1、d） 酰胺的还原e） 硝基的还原f） 叠氮的还原g） Hoffman降解h） 羧酸通过Cris 重排2. 羧酸衍生物的合成a） 酰胺化的反应b） 酯化反应c） 腈转化为酯和酰胺d） 钯催化的插羰反应e） 酯交换为酰氨3. 羧酸的合成a） 醇氧化b） 酯水解c） 酰胺的水解d） 腈的水解e） 有机金属试剂的羰基化反应f） 芳香甲基的氧化4. 醛酮的合成a） Weinreb 酰胺合成醛酮b） 醇氧化c） 酯的直接还原d） 有机金属试剂对腈加成合成酮5. 脂肪卤代物的合成a） 醇转化为脂肪溴代物通过PBr3 转化通过PPh3 与 CBr4 转化 HBr直接交换 通过相应的氯代物或磺酸酯与LiBr交换
2、、b） 醇转化为脂肪氯代物通过SOCl2转化通过PPh3 与 CCl4 转化 HCl直接交换c） 醇转化为脂肪碘代物通过PPh3 与I2 转化 通过相应的氯代物或磺酸酯与NaI交换6. 芳香卤代物的合成a） Sandermyyer 重氮化卤代b） 直接卤代c） 杂环的酚羟基或醚的卤代7. 醇的合成a） 羧酸或酯的还原b） 醛酮的还原c） 卤代烃的水解d） 吡啶的氧化转位8. 酚的合成a） Sandermayer 重氮化反应b） 醚的水解c） Bayer-vigerlar 氧化d） 硼酸的氧化9. 腈的合成a） 磺酸酯或卤代烃的取代b） 酰胺的脱水c） 芳卤代烃的氰基取代10. 硝化反应11.
3、醚的合成a） 芳香醚的合成酚与烷基卤代烃的直接烷基化Mitsunobu 芳香醚化Buckwald芳香醚化b） 脂肪醚的合成醇的醚化12. 脲的合成a） 胺与异腈酸酯的反应b） 用三光气合成脲c） 羰基二咪唑（CDI）合成脲d） 对硝基苯酚碳酰胺合成脲13. 烯烃的合成a） Wittig 反应b） 羟基的消除c） Wittig-Horner 反应合成 , -不饱和酯14. 磺酸及磺酰氯的合成a） 氯磺化反应合成磺酰氯b） 从硫醇合成磺酰氯c） 磺化反应15. 氨基酸的合成a） Streck 反应合成b） 手性氨基酸的合成16. 偶联反应a） Suzuki Coupling b） Buckwald
4、 芳胺化，芳酰胺化、c） Heck 反应17. Mitsunobu 反应a） 醇的反转 b） 胺的取代18. 脱羟基反应19. 酮还原为亚甲基20. 氨的保护及脱保护策略a） 用碳酰胺作保护基 b） 苄基保护21. 醇的保护及脱保护策略a） 用硅醚进行保护b） 其他醚类保护22. 羧基的保护Boc脱保护-1格氏反应-1还原胺化-2卤化反应-2Suzuki coupling-2磺化反应-3酯化反应-3水解反应-3硝化反应-4n-BuLi-4LiAlH4还原-4POCl3的杂环氯代-5NaH-5NBS-5氢化反应-6m-CPBA-6EDC-6用三光气成脲-7芳卤用n-BuLi处理后与Weinreb
5、酰胺成酮-7Boc上保护To a solution of A （2.72 g, 13.9 mmol） and tetramethylammonium hydroxide pentahydrate （5.62 g, 31.0 mmol） in acetonitrile （270 mL） was added di-tert-butyldicarbonate （3.79 g; 17.4 mmol） and the resulting solution was allowed to stir 18 h at rt and concentrated. The residue was partitione
6、d between Et2O/H2O; the phases were separated and the aqueous phase extracted twice more with Et2O. The aqueous phase was brought to pH 4 with solid citric acid and extracted with CHCl3 （3.x.100 mL）. The organic extracts were combined, dried （Na2SO4） and concentrated to afford 2.58 g （63 percent） B
7、as a white foam.ReturnBoc脱保护Tert-Butyl 2-（2-methoxyphenoxy）ethylcarbamate （23.8 g, 89 mmol） in dichloromethane （10 ml） was cooled to 0 deg C and stirred as a mixture of trifluoroacetic acid: dichloromethane （1:1, 40 ml） was added dropwise. The mixture was allowed to warm to rt, stirred for 2 hours a
8、nd concentrated in vacuo. The residue was taken back up in dichloromethane （100 ml） and the solution was washed with saturated aqueous sodium hydrogen carbonate （3*20 ml） and aqueous sodium hydroxide （10percent, 3*20 ml）, dried （Na2SO4）, filtered and concentrated in vacuo to provide 2-（2-methoxyphen
9、oxy）ethylamine （13 g, 88percent yield） as a light yellow solid.格氏反应A stirred mixture of magnesium turnings （23.6 g, 0.98 mol） and Et2O （200 mL） under nitrogen is treated with a crystal of iodine and about 5percent of a solution of bromoethane （56.3 ml, 0.75 mol） in Et2O （375 mL）. When the reaction s
10、tarts, the remainder of the bromoethane solution is added, dropwise at a rate sufficient to maintain a gentle reflux. After the addition, stirring is continued for 1 hour. To this solution of ethylmagnesium bromide was slowly added a solution of 4-cyanopyridine （39 g, 0.375 mol） in Et2O （750 ml）. Th
11、e reaction mixture was warmed at reflux for 12 hours, treated with concentrated H2SO4 （125 ml）/H2O （125 ml）, and then washed three times with Et2O （250 ml）. The aqueous portion was made basic （PH 9） with 15percent NaOH solution and extracted five times with 250 ml portions of Et2O. The combined Et2O
12、 extracts were dried （MgSO4）, and the solvent was removed under reduced pressure to afford a brown oil （48.4 g, 95percent）.还原胺化A solution of 2-amino-4-ethylphenol （1.00 g. 7.28 mmol）, 2-naphthaldehyde （1.13 g, 7.28 mmol）, and p-toluenesulfonic acid （0.05 g） in methanol （50 ML） was stirred at room te
13、mp for 24 h. To the resultant solution, sodium borohydride （0.82 g, 22 mmol） was added in small portions. After addition was completed, the mixture was stirred at room temperature for 30 min and concentrated under vacuum. The residue was then subjected to column chromatography on silica gel eluted w
14、ith 10percent ethyl acetate in hexane and followed by recrystallization （aqueous methanol） yielded 450 mg （22percent） of analytically pure product.卤化反应To a stirred solution of 8-methyl-1-nitro-naphthalene （10.6g, 56.32 mmol） and iron （III） chloride （0.45 g, 2.77 mmo） in CCl4 （150 ml） heated to 60C w
15、as added dropwise （3.0 ml, 58.23 mmol） of bromine. After one hour, the reaction mixture was poured into saturated NaHCO3 solution, and the layers were separated. The aqueous layer was re-extracted with CH2Cl2. The combined organic layers were dried （MgSO4） and the solvent was removed under reduced p
16、ressure. The crude residue was recrystallized from ethanol and the mother liquors were concentrated and then flash chromatographed on silica, eluding hexanes:ethyl acetate （12: 1）.Suzuki coupling To a mixture of 4-（4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl）-1H-indole （2 g, 8.2 mnmol） and 3-bromoben
17、zene （0.87 ml, 8.3 mmol） in THF （28 ml） were added palladium catalyst Pd（PPh3）4 （284 mg, 0.25 mmol） and the freshly prepared sodium hydroxide solution （984 mg in 9 ml of water）.The system was degassed and then charged with nitrogen for three times. The mixture was stirred under nitrogen at 70 C oil
18、bath for 6 hours. The reaction solution was cooled to room temperature, diluted with ethyl acetate and separated from water layer. The ethyl acetate solution was washed by brine, dried over Na2SO4 and concentrated. The residue was purified on a silica gel column eluding with hexanes: EtOAc 9:1 to gi
19、ve 1.38 g （78%yield） of 4-phenyl-1H-indole as a colorless liquid.磺化反应Chlorosulfonic acid （4.66g, 40 mmol） is added dropwise to a cold （0C） solution of 2,3-dihydro-2-trifluoroacetyl-1H-Benzdeisoquinoline （2.9g, 8 mmol） in chloroform （800 ml）. The resulting solution is stirred at 0C for 30 minutes. Th
20、e cold bath is then removed and the solution is stirred at room temperature for 1 hour then cautiously poured into ice water. The organic layer is separated, dried over magnesium sulfate and concentrated to afford the title compound. The crude product is purified by column chromatography eluted with
21、 10% acetic ether in petroleum ether （2.36 g, 81% yield）.酯化反应A mixture of 4-hydroxymethylnaphthoic acid （10 g, 50 mmol）, methanol （300 ml）, and concentrate H2SO4 （2 ml） was refluxed overnight. The insolubles were filtered off and the filtrate was concentrated. The residue was taken up in ethyl aceta
22、te and washed with aqueous NaHCO3 （2*）, brine, dried over MgSO4, and concentrated to give a yellow oil. Silica gel column chromatography using ethyl acetate/hexane （1/3） gave the desired product as a yellow oil （3.3 g, 35%yield）.水解反应A solution of 1-Methyl-naphthalene-2-carboxylic acid methyl ester （
23、7.20g, 35mmol） and 2N sodium hydroxide （35ml） in tetrahydrofuran （130ml） was stirred under reflux for 18 hours. The mixture was neutralised using 2N hydrochloric acid, and extracted with dichloromethane （3x）. The combined organic solutions were dried （MgSO4）, and evaporated under reduced pressure. T
24、he crude product was purified by column chromatography on silica gelusing an elution gradient of dichloromethane: methanol （100:0 to 97:3） to afford the title compound as a solid （3.11g, 47.8%yield）.硝化反应To a cold （0C） suspension of 1-methylnaphthalene （5 g, 35.2 mmol） in HNO3 was added H2SO4 （5 ml） dropwise. After stirring the reaction for one hour, the solution was
