Class 3

Question 1

What kind of bond is made/broken in a substitution reaction?

Answer 1

One sigma bond exchanged for another sigma bond.

Question 2

What are the differences between an SN1 and SN2 reaction?

Answer 2

SN1:

Stereochemistry is not necessarily retained
Substitution occurs at primary center not tertiary

Question 3

How do nucleophiles attack and what does this cause?

Answer 3

“Concerted” backside attack. Causes the molecule to “flatten out” as one bond is forming while the other is breaking. This is a high energy “pentavalent” transition state.

Question 4

Do SN1 or SN2 reactions require a stronger nucleophile?

Answer 4

SN2

Question 5

In regards to carbon substitution, what is preferred for SN2 reactions?

Answer 5

CH3

Question 6

What is the rate law for SN2 reactions?

Answer 6

Rate = k[E+][Nu-]

SN2

Question 7

What solvent is used for SN2 reactions?

Answer 7

Polar, aprotic (e.g. acetone, DMSO, DMF)

Question 8

How can you turn OH into a good leaving group?

Answer 8

1. Acid catalyze to OH2+
   HCl is a popular acid for this
2. Replace with TslCl

Question 9

How many steps are in an SN1 reaction?

Answer 9

2!

1. Carbocation formation; this is the slow, rate-limiting step
2. Nucleophilic attack

Question 10

How many steps are in a SN2 reaction?

Answer 10

1! Concerted LG leaving/Nu attack

Question 11

How does a SN1 nucleophile attack?

Answer 11

Can attack on EITHER side of the p orbital (carbocation) so we get BOTH stereoisomers in the product

Question 12

In regards to carbon substitution, what is preferred for SN1 reactions?

Answer 12

3 -> 2 ->->->1 ->->-> CH3

Really only tertiary or secondary carbons will ever successfully form a carbocation intermediate. Poorly subtsituted carbocats. won’t be inductively stabilized enough

Question 13

What is the rate law for an SN1 reaction?

Answer 13

Rate = k[E+]

Question 14

What kind of nucleophile is desired for an SN1 reaction?

Answer 14

A relatively weak nucleophile is preferred

Question 15

What solvent is used for SN1 reactions?

Answer 15

Polar, protic (e.g. H2O, ROH)

Question 16

What are the two ways in which a carbonyl is reactive?

Answer 16

1. The carbonyl carbon is electrophilic

2. The alpha carbon is acidic

Question 17

What is tautomerization?

Answer 17

Rapid equilibration between structural isomers.

Question 18

If the MCAT asks for deuterium exchange using D2O, what are they asking you to find?

Answer 18

How many acidic hydrogens there are.

Think: hydrogens attached to alpha carbons

Question 19

What bonds are made/broken in a nucleophilic addition reaction?

Answer 19

1 pi bond becomes 2 sigma bonds.

Question 20

What precursor step do you need to do a nucleophilic addition with a weak nucleophile?

Answer 20

First acid catalyze carbonyl to an O-H bond, then nucleophile attacks

Question 21

Aldehyde and ketone reactants yield ______ and _______ _________, respectively. Via what type of reaction?

Answer 21

Primary and secondary alcohols.

Via reduction!

Question 22

What are common reducing agents of carbonyls?

Answer 22

1. NaBH4 or LiAlH4

2. Acid work up (H3O+)

Question 23

How do you form a Grignard Reagent?

Answer 23

CH3Br + Mg —–> (ether) Ch3MgBr

Question 24

What is a Grignard agent useful for?

Answer 24

Forming a new carbon-carbon bond using a carbonyl. The carbonyl will then become an OH in the acid work up step.

Question 25

If a nucleophile is on a more EN atom, is it a stronger or weaker nucleophile?

Answer 25

Weaker/worse cause that EN atom really likes to draw in and hold onto its electrons.

Question 26

What is an acetal and hemiacetal?

Answer 26

Acetal is a carbon bonded to OR and OR Hemiacetal is a carbon bonded to OR and OH

Question 27

How do you form a hemiacetal and acetal?

Answer 27

With a carbonyl: 1. H+ and R'OH Hemiacetal, do this once. Acetal, do this twice.

Question 28

How is an imine formed?

Answer 28

Forms when a primary amine (RNH2) is the nucleophile (attacks a carbonyl)

Question 29

How is an enamine formed?

Answer 29

Forms when a secondary amine (R2NH2) is the nucleophile (attacks a carbonyl)

Question 30

Do imines and enamines need to be acid catalyzed?

Answer 30

Yes

Question 31

What additional step is needed in forming an enamine?

Answer 31

Carbon must be deprotonated using water -> allows electrons from nitrogen pi bond to push up and alleviate positive charge on nitrogen.

Question 32

Can an enamine be nucleophilic?

Answer 32

Yes. The alpha carbon is acidic like an enolate

Question 33

What do you use to pull off the acidic H on an enolate, imine, enamine?

Answer 33

base

Question 34

What is the product of an aldol reaction?

Answer 34

beta-hydroxy carbonyl or an | alpha,beta-unsaturated carbonyl

Question 35

What is the difference between a kinetic enolate and a thermodynamic enolate?

Answer 35

Kinetic enolate is less substituted, less stable, but forms faster and at lower temperatures. Usually can be formed using a bulkier base. Thermodynamic enolates are more substituted, more stable, and forms at high temperatures with small bases.

Question 36

Are carboxylic acids highly polar and form many H bonds? What is the consequence of this?

Answer 36

Yes. Therefore have a high BP

Question 37

How can you reduce a carboxylic acid to a primary alcohol?

Answer 37

1. LiAlH4 | 2. H3O+

Question 38

How does a nucleophilic addition-elimination reaction work?

Answer 38

1. Nucleophile attacks a carbonyl thats also bound to an electronegative species, pushing electrons onto the oxygen 2. Electrons on oxygen push back down, kicking out the EN species.

Question 39

How can your form an ester?

Answer 39

Carboxylic acid + primary alcohol in acidic conditions

Question 40

What is saponification?

Answer 40

Using an ester and a strong base (like OH-) will form a carboxylate anion, kicking off OEt. The carboxylate anion can be made into a carboxylic acid with an additional acid work up

Question 41

What are some major carboxylic acid derivatives and what are there relative reactivities? What can be made into what?

Answer 41

1. Acid chloride 2. Acid Anhydride 3. Ester 4. Amide (in order from best to worst LG/reactivity) Anything in the above list can be made from anything below it.

Question 42

What makes a good leaving group?

Answer 42

A good leaving group has more stability in solution

Question 43

What does a transesterification do?

Answer 43

Swaps out R groups in an ester (--OR)

Question 44

Can you make an amide directly from a carboxylic acid and an amine? Why?

Answer 44

No because a proton transfer will occur first. The solution is to treat an amine with some other carboxylic acid derivative.

Question 45

How can you make a bad electrophile into a better one?

Answer 45

Protonate it to give it a + charge | OR make the nucleophile a stronger nucleophile by deprotonating it.