Chemistry: add notable one-step reaction procedure
Okumaya devam et...
← Previous revision | Revision as of 12:07, 7 May 2024 |
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| [[Celgene Corporation]] originally synthesized thalidomide using a three-step sequence starting with [[Glutamate|<small>L</small>-glutamic acid]] treatment, but this has since been reformed by the use of [[Glutamine|<small>L</small>-glutamine]].<ref name="synth">{{cite journal| vauthors = Muller GW, Konnecke WE, Smith "*****", Khetani VD | date=19 March 1999|title=A Concise Two-Step Synthesis of Thalidomide | journal=Organic Process Research & Development|volume=3|issue=2|pages=139–140|doi=10.1021/op980201b }}</ref> As shown in the image below, ''N''-carbethoxyphthalimide (1) can react with <small>L</small>-glutamine to yield ''N''-phthaloyl-<small>L</small>-glutamine (2). Cyclization of ''N''-phthaloyl-<small>L</small>-glutamine occurs using [[carbonyldiimidazole]], which then yields thalidomide (3).<ref name="synth" /> Celgene Corporation's original method resulted in a 31% yield of ''S''-thalidomide, whereas the two-step synthesis yields 85–93% product that is 99% pure. | [[Celgene Corporation]] originally synthesized thalidomide using a three-step sequence starting with [[Glutamate|<small>L</small>-glutamic acid]] treatment, but this has since been reformed by the use of [[Glutamine|<small>L</small>-glutamine]].<ref name="synth">{{cite journal| vauthors = Muller GW, Konnecke WE, Smith "*****", Khetani VD | date=19 March 1999|title=A Concise Two-Step Synthesis of Thalidomide | journal=Organic Process Research & Development|volume=3|issue=2|pages=139–140|doi=10.1021/op980201b }}</ref> As shown in the image below, ''N''-carbethoxyphthalimide (1) can react with <small>L</small>-glutamine to yield ''N''-phthaloyl-<small>L</small>-glutamine (2). Cyclization of ''N''-phthaloyl-<small>L</small>-glutamine occurs using [[carbonyldiimidazole]], which then yields thalidomide (3).<ref name="synth" /> Celgene Corporation's original method resulted in a 31% yield of ''S''-thalidomide, whereas the two-step synthesis yields 85–93% product that is 99% pure. |
| In 2023, it is reported that [[phthalic anhydride]] and [[Glutamine|<small>L</small>-glutamine]] under suitable conditions can react directly to form thalidomide. In the procedure, phthalic anhydride and <small>L</small>-glutamine are grounded and added into [[toluene]] solvent. The solution, along with [[triethylamine]] and [[acetic anhydride]], is refluxed at ~110°C for 9 hours; after that the solution goes though a simple [[vacuum filtration]] procedure to obtain the product.<ref>{{Cite journal |last=Savini |first=Emanuel Bruno |last2=Bandieri |first2=Edoardo |date=2023 |title=One step synthesis of thalidomide |url=https://cssp.chemspider.com/Article.aspx?id=964 |journal=[[ChemSpider]] |language=en}}</ref> | |
| [[File:Thalidomide_syntehsis.png|center|thumb|567x567px|Muller et al.'s two-step thalidomide synthesis]] | [[File:Thalidomide_syntehsis.png|center|thumb|567x567px|Muller et al.'s two-step thalidomide synthesis]] |
Okumaya devam et...