This document summarizes Chapter 22 of an organic chemistry textbook. It discusses various reactions of carbonyl compounds including alpha substitution, condensations with aldehydes/ketones/esters, and keto-enol tautomerism. Specific reactions covered include halogenation, aldol condensation, Claisen condensation, malonic ester synthesis, and acetoacetic ester synthesis. Mechanisms are provided for reactions such as enolate formation, aldol addition, Claisen condensation and decarboxylation of alkylmalonic acids. Examples are given to illustrate reactions like the malonic ester synthesis and alkylation of acetoacetic ester.
These slides include Hell-Volhard-Zelinski reaction introduction and mechanism. The mechanism is full of animation but SlideShare does not allow it. If you need this presentation, contact me.
Aldol Condensation || with Mechanism || Aldehyde Chemical Rxn| ALDOL Reactio...Anjali Bhardwaj
Aldol Condensation reaction in Aldehydes
You can watch this lecture video on youtube
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These slides include Hell-Volhard-Zelinski reaction introduction and mechanism. The mechanism is full of animation but SlideShare does not allow it. If you need this presentation, contact me.
Aldol Condensation || with Mechanism || Aldehyde Chemical Rxn| ALDOL Reactio...Anjali Bhardwaj
Aldol Condensation reaction in Aldehydes
You can watch this lecture video on youtube
https://youtu.be/bnQn7LunefE
Subscribe the channel
Follow at twitter:@LifeHobbies
Follow at Instagram:anlifehobbies
Crown ethers
NOMENCLATURE
GENERAL SYNTHESIS OF CROWN ETHER
AZA CROWN
CRYPTAND
APPLICATIONS
1. SYNTHETIC APPLICTION
Esterification
Saponification
Anhydride formation
Potassium permanganate oxidation
Aromatic substitution reactions
Elimination reactions
Displacement reaction
Generation of carbenes
Superoxide anion
Alkylations – 1. o-alkylations
2. c-alkylations
3. n-alkylations
2. ANALYTICAL APPLICATION
Determination of gold in geological samples
Super critical fluid extraction of trace metal from solid and liquid materials
Application of ionic liquids in analytical chemistry
Oxidation and determination of aldehydes
Crown ethers are used in the laboratory as phase transfer catalyst
OTHER APPLICATION
It is used in photocynation
Resolution of racemic mixture
Benzoin condensation
Hetrocyclisation
Synthesis of furanones
Acetylation of secondary amines in presence of primary amine
Protecting group (PG) is a small molecule, to mask temporarily the a specific functional group of a molecule from undergoing reaction, allowing the rest of the functional groups present in the molecule to react without affecting the original reactivity and leave from the host molecule without affecting the rest of the functional groups.
The addition of protecting groups to functional groups is termed ‘protection’ and removal of protecting group is ‘deprotection’.
Ullmann Reaction and Gomberg - Bechmann ReactionEinstein kannan
It contains two naming reactions like Ullmann and Gomberg- Bechmann reaction. Mechanism of Ullmann reaction, exercise problems are included. What is the mechanism behind the Gomberg-Bechmann reaction and its applications and some exercise problems also included from organic naming reaction books. Applications of Ullmann coupling also included. Reference books for this topic is mentioned the last slide.
When there are two functional groups of unequal reactivity within a molecule, the more reactive group can be made to react alone, but it may not be possible to react the less reactive functional group selectively.
A group the use of which makes possible to react a less reactive functional group selectively in presence of a more reactive group is known as protecting group.
A protecting group blocks the reactivity of a functional group by converting it into a different group which is inert to the conditions of some reaction(s) that is to be carried out as part of a synthetic route
Crown ethers
NOMENCLATURE
GENERAL SYNTHESIS OF CROWN ETHER
AZA CROWN
CRYPTAND
APPLICATIONS
1. SYNTHETIC APPLICTION
Esterification
Saponification
Anhydride formation
Potassium permanganate oxidation
Aromatic substitution reactions
Elimination reactions
Displacement reaction
Generation of carbenes
Superoxide anion
Alkylations – 1. o-alkylations
2. c-alkylations
3. n-alkylations
2. ANALYTICAL APPLICATION
Determination of gold in geological samples
Super critical fluid extraction of trace metal from solid and liquid materials
Application of ionic liquids in analytical chemistry
Oxidation and determination of aldehydes
Crown ethers are used in the laboratory as phase transfer catalyst
OTHER APPLICATION
It is used in photocynation
Resolution of racemic mixture
Benzoin condensation
Hetrocyclisation
Synthesis of furanones
Acetylation of secondary amines in presence of primary amine
Protecting group (PG) is a small molecule, to mask temporarily the a specific functional group of a molecule from undergoing reaction, allowing the rest of the functional groups present in the molecule to react without affecting the original reactivity and leave from the host molecule without affecting the rest of the functional groups.
The addition of protecting groups to functional groups is termed ‘protection’ and removal of protecting group is ‘deprotection’.
Ullmann Reaction and Gomberg - Bechmann ReactionEinstein kannan
It contains two naming reactions like Ullmann and Gomberg- Bechmann reaction. Mechanism of Ullmann reaction, exercise problems are included. What is the mechanism behind the Gomberg-Bechmann reaction and its applications and some exercise problems also included from organic naming reaction books. Applications of Ullmann coupling also included. Reference books for this topic is mentioned the last slide.
When there are two functional groups of unequal reactivity within a molecule, the more reactive group can be made to react alone, but it may not be possible to react the less reactive functional group selectively.
A group the use of which makes possible to react a less reactive functional group selectively in presence of a more reactive group is known as protecting group.
A protecting group blocks the reactivity of a functional group by converting it into a different group which is inert to the conditions of some reaction(s) that is to be carried out as part of a synthetic route
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Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Richard's entangled aventures in wonderlandRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
2. Chapter 22 2
Alpha Substitution
Alpha substitution is the substitution of one of the
hydrogens attached to the alpha-carbon for an
electrophile.
The reaction occurs through an enolate ion
intermediate.
3. Chapter 22 3
Condensation with an Aldehyde or
Ketone
The enolate ion attacks the carbonyl group to form an
alkoxide.
Protonation of the alkoxide gives the addition
product: a -hydroxy carbonyl compound.
4. Chapter 22 4
Condensation with Esters
The enolate adds to the ester to form a tetrahedral
intermediate.
Elimination of the leaving group (alkoxide) gives the
substitution product (a -carbonyl compound).
5. Chapter 22 5
Keto–Enol Tautomers
O
H
H
OH
H
keto form
(99.99%)
enol form
(0.01%)
Tautomerization is an interconversion of
isomers that occur through the migration of a
proton and the movement of a double bond.
Tautomers are not resonance form.
6. Chapter 22 6
Base–Catalyzed Tautomerism
In the presence of strong bases, ketones and aldehydes act as
weak proton acids.
A proton on the carbon is abstracted to form a resonance-
stabilized enolate ion with the negative charge spread over a
carbon atom and an oxygen atom.
The equilibrium favors the keto form over the enolate ion.
7. Chapter 22 7
Acid-Catalyzed Tautomerism
In acid, a proton is moved from the -carbon
to oxygen by first protonating oxygen and
then removing a proton from the carbon.
8. Chapter 22 8
Racemization
For aldehydes and ketones, the keto form is greatly
favored at equilibrium.
If a chiral carbon has an enolizable hydrogen atom, a
trace of acid or base allows that carbon to invert its
configuration, with the enol serving as the
intermediate. This is called racemization.
9. Chapter 22 9
Acidity of Hydrogens
pKa for H of aldehyde or ketone ~20.
Much more acidic than alkane or alkene
(pKa > 40) or alkyne (pKa = 25).
Less acidic than water (pKa = 15.7) or
alcohol (pKa = 16–19).
Only a small amount of enolate ion is
present at equilibrium.
10. Chapter 22 10
Formation and Stability of
Enolate Ions
The equilibrium mixture contains only a small
fraction of the deprotonated, enolate form.
11. Chapter 22 11
Energy Diagram of Enolate
Reaction
Even though the keto–enol tautomerism equilibrium
favors the keto form, addition of an electrophile shifts
the equilibrium toward the formation of more enol.
12. Chapter 22 12
Synthesis of Lithium
Diisopropylamine (LDA)
LDA is made by using an alkyllithium reagent
to deprotonate diisopropylamine.
13. Chapter 22 13
Enolate of Cyclohexanone
When LDA reacts with a ketone, it abstracts
the -proton to form the lithium salt of the
enolate.
14. Chapter 22 14
The Halogenation of Ketones
When a ketone is treated with a halogen and a base,
an halogenation reaction occurs.
The reaction is called base-promoted, rather than
base-catalyzed, because a full equivalent of the base
is consumed in the reaction.
15. Chapter 22 15
Base-Promoted Halogenation
Mechanism
The base-promoted halogenation takes place by a
nucleophilic attack of an enolate ion on the
electrophilic halogen molecule.
The products are the halogenated ketone and a
halide ion.
16. Chapter 22 16
Multiple Halogenations
The -haloketone produced is more reactive than
ketone because the enolate ion is stabilized by the
electron-withdrawing halogen.
The second halogenation occurs faster than the first.
Because of the tendency for multiple halogenations
this base-promoted halogenation is not widely used
to prepare monohalogenated ketones.
O
H
Cl
Cl2
OH , H2O
_
O
Cl
Cl
O
Cl
ClCl
O
Cl
ClCl
Cl
17. Chapter 22 17
Bromoform Reaction
A methyl ketone reacts with a halogen under
strongly basic conditions to give a
carboxylate ion and a molecule of haloform.
The trihalomethyl intermediate is not isolated.
18. Chapter 22 18
Mechanism of Haloform
Formation
The trihalomethyl ketone reacts with hydroxide ion to
give a carboxylic acid.
A fast proton exchange gives a carboxylate ion and a
haloform.
When Cl2 is used, chloroform is formed; Br2 forms
bromoform ; and I2 forms iodoform.
19. Chapter 22 19
Positive Iodoform Test
for Alcohols
The iodine oxidizes the alcohol to a methyl
ketone and it will give a positive iodoform test.
Iodoform (CHI3) is a yellow solid that will
precipitate out of solution.
20. Chapter 22 20
Propose a mechanism for the reaction of 3-pentanone with sodium hydroxide and bromine to give 2-
bromo-3-pentanone.
In the presence of sodium hydroxide, a small amount of 3-pentanone is present as its enolate.
The enolate reacts with bromine to give the observed product.
Solved Problem 1
Solution
21. Chapter 22 21
Acid-Catalyzed α Halogenation
Ketones also undergo acid-catalyzed halogenation.
Acidic halogenation may replace one or more alpha
hydrogens depending on how much halogen is used.
Acetic acid serves as both the solvent and the acid
catalyst.
22. Chapter 22 22
Mechanism of Acid-Catalyzed
α Halogenation
The mechanism of acid-catalyzed halogenation
involves attack of the enol form of the ketone on the
electrophile halogen molecule.
Loss of a proton gives the haloketone and the
hydrogen halide.
23. Chapter 22 23
Propose a mechanism for the acid-catalyzed conversion of cyclohexanone to 2-chlorocyclohexanone.
Under acid catalysis, the ketone is in equilibrium with its enol form.
The enol acts as a weak nucleophile, attacking chlorine to give a resonance-stabilized intermediate.
Loss of a proton gives the product.
Solved Problem 2
Solution
24. Chapter 22 24
Hell–Volhard–Zelinsky (HVZ)
Reaction
The HVZ reaction replaces a hydrogen atom with a
bromine atom on the alpha-carbon of a carboxylic
acid ( -bromoacid).
The acid is treated with bromine and phosphorus
tribromide, followed by hydrolysis.
25. Chapter 22 25
Hell–Volhard–Zelinski Reaction:
Step 1
The enol form of the acyl bromide serves as a
nucleophilic intermediate.
The first step is the formation of acyl bromide, which
enolizes more easily than does the acid.
26. Chapter 22 26
Hell–Volhard–Zelinski Reaction:
Step 2
The enol is nucleophilic, so it attacks bromine
to give the alpha-brominated acyl bromide.
In the last step of the reaction, the acyl
bromide is hydrolyzed by water to the
carboxylic acid.
27. Chapter 22 27
Alkylation of Enolate Ions
Because the enolate has two nucleophilic sites (the
oxygen and the carbon), it can react at either of
these sites.
The reaction usually takes place primarily at the
carbon, forming a new C—C bond.
28. Chapter 22 28
Alkylation of Enolate Ions
LDA forms the enolate.
The enolate acts as the nucleophile and attacks the
partially positive carbon of the alkyl halide, displacing
the halide and forming a C—C bond.
29. Chapter 22 29
Enamine Formation
Ketones or aldehydes react with a secondary
amine to form enamines.
The enamine has a nucleophilic -carbon,
which can be used to attack electrophiles.
30. Chapter 22 30
Mechanism of Enolate Formation
An enamine results from the reaction of a
ketone or aldehyde with a secondary amine.
31. Chapter 22 31
Electrostatic Potential Map of an
Enamine
The electrostatic potential map (EPM) of a simple
enamine shows a high negative electrostatic potential
(red) near the -carbon atom of the double bond.
This is the nucleophilic carbon atom of the enamine.
32. Chapter 22 32
Alkylation of an Enamine
Enamines displace halides from reactive alkyl
halides, giving alkylated iminium salts.
The alkylated iminium salt can be hydrolyzed
to the ketone under acidic conditions.
33. Chapter 22 33
Acylation of Enamines
The enamine attacks the acyl halide, forming an acyl
iminium salt.
Hydrolysis of the iminium salt produces the -
diketone as the final product.
34. Chapter 22 34
Aldol Condensation
Under basic conditions, the aldol condensation involves the
nucleophilic addition of an enolate ion to another carbonyl
group.
When the reaction is carried out at low temperatures, the -
hydroxy carbonyl compound can be isolated.
Heating will dehydrate the aldol product to the unsaturated
compound.
35. Chapter 22 35
Base-Catalyzed Aldol
Condensation: Step 1
During Step 1, the base removes the -
proton, forming the enolate ion.
The enolate ion has a nucleophilic -carbon.
36. Chapter 22 36
Base-Catalyzed Aldol
Condensation: Step 2
The enolate attacks the carbonyl carbon of a
second molecule of carbonyl compound.
38. Chapter 22 38
Dehydration of Aldol Products
Heating a basic or acidic aldol dehydration of the
alcohol functional group.
The product is a , -unsaturated conjugated
aldehyde or ketone.
An Aldol condensation, followed by dehydration,
forms a new carbon–carbon double bond.
41. Chapter 22 41
Propose a mechanism for the base-catalyzed aldol condensation of acetone (Figure 22-2).
The first step is formation of the enolate to serve as a nucleophile.
The second step is a nucleophilic attack by the enolate on another molecule of acetone. Protonation
gives the aldol product.
Solved Problem 3
Solution
42. Chapter 22 42
Aldol Cyclization
Intramolecular aldol reactions of diketones are often
used for making five- and six-membered rings.
Rings smaller or larger than five or six members are
not favored due to ring strain or entropy.
44. Chapter 22 44
Claisen Condensation
The Claisen condensation results when an
ester molecule undergoes nucleophilic acyl
substitution by an enolate.
46. Chapter 22 46
Crossed Claisen
Two different esters can be used, but
one ester should have no hydrogens.
Useful esters are benzoates, formates,
carbonates, and oxalates.
Ketones (pKa = 20) may also react with
an ester to form a -diketone.
47. Chapter 22 47
Crossed Claisen Condensation
In a crossed Claisen condensation, an ester
without hydrogens serves as the
electrophilic component.
48. Chapter 22 48
Crossed Claisen Condensation
with Ketones and Esters
Crossed Claisen condensation between ketones and
esters are also possible.
Ketones are more acidic than esters, and the ketone
component is more likely to deprotonate and serve as
the enolate component in the condensation.
49. Chapter 22 49
Crossed Claisen Mechanism
The ketone enolate attacks the ester, which
undergoes nucleophilic acyl substitution, and
thereby, acylates the ketone.
50. Chapter 22 50
Propose a mechanism for the self-condensation of ethyl acetate to give ethyl acetoacetate.
The first step is formation of the ester enolate. The equilibrium for this step lies far to the
left; ethoxide deprotonates only a small fraction of the ester.
The enolate ion attacks another molecule of the ester; expulsion of ethoxide ion gives ethyl
acetoacetate.
Solved Problem 4
Solution
51. Chapter 22 51
In the presence of ethoxide ion, ethyl acetoacetate is deprotonated to give its enolate. This exothermic
deprotonation helps to drive the reaction to completion.
When the reaction is complete, the enolate ion is reprotonated to give ethyl acetoacetate.
Solved Problem 4 (Continued)
Solution (Continued)
52. Chapter 22 52
Show what ester would undergo Claisen condensation to give the following -keto ester.
First, break the structure apart at the bond ( to the ester carbonyl). This is the bond formed in
the Claisen condensation.
Solved Problem 5
Solution
53. Chapter 22 53
Next, replace the proton that was lost, and replace the alkoxy group that was lost from the carbonyl.
Two molecules of methyl 3-phenylpropionate result.
Now draw out the reaction. Sodium methoxide is used as the base because the reactants are methyl
esters.
Solved Problem 5 (Continued)
Solution (Continued)
55. Chapter 22 55
Malonic Ester Synthesis
The malonic ester synthesis makes substituted
derivatives of acetic acids.
Malonic ester is alkylated or acylated on the carbon
that is alpha to both carbonyl groups, and the
resulting derivative is hydrolyzed and allowed to
decarboxylate.
56. Chapter 22 56
Decarboxylation of the
Alkylmalonic Acid
Decarboxylation takes place through a cyclic
transition state, initially giving an enol form
that quickly tautomerizes to the product.
59. Chapter 22 59
Show how the malonic ester synthesis is used to prepare 2-benzylbutanoic acid.
2-Benzylbutanoic acid is a substituted acetic acid having the substituents Ph–CH2– and CH3CH2–.
Adding these substituents to the enolate of malonic ester eventually gives the correct
product.
Solved Problem 6
Solution
60. Chapter 22 60
Acetoacetic Ester Synthesis
The acetoacetic ester synthesis is similar to
the malonic ester synthesis, but the final
products are ketones.
61. Chapter 22 61
Alkylation of Acetoacetic Ester
Ethoxide ion completely deprotonates acetoacetic
ester.
The resulting enolate is alkylated by an unhindered
alkyl halide or tosylate to give an alkylacetoacetic
ester.
62. Chapter 22 62
Hydrolysis of Alkylacetoacetic
Ester
Acidic hydrolysis of the alkylacetoacetic ester initially
gives an alkylacetoacetic acid, which is a -keto acid.
The keto group in the -position promotes
decarboxylation to form a substituted version of
acetone.
63. Chapter 22 63
Show how the acetoacetic ester synthesis is used to make 3-propylhex-5-en-2-one.
The target compound is acetone with an n-propyl group and an allyl group as substituents:
Solved Problem 7
Solution
64. Chapter 22 64
Hydrolysis proceeds with decarboxylation to give the disubstituted acetone product.
With an n-propyl halide and an allyl halide as the alkylating agents, the acetoacetic ester synthesis
should produce 3-propyl-5-hexen-2-one. Two alkylation steps give the required substitution:
Solved Problem 7 (Continued)
Solution (Continued)
65. Chapter 22 65
Conjugate Additions: The
Michael Reaction
, -unsaturated carbonyl compounds have unusually
electrophilic double bonds.
The -carbon is electrophilic because it shares the
partial positive charge of the carbonyl carbon through
resonance.
66. Chapter 22 66
1,2-Addition and 1,4-Addition
When attack occurs at the carbonyl group,
protonation of the oxygen leads to a 1,2-addition.
When attack occurs at the β-position, the oxygen
atom is the fourth atom counting from the
nucleophile, and the addition is called a 1,4-addition.
68. Chapter 22 68
1,4-Addition of an Enolate to
Methyl Vinyl Ketone (MVK)
An enolate will do a 1,4-attack on the -
unsaturated ketone (MVK).
69. Chapter 22 69
Show how the following diketone might be synthesized using a Michael addition.
A Michael addition would have formed a new bond at the carbon of the acceptor. Therefore,
we break this molecule apart at the bond.
Solved Problem 8
Solution
70. Chapter 22 70
Robinson Annulation
With enough base, the product of the Michael
reaction undergoes a spontaneous intramolecular
aldol condensation, usually with dehydration, to give
a six-membered ring—a conjugated cyclohexenone.