Sampler to AGOCM.pdf - Curved Arrow Press

56 Pages·2008·1.73 MB·English

A Sampler to
A Guide to
Organic Chemistry Mechanisms
A Guided Inquiry Workbook
Easy to Follow Curved Arrows
This sampler contains problems from all chapters. It uses topics common to organic
chemistry textbooks and no additional introduction is provided. Therefore, you should
recognize the subject matter and its similarity to your textbook.
In Part A, you simply need to add the curved arrows or predict the equilibrium for acid-
Peter Wepplo
base reactions.
In Part B, you will need to add the intermediates or products as well as the curved arrows.
In Part C, you will need to write a complete mechanism. The problems are the same
problems, but written in a manner quite similar to your textbook. If you have diffi culty
with Part C, then you will have diffi culty with the problems from you textbook as well.
You should return to Parts A or B to practice the mechanism.
Part D give a completed mechanism.
Curved Arrow Press
The Notes are not the complete notes for the sampler, they are simply representative of
Princeton, New Jersey
notes that are present in A Guide to Organic Chemistry Mechanisms.
A Sampler to
A Guide to
Organic Chemistry Mechanisms
A Guided Inquiry Workbook
Easy to Follow Curved Arrows
Peter Wepplo
Curved Arrow Press
Princeton, New Jersey
ISBN-10: 0-9779313-0-7
ISBN-13: 978-0-9779313-0-9
Copyright © 2008 Peter Wepplo. All rights reserved.
Printed 2008

No part of this work may be reproduced, or transmitted in any form
or by any means, electronic or mechanical, including photocopying
and recording, or by information storage or retrieval system
without the prior written permission of Peter Wepplo.

An exception is granted to the original registered purchaser of
this book from Curved Arrow Press or agents on its behalf. That
purchaser may photocopy pages for personal use. This allowance
does not transfer upon resale, loan, or any other manner of
acquiring the book from any other source.

Address inquiries to P. Wepplo,
[email protected]
45 Wilton St., Princeton, NJ 08540
Printed in the United States of America
10 9 8 7 6 5 4 3 2
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
1 — Getting Ready for Reactions
Guide to Drawing Resonance Structures
Resonance Structures
If you are unfamiliar with the use of the curved arrow, refer to the discussion in the Notes section. A good place to start pushing
electrons is in drawing resonance structures. They have the elements of electron movement, but the problems will be more limited
in scope.
Resonance Structures of Anions
The principle for understanding resonance structures is to understand that electrons will operate by a push-pull mode or model. If
there’s a net negative charge, it will be the electrons of the atom with the negative charge that will push toward the pi bond. We will
start our curved arrow with those electrons. Continue to move them toward any neighboring pi bonds (push) to create and break new
bonds. You should note that two curved arrows are required to avoid structures with more than eight valence electrons.
For the following examples, add curved arrows, where needed, to show how the electrons move to form the next structure. For 1-6,
the first and last structures are the same. In that case, you are converting it back to the starting structure.
1.
O O O O O O
C C C
H H H
2.
H2C O H2C O H2C O
C C C
H H H
2 -Acid-Base Chemistry
1. For this example, the acids and bases are labeled. HF is the strongest acid as it has the lower pK. Therefore, F-, its
a
conjugate base, is the weakest base.
O O
+
H3C C O H F H3C C O H + F
Base Acid Conjugate Acid Conjugate Base
L/R pK 3.2 pK 4.75 weakest base
a a
Notice the curved arrows. They describe the reaction that is taking place. We could write the following sentences to describe
the curved arrows.
A bond is being made between the oxygen and hydrogen atom with the electrons from the oxygen atom.
A bond is being broken between the hydrogen and the fluorine atom with the electrons remaining attached to the fluorine
atom.
3.
H
+
H O H + H F H O H F

L/R weakest base pK 3.2 pK -1.7
a a
Part A - Page 1
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
4.
H
H S H + H N H H S + H N H
H H

L/R 7.0 weakest base 9.2
3 - Substitution Reactions
S 2 Substitution Reactions
N
1. An S 2 reaction of 1-chlorobutane with sodium iodide to give 1-iodobutane. (See Notes.)
N
I
I
H3C H H3C
H H
Cl H
Cl
2. An S 2 reaction of 1-chlorobutane with ethoxide to give 1-ethoxybutane (butyl ethyl ether). (See Notes.)
N
O Et
CH3 H CH3 O Et CH3
H
H
H
Cl Cl 91% 9%
S 1 Substitution Reactions
N
20. An S 1 solvolysis reaction of t-butyl iodide to give t-butyl alcohol. (See Notes.)
N
H H
CH3 (H2O) CH3 O H CH3 H O H CH3
CH3 C I CH3 C CH3 C O CH3 C O
CH3 I CH3 CH3 H CH3 H
H3O
21. An S 1 solvolysis reaction of (R)-(1-chloroethyl)benzene to give rac-1-phenylethanol.
N
H H
dioxane-
O H O H
H2O
CH3 CH3 CH3 CH3
H
Cl H Cl H H O H3O H O
H H
4 — Elimination Reactions
Alkene Formation
1. An E2 elimination reaction of hydrogen chloride from 1-chlorooctadecane with potassium t-butoxide to give 1-octadecene.
(See Notes.)
CH3
O CH3
H H CH3
C15H31 C15H31 C15H31 O-t-Bu
Cl H O t-Bu Cl 86% 14%
Part A - Page 2
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
3. An E2 elimination reaction of 2-bromo-2-methylbutane to give 2-methyl-2-butene, a Zaitsev product.
OCH2CH3
H H
CH3 CH3
CH3 CH3 CH3
CH3 Br HOCH2CH3 Br CH3 CH3
71% 29%
10. An E1cb elimination reaction of 3-chloro-3-methylcyclohexanone with t-butoxide to give 3-methyl-2-cyclohexenone. (See
Notes.)
O O O
O t-Bu
H
H
H
CH3 CH3
Cl HO t-Bu Cl Cl CH3
Acetylene Formation
20. A synthesis of 3-hexyne from trans-3-hexene by bromination and two elimination reactions. (See Notes.)
NH2 NH2
Br2
Br
Et C C Et
H H
Br2 Chap. 5.13 Br H NH3 Br Br NH3 Br
syn
elimination
Br Et slow
Et H Et H
NH2
H Et Br H
Br Br
5 — Electrophilic Addition to Alkenes and Alkynes
Addition of HX and H O to Alkenes
2
1. Addition of hydrogen bromide to propene to give 2-bromopropane. (See Notes.)
H Br Br
H H H
Br
C C C
H3C CH2 H3C CH3 H3C CH3
Br
7. Addition of hydrogen bromide to 3-methyl-1-butene to give after rearrangement, 2-bromo-2-methylbutane. (See Notes.)
Br
H H Br H H H H Br H3C CH3
H CH3 55%
H3C CH2 H3C CH3 H3C CH3
CH3 CH3 CH3 Br
Br IIo carbocation IIIo carbocation
CH3 CH3
CH3 45%
Part A - Page 3
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
10. Addition of hydrogen chloride to 2-methyl-1,3-butadiene (isoprene) to give, 3-chloro-3-methyl-1-butene, the kinetic product,
or 1-chloro-3-methyl-2-butene, the thermodynamic product. (See Notes.)
Cl
CH3 CH3 Cl
CH2 CH2
H Cl CH3 CH3
CH3 IIIo greater contributor Kinetic product
CH2
H2C
Cl Cl
CH3 CH3
CH2
CH3 CH3 Cl
Thermodynamic product
15. Bromination of methylcyclohexene to give (1R,2R)- and (1S,2S)-2-bromo-1-methylcyclohexanol. (See Notes.)
H
CH3 Br Br Br CH3 fast Br CH3 HO H Br CH3 O H HO H Br CH3 O H
Br Step intermediate H3O
21. Addition of bromine to ethynylcyclopentane to give (E)-(1,2-dibromovinyl)cyclopentane and (1,1,2,2-tetrabromoethyl)
cyclopentane. (See Notes.)
Br
Br Br Br Br Br
fast
C C H C C H C C H C C H
Br
Br
6 — Rearrangement Reactions
Baeyer-Villiger Oxidation
1. Acid catalyzed Baeyer-Villiger oxidation of 2,2-dimethylcyclopentanone with peracetic acid. (See Notes.)
H O O O
H H O O H O
O H O O O H
O O O O
H H H
cont'd
H2O
O H
O O
H H
O O
cont'd
O
H H3O
O
Part A - Page 4
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
7 — Electrocyclic Reactions
Diels Alder Reactions
1. A Diels-Alder reaction between 1,3-butadiene and 2-propenal (acrolein).
d d
O O
22 11 b cH 2 1 b cH
33 a 3 a
44 4
8. A reverse-forward Diels-Alder reaction between cyclopentadiene and maleic anhydride.
O O
H
heat
O O
H
O O
8 — Carbonyl Addition and Addition-Elimination Reactions
Grignard Addition to a Carbonyl Group
1. Addition of methyl magnesium bromide to cyclohexanone to give 1-methylcyclohexanol (for formation of Grignard reagents,
see Notes).
Step 1 Step 2
H
O CH3 MgBr O CH3 H O H H O CH3
MgBr H2O
Wittig Reaction
5. Wittig reaction, Step 1, formation of Wittig reagent. (See Notes.)
Ph
H
Ph
H P PPhh H Ph Li C(HB2uCLHi)2CH2CH3 CH3 C PPh Ph
Ph
CH3 C H CH3 C P
Ph
Br H H Ph
Br Li CH3(CH2)2CH3 CH3 C P Ph
Ph
Step 2, reaction with benzaldehyde
Ph
H
Ph Ph
CH3 C P Ph H Ph H Ph CH3 H
Ph CH3 P Ph CH3 P Ph C
C6H5 C O
H fast C6H5 O C6H5 O C
H H C6H5 H
Ph Ph
major
+ + P Ph +
Ph Ph O minor
slow H Ph H Ph
CH3 H
CH3 P Ph CH3 P Ph C
H O H O C
C6H5 C6H5 H C6H5
Part A - Page 5
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
10. Formation of the cyanohydrin (2-hydroxy-2-methylpropanenitrile) from acetone. (See Notes.)
C N H
H C N
O O O
C C C
H3C CH3 H3C CH3 H3C CH3
C C
N C N N
23. Base hydrolysis of octyl isobutyrate to give octanol and isobutyric acid. Step 1, treatment with base. (See Notes.)
O H
O O H O O
C O C8H17 C O C8H17 C cont'd
O O H
H O H
H
H O H
O
C + H O C8H17 O C8H17
O
O H
9 — Reactions of Enols and Enolates
9. Enolization and alkylation of ethyl propionate with benzyl bromide. (See Notes.)
N
O O Ph Br O
H
O H O H O
CH3 HN(C3H7)2 CH3 Br CH3
14. Acid catalyzed bromination of acetophenone to give α-bromoacetophenone. (See Notes.)
H H
O HBrB2r O Br O Br Br
H HOAc H H
cont'd
H H
H H H
H Br Br
H
O Br O
Br
Br
H
H
H H Br H
10 — Dehydration/Halogenation Agents
3. Reaction of 1-butanol with tosyl chloride and pyridine to give butyl tosylate. (See Notes.)
O
Cl S CH3
H O H O N
O O S CH3 cont'd
Cl O
N
H
Cl
O O
O S CH3 O S CH3
Cl O O
Part A - Page 6
Curved Arrow Press A Guide to Organic Chemistry Mechanisms©
7. Reaction of triphenylphosphine, carbon tetrachloride and cyclopentanol to give chlorocyclopentane. (See Notes.)
Cl
Cl C Cl
Cl Cl
Ph Cl Ph Ph
Ph P Ph P Cl Ph P O Cl
Ph Ph Ph
Cl Ph
C Cl Ph P O
Cl Ph
H
O O
Cl
HC Cl
Cl
11 — Reduction Reactions
2. Sodium borohydride reduction of cyclopentanone to cyclopentanol.
H H
O H B H O H O CH3 HO H
H
BH3 O CH3
Wolff Kischner Reduction
12. Reaction of the ketone with hydrazine under basic conditions to form the hydrazide.
H
O H N N H O CH3H OH O CH3H
N N H OH
CH3 H N H N H
cont'd
H H H
H2O OH
HO CH3H CH3 H CH3 H
OH
N N N
N H N H N H
H
OH H H2O
12 — Oxidation Reactions
Chromic Acid Oxidation
1. Chromic acid oxidation (Jones oxidation) of 3-methyl-2-butanol to 3-methyl-2-butanone. (See Notes.)
OH
O Several steps
VI IV O
HO OCr OH HO O H OH H H3O H OH O H2O HOCr OH
O O Cr OH O Cr O
H H O O H HO OH
H3O
H
Part A - Page 7