Chemistry Chapter 11: Organic Reaction Mechanisms Flashcards
SN1 is what rate order
First rate order, depends on substrate concentration only
What are the steps of the SN1 mechanism?
Step 1: formation of a carbocation (slow)
Step 2: nucleophilic attack (fast)
Anything that increases the stability of the _________ in an SN1 reaction will increase the rate of reaction
Carbocation
In SN1, what is the substitutent on carbon?
Tertiary > secondary (primary won’t work)
How many steps in SN1?
2
Key mechanism in SN1
Carbocation stability
Strength on nucleophile for SN1
Doesn’t matter- can be weak
Solvent for SN1
Polar protic
Stereochemistry for SN1
Not preserved (racemic)
Key mechanism in SN2
Steric hindrance
Rate law dependence for SN2
Bimolecular (substrate and nucleophile concentrations)
Number of steps for SN2
1
Substituents on carbon (SN2)
Methyl (best) > primary > secondary
Strength of nucleophile for SN2
Strong (and non-bulky)
Solvent for SN2
Polar aprotic
Polar aprotic solvents are polar solvents that lack acidic protons and cannot form hydrogen bonds
Stereochemistry for SN2
Inverted (backside attack)
Solvents that can donate a proton
Polar protic (ie OH or NH) water, ethanol etc. polar protic engage in hydrogen bonding to the leaving group which stabilizes the carbocation
Solvent that contain a permanent dipole due to a polar bond (typically C=O) but can’t act as hydrogen bond donors
Polar aprotic solvents. Used in SN2 reactions, such as acetone and DMSO
In carboxylic acids, what is typically the electrophile and why?
C=O carbonyl carbons (because the oxygen has a partial negative charge and the C has a partial positive charge). The OH group makes the carbonyl carbons even more subject to nucleophile attack
Fischer Esterification
An example of nucleophile substitution at a carboxylic acid group.
An acid-catalyzed technique for turning a carboxylic acid into an ester.
You replace the OH group of the COOH carboxylic acid with the OR functional group characteristic of an ester
How to perform an Fischer Esterification
Carboxylic acid is mixed with an alcohol under acidic conditions
Steps of an Fischer Esterification
1) pronation of carbonyl O
2) nucleophilic addition by alcohol
3) Proton transfer x 2
4) OH2 group leaves
6) deprotonation by base
7) ester formed
Fischer Esterification can be reversed by
Hydrolysis
Imine formation is what type of reaction
Nucleophile substitution
Describe Imine formation
Occurs at carbonyl carbon (NOT a carboxylic acid group)
1) protonation of carbonyl oxygen
2) nucleophilic attack of the nitrogen atom of the amine and joins carbonyl carbon and amine to form tetrahedral intermediate
3) Proton transfer from amine to OH group
4) N lone pair attacks to form double bond and H2O leaves
5) N is deprotonated to remove positive charge
Schiff’s base
An Imine with an additional carbon substituent (C=N-R)
Hemiacetals formed from
Nucleophillic addition reactions at carbonyl carbon (aldehydes)
Hemiketals are formed how?
Nucleophillic addition at carbonyl carbon of ketones
How to form acetals and ketals?
Repeat reaction with excess alcohol
Nucleophillic addition reactions
Nucleophilic attacks carbonyl carbon without a leaving group
Keto-enol tautomerism can be catalyzed by either
Acid or base, alpha hydrogen is critical in both
When is the alpha hydrogen removed in a base catalyzed mechanism vs acid catalyzed mechanism for keto-enol tautomerism?
First step for base, second step for acid
What is enolate chemistry?
Resonance stabilized negative charge on alpha carbon allows carbon to be a nucleophile
What are 4 reactions that involve enolates
Aldol condensation
Retro-aldol
Michael addition
Robinson Annulation
Aldol Condensation
Nucleophilic alpha carbon attacks electrophilic carbonyl C to form a new C-C bond, forming aldol which then continues to react to form a alpha-beta unsaturated ketone
Retro-Aldol
Reverse of the Aldol condensation process
Michael Addition
An enolate attacks the beta carbon of a alpha, beta unsaturated aldehyde/ketone resulting a compound containing a1,5 di carbonyl
Robinson Annulation
Michael addition followed by an Aldol condensation
Steps of a base-catalyzed aldol condensation
1) Enolate attack
2) deprotonation
3) Reduction
4) Reprotonation
The substrate for SN2 reactions occur BEST if it’s
Methyl, primary or secondary
Secondary substrates would undergo
SN1 OR SN2
A double bond to an oxygen becomes a double bond to a nitrogen following a nucleophilic attack on a carbonyl carbon creates what
Imine
What is DMSO and what reactions is it used for?
DMSO is a polar aprotic solvent used in SN2 reactions
What is LDA and what is it used for?
LDA (lithium diisopropylamide) is a strong, bulky base. It is used because its steric hindrance minimizes unwanted side reactions, making it ideal for reactions requiring precise control, such as
Kinetic enolate formation (favoring the less-substituted alpha-carbon)
How do you create a kinetic enolate?
-formed most quickly, less stable long term
-rapid, irreversible
-low temp
** use a strong bulky base like LDA
-double bond formed on the less substituted
What are the characteristics of a thermodynamic enolate?
-slower to form but more stable long term
-need higher temp
-use a weak, less bulky base
-reversible
-double bond forms on the more substituted carbon
Methoxide (NaOCH3) is a strong or weak base?
A strong base
Base-catalyzed Aldol condensation involves an enol or enolate?
Enolate
Acid catalyzed adol condensation involves an enol or enolate?
Enol
If using a ketone for adol condensation, what do you have to look out for?
Multiple products form because the alpha hydrogens are not identical
What does a Michael addition result in?
Enolate attacks a alpha beta unsaturated ketone to form a compound with a 1,5- dicarbonyl group
What does the Robinson Annulation result in?
Michael addition followed by an Aldol condensation results in a alpha beta unsaturated ketone which is cyclic
Robinson Annulation is important in the formation of what
Steroid hormones because this reaction forms a ring structure
How do you perform a cross-Aldol reaction?
1) start with 1 aldehyde or ketone to create an enolate
2) add a strong hindered base such as LDA
3) add the second aldehyde or ketone
This is a mixed aldol condensation reaction
The catalytic base will take THE MOST ACIDIC hydrogen (found on the alpha carbon between the 2 ketones- most acidic because the conjugate base is the most stable)
The carbonyl carbon of the cyclopentanone will act as an electrophile, and undergo nucleophilic attack from the alpha carbanion forming a double bond after removal of the water from the intermediate. This gives us a cyclopentane double bonded to the carbon between the two carbonyls groups.
In aldol condensations, a bond is formed between which two carbons?
the alpha carbon of one molecule (bearing an enolate ion) reacts with the carbonyl carbon of another molecule to form a new carbon-carbon bond.
Enols vs enolates
Enolates have a charge
SN1 uses what kind of solvent and why?
Polar protic solvents because they stabilize the carbocation intermediate and solvate the leaving group, facilitating its departure.
SN2 uses what kind of solvent and why?
polar aprotic solvents because they do not solvate the nucleophile, keeping it strong and reactive for the backside attack.
