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ADVANCED ORGANIC CHEMISTRY-I (MPC 102T) UNIT-I: Study of mechanism

and synthetic applications of following named Reactions

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

Carl Ulrich Franz Mannich

 Carl Ulrich Franz Mannich (March 8, 1877 in Breslau – March 5, 1947 in
Karlsruhe) was a German chemist.
 From 1927 to 1943 he was professor for pharmaceutical chemistry at the
University of Berlin.
 His areas of expertise were keto bases, alcohol bases, derivatives of piperidine,
papaverine, lactones and also Digitalis-glycosides.
 The Mannich reaction was named after his discovery of the mechanism in 1912

Ivar Karl Ugi

 Ivar Karl Ugi (9 September 1930 in Saaremaa, Estonia – 29 September 2005 in
Munich) was an Estonian-born German chemist who made major contributions
to organic chemistry.
 The one pot reaction of a ketone or aldehyde, an amine, an isocyanide and a
carboxylic acid to form a bis-amide is generally known as Ugi reaction.

Fritz Ullmann
 Fritz Ullmann (July 2, 1875 in Fürth – March 17, 1939 in Berlin) was a German
chemist.
 Ullmann was born in Fürth and started studying chemistry in Nuremberg, but
received his PhD of the University of Geneva for work with Carl Gräbe in 1895.
 They named after themselves the following reactions: the Ullmann reaction, the
Ullmann condensation, the Graebe-Ullmann synthesis, the Goldberg reaction
and the illustrious Jordan-Ullmann-Goldberg synthesis.

Traugott Sandmeyer
 Traugott Sandmeyer (September 15, 1854 – April 9, 1922) was a Swiss chemist
after whom the Sandmeyer reaction, which he discovered 1884, was named.
 He also worked on the synthesis of isatin. And several reactions have been
named after him: Sandmeyer isonitrosoacetanilide isatin synthesis(1919) and
Sandmeyer diphenylurea isatin synthesis(1903).
 Sandmeyer began his career in industry in 1888 with Johann Rudolf Geigy-
Merian, who was the owner of the chemical factory J. R. Geigy & Cie (later
Ciba Geigy, now Novartis). Sandmeyer was involved in the development of
several dyes and invented a new synthesis for indigo.

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 1
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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 MANNICH REACTION
- The Mannich reaction is an organic reaction used to convert a primary or secondary amine and two carbonyl
compound (one non‑enolizable and one enolizable) to a β‑amino carbonyl compound, also known as a Mannich
base, using an acid or base catalyst.
- The Mannich reaction is an example of nucleophilic addition of an amine to a carbonyl group followed by
dehydration to the Schiff base. The Schiff base is an electrophile which reacts in the second step in an electrophilic
addition with a compound containing an acidic proton (which is, or had become an enol). The Mannich reaction is
also considered a condensation reaction.
- The reaction is named after chemist Sir Carl Mannich.
- General Reaction:

- Reaction Mechanism:

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- Applications:

The MannichReaction is employed in the organic synthesis of numerous compounds. Examples include:
 Alkyl amines
 Peptides, nucleotides, antibiotics, and alkaloids (e.g. Tropinone)
 Agrochemicals, such as plant growth regulators
 Polymers
 Catalysts
 Formalin tissue crosslinking
 Pharmaceutical drugs (e.g. Rolitetracycline (the Mannich base of tetracycline), fluoxetine (antidepressant),
tramadol, and tolmetin (anti-inflammatory drug) and azacyclophanes)
 Soap and detergents. These compounds are used in a variety of cleaning applications, automotive fuel
treatments, and epoxy coatings polyetheramines from substituted branched chain alkyl ethers.
 α,β-unsaturated ketones via the thermal degradation of Mannich reaction products (e.g. Methyl vinyl ketone
from 1-Diethylamino-3-butanone).

Note By:
 Enolizable Aldehyde: An enolizable aldehyde is an aldehyde whose molecule has one or more alpha
hydrogens.

 Non-Enolizable Aldehyde: A non-enolizable aldehyde is an aldehyde whose molecule has no alpha

hydrogens.

 Non-Enolizable Ketone: A non-enolizable ketone is a ketone whose molecule has no alpha hydrogens.

 Enolizable ketone: An enolizable ketone is a ketone whose molecule has one or more alpha hydrogens.

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 3
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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 UGI REACTION
- The Ugi reaction is a multicomponent reaction in organic chemistry involving a ketone or aldehyde, an amine, an
isocyanide and a carboxylic acid to form a BISAMIDE.
- The reaction is named after Sir Ivar Karl Ugi.
- General Reaction:

- Reaction Mechanism

 Step-1: Imine formation with amine versus ketone

 Step-2: Proton exchange
 Step-3: Nucleophilic addition of the isocyanide
 Step-4: Nuclephilic addition of the carboxylic acid anion
 Step-5: Mumm rearrangement

- Applications:
 Isoquinolines from Ugi and Heck reactions.
 Indinavir can be prepared using the Ugi reaction.
 Additionally, many of the caine type anesthetics are synthesized using this reaction. Examples include
lidocaine and bupivacaine

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 4
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

NOTE BY:

 MUMM REARRANGEMENT
 The Mumm rearrangement is an organic reaction and a rearrangement reaction.
 It describes a 1,3(O-N) acyl transfer of an acyl imidate or isoimide group to an imide.

 INDINAVIR
 It is a protease inhibitor used as a component of highly active antiretroviral therapy to treat HIV/AIDS.
 The most common side effects of indinavir include:
- Gastrointestinal disturbances (abdominal pain, diarrhea, nausea, vomiting)
- General malaise and fatigue
- Nephrolithiasis/urolithiasis (the formation of kidney stones), which sometimes may lead to more severe
condition including kidney failure
- Metabolic alterations including hyperlipidemia (cholesterol or triglyceride elevations) and hyperglycemia
- Alterations in body shape (lipodystrophy), colloquially known as "Crix belly".
- Indinavir inhibits urinary nitrous oxide production and may inhibit nitric oxide production. Treatment with
this drug is frequently associated with renal abnormalities, sterile leukocyturia, and reduced creatinine
clearance.

 CAINE TYPE ANESTHETICS

 Amide group anesthetics is known as caine type anesthetics like, Articaine, Bupivacaine, Cinchocaine,
Etidocaine, Levobupivacaine, Lidocaine/Lignocaine, Mepivacaine, Prilocaine etc.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 ULLMANN REACTION
- The Ullmann reaction or Ullmann coupling is a coupling reaction between aryl halides and copper. The reaction
is named after Sir Fritz Ullmann.
- Ullmann Reaction is the synthesis of symmetric biaryls via copper catalysed coupling.
- General Reaction:

 A typical example is the coupling of 2 molecules of ortho-chloronitrobenzene reactants to form

2,2'dinitrobiphenyl with a copper bronze alloy.

- Mechanism of the Ullmann Reaction

 Biaryls are available through coupling of the aryl halide with an excess of copper at elevated temperatures
(200 °C). The active species is a copper(I)compound which undergoes oxidative addition with the second
equivalent of halide, followed by reductive elimination and the formation of the aryl-aryl carbon bond.

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 6
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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 SANDMEYER REACTION
- The Sandmeyer reaction is a chemical reaction used to synthesize aryl halides from aryl diazonium salts.
- It is an example of a radical nucleophilic aromatic substitution.
- This reaction involves replacement of the diazonium group by chlorine or bromine.
- Sandmeyer reaction affords a useful method for introducing halogen substitute at the desired position of an
aromatic ring.
- The reaction was discovered in 1884 by Swiss chemist Sir Traugott Sandmeyer.
- General Reaction:

- Reaction mechanism:

- Synthetic Applications:
 Variations on the Sandmeyer reaction have been developed to fit multiple synthetic applications. These
reactions typically proceed through the formation of an aryl diazonium salt followed by a reaction with a
copper (I) salt to yield a substituted arene according to the scheme below.

 Hydroxylation: The Sandmeyer reaction can also be used to convert aryl amines to phenols proceeding
through the formation of an aryl diazonium salt as shown below.

Due to its wide synthetic applicability, the Sandmeyer reaction is complementary to electrophilic aromatic substitution.

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 7
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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

Sir Arthur Michael

 Sir Arthur Michael (August 7, 1853 – February 8, 1942) was an American organic
chemist who is best known for the Michael reaction.
 Activities and honors: National Academy of Sciences (1889)

Sir Oyo Mitsunobu

 Professor Oyo Mitsunobu (1934-2003) developed one of the most remarkable and
useful reactions in the history of organic chemistry, the Mitsunobu process.

Sir Walter Dieckmann

 Sir Walter Dieckmann (8 October 1869-12 January 1925) was a German chemist.
 Dieckmann studied at the University of Munich and became an assistant of Adolf
von Baeyer.
 The Dieckmann condensation is the intramolecular chemical reaction is named
after him.

Sir Johann Friedrich Wilhelm Adolf von Baeyer

 Sir Adolf von Baeyer (31 October 1835-20 August 1917) was a German chemist
who synthesised indigo and developed a nomenclature for cyclic compounds (that
was subsequently extended and adopted as part of the IUPAC organic
nomenclature). Strain theory, in chemistry, a proposal made by him in 1885.
 His name is reflected in various "name reactions" as the Baeyer-Villiger
Oxidation and Baeyer's reagent.
 In the year 1905 recipient of the Nobel Prize in Chemistry.

Sir Victor Villiger

 Sir Victor Villiger (1 September 1868 – 10 June 1934) was a Swiss-born German
chemist and the discoverer of the Baeyer-Villiger oxidation.
 He studied at University of Geneva and, following his graduation and Doctoral
advisor with Adolf von Baeyer at the University of Munich.
 He started working at BASF in Ludwigshafen in 1905.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 MICHAEL ADDITION REACTION

- The Michael addition is an organic reaction used to convert an activated methylene and a conjugated olefin to the
corresponding addition product using a base catalyst followed by an acid work-up.
- The activated methylene is essentially a methylene bonded to electron withdrawing groups that would stabilize the
negative change that forms after deprotonation by the base. This deprotonation results in an enolate which in turn
does a 1,4 addition to the conjugated olefin.
- An acid work-up then provides the final Michael addition product.
- The Michael addition reaction, focusing on Sir Arthur Michael, an American chemist, after whom it is named.
- General Reaction:

- Reaction Mechanism:

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- General reaction:

- Reaction Mechanism

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.

- Application of Michael addition reaction:

 Michael addition reaction has been a very classical reaction in the field of organic synthesis.
 It is widely used to synthesize all kinds of natural products and drugs.
 Since the beginning of 21st century, people's environmental awareness has been enhanced and the research on
green chemistry has been advanced.
 The Michael addition method with high efficiency, simplicity and greenness has been the goal pursued by
organic chemists.

Note By:
Acid work-up: In chemistry, work-up refers to the series of manipulations required to isolate and purify the product(s) of a
chemical reaction. Typically, these manipulations may include: quenching a reaction to deactivate any unreacted reagents.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 MITSUNOBU REACTION
- The Mitsunobu reaction is an organic reaction used to convert a primary or secondary alcohol into a variety of
compounds using diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) and
triphenylphosphine.
- The final product depends on the acidic reagent (the conjugate acid of the nucleophile).
- The alcohol undergoes an inversion of stereochemistry.
- It was discovered by Sir Oyo Mitsunobu (1934–2003).
- General Reaction:

Diethyl Azodicarboxylate (DEAD) Triphenylphosphine (PPh3)

Diisopropyl Azodicarboxylate (DIAD) Triphenylphosphine oxide

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- Reaction Mechanism:

- Application of Mitsunobu reaction:

 The Mitsunobu reaction has been applied in the synthesis of aryl ethers.
 The reaction has been used to synthesize quinine, colchicine, sarain, morphine, stigmatellin, eudistomin,
oseltamivir, strychnine, and nupharamine.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 DIECKMANN CONDENSATION
- The Dieckmann condensation is the intramolecular chemical reaction of diesters with base to give β-ketoesters.
- It is named after the German chemist Sir Walter Dieckmann.
- General reaction:

- Reaction Mechanism:

- Application of the Dieckmann Condensation

 The Dieckmann condensation is commonly used in preparation of cyclic indole.
 The heterocyclic indole can be biologically active against cancer.
 The application of the Dieckmann condensation in the formation of five-membered pyrrole rings.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 BAEYER-VILLIGER OXIDATION
- Baeyer-Villiger oxidation is the oxidation of a ketone to a carboxylic acid ester using a peroxyacid as the oxidizing
agent.
- The reaction is named after Sir Adolf Baeyer and Sir Victor Villiger.

- Cyclic ketones give cyclic esters which are also known as lactones.

Note By:
PEROXY ACID
 A peroxy acid (often spelled as one word, peroxyacid, and sometimes called peracid) is an acid which contains an acidic –
OOH group. The two main classes are those derived from conventional mineral acids, especially sulfuric acid, and the
organic derivatives of carboxylic acids.
 A peroxyacid or peroxycarboxylic acid or peracid is a compound that has the following general structural formula.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- Reaction Mechanism:

Step 1:
An acid/base reaction. Protonation of the carbonyl
activates it while creating a more reactive nucleophile, the
percarboxylate.

Step 2:
Now the nucleophilic O attacks the carbonyl C with the
electrons from the C=O π bond going to the positive O.

Step 3:
Electrons from the O come back (this reforms the π bond
of the C=O) and we migrate the C-C electrons to form a
new C-O bond displacing the carboxylate as a leaving
group.

Step 4:
Finally an acid/base reaction reveals the C=O and
therefore the ester product.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

Sir Zdenko Hans Skraup

 Skraup (March 3, 1850 – September 10, 1910) was a Czech-Austrian chemist who
discovered the Skraup reaction, the first quinoline synthesis.
 He received his Ph.D. from the University of Giessen on March 17, 1875.
 He finished his habilitation at the University of Vienna in 1879, but because his degree
was from a German university he had to wait until 1881 till he became professor at the
Vienna Trade Academie.

Sir Oskar Gustav Doebner

 Oskar Gustav Doebner, (20. November 1850 in Meiningen-28. March 1907 in
Marseille) was a Dutch Chemist (Organic Chemistry). English Professor of University
Halle.

Sir Wilhelm von Miller

 Wilhelm von Miller (9th December 1848 – 1st March 1899) was a Dutch Chemist.
 “He then studied at the Technische Hochshule in Vienna and in 1887 went to Munich
to read organic chemistry under Professor W. von Miller. After taking his doctorate, he
remained as Professor von Miller's assistant and later accepted a similar position as
assistant to the physicist Professor Kundt in Berlin.”

Sir Anton Vilsmeier

 Dr. Anton Vilsmeier (June 12, 1894 – February 12, 1962) was a German chemist who
together with Erich Haack discovered the Vilsmeier-Haack reaction.
 Vilsmeier discovered the aldehyde synthesis reaction which bears his name in 1926,
and it was published in 1927, the year that he began to work for BASF (German
chemical company) in Ludwigshafen. He retired in 1959, and died in 1962 in
Ludwigshafen.

Sir Adrian Gibbs Brook

 Adrian Gibbs Brook, (21st May 1924 – 10th July 2013) was a Canadian Chemist.
 He obtained his Ph.D. degree in Organic Chemistry from the University of Toronto in
1950. After 3 years of teaching and post-doctoral studies abroad, he carries out
research in the area of Organ silicon Chemistry.
 This new chemistry was recognized and honoured by Fellowship in The Chemical
Institute of Canada (CIC), The Royal Society of Canada, the Kipping Award in 1973,
the CIC meda1 in 1985, the Killam Memorial Prize in 1994 and being named as
University Professor (1987) by the University of Toronto together with its award of an
Honourary Doctor of Science degree in 2006.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 BROOK REARRANGEMENT
- The Brook rearrangement in organic chemistry is a rearrangement reaction in which an organosilyl group switches
position with a hydroxyl proton over a carbon to oxygen covalent bond under the influence of a base. The
reaction product is SILYL ETHER.
- It is named for the Canadian chemist Sir Adrian Gibbs Brook.
- General Reaction:

- Reaction Mechanism:
 The reaction mechanism for this rearrangement starts with proton abstraction of the hydroxyl group by base to
the alkoxide anion.
 This nucleophile attacks the silicon atom in a nucleophilic displacement with the methylene group as the
leaving group.
 The proposed transition state for this reaction step is a three-membered ring with the degree of Si-O bond
making in step with the Si-C bond breaking process.
 The additional electron pair is now transferred from oxygen to a carbanion which quickly abstracts a proton
from a proton source such as solvent to form the final Silyl Ether.

Organosilicon compounds or organosilyl group are organometallic compounds containing carbon–silicon bonds.

Silyl ethers are a group of chemical compounds which contain a silicon atom covalently bonded to an alkoxy
group.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 DOEBNER-MILLER REACTION
- The Doebner–Miller reaction is the organic reaction of an aniline with α,β-unsaturated carbonyl compounds to
form Quinolines.
- This reaction is also known as the Skraup-Doebner-Von Miller quinoline synthesis, and is named after the Czech
chemist Sir Zdenko Hans Skraup and the Germans chemist Sir Oscar Döbner (Doebner) and Sir Wilhelm von
Miller.
- When the α,β-unsaturated carbonyl compound is prepared in situ from two carbonyl compounds (via an Aldol
condensation), the reaction is known as the Beyer method for quinolines.
- General Reaction:

- Reaction Mechanism:

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 SHARPLESS ASYMMETRIC EPOXIDATION

- The Sharpless Epoxidation is an enantioselective epoxidation of allylic alcohols.

- The Sharpless epoxidation is an organic reaction used to steroselectively convert an allylic alcohol to an epoxy
alcohol using a titanium isopropoxide catalyst, t‑butyl hydroperoxide (TBHP), and a chiral diethyl tartrate
(DET).
- The Sharpless epoxidation only works for alkenes adjacent to an alcohol (CH2OH).

tert-Butyl hydroperoxide (tBuOOH) Diethyl tartrate (±DET)

Diisopropyl tartrate (DIPT) is a

diester of tartaric acid. Titanium isopropoxide or titanium tetraisopropoxide (TTIP)
Ti{OCH(CH3)2}4.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 VILSMEIER‑HAACK REACTION
- The Vilsmeier‑Haack reaction is an organic reaction used to convert an electron rich aromatic ring to an aryl
aldehyde using DMF, an acid chloride, and aqueous work‑up.
- Vilsmeier‑Haack reaction Also known as Vilsmeier-Haack formylation.
- General Reaction:

- Reaction Mechanism:

Phosphoryl chloride (commonly called phosphorus oxychloride) is a

colourless liquid with the formula POCl3. It hydrolyses in moist air
releasing phosphoric

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

 OZONOLYSIS
- Ozonolysis is a reaction between alkenes and ozone, in which the alkenes are cleaved into a pair of carbonyl
compounds.
- Ozonolysis of Alkenes General Reaction:

- Reaction type:
 Electrophilic Addition
 Overall transformation : C=C to 2 x C=O
 Ozonolysis implies that ozone causes the alkene to break (lysis)
 Reagents : ozone followed by :
o a reducing workup, either Zn in acetic acid or dimethyl sulfide, [(CH3)2S]
o an oxidising workup, usually H2O2 (under these conditions, carboxylic acids are obtained instead of
aldehydes)
 It is convenient to view the process as cleaving the alkene into two carbonyls
o The substituents on the C=O depend on the substituents on the original C=C.
o The workup determines the oxidation state of the products

- Resonance in Ozone: Ozone (O3) is an oxide of oxygen. It is a resonance hybrid that functions in chemical
reactions as though the terminal oxygen’s bear the positive and negative charge.

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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- Mechanism for Reaction of Alkene Ozonolysis:

Step 1:
The π electrons act as the nucleophile, attacking the ozone at
the electrophilic terminal O. A second CO is formed by the
nucleophilic O attacking the other end of the C=C.

Step 2:
The cyclic species called the malozonide rearranges to the
ozonide.

Step 3:
The ozonide decomposes on workup. Reductive workup with
(usually Zn / acetic acid) gives the two carbonyl groups.

- Ozonolysis of alkynes:
 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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ADVANCED ORGANIC CHEMISTRY – I (MPC 102T) UNIT- I: Study of mechanism and synthetic applications of
following named Reactions

- The Molozonide:
 Ozone reacts with an alkene via a cycloaddition reaction to form an unstable 5-membered ring called a
molozonide.
 The 5-membered ring of the unstable molozonide has a plane of symmetry that passes through the central
oxygen and the CC bond. In the decomposition of the molozonide, not only is a weak O-O bond broken but a
relatively strong CC σ-bond is also broken. Because of the symmetry, there are two mechanistic pathways by
which the molozonide can collapse. In each pathway one of the carbonyl compounds is formed along with a
species known as a zwitterion.

Lecturer Notes_Dr. Sumanta Mondal_M. Pharm (Pharmaceutical Chemistry) _GITAM University Page | 23
E-mail: logonchemistry@gmail.com; phytochemistry@rediffmail.com
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