| 97% |
With Caswell No. 744A at 120℃; for 0.25h; |
|
| 96% |
With Caswell No. 744A at 120℃; for 1.5h; Green chemistry; |
|
| 96% |
With Caswell No. 744A for 3h; Heating; |
|
| 96% |
With Caswell No. 744A In lithium hydroxide monohydrate at 100℃; for 0.0833333h; |
|
| 96% |
With Caswell No. 744A at 120℃; for 0.0833333h; |
|
| 96% |
With Caswell No. 744A In N,N-dimethyl-formamide at 120℃; |
|
| 96% |
With Caswell No. 744A; C12H16CuN4O4(2+)*2BF4(1-) In N,N-dimethyl-formamide at 130℃; for 0.366667h; Microwave irradiation; |
General procedure for the synthesis of 5-substituted-1H-tetrazoles (7a)
General procedure: In a roundbottomed flask, a mixture of benzonitrile 6a (0.052 g, 0.50 mmol, 1.0 equiv) and NaN3(0.048 g, 0.75 mmol, 1.5 equiv) was added to a 5 mL DMF containing 10 mol% of ionic liquid-supported Cu(II) catalyst 5. The reaction mixture was irradiated under microwave heating at 320 W for 20 min at 130 °C. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was precipitated with cold ether and filtered through a fritted funnel to remove the catalyst. The filtrate was acidified with 5 N HCl (10 ml) to neutralize the product and extracted with ether (2 × 10 ml). The combined organic layer was dried over anhydrous MgSO4.The combined filtrate was subjected to evaporation to obtain the pure compound 5-phenyl-1H-tetrazoles 7a as the product. |
| 95% |
With Caswell No. 744A In N,N-dimethyl-formamide at 50℃; for 1.5h; Green chemistry; |
|
| 95% |
With Nano TiO2/SO42- for 0.75h; Green chemistry; |
13 5-(3-Chlorophenyl)-1H-tetrazole (3j)
General procedure: In a round-bottom flask, benzonitrile (1 mmol), sodiumazide (1 mmol), and nano TiO2/SO42 (0.2 g) were charged.Then the reaction mixture was stirred in distilleddimethylformamide (1 mL) at 120 8C. The progress ofthe reaction was followed by TLC (75:25 ethyl acetate:n-hexane). After completion of the reaction, the catalystwas separated by centrifugation, washed with doublydistilled water and acetone, and the centrifugate wastreated with 5 N HCl (20 mL) under vigorous stirring. Theaqueous solution finally obtained was extracted twice with ethyl acetate. The combined organic phase was washedwith water and concentrated to precipitate the crudecrystalline solid. All products were characterized by NMR,IR, mass spectra, and CHN analysis and the data for theknown compounds were found to be identical with theliterature. The complete spectroscopic data are describedin the supporting information. Yield: 95%. White solid. M.p. 137-139 8C (lit. [14] 138-139 8C).1H-NMR(250 MHz,DMSO-d6):d = 4.80(brs,1H),7.59(s,2H),7.95-8.00(m,2H),ppm.13C-NMR(125 Hz,DMSO-d6):d = 125.5, 126.4, 129.3, 130.8, 131.3, 133.9, 154.7 ppm. IR(KBr): n = 3068, 2968, 2430, 1558, 1473, 891 cm1. |
| 95% |
Stage #1: meta-chloro-benzonitrile With Caswell No. 744A In lithium hydroxide monohydrate at 100℃; for 0.666667h; Green chemistry;
Stage #2: With hydrogenchloride In lithium hydroxide monohydrate at 20℃; for 0.00833333h; Green chemistry; chemoselective reaction; |
|
| 95% |
With Caswell No. 744A In lithium hydroxide monohydrate at 90℃; for 0.583333h; |
2.6. General process for the synthesis of 1 H - tetrazoles
General procedure: Fe 3 O 4 CreatinineZr was added (70 mg) to a mixture of NaN 3 (1.2 mmol), nitrile (1 mmol), and H 2 O (3 mL) at 90 °C. At the end of the reaction (monitored by TLC), the Fe 3 O 4 CreatinineZr was separated using magnetic decantation. The organic layer was pre- served with 10 mL of 5 N HCl and washed with water. The product was dried over anhydrous Na 2 SO 4 ( Scheme 4 ). |
| 95% |
With Caswell No. 744A In lithium hydroxide monohydrate at 90℃; for 0.25h; |
General process for the synthesis of 5-substituted 1H-tetrazoles
General procedure: The CoFe2O4Amino glycol/Ce system was tested in the synthesis of 5-substituted1H-tetrazoles. Nitrile (1 mmol), NaN3(1.2 mmol), and CoFe2O4Amino glycol/Ce(70 mg) were added to H2O(3 mL) at 90 °C for the necessary time. After completionof the reaction (checked by TLC), the organic layer was filtered to separate the catalyst,preserved with HCl (4 N, 10 mL), and extracted with EtOAc. The extracted organicwas washed with water and dried over anhydrous Na2SO4 |
| 94% |
With Caswell No. 744A at 120℃; for 1h; |
|
| 94% |
With Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 10h; |
|
| 93% |
With monoaluminum phosphate; Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 12h; |
|
| 93% |
Stage #1: meta-chloro-benzonitrile With β-cyclodextrins In N,N-dimethyl-formamide at 20℃; for 0.25h;
Stage #2: With Caswell No. 744A; ammonia hydrochloride In N,N-dimethyl-formamide at 120℃; for 1h; |
|
| 93% |
With Caswell No. 744A at 120℃; for 2h; |
|
| 93% |
With Caswell No. 744A In dimethyl sulfoxide at 120℃; for 1.5h; |
|
| 93% |
With Caswell No. 744A at 120℃; for 5.5h; Green chemistry; |
4.4. General procedure for the synthesis of 5-substituted-1H-tetrazoles derivatives
General procedure: In a round-bottomed flask, a mixture of nitrile (1 mmol) and sodium azide (1.2 mmol) in the presence of 40 mg of Fe3O4*SBTU*Ni(II) was stirred at 120 °C in PEG for an appropriate time (monitored by TLC). Then, the reaction mixture was cooled down to room temperature. After magnetic separation of catalyst, HCl (4 N, 10 mL) was added to the filtrate and the product extracted with ethyl acetate (2 × 10 mL). The organic layer was washed with water several times, dried with anhydrous Na2SO4 and concentrated to give the crude solid crystalline product. |
| 93% |
With Caswell No. 744A at 120℃; for 2.83333h; |
|
| 93% |
With Caswell No. 744A; C32H25ClCuN6O9 In dimethyl sulfoxide at 110℃; for 5h; |
|
| 92% |
With Caswell No. 744A; propane-1,2,3-triol at 110℃; for 1.3h; |
|
| 92% |
With Caswell No. 744A at 120℃; for 0.916667h; |
2.7 General Procedure for Preparation of 5-Substituted 1H-Tetrazoles
General procedure: A mixture of sodium azide (1.1mmol) and nitrile (1mmol) in the presence of 0.05g of catalyst [Fe3O4SiO2DOPBenPyr-Ni(II)], was stirred at 120°C in PEG-400. After completion of the reaction (observed by TLC), the reaction mixture was cooled down, and catalyst was isolated by an external magnet, then 10mL HCl (4N) and 20mL H2O was added to the residue solution. The products extracted with ethyl acetate (20mL). The organic solvent was dried over anhydrous sodium sulfate, and concentrated to give the crude solid product. The precipitate was crystallized in a mixture of water and ethanol, and the pure 5-substituted 1H-tetrazoles were obtained in good to excellent yields (70-94%). |
| 91% |
With Caswell No. 744A; 1H,4H-piperazine-N,N'-diium hydrogensulfate at 100℃; for 2.15h; |
General procedure: 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 white |
| 91% |
With Caswell No. 744A at 120℃; for 8h; |
|
| 91% |
With Caswell No. 744A at 120℃; for 10h; |
|
| 91% |
With Caswell No. 744A at 120℃; for 4h; Green chemistry; |
2.4 General procedure for the synthesis of 5-substituted 1H-tetrazoles
General procedure: A mixture of sodium azide (1.2mmol) and nitrile (1mmol) in the presence of 20mg of Fe3O4MCM-41Cu-P2C, was stirred at 120°C in PEG. After completion of the reaction (observed on TLC), the reaction mixture was cooled to ambient temperature and the catalyst was separated by magnetic field. HCl (4N, 10mL) added to the filtrate and corresponding tetrazole extracted with ethyl acetate (2×10mL). The resulting organic layer was washed with distilled water, dried over anhydrous sodium sulfate, and concentrated to give the crude crystalline solid. |
| 91% |
With Caswell No. 744A at 120℃; for 1h; |
|
| 90% |
With Caswell No. 744A; 4-(dimethylamino)pyridinium acetate In neat (no solvent) at 100℃; for 2h; |
Typical procedure for the preparation of 5-(3-pyridyl)- 1H-tetrazole (Table 2, entry8):
General procedure: 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 |
| 90% |
With Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 2h; |
2.2 General procedure for the synthesis of5-substituted 1H-tetrazoles
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol),catalyst (25 mg), and DMF (3 mL) was taken in a 5 mLround bottomed flask and heated at 120C. After completionof the reaction (observed on TLC) the reactionmixture was cooled to r.t. and separated from catalyst bycentrifugation. The solvent was removed under reducedpressure. The residue was dissolved in water (5 mL) andacidified with HCl (37%). The precipitation was filteredand crystallized in a mixture of water and ethanol. Furtherpurification with column chromatography was notnecessary. |
| 90% |
With Caswell No. 744A at 120℃; for 3h; |
General Procedure for the Synthesis of 1,5-Substituted Tetrazoles
General procedure: To a stirred mixture of sodium azide (1.2 mmol) in PEG-400(2 mL), a nitrile compound (1 mmol) and NiNP-PNF (200 mL) were added and heated at 120°C under atmospheric conditions.The reaction progress was monitored by TLC. Upon reaction completion, the mixture was allowed to cool to ambient temperature and then filtered and extracted with ethyl acetate. The organic layer was washed with 1N HCl, dried with anhydrous Na2SO4, and filtered to afford pure 5-substituted tetrazoles. |
| 89% |
With Caswell No. 744A; ammonium acetate In N,N-dimethyl-formamide at 120℃; for 0.83h; |
|
| 89% |
With Caswell No. 744A; diisopropylethylammonium acetate at 90℃; for 0.5h; Green chemistry; |
General procedure for the synthesis of 5-substituted-(1H)-tetrazoles (3a-p)
General procedure: A mixture of benzonitriles (2a-p) (0.009 mol), sodium azide (0.009 mol) was dissolved in DIPEAc (5 ml) and allowed to stirr for 30 min at 80° FontWeight="Bold" FontSize="10" C. After completion of the reaction (monitored by thin-layer chromatography, TLC), the reaction mixture was cooled to room temperature and poured on crushed ice. To it 5N HCl (10 mL) was added and stirred vigorously. Otained solid products was filtered and crystallized from ethanol. The synthesized compounds were confirmed by Melting points, IR, 1H and 13C NMR which were in good agreement with those reported in the literature. |
| 89% |
With trimethylsilylazide at 140℃; for 4h; Sealed tube; |
|
| 88% |
With Caswell No. 744A at 120℃; for 8h; |
|
| 88% |
With Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 24h; |
4 Example 4: Preparation of compound III.
In a 250 mL three-necked flask were sequentially added 0.34 g of m-chlorobenzonitrile (2.5 mmol)0.32 g of sodium azide (5.5 mmol),Example 1 The resulting 0.03 g of graphene was preparedAnd dry 5 mL DMF,Fitted with a stirrer, reflux condenser, thermometer,While stirring, the temperature was raised to 120 ° C,The reaction temperature 24h.The catalyst was centrifuged, the catalyst was washed three times with 5 mL of ethyl acetate, dried and reserved for reuse. The pH of the solution was adjusted to neutral with 6N hydrochloric acid and the mixture was extracted with 60 mL of ethyl acetate. The upper organic layer was taken and washed twice with 20 mL of water After drying the organic solvent,Obtained as a white solid, dried at 50 ° C under vacuum, weighed 0.39g, 88% yield, |
| 87% |
With Caswell No. 744A; copper(II) ferrite In N,N-dimethyl-formamide at 120℃; for 12h; |
Typical procedure for the synthesis of 5-Substituted 1H-Tetrazoles:
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), catalyst (40 mol%) and DMF (3 mL) was taken in a round-bottomed flask and stirred at 120 °C temperature for 12 h. 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 (30 mL) and 5 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was again extracted with ethyl acetate (20 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. refText |
| 87% |
With Caswell No. 744A In ethanol at 80℃; for 5h; |
|
| 86% |
With Caswell No. 744A In N,N-dimethyl-formamide at 110℃; for 4h; Green chemistry; regioselective reaction; |
|
| 85% |
With Caswell No. 744A; ammonium acetate In N,N-dimethyl-formamide at 70℃; for 2h; |
2.3 General procedure for the synthesis of 5-substituted-1H-tetrazoles derivatives in the presence of a catalytic amount of the [AMWCNTs-O-Cu(II)-PhTPY] and recycling of the heterogeneous catalyst
General procedure: The [AMWCNTs-O-Cu(II)-PhTPY] heterogeneous catalyst was subjected to 5 successive reuses under the reaction conditions: For each reaction, nitrile (1.0mmol), NaN3 (1.3mmol) and NH4OAc (1.0mmol) were mixed and stirred in DMF (1mL) in the presence of 4mol-% of [AMWCNTs-O-Cu(II)-PhTPY] at 70°C in an uncapped vial. After the completion of the reaction, as monitored by TLC using n-hexane/ethyl acetate, the mixture was diluted by H2O (5mL), then the mixture was vacuum-filtered onto a sintered-glass funnel, and the residue was consecutively washed with ethyl acetate (30mL), water (5mL). The heterogeneous catalyst was recharged for another reaction run. The combined supernatant and organic washings were extracted with ethyl acetate (3×10mL), the combined organic layer was dried over anhydrous Na2SO4. Removal of the solvent under vacuum, followed by purification on silica gel using hexane/ethyl acetate as the eluent afforded the pure products. |
| 85% |
With Caswell No. 744A; activated Fuller’s earth In dimethyl sulfoxide at 120℃; for 2h; Green chemistry; |
General procedure for the synthesis of 5-aryl 1-H -tetrazoles
General procedure: To a DMSO (3 ml) solution of nitrile (1 mmol), and sodium azide (1.5 mmol), was added catalyst (10 wt %). The reaction mixture was stirred to 120 0C in an oil bath. The reaction was monitored by TLC. After completion of the reaction, the mixture was filtered to separate the catalyst. The filtrate was quenched with water (30 ml), acidified with 5N HCl (20 ml) to precipitate the product, extracted with ethyl acetate (2 X 20 ml). The combined organic layers were washed with water, dried over sodium sulphate and evaporated under reduced pressure to give the product. |
| 85% |
With Caswell No. 744A In N,N-dimethyl-formamide at 110℃; |
|
| 85% |
With Caswell No. 744A; N,N-diethylethanamine hydrochloride |
10
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 100°C 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: 214-216°C. 1H NMR (500MHz, DMSO-d6): δ 8.04-7.02 (m, 2H), 7.62-7.57 (m, 3H) |
| 83% |
With iron(III) oxide; Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 36h; |
|
| 83.5% |
With Caswell No. 744A In N,N-dimethyl-formamide at 120℃; for 24h; |
|
| 83% |
With Caswell No. 744A In lithium hydroxide monohydrate at 90℃; for 1.5h; |
2.12. General process for the synthesis of 5-substituted 1 H -tetrazoles
General procedure: The resulting CoFe 2 O 4 Amino glycol/Gd system was tested in the synthesis of 5-substituted 1 H -tetrazoles. Nitrile (1mmol), NaN 3 (1.2 mmol) and CoFe 2 O 4 Amino glycol/Gd (70 mg) were added to H 2 O (3 mL) at 90 °C for requisite time. After completion of the re- action (checked by TLC), the organic layer was filtered to separate the catalyst, preserved with HCl (4 N, 10 mL), and extracted with EtOAc. The extract was washed with water and dried over anhy- drous Na 2 SO 4 . |
| 80% |
With Caswell No. 744A; [Cu(phen)(PPh3)2]NO3 In lithium hydroxide monohydrate; isopropanol at 65℃; for 0.25h; Inert atmosphere; Microwave irradiation; Green chemistry; |
General procedure for synthesis of 5-substituted 1H-tetrazoles (2)
General procedure: In a round-bottomed flask, a mixture of organic nitrile 1 (1.0 equiv) and NaN3 (1.5 equiv) was added to 5 ml solution of H2O-IPA (1:1) containing 10 mol% [Cu(phen)(PPh3)2]NO3 as catalyst under N2 atmosphere. The reaction mixture was irradiated under microwave heating at 245 W for 15-25 min at 65°C. Reaction progress was monitored by thin-layer chromatography (TLC). After reaction completion, the mixture was filtered to remove the catalyst. The filtrate was acidified with 5 N HCl (20 ml) to neutralize the product, extracted with ethyl acetate (2 9 10 ml). The combined organic layer was dried over anhydrous MgSO4. The combined filtrate was subjected to evaporation to obtain the crude compound, which was purified over silica gel column (60-120 mesh) using 50 % ethyl acetate in hexane as eluent to obtain corresponding 5-substituted 1H-tetrazoles 2 as product. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
