Name oxidation reaction

Important name oxidation reactions

1. Oxidation Reactions Presented By:- Ganesh Dashrath Ahire Reg. No- 20MCM3133 M.S. (Pharm) 1 st Year (2 nd Semester) Department of Medicinal Chemistry National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Mohali, Punjab, India 1 LS-610 Credit Seminar

2. Introduction 1. Oxidation Oxidation is loss of electrons during a reaction by a molecule or atom Oxidation is gain of oxygen and loss of hydrogen by molecule 2. Oxidizing agent / Oxidant - Agent which accepts or receives electron from another substance and get reduced - It causes another substance to be oxidized. 2

3. 1 . Dakin Oxidation Oxidation reaction in which ortho/para hydroxylated phenyl aldehyde converted to benzenediol and carboxylate. Oxidizing agent – Hydrogen peroxide General Reaction scheme Oxidation Reaction and oxidizing agents 3

4. Mechanism of Dakin oxidation reaction Steps involved Nucleophile addition of hydroperoxide anion to carbonyl carbon [1,2]-aryl migration and hydroxide elimination Nucleophilic addition of hydroxide ion to ester carbonyl carbon Elimination of phenoxide ion 4

5. Application of Dakin oxidation reaction Synthesis of benzenediols e.g., catechol Synthesis of guaiacol which is precursor in the synthesis of several flavorants Synthesis of hydroquinone which is a common photograph-developing agent Synthesis of indolequinones which is natural originating compound with anti-biotic, anti-fungal and anti-tumor property 5

6. 2. Oppenauer Oxidation General Reaction scheme Selective oxidation of 2 o alcohols reaction in which conversion of secondary alcohols to ketone Oxidizing agent - Aluminum isopropoxide 6

7. Mechanism of Oppenauer oxidation reaction Steps involved Complex formation between alcohol and aluminum Deprotonation of complex Formation of six membered transition state Hydride transfer from alpha carbon of alcohol to the carbonyl of acetone 7

8. Applications of Oppenauer Oxidation reaction In the preparation of Codeinone from codeine Synthesis of hormones such as progesterone from pregnenolone Synthesis of lactones from 1,4 and 1,5 diols Chem. Rev.   2006 , 106 , 2943–89 ChemPlusChem .  1976 , 41 : 1056–1065 8

9. 3. Oppenauer -Woodward oxidation General Reaction scheme Modification of oppenauer oxidation Woodward used potassium tert-butoxide in place of alkoxide 9

10. 4. Moffatt Oxidation General Reaction scheme Reaction in which 1 o or 2 o alcohol converted to aldehyde or ketone Oxidizing agent – DMSO and DCC 10

11. Mechanism of Moffatt oxidation reaction Steps involved Attack of DMSO to the DCC Again Protonation of DCC Addition of alcohol oxygen on the sulphur atom Decomposition of sulfenate intermediate and elimination of 1,3-dicyclohexylurea 11

12.   J.Med.Chem . 1997,  41 , 1056–1065 Applications of Moffatt o xidation reaction Moffatt oxidation provides metal free pathway to oxidize 1 o or 2 o alcohol to aldehyde or ketone Conversion of protected nucleosides to 5’- carboxaldehyde analogue 12

13. 5. Parikh-Doering oxidation General Reaction scheme - Reaction in which 1 o or 2 o alcohol converted to aldehyde or ketone Oxidizing agent – DMSO DMSO is activated by Sulfur trioxide and pyridine complex Reaction proceeds in presence of base Used in Nicolaou cortistatin total synthesis. Cortistatin is anti-inflammatory peptide Applications of Parikh-Doering oxidation J. Am. Chem. Soc. 2009, 131 , 10587-10597 13

14. Mechanism of Parikh-Doering oxidation reaction Steps involved Reaction between DMSO and sulfur trioxide Nucleophilic attack by alcohol and deprotonation by pyridine Deprotonation by base 14

15. 6 . Jones Oxidation General Reaction scheme Reaction in which 1 o or 2 o alcohol converted to carboxylic acid and ketone Oxidizing agent – Chromic trioxide and sulfuric acid 15

16. Mechanism of Jones o xidation reaction Steps involved Formation of chromic acid in situ Formation of chromate ester Intramolecular arrangement in presence of base 16

17. Applications of Jones oxidation reaction Jones reagent was used in breath analyzers. Jones reagent oxidizes ethanol to acetic acid and itself get reduced. Reduced reagent is greenish brown in color. More the reagent reduced to green color more wasted the person. oxidation of secondary alcohols to ketones Oxidation of primary alcohols to carboxylic acids 17

18. 7 . Corey Kim Oxidation General Reaction scheme - Reaction in which 1 o or 2 o alcohol converted to aldehyde or ketone - Oxidizing agent - N-Chlorosuccinimide 18

19. Mechanism of Corey-Kim o xidation reaction Steps involved – NCS and Dimethyl sulfide reacts and forms active species Nucleophilic addition of alcohol oxygen to electrophilic sulfur Deprotonation of sulfenate intermediate by base Hydride transfer from alcohol to carbon 19

20. Applications of Corey-Kim Oxidation reaction Corey-Kim oxidation protocol employed in the synthesis of novel bicyclic macrolide drug candidate EDP-420 Cook et al. implemented successful synthesis of indole alkaloids such as polyneuridine , macusine which showing different biological activity. They used Corey-Kim oxidation in their reaction pathway Monatsh chem . 2016 , 147 , 961-987 20

21. 8. Wacker-Tsuji Oxidation General Reaction scheme Wacker oxidation reaction concerns about ethene to ethanal Wacker-Tsuji reaction is lab scale modification to generate ketones Oxidizing agent – Palladium in presence of oxygen Redox cocatalyst- copper Wacker oxidation used in the synthesis of macrolide Elaiolide Synthesis of Hennoxazole A Applications of Wacker-Tsuji Oxidation Tetrahedron . 2008 , 64 , 4718 Tetrahedron. 2001 , 57, 6311 21

22. Mechanism of Wacker-Tsuji oxidation reaction Steps involved- Pd and alkene complex formation Hydroxy palladation Hydride transfer Beta elimination and formation of product 22

23. 9. Criegee Oxidation General Reaction scheme Reaction in which vicinal diols converted into aldehydes and ketones Oxidizing agent – lead tetraacetate Glycol cleavage in natural product synthesis Synthesis of aldehydes and ketones from vicinal diols Applications of Criegee oxidation 23

24. Mechanism of Criegee o xidation reaction 24

25. 10. Hass Bender Oxidation General Reaction scheme Reaction in which benzyl halides converted into benzaldehydes Oxidizing agent – sodium salt of 2-nitropropane Applications of Hass-Bender oxidation Synthesis of aromatic aldehydes which are useful as flavors, fragrances and pharmaceutical precursors 25

26. Mechanism of Hass Bender oxi dation reaction Steps involved Deprotonation of 2-nitropropane Formation of in-situ oxidant Attack of oxidant on benzyl carbon Formation of dimethyl oxime and forms product 26

27. 11. Lindgren- pinnick Oxidation General Reaction scheme - Reaction in which aldehydes are selectively converted into acids - Oxidizing agent – sodium chlorite 27

28. Mechanism of Lindgren- pinnick o xidation reaction Steps involved Formation of active oxidant Then chlorous acid adds to the carbonyl carbon Aldehydic Hydrogen transfer to the oxygen on chlorine 28

29. Thank You 29