* 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] Green Chemistry, 2014, vol. 16, # 5, p. 2807 - 2814
[2] Tetrahedron Letters, 2005, vol. 46, # 51, p. 8959 - 8963
[3] Organic and Biomolecular Chemistry, 2012, vol. 10, # 35, p. 7120 - 7133
2
[ 2973-77-5 ]
[ 74-88-4 ]
[ 108940-96-1 ]
Yield
Reaction Conditions
Operation in experiment
100%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 15 h; Inert atmosphere
2,4-dibromo-3-methoxy-benzaldehyde (Compound 1) was dissolved in dry DMF, Add excess methyl iodide and potassium carbonate, stir under nitrogen at room temperature overnight, Extraction gave compound 2.
97%
With potassium carbonate In N,N-dimethyl-formamide
(2) 3,5-Dibromo-4-methoxybenzaldehyde To a solution of 3,5-dibromo-4-hydroxybenzaldehyde (5.00 g, 17.9 mmol) in DMF (100 ml) were added potassium carbonate (3.22 g, 23.3 mmol) and iodomethane (1.45 ml, 23.3 mmol), and the mixture was stirred at room temperature for 10 hours. The obtained mixture was poured into water and extracted with ethyl acetate. The extracts were collected, washed with water and dried over magnesium sulfate anhydride, and the solvent was removed under reduced pressure to give the object compound as a solid. 5.10 g (yield: 97.0percent) 1H-NMR (CDCl3) δ; 3.97 (3H, s), 8.03 (2H, s), 9.80 (1H, s). IR (KBr) cm-1; 1707, 1694, 1547, 1470, 1368, 1264, 1190, 987, 747, 731.
97%
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 3 h;
To a solution of 3,5-dibromo-4-hydroxybenzaldehyde (1.00 g, 3.57 mmol) and methyl iodide (MeI, 0.5 mL, 1.14 g, 8.03 mmol) in DMF (15 mL) was added anhydrous potassium carbonate (K2CO3, 0.992 g, 7.18 mmol). The reaction mixture was stirred at 55 °C for 3 h, cooled to room temperature, and quenched by addition of water (80 mL). The resultant white precipitate was filtered under vacuum, washed with water (40 mL), and dried to give the anisaldehyde intermediate (1.02 g, 3.47 mmol, 97percent) as a white solid: mp 90-91 °C; IR (NaCl) 1688 cm-1 (CO), 1546 cm-1 (CC); 1H NMR (300 MHz, CDCl3) δ 9.86 (s, 1H, CHO), 8.03 (s, 2H, ArH), 3.97 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) δ 188.6 (CHO), 159.2 (C), 134.3 (C), 134.0 (CH), 119.3 (C), 60.8 (OCH3).
83%
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18 h;
3,5-Dibromo-4-hydroxybenzaldehyde(1.40 g, 5.01 mmol), iodomethane (0.37 mL, 5.94 mmol), and K2CO3(845 mg, 6.11 mmol) were stirred in DMF (5.0 mL) at room temperature.After 18 h, the reaction was extracted into EtOAc (100 mL) and washed with H2O (2x25 mL) and brine (25 mL), dried over Na2SO4, filtered, and concentrated.Flash chromatographic purification over silica (9:1 hexanes:EtOAc) afforded3,5-dibromo-4-methoxybenzaldehydeas a white solid (1.22 g, 83percent).1H-NMR (500 MHz, CDCl3)d9.86 (s, 1H), 8.03 (s, 2H), 3.97 (s, 3H);13C-NMR (125 MHz, CDCl3)d188.43, 159.12, 134.20, 133.91, 119.31, 60.88; GC-MS 292m/z[MH]+, C8H6Br2O2requires 292; RP-HPLC: >99percent pure.
81%
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 3 h;
Potassium carbonate (100mg, 0.72mmol) was added to a solution of 3,5-dibromo-4-hydroxybenzaldehyde (100mg, 0.36mmol) and methyl iodide (51µL, 0.81mmol) in DMF (1.5mL). The mixture was stirred at 55 °C for 3h. After cooling to room temperature water (8mL) was added and the resulting precipitate was filtered and dried in vacuum to give 85mg (81percent) as a colorless solid. HPLC: Rt=7.04min. 1H-NMR (CDCl3, 500MHz): [ppm] = 9.86 (s, 1H), 8.03 (s, 2H), 3.97 (s, 3H). 13C-NMR (CDCl3, 125MHz): [ppm]= 188.5, 159.3, 134.4, 134.1, 119.5, 61.0.
3.62 g
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24 h; Inert atmosphere
Bromine (1.63 mL, 31.5 mmol) in acetic acid (5 mL) was added dropwise to a mixture of 4-hydroxybenzaldehyde (1.85 g,15 mmol) and sodium acetate (3.85 g, 46.5 mmol) in acid acetic (35 mL) at room temperature over 20 min. The reaction mixture was stirred for 1 h at room temperature. H2O (75 mL) was added and the solid was filtered, washed with H2O and dried under high vacuum to afford 3,5-dibromo-4-hydroxybenzaldehyde 14 as a white solid. To a stirred solution of 14 in DMF (50 mL) was added K2CO3 (4.15 g, 30 mmol) in portions, followed by the addition of MeI (3.9 mL, 60 mmol), and the mixture was stirred at room temperature for 24 h. The reaction mixture was taken in EtOAc (100 mL)and washed successively with H2O (50 mL), 1 M HCl (50 mL), saturated solution of NaHCO3 (50 mL), and brine (2 50 mL). The organic layer was dried with Na2SO4, filtered and concentrated under vacuum. The crude product was purified by chromatography on silica gel by using cyclohexane/EtOAc (90:10) as eluent to give3,5-dibromo-4-methoxybenzaldehyde 3c as a white solid in 82percent yield (3.62 g, 12.3 mmol).
Reference：
[1] Tetrahedron Letters, 2011, vol. 52, # 2, p. 212 - 214
[2] Patent: CN104672104, 2017, B, . Location in patent: Paragraph 0059; 0065
[3] Patent: US2003/144338, 2003, A1,
[4] Tetrahedron, 2011, vol. 67, # 49, p. 9484 - 9490
[5] Journal of Chemical Research, 2015, vol. 39, # 6, p. 336 - 339
[6] Journal of Medicinal Chemistry, 2014, vol. 57, # 10, p. 4263 - 4272
[7] Tetrahedron Letters, 2010, vol. 51, # 37, p. 4812 - 4814
[8] Tetrahedron Letters, 1998, vol. 39, # 42, p. 7665 - 7668
[9] Journal of the American Chemical Society, 2010, vol. 132, # 4, p. 1359 - 1370
[10] Journal of Medicinal Chemistry, 2008, vol. 51, # 20, p. 6348 - 6358
[11] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 15, p. 3441 - 3449
[12] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 19, p. 4630 - 4637
[13] Chemistry - A European Journal, 2015, vol. 21, # 13, p. 4913 - 4917
[14] European Journal of Medicinal Chemistry, 2014, vol. 74, p. 541 - 551
[15] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 13, p. 3618 - 3628
3
[ 2973-77-5 ]
[ 77-78-1 ]
[ 108940-96-1 ]
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1984, # 2, p. 231 - 238
With bromine; sodium acetate; In hexane; acetic acid;
(1) 3,5-Dibromo-4-hydroxybenzaldehyde To a solution of 4-hydroxybenzaldehyde (11.0 g, 90.0 mmol) and sodium acetate (22.9 g, 279 mmol) in acetic acid (150 ml) was added dropwise a solution of bromine (30.2 g, 190 mmol) in acetic acid (50 ml) at room temperature, and the reaction solution was stirred at room temperature for 1 hour and the solvent was removed under reduced pressure. To the residue was added hexane and the obtained crystals were filtered out, washed with water and subjected to air drying to give the object compound as crystals. 24.5 g (yield: 97.2%) 1H-NMR (CDCl3) delta; 6.42 (1H, bs), 8.00 (2H, s), 9.80 (1H, s). IR (KBr) cm-1; 3148, 1674, 1580, 1549, 1476, 1381, 1304, 1201, 1121, 874, 741, 658.
90%
With bromine; sodium acetate; acetic acid; at 5 - 20℃;
General procedure: To a cooled solution (5 C) of 3-hydroxybenzaldehyde(0.409 mmol, 0.500 g) in glacial acetic acid (8.0 mL, 0.14 mol), Br2(0.12 mL, 2.3 mmol) was added and stirred for 3 h at r.t. Aftercompletion of the reaction, the reaction was quenched with saturatedNa2S2O3 solution and the solventwas removed under vacuumpressure. The reaction mass was then extracted with ethyl acetate.The organic layer was dried prior to being purified by RP-HPLCcolumn to give brominated compounds.
With bromine; sodium acetate; acetic acid; at 20℃; for 1.16667h;Inert atmosphere;
Bromine (1.63 mL, 31.5 mmol) in acetic acid (5 mL) was added dropwise to a mixture of 4-hydroxybenzaldehyde (1.85 g,15 mmol) and sodium acetate (3.85 g, 46.5 mmol) in acid acetic (35 mL) at room temperature over 20 min. The reaction mixture was stirred for 1 h at room temperature. H2O (75 mL) was added and the solid was filtered, washed with H2O and dried under high vacuum to afford 3,5-dibromo-4-hydroxybenzaldehyde 14 as a white solid. To a stirred solution of 14 in DMF (50 mL) was added K2CO3 (4.15 g, 30 mmol) in portions, followed by the addition of MeI (3.9 mL, 60 mmol), and the mixture was stirred at room temperature for 24 h. The reaction mixture was taken in EtOAc (100 mL)and washed successively with H2O (50 mL), 1 M HCl (50 mL), saturated solution of NaHCO3 (50 mL), and brine (2 50 mL). The organic layer was dried with Na2SO4, filtered and concentrated under vacuum. The crude product was purified by chromatography on silica gel by using cyclohexane/EtOAc (90:10) as eluent to give3,5-dibromo-4-methoxybenzaldehyde 3c as a white solid in 82% yield (3.62 g, 12.3 mmol).
With methanol; Methyl formate; copper(l) chloride; at 115℃; for 2h;Autoclave; Green chemistry;
General procedure: A Teflon-lined autoclave (25 mL) was charged with MeONa (1.08 g, 20.0 mmol), MeOH (10 mL), CuCl (40 mg, 0.40 mmol), HCOOMe (0.25 mL, 0.97 g/mL, 4.0 mmol), and monohaloarene (10.0 mmol) then heated to 115 C, with stirring, for 2 h. After completion of the reaction, the reactor was cooled to room temperature. The mixture was stirred for 0.5 h in the open, then concentrated to recover pure MeOH. Diethyl ether (15 mL) and dilute hydrochloric acid (1.6 M, 15 mL) were added to the residue. The mixture separated into two layers, and the aqueous phase was extracted with diethyl ether (15 mL x 3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated to give a residue which was purified by column chromatography on silica gel (mobile phase: petroleum ether-ethyl acetate 15:1) to furnish 1 (conversion and selectivity were determined by GC-MS analysis). The purity of the recovered MeOH was measured as more than 99 % by GC, and the water content of the recovered MeOH was measured as less than 0.12 % by use of the Karl Fischer method.
With oxygen; cobalt(II) diacetate tetrahydrate; sodium hydroxide; In ethylene glycol; at 80℃; under 760.051 Torr; for 8h;
General procedure: a mixture of substrate 1a(1 mmol), cobalt salt (n1mol%) and NaOH (n2 equiv)in EG (5 mL) was stirred with O2 (1 atm) being bubbled, under 80 oCfor 8 h. Hydrochloric acid (10 mL, 2%) and methyl tert-butyl ether (MTBE, 10 mL) were successively added to the reactionmixture. The organic layer was separated, and the aqueous phase was furtherextracted with MTBE(10 mL × 2). The combined organic phase was dried over anhydrous sodium sulfateand concentrated to give a residue, which was purified by column chromatographyon silica gel (eluents: petroleum ether/ethyl acetate, 10/1) to provide thedesired products 2a.
With oxygen; sodium hydroxide; In 2-methoxy-ethanol; at 80℃; for 33h;
General procedure: In a typical procedure, NaOH (5.4 g, 135 mmol) was first dissolvedwith 20 g EGME in a four-necked round-bottom flask, then 50 mmolsubstrate and 0.04 g catalyst (cobalt/substrate molar ratio, 0.4%) wereadded to the above solution. The flask was equipped with a condenser,a stirrer and an air-vent needle for continuous flow of 100 mL min-1 O2. The stirring speed was 600 rpm to minimize the effect of mass transfer (Fig. S1). The reaction temperature is 80 C and the reaction time is 7 h. After the reaction, the CoOxCN was separated by an externalmagnet for reuse and the decanted reaction solution was dilutedwith water. A high performance liquid chromatography (HPLC)(Shimadzu LC-20AT) equipped with a UV detector connected to a C18reversal pillar (size: 250×4.6 mm) was used for product analysis. Amixture of methanol and water (volume ratio, 40:60) was used asmobile phase at a flow rate of 1.0 mL min-1. The column temperaturewas 40 C and the UV detection wavelength was 230 nm. HPLC andhigh performance liquid chromatography-mass spectrum (HPLC-MS)were used to test the products and intermediates by comparison withstandard chemicals. The conversions (conv.) of p-cresols, yields (Yi) ofp-hydroxybenzaldehydes, selectivity (Si) of p-hydroxybenzaldehydesand turnover numbers (TONs) of catalysts are defined as followingequations:
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper diacetate; In water; acetonitrile; at 20℃; for 4h;Green chemistry;
General procedure: A mixture of alcohol (5.0 mmol), Cu(OAc)2 (9.1 mg, 0.05 mmol), and TEMPO (7.8 mg, 0.05 mmol) in CH3CN/H2O (5/10 mL) was stirred at room temperature for specified time. After completion of the reaction (monitored by TLC, eluents: petroleum ether/ethyl acetate = 4/1), dichloromethane (10 mL) was added to the resulting mixture. The dichloromethane phase was separated, and the aqueous phase was further extracted with dichloromethane (10 mL × 2). The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a residue, which was purified by column chromatography (eluents: petroleum ether/ethyl acetate = 10/1) to provide the desired product.
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 15h;Inert atmosphere;
2,4-dibromo-3-methoxy-benzaldehyde (Compound 1) was dissolved in dry DMF, Add excess methyl iodide and potassium carbonate, stir under nitrogen at room temperature overnight, Extraction gave compound 2.
97.0%
With potassium carbonate; In N,N-dimethyl-formamide;
(2) 3,5-Dibromo-4-methoxybenzaldehyde To a solution of 3,5-dibromo-4-hydroxybenzaldehyde (5.00 g, 17.9 mmol) in DMF (100 ml) were added potassium carbonate (3.22 g, 23.3 mmol) and iodomethane (1.45 ml, 23.3 mmol), and the mixture was stirred at room temperature for 10 hours. The obtained mixture was poured into water and extracted with ethyl acetate. The extracts were collected, washed with water and dried over magnesium sulfate anhydride, and the solvent was removed under reduced pressure to give the object compound as a solid. 5.10 g (yield: 97.0%) 1H-NMR (CDCl3) delta; 3.97 (3H, s), 8.03 (2H, s), 9.80 (1H, s). IR (KBr) cm-1; 1707, 1694, 1547, 1470, 1368, 1264, 1190, 987, 747, 731.
97%
With potassium carbonate; In N,N-dimethyl-formamide; at 55℃; for 3h;
To a solution of 3,5-dibromo-4-hydroxybenzaldehyde (1.00 g, 3.57 mmol) and methyl iodide (MeI, 0.5 mL, 1.14 g, 8.03 mmol) in DMF (15 mL) was added anhydrous potassium carbonate (K2CO3, 0.992 g, 7.18 mmol). The reaction mixture was stirred at 55 C for 3 h, cooled to room temperature, and quenched by addition of water (80 mL). The resultant white precipitate was filtered under vacuum, washed with water (40 mL), and dried to give the anisaldehyde intermediate (1.02 g, 3.47 mmol, 97%) as a white solid: mp 90-91 C; IR (NaCl) 1688 cm-1 (CO), 1546 cm-1 (CC); 1H NMR (300 MHz, CDCl3) delta 9.86 (s, 1H, CHO), 8.03 (s, 2H, ArH), 3.97 (s, 3H, OCH3); 13C NMR (75 MHz, CDCl3) delta 188.6 (CHO), 159.2 (C), 134.3 (C), 134.0 (CH), 119.3 (C), 60.8 (OCH3).
83%
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 18h;
3,5-Dibromo-4-hydroxybenzaldehyde(1.40 g, 5.01 mmol), iodomethane (0.37 mL, 5.94 mmol), and K2CO3(845 mg, 6.11 mmol) were stirred in DMF (5.0 mL) at room temperature.After 18 h, the reaction was extracted into EtOAc (100 mL) and washed with H2O (2x25 mL) and brine (25 mL), dried over Na2SO4, filtered, and concentrated.Flash chromatographic purification over silica (9:1 hexanes:EtOAc) afforded3,5-dibromo-4-methoxybenzaldehydeas a white solid (1.22 g, 83%).1H-NMR (500 MHz, CDCl3)d9.86 (s, 1H), 8.03 (s, 2H), 3.97 (s, 3H);13C-NMR (125 MHz, CDCl3)d188.43, 159.12, 134.20, 133.91, 119.31, 60.88; GC-MS 292m/z[MH]+, C8H6Br2O2requires 292; RP-HPLC: >99% pure.
81%
With potassium carbonate; In N,N-dimethyl-formamide; at 55℃; for 3h;
Potassium carbonate (100mg, 0.72mmol) was added to a solution of 3,5-dibromo-4-hydroxybenzaldehyde (100mg, 0.36mmol) and methyl iodide (51muL, 0.81mmol) in DMF (1.5mL). The mixture was stirred at 55 C for 3h. After cooling to room temperature water (8mL) was added and the resulting precipitate was filtered and dried in vacuum to give 85mg (81%) as a colorless solid. HPLC: Rt=7.04min. 1H-NMR (CDCl3, 500MHz): [ppm] = 9.86 (s, 1H), 8.03 (s, 2H), 3.97 (s, 3H). 13C-NMR (CDCl3, 125MHz): [ppm]= 188.5, 159.3, 134.4, 134.1, 119.5, 61.0.
3.62 g
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24h;Inert atmosphere;
Bromine (1.63 mL, 31.5 mmol) in acetic acid (5 mL) was added dropwise to a mixture of 4-hydroxybenzaldehyde (1.85 g,15 mmol) and sodium acetate (3.85 g, 46.5 mmol) in acid acetic (35 mL) at room temperature over 20 min. The reaction mixture was stirred for 1 h at room temperature. H2O (75 mL) was added and the solid was filtered, washed with H2O and dried under high vacuum to afford 3,5-dibromo-4-hydroxybenzaldehyde 14 as a white solid. To a stirred solution of 14 in DMF (50 mL) was added K2CO3 (4.15 g, 30 mmol) in portions, followed by the addition of MeI (3.9 mL, 60 mmol), and the mixture was stirred at room temperature for 24 h. The reaction mixture was taken in EtOAc (100 mL)and washed successively with H2O (50 mL), 1 M HCl (50 mL), saturated solution of NaHCO3 (50 mL), and brine (2 50 mL). The organic layer was dried with Na2SO4, filtered and concentrated under vacuum. The crude product was purified by chromatography on silica gel by using cyclohexane/EtOAc (90:10) as eluent to give3,5-dibromo-4-methoxybenzaldehyde 3c as a white solid in 82% yield (3.62 g, 12.3 mmol).
3,5-Dibromo-4-(N,N-dimethylsulfamoyl)benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
88%
With N,N-dimethyl-cyclohexanamine; at 80 - 90℃; for 4h;
To a solution of <strong>[2973-77-5]3,5-dibromo-4-hydroxybenzaldehyde</strong> (5.0 g, 17.86 mmol) in N,N-dimethylcyclohexylamine (30 mL) at 80-90 C., was added N,N-dimethylsulfamoyl chloride (30 mL). The mixture was stirred at this temperature for 4 h, transferred to a separating funnel and diluted with EtOAc (100 mL). The organic layer was washed with water (2×200 mL), 6M HCl (aq.) (200 mL), brine (2×200 mL), dried (Na2SO4) and filtered. Concentration in vacuo of the combined filtrates gave a dark amber oil which solidified on standing. The product was stirred in n-hexane, filtered and air-dried to give OBS02013 as a pale cream solid (6.09 g, 88%). TLC [SiO2, EtOAc-n-hexane (1:1)] Rf=0.73; 1H-NMR (270 MHz, CDCl3)=3.14 (6H, s), 8.06 (2H, s), 9.88 (1H, s).
N-(2,6-Dichloro-phenyl)-N'-[1-(3,5-dichloro-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
N-(2,6-Dichloro-phenyl)-N'-[1-(3,5-difluoro-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
C15H12N2O4[ No CAS ]
N-(3,5-Dichloro-phenyl)-N'-[1-(2-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
N-(3,5-Dichloro-phenyl)-N'-[1-(4-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
C15H12N2O4[ No CAS ]
N-(2,6-Dichloro-phenyl)-N'-[1-(4-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
C15H12N2O4[ No CAS ]
N-(2,6-Dichloro-phenyl)-N'-[1-(3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
N-(3,5-Dichloro-phenyl)-N'-[1-(3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
C15H12N2O4[ No CAS ]
C15H12N2O4[ No CAS ]
C15H12N2O4[ No CAS ]
N-(3-Trifluoromethyl-phenyl)-N'-[1-(3-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
N-(2-Trifluoromethyl-phenyl)-N'-[1-(2-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
4-{N'-[1-(3,5-Dibromo-4-hydroxy-phenyl)-meth-(E)-ylidene]-hydrazino}-benzoic acid[ No CAS ]
N-(3-Trifluoromethyl-phenyl)-N'-[1-(2-trifluoromethyl-phenyl)-meth-(E)-ylidene]-hydrazine[ No CAS ]
2,6-dibromo-4-[(3-trifluoromethyl-phenyl)-hydrazonomethyl]-phenol[ No CAS ]
2,6-dibromo-4-[(2-trifluoromethyl-phenyl)-hydrazonomethyl]-phenol[ No CAS ]
4-{N'-[1-(4-Hydroxy-3,5-diiodo-phenyl)-meth-(E)-ylidene]-hydrazino}-benzoic acid[ No CAS ]
3-{N'-[1-(4-Hydroxy-3,5-diiodo-phenyl)-meth-(E)-ylidene]-hydrazino}-benzoic acid[ No CAS ]
2,6-diiodo-4-[(2-trifluoromethyl-phenyl)-hydrazonomethyl]-phenol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Combinatorial reaction / High throughput screening (HTS);
Libraries were prepared in a single compound per well format. Stock solutions of all aldehydes (0.5 M) and aryloxyamines (0.4 M) were prepared in DMSO. A Gilson 215 Liquid Handler equipped with a 1 mL syringe, 1.1 mL tubing, and a 13 mm I.D. probe was used to distribute all solutions into a 96 well (2 mL volume) polypropylene plate at a rate of 0.3 mL/min. To make 0.5 mL of a 0.1 M solution of each oxime ether, 100 muL (0.05 mmol, 1 eq.) of aldehyde, 156 muL (0.63 mmol, 1.25 eq.) of aryloxyamine, and 244 muL of 0.164 M acetic acid, were distributed to each well of the plate. The plate was covered and agitated for 24 h at room temperature using a dual action shaker. The reactions were diluted to 720 muM in DMSO and analyzed by LC-MS to determine yield, purity, and identity. Compounds were stored frozen at -20 C. after synthesis. Reaction yield was determined using the integrated value of aldehyde that remained in the reaction mixture. Calibration curves of all aldehydes were made and the yield of each oxime ether was calculated assuming all the aldehyde that reacted quantitatively formed oxime ether; i.e. if 5% of aldehyde remained in the reaction mixture the yield of oxime ether would be 95%. Yields ranged from 98-100% and >95% purity in all wells.
With acetic acid In water; dimethyl sulfoxide at 20℃; for 24h; Combinatorial reaction / High throughput screening (HTS);
Libraries were prepared in a single compound per well format. Stock solutions of all aldehydes (0.5 M) and aryloxyamines (0.4 M) were prepared in DMSO. A Gilson 215 Liquid Handler equipped with a 1 mL syringe, 1.1 mL tubing, and a 13 mm I.D. probe was used to distribute all solutions into a 96 well (2 mL volume) polypropylene plate at a rate of 0.3 mL/min. To make 0.5 mL of a 0.1 M solution of each oxime ether, 100 μL (0.05 mmol, 1 eq.) of aldehyde, 156 μL (0.63 mmol, 1.25 eq.) of aryloxyamine, and 244 μL of 0.164 M acetic acid, were distributed to each well of the plate. The plate was covered and agitated for 24 h at room temperature using a dual action shaker. The reactions were diluted to 720 μM in DMSO and analyzed by LC-MS to determine yield, purity, and identity. Compounds were stored frozen at -20° C. after synthesis. Reaction yield was determined using the integrated value of aldehyde that remained in the reaction mixture. Calibration curves of all aldehydes were made and the yield of each oxime ether was calculated assuming all the aldehyde that reacted quantitatively formed oxime ether; i.e. if 5% of aldehyde remained in the reaction mixture the yield of oxime ether would be 95%. Yields ranged from 98-100% and >95% purity in all wells.
6-cyano-3-(3,5-dibromo-4-hydroxy-benzylidene)-1,3-dihydro-indol-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With p-toluenesulfonic acid monohydrate; In toluene;
Example 179 6-Cyano-3-(3,5-dibromo-4-hydroxy-benzylidene)-1,3-dihydro-indol-2-one <strong>[199327-63-4]6-cyano-1,3-dihydro-indol-2-one</strong> (46.3 mg, 0.29 mmol) and 3,5-dibromo-4-hydroxybenzaldehyde (80 mg, 0.39 mmol) and p-toluenesulfonic acid monohydrate (1 mg, 0.005 mmol) were treated with toluene (30 mL) and the reaction refluxed with stirring with a Dean-Stark water trap attached for 1.5 h. During this time an orange solid deposited, which, on cooling, was filtered off, washed with toluene and dried in vacuo at 125 C. for 3 days to give 80 mg of 6-cyano-3-(3,5-dibromo-4-hydroxy-benzylidene)-1,3-dihydro-indol-2-one; 1H-NMR (DMSO-d6): delta11.05 (bs, 1H), 8.86 (s, 2H), 7.97 (s, 1H), 7.85 (d, J=7.9 Hz, 1 H), 7.50 (d, J=7.9 Hz, 1 H), 7.20 (s, 1H). Mass spectrum (negative ion electrospray): m/z=417 (M-1, 48%), 419 (M-1, 100%), 421 (M-1, 48%).
3,5-Dibromo-4-(4-methoxybenzyloxy)benzaldehyde (C)[0464] To a stirred solution of <strong>[2973-77-5]3,5-dibromo-4-hydroxybenzaldehyde</strong> (5.30 g, 18.9 mmol) in anhydrous DMF (15 mL) under nitrogen was added potassium carbonate (5.50 g, 19.9 mmol) and the mixture was stirred for 10-15 min during which time vigorous effervescence was observed. 4-methoxybenzyl chloride (2.70 mL, 19.9 mL) was then added and the mixture was heated at 60 C for 20 h. The mixture was filtered and the filtrate was <n="147"/>evaporated. The residual oil was then poured into water (100 mL) and the mixture was stirred for 1-2 h. The resulting solid was collected by filtration, washed with water and dried under vacuum at 60 C to leave 6.63 g (88%) of the title compound as a pale brown solid. 1H NMR (DMSOd6) 3.82 (3 H, s), 5.06 (2 H, s), 7.02 (2 H, d), 7.53 (2 H, d), 8.24 (2 H, s), 9.95 (1 H, s)
The appropriate aldehyde (15 mmol) was added to a mixture of appropriate substituted 2H-l,4-benzoxazin-3(4H)-one (10 mmol), acetic anhydride (4 ml) and triethylamine (2 ml). The reaction mixture was refluxed for 7 h, left overnight at room temperature and poured into crushed ice. The obtained solid was collected by filtration and washed with acetonitrile (70-88% yield). The crude product was purified by recrystallisation from ethanol.
With piperidine; In methanol; at 100℃; for 0.5h;Microwave irradiation;
General procedure: Equimolar amounts (0.3 mmol) of 5-chlorooxindole/oxindole and aldehyde were dissolved in methanol (1 ml), a drop of piperidine (30 mul) was added and the mixture heated at 100C under microwave irradiation for 30 min. The reaction mixture was cooled to room temperature and the resulting precipitate was removed by filtration, carefully washed with methanol and recrystallized at least once from methanol to give the desired product in good yield.
97%
With pyridine; In methanol; at 100℃; for 0.5h;Microwave irradiation;
General procedure: A suspension of indolinone (0.3mmol), aldehyde (0.3mmol) and pyridine (30muL) in methanol (1mL) were heated under microwave irradiation at 100 C for 30 minutes. The reaction mixture was cooled to room temperature and the resulting precipitate was removed by filtration, carefully washed with methanol and dried in vacuo. When no precipitate was observed methanol was removed under vacuum and the residue was purified by silica gel chromatography to give the desired product.
4-[1-(3,5-Dibromo-4-hydroxy-phenyl)-meth-(E)-ylidene]-2-methyl-4H-oxazol-5-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With zinc(II) oxide; In ethanol; at 25℃; for 0.316667h;
General procedure: A mixture of the required aldehyde (1 mmol), N-benzoylglycine/N-acetylglycine (1 mmol),acetic anhydride (3 mmol), ZnO as a catalyst (0.05 mmol) and 15 mL ethanol was stirred atroom temperature, 25 C (Scheme 1). After a certain period, the syrupy reaction mixture was solidified and the reaction was completed (Table I). After the final product had been obtained,20 mL more of cold ethanol was added. The solid was filtered off, dried and washed with hotwater before recrystallization of the product.
With zinc(II) oxide; In ethanol; at 25℃; for 0.25h;
General procedure: A mixture of the required aldehyde (1 mmol), N-benzoylglycine/N-acetylglycine (1 mmol),acetic anhydride (3 mmol), ZnO as a catalyst (0.05 mmol) and 15 mL ethanol was stirred atroom temperature, 25 C (Scheme 1). After a certain period, the syrupy reaction mixture was solidified and the reaction was completed (Table I). After the final product had been obtained,20 mL more of cold ethanol was added. The solid was filtered off, dried and washed with hotwater before recrystallization of the product.
With oxygen; cobalt(II) diacetate tetrahydrate; sodium hydroxide; In ethylene glycol; at 80℃; under 760.051 Torr; for 4h;
General procedure: a mixture ofsubstrate 3a (0.5 mmol), Co(OAc)2·4H2O (0.005 mmol, 1.3 mg) and NaOH (1.0 mmol, 40mg) in EG (5 mL) was stirred with O2 (1 atm) being bubbled at 80 oC for 4 h. Hydrochloricacid (10 mL, 2%) and MTBE (10mL) were successively added to the reaction mixture. The organic layer wasseparated, and the aqueous phase was further extracted with MTBE (10 mL × 2). The combined organic phase wasdried over anhydrous sodium sulfate and concentrated to give a residue, whichwas purified by column chromatography on silica gel (eluents: petroleumether/ethyl acetate, 10/1) to provide the desired product 2a.
General procedure: In a 0.5e2 mL microwave vial were added 5 mg of clay K10,2,4,6-tribromo-3-methoxy-benzaldehyde (12 mg, 0.031 mmol,1 eq.), N,N-dimethyl 1,3-propane diamine (4 mL, 0.031 mmol, 1 eq.)and 100 mL of MeOH. The mixture was stirred for 2 min, sealed andthen irradiated for 10 min at 65 C. A mixture of 5 mg of clay K10with sodium borohydride 95% (1.25 mg, 0.031 mmol, 1 eq.) wasthen added to the reaction mixture, it was sealed and irradiated for5 min at 100 C. It was then diluted with MeOH, filtered, concentratedto dryness and purified by Flash chromatography (silica gel,DCM/MeOH/NEt3 80/20/0.01) to give 1 (8.5 mg, 58% yield).
With dodecatungstosilic acid; phosphorus pentoxide In neat (no solvent, solid phase) at 20℃; for 0.0333333h; Green chemistry;
General method for the synthesis of Schiff bases 1-25
General procedure: A mixture of 1-aminoanthraquinone (1 mmol), a substituted aromatic aldehyde or ketone (1 mmol) and dodecatungstosilicic acid/P2O5 (0.2 g, 1 mol % of 1-aminoanthraquinone/P2O5) as a catalyst was ground in a mortar with a pestle under solvent-free conditions at room temperature for 1-3 min, Scheme 1. The reaction mixture turned to a pasty material that indicated the completion of the reaction. Crushed ice was added to afford precipitates of the Schiff bases. In order to remove the catalyst, the product was washed several times with ice-cold water. The solid products were obtained in excellent yield.
5-(3,5-dibromo-4-hydroxybenzylidene)-2-thioxodihydro-4,6(1H,5H)-pyrimidinedione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
89%
With sodium hydroxide; at 20℃; for 12h;
General procedure: The syntheses of thiobarbituric acid derivatives (1-27) were carried out by the reaction of thiobarbituric acid (1 mmol) with different aromatic aldehyde (1 mmol) in the presence of 10 ml of 20% NaOH. The reaction mixture was stirred for 12 h. The completion of reaction was monitored by periodic TLC. The completion of the reaction was monitored periodically by TLC. After completion of the reaction, the mixture was poured into crushed ice followed by acidification with dilute HCl. The product precipitated as a solid which was filtered, dried and recrystallized from ethanol.
55.9%
In ethanol; water; at 20℃; for 10.5h;
Ethanol (4-8 mL) and H2O (4-8 mL) Various aldehydes (1.52-1.97 mmol) and thiobarbituric acid (0.9-1. 1.1 eq.) In toluene was heated to room temperature or 80C. A precipitate was formed during the heating reaction. The precipitate was filtered through reduced pressure volatilization of ethanol, and the precipitate was filtered without volatilization of the ethanol under reduced pressure. Taking into account the physical properties of the residual aldehyde derivative and thiobarbituric acid after the reaction, the filtered solid was washed with ethanol and / or methylene chloride and water to give the above compound. According to the above synthesis method, in a solvent of ethanol (4-8 mL) and H2O (4-8 mL) A suspension of <strong>[2973-77-5]3,5-dibromo-4-hydroxybenzaldehyde</strong> (1.52-1.97 mmol) and thiobarbituric acid (0.9-1.1 eq.) Was reacted at room temperature for 10.5 hours to give 1 l of the yellow solid compound 55.9 % Yield.
With pyridine; In methanol; at 100℃; for 0.5h;Microwave irradiation;
General procedure: A suspension of indolinone (0.3mmol), aldehyde (0.3mmol) and pyridine (30muL) in methanol (1mL) were heated under microwave irradiation at 100 C for 30 minutes. The reaction mixture was cooled to room temperature and the resulting precipitate was removed by filtration, carefully washed with methanol and dried in vacuo. When no precipitate was observed methanol was removed under vacuum and the residue was purified by silica gel chromatography to give the desired product.
3,3′-((3′′,5′′-dibromo-4-hydroxyphenyl)methylene)bis(4-hydroxy- 2H-chromen-2-one)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With tetraethylammonium bromide; In water; for 2h;Reflux;
General procedure: 6-Fluoro-4-hydroxy /6-chloro-4-hydroxy /4-hydroxy coumarin(1 mmol), and a variety of aromatic aldehydes (0.5 mmol), as well as 10 mol% of tetraethylammonium bromide (TEAB) were dissolved indistilled water (15 mL) in a 100 mL round-bottommed flask. The reactionmixture was refluxed for 2 h. Periodic TLC was taken to check theprogress of reaction. Resulting precipitates were filtered, and washedwith distilled water. This afforded products 1-44 in high yields.
(E)-3-(3,5-dibromo-4-hydroxyphenyl)-1-(2,5-dichlorothiophen-3-yl)prop-2-en-1-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With potassium hydroxide; In methanol; at 20℃; for 10h;
General procedure: An equimolar mixture of the aryl aldehyde, KOH were dissolved in MeOH (50 mL). To this solution 3-acetyl-2,5-dichlorothiophene, 3, in MeOH (10 mL) was added dropwise. After theaddition was completed, the reaction mixture was stirred at r.t.for 10 h. The precipitate formed was fltered o, washed withMeOH and dried without any further purifcation.
(3,5-bis-benzyloxy-benzyl)-triphenyl-phosphonium; chloride[ No CAS ]
C28H22Br2O3[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
The stirred solution of phosphorus ylide 12 (1.3g, 2.2mmol) in dry toluene (40mL) under argon atmosphere was added to a solution of n-BuLi (2.2mL, 12.0mmol) in n-hexane. After stirring for 30min, aldehyde 13 (0.5g, 1.8mmol) was added and then stirred for an additional 6h under refluxing at 110C, after which ethanol (10mL) was added. The reaction mixture was concentrated and extracted with EtOAc (50mL) for three times, washed with water, brine and then dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified on a silica gel column chromatography (petroleum ether: EtOAc=8: 1) to give stilbene 14 (0.73g, 74%) as a pale white solid. m.p.: 132-134C, 1H NMR (400MHz, CDCl3): delta=5.07 (s, 4H), 5.91 (br s, 1H), 6.57 (br s, 1H), 6.73 (br s, 2H), 6.84 (d, J=16.4Hz, 1H), 6.89 (d, J=16.4Hz, 1H), 7.33-7.45 (m, 10H), 7.58 (br s, 2H) ppm; 13C NMR (150MHz, CDCl3): delta=70.1 (2C), 101.9, 105.8 (2C), 110.2, 125.9, 127.5 (4C), 128.0 (2C), 128.6 (5C), 129.2, 129.9 (2C), 132.4, 136.8 (2C), 138.7, 148.7, 160.2 (2C) ppm; HRMS (ESI): m/z calcd. for C28H22Br2O3+H: 566.9988; found: 566.9997.
9-(3,5-dibromo-4-hydroxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87.5%
With N,N'-bis(3-sulfopropyl)triethylenediaminium bis(hydrogensulfate); ammonium acetate; In ethanol; at 80℃; for 4h;
General procedure: The catalyst ionic liquid was prepared according to the literature procedure [28]. To a mixture of 1,3-cyclohexanedione/dimedone (2mmol), arylaldehyde (1mmol), and ammonium acetate (3mmol) in 5mL of anhydrous ethanol, and 0.02g of ionic liquid was added and stirred at 80C for 4h. After completion of the reaction (TLC monitoring), the mixture was cooled to room temperature. The resulting precipitate was filtered off and washed with ethanol before drying to afford the pure 1,8-acridinedione intermediates in good yields (50-80%) which were submitted to the following step without further purification [33].
2-amino-4-(3,5-dibromo-4-hydroxyphenyl)-6-(2,4-dichlorophenyl)nicotinonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
81%
With ammonium acetate; In ethanol; at 70℃; for 0.2h;Microwave irradiation; Green chemistry;
General procedure: Aldehyde (0.005 mol), methyl ketones (0.005 mol)malononitrile (0.005mol), ammonium acetate (0.02 mol) and5 mL ethanol were taken in a microwave tube and weresubected to microwave irradiation at 70C for 12 min,(CEM Discover reaction system, USA) after cooling to roomtemperature, the solid product was filtered off andrecrystallized using a mixture of ethanol and water (Scheme1).
3-(3,5-dibromo-4-hydroxybenzylidene)-5-(furan-2-carbonyl)indolin-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
65%
With piperidine; In ethanol; at 80℃; for 16h;Inert atmosphere;
General procedure: Piperidine (8.7 muL, 0.088 mmol), 3,5-difluoro-4-hydroxybenzaldehyde (69.5 mg, 0.44 mmol) and S3 (100.0 mg, 0.44 mmol) were dissolved in EtOH (2.0 mL). The mixture was heated to 80 oC for 16 h. The orange solid was filtered and washed with 1N HCl and Et2O to afford 3 (114.0 mg, 70%, mixture of E/Z isomers).
4-hydroxy-3,5-bis(2,2,2-trifluoroethoxy)benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
53%
With copper dichloride; In N,N-dimethyl-formamide; at 80 - 115℃;
In a flask equipped with a Claisen distillation apparatus, freshly cut sodium (0.69 g, 30 mmol)was added to trifluoroethanol (10 mL)at rt and the mixture was stirred until a complete dissolution of sodium. The mixture was then heated at 80-90 C to distill off portion of trifluoroethanol with the help of in house vacuum. Then,a solution of <strong>[2973-77-5]3,5-dibromo-4-hydroxybenzaldehyde</strong> (10, 0.5 g,1.79 mmol) and copper (II) chloride (0.20 g, 1.49 mmol) in DMF(4 mL) was added in one portion. The blue mixture was heated and distilled at 110-115 C overnight. The reaction was cooled to RT,then water was added and the undesired precipitate was filtered off. The filtrate was partitioned between EtOAc and water. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo to give 0.30 g (53%) of title compound as a brown solid, which was used without further purification. 1H NMR(400 MHz, DMSO-d6) delta 4.62 (q, J=9.6, 19.0 Hz, 4H), 6.96 (s, 2), 9.20(s, 1H).
3,3′-((3′′,5′′-dibromo-4′′-hydroxyphenyl)methylene)bis(6-chloro-4-hydroxy-2H-chromen-2-one)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
With tetraethylammonium bromide In water for 2h; Reflux;
4.2. General procedure for the syntheses of bis-coumarin derivatives 1-44
General procedure: 6-Fluoro-4-hydroxy /6-chloro-4-hydroxy /4-hydroxy coumarin(1 mmol), and a variety of aromatic aldehydes (0.5 mmol), as well as 10 mol% of tetraethylammonium bromide (TEAB) were dissolved indistilled water (15 mL) in a 100 mL round-bottommed flask. The reactionmixture was refluxed for 2 h. Periodic TLC was taken to check theprogress of reaction. Resulting precipitates were filtered, and washedwith distilled water. This afforded products 1-44 in high yields.
With silica chloride; In neat (no solvent); at 120℃; for 4h;
General procedure: To the flask containing a mixture of substituted benzaldehyde (1mmole) and 2-aminophenol (1mmole) was added silica chloride(1 eq) and was heated on a sand bath at 120 C, TLC was taken afterevery 1 h. After 4 h, TLC showed appearance of new spot. The productwas isolated by first separating out the catalyst by filtration using organicsolvent; the organic layer was dried using anhydrous sodiumsulfate and evaporated under vacuum. The solid thus obtained was recrystallized using petroleum ether and its % yield and melting pointswere determined. The results are tabulated in Table 1 and Table 2.
4-((quinolin-4-yl)amino)benzoylhydrazide[ No CAS ]
(E)-N'-(3,5-dibromo-4-hydroxybenzylidene)-4-(quinolin-4-ylamino)benzohydrazide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
With trifluoroacetic acid; In ethanol; for 8h;Reflux;
General procedure: A mixture of the appropriate substituted aldehydes (0.2mol) and 4-(quinolin-4-ylamino) benzohydrazide 4 (55.0mg, 0.2mmol) in absolute ethanol (5mL) containing two drops of trifluoroacetic acid was stirred and refluxed for 8h. Then, the reaction mixture was cooled to room temperature, and the solvent was removed by reduced pressure distillation. The residue was purified by column chromatography (DCM/MeOH/Triethylamine, 200:10:1 (v/v/v)) to get (E)-N?-Substituted methylene-4-(Quinoline-4-Amino) benzoylhydrazides 5a-5p.
With piperidine; acetic acid; In acetonitrile; at 85℃; for 8h;Molecular sieve;
1) 3,5-dibromo-4-benzaldehyde (0.8g, 2.9mmol) was dissolved in acetonitrile (20mL), and piperidine (1.6mL) and acetic acid (0.8mL) were added respectively.Add an appropriate amount of molecular sieve, stir, warm to 85 C, add EWGO (0.5g, 2.4mmol), and continue the reaction for 8h.After the reaction, the molecular sieves were removed by filtration, ethyl acetate (50 mL) was added, and a 1M aqueous hydrochloric acid solution was used to wash.The crude product was filtered and purified by column chromatography with dichloromethane as the eluent.The compound PSO-Br (0.42 g, 37.4%) was obtained as a yellow solid.
(2Z)-2-[(3,5-dibromo-4-hydroxyphenyl)methylidene]benzofuran-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With hydrogenchloride In water; isopropyl alcohol at 80℃;
4.1.4. General procedure of synthesis of aurones 9-15
General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
(2Z)-7-chloro-2-[(3,5-dibromo-4-hydroxyphenyl)methylidene]benzofuran-3-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
35%
With hydrogenchloride In water; isopropyl alcohol at 80℃;
4.1.4. General procedure of synthesis of aurones 9-15
General procedure: 100 mg of 1-benzofuran-3(2H)-ones, equimolar amount of corresponding substituted benzaldehyde and 1 drop of conc. hydrochloric acid were mixed with 1-3 ml of isopropanol. Mixture was heated on the water bath at 80 °C during 2-8 h. In the case of 1-benzofuran-3(2H)-ones 28 and 29 mixtures were kept at 80 °C for 16 h. Yellow, red or brown precipitates were filtered and washed with ethyl acetate. If obtained products contained impurities (in the most cases of starting aldehyde)- they were recrystallized from 0.2 to 1 ml DMF and washed with ethyl acetate.
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
