This document discusses the Shapiro reaction, which was discovered by Robert H. Shapiro in 1967. The reaction involves converting aryl sulfonyl hydrazones of aldehydes and ketones into olefins using alkyl lithium reagents, grignard reagents, or alkali metal amides at -78°C. The reaction mechanism proceeds through deprotonation, elimination, and loss of nitrogen to form alkenyl intermediates. The Shapiro reaction has been used in the total synthesis of natural products like phytocassane D and in the formation of ring B in the Nicolaou Taxol total synthesis.

1. SHAPIRO REACTION
[TOSYL HYDRAZONE DECOMPOSITION]
SUBMITTED BY :
RINSHANA FATHIMA ABDUL AZEEZ
FIRST YEAR M.PHARM
PHARMACEUTICAL CHEMISTRY
AL SHIFA COLLEGE OF PHARMACY
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2. • Discovered by Robert H. Shapiro in 1967
• Shapiro reaction (1967) involves the conversion of aryl sulfonyl
hydrazones of aldehydes and ketones into olefins by reacting
with alkyl lithium reagent, grignard reagent, or alkali metal
amide.[1]
• This reaction is carried out at a temperature of -78℃
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3. The reaction similar to Bamford Stevens reaction where bases such
as Na, NaOMe, LiH, NaH, NaNH2, etc. are used.
Another major difference between the two reactions is that Shapiro
reaction yields less substitued olefins as kinetcic products (the
product that predominates when the reaction is done at low
temperature.) While Bamford Stevens reaction yields more
substituted olefins as the thermodynamic product (the product that
predominates when the reaction is done at high temperature.)[2]
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4. GENERAL SCHEME
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5. • Tosyl hydrazone is a functional group with the general structure
RR'C=N-NH-Ts , where Ts is a tosyl group.
• Tosyl or Toluene sulfonyl group with the molecular formula
CH3C6H4SO2
• This is used as “Protecting Group” for alcohols and amines.
• Proctecting groups are introduced in to a molecule by chemical
modification of a functional group to obtain chemoselectivity in a
multistep reaction. 5

6. MECHANISM
1. Deprotonation of -NH proton from aryl sulfonyl hydrazone.
2. Second deprotonation adjacent to the hydrazone group to give
a dianion.
3. Elimination of toluene sulfinate to form an intermediate
(carbanion mechanism).
4. Loss of N2 to form alkenylithium species which is then
protonated (treated with an electrophile) to give olefins.[1]
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7. MECHANISM
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8. 8

9. 9
Assymetrical highly substituted enolates are thermodynamically
more stable.

10. 10

11. 11
BREDT'S RULE
States that “a double bond
cannot be placed at the
bridgehead of a bridgehead
ring system, unless the rings are
large enough.”

12. • Synthesis of an allylic alchol, which is an intermediate in the synthesis of
Mequitazine, Which is an H1 anti histaminic used to treat allergies and
rhinitis. [5]
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SYNTHETIC APPLICATIONS

13. • (-)-phytocassane D was synthesized from (R)-Wieland Miescher Ketone
by this reaction, for determining the absolute configuration of the
phytocassane group of the phytoalexins.[3]
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WMK is a racemic bicyclic
diketone used in the total
synthesis of more than 50 natural
compounds

14. • Shapiro reaction is involved in the formation of ring B in the Nicolaou
Taxol total synthesis.[4]
A
B
D
C
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15. • A class of Chiral indenes (Verbindenes) was prepared from Verbenone
by utilising Shapiro reaction as one of the key transformation step.[3]
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16. REFERENCE
1. Jie Jack Li; Name Reactions: A Collection of Detailed Mechanisms and
Synthetic Applications Fifth Edition; Springer Science & Business Media,
30-Jan-2014; Page no. 544
2. Jie Jack Li; Name Reactions Third Edition; Springer Science & Business
Media, 2006; Page no.529
3. Laszlo Kurti, Barbara Czako; Strategic Applications of Named Reactions
in Organic Synthesis; Elsevier, 29-Apr-2005; Page no. 37
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17. 4. Pei-Qiang Huang, Zhu-Jun Yao, Richard P. Hsung; Efficiency in Natural
Product Total Synthesis; John Wiley & Sons, 24-Jul-2018; Page no.9-
93.
5. https://patents.google.com/patent/US20100105897
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REFERENCE

18. THANK YOU
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