Unit 4 (Lesson 21-27)

Question 1

what facilitates nucleophilic substitution occurring on CAD

Answer 1

facilitated by the presence of a leaving group on the carbonyl carbon

Question 2

leaving group example

Answer 2

OR, Cl, NH2, OCOR

Question 3

not leaving group example

Answer 3

H, R, Ar

Question 4

reactivity of carboxylic acid derivatives is based on

Answer 4

1. leaving group ability of X
2. Electrophilicity of carbonyl carbon
3. Steric hindrance

Question 5

strongest resonance contributing structure has

Answer 5

negative O and positive N

Question 6

why are amides particularly ureactive toward nucleophilic attack

Answer 6

due to the resonance contribution from N

Question 7

order of reactivity of carbonyl derivatives (most to least)

Answer 7

acid chloride > anhydride > ester > amide > carboxylate

Question 8

reactivity of carboxylic acid derivative increases/decreases with decreasing basicity of leaving group

Answer 8

increases

Question 9

why is acid chloride not found in nature

Answer 9

because it is so reactive

Question 10

how do you make acid chloride from an acid/carboxylate

Answer 10

SOCl2, or PCl3

Question 11

do acid halides require any acid or base to facilitate substitution

Answer 11

no - already extremely reactive

Question 12

three different reaction perturbations with acyl halides

Answer 12

1.) negatively charged nucleophile
2.) neutral nucleophile
3.) neutral nucleophile with catalytic acid

Question 13

reactants for hydrolysis of an acid chloride

Answer 13

H2O
* deprotonate before kicking out Cl

Question 14

to from amide:

Answer 14

• at least 2 equivalents of amine must be used to push the reaction to completion
• add 1 equivalent of a primary or secondary amine AND one equivalent of a tertiary amine (pyridine)

Question 15

what are the methods for forming an anhydride

Answer 15

• from an acid halide
• from a carboxylic acid

Question 16

anhydride to ester

Answer 16

ROH(alcohol) or RO- + pyridine

Question 17

carboxylate/acid to an ester

Answer 17

ROH (alcohol)
H+ (catalytic acid)

[strong base/CH3Br, alc/pyridine] –> will work as well

Question 18

what controls the rate of reaction for the esterification of carboxylic acids

Answer 18

steric hinderance
- proceeds through a series of reversible steps

Question 19

carboxylic acids only undergo nucelophilic acyl substitution when they are in their () forms

Answer 19

acidic
WHY – basic form makes it resistant to an approach from an electrophile –> carboxylate ions less reactive than amides in nucleophilic acyl substitution

Question 20

why are esters not strongly electrophilic

Answer 20

due to the strong resonance contribution from the oxygen
– reactions with esters require better nucleophiles or stronger conditions than reactions with acid chlorides and anhydrides

Question 21

three different reaction perturbations for esters

Answer 21

1.) negatively charged nucleophile
2.) neutral nucleophile (must be good nucleophile)
3.) neutral nucleophile with catalytic acid

Question 22

the strength of the () and () determines the reaction conditions and mechanisms

Answer 22

electrophile, nucleophile

Question 23

transesterification

Answer 23

one alcohol is used in excess to drive the equilibrium in the desired direction

Question 24

basic conditions

Answer 24

no (+) intermediates

Question 25

acidic conditions

Answer 25

no (-) intermediates

Question 26

true/false: esters and carboxylic acids are around the same energy/reactivity

Answer 26

true

Question 27

will an ester and H2O molecule react

Answer 27

no -- needs an acid catalyst

Question 28

which of the carboxylic acid derivatives are unlikely to undergo a nucleophilic reaction with a Grignard reagent

Answer 28

amides and carboxylic acids WHY -- protic hydrogens

Question 29

true/false: addition to the ketone is faster than the addition to the ester

Answer 29

true

Question 30

true/false" addition to the aldehyde his faster than the addition to the ester

Answer 30

true

Question 31

DiBAL-H reduction of esters leads to what

Answer 31

aldehyde formation

Question 32

true/false: carboxylic acids can be reduced to primary alcohols with LiAlH4

Answer 32

true

Question 33

NaBH3CN

Answer 33

- selective - only reduces imines and enamines to secondary and tertiary amines

Question 34

amide to carboxylate/acid

Answer 34

1 eq HCl, H2O, heat or NaOH then H3O+, heat

Question 35

why are amides not very electrophulluc

Answer 35

due to the strong resonance contribution from the nitrogen -- recall 2 peaks for N-CH3's of an amide in an H1NMR due to the barrier of rotation around the C-N bond

Question 36

are amides stable

Answer 36

yes - very - due to excellent orbital overlap and resonance contribution

Question 37

what do reactions with amides require

Answer 37

very good nucleophiles and/or strong bases

Question 38

2 different reaction perturbations for amides

Answer 38

1.) negatively charged nucleophile 2.) neutral nucleophile with catlalytic acid/base and heat

Question 39

amide hydrolysis: acidic conditons

Answer 39

no negatively charged intermediates pattern of intermediates: (charge --> neutral --> charge)

Question 40

amide hydrolysis: basic conditions

Answer 40

no positively charged intermediates pattern of intermediates: (charge --> neutral --> charge)

Question 41

how can nitriles be transformed in to carboxylic acid

Answer 41

through hydrolysis or an amine via reduction

Question 42

true/false

Answer 42

the sp-hydridized carbon of a nitrile is moderately electrophilic and reacts with a strong base or in the presence of a strong acid c-c bond is made

Question 43

2 reaction perturbations for nitriles

Answer 43

1.) negatively charged nucleophile 2.) neutral nucleophile with acid (1.0 equiv) and heat

Question 44

fischer esterification only works if alcohol has less than () carbons

Answer 44

three

Question 45

electron withdraw from the carbonyl carbon increases/decreases its electrophilicity

Answer 45

increases

Question 46

true/false: the carbonyl carbon is electrophilic and is susceptible to nucleophilic attack under the right condittions

Answer 46

true