* 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.
With tert.-butylhydroperoxide In water at 60℃; for 12 h;
General procedure: A 15‐mL RBF was charged with substrate (0.5 mmol),MnOx‐N(at)C catalyst (1 mg, pyrolysis at 600 °C) and TBHP (1.5mmol, 65percent in H2O). The flask was then sealed, and the mixturewas heated at 60 °C for 12 h. The reaction was cooled to roomtemperature and diluted with ethyl acetate (4 mL), before beingcentrifuged at 10000 r/min for 1 min to separate the catalyst.The supernatant was removed and the catalyst waswashed with ethyl acetate (5 × 4 mL). The supernatant wassubsequently combined the ethyl acetate wash solutions andevaporated to dryness to give a residue, which was purified byflash column chromatography over silica gel (ethyl acetate/n‐hexane = 1:10, v/v).
Reference：
[1] Chinese Journal of Catalysis, 2016, vol. 37, # 8, p. 1216 - 1221
2
[ 290-37-9 ]
[ 127-17-3 ]
[ 22047-25-2 ]
Reference：
[1] Journal of Organic Chemistry, 1991, vol. 56, # 8, p. 2866 - 2869
3
[ 290-37-9 ]
[ 75-07-0 ]
[ 22047-25-2 ]
Reference：
[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 17, p. 3288 - 3296
4
[ 19847-12-2 ]
[ 22047-25-2 ]
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 5, p. 1838 - 1843
5
[ 19847-12-2 ]
[ 917-64-6 ]
[ 22047-25-2 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1999, vol. 64, # 7, p. 1159 - 1179
[2] Collection of Czechoslovak Chemical Communications, 1996, vol. 61, # 7, p. 1093 - 1101
[3] Molecules, 2009, vol. 14, # 10, p. 4197 - 4212
6
[ 19847-12-2 ]
[ 75-16-1 ]
[ 22047-25-2 ]
Reference：
[1] Journal of the American Chemical Society, 1952, vol. 74, p. 3617,3618,3620
[2] Patent: US2677686, 1952, ,
7
[ 61892-81-7 ]
[ 22047-25-2 ]
[ 138836-01-8 ]
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 5, p. 1838 - 1843
8
[ 86461-64-5 ]
[ 22047-25-2 ]
[ 138836-03-0 ]
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 5, p. 1838 - 1843
9
[ 98-96-4 ]
[ 22047-25-2 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1996, vol. 61, # 7, p. 1093 - 1101
10
[ 290-37-9 ]
[ 75-07-0 ]
[ 22047-25-2 ]
[ 39248-49-2 ]
Reference：
[1] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 497 - 500
11
[ 138835-87-7 ]
[ 22047-25-2 ]
Reference：
[1] Journal of the American Chemical Society, 1992, vol. 114, # 5, p. 1838 - 1843
[2] Journal of the American Chemical Society, 1992, vol. 114, # 5, p. 1838 - 1843
12
[ 56-87-1 ]
[ 50-99-7 ]
[ 290-37-9 ]
[ 109-08-0 ]
[ 123-32-0 ]
[ 5910-89-4 ]
[ 22047-25-2 ]
[ 13360-65-1 ]
[ 108-50-9 ]
[ 14667-55-1 ]
[ 13925-07-0 ]
[ 13360-64-0 ]
Reference：
[1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 4, p. 2470 - 2478
13
[ 56-45-1 ]
[ 56-87-1 ]
[ 50-99-7 ]
[ 290-37-9 ]
[ 109-08-0 ]
[ 123-32-0 ]
[ 5910-89-4 ]
[ 22047-25-2 ]
[ 13360-65-1 ]
[ 108-50-9 ]
[ 14667-55-1 ]
[ 13925-03-6 ]
[ 13360-64-0 ]
Reference：
[1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 4, p. 2470 - 2478
14
[ 288-32-4 ]
[ 22047-25-2 ]
[ 20671-53-8 ]
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1982, vol. 18, p. 6 - 10[2] Zhurnal Organicheskoi Khimii, 1982, vol. 18, # 1, p. 9 - 14
15
[ 56-87-1 ]
[ 50-99-7 ]
[ 290-37-9 ]
[ 109-08-0 ]
[ 123-32-0 ]
[ 5910-89-4 ]
[ 22047-25-2 ]
[ 13360-65-1 ]
[ 108-50-9 ]
[ 14667-55-1 ]
[ 13925-07-0 ]
[ 13360-64-0 ]
Reference：
[1] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 4, p. 2470 - 2478
16
[ 22047-25-2 ]
[ 19847-11-1 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 21, p. 6385 - 6397
17
[ 22047-25-2 ]
[ 94777-52-3 ]
Yield
Reaction Conditions
Operation in experiment
96 %Spectr.
With C22H25Cl2N3ORuS2; potassium hydroxide In isopropyl alcohol at 82℃; for 14 h;
General procedure: Catalyst (0.1mol percent) and KOH (1mmol) were dissolved in 2-propanol (4mL). To this solution, substrate (1mmol) was added and the mixture was refluxed (82°C). The progress of the reaction was monitored by GC at regular intervals. After the completion of the reaction, the reaction mixture was cooled to room temperature and filtered through silica gel or alumina bed, and eluted using 50percent ethyl acetate-hexane mixture. The eluted solution was reduced and analyzed by GC and/or GCMS.
Reference：
[1] Journal of Organic Chemistry, 1992, vol. 57, # 17, p. 4756 - 4761
[2] Organic Letters, 2005, vol. 7, # 12, p. 2505 - 2508
[3] Bioscience, Biotechnology and Biochemistry, 2011, vol. 75, # 6, p. 1055 - 1060
[4] Organic and Biomolecular Chemistry, 2015, vol. 13, # 6, p. 1768 - 1777
[5] Organic and Biomolecular Chemistry, 2017, vol. 15, # 43, p. 9169 - 9175
[6] Journal of Organometallic Chemistry, 2018, vol. 876, p. 57 - 65
18
[ 22047-25-2 ]
[ 132426-19-8 ]
Reference：
[1] Journal of Medicinal Chemistry, 1998, vol. 41, # 13, p. 2436 - 2438
[2] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 15, p. 4374 - 4377
[3] European Journal of Inorganic Chemistry, 2015, vol. 2015, # 21, p. 3550 - 3561
[4] PLoS ONE, 2016, vol. 11, # 5,
19
[ 22047-25-2 ]
[ 179323-60-5 ]
Yield
Reaction Conditions
Operation in experiment
75%
Stage #1: With ammonium acetate; sodium cyanoborohydride In methanol at 20℃;
Preparation 8; 1-Pyrazin-2-yl-ethyl Amine; The synthetic procedure used in this preparation is outlined below in Scheme J. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
Stage #1: With ammonium acetate; sodium cyanoborohydride In methanol at 20℃;
Preparation 4; 1-Pyrazin-2-yl-ethylamine; The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
Stage #1: at 20℃; Stage #2: With sodium hydroxide In water
Preparation 4 1-Pyrazin-2-yl-ethylamine The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 1.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
Stage #1: With ammonium acetate; sodium cyanoborohydride In methanol at 20℃;
Preparation 4 1-Pyrazin-2-yl-ethyl amine The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
Stage #1: With ammonium acetate; sodium cyanoborohydride In methanol at 20℃; Stage #2: With sodium hydroxide In water
Preparation 4 1-Pyrazin-2-yl-ethylamine The synthetic procedure used in this preparation is outlined below in Scheme E. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
Stage #1: at 20℃; Stage #2: With sodium hydroxide In water
Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
at 20℃;
Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
75%
With ammonium acetate; sodium cyanoborohydride In methanol at 20℃;
The synthetic procedure used in this preparation is outlined below in Scheme D. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75percent. MS (M+H)=124.
40%
With ammonium acetate; sodium cyanoborohydride In methanol at 23℃; for 17 h;
[0146] To a stirred solution of compound I (2 g; 16.4 mmol; 1 eq) in methanol (20 mL) were added ammonium acetate (12.6 g; 164 mmol; 10 eq) and sodium cyanoborohydride (1 g; 16.4 mmol; 1 eq) and the resulting mixture was stirred at 23 °C for 17 h. The mixture was quenched with water (50 mL) and the organic components were extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and the solvents were removed in vacuo to afford crude compound, which was purified by silica gel (230-400 mesh) column chromatography, eluting with 10percent MeOH/CH2C12, to afford the title compound (0.8 g, 40percent). 1H NMR (CDC13) ö 8.60 (s, 1H), 8.49 (m, 1H), 8.43 (d, 1H, J= 2Hz), 4.20 (m, 1H), 1.45 (d, 3H, J= 7Hz).
With NH4S2O8; silver nitrate; trifluoroacetic acid In dichloromethane; water at 40℃; for 2.5h;
26%
With ferrous(II) sulfate heptahydrate; ammonium peroxydisulfate; sulfuric acid In dichloromethane; water at 40℃;
Typical procedure for the non-noble metal catalyzed Minisci acylation reaction
General procedure: N-heteroarene (1 mmoL, 80 mg), α-keto acid (3 mmol), Formic acid (1 mmol, 38 μL), ammonium persulfate (3 mmoL, 685 mg), ferrous sulfate heptahydrate (0.08 mmoL, 22 mg) and 20 mL of mixed solvent (DCM: H2O = 3: 1) , 0.1 mL DMSO was added into a 25 mL round-bottomed flask. The mixture was stirred at 40 oC until TLC analysis indicating that the reaction was complete (witnessed by the disappearance of the N-heteroarene). After separation of organic phase, the residue was neutralized by 0.1 M sodium hydroxide solution, then extracted with DCM (3×20 mL), combined the organic phases, dried over Na2SO4, and concentrated in vacuo. The residue was N-heteroarene (1 mmoL, 80 mg), α-keto acid (3 mmol), Formic acid (1 mmol, 38 μL), ammonium persulfate (3 mmoL, 685 mg), ferrous sulfate heptahydrate (0.08 mmoL, 22 mg) and 20 mL of mixed solvent (DCM: H2O = 3: 1) , 0.1 mL DMSO was added into a 25 mL round-bottomed flask. The mixture was stirred at 40 oC until TLC analysis indicating that the reaction was complete (witnessed by the disappearance of the N-heteroarene). After separation of organic phase, the residue was neutralized by 0.1 M sodium hydroxide solution, then extracted with DCM (3×20 mL), combined the organic phases, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel using a mixture of petroleum ether/EtOAc (v : v = 20 : 1) as eluent to afford the desired pure product. Analytical Data of the prepared compounds 1-(Pyrazin-2-yl)ethan-1-one (3a)3 White solid; m.p.: 77-78 oC; 1H NMR (400 MHz, CDCl3) δ 2.74 (s, 3H), 8.67 (s, 1H), 8.77 (d, J = 2.0 Hz, 1H), 9.25 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 25.7, 143.5, 143.5, 147.7, 199.3.
With C22H25Cl2N3ORuS2; potassium hydroxide; In isopropyl alcohol; at 82℃; for 14h;Catalytic behavior;
General procedure: Catalyst (0.1mol %) and KOH (1mmol) were dissolved in 2-propanol (4mL). To this solution, substrate (1mmol) was added and the mixture was refluxed (82C). The progress of the reaction was monitored by GC at regular intervals. After the completion of the reaction, the reaction mixture was cooled to room temperature and filtered through silica gel or alumina bed, and eluted using 50% ethyl acetate-hexane mixture. The eluted solution was reduced and analyzed by GC and/or GCMS.
In 5,5-dimethyl-1,3-cyclohexadiene at 140℃; for 20h; Inert atmosphere; Schlenk technique;
73%
In xylene Heating;
38%
In methanol for 10h; Reflux;
for 19h; Heating / reflux;
7.1
Step 1 3-(dimethylamino)-1-(2-pyrazinyl)-2-propen-1-one This compound was prepared by version of the method described in the document (Japanese Unexamined Patent Publication (Kokai) No. 6-87834). To 5.00 g of 2-acetylpyrazine, 5.37 g of N,N-dimethylformamide dimethyl acetal was added and the mixture was heated at reflux for 19 hours. The reaction solution was air-cooled and the deposited crystal was dissolved in ethyl acetate and then concentrated under reduced pressure. After adding a small amount of diethyl ether, the deposited crystal was collected by filtration and then washed in turn with diethyl ether and diisopropyl ether to obtain 5.20 g of the objective compound as a brown crystal. 1H-NMR(CDCl3)δ: 3.01(3H, s), 3.21(3H, s), 6.36(1H, d), 7.95(1H, d), 8.61(2H, m), 9.33(1H, s)
Reflux;
Step b
General procedure: Aryl ketone 2 (1.0 equiv) and N,N-dimethylformamide dimethyl acetal (5.0-10.0 equiv) were refluxed until the starting materials were consumed, as determined by TLC. Then the solvent was evaporated under reduced pressure until DMF-DMA was fully removed. The crude products can be straight used for step c. Yield: 100%
14 EXAMPLE 14 3-Oxo-3-pyrazin-2-yl-propionic acid ethyl ester
According to the procedure of Example 1, 3-oxo-3-pyrazin-2-yl-propionic acid ethyl ester was prepared from 2-acetylpyrazine, diethyl carbonate and sodium hydride.
Preparation 8; 1-Pyrazin-2-yl-ethyl Amine; The synthetic procedure used in this preparation is outlined below in Scheme J. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
Preparation 4; 1-Pyrazin-2-yl-ethylamine; The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
Preparation 4 1-Pyrazin-2-yl-ethylamine The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 1.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
Preparation 4 1-Pyrazin-2-yl-ethyl amine The synthetic procedure used in this preparation is outlined below in Scheme F. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
Preparation 4 1-Pyrazin-2-yl-ethylamine The synthetic procedure used in this preparation is outlined below in Scheme E. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
With methanol; ammonium acetate; sodium cyanoborohydride; at 20.0℃;
Preparation 21-Pyrazin-2-yl-ethylamineThe synthetic procedure used in this preparation is outlined below in Scheme C. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dichloromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
75%
With ammonium acetate; sodium cyanoborohydride; In methanol; at 20.0℃;
The synthetic procedure used in this preparation is outlined below in Scheme D. To a solution of 1-pyrazin-2-yl-ethanone (2.0 g, 15.85 mmol) and ammonium acetate (19.337 g, 158.5 mmol) in methanol (50 mL) was added sodium cyanoborohydride (0.7 g, 11.1 mmol) in one portion. The reaction mixture was stirred overnight at room temperature. After removal of methanol, water (20 mL) was added to the residue and the resulting solution was basified by addition of sodium hydroxide to pH=13. The aqueous solution was extracted with dicholromethane and the combined organic phase was dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 14.62 g of 1-pyrazin-2-yl-ethylamine, yield: 75%. MS (M+H)=124.
40%
With ammonium acetate; sodium cyanoborohydride; In methanol; at 23.0℃; for 17.0h;
[0146] To a stirred solution of compound I (2 g; 16.4 mmol; 1 eq) in methanol (20 mL) were added ammonium acetate (12.6 g; 164 mmol; 10 eq) and sodium cyanoborohydride (1 g; 16.4 mmol; 1 eq) and the resulting mixture was stirred at 23 C for 17 h. The mixture was quenched with water (50 mL) and the organic components were extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, filtered and the solvents were removed in vacuo to afford crude compound, which was purified by silica gel (230-400 mesh) column chromatography, eluting with 10% MeOH/CH2C12, to afford the title compound (0.8 g, 40%). 1H NMR (CDC13) oe 8.60 (s, 1H), 8.49 (m, 1H), 8.43 (d, 1H, J= 2Hz), 4.20 (m, 1H), 1.45 (d, 3H, J= 7Hz).
With ammonium acetate; sodium cyanoborohydride;silica gel; In methanol; dichloromethane; water;
Step A: 1-(Pyrazin-2-yl)ethylamine To a solution of 2-acetylpyrazine (206.7 mg, 1.7 mmol) and ammonium acetate (1.3 g, 17 mmol) in methanol (5.0 mL) was added sodium cyanoborohydride (75 mg, 1.19 mmol) followed by 3 A molecular sieves (0.85 g). The reaction mixture was stirred for 1 day at room temperature. It was acidified to pH 2 with concentrated HCl then filtered, and the solid was washed with methanol and H2O. The filtrate was concentrated in vacuo. The residue was dissolved in water and was made basic (pH 10-12) with 5N NaOH. The aqueous layer was extracted with CH2Cl2 several times while maintaining ~pH 10. The combined extracts were dried over Na2SO4, filtered, and concentrated the solvent in vacuo. The crude product was purified by preparative thin layer chromatography eluding with 5% 2M NH3 in MeOH/CH2Cl2 to give 74 mg of the title compound. 1H NMR (500 MHz, CDCl3): 8.61 (s, 1H); 8.5 (d, J=1.6 Hz, 1H); 8.44 (d, J=1.6 Hz, 1H); 4.21 (q, J=6.8 Hz, 1H); 1.46 (d, J=6.8 Hz).
Stage #1: acetylpyrazine; 4,4'-diamino diphenyl methane In methanol for 24h; Molecular sieve 3Å; Heating / reflux;
Stage #2: iron(II) chloride In methanol for 24h; Heating / reflux;
Stage #3: With ammonium hexafluorophosphate In methanol
To a stirred solution of acetylpyrazine (0.041 g, 0.30 mmol) and ground 3 Å dried molecular sieves in methanol was added dropwise 4,4'methyledianiline (0.029 g, 0.15 mmol) in methanol and a few drops of glacial acetic acid. The mixture was heated under reflux for 24 h. The molecular sieves were removed by filtration and the filtrate treated with FeCl2 4H2O (0.019 g, 0.10 mmol) and refluxed for 2 hours. The purple solution was treated with methanolic ammoniumhexafluorophosphate solution, the resulting precipitate were filtered off and dried over P4O10. recrystalization from CH3CN/diisopropylether afforded 0.052g, yield 58% of purple crystals of [Fe2L3](PF6) 1HNMR (300MHz, CD3CN, 298K) d = 9.68 (1H, br, H6/5) 8.82 (1H, br, H3), 7.37 (2H, br, H6/5, HPh), 6.77 (1H, d, J = 7.0 Hz, HPh), 6.77 (1H, d, J = 7.0 Hz, HPh), 4.65 (1H, d, J = 6.4 Hz, HPh), 4.04 (1H, s, CH2), 2.47 (3H, s, CH3).
4-cyclohexyl-1-(1-(pyrazin-2-yl)ethylidene)thiosemicarbazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
In methanol for 4h; Reflux;
2.1. Synthesis of H 2 L
The cyclohexyl isothiocyanate (0.706 g, 5 mmol) and hy- drazine hydrate (0.250 g, 5 mmol) solutions based in ethanol were well agitated for 1 hour until a white precipitate of N(4)- cyclohexylthiosemicarbazide was obtained. Thereafter filtration, washing and drying steps were performed and the recrystal- lized precipitate was obtained from ethanol. The solution of N(4)- cyclohexylthiosemicarbazide (0.346 g, 1 eq, 2mmol) in methanol (30 mL) was mixed with methanolic solution of 2-acetylpyrzine (0.256 g, 1eq, 2.1 mmol) (5 mL). The reaction was continued for 4 hours after the incorporation of few drops of acetic acid. No sud- den product formation was observed. After the continuous reflux for 6 hours, the thus obtained sample was cooled overnight. The crystalline product was then collected followed by thorough wash- ing with acetonitrile. Fine single crystals obtained after the slow evaporation of methanol at room temperature in 6 days were used for single crystal XRD. H 2 L (pale yellow). Yield: 0.465g (84 %), M.P. 212-214 0 C, Anal. Calc. for C 13 H 19 N 3 S 2 : C, 56.42; H, 6.93; N, 25.43; S, 11.34. Found: C, 56.29; H, 6.90; N, 25.25; S, 11.56 %.IR data (KBr, cm -1 ) 3288m, 3221br, ν(N-H), 1618m ν(C = N), 1203s ν(C = S), 1109m ν(N-N); UV-Visible [DMSO, δin nm (cm -1 ) ( εM -1 cm -1 )]: 268 (37313)(27100), 343 (29154) (7050 0); 1 H-NMR (40 0 MHz, CDCl 3 , δppm)1.45 (4H, m, -CH 2 ), 1.65 (2H, m, -CH 2 ), 1.77 (4H, m, -CH 2 ), 2.15 (3H, s, CH 3 ),4.32 (1H, m, -CH), 7.48 (1H, br, -NH) 8.55 (2H, m, Ar), 8.69 (1H, br, N-NH), 9.20(1H, s, Ar). 13 C-NMR (100 MHz, CDCl 3 ):176.60 (1C, C = S), 150.13 (1C, C = N), 145.11, 144.03, 143.28, 142.43 (4C, Ar), 53.31, 32.58, 25.49, 24.75 (6C, Cy) 11.03 (1C, CH 3 ); ESI MASS: 264.56 (m + 1)
With acetic acid In methanol for 4h; Reflux;
5.2.1. Synthesis of ligand
Cyclohexyl isothiocyanate (1.41 g, 10 mmol) and hydrazine hydrate (0.50 g, 10 mmol), each dissolved in 20 mL methanol were mixed with constant stirring. The stirring was continued for 1 h and the white product, N(4)-cyclohexyl thiosemicarbazide formed was filtered, washed, dried and recrystallized from methanol. A methanolic solution of N(4)-cyclohexyl thiosemicarbazide (0.52 g, 3 mmol) was then refluxed with 2-acetylpyrazine (0.37 g, 3 mmol) in 10 mL methanol continuously for 4 h after adding a few drops of acetic acid. Yellow crystals separated on cooling were washed and recrystallorized from methanol. Yield: 75% -C13 H19 N5 S (277): calcd. C 56.32, H 6.86, N 25.27; found C 55.74, H 6.71, N 25.58. 1H NMR (DMSO-d6, δ ppm): 10.37 (s, 1H, NH), 9.58 (d, J = 7.2Hz, 1H, C4N2H3), 8.62-8.61(m, 2H, C4N2H3, NH), 8.30 (d, J = 7.2Hz, 1H, C4N2H3), 1.86-1.13 (m, 11H, C6H11), 2.35(s, 3H, CH3). ESI-MS (m/z): 300.1 = [HL + Na+], calc. mass = 300.1.
(E)-3-chloro-6-[2-(pyrazin-2-ylmethylene)hydrazinyl]pyridazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85.6%
With acetic acid; In methanol; for 8h;
General procedure: L was synthesized by refluxing 1-(pyrazin-2-yl)ethanone, 3-chloro-6-hydrazinylpyridazine,and three drops of glacial acetic acid in methanol for 8 h. Yield: 85.6% [14]. A mixture ofL (0.1 mM, 24.8 mg) and Pb(NO3)2 (0.1 mM, 33.3 mg) was placed in 20 mL methanol andmixed. Dark yellow block crystals suitable for X-ray single crystal diffraction were obtainedby slow evaporation of the solution for two weeks. Yield: 54.5%. Elemental Calcd forC10H13ClN8O8Pb: C, 19.50; H, 2.13; N, 18.19%. Found: C, 19.32; H, 2.01; N, 18.32%. IRdata (cm-1): 3444 s, 1594 m, 1441 m, 1385 versus 13,282 m, 1143 m, 844 w.
4-chloro-6-[2-(1-(pyrazin-2-yl)ethylidene)hydrazinyl]pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86.3%
With acetic acid; In methanol; for 4h;Reflux;
A stirred solution of 1-(pyrazin-2-yl)ethanone (1.24 g, 0.01 mol) in methanol (20 ml) was added dropwise to a solution of <strong>[5767-35-1]4-chloro-6-hydrazinylpyrimidine</strong> (1.44 g,0.01 mol) in methanol (30 ml) plus three drops of glacial acetic acid. The mixture was refluxed for 4 h and then cooled to room temperature. The precipitated solid was filtered off and washed with cold methanol to obtain a white solid. Yield: 86.3 %. 1H NMR (400 MHz, DMSO) d ppm: 11.16 (s, 1H), 8.62-8.53 (m, 5H), 9.46 (s, 1H), 7.48(s, 1H), 2.40 (s, 3H). (Fig. S1). 13C NMR (100 MHz,DMSO) dppm: 162.94, 159.80, 158.21, 150.26, 148.14,143.83, 143.13, 142.63, 102.99, 11.91. (Fig. S2). ESI-MS (DMF, positive ion mode): m/z = 249.07([M + H]+), C10H9ClN6 theoretical mass: 248. (Fig. S3). IR/cm-1(KBr):1565 (s), 1369 (m), 3150 (m), 3438 (m).
With tert.-butylhydroperoxide; In water; at 60℃; for 12h;
General procedure: A 15?mL RBF was charged with substrate (0.5 mmol),MnOx?N(at)C catalyst (1 mg, pyrolysis at 600 °C) and TBHP (1.5mmol, 65percent in H2O). The flask was then sealed, and the mixturewas heated at 60 °C for 12 h. The reaction was cooled to roomtemperature and diluted with ethyl acetate (4 mL), before beingcentrifuged at 10000 r/min for 1 min to separate the catalyst.The supernatant was removed and the catalyst waswashed with ethyl acetate (5 × 4 mL). The supernatant wassubsequently combined the ethyl acetate wash solutions andevaporated to dryness to give a residue, which was purified byflash column chromatography over silica gel (ethyl acetate/n?hexane = 1:10, v/v).
4-(6-methoxy-2-naphthyl)-2,6-di(pyrazin-2-yl)pyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
54%
With ammonium hydroxide; potassium hydroxide; In ethanol; at 20℃; for 24h;
General procedure: Ketone (20 mmol) (2-acetylpyridine, 2-acetylthiazole or 2-acetylpyrazine)was added to a solution of aldehyde (10 mmol) (4-methoxybenzaldehyde,4-methoxy-1-naphthaldehyde or 6-methoxy-2-naphthaldehyde) in EtOH (75 mL). KOH (1.54 g, 27.5 mmol) and NH3(aq)(35 mL) were then added. The solution was stirred at room temp. for 24 h. The solid was collected by filtration and washed with H2O. Recrystallization from ethanol (L1,L4, L7) or toluene (L2, L3, L5, L6, L8,L9) afforded a crystalline solid.
With ammonium hydroxide; potassium hydroxide In ethanol for 5h; Inert atmosphere;
1 1) 2-(4-(4-bromophenyl)-6-(pyrazin-2-yl)pyridin-2-yl)pyrazine (2-(4-(4-bromophenyl)-6-(pyrazin-2- Synthesis of yl)pyridin-2-yl)pyrazine)
In a nitrogen atmosphere, 2-Acetylpyrazine (9.7 g, 80 mmol), 4-bromobenzaldehyde (7.4 g, 40 mmol) was added to ethanol (EtOH) (200 mL).After dissolving, potassium hydroxide (KOH) (4.48 g, 80 mmol) and aqueous ammonia (aq NH3) (120 mL, 28-30%, 50 mmol) were added and stirred for 5 hours. After the reaction was over, the precipitated solid was filtered under reduced pressure and washed with ethanol (3 × 20 mL). Compound by recrystallization from methylene chloride-methanol (MC-MeOH)2-(4-(4-bromophenyl)-6-(pyrazin-2-yl)pyridin-2-yl)pyrazine(2-(4-(4-bromophenyl)-6-(pyrazin-2-yl)pyridin-2-yl)pyrazine) (9.8 g yield 62.8%) was obtained.
54.7%
With ammonium hydroxide; potassium hydroxide In methanol for 12h; Reflux;
44.1%
With ammonium hydroxide; sodium hydroxide In ethanol at 20℃; for 6h;
4 Synthesis of Intermediate 4
A magnetic stirrer is added to the 250ml single-mouth eggplant bottle.Then add 1.85 g of p-bromobenzaldehyde, 2.44 g of 2-acetylpyrazine and 40 ml of ethanol.After stirring to completely dissolve, add 0.40 g of NaOH and 30 ml of concentrated ammonia water, and stir at room temperature for 6 hours.Filtration under reduced pressure, the filter cake was washed with ethanol and deionized water, and dried in vacuo to give Intermediate 4 as white solid, yield 1.75 g, yield 44.1%.The product was not further purified and the next reaction was carried out directly.
39%
Stage #1: acetylpyrazine; 4-bromo-benzaldehyde In ethanol for 0.0833333h;
Stage #2: With ammonia; potassium hydroxide In ethanol; water at 20℃; for 24h;
Synthesis procedure for obtaining of II
General procedure: 4-Bromobenzaldehyde (1.85 g, 10 mmol), 2-acetylderivative (20 mmol) and 60 mL ethanol were placed in 200 mL conical flask and mixed for 5 minutes. Then potassium hydroxide (1.54 g, 27.5 mmol) and 30 mL concentrated solution of ammonia were added. The resulting solution was stirred at room temperature for 24 hours. Obtained solid was collected by filtration and washed with 100 mL of water, 25 mL of ethanol and 25 mL of diethyl ether. II (in synthesis route for obtaining of 11) (1.52 g, 39%) as a white solid 1H NMR (400 MHz, CDCl3) δ 9.87 (s, 2H), 8.68 (d, J = 8.6 Hz, 6H), 7.77 - 7.70 (m, 2H), 7.70 - 7.62 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 154.78, 150.75, 149.76, 145.07, 143.81, 143.74, 136.90, 132.52, 128.92, 124.19, 119.69
(E)-3-hydroxy-N′-(1-(pyrazin-2-yl)ethylidene)benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
64%
In ethanol at 65℃; for 4h;
(E)-3-hydroxy-N′-(1-(pyrazin-2-yl)ethylidene)benzohydrazide (HL2):
A solution of 2-acetylpyrazine (1.22g, 10mmol) in ethanol (20mL) was slowly added to a solution of 3-hydroxybenzohydrazide (1.52g, 10mmol) in ethanol (20mL). The mixture solution was then refluxed at 65°C for 4h; after that, it was cooled down, suction filtered, and then washed with cold ethanol. The final product (1.65g, 64% yield) was obtained by air-drying. MS, NMR, IR, and UV data are shown in the Supporting information (Section S1).
(E)-N'-[1-(2-pyrazinyl)ethylidene]pyrazine-2-carbohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With acetic acid; In ethanol; for 12h;Reflux;
General procedure: To a stirred solution of the acid hydrazide 5 (2mmol, 0.27g) in absolute ethanol (10ml), the appropriate heteroaromatic ketone or substituted pyrazolaldehyde (2mmol) was added in the presence of catalytic amount of glacial acetic acid (5 drops), the mixture was refluxed for 12-16h. The product obtained was filtered, washed with diethyl ether, dried and recrystallized from ethanol.
With sulfuric acid; In 1,2-dichloro-ethane; at 70 - 80℃;Inert atmosphere;
In a three-necked 1000ml bottle, under nitrogen,Add 50 g of starting material C (181 mmol) and 21.9 g of starting material D (181 mmol),Add 300ml of dichloroethane,Add 6 ml of concentrated sulfuric acid.The temperature was raised to 70 to 80 C for heat preservation. TLC detects that the reaction of the raw materials is complete. Cool to room temperature, add 100 ml of water, separate the layers, and wash the organic layer with water to neutrality. It was dried over sodium sulfate, concentrated under reduced pressure, and recrystallized from toluene to obtain 52.3 g of a yellow solid compound C with a yield of 80% and a purity of 98.5%.
Synthesis of HL2
2-acetylpyrazine (2.44 g, 20 mmol) and 4-dimethyl-3- thiosemicarbazide (2.34 g, 20 mmol) were mixed in methanol (20 mL). Twenty drops of acetic acid were added and the solution was refluxed for 4 h under 72 C. The solution was cooled down and filtered, and pale-yellow powder was acquired and washed by methanol. Elemental Anal. Calcd. (%) for C9H13N5S: C, 48.41; H, 5.87; N, 31.36. Found: C, 48.48, H, 5.76, N, 31.42.
With sodium hydroxide In water monomer at 120℃; for 3h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
With sodium hydroxide In water monomer at 120℃; for 3h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
With sodium hydroxide In water monomer at 120℃; for 1h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
With sodium hydroxide In water monomer at 120℃; for 1h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
With sodium hydroxide In water monomer at 120℃; for 4h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
With sodium hydroxide In water monomer at 120℃; for 4h; Sealed tube;
Preparation of Maillard reaction products derived from Met/Glcmodel and MG-ARP model
General procedure: Aqueous solutions of Met/Glc (each reagent at 0.2 mol/L) and MG-ARP model (0.2 mol/L) were prepared, and their pH values were adjusted to 7.5 ± 0.1 with NaOH (6 mol/L). The model solutions were heated in sealed vials at 100 ± 1, 120 ± 1, or 130 ± 1 °C for different times (0, 30, 60, 120, 180, and 240 min) with continuous stirring. Meanwhile, a 0.2 mol/L solution of Met alone was treated under the same conditions as the control. The final reaction products derived from the above models were cooled in ice water for further analysis.
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