* 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] Trans. roy. Soc. Canada, 1934, vol. <3> 28 III, p. 97,98
[2] Trans. roy. Soc. Canada, 1934, vol. <3> 28 III, p. 97,98
2
[ 100-52-7 ]
[ 696-41-3 ]
Yield
Reaction Conditions
Operation in experiment
69%
With potassium hydrogensulfate; isoquinolinium dichromate; potassium iodide In water at 20℃; Sonication
General procedure: The general method for ultrasonically assisted brominationreaction is almost similar to conventional reaction as mentionedabove. A centimolar (0.01 mol) organic substrate (phenols,anilines, or acetanilides), 0.001 mol potassium halide(KBr), about 50 mg of dilute KHSO4, and hypervalent Cr(VI) reagent (IQCC or IQDC) were suspended in about30 mL solvent (DCE or ACN) in a previously cleaned roundbottom(R.B) flask placed in a sonicator. The reaction mixtureis sonicated at room temperature about 30–40 min. Progressof the reaction was monitored by TLC technique. Workupprocedure after completion of the reaction mixture is similarto the one described previously.
Reference:
[1] Journal of Organic Chemistry, 2002, vol. 67, # 24, p. 8622 - 8624
[2] Journal of Organic Chemistry, 1990, vol. 55, # 11, p. 3552 - 3555
[3] Organic Preparations and Procedures International, 2002, vol. 34, # 6, p. 647 - 651
[4] Journal of Organic Chemistry, 1993, vol. 58, # 8, p. 2058 - 2060
[5] Russian Journal of Organic Chemistry, 2007, vol. 43, # 9, p. 1278 - 1281
[6] Synthesis, 2008, # 3, p. 401 - 404
[7] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2016, vol. 46, # 6, p. 832 - 837
[8] European Journal of Organic Chemistry, 2017, vol. 2017, # 22, p. 3234 - 3239
[9] Synthesis, 1999, # 5, p. 748 - 750
[10] Tetrahedron Letters, 2000, vol. 41, # 47, p. 9101 - 9104
[11] Synthesis, 2006, # 7, p. 1195 - 1199
[12] Russian Journal of Organic Chemistry, 2007, vol. 43, # 9, p. 1291 - 1296
[13] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1980, vol. 34, # 1, p. 47 - 52
[14] Tetrahedron, 2004, vol. 60, # 41, p. 9113 - 9119
[15] Journal of Medicinal Chemistry, 1981, vol. 24, # 5, p. 535 - 544
[16] Zhurnal Obshchei Khimii, 1953, vol. 23, p. 1022; engl. Ausg. S. 1071
[17] Journal of the Chemical Society, 1952, p. 150,152
[18] Chemical Communications (London), 1966, p. 650
[19] Russian Journal of Organic Chemistry, 2008, vol. 44, # 6, p. 935 - 936
3
[ 884507-44-2 ]
[ 696-41-3 ]
Yield
Reaction Conditions
Operation in experiment
88%
With Selectfluor In acetonitrile at 20℃; for 0.333333 h;
General procedure: To a suspension of 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (1, 0.975 mmol) in MeCN(3 mL) the amine (2, 0.75 mmol) dissolved in MeCN (3 mL) was added dropwise at r.t. The reaction was stirred at r.t. for another20 min. The solvent was evaporated, and the obtained residuewas purified via flash column chromatography using silica gel as stationary phase.
With Selectfluor In acetonitrile at 20℃; for 0.333333 h;
General procedure: To a suspension of 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (1, 0.975 mmol) in MeCN(3 mL) the amine (2, 0.75 mmol) dissolved in MeCN (3 mL) was added dropwise at r.t. The reaction was stirred at r.t. for another20 min. The solvent was evaporated, and the obtained residuewas purified via flash column chromatography using silica gel as stationary phase.
With pyridinium chlorochromate In dichloromethane at 20℃; for 2 h;
3-Iodobenzaldehyde (12) A suspension of pyridinium chlorochromate (2.45 g, 11.4 mmol) and dry celite (-2. 00 g) in dry dichloromethane (20 ml) was stirred at room temperature for 15 min. 3-Iodobenzyl alcohol (11) (1.02 g, 4.35 mmol) in dry dichloromethane (5 ml) was added. The suspension was shielded from light and stirred at room temperature for 2 h after which it was diluted with ether, and filtered through celite. The cloudy brown filtrate was concentrated to a red- brown gummy paste which was re-dissolved in dichloromethane and passed through a short silica column, eluting with dichloromethane. This gave a clear, colourless solution which was concentrated to give 3-iodobenzaldehyde (12) as a white solid (0.953 g, 95percent). 1H nmr (400 Mz, CDC13) : 67. 29 (t, J 7. 8 Hz, 1H) H5; 7.85 (brd, J 7. 8 Hz, 1H) H6; 7.96 (brd, J7. 8 Hz, 1H) H4; 8.21 (brs, 1H) H2; 9.93 (s, 1H) CHO.
80%
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide In dichloromethane; acetonitrile at 20℃; for 3 h; 4 A molecular sieves
A solution of 3-iodobenzyl alcohol (Aldrich, 4.72g, 20 mmol) in dichloromethane (50mL) and acetonitrile (5mL) was treated sequentially with 4 A molecular sieves powder (5g), tetra-n-propyl ammoniumperruthenate (0. 1 g) and N-methyl morpholine-N-oxide (2.34g, 40mmol). After stirring at ambient temperature for 3h, the reaction mixture was diluted with hexane and subjected to flash column chromatography over silica gel (230-400mesh) using 6-10percent ethyl acetate in hexane as the eluent to afford the title compound (3.7g, 80percent). It was used as such for the next step.
80%
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide In dichloromethane; acetonitrile at 20℃; for 3 h; Molecular sieve
3-Iodo-benzaldehyde; A solution of 3-iodobenzyl alcohol (Aldrich, 4.72g, 20 mmol) in dichloromethane (50mL) and acetonitrile (5mL) was treated sequentially with 4 A molecular sieves powder (5g), tetra-n-propyl ammoniumperruthenate (0. lg) and N- methyl morpholine-N-oxide (2.34g, 40mmol). After stirring at ambient temperature for 3h, the reaction mixture was diluted with hexane and subjected to flash column chromatography over silica gel (230-400mesh) using 6-10percent ethyl acetate in hexane as the eluent to afford the title compound (3.7g, 80percent). It was used as such for the next step
90 %Chromat.
With dihydrogen peroxide In water; acetonitrile for 4 h; Reflux
General procedure: In a 25 mL round-bottomed flask equipped with a reflux condenser, a mixture of 1 g PWM/SiO2(M = Cr, Mn, Fe, Co, Ni, and Cu)catalyst containing 0.03 mmol POM, 3 mL acetonitrile and 1 mmol of alcohol was added. Then 1 mL of H2O2 30percent was added and the mixture was refluxed for 2 h with stirring. The progress of the reaction was monitored by GC equipped with a flame ionization detector and a silica pack column. At the end of reaction, the catalyst was filtered out and 10 mL NaHCO3 10percent was added. The organic phase extracted with chloroform and dried. Flash chromatography on a short column of silica gel with ethyl acetate:n-hexane as eluent gave pure products.
Reference:
[1] Advanced Synthesis and Catalysis, 2004, vol. 346, # 7, p. 767 - 776
[2] Patent: WO2005/82894, 2005, A1, . Location in patent: Page/Page column 41-42
[3] Bulletin of the Chemical Society of Ethiopia, 2013, vol. 27, # 1, p. 131 - 136
[4] Bioorganic and Medicinal Chemistry Letters, 1999, vol. 9, # 20, p. 3047 - 3052
[5] Tetrahedron Asymmetry, 2001, vol. 12, # 4, p. 585 - 596
[6] European Journal of Organic Chemistry, 2008, # 19, p. 3328 - 3334
[7] Synthetic Communications, 1988, vol. 18, # 1, p. 69 - 76
[8] Patent: WO2005/58301, 2005, A1, . Location in patent: Page/Page column 78
[9] Patent: WO2005/58798, 2005, A2, . Location in patent: Page/Page column 49
[10] Journal of the American Chemical Society, 2018, vol. 140, # 28, p. 8652 - 8656
[11] Chemistry - A European Journal, 2002, vol. 8, # 9, p. 2005 - 2010
[12] Advanced Synthesis and Catalysis, 2003, vol. 345, # 12, p. 1341 - 1352
[13] Tetrahedron, 1994, vol. 50, # 28, p. 8301 - 8316
[14] International Journal of Chemical Kinetics, 1997, vol. 29, # 1, p. 9 - 16
[15] Journal of Chemical Research, Miniprint, 1998, # 9, p. 2251 - 2272
[16] Journal of the American Chemical Society, 1999, vol. 121, # 39, p. 9073 - 9087
[17] Journal of Chemical Research, 2004, # 9, p. 581 - 584
[18] Journal of the Chemical Society. Perkin Transactions 2, 2002, # 6, p. 1151 - 1157
[19] Advanced Synthesis and Catalysis, 2003, vol. 345, # 4, p. 497 - 505
[20] Patent: US2006/111394, 2006, A1, . Location in patent: Page/Page column 14-15
[21] Tetrahedron, 2009, vol. 65, # 34, p. 6805 - 6809
[22] E-Journal of Chemistry, 2011, vol. 8, # 1, p. 264 - 268
[23] Journal of Molecular Catalysis A: Chemical, 2014, vol. 392, p. 8 - 15
[24] Journal of the Iranian Chemical Society, 2016, vol. 13, # 8, p. 1463 - 1470
[25] Angewandte Chemie - International Edition, 2018, vol. 57, # 33, p. 10535 - 10539[26] Angew. Chem., 2018, vol. 130, # 33, p. 10695 - 10699,5
6
[ 625-95-6 ]
[ 696-41-3 ]
Reference:
[1] Journal of the American Chemical Society, 2002, vol. 124, # 10, p. 2245 - 2258
[2] Journal of the American Chemical Society, 2001, vol. 123, # 13, p. 3183 - 3185
[3] Journal of the Chemical Society, 1949, p. 1089,1096
Reference:
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1988, p. 1015 - 1020
[2] Bulletin of the Chemical Society of Japan, 1988, vol. 61, p. 3717 - 3722
12
[ 69113-59-3 ]
[ 696-41-3 ]
Reference:
[1] Huaxue Xuebao, 1958, vol. 24, p. 141,143[2] Chem.Abstr., 1959, p. 6134
13
[ 1711-10-0 ]
[ 696-41-3 ]
Reference:
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1980, vol. 34, # 1, p. 47 - 52
14
[ 139-02-6 ]
[ 81447-69-0 ]
[ 101-84-8 ]
[ 591-50-4 ]
[ 696-41-3 ]
Reference:
[1] Journal of the American Chemical Society, 1982, vol. 104, # 14, p. 3917 - 3923
15
[ 99-61-6 ]
[ 696-41-3 ]
Reference:
[1] Journal of the Chemical Society, 1896, vol. 69, p. 1008
16
[ 7732-18-5 ]
[ 696-41-3 ]
Reference:
[1] Journal of the Chemical Society, 1896, vol. 69, p. 1008
17
[ 696-41-3 ]
[ 108-24-7 ]
[ 41070-12-6 ]
Reference:
[1] Trans. roy. Soc. Canada, 1934, vol. <3> 28 III, p. 97
18
[ 696-41-3 ]
[ 77123-56-9 ]
Reference:
[1] Russian Chemical Bulletin, 2002, vol. 51, # 1, p. 128 - 134[2] Izvestiya Akademi Nauk, Seriya Khimicheskaya, 2002, # 1, p. 122 - 127
[3] Tetrahedron, 1998, vol. 54, # 27, p. 7721 - 7734
[4] European Journal of Medicinal Chemistry, 2016, vol. 116, p. 46 - 58
With potassium hydrogensulfate; isoquinolinium dichromate; potassium iodide; In water; at 20℃;Sonication;
General procedure: The general method for ultrasonically assisted brominationreaction is almost similar to conventional reaction as mentionedabove. A centimolar (0.01 mol) organic substrate (phenols,anilines, or acetanilides), 0.001 mol potassium halide(KBr), about 50 mg of dilute KHSO4, and hypervalent Cr(VI) reagent (IQCC or IQDC) were suspended in about30 mL solvent (DCE or ACN) in a previously cleaned roundbottom(R.B) flask placed in a sonicator. The reaction mixtureis sonicated at room temperature about 30-40 min. Progressof the reaction was monitored by TLC technique. Workupprocedure after completion of the reaction mixture is similarto the one described previously.
With iodine; In 1,2-dichloro-ethane; at 40℃;
A 25 mL two-necked round bottom flask was fitted with condenser. Initially 0.1 g substrate (0.001 mol) was added to the flask followed by 10 mL solvent. After this 0.28 g iodine (0.001 mol) was added to the same flask followed by addition of 0.02 g catalyst. The reaction was carried out at different temperatures (Table 1) for 2-6 hrs. After completion of the reaction, 5 mL water was added to the reaction flask to stop the reaction. The reaction was monitored by GC analysis.
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 2h;
3-Iodobenzaldehyde (12) A suspension of pyridinium chlorochromate (2.45 g, 11.4 mmol) and dry celite (-2. 00 g) in dry dichloromethane (20 ml) was stirred at room temperature for 15 min. 3-Iodobenzyl alcohol (11) (1.02 g, 4.35 mmol) in dry dichloromethane (5 ml) was added. The suspension was shielded from light and stirred at room temperature for 2 h after which it was diluted with ether, and filtered through celite. The cloudy brown filtrate was concentrated to a red- brown gummy paste which was re-dissolved in dichloromethane and passed through a short silica column, eluting with dichloromethane. This gave a clear, colourless solution which was concentrated to give 3-iodobenzaldehyde (12) as a white solid (0.953 g, 95%). 1H nmr (400 Mz, CDC13) : 67. 29 (t, J 7. 8 Hz, 1H) H5; 7.85 (brd, J 7. 8 Hz, 1H) H6; 7.96 (brd, J7. 8 Hz, 1H) H4; 8.21 (brs, 1H) H2; 9.93 (s, 1H) CHO.
80%
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide; In dichloromethane; acetonitrile; at 20℃; for 3h;4 A molecular sieves;
A solution of 3-iodobenzyl alcohol (Aldrich, 4.72g, 20 mmol) in dichloromethane (50mL) and acetonitrile (5mL) was treated sequentially with 4 A molecular sieves powder (5g), tetra-n-propyl ammoniumperruthenate (0. 1 g) and N-methyl morpholine-N-oxide (2.34g, 40mmol). After stirring at ambient temperature for 3h, the reaction mixture was diluted with hexane and subjected to flash column chromatography over silica gel (230-400mesh) using 6-10% ethyl acetate in hexane as the eluent to afford the title compound (3.7g, 80%). It was used as such for the next step.
80%
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide; In dichloromethane; acetonitrile; at 20℃; for 3h;Molecular sieve;
3-Iodo-benzaldehyde; A solution of 3-iodobenzyl alcohol (Aldrich, 4.72g, 20 mmol) in dichloromethane (50mL) and acetonitrile (5mL) was treated sequentially with 4 A molecular sieves powder (5g), tetra-n-propyl ammoniumperruthenate (0. lg) and N- methyl morpholine-N-oxide (2.34g, 40mmol). After stirring at ambient temperature for 3h, the reaction mixture was diluted with hexane and subjected to flash column chromatography over silica gel (230-400mesh) using 6-10% ethyl acetate in hexane as the eluent to afford the title compound (3.7g, 80%). It was used as such for the next step
To a solution of oxalyl chloride (8.72 ml, 99.33 mmol) in anhydrous methylene chloride (240 ml) at -78 C. was added anhydrous dimethyl sulfoxide (14.12 ml, 199 mmol). After stirring for 15 minutes, 3-iodobenzyl alcohol was dissolved in 50 ml anhydrous methylene chloride and added dropwise to the chilled solution via syringe over four minutes. After 30 minutes, triethylamine (41.04 ml, 295 mmol) was added and stirred at -78 C. for one hour before being warmed to 0 C. After one hour, the reaction was poured into water (1 L) and the layers separated. The aqueous layer was extracted with diethyl ether (4×150 ml) and the combined organic extracts dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Chromatography (SiO2, 300 g, 2:8 ethyl acetate/hexanes) yielded the product as an oil (26.83 g): 1H NMR (CDCl3, 300 MHz) delta 9.92 (s, 1H), 8.21 (s, 1H), 7.95 (d, 1H, J=7.0 Hz), 7.85 (d, 1H, J=7.5 Hz), 7.29 (t, 1H, J=8 Hz).
90%Chromat.
With dihydrogen peroxide; In water; acetonitrile; for 4h;Reflux;
General procedure: In a 25 mL round-bottomed flask equipped with a reflux condenser, a mixture of 1 g PWM/SiO2(M = Cr, Mn, Fe, Co, Ni, and Cu)catalyst containing 0.03 mmol POM, 3 mL acetonitrile and 1 mmol of alcohol was added. Then 1 mL of H2O2 30% was added and the mixture was refluxed for 2 h with stirring. The progress of the reaction was monitored by GC equipped with a flame ionization detector and a silica pack column. At the end of reaction, the catalyst was filtered out and 10 mL NaHCO3 10% was added. The organic phase extracted with chloroform and dried. Flash chromatography on a short column of silica gel with ethyl acetate:n-hexane as eluent gave pure products.
With dihydrogen peroxide; In water; acetonitrile; at 85℃; for 5.15h;
The typical procedure is the following: 3 mL CH3CN,0.01 mmol catalyst, and 1 mmol Benzyl alcohol were added to round-bottomed flask equipped with a reflux condenser.Then, 1 mmol aqueous H2O2 was dropwise added with in 5 min under stirring. The reaction time was counted after the addition of aqueous H2O2, and the reaction mixture was sampled periodically. The typical reaction temperature is 85 C, and reaction time is 3-7 h. The progress was monitored by TLC (EtOAc/n-hexane, 1/5). After completionof the reaction, the catalyst was separated from the product by filtration and the liquid was analyzed by a gas chromatograph.
A stirred, cooled (-78C) solution of triethylphosphonoacetate (11. 44g, 51mmol) in anhydrous tetrahydrofuran (100mL) was treated with a 1.6M solution of n-butyl lithium in hexanes (30mL, 48mmol). After 10 min, the reaction mixture was cannulated into a cooled (-78C) solution of 4-iodo- benzaldehyde (3.7g, 16mmol) in tetrahydrofuran (20mL). The reaction mixture was allowed to warm to 0C over lh. It was quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether (x2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford an oil that was subjected to flash column chromatography over silica gel (230-400mesh) using 8-10% ethyl acetate in hexane as the eluent to afford the title compound (4.6g, 95%). 'H NMR (300 MHz, CDC13) : 8 7. 83 (s, 1H), 7.65 (dd, 1H, J= 7.9, 2Hz), 7.53 (d, 1H, J= 15.8Hz), 7.43 (dd, 1H, J= 7. 6,2Hz), 7.07 (dd, 1H, J= 7. 6,7. 9Hz), 6.38 (d, 1H, J= 15.8Hz), 4.24 (q, 2H, J= 6. 9Hz), 1.34 (t, 3H, J= 6. 9Hz).
Ethyl-3-iodo-cinnamate (Reagent 6); A stirred, cooled (-78C) solution of triethylphosphonoacetate (11. 44g, 51mmol) in anhydrous tetrahydrofuran (lOOmL) was treated with a 1.6M solution of n-butyl lithium in hexanes (30mL, 48mmol). After 10 min, the reaction mixture was cannulated into a cooled (-78C) solution of 4-iodo-benzaldehyde (3.7g, 16mmol) in tetrahydrofuran (20mL). The reaction mixture was allowed to warm to 0C over 1h. It was quenched with saturated aqueous ammonium chloride solution and extracted with diethyl ether (x2). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to afford an oil that was subjected to flash column chromatography over silica gel (230-400mesh) using 8- 10% ethyl acetate in hexane as the eluent to afford the title compound (4.6g, 95%). 1H NMR (300 MHz, CDCl3) : 8 7.83 (s, 1H), 7.65 (dd, 1H, J= 7.9, 2Hz), 7.53 (d, 1H, J= 15.8Hz), 7.43 (dd, 1H, J= 7.6, 2Hz), 7. 07 (dd, 1H, J = 7.6, 7.9Hz), 6. 38 (d, 1H, J= 15.8Hz), 4.24 (q, 2H, J= 6.9Hz), 1.34 (t, 3H, J= 6.9Hz).
92%
Triethyl phosphonoacetate (9.21 g, 41.12 mmol) in tetrahydrofuran (65 mL) was treated with 2.5 M n-butyl lithium in hexanes (12.82 mL, 32.07 mmol) at -78 C. The resulting mixture was stirred for 10 min and added via a cannula to a pre-cooled solution at -78 C of <strong>[696-41-3]3-iodobenzaldehyde</strong> (4.77 g, 20.56 mmol) in tetrahydrofuran (20 mL). The resulting mixture was stirred at -78 C for 40 min and slowly warmed to ambient temperature for 45 min. The reaction was quenched with saturated aqueous NH4Cl (200 mL). The aqueous solution was extracted with diethyl ether. The resulting organic layer was dried over magnesium sulfate and evaporated. The residue was purified by silica gel chromatography (90:10 hexanes/ethyl acetate) to give 5.71 g (92%) of compound 1a as a yellow oil; 1H NMR (CDCl3) delta 1.32 (t, J = 7.1 Hz, 3H); 4.24 (q, J = 7.1 Hz, 2H); 6.39 (d, J = 16.0 Hz, 1H); 7.09 (dd, J = J' = 7.8 Hz, 1H); 7.43-7.46 (m, 1H); 7.54 (d, J = 16.0 Hz, 1H); 7.64-7.69 (m, 1H); 7.83-7.86 (m, 1H).
With hydrogenchloride; NaH; ammonium chloride; In tetrahydrofuran; ethyl acetate; mineral oil;
Example 1A ethyl (2E)-3-(3-iodophenyl)acrylate To a suspension of NaH (60% dispersion in mineral oil) (120 mg, 3.0 mmol) in THF (20 mL) was added triethyl phosphonoacetate (436 muL, 2.2 mmol) dropwise. <strong>[696-41-3]3-iodo-benzaldehyde</strong> (465 mg, 2.0 mmol) was added after the bubbling has stopped. The reaction mixture was stirred at room temperature for 15 minutes. Solid NH4Cl was added, followed by 1N HCl to quench the reaction. The mixture was taken up in ethyl acetate and water. The organic phase was washed with aqueous NaHCO3, brine, dried (MgSO4), filtered and concentrated under reduced pressure and purified by flash chromatography on silica gel with hexane/ethyl acetate (4:1) to provide the titled compound (605 mg).
With sodium hydride; In tetrahydrofuran; at 20℃; for 0.25h;
To a suspension of NaH (60% dispersion in mineral oil) (120 mg, 3.0 mmol) in THF (20 mL) was added triethyl phosphonoacetate (436 muL, 2.2 mmol) dropwise. <strong>[696-41-3]3-iodo-benzaldehyde</strong> (465 mg, 2.0 mmol) was added after the bubbling has stopped. The reaction mixture was stirred at room temperature for 15 minutes. Solid NH 4Cl was added, followed by 1N HCl to quench the reaction. The mixture was taken up in ethyl acetate and water. The organic phase was washed with aqueous NaHCO 3, brine, dried (MgSO 4), filtered and concentrated under reduced pressure and purified by flash chromatography on silica gel with hexane/ethyl acetate (4:1) to provide the titled compound (605 mg).
General procedure: A two-necked round bottom flask was dried using heat gun under reduced pressure and filled with argon. To this flask was added NaH (500 mg, 60% dispersion in mineral oil, 12.5 mmol, 1.25 eq) and the flask was evacuated and refilled with argon (×3). To the flask was added THF (25 mL) and the suspension was cooled to 0 C, then triethyl phosphonoacetate (2.5 mL, 12.5 mmol, 1.25 eq) was carefully added (CAUTION: evolution of H2 gas). The resultant mixture was stirred for 30 min at 0 C and then 4-chlorobenzaldehyde (1.41 g, 10 mmol, 1.0 eq) was added at the same temperature. The reaction was stirred for additional 1 h at 0 C and then quenched with saturated aq. NaHCO3 followed by extraction with Et2O (×3). Combined organic layer was washed with brine (×1), dried over Na2SO4 and filtered. Volatiles were removed under reduced pressure and the residue was purified by flash column chromatography on silica gel (eluent: hexane/EtOAc 10:1) to afford the title compound as a colorless oil in 78% yield (1.63 g).
With potassium phosphate;palladium diacetate; In N,N-dimethyl acetamide; at 140℃; for 24h;
A 10 mL Schenk tube was dried in oven and loaded under N2 with K3PO4 (2.37 g,11.16 mmol) and DMA (2.0 mL). 3-iodobenzaldeide (1.85 g, 7.97 mmol) and n- butylacrylate (2.28 mL, 15.94 mmol) were then added by syringe. A solution of EPO <DP n="27"/>Pd(OAc)2 (0.18 g, 0.797 mmol) in DMA (0.5 mL) was further added by syringe. The Schlenk tube was then sealed under nitrogen and placed in a pre-heated oil bath at 140 0C, and the reaction mixture was stirred for 24 h. After cooling to room temperature, the reaction mixture was poured in water (50 mL) and extracted with ethyl acetate (3 x 50 mL). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated under vacuum to dryness. The crude product was purified by chromatographic column on silica gel, eluting with n- hexane/ethylacetate/methanol 12/3/1 (yield: 47%). 1H NMR (CDCI3) delta: 0.91-0.96 (t, 3H, OCH2CH2CH2CH3), 1.39-1.42 (m, 2H, OCH2CH2CH2CH3), 1.65-1.68 (m, 2H, OCH2CH2CH2CH3), 4.17-4.21 (m, 2H, OCH2CH2CH2CH3), 6.48-6.53 (d, 1 H, ArCH=CHCO), 7.52-7.54 (m, 1 H, benzene H-5), 7.53-7.75 (m, 2H, ArCH=CHCO and benzene H-6), 7.84-7.86 (m, 1 H, benzene H-4), 7.99 (m, 1 H, benzene H-2), 10.01 (s, 1 H1 CHO).
With copper(l) iodide; triethylamine;bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; at 20℃; for 2h;
1.14. a 3-[2-(6-Benzyloxy-pyridazin-3-yl)-ethynyl]-benzaldehydeA solution of 3.12 g (13.45 mmol) <strong>[696-41-3]3-iodo-benzaldehyde</strong> in 100 ml dry THF is degassed as described in example 1111. a. 625 mg (0.89 mmol) bis-(triphenylphosphin)-palladium-ll-chloride and 170 mg (0.89 mmol) copper iodide are added and the reaction mixture is degassed again. Then 3.39 g (16.13 mmol) 3-benzyloxy-6-ethynyl-pyridazine and 5.27 ml (37.84 mmol) triethylamine are added and the mixture is stirred for 2 hours at room temperature. The mixture is poured onto water and extracted with dichloromethane. The organic layer is dried over sodium sulphate and concentrated. The residue is purified by silica gel column chromatography with petrolether/ethyl acetate (1 :1 ) as eluent. The solid is washed with diisopropylether and dried. Yield: 2.26 g (54 % of theory), Ci0Hi4N2O2 <n="78"/>EII Mass spectrum: m/z = 315 [M+H]+
With ammonium acetate In ethanol Heating / reflux;
(+-)-3-Amino-3-(3-iodo-phenyl)-propionic acid (20)
Malonic acid (2.2 g, 21.5 mmol) and 3-iodobenzaldehyde (5 g, 21.5 mmol) were suspended in ethanol (50 mL) and ammonium acetate (1.66 g, 21.5 mmol) was added and the reaction heated to a reflux overnight. The reaction was cooled to room temperature filtered and washed with ethanol followed by ether and dried to afford the product (3.4 g, 11.6 mmol, 54%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.80 (s, 1H), 7.64 (dd, J=7.8 Hz, 1H), 7.42 (dd, J=7.6 Hz, 1H), 7.16 (dd, J=7.8 Hz, 1H), 7.14 (dd, J=7.6 Hz, 1H), 4.21 (m, 1H), 2.36 (m, 2H).
Step 1) 1-(3-Iodo-phenyl)-pent-4-en-1-ol To a stirred solution of <strong>[696-41-3]3-iodo-benzaldehyde</strong> (3.0 g, 12.93 mmol) in dry THF (45 mL) at -78 C. under nitrogen was added 0.5 M 3-butenyl magnesium bromide in THF (25.86 mL, 12.93 mmol) over 20 min. The reaction was stirred for 0.5 h and allowed to warm to -30 C. over 1 h and then quenched with sat ammonium chloride (20 mL). The reaction was diluted with water (10 mL) and then extracted with ethyl acetate (2*50 mL). The extracts were dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (5% to 10% ethyl acetate/petroleum ether) gave the title compound as a clear oil (3.5 g, 95%) and was used directly in the next step.
With potassium carbonate In ethanol; water at 50℃; for 19h;
95%
With potassium carbonate; palladium dichloride; 1-butyl-2-(diphenylphosphanyl)-3-methylimidazolium hexafluorophosphate In water at 60℃; for 24h; Sonication;
4.2. General procedure for performing of Suzuki coupling reaction
General procedure: PdCl2 (0.01 mmol, 2 mg)was dissolved in 1 mL distilledwater bysonication and 0.1mL of resulting solution was added to a 5 mLflask containing 3 (0.4 mmol, 129 mg) and H2O (1 mL), and themixture stirred for 1 h at room temperature. Then, aryl halide(0.5 mmol), arylboronic acid (0.75 mmol), K2CO3 (0.75 mmol) wereadded and the reaction mixture was stirred at 60 C, for ArI, and80 C for aryl bromides. Progress of the reactions were monitoredby GC. Afterwards, crude product was extracted using ethyl acetateor n-hexane (3x5 mL) and further purified by column or platechromatography.
90%
With C30H32N4O12P2Pd; potassium carbonate In ethanol; water at 20℃; for 24h;
2.2. General procedure for conducting Suzuki-Miyaura coupling reaction
General procedure: Aryl halide (0.5 mmol), arylboronic acid (0.75 mmol), K2CO3 (0.75mmol), and the Pd(L8)2 catalyst (0.65 mol%) were added to a 5 ml flaskcontaining a mixture of solvents (H2O:EtOH with 1:1 ratio, 2 mL). Thereaction mixture was stirred at R.T. for aryl iodides and aryl bromidesand 80 C for aryl chloride for 24 h. The progress of the coupling reactionwas monitored by GC. Then, the crude product was extractedusing ethyl acetate (3 × 5 mL). The products were purified using columnand plate chromatography on silica gel.
18 %Chromat.
With potassium hydroxide In methanol at 50℃; for 20h;
With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 1h;
To a stirred solution of <strong>[696-41-3]3-iodobenzaldehyde</strong> (200 mg, 0.862 mmol) in dry CH2Cl2 (10 mL)was added pyrrolidine (61.3 mg, 0.862 mmol). After 10 mins, sodium triacetoxyborohydride (190 mg, 0.90 mmol) was added and the reaction mixture was stirred at room temperature for1 h, then it was washed with saturated sodium bicarbonate solution, dried, and concentratedin vacuo. The crude was filtered through an isolute SCX-2 cartridge to give the titlecompound (205 mg, 83%);
55%
Reference Example 134 1-(3-iodobenzyl)pyrrolidine To pyrrolidine (0.2 mL) in methanol (10 mL) was added a solution of <strong>[696-41-3]3-iodobenzaldehyde</strong> (565 mg) in tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for 12 hr. Sodium borohydride (109 mg) was added at 0 C., and the mixture was stirred at room temperature for 2 hr, and concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. 1 mol/L Hydrochloric acid was added to the extract, and the aqueous layer was washed with ethyl acetate. The obtained aqueous layer was basified with 1 mol/L aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a yellow oil (382 mg, yield 55%). 1H-NMR (CDCl3) delta: 1.76-1.82 (4H, m), 2.46-2.51 (4H, m), 3.54 (2H, s), 7.03 (1H, t, J=7.5 Hz), 7.27-7.30 (1H, m), 7.55-7.58 (1H, m), 7.69-7.70 (1H, m).
Reference Example 136 tert-butyl ({4-(2-fluorophenyl)-5-[(3-formylphenyl)thio]-1,3-thiazol-2-yl}methyl)methylcarbamate To a solution of 2-ethylhexyl 3-[2-[(tert-butoxycarbonyl)(methyl)amino]methyl}-4-(2-fluorophenyl)-1,3-thiazol-5-yl]thio}propanoate (749 mg) in ethanol (10 mL) was added sodium ethoxide (381 mg) at 0 C., and the mixture was stirred at room temperature for 4 hr, and concentrated under reduced pressure. A mixture of the residue, <strong>[696-41-3]3-iodobenzaldehyde</strong> (489 mg), tris(dibenzylideneacetone)dipalladium(0) (35 mg) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthine (81 mg) in toluene (10 mL) was stirred at 80 C. for 3 hr. The reaction mixture was allowed to cool to room temperature, water was added, and the mixture was extracted with ethyl acetate. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=4:1) to give the title compound as a yellow oil (676 mg, yield quantitative). 1H-NMR (CDCl3) delta: 1.47 (9H, brs), 3.00 (3H, brs), 4.69 (2H, brs), 7.10-7.20 (3H, m), 7.34-7.50 (3H, m), 7.65-7.68 (2H, m), 9.90 (1H, s).
With Selectfluor; In acetonitrile; at 20℃; for 0.333333h;
General procedure: To a suspension of 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (1, 0.975 mmol) in MeCN(3 mL) the amine (2, 0.75 mmol) dissolved in MeCN (3 mL) was added dropwise at r.t. The reaction was stirred at r.t. for another20 min. The solvent was evaporated, and the obtained residuewas purified via flash column chromatography using silica gel as stationary phase.
With Selectfluor; In acetonitrile; at 20℃; for 0.333333h;
General procedure: To a suspension of 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane ditetrafluoroborate (1, 0.975 mmol) in MeCN(3 mL) the amine (2, 0.75 mmol) dissolved in MeCN (3 mL) was added dropwise at r.t. The reaction was stirred at r.t. for another20 min. The solvent was evaporated, and the obtained residuewas purified via flash column chromatography using silica gel as stationary phase.
With bis-triphenylphosphine-palladium(II) chloride; copper(l) iodide; triethylamine; In tetrahydrofuran; at 20℃; for 9h;Inert atmosphere;
To a mixture of compound 1 (326 mg, 2.5 mmol), compound 214 (582 mg, 2.5 mmol), and PdCl2(PPh3)2 (37 mg, 0.05 mmol) in a flame-dried Schlenk tube were added THF (15 mL) and Et3N (5 mL) under argon atmosphere and followed by the addition of CuI (10 mg, 0.05 mmol) 10 min later. The mixture was stirred at room temperature for 9 h and then water (20 mL) and brine (20 mL) were added. After being extracted with ethyl acetate (3×30 mL), the combined organic phase was washed with brine and dried over sodium sulfate. Upon removal of the solvent under reduced pressure, the resulting residue was purified by column chromatography (petroleum ether/dichloromethane 1:1) to give compound 3 as a pale yellow solid (487 mg, 83%). Mp 77-78 C. 1H NMR (300 MHz, CDCl3): delta 7.49 (t, J=7.2 Hz, 1H), 7.54-7.64 (m, 2H), 7.67 (d, J=7.5 Hz, 1H), 7.81 (d, J=7.5 Hz, 1H), 7.90 (d, J=7.5 Hz, 1H), 7.96 (d, J=7.5 Hz, 1H), 8.07 (s, 1H), 10.03 (s, 1H), 10.63 (s, 1H). 13C NMR (100 MHz, CDCl3): delta 86.4, 94.5, 123.6, 126.0, 127.6, 129.1, 129.3, 129.7, 132.9, 133.4, 133.9, 135.9, 136.6, 137.1, 191.3, 191.3. MS (EI): m/z 234 [M]+. HRMS (EI): calcd for C16H10O2 [M]+: 234.0681, found 234.0687. IR (KBr, cm-1): 3064, 2834, 2732, 2208, 1703, 1591, 1284, 1200.
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 0 - 20℃; for 1.66667h;
14.4: (3-iodo-benzyl)-dimethyl-amine To a cold (0C) solution of <strong>[696-41-3]3-iodo-benzaldehyde</strong> (3g, 12.9 mmol) in anhydrous dichloromethane (130 ml) were added acetic acid (1.9ml) and N,N-dimethylacetamide. The yellow solution is stirred 10 minutes at 0C and sodium triacetoxyborohydride (6.85g, 32.33 mmoles) is added by portions. The resulting mixture is stirred at room temperature for 90 minutes and evaporated to dryness under reduced pressure. Ethyl acetate and a saturated aqueous hydrogen carbonate solution were added to the residue and the two layers were separated The organic phase was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to yield (3-iodo-benzyl)-dimethyl-amine (3.05g, 90%) as a brown oil. LC/MS (Method LC8): Rt = 0.86 min; m/z = 262 [M+H]+.
90%
14.4: (3-iodo-benzyl)-dimethyl-amineTo a cold (0C) solution of <strong>[696-41-3]3-iodo-benzaldehyde</strong> (3g, 12.9 mmol) in anhydrous di- chloromethane (130 ml) were added acetic acid (1 .9ml) and N,N-dimethylacetamide. The yellow solution is stirred 10 minutes at 0C and sodium triacetoxyborohydride (6.85g, 32.33 mmoles) is added by portions. The resulting mixture is stirred at room temperature for 90 minutes and evaporated to dryness under reduced pressure. Ethyl acetate and a saturated aqueous hydrogen carbonate solution were added to the residue and the two layers were separated The organic phase was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to yield (3-iodo-benzyl)-dimethyl-amine (3.05g, 90%) as a brown oil.LC/MS (Method LC8): Rt = 0.86 min; m/z = 262 [M+H]+.
14.4: (3-iodo-benzyl)-dimethyl-amine To a cold (0 C.) solution of <strong>[696-41-3]3-iodo-benzaldehyde</strong> (3 g, 12.9 mmol) in anhydrous dichloromethane (130 ml) were added acetic acid (1.9 ml) and N,N-dimethylacetamide. The yellow solution is stirred 10 minutes at 0 C. and sodium triacetoxyborohydride (6.85 g, 32.33 mmoles) is added by portions. The resulting mixture is stirred at room temperature for 90 minutes and evaporated to dryness under reduced pressure. Ethyl acetate and a saturated aqueous hydrogen carbonate solution were added to the residue and the two layers were separated The organic phase was washed with water, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum to yield (3-iodo-benzyl)-dimethyl-amine (3.05 g, 90%) as a brown oil. LC/MS (Method LC8): Rt=0.86 min; m/z=262 [M+H]+.
6 EXAMPLE 6
To an aryl iodide substrate (0.2 mmol) were added a CuC2F5 solution prepared as described in Example 5(0.35 mL; 1.2 equiv) and 1,3-bis(trifluoromethyl)benzene (internal standard; 15.5 mL). This mixture was kept at 23°C or50°C or first at 23°C and then at 50°C for a certain period of time. The conversions of the CuC2F5 and yields of thecorresponding pentafluoroethylated products were determined by quantitative 19F NMR analysis. Conversion of thestarting aryl iodide was determined by GC-MS. See Table 1 for specifics.
99 %Spectr.
With triethylamine tris(hydrogen fluoride) at 23 - 50℃; for 34h; Inert atmosphere; Sealed tube;
With dmap; ammonium acetate; In ethanol; at 40℃; for 1h;
General procedure: A mixture of an aldehyde (1) (1.0 equiv), 2-aminobenzophenone (2) (1.0equiv), NH4OAc (3) (2.0 equiv), and DMAP (0.2 equiv.) in absolute EtOH (5 ml)was stirred at 40 C for the stipulated period of time (see Tables 2 and 3). Aftercompletion of the reaction, as monitored by TLC, the mixture was poured intoice-cold H2O and the solid product was filtered, washed with H2O (3-5 mL) anddried. The crude product was recrystallized from EtOAc to give puredihydroquinazolines. For compounds 4c, 4g, 4m, and 4p, after cooling, H2Owas added and the product was extracted with EtOAc (3 15 mL). Thecombined organic extract was washed with H2O, dried (anhyd Na2SO4) and thesolvent removed followed by flash column chromatography over silica gel (60-120 mesh) to furnish the desired product.
General procedure: Triton B (40% in MeOH, 7.30 mL, 17.5 mmol) was added dropwise to a solution of ethyl 2-[bis(2-isopropylphenoxy) phosphoryl]acetate (5.30 g, 13.1 mmol) in THF (150 mL) at -78 C under Ar. After 15 min of stirring, a solution of 2-methylbenzaldehyde (59) (1.50 g, 12.5 mmol) in THF (50 mL) was added dropwise to the solution. After 10 h of stirring, the mixture was quenched with satd. aq. NH4Cl (30 mL) and extracted with EtOAc (3 x 30 mL). The organic layer was washed successively with H2O, satd. aq. (20 mL) NaHCO3 (20 mL) and brine (20 mL), then dried (MgSO4), filtered and concentratedin vacuo.; Z-selective olefination of <strong>[696-41-3]3-iodobenzaldehyde</strong> (87) was performedusing the procedure described above to provide (Z)-ethyl3-(3-iodophenyl)acrylate (cis-143) (94%, Z:E = 98:2, determinedby 1H-NMR spectrum) (silica gel CC, EtOAc/hexane, 5:95) as acolorless oil: 1H-NMR (CDCl3, 270 MHz) d: 1.26 (t, J = 7.2 Hz, 3H,-CH3), 4.19 (q, J = 7.2 Hz, 2H, -CH2-), 5.98 (d, J = 12.6 Hz, 1H,CH-CO2-), 6.85 (d, J = 12.6 Hz, 1H, Ar-CH), 7.10 (t, J = 7.8 Hz,1H, Ar-H), 7.53, 7.66 (d, J = 7.8 Hz, each 1H, Ar-H), 7.90 (s, 1H,Ar-H).
With hydroxylamine hydrochloride; caesium carbonate; In water; dimethyl sulfoxide; at 125℃; for 48h;
General procedure: Aldehyde (0.5mmol), NH2OH·HCl (0.6mmol) and Cs2CO3 (0.6mmol) were stirred at 125C for 48h in a 3:1 mixture of DMSO-H2O (2mL) under air. The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent. After completion, the reaction mixture was cooled to room temperature and treated with water (1mL). The resulting mixture was extracted with ethyl acetate (3×5mL). Drying (Na2SO4) and evaporation of the solvent gave a residue that was purified on silica gel column chromatography using ethyl acetate and hexane. The purified products were identified by 1H NMR spectra and the melting points comparison with the literature data.
General procedure: A mixture of 2-acetyl-5-chlorothiophene (0.01 mol) and substituted benzaldehyde (0.01 mol) wasdissolved in methanol (20 mL). A catalytic amount of NaOH was added to the solution dropwise withvigorous stirring. The reaction mixture was stirred for about 3-4 h at room temperature. The resultantcrude products were filtered, wash successively with distilled water and recrystallized from ethanol to get the corresponding chalcone. Crystals suitable for X-ray diffraction studies were obtained by the slowevaporation technique using a suitable solvent.
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 9h;Inert atmosphere;
General procedure: To a 10 mL glass tube aryl halide (1 mmol), K4FeCN6(0.6 mmol,220 mg), K2CO3(1.5 mmol, 207 mg), catalyst (10 mg), and 2 mL DMFwere added and mixture was stirred for appropriate reaction timeat 120C under argon atmosphere. The progress of the reactionwas monitored by GC analysis. After completion of the reaction,reaction mixture was washed with 5 mL water and crude productwas isolated using dichloromethane (5× 1 mL). Organic extractswere combined together, evaporated and purified by flash chro-matography using hexane/EtOAc to give the desired aryl cyanideproducts.
92%Chromat.
With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 9h;Inert atmosphere;
General procedure: To a 10 mL glass tube aryl halide (1 mmol), K4FeCN6(0.6 mmol,220 mg), K2CO3(1.5 mmol, 207 mg), catalyst (10 mg), and 2 mL DMFwere added and mixture was stirred for appropriate reaction timeat 120C under argon atmosphere. The progress of the reactionwas monitored by GC analysis. After completion of the reaction,reaction mixture was washed with 5 mL water and crude productwas isolated using dichloromethane (5× 1 mL). Organic extractswere combined together, evaporated and purified by flash chro-matography using hexane/EtOAc to give the desired aryl cyanideproducts.
With sulfated anatase titania; In neat (no solvent); at 20℃; for 0.05h;Green chemistry;
General procedure: A mixture of 1 mmol of benzaldehyde and 2 mmol of indole with 100 mg of TiO2-SO42-were mixed and ground in a pestle and mortar at room temperature. The progress of the reaction was monitored by TLC. After completion of there action, ethyl acetate was added to the mixture and agitated.The catalyst was filtered off and washed with ethylacetate and the washings were combined. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated under vacuum. Product was obtained as thick viscous oil, which on standing solidified as pink solid. The structure of product obtained was confirmed by1H NMR,13C NMR, and GC-MS analysis.
60%
With BiCl3-loaded montmorillonite K10; In neat (no solvent); at 20℃; for 0.0666667h;Green chemistry;
General procedure: BiCl3-MK10 catalyst (0.1 g) was added to a mixture of indole (2 mmol) and aldehyde (1 mmol), and the mixture was ground in a mortar with a pestle at room temperature. After completion of the reaction (tested by thin-layer chromatography, TLC), ethyl acetate was added and the insoluble catalyst was removed by filtration. The filtrate was dried over anhydrous Na2SO4. The solvent was evaporated under vacuum to furnish the product. All the products were characterized by GC-MS, and selected compounds were characterized by 1H and 13C NMR. NMR data for three representative compounds are given below.
With water; palladium diacetate; potassium carbonate; at 20℃; under 760.051 Torr; for 5h;
General procedure: A 25-mL flask was charged with Pd(OAc)2 (1.2 mg, 0.005 mmol), 1-iodo-4-nitrobenzene (1a, 127.0 mg, 0.5 mmol), K2CO3 (141.0 mg, 1.0 mmol), H2O (0.5 mL), and PEG 400 (2.0 mL); the flask was subjected to standard cycles (3 ×) of evacuation and back-filling with dry and pure CO. The mixture was stirred at r.t. for the indicated time. The mixture was poured into sat. aq NaCl (15 mL), acidified to pH 3 with 3 M aq HCl, and extracted with EtOAc (3 × 15 mL). The solvent was removed from the combined organic phases on a rotary evaporator. The crude product was purified by column chromatography (silica gel, PE?EtOAc?HCO2H, 25:1:1) to afford 2a as a light yellow solid; yield: 75mg (90percent); mp 238.0?239.3 °C. 1H NMR (400 MHz, DMSO-d6): delta = 13.68 (br s, 1 H), 8.30 (d, J = 8.0 Hz,2 H), 8.14 (d, J = 8.0 Hz, 2 H). 13C NMR (100 MHz, DMSO-d6): delta = 165.9, 150.0, 136.4, 130.7, 123.8.
With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 100℃; for 0.166667h; Microwave irradiation;
L Intermediate L: Preparation of 3-(1H-imidazol-1-yl)benzaldehyde
[00248] To a solution of 3-iodobenzaldehyde (300 mg, 1.29 mmol) in DMF (3 mL) was added lH-imidazole (0.13 g, 1.94 mmol), CS2CO3 (1.26 g, 3.87 mmol) and copper(I) iodide (0.05 g, 0.26 mmol). The reaction mixture was heated to 100 °C and stirred at that temperature for 10 min under microwave irradiation. Water was added to the reaction vessel and the resulting biphasic mixture was transferred to a separatory funnel. The aqueous was washed with EtOAc (3 x 30 mL). The combined organics were dried over anhydrous Na2S04, filtered and concentrated in vacuo. The resulting oil was purified by flash column chromatography to provide 3-(lH-imidazol-l-yl)benzaldehyde (100 mg, 0.58 mmol) as a brown oil . LC/MS [M+H]+ = 173.2.
With diethylamino-sulfur trifluoride; In dichloromethane; at -78 - 20℃; for 18h;
(A) A stirred solution of <strong>[696-41-3]3-iodobenzaldehyde</strong> (25.0 g, 108.2 mmol, 1.0 eq) in DCM (400 ml) was cooled to -78 C and treated with DAST (57.0 ml, 432.9 mmol, 4.0 eq) in a dropwise manner. The RM was maintained at -78 C for 2 h, allowed to warm to RT and stirred for 16 h. The RM was quenched with cold water (100 ml), adjusted to a basic pH with sat. aq. NaHC03 and extracted with DCM (200 ml x 3). The combined organic layers were washed with water (300 ml x 2) and brine (300ml), dried (Na2S0 ), filtered and concentrated. The residue upon purification by flash chromatography (silica gel; PE - EtOAc; 100:0 to 95:5) afforded 1 -(difluoromethyl)-3-iodobenzene (23.0 g, 85%).
82.5%
With diethylamino-sulfur trifluoride; In dichloromethane; at 0 - 23℃; for 19h;
DAST (27mL, 172.41 mmol) was added to a solution of 3-lodo benzaldehyde (lOg, 43.l0mmol) in DCM (l5OmL) at 0C over a period of 10 mm. The RM was warmed to RT and stirred for 19 h.The RM was carefully quenched into ice water and extracted with DCM (2x1 5OmL).The combined organic layer waswashed with sat. NaHCO3 solution, water(lOOmL), brine(lOOmL), dried over Na2SO4 and concentrated toget crude. The crude compound was purified by CC (0-5% EtOAc in PE) to obtain 9.Og (82.5%) of 1-(difluoromethyl)-3-iodobenzene as yellow oil.
74%
With (bis-(2-methoxyethyl)amino)sulfur trufluoride; at 20℃;
The mixture of <strong>[696-41-3]3-iodobenzaldehyde</strong> (1, 4.00 g, 17.2 mmol) in Deoxo-Fluor (12 mL) was stirred at room temperature overnight. Then it was diluted with dichloromethane (150 mL) followed by dropwise addition of 10% aqueous solution of potassium carbonate (200 mL) at 0 C. Phases were separated; organic layer was dried over anhydrous sodium sul- fate, filtered and evaporated. The residue was subjected to flash column chromatog- raphy (Silicagel 60, 0.040-0.063 mm; eluent: cyclohexane) to afford l-(difluoromethyl)- 3-iodobenzene (2) as colorless oil. Yield : 3.22 g (74%). RF (Si02, cyclohexane) : 0.50. *H NMR spectrum (300 MHz, CDCI3, deltaEta) : 7.89-7.85 (m, 1 H); 7.85-7.79 (m, 1 H); 7.52- 7.46 (m, 1 H); 7.24-7.17 (m, 1 H); 6.59 (t, J = 56.2 Hz, 1 H).
With C31H28ClN4Pd; potassium tert-butylate; In ethanol; at 20℃;
General procedure: In a reaction tube, 1-iodo-3-methylbenzene (0.5mmol, 1equiv), (4-methoxyl phenyl)boronic acid (0.75mmol, 1.5equiv) and KOtBu (1mmol, 2equiv) were dissolved in 3mL anhydrous EtOH. The reaction mixture was stirred at ambient temperature and monitored by TLC. After completion, 10 mL water was added to the resulting mixture, then it was extracted with ethyl acetate (3×10mL). The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (petroleum ether as the eluent) to obtain the desired product.
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In N,N-dimethyl-formamide at 150℃; Inert atmosphere;
1 5.1.1 Synthesis of biphenyl-3-carbaldehyde derivatives (7)
General procedure: 2-Methoxyphenylboronic acid 6 (1.2mmol), Pd(PPh3)4 (0.1mmol) and Na2CO3 (1.5mmol) were added to a solution of benzaldehyde 5 (1.0mmol) in DMF (20ml). The mixture was stirred for overnight at 150°C. After cooling down to room temperature, the reaction mixture was quenched with saturated NaHCO3 and then extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated. The residue was purified by column chromatography on silica gel (Hexane:Ether=10:1) to obtain desired product 7 in 64-98% yields.
7-hydroxy-2-(3-iodophenyl)-4H-chromen-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
61.5%
General procedure: As outlined in Schemes 1 and 2, under anhydrous andanaerobic conditions, ZnCl2 (0.05 mol) was added to themixture of resorcinol (0.1 mol) and chloroacetonitrile (0.12mol) in diethyl ether (50 mL) cooled to 0C. The mixturewas reacted with anhydrous hydrogen chloride gas for 12hours. Intermediate compound 1, chrysin derivatives 2-5were synthesized according to Scheme 2. The Baker-VenKataraman reaction was employed in the synthesis ofchrysin derivatives [31]. 2, 4-dihydroxybenzoyl chloride (86mmol) was obtained after recrystallization with water. 2-Iodobenzaldehyde, <strong>[696-41-3]3-iodobenzaldehyde</strong>, 2-fluorine-5-iodobenzaldehyde or 3-iodo-4,5-dimethoxy benzaldehyde(12 mmol) and 10% NaOH (20 mL) were added to a solutionof compound 1 (10 mmol) in alcohol (5 mL). The mixturewas stirred at room temperature for 72 hours. Then the solutionwas acidified with 10% aqueous HCl to pH= 7 andstirred for another 48 hours at room temperature. The crudeproduce was purified by column chromatography (ethylacetate/ petroleum ether = 1:1) to get products, compound2: 7-hydroxy-2-(2-iodophenyl)-4H-chromen-4-one yielded62.7%, compound 3: 7-hydroxy-2-(3-iodophenyl)-4Hchromen-4-one yielded 61.5%, compound 4: 2- (2-fluoro-5-iodo- phenyl)-7-hydroxy-4H-chromen-4-one yielded 60.8%,compound 5:7-hydroxy-2-(3- iodo-4,5-di- methoxyphenyl)-4H-chromen-4-one yielded 62.3%. All compounds were yellow products.
61.5%
General procedure: Synthesis of iodo-chrysin derivatives was accomplishedfollowing the general methods shown in Schemes 1 and 2.As outlined in Schemes 1 and 2, under anhydrous andanaerobic conditions, ZnCl2 (0.05 mol) was added to themixture of resorcinol (0.1 mol) and chloroacetonitrile (0.12mol) in diethyl ether (50 mL) cooled to 0C. The mixturewas reacted with anhydrous hydrogen chloride gas for 12hours. Intermediate compound 1, chrysin derivatives 2-5were synthesized according to Scheme 2. The Baker-VenKataraman reaction was employed in the synthesis ofchrysin derivatives [31]. 2, 4-dihydroxybenzoyl chloride (86mmol) was obtained after recrystallization with water. 2-Iodobenzaldehyde, <strong>[696-41-3]3-iodobenzaldehyde</strong>, 2-fluorine-5-iodobenzaldehyde or 3-iodo-4,5-dimethoxy benzaldehyde(12 mmol) and 10% NaOH (20 mL) were added to a solutionof compound 1 (10 mmol) in alcohol (5 mL). The mixturewas stirred at room temperature for 72 hours. Then the solutionwas acidified with 10% aqueous HCl to pH= 7 andstirred for another 48 hours at room temperature. The crudeproduce was purified by column chromatography (ethylacetate/ petroleum ether = 1:1) to get products, compound2: 7-hydroxy-2-(2-iodophenyl)-4H-chromen-4-one yielded62.7%, compound 3: 7-hydroxy-2-(3-iodophenyl)-4Hchromen-4-one yielded 61.5%, compound 4: 2- (2-fluoro-5-iodo- phenyl)-7-hydroxy-4H-chromen-4-one yielded 60.8%,compound 5:7-hydroxy-2-(3- iodo-4,5-di- methoxyphenyl)-4H-chromen-4-one yielded 62.3%. All compounds were yellowproducts.
With di-mu-iodobis(tri-t-butylphosphino)dipalladium(l); N-ethyl-N,N-diisopropylamine; In toluene; at 100℃; for 15h;Inert atmosphere; Sealed tube; Glovebox;
General procedure: Aryl iodide 3 (0.2 mmol, 1.0 equiv), acrylate/styrene 4 (0.202 mmol, 1.01 equiv), DIPEA (28.4 mg, 0.22 mmol, 1.1 equiv), and Pd(I)-iodo dimer 2 (1.3 mg, 0.0015 mmol, 0.75 mol%) were weighed into a 4 mL screw cap vial, purged with argon, and dissolved in anhydrous toluene(1.5 mL). The vial was capped with a PTFE-lined screw cap and sealed with PTFE tape prior to heating to 100 C under stirring by using an aluminum heating block outside the glovebox. After 15 h, the reaction mixture was allowed to cool to r.t. and diluted with EtOAc (to 20 mL); excess base was quenched by the addition of sat. aq NH4Cl (20 mL). The organic phase was separated and the aqueous layer was extracted with EtOAc (2*20 mL). The combined organic layer was dried over MgSO4 and the solvent was removed under reduced pressure. The obtained crude product was purified by flash column chromatography.
With triethylsilane; palladium diacetate; sodium hydrogencarbonate; sodium carbonate; at 20℃; under 760.051 Torr; for 48h;
General procedure: A flask was charged with aryl iodide 1 (0.5 mmol), Pd(OAc)2 (2.4 mg, 0.01mmol), Na2CO3 (53.1 mg. 0.5 mmol), NaHCO3 (42.0 mg, 0.5 mmol), and PEG-400 (2 g) beforestandard cycles evacuation and backfilling with dry and pure carbon monoxide. Triethylsilane(162.8 mul, 1.0 mmol) was added successively. Then, the mixture was stirred at room temperaturefor the indicated time. At the end of the reaction, the reaction mixture was extracted with diethylether (3 × 10 mL). The organic phases were combined, and the volatile components wereevaporated under reduced pressure. The crude product was purified by column chromatography onsilica gel (petroleum ether / diethyl ether).
2,2-difluoro-1-(3-iodophenyl)-2-(phenylsulfonyl)ethan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
General procedure: In the glove box, zinc powder (206.0 mg, 3.15 mmol) was added into a Schlenk tube. Anhydrous DMF (10.5 mL) was added and the mixture was stirred at room temperature. Chlorotrimethylsilane (66.5 muL, 0.52 mmol) was then added into the mixture to activate zinc powder. Five minutes later, PhSO2CF2Br (2) (2.1 mmol) was added into the suspension. The reaction proceeded smoothly in 15 min to give (phenylsulfonyl)difluoromethylzinc reagent (?XZnCF2SO2Ph?, 3). The mixture was kept at room temperature to precipitate the remaining zinc powder, and the solution was directly used for next step. In the glove box, 2-naphthaldehyde (156.2 mg, 1.0 mmol) was added into another Schlenk tube. Anhydrous DMF (5 mL) was added and the mixture was stirred at room temperature. The DMF solution of ?XZnCF2SO2Ph? (3) (10 mL, corresponding to the reaction of ca. 2.0 mmol of PhSO2CF2Br and ca. 3.0 mmol of zinc powder) was added to the solution of 2-naphthaldehyde dropwise. The mixture was stirred at room temperature for 5 h, and aqueous HCl (2 M, 10 mL) was added to quench the reaction. After extraction with ethyl acetate for three times, the organic phase was washed with brine, and then dried over anhydrous Na2SO4. After the solution was filtered and evaporated under vacuum, the residue was subjected to silica gel column chromatography (eluting with petroleum ether/ethyl acetate) to give the corresponding difluoromethylated carbinol 4a as a white solid (307.5 mg, 88%).
With sodium metabisulfite In N,N-dimethyl-formamide Reflux;
4 * Preparation of intermediates 3-13-A
A mixture of 3-iodobenzaldehyde (4.64,20 mmol), N-methyl-o-phenylenediamine (2.44,20 mmol), sodium metabisulfite (5.73 g, 30 mmol) and dimethylformamide 200ML was added to the reaction flask,Heated to reflux overnight. Cooling, the reaction solution into 500ML cold water, keep stirring, a solid precipitation. Rinse with ethanol and rinse with petroleum ether and finally dry to give 3-13-A (3.91 g, 80%).
80%
With sodium metabisulfite In N,N-dimethyl-formamide Reflux;
1 Preparation of Intermediate 3-1-A
3-Iodobenzaldehyde (4.64, 20 mmol), N-methyl-o-phenylenediamine (2.44, 20 mmol), sodium metabisulfite(5.73 g, 30 mmol), dimethylformamide 200 mL was added to the reaction flask and heated to reflux overnight. Cool, pour the reaction solutionInto the 500ML cold water, stirring constantly, a solid precipitation. Rinse first with ethanol, then with petroleum ether, and finally dry to give 3-1-A(3.91 g, 80%).
With copper(l) iodide; di-tert-butyl peroxide; In ethyl acetate; at 120℃;
General procedure: Benzaldehyde (1.0 mmol), TMTD (1.1 mmol), CuI (10 mol%), and DTBP (4.0 equiv) were added to a dried sealed tube equipped with a septum and magnetic stirrer bar, EtOAc (2 mL) was then added. (Caution. The sealed tube is a pressure-proof tube with a septum.) The mixture was stirred at 120 C and checked by thin-layer chromatography (TLC) until the starting material was consumed (ca. 7-8 h). The reaction was cooled to r.t., quenched with sat. NH4Cl solution (5 mL), and then extracted with EtOAc (3 × 10 mL). The crude solution was dried over anhydrous Na2SO4 and evaporated under vacuum. The residue was purified by flash column chromatography to afford the desired product.
diethyl (3-chlorophenylamino)(3-iodophenyl)methylphosphonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
With sodium dithionite; In dimethyl sulfoxide; at 120℃;
General procedure: Typical procedure for one-pot synthesis of alpha-aminophosphonates: A mixture of nitro compound (1.0 mmol), aldehyde (1.0 mmol), DEP (1.0 mmol), and sodium dithionite (1.0 mmol) in DMSO (1.0 mL) were stirred at 120 C for the appropriate amount of time (3-4 h). After completion of the reaction as indicated by the TLC and LCMS, the reaction mixture was poured into water (5 mL), and then extracted with ethyl acetate (2 10 mL). The combined organic extracts were washed with saturated brine solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by recrystallization from diethyl ether (solid products) or purified by column chromatography using silica gel (100-200 mesh size) and eluting with hexane/ethyl acetate of increasing polarity to obtain the pure compound. When the above reaction was performed with 5-nitrobenzofuran (entry 16 in Table 2), the double bond between 2 and 3 carbons gets reduced by the sodium dithionite.
With copper diacetate; sodium carbonate; In toluene; at 110℃; for 12h;
100ml three-necked flaskM-iodobenzaldehyde(10.8mmol, 2.51g),Benzoquinone hydrochloride(21.6mmol, 3.80g), Na2CO3 (21.6 mmol, 2.2 g),Cu(OAc) 2 (1.08 mmol, 0.21 g),The molar ratio is charged at 1:2:2:0.1.The solvent was chosen to be 50 g of toluene.The reaction was controlled to stir at 110 C for 12 h.filter,Washed,Recrystallization from absolute ethanol,The obtained cake was vacuum dried to obtain a product of 4.05 g.The yield was 86%.
With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; In 2,2,2-trifluoroethanol; water; at 100℃; for 12h;Inert atmosphere;
0.2 mmol of <strong>[696-41-3]3-iodobenzaldehyde</strong>,0.4 mmol amidating reagent, 0.01 mmol [RhCp*Cl2]2 0.04mmol silver hexafluoroantimonate,0.4mmol water, 1mL trifluoroethanol was added to a 10mL reaction tube, argon purged, sealed and reacted at 100 C for 12h, cooled to room temperature, filtered through diatomaceous earth, distilled under reduced pressure, and purified to obtain a yellow solid-like compound ( 6), the yield is 70%.
ethyl 1-(2-(3-iodobenzoyl)-4-methoxyphenyl)-4-methyl-5-phenyl-1H-pyrazole-3-carboxylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With tert.-butylhydroperoxide; palladium(II) trifluoroacetate; In 1,2-dichloro-ethane; at 100℃; for 12h;Inert atmosphere;
General procedure: A mixture of substrate 1g (100.9 mg, 0.3 mmol), 2 (0.6 mmol), Pd(TFA)2 (10.0 mg, 10 mol%), TBHP (67.6 mg, 2.5 equiv) in DCE (2.0 mL) was charged in a glass sealed-tube and stirred under N2 atmosphere at 100 0C for 12 h. Upon completion of the reaction, saturated brine (15 mL) and dichloromethane (15 mL) were added to the mixture, then the aqueous layer was extracted with dichloromethane (15 mL × 2). The combined organic layer was dried over anhydrous MgSO4. Finally, the solution was concentrated in vacuo to provide a crude product, which was further purified via a column chromatography on silica gel (eluents: petroleum ether/ethyl acetate = 10:1) to supply the product 4.
With (1,2-dimethoxyethane)dichloronickel(II); N,N,N,N,-tetramethylethylenediamine; (4,4'-di-tert-butyl-2,2'-dipyridyl)-bis-(2-phenylpyridine(-1H))-iridium(III) hexafluorophosphate; water; N-ethyl-N,N-diisopropylamine; In dimethyl sulfoxide; at 80℃; under 760.051 Torr; for 24h;Schlenk technique; Sealed tube; Irradiation;
General procedure: Aryl-halide (0.2 mmol, 1 equiv.), Ir(dtbbpy)(ppy)2PF6 (1.8 mg, 0.002 mmol, 1 mol %), NiCl2.glyme (4.4mg, 0.02 mmol, 10 mol %), DMSO (2.0 mL) was added to a 10 mL schlenk flask equipped with a magnetic stirrer bar. This resulting mixture was sealed and degassed via vacuum evacuation and subsequent backfill with ethylene for three times. Then, N,N,N?,N?-tetramethylethylenediamine, TMEDA(60 muL, 2 equiv.), N,N-diisopropylethylamine, DIPEA (70 muL, 2 equiv.) and H2O (7.2 muL, 2 equiv.) were subsequently added in this order. The mixture was then irradiated with blue LED (2 meter strip, 18 W)with ethylene balloon for 24 hours at 80oC (Figure S1). The reaction was added water (30 mL) and extracted with ethyl acetate (10 mL) three times. Combined organic layer was successively washed with brine three times and dried over Na2SO4 and concentrated under reduced pressure. The residue was then subjected to flash column chromatography (hexane or hexane/ethyl acetate) to yield theproduct
3-[[dimethyl(oxo)-λ6-sulfanylidene]amino]benzaldehyde[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
With (1,2-dimethoxyethane)dichloronickel(II); [4,4′-bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis{3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-κN]phenyl-κC}iridium(III) hexafluorophosphate; triethylamine; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 29℃; for 16h; Irradiation; chemoselective reaction;
General Procedure
General procedure: Ir[dF(CF3)ppy]2(dtbpy))PF6(5.6 mg, 4.99 µmol) was added to a stirred solution of aryl iodide (1.00 mmol), iminodimethyl-λ6-sulfanone (102 mg, 1.10 mmol), 4,4'-di-tert-butyl-2,2'-bipyridine (20 mg, 0.07 mmol), TEA (0.279 mL, 2.00 mmol) and NiCl2(glyme) (11 mg, 0.05 mmol) in acetonitrile (5.6 mL). The resulting mixture was irradiated with a blue LED (450 nm, Penn Optical Photoreactor m1) and stirred at 29 °C for 16 hours. The reaction mixture was quenched with saturated aqueous NaHCO3(2 mL) and extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure.The resulting residue was purified by flash silica chromatography to afford the corresponding products.
With 4,4'-dimethyl-2,2'-bipyridines; 1,2-bis(diphenylphosphino)ethane nickel(II) chloride; methylphenylsilane; acetic anhydride; In tetrahydrofuran; at 60℃; for 8h;Schlenk technique; Inert atmosphere;
In a dry 10mL Schlenk reaction tube, add 3-iodobenzoic acid (124mg, 0.50mmol), and then add L3 (9mg, 0.050mmol), NiCl2 (dppe) (9.6mg, 0.025mmol) in order, under the protection of argon, THF (1.0 mL) was added,Acetic anhydride (95 muL, 1 mmol), H2SiMePh (76 muL, 0.55 mmol),Reaction at 60 C for 8h.After the reaction is completed, extraction is performed, and the solvent is removed under reduced pressure.Column chromatography (petroleum ether / ethyl acetate = 13/1, volume ratio) gave the target product C.Experimental data of the compound Experimental data of the compound:White solid, isolated yield 78%,
1-iodo-3-[(Z)-2-phenyl-2-(phenylsulfonyl)ethenyl]benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
47%
With diethyl chlorophosphate; lithium hexamethyldisilazane In tetrahydrofuran at -78 - 0℃; for 2h; Inert atmosphere;
One-Shot Synthesis of Ethenyl Sulfone 1a from Benzyl Sulfone (representative).
General procedure: To a 50 mL of two-neck round-bottomed flask charged with a magnetic stirrer bar were addedbenzyl sulfone (279 mg, 1.2 mmol) in dehydrated THF (12 mL), benzaldehyde (106 mg, 1.0 mmol)and diethyl chlorophosphate (207 mg, 1.2 mmol). A solution of lithium bis(trimethylsilyl)amide (1.3M in THF, 1.7 mL, 2.2 mmol) was added dropwise at -78 °C, and the mixture was stirred at -78 °C for 1 h and at 0 °C for additional 1 h. The reaction mixture was quenched with 5 mL of saturatedNH4Cl aq., and the organic and aqueous layers were separated. The organic layer was extracted withEtOAc, and combined organic layer was washed with water and brine. The organic layer was driedover MgSO4, and the solvents were removed under reduced pressure. The crude product wassubjected to a flash chromatography (EtOAc/CH2Cl2/hexane, 1:1:8) and recrystallization (MeOH) toafford the desired ethenyl sulfone 1a (181 mg) in 56% yield.
(E)-2-(3-iodophenyl)-1-phenyl-1-phenylsulfonylethene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
Stage #1: Benzyl phenyl sulfone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.166667h;
Stage #2: m-iodobenzaldehyde In tetrahydrofuran at -78℃; for 0.5h;
Stage #3: With diethyl chlorophosphate In tetrahydrofuran at -78℃; for 1h;
(E)-1,2-Diphenyl-1-phenylsulfonylethene (2a);[18a] Typical Procedure
General procedure: To benzyl sulfone (232 mg, 1.0 mmol) in THF (8.0 mL) was added LiHMDS (1.3 M in THF, 0.81 mL, 1.05 mmol) at -78 °C, and the mixture was stirred for 10 min. To the solution was added benzaldehyde (127 mg, 1.2 mmol), and the mixture was stirred for 30 min. Diethyl chlorophosphate (207 mg, 1.2 mmol) was added, and the mixture was stirred for 1 h. Then, LiHMDS (1.3 M in THF, 0.92 mL, 1.2 mmol) was added at -78 °C, and the mixture was stirred at r.t. for 1 h. To this mixture were added EtOAc (20 mL) and sat. aq NH4Cl (20 mL), and the organic and aqueous layers were separated. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with H2O and brine. The organic layer was dried (MgSO4) and evaporated. The crude product was subjected to column chromatography on silica gel (hexane/EtOAc 8:2) and to recrystallization (MeOH) to afford 2a as a white solid;
With potassium phosphate; palladium diacetate; XPhos In N,N-dimethyl-formamide at 70℃; for 16h;
10 3-((3-(Dimethylphosphoryl)phenyl)amino)benzaldehyde
A solution of (3-aminophenyl)dimethylphosphine oxide (100 mg, 0.59 mmol), 3- iodobenzaldehyde (165 mg, 0.71 mmol), Pd(OAc)2(6.6 mg, 0.03 mmol), Xantphos (17 mg, 0.03 mmol), and K3PO4 (150 mg, 0.71 mmol) in DMF (2 mL) stirred at 70°C for 16 h. The reaction mixture was then concentrated under reduced pressure, and purified by silica gel column chromatography (eluting petroleum ether/EtOAc = 4/1) to give the title compound as a white solid (50 mg, 26.4%).