Industrial Consultancy & Sponsored Research (IC&SR) , IIT Madras
Transition Metal-free Denitrative C-s Cross Coupling of
2’- Nitrochalcones for the Synthesis of Thiochromanones
Technology Category/Market
Category-Chemicals, Pharmaceuticals & Drugs
Applications – Pharmaceuticals, Thioflavanones with antifungal, antibacterial, and antioxidant properties can be explored for their therapeutic potential in Medicine, and has applications in Biotechnology, Chemicals Industry.
Industry – Pharmaceuticals and Healthcare, Drug Development, Biotechnology
Market – The global industrial Catalyst market size was USD 20.4 Billion in 2022 and is expected to reach USD 34.6 Billion in 2032, and register a revenue CAGR of 5.3%.
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Problem Statement
- Conventional methods for synthesizing thioflavanones have several drawbacks:
- Expensive and toxic metal-catalysts.
- Sensitive ligands are required.
- Smelly sulfur sources are utilized.
- High-temperature conditions are necessary.
- Unavoidable by-products are generated.
- Multistep synthesis is involved.
- Air-sensitive starting materials are used.
- These limitations make existing protocols less suitable for industrial production.
- The inventors devised a new protocol to address these issues and make the process more useful for industrial production.
Technology
- The present disclosure relates to a transition-metal free synthesis of thiochromanone and its derivatives from 2’-nitrochalcones as starting material, iodine as a catalyst, sodium acetate as base and xanthate as an odorless sulfur surrogate.
- The main aspect of the present disclosure provides a process for synthesizing thiochromanones, wherein the process comprising the steps of:
- Adding 2’-nitrochalcone, potassium ethyl xanthate, iodine and sodium acetate base to oven-dried reaction tube to form a reaction mixture;
- Adding DMSO in the reaction mixture of step (a);
- Keeping the reaction mixture of step (b) in pre-heated oil bath having a temperature of 80 oC for a time ranging from 3 to 8 hours to obtain a reaction mixture of thiochromanone;
- Decreasing the temperature of thiochromanone reaction mixture of step (c) to room temperature and extracting the crude product with organic solvents;
- Brine wash the extracted crude product of step (d) and drying over anhydrous Na2SO4;
- Removing the solvents and separation of crude product using organic solvents to obtain the final product.
Key Features/Value Proposition
- Having the initial result in hand, the reaction condition was systematically optimized by screening all the parameters.
- After extensive optimization, the best result was obtained with 3 equiv. of xanthate, 1 equiv. of sodium acetate and 20 mol% iodine in DMSO solvent at 80 oC to yield the desired 2- arylthiochromanones.
- Thiochromanones were observed in moderate to good yield from 65% to 90%.
- Developed methodology can be used without any modification.
- Easily accessible and inexpensive raw materials such as 2’-nitrochalcones have been utilized as starting material.
- The protocol evades the use of toxic transition metals as catalyst.
- Environmentally friendly and safer process.
Areas of Application
- The methodology can be utilized to attain 3’-hydroxythioflavanone with a hydroxyl group at the 3’-position. The molecule is known to exhibit high antioxidant activity as well as potent inhibition of NO production in LPS-induced macrophage cells.
- Various other thioflavanones can be prepared which display biological properties such as antifungal, antibacterial and antioxidant properties.
- Hydrazone derivatives of thiochromanones can be prepared by post synthetic modification of these thiochromanones which show enhanced antileishmanial activity.
- The thiochromanones can be oxidized to thiochromenones very easily on reacting with catalytic amount of iodine and DMSO as solvent.
- Thiochromenones also tend to various show biological properties.
Questions about this Technology?
Contact for Licensing
Research Lab
Prof. Govindasamy Sekar
Department of Chemistry
Intellectual Property
- IITM IDF Ref. 2280
- IN 408736 – Patent Granted
Technology Readiness Level
TRL – 3
Proof of concept stage.