| Indole derivates are the heterocyclic compounds distributing most broadly in the world, which are intermediates of medicines, agrochemicals, dyestuffs and other fine chemicals. 4-nitroindole,5-bromoindole and 6-methoxyindole are important indole derivates, there has been no synthetic report about them in our country by now.In this paper, the synthetic routes of 4-nitroindole,5-bromoindole and 4-methoxy-2-nitrotoluene which are the intermediate of 6-methoxyindole were designed,the technologic conditions were studied and the mechanism were discussed respectively.The 2-methyl-3-nitroaniline was taken as the starting material, 4-nitroindole was synthesized through condensation and cyclization reactions. The influencing factors were studied, the optimized technologic conditions were given: 2-methyl-3-nitroaniline and triethyl orthoformate (n(2-methyl-3-nitroaniline)/ n(triethyl orthoformate)=1:1.3) reacted for 3.0 hr at 120℃in the presence of p-toluenesulfonic acid to afford Ethyl 2-methyl-3-nitrophenylformidate , mp.50-56℃,yield 82.58%. Recrystallized from hexyl hydride, mp.56-58℃, yield 93.2%; Ethyl 2-methyl-3-nitrophenylformidate and potassium ethoxide and diethyl oxalate (n(ethyl2-methyl-3-nitrophenylformimidate)/n(potassium ethoxide and diethyl oxalate)=1:1.15) reacted for 1.5 hr at 35℃to afford 4-nitroindole, mp.160-175℃, yield 98.9%. The product recrystallized from water-acetic acid, mp.180-190℃,yield 65.13%,then vacuum sublimate , mp.198-202℃, yield 62.5% .Overall yield 30.98%, the structure of product was confirmed by IR and 1HNMR. Then, the mechanism and kinetics of Ethyl 2-methyl-3- nitrophenylformidate were studied through experiments, the equation of reactive velocity was deduced: -dCA/dt=kCA2CB3.The indole was taken as the starting material, the 5-bromoindole was synthesized through three steps reactions. The pivotal influencing factors were studied, the optimized technologic conditions were given: In 80ml water ,pH=4,0.1mol indole and sodium bisulfite reacted for 20 hr at 30℃to afford sodium indole- 2-sulfonate, yield 96.4%; Sodium indole- 2-sulfonate and acetic anhydride (n(sodiumindole-2 -sulfonate)/n(acetic anhydride)=1:15) reacted for 2hr at 70℃to afford sodium N-acetylindoline-2-sulfonate , yield 81.97%; Sodium N-acetylindoline-2-sulfonate and bromine (n(sodium N-acetylindoline -2-sulfonate)/ n(bromine)=1:1.1) reacted below 5℃to afford 5-bromoindole , mp.86-90℃,yield 91.21%; Recrystallized from cyclohexylbenzene, mp.90-92℃, yield 82.2%. Overall yield 59.25%. Compared with other methods, this method has the advantages of milder reaction conditions, easily-handled manipulationt,lower cost of the materials and easier industrialization.The p-toluidine was taken as the starting material, 4-methyl-3-nitrophenol was synthesized through nitration, diazotization and hydrolyzation, then methylation to afford 4-methoxy-2-nitrotoluene. The pivotal influencing factors were studied, the optimized technologic conditions were given: p-toluidine reacted for 3 hr below 5℃with nitrosonitric acid , yield 78.12%; then followed by diazotization in the solution of 60% sulfuric acid with nitrite sodium,then hydrolyzed at 120℃to afford 4-methyl-3-nitrophenol, yield 15.63%,mp.70-74℃;Recrystallized from tetrachloride, mp.75-76℃, yield 80%. In the solution of 4-methyl-3-nitrophenol, potassium carbonate was added one-off at first,then dimethyl sulphate was dropwised, the mixture reacted for 2hr at 25℃to afford 4-methoxy-2-nitrotoluene, yield 91.05%.
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