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CAS No. : | 95-14-7 |
Formula : | C6H5N3 |
M.W : | 119.12 |
SMILES Code : | N1N=NC2=C1C=CC=C2 |
MDL No. : | MFCD00005699 |
InChI Key : | QRUDEWIWKLJBPS-UHFFFAOYSA-N |
Pubchem ID : | 7220 |
GHS Pictogram: |
![]() ![]() ![]() |
Signal Word: | Danger |
Hazard Statements: | H302-H318-H411 |
Precautionary Statements: | P264-P270-P280-P301+P312-P305+P351+P338-P330-P337+P313-P403-P501 |
Class: | 9 |
UN#: | 3077 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With bromine; nitric acid; at 60 - 80℃; for 49h; | General procedure: A slightly modification of the previously described procedure [39] was used. 1H-Benzimidazole (31, 3g) or 193 1H-benzotriazole (32, 3g) was dissolved in a mixture of 69% 194 HNO3 (50mL) and 100% HNO3 (3mL). Next, the solution was heated to a temperature of 80C and 195 Br2 (6 equiv.) was added drop by drop within 1h. The reaction mixture was then vigorously stirred at 60C for 48h, and after this time it was cooled to room temperature, the excess of unreacted Br2 was removed in the flow of 196 nitrogen and trapped in a 20% aqueous solution of 197 Na2S2O5 (100mL). Next, the content of the flask was poured into mixture of ice-cold 15 H2O (200mL) and saturated aqueous solution of Na2S2O5 (10mL). The resulting orange precipitate was filtered off and washed with H2O (50mL) and EtOH (50mL). The resulting crude product was washed several times with hot MeOH (50mL) yielding 198 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi, 33, 5.56g, 12.82mmol, 50%) or 4,5,6,7-tetrabromo-1H-benzotriazole (TBBt, 34, 7.45g, 17.14mmol, 68%) as white solids, respectively. The identity of both polybrominated products (33 and 34) was confirmed by high-resolution mass spectrometry (HRMS). The 1H, 13C NMR and melting point values were consistent with the literature data. For 48 TBBi 33: white solid; mp 339-340C (MeOH) [339C (no data)] [88]; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C7H3Br4N2+ m/z: 434.6983, Found 434.7024; [2M+H]+ Calcd for C14H5Br8N4+ m/z: 868.3893, Found 868.4806. For TBBt 34: white solid; mp 264-266C (MeOH) [262-266C (acetic acid)] [89]; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C9H7Br5N3+ m/z: 435.6941, Found 435.6629. |
59% | With bromine; nitric acid; at 60 - 80℃; for 49h;Inert atmosphere; Irradiation; | 1H-Benzotriazole 4 (6 g, 50.4 mmol) was dissolved in a mixture of 69% HNO3 (150 mL) and fuming 100% HNO3 (10 mL). Next, the solution was heated to a temperature of 80 C and Br2 (48.3 g, 302 mmol, 15 mL) was added dropwise within 1 h. The reaction mixture was stirred vigorously using mechanical stirrer at 60 C for 48 h and irradiated by exposure to UV light. Subsequently, content of the flask was cooled to room temperature, the excess of unreacted bromine was removed in the gentle flow of nitrogen and trapped into a 20% solution of sodium pyrosulfite (150 mL). The suspension was poured into mixture of ice-cold H2O (300mL) and saturated Na2S2O5 (20mL). The resulting yellowish precipitate was filtered off, and washed with H2O (100mL) and EtOH (100mL), respectively. The obtained crude product was refluxed several times in the mixture of MeOH (50mL) and i-PrOH (25mL), and hot saturated solution was filtered off yielding white crystals 5 (13g, 29.9mmol, 59%). The purity of the compound 5 was confirmed by high-resolution mass spectrometry (HRMS). The 1H, 13C NMR and m.p. were consistent with the literature data [46]. White solid; mp 264-266C; Rf [CHCl3/MeOH (99:1, v/v)] 0.16; HRMS (ESI+, m/z): [M+H]+calcd=435.6941, [M+H]+found=435.6629. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With sodium hydroxide; In ethanol; water; acetone; at 0 - 20℃; for 0.5h; | Preparation of Intermediate 10; Intermediate 10 [0214] A solution of cyanogen bromide (1.3 g, 12.6 mmol) in acetone (5 mL) was added portion- wise slowly to a mixture of benzotriazole (3 g, 25.2 mmol, 2 eq) in EtOH (50 mL) followed by 10% aqueous NaOH (6 mL, 12.6 mmol, 1 eq) at 0 C. The reaction mixture was then stirred at RT for 30 min. Solid formation was observed. The solid was filtered and washed with cold EtOH. The resulting material was recrystallized from benzene to afford Intermediate 10 (2.2 g, 33%) as a white solid. 1H NMR: (DMSO-d6) delta 11.76 (s, 1H), 8.29- 8.39 (m, 2H), 7.86-8.09 (m, 2H), 7.44-7.72 (m, 4H), MS: 264 [M + H]+; TLC: 30% EtOAc in hexane: Rf: 0.50. |
33% | With sodium hydroxide; In ethanol; water; acetone; at 0 - 20℃; | [0227] A solution of cyanogen bromide (1.3 g, 12.6 mmol) in acetone (5 mL) was added 1985 portion- wise slowly to a mixture of benzotriazole (3 g, 25.2 mmol, 2 eq) in EtOH (50 mL) 1986 followed by 10% aqueous NaOH (6 mL, 12.6 mmol, 1 eq) at 0 C. The reaction mixture was 1987 then stirred at RT for 30 min. Solid formation was observed. The solid was filtered and 1988 washed with cold EtOH. The resulting material was recrystallized from benzene to afford 1989 Intermediate 10 (2.2 g, 33%) as a white solid. 1H NMR: (DMSO-d6) delta 11.76 (s, 1H), 8.29- 1990 8.39 (m, 2H), 7.86-8.09 (m, 2H), 7.44-7.72 (m, 4H), MS: 264 [M + H]+; TLC: 30% EtOAc in 1991 hexane: Rf: 0.50. |
33% | With sodium hydroxide; In ethanol; water; acetone; at 0 - 20℃; for 0.5h; | A solution of cyanogen bromide (1.3 g, 12.6 mmol) in acetone (5 mL) was added portion-wise slowly to a mixture of benzotriazole (3 g, 25.2 mmol, 2 eq) in EtOH (50 mL) followed by 10% aqueous NaOH (6 mL, 12.6 mmol, 1 eq) at 0C. The reaction mixture was then stirred at RT for 30 min. Solid formation was observed. The solid was filtered and washed with cold EtOH. The resulting material was recrystallized from benzene to afford Intermediate 10 (2.2 g, 33%) as a white solid. 1H NMR: (DMSO-d6) delta 11.76 (s, 1H), 8.29-8.39 (m, 2H), 7.86-8.09 (m, 2H), 7.44-7.72 (m, 4H), MS: 264 [M+H]+; TLC: 30% EtOAcin hexane: Rf: 0.50. |
23% | With ethanol; sodium hydroxide; In acetone; at 0℃; | Step lBenzotriazole [42] (1 1.8 g, 0.05 mol) was dissolved in ethanol (200 ml). To this solution kept at 0 C was added cyanogen bromide (5.0 g, 0.025 mol) in acetone (20 ml) followed by a 10% solution of NaOH (0.025 mol). The white precipitate was filtered off and washed with ice cold ethanol and recrystallized from benzene to give pure [43] as white micro needles in 23% yield. ESIMS: 264 (M+ + 1) |
With sodium hydroxide; In ethanol; water; acetone; at 0℃; for 5h; | EXAMPLE 81; A^-{(3i?)-l-[l-methyl-5-(4-methylphenyl)-17/-l,2,4-triazol-3-yl]pyrrolidin-3-yI}-l//-pyrazolo[3,4-c/]pyrimidin-4-amine; Step A: l,l-di(lH-l,2,3-benzotriazol-l-yl)methanimine; To a stirred solution of benzotriazole (11.2 g, 94.4 mmol) in ethanol (150 mL) at 0C was added a solution of cyanogen bromide (5.00 g, 47.2 mmol) in acetone (20 mL) dropwise, followed by aqueous sodium hydroxide (0.05 mmol of NaOH in 20 ml of H20). The reaction was stirred for 5 hours and the resulting white precipitate was collected by filtration. The solid was washed with cold ethanol to give title compound (10.0 g). This material was sufficiently pure for the next step. MS 264 (M+l). | |
71.21 g | With sodium hydroxide; In ethanol; water; acetone; for 0.25h;Cooling with ice; | (1) Benzotriazole (112.5 g) was dissolved in ethanol (2 L), and a solution of cyano bromide (50 g) in acetone (200 mL) was added dropwise under ice cooling. An aqueous solution of sodium hydroxide (18.9 g) dissolved in water (170 mL) was then added dropwise, and the mixture was stirred at the same temperature for 15 minutes. The deposit was filtered, washed with cold ethanol and subsequent dried to obtain Compound 1 (71.21 g) as a colorless solid. MS (m/z): 264 [M+H]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In ethanol; at 20℃; for 14h; | N-[3,5-bis(trifluoromethyl)benzyl]-N-[2-{1-methyl(pyridin-4-ylmethyl)amino]propyl}-5-(trifluoromethyl)benzyl]-2H-tetrazol-5-amine 0.132M solutions of benzotriazole (790 mg/50 ml), triethylamine (0.83 ml/50 ml) and aldehyde from Preparation 8 (3 g/50 ml) in ethanol were prepared.To the solution of amine (60 mmol) in ethanol was added benzotriazole solution (450 uL, 54 mmols), triethylamine solution (450 uL, 54 mmols), and the aldehyde solution (450 uL, 54 mmols) via the TECAN (Model: Genesis RSP 150 TECAN US, Durham, N.C., USA). Reaction mixtures were shaken at room temperature for 14 hours. Organic solvents were evaporated on Genevac HT-24 (Barnstead Genevac, Valley Cottage, N.Y., USA). Toluene (1500 uL) was added followed by 3M ethyl magnesium bromide in ether (80 uL, 240 mmol) via the TECAN. Reaction mixture was heated to 80 C. for 2 hours. Reaction mixture was cooled, diluted with ethyl acetate (2 ml), quenched with saturated aqueous NH4Cl (2 ml) then shaken. The aqueous layer was removed. Organic layer was evaporated. Residue was diluted in 1 ml of DMSO, filtered and purified. MS (ES+) Calc: 645.2, Found: 646.3 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | General procedure: To a stirred solution of benzotriazole (17.15 g, 143.9 mmol) in CH2Cl2 (200 mL), thionyl chloride(4.28 g, 2.61 mL, 35.9 mmol) was added dropwise. After stirring the resulting mixture for 30 min,3-(3-furyl)acrylic acid [20] (5.00 g, 35.9 mmol) was added and the mixture stirred at rt for a further3 h. The mixture was then filtered and the solid washed with CH2Cl2. The combined filtrate waswashed with 2M aq. NaOH water, then brine. Drying and evaporation, followed by recrystallizationof the residue (CH2Cl2), gave 31 (3.25 g, 38%) as colorless needles, m.p. 169-170 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Thionyl chloride (1.5 mL, 20 mmol) was added to a solution of benzotriazole (9.6 g, 80 mmol) in THF (100 mL) and the solution was stirred at room temperature for 30 min. Dicarboxylic acids lg-i (10 mmol) in THF (50 mL) were added to the mixture which was stirred at room temperature for 24-48 hours. The precipitate was filtered and washed with THF (50 mL). The solvent was removed under vacuum from the combined filtrate. To the residue, CHC13 (150 mL) was added; the mixture was washed with water (30 ml) and saturated Na2C03 (3 x 30 mL). The organic layer was dried over anhydrous Na2S04, then it was filtered and the solvent was evaporated under vacuum to obtain a solid, which was recrystallized from an appropriate solvent or solvent mixture to obtain the pure compounds 2g-i. (5-Methylbenzene-l,3-diyl)bis(lH-benzotriazol-l-ylmethanone) (2g) White microcrystals; yield: 70percent; mp 183-185 °C. *H NMR (300 MHz, CDC13): delta = 8.82 (br s, 1 H), 8.38 (d, / = 8.4 Hz, 2 H), 8.31 (br s, 2 H), 8.14 (d, / = 8.4 Hz, 2 H), 7.71 (t, J = 7.7 Hz, 2 H), 7.54 (t, / = 7.8 Hz, 2 H), 2.60 (s, 3 H). 13C NMR (75 MHz, CDC13): delta = 165.9, 146.0, 139.2, 136.9, 32.5, 132.4, 132.1, 130.8, 126.8, 120.5, 115.0, 21.7. Anal. Calcd for 21H14N602: C, 65.96; H, 3.69; N, 21.98. Found: C, 65.64; H, 3.66; N, 21.96. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid; In toluene; for 24h;Reflux; | General procedure: The enamides were prepared according to a modified procedure reported by Lang and coworkers1:A mixture of the appropriate benzamide (1 equiv.), phenylacetaldehyde (1 equiv.),benzotriazole (1 equiv.) and p-TsOH (0.1 equiv.) in toluene was heated to reflux for 24 h.Water formed during the reaction was removed azeotropically by a Dean-Stark apparatus. Thesolvent was removed under reduced pressure and the residue was submitted to a short filtercolumn to remove unreacted starting material. The obtained crude product was dissolved indry THF, cooled to 0 C and NaH (60% in mineral oil, 1.5 eq) was added portionwise. Thereaction mixture was stirred at room temperature until full consumption of the startingmaterial. Then Et2O was added, washed with K2CO3 and the aqueous phase was extractedthree times with Et2O. The combined organic layers were dried over Na2SO4 and the solventwas removed under reduced pressure. The crude product was purified by flashchromatography using cyclohexane and EtOAc (+1% v/v NEt3) to obtain both isomers |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With aluminum tri-bromide; carbon tetrabromide; In neat (no solvent); at 15 - 20℃; for 0.0833333h;Green chemistry; | General procedure: A mixture of the appropriate adamantane/norbornane (1 mmol), amine (1 mmol), AlBr3 (0.5 mmol) and CBr4 (0.5 mmol) was ground in a mortar and pestle at room temperature till the completion of reaction as indicated by TLC (5-10 min). The product of azole derivatives were purified by recrystallization from ethyl alcohol, and the other amine derivatives were purified by column chromatography using ethyl acetate and petroleum ether mixtures as the mobile phase. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With caesium carbonate; In N,N-dimethyl-formamide; at 23℃; for 20h;Inert atmosphere; | Under N2 atmosphere, to a mixture of lH-benzo[d] [ 1, 2 , 3] triazole (0.890 g, 7.50 mmol, 1.50 equiv) and CS2CO3 (2.44 g, 7.50 mmol, 1.50 equiv) in DMF (25.0 mL, 0.300 M) was added <strong>[456-24-6]2-fluoro-5-nitropyridine</strong> (0.71 g, 5.00 mmol, 1.00 equiv) and the reaction mixture was stirred at 23 °C for 20 h. The reaction mixture was poured to LiCl solution (100 mL) , 15 extracted with EtOAc. The combined organic layers was dried (MgSO^), filtered and concentrated in vacuo. The residue was recrystalized from hexanes/EtOAc, to afford the title compound as a yellow solid (0.870 g, 3.61 mmol, 72percent yield). Rf = 0.54 (hexanes : EtOAc 5:1 (v/v) ) . NMR (700 MHz, (CD3)2SO, 25 °C, delta) : 9.52 (br. s., 1H) , 8.90 (d, J = 20 9.03 Hz, 1H), 8.65 (d, J = 8.17 Hz, 1H) , 8.51 (d, J = 9.04 Hz, 1H) , 8.28 (d, J = 8.17 Hz, 1H) , 7.82 (t, J = 7.53 Hz, 1H) , 7.63 (t, J = 7.53 Hz, 1H) . 13C NMR (175 MHz, (CD3)2SO, 25 °C, delta) : 153.8, 146.3, 145.1, 142.7, 135.4, 130.9, 130.2, 126.1, 120.1, 114.7, 114.3 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | To a solution of 9b (11.0 g, 33.0 mmol) in CH2Cl2 (100 mL) were added SOCl2 (7.2 mL, 99.0 mmol) andDMF (1.0 mL, 13.2 mmol) at 0 °C, and the reaction mixture was stirred at room temperature for 4 h.Then, the reaction mixture was concentrated under reduced pressure. The crude mixture was applied tofollowing reaction without further purification.To a solution of crude material in CH2Cl2 (110 mL) were added Et3N (4.6 mL, 33.0 mmol) andbenzotriazole (3.9 g, 33.0 mmol) at 0 °C under an Ar atmosphere, the reaction mixture was stirred for 12h at room temperature. Then, the reaction mixture was quenched with sat. NH4Cl solution and extractedwith CH2Cl2. The organic layer was washed with 3 M NaOH aq., dried over anhydrous MgSO4 andconcentrated under reduced pressure. The residue was recrystallized from n-hexane/CH2Cl2 to afford 10b(11.4 g, 77percent) as a white powder.IR (film) 3062, 3032, 2916, 2870, 1692, 1597, 1514, 1360, 1271, 1144 cm-1; 1H NMR (500 MHz, CDCl3): 8.35 (d, J = 8.6 Hz, 1H), 8.17 (d, J = 8.6 Hz, 1H), 7.97 (dd, J1 = 8.6, J2 = 1.8 Hz, 1H), 7.94 (d, J = 2.5Hz, 1H), 7.69 (td, J1 = 8.6, J2 = 0.95 Hz, 1H), 7.54 (td, J1 = 8.6, J2 = 0.95 Hz, 1H), 7.53-7.45 (m, 4H),7.43-7.30 (m, 6H), 7.07 (d, J = 8.6 Hz, 1H), 5.22 (s, 2H), 5.19 (s, 2H); 13C NMR (67.8 MHz, CDCl3):165.5, 153.9, 148.3, 145.7, 136.5, 136.2, 132.6, 130.2, 128.6, 128.5, 128.1, 128.0, 127.4, 127.1, 126.1,123.6, 120.0, 117.5, 114.8, 112.9, 71.3, 70.8; MS (FAB): m/z 435 (M+H)+; HRMS (FAB) calcd forC27H21N3O3+, (M+H)+ 435.1583, found 435.1555. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.5% | In toluene; at 80℃; for 18h;Inert atmosphere; | Under a nitrogen atmosphere, 60 g of benzotriazole and 100 mL of toluene were added to a 500 mL three-necked flask and stirred until the benzotriazole was completely dissolved; To the above-mentioned three-necked flask, 60 mL of a toluene solution containing 135 g of 2,4,6-trimethylbenzyl bromide dissolved therein was added dropwise slowly and the mixture was allowed to react at 80 C for 18 hours. After completion of the reaction, the reaction mixture was concentrated under reduced pressure, and the residue was subjected to column chromatography separation using to a mixed solvent of dichloromethane and petroleum ether as an eluent with a volume ratio of 3: 1 .to obtain 2- (2',4?,6?-trimethylbenzyl) benzotriazole bromide salt ionic liquid.yield 50.5% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; at 60℃; for 6h; | Benzotriazole (6.0 g, 50 mmol) and 3-chloro-2-hydroxy-l-propanesulfonic acid sodium salt hydrate (10.8 g, 55 mmol) were dissolved in 40 mL of distilled water at room temperature. To the stirred solution, 4.0 g of 50% aqueous sodium hydroxide solution was added dropwise, and the solution was heated to 60 C for 6 hours. The solution was allowed to cool to room temperature, and the water was evaporated at reduced pressure. The resulting solid was washed with 30 mL of methanol and dried at room temperature to provide 15.0 g of white solid. |