| 82% |
|
General procedure: B(C6F5)3 (67.3 mg, 0.13 mmol, 5 mol %) was added to a stirred solution of 3,4-dichlorobenzaldehyde (172 mg, 1 mmol) and NaN3 (97.5 mg, 1.5 mmol) in DMF (5 mL) and was heated at 120 C. After completion of reaction (as monitored by TLC), the reaction mixture was cooled to room temperature and was added 5 mL of cold water followed by 10 mL of 2 N HCl and 10 mL of ethyl acetate. The resulting mixture was stirred vigorously for 15 min. The organic layer was separated and aqueous layer was again extracted with ethyl acetate (3 × 15 mL). The combined organic layer was washed with water and dried over anhydrous sodium sulfate and was evaporated under reduced pressure. The crude product was purified by column chromatography (silica gel, EtOAc/hexane 9:1) to obtain pure 5-(3,4-dichlorophenyl)-1H-tetrazole. The known compounds were characterized and confirmed by comparison of their spectral data and physical properties with reported literature. |
| 78% |
With sodium azide; In N,N-dimethyl-formamide; at 110℃; for 6h;Green chemistry; |
General procedure: A mixtureof benzonitrile and sodium azide was added to 0.5g of 30mol% CAN supportedHY-zeolite in DMF. Then the reaction mixture was stirred at 110 C forspecified time. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction the catalyst was removed by simple filtration andthe filtrate was treated with 1N HCl solution followed by extraction with ethylacetate twice. The combined organic layer was finally washed with water anddried over anhydrous sodium sulfate and was evaporated under reduced pressure.The crude product was recrystallized from hot ethanol to obtain pure 5-phenyl-1H-tetrazole. The same procedure has beenfollowed for other tetrazole derivatives. All the synthesized compounds except 10& 11 (Table 4) are known compounds and their spectral dataand physical properties are identical with those reported in literature. |
| 78% |
With trimethylsilylazide; dibutyltin diacetate; In toluene; at 50℃; for 60h; |
General procedure: TMSN3 (0.52 mL, 4 mmol) and Bu2Sn(OAc)2 (0.56 mL, 2 mmol) were added to a solution of nitrile 1 (2 mmol) in benzene (2 mL). After stirring for 60 h at 30 C, the benzene was evaporated to give a crude residue, which was purified by column chromatography to give tetrazole 2. |
| 76% |
With lithium tetraazidoborate; ammonium acetate; In methanol; N,N-dimethyl-formamide; at 120℃; for 8h; |
General procedure: NH4OAc (15 mg) was added to a mixture of benzonitrile(103 mg, 1 mmol) and LiB(N3)4(93 mg, 0.5 mmol) in DMF/MeOH (9/1) solution (5 mL) and stirred the mixture was at 100 oC for 8 h. After completion of reaction (monitored by TLC),the mixture was cooled to room temperature and diluted with ethyl acetate. Theresulting solution was washed with 1 M HCl, dried over anhydrous Na2SO4, and concentrated. An aqueous solution of NaOH (1 M) was added to the residue, and the mixture was stirred for 30 min at room temperature. The resulting solution was washed with ethyl acetate, and then 2 MHCl was added until the pH value of the water layer became 1~2. The aqueouslayer was extracted with ethyl acetate three times, and the combined organic layerswere washed with 1M HCl.The organic layer was dried over anhydrous Na2SO4 and concentrated to furnish pure 5-phenyl-1-H-tetrazole 1b as a white solid (125 mg) in 86% yield. |
| 74% |
With trimethylsilylazide; di(n-butyl)tin oxide; sodium hydrogencarbonate; In toluene; |
EXAMPLE 12 5-(2-Bromophenyl)tetrazole A mixture of 2-cyanophenyl bromide (1.00 g, 5.49 mmol), dibutyltin oxide (90.4 mg, 0.549 mmol) and trimethylsilyl azide (1.26 g, 10.98 mmol) in toluene (10.9 mL) were heated at 93 C. for 72 hours. The solvent was removed under reduced pressure and chased with methanol. The residue obtained was partitioned between ethyl acetate (25 mL) and 10% sodium bicarbonate solution (25 mL). The organic phase was extracted with an additional aliquot of 10% sodium bicarbonate solution. The combined aqueous extracts were acidified to pH 2 with 10% hydrochloric acid and extracted with ethyl acetate (2*25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo to give the title compound (190 mg. 74%) as a white solid. 1 H NMR (CD3 OD, 300 MHz) delta7.48-7.6 (m, 2H), 7.70 (dd, J=2 Hz, 7 Hz, 1H), 7.84 (dd, J=1 Hz, 6 Hz, 1H). HRMS (DCl/NH3) m/e, calcd for C7 H6 N479 Br: 224.9776, found 224.9762. IR (KBr) 3440, 2600, 1602, 1056, 748 cm-1. Anal calc for C7 H6 N4 Br: C, 37.36; H, 2.24; N, 24.90. Found: C, 37.44; H, 2.25; N, 24.77. |
| 60% |
With sodium azide; triethylamine hydrochloride; |
General procedure: A mixture of a benzonitrile, 3a (310mg, 3mmol), 28 sodium azide (586mg, 9 mmol), and 29 triethylamine hydrochloride (1.24 g, 9 mmol) in 30 toluene (80 mL) was heated to 100C for 24h with stirring. After cooling, the reaction mixture was extracted with water. Then, 36% 31 HCl was added dropwise to the aqueous layer. Precipitation occurred, which was filtered off and washed with water to provide 32 4a as white solid (395mg, 90%). Mp: 214-216C. 1H NMR (500MHz, DMSO-d6): delta 8.04-7.02 (m, 2H), 7.62-7.57 (m, 3H) |
| 9.1 g (73%) |
With potassium hydroxide; ammonium chloride; In water; N,N-dimethyl-formamide; |
Step 2) 5-(2-Bromophenyl)-1H-tetrazole A mixture of 2-bromobenzonitrile (10.0 g, 0.055 mol), sodium azide (3.9 g, 0.060 mol), ammonium chloride (3.2 g, 0.060 mol), and DMF (90 mL) was heated at 100 C. for 18 h. The mixture was concentrated, taken up in water, and made basic (pH 9) with 1N KOH. The aqueous mixture was extracted with ether (discarded) and acidified with 2N HCl. The precipitate was collected by filtration to give 9.1 g (73%) of product as an off-white solid, mp 179-181 C. 1 H NMR (DMSO-d6): d 7.56 (m, 2H), 7.69 (dd, J=7.0 Hz, 2.1 Hz, 1H), 7.86 (dd, J=7.6 Hz, 1.3 Hz, 1H). |
| 9.1 g (73%) |
With potassium hydroxide; ammonium chloride; In water; N,N-dimethyl-formamide; |
Step 2 5-(2-Bromophenyl)-1H-tetrazole A mixture of 2-bromobenzonitrile (10.0 g, 0.055 mol), sodium azide (3.9 g, 0.060 mol), ammonium chloride (3.2 g, 0.060 mol), and DMF (90 mL) was heated at 100 C. for 18 h. The mixture was concentrated, taken up in water, and made basic (pH 9) with 1N KOH. The aqueous mixture was extracted with ether (discarded) and acidified with 2N HCl. The precipitate was collected by filtration to give 9.1 g (73%) of product as an off-white solid, mp 179-181 C. 1 H NMR (DMSO-d6): delta 7.56 (m, 2H), 7.69 (dd, J=7.0 Hz, 2.1 Hz, 1H), 7.86 (dd, J=7.6 Hz, 1.3 Hz, 1H). |
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