* 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.
Reference：
[1] Australian Journal of Chemistry, 1999, vol. 52, # 11, p. 1029 - 1033
2
[ 623-03-0 ]
[ 16687-61-9 ]
Yield
Reaction Conditions
Operation in experiment
99%
With sodium azide; ammonium cerium (IV) nitrate In N,N-dimethyl-formamide at 110℃; for 6 h; Inert atmosphere; Green chemistry
General procedure: sodiumazide (1.5 mmol) was added to a magnetically stirred solution of nitrile 1a(1 mmol) in anhydrous DMF and the CAN (10 mmol percent) was added. The reactionmixture was constantly stirred for another 6 h at 110 C under nitrogenatmosphere. After the completion of reaction as seen by TLC, the reactionmixture was brought to room temperature and the solvent was evaporatedunder vacuum. The crude thus obtained, was dissolved in ethyl acetate (20 mL)and solution was washed with acidified water (4 M HCl, 15 mL) twice.Separated organic layer was washed with brine solution dried overanhydrous Na2SO4, and solvent was removed under high vacuum to obtaintetrazole 1b as a white crystalline solid in 97percent yield.
99%
With sodium azide In N,N-dimethyl-formamide at 120℃; for 4 h;
General procedure: Cu(II)-NaY (0.1 g) was added to a mixture of benzonitrile (0.206 g, 2.0 mmol) and sodium azide (0.169 g, 2.6 mmol) in DMF (5 mL) and mixture was stirred at 120 °C for 3 h. After completion of reaction (as monitored by TLC), the catalyst was centrifuged, washed with ethyl acetate and the centrifugate was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL) and stirred vigorously. 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 and concentrated to give the crude solid crystalline 5-phenyltetrazole. The product was characterizedby 1H NMR , 13C NMR and mass spectroscopic analysis.
97%
With sodium azide In N,N-dimethyl-formamide at 90℃; for 3 h;
General procedure: In a double-necked round bottom flask (100 mL) equippedwith a condenser was added a mixture consisting ofnitrile (0.005 mol), NaN3 (0.006 mol), and monodisperse Pt NPsVC in DMF (1.5 mL). The mixture washeated at reflux until TLC monitoring indicated no furtherimprovement in the conversion. The reaction mixture wasthen cooled to room temperature, vacuum-filtered usinga sintered-glass funnel and the residue was washed withethyl acetate (3×10 mL). The filtrate was treated with5 mL HCl (4 mol L−1 to reach pH= 3 and it was allowedto stir for 30 minutes. Subsequently, the organic layer wasseparated, dried over anhydrous Na2SO4 and evaporated.The crude product was purified by recrystallization and/orcolumn chromatography on silica gel eluted with propersolvents to get pure 5-Phenyl 1H-tetrazole.
96%
With sodium azide In water at 100℃; for 2 h; Green chemistry
General procedure: Benzonitrile (1 mmol, 0.103 g), sodium azide (1.1 mmol, 0.0759 g), and 2 mL water were taken in a reaction tube and stirred at room temperature to make homogeneous suspension, and then 20 wtpercent catalyst (ZnO–RGO) was added to the reaction mixture. The reaction mixture was heated to 100 °C for 2 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and centrifuged. The filtrate was treated with 5N HCl (10 mL) and then with ethyl acetate. The organic layer was separated, washed with deionized water, and then dried over anhydrous sodium sulfate and concentrated to give the crude solid crystalline 5-phenyl-1H-tetrazole. It was recrystallized from n-hexane, ethyl acetate, and the yield was about 0.143 g.
95%
at 120℃; for 4 h;
General procedure: A mixture of the required nitrile (1 mmol), sodium azide(1 mmol) and the catalyst MNP (0.05 g) was stirred at 120° C in PEG (1 mL) as solvent. After completion of the reaction, as indicated by TLC, the mixture was cooled to room temperature and diluted with 1:1 H2O:Ethyl acetate(10 mL) and then stirred at ambient temperature (10 min). The catalyst was removed by applying a magnetic field, and the decantate was treated with HCl (4 N, 10 mL). The organic layer was separated, washed with water, dried over sodium sulfate and concentrated to precipitate the crude crystalline solid. The pure tetrazoles were characterized bytheir spectroscopic data and melting points.
95%
With sodium azide; aminosulfonic acid In N,N-dimethyl-formamide at 120℃; for 5 h;
General procedure: A mixture of 4-nitrobenzonitrile (0.296 g, 2 mmol), sodium azide (0.195 g, 3 mmol), and sulfamic acid (0.0097 g, 0.1 mmol) was stirred at 120°C in DMF (5 mL) for the appropriate time (Table 2) until TLC (4:1 n-hexane:ethyl acetate) indicated no further progress in the conversion. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature, then 20 mL diethyl ether was added to the mixture and stirred for 10 minutes. The catalyst was separated by simple gravity filtration, washed with diethyl ether (2 £ 10 mL) and dried at 40°C for 30 min. The recovered catalyst wasused for three additional cycles and gave the tetrazole in 95, 85 and 75percent (with 4-nitrobenzonitrile). The filtrate was treated with ethyl acetate (30 mL) and 6 N HCl(20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to give 5-(4-nitrophenyl) tetrazole (0.363 g), 95percent yield.
95%
at 120℃; for 2 h;
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.
95%
at 120℃; for 0.333333 h; Green chemistry
General procedure: To a suspension of the catalyst (0.004 g) in PEG (2 mL), nitrile (1 mmol) and sodium azide (1.2 mmol) were added and the mixture was stirred vigorously at 120 °C for the required time (Table 6). After the reaction was completed (as monitored by TLC), the catalyst was separated with a magnet. HCl (4 N, 10 mL) was then added to the residue, and the tetrazole was extracted with ethyl acetate. The organic extract was washed with distilled water, dried over anhydrous Na2SO4 and then evaporated to give the desired tetrazole.
95%
With sodium azide; C19H17N3O4(2-)*Cu(2+) In ethylene glycol at 120℃; for 3 h;
General procedure: In 25mL round-bottomed flask, sodium azide (0.076g, 1.2mmol) and polymeric copper (II) complex (0.005g) were added to a solution of benzonitrile (0.103g, 1mmol) in ethylene glycol (3mL) with stirring at room temperature. The reaction temperature was raised up to 120°C for 3h. The reaction was monitored by TLC at regular intervals. After completion of the reaction, the reaction mixture was cooled to room temperature and treated with 10mL HCl (2N) and extracted with 10mL ethyl acetate. The resulted organic layers were separated and washed with 2×10mL distilled water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel (100–200 mesh) to afford the corresponding products.
94%
With sodium azide In N,N-dimethyl-formamide at 110℃; for 2.5 h; Green chemistry
General procedure: A mixtureof benzonitrile and sodium azide was added to 0.5g of 30molpercent 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.
94%
at 140℃; for 0.833333 h; Green chemistry
General procedure: NaN3 (0.975 g, 15 mmol)was dissolved in DES (10 mL) at room temperature by stirring until a clear solution was formed. Then benzonitrile (10 mmol) was added. The reaction mixture was constantly stirred at 140 °C and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the cold water (10 mL). The solid was obtained and filtered. The obtained solid is taken into cold water (10 mL). Then it was acidified carefully to pH 5 with 5 M HCl. The organic material was extracted thrice with ethyl acetate; the resultant organic layer was washed with distilled water, dried over anhydrous sodium sulfate, and concentrated to give the crude solid crystalline 5-substituted 1H-tetrazole. The resulting product, although evident as a single compound by TLC, was purified by simple recrystallization from aqueous ethanol giving pure 5-substituted 1H-tetrazoles.
94%
With sodium azide; <i>L</i>-proline In N,N-dimethyl-formamide at 110℃; Green chemistry
General procedure: The mixture of organic nitrile (1 mmol), NaN3 (1.25 mmol) and L-proline (30 molpercent) in DMF (5mL) was stirred at 110 °C for 1-2 h. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the reaction mixture was allowed to cool to room temperature. Thecooled reaction mixture was poured in ice water (15 mL) with stirring. The resulting mixture wasacidified with dilute HCl under vigorous stirring. The solid product* was filtered under suction,washed with sufficient cold water till free of acid. The product was air dried to obtain the pureproduct.*In cases where solid product was not obtained after acidification, like benzyl cyanide andaliphatic nitriles, the acidified aqueous phase was extracted with ethyl acetate (2 X 20 mL), thecombined organic phase was washed with brine, dried over anhydrous sodium sulfate andconcentrated in vacuo to get the corresponding pure product.
93%
With sodium azide In dimethyl sulfoxide at 85℃; for 12 h;
General procedure: General procedure for the synthesis of Tetrazole. A mixture of benzonitrile (103 mg, 1 mmol), sodium azide (97.5 mg, 1.5 mmol), and 3 mL DMSO solvent was added in a 25 mL round bottomed flask. Further (50 mg, 23 mol percent, w/w) catalyst was added to the reaction mixture. The reaction mixture was heated to 85 °C for 12 h. After completion of the reaction (as monitored by TLC), the catalyst was separated by simple filtration, washed with diethyl ether and the filtrate was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL) and stirred vigorously. 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 and dried over anhydrous sodium sulfate and were evaporated under reduced pressure to give the product. The product was purified by the column chromatography. The structure was confirmed by spectral analysis (1H NMR, mass and elemental analysis).
93%
With sodium azide In N,N-dimethyl-formamide at 110℃; for 4 h;
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.
93%
With sodium azide; Acetate de N,N-dimethylamino-4 pyridinium In neat (no solvent) at 100℃; for 2 h;
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
93%
With sodium azide; silver(I) triflimide In toluene at 85℃; for 3 h;
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.
93%
at 100℃; for 2 h;
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
93%
With sodium azide; copper(II) nitrate trihydrate In N,N-dimethyl-formamide at 120℃; for 16 h;
General procedure: Cu(NO3)2·3H2O (0.10 mmol), the appropriate nitrile 1 (1.0 mmol), NaN3(2.0 mmol) and DMF (1 mL) were added to a 50 mL round-bottomed flask equipped with a magnetic stirrer. The reaction mixture was stirred in an oil bath at 120 °C for 16 h. After cooling to room temperature, the reaction was acidified HCl (3 M, pH 1.0). Ethyl acetate (~30 mL) wasadded, and stirring was continued until no solid was present. The organic layer was separated, and the aqueous layer was extracted with ethylacetate twice. The combined organic layers were washed with saturatedbrine, and concentrated in vacuo. The residue was purified by columnchromatography (silica gel, EtOAc-PE) to afford the product 2.
92%
With Nano TiO2/SO42- In N,N-dimethyl-formamide for 2 h; Green chemistry
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: 92percent. White solid. M.p. 262–263 8C (lit. [11] 261–263 8C) 1H-NMR (250 MHz; DMSO-d6): d 8.04 (d, 2H,J = 8.52 Hz, Ar–H), 7.62 (d, 2H, J = 8.52 Hz, Ar–H), 4.15 (brs,1H,–NH); 13C-NMR (62.9 MHz, DMSO-d6): d 154.8, 135.8,129.4, 128.6, 123.1; IR (KBr): n = 3419, 2927, 2816, 2723,1602, 1457, 1437, 1383, 1350, 1161, 1095, 1055, 875,765 cm1.
91%
With sodium azide In N,N-dimethyl-formamide at 90℃; for 8 h; Inert atmosphere
General procedure: 5-Benzyl-1H-tetrazole (2a). To a DMF solution of benzyl cyanide (1a, 100 mg, 0.85 mmol) and NaN3(67 mg, 1.02 mmol, 1.2 eq) was added OSU-6 (15 mg, 15 wtpercent relative to 1a). The reaction mixturewas heated at 90 °C (oil bath temperature 95–100 °C) for 4 h at which time TLC indicated the reactionwas complete. The crude reaction mixture was filtered to remove the catalyst, and the filtrate was added to water and extracted with EtOAc (3 x 15 mL). The combined extracts were washed with H2O (3 x 15 mL) and saturated aq. NaCl (1 x 15 mL), dried (MgSO4), filtered, and concentrated under vacuum to give 2a (129 mg, 94percent).
91%
at 120℃; for 10 h; Green chemistry
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.
90%
With sodium azide; ammonium acetate In N,N-dimethyl-formamide at 70℃; for 2.5 h;
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-percent 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.
90%
With lithium tetraazidoborate; ammonium acetate In methanol; N,N-dimethyl-formamide at 100℃; for 8 h;
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. The resulting 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 M HCl was added until the pH value of the water layer became 1~2. The aqueous layer was extracted with ethyl acetate three times, and the combined organic layers were 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 86percent yield.
90%
With sodium azide; copper(l) chloride In N,N-dimethyl-formamide at 120℃; for 12 h;
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and copper(I) chloride (4 mole percent) in DMF (2 mL) was stirred at 120 °C for the appropriate time period. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled and treated with 5 mL of HCl (4 mol L−1) and 10 mL of ethyl acetate, successively. The ethyl acetate extract was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The product thus obtained was recrystallised from acetic acid to afford pure 5-substituted 1H-tetrazoles.
90%
With sodium azide; activated Fuller’s earth In dimethyl sulfoxide at 120℃; for 1.5 h; Green chemistry
General procedure: To a DMSO (3 ml) solution of nitrile (1 mmol), and sodium azide (1.5 mmol), was added catalyst (10 wt percent). 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.
90%
at 90℃; for 0.5 h; Green chemistry
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.
90%
With sodium azide; (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate In water; isopropyl alcohol at 65℃; for 0.25 h; Inert atmosphere; Microwave irradiation; Green chemistry
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 molpercent [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 percent ethyl acetate in hexane as eluent to obtain corresponding 5-substituted 1H-tetrazoles 2 as product.
89%
With sodium azide; copper(II) ferrite In N,N-dimethyl-formamide at 120℃; for 12 h;
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), catalyst (40 molpercent) 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
89%
With sodium azide; scandium tris(trifluoromethanesulfonate) In water; isopropyl alcohol at 160℃; for 1 h; Microwave irradiation; Sealed tube
General procedure: Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (2c) was achieved as follows: 4-chlorobenzonitrile 1c (274 mg, 2 mmol), NaN3 (260 mg, 4 mmol), Sc(OTf)3(197 mg, 0.4 mmol), and 8mL of a 3:1 isopropanol=water mixture were added to a30-mL Pyrex microwave vessel and capped. The microwave vessel was then placedin a Milestone Start Synth microwave reactor. The reaction was magnetically stirredand heated for 1 h at 160 C. The reaction was monitored by thin-layer chromatography(TLC) using an ether=hexane mixture (typically 50=50) for development.The reaction mixture was then diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (215mL). The aqueous sodium bicarbonatelayer was cooled with ice and acidified to a pH of 2 or less with concentratedhydrochloric acid, which was added dropwise. The precipitate formed was extractedwith ethyl acetate (315 mL). The combined organic layers were dried with anhydroussodium sulfate and decanted into a tared round-bottom flask. The organiclayer was concentrated under reduced pressure by rotary evaporation at 40 C andthen under high vacuum. The tetrazole product was recrystallized from ethyl acetateand hexane. All reagents mentioned were not unpurified.NMR spectra were acquired on a spectrometer at 300MHz for 1H and 75MHzfor 13C acquisitions. All 1H NMR spectra were taken in dimethylsulfoxide (DMSOd6)using DMSO as a standard at 2.52 ppm. All 13C NMR spectra were taken inDMSO-d6 using DMSO as a standard at 40.5 ppm. An IR spectrum was obtainedusing a Fourier transform infrared (FTIR) spectrophotometer. A melting point wasalso obtained for the solid products. 5-(4-Chlorophenyl)-1H-tetrazole (2c) is a whitesolid. IR (KBr, thin film) vmax (cm1): 3385 (br), 1645 (m), 1634 (m); 1H NMR(DMSO-d6, d): 11.60 (s, br, 1H), 8.07 (d, J8.28 Hz, 2H), 7.70 (d, J8.25 Hz,2H); 13C NMR (DMSO-d6, d): 155.8 (br), 136.9, 130.6, 129.7, 124.1; mp 250251 C.
89%
With sodium azide In N,N-dimethyl-formamide at 120℃; for 1.5 h;
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 (37percent). The precipitation was filteredand crystallized in a mixture of water and ethanol. Furtherpurification with column chromatography was notnecessary.
88%
at 120℃; for 1.83333 h;
General procedure: In order to the synthesis of 5-substituted tetrazoles, 0.005g of SBA-15(at)serine(at)Pd was added to a mixture of nitrile (1mmol) and sodium azide (1.2mmol) under stirring conditions at 120°C in PEG, and the completion of the reaction progress was monitored by TLC with n-hexane-ethylacetate (4:1). Then, the catalyst was separated by simple filtration after completion of reaction. Finally, HCl (4N, 10mL) added to the filtrate and then the resultant organic layers were extract with ethyl acetate and washed with distilled water in order to give corresponding tetrazole.
84%
With sodium azide In N,N-dimethyl-formamide at 120℃; for 6 h;
General 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 Na2SO4 and then was evaporated. The crude products were obtained in excellent yields. All products were characterized by 1H, 13C NMR, FT-IR, and melting point which were in agreement with literature. We have reported the spectral data of some aromatic and heteroaromatic synthesized compounds
84%
With sodium azide In methanol; N,N-dimethyl-formamide at 20 - 100℃; for 8 h;
General procedure: A mixture of benzonitrile (1 mmol), sodium azide (2 mmol), Ln(OTf)3-SiO2 (2008 mg) and DMF/MeOH (4:1, 5 mL) in a pressure vial was initially stirred at room temperature. After 30 min, the temperature of the reaction mixture was raised to 100 °C and stirred for another 7 h. After consumption of 1a (as indicated by TLC), the catalyst was separated by filtration and the filtrate was treated with ethyl acetate (15 mL). The organic layer was washed with 4 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layer was washed with water (2 × 10 mL), dried over anhydrous sodium sulfate and concentrated to afford white crystalline solid.5-Phenyl-1H-tetrazole(3a)IR (KBr, cm−1): 3331, 2907, 2850, 2611, 1607, 1485, 1433, 1050, 828, 742. 1H NMR (300 MHz, CDCl3): 8.04–8.007 (m, 1H), 7.611–7.574 (m, 2H). 13C NMR (75 MHz, CDCl3): 156.03, 131.19, 129.08, 126.805, 123.924. MS: m/z = 146 [M]+.
82%
With indium(III) chloride; sodium azide In water; isopropyl alcohol at 160℃; Microwave irradiation
General procedure: Synthesis of 4-acetylbenzotetrazole (2c). 4-Acetylbenzonitrile 3c (290 mg, 2 mmol), NaN3 (260 mg, 4 mmol), InCl3(89 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel and capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 hour at 160 oC. The pressure in the vessels was not determined. The reaction was monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reaction mixture was diluted with saturated aqueous sodium bicarbonate (20mL) and washed with ethyl acetate (2 x 15 mL). The aqueous sodium bicarbonate layer was cooled to 0 oC and acidified to a pH of 2 or less with concentrated hydrochloric acid,which was added drop-wise. The precipitate formed was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate and decanted into a tared round bottom flask. The organic layer was concentrated under reduced pressure. The tetrazole product was recrystallized from ethyl acetate and hexane. All reagents mentioned above were used unpurified
80%
With sodium azide; silver nitrate In N,N-dimethyl-formamide at 20 - 120℃; for 5 h;
General procedure: Sodiumazide (0.378 g, 0.046 mmol) was added to a solution of AgNO3 (5 mg, 10 mmol)in DMF (5 ml) and reaction mixture was stirred for 5 min, to this stirredsolution benzonitrile 1a (0.4 ml, 0.033 mmol) was added dropwise over theperiod of 1 min at room temperature and stirring continued for 10 min at thesame temperature and then heated at 120 C for 5 h. After consumption of 1a,the reaction mixture was cooled to room temperature and chilled by addingcrushed ice into the reaction mixture followed by addition of 2 N HCl tillreaction mixture reached the pH 2. The reaction mixture was then extractedwith ethyl acetate. The organic layer was dried with anhydrous Na2SO4, andconcentrated to obtain tetrazole 2a in 83percent yield as an off white solid (268 mg).
80%
With sodium azide In N,N-dimethyl-formamide at 120℃; for 16 h;
General procedure: In a round-bottom flask, 0.2 g benzonitrile (2 mmol) and0.4 g sodium azide (6 mmol), were added to 10 mL DMF.To this mixture, 20 mg of functionalized KIT-6 was addedand the reaction mixture was refluxed. The progress ofreaction was monitored by TLC (75:25 ethyl acetate/nhexane).After completion of the reaction, the reactionmixture was cooled and filtered. The solid materials werewashed three times with acetone and then with the water.The catalyst was collected and dried to activation for nextrun. The product was obtained by acidification of solutionwith hydrochloric acid (5 mL, 6 M). The precipitate wasfiltered and recrystallized from a water/ethanol mixture toget pure product as a white powder, yield: 88percent.
77%
With sodium azide; lead(II) chloride In N,N-dimethyl-formamide at 120℃; for 8 h; Inert atmosphere
General procedure: Benzonitrile (103 mg, 1 mmol) and sodium azide (97.5 mg, 1.5 mmol) were dissolved in 2 ml of dry DMF in a 25 ml round bottom flask. PbCl2 (27.8 mg, 0.1 mmol, 10 mol percent) was added to the reaction mixture and stirred at 120 °C for 8 h under nitrogen. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature and 10 ml of ice water was added followed by addition of 3 N HCl until the reaction mixture became strongly acidic (pH 2-3). The reaction mixture was extracted three times with 20 ml ethyl acetate. The organic layer was washed with brine solution and dried over anhydrous sodium sulfate, and was evaporated under reduced pressure to give a white solid product of 5-phenyl 1H-tetrazole with 81percent yield.
75%
With sodium azide; ammonium chloride In N,N-dimethyl-formamide for 24 h; Reflux
General 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.
74%
With sodium azide In N,N-dimethyl-formamide for 24 h; Sealed tube; Green chemistry
General procedure: The benzonitrile derivatives (2 mmol), sodium azide (3.2 mmol), and DMF (2 mL) were mixed in a sealed tube, then 30 mg of catalyst MSS-SO3H (or catalyst MSS-SO3Zn) was added into the tube, which was heated for 24 h under 140 C. After 24 hours’ reaction,the catalyst was separated by magnetic force, and the solution was poured into water.The liquid was acidified to pH 1, then ethyl acetate was added to extract the tetrazoles. Carefully evaporating the solvent under reduced pressure, we got the isolated tetrazoles. A sample for characterization was purified on a flash silica column.
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With C25H19N3ORuS; potassium <i>tert</i>-butylate In iso-butanol at 120℃; for 0.5 h; Inert atmosphere
General procedure: A flask (25 mL) containing ruthenium(II) complex (1 Mpercent) and 2-butanol (5 mL) was stirredfor 5 min under an argon atmosphere at room temperature. Afterwards, KOtBu(0.05 mM) was added and the mixture was stirred for another 5 min. Then, the nitrile(0.5 mM) was added and placed on a hot plate at 120 °C for 30 min. After completion ofthe reaction, the catalyst was removed from the reaction mixture by addition of petroleumether followed by filtration and subsequent neutralization with 1 M HCl. The ether layerwas filtered through a short path of silica gel by column chromatography. To the filtrate,hexadecane was added as a standard and the yield was determined by GC.
86%
With sodium tetrahydroborate; iron(III) oxide In methanol at 40℃; for 0.666667 h; Sonication
General procedure: To the solution of substrate (10 mmol) in dry methanol (25 mL), Fe3O4 nanoparticles (50 mg) were added and the solution was sonicated for 10 min and then vigorously stirred at 40 °C. Sodium borohydride (30 mmol) was added in small lots cautiously while stirring the solution for 30 min and the progress of the reaction was monitored by thin layer chromatography (TLC). After the completion of reaction, the catalyst was separated by using external magnet and the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine solution and then separated and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography over silica gel (100–200 mesh) using ethyl acetate-hexane mixture (varying concentration) as the eluent. All products were analyzed by IR and NMR spectra which were in good agreement with the reported values [5, 10].
Reference：
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[8] Tetrahedron, 1992, vol. 48, # 21, p. 4301 - 4312
[9] Tetrahedron, 2002, vol. 58, # 11, p. 2211 - 2213
[10] Journal of the Chemical Society, 1946, p. 466
[11] Journal of the American Chemical Society, 1951, vol. 73, p. 242
[12] Synthesis, 1981, # 8, p. 605 - 606
[13] European Journal of Inorganic Chemistry, 2011, # 22, p. 3381 - 3386
[14] Chemistry - A European Journal, 2013, vol. 19, # 14, p. 4437 - 4440
[15] Patent: US8563753, 2013, B2, . Location in patent: Page/Page column 17; 18; 19; 20
[16] European Journal of Organic Chemistry, 2015, vol. 2015, # 27, p. 5944 - 5948
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[22] Catalysis Science and Technology, 2018, vol. 8, # 2, p. 499 - 507
5
[ 623-03-0 ]
[ 21913-13-3 ]
[ 104-86-9 ]
Reference：
[1] Synthetic Communications, 2002, vol. 32, # 8, p. 1265 - 1269
[2] Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 3, p. 808 - 810
[3] Chemical and Pharmaceutical Bulletin, 1989, vol. 37, # 3, p. 808 - 810
[4] Justus Liebigs Annalen der Chemie, 1926, vol. 449, p. 264
[5] Journal of the American Chemical Society, 1939, vol. 61, p. 3564
Reference：
[1] New Journal of Chemistry, 2003, vol. 27, # 2, p. 409 - 413
8
[ 623-03-0 ]
[ 15184-98-2 ]
[ 104-86-9 ]
[ 100-46-9 ]
Reference：
[1] Journal of Organic Chemistry, 2001, vol. 66, # 6, p. 1999 - 2004
9
[ 623-03-0 ]
[ 21913-13-3 ]
[ 104-86-9 ]
[ 873-76-7 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1990, vol. 38, # 8, p. 2097 - 2101
[2] Chemical and Pharmaceutical Bulletin, 1990, vol. 38, # 8, p. 2097 - 2101
With copper(l) iodide; caesium carbonate; dimethylbiguanide In N,N-dimethyl-formamide at 20 - 110℃; for 12.1667 h;
General procedure: A 25 mL flask with a magnetic stirring bar was charged with CuI(9.6 mg, 0.05 mmol), metformin (0.1 mmol), Cs2CO3 (652 mg,2.0 mmol), imidazole (1.0 mmol), an aryl halide (1.1 mmol), andDMF (5 mL). The mixture was stirred for 10 min at room temperature,and then heated to 110∘C for the appropriate amount of time(see Table 2). The progress of the reaction was monitored by TLC.After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product.
Reference：
[1] Journal of the American Chemical Society, 2005, vol. 127, # 28, p. 9948 - 9949
[2] Synthesis, 2009, # 15, p. 2517 - 2522
[3] RSC Advances, 2015, vol. 5, # 112, p. 92121 - 92127
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[5] Journal of Organic Chemistry, 2007, vol. 72, # 22, p. 8535 - 8538
[6] Synthetic Communications, 2008, vol. 38, # 4, p. 626 - 636
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[8] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3151 - 3159
[9] Tetrahedron Letters, 2013, vol. 54, # 52, p. 7095 - 7099
[10] Tetrahedron, 2008, vol. 64, # 10, p. 2471 - 2479
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[13] Polyhedron, 2012, vol. 34, # 1, p. 143 - 148
[14] Synthesis, 2010, # 9, p. 1505 - 1511
[15] Journal of Organic Chemistry, 2009, vol. 74, # 20, p. 7951 - 7954
[16] Monatshefte fur Chemie, 2004, vol. 135, # 4, p. 419 - 423
[17] Synlett, 2006, # 14, p. 2195 - 2198
12
[ 288-13-1 ]
[ 623-03-0 ]
[ 25699-83-6 ]
Yield
Reaction Conditions
Operation in experiment
51%
With copper(l) iodide; 1,10-phenanthroline N-oxide; caesium carbonate In N,N-dimethyl-formamide at 120℃; Inert atmosphere
To the three-necked flask, CuI (19 mg, 0.1 mmol, 10 molpercent), 1,10-phenanthroline-N-oxide (39 mg, 0.2 mmol, 20 molpercent) and Cs2CO3 (650 mg, 2.0mmol). The reaction flask was evacuated under argon. p-cyanochlorbenzene (138 mg, 1.0mmol), pyrazole (102 mg, 1.5 mmol) and DMF (2 mL) were added under an atmosphere of argon gas. The reaction was carried out at 120 °C for 72 hours until the starting reaction was complete (the reaction was complete by TLC). After completion of the reaction, a brown oil was obtained which was diluted with ethyl acetate. The inorganic salt was removed by filtration and the solvent was removed by rotary evaporation. The residue was purified by silica gel column chromatography using petroleum ether / ethyl acetate as eluant to give 1-(4-carbonitrilephenyl)pyrazole as a pale yellow oil in a yield of 51percent.
Reference：
[1] Advanced Synthesis and Catalysis, 2007, vol. 349, # 17-18, p. 2673 - 2676
[2] Chemistry - A European Journal, 2014, vol. 20, # 18, p. 5231 - 5236
[3] Journal of Organic Chemistry, 2011, vol. 76, # 9, p. 3151 - 3159
[4] RSC Advances, 2016, vol. 6, # 64, p. 59550 - 59564
[5] Patent: CN104356131, 2016, B, . Location in patent: Paragraph 0316-0327
Reference：
[1] Journal of Medicinal Chemistry, 1991, vol. 34, # 3, p. 1110 - 1116
15
[ 110-85-0 ]
[ 623-03-0 ]
[ 68104-63-2 ]
Yield
Reaction Conditions
Operation in experiment
95%
Stage #1: With sodium t-butanolate In tetrahydrofuran; toluene at 90℃; for 8 h; Stage #2: With hydrogenchloride In water Stage #3: With sodium hydroxide In water
Example 6 4-Cyanochlorobenzene (13.8 g, 100 mmol) and piperazine (12.9 g, 150 mmol) were dissolved in a mixture of 120 ml of toluene and 80 ml of tetrahydrofuran, and degassed at room temperature by passing nitrogen through for 15 min. Dry sodium tert-butoxide (13.5 g, 140 mmol) was added and the mixture was degassed for a further 10 min. In a separate vessel, [2-(2,4,6-triisopropylphenyl)phenyl]dicyclohexylphosphine (95 mg, 0.2 mmol) and (dibenzylideneacetone)palladium (40 mg, 0.05 mmol) were stirred under nitrogen in 10 ml of degassed tetrahydrofuran. After 30 min, this catalyst solution was introduced dropwise at room temperature into the larger flask with the aid of a transfer needle. On completion of addition, the reaction was heated to internal temperature 90° C. After 8 h, the reaction was allowed to cool to 50° C. and the precipitated solid was filtered off. The filtrate was extracted with dilute hydrochloric acid at pH 3. The aqueous phase was removed and adjusted to pH 10 with the aid of sodium hydroxide solution. The precipitated white solid was filtered off and dried under reduced pressure. 17.8 g (95 mmol, 95percent of theory) of N-(4-cyanophenyl)piperazine were obtained. The product content of the solid was determined to be >99percent by quantitative proton NMR.
Reference：
[1] Australian Journal of Chemistry, 1999, vol. 52, # 11, p. 1029 - 1033
20
[ 267877-39-4 ]
[ 623-03-0 ]
[ 79965-68-7 ]
[ 539-03-7 ]
[ 140-53-4 ]
Reference：
[1] Australian Journal of Chemistry, 1999, vol. 52, # 11, p. 1029 - 1033
21
[ 123-75-1 ]
[ 623-03-0 ]
[ 10282-30-1 ]
Yield
Reaction Conditions
Operation in experiment
91%
With potassium carbonate In neat (no solvent) at 120℃; for 24 h;
General procedure: In a conical flask (10 mL) a mixture of aryl halide (1 mmol),amine (3 mmol), K2CO3 (2 mmol), and Pd-PFMN catalyst (0.06 g, 1.2 molpercent) was stirred for 24 h. Afterward, themixture was cooled down to room temperature and the catalystwas magnetically separated from the reaction mixtureand washed with diethyl ether (2 × 10 mL) followed bydeionized and oxygen-free water (2 × 10 mL). The reusedcatalyst was dried for the next run. The aqueous phase wasextracted with diethyl ether (2 × 10 mL) and the combinedorganic phases were dried over Na2SO4. The products werepurified by column chromatography (hexane/ethyl acetate)to obtain the desired purity.
83%
With bis{1,1’-diphenyl-3,3’-methylenediimidazoline-2,2’-diylidene}nickel(II) dibromide; potassium <i>tert</i>-butylate In 1,4-dioxane at 90℃; for 4 h; Inert atmosphere; Schlenk technique
General procedure: Under an N2 atmosphere, KOtBu (1.3 mmol), complex 1 (1 mol percent), dioxane (2 ml), amines (1.3 mmol) and aryl chlorides (1.0 mmol) were successively added into a Schlenk tube. The mixture was stirred vigorously at 90 °C for 4 h. Then the solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel (eluent: PE/EA = 15:1) to give the pure products. The reported yields are the average of two runs.
33%
at 100℃; for 24 h; closed vessel
To commercially available 4-chlorobenzonitrile 17 (5 g, 36 mmol) 12 ml of pyrrolidine were added and the reaction was heated at 100°C for 24 hours in closed vessel. The reaction was evaporated and the residue was dissolved in AcOEt and washed with water and brine. The purification of the crude residue by chromatographic column using AcOEt 1 / Petroleum ether 9 as eluant gave 1.68 g of a pale yellow solid. Yield = 33percent 'HNMR (DMSO, 200 MHz) δ 1.96 (4H, m), 3.28 (4H, m), 6.58 (2H, d, J = 9 Hz), 7.51 (2H, d, J = 9 Hz)
33%
at 100℃; for 24 h; Sealed vessel
Example 15: 1-(4-(pyrrolidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea (scheme 1) Preparation of 4-(pyrrolidin-1-yl)benzonitrile 181 (scheme 9) To commercially available 4-chlorobenzonitrile (5 g, 36 mmol) 12 ml of pyrrolidine were added and the reaction was heated at 100°C for 24 hours in closed vessel. The reaction was evaporated and the residue was dissolved in AcOEt and washed with water and brine. The purification of the crude residue by chromatographic column using AcOEt 1 / Petroleum ether 9 as eluant gave 1.68 g of a pale yellow solid. Yield = 33percent 1HNMR (DMSO, 200 MHz) δ 1.96 (4H, m), 3.28 (4H, m), 6.58 (2H, d, J = 9 Hz), 7.51 (2H, d, J = 9 Hz)
Reference：
[1] Journal of the Iranian Chemical Society, 2015, vol. 12, # 11, p. 2057 - 2064
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[5] Tetrahedron, 2008, vol. 64, # 23, p. 5604 - 5619
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[7] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 2, p. 217 - 222
[8] Bulletin of the Chemical Society of Japan, 1991, vol. 64, # 1, p. 42 - 49
[9] Chemistry Letters, 1987, p. 1187 - 1190
[10] Patent: WO2011/120604, 2011, A1, . Location in patent: Page/Page column 44; 134
[11] Patent: EP2377850, 2011, A1, . Location in patent: Page/Page column 17
With nitronium tetrafluoborate In acetonitrile at 0 - 20℃; for 20 h;
In dry acetonitrile (40 ml) was dissolved 4-chlorobenzonitrile (4g, 29.2 mmol), and nitronium tetrafluoroborate (7.7g, 58.39 mmol) was added therto at 0 °C. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was poured into cold water. The white solid precipitated out was collected by filtration, and the filterate was washed with water and dried. The compound (4.0g, 75.47percent) thus obtained was used for next step without purification.
Reference：
[1] Journal of Medicinal Chemistry, 1990, vol. 33, # 4, p. 1252 - 1257
[2] Patent: WO2014/24056, 2014, A1, . Location in patent: Page/Page column 40
[3] MedChemComm, 2017, vol. 8, # 10, p. 2003 - 2011
[4] Journal of Medicinal Chemistry, 1991, vol. 34, # 3, p. 1110 - 1116
[5] Recueil des Travaux Chimiques des Pays-Bas, 1922, vol. 41, p. 36
[6] Journal of the Chemical Society, 1927, p. 1117
[7] Journal of the Chemical Society, 1934, p. 1672,1676
[8] Journal of the American Chemical Society, 1961, vol. 83, p. 4564 - 4571
[9] Journal of the American Chemical Society, 1962, vol. 84, p. 1026 - 1032
[10] RSC Advances, 2016, vol. 6, # 27, p. 23038 - 23047
24
[ 623-03-0 ]
[ 7697-37-2 ]
[ 939-80-0 ]
Reference：
[1] Journal of the Chemical Society, 1927, p. 1117
25
[ 623-03-0 ]
[ 57381-49-4 ]
Reference：
[1] Angewandte Chemie - International Edition, 2014, vol. 53, # 44, p. 11890 - 11894[2] Angew. Chem., 2014, vol. 126, # 44, p. 12084 - 12088,5
[3] Angewandte Chemie - International Edition, 2015, vol. 54, # 13, p. 4041 - 4045[4] Angew. Chem.,
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 9, p. 2473 - 2477[6] Angew. Chem., 2017, vol. 129, p. 2513 - 2517,5
With dmap; bis(η3-allyl-μ-chloropalladium(II)); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,3,5-trimethyl-benzene at 140℃; for 20 h; Inert atmosphere
General procedure: after standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd source (see Table 1, Table 2, Table 3 and Table 4), ligand (see Table 1, Table 2, Table 3 and Table 4), N,N-dimethylpyridin-4-amine (DMAP, see Table 1, Table 2, Table 3 and Table 4), and ethyl potassium malonate (see Table 1, Table 2, Table 3 and Table 4). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, aryl halide (see Table 1, Table 2, Table 3 and Table 4) and solvent (see Table 1, Table 2, Table 3 and Table 4) were added by syringe. The tube was sealed and stirred at room temperature for 10 min. Then the tube was connected to the Schlenk line, which was full of argon, stirred in a preheated oil bath (140-150 °C) for the appointed time (20-25 h). Upon completion of the reaction, the mixture was cooled to room temperature and diluted with diethyl ether, and the yields were determined by gas chromatography using 1,3-dimethoxybenzene as the internal standard.
Reference：
[1] Tetrahedron, 2012, vol. 68, # 9, p. 2113 - 2120
[2] Angewandte Chemie - International Edition, 2011, vol. 50, # 19, p. 4470 - 4474
30
[ 623-03-0 ]
[ 105-53-3 ]
[ 1528-41-2 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2011, vol. 353, # 9, p. 1565 - 1574
Stage #1: With lithium hexamethyldisilazane In tetrahydrofuran at 20℃; for 4 h; Stage #2: With hydrogenchloride In tetrahydrofuran; isopropyl alcohol at 0℃;
Into a 50 mL dry reaction flask charged with 1 M LiHMDS in THF (22 mmol), p- chlorobenzonitrile (2.76 g, 20.0 mmol) in 2 mL of THF is added, and the reaction mixture is kept stirring at RT for 4 h, at which point 5-6 N HCI (in/PrOH, 15 mL) is added. The crude reaction mixture is kept at 0 0C overnight.The precipitated product is filtered, washed with diethyl ether to yield 3.5 g(93percent) of the compound of formula 2b as a white solid, m.p. 238 0C (lit m.p. 243-245 0C) (E. Ragona, D. L. Nelson, M. Mares-Guis, J. Amer. Chem. Soc. EPO <DP n="74"/>1975, 97, 6844-6848). - IR (KBr): nu(tilde) = 3239 crrf1, 3054, 1678, 1460, 1401 , 1036, 715. - 1H NMR (250 MHz, [D6]DMSO): δ = 7.60-7.77 (m, 2 H), 7.85-7.97 (m, 2 H), 8.4 (br. s, 3 H, NH). - 13C NMR (62.9 MHz, [D6]DMSO), δ = 126.79 (Cquat), 129.36 (+), 130.57 (+), 139.1 (Cquat), 165.1 (NCN).
71%
Stage #1: With hydrogenchloride In ethanol; chloroform at -78 - 20℃; Stage #2: With ammonium carbonate In ethanol at 20℃; for 72 h;
Hydrogen chloride gas was passed through a solution of 4-chlorobenzonitrile (9b, 25.0 g) in chloroform (350 mL) and ethanol (100 mL) at −78 °C for 0.5 h. Then the solution was warmed up to room temperature, and stirred at room temperature overnight. The solution was evaporated in vacuo, and the resulting residue was dissolved with ethanol (500 mL). To the solution was added ammonium carbonate (90.0 g), and the reaction mixture was stirred at room temperature for 3 days. To the mixture was added water (300 mL), and ethanol was removed by concentration in vacuo. The resulting solid was collected by filtration, washed with water and dried in vacuo to give 12b (25.4 g, 71percent) as a white solid: 1H NMR (DMSO-d6) δ 2.60–4.80 (2H, br), 7.53 (2H, d, J = 8.8 Hz), 7.81 (2H, d, J = 8.8 Hz), 7.50–9.50 (2H, br); FAB-MS m/z 155, 157 [(M+H)+].
Reference：
[1] European Journal of Organic Chemistry, 2006, # 12, p. 2753 - 2765
[2] Patent: WO2006/94604, 2006, A1, . Location in patent: Page/Page column 62; 63; 72; 73
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 17, p. 5235 - 5246
[4] Journal of the American Chemical Society, 1985, vol. 107, # 9, p. 2743 - 2748
[5] Patent: US6218538, 2001, B1,
[6] European Journal of Organic Chemistry, 2014, vol. 2014, # 17, p. 3614 - 3621
[7] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 29 - 43
[8] Tetrahedron Letters, 2018, vol. 59, # 4, p. 361 - 364
38
[ 623-03-0 ]
[ 84459-33-6 ]
Reference：
[1] Angewandte Chemie - International Edition, 2017, vol. 56, # 9, p. 2473 - 2477[2] Angew. Chem., 2017, vol. 129, p. 2513 - 2517,5
39
[ 623-03-0 ]
[ 201230-82-2 ]
[ 6638-79-5 ]
[ 116332-64-0 ]
Reference：
[1] Organic Letters, 2006, vol. 8, # 21, p. 4843 - 4846
[2] Journal of Organic Chemistry, 2008, vol. 73, # 18, p. 7102 - 7107
40
[ 623-03-0 ]
[ 126747-14-6 ]
Reference：
[1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
Reference：
[1] Journal of Medicinal Chemistry, 2005, vol. 48, # 6, p. 2229 - 2238
44
[ 623-03-0 ]
[ 118753-70-1 ]
[ 218451-34-4 ]
Yield
Reaction Conditions
Operation in experiment
41%
With sodium hydride In N,N-dimethyl-formamide at 60℃; Cooling with ice; Inert atmosphere
Example 39A2tert-butyl 4-(4-chlorophenyl)-4-cyanopiperidine- 1 -carboxylate To a mixture of Example 39A1 (3.5 g, 14.5 mmol) and 4-Chloro-benzonitrile (2.0 g, 13.2 mmol) in DMF (50 ml) was added NaH (2.1 g, 43.5 mmol) in portions with ice- bath under nitrogen atmosphere. After addition, the mixture was heated to 60 °C and stirred overnight. After cooling to room temperature, the mixture was poured into ice water (200 mL) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated. The residue was purified on silica column to afford Example 39A2 (1.8 g, 41percent) as a white solid.
With sodium azide; ammonium cerium (IV) nitrate; In N,N-dimethyl-formamide; at 110℃; for 6h;Inert atmosphere; Green chemistry;
General procedure: sodiumazide (1.5 mmol) was added to a magnetically stirred solution of nitrile 1a(1 mmol) in anhydrous DMF and the CAN (10 mmol %) was added. The reactionmixture was constantly stirred for another 6 h at 110 C under nitrogenatmosphere. After the completion of reaction as seen by TLC, the reactionmixture was brought to room temperature and the solvent was evaporatedunder vacuum. The crude thus obtained, was dissolved in ethyl acetate (20 mL)and solution was washed with acidified water (4 M HCl, 15 mL) twice.Separated organic layer was washed with brine solution dried overanhydrous Na2SO4, and solvent was removed under high vacuum to obtaintetrazole 1b as a white crystalline solid in 97% yield.
99%
With sodium azide; In N,N-dimethyl-formamide; at 120℃; for 4h;
General procedure: Cu(II)-NaY (0.1 g) was added to a mixture of benzonitrile (0.206 g, 2.0 mmol) and sodium azide (0.169 g, 2.6 mmol) in DMF (5 mL) and mixture was stirred at 120 C for 3 h. After completion of reaction (as monitored by TLC), the catalyst was centrifuged, washed with ethyl acetate and the centrifugate was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL) and stirred vigorously. 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 and concentrated to give the crude solid crystalline 5-phenyltetrazole. The product was characterizedby 1H NMR , 13C NMR and mass spectroscopic analysis.
97%
With sodium azide; In N,N-dimethyl-formamide; at 90℃; for 3h;Catalytic behavior;
General procedure: In a double-necked round bottom flask (100 mL) equippedwith a condenser was added a mixture consisting ofnitrile (0.005 mol), NaN3 (0.006 mol), and monodisperse Pt NPsVC in DMF (1.5 mL). The mixture washeated at reflux until TLC monitoring indicated no furtherimprovement in the conversion. The reaction mixture wasthen cooled to room temperature, vacuum-filtered usinga sintered-glass funnel and the residue was washed withethyl acetate (3×10 mL). The filtrate was treated with5 mL HCl (4 mol L-1 to reach pH= 3 and it was allowedto stir for 30 minutes. Subsequently, the organic layer wasseparated, dried over anhydrous Na2SO4 and evaporated.The crude product was purified by recrystallization and/orcolumn chromatography on silica gel eluted with propersolvents to get pure 5-Phenyl 1H-tetrazole.
96%
With sodium azide; In water; at 100℃; for 2h;Green chemistry;Catalytic behavior;
General procedure: Benzonitrile (1 mmol, 0.103 g), sodium azide (1.1 mmol, 0.0759 g), and 2 mL water were taken in a reaction tube and stirred at room temperature to make homogeneous suspension, and then 20 wt% catalyst (ZnO-RGO) was added to the reaction mixture. The reaction mixture was heated to 100 C for 2 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and centrifuged. The filtrate was treated with 5N HCl (10 mL) and then with ethyl acetate. The organic layer was separated, washed with deionized water, and then dried over anhydrous sodium sulfate and concentrated to give the crude solid crystalline 5-phenyl-1H-tetrazole. It was recrystallized from n-hexane, ethyl acetate, and the yield was about 0.143 g.
96%
With sodium azide; at 120℃; for 3h;Green chemistry;
General procedure: A mixture of sodium azide (1.2mmol) and nitrile (1mmol) in the presence of 20mg of Fe3O4MCM-41Cu-P2C, was stirred at 120C 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.
95%
With sodium azide; at 120℃; for 4h;
General procedure: A mixture of the required nitrile (1 mmol), sodium azide(1 mmol) and the catalyst MNP (0.05 g) was stirred at 120 C in PEG (1 mL) as solvent. After completion of the reaction, as indicated by TLC, the mixture was cooled to room temperature and diluted with 1:1 H2O:Ethyl acetate(10 mL) and then stirred at ambient temperature (10 min). The catalyst was removed by applying a magnetic field, and the decantate was treated with HCl (4 N, 10 mL). The organic layer was separated, washed with water, dried over sodium sulfate and concentrated to precipitate the crude crystalline solid. The pure tetrazoles were characterized bytheir spectroscopic data and melting points.
95%
With sodium azide; aminosulfonic acid; In N,N-dimethyl-formamide; at 120℃; for 5h;
General procedure: A mixture of 4-nitrobenzonitrile (0.296 g, 2 mmol), sodium azide (0.195 g, 3 mmol), and sulfamic acid (0.0097 g, 0.1 mmol) was stirred at 120C in DMF (5 mL) for the appropriate time (Table 2) until TLC (4:1 n-hexane:ethyl acetate) indicated no further progress in the conversion. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature, then 20 mL diethyl ether was added to the mixture and stirred for 10 minutes. The catalyst was separated by simple gravity filtration, washed with diethyl ether (2 £ 10 mL) and dried at 40C for 30 min. The recovered catalyst wasused for three additional cycles and gave the tetrazole in 95, 85 and 75% (with 4-nitrobenzonitrile). The filtrate was treated with ethyl acetate (30 mL) and 6 N HCl(20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (20 mL). The combined organic layers were dried over anhydrous sodium sulfate and evaporated under reduced pressure to give 5-(4-nitrophenyl) tetrazole (0.363 g), 95% yield.
95%
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)
95%
With sodium azide; at 120℃; for 2h;
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 120C 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.
95%
With sodium azide; at 120℃; for 0.333333h;Green chemistry;
General procedure: To a suspension of the catalyst (0.004 g) in PEG (2 mL), nitrile (1 mmol) and sodium azide (1.2 mmol) were added and the mixture was stirred vigorously at 120 C for the required time (Table 6). After the reaction was completed (as monitored by TLC), the catalyst was separated with a magnet. HCl (4 N, 10 mL) was then added to the residue, and the tetrazole was extracted with ethyl acetate. The organic extract was washed with distilled water, dried over anhydrous Na2SO4 and then evaporated to give the desired tetrazole.
95%
With sodium azide; C19H17N3O4(2-)*Cu(2+); In ethylene glycol; at 120℃; for 3h;Catalytic behavior;
General procedure: In 25mL round-bottomed flask, sodium azide (0.076g, 1.2mmol) and polymeric copper (II) complex (0.005g) were added to a solution of benzonitrile (0.103g, 1mmol) in ethylene glycol (3mL) with stirring at room temperature. The reaction temperature was raised up to 120C for 3h. The reaction was monitored by TLC at regular intervals. After completion of the reaction, the reaction mixture was cooled to room temperature and treated with 10mL HCl (2N) and extracted with 10mL ethyl acetate. The resulted organic layers were separated and washed with 2×10mL distilled water, dried over anhydrous sodium sulphate and evaporated under reduced pressure. The residue was then purified by column chromatography on silica gel (100-200 mesh) to afford the corresponding products.
95%
With sodium azide; C12H16CuN4O4(2+)*2BF4(1-); In N,N-dimethyl-formamide; at 130℃; for 0.333333h;Microwave irradiation;
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.
94%
With sodium azide; In N,N-dimethyl-formamide; at 110℃; for 2.5h;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.
94%
With sodium azide; ChCl*2ZnCl2; at 140℃; for 0.833333h;Green chemistry;
General procedure: NaN3 (0.975 g, 15 mmol) was dissolved in DES (10 mL) at room temperature by stirring until a clear solution was formed. Then benzonitrile (10 mmol) was added. The reaction mixture was constantly stirred at 140 C and monitored by TLC. After completion of the reaction, the reaction mixture was cooled to room temperature and poured into the cold water (10 mL). The solid was obtained and filtered. The obtained solid is taken into cold water (10 mL). Then it was acidified carefully to pH 5 with 5 M HCl. The organic material was extracted thrice with ethyl acetate; the resultant organic layer was washed with distilled water, dried over anhydrous sodium sulfate, and concentrated to give the crude solid crystalline 5-substituted 1H-tetrazole. The resulting product, although evident as a single compound by TLC, was purified by simple recrystallization from aqueous ethanol giving pure 5-substituted 1H-tetrazoles.
94%
With sodium azide; L-proline; In N,N-dimethyl-formamide; at 110℃;Green chemistry;
General procedure: The mixture of organic nitrile (1 mmol), NaN3 (1.25 mmol) and L-proline (30 mol%) in DMF (5mL) was stirred at 110 C for 1-2 h. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the reaction mixture was allowed to cool to room temperature. Thecooled reaction mixture was poured in ice water (15 mL) with stirring. The resulting mixture wasacidified with dilute HCl under vigorous stirring. The solid product* was filtered under suction,washed with sufficient cold water till free of acid. The product was air dried to obtain the pureproduct.*In cases where solid product was not obtained after acidification, like benzyl cyanide andaliphatic nitriles, the acidified aqueous phase was extracted with ethyl acetate (2 X 20 mL), thecombined organic phase was washed with brine, dried over anhydrous sodium sulfate andconcentrated in vacuo to get the corresponding pure product.
93%
With sodium azide; In dimethyl sulfoxide; at 85℃; for 12h;
General procedure: General procedure for the synthesis of Tetrazole. A mixture of benzonitrile (103 mg, 1 mmol), sodium azide (97.5 mg, 1.5 mmol), and 3 mL DMSO solvent was added in a 25 mL round bottomed flask. Further (50 mg, 23 mol %, w/w) catalyst was added to the reaction mixture. The reaction mixture was heated to 85 C for 12 h. After completion of the reaction (as monitored by TLC), the catalyst was separated by simple filtration, washed with diethyl ether and the filtrate was treated with ethyl acetate (30 mL) and 5 N HCl (20 mL) and stirred vigorously. 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 and dried over anhydrous sodium sulfate and were evaporated under reduced pressure to give the product. The product was purified by the column chromatography. The structure was confirmed by spectral analysis (1H NMR, mass and elemental analysis).
93%
With sodium azide; In N,N-dimethyl-formamide; at 110℃; for 4h;
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol), Cu complex catalyst (0.4 mol%) 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.
93%
With sodium azide; Acetate de N,N-dimethylamino-4 pyridinium; In neat (no solvent); at 100℃; for 2h;
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
93%
With sodium azide; silver(I) triflimide; In toluene; at 85℃; for 3h;
General procedure: A mixture of the appropriate nitrile (1 mmol), NaN3 (1.5 mmol),toluene (2 mL) and AgNTf2 (5 mol%) 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.
93%
With sodium azide; piperazinium dihydrogen sulfate; at 100℃; for 2h;
General procedure: In a roundbottom flask in 100C, 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 100C, 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
93%
With sodium azide; copper(II) nitrate trihydrate; In N,N-dimethyl-formamide; at 120℃; for 16h;
General procedure: Cu(NO3)2·3H2O (0.10 mmol), the appropriate nitrile 1 (1.0 mmol), NaN3(2.0 mmol) and DMF (1 mL) were added to a 50 mL round-bottomed flask equipped with a magnetic stirrer. The reaction mixture was stirred in an oil bath at 120 C for 16 h. After cooling to room temperature, the reaction was acidified HCl (3 M, pH 1.0). Ethyl acetate (~30 mL) wasadded, and stirring was continued until no solid was present. The organic layer was separated, and the aqueous layer was extracted with ethylacetate twice. The combined organic layers were washed with saturatedbrine, and concentrated in vacuo. The residue was purified by columnchromatography (silica gel, EtOAc-PE) to afford the product 2.
92%
With Nano TiO2/SO42-; In N,N-dimethyl-formamide; for 2h;Green chemistry;
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: 92%. White solid. M.p. 262-263 8C (lit. [11] 261-263 8C) 1H-NMR (250 MHz; DMSO-d6): d 8.04 (d, 2H,J = 8.52 Hz, Ar-H), 7.62 (d, 2H, J = 8.52 Hz, Ar-H), 4.15 (brs,1H,-NH); 13C-NMR (62.9 MHz, DMSO-d6): d 154.8, 135.8,129.4, 128.6, 123.1; IR (KBr): n = 3419, 2927, 2816, 2723,1602, 1457, 1437, 1383, 1350, 1161, 1095, 1055, 875,765 cm1.
91%
With sodium azide; In N,N-dimethyl-formamide; at 90℃; for 8h;Inert atmosphere;
General procedure: 5-Benzyl-1H-tetrazole (2a). To a DMF solution of benzyl cyanide (1a, 100 mg, 0.85 mmol) and NaN3(67 mg, 1.02 mmol, 1.2 eq) was added OSU-6 (15 mg, 15 wt% relative to 1a). The reaction mixturewas heated at 90 C (oil bath temperature 95-100 C) for 4 h at which time TLC indicated the reactionwas complete. The crude reaction mixture was filtered to remove the catalyst, and the filtrate was added to water and extracted with EtOAc (3 x 15 mL). The combined extracts were washed with H2O (3 x 15 mL) and saturated aq. NaCl (1 x 15 mL), dried (MgSO4), filtered, and concentrated under vacuum to give 2a (129 mg, 94%).
91%
With sodium azide; at 120℃; for 10h;Green chemistry;
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.
90%
With sodium azide; ammonium acetate; In N,N-dimethyl-formamide; at 70℃; for 2.5h;
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 70C 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.
90%
With lithium tetraazidoborate; ammonium acetate; In methanol; N,N-dimethyl-formamide; at 100℃; 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. The resulting 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 M HCl was added until the pH value of the water layer became 1~2. The aqueous layer was extracted with ethyl acetate three times, and the combined organic layers were 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.
90%
With sodium azide; copper(l) chloride; In N,N-dimethyl-formamide; at 120℃; for 12h;
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and copper(I) chloride (4 mole %) in DMF (2 mL) was stirred at 120 C for the appropriate time period. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was cooled and treated with 5 mL of HCl (4 mol L-1) and 10 mL of ethyl acetate, successively. The ethyl acetate extract was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The product thus obtained was recrystallised from acetic acid to afford pure 5-substituted 1H-tetrazoles.
90%
With sodium azide; activated Fuller?s earth; In dimethyl sulfoxide; at 120℃; for 1.5h;Green chemistry;
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.
90%
With sodium azide; N,N-diisopropylethylammonium acetate; at 90℃; for 0.5h;Green chemistry;
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.
90%
With sodium azide; (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate; In water; isopropyl alcohol; at 65℃; for 0.25h;Inert atmosphere; Microwave irradiation; Green chemistry;Catalytic behavior;
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 65C. 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.
90%
With sodium azide; at 100℃; for 2.08333h;Green chemistry;Catalytic behavior;
General procedure: A mixture of nitrile (1mmol), sodium azide (1.2mmol), Fe3O4(at)L-aspartic-Gd (0.05g) in PEG (2mL) at 100C was stirred in appropriate time. After the completion of reaction, HCl (4N, 10mL) was added to mixture. Then, the resultant organic layer was extracted with ethyl acetate and washed with distilled water to obtain corresponding tetrazoles. It was purifies over preparatory TLC.
89%
With sodium azide; copper(II) ferrite; In N,N-dimethyl-formamide; at 120℃; for 12h;
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
89%
With sodium azide; scandium tris(trifluoromethanesulfonate); In water; isopropyl alcohol; at 160℃; for 1h;Microwave irradiation; Sealed tube;
General procedure: Synthesis of 5-(4-chlorophenyl)-1H-tetrazole (2c) was achieved as follows: 4-chlorobenzonitrile 1c (274 mg, 2 mmol), NaN3 (260 mg, 4 mmol), Sc(OTf)3(197 mg, 0.4 mmol), and 8mL of a 3:1 isopropanol=water mixture were added to a30-mL Pyrex microwave vessel and capped. The microwave vessel was then placedin a Milestone Start Synth microwave reactor. The reaction was magnetically stirredand heated for 1 h at 160 C. The reaction was monitored by thin-layer chromatography(TLC) using an ether=hexane mixture (typically 50=50) for development.The reaction mixture was then diluted with saturated aqueous sodium bicarbonate(20 mL) and washed with ethyl acetate (215mL). The aqueous sodium bicarbonatelayer was cooled with ice and acidified to a pH of 2 or less with concentratedhydrochloric acid, which was added dropwise. The precipitate formed was extractedwith ethyl acetate (315 mL). The combined organic layers were dried with anhydroussodium sulfate and decanted into a tared round-bottom flask. The organiclayer was concentrated under reduced pressure by rotary evaporation at 40 C andthen under high vacuum. The tetrazole product was recrystallized from ethyl acetateand hexane. All reagents mentioned were not unpurified.NMR spectra were acquired on a spectrometer at 300MHz for 1H and 75MHzfor 13C acquisitions. All 1H NMR spectra were taken in dimethylsulfoxide (DMSOd6)using DMSO as a standard at 2.52 ppm. All 13C NMR spectra were taken inDMSO-d6 using DMSO as a standard at 40.5 ppm. An IR spectrum was obtainedusing a Fourier transform infrared (FTIR) spectrophotometer. A melting point wasalso obtained for the solid products. 5-(4-Chlorophenyl)-1H-tetrazole (2c) is a whitesolid. IR (KBr, thin film) vmax (cm1): 3385 (br), 1645 (m), 1634 (m); 1H NMR(DMSO-d6, d): 11.60 (s, br, 1H), 8.07 (d, J8.28 Hz, 2H), 7.70 (d, J8.25 Hz,2H); 13C NMR (DMSO-d6, d): 155.8 (br), 136.9, 130.6, 129.7, 124.1; mp 250251 C.
89%
With sodium azide; In N,N-dimethyl-formamide; at 120℃; for 1.5h;
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.
89%
With sodium azide; In water; at 100℃; for 0.75h;Green chemistry;Catalytic behavior;
General procedure: To a stirred suspension of Fe3O4(at)Tryptophan-La (0.006 g) in H2O(2 mL) aryl nitrile (1.0 mmol) and sodium azide(1.2 mmol) was added and heated at 100 C. After the completionof reaction (monitored by TLC), the catalyst was separatedby magnet and then the reaction mixture was dilutedwith HCl (4 N, 10 mL). Finally, the resultant organic layer was extracted with ethyl acetate and concentrated to obtain corresponding tetrazoles.
89%
With sodium azide; at 130℃; for 2.33333h;Catalytic behavior;
General procedure: A mixture of NaN3 (1.7mmol) and benzonitrile derivative (1mmol) in the presence of 0.050g of Cu-TBA(at)biochar, were stirred at 130C in PEG-400; after completion of the reaction (observed by TLC), the reaction mixture was cooled down, and reaction mixture was diluted by water and ethyl acetate. Then, the catalyst was isolated by simple filtration. The remained catalyst was washed with water and ethyl acetate for several times. Then, aqueous solution of HCl (4N, 10mL) was added to the filtrated solution. The pure products extracted with ethyl acetate from water. The organic solvent was dried over anhydrous sodium sulfate, and concentrated to give the crude solid product. High purity of products was achieved using thin layer chromatography in a mixture of n-hexane and acetone as mobile phase.
88%
With sodium azide; at 120℃; for 1.83333h;
General procedure: In order to the synthesis of 5-substituted tetrazoles, 0.005g of SBA-15(at)serine(at)Pd was added to a mixture of nitrile (1mmol) and sodium azide (1.2mmol) under stirring conditions at 120C in PEG, and the completion of the reaction progress was monitored by TLC with n-hexane-ethylacetate (4:1). Then, the catalyst was separated by simple filtration after completion of reaction. Finally, HCl (4N, 10mL) added to the filtrate and then the resultant organic layers were extract with ethyl acetate and washed with distilled water in order to give corresponding tetrazole.
84%
With sodium azide; In N,N-dimethyl-formamide; at 120℃; for 6h;
General procedure: A mixture of nitrile (1 mmol), sodium azide (1.5 mmol) and catalyst (0.02 g, contains 0.4 mol% 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 Na2SO4 and then was evaporated. The crude products were obtained in excellent yields. All products were characterized by 1H, 13C NMR, FT-IR, and melting point which were in agreement with literature. We have reported the spectral data of some aromatic and heteroaromatic synthesized compounds
84%
With sodium azide; In methanol; N,N-dimethyl-formamide; at 20 - 100℃; for 8h;
General procedure: A mixture of benzonitrile (1 mmol), sodium azide (2 mmol), Ln(OTf)3-SiO2 (2008 mg) and DMF/MeOH (4:1, 5 mL) in a pressure vial was initially stirred at room temperature. After 30 min, the temperature of the reaction mixture was raised to 100 C and stirred for another 7 h. After consumption of 1a (as indicated by TLC), the catalyst was separated by filtration and the filtrate was treated with ethyl acetate (15 mL). The organic layer was washed with 4 N HCl (20 mL). The resultant organic layer was separated and the aqueous layer was extracted with ethyl acetate (15 mL). The combined organic layer was washed with water (2 × 10 mL), dried over anhydrous sodium sulfate and concentrated to afford white crystalline solid.5-Phenyl-1H-tetrazole(3a)IR (KBr, cm-1): 3331, 2907, 2850, 2611, 1607, 1485, 1433, 1050, 828, 742. 1H NMR (300 MHz, CDCl3): 8.04-8.007 (m, 1H), 7.611-7.574 (m, 2H). 13C NMR (75 MHz, CDCl3): 156.03, 131.19, 129.08, 126.805, 123.924. MS: m/z = 146 [M]+.
82%
With indium(III) chloride; sodium azide; In water; isopropyl alcohol; at 160℃;Microwave irradiation;
General procedure: Synthesis of 4-acetylbenzotetrazole (2c). 4-Acetylbenzonitrile 3c (290 mg, 2 mmol), NaN3 (260 mg, 4 mmol), InCl3(89 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel and capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 hour at 160 oC. The pressure in the vessels was not determined. The reaction was monitored by TLC using an ether/hexane mixture (typically50/50) for development. After cooling, the reaction mixture was diluted with saturated aqueous sodium bicarbonate (20mL) and washed with ethyl acetate (2 x 15 mL). The aqueous sodium bicarbonate layer was cooled to 0 oC and acidified to a pH of 2 or less with concentrated hydrochloric acid,which was added drop-wise. The precipitate formed was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were dried over anhydrous sodium sulfate and decanted into a tared round bottom flask. The organic layer was concentrated under reduced pressure. The tetrazole product was recrystallized from ethyl acetate and hexane. All reagents mentioned above were used unpurified
80%
With sodium azide; silver nitrate; In N,N-dimethyl-formamide; at 20 - 120℃; for 5h;
General procedure: Sodiumazide (0.378 g, 0.046 mmol) was added to a solution of AgNO3 (5 mg, 10 mmol)in DMF (5 ml) and reaction mixture was stirred for 5 min, to this stirredsolution benzonitrile 1a (0.4 ml, 0.033 mmol) was added dropwise over theperiod of 1 min at room temperature and stirring continued for 10 min at thesame temperature and then heated at 120 C for 5 h. After consumption of 1a,the reaction mixture was cooled to room temperature and chilled by addingcrushed ice into the reaction mixture followed by addition of 2 N HCl tillreaction mixture reached the pH 2. The reaction mixture was then extractedwith ethyl acetate. The organic layer was dried with anhydrous Na2SO4, andconcentrated to obtain tetrazole 2a in 83% yield as an off white solid (268 mg).
80%
With sodium azide; In N,N-dimethyl-formamide; at 120℃; for 16h;
General procedure: In a round-bottom flask, 0.2 g benzonitrile (2 mmol) and0.4 g sodium azide (6 mmol), were added to 10 mL DMF.To this mixture, 20 mg of functionalized KIT-6 was addedand the reaction mixture was refluxed. The progress ofreaction was monitored by TLC (75:25 ethyl acetate/nhexane).After completion of the reaction, the reactionmixture was cooled and filtered. The solid materials werewashed three times with acetone and then with the water.The catalyst was collected and dried to activation for nextrun. The product was obtained by acidification of solutionwith hydrochloric acid (5 mL, 6 M). The precipitate wasfiltered and recrystallized from a water/ethanol mixture toget pure product as a white powder, yield: 88%.
77%
With sodium azide; lead(II) chloride; In N,N-dimethyl-formamide; at 120℃; for 8h;Inert atmosphere;
General procedure: Benzonitrile (103 mg, 1 mmol) and sodium azide (97.5 mg, 1.5 mmol) were dissolved in 2 ml of dry DMF in a 25 ml round bottom flask. PbCl2 (27.8 mg, 0.1 mmol, 10 mol %) was added to the reaction mixture and stirred at 120 C for 8 h under nitrogen. After completion of the reaction (as monitored by TLC), the reaction mixture was cooled to room temperature and 10 ml of ice water was added followed by addition of 3 N HCl until the reaction mixture became strongly acidic (pH 2-3). The reaction mixture was extracted three times with 20 ml ethyl acetate. The organic layer was washed with brine solution and dried over anhydrous sodium sulfate, and was evaporated under reduced pressure to give a white solid product of 5-phenyl 1H-tetrazole with 81% yield.
75%
With sodium azide; ammonium chloride; In N,N-dimethyl-formamide; for 24h;Reflux;
General 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.
74%
With sodium azide; In N,N-dimethyl-formamide; for 24h;Sealed tube; Green chemistry;
General procedure: The benzonitrile derivatives (2 mmol), sodium azide (3.2 mmol), and DMF (2 mL) were mixed in a sealed tube, then 30 mg of catalyst MSS-SO3H (or catalyst MSS-SO3Zn) was added into the tube, which was heated for 24 h under 140 C. After 24 hours? reaction,the catalyst was separated by magnetic force, and the solution was poured into water.The liquid was acidified to pH 1, then ethyl acetate was added to extract the tetrazoles. Carefully evaporating the solvent under reduced pressure, we got the isolated tetrazoles. A sample for characterization was purified on a flash silica column.
61%
With bismuth(III) chloride; sodium azide; In water; isopropyl alcohol; at 160℃; for 1h;Microwave irradiation;
General procedure: 2-Furonitrile 1m (186 mg, 2 mmol), NaN3 (260 mg, 4 mmol), BiCl3 (126 mg, 0.4 mmol), and 8 mL of a 3:1 isopropanol/water mixture were added to a 30-mL Pyrex microwave vessel, which was then capped. The microwave vessel was then placed in a Milestone Start Synth microwave reactor. The reaction was magnetically stirred and heated for 1 h at 150C. The reaction was monitored by thin-layer chromatography (TLC) using an ether/hexane mixture (typically 50/50) for development. The reaction mixture was then diluted with saturated aqueous sodium bicarbonate (20 mL) and was hed with ethyl acetate (2×15 mL). The aqueous sodium bicarbonate layer was cooled with ice and acidified to a pH of 2 or less with concentrated hydrochloric acid, which was added dropwise. The precipitate formed was extracted with ethyl acetate (3×15 mL). The combined organic layers were dried with anhydrous sodium sulfate and decanted into a tared round-bottom flask. The organic layer was concentrated under reduced pressure by rotary evaporation at 40C and then under high vacuum. The tetrazole product was recrystallized from ethyl acetate and hexane.
292 mg of granular sodium azide (4.5 mmol) are added to a cold solution of diethyl aluminum chloride (4.5 mmol, 1.8 M in toluene) diluted in 2.5 ml of toluene, and the mixture is stirred at room temperature for 4h. 473 mg of 4-Chlorobenzonitrile are added to the stirred solution, and the reaction mixture is heated up to 135C (e. t. ) and stirred over the night. Complete conversion is observed by HPLC. 5 ml of toluene are added to the mixture, then the solution is added drop wise to a cold solution of HCl 6N. 10 ml of ethyl acetate are added and the solution extracted. The aqueous phase is washed twice with 10 ml portion of ethyl acetate. The combined organic phases are washed with 10 mi portion of HCI 2N and finally with 10 ml of water. The solvent is removed and the product is dried in vacuum at 60C over the night to give the product. m. p. : 255-257 C Tic : Rf-value : 0.40, toluene : EtOAc: AcOH (20: 20: 1); SiO2-plate. HPLC: Hewlett Packard, solvents. H3PO4, acetonitrile/water ; flow : 2 ml/min ; injection: 5.0 mul ; wavelength 220 nm, 40 C ; flow : 2 ml/min ; injection: 5.0 mul ; Column : Merck, Chromolith performance RP-18e 100-4.6 mm. Rt. Time: 6.184 min
With lithium chloride; In 2-methoxy-ethanol;
a) 5-(4-chlorophenyl)-tetrazole 4-chlorobenzonitrile (15.3 pbw), lithium chloride (9.1 pbw) and sodium azide (15.7 pbw) are heated to reflux for 24 hours in 450 pbv of 2-methoxy-ethanol. After cooling, the mixture is poured into 1000 pbv of water. The mixture obtained is filtered, cooled to 0 C. and acidified to pH=3. The precipitate that deposits is removed by filtration, washed with water and dried. Yield: 18 pbw of 5-(4-chlorophenyl)tetrazole.
With sodium azide; In N,N-dimethyl-formamide; at 120℃; for 12h;Inert atmosphere; Green chemistry;
General procedure: A mixture of aryl halide (1.0 mmol), K4[Fe(CN)6](0.22 mmol), 0.05 g [PS-ttet-Pd(II)], and sodium carbonate(1.0 mmol) was stirred in 5 cm3 DMF at 120 C for 1 h under an argon atmosphere. To the aryl nitrile compound generated in situ was added sodium azide (1.5 mmol) and the mixture was stirred at 120 C for appropriate time. After completion of the reaction (as indicated by TLC), the catalyst was centrifuged, washed with EtOH and the residue was diluted with 35 cm3 ethyl acetate and 20 cm3 HCl(4 N) and stirred vigorously. The resultant organic layer was separated and the aqueous layer was extracted with 25 cm3 ethyl acetate. The combined organic layer was washed with 8 cm3 water and concentrated to give a crude product. Column chromatography using silica gel gave thepure product. All products were characterized by 1H NMR and melting point which were in agreement with literature
With sodium azide; N,N-dimethylammonium chloride; In N,N-dimethyl-formamide; at 110 - 115℃; for 8h;
General procedure: Sodium azide, 11.4 mmol, and dimethylamine hydrochloride, 11.2 mmol, were dissolved in 10 mL of DMF, 10 mmol of the corresponding nitrile and 5 mL of DMF were added, and the resulting suspension was heated for 8 h at 110-115C. The mixture was cooled and filtered from the precipitate of sodium chloride, and the precipitate was washed with 10 mL of DMF on a filter. The filtrate was diluted with 30 mL of cold water and acidified with 10% aqueous HCl to pH 2-3. The precipitate was filtered off, thoroughly washed with cold water (3*30 mL), and dried in air. The physical constants and spectral parameters of 3a-3j were in agreement with published data [13, 14].
With sodium azide; In N,N-dimethyl-formamide; at 120℃;
General procedure: Nano-Fe3O4(at)TiO2/Cu2O (20 mg) and K4[Fe(CN)6].3H2O (0.09 g, 0.22 mmol), wasadded to a solution of aryl iodide (1 mmol) in distilled DMF (2 mL) and the reactionmixture was stirred under heating at 120 C for the appropriate time to obtain the nitrilecompound. To the nitrile compound generated in situ was added sodium azide (SafetyNote: Sodium azide is highly toxic. All workers should be thoroughly familiar with itssafe use before attempting experiments and proper personal protective gear must beused. 0.1g, 1.5 mmol) and the reaction was continued until the complete conversion ofthe nitrile to the tetrazole during 5 hours. After the completion of the reaction (as monitoredby TLC, 75:25 ethyl acetate: n-hexane), the catalyst was easily separated out fromthe reaction mixture by using an external magnet, washed with acetone, dried in theoven and re-used for a consecutive run under the same reaction conditions. After theseparation of the catalyst the crude material was then taken up in ethyl acetate andwashed with HCl (5 N) and the layers separated. The combined organic layers werethen washed with water and concentrated to obtain the crude product. The crude productwas purified by short column chromatography to obtain the pure products in highyield (see Tables 1 and 2). All the products are known compounds and the spectral dataand melting points were identical to those reported in the literature.
With nitronium tetrafluoborate; In acetonitrile; at 0 - 20℃; for 20h;
In dry acetonitrile (40 ml) was dissolved 4-chlorobenzonitrile (4g, 29.2 mmol), and nitronium tetrafluoroborate (7.7g, 58.39 mmol) was added therto at 0 C. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was poured into cold water. The white solid precipitated out was collected by filtration, and the filterate was washed with water and dried. The compound (4.0g, 75.47%) thus obtained was used for next step without purification.
Into a 50 mL dry reaction flask charged with 1 M LiHMDS in THF (22 mmol), p- chlorobenzonitrile (2.76 g, 20.0 mmol) in 2 mL of THF is added, and the reaction mixture is kept stirring at RT for 4 h, at which point 5-6 N HCI (in/PrOH, 15 mL) is added. The crude reaction mixture is kept at 0 0C overnight.The precipitated product is filtered, washed with diethyl ether to yield 3.5 g(93%) of the compound of formula 2b as a white solid, m.p. 238 0C (lit m.p. 243-245 0C) (E. Ragona, D. L. Nelson, M. Mares-Guis, J. Amer. Chem. Soc. EPO <DP n="74"/>1975, 97, 6844-6848). - IR (KBr): nu(tilde) = 3239 crrf1, 3054, 1678, 1460, 1401 , 1036, 715. - 1H NMR (250 MHz, [D6]DMSO): delta = 7.60-7.77 (m, 2 H), 7.85-7.97 (m, 2 H), 8.4 (br. s, 3 H, NH). - 13C NMR (62.9 MHz, [D6]DMSO), delta = 126.79 (Cquat), 129.36 (+), 130.57 (+), 139.1 (Cquat), 165.1 (NCN).
71%
Hydrogen chloride gas was passed through a solution of 4-chlorobenzonitrile (9b, 25.0 g) in chloroform (350 mL) and ethanol (100 mL) at -78 C for 0.5 h. Then the solution was warmed up to room temperature, and stirred at room temperature overnight. The solution was evaporated in vacuo, and the resulting residue was dissolved with ethanol (500 mL). To the solution was added ammonium carbonate (90.0 g), and the reaction mixture was stirred at room temperature for 3 days. To the mixture was added water (300 mL), and ethanol was removed by concentration in vacuo. The resulting solid was collected by filtration, washed with water and dried in vacuo to give 12b (25.4 g, 71%) as a white solid: 1H NMR (DMSO-d6) delta 2.60-4.80 (2H, br), 7.53 (2H, d, J = 8.8 Hz), 7.81 (2H, d, J = 8.8 Hz), 7.50-9.50 (2H, br); FAB-MS m/z 155, 157 [(M+H)+].
With ammonium chloride; sodium methylate; In methanol;
PREPARATION 8 4-Chlorobenzamidine Monohydrochloride To a solution of 4-chlorobenzonitrile (5.0 g) in methanol (40 ml) was added sodium methoxide (0.20 g) and the reaction was stirred at room temperature for 3 days. Ammonium chloride (1.94 g) was added and the reaction was stirred overnight. The reaction was filtered and the filtrate concentrated to an oil. After the addition of ether the off-white precipitate was collected and dried to give the title compound (3.62 g). Electrospray MS m/z 155 [M+H]+.
General procedure: A 100 mL flask was charged with 30 mL of anhydrous MeOH, 10 mmol of the arylnitrile, and 1.0 mmol of sodium methoxide. The complex was protected from moisture and stirred for 48 h. Then, 10 mmol of NH4Cl was added and stirring was continued for 24 h. Unreacted NH4Cl was filtered, and methanol was stripped from the filtrate to afford the product aryl amidine hydrochlorides, which was dissolved in 2.5 mL 8M sodium hydroxide aqueous solution and stirred for 1 h. Then chloroform (20 ml x 3) and H2O (20 ml x 3) were added successively to extract the product, and the combined organic layer was dried with anhydrous MgSO4 and then evaporated under vacuum to remove the organic solvent to give the desired arylamidine.
With copper(l) iodide; caesium carbonate; dimethylbiguanide; In N,N-dimethyl-formamide; at 20 - 110℃; for 12.1667h;
General procedure: A 25 mL flask with a magnetic stirring bar was charged with CuI(9.6 mg, 0.05 mmol), metformin (0.1 mmol), Cs2CO3 (652 mg,2.0 mmol), imidazole (1.0 mmol), an aryl halide (1.1 mmol), andDMF (5 mL). The mixture was stirred for 10 min at room temperature,and then heated to 110?C for the appropriate amount of time(see Table 2). The progress of the reaction was monitored by TLC.After completion of the reaction, the mixture was extracted with EtOAc (5 1 mL) and the organic phase separated and evaporated. Further purification by column chromatography gave the desired coupled product.
With iron(III) chloride; tert-Amyl alcohol; sodium; at 100 - 120℃; for 3h;
Sodium metal (2.30g, 100mmol), tert-amyl alcohol (50mL) and a catalytic amount of ferric chloride were added to a three-necked reaction flask, after stirring at 100 C for 1 hour, it was cooled to 50 C. After adding p-chlorobenzonitrile (5.48 g, 40 mmol) and heating the mixture to 100 C, a solution of <strong>[924-88-9]diisopropyl succinate</strong> (4.00 g, 20 mmol) in t-amyl alcohol was slowly added dropwise. After completion of the dropwise addition, the reaction was performed at 120 C for 3 hours. Cool to room temperature.Slowly add glacial acetic acid to adjust the pH to 7.0. Methanol and water (1: 2, v: v, 100 mL) were then added and refluxed for 2 hours. Cooled to filter and dried to give a pale red powdery solid (5.01 g). Yield: 70.5%
43%
Under nitrogen condition, potassium tert-butoxide (2.25 g, 0.02 mol) was dissolved in150 mL of tert-amyl alcohol for 15 min and the mixture was heated to 110. Iron(III) chloride (s.a) was added and stirred for 30 min then 4-chlorobenzonitrile (1.5 g, 0.01 mol) was added and stirred for 1 hr at the same temperature. Diisopropyl succinate (1.01g, 0.005 mol) was dissolved in 30 mL of tert-amyl alcohol and dropwised to the mixture for 3 hr. Then 60 mL of water was poured into mixture and stirred for 20 hr at the same temperature. After reaction, the mixture was cooled to room temperature. The mixture was filtered off and washed by water, methanol. The red pigment was purified by 50 mL methanol and stirred for 30 min at 60. After stirring, the solution was filtered off and dried under vacuum to obtain Pigment 1 in 43% yield. C18H10Cl2N2O2, Found C: 60.21 H:2.84 N: 7.73, MS (m/z) 356(M+).
450.0 parts of t-amyl alcohol and 15.45 parts of solid sodium were poured into separable wide mouth flask of 1L volume equipped with agitating blade made of glass, thermometer, nitrogen inlet tube, reflux condenser, and dropping funnel. The mixture was heated in oil bath at 130 C, and a small amount of iron(III) trichloride was added. After metal sodium vanished pe rfectly, mixture of 45. 51 parts of 4-chlorobenzonitrile, 1.50 parts of 3-methoxybenzonitrile, 50.76 parts of diisopropylsuccinimide and 90.0 parts of t-amyl alcohol was added within 2 hours. Then, reaction liquid temperature was reduced to 85 C, and reaction mixture was stirred for 2 hours more. Temperature was reduced to 40 C, and reaction mixture was poured into next reactor containing mixture of 900 parts of ion exchanged water,900 parts of methanol, and 360 parts of sulfuric acid at 40 C within 30 minutes. Then the pigment was conditioned at 40 C for 18 hours. After filtering and drying, 45.6 parts of crude pigment powder of red 3,6-bis(4-chlorophenyl)-1,4-diketo-pyrrolo[3,4-C]pyrrole (having same chemical structure as C. I. Pigment Red 254 expressed in the above formula). 40 parts of the crude pigment was suspended stirring in 800 parts of dimethylacetamide in separable wide mouth flask of 1L volume, and was further heated stirring at 140 C for 5 hours. After filtering, washing and drying, 37.9 parts of a red pigment was obtained. The pigment had mean particle diameter in the range between 0.40 and 0.70 mum.
1 18 g of tert-amyl alcohol are reacted under inert gas with 18.4 g of sodium at 1300C (bath temperature) to form sodium tert-amylate. A mixture, heated to 600C, of 56.7 g of 4-chlorobenzonitrile, 37.3 g of <strong>[924-88-9]succinic acid diisopropyl ester</strong> and 118 g of tert-amyl alcohol is then metered in over 2 hours, the internal temperature being lowered to 85C. Then a further 12.4 g of <strong>[924-88-9]succinic acid diisopropyl ester</strong> are subsequently metered in over 3 hours. The resulting suspension is stirred for a further 18 hours and is then cooled to 400C. The suspension is then metered into a mixture, previously prepared and cooled to -10C, of 177 g of methanol, 400 g of ice/ water, 73 g of a 10 % aqueous suspension of the product according to Example 2 of EP 0485337 and 49.5 g of sulfuric acid over 50 minutes, the temperature being maintained between -14C and -8C by jacket cooling and by adding, in portions, a further 800 g of ice. After the addition is complete, the reaction vessel is rinsed with 16 g of tert-amyl alcohol and this mixture is added to the protonation mixture. Stirring is then carried out for a further 2.5 hours at from -8C to +3C to complete the reaction, and filtration is then carried out. The filter cake is washed first with 1000 g of water and then with 3200 g of methanol and finally with 6000 g of water again until the washings are colourless and salt-free and it is then dried for 18 hours at 800C / 104 Pa. There are obtained 73 g of a finely divided pigment mainly of formula The analytical data correspond to those of Example 4.
31 parts of 4-chlorobenzonitrile are introduced into 30% sodium amoxide (prepared from 9.3 parts of sodium and 143 parts of amyl alcohol) and heated to 100 C. 30 parts of <strong>[924-88-9]diisopropyl succinate</strong> are added within two hours and the pigment salt suspension obtained is subsequently stirred at 100 C. for a further four hours.The thereby obtained disodium salt of the pigment is converted into the pigment by hydrolysis of the hot disodium salt suspension, cooled to 80 C., by pouring onto 420 parts of neutral water.Isolation and washing with methanol and water gives a pigment which has a maximum of the frequency distribution (the mode of the distribution) of the crystalline particles at 167 nm. The BET surface area of the pigment is 63 m2/g.
With sodium t-butanolate; at 100℃; for 3h;Inert atmosphere;
In the p- chlorobenzonitrile 2,475g, and 100 under the nitrogen (N(sub)2(/sub)) using the "All in one reactor (Drais Mannheim Germany) " the <strong>[924-88-9]diisopropyl succinate</strong> 2,181g and sodium t- butyrate 2,869g, it was stirred for 3hours and it reacted. In 130 the mixture, after it was stirred in 30 min. and it reacted at the addition it cooled to 60. After the reactant was washed with the methanol aqueous solution (50%) of 100 L it dried using the hot air dryer in 150 for 12 hours and the tempering (crude) diketopyrrolopyrrole (DPP red 254) pigment of the red solid powder state was manufactured. The tempering diketopyrrolopyrrole pigment was observed through the transmission electron microscope (transmission electron microscope (TEM): JEM-2000, JEOL, Japan). Then the particle was uneven and cohesion was high and color had the brown color and it was the state that it commercially could not use (fig. 1).
5.01 g
Sodium metal (2.30 g, 100 mmol),Tert-amyl alcohol (50 mL) and a catalytic amount of ferric chloride were added to the three-neck reaction flask, and after stirring at 100 C. for 1 hour, it was cooled to 50 C. After addition of p-chlorobenzonitrile (5.48 g, 40 mmol) the mixture was addedUpon heating to 100C, a solution of <strong>[924-88-9]di-isopropyl succinate</strong> (4.00 g, 20 mmol) in tert-amyl alcohol was slowly added dropwise. After completion of the addition, the reaction was carried out at 120C for 3 hours. Cool to room temperature. Slowly add glacial acetic acid to adjust the pH to 7.0, then add methanol and water (1:2, v:v,100 mL), reflux for 2 hours. Cool filtered and dried to a pale red powder solid (5.01 g).
5.01 g
With iron(III) chloride; In tert-Amyl alcohol; at 100 - 120℃; for 3h;
Sodium metal (2.30 g, 100 mmol), tert-amyl alcohol (50 mL) and a catalytic amount of ferric chloride were placed in a three-necked reaction flask, stirred at 100 C for 1 hour and then cooled to 50 C.Add p-chlorobenzonitrile (5.48g, 40mmol) and add the mixtureHeat to 100 C,A solution of <strong>[924-88-9]diisopropyl succinate</strong> (4.00 g, 20 mmol) in tert-amyl alcohol was slowly added dropwise.After completion of the dropwise addition, the reaction was carried out at 120 C for 3 hours.Cool to room temperature. Slowly add glacial acetic acid to adjust the pH to 7.0, then add methanol and water (1:2, v: v, 100 mL) and reflux for 2 hours.Cool filtered and dried to give a pale red powder solid (5.01 g).
38.8 g (1.68 mol) of sodium cut into small pieces and a spatula tip of Fecal3 are introduced into 375 mi of tert-amyl alcohol in a 1 litre sulfonating flask and heated to reflux (bath tempe- rature of 130C). To the resulting clear solution there is then added a solution of 72.3 g (0. 53 mol) of 3-chlorobenzonitrile, 31.0 g (0.23 mol) of 4-chlorobenzonitrile, 14.2 g (0. 038 mol) of 4-octadecylthiobenzonitrile and also 92.9 ml (0.45 mol) of <strong>[924-88-9]succinic acid diisopropyl ester</strong> (SAI) in 225 mi of tert-amyl alcohol via a heated dropping funnel over 3 hours, the bath tem- perature being set at 95C at the beginning. After the addition is complete, a further 15.5 mi (0.075 mol) of SAI are added over 30 minutes. The reaction mixture is then cooled to 50C and transferred to a mixture of 375 ml of methanol and 1125 ml of water at room temperature over 30 minutes. After the addition is complete, stirring is carried out overnight to complete the reaction. The orange suspension is filtered and washed with methanol and then with water. After drying overnight at 80C and 200 mbar in a drying cabinet, there are obtained 136.9 g (91 % of theory) of a pigment which in PVC results in a transparent, tinctorially strong, orange coloration.
With sodium tert-pentoxide; at 20 - 100℃; for 2h;Neat (no solvent);
1.0 kilo mole of a nitrile of the formula R'-CN and 1.0 kilo mole of the formula R"-CN, wherein R'and R"ARE different and are as defined in Table II (Examples 16-20) and 3.4 kilo mole of sodium tert-amylate are placed at 20-25 C in a 10000 ml"All In One REACTOR" (OF, DRAIS Mannheim Germany). By means of a metering pump, 1.2 kilo moles of <strong>[924-88-9]diisopropyl succinate</strong> are added at the reaction temperature indicated in Table II over the period of time also indicated therein, while continuously distilling off the alcohol mixture. When the addition is complete, the mixture is kept for 2 hours at the reaction temperature and then hydrolyse and worked up as in Example 2 to give the pigment mixture of the formulas XXIII, XXIV and XXV of Table 2.
With sodium t-butanolate; at 20 - 87℃; under 37.5038 - 600.06 Torr;Neat (no solvent);
1527.4 g <strong>[924-88-9]diisopropyl succinate</strong>, 1732.5 g of p-chlorobenzonitrile and 2013 g sodium TERT-BUTYLATE are placed in a 10000 ml"All In One REACTOR" OF (Drais Mannheim Germany) at 20-25 C. Under stirring and nitrogen flow the mixture is heated to 87 C (inside temperature). From 50 C onwards the reaction mixture becomes considerably thicker and is finally converted into a paste. As soon as the inside temperature of 87 C is reached, a vacuum of 800 mbar is applied at the outlet of the condenser which is then gradually reduced to 50 mbar, thereby allowing the mixture of isopropyl alcohol and tart-butyl alcohol to distil off. The inside temperature first drops to 75 C and thereafter rises again to 85 C as soon as the mixture of alcohols is completely distilled off. The reaction mass becomes crumbly and finally largely disintegrates into an almost semi- powdery material. After the distillation of the residual mixture of alcohols, the reaction mixture is stirred for another 30 minutes at 87 C under vacuum of 50 mbar. The mixture is cooled to 60 C and the material is emptied into a steel container. The yield is 2950 g of the crude compound of formula XIX of example 21 of 81. 4% purity (approximately 95% of theory, based on p- chlorobenzonitrile).
90%
With sodium t-butanolate; at 20 - 120℃; for 5h;Neat (no solvent);
2475 g of p-chlorobenzonitrile, 2181. 6 g <strong>[924-88-9]diisopropyl succinate</strong> and 2869. 2 g sodium tert- butylate are placed at 20-25 C in a 10000 ML"ALL In One REACTOR" of (Drais Mannheim Germany). Under stirring and nitrogen flow the mixture is heated to 100 C within 60 minutes. From 80 C onwards the reaction mixture becomes considerably thicker and is finally converted into a paste. From 80-85 C onwards a rapid formation of alcohol vapours is observed. The temperature is maintained at 99 to 100 C for three hours, thereby allowing the mixture of isopropyl alcohol AND TERT-BUTYL alcohol to distil off. The reaction mass becomes crumbly and finally largely disintegrates into an almost semi-powdery material. The reaction mixture is heated to 120 C in 30 minutes and kept at 120 C for 30 minutes. The mixture is cooled to 50 C. The material is emptied into a polyethylene sack, tightly fitted to the outlet of the reactor ; affording 3248 g (90 % of theory, based on p-chlorobenzonitrile) of pigment of the formula XIX. Approximately 200 g (5.54 % of theory, based on p- chlorobenzonitrile) of the product are still contained in the reactor to be used in the next batch. The total yield thus corresponds to approximately 3448 g (approximately 95.54 % of theory, based on p-chlorobenzonitrile). This product produces an intense red colour when dispersed with stirring into a state-of-the- art waterborne paint system.
87%
With sodium isopropylate; at 20 - 120℃; for 6.41667h;Neat (no solvent);
2750 g OF P-CHLOROBENZONITRILE and 2950 g sodium iso-propylate are placed at 20-25 C in a 10000 ML"ALL In One Reactor" of (Drais Mannheim Germany). Under stirring and nitrogen flow the mixture is heated to 90 C within 60 minutes. As soon as this temperature has been reached, 2424 g <strong>[924-88-9]diisopropyl succinate</strong> are added over 145 minutes by means of a metering pump. The temperature is kept CONSTANTLY AT 98-99 C and isopropyl alcohol is distilled off. The temperature is maintained at 99 to 100 C FOR two hours. The reaction mixture is heated to 120 C in 30 minutes and kept at 120 -C FDR 30 minutes. The mixture is cooled to 50 C. The material is emptied into a polyethylene sack tightly fitted to the outlet of the reactor ; the yield is 3490 g (approximately 87% of theory, based on P-CHLOROBENZONITRILE) of the compound of formula XIX. For the hydrolysis, 1000 G of the above reaction mixture is slowly added to 10000 ML of water at 80 C TEMPERATURE. THE resultant pigment suspension is heated to 95 C and kept at 95 C for two hours. Thereafter, it is filtered at about 80 C, washed with water until the washings run colourless, and dried AT 80 C in vacuum ; affording 872 g (98 % of theory, based on the compound of formula XIX) of a very finely divided pigment of the formula XX. The crude pigment is then finished by treating with seven volume parts of dimethyl formamide at 130 C for three hours. The suspension is filtered at 100 C, washed with the same volume of dimethyl formamide heated to 100 C followed by water at 70 C. The press cake is dried at 100 C yielding A bright red product.
A 500 ml glass reactor is charged with 150 ml of ANHYDROUS TER-AMYL alcohol under nitrogen. 4. 6 g (0.2 moles) of sodium are added thereto and the mixture is heated to and maintained at 100- 105 C FOR 12 hours. To the resulting solution are then added at 80 C, 20.6 g (0. 15 moles) of 4- chlorobenzonitrile. Subsequently 20.1 g (0. 01 moles) of <strong>[924-88-9]diisopropyl succinate</strong> are metered in at 96 C. over 3 hours. The isopropanol formed during the reaction along with some ter-amyl alcohol is allowed to distil off simultaneously during the addition. The reaction mixture is stirred for another 4 hours after the. addition OF DIISOPROPYL SUCCINATE. IS complete. Thereafter the reaction mixture is transferred to a 500 ml round bottomed flask and the residual ter-amyl alcohol is distilled off on a rotavap (Buechi). under vacuum to yield the compound of Formula XIX as a dark red powder.
The reaction is carried out under an inert atmosphere in a 5-necked 1.5 litre sulfonating flask provided with a thermometer, a mechanical stirrer, a dropping funnel and a reflux condenser. The protonation and conditioning step is carried out in a 5-necked 2. 5 litre sulfonating flask provided with a thermometer, a mechanical stirrer and a reflux condenser. 22.96 g (1.0 mol) of sodium are added to a solution of 200 g of tert-amyl alcohol and a cata- lytic amount of Fe (III) CI3 at 112C. The sodium dissolves, with the formation of sodium tert- amylate and H2, over 60 minutes at 112C. Then 66.21 g (0. 48 mol) of p-chlorobenzonitrile, 5.95 g (0.016 mol) of p-octadecylthiobenzonitrile and 48. 16 g (0.238 mol) of <strong>[924-88-9]succinic acid diisopropyl ester</strong> (SAI) are dissolved in 121 g of tert-amyl alcohol at 90C and added over 2 hours to the reaction mixture. In the first hour of addition the internal temperature is main- tained at 112C but is then reduced to 85C. A further 16.06 g (0.08 mol) of SAI are then added over 3 hours and the reaction mixture is stirred at 85C for a further 4 hours and cool- ed to room temperature. The reaction mixture is then transferred into a solution of 552 ml of water and 522 ml of methanol at room temperature over 20 minutes. The resulting mixture is heated to 50C and stirred at that temperature for 4 hours. The dark-red precipitate is then filtered off, washed with 8 litres each of methanol and water and dried at 80C and 200 mbar in a drying cabinet. 88.3 g (96 % of theory) of a red mixture comprising the pigments of for- mulae (103) and (104) are obtained, which in PVC results in a transparent red coloration.
The reaction is carried out under an inert atmosphere in a 5-necked 1.5 litre sulfonating flask provided with a thermometer, a mechanical stirrer, a dropping funnel and a reflux condenser. The protonation and conditioning step is carried out in a 5-necked 2. 5 litre sulfonating flask provided with a thermometer, a mechanical stirrer and a reflux condenser. 44. 5 g (1.9 mol) of sodium are added to a solution of 348 g of ter-amyl alcohol and a cataly- tic amount of Fe (III) CI3 at 115C. The sodium dissolves, with the formation of sodium tert- amylate and H2, over 40 minutes at 115C. Then 137.6 g (1.0 mol) of p-chlorobenzonitrile, 12.3 g (32 mmol) of p-octadecylthiobenzonitrile and 94.2 g (0.46 mol) of succinic acid diiso- propyl ester (SAI) are dissolved in 220 g of tert-amyl alcohol at 60C and added over 2 hours to the reaction solution. In the first hour of addition the internal temperature is maintained at 115C but is then slowly reduced to 85C. A further 31. 0 g (0.15 mol) of SAI are then added over 3 hours. Over a further 3 hours, 160 g of an azeotropic mixture of isopropanol and tert- amyl alcohol are then distilled off under reduced pressure (350 mbar) at 85C. The reaction mixture is cooled to room temperature and, over 2.5 hours, added to a mixture of 349 g of ice, 170 g of methanol and 163 g of 60 % sulfuric acid at 0C. During the addition, there are added a further 231 g of MeOH and a total of 1440 g of ice in portions. The resulting mixture is stirred at 0C for 5 hours. The dark-red precipitate is filtered off, washed with 5 litres each of methanol and water and dried at 80C and 200 mbar in a drying cabinet. There are obtai- ned 170 g (88 %) of a red mixture comprising the pigments of formulae (103) and (104), which in PVC results in a transparent red coloration.
EXAMPLE 1 Co-synthesis of 3,6-di(4-chlorophenyl)-1,4-diketopyrrolo[3,4-c]pyrrole with trans-2,2'-bis(4H-1,4-benzothiazine)-indigo: 60/40 molar-percent A reactor of 1500 ml is charged with 400 ml of ter-amyl alcohol under nitrogen. 50 ml of teramyl alcohol are distilled off the reactor. 18.4 g (0.80 moles) of sodium are added and the mixture is heated to 95-102 C. The molten sodium is then maintained overnight at 100-105 C. with vigorous stirring. To the resulting solution are then added at 60 C., 62.5 g (0.44 moles) of 4-chlorobenzonitrile. Subsequently 58 g (0.286 moles) of <strong>[924-88-9]diisopropyl succinate</strong> are metered in at 96 C. over 2 hours. The resulting isopropanol is distilled off at the same time.
With sodium;
EXAMPLE 2 Co-synthesis of 3,6-di(4-chlorophenyl)-1,4-diketopyrrolo[3,4-c]pyrrole with 7,7'-dichloro-trans-2,2'-bis(4H-4-benzothiazine)-indigo; 60/40 molar-percent A reactor of 1500 ml is charged with 400 ml of ter-amyl alcohol under nitrogen. 50 ml of teramyl alcohol are distilled off the reactor. 18.4 g (0.80 moles) of sodium are added and the mixture is heated to 95-102 C. The molten sodium is then maintained overnight at 100-105 C. with vigorous stirring. To the resulting solution are then added at 80 C., 62.5 g (0.44 moles) of 4-chlorobenzonitrile. Subsequently 58 g (0.286 moles) of <strong>[924-88-9]diisopropyl succinate</strong> are metered in at 96 C. over 2 hours. The resulting isopropanol is distilled off at the same time.
With sodium;
EXAMPLE 3 Co-synthesis of 3,6-di(4-chlorophenyl)-1,4-diketopyrrolo[3,4-c]pyrrole with trans-2,2'-bis(4H-1,4-benzothiazine)-indigo: 50/50 by weight A reactor of 1500 ml is charged with 400 ml of ter-amyl alcohol under nitrogen. 50 ml of ter-amyl alcohol are distilled off the reactor. 18.4 g (0.80 moles) of sodium are added and the mixture is heated to 95-102 C. The molten sodium is then maintained overnight at 100-105 C. with vigorous stirring. To the resulting solution are then added at 80 C., 62.5 g (0.44 moles) of 4-chlorobenzonitrile. Subsequently 58 g (0.286 moles) of <strong>[924-88-9]diisopropyl succinate</strong> are metered in at 96 C. over 2 hours. The resulting isopropanol is distilled off at the same time.
With potassium fluoride;palladium diacetate; In tetrahydrofuran;
EXAMPLE 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound.
159 mg (89%)
With potassium fluoride;palladium diacetate; In tetrahydrofuran;
Example 32 Synthesis of 4-cyanobiphenyl An oven dried resealable Schlenk tube was evacuated and backfilled with argon and charged with palladium acetate (2.2 mg, 0.01 mmol, 1.0 mol percent), 2-(di-tert-butylphosphino)biphenyl (6.0 mg, 0.020 mmol, 2.0 mol percent), phenylboronic acid (183 mg, 1.5 mmol), potassium fluoride (174 mg, 3.0 mmol), and 4-chlorobenzonitrile (136 mg, 1.0 mmol). The tube was evacuated and backfilled with argon, and THF (1 mL) was added through a rubber septum. The tube was sealed with a teflon screwcap, and the reaction mixture was stirred at room temperature until the starting aryl chloride had been completely consumed as judged by GC analysis. The reaction mixture was then diluted with ether (30 mL) and poured into a separatory funnel. The mixture was washed with water (20 mL), and the aqueous layer was extracted with ether (20 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography on silica gel to afford 159 mg (89percent) of the title compound.
EXAMPLE 15 Preparation of 4-chloro deoxybenzoin To a 1-liter, three-neck flask is added 9.72 g of magnesium and 200 ml ether. A solution of 38 g benzyl chloride in ether is added at such a rate that gentle reflux is maintained. After reflux subsides, 33 g of 4-chlorobenzonitrile is added dropwise. The mixture is refluxed overnight. After cooling, the reaction is treated with concentrated HCl and stirred for 2 hours. The ether phase is separated, dried over Na2 SO4, and the solvent removed yielding 53.4 g of solid. Recrystallization from carbon tetrachloride-hexane yields 40 g of 4-chlorodeoxybenzoin, M.P. 104.5-106 C. Similarly prepared are 3-chloro deoxybenzoin, 3-methyl deoxybenzoin, 4-methyl deoxybenzoin, 3'-methyl deoxybenzoin, 4'-methyl deoxybenzoin, 3'-chloro deoxybenzoin, 2'-chloro deoxybenzoin, 2-chloro deoxybenzoin. The following examples show the use of the monohydrazones of the invention in reducing the phytotoxicity of triazine herbicides.
With caesium carbonate; In dimethyl sulfoxide; at 120℃; for 24h;Sealed tube;
General procedure: A 5 mL reaction tube was charged with Phen-MCM-41-CuBr (36 mg, 0.025 mmol), amidine 4 (0.75 mmol), nitrile 2 (0.5 mmol), Cs2CO3 (489 mg, 1.5 mmol), and DMSO (1.5 mL) under an air atmosphere. The reaction tube was sealed and placed in an oil bath at r.t. The reaction mixture was stirred at 120 °C for 24 h. After cooling to r.t., the reaction mixture was diluted with EtOAc (10 mL) and filtered. The supported copper catalyst was washed with water (2 5 mL) and acetone (2 5 mL), and reused in the next run. The filtrate was washed with 5percent aqueous NaHCO3 and brine. The organic layer was dried over Mg-SO4 and concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (hexane/EtOAc, 3:2) to provide the desired product 5.
With caesium carbonate;palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; for 16h;Heating; Reflux; Inert atmosphere;
Step-I: tert-Butyl 8-(4-cyanophenyl)-2,8-diazaspiro[4.5]decane-2-carboxylate Cesium carbonate (1.35 g, 4.16 mmol, 2.0 eq.) was added to a stirred solution of <strong>[336191-17-4]ter<strong>[336191-17-4]t-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate</strong></strong> (500 mg, 2.08 mmol, 1.0 eq.) and 4-chlorobenzonitrile (390 mg, 2.08 mmol, 1.0 eq.) in toluene (30 ml) and the reaction mixture was degassed with nitrogen for 15 min. BINAP (52 mg, 0.083 mmol, 0.04 eq.) and Pd(OAc)2 (10 mg, 0.0416 mmol, 0.02 eq.) were added and the resulting reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered through celite and the filtrate was evaporated under reduced pressure to afford the crude product which was purified by column chromatography (silica gel; 15-20% EtOAdhexanes) to yield the pure product as an oil. Yield: 49% (350 mg, 1.026 mmol).
Example 1 The first step 200 g tert-amyl alcohol that had been dried over molecular sieve and 140 g sodium tert-amyl alkoxide were introduced under a nitrogen atmosphere into a stainless steel reactor fitted with a reflux condenser and heating to 100C was performed with stirring to produce an alcoholate solution. Separately, 88 g <strong>[924-88-9]diisopropyl succinate</strong>, 97.0 g 4-chlorobenzonitrile, and 3.9 g 4-cyanobiphenyl were introduced into a 500 mL glass flask and were dissolved by heating to 90C with stirring to produce a solution of their mixture. This hot solution of the mixture was gradually added dropwise at a constant rate over 2 hours with vigorous stirring into the above-described alcoholate solution heated to 100C. After the completion of dropwise addition, heating and stirring were continued for 2 hours at 90C to obtain the alkali metal salt of a diketopyrrolopyrrole pigment composition.
Example 13 A finely divided diketopyrrolopyrrole pigment composition was obtained by performing the same first step and second step as in Example 1, but in this case changing the 97.0 g 4-chlorobenzonitrile and 3.9 g 4-cyanobiphenyl of Example 1 to 95.0 g 4-chlorobenzonitrile and 5.8 g 4-tert-butylbenzonitrile. According to TEM observation, the particles in the resulting finely divided diketopyrrolopyrrole pigment composition were round and had a primary particle diameter of 20 to 40 nm. The yield was 82.5 g.
Example 5 A finely divided diketopyrrolopyrrole pigment composition was obtained by performing the same first step and second step as in Example 1, but in this case changing the 97.0 g 4-chlorobenzonitrile and 3.9 g 4-cyanobiphenyl of Example 1 to 74.8 g 4-chlorobenzonitrile and 27.7 g 1-naphthonitrile. According to TEM observation, the particles of the resulting finely divided diketopyrrolopyrrole pigment composition were round and had a primary particle diameter of 20 to 40 nm. The yield was 61.7 g.
With potassium carbonate; In butan-1-ol; at 150℃; for 2h;Microwave irradiation;
Preparation Example 8 A mixture of tert-butyl 4-(hydrazinocarbonyl)piperidine-1-carboxylate (1.0 g), 4-chlorobenzonitrile (1.7 g), potassium carbonate (0.28 g), and butanol (8.0 mL) was heated at 150C for 2 hours using a microwave device. After leaving to be cooled, the solvent was evaporated under reduced pressure, and the residue was azeotroped with toluene. The residue was purified by silica gel column chromatography (chlaroform/methanol=100/0 to 90/10). To the purified product was added diisopropyl ether, and the resulting solid was collected by filtration and dried under reduced pressure to obtain tert-butyl 4-[3-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl]piperidine-1-carboxylate (0.62 g).
With dmap; bis(eta3-allyl-mu-chloropalladium(II)); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,3,5-trimethyl-benzene; at 140℃; for 20h;Inert atmosphere;
General procedure: after standard cycles of evacuation and back-filling with dry and pure nitrogen, an oven-dried Schlenk tube equipped with a magnetic stirring bar was charged with Pd source (see Table 1, Table 2, Table 3 and Table 4), ligand (see Table 1, Table 2, Table 3 and Table 4), N,N-dimethylpyridin-4-amine (DMAP, see Table 1, Table 2, Table 3 and Table 4), and ethyl potassium malonate (see Table 1, Table 2, Table 3 and Table 4). The tube was evacuated and backfilled with argon (this procedure was repeated three times). Under a counter flow of argon, aryl halide (see Table 1, Table 2, Table 3 and Table 4) and solvent (see Table 1, Table 2, Table 3 and Table 4) were added by syringe. The tube was sealed and stirred at room temperature for 10 min. Then the tube was connected to the Schlenk line, which was full of argon, stirred in a preheated oil bath (140-150 C) for the appointed time (20-25 h). Upon completion of the reaction, the mixture was cooled to room temperature and diluted with diethyl ether, and the yields were determined by gas chromatography using 1,3-dimethoxybenzene as the internal standard.
General procedure: To a solution of N,N-dimethyl benzamide (298 mg, 2 mmol) in dry THF (4 mL) was added DIBAL-H (1.04 M in hexane, 2.3 mL, 1.2 equiv) at -78 C. The mixture was stirred for 1.5 h under an argon atmosphere at from -70 C to -40 C slowly. Then, aq NH3 (concentration: 28.0-30.0%, 4 mL) and I2 (762 mg, 3.0 equiv) were added at 0 C, and the reaction mixture was stirred for 2 h at room temperature. Reaction mixture was poured into saturated aq Na2SO3 solution (10 mL) and extracted with ethyl acetate (15 mL×3). The organic layer was dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was purified by short column chromatography on silica gel (eluent: hexane/ethyl acetate=4:1) to afford benzonitrile in 67% yield (138 mg).Most of the present prepared nitriles are commercially available and they are identified with authentic nitrile compounds.
General procedure: A solution of the corresponding aromatic aldehyde (0.8-10.3 mmol), 2-sulfanylacetic acid (1.0-1.3 equiv) and the corresponding aromatic nitrile (1.0-1.3 equiv) and triethylamine (1.5-15.0 equiv) in methanol was refluxed over night. The reaction mixture was evaporated under reduced pressure and the crude product was recrystallized from ethanol and washed with acetone.
With bis[1,3-bis(4-ethylbenzyl)perhydrobenzimidazol-2-ylidene]dichloropalladium(II); potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 20h;Schlenk technique; Inert atmosphere; Green chemistry;
General procedure: The heteroaryl derivative (2 mmol), aryl chloride (1 mmol) and KOAc (2 mmol) were introduced in a Schlenk tube equipped with a magnetic stirring bar. Pd complex (0.01 mmol) and DMAc (2 mL) were added and the Schlenk tube was purged several times with argon. The Schlenk tube was placed in a preheated oil bath at 150 C, the reaction mixture was stirred for 20 h. Then, the reaction mixture was analysed by gas chromatography to determine the conversion of the aryl chloride. The solvent was removed by heating the reaction vessel under vacuum and the residue was charged directly onto a silica-gel column. The products were eluted by using an appropriate ratio of diethyl ether and pentane.
8-chloro-3-methyl-3H-pyrazolo[4,3-a]acridine-11-carbonitrile[ No CAS ]
1-(4-chlorophenyl)-6-methyl-6H-isoxazolo[4,3-e]-indazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
9%; 63%
With potassium hydroxide; In methanol; for 48h;Reflux;
General procedure: 1-Alkyl-5-nitro-1H-indazole 1 (1.77 g, 10 mmol) andnitrile 2a-e (12 mmol) were added with stirring to asolution of KOH (30 g, 535 mmol) in methanol (70 ml).The mixture was refluxed for 48 h and then poured intowater. The precipitate was filtered off, washed with water,and air-dried to give crude product 5a-e with admixture ofside product 4a-e. Washing the crude product withacetone, evaporation of the filtrate, and recrystallization ofthe residue from MeOH gave pure compound 5a-e, whilecrude compound 4a-e remained as precipitate on the filter.Compound 4a-e was purified by recrystallization fromEtOH
3-(4-chlorophenyl)-5-methoxymethyl-1H-1,2,4-triazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
412 mg
To a solution of sodium methoxide in dry methanol (0.5M; 4 ml.) was added 4- chlorobenzonitrile (1 .38 g, 10 mmol). The resulting suspension was stirred at room temperature under argon for 2.5h. A solution of <strong>[20605-41-8]methoxyacetic acid hydrazide</strong> (1 .04 g, 10 mmol) in dry methanol (10 ml.) was added to the mixture, resulting in a clear solution, which was heated to reflux for 3h and then stirred at room temperature overnight. The mixture was concentrated under reduced pressure and purified by flash column chromatography eluting with 20percent to 60percent ethyl acetate in petroleum ether to afford 3-(4-chlorophenyl)-5- methoxymethyl-1 H-1 ,2,4-triazole as a white solid (412 mg, 1.84 mmol).
4-chlorobenzonitrile (1.500 g, 10.904 mmol), titanium isopropoxide (4.842 mL, 16.355 mmol) and ethylmagnesium bromide (1.00 M solution, 25.078 mL, 25.078 mmol) was dissolved in 2-methoxy-2-methylpropane (MTBE, 150 mL) at 0 C and stirred at room temperature for 1 hour, and at 0 C boron trifluoroetherate (2.691 mL, 21.807 mmol) was added, and further stirred at room temperature for 17 hours. Then, water (10 mL) was added to the reaction mixture at room temperature, and the reaction was terminated by stirring for 10 minutes. The reaction mixture was poured into saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and water was removed with anhydrous magnesium sulfate, followed by filtration and concentration under reduced pressure. The concentrate was dissolved in ethyl acetate, and hydrochloric acid (1.00 M solution in EtOAc, 11.994 mL, 11.994 mmol) was added and stirred. The precipitated solid was filtered, washed with ethyl acetate and dried to give the title compound (1.120 g, 50.3%) as a white solid.
With caesium carbonate; In dimethyl sulfoxide; at 60℃;
4-Chlorobenzonitrile (0.55 g, 4.0 mmol) was dissolved in DMSO (80 mL) and then 1,3-dihydro-2,1-benzoxaborole-1,5-diol(0.75 g, 5.0 mmol) and cesium carbonate (1.95 g, 6.0 mmol) were added and the mixture was stirred at 60 C. for reactionThe reaction was quenched by the addition of water (50 mL) and extracted with ethyl acetate (3 x 30 mL). The organic phases were combined, washed with water (2 x 50 mL)Washed, dried over sodium sulfate, filtered, concentrated and purified to give the product 0.71 g, 95% yield, purity 95.0%.
With hydrogenchloride; zinc(II) chloride; In water; 1,2-dichloro-ethane; at 90℃; for 7h;Reflux;
The specific steps of the preparation method of 4-chloro-4'-hydroxybenzophenone of this embodiment include:Dichloroethane 550ml was added to the reactor.Phenol 120g,P-chlorophenyl nitrile 146g,Anhydrous zinc chloride 22g and Dowex 50W resin Dow Chemicals 7g,Stirring, temperature control at 90 °C continuous flow of dry hydrogen chloride gas, the gap during the detection of material reaction conditions, until the complete reaction of chlorobenzene,After cooling to room temperature, 450 ml of a 30percent aqueous solution of hydrochloric acid was added and the mixture was heated to reflux for 7 hours.After the intermediates are hydrolyzed, the mixture is cooled to room temperature, and the layers are separated and washed with water. Dichloroethane is recovered from the organic layer. The residue is dissolved in 200 ml of a 15percent aqueous solution of sodium hydroxide, decolorized with activated charcoal 8 g, acidified and extracted. Filter and dry to obtain a pale yellow solid4-chloro-4'-hydroxybenzophenone,The content was 99.2percent, and the yield was 88.1percent.
88.2%
Dichloroethane 600ml, phenol 120g, p-chlorobenzonitrile 146g, were added to the reactor. 25 g of anhydrous zinc chloride and 8 g of Amberlyst 15 resin produced by Dow Chemical, Stirring, temperature control at 90°C, continuous introduction of dry hydrogen chloride gas, During the ventilation process, the material in the gap is tested for reaction until complete reaction to chlorobenzonitrile. Cool to room temperature and add 500ml of a 30percent strength aqueous solution of hydrochloric acid and heat up to reflux. Reaction 5h, until the intermediate is hydrolyzed, then cooled to room temperature, layered, washed with water, Dichloroethane is recovered in the organic layer, The residue was dissolved in 250 ml of a 15percent aqueous sodium hydroxide solution. Decolorization with activated charcoal 8g, acid precipitation, suction filtration, Drying to give a pale yellow solid is 4-chloro-4'-hydroxybenzophenone. The content was 99.2percent and the yield was 88.2percent.
Under a nitrogen atmosphere,40 parts of tert-amyl alcohol dehydrated by molecular sieve and 28 parts of sodium tert-amyl alkoxide were mixed and heated to 100 C. with stirring to prepare an alcoholate solution.On the other hand, a mixture of 24 parts of tert-amyl alcohol dehydrated with molecular sieve, 17.6 parts of <strong>[924-88-9]diisopropyl succinate</strong> and 20 parts of 4-chlorobenzonitrile was heated and dissolved at 90 C. while stirring, It was adjusted. The heated solution of this mixture was slowly added dropwise at a constant rate over 2 hours with vigorous stirring into the previously prepared alcoholate solution. After completion of the dropwise addition, the mixture was heated and stirred at 90 C. for 2 hours to obtain a reaction solution of dichlorodiketopyrrolopyrrole.Next, 120 parts of methanol, 120 parts of water and 23.4 parts of acetic acid were mixed and cooled to 0 C. While stirring this cooled mixture with vigorous stirring, the reaction solution of dichlorodiketopyrrolol obtained at 90 C. previously obtained was added thereto while cooling with a refrigerant so as to keep the temperature at 5 C. or less. After stirring this solution at 40 C. for 1 hour, the dichlorodiketopyrrolate pigment was filtered off using a Nutsche. Thereafter, 120 parts of methanol and 200 parts of water were sprinkled and washed. The filtered pigment was dried at 80 C. for 24 hours to obtain 22.3 parts of the intended pigment.
With palladium diacetate; tetra-(n-butyl)ammonium iodide; caesium carbonate; tricyclohexylphosphine; In N,N-dimethyl-formamide; at 110℃; for 4.0h;Inert atmosphere;
General procedure: The representative cross-coupling procedure given for Table 2 was followed with the following reagents and conditions: arylchloride 1c-1e (0.875 mmol,3.5 equiv.), BiAr3 (0.25 mmol, 1 equiv.), Pd(OAc)2 (0.025 mmol, 0.1 equiv.),PCy3 (0.1 mmol, 0.4 equiv.), Cs2CO3 (0.75 mmol, 3 equiv.), TBAI (1.25 mmol,5 equiv.) and DMF (3 mL) at 110 C for 4 h.
With sodium carbonate; In sulfolane; water; toluene; at 160 - 200℃; for 3h;Inert atmosphere;
75.27g 6,6'-dihydroxy-2,2'-bipyridine (0.4mol) was added to a 1000ml four-necked flask with mechanical stirring, water separator, nitrogen inlet, thermometer under room temperature nitrogen protection, 52.95 g fine sodium carbonate (0.5mol), 121g p-chlorobenzonitrile (0.88mol) and 800ml sulfolane, 100ml toluene, warmed to 160 C reflux water, until the water is finished to end the water, after the water is finished The water and most of the toluene are removed, and the temperature is raised to 200 C with stirring. After about 3 hours of reaction, the reaction is completed. After cooling, the product is poured into 400 ml of water which is stirred at a high speed, filtered, washed with water, and dried to obtain 6,6'-dihydroxyl. -2,2'-bipyridyl diether dicarbonitrile.
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