This document summarizes four organic reactions: 1. The Mitsunoba reaction converts alcohols to esters, acids, or ethers using triphenylphosphine and diethyl azodicarboxylate. It proceeds through an oxyphosphonium ion intermediate and inversion of stereochemistry. 2. The Mannich reaction aminomethylates carbonyl compounds with formaldehyde and a primary or secondary amine to form beta-amino carbonyl compounds. It involves initial formation of an iminium ion. 3. The Vilsmeier-Haack reaction uses phosphorus oxychloride to convert substituted amides to chloroiminium ions which react with arenes to form aromatic al

1. ORGANIC REACTION
1.Mitsunoba reaction
2.Mannich reaction
3.Vilsmeier-haack reaction
4.Sharpless asymmetric epoxidation
PREPARED BY : AZMIN M MOGAL
( M.PHARM ; SEM -1)
GUIDED BY : Mrs. MONIKA KAKDIYA
DEPARTMENT : PHARMACEUTICAL CHEMISTRY
(ADVANCED ORGANIC CHERMISTRY-1)

2. 1.MITSUNOBA REACTION
The Mitsunobu reaction is an organic reaction that converts an ALCOHOL into
a variety of functional groups, such as an ester , acid ,ethers, etc. using
triphenylphosphine and an azodicarboxylate such as diethyl azodicarboxylate
(DEAD) or diisopropyl azodicarboxylate (DIAD). The alcohol undergoes an
inversion of stereochemistry. It was discovered by Oyo Mitsunobu (1934–
2003).
2Alcohol
Ester

3. REACTION MECHANISM
3
DEAD Betaine intermediate
Deprotonation
of carboxylic
acid
Ion pair
Oxyphosphonium
ion
Triphenyl phosphine
oxide
Deprotonation of
alcohol
By DEAD
Nucleophilic attack

4. The reaction mechanism of the Mitsunobu reaction is fairly complex.
The identity of intermediates and the roles they play has been the
subject of debate.
Initially, the triphenyl phosphine (2) makes a nucleophilic attack upon
diethyl azodicarboxylate (1) producing a betaine intermediate 3,
which deprotonates the carboxylic acid (4) to form the ion pair 5.
DEAD itself deprotonates the alcohol (6) forming an alkoxide that
can form the key oxyphosphonium ion 8. The ratio and
interconversion of intermediates 8–11 depend on the carboxylic acid
pKa and the solvent polarity.Although several phosphorus
intermediates are present, the attack of the carboxylate anion upon
intermediate 8 is the only productive pathway forming the desired
product 12 and triphenylphosphine oxide (13).
4

5. APPLICATION
 Formation of 4- phenyl butyl 4-nitrobenzoate by mitsunoba reation.
5
4-phenylbutyl 4-nitrobenzoate4- nitro benzoic acid

6. 2.MANNICH REACTION
The Mannich reaction is an organic reaction which consists of an amino
alkylation of an acidic proton placed next to a carbonyl functional group with
formaldehyde and ammonia or any primary or secondary amine. The final
product is a β-amino-carbonyl compound also known as a Mannich base.
Reactions between aldimines and α-methylene carbonyls are also considered
Mannich reactions because these imines form between amines and aldehydes.
The reaction is named after Chemist Carl Mannich.
6
H+
Mannich base

7. REACTION MECHANISM
 Initially an iminium ion is formed due to nucleophilic addition of amine to formaldehyde
and subsequent loss of water molecule.
7

8. Since the reaction is carried out in acidic conditions, the enolizable carbonyl
compound is converted to enol form, which attacks the iminium ion at
positively charged carbon adjacent to nitrogen to give finally a
β-aminocarbonyl compound
8

9. APPLICATION
 4-(dimethylamino)butan-2-one is obtained when acetone reacts with formaldehyde and
dimethylaminium chloride.
9
4-(dimethylamino)butan-2-one

10. 10

11. 3.VILSMEIER-HAACK REACTION
 The Vilsmeier–Haack reaction (also called the Vilsmeier reaction) is the chemical
reaction of a substituted amide (1) with phosphorus oxychloride and an electron-rich
arene (3) to produce an aryl aldehyde or ketone (5). The reaction is named after
Anton Vilsmeier and Albrecht Haack. The reaction of a substituted amide with
phosphorus oxychloride gives a substituted chloroiminium ion (2), also called the
Vilsmeier reagent. The initial product is an iminium ion (4b), which is hydrolyzed to
the corresponding aromatic ketone or aldehyde during workup.
11Substituted amide
Chloroiminium ion
Or
Vilsmeier reagent Iminium ion

12. REACTION MECHANISM
 The reaction of the amide with phosphorus oxychloride produces an electrophilic iminium cation. The
subsequent electrophilic aromatic substitution produces an iminium ion intermediate, which is hydrolyzed to
give the desired aryl ketone or aryl aldehyde
12
Arene
Choloroiminium ion
Substituted amide
Phosphorus
oxychloride
Iminium ion Aldehyde

13. APPLICATION
One recent application of this reaction involved a new synthetic
route to tris(4-formylphenyl)amine from triphenylamine which by
known procedures resulted in a poor chemical yield of 16%. It was
found that this low yield was caused by deactivation of the remaining
benzene ring by the imine groups on the other two phenyl groups in
the third formylation step. The procedure was modified by taking the
reaction to a diimine compound followed by hydrolysis to the di-
formyl compound and then (with final position reactivated) a
separate formylation to the trisubstituted compound.
13

14. 14

15.  Production of 1-(pyridin-3-yl)-1H-pyrrole-2-carbaldehyde by vilsmeier hack reaction
15

16. 4.SHARPLESS ASYMMETRIC
EPOXIDATION
 The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare
2,3-epoxyalcohols from primary and secondary allylic alcohols
16

17.  Stereochemistry of resulting epoxide is determined by the diastereomers of the chiral
tartarate diester (diethyl tartrate / DET)
 Only 5–10 mol% of the catalyst in the presence of 3Å molecular sieves is necessary.
 The Sharpless epoxidation's success is due to five major reasons by Martijn Patist.
I. Epoxide can be easily converted to diols, aminoalcohols or ethers, so
formation of chiral epoxide is very important step in the synthesis of natural
products.
II. The Sharpless epoxidation reacts with many primary and secondary allylic
alcohols.
III. The products of the Sharpless epoxidation frequently have enantiomeric
excesses above 90%.
IV. Products of the Sharpless epoxidation are predictable using the Sharpless
Epoxidation model.
V. the reactants for the Sharpless epoxidation are commercially available and
relatively cheap. 17

18. REACTION
MECHANISM
18

19. 19