3-(2H-Tetrazol-5-yl)pyridine

General procedure: A screw capped vial was charged with nitrile (2 mmol), NaN3(2.4 mmol, 1.2 equiv.) and tetrabutylammonium bromide (2.4 mmol, 1.2 equiv.). The resulting mixture was stirred at 105 °C and monitoredby TLC. After completion of the reaction, the reaction mixture wascooled to room temperature and dissolved with water (5 mL). Then, theaqueous solution was acidified with 1M HCl to pH = 3. If a precipitatewas formed, the suspension was filtered and the filter cake was washedwith water to afford the pure product. Otherwise, the aqueous solutionwas extracted with EtOAc (3 × 4 mL). The organic phase was washedwith 1M HCl (3 × 4 mL), dried with anhydrous Na2SO4, filtered andevaporated under vacuum to afford the pure product.To a round-bottomed flask containing 4-(N, N-dimethylamino)pyridiniumacetate (0.15 mmol, 0.02 g) at 100 C, 3-cyanopyridine (1.0 mmol, 0.104 g) andsodium azide (1.0 mmol, 0.06 g) were added and the mixture was stirred. After1 h, the reaction was complete. The mixture was cooled and washed with coldEtOH (2 5 mL), each time it was permitted to stir for 1 h. Filtration followed bydrying of the precipitate gave the corresponding pure tetrazole as a white solid.Yield (0.14 g, 94percent); mp 242–244 C; 1H NMR (400 MHz, DMSO-d6) d (ppm): 9.10(s, 1H), 8.42 (d, J = 7.9 Hz, 1H), 8.22 (d, J = 7.9 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H); 13CNMR (100 MHz, DMSO-d6) d (ppm): 162.7, 151.9, 149.8, 137.1, 126.4, 125.3; IR(KBr) v (cm1): 3389, 2129, 2036, 1644, 1423, 1144, 1014, 754, 639, 410.General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), Cu complex catalyst (0.4 molpercent) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 110 °C temperature. After completion of the reaction the catalyst was separated from the reaction mixture with an external magnet and reaction mixture was treated with ethyl acetate (2 × 20 mL) and 1 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (2 × 15 mL). The combined organic layers were washed with water, concentrated, and the crude material was chromatographed on silica gel (Hexane-EtoAc, 1:1) to afford the pure product.General procedure: A mixture of the appropriate nitrile (1 mmol), NaN3 (1.5 mmol), toluene (2 mL) and AgNTf2 (5 molpercent) was placed in a round bottomed flask and heated at 85 oC. The progress of the reaction was monitored by TLC. After the completion of the reaction, the reaction mixture was cooled and treated with ethyl acetate (15 mL) and 1M HCl (15 mL)and stirred vigorously. The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (3 × 10 mL). The combined organic layer was washed with water and concentrated to give the pure tetrazole. All the products are known compounds and the spectral data and melting points were identical to those reported in the literature. The disappearance of one strong and sharp absorption band (CN stretching band), and the appearance of an NH stretching band in the IR spectra, were characteristic of the formation of 5-substituted 1H-tetrazoles.In a roundbottom flask in 100°C, consecutively, the catalyst (0.015mmol, 0.004 g), 3-cyanopyridine (1.0 mmol, 0.104 g) andsodium azide (1.0 mmol, 0.065 g) were added and the mixturewas stirred for 90 min until it was completed. Then, thereaction mixture was cooled to room temperature andwashed with ethanol (25 mL). After filtration, the white In a roundbottom flask in 100°C, consecutively, the catalyst (0.015mmol, 0.004 g), 3-cyanopyridine (1.0 mmol, 0.104 g) andsodium azide (1.0 mmol, 0.065 g) were added and the mixturewas stirred for 90 min until it was completed. Then, thereaction mixture was cooled to room temperature andwashed with ethanol (25 mL). After filtration, the whiteGeneral procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and catalyst (0.02 g, contains 0.4 molpercent of Cu(II)) in DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 °C. The progress of the reaction was followed by thin-layer chromatography (TLC). After completion of the reaction, the reaction mixture was cooled to room temperature and diluted with ethyl acetate (3×20 mL). The catalyst was removed by using magnetic field or filtration and then the resulting solution was washed with 1N HCl, dried over anhydrous NaGeneral procedure: NHGeneral procedure: In a typical procedure, 5-aryl-1H-tetrazoles (1–24) were synthesized by adding aryl nitriles (1 eq.), sodium azide (1.2 eq.), and ammonium chloride (1 eq.) in solvent, the mixture was refluxed for 24 h. Progress of the reaction was monitored by thin layer chromatography. After completion of the reaction, 2.5 mL of 2M NaOH was added and the solution was stirred for half an hour. The reaction mixture was concentrated on reduced pressure, and dissolved in water. 3M HCl was added to the reaction mixture until precipitates formed. The precipitates were filtered and washed with distilled water. The yields of title compounds were found to be moderate to high.[0342] 3-(1H-tetrazol-5-yl)pyridine (64). To a solution of 3-cyanopyridine (1. 1 g, 10.6 mmol) in DMF (15 mL) was added ammonium chloride (718 mg, 13.4 mmol) and sodium azide (824 mg, 12.7 mmol) and the resultant slurry was vigorously stirred at 90 °C for 15 h. The DMF was removed in vacuo, the residue was dissolved in aqueous potassium hydroxide (1 M, 20 mL), washed with EtOAc (2 x 25 mL), the aqueous layer was adjusted to pH No. 3 with aqueous HCl (6 N) and the solid was collected by filtration to afford the title compound 64 (904 mg, 46 percent yield) as a white solid: mp = 239-241 °C dec. ; 1H NMR (CDC13) b 9.21 (m, 1H), 8.76 (m, 1H), 8.39 (m, 1H), 7.64 (m, 1H) ; LRMS (ESI) m/z calcd for C6H6N5 [M + H] + 148, found 148; HRMS (ESI) m/z calcd for C6H6Ns [M + H] + 148.0623, found 148.0624 ; HPLC > 99percent (tR = 4. 88 min, 60 (A): 40 (B): 0.009 (C); tR = 3.74 min, 60 (A): 40 (B): 0.02 (C) ).General procedure: InClStep-1: To a mixture of 3-cyanopyridine (12 g, 115 mmol) and trimethylsilyl azide (20 ml, 150 mmol), was added a solution of 0.1 M tetra-n-butylammonium fluoride in THF (57 ml, 56 mmol) at 25-30° C. temperature. The resulting mixture was heated at 80° C. for overnight. The mixture is allowed to warm at 25-30° C. temperature and then quenched in ice-water mixture. Solid precipitated out was filtered and washed with water (2.x.25 ml) and dried under vacuum to provide step-1 compound in 62percent (10.5 g) yield. MS: 148 (M+1).

Molecular Weight:147.14
XLogP3:0.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:147.05449518
Monoisotopic Mass:147.05449518
Topological Polar Surface Area:67.4
Heavy Atom Count:11
Complexity:128
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes