第三期-顧振華

1、1 談?wù)剬?shí)驗(yàn)室安全和實(shí)驗(yàn)的個人體會 導(dǎo)師：麻生明 研究員 匯報(bào)人：顧振華 有機(jī)所楓林論壇有機(jī)所楓林論壇 往者可諫 來者可追 2 主要內(nèi)容 實(shí)驗(yàn)室安全 個人的實(shí)驗(yàn) 科學(xué)的信譽(yù)問題 Giving Proper Credit 3 溶劑溶劑 (1) 對神經(jīng)系統(tǒng)破壞：對神經(jīng)系統(tǒng)破壞： 抑制神經(jīng)系統(tǒng)的傳導(dǎo)沖動功能，產(chǎn)生麻醉，神經(jīng)系統(tǒng)障礙或引起神經(jīng)炎等。酒精、苯、 氯化乙醇、二氯乙烷、汽油、甲酸戊酯、醋酸戊酯、二甲苯、三氯乙烯、丁醇、松節(jié) 油、煤油、丙酮、三氯甲烷、異丙苯等。 (2) 對肝臟機(jī)能損傷：對肝臟機(jī)能損傷： 損傷肝臟機(jī)能，引起惡心、嘔吐、發(fā)燒、黃疸炎及中毒性肝炎；一般氯化烴類均會引 起肝臟中毒現(xiàn)象

2、。四氯化碳、氯仿、三氯乙烯、四氯乙烷、苯及其衍生物等。 (3) 對腎臟機(jī)能破壞對腎臟機(jī)能破壞： 腎臟為毒物排泄器官，故最易中毒，且因血氧量減少，亦足以使腎臟受害，發(fā)生腎炎 及腎病。烴類之鹵化物、苯及其衍生物、二元醇及其單醚類、四氯化碳、乙醇等。 (4) 對造血系統(tǒng)破壞：對造血系統(tǒng)破壞： 破壞骨髓造成貧血現(xiàn)象。苯及其衍生物(硝基苯)如甲苯、氯化苯、二元醇等。 (5) 對粘膜及皮膚刺激：對粘膜及皮膚刺激： 刺激粘膜，使鼻粘膜出血，喉頭發(fā)炎，嗅覺喪失或因皮膚敏感產(chǎn)生紅腫、發(fā)癢、紅斑 及壞疽病等。三氯甲烷、醚、苯、丙酮、甲醇、石油、氯酚、二氯乙烯、四氯化碳等。 4 控溫儀 毛細(xì)管 溫度計(jì)、溫度計(jì)套管

3、核磁管 高溫高壓反應(yīng) 5 操作規(guī)范 整潔、有章程 （洗瓶、藥品的存放(苯胺)，稱量、取用(雙層手套法、注射 器的正確使用)、了解不同試劑的性質(zhì)(液氨)） 過柱 溶劑的轉(zhuǎn)移,溶劑球的固定,防護(hù)鏡 不要“意氣用事” 試管,蒸餾 “空中接力” 6 多借鑒別人的經(jīng)驗(yàn) LiAlH4：Workup best conducted by “1,2,3-method” for 1.0 g LiAlH4 used, added 1 mL H2O (slowly) then 2 mL of 10% aqueous NaOH, then 3 mL of H2O 無故亂翻書 8 : 2規(guī)則 7 全合成：廣度廣度 方法學(xué)

4、：深度深度 2. Corey-Bakshi-Shibata reduction Corey-Chaykovsky-epoxidation (Corey-ylide) Corey-Fuchs reaction Corey-Kim oxidation Corey-Winter olefin Synthesis 3. Coupling Reaction John F. Hartwig 根深則葉茂 1. Phil Baran Chemical (b) The 1H NMR spectrum after 4 hours; (c) The 1H NMR spectrum after 6 hours; (d

5、) The 1H NMR spectrum after 27 hours 17 H H R2 E E O OR1 O OR1 R2 E E H 1,7-H shift 1,7-H shift O O R2 E R1 E O O R2 E R1 E 18 Path A 78 O OR3 R2R1 O OR3 R1 R2 2+2 cycloaddtion O OR3 R2 R1 1,5-H shift O OR3 R2 R1 electrocyclic rearrangement 45Int22Int23 H H Path B 4578Int24 O OR3 R2R1 O OR3 R1 R2 1,

6、5-H shift8-electro- cyclization O OR3 R2 R1 H xylene O R3 R4 O 100 oC, 6 h O O R2 R3R4 R1 R2 R1 19 H H O H H O H H O H H O + O xylene 83a 84aa84ab 81% 1 : 1.3 80 oC, 3 h O Int25 Diels-Alder Reaction O O O Br + R O O R O X R (a) Ph3PBr2, CH2Cl2, Et3N (b) Ph3PI2, CH3CN, Et3N (c) (TfO)2O, CH2Cl2, Py Zn

7、Br Pd(0) R 20 83a O X = O, 86a X = NEt, 86b X = NPh, 86c + X O O xylene, 55 oC H H H X O O H O 87 86 X = O, 49%, 87aa X = NEt, 77%, 87ab X = NPh, 91%, 87ac 21 R R Increasing the steric hindranceX H H O H H O H H O H H O + O 84aa84ab Int25 O ? O D-A -electrorearrangement 22 O xylene R = Me, 83b 90 oC

8、, 2 h O R R 56%, 90b O n-Bu R = n-Bu, 83c R = Ph, 83d 57%, 90c; 8%, 91c 77%, 90d 91c 23 O 90b O 91b NEt O O xylene, 55 oC H Me H EtN O O H O 87bb86b + 24 h, 53%a a 28% of 90b was recovered 86b Diels-Alder Reaction 24 45vf O OR EtEt H 7%, Z-94vf O O R Et Et 29%, E-94vf O O R + Et Et xylene reflux, 6

9、h + Other unidentified products Int26a O OR Et Et H 1,7-H shift1,5-H shift R = -Naphthyl O OR Et Et H Int26b 25 45fc, R1 = Me 45ff, R1 = Et O OPh R1R1 O O Ph xylene reflux a 10% of 45ff was recovered 3.5 h, 67%, E-94fc 6 h, 64%, E-94ffa O O Ph R1 R1 R1 R1 H 26 ORTEP representation of trans-96sc O OP

10、h O OPh xylene sealed, 200 oC 5 hO OPh 70%, trans/cis = 1.9 : 1 45sc 96sc 27 R3 45 O O R3 R2R1 1,5-H shift O O R3 R2 R1 O O R3 R2 R1 R4 R4 R4 Int24 O O R3 R2R1 R4 H H Int28 O O R3 R2R1 R4 H H 1,5-H shift H O OR LUMO * HOMO R O OH LUMO * HOMO R = CH=CH2 R = CH=CH2 (H) (H) R4 R2 R1 R2 R1 R3 R4 28 O O

11、H3C H3C Ph D D D D D xylene, 110 oC 6 h, 64% O OPh H3C CH3 D D DD D 45gc-d5 78gc-d5 4 8 97% 98%D 97%D 97%D 98%D 84%D 93%D 5 6 3%D 29 13c-d6-d 44c-d6-d 45gc-d6 44c-d6 MgBr a-b OH CD3D3C (D)/H c OCO2Me CD3D3C (D)/H e O OPh D3C D3C H d OCO2Me CD3D3C H Conditions: (a) C2H5Br, Mg, THF, then acetylene; (b

12、) CD3COCD3, 34%; (c) NaH, Et2O, then ClCO2Me, 71%; (d) n-BuLi, Et2O, -78 oC; then H2O, -78 oC, 38%; (d) 2-allyl-4-phenylbuta-2,3-dienoic acid, Pd(OAc)2/TFP, K2CO3, DMSO, 54%, 95%D. 30 O OPh D3C D3C 45gc-d6 95%D xylene, 110 oC 6 h, 84% O D3C CD3 OPh 85%D 78gc-d6 H D60%D 4 31 O OR1 H 1,5-H shift O OR1

13、 8-electro- cyclization O OR1 H O OR1 H 1,5-H shift 1,7-H shift 1,7-H shift 45 Int28 Int24 78 101 R2 R2 R2 R2 O OR1 R2 The plausible pathway 32 O OR O OR O OR O OR O OR O OR E E O O Ph R O O OR E E Ph OR 1,5-H shift 1,5-H shift 1,5-H shift 1,7-H shift 8-electro- cyclization 6-electro- cyclization 1,

14、7-H shift 1,7-H shift M H H H H E = CO2Me 33 Giving Proper Credit Chemical thus these retractions came as a surprise to me. I strongly protest that the retractions were made without my knowledge. Sezen: During the past week, I have tried to contact professor Sames about the retraction of papers with

15、out any success. I have reserved copies of experimental data, which support the original claims of these publications, but was not given a chance to present these data. I am also prepared to perform the reactions under the supervision of professor Sames if I am given a chance.“ Columbia University h

16、as forbidden Sames to speak to the media about Sezen or the universitys investigation. The scientists Sezen identified as being able to reproduce her work are both members of the Sames group. They declined to verify her assertions or otherwise speak with C&EN. 37 Four more papers are being retracted

17、 by Columbia University Professor of Chemistry, Dalibor Sames. Sezen has cried foul over the retractions, maintaining that she has never been properly notified or consulted. Whats more, she claims not only that her work can be reproduced but that it has been reproduced by other members of the Sames group (C&EN, March 23). Her assertions cannot be verified because no one in the Sames group has been willing to speak with C&EN. Sezen now also claims that Sam