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Section: 20.2 What is the correct IUPAC name for the following?
H Cl O
O Br
a. (E)-7-bromohept-5-en-4-one
b. (Z)-7-bromohept-5-en-4-one c. (E)-1-bromohept-2-en-4-one d. (Z)-1-bromohept-2-en-4-one
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What would the resonance hybrid look like for this carbonyl?
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Consider the factors: resonance, induction, and sterics. Which should be MORE REACTIVE as an electrophile, aldehydes or ketones? Explain WHY.
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We want to analyze how nucleophiles attack carbonyls and why some nucleophiles react and others dont.
Example attack:
If the nucleophile is weak, or if the attacking nucleophile is a good leaving group, the reverse reaction will dominate.
Reverse reaction:
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If the nucleophile is strong AND NOT a good leaving group, then the full ADDITION will occur (Mechanism 20.1).
The intermediate carries a negative charge, so it will pick up a proton to become more stable.
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If the nucleophile is weak and reluctant to attack the carbonyl, HOW could we improve the electrophile? We can make the carbonyl more electrophilic:
Adding an acid will help. HOW?
Consider the factors that make it electrophilic in the first place (resonance, induction, and sterics).
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With a weak nucleophile, the presence of an acid will make the carbonyl more attractive to the nucleophile so the full ADDITION can occur (Mechanism 20.2).
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Acetone
Formaldehyde
Hexafluoroacetone
How do the following factors affect the equilibria: entropy, induction, sterics?
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Klein, Organic Chemistry 1e
To avoid the unstable intermediate with two formal charges, the reaction can be catalyzed by a base (Mechanism 20.3).
How does the base increase the rate of reaction? Will it make the reaction more product-favored?
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How does the acid increase the rate of reaction? Will it make the reaction more product-favored?
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Notice that the reaction is under equilibrium and that it is acid catalyzed. Analyze the complete mechanism (Mechanism 20.5) on the next slide. Analyze how the acid allows the reaction to proceed through lower energy intermediates.
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Klein, Organic Chemistry 1e
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After the hemiacetal is protonated in Mechanism 20.5, the water leaving group leaves. Instead, you might imagine an INTERMOLECULAR collision that causes the water to leave.
5 and 6-membered cyclic acetals are generally product favored How do entropy, induction, sterics, and Le Chteliers principle affect the equilibrium? 20 -23
Klein, Organic Chemistry 1e
Both the forward and reverse reactions are acid catalyzed. How does the presence of water affect which side the equilibrium will favor?
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Klein, Organic Chemistry 1e
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The mechanism requires an acid catalyst. Note that the optimal pH to achieve a fast reaction is around 4 or 5.
Why does the reaction slow down below pH 4? Why does the reaction slow down when the pH is greater than 5?
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Section: 20.6
5. What is the product(s) of the following reaction?
O NH2 [H+] -H2O
A.
HN
B.
C.
D.
HN
N H [H+] -H2O
A.
N
B.
N
C.
N
D.
N
Hydrazine attacks the carbonyl via Mechanism 20.6 to form the hydrazone, which is structurally similar to an imine. The second part of the mechanism is shown on the next slide (Mechanism 20.8).
Copyright 2012 John Wiley & Sons, Inc.
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A.
NH2
B.
NH2
C.
OH
D.
Avoid high energy intermediate with two formal charges Acid protonates leaving group so that it is stable and neutral upon leaving Last step of mechanism involves a proton transfer forming a neutral product
Overall: under acidic conditions, reaction species should either be neutral or have a +1 formal charge.
Copyright 2012 John Wiley & Sons, Inc.
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8. List the steps in order for each of the following types of mechanisms (steps may need to be repeated)?
A. B. C.
A. B. C. D. E.
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1. A thioacetal is formed via an acid catalyzed nucleophilic addition mechanism. 2. Raney Ni transfers H2 molecules to the thioacetal converting it into an alkane.
Recall the Clemmenson (Section 19.6) reduction can also be used to promote this conversion.
Copyright 2012 John Wiley & Sons, Inc.
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Reagents that produce hydride ions include LiAlH4 (LAH) and NaBH4. Hydrides will react readily with carbonyls.
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Will the reaction be more effective under acidic or under basic conditions? WHY? Show a complete mechanism (Mechanism 20.9). Analyze the reversibility (or irreversibility )of each step. Describe necessary experimental conditions. Why are there two steps in the reaction?
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Carbon doesnt often act as a nucleophile. WHY? What ROLE does carbon most often play in mechanisms? To be a nucleophile, carbon must have a pair of electrons it can use to attract an electrophile:
1. A carbanion with a -1 charge and an available pair of electrons. However, carbanions are relatively unstable and reluctant to form. 2. A carbon attached to a very low electronegativity atom such as a Grignard.
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1) CH3CH2CH3MgBr 2) H2O
A.
-O
B.
OH
C.
HO
D.
20.10 Cyanohydrin
The cyanide ion can act as a nucleophile.
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20.10 Cyanohydrin
Advantage: synthetic utility
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A.
HO CN
B.
NH2 HO
C.
OH HO O
D.
CN
Similar to the Grignard, one carbon is a nucleophile and the other is an electrophile.
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What factors allow the ylide to stabilize its formal negative charge? Why is the charged resonance contributor the major contributor?
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Klein, Organic Chemistry 1e
Which of the steps in the reaction is mostly likely the slowest? WHY? The formation of the especially stable triphenylphoshine oxide drives the equilibrium forward.
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To make an ylide, you start with an alkyl halide and triphenylphosphine. Example:
The first step is a simple substitution. The second step is a proton transfer.
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Overall, the Wittig reaction allows two molecular segments to be connected through a C=C. Example:
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Use a retrosynthetic analysis to determine a different set of reactants that could be used to make the target.
Copyright 2012 John Wiley & Sons, Inc.
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Section: 20.10
12. What is the product of the following reaction?
(C6H5)3P-CH2
A.
B.
C.
D.
20.11 Baeyer-Villiger
An oxygen is inserted between a carbonyl carbon and neighboring group. Mechanism 20.13 shows the movement of electrons.
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20.11 Baeyer-Villiger
Which step in the equilibrium is most likely the slowest? WHY? Note the last step is not reversible. WHY?
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MCPBA
A.
O
B.
O O
C.
O O
D.
O O
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Alternate Answer:
Section: 20.12 14. What is the correct order of reagents to achieve the following synthesis.
HINT: If the reactant has two isolated pi bonds when treated with a Wittig reagent, a mixture of products will form and the synthesis will fail (same problem if there are two carbonyl groups when performing a reaction that involves a carbonyl group). a. b. c. d. e. f. g. h. i. j. k. l. m. n. o. HOCH2CH2OH/H+ HSCH2CH2SH/H+ CH3NH2/H+ (CH3)2NH/H+ 1) LAH 2) H2O 1) CH3MgBr 2) H2O PCC, CH2Cl2 1) KMnO4, NaOH, heat 2) H3O+ 1) HCN/KCN 2) LAH 3) H2O CH3CH=PPh3 Dilute H2SO4 1) Hg(OAc)2, H2O 2) NaBH4 MCPBA TMSCl, Et3N TBAF
O
A. l, g, c B. l, g, d C. l, n, j, o, c D. j, l, g, c E. j, l, g, d
typical carbonyl
Aldehydes also give WEAK peaks around 27002800 cm-1 for the CH stretch.
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Klein, Organic Chemistry 1e
In the 13C NMR, the carbonyl carbon generally appears around 200 ppm.
Copyright 2012 John Wiley & Sons, Inc.
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