = O$ ), where carbon is double-bonded to oxygen. In an aldehyde, the carbonyl is at the end of a carbon chain. In a ketone, the carbonyl is within the chain.

These functional groups are important intermediates in organic synthesis because the carbonyl carbon is often reactive and can be converted into many other functional groups.

Nomenclature

Aldehydes typically end in “-al,” as in methanal (formaldehyde) or ethanal (acetaldehyde). Ketones generally end in “-one,” as in propanone (acetone) or butanone.

Common names are widely used, while systematic IUPAC names are based on the longest carbon chain containing the carbonyl group.

Physical properties

Aldehydes and ketones often have higher boiling points than comparable alkanes because the $C = O$ bond is polar. However, because they cannot donate hydrogen bonds, their boiling points are generally lower than those of alcohols.

Many low-molecular-weight aldehydes and ketones are water-soluble because the carbonyl oxygen can accept hydrogen bonds from water.

Important reactions

The carbonyl bond is polarized, leaving the carbonyl carbon partially positive. That electrophilic carbon is a common site for nucleophilic attack, which explains many of the characteristic reactions of aldehydes and ketones.

Nucleophilic addition reactions at $C = O$ bond

In nucleophilic addition, a nucleophile attacks the electrophilic carbonyl carbon. The $π$ bond breaks, giving an alkoxide intermediate. Depending on conditions, that intermediate may be protonated or converted into other derivatives.

Acetal, hemiacetal
When an alcohol reacts with an aldehyde or ketone, a hemiacetal or hemiketal forms first. With excess alcohol under acidic conditions, the hemiacetal can convert into an acetal, where two $- OR$ groups are attached to the same carbon.
Imine, enamine
A primary amine reacts with an aldehyde or ketone to form an imine, where the carbonyl oxygen is replaced by a double-bonded nitrogen. Secondary amines can form an enamine, where an α hydrogen shifts to give a $C = C - N$ linkage.
Hydride reagents
Reagents such as sodium borohydride ( $N a B H_{4}$ ) or lithium aluminum hydride ( $L i A l H_{4}$ ) deliver hydride to the carbonyl carbon. This reduces aldehydes to primary alcohols and ketones to secondary alcohols.
Cyanohydrin
Addition of hydrogen cyanide to a carbonyl forms a cyanohydrin, which has both a $- CN$ and an $- O H$ attached to the former carbonyl carbon.

Oxidation of aldehydes
Aldehydes can be oxidized to carboxylic acids under relatively mild conditions. Ketones generally resist oxidation unless conditions are strong enough to break carbon-carbon bonds.

Reactions at adjacent positions: enolate chemistry
An enolate forms when an α hydrogen is removed, producing a resonance-stabilized anion. Enolates are key intermediates in many reactions, including aldol condensation.

Keto-enol tautomerism ( $α$ -racemization)
Aldehydes and ketones with an $α$ hydrogen can interconvert between keto and enol forms through proton shifts. This equilibrium can lead to racemization at the α carbon if that carbon is chiral.
Aldol condensation, retro-aldol
Enolates can attack other carbonyl compounds to form aldol products. Under some conditions, the aldol product dehydrates to form an $α$ , $β$ -unsaturated carbonyl. The reverse process, retro-aldol, breaks the bond formed in the aldol reaction and regenerates smaller carbonyl compounds.
Kinetic versus thermodynamic enolate
The kinetic enolate forms faster under conditions that favor the lowest activation energy (often low temperature with a strong, bulky base), typically by removing the most accessible proton. The thermodynamic enolate is more stable and is favored at higher temperatures or with weaker bases, typically giving the more substituted double bond.

Reaction mechanisms for base- and acid-catalysed aldol condensation

General principles
Carbonyl reactivity is largely controlled by the polarity of the $C = O$ bond and by how accessible the carbonyl carbon is to an incoming nucleophile. Substituents can change electron density at the carbonyl carbon, and steric bulk can slow nucleophilic approach.

Effect of substituents on reactivity of $C = O$ ; steric hindrance
Electron-withdrawing substituents increase the electrophilicity of the carbonyl carbon, making nucleophilic addition more favorable. Bulky substituents hinder approach to the carbonyl center and can reduce reaction rates.
Acidity of $α$ -H; carbanions
$α$ Hydrogens next to a carbonyl are more acidic than typical alkyl $C - H$ bonds because deprotonation forms a resonance-stabilized carbanion (the enolate). This increased acidity enables many aldol-type and related transformations in synthetic chemistry.

Carbohydrate Classification

Three main classes: monosaccharides, disaccharides, polysaccharides
All sugars end in “-ose”; prefixes like “deoxy” indicate $- O H$ replaced by $- H$
$α$ / $β$ specifies anomeric $- O H$ orientation relative to $C H_{2} O H$

Absolute Configuration (D/L)

Determined by the chiral carbon farthest from the carbonyl in open-chain form
D = $- O H$ on right (like D-glyceraldehyde); L = mirror image
Independent of R/S (Cahn-Ingold-Prelog) designation

Cyclic Structures

Cyclization forms hemiacetal (aldose) or hemiketal (ketose) via internal alcohol attack on carbonyl
Six-membered ring = pyranose; five-membered ring = furanose
Chair conformation more stable than boat due to reduced steric strain

Epimers and Anomers

Epimers: differ at one chiral center (not the anomeric carbon)
Anomers: differ only at the anomeric carbon ( $α$ vs. $β$ )
Mutarotation: interconversion between $α$ and $β$ forms in solution, changing optical rotation

Glycosidic Bonds and Hydrolysis

Glycosidic bonds link monosaccharides in di- and polysaccharides
Cleaved by acid or glycosidase enzymes

Keto-Enol Tautomerism in Sugars

Open-chain aldehyde/ketone form can convert through enediol intermediate
Allows aldose↔ketose interconversion, especially under basic conditions

Key Disaccharides

Sucrose: $α$ -glucose + $β$ -fructose (anomeric carbons linked)
Lactose: $β$ -galactose + glucose via $β$ -1,4 bond
Maltose: two glucose units via $α$ -1,4 bond

Key Polysaccharides

Starch: $α$ -1,4 linked glucose; plant energy storage
Glycogen: $α$ -1,4 with frequent $α$ -1,6 branches; animal energy storage
Cellulose: $β$ -1,4 linked glucose; structural role in plant cell walls

Aldehyde and Ketone Nomenclature

Aldehydes end in “-al” (carbonyl at chain end); ketones end in “-one” (carbonyl within chain)
IUPAC names based on longest chain containing $C = O$

Physical Properties

More polar than alkanes → higher boiling points; lower than alcohols (no H-bond donation)
Low-MW forms water-soluble via H-bond acceptance by carbonyl oxygen

Nucleophilic Addition at $C = O$

Electrophilic carbonyl carbon attacked by nucleophile; $π$ bond breaks
Key products:
- Hemiacetal/acetal: alcohol + aldehyde/ketone
- Imine: primary amine replaces $C = O$ ; enamine: secondary amine gives $C = C - N$
- Cyanohydrin: HCN addition gives $- CN$ and $- O H$ on former carbonyl carbon
- Reduction: $N a B H_{4}$ or $L i A l H_{4}$ delivers hydride → aldehyde→1° alcohol, ketone→2° alcohol

Oxidation

Aldehydes readily oxidized to carboxylic acids
Ketones resist oxidation under mild conditions

Enolate Chemistry

$α$ -H is acidic due to resonance-stabilized enolate carbanion
Keto-enol tautomerism can cause racemization at $α$ carbon
Aldol condensation: enolate attacks carbonyl → $β$ -hydroxy carbonyl; may dehydrate to $α, β$ -unsaturated product
Retro-aldol is the reverse; regenerates smaller carbonyl fragments

Kinetic vs. Thermodynamic Enolate

Kinetic: faster-forming, less substituted; favored at low temp with strong bulky base
Thermodynamic: more stable, more substituted; favored at higher temp or weaker base

Substituent Effects and Reactivity

Electron-withdrawing groups increase carbonyl electrophilicity → faster nucleophilic addition
Steric bulk slows nucleophilic approach to $C = O$

Carbohydrates

Common examples include glucose, a major cellular fuel, and fructose, found in fruits and in table sugar.

Nomenclature and classification, common names

Monosaccharides: Single sugar units such as glucose ( $C_{6} H_{12} O_{6}$ ), galactose, and fructose.
Disaccharides: Two monosaccharides linked by a glycosidic bond (e.g., sucrose, lactose, maltose).
Polysaccharides: Long chains of monosaccharides (e.g., starch, glycogen, cellulose).
Prefixes:
- deoxy indicates removal of an $- O H$ group, replaced by $- H$ .
- D/L denotes the absolute configuration relative to D-glyceraldehyde or L-glyceraldehyde.
- $α$ / $β$ specifies the anomeric configuration in cyclic sugars, based on whether the anomeric $- O H$ group is on the opposite side or the same side as the $C H_{2} O H$ group.
All sugars end in -ose (e.g., glucose, fructose, galactose).

Absolute configuration

Cyclic structure and conformations of hexoses

For six-carbon aldoses (e.g., glucose), a six-membered pyranose ring is common. For ketoses (e.g., fructose), a five-membered furanose ring may form.

Chair and boat conformations can occur, with the chair form generally more stable because it minimizes steric hindrance.

Epimers and anomers

Epimers differ in configuration at one chiral center, excluding the newly formed anomeric center in the ring form.
Anomers differ specifically at the new chiral center (the anomeric carbon) created during cyclization.
- $α$ anomer: The anomeric $- O H$ is oriented opposite the $C H_{2} O H$ group.
- $β$ anomer: The anomeric $- O H$ is oriented on the same side as the $C H_{2} O H$ group.

Mutarotation is the interconversion between $α$ and $β$ forms in solution, which changes the observed optical rotation.

Hydrolysis of the glycoside linkage

Keto-enol tautomerism of monosaccharides

This tautomerism is not always prominent at physiological pH, but it helps explain aspects of sugar reactivity and interconversion.

Disaccharides

Sucrose: Formed by $α -glucose$ and $β$ -fructose linked at their anomeric carbons.
Lactose: Consists of β-galactose joined to glucose ( $α$ or $β$ ) through a 1→4 glycosidic bond.
Maltose: Composed of two glucose units connected via a dehydration reaction, typically $α -1,4$ linkage.

Polysaccharides

Starch: Predominantly $α -1,4$ glycosidic bonds linking glucose; used by plants for energy storage.
Glycogen: Similar to starch but with more frequent $α -1,6$ branches, making it a highly branched energy reserve in animals.
Cellulose (not mentioned above but commonly noted): Features $β -1,4$ linked glucose units, providing structural support in plant cell walls.

Aldehydes and ketones

These functional groups are important intermediates in organic synthesis because the carbonyl carbon is often reactive and can be converted into many other functional groups.

Nomenclature

Aldehydes typically end in “-al,” as in methanal (formaldehyde) or ethanal (acetaldehyde). Ketones generally end in “-one,” as in propanone (acetone) or butanone.

Common names are widely used, while systematic IUPAC names are based on the longest carbon chain containing the carbonyl group.

Physical properties

Many low-molecular-weight aldehydes and ketones are water-soluble because the carbonyl oxygen can accept hydrogen bonds from water.

Important reactions

Nucleophilic addition reactions at $C = O$ bond

Acetal, hemiacetal
When an alcohol reacts with an aldehyde or ketone, a hemiacetal or hemiketal forms first. With excess alcohol under acidic conditions, the hemiacetal can convert into an acetal, where two $- OR$ groups are attached to the same carbon.
Imine, enamine
A primary amine reacts with an aldehyde or ketone to form an imine, where the carbonyl oxygen is replaced by a double-bonded nitrogen. Secondary amines can form an enamine, where an α hydrogen shifts to give a $C = C - N$ linkage.
Hydride reagents
Reagents such as sodium borohydride ( $N a B H_{4}$ ) or lithium aluminum hydride ( $L i A l H_{4}$ ) deliver hydride to the carbonyl carbon. This reduces aldehydes to primary alcohols and ketones to secondary alcohols.
Cyanohydrin
Addition of hydrogen cyanide to a carbonyl forms a cyanohydrin, which has both a $- CN$ and an $- O H$ attached to the former carbonyl carbon.

Keto-enol tautomerism ( $α$ -racemization)
Aldehydes and ketones with an $α$ hydrogen can interconvert between keto and enol forms through proton shifts. This equilibrium can lead to racemization at the α carbon if that carbon is chiral.
Aldol condensation, retro-aldol
Enolates can attack other carbonyl compounds to form aldol products. Under some conditions, the aldol product dehydrates to form an $α$ , $β$ -unsaturated carbonyl. The reverse process, retro-aldol, breaks the bond formed in the aldol reaction and regenerates smaller carbonyl compounds.
Kinetic versus thermodynamic enolate
The kinetic enolate forms faster under conditions that favor the lowest activation energy (often low temperature with a strong, bulky base), typically by removing the most accessible proton. The thermodynamic enolate is more stable and is favored at higher temperatures or with weaker bases, typically giving the more substituted double bond.

Effect of substituents on reactivity of $C = O$ ; steric hindrance
Electron-withdrawing substituents increase the electrophilicity of the carbonyl carbon, making nucleophilic addition more favorable. Bulky substituents hinder approach to the carbonyl center and can reduce reaction rates.
Acidity of $α$ -H; carbanions
$α$ Hydrogens next to a carbonyl are more acidic than typical alkyl $C - H$ bonds because deprotonation forms a resonance-stabilized carbanion (the enolate). This increased acidity enables many aldol-type and related transformations in synthetic chemistry.

Carbohydrate Classification

Three main classes: monosaccharides, disaccharides, polysaccharides
All sugars end in “-ose”; prefixes like “deoxy” indicate $- O H$ replaced by $- H$
$α$ / $β$ specifies anomeric $- O H$ orientation relative to $C H_{2} O H$

Absolute Configuration (D/L)

Determined by the chiral carbon farthest from the carbonyl in open-chain form
D = $- O H$ on right (like D-glyceraldehyde); L = mirror image
Independent of R/S (Cahn-Ingold-Prelog) designation

Cyclic Structures

Cyclization forms hemiacetal (aldose) or hemiketal (ketose) via internal alcohol attack on carbonyl
Six-membered ring = pyranose; five-membered ring = furanose
Chair conformation more stable than boat due to reduced steric strain

Epimers and Anomers

Epimers: differ at one chiral center (not the anomeric carbon)
Anomers: differ only at the anomeric carbon ( $α$ vs. $β$ )
Mutarotation: interconversion between $α$ and $β$ forms in solution, changing optical rotation

Glycosidic Bonds and Hydrolysis

Glycosidic bonds link monosaccharides in di- and polysaccharides
Cleaved by acid or glycosidase enzymes

Keto-Enol Tautomerism in Sugars

Open-chain aldehyde/ketone form can convert through enediol intermediate
Allows aldose↔ketose interconversion, especially under basic conditions

Key Disaccharides

Sucrose: $α$ -glucose + $β$ -fructose (anomeric carbons linked)
Lactose: $β$ -galactose + glucose via $β$ -1,4 bond
Maltose: two glucose units via $α$ -1,4 bond

Key Polysaccharides

Starch: $α$ -1,4 linked glucose; plant energy storage
Glycogen: $α$ -1,4 with frequent $α$ -1,6 branches; animal energy storage
Cellulose: $β$ -1,4 linked glucose; structural role in plant cell walls

Aldehyde and Ketone Nomenclature

Aldehydes end in “-al” (carbonyl at chain end); ketones end in “-one” (carbonyl within chain)
IUPAC names based on longest chain containing $C = O$

Physical Properties

More polar than alkanes → higher boiling points; lower than alcohols (no H-bond donation)
Low-MW forms water-soluble via H-bond acceptance by carbonyl oxygen

Nucleophilic Addition at $C = O$

Electrophilic carbonyl carbon attacked by nucleophile; $π$ bond breaks
Key products:
- Hemiacetal/acetal: alcohol + aldehyde/ketone
- Imine: primary amine replaces $C = O$ ; enamine: secondary amine gives $C = C - N$
- Cyanohydrin: HCN addition gives $- CN$ and $- O H$ on former carbonyl carbon
- Reduction: $N a B H_{4}$ or $L i A l H_{4}$ delivers hydride → aldehyde→1° alcohol, ketone→2° alcohol

Oxidation

Aldehydes readily oxidized to carboxylic acids
Ketones resist oxidation under mild conditions

Enolate Chemistry

$α$ -H is acidic due to resonance-stabilized enolate carbanion
Keto-enol tautomerism can cause racemization at $α$ carbon
Aldol condensation: enolate attacks carbonyl → $β$ -hydroxy carbonyl; may dehydrate to $α, β$ -unsaturated product
Retro-aldol is the reverse; regenerates smaller carbonyl fragments

Kinetic vs. Thermodynamic Enolate

Kinetic: faster-forming, less substituted; favored at low temp with strong bulky base
Thermodynamic: more stable, more substituted; favored at higher temp or weaker base

Substituent Effects and Reactivity

Electron-withdrawing groups increase carbonyl electrophilicity → faster nucleophilic addition
Steric bulk slows nucleophilic approach to $C = O$

Carbohydrates

Nomenclature and classification, common names

Absolute configuration

Cyclic structure and conformations of hexoses

Epimers and anomers

Hydrolysis of the glycoside linkage

Keto-enol tautomerism of monosaccharides

Disaccharides

Polysaccharides

Aldehydes and ketones

Nomenclature

Physical properties

Important reactions

Nucleophilic addition reactions at C=O bond

Carbohydrates, aldehydes and ketones

Carbohydrates

Nomenclature and classification, common names

Absolute configuration

Cyclic structure and conformations of hexoses

Epimers and anomers

Hydrolysis of the glycoside linkage

Keto-enol tautomerism of monosaccharides

Disaccharides

Polysaccharides

Aldehydes and ketones

Nomenclature

Physical properties

Important reactions

Nucleophilic addition reactions at C=O bond

Nucleophilic addition reactions at $C = O$ bond

Nucleophilic addition reactions at $C = O$ bond