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Structure of 1003-31-2 * Storage: {[proInfo.prStorage]}
* 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] Justus Liebigs Annalen der Chemie, 1924, vol. 437, p. 19
2
[ 60-29-7 ]
[ 506-77-4 ]
[ 1003-09-4 ]
[ 1003-31-2 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1924, vol. 437, p. 19
3
[ 1003-31-2 ]
[ 20300-02-1 ]
Yield
Reaction Conditions
Operation in experiment
80%
With hydrogen sulfide In dimethyl sulfoxide at 20℃;
General procedure: The corresponding nitrile (100 mmol) prepared as described previously18 was dissolved in DMSO (25 mL) and H2S was slowly bubbled through the solution until no more gas was consumed. The solution was stirred at r.t. and the reaction progress was monitored by TLC (acetone). H2O was added to precipitate the product, the solid formed was collected by filtration, and recrystallized from DMF.
Reference：
[1] Synthetic Communications, 2005, vol. 35, # 5, p. 761 - 764
[2] Synthesis (Germany), 2014, vol. 46, # 1, p. 126 - 134
[3] Journal of the American Chemical Society, 1955, vol. 77, p. 4062,4064
[4] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 8, p. 1167 - 1170
[5] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 7; 8
[6] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 8
[7] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 8
[8] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 8
[9] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 8
[10] Patent: US2005/228179, 2005, A1, . Location in patent: Page/Page column 8
[11] Synthesis, 2010, # 10, p. 1603 - 1608
[12] Chemistry of Materials, 2013, vol. 25, # 9, p. 1927 - 1934
[13] Journal of the American Chemical Society, 2015, vol. 137, # 17, p. 5670 - 5673
4
[ 1003-31-2 ]
[ 68-12-2 ]
[ 21512-16-3 ]
Yield
Reaction Conditions
Operation in experiment
76%
Stage #1: With n-butyllithium; diisopropylamine In tetrahydrofuran at -70℃; for 1 h; Inert atmosphere Stage #2: at -78 - -70℃; for 1.5 h; Inert atmosphere Stage #3: With water; citric acid In tetrahydrofuran
Method C5- Formylthiophene-2-carbonitrile (Intermediate compound)Under inert atmosphere BuLi (1 1 .7 ml, 29.3 mmol, 2.5 M) was added to a mixture of diisopropylamine (4.1 ml, 29.3 mmol) and THF (150 ml) at below - 70°C. When addition was finished, the mixture was allowed to reach room- temperature. The mixture was cooled back to -70°C again, where 2- thiophenecarbonitrile (3.0 g, 26.7 mmol), solved in THF (15 ml) was added drop- wise and stirred an additional hour. At -78°C. DMF (8.2 ml, 106.6 mmol) was added below -70°C. The mixture was stirred for 1 .5 h at -78°C. Citric acid (10 g) was added to the reaction-mixture. The reaction-mixture was poured out on water. The aqueous phase was extracted with diethylether. The product was dried and evaporated. The reaction mixture was purified by silica gel column chromatography using 10-50percent heptane/EtOAc as solvent. The product was isolated as a solid. Yield 2.8 g (76percent).
With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate
EXAMPLE 65 STR100 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6 M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84%
With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate
EXAMPLE 65 STR95 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84%
With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate
A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
84%
With n-butyllithium; diisopropylamine; citric acid In tetrahydrofuran; <i>N</i>-methyl-acetamide; water; ethyl acetate
EXAMPLE 65 STR106 A) Preparation of 2-cyano-5-formylthiophene To a flame-dried 3 neck 1 L round bottom flask was added diisopropylamine (9 mL, 66 mmol) and THF (150 mL) under a nitrogen atmosphere. The flask was cooled to an internal temperature of -78° C. (dry ice/acetone). To this stirring solution was added n-butyllithium (1.6M in hexanes, 41.3 mL, 66.1 mmol) via syringe and the mixture was allowed to stir for 5 min. To this solution was added a solution of 2-thiophenecarbonitrile (6.55 g, 60 mmol) in THF (30 mL) over 10 min. The resulting bright red solution was allowed to stir at -78° C. for 45 min, at which time dimethylformamide (23.3 mL, 300 mmol) was added via syringe. This mixture was allowed to stir for 2 h at -78° C. and then solid citric acid (about 10 g) was added followed by water (60 mL). Volatile solvents were removed in vacuo and the residue was partitioned between diethyl ether and brine (200 mL each). Layers were separated and the aqueous phase was washed once with diethyl ether. The combined organic phase was washed once with brine, dried (MgSO4), filtered and concentrated in vacuo to give a yellow solid which was purified by silica gel chromatography using an ethyl acetate/hexanes gradient (hexanes to 50percent ethyl acetate/hexanes). Fractions containing pure product were pooled and concentrated in vacuo to give 6.9 g (84percent) of 2-cyano-5-formyl-thiophene.
50 %Chromat.
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 0.75 h; Stage #2: With N,N-dimethyl-formamide; methylbutenedioic acid In water at -78℃; for 20 h;
A solution of diisopropylamine (35.3 ml, 0.251 moles) in tetrahydrofuran (500 ml) was cooled to -78 C. under a nitrogen blanket. To this was added 1.6M n-butyllithium in hexanes (157 ml, 0.251 moles) and allowed to stir for 5 min. Then slowly added thiopene-2-carbonitrile (21.33 ml, 0.229 moles) in tetrahydrofuran (115 ml) and allowed to stir. After 45 min. was added NN-dimethylformamide (88.66 ml, 1.145 moles) at -78 C. Citric acid (40 g) was added after 2 h. followed by water (240 ml) and stirred for 18 h. The reaction was concentrated in vacuo, transferred to a separatory funnel, diluted with brine, and extracted twice with ether. The combined ether layers were washed with brine, dried over magnesium sulfate, filtered, and the solvent removed in vacuo. Chromatography yielded 15.8 g (50percent) of 2-cyano-5-formylthiophene (EX-55A) as a brown solid: 1H NMR (300 MHZ, CDCl3) d 10.02 (s, 1H), 7.79 (m, 1H), 7.30 (m, 1H).
Reference：
[1] Patent: US5914319, 1999, A,
[2] Patent: US5707966, 1998, A,
[3] Patent: US5710130, 1998, A,
[4] Patent: US5726159, 1998, A,
[5] Patent: US5705487, 1998, A,
[6] Patent: US6664255, 2003, B1, . Location in patent: Page column 117
6
[ 1003-31-2 ]
[ 16689-02-4 ]
[ 42137-24-6 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1955, p. 1614
7
[ 1003-31-2 ]
[ 16689-02-4 ]
Reference：
[1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1982, vol. 18, # 2, p. 127 - 130[2] Khimiya Geterotsiklicheskikh Soedinenii, 1982, vol. 18, # 2, p. 167 - 170
8
[ 1003-31-2 ]
[ 7697-37-2 ]
[ 108-24-7 ]
[ 16689-02-4 ]
[ 42137-24-6 ]
Reference：
[1] Bulletin de la Societe Chimique de France, 1955, p. 1614
9
[ 1003-31-2 ]
[ 105-36-2 ]
[ 13669-10-8 ]
Reference：
[1] Green Chemistry, 2017, vol. 19, # 6, p. 1420 - 1424
10
[ 1003-31-2 ]
[ 18945-81-8 ]
Yield
Reaction Conditions
Operation in experiment
88%
Stage #1: With 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex In tetrahydrofuran at 25℃; for 2 h; Stage #2: With iodine In tetrahydrofuran at 25℃; for 1 h;
General procedure: In a flame-dried flask flushed with nitrogen, the heterocyclic nitrile (1 mmol) wasdissolved in THF (1.5 mL). TMPMgCl·LiCl (1.0 M in THF, 1.8 mL, 1.8 mmol) wasadded dropwise at 25°C and the mixture was stirred for 2h (for substrate 1a, metalationwas best performed in 1 h). The completion of the metalation was checked by GC analysisof reaction aliquots quenched with a solution of I2 in dry THF. After that, a solution ofthe electrophile (2 mmol) in THF (2 mL) was added dropwise at 0°C and the reactionstirred for 1 hour at 25°C. The reaction mixture was quenched with sat. aq. NaHSO3 orNH4Cl solution (5 mL), extracted with ethyl acetate (3x15 mL) and dried over anhydrousMgSO4. After the filtration, solvent was evaporated in vacuo.
With N-Bromosuccinimide; bromine; acetic anhydride In acetic acid at 20℃; for 3 h;
5-Bromo-2-thiophenecarbonitrile To a solution of the available 2-thiophenecarbonitrile (2.22 g, 20.3 [MMOL)] in a mixture of acetic acid (1.22 g, 20.3 [MMOL)] and acetic anhydride (8.3 g, 81.3 [MMOL)] was [ADDED NBS (3.62 G, 1.0 EQ. ) AND BROMINE (1.05 ML, 1.0 EQ. ) AND THE REACTION MIXTURE] was stirred at rt for 3 hours. Water and ice were added and also a saturated sodium bisulfite solution. After extraction with DCM, the organic layer was washed with a saturated [NAHC03] solution, dried over [NA2SO4] and evaporated. The title compound was obtained as a orange liquid (3.74 g, 20 [MMOL)] in a quantitative yield ; GC/MS : [M+] C5H2BrNS 188
75%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃; for 6 h; Darkness
(1) Weighing 4 g 2-cyanothiophene (32.47 mmol) is dissolved in 30 ml DMF, taking 3.6 g NBS is slowly added to the mixture in stirring 15 min, all in the dark after adding the reaction under the room temperature condition 6 h. After the completion of the reaction methylene chloride and aqueous phase extraction purification, congeals the organic layer to dry column chromatography purification, the developing agent is the volume ratio of 1:3 of dichloromethane: petroleum ether mixed solvent, to obtain 4-bromo-2-cyanothiophene, the yield is 75percent.
Reference：
[1] Patent: WO2004/6922, 2004, A1, . Location in patent: Page/Page column 53
[2] Patent: CN108530419, 2018, A, . Location in patent: Paragraph 0058; 0059
[3] Heterocycles, 1997, vol. 46, # 1, p. 489 - 501
N-(3,5-dibromo-pyrazin-2-yl)-thiophene-2-carboxamidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
68%
A stirred solution of 3, 5-dibromo-pyrazin-2-ylamine (500 mg, 1.98 MMOL), <strong>[1003-31-2]thiophene-2-carbonitrile</strong> (260 uL, 2.04 mmol) and AIDS (232 mg, 1.74 mmol) in dichloroethane (5 ml) was heated at 115 oC overnight. The mixture was allowed to cool to room temperature and diluted with water (5 mL). After 30 minutes, the resulting precipitate was collected and purified by column chromatography (SI02, THF) to afford 488 mg (68%) of N- (3, 5-dibromo-pyrazin-2-yl)-thiophene-2- carboxamidine as a yellow SOLID. 1H NMR (300 MHz, DMSO-d6) 8 7.22 (t, J = 3.9 Hz, 1H), 7.83 (dd, J= 4. 8 Hz, 1H), 7.99 (d, J = 4.1 Hz, 1H), 8.49 (s, 1H), 8. 88 (br. s, 1H).
With copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonium hydroxide; at 100℃; for 24h;
The reactants used were thiophene-2-methanol (i.e., Het in the formula (III) was 2-thienyl) 1.0 mmol(114.2 mg), the experimental method and procedure were the same as Example 1, ammonia water (1.6 mol / L) 5.0 mL, and the amount of catalyst cuprous iodide was5 mol% (9.5 mg), the amount of TEMPO was 5 mol% (7.8 mg), the reaction temperature was 100 C, the reaction time was 24 h, and the crude productPurification by column chromatography (petroleum ether: ethyl acetate = 5: 1) gave the pure title product, yield 104.7 mg yield 96%.
87%
With ammonium hydroxide; dihydrogen peroxide; In water; acetonitrile; at 30℃; for 3h;
General procedure: In a typical experiment, alcohol (10 mmol), aqueous NH3*H2O (30 mmol), FeCl4-IL-SiO2 (0.5 g), and CH3CN (10 mL) were added to a round-bottomed flask. Then, aqueous 30 % H2O2 (21 mmol) was gradually added into the reactor at room temperature. The obtained mixture was stirred at 30 C for appropriate time (Table 4). The reaction was monitored by TLC and GC. After completion of the reaction, the catalyst was recovered by filtration. Evaporation of the solvent under reduced pressure gave the crude product. Further purification was achieved by flash column chromatography on a silica gel (petroleum ether/ethyl acetate, 5:1) to give the desired product. Fresh substrates were then recharged to the recovered catalyst and then recycled under identical reaction conditions.
86%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonium acetate; oxygen; nitric acid; acetic acid; at 50℃; under 760.051 Torr; for 12h;Sealed tube;
General procedure: 0.5 mmol substrate, 1.5 mmol NH4OAc, 0.15 mmol TEMPO, 2 mL AcOH and 0.15 mmol HNO3 weresuccessively added to a dried 45 mL tube filled with 1atm oxygen. Then the reaction tube was sealed andplaced in a constant-temperature oil bath to perform the reaction for 12 h. Once the reaction time wasreached, the mixture was cooled to room temperature. Then the mixture was alkalized to pH 7-8 with sodiumhydroxide aqueous solution. GC analysis of organic phase provided the GC yields of the products.Subsequently, the crude product from another parallel experiment was purified by column chromatography,and identified by 1H-NMR, 1C-NMR or GC-MS
84%
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene; ammonium acetate; In water; acetonitrile; at 20℃; for 9h;
General procedure: To a solution of alcohol (1 mmol) in MeCN-H2O (9:1, 3 mL) were successively added TEMPO (7.8 mg,5 mol%), NH4OAc (0.308 g, 4 equiv), and PhI(OAc)2 (0.708g, 2.2 equiv). The suspension was stirred at roomtemperature (progress of the reaction was monitored byTLC) for the reaction time indicated in Table 2. The resultantclear two-phase reaction mixture was concentrated, dilutedwith H2O and Et2O, and the organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure.The residue was purified by flash column chromatography(PE-Et2O or PE-CH2Cl2) to give 2.
73%
With 1,4-diaza-bicyclo[2.2.2]octane; TEMPOL; ammonia; copper(l) chloride; In water; acetonitrile; at 20℃; for 24h;
General procedure: To a 25-mL Schlenk tube equipped with a magnetic stirrer, CuCl (0.05 mol, 5 mol%), DABCO (0.10 mol, 10 mol%), 4-HO-TEMPO (0.05 mmol, 5 mol%) were added. Substrates 1 (1 mmol) and NH3 (aq, 25-28%, 3 mmol, 3.0 equiv) in CH3CN (2 mL) were added subsequently. Then the reaction mixture was stirred at room temperature for 24 h in the presence of an air balloon. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4. Subsequently, the combined organic layer was concentrated under reduced pressure and the crude product was purified by column chromatography to afford the corresponding products.
With sulfur; cobalt(II) nitrate; In neat (no solvent); at 90℃; for 0.0666667h;Microwave irradiation;
General procedure: A mixture of nitrile (0.5 mmol), 2-aminoethanol (4) (0.65 mmol, 0.040 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur (0.05 mmol, 0.0016 g) was stirred at 90 C or subjected to microwave irradiation (90 C, 800 W) for appropriate time. For the synthesis of monooxazolines, dicyanobenzene (0.5 mmol), 2-aminoethanol (4) (0.65 mmol, 0.040 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur(0.05 mmol, 0.0016 g) was stirred at 90 C for 3 h or subjected to microwave irradiation (90 C, 800 W) for 3 min. For the synthesis of bis-oxazoline, dicyanobenzene (0.5 mmol), 2-aminoethanol (4) (2.6 mmol, 0.159 g), Co(NO3)2 (0.02 mmol, 0.036 g), and sulfur (0.05 mmol, 0.0016 g) was stirred at 110 C for 10 h or subjected to microwave irradiation (110 C, 800 W) for 8 min. After completionof the reaction (detected by TLC), the reaction mixture was cooled to room temperature, ethyl acetate (6 mL) was added and the catalyst was separated by the filtration. Following concentration under reduced pressure, the residue was purified by silica gel chromatography to give pure product (5a-r).
87%
With [RuCl(CO)(PPh3)2(2-((2,6-dimethylphenylimino)methyl)quinolin-8-ol)]; In neat (no solvent); at 90℃; for 5h;
General procedure: Nitrile (1 mM), ethanolamine (3 mM) and ruthenium(II) complex (4 M%) were mixed and stirred for 5 h at 90 C. After completion of the reaction, the mixture was cooled to room temperature, diluted with ethyl acetate (10 mL) and filtered. The solid material (catalyst) was washed with ethyl acetate, dried and then reused in the next run. The filtrate was concentrated and the resulting residue was purified by column chromatography on silica gel using petroleum ether/ethyl acetate (50:50) as eluent, to afford the desired product. The products were characterized by 1H NMR [36].
80%
With Cu(II) immobilized on Fe3O4-agarose nanomagnetic catalyst functionalized with ethanolamine phosphate-salicylaldehyde Schiff base; In dimethyl sulfoxide; at 100℃; for 2h;
General procedure: Benzonitrile (0.1 g, 1 mmol), 2-aminoethanol (0.09 g, 1.5 mmol), and Fe3O4 Agarose/SAEPH2 /Cu(II) nanomagnetic catalyst (0.05 g, 14 mol%) were added to DMSO (2 mL) at 100 C. The resultant mixture was stirred and controlled by TLC. After completion of the reaction, the reaction mixture was cooled and the nanomagnetic catalyst was separated by an external magnetic field. Then water (2 x 10 mL) was added to the reaction mixture and the mixture was extracted with ethyl acetate (2 x 10 mL). The organic layer was evaporated and the residue was puried by thin layer chromatography using ethyl acetate/n-hexane (1/1) as eluent. The pure 2-phenyl-4,5-dihydro-1,3-oxazole was obtained with a 95% yield (0.13 g).
With potassium carbonate; In ethylene glycol; glycerol; at 110℃; for 72h;Inert atmosphere;
K2CO3 (0.12g, 0.1 equiv.) and glycerol(10ml) were charged to a schlenk flask and placed under an argon atmosphere. To this was addednitrile 6B (1.0g, 1.0 equiv), 2-amino-2-methyl propan-1-ol (1.63g, 1.7 equiv.) and dry ethyleneglycol (12ml). The resulting clear colourless solution was heated to 110 C for 72 hr to form apurple solution. This was cooled and quenched into sat. aq. NH4Cl (100ml) and extracted withdiethyl ether (3 x 100ml). Combined organic was dried (Mg2SO4) and stripped to give a purple oil,this was purified by filtration through a short alumina plug (washing with Et2O) to give a clearyellow oil (1.52g, 93%)
With hydroxylamine; In ethanol; water; for 2h;Reflux;
To a stirred solution of <strong>[1003-31-2]thiophene-2-carbonitrile</strong> (2.5 g, 23.0mmol) in ethanol (40 mL) was added 50% aqueous hydroxylamine solution (3 mL). The mixture was heated to reflux for 2 h. Then, the solvent was removed by rotary evaporation and the residue was dissolved in ethyl acetate (100mL) and washed one time with water (20 mL). The organic layer was separated and dried over anhydrous Na2SO4. After filtration and removal of the organic solvent by rotary evaporation, (Z)-N'-hydroxythiophene-2-carboxamidine was obtained as a white solid. Yield: 3.0 g (92%). mp 96-97 C; 1H NMR (300 MHz, CDCl3) 7.32 (dd, 1 H), 7.29 (dd, 1 H),7.05 (dd, 1 H), 4.89 (brd s, 2 H). (Z)-N'-hydroxythiophene-2-carboxamidine (2.5 g, 17.6 mmol) was dissolved in 50 mL of toluene and the solution was cooled to 0 C. After 15 min, pyridine (1.45 mL, 18 mmol) and 2-thiophenecarbonyl chloride (1.92 mL, 18 mmol) were added and stirred for 2 h at 0 C. Then, the ice bath was removed and the mixture was refluxed for 15 h. The insoluble material was filtered off in hot condition and the filtrate was concentrated by rotary evaporation. The crude material was purified by column chromatography (silica gel, hexane:ethyl acetate, 90:1, v/v) to afford pure compound 1 as a white solid. Yield: 3.5 g (93%). mp 131-132 C; 1H NMR (300 MHz, CDCl3) 7.96 (dd, 1 H), 7.86 (dd, 1 H), 7.67 (dd, 1 H), 7.52 (dd,1 H), 7.22 (dd, 1 H), 7.17 (dd, 1 H); 13C NMR (75 MHz,CDCl3) 132.4, 132.3, 130.0, 129.6, 128.8, 128.2; HRMS(EI+, m/z) [M+] Calcd for C10H6N2OS2 233.9922, found 233.9926
With potassium hydroxide; In dimethyl sulfoxide; at 80℃; for 16h;
6-(thiophen-2-yl)-1,3,5-triazine-2,4-diamine (1): 2-thiophenecarbonitrile (1.90 g, 17.4 mmol), N-cyanoguanidine (1.83 g, 21.72 mmol) and KOH (0.10 g, 1.7 mmol) were put in 10 mL of DMSO. The colourless solution was heated at 80C for 16 h and became yellow. The solvent was removed in vacuum and the crude product was triturated with cooled CH2Cl2 (4 x 100 mL at 0 C) and extract with hot dioxane (100 mL at 100 C). The solvent was removed in vacuum and 1 was isolated as a white solid. Yield: 2.99 g (89 %). 1H NMR (DMSO-d6): delta = 7.80 (dd, 3JH-H = 3.7, 3JH-H = 1.0, 1H, Ar), 6.93 (dd, 3JH-H = 4.8, 3JH-H = 1.0, 1H, Ar), 6.84 (dd, 3JH-H = 4.8, 3JH-H = 3.7, 1H, Ar), 6.76 (br. s, 4H, NH2 amine). 13C{1H} NMR (DMSO-d6): delta = 167.1, 166.6 (C3H4N5), 143.0, 130.4, 128.8, 128.0 (C4H3S).
With copper diacetate; acetonitrile; for 0.25h;Reflux;
To a 25 mL round-bottom flask equipped with magnetic stirrer were added thiophene-2-carbaldehyde oxime (254 mg, 2 mmol), cupric acetate (Cu(OAc)2)36 mg (0.2 mmol) and acetonitrile (5 mL). The mixture was heated to reflux for 0.25 h. After cooling to room temperature, the solution was directly evaporated to dryness and the residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane=1:15) to give thiophene-2-carbonitrile as a colourless liquid (143 mg, 61%). 1H NMR (500 MHz, CDCl3): delta 7.14 (m, 1H), 7.62 (m, 1H), 7.65 (m, 1H). Data are in good agreement with the literature.23
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