Nucleophilic substituions = SN1 and SN2

Question 1

nucleophile always attacks the ______

Answer 1

electrophile

Question 2

Explain what the Transition state is:

Answer 2

theoretical representation of the high energy point between starting materials and products. It does not physically exist

(a moment when a bond is forming and breaking)

Question 3

How many steps in the Sn2 reaction?

Answer 3

1 with NO intermediate formation

Question 4

What is SN2?

Answer 4

Substitution Nucleophilic Bimolecular reaction

Question 5

Bimolecular reactions

Answer 5

two species are involved in the rate determining step (slowest step of a reaction)

Question 6

What is involved in the rate-limiting step?

Answer 6

BOTH - Nucleophile and electrophile

Question 7

Transition state: bond to the nucleophile (hydroxide) is partially ______ and the bond to the leaving group (bromide) is partially _______

Answer 7

formed
broken

Question 8

Omeprazole is a….

Answer 8

proton pump inhibitor that decreases the amount of acid produced in the stomach

Question 9

Factors Affecting SN2 reaction: nucleophile

Answer 9

1) strength of nucleophile
2) Nucleophilicity increases
3) Nucleophilicity decreases
4) Bulkiness of the nucleophiles

Question 10

define Basicity

Answer 10

the equilibrium constant for abstracting an acidic proton;
forms a new bond to a proton, it has reacted as a base

Question 11

define Nucleophilicity

Answer 11

the rate of attack on an electrophilic carbon atom;
forms a new bond to carbon, it has reacted as a nucleophile

Question 12

1. strength of nucleophiles

Answer 12

Species with negative charge: stronger nucleophile than a similar neutral species. Base is a stronger nucleophile than its conjugate acid

Question 13

2. Nucleophilicity decreases

Answer 13

from left to right in the periodic table, following the increase in electronegativity (tightly held non-bonding electrons that are less reactive toward forming new bonds)

Question 14

3. Nucleophilicity increases

Answer 14

down the periodic table, following the increase in size and polarizability (more electrons far from the nucleolus)

Question 15

e- are more ______ held > move more freely toward a +ive charge > stronger bonding, enhancing atom’s ability to begin to form a bond at a relatively long distance

Answer 15

loosely

Question 16

4. Bulkiness of Nucleophiles

Answer 16

Nucleophile: an ion or a molecule must get close to a carbon atom to attack it

Bulky groups on the nucleophile hinder this close approach, slow the reaction rate

Question 17

What is a steric hindrance?

Answer 17

he slowing of chemical reactions due to steric bulk

manifested in intermolecular reactions, whereas discussion of steric effects often focus on intramolecular interactions

exploited to control selectivity, such as slowing unwanted side-reactions

Question 18

Protic solvents meaning and characteristics?

Answer 18

OH/NH groups (i.e. alcohols)

H-bonds to negatively charged nucleophiles

Very good in solubilising reagents

Question 19

Aprotic solvents meaning and characteristics?

Answer 19

without OH/NH groups (i.e. hexane).

Enhance nucleophilicity of anions

Anions are more reactive

Relatively weak solvating ability

Question 20

POLAR aprotic solvents: no OH or NH

Answer 20

Enhance solubility
Acetonitrile, dimethylformamide (DMF), acetone, and dimethyl sulfoxide (DMSO)

From alcohol to DMSO often enhances the rate of an SN2 reaction

Reverse the nucleophilicity order (F->Cl-…)

Question 21

Factors Affecting SN2 reaction: substrate

Answer 21

Leaving-Group Effects on the Substrate

Polarise C-X bond (making the carbon atom electrophilic)

Leaves with the pairs of electrons

Question 22

Factors Affecting SN2 reaction: substrate
name 2

Answer 22

1. Electron withdrawing: polarise the carbon atom and stabilises the negatively charged transition state. Halogen, oxygen, nitrogen, sulphur
2. Stable once has left:
   weak base (i.e. Cl-, Br-, I-), so conjugate bases of strong acids (i.e. HCl, HBr, HI)

Question 23

______ bases are poor leaving groups

Answer 23

strong
(-OH/-NH2)

Question 24

neutral molecules can be good leaving groups example =

Answer 24

H2O, alcohols, amines

+NMe3 > TsO- > I— > Br — > +OH2 > Cl— > F— > OH—

Question 25

REMEMBER - not only halogens are _____ leaving group and not only ____ species are formed

Answer 25

good
negative (-ive)

Question 26

the Sn2 reaction is highly dependant on the structure of the ________

Answer 26

electrophile

Question 27

steric_____ of the electrophile influences the mechanism of the reaction

Answer 27

bulk

Question 28

different names fir the steric effects on the substrate:

Answer 28

a) Methyl derivative - 3H group
Very Fast

b) Primary Carbon - 1 diff group + 2H
Fast

c) Secondary Carbon - 2 diff group +1H
Slow

d) Tertiary Carbon - 3 diff group
SN2 Not Possible!

Question 29

the more different groups are in the compound; the ______ the reaction.

Answer 29

slower

Question 30

To avoid side-effects from unwanted isomers you recommend to a drug development researchers that only the RR isomer of Labetalol should be _______

Answer 30

available

Question 31

SN1 reaction
Reaction-rate:

Answer 31

does not depend on the concentration of the nucleophile but depends only on the concentration of the substrate (electrophile)

Question 32

What type of reaction is SN1?

Answer 32

Substitution Nucleophilic, Unimolecular reaction

Question 33

Unimolecular reactions:

Answer 33

only one specie is involved in the rate determining step (defined as the slowest step of a reaction)

Question 34

steps of SN1
3 steps

Answer 34

Step 1: Formation of carbocation (rate limiting)
Step 2: Nucleophilic attack on the carbocation
Final Step: Loss of proton to solvent

Question 35

what type of reaction is an SN1 reaction?

Answer 35

racemisation

Question 36

Factors Affecting SN1 reaction: substrate = Substituent effect

Answer 36

EASIER the formation of the carbocation intermediate, the faster the SN1 The MORE STABLE the carbocation, the faster the SN1

Question 37

➜Lots of electron density

Answer 37

+ve charge stabilised

Question 38

➜low electron density

Answer 38

+ve charge poorly stabilised

Question 39

bulk effects in SN1

Answer 39

tertiary - fast SN1
Secondary Intermediate
Primary - SN1 Not possible

Question 40

Resonance stabilisation

Answer 40

carbocation promotes the SN1 reaction

Question 41

Leaving-Group Effects: weak base

Answer 41

very stable after it leaves with the pair of electrons that bonded it to carbon

Question 42

Protic solvent

Answer 42

polar solvents stabilise ions, therefore favour SN1. H2O, alcohols

Question 43

Carbocations often rearrange to form more ______ carbocations

Answer 43

stable

Question 44

The rearrangement could involve a –CH3 group (movement of a methyl group)
to give a ______ ______

Answer 44

Methyl shift

Question 45

Test yourself:

Answer 45

One step
Favours strong nucleophiles
Racemizes stereochemistry
Could involve carbocation rearrangements
Has a carbocation intermediate
Best in protic solvents (Water, alcohols..)
Two steps
Inverts stereochemistry
Best in aprotic solvents