Pi bonds as Electrophiles: Reactions of Ketones and Aldehydes Flashcards
Aldehyde (Reaction Mech)
r-C(=O)-H
Ketone (Reaction Mech)
R-C(=O)-R
Carbonyl Groups as Electrophiles
Oxygen is more electronegative than carbon so a carbonyl (C=O) has a permanent dipole.
The resonance form has an incomplete octet on the C
Therefore, this (the carbonyl) is a great electrophile.
What are the 2 steps in a basic Nucleophilic addition to Electrophilic aldehydes and ketones?
Step 1: Nucleophilic attack
Step 2: Protonation to get an alcohol
Alkoxide
An ion with a negative formal charge on oxygen atom bonded to an sp3 carbon atom
What is the angle of the Nucleophilic attack and what does it do to the carbon being attacked?
105 degrees and converts the sp^2 carbon to a charged sp^3 carbon (aka an alkoxide)
Stereochemistry of Nucleophilic additions?
If all the groups including the nucleophile are different, then there is a chiral center with a R and S configuration
What is more reactive; aldehydes or ketones?
Aldehydes are slightly more reactive towards nucleophilic attack due to steric and electronic effects
Aldehydes greater reactivity due to steric strain
Aldehydes have only one substituent ( 1 R group and 1 H). The hydrogen atom is small and doesn’t create significant steric hindrance, making the carbonyl carbon more exposed and easier for nucleophiles (like a Grignard reagent or water) to attack.
In ketones, both substituents attached to the carbonyl carbon are larger alkyl or aryl groups. These groups create steric hindrance around the carbonyl carbon, making it more difficult for nucleophiles to approach and attack the carbonyl carbon.
Steric Hinderance
The prevention or slowing down of a chemical reaction due to the physical presence of bulky groups or atoms around a reaction center.
Aldehydes greater reactivity due to Electronic Effects
Electronic Effects
Refer to the way electron distribution in a molecule is influenced by the presence of different groups attached to a central atom. These effects can either increase or decrease the electron density at a reaction site, making it more or less reactive.
- Induction
- Resonance
Induction
This happens when atoms or groups attached to the central atom pull electron density away from or push electron density towards the reaction center via sigma bonds. This influence happens because different atoms have different electronegativity values, which determines how they attract or repel electrons in a bond.
Resonance Effect
This involves the delocalization of electrons through pi bonds or lone pairs, which can affect the electron density on a molecule.
Types of Nucleophiles - Carbon Types
- R-MgBr: The carbon is very nucleophilic because the Mg-Br bond is highly polarized, making the carbon highly electron-rich and reactive toward electrophiles
- R-Li: Lithium is highly electropositive, which makes the carbon in the R-Li bond very nucleophilic and reactive in addition reactions
- R-C≡C: The triple bond between carbon atoms in alkynes has a high electron density because of the multiple bonds between carbon atoms.
- Nitrile: has a triple bond between carbon and nitrogen. The carbon in the nitrile group is electron-rich and can act as a nucleophile in various reactions
Types of Nucleophiles - Hydrogen-Based
- Hydride donors (NaBH₄, LiAlH₄):
Sodium borohydride (NaBH₄) and lithium aluminum hydride (LiAlH₄) are strong nucleophiles that release hydride ions (H⁻)
These hydrides are highly nucleophilic and are often used in reductions, such as reducing aldehydes and ketones to alcohols.
Types of Nucleophiles - Oxygen-Based
- H2O; It donates electron density from the lone pairs on the oxygen to electrophilic centers.
- Hydroxide ion; Hydroxide ion (HO⁻) is a much stronger nucleophile than water, as the negative charge on the oxygen makes it highly electron-rich. Hydroxide ions are often involved in nucleophilic substitution and elimination reactions.
Grignard Reagents
important class of organometallic compounds that contains a carbon bonded to a Mg atom.
The carbon acts as a carbanion
Organometallic compounds
Families of compounds in which carbon is bonded to an electropositive metal.
Carbanion
negatively charged carbon
What solvent is used for Grignard reagents
Et2O
- it helps stabilize the very reactive reagents
Grignard properties and reactivity
They are very strong bases and will react with any acidic hydrogen (Oh, NH, SH, H2O…
Good nucleophiles with carbonyls (C-C bond forming reactions)
Organolithiums
Also react with carbonyls
- Strong bases
Hydrides (H-)
a H atom with increased electron density
- a nucleophilic Hydrogen
Hydride nucleophiles are
Carbonyl Reduction Reactions
Hydride sources for Carbonyl reduction reactions
NaBH4
- Mild sources
- usually uses alcohol solvents
LiAlH4
- Strong hydride source (more reactive)
- Reactions run in aprotic solvents life Et2O
Oxygen as Nucleophiles - Water
Water can react with aldehydes and ketones to form gem-diols (or hydrates) in a reversible reaction
Gem = Geminal
Atoms or functional groups attached to the same atom
Catalyzed Hydration Reactions
- Base-catalyzed hydration
- Acid-catalyzed Hydration
Base-catalyzed hydration
The hydroxide ion (OH⁻) attacks the alkene, adding an -OH group to one carbon of the double bond and a -H to the other.
-No carbocation intermediate
- Produces alcohol
Acid-catalyzed Hydration
The proton (H⁺) first adds to the alkene, creating a carbocation, and then water adds to this carbocation to form an alcohol.
- Carbocation intermediate
- produces alcohol (with Markovnikov’s rule
Carbocation
a positively charged species that contains a carbon atom with only six electrons in its valence shell instead of the usual eight, making it highly reactive and unstable.
Hemiacetals and Hemiketals
Hemiacetals and hemiketals are functional groups that form when an alcohol reacts with an aldehyde or a ketone, respectively
Markovnikov’s Rule
proton adds to the carbon with more H’s
How does catalysis occur in hemi-group formation
Acids or bases first protonate the ketone of aldehyde’s O, then protonation and finally deprotonation to reform the catalyst
Inter- versus Intramolecular Hemiacetals
Equilibrium
Acyclic hemiacetals are not favored
Cyclic hemiacetals are favored
Anomers
a specific type of stereoisomer that occur in cyclic sugars
They are formed when the carbonyl carbon (the anomeric carbon) in the sugar reacts with one of the hydroxyl groups on the same molecule, forming a cyclic structure. Anomers differ in the orientation of the hydroxyl group (OH) attached to the anomeric carbon.
