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HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
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USD 150+
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Structure of 554-14-3 * 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.
With N-Bromosuccinimide; dibenzoyl peroxide In chloroform at 20 - 70℃;
Take 2-methylthiophene 98g, dissolved in 400 ml of chloroform, After adding BPO4.84g, the system was heated to 70°C, 180 g of NBS was added in batches, and the addition was completed for 1h. After the addition, the system was incubated for 7h, cooled to room temperature, and stirred overnight.After filtration, the filtrate is decompressed to recover the solvent.The residual liquid was distilled under reduced pressure to obtain 171 g of a yellow liquid in a yield of 98percent.
78%
With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane for 1 h; Reflux
To a stirred solution of 2-methyl thiophene (3 g, 30.61 mmol) in CCI4 (75 ml) was added N-bromo succinimide (2.67 g, 15.00 mmol), followed by benzoyl peroxide (60 mg, 6.0 mmol) at 20-35°C and the reaction mixture was refluxed for 1 h. The progress of the reaction was monitored by TLC. After cooling to 20-35°C, hexane (300 ml) was added to the reaction mixture, the resultant precipitate was removed via filtration and the filtrate was collected, concentrated to get the desired compound as a brown liquid (4.2 g, 78percent). NMR (400 MHz, CDC ) δ 7.33-7.24 (m, 1H), 7.1 1 (d, J = 4.4 Hz, 1H), 6.93 (dd, J = 4.9, 3.4 Hz, IH), 4.75 (s, 2H).
Reference：
[1] Organic and Biomolecular Chemistry, 2010, vol. 8, # 23, p. 5431 - 5441
[2] Patent: CN107540654, 2018, A, . Location in patent: Paragraph 0044; 0045
[3] Patent: WO2013/80222, 2013, A1, . Location in patent: Page/Page column 37
[4] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 2, p. 424 - 430
[5] Russian Chemical Bulletin, 2000, vol. 49, # 9, p. 1544 - 1547
[6] Journal of Medicinal Chemistry, 2002, vol. 45, # 20, p. 4559 - 4570
[7] Russian Chemical Bulletin, 2007, vol. 56, # 5, p. 967 - 974
[8] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1988, p. 803 - 808
[9] Journal of the American Chemical Society, 1949, vol. 71, p. 1201,1203
[10] Journal of the American Chemical Society, 1953, vol. 75, p. 3517
[11] Organic Letters, 2006, vol. 8, # 18, p. 4085 - 4088
[12] Canadian Journal of Chemistry, 2008, vol. 86, # 7, p. 668 - 675
[13] Molecular Crystals and Liquid Crystals, 2010, vol. 520, p. 186 - 192
[14] Molecular Crystals and Liquid Crystals, 2011, vol. 539, p. 442 - 448
[15] Molecular Crystals and Liquid Crystals, 2009, vol. 504, # 1, p. 196 - 203
[16] Molecular Crystals and Liquid Crystals, 2009, vol. 504, # 1, p. 204 - 211
[17] Dyes and Pigments, 2015, vol. 119, p. 30 - 40
[18] Patent: US2727906, 1951, ,
5
[ 554-14-3 ]
[ 7726-95-6 ]
[ 45438-73-1 ]
Reference：
[1] Journal of the American Chemical Society, 1953, vol. 75, p. 3517
6
[ 554-14-3 ]
[ 56-23-5 ]
[ 128-08-5 ]
[ 94-36-0 ]
[ 45438-73-1 ]
Reference：
[1] Journal of the American Chemical Society, 1949, vol. 71, p. 1201,1203
7
[ 554-14-3 ]
[ 68-12-2 ]
[ 13679-70-4 ]
Yield
Reaction Conditions
Operation in experiment
99%
Stage #1: With ethylmagnesium chloride; N-cyclohexyl-cyclohexanamine In tetrahydrofuran at 60℃; for 24 h; Inert atmosphere Stage #2: at 20℃; for 1 h;
General procedure: To a solution of 0.99 M EtMgCl (0.61 mL, 0.6 mmol) in THF were added dicyclohexylamine (0.01 mL, 0.05 mmol), and 2-methylthiophene (1a, 0.048 mL, 0.50 mmol) dropwise under an nitrogen atmosphere. After stirring at 60 °C for 24 h, 1.4 mL of THF and N,N-dimethylformamide (0.5 mL, 6.46 mmol) were successively added and stirring was continued for further 1 h. The mixture was quenched by saturated aqueous solution of ammonium chloride (1.0 mL) and the solution was poured into the mixture of diethyl ether/water to result in separation into two phases. Aqueous was extracted with diethyl ether twice and the combined organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to leave a crude oil, which was purified by column chromatography on silica gel (hexane/EtOAc = 20/1) to afford 62.3 mg of 2-formyl-5-methylthiophene (1a-CHO, colorless oil, 99percent).
80.2%
Stage #1: at 0 - 35℃; for 18 h; Stage #2: With sodium hydroxide; water In diethyl ether
Reference Example 1: Synthesis of 2-formyl-5-methylthiophene Into a 50 ml, three-necked flask equipped with a magnetic stirrer, a reflux condenser and a thermometer were added 10.9 g (0.15 mol) of dimethylformamide and 15.3 g (0.15 mol) of phosphorus oxychloride. The mixture was cooled to 0 °C with stirring. Then, 9.8 g (0.1 mol) of 2-methylthiophene was added to the system, followed by stirring at 25 to 35°C for 18 hours. To the reaction mixture were added 30 ml of water and 50 ml of ether. Further, an aqueous solution containing 23percent of sodium hydroxide was added carefully until a pH of >11 was reached. The mixture was subjected to phase separation. Then, there were conducted washing with a saturated aqueous sodium chloride solution, drying over anhydrous sodium sulfate, and distillation under reduced pressure for ether removal. The residue was subjected to Kugel-rohr distillation to obtain 10.1 g of a colorless oil. The oil contained, as a component, >99.9percent (in terms of areal ratio of gas chromatography) (yield: 80.2percent) of 2-formyl-5-methylthiophene. Gas mass chromatography was conducted to confirm a molecular ion peak [M+] of 126.
Reference：
[1] Tetrahedron Letters, 2012, vol. 53, # 9, p. 1173 - 1176
[2] Dyes and Pigments, 2014, vol. 106, p. 154 - 160
[3] Patent: EP1555257, 2005, A1, . Location in patent: Page/Page column 25-26
[4] Pharmaceutical Chemistry Journal, 1989, vol. 23, # 7, p. 592 - 596[5] Khimiko-Farmatsevticheskii Zhurnal, 1989, vol. 23, # 7, p. 840 - 843
[6] Journal of Organic Chemistry, 2010, vol. 75, # 4, p. 1047 - 1060
[7] Journal of Materials Chemistry, 2007, vol. 17, # 12, p. 1166 - 1177
[8] Journal of the American Chemical Society, 1953, vol. 75, p. 989
[9] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 1221 - 1230
[10] Advanced Synthesis and Catalysis, 2010, vol. 352, # 13, p. 2116 - 2120
[11] Dyes and Pigments, 2011, vol. 91, # 3, p. 404 - 412
[12] Applied Organometallic Chemistry, 2013, vol. 27, # 5, p. 283 - 289
[13] Chemical Communications, 2015, vol. 51, # 18, p. 3842 - 3845
8
[ 554-14-3 ]
[ 75-27-4 ]
[ 13679-70-4 ]
Yield
Reaction Conditions
Operation in experiment
75%
Stage #1: With 1,1'-bis-(diphenylphosphino)ferrocene; potassium phosphate; palladium diacetate; acetic anhydride; silver carbonate In acetonitrile at 60℃; for 24 h; Schlenk technique; Inert atmosphere Stage #2: With hydrogenchloride In dichloromethane at 30℃;
General procedure: To a 50 mL of Schlenk tube were added 1 or 3 (0.2 mmol, 1.0 equiv), Pd(OAc)2 (10 molpercent), dppf (10 molpercent) under air, followed by K3PO4·3H2O (0.3 mmol, 1.5 equiv) and Ag2CO3 (0.3 mmol, 1.5 equiv) . The mixture was then evacuated and back filled with N2 (3 times). Bromodichoromethane (0.4 mmol, 2.0 equiv), Ac2O (2 mmol, 190 uL) and CH3CN (1 mL) were added subsequently. The Schlenk tube was screw capped and put into a preheated oil bath (60 °C). After stirring for 24 hours, the reaction mixture was cooled to room temperature, diluted with CH2Cl2 and Ethyl Acetate, then filtered with a pad of silica gel. The isolated yield was given by a hydrolysis pathway, in which the concentrated reaction mixture was diluted with 5 mL CH2Cl2 and 10 mL 3 N HCl and stirred over night. The reaction mixture was extracted with dichloromethane (3 times) and the solvent was removed under rotary evaporation. The residue was then purified by a preparative TLC to give product 2 or 4.
Reference：
[1] Journal of the Chemical Society, 1950, p. 2130,2134
[2] Journal of Organic Chemistry, 1949, vol. 14, p. 790,795
[3] Journal of the American Chemical Society, 1950, vol. 72, p. 1422
[4] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
11
[ 554-14-3 ]
[ 96-43-5 ]
[ 68-12-2 ]
[ 13679-70-4 ]
[ 7283-96-7 ]
Reference：
[1] Journal of Organic Chemistry, 2010, vol. 75, # 4, p. 1047 - 1060
12
[ 554-14-3 ]
[ 13679-70-4 ]
Reference：
[1] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1911, vol. 43, p. 804 Anm.[2] Chem. Zentralbl., 1911, vol. 82, # II, p. 1239
[3] Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1914, vol. 46, p. 792[4] Chem. Zentralbl., 1915, vol. 86, # I, p. 837
13
[ 111-65-9 ]
[ 554-14-3 ]
[ 872-55-9 ]
[ 1551-27-5 ]
[ 638-02-8 ]
[ 1455-20-5 ]
[ 40323-88-4 ]
Reference：
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1985, vol. 34, p. 2489 - 2492[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 12, p. 2690 - 2693
Reference：
[1] Justus Liebigs Annalen der Chemie, 1921, vol. 424, p. 22
17
[ 111-65-9 ]
[ 554-14-3 ]
[ 872-55-9 ]
[ 1551-27-5 ]
[ 638-02-8 ]
[ 1455-20-5 ]
[ 40323-88-4 ]
Reference：
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1985, vol. 34, p. 2489 - 2492[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 12, p. 2690 - 2693
18
[ 142-82-5 ]
[ 188290-36-0 ]
[ 554-14-3 ]
[ 872-55-9 ]
[ 1551-27-5 ]
[ 638-02-8 ]
[ 40323-88-4 ]
Reference：
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1985, vol. 34, p. 2489 - 2492[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1985, # 12, p. 2690 - 2693
19
[ 554-14-3 ]
[ 765-58-2 ]
Yield
Reaction Conditions
Operation in experiment
70%
With bromine In 1,4-dioxane at 20℃; for 3 h; Inert atmosphere
A solution of 48.0 gbromine (0.3 mol) in 260 cm3 of dioxane was slowlyadded to a solution of 29.4 g 2-methylthiophene (23,0.3 mmol) in 140 cm3 of dioxane. The reaction mixturewas stirred for 3 h at room temperature, then cooled to0 C. A saturated aqueous sodium bicarbonate solutionwas then carefully added and the mixture was extractedwith ethyl acetate. The organic layer was dried oversodium sulfate and evaporated under reduced pressure. The remainder was purified by distillation to deliver37.2 g 2-bromo-5-methylthiophene (24, 0.21 mol, 70percent).B.p.: 68–70 C (20 mbar); 1H NMR (400 MHz, CDCl3):d = 2.42 (s, 3H), 6.51 (d, 1H, J = 3.6 Hz), 6.83 (d, 1H,J = 3.6 Hz) ppm; LC–MS: tR = 1.65 min; MS: m/z = 176, 178 ([M?1]?, [M?3]?).
69%
With N-Bromosuccinimide; acetic acid In chloroform at 0℃; for 1 h; Darkness
NBS (1.1 eq, 4.0g, 22.7 mmol) was added to a solution of 2-methylthiophene (1.0 eq., 2 mL, 20.7 mmol) in a mixture of chloroform/AcOH (10:1, 20 mL) at 0 C in the absence of light. The mixture reaction was stirred at 0 C for 1h. Then the mixture was warmed to rt for 12 hours. The reaction was quenched with aqueous sat. NaHCO3 solution. The organic layer was dried (MgSO4), filtered and the solvents were evaporated in vacuo. The crude product was purified (FCC, SiO2, 0-100 percent EtOAc in heptane) to provide the title compound (2.5 g, 69percent).1H NMR (300 MHz, CDCl3) δ 6.83 (d, J = 3.6 Hz, 1H), 6.52 (d, J = 2.5 Hz, 1H), 2.43 (s, 3H).
Reference：
[1] Journal of Organic Chemistry, 2014, vol. 79, # 4, p. 1836 - 1841
[2] Synthesis, 2002, # 9, p. 1133 - 1135
[3] Green Chemistry, 2018, vol. 20, # 19, p. 4448 - 4452
[4] Synthesis, 2011, # 2, p. 207 - 209
[5] European Journal of Organic Chemistry, 2018, vol. 2018, # 20, p. 2592 - 2602
[6] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 743 - 748
[7] Australian Journal of Chemistry, 2005, vol. 58, # 5, p. 321 - 326
[8] RSC Advances, 2015, vol. 5, # 23, p. 18075 - 18086
[9] Journal of Organic Chemistry, 1993, vol. 58, # 11, p. 3072 - 3075
[10] Journal of Materials Chemistry C, 2014, vol. 2, # 15, p. 2674 - 2683
[11] Monatshefte fur Chemie, 2018, vol. 149, # 4, p. 791 - 799
[12] Patent: WO2018/67786, 2018, A1, . Location in patent: Page/Page column 134
[13] European Journal of Organic Chemistry, 2011, # 18, p. 3301 - 3312
[14] Journal of the American Chemical Society, 1951, vol. 73, p. 4018
[15] Journal of the American Chemical Society, 1949, vol. 71, p. 1201,1203
[16] Phosphorus, Sulfur and Silicon and the Related Elements, 1990, vol. 53, # 1-4, p. 29 - 35
[17] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1983, p. 813 - 820
[18] Journal of Materials Chemistry, 2002, vol. 12, # 9, p. 2706 - 2721
[19] Molecular Crystals and Liquid Crystals Science and Technology Section A: Molecular Crystals and Liquid Crystals, 2001, vol. 364, p. 881 - 888
[20] Molecules, 2009, vol. 14, # 3, p. 1013 - 1031
[21] Dyes and Pigments, 2013, vol. 99, # 3, p. 995 - 1003
[22] Journal of Physical Organic Chemistry, 2017, vol. 30, # 1,
[23] Molecular Crystals and Liquid Crystals, 2017, vol. 644, # 1, p. 240 - 248
[24] Molecular Crystals and Liquid Crystals, 2018, vol. 662, # 1, p. 157 - 164
With MoO4(AlCl2)2 In neat (no solvent) at 20℃; for 18 h; Green chemistry
General procedure: The Friedel-Crafts acylation of Anisole (1 g, 9.26 mmol)(Aldrich, 99.0percent) with propionyl chloride (5 equiv.)(Aldrich, 99.0percent) using the prepared MoO4(AlCl22(5 wtpercent, 10 mg) catalyst was carried out in a magneticallystirred two-necked round bottom flask fitted witha guard tube (CaCl2, activated at 150 C for 2 h. Thepresent reaction mixture stirred at room temperature up tothe completion of reaction. Reaction progress was monitoredby thin layer chromatography (TLC). After completionof the reaction, reaction mixture was filtered andsolid catalyst was separated out. The separated solid catalystcan be recycled in next attempt of Friedel-Craftsacylation reaction. The reaction mixture was washed withdichloromethane (DCM) and water, the same process wasdone triplicate and collected the organic layer. The organiclayer was then dried over anhydrous sodium sulfate andconcentrated on rotary evaporator and crude acylated productwas obtained and purified on column chromatography.
Reference：
[1] European Journal of Organic Chemistry, 2010, # 31, p. 6033 - 6037
[2] European Journal of Organic Chemistry, 2016, vol. 2016, # 18, p. 3126 - 3129
[3] Journal of Nanoscience and Nanotechnology, 2015, vol. 15, # 10, p. 8243 - 8250
[4] Journal of Heterocyclic Chemistry, 1982, vol. 19, p. 701 - 702
[5] Chemische Berichte, 1886, vol. 19, p. 1858
[6] Chemische Berichte, 1886, vol. 19, p. 3275
[7] Justus Liebigs Annalen der Chemie, 1921, vol. 424, p. 22
[8] Chemische Berichte, 1926, vol. 59, p. 2205
[9] Journal of Heterocyclic Chemistry, 2013, vol. 50, # 4, p. 891 - 898
31
[ 554-14-3 ]
[ 108-24-7 ]
[ 13679-74-8 ]
Yield
Reaction Conditions
Operation in experiment
67%
at 25 - 35℃; for 49 h;
EXAMPLE 7 5.9 g of activated clay (product of Nacalai Tesque, Inc.) and 25.5 g (0.25 moles) of acetic anhydride were introduced into a 100 ml 4-necked flask equipped with a stirrer, condenser, thermometer, and dropping funnel. 24.6 g (0.25 moles) of 2-methylthiophene was added dropwise at 25°C to 35°C over 1 hour. After the dropwise addition, the reaction was allowed to proceed at 30°C for 48 hours. After the reaction, the activated clay was separated by filtration to give a black filtrate. The filtrate was subjected to distillation to remove unreacted 2-methylthiophene, acetic anhydride, and by-product acetic acid, thus giving 23.5 g (0.17 moles) of 2-acetyl-5-methylthiophene.
Reference：
[1] Patent: EP1695972, 2006, A1, . Location in patent: Page/Page column 7
[2] Journal of the American Chemical Society, 1947, vol. 69, p. 3093,3095
[3] Journal of the American Chemical Society, 1950, vol. 72, p. 3695,3696, 3697
[4] European Journal of Organic Chemistry, 2004, # 19, p. 4003 - 4013
32
[ 554-14-3 ]
[ 2530-10-1 ]
Reference：
[1] Chemische Berichte, 1887, vol. 20, p. 1747
[2] Dyes and Pigments, 2014, vol. 106, p. 154 - 160
33
[ 554-14-3 ]
[ 124-38-9 ]
[ 1918-79-2 ]
Reference：
[1] Organic Letters, 2016, vol. 18, # 11, p. 2576 - 2579
[2] Bulletin of the Chemical Society of Japan, 2012, vol. 85, # 3, p. 369 - 371
[3] RSC Advances, 2014, vol. 4, # 26, p. 13430 - 13433
[4] Molecular Crystals and Liquid Crystals (1969-1991), 1990, vol. 193, p. 167 - 170
34
[ 554-14-3 ]
[ 1918-79-2 ]
Reference：
[1] Chemistry Letters, 1983, p. 127 - 128
[2] Journal of the American Chemical Society, 1948, vol. 70, p. 1646
[3] Journal of the American Chemical Society, 1934, vol. 56, p. 1127
[4] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
[5] Journal of the American Chemical Society, 1950, vol. 72, p. 3695,3696, 3697
[6] Journal of the American Chemical Society, 1950, vol. 72, p. 3695,3696, 3697
35
[ 554-14-3 ]
[ 108-24-7 ]
[ 1918-79-2 ]
Reference：
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 1221 - 1230
36
[ 201230-82-2 ]
[ 636-72-6 ]
[ 554-14-3 ]
[ 1918-77-0 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1998, vol. 71, # 3, p. 723 - 734
37
[ 554-14-3 ]
[ 29421-99-6 ]
Reference：
[1] Justus Liebigs Annalen der Chemie, 1934, vol. 513, p. 281,291
[2] Justus Liebigs Annalen der Chemie, 1934, vol. 513, p. 281,291
Reference：
[1] European Journal of Organic Chemistry, 2011, # 18, p. 3301 - 3312
41
[ 554-14-3 ]
[ 19432-66-7 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 2011, vol. 59, # 6, p. 797 - 798
42
[ 554-14-3 ]
[ 150-46-9 ]
[ 162607-20-7 ]
Yield
Reaction Conditions
Operation in experiment
85%
With n-butyllithium In tetrahydrofuran at 78℃;
2-methyl-thiophene 3.6g (17.3mmol) at -78°C reacted with n-butyl lithium and triethyl borate, 5-methyl-thiophen-2-yl boronic acid to 4.42g (yield: 85percent) was formed . 4.42g of 5-methyl-thiophen-2-yl boronic acid react with 5-bromo-2-iodo-benzoic acid methyl ester and 80°C by the Suzuki coupling (Suzuki coupling) 7.78g of Intermediate 1 (yield: 80 percent) it was synthesized. Intermediate 1 react with CH3MgCl by cyclization (cyclization) with the 3.14g (yield: 40percent) intermediate 2 was synthesized . intermediate 2 was reacted with 9-phenyl-anthracene boronic acid and by Suzuki coupling compound 1 (3.3g, yield: 60percent) was obtained. Compound 1 was confirmed by 1HNMR and MS.
Reference：
[1] Patent: KR2015/96594, 2015, A, . Location in patent: Paragraph 0290; 0291; 0292
43
[ 554-14-3 ]
[ 162607-20-7 ]
Reference：
[1] Patent: US6342610, 2002, B2, . Location in patent: Page column 110
[2] Chemistry - A European Journal, 2012, vol. 18, # 13, p. 4010 - 4025
[3] Organic Letters, 2012, vol. 14, # 16, p. 4266 - 4269
Reference：
[1] Canadian Journal of Chemistry, 2007, vol. 85, # 1, p. 12 - 20
[2] Journal of Molecular Structure, 2007, vol. 833, # 1-3, p. 23 - 29
[3] Acta Crystallographica Section C: Crystal Structure Communications, 2005, vol. 61, # 10, p. o599-o601
[4] Chimia, 2003, vol. 57, # 4, p. 169 - 172
[5] Tetrahedron, 2011, vol. 67, # 23, p. 4236 - 4242
[6] European Journal of Organic Chemistry, 2011, # 18, p. 3301 - 3312
[7] Journal of the American Chemical Society, 2011, vol. 133, # 42, p. 17027 - 17036
[8] Patent: US2014/191168, 2014, A1,
[9] Dyes and Pigments, 2015, vol. 115, p. 102 - 109
[10] Beilstein Journal of Organic Chemistry, 2016, vol. 12, p. 1103 - 1110
[11] Patent: CN104098555, 2017, B,
[12] Patent: CN104892588, 2017, B,
[13] Patent: CN106905312, 2017, A,
[14] Patent: CN104292234, 2017, B,
[15] Angewandte Chemie - International Edition, 2018, vol. 57, # 37, p. 12086 - 12091[16] Angew. Chem., 2018, vol. 130, p. 12262 - 12267,6
46
[ 554-14-3 ]
[ 134135-41-4 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 5, p. 743 - 748
47
[ 554-14-3 ]
[ 25015-63-8 ]
[ 476004-80-5 ]
Yield
Reaction Conditions
Operation in experiment
74%
With (iPrPNP)CoCH2SiMe3 In neat (no solvent) at 60℃; for 24 h;
EXAMPLE 9 - Borylation of Aromatic Five-Membered Heterocycle According to the reaction scheme illustrated in Figure 2(a), a scintillation vial (with a magnetic stir bar) was charged with cobalt complex (0.01 mmol) selected from 1-4, 2 methylfuran (1 mmol) and pinacolborane (1 mmol). The reaction was monitored by the analysis of an aliquot of the mixture by GC-FID. The mixture was allowed to stir to completion at room temperature and was quenched by exposure to air. The resulting solid was solubilized in CDC13, 1 ] 3 passed through a plug of silica gel in a Pasteur pipette and then analyzed by H and C NMR spectroscopy without further purification. If desired, the foregoing reaction can also be administered in 2 ml of tetrahydrofuran (THF). Figure 2(a) provides conversion percentages for cobalt complexes 1-4 with values in parenthesis as isolated yields. Further, Figure 2(b) details additional borylation products achieved with Co complexes 2 and 3 according to the foregoing reaction parameters.
Reference：
[1] Organic Letters, 2012, vol. 14, # 16, p. 4266 - 4269
[2] Patent: WO2015/89119, 2015, A1, . Location in patent: Page/Page column 34
[3] Chemistry - An Asian Journal, 2010, vol. 5, # 7, p. 1657 - 1666
[4] Tetrahedron, 2008, vol. 64, # 26, p. 6103 - 6114
[5] Organometallics, 2015, vol. 34, # 19, p. 4732 - 4740
[6] Organic Syntheses, 2005, vol. 82, p. 126 - 133
48
[ 554-14-3 ]
[ 73183-34-3 ]
[ 476004-80-5 ]
Reference：
[1] Organic Letters, 2012, vol. 14, # 16, p. 4266 - 4269
[2] Journal of the American Chemical Society, 2015, vol. 137, # 38, p. 12211 - 12214
[3] Bulletin of the Chemical Society of Japan, 2017, vol. 90, # 3, p. 332 - 342
[4] Tetrahedron Letters, 2002, vol. 43, # 32, p. 5649 - 5651
[5] Advanced Synthesis and Catalysis, 2003, vol. 345, # 9-10, p. 1103 - 1106
[6] Organic Syntheses, 2005, vol. 82, p. 126 - 133
[7] Chemical Communications, 2017, vol. 53, # 77, p. 10640 - 10643
EXAMPLE 7 5.9 g of activated clay (product of Nacalai Tesque, Inc.) and 25.5 g (0.25 moles) of acetic anhydride were introduced into a 100 ml 4-necked flask equipped with a stirrer, condenser, thermometer, and dropping funnel. 24.6 g (0.25 moles) of 2-methylthiophene was added dropwise at 25C to 35C over 1 hour. After the dropwise addition, the reaction was allowed to proceed at 30C for 48 hours. After the reaction, the activated clay was separated by filtration to give a black filtrate. The filtrate was subjected to distillation to remove unreacted 2-methylthiophene, acetic anhydride, and by-product acetic acid, thus giving 23.5 g (0.17 moles) of 2-acetyl-5-methylthiophene.
With MoO4(AlCl2)2; In neat (no solvent); at 20℃; for 18h;Green chemistry;
General procedure: The Friedel-Crafts acylation of Anisole (1 g, 9.26 mmol)(Aldrich, 99.0%) with propionyl chloride (5 equiv.)(Aldrich, 99.0%) using the prepared MoO4(AlCl22(5 wt%, 10 mg) catalyst was carried out in a magneticallystirred two-necked round bottom flask fitted witha guard tube (CaCl2, activated at 150 C for 2 h. Thepresent reaction mixture stirred at room temperature up tothe completion of reaction. Reaction progress was monitoredby thin layer chromatography (TLC). After completionof the reaction, reaction mixture was filtered andsolid catalyst was separated out. The separated solid catalystcan be recycled in next attempt of Friedel-Craftsacylation reaction. The reaction mixture was washed withdichloromethane (DCM) and water, the same process wasdone triplicate and collected the organic layer. The organiclayer was then dried over anhydrous sodium sulfate andconcentrated on rotary evaporator and crude acylated productwas obtained and purified on column chromatography.
Example 1;9 Preparation of l,2-bis(5-methylthiophen-2-yl)disulfane; Step 1 : Thiophene 1 (4.4 mL, 51 mmol) was added to a solution of ClSO2OH (10 mL, 155 mmol) in CH2Cl2 (100 mL) at O0C during 0.5 hrs. The reaction solution was stirred at this temperature for another 3 hrs. Then, the reaction mixture was poured into ice-water and extracted with CH2Cl2 twice. The organic layer was washed with brine, concentrated and 6.0 g 5-methylthiophene-2-sulfonyl chloride 2 was obtained as a light oil, yield 59.5%.
59.5%
With chlorosulfonic acid; In chloroform; at -60 - 15℃; for 3h;
Step 1 : Thiophene 1 (4.4 mL, 51 mmol) was added to a solution of ClSO2OH (10 mL, 155 mmol) in CH2Cl2 (100 mL) at 0C during 0.5 hour. The reaction solution was stirred at this temperature for another 3 hours. Then, the reaction mixture was poured into ice-water and extracted with CH2Cl2 twice. The organic layer was washed with brine, concentrated and 6.0 g 5 -methyl thiophene-2-sulfonyl chloride 2 was obtained as a light oil, yield 59.5%.
59.5%
With chlorosulfonic acid; In dichloromethane; at 0℃; for 3h;
Step 1 : Thiophene 1 (4.4 niL, 51 mmol) was added to a solution of ClSO2OH (10 niL, 155 mmol) in CH2Cl2 (100 mL) at O0C during 0.5 hr. The reaction solution was stirred at this temperature for another 3 hrs. Then, the reaction mixture was poured into ice-water and extracted with CH2Cl2 twice. The organic layer was washed with brine, concentrated and 6.0 g of 5-methylthiophene-2-sulfonyl chloride 2 was obtained as a light oil, yield 59.5%.
15%
With chlorosulfonic acid; In dichloromethane; at 0℃; for 3.5h;
2-methylthiophene (4.4 mL, 51 mmol) was added to a solution of CH2Cl2 (100 mL) containing ClSO3OH (10mL, 155 mmol) at 0 C over a period of 30 min. At this temperature, the mixture was stirred for another 3 h. The mixturewas then poured into ice water (100 mL), and extracted with CH2Cl2 (2 3 50 mL). The organic layer was collected,washed with saturated aqueous NaCl solution (100 mL), dried by sodium sulfate, and suction filtration. The resultingfiltrate was distilled under reduced pressure to give 1.5 g of the intermediate 5-methylthiophene-2-sulfonyl chloride, yield15%.
With chlorosulfonic acid; In chloroform; at -5 - 0℃; for 3h;
STEP08: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; 2-Methyl thiophene (50gm, 0.51mol) in chloroform was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform (100ml) at -50C to O0C. The reaction mixture was maintained at O0C for 3hrs and the crude reaction material was slowly dumped into ice cold water, followed by extraction with chloroform (100ml x 2). The combined extract was washed with water and brine and dried over anhydrous sodium sulphate, and evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as brown colored liquid.; STEP04: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; A solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The temperature of the reaction mixture was maintained at O0C for 3hrs. The crude reaction mass was <n="95"/>slowly dumped into ice cold water, followed by extraction with chloroform (100mlx2). The combined extract was washed with water and brine and dried over anhydrous sodium sulphate, and evaporated under vacuum to give 16gm of 5-Methyl thiophene-2-sulphonyl chloride as brown colored liquid.; STEPlO: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; A solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform was added to the solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The reaction temperature was then maintained at O0C for 3hrs. The crude reaction mass was slowly dumped into the ice cold water, followed by extraction with chloroform (100mlx2). The <n="117"/>combined extract was washed with water and brine, dried over anhydrous sodium sulphate and evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as a brown colored liquid.; STEP04: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; o oA solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform (100ml) was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The reaction mixture was maintained at O0C for 3hrs. The crude reaction mass was slowly dumped into ice cold water, followed by extraction with chloroform (100mlx2). The combined extract was washed with water and brine. Finally the organic layer was dried over anhydrous sodium sulphate, evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as a brown colored liquid.; STEP04: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; A solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The reaction mixture was maintained at O0C for 3hrs and the crude reaction mass was then slowly <n="141"/>dumped into the ice cold water, followed by extraction with chloroform (100mlx2). The combined extract was washed with water and brine. Finally the organic layer was dried over anhydrous sodium sulphate, evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as a brown colored liquid.; STEPIl: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; A solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The reaction mixture was then maintained at O0C for 3hrs. The crude reaction mass was slowly dumped into ice cold water, followed by extraction with chloroform (100ml x2). The combined extract was washed with water and brine. Finally organic layer was dried over anhydrous sodium sulphate, evaporated under vacuum to give 16gm of 5-methyl thiophene-2- sulphonyl chloride as brown colored liquid.; STEPIl: Synthesis of 5-methyl thiophene-2-sulphonyl chloride; The solution of 2-methyl ihiophene (50gm, 0.51mol) in chloroform (100ml) was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to O0C. The reaction mixture was maintained at O0C for 3hrs. The crude reaction mass was slowly dumped into the ice cold water, followed by extraction with chloroform (100mlx2). The combined extract was washed with water and brine. Finally the organic layer was dried over anhydrous sodium sulphate, evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as a brown colored liquid.; STEPIl: Synthesis of 5-methgammal thiophene-2-sulphonyl chloride; A solution of 2-methyl thiophene (50gm, 0.51mol) in chloroform was added to a solution of chloro sulphonic acid (105ml, 1.53mol) in chloroform at -50C to 0 C. The reaction mixture was then maintained at O0C for 3hrs. The crude reaction mass was slowly dumped into the ice cold water, followed by extraction with chloroform (100mlx2). The combined extract was washed with water and brine. Finally the organic layer was dried over anhydrous sodium sulphate, and evaporated under vacuum to give 16gm of 5-methyl thiophene-2-sulphonyl chloride as a brown colored liquid.; STEP09: Synthesis of...
With (iPrPNP)CoCH2SiMe3; In neat (no solvent); at 60℃; for 24h;
EXAMPLE 9 - Borylation of Aromatic Five-Membered Heterocycle According to the reaction scheme illustrated in Figure 2(a), a scintillation vial (with a magnetic stir bar) was charged with cobalt complex (0.01 mmol) selected from 1-4, 2 methylfuran (1 mmol) and pinacolborane (1 mmol). The reaction was monitored by the analysis of an aliquot of the mixture by GC-FID. The mixture was allowed to stir to completion at room temperature and was quenched by exposure to air. The resulting solid was solubilized in CDC13, 1 ] 3 passed through a plug of silica gel in a Pasteur pipette and then analyzed by H and C NMR spectroscopy without further purification. If desired, the foregoing reaction can also be administered in 2 ml of tetrahydrofuran (THF). Figure 2(a) provides conversion percentages for cobalt complexes 1-4 with values in parenthesis as isolated yields. Further, Figure 2(b) details additional borylation products achieved with Co complexes 2 and 3 according to the foregoing reaction parameters.
With PdCl(C3H5)(dppb); potassium acetate; In N,N-dimethyl acetamide; at 150℃; for 20h;Inert atmosphere;
In a typical experiment, the bromopyridine (1 mmol), heteroaromatic derivative (2 mmol), KOAc (0.196 g, 2 mmol) and PdCl(C3H5)(dppb) (6.8 mg, 0.01 mmol), were dissolved in DMAc (4 mL) under an argon atmosphere. The reaction mixture was stirred at 100 C or 150 C (see schemes) for 20 h. After evaporation of the solvent, the product was purified by silica gel column chromatography.
With NHC-Pd(II)-Im; potassium tert-butylate; copper(II) oxide; In tetrahydrofuran; at 130℃; for 12h;Inert atmosphere; Sealed tube;
General procedure: Under N2 atmosphere, NHC-Pd(II)-Im complex 1 (1.0 mol %), CuO (10.0 mol %), benzothiophene 2a (0.5 mmol), KOtBu (1.0 mmol), dry THF (2.0 mL) and chlorobenzene 3a (0.6 mmol) were successively added into a sealed tube. The mixture was stirred vigorously at 130 C for 6 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel to afford pure product 4a.
79%
With NHC-Pd(II)-Im; potassium tert-butylate; copper(II) oxide; In tetrahydrofuran; at 130℃;
General procedure: Under nitrogen, the azocycloalkane-palladium complex (16. Omg, 5. Omol%), copper oxide (4. Omg,10 · Omo 1%), potassium tert-butoxide (112.3 mg, 1 Ommo 1), dry tetrahydrofuran (2 · OmL), 2-methylthiophene (98 yL,1. Ommo 1) and chlorobenzene (52yL, 0.5 mmo 1) were added sequentially to the tube. The mixture was heated at 130 C for 12 hours. stopThe mixture was allowed to cool to room temperature and the solvent was removed by rotary evaporator. The residue was purified by flash column chromatography to give pureThe product was the yield of the product after isolation and purification.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 120℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24.0h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 percent ethyl ether in petroleum ether as eluent to provide the corresponding product.
With silver (II) carbonate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; lithium acetate; palladium diacetate; tricyclohexylphosphine; In 1,2-dimethoxyethane; at 100℃; for 24h;Schlenk technique; Inert atmosphere;
General procedure: In a glove box, a 25 mL of Schlenk tube equipped with a stir bar was charged with Pd(OAc)2 (0.03 mmol, 0.1 equiv), PCy3 (0.03 or 0.06 mmol, 0.1 or 0.2 equiv), LiOAc (0.45 mmol, 1.5 equiv) (or NaOAc), TEMPO (0.12 mmol, 0.4 equiv), Ag2CO3 (0.9 mmol, 3 equiv). The tube was fitted with a rubber septum and removed out of the glove box. DME (2 mL), propiophenone (0.9 mmol, 3.0 equiv) and thiophene (0.3 mmol, 1.0 equiv) were added in turn to the Schlenk tube through the rubber septum using syringes, and then the septum was replaced with a Teflon screwcap under nitrogen flow (if the thiophene or the substituted propiophenone was solid, it was added to the tube in the glove box). The reaction mixture was stirred at 100 oC or 120 oC for 24 h. After cooling down, the reaction mixture was diluted with 10 mL of ethyl ether, filtered through a pad of silica gel, followed by washing the pad of the silica gel with the same solvent (20 mL), concentrated under reduced pressure. The residue was then purified by flash chromatography on silica gel with 2-15 % ethyl ether in petroleum ether as eluent to provide the corresponding product.
2-methyl-thiophene 3.6g (17.3mmol) at -78°C reacted with n-butyl lithium and triethyl borate, 5-methyl-thiophen-2-yl boronic acid to 4.42g (yield: 85percent) was formed . 4.42g of 5-methyl-thiophen-2-yl boronic acid react with 5-bromo-2-iodo-benzoic acid methyl ester and 80°C by the Suzuki coupling (Suzuki coupling) 7.78g of Intermediate 1 (yield: 80 percent) it was synthesized. Intermediate 1 react with CH3MgCl by cyclization (cyclization) with the 3.14g (yield: 40percent) intermediate 2 was synthesized . intermediate 2 was reacted with 9-phenyl-anthracene boronic acid and by Suzuki coupling compound 1 (3.3g, yield: 60percent) was obtained. Compound 1 was confirmed by 1HNMR and MS.
With gold(III) chloride; In acetonitrile; at 30℃; for 8h;
General procedure: To a stirred solution of ortho-alkynylbenzaldehyde (1, 0.2 mmol) and thiophene compound (2, 1.0 mmol, 5 equiv.) in acetonitrile (2 mL) was added AuCl3 (3a, 5 mol%) at room temperature in air. The resulting mixture was warmed to 30 C. After completion of the reaction monitored by TLC analysis, generally for 8 h, the mixture was condensed and purified by flash column chromatography on silica gel (300-400 mesh) with petroleum ether/ethyl acetate as the eluent to provide the desired product 4.
With gold(III) chloride; In acetonitrile; at 30℃; for 8h;
General procedure: To a stirred solution of ortho-alkynylbenzaldehyde (1, 0.2 mmol) and thiophene compound (2, 1.0 mmol, 5 equiv.) in acetonitrile (2 mL) was added AuCl3 (3a, 5 mol%) at room temperature in air. The resulting mixture was warmed to 30 C. After completion of the reaction monitored by TLC analysis, generally for 8 h, the mixture was condensed and purified by flash column chromatography on silica gel (300-400 mesh) with petroleum ether/ethyl acetate as the eluent to provide the desired product 4.
With gold(III) chloride; In acetonitrile; at 30℃; for 8h;
General procedure: To a stirred solution of ortho-alkynylbenzaldehyde (1, 0.2 mmol) and thiophene compound (2, 1.0 mmol, 5 equiv.) in acetonitrile (2 mL) was added AuCl3 (3a, 5 mol%) at room temperature in air. The resulting mixture was warmed to 30 C. After completion of the reaction monitored by TLC analysis, generally for 8 h, the mixture was condensed and purified by flash column chromatography on silica gel (300-400 mesh) with petroleum ether/ethyl acetate as the eluent to provide the desired product 4.
With gold(III) chloride; In acetonitrile; at 30℃; for 8h;
General procedure: To a stirred solution of ortho-alkynylbenzaldehyde (1, 0.2 mmol) and thiophene compound (2, 1.0 mmol, 5 equiv.) in acetonitrile (2 mL) was added AuCl3 (3a, 5 mol%) at room temperature in air. The resulting mixture was warmed to 30 C. After completion of the reaction monitored by TLC analysis, generally for 8 h, the mixture was condensed and purified by flash column chromatography on silica gel (300-400 mesh) with petroleum ether/ethyl acetate as the eluent to provide the desired product 4.
With copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In acetonitrile; at 20℃;Green chemistry;
General procedure: To a solution of benzylamine (0.6 mmol), indole (1.0 mmol) and CuI (0.1 mmol ) in CH3CN (1 mL) was added TEMPO (0.15 mmol) under atmosphere and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc/PE = 1:4) to yield the corresponding product.
With copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In acetonitrile; at 20℃;Green chemistry;
General procedure: To a solution of benzylamine (0.6 mmol), indole (1.0 mmol) and CuI (0.1 mmol ) in CH3CN (1 mL) was added TEMPO (0.15 mmol) under atmosphere and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc/PE = 1:4) to yield the corresponding product.
With copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In acetonitrile; at 20℃;Green chemistry;
General procedure: To a solution of benzylamine (0.6 mmol), indole (1.0 mmol) and CuI (0.1 mmol ) in CH3CN (1 mL) was added TEMPO (0.15 mmol) under atmosphere and the mixture was stirred at room temperature for overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: EtOAc/PE = 1:4) to yield the corresponding product.
2,4-dichloro-5-fluoro-6-(5-methylthiophen-2-yl)pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
22%
To a solution of 2-methylthiophene (1.00 g, 10.00 mmol) in anydrous tetrahydrofuran(20 mL) was added n-butyllithium (4.10 mL, 10.0 mmol, 2.5 mol/L) at -15 C, and the mixturewas stirred for 1 h at -15 oc. Then to the mixture was addeddichloro(N,N,N,N-tetramethylethylenediamine)zinc(II) (850 mg, 3.40 mmol), and the resultingmixture was stirred for 1 h maintaining at this temperature. Then palladium dichloride ( 180 mg,1.0 mmol), triphenylphosphine (530 mg, 2.0 mmol) and <strong>[6693-08-9]2,4,6-trichloro-5-fluoropyrimidine</strong> (2.30g, 11.0 mmol) were added to the mixture in tum. The resulting mixture was heated to 55 ocunder nitrogen protection, and then stirred at this temperature overnight. To the reaction mixturewas added water (50 mL), and the resulting mixture was extracted with ethyl acetate (50 mL x 3).The combined organic layers were washed with saturated brine (50 mL), dried over anhydroussodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purifiedby silica gel column chromatography (PE) to give the title compound as a white solid (587 mg,22 %).MS (ESI, pos.ion) m/z: 262.9 [M+Ht;PCT/CN2017/1161541H NMR (400 MHz, CDCb) 8(ppm) 7.86 (dd, J = 3.7, 1.6 Hz, 1H), 6.93 (d, J = 3.7 Hz, 1H),2.61 (s, 3H).
With Co/HZSM-5; at 300℃; under 760.051 Torr;Inert atmosphere; Flow reactor;
General procedure: The reactions were carried out under atmospheric pressure in a flow setup with a fixed bed of catalyst (grain size 0.25-0.5 mm). A fresh portion of the catalyst was used in each run. The system was maintained at a constant temperature. Helium was passed from a cylinder to saturators filled with dimethyl disulfide and thiophene and maintained at a required temperature. The gas mixture was fed into the reactor heated to a required temperature. Samples of the gas mixture were withdrawn intermittently for analysis. High-boiling products were trapped in a cold receiver. The products were identified by GC/MS using an Agilent 7000 gas chromatograph coupled with a Triple Quadmass-selective detector (HP-5MS capillary column, 30 m x 0.25 mm). Quantitative analysis of the product mixtures was performed with an LKhM-8MD chromatograph equipped with a thermal conductivity detector and a 2-m x 3-mm column packed with XE-60 on Chromaton AW-LMCS; carrier gas helium. The contact time was equal to the ratio of the catalyst volume (cm3) to the gas mixture flow rate (cm3/s) at room temperature under atmospheric pressure. The conversions of thiophene and dimethyl disulfide and the yields were calculated with respect to the initial reactants and reacted substrate.
With Fe(1,2-bis(dimethylphosphino)ethane)2Cl2; sodium 2-ethylhexanoic acid; In tetrahydrofuran; at 60℃; for 48h;Inert atmosphere; Schlenk technique; Irradiation; Glovebox;
General procedure: In an argon-filled glovebox, dmpe2FeCl2 1 (8.6 mg, 0.02 mmol), sodium 2-ethylhexanoate (6.6 mg,0.04 mmol), HBpin (87 L, 0.6 mmol), substrate (0.5 mmol), and THF (1 mL) were added to a 1.7 mL sample vial and shaken to ensure full dissolution. The vial was placed under blue light radiation for 48 h and then allowed to cool to room temperature. Yields determined by 1H-NMR spectroscopy ofthe crude reaction mixtures using 1,3,5-trimethoxybenzene as an internal standard [0.5 mL; standard solution = 1,3,5-trimethoxybenzene (0.336 g, 2.0 mmol) in diethyl ether (10 mL)]. Product ratios were determined by 1H-NMR spectroscopy of the crude reaction mixtures.
Chemistry
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Material Science
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