上游文通大学 SHANGHAI JAO TONG UNIVERSITY 苯佐卡因的合成 上海交通大学 1日g日
苯佐卡因的合成 上海交通大学
上泽通大学 SHANGHAI JLAO TONG UNIVERSITY 苯佐卡因的合成 COOH COOC2H5 COOC2Hs C2H5OH [H] NO2 NO2 NO2 NH2 COOH COOH [o] COOC2H5 H C2H5OH NO2 NO2 NH2 NH2 COOH COOC2H5 ol C2H5OH NO2 NH2 NH2 NH2
苯佐卡因的合成 苯佐卡因的合成 O COOH COOC 2 H 5 COOC 2 H 5 C H O H H 苯佐卡因的合成 NO 2 NO 2 NO 2 NH 2 C H 2 H 5 O H 1 2 COOH COOH O COOC 2 H 5 H NO 2 NO 2 NH 2 NH 2 C 2 H 5OH H 2 COOH H C O O C 2 H 5 NO 2 N H N H H C O O C 2 H 5 C 2 H 5OH O 3 2 N H 2 N H 2 NH 2
上游充通大学 SHANGHAI JLAO TONG UNIVERSITY ●●
上游充通大学 SHANGHAI JIAO TONG UNIVERSITY 氧化反应 1)Zhurnal Obshchei Khimii (1945),15 962-6.H2S04(75 g.,58%),20 g. p-nitrotoluene,60 g.MnO2,and 150 g.com.concd.H2S04 gave 80-2%p- nitrobenzoic acid in 3.5-4 hrs.at 135-45 and 74-5%at 70-90 for 10-12 hrs. It is essential to use very finely powd.MnO2 2)Zhurnal Prikladnoi Khimii(Sankt-Peterburg,Russian Federation)(1961), 34947-50. Me CO2H S:H2S04 02N 02N 80% NOTE: classification:Benzylic oxidation;Conditions:Mno2 H2S04;110 deg 4h; #Comments:other examples, Reactants:1,Solvents:1, Steps:1,Stages:1
氧化反应 1) Zhurnal Obshchei Khimii (1945), 15 962-6. H2SO4 (75 g., 58%), 20 g. p-nitrotoluene 60 g MnO2 and 150 g com concd H2SO4 gave 80 nitrotoluene, 60 g. MnO2, and 150 g. com. concd. H2SO4 gave 80-2% pnitrobenzoic acid in 3.5-4 hrs. at 135-45 and 74-5% at 70-90 for 10-12 hrs. It is essential to use very finely powd. MnO2. 2）Zhurnal Prikladnoi Khimii (Sankt Zhurnal Prikladnoi Khimii (Sankt-Peterburg Russian Federation) (1961) Peterburg, Russian Federation) (1961), 34 947-50. Me S:H2S O4 CO2H O2N O2N O2N 80% NOTE: Classification: Benzylic oxidation; # Conditions: MnO2 H2SO 4; 110 deg 4h; # Comments: other examples, Reactants: 1, Solvents: 1, Steps: 1, Stages: 1
上泽发夏大学 SHANGHAI JIAO TONG UNIVERSITY 3)Chemische Berichte (1947),80 485-93.The p-acid was obtained in 90%yield by treating 50 g.p-O2NC6H4Me and 375 g.Na2Cr207 in 400 cc. water dropwise,with vigorous stirring,under a reflux condenser,with 250 cc concd.H2S04,kept boiling (about 1 hr.)until drops of the nitrotoluene no longer appeared in the condenser,pouring upon ice,washing the ppt.with dil.HCI,and purifying it by repptn.from NaOH.m-O2NC6H4Me gave 85% of the acid with 300 g.Na2Cr207 and 200 cc.H2S04. e CO2 R:Na2Cr207,R:H2804,S:H20 02N 02N 90号 NOTE:Classification:Benzylic oxidation;Conditions:Na2Cr207;H2S04 820, Reactants:1,Reagents:2,Solvents:1, Steps:1,Stages:1
3)Chemische Berichte (1947), 80 485-93. The p-acid was obtained in 90% yield by treating 50 g. p-O2NC6H4Me and 375 g. Na2Cr2O7 in 400 cc. wat d i ith i ti i d fl d ith 250 ter dropwise, with vigorous stirring, un der a reflux con denser, with 250 cc. concd. H2SO4, kept boiling (about 1 hr.) until drops of the nitrotoluene no longer appeared in the condenser, pouring upon ice, washing the ppt. with dil HCl and purifying it by repptn from NaOH m dil. HCl, and purifying it by repptn. from NaOH. m -O2NC6H4Me gave 85% O2NC6H4Me gave 85% of the acid with 300 g. Na2Cr2O7 and 200 cc. H2SO4. M e R:N a 2 C r 2 O 7, R:H 2 S O 4, S:H 2 O C O 2 H O 2 N O 2 N 9 0 % N O T E: C l a s s i f i c a t i o n: B e n z y l i c o x i d a t i o n; # C o n d i t i o n s: N a 2 C r 2 O 7; H 2 S O 4 H 2 O, R e a c t a n t s: 1, R e a g e n t s: 2, S o l v e n t s: 1, S t e p s: 1, S t a g e s: 1
上泽通大学 SHANGHAI JIAO TONG UNIVERSITY 4)Journal of Organic Chemistry (1986),51(15),2880-3. MeC6H4R(R=H,4-NO2,3-NO2,2-NO2,4-CI,2-CI,4-Br,2-Br,4-cyano),ring- substituted with electron-withdrawing substituents,were oxidized to RC6H4CO2H. The oxidn.system is biphasic consisting of an org.phase(CICH2CH2CI)and an aq. sodium hypochlorite phase with both Ru and quaternary ammonium salts acting as catalysts.Yields are essentially quant.after 2 h at room temp.with a hypochlorite to toluene ratio of 4.5:1 provided the pH of the aq.phase is maintained between 8.0 and 10.5.Kinetic studies show the reaction to be first order in the substrate,zero order in sodium hypochlorite,and combined first order in the catalysts.The reaction mechanism is also discussed. Me 1.1 R:Naocl,R:Bu4N+.Br-,R:H2S04,C:RuC13, CO2H S:C1CH2CH2C1,S:H20 1.2 R:NaO,S:H20 O2N NOTE:hydroxide maintains pH, Reactants:1,Reagents:4,Catalysts:1,Solvents:2, Steps:1,Stages:2
4) Journal of Organic Chemistry (1986), 51(15), 2880-3. MeC6H4R (R = H, 4-NO2, 3-NO2, 2-NO2, 4-Cl, 2-Cl, 4-Br, 2-Br, 4-cyano), ringsubstituted with electron-withdrawing substituents, were oxidized to RC6H4CO2H. Th id i bi h i i i f h (ClCH2CH2Cl) d The oxidn. system is biphasic consisting of an org. phase (ClCH2CH2Cl) and an aq. sodium hypochlorite phase with both Ru and quaternary ammonium salts acting as catalysts. Yields are essentially quant. after 2 h at room temp. with a hypochlorite to toluene ratio of 4.5:1 provided the pH of the aq. phase is maintained between 8.0 and toluene ratio of 4.5:1 provided the pH of the aq. phase is maintained between 8.0 and 10.5. Kinetic studies show the reaction to be first order in the substrate, zero order in sodium hypochlorite, and combined first order in the catalysts. The reaction mechanism is also discussed. Me 1.1 R:NaOCl, R:Bu4N+ Br-, R:H2SO4, C:RuCl3, CO2H • O2N 1.2 R:NaOH, S:H2O S:ClCH2CH2Cl, S:H2O O2N NOTE: hydroxide maintains pH, Reactants: 1, Reagents: 4, Catalysts: 1, Solvents: 2, Steps: 1, Stages: 2
上泽充通大学 SHANGHAI JIAO TONG UNIVERSITY 5)Zhurnal Prikladnoi Khimii(Sankt-Peterburg,Russian Federation)(1988), 61(5),1069-73. ·6)U.S.S.R.(1988), Oxidn.of RMe(R=p-O2NC6H4,2,4-CI2C6H3)to RCO2H(same R)with 35%HNO3 at 200 proceeded with an induction period followed by rapid reaction and attenuation.The induction period was reduced to a diffusion- controlled min.by mixing preheated reactants.Rapid cooling of the reaction mixt.to 20 decreased byproduct formation.Math.and graphical representations of the process were given. Me CO2H R:HNO3,S:H20 O2N O2N NOTE:Reactants:1,Reagents:1,Solvents:1, steps:1,stages:1
• 5) Zhurnal Prikladnoi Khimii (Sankt-Peterburg, Russian Federation) (1988), 61(5), 1069-73. • 6) ( ), U.S.S.R. (1988), • Oxidn. of RMe (R = p-O2NC6H4, 2,4-Cl2C6H3) to RCO2H (same R) with 35% HNO3 at 200 ° proceeded with an induction period followed by rapid reaction and attenuation. The induction period was reduced to a diffusion reaction and attenuation. The induction period was reduced to a diffusion - controlled min. by mixing preheated reactants. Rapid cooling of the reaction mixt. to 20 ° decreased byproduct formation. Math. and graphical re p pg resentations of the process were given. M e C O 2 H O 2 N R:H N O 3, S:H 2 O O 2 N N O T E: R e a c t a n t s: 1, R e a g e n t s: 1, S o l v e n t s: 1, S t e p s: 1, S t a g e s: 1
上游充通大学 SHANGHAI JLAO TONG UNIVERSITY 7)WO 2003031634 A1 The invention relates to a method for selective oxidn.of toluene derivs.by microbial peroxidases from the Coprinus species of microorganisms. CO2H R:E202,C:Peroxidase,S:Me2CO,S:H20,rt + 4-02NC6H4CHO NOTE:biotransformation,enzymic,described medium,aldehyde major product, Coprinus spec.DSM 14525 used to obtain peroxidase,buffered soln., Reactants:1,Reagents:1,Catalysts:1,Solvents:2, Steps:1,Stages:1 8)Synlett (2004),(3),531-533.Urea-hydrogen peroxide complex (UHP)has been found to be an efficient oxidizing agent for the oxidn.of various alkyl benzenes/naphthalene/tetralin under microwave irradn.in solvent-free conditions. CO2 Me R:Urea,R:H202,3 min 02N 83% NOTE:green chem.,microwave irradn.,alternative reaction conditions gave lower yield,no solvent, Reactants:1,Reagents:2, Steps:1,Stages:1
7) WO 2003031634 A1 The invention relates to a method for selective oxidn. of toluene derivs. by microbial peroxidases from the Coprinus species of microorganisms. Me O2N R:H2O 2, C:Peroxidase, S:Me2CO, S:H2O, rt CO2H O2N + 4-O2NC6H4CHO NOTE: biotransformation, enzymic, described medium, aldehyde major product, Coprinus spec. DSM 14525 used to obtain peroxidase, buffered soln., Reactants: 1, Reagents: 1, Catalysts: 1, Solvents: 2, Steps: 1, Stages: 1 8) Synlett (2004), (3), 531-533. Urea-hydrogen peroxide complex (UHP) has been found to be an efficient oxidizing agent for the oxidn of (UHP) has been found to be an efficient oxidizing agent for the oxidn. of various alkyl benzenes/naphthalene/tetralin under microwave irradn. in solvent-free conditions. Me O2N R:Ure a, R:H2O2, 3 min CO2H O2N 83% NOTE: green chem., microwave irradn., alternative reaction condit ions gave lower yield, no solvent, Reactants: 1, Reagents: 2, Steps: 1, Stages: 1
9)Huaxue Shijie (2001),42(11),595-598.The catalytic synthesis of o-,p- nitrobenzoic acid (ONBA,PNBA)was studied with quaternary ammonium salt A-1 as phase transfer catalyst(PTC).The effects of different factors, such as PTC amt.,PTC activity,reaction temp.and time,KMnO4 amt.and basicity and acidity of reaction system on the synthesis were discussed. Under the optimal reaction conditions in which the reaction underwent for 3 h at 95 with A-1 as PTC in neutral reaction system,and the mole ratio of KMnO4 to nitrotoluene was 2.5:1,the yields of ONBA and PNBA were 95.0%and 92%resp.The results showed that A-1 was a good PTC for the synthesis of ONBA and PNBA from the oxidn.of nitrotoluene by KMnO4. 10)Hecheng Huaxue(2002),10(1),37-40. CO2H Me R:KMn04,S:H20 02N 95号 NOTE:phase transfer catalyst A-1, Reactants:1,Reagents:1,Solvents:1, steps:1,stages:1
• 9) Huaxue Shijie (2001) 42(11) 595 Huaxue Shijie (2001), 42(11), 595-598 The catalytic synthesis of o 598. The catalytic synthesis of o-, pnitrobenzoic acid (ONBA, PNBA) was studied with quaternary ammonium salt A-1 as phase transfer catalyst (PTC). The effects of different factors, such as PTC amt., PTC activity, reaction temp. and time, KMnO4 amt. and basicity and acidity of reaction system on the synthesis were discussed basicity and acidity of reaction system on the synthesis were discussed. Under the optimal reaction conditions in which the reaction underwent for 3 h at 95° with A-1 as PTC in neutral reaction system, and the mole ratio of KMnO4 to nitrotoluene was 2.5:1, the yields of ONBA and PNBA were 95 0% and 92% resp The results showed that A 95.0% and 92% resp. The results showed that A-1 was a good PTC for the 1 was a good PTC for the synthesis of ONBA and PNBA from the oxidn. of nitrotoluene by KMnO4. 10）Hecheng Huaxue (2002), 10(1), 37-40. CO2H Me O2N R:KMn O4, S:H2O CO2H O2N 95% NOTE: phase transfer catalyst A-1, Reactants: 1, Reagents: 1, Solvents: 1, Steps: 1, Stages: 1
11)Solvent-free benzylic oxidations using urea-hydrogen peroxide complex(UHP)under microwave irradiation.Paul,Satya;Nanda,Puja; Gupta,Rajive.Department of Chemistry,University of Jammu,Jammu Tawi,India.Synlett (2004),(3),531-533. CO2H Me R:Urea,R:H202,50 H2N H2N 79号 NOTE:green chem.,microwave irradn.,no solvent, Reactants:1,Reagents:2, Steps:1,stages:1
• 11）Solvent-free benzylic oxidations using urea-hydrogen peroxide complex (UHP) under microwave irradiation Paul Satya; Nanda Puja; complex (UHP) under microwave irradiation. Paul, Satya; Nanda, Puja; Gupta, Rajive. Department of Chemistry, University of Jammu, Jammu Tawi, India. Sy ( ) () nlett (2004), (3), 531-533. Me R:Ure a, R:H2O2, 50 s CO2H H2N H2N 79% NOTE: green chem., microwave irradn., no solvent, Reactants: 1, Reagents: 2, Steps: 1, Stages: 1