Kathleen Floyd, Lori Gonnet, Tomislav Friščić and James Batteas
{"title":"研磨环境对铜催化机械化学合成甲苯磺酰胺的影响","authors":"Kathleen Floyd, Lori Gonnet, Tomislav Friščić and James Batteas","doi":"10.1039/D4MR00031E","DOIUrl":null,"url":null,"abstract":"<p >We provide a systematic investigation of the role of atmospheric oxygen and choice of milling assembly (<em>i.e.</em>, the milling jar and ball materials) on a prototypical medicinal mechanochemistry reaction: the copper-catalysed coupling of isocyanate and sulfonamide to form the sulfonylurea tolbutamide. Using in-house developed equipment for work under controlled-atmosphere milling conditions, we reveal that the reaction is in fact catalysed by Cu(<small>II</small>) species, with the conventionally used CuCl acting as a pre-catalyst, which becomes activated <em>via</em> aerobic oxidation during milling. Unexpectedly, the choice of milling jar material was found to have a profound effect on the coupling, with aluminium jars effectively “shutting down” reactivity, most likely by preventing CuCl oxidation. Hence, opposite to direct mechanocatalysis, a term used to describe reactions promoted by the milling jar or ball material, this observation reveals the possibility of direct mechanoinhibition – <em>i.e.</em>, the inhibition of a mechanochemical reaction by the jar. These results highlight the importance of systematic investigations of both the milling assembly, as well as atmosphere, in understanding and controlling organic mechanochemical transformations.</p>","PeriodicalId":101140,"journal":{"name":"RSC Mechanochemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2024/mr/d4mr00031e?page=search","citationCount":"0","resultStr":"{\"title\":\"The role of the milling environment on the copper-catalysed mechanochemical synthesis of tolbutamide†\",\"authors\":\"Kathleen Floyd, Lori Gonnet, Tomislav Friščić and James Batteas\",\"doi\":\"10.1039/D4MR00031E\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >We provide a systematic investigation of the role of atmospheric oxygen and choice of milling assembly (<em>i.e.</em>, the milling jar and ball materials) on a prototypical medicinal mechanochemistry reaction: the copper-catalysed coupling of isocyanate and sulfonamide to form the sulfonylurea tolbutamide. Using in-house developed equipment for work under controlled-atmosphere milling conditions, we reveal that the reaction is in fact catalysed by Cu(<small>II</small>) species, with the conventionally used CuCl acting as a pre-catalyst, which becomes activated <em>via</em> aerobic oxidation during milling. Unexpectedly, the choice of milling jar material was found to have a profound effect on the coupling, with aluminium jars effectively “shutting down” reactivity, most likely by preventing CuCl oxidation. Hence, opposite to direct mechanocatalysis, a term used to describe reactions promoted by the milling jar or ball material, this observation reveals the possibility of direct mechanoinhibition – <em>i.e.</em>, the inhibition of a mechanochemical reaction by the jar. These results highlight the importance of systematic investigations of both the milling assembly, as well as atmosphere, in understanding and controlling organic mechanochemical transformations.</p>\",\"PeriodicalId\":101140,\"journal\":{\"name\":\"RSC Mechanochemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-05-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.rsc.org/en/content/articlepdf/2024/mr/d4mr00031e?page=search\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"RSC Mechanochemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2024/mr/d4mr00031e\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC Mechanochemistry","FirstCategoryId":"1085","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/mr/d4mr00031e","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The role of the milling environment on the copper-catalysed mechanochemical synthesis of tolbutamide†
We provide a systematic investigation of the role of atmospheric oxygen and choice of milling assembly (i.e., the milling jar and ball materials) on a prototypical medicinal mechanochemistry reaction: the copper-catalysed coupling of isocyanate and sulfonamide to form the sulfonylurea tolbutamide. Using in-house developed equipment for work under controlled-atmosphere milling conditions, we reveal that the reaction is in fact catalysed by Cu(II) species, with the conventionally used CuCl acting as a pre-catalyst, which becomes activated via aerobic oxidation during milling. Unexpectedly, the choice of milling jar material was found to have a profound effect on the coupling, with aluminium jars effectively “shutting down” reactivity, most likely by preventing CuCl oxidation. Hence, opposite to direct mechanocatalysis, a term used to describe reactions promoted by the milling jar or ball material, this observation reveals the possibility of direct mechanoinhibition – i.e., the inhibition of a mechanochemical reaction by the jar. These results highlight the importance of systematic investigations of both the milling assembly, as well as atmosphere, in understanding and controlling organic mechanochemical transformations.