Reaction & Reagents info
- Moffatt Oxidation (DMSO, DCC, Bronsted acid) is a mild oxidizing system that converts primary alcohol to aldehyde and secondary alcohol to ketone
- The effective Bronsted acid (i.e proton source) is H3PO4 or py.TFA. Usually, HCl, TFA or H2SO4 are not good proton sources for this oxidation
- It is one of the series of oxidations involving DMSO (refer to DMSO-activated oxidations)
Advantages
- Inexpensive oxidation method on manufacturing scale
- Unlike Swern oxidation that requires cryogenic condition (-78 oC), Moffatt oxidation is performed at room temperature
- Also, it is less toxic, compared to chromium-based alternatives (PCC and PDC)
Disadvantages
- The liberation of gas viz., malodrous dimethylsulphide (Me2S) is to be handled appropriately
- The by-product from DCC namely Dicyclohexylurea could be difficult to remove from the product, unless it is precipitated during the work-up
Useful Links on Reagent & Reaction:
- DMSO –DCC (Pfitzner-Moffatt Oxidation) (Reagent Guide, ACS Green Chemistry Institute) – Green Chemistry info.
- Pfitzner-Moffat oxidation (SynArchive) – Excellent compilation of reaction schemes with references
Mechanism
General Oxidation Mechanism
DMSO, as such, is not a good oxidising agent. However, it needs to be activated by an activator [such as (COCl)2 in Swern Oxidation, DCC in Moffatt oxidation] so that DMSO shall act effective oxidising agent (refer to DMSO-activated Oxidations)
Activation of DMSO by DCC
Moffatt Oxidation
Additional details
General Procedure:
To a solution of substrate (alcohol; 1 eq.), DCC (3 eq.) in dry DMSO (5 Vol) is added crystalline orthophosphoric acid (1.5 eq.). The mixture is stirred at RT for 6 h. The reaction is monitored by TLC.
The reaction mixture is then diluted with CH2Cl2 (10 Vol) or EtOAc (10 Vol) and the resultant by-product (Dicyclohexylurea) is filtered. The filtrate is washed with water and layers separated. The aqueous layer is extracted with DCM (10 Vol) or EtOAc (10 Vol). The organic layers are combined and washed with water (10 Vol) and brine solution (5 Vol). The resultant organic layer is dried over Na2SO4 and concentrated. The crude product shall be used for next reaction or if required, is purified by column chromatography.
Note:
- The reaction is usually done at RT
Typical Procedure:
WO2019202345, page no. 36
Moffatt oxidation could be carried out on large-scale. However, the reaction involves the liberation of 1 eq. gas, Me2S (dimethylsulphide) and appropriate safety controls are to be ensured while performing manufacturing. This reaction results in a by-product namely Dicyclohexylurea that often poses problems during isolation.
- The liberation of gas viz., malodrous dimethylsulphide (Me2S) is to be handled appropriately
- Unlike Swern oxidation that requires cryogenic condition (-78 oC), Moffatt oxidation is performed at room temperature
Green Chemistry Aspects:
Swern oxidation could be carried out on large-scale. However, the reaction involves the liberation of 1 eq. each of the gases such as Me2S (dimethylsulphide), CO (carbon monoxide), CO2. Appropriate safety controls are to be ensured while performing manufacturing. During work-up, HCl gets converted to amine salt (such as NEt3.HCl).
- Swern Oxidation is one of the inexpensive methods to manufacture aldehydes or ketones from Alcohols
- The liberation of gases viz., malodrous dimethylsulphide (Me2S), poisonous carbon monoxide (CO) and CO2 are to be handled appropriately
- It is important to maintain the reaction mixture at -78 oC. If the temperature is not maintained, there is a possibility of formation of mixed thioacetals (see mechanism in General Info section)