Orgo Week 2. One Sick Summer

Front 1

This reaction type removes a halide, add some other group

Back 1

Substitution Rxn

Front 2

This removes a halide and an adjacent hydrogen atom to yield an alkene

Back 2

Elimination Rxn

Front 3

What is a beta hydrogen?

Back 3

In an ELIMINATION reaction. It is the hydrogen adjacent to the carbon that the halide attaches to. (alpha H is on same C, gamma is past beta).

The beta carbon is removed to make room for the alkene (double) bond.

Front 4

What is SN2?

Back 4

Substition
Nucleophilic
Bimolecular

Front 5

What is the bromine called here? (Add image)

Back 5

Leaving Group

Front 6

What is a bimolecular reaction?

Back 6

Two molecules are involved in the transition state.

Front 7

Nucleophile in SN2

Back 7

Something with a lone pair

Front 8

Electrophile in SN2

Back 8

Alkyl halide w/ sig* C-X antibonding orbital.

Front 9

Rate law for SN2

Back 9

It is bimolecular, first order in both reactants, second order overall.

Rate = k[CN-][R-X]

Front 10

This happens to the stereochemistry of all SN2 reactions

Back 10

INVERSION.

Nucleophile approaches from side opposite of the Carbon. The carbon is between the attacker and the leaving group.

This puts a new atom on the crowded hemisphere of the tetrahedron. Crowding is releived by inversion.

Front 11

What happens to the molecular geometry in the transition state of the SN2 attack?

Back 11

When the bond is halfway broken/halfway formed, the sp3 tetrahedral CARBON becomes SP2 TRIGONAL PLANAR.

Then, the geometry INVERTS.

Front 12

In a backside attack of SN2, what happens to R and S stereochemistry?

Back 12

The geometry of the bond inverts 100% of the time. Whether there is a change in R/S depends on the priority of the bonds.

Front 13

What are steric requirements of SN2 reactions?

Back 13

The backside attack into sigma* C-X antibonding orbitals requires access to the orbital.

Steric crowding restricts the ability for the nucleophile to attack.

Front 14

beta branching w/r/t SN2

Back 14

you can have a primary alkyl halide that has a lot of substituents on the beta carbon. These can severly restrict nucleophile access.

Front 15

What is the relative reaction rate of isopropyl bromide to methyl bromide?

What about t-butyl bromide?

Back 15

Isopropyl bromide is a secondary alkyl halide. There is some crowding in the nucleophile's target area and the reaction rate will be slower than methyl bromide.

tert-butyl bromide has a tiny target area and likely won't react.

Front 16

Describe a secondary alkyl halide.

Back 16

A halogen that isattached to a carbon. The carbon will have one hydrogen attached and two substituents.

Front 17

What makes the best nucleophile in SN2 reactions?

Back 17

It follows the electronegativity trend.

Front 18

Name some excellent nucleophiles in SN2 rxns.

Back 18

N///C-
H-S-
I-

Front 19

Name some "good" nucelophiles in SN2 rxns.

Back 19

HO-
Br-
-N=N=N-
H3N

Front 20

Name some "MODERATE/POOR" nucelophiles in SN2 rxns.

Back 20

Cl-
CH3COO-
F-
H2O

Front 21

Describe nucleophilicity in the context of electronegativity.

Back 21

Electronegativity affects the energy of the orbital. A more electronegative atom will want to hold on to it's electrons tighter, therefore creating a stronger bond with lower energy. Thus, an atom with higher electronegativity will generally be a poorer SN2 nucleophile.

Front 22

A stronger/poorer SN2 nucleophile is related to basicity

Back 22

False.

Front 23

Name some good SN2 Leaving Groups

Back 23

I-
Br-
Cl-
-OSO2R
H2O

Front 24

Name some POOR leaving groups.

Back 24

F-
HS-
-C///N
HO-
RO-

Front 25

SN2 Leaving Groups most important trend.

Back 25

Basicity. The weaker base will be the better leaving group.

Generally, anything that is a weak base is weaker than H2O.

Front 26

A strong base will be a _______ SN2 leaving group.

Back 26

Poor.

Front 27

Conjugate bases of strong acids are ________ leaving groups in SN2

Back 27

good

Front 28

Iodine is _____ nucleophile and a _____ leaving group in SN2. Why?

Back 28

Good / Good

Nu: is related to HOMO energy. LG is related to basicity.

Front 29

Mechanism of SN2

Back 29

Single step.
Nu: l.p. HOMO attacks sigma*R-X in "backside"

bimolecular.

Front 30

Stereochemistry of SN2 rxn

Back 30

NU: attacks sigma*C-X in "backside" behind the carbon.

As a result, "inversion" of stereochemistry.

Front 31

Three things affect the speed of a SN2 reaction.

Back 31

Steric effects
Nucleophilicity
Leaving-group ability

Front 32

Expand upon requirements for a rapid SN2 reaction.

Back 32

1. Steric: want to give the nucleophile access to the sigma*C-X with a methyl or primary halide.
2. Nucleophilicity - want high energy lone pair HOMO (C,S,P,I) with negative charge
3.) Leaving group: want very weak base (CB of strong acid)

Front 33

What does a negative charge do to orbital energy?

Back 33

It makes it higher.

Front 34

pKa of CH4

Back 34

48

Front 35

pKa of NH3

Back 35

35

Front 36

pKa of HC///CH, and what is this?

Back 36

Acetylene, 24

Front 37

Why is basicity a factor in leaving group ability in SN2?

Back 37

In an acid/base reaction, we are breaking a H-X bond into H+ and X-. the H-X bond strength turns out to be highly correlated to the C-X bond strength in alkyl halides.

Front 38

How does a primary alkyl halide have a poor SN2 reaction rate?

Back 38

Beta branching.

Front 39

pKa of MeOH

Back 39

16

Front 40

pKa of H2O

Back 40

16

Front 41

pKa of NH4+

Back 41

9

Front 42

pKa of HCN

Back 42

9

Front 43

pKa of H3COOH

Back 43

5

Front 44

pKa of H3O+

Back 44

-2

Front 45

pKa of HCl

Back 45

-7

Front 46

In E2, what stereochemistry must exist (in transition state) w/r/t the atoms being eliminated?

Back 46

Must be anti.

Front 47

What product results from syn conformation in E2 reaction?

Back 47

Nothing, the product is not observed. Eliminated atoms must be anti conformation. RB113

Front 48

Rate Law for E2

Back 48

It is single step bimolecular, so

Rate = k[B:-][R-X]

Front 49

What is E2

Back 49

Elimination, bi-molecular

Front 50

In E2, what two orbital interactions occur?

Back 50

First, the lone pair from the base nucleophile interact with sigma*C-H. This removes a proton but does not attach. RB114

Next, the electrons from sigma*C-H need to go somewhere - they interact with sigma*C-Br.

Thus, anti conformation is required for these to orbitals to overlap.

Front 51

RB115

Back 51

RB115

Front 52

An E2 reaction, 2-bromopentane yields 41% cis, 14% trans, and 25% terminal alkene. Explain the distribution and the missing 20%

Back 52

-more substituted alkenes are more stable, so terminal alkenes are less favored.

-for the cis alkene to form (given the anti conformation required) the target sigma*C-H bond is more restricted

-an SN2 reaction can occur for the other 20% because???

Front 53

Most important factor in SN2 reaction

Back 53

Good sterics. Typically a primary halide is best.

Don't overlook the sterics of the nucleophile. Big fat t-butoxide can have difficulty attacking a target because of size.

Front 54

Most important factor in E2 reaction

Back 54

Needs a strong base.

Front 55

Is OH- a good base?

Back 55

Yes