1. Introduction
鏈€杩戞垜鏈嬪弸鍦堥噷瓒婃潵瓒婂鐨勪汉寮€濮嬪彂鐑1]锛岃繖鏃跺ぇ瀹舵湁蹇呰閲囩敤閫€鐑ц嵂鍝佽繘琛岄檷娓2]銆傚父瑙佺殑閫€鐑ц嵂鍖呮嫭甯冩礇鑺?/strong>銆?strong>瀵逛箼閰版皑鍩洪厷銆?strong>涔欓叞姘存潹閰?/strong>绛塠3]銆?/p>
濂堜綍杩戞湡閫€鐑ц嵂鐭己[4]锛岃澶氭湅鍙嬩拱涓嶅埌鑽紝鏈変汉鐢氳嚦钀岀敓鍑轰簡鍦ㄥ鑷埗閫€鐑ц嵂鐨勫ぇ鑳嗘兂娉曪紒涓嶈繃浠庣瀛︾殑瑙掑害璁诧紝杩欏苟闈炰笉鍙疄鐜帮紒
濡傛灉浣犲湪灏忓浜屽勾绾у杩囦竴浜涘寲瀛︾煡璇嗭紝鎴戜滑涔熷彲浠ュ埄鐢ㄥ父瑙佺殑鍘熸枡鍜岃澶囷紝鍦ㄥ鑷鍒跺涓€浜涢€€鐑ц嵂銆?/p>
涓嬮潰鎴戜滑灏嗕负澶у鎺ㄨ崘涓€绉?strong>甯冩礇鑺殑鍚堟垚璺緞锛屽ぇ瀹跺彲浠ュ涔犱竴涓嬨€傚鏋滀綘瑙夊緱鐑ф湁浣欏姏锛屼笉瑕佽汉搴婁笂鎹傜潃琚瓙纭墰锛岃捣鏉ュ姩涓€鍔ㄣ€?/p>
2. Materials and methods
甯冩礇鑺槸涓€绉嶈В鐑晣鐥涚殑闈炵斁浣撴姉鐐庤嵂锛屾棦鏄晢鍝佸悕锛屼篃鏄湁鏁堟垚鍒嗙殑鍖栧鍚嶃€傚畠鏄竴绉嶅悕涓?strong>ibuprofen鐨勫垎瀛愶紝涓枃鍚?strong>2-(4-寮備竵鍩鸿嫰鍩?-涓欓吀锛岀畝绉?strong>瀵瑰紓涓佸熀鑻笝閰?/strong>[5]銆?/p>
铏界劧鑽洅涓婄殑灏忕孩浜哄Э鍔垮鏉傦紝浣嗚繖涓垎瀛愬叾瀹炲緢绠€鍗曪紒涓棿涓€涓?strong>鑻?/strong>锛屽乏杈逛竴涓?strong>寮備竵鍩?/strong>锛屽彸杈逛竴涓?strong>灏忎笝閰?/strong>锛屾病浜嗐€傝繖鐜╂剰鐨勫悎鎴愯繃绋嬶紝鍑轰釜鏈夋満鍖栧鏈熸湯澶ч閮藉珜瀹规槗浜嗐€?/p>
2.1聽Preliminary
濡傛灉浣犳濂戒粠浜嬮姘磋涓氱殑璇濓紝閭ｄ綘瀹跺悗闄㈤噷鍙兘浼氬父澶囨湁寮備竵鑻€?/strong>姣曠珶寮備竵鑻湁妯辨鑸殑棣欑敎鍛筹紝鏄姘寸殑甯歌鍘熸枡銆傝繖鏍蜂綘灏卞彲浠ョ洿鎺ヤ粠寮備竵鑻悎鎴愬竷娲涜姮浜哰6]锛岄潪甯告柟渚匡紝姣斿叾瀹冨彂鐑х殑鏈嬪弸鍗犳嵁浜嗗厛鍙戜紭鍔匡紒
瑕佹槸浣犲湪瀹堕噷娌℃壘鍒板紓涓佽嫰锛屼篃瀹屽叏涓嶇敤鎷呭績锛?strong>鎴戜滑灏卞鍑犳锛屼粠鑻紑濮嬪悎鎴愬紓涓佽嫰銆?/strong>
鏈夌殑鏈嬪弸璇达紝閭ｆ垜瀹朵篃娌℃湁鑻晩锛?/strong>涔熶笉鐢ㄦ媴蹇冿紝鎴戜滑灏卞厛鍚堟垚鑻紒鑻彲浠ヤ粠鐓ょ劍娌逛腑鍒嗙鍑烘潵[7]锛岀叅鐒︽补鍙互閫氳繃鐤媯鎶界儫寰楀埌銆?/p> 鏈夌殑鏈嬪弸璇达紝绛夋垜鎶藉畬杩欎箞澶氱儫锛屽彂涓嶅彂鐑у鎴戝簲璇ュ凡缁忎笉閲嶈浜嗏€?/strong>閭ｆ垜浠彲浠ュ啀鎹釜鎬濊矾锛岄€氳繃鐭宠剳娌圭殑鍌寲閲嶆暣寰楀埌鑻€?/p> 棣栧厛閭€璇蜂綘鍦ㄧ偧娌瑰巶宸ヤ綔鐨勫摜浠粰浣犻棯閫佷竴涓婊＄簿鍒剁煶鑴戞补鐨勎?600脳13524脳24鐨勫崸寮忕綈锛岃繖鏍峰師鏂欑粷瀵瑰鐢ㄤ簡銆傚啀鎵句綘鐨勯搧鍖犲摜浠墦閫?涓€愰珮鍘嬪弽搴斿櫒锛屽鏋滄病鏈夌殑璇濆彲浠ョ敤楂樺帇閿呬唬鏇裤€傛渶鍚庢壘浣犵殑鍖栧鍗氬＋鍝ヤ滑鎼炰竴浜涙哀鍖栭摑-閾傞摷鍌寲鍓傘€?/p> 涓囦簨淇卞锛屾姇鏂欏紑杞?/strong>锛佺煶鑴戞补鍦ㄩ攨閲屽彂鐢?strong>鍌寲閲嶆暣鍙嶅簲锛屽彲浠ュ緱鍒拌嫰銆佺敳鑻€佷簩鐢茶嫰绛夎姵鐑冦€傝繖涔熸槸鐭虫补鐐煎寲琛屼笟鍒跺鑻殑涓€绉嶄富娴佹柟娉曘€?/p> 缁嗚妭鍐冲畾鎴愯触锛屾搷浣滄椂瑕佹敞鎰忎互涓嬪嚑鐐癸細锛?锛夐噸鏁村弽搴旈渶瑕?00掳C浠ヤ笂锛屾墍浠ョ伓鍙伴噷璁板緱澶氭坊鐐规煷锛岀伀瑕佺儳寰楁椇锛涳紙2锛夊悗缁垎绂讳骇鍝侀渶瑕?0绫抽珮鐨勭簿棣忓锛屾埧瀛愮殑鎸戦珮瑕佺暀鍑虹┖闂达紝瀹跺叿涔熸渶濂芥惉绌轰竴鐐癸紱锛?锛夐噸鏁翠骇鐢熺殑姘㈡皵涓嶈闅忔墜涓㈠瀮鍦炬《锛屽彲浠ユ敹闆嗚捣鏉ョ敓鐏倰鑿滐紝鐕冪儳鍚庣敓鎴愮殑姘磋繕鍙互椤轰究鐓叉堡锛岀幆淇濆張濂藉枬銆?/p> 鏈夌殑鏈嬪弸璇存垜瀹舵病鏈夌煶鑴戞补鍟娾€︹€﹂偅浣犱篃鍙互鐢ㄧ敳鑻鍖栧埗鑻紝鎴栬€呬箼鐐斾笁鑱氬埗鑻€傛柟娉曞緢澶氾紝浣犲閲屾€诲緱鏈夌偣涓滆タ鍚с€?/p> 2.2 Synthesis 鏈変簡鑻箣鍚庡氨鍙互寮€骞蹭簡锛?strong>鏈変簺鍚屽涓€鐪嬪埌鑻紝灏变細涓嶇敱鑷富鍦颁娇鐢ㄥ倕鍏嬬兎鍩哄寲鏉ュ緱鍒板紓涓佽嫰銆?/strong> 
浣嗚繖涓柟娉曞鏄撳嚭鐜板垎瀛愬唴閲嶆帓锛屼粠鑰屽緱鍒颁綘骞朵笉鎯宠鐨勫壇浜х墿浠蹭竵鑻?/strong>[8]锛岀劧鍚庡氨搴熶簡銆?/p> 
姣旇緝濂界殑鍋氭硶鏄潪甯稿埡婵€鍦颁娇鐢ㄨ嫰鍜屽紓涓侀叞姘湪AlCl3浣滅敤涓嬪倕鍏嬮叞鍩哄寲锛屽緱鍒拌嫰鍩哄紓涓欏熀閰€?/strong>寮備竵閰版隘澶у瀹堕噷鍙兘閮芥湁锛屼絾濡傛灉浣犲娌℃湁AlCl3鐨勮瘽锛屽彲浠ョ敤鐩愰吀鎶婁綘浠鐨勯摑閿呮憾瑙ｆ帀銆傜洂閰镐篃鏄撳緱锛屽彲浠ヤ拱娲佸帟鐏碉紝鎴栬€呴€氳繃鎻愬彇瀹ゅ弸鍛曞悙鐨勮儍閰稿緱鍒般€?/p> 
杩欐鍙嶅簲娌″暐闅惧害锛屼絾杩樻槸璁板緱閭ｅ彞璇濓紝缁嗚妭鍐冲畾鎴愯触銆傚倕鍏嬮叞鍩哄寲鍙嶅簲涓嶈兘鏈夋按锛屾墜涓€瀹氳寰楄鎿﹀共涓€浜涖€?/p>
涓嬩竴姝ユ槸鎶婇叜杩樺師锛岄渶瑕佽偧銆?strong>濡傛灉浣犲閲屾伆濂芥湁鐏閭ｅ氨濂藉姙浜嗭紝鍙互鍙栦竴浜涚伀绠殑鐕冩枡鑲硷紝杩涜濡欒叮妯敓鐨勬矁灏斿か-鍑儨绾?榛勯福榫欒繕鍘熷弽搴斻€?/strong>婧跺墏涔熷緢绠€鍗曪紝灏辩敤鍜变滑鏃ュ父鐢ㄧ殑寮€濉為湶涓殑鐢樻补鍜屽仛纰辨按闈㈠寘鐢ㄧ殑鐑х⒈灏辫銆?/p>
濡傛灉浣犲娌℃湁鐏锛屽綋鐒舵湁鐐瑰彲鎯滐紝浣嗕篃鍙互閫€鑰屾眰鍏舵閫夌敤鍏嬭幈闂ㄦ．杩樺師娉曘€?/strong>鍙渶瑕佷竴鐐归攲姹炲悎閲戝拰鐩愰吀灏卞彲浠ヤ簡銆?/p> 
鑷虫浣犲凡缁忔垚鍔熷緱鍒颁簡寮備竵鍩鸿嫰銆傚鏋滀綘宸茬粡鐑ц捣鏉ヤ簡锛屾拺浣忥紒鑳滃埄鍦ㄦ湜锛屽氨杩樺樊涓夋灏卞彲浠ュ緱鍒板竷娲涜姮浜嗐€?/p>
绗竴姝ユ垜浠鎵穻鎵堝湴浣跨敤寮備竵鍩鸿嫰鍜屼箼閰搁厫鍙嶅簲寰楀埌寮備竵鍩鸿嫰涔欓叜銆?/strong>涔欓吀閰愬彲浠ョ敤鍘ㄦ埧閲岀殑閱嬪拰浜旀哀鍖栦簩纾疯劚姘村埗澶囷紝鏄撳緱銆傝繖涓€姝ラ毦鍦ㄦ憾鍓傛槸姘㈡盁閰革紝鑵愯殌鎬ф瀬寮猴紝鎵嬪鐪肩僵鍙ｇ僵涓€瀹氭埓濂姐€?/p> 绗簩姝ユ垜浠悢棣栧紕濮垮湴灏嗗紓涓佸熀鑻箼閰敤鍏板凹闀嶅偓鍖栨阿鍖栵紝杩樺師鎴愰唶銆?/strong>濡傛灉涔嬪墠浣犳槸鑷繁鍔ㄦ墜鍌寲閲嶆暣鍒跺鐨勮嫰锛岃繖鏃跺氨鏈夌幇鎴愮殑姘㈡皵鍙互鐢ㄤ簡锛岄潪甯告柟渚裤€?/p> 鏈€鍚庝竴姝ユ垜浠笉鐢辫嚜涓诲湴鍦ㄩ挴鍌寲涓嬪姞鍏ヤ竴姘у寲纰冲弽搴旓紝灏卞彲浠ュ緱鍒板竷娲涜姮浜嗭紒鏈€濂界敤鍘ㄦ埧鐨勬娊娌圭儫鏈烘墦閫犱竴涓€氶鍘紝闃叉涓€姘у寲纰充腑姣掓垨鑰呯垎鐐搞€?/p> 杩欑鏂规硶鍙獴oots-Hoechst-Celanese鍚堟垚娉昜9]锛屾槸鐩墠宸ヤ笟鐣屽嚑涔庢渶楂樻晥鐨勩€傚鏋滀綘浠庤嫰寮€濮嬪悎鎴愶紝澶ф瑕佷笁澶╋紝宸笉澶氬悎鎴愬嚭鏉ヤ篃灏遍€€鐑т簡銆?/p> 浣嗗鏋滀綘鍦ㄥ墠涓€闃靛瓙鐨勫洡璐ф疆涓伆濂藉洡浜嗗紓涓佸熀鑻紝閭ｅ氨鑳藉揩浜轰竴姝ワ紝澶ф涓€澶╁氨鑳藉緱鍒板竷娲涜姮锛岃繕鏉ュ緱鍙婁翰鎵嬫不娌昏嚜宸便€?/strong> 杩欎釜鍚堟垚璺嚎鐨勫師瀛愬埄鐢ㄧ巼澶ф80%銆傝€屼笖鏈€鍚庝袱姝ラ兘鏄噾灞炲偓鍖栧墏鍙嶅簲锛岀瓑浣犱笅娆″啀鍙戠儳浜嗭紝鍌寲鍓備篃鍙互閲嶅鍒╃敤銆傚鏋滀綘鍚冭嵂涔嬪墠涓嶆斁蹇冭嚜宸辩殑鍚堟垚鎶€鏈紝鍙互鍘绘墦涓牳纾佺湅绾害锛屽竷娲涜姮鐨勬牳纾佸浘鎴戞斁鍦ㄨ繖閲孾10]锛屼緵澶у瀵圭収銆傛垜浠竴瀹氳鍚冨緱瀹夊績锛岀儳寰楁斁蹇冦€?/p> 
3. Conclusions and聽prospects
濡傛灉浣犳兂鎸戞垬鑷繁鐨勫姩鎵嬭兘鍔涳紝鎴栬€呯尞鐖卞績甯姪浣犵殑宸﹂偦鍙宠垗锛岃繖閲岃繕鏈変袱鏉¤矾寰勫彲渚涘ぇ瀹堕€夋嫨銆?/p>
涓€绉嶆槸鍙戠幇甯冩礇鑺嵂鏁堢殑Boots鍏徃鏈€鏃╃殑鍚堟垚娉昜11]銆傛楠ゆ瘮杈冨锛屽鏋滀綘鍙戠儳鍒氬ソ鎶婅剳瀛愮儳寰楀鏈夋満鍖栧姣旇緝鍏村锛屽彲浠ヨ€冭檻銆?/p>
鍙︿竴绉嶇敤鍒板ぇ瀹堕兘寰堢啛鎮夌殑鏍兼皬璇曞墏[12]锛屾渶澶х殑闅剧偣灏辨槸瑕佸湪鏃犳按鏉′欢涓嬭繘琛岋紝鐜板湪姝ｅソ鍐骞茬嚗锛屼篃鏄瘮杈冮€傚悎鐨勩€?/p>
褰撶劧锛屼互涓婇兘鏄笉寰楀凡涔嬫硶锛岀澶у鏈€濂界敤涓嶄笂銆傛渶杩戝彂鐑х殑鏈嬪弸澶氾紝鎴戣嚜宸变篃宸茬粡鐑ц繃涓€杞紝浜庢槸绱㈡€х儳涓綔涔愶紝缁欏ぇ瀹跺垎浜偣鍖栧灏忔妧宸с€傚ぇ瀹惰寰楀鍠濈儹姘达紝绁濆ぇ瀹舵棭鏃ュ悍澶嶏紒
Acknowledgements
鎰熻阿Marc鑰佸笀鍙婂叾甯堥棬鍏勫紵濮愬瀵规湰鏂囩殑甯姪鍜屽惎鍙戯紒
References
[1] 姣曞. 寰崥[WB].聽2022.12.16. https://weibo.com/3905559211/MjPtXvy78
[2] 鍖椾含鍗仴濮? http://wjw.beijing.gov.cn/wjwh/ztzl/xxgzbd/gzbdzcfg/202212/t20221207_2872708.html
[3]聽Sullivan, Janice E., Henry C. Farrar, Section on Clinical Pharmacology and Therapeutics, and Committee on Drugs. "Fever and antipyretic use in children."聽Pediatrics聽127, no. 3 (2011): e20103852.
[4] 鐜悆鏃舵姤. 涓哄暐閫€鐑ц嵂缂鸿揣锛熷巶瀹剁粰鍑鸿繖涓師鍥燵WX]. 2022.12.18. https://mp.weixin.qq.com/s/e2KGOcwoQ9i33OkG7PpT3A
[5]聽https://en.wikipedia.org/wiki/Ibuprofen
[6]聽Ahmadi, Abbas, Marzie Daniali, Sara Kazemi, Samira Azami, and Noshin Alizade. "Synthesis of ibuprofen with modified and economical process as an NSAID drug."Journal of Applied Chemical Research8, no. 3 (2014): 91-95.
[7]聽Mansfield, Charles Blachford. "Untersuchung des steinkohlentheers."聽Justus Liebigs Annalen der Chemie聽69.2 (1849): 162-180.
[8]聽https://www.sciencesnail.com/science/synthesis-of-ibuprofen-from-benzene
[9]聽Elango, Varadaraj, Mark Alan Murphy, Brad Lee Smith, Kenneth G. Davenport, Graham N. Mott, and Gary L. Moss. 1991. Process for producing ibuprofen. European Union EP0284310B1, filed March 18, 1988, and issued September 11, 1991. https://patents.google.com/patent/EP0284310B1/en.
[10]聽Mizrahi, Boaz, and Abraham J. Domb. "Anhydride prodrug of ibuprofen and acrylic polymers."Aaps Pharmscitech10, no. 2 (2009): 453-458.
[11]聽Ha, Min-Woo, and Seung-Mann Paek. "Recent Advances in the Synthesis of Ibuprofen and Naproxen."Molecules26, no. 16 (2021): 4792.
[12]聽Kjonaas, Richard A., Peggy E. Williams, David A. Counce, and Lindsey R. Crawley. "Synthesis of ibuprofen in the introductory organic laboratory."Journal of Chemical Education88, no. 6 (2011): 825-828.
璋㈣阿锛屾洿鐑ц剳浜?/strong>
