Unit 3

Question 1

Acid base properties of alcohols and ethers (deprotonated)

Answer 1

• alcohol —-> alkoxide (O-R-) when deprotonated
• water —-> OH-

Question 2

Deprotonation requires what

Answer 2

• very strong bases (stronger than NaOH)
• eg LDA, NaH, NaNH2

Question 3

Alcohols and ethers acid-base (when protonated)

Answer 3

Ethers —-> OHR2+
Alcohols —-> OH2R+
Oxonium

Question 5

How to convert a Oxygen leaving group into a good one

Answer 5

• protonate it - which ‘activates’ it.
• (eg oxonium ion)
• protonate using a very very strong acid
• eg HCl/HBr/H2SO4

Question 6

Strong acid andn alcohol/ether synthesis mechanisms

Answer 6

Methyl - sn2
1- sn2/e2
2- sn1/e1
3- sn1/e1
For 2 and 3 carbocation rearrangements are possible

Question 8

What happens with more hindered (so primary branched and secondary electrophiles) if we want a substitution product?

Answer 8

• we cannot use strong bases anymore, as E2 will dominate.
• are capable of sn2 - so will need a STRONG Nu and weak base.

Question 9

Points for ‘masked hydroxide synthesis for alcohols’

Answer 9

• works for 1 hindered and secondary electrophiles
• uses a weak base and good Nu (so uses NaOAc, sodium acetate) - deprotonated COOH

Question 10

Why is NaOAc a weak base, good u?

Answer 10

• good Nu because negative charge on O
• however, weak base because charge is delocalised across resonance in C=O bond, charge is not trapped.

Question 11

‘Masked’ hydroxide synthesis for alcohols from haloalkane steps

Answer 11

1 - Sn2 (make sure to show inversion)
2 - SnAc mechanism - you cleave the formed ester, then ‘unmask’ the OH (meaning that that C-O bond is broken, then that OH will be exposed, using NaOH for ester hydrolysis)

Question 12

SnAc mechanism overview and characteristics

Answer 12

• causes substitution at a carbonyl group
• mechanism for esters and carboxyllic acids
• carbonyl is always the electrophile - single bonded O group is LG
• C=O bond offers a new a LUMO - which means a new mechanism

Question 13

HOMO (Nu) and LUMO (E-LG) for SnAc mechanism

Answer 13

• O sp3 orbital (in the OH Nu)
• C-O pi star orbital, which breaks the pi bond first.

Question 14

If we are adding NaOH back in for the SnAc mechanism, then why doesn’t it go through E2? OH- is a strong base!

Answer 14

• because of the LUMO - presence of pi bond opens possibility of breaking that first instead of sigma bond
• that C-O LUMO more energetically favorable for Nu.

Question 16

Alcohols and ethers with strong acid makes what

Answer 16

• water LG
• methyl or primary: Sn2/E2
• secondary/tertiary: Sn1/E1

Question 17

How to classify acid for the mechanism?

Answer 17

Elimination: non-nucleophillic acid (eg H2SO4)
Substitution: nucleophillic acid (eg HCl)

Question 18

Complications using H-X in alcohols

Answer 18

• carbocations can form at secondary and tertiary, possible rearrangements possible
• this may generate multiple stereoisomers - multiple products
• HX can react with multiple functional groups

Question 20

Alcohol activation reagents and their effects (4)

Answer 20

• nucleophilic acid, (HBr, HCl) - rearrangements, forms carbocation with secondary and tertiary products
• PCl3/PBr3 - sn2, so inversion
• Pyridine, SOCL2 - SnAc, sn2, inversion
• Sulfonyl Chlorides and pyridines, SnAc, no change at inversion

Question 21

Epoxides act most as?

Answer 21

• electrophiles

Question 22

How to make an epoxide

Answer 22

• Halohydrin starting material (intramolecular Williamson ether synthesis)
• strong base to convert alcohol to alkoxide species (eg NaH, OH-)

Question 23

How do epoxides open under basic/nucleophillic conditions?

Answer 23

• in basic conditions, Nu attacks the less substituted side.
• going to open with an Sn2 mechanism - needs good Nu.

Question 24

Points for hydride and organometallic Nu

Answer 24

• reagents are VERY strong bases and good Nu
• Use ether solvents, no protic solvents
• ALWAYS Sn2

Question 28

Reactivity of carbonyls under reversible conditions (6)

Answer 28

- OH- acts as a base - pKa of OH- is going to be very similar to a carbon - OH- deprotonates, doesn’t touch the C=O, but forms a carbanion. - resonance stabilized species formed, which makes the a C rather acidic. - the carbanion acts as a nucleophile - stronger resonance contributor is when there is a C=C bond and O has negative charge.

Question 30

Tautomers

Answer 30

- constitutional isomers that differ in the location of a pi bond and a H atom. - Tautomerization: interconversion between tautomers

Question 31

Generating enolate nucleophiles (basic conditions)

Answer 31

- OH- acts as a base, deprotonates C on the end, breaks C=O bond, forms stronger resonance contributor with C=C and O- - this enolate species can now act as a nucleophile

Question 32

Generating enol nucleophiles (acidic conditions)

Answer 32

- carbonyl O first deprotonates whatever strong acid is available (activating carbonyl) - weak base then goes in, attacks H on C-H bond, arrow goes from C-H to C-C bond, then double bond breaks (C=O) - forms enol species which is just an enolate with a OH instead of O-.