Industrial Consultancy & Sponsored Research (IC&SR) , IIT Madras

Phosphorus Pentoxide as an Effective Coupling Reagent for Synthesis of Amides

Technology Category/Market

Technology: Detecting Faecal Pigments in water using solid-state Green Fluorescence on Metal Salts

Industry: Waste-water treatment; Applications: Water Treatment;

Market: The global water testing market is projected to reach USD 5.40B by 2028, at a CAGR of 5.57% during (2023-2028).

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Problem Statement

  • In the present era, the biological process of producing long peptides is known as protein biosynthesis & synthetic peptides are used either as drugs or in the diagnosis of disease.
  • Based on the prior arts literature survey, it is noted that though the reagents provide excellent yields & low racemization for the coupling reaction, but they are relatively expensive & the guanidium by product has to be removed by column chromatography. Further it is noted in different scenario of Benzotraizol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP) reagents which liberate hexamethylphosphoramide (HMPA), which is highly carcinogenic.
  • Hence, there is a need to develop cheap, efficient, non-toxic & non-carcinogenic coupling reagents for peptide synthesis & present invention has addressed the issues efficiently.

Technology

Present invention describes a process for synthesizing amides in one-pot via in-situ formation of anhydride in presence of a coupling reagent.

The process comprising the steps of:

  • preparing a solution of 1.2 equivalent part of acid in THF;
  • adding equivalents part of coupling reagent to the mixture
  • allowing the resulting mixture to stir at room temperature for 30 min;
  • subsequently, adding 1 equivalent part of amine, equivalent part of base , & equivalent part of catalyst to the resultant mixture;
  • extracting the mixture with Ethyl cetate (EtOAc) and sequentially washing the mixture with saturated bicarbonate solution, 10% HCl solution and saturated Sodium Chloride (NaCl) solution
  • drying the organic layer formed over anhydrous Sodium sulfate (Na2SO4);
  • Filtering & Concentrating the filtrate in vacuo; &
  • purifying and isolating the desired amide using column chromatography, wherein negligible by-product formation or minimal racemization occurs.

Further, one-pot in reaction between the carboxylic acid & amine takes place in presence of 4 equivalent P2O5 & in presence of 3 equivalent part of diisopropylethylamine & 0.2 equivalent part of catalytic amounts of DMAP.

Key Features/Value Proposition

Technical Perspective:

  • Present patent provides a coupling agent, wherein phosphorous pentoxide acts as a coupling agent for synthesis of amides from acids & amines, thereby resulting in minimal racemization

Industrial Perspective:

  • Minimize the formation of organic by product.
  • Present Patent is utilizing a coupling agent of phosphorous pentoxide which is extremely cheap, efficient, non-toxic & non- carcinogenic in nature, when used as a coupling agent during amide synthesis.
  • Cost-effective process & the separation of the product are very simple makes it an extremely attractive reagent for peptide synthesis.
  • Applicable in drugs or in the diagnosis of disease.
Questions about this Technology?

Contact for Licensing

Research Lab

Prof. Nandita Madhavan

Department of Chemistry

Intellectual Property

  • IITM IDF Ref. 1603

  • Patent No.339439

Technology Readiness Level

TRL- 3

 Proof of Concept & validated in Lab

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