organic named reactions by sameera patel

1. NAME: SAMEERA PATEL
M-PHARM SEM-1
SUBJECT:ADVANCED ORGANIC CHEMISTRY-1
GUIDED UNDER: MRS. MONICA KAKADIYA
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2. 2

3.  The Baeyer–Villiger oxidation is an organic reaction
that forms an ester from a ketone or a lactone from a
cyclic ketone, using peroxyacids or peroxides as the
oxidant.
 The reaction is named after Adolf von Baeyer and
Victor Villiger who first reported the reaction in 1899.
3

4.  In the first step of the reaction mechanism, the
peroxyacidprotonates the oxygen of the carbonyl
group.
 This makes the carbonyl group more susceptible to
attack by the peroxyacid.
 Next, the peroxyacid attacks the carbon of the
carbonyl group forming what is known as the Criegee
intermediate.
 Through a concerted mechanism, one of the
substituents on the ketone migrates to the oxygen of
the peroxide group while a carboxylic acid leaves.
 This migration step is thought to be the rate
determining step.
 Finally, deprotonation of the oxocarbenium ion
produces the ester.
4

5. Criegee intermediate
5

6.  The products of the Baeyer–Villiger oxidation
are believed to be controlled through both
primary and secondary stereoelectronic effects.
 The primary stereoelectronic effect in the
Baeyer–Villiger oxidation refers to the necessity
of the oxygen-oxygen bond in the peroxide
group to be antiperiplanar to the group that
migrates.
 The secondary stereoelectronic effect refers to
the necessity of the lone pair on the oxygen of
the hydroxyl group to be antiperiplanar to the
migrating group.
 This migration step is also assisted by two or
three peroxyacid units enabling the hydroxyl
proton to shuttle to its new position.
 The migratory ability is ranked tertiary >
secondary > aryl > primary
 Electron-withdrawing group on the substituent
decrease the rate of migration.
6

7.  Zoapatanol
• Zoapatanol is a biologically active molecule that
occurs naturally in the zeopatle plant, which has been
used in Mexico to make a tea that can induce
menstruation and labor.
• In 1981, Vinayak Kane and Donald Doyle reported a
synthesis of zoapatanol.
• They used the Baeyer–Villiger oxidation to make
a lactone that served as a crucial building block that
ultimately led to the synthesis of zoapatanol
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8. 8

9.  Steroids
• In 2013, Alina Świzdor reported the
transformation of
the steroid dehydroepiandrosterone to anticancer
agent testololactone by use of a Baeyer-Villiger
oxidation induced by fungus that produces
Baeyer-Villiger monooxygenases.
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10.  The Baeyer–Villiger oxidation reaction is also
useful for the following studies:
 Synthesis of lactones from mesomeric cyclohexanones.
 Synthesis of 3-hydroxyindole-2-carboxylates.
 Conversion of non-activated [18F]fluorobenzaldehydes to
[18F]fluorophenols with high radiochemical yield.
 Synthesis of dibenzo-18-crown-6, dibenzo-21-crown-7, and
dihydroxydibenzo-18-crown-6.
 One-pot chemoenzymatic synthesis of g-butyrolactones.
 Metal-free synthesis of vinyl acetates.
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11. 11

12.  The Shapiro reaction or tosylhydrazone
decomposition is an organic reaction in which
a ketone or aldehyde is converted to
an alkene through an intermediate hydrazone in
the presence of 2 equivalents of strong base.
 The reaction was discovered by Robert. H.
shapiro in 1967.
 The Shapiro reaction was used in the Nicolaou
Taxol total synthesis
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13.  In a prelude to the actual Shapiro reaction a ketone or
an aldehyde is reacted with p-toluenesulfonylhydrazide to
a p-toluenesulfonylhydrazone (or tosylhydrazone) which is
an imine or hydrazone.
 Two equivalents of a strong base, such as n-butyllithium,
then abstract first the proton from the hydrazone and
then the less acidic proton α to the hydrazone carbon,
leaving a carbanion.
 The carbanion undergoes an elimination
reaction producing a carbon–carbon double bond.
 This tosyl acts as a leaving group in the formation of
a diazonium anion, from which a nitrogen molecule is
then lost.
 The result is a vinyllithium at the position where the
nitrogen had been attached. This organolithium carbon is
both nucleophilic and basic.
 It can be reacted with various electrophiles or simply
neutralized with water or an acid.
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14. 14

15.  An Application of the Shapiro Reaction in Total Synthesis
The Shapiro reaction has been used to generate olefins en route to
complex natural products. K. Mori and coworkers wanted to determine
the absolute configuration of the phytocassane group of a class of
natural products called phytoalexins. This was accomplished by
preparing the naturally occurring (–)-phytocassane D from (R)-Wieland-
Miescher ketone. En route to (–)-phytocassane D, a tricyclic ketone
was subjected to Shapiro reaction conditions to yield the cyclic alkene
product. [12]
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16. 16

17.  The Suzuki reaction is an organic reaction, classified as
a coupling reaction, where the coupling partners are a boronic
acid and an organohalide catalyzed by a palladium(0) complex.
 It was first published in 1979 by Akira Suzuki and he shared
the 2010 Nobel Prize in Chemistry with Richard F. Heck and Ei-
ichi Negishi for their effort for discovery and development of
palladium-catalyzed cross couplings in organic synthesis.
 In many publications this reaction also goes by the
name Suzuki–Miyaura reaction and is also referred to as
the Suzuki coupling.
 It is widely used to synthesize poly-olefins, styrenes, and
substituted biphenyls.
 The general scheme for the Suzuki reaction is shown below
where a carbon-carbon single bond is formed by coupling
an organoboron species (R1-BY2) with a halide (R2-X) using
a palladium catalyst and a base.
17

18.  The mechanism of the Suzuki reaction is best viewed from
the perspective of the palladium catalyst.
 The first step is the oxidative addition of palladium to
the halide 2 to form the organopalladium species 3.
 Reaction with base gives intermediate 4, which
via transmetalation with the boron-ate complex 6 (produced
by reaction of the boronic acid 5 with base) forms
the organopalladium species 8.
 Reductive elimination of the desired product 9 restores the
original palladium catalyst 1 which completes the catalytic
cycle.
 The Suzuki coupling takes place in the presence of a base
and for a long time the role of the base was never fully
understood.
 The base was first believed to form a trialkyl borate (R3B-
OR), in the case of a reaction of an trialkylborane (BR3)
and alkoxide (−OR); this species could be considered as being
more nucleophilic and then more reactive towards the
palladium complex present in the transmetalation step.
18

19.  Duc and coworkers investigated the role of the base in the
reaction mechanism for the Suzuki coupling and they found
that the base has three roles:
 Formation of the palladium complex [ArPd(OR)L2],
 formation of the trialkyl borate and
 the acceleration of the reductive elimination step by
reaction of the alkoxide with the palladium complex.
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20.  In most cases the oxidative Addition is the rate determining step of
the catalytic cycle.
 During this step, the palladium catalyst is oxidized from
palladium(0) to palladium(II).
 The palladium catalyst 1 is coupled with the alkyl halide 2 to yield
an organopalladium complex 3. As seen in the diagram below,
the oxidative addition step breaks the carbon-halogenbond where
the palladium is now bound to both the halogen and the R group.
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21.  The oxidative addition initially forms the cis–
palladium complex, which rapidly isomerizes to
the trans-complex.
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22.  Transmetalation is an organometallic reaction where ligands are
transferred from one species to another.
 In the case of the Suzuki coupling the ligands are transferred
from the organoboron species 6 to the palladium(II)
complex 4 where the base that was added in the prior step is
exchanged with the R1 substituent on the organoboron species
to give the new palladium(II) complex 8.
 The exact mechanism of transmetalation for the Suzuki coupling
remains to be discovered.
 The organoboron compounds do not undergo transmetalation in
the absence of base and it is therefore widely believed that the
role of the base is to activate the organoboron compound as
well as facilitate the formation of R2-Pdll-OtBu from R2-Pdll-X
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23. 23

24.  The final step is the reductive elimination
step where the palladium(II) complex (8)
eliminates the product (9) and regenerates
the palladium(0) catalyst(1).
Using deuterium labelling, Ridgway et
al. have shown the reductive elimination
proceeds with retention of stereochemistry
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25. 1. The Suzuki coupling has been frequently
used in syntheses of complex compounds.
 The Suzuki coupling has been used on
a citronellal derivative for the synthesis
of caparratriene, a natural product that is highly
active against leukemia:
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26. The last step in the synthesis of Myxalamide A
 „Polyene antibiotic „Isolated from the bacterium
Myxococcus xanthus
 „Observed to have antibiotic and antifungal
activity
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28.  Oximidines were first isolated in 1999 from
Pseudomonas sp. Q52002. „
 Highly biologically active
 „Affect the cell cycle at the G1 Phase „
Coupling used in the synthesis of the macro-
cyclic ring
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29. 29

30. 30

31.  Ozonolysis is an organic reaction where
the unsaturated bonds of alkenes, alkynes,
or azo compounds are cleaved with ozone.
 Alkenes and alkynes form organic compounds in
which the multiple carbon–carbon bond has
been replaced by a carbonyl group, while azo
compounds form nitrosamines.
 The outcome of the reaction depends on the
type of multiple bond being oxidized and
the work-up conditions.
31

32.  Alkenes can be oxidized with ozone to form alcohols
, aldehydes or ketones, or carboxylic acids.
 In a typical procedure, ozone is bubbled through a solution of the
alkene in methanol at −78 °C until the solution takes on a
characteristic blue color, which is due to unreacted ozone.
 This indicates complete consumption of the alkene.
 Alternatively, various other chemicals can be used as indicators of
this endpoint by detecting the presence of ozone.
 If ozonolysis is performed by bubbling a stream of ozone-enriched
oxygen through the reaction mixture, the gas that bubbles out can
be directed through a potassium iodide solution.
 When the solution has stopped absorbing ozone, the ozone in the
bubbles oxidizes the iodide to iodine, which can easily be observed
by its violet color.
 For closer control of the reaction itself, an indicator such as Sudan
Red IIIcan be added to the reaction mixture. Ozone reacts with this
indicator more slowly than with the intended ozonolysis target.
 The ozonolysis of the indicator, which causes a noticeable color
change, only occurs once the desired target has been consumed.
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33.  After completing the addition a reagent is then added to
convert the intermediate ozonide to a carbonyl derivative.
 Reductive work-up conditions are far more commonly used
than oxidative conditions.
 The use of triphenylphosphine, thiourea, zinc dust,
or dimethyl sulfide produces aldehydes or ketones while the
use of sodium borohydride produces alcohols.
 The use of hydrogen peroxide produces carboxylic acids.
 Recently, the use of amine N-oxides has been reported to
produce aldehydes directly.
 Other functional groups, such as benzyl ethers, can also be
oxidized by ozone.
 It has been proposed that small amounts of acid may be
generated during the reaction from oxidation of the solvent,
so pyridine is sometimes used to buffer the reaction.
 Dichloromethane is often used as a 1:1 cosolvent to
facilitate timely cleavage of the ozonide.
 Azelaic acid and pelargonic acid are produced from
ozonolysis of oleic acid on an industrial scale. 33

34.  In the generally accepted mechanism proposed
by Rudolf Criegee in 1953, the alkene and ozone form
an intermediate molozonide in a 1,3-dipolar
cycloaddition .
 Next, the molozonide reverts to its
corresponding carbonyl oxide (also called the Criegee
intermediate or Criegee zwitterion ) and aldehyde or
ketone in a retro-1,3-dipolar cycloaddition.
 The oxide and aldehyde or ketone react again in a 1,3-
dipolar cycloaddition or produce a relatively
stable ozonide intermediate (a trioxolane ). 34

35. 35

36.  Ozonolysis of alkynes generally gives an acid
anhydride or diketone product, not complete
fragmentation as for alkenes.
 A reducing agent is not needed for these reactions.
 The exact mechanism is not completely known.
 If the reaction is performed in the presence of water, the
anhydride hydrolyzes to give two carboxylic acids.
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37.  Bleaching
The color in colored materials is often due to conjugated carbon-
carbon double bonds in the molecules that make it up. A
conjugated molecule has carbon-carbon double bonds alternating
with carbon-carbon single bonds.
Ozone adds to some of the carbon-carbon double bonds and
eliminates the color.
Using ozone as a bleach can be better for the environment than
bleaches like Clorox (NaOCl) because it doesn't add harmful
byproducts in water.
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38.  Chemical Synthesis: Ozonolysis
Ozone reacts with carbon-carbon
double bonds. In combination
with other reactants, it adds
oxygen and breaks these bonds.
Ozonolysis is an important step
in the synthesis of many
pharmaceutical agents.
Ozone reacts with the double
bond in this molecule. After
several steps (not shown here) a
new molecule with a C-OH unit is
formed. Molecules that have
carbon connected to OH groups
are called alcohols.
In this example, ozone again
reacts with a carbon-carbon
double bond. After additional
steps, the product of the
reaction is a new molecule with
a CHO unit. Molecules like this
are called aldehydes.
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39. 39

40.  The Michael reaction or Michael addition is
the nucleophilic addition of a carbanion or
another nucleophile to an α,β-unsaturated
carbonyl compound.
 It belongs to the larger class of conjugate
additions.
 This is one of the most useful methods for the
mild formation of C–C bonds.
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41.  In this scheme the R and R' substituents on
the nucleophile (a Michael donor) are electron-
withdrawing groups such as acyl and cyano making
the methylene hydrogen acidic forming the
carboanion on reaction with base B:.
 The substituent on the activated alkene, also called
a Michael acceptor, is usually a ketone making it
an enone, but it can also be a nitro group.
 Reagents : commonly bases such as NaOH or KOH.
 The first step is the formation of the enolate.
 Enolates tend to react with α,β-unsaturated ketones
via conjugate addition.
 A conjugate addition with a carbanion nucleophile is
known as the Michael reaction or Michael addition.
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42. 42

43.  The reaction mechanism is 1 (with R an alkoxy group)
as the nucleophile:
 Deprotonation of 1 by base leads
to carbanion 2 stabilized by its electron-withdrawing
groups.
 Structures 2a to 2c are three resonance
structures that can be drawn for this species, two of
which have enolate ions.
 This nucleophile reacts with the electrophilic
alkene 3 to form 4 in a conjugate addition reaction.
 Proton abstraction from protonated base (or solvent)
by the enolate 4 to 5 is the final step
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44. 44
•Reagents : commonly bases such as NaOH or KOH.
The first step is the formation of the enolate.
•Enolates tend to react with α,β-unsaturated ketones
via conjugate addition.
•A conjugate addition with a carbanion nucleophile is
known as the Michael reaction or Michael addition.

45.  MECHANISM OF THE MICHAEL
ADDITION
 Step 1:
First, an acid-base reaction.
Hydroxide functions as a base
and removes the acidic α-
hydrogen giving the reactive
enolate.
 Step 2:
The nucleophilic enolate attacks
the conjugated ketone at the
electrophilic alkene C in a
nucleophilic addition type
process with the electrons being
pushed through to the
electronegative O, giving an
intermediate enolate.
 Step 3:
An acid-base reaction. The
enolate deprotonates a water
molecule recreating hydroxide
and the more favourable
carbonyl group.
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