Week 12 Announcements Before the lab next week:

Read Experiment 10 - Aldol Pre-lab 10 Notebook Items Complete online Pre-lab 10 Experiment 8 & 9 Post-labs due next week You will check-out of lab next week after completing the Aldol lab See page 131 in the lab manual for details Final Exam scheduled for Monday, Nov. 30 from 7 to 9p Email me ASAP if this time is a conflict for you! (if you havent already)
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Formation of Enols and Enolates

from Aldehydes and Ketones
Acidic Conditions (Enol formation):
H O R(H) H H OH R(H)

enol
OH R(H) + H

The interconversion of two isomers via a proton and double bond shift is called tautomerization.

nucleophilic here

Basic Conditions (Enolate formation):

enolate
O R(H) H O R(H) + BH

The !-proton of the carbonyl is somewhat acidic because its conjugate base is resonance stabilized.

also nucleophilic here

The Aldol Condensation

aldehyde or a ketone In the aldol condensation, two molecules of an ____________________ !-hydroxycarbonyl combine to form a ____________________.
O H O H H O OH "

!-hydroxyaldehyde

new carbon-carbon bond

self-aldol In a ___________ condensation, two molecules of the same aldehyde or ketone react to form the product, like that shown above. crossed-aldol In a ______________ condensation, one molecule of an aldehyde or ketone reacts with a different aldehyde or ketone to form the product.

The Base Catalyzed Aldol Reaction Mechanism

O H + O NaOH OH O

O O H OH

enolate formation

O O H

addition

H O O

OH OH O + OH

proton transfer

Synthesis of trans-p-Anisalacetophenone
new carbon-carbon bond
O + H O O O O NaOH + H2O

acetophenone

p-anisaldehyde

trans-p-anisalacetophenone

Formation of !-hydroxyketone:

OH

1st Step
O

Followed by dehydration to give product:

O OH O + H O O OH

OH
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The Cannizzaro Disproportionation

2 R O H OH R O OH + R OH

A Redox Reaction

aldehyde

carboxylic acid

alcohol

The Mechanism:
O R H OH HO R O H

addition

HO R

O H R

O H R

O OH

hydride transfer

O R OH

~H+ + R O R

O O

OH

proton transfer

1H

NMR of trans-p-Anisalacetophenone
O H

integration
H O

coupling constant & integration multiplicity, integration & chemical shift

Remember, when assigning peaks in the NMR spectrum, start with the easiest assignments first.

Representative J-Values
O H

O
H H

H Ho

Hm

Hp

J = 6.5 - 8.5 Hz

J = 1.0 - 3.0 Hz

J = 0 - 1.0 Hz (often not observed)

Ha Hb Ha

Hb

Ha

Hb

0 - 3 Hz

11 - 19 Hz

6 - 11 Hz

!,"-Unsaturated Carbonyl Chemical Shifts

O H

J = 15.6 Hz

J = 15.6 Hz

!,"-Unsaturated Carbonyl Chemical Shifts

How can we tell which alkene proton is which?
O H" H! O H" H!

less shielded

more shielded

H beta to carbonyl

H alpha to carbonyl

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Aromatic Proton Chemical Shifts

Similar arguments can be made to distinguish the aromatic protons.
O H" H! O H" H! O H" H! O H" H!

H" H!

H" H!

H" H!

H" H!

Which aromatic protons are the most downfield (higher ppm)?

That is, which are the least shielded (lower electron density)?

!+ !+

!+ !+
O

!+

The partially positive positions on both rings are less shielded than the other positions.
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Aromatic Proton Chemical Shifts

O H" H! O H" H! O H" H! O H" H!

Which aromatic protons are the most upfield (lower ppm)?

That is, which are the most shielded (higher electron density)?
O

!" !"
O

The partially negative positions are more shielded.

!+ !+
O

!+ !+ !"

!"
O

!+

Use the above resonance arguments and electronegativity arguments to finish up the assignments.
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Putting It All Together...

The rest of the assignments are up to you.
!+ !+
O

!+ !+ !"

!"
O

!+

Use aromatic coupling information to help and to verify assignments.

H!

Hpara

H"

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For Next Week#s Lecture... Next weeks lecture will be a review session in preparation for the Final Exam.

Focus on Spectroscopy Come prepared with questions about any portion of the course Final Exam locations TBA next week A note on possible TA strike

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