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Structure of 402-31-3 * 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.
Reference：
[1] Journal of Organic Chemistry USSR (English Translation), 1991, vol. 27, # 1.2, p. 108 - 112[2] Zhurnal Organicheskoi Khimii, 1991, vol. 27, # 1, p. 125 - 129
[3] Journal of the American Chemical Society, 1948, vol. 70, p. 1317
[4] Journal of the American Chemical Society, 1949, vol. 71, p. 1490
[5] Patent: US4351975, 1982, A,
7
[ 402-31-3 ]
[ 328-70-1 ]
Yield
Reaction Conditions
Operation in experiment
80%
at 0 - 10℃; for 4 h;
EXAMPLE 1 1,3-Bis(trifluoromethyl)benzene (1 kg) was added to concentrated sulphuric acid (4 kg).The mixture was agitated and cooled to 5° C. DBDMH (668 g) was added over 4 hours keeping the temperature between 0° C. and 10° C. The mixture was allowed to separate and the organic phase washed with water and a dilute solution of sodium bisulphite.The product was fractionally distilled to give 3,5-bis(trifluoromethyl)bromobenzene 1100 g (80percent) of 99percent purity.
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 9, p. 3695 - 3698
[2] Journal of Organic Chemistry USSR (English Translation), 1991, vol. 27, # 1.2, p. 108 - 112[3] Zhurnal Organicheskoi Khimii, 1991, vol. 27, # 1, p. 125 - 129
[4] Tetrahedron Letters, 1998, vol. 39, # 52, p. 9621 - 9622
[5] Synlett, 1999, # 8, p. 1245 - 1246
[6] Patent: US2004/19243, 2004, A1, . Location in patent: Page 3
[7] Chemistry - A European Journal, 2012, vol. 18, # 52, p. 16938 - 16946
[8] Journal of the American Chemical Society, 1950, vol. 72, p. 1651
[9] Bulletin de la Societe Chimique de France, 1962, p. 587 - 593
8
[ 402-31-3 ]
[ 328-70-1 ]
Reference：
[1] Patent: US6350915, 2002, B1, . Location in patent: Example 1
[2] Chemische Berichte, 1996, vol. 129, # 2, p. 233 - 235
9
[ 109-65-9 ]
[ 402-31-3 ]
[ 328-70-1 ]
[ 118527-30-3 ]
[ 327-75-3 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[2] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[3] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
Reference：
[1] Journal of Organic Chemistry, 2003, vol. 68, # 9, p. 3695 - 3698
12
[ 402-31-3 ]
[ 328-73-4 ]
Reference：
[1] Journal of the Chemical Society - Perkin Transactions 1, 1996, # 14, p. 1659 - 1664
[2] Journal of the American Chemical Society, 1953, vol. 75, p. 4967
[3] Organic Letters, 2013, vol. 15, # 1, p. 140 - 143
13
[ 402-31-3 ]
[ 28186-62-1 ]
[ 328-73-4 ]
Reference：
[1] Journal of Fluorine Chemistry, 1992, vol. 57, p. 307 - 321
14
[ 402-31-3 ]
[ 454-92-2 ]
[ 328-73-4 ]
Reference：
[1] Journal of Fluorine Chemistry, 1992, vol. 57, p. 307 - 321
15
[ 109-65-9 ]
[ 402-31-3 ]
[ 328-70-1 ]
[ 118527-30-3 ]
[ 327-75-3 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[2] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[3] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
16
[ 402-31-3 ]
[ 327-75-3 ]
Reference：
[1] Journal of Fluorine Chemistry, 2002, vol. 117, # 2, p. 167 - 172
17
[ 109-65-9 ]
[ 402-31-3 ]
[ 328-70-1 ]
[ 118527-30-3 ]
[ 327-75-3 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[2] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[3] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
18
[ 402-31-3 ]
[ 88444-81-9 ]
Reference：
[1] Bulletin of the Chemical Society of Japan, 1988, vol. 61, # 5, p. 1625 - 1632
[2] Journal of Fluorine Chemistry, 1983, vol. 23, p. 497
Reference：
[1] Chemistry - A European Journal, 2017, vol. 23, # 24, p. 5663 - 5667
[2] Advanced Synthesis and Catalysis, 2010, vol. 352, # 10, p. 1662 - 1666
[3] Organometallics, 2010, vol. 29, # 13, p. 3019 - 3026
[4] Organometallics, 2010, vol. 29, # 13, p. 3019 - 3026
[5] Journal of the American Chemical Society, 2015, vol. 137, # 15, p. 5193 - 5198
[6] Journal of the American Chemical Society, 2014, vol. 136, # 10, p. 4003 - 4011
[7] Chemical Communications, 2015, vol. 51, # 100, p. 17662 - 17665
[8] Dalton Transactions, 2015, vol. 44, # 29, p. 13007 - 13016
[9] Journal of the American Chemical Society, 2005, vol. 127, # 41, p. 14263 - 14278
[10] Organic Letters, 2007, vol. 9, # 5, p. 757 - 760
[11] Journal of the American Chemical Society, 2007, vol. 129, # 50, p. 15434 - 15435
[12] Synlett, 2009, # 1, p. 147 - 150
[13] Tetrahedron Letters, 2009, vol. 50, # 45, p. 6176 - 6179
[14] Organic Letters, 2010, vol. 12, # 24, p. 5700 - 5703
[15] Angewandte Chemie - International Edition, 2012, vol. 51, # 15, p. 3642 - 3645
[16] Angewandte Chemie - International Edition, 2013, vol. 52, # 3, p. 933 - 937[17] Angew. Chem., 2012, vol. 125, # 3, p. 967 - 971,5
[18] Organic Letters, 2013, vol. 15, # 1, p. 140 - 143
[19] Journal of Organic Chemistry, 2017, vol. 82, # 19, p. 10070 - 10076
21
[ 402-31-3 ]
[ 25015-63-8 ]
[ 69807-91-6 ]
Yield
Reaction Conditions
Operation in experiment
58%
Stage #1: at 20℃; for 1 h; Schlenk technique; Inert atmosphere Stage #2: at 120℃; for 16 h; Schlenk technique; Inert atmosphere
General procedure: [RuCl2(p-cymene)]2 (2.3 mg, 3.8 μmol) and TpMe2K (2.5 mg, 7.5 μmol)were placed in a resealable Schlenk tube. The tube was evacuated,backfilled with dinitrogen and then charged with the arene 2 (5 mmol).After stirring the mixture at room temperature for 1 h, pinacolborane(1; 36 μL, 0.25 mmol) was added. The reaction mixture was thenstirred at 120 °C for 16 h. After the reaction, the mixture was analysedby GC and GC−MS. The volatile material was removed in vacuo, andthe residue was purified by Kugelrohr distillation.
Reference：
[1] Dalton Transactions, 2015, vol. 44, # 29, p. 13007 - 13016
[2] Organic and Biomolecular Chemistry, 2015, vol. 13, # 41, p. 10336 - 10340
[3] Organic letters, 2001, vol. 3, # 18, p. 2831 - 2833
[4] Journal of the American Chemical Society, 2000, vol. 122, # 51, p. 12868 - 12869
[5] Journal of the American Chemical Society, 2000, vol. 122, # 51, p. 12868 - 12869
[6] Bulletin of the Chemical Society of Japan, 2006, vol. 79, # 12, p. 1980 - 1982
[7] Journal of the American Chemical Society, 2000, vol. 122, # 51, p. 12868 - 12869
[8] Journal of Chemical Research, 2016, vol. 40, # 7, p. 393 - 396
[9] Advanced Synthesis and Catalysis, 2004, vol. 346, # 13-15, p. 1655 - 1660
[10] Patent: US2004/30197, 2004, A1, . Location in patent: Page 21
[11] Bulletin of the Chemical Society of Japan, 2006, vol. 79, # 12, p. 1980 - 1982
EXAMPLE 3 STR6 130 parts of chlorosulfonic acid are introduced, at room temperature, into a reaction vessel, and 42.8 parts of 1,3-bis-(trifluoromethyl)-benzene and 2 parts of iodine are added. The suspension is cooled to 0 and 30 parts of chlorine are introduced in the course of 5 hours at 0 to 5. The suspension is then poured out onto ice and the organic phase is separated from the aqueous phase. The organic phase is washed neutral with ice-cold water and is dried over calcined sodium sulfate. 38 parts of 5-chloro-1,3-bis-(trifluoromethyl)-benzene, of boiling point 111 to 112, are obtained. Analysis for chlorine - calculated: 14.28%, found: 14.02%. Analysis for fluorine - calculated: 45.8%, found: 45.4%.
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; sulfuric acid In acetic acid at 45℃; for 4h;
93%
With sulfur tetrafluoride; hydrogen fluoride; bromine at 120℃; for 12h;
84%
With N-Bromosuccinimide; sulfuric acid In trifluoroacetic acid for 51h; Ambient temperature;
84%
With N-Bromosuccinimide; sulfuric acid; trifluoroacetic acid at 25℃; for 51h;
80%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; sulfuric acid at 0 - 10℃; for 4h;
1 EXAMPLE 1
EXAMPLE 1 1,3-Bis(trifluoromethyl)benzene (1 kg) was added to concentrated sulphuric acid (4 kg).The mixture was agitated and cooled to 5° C. DBDMH (668 g) was added over 4 hours keeping the temperature between 0° C. and 10° C. The mixture was allowed to separate and the organic phase washed with water and a dilute solution of sodium bisulphite.The product was fractionally distilled to give 3,5-bis(trifluoromethyl)bromobenzene 1100 g (80%) of 99% purity.
72%
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; sulfuric acid; acetic acid In water at 5 - 45℃; for 4h;
With antimonypentachloride; bromine; chlorine at 125℃;
2.g EXAMPLE 2
g. 0.3% of 1,3-bis-(trifluoromethyl)-benzene. 48 g (which corresponds to a yield of 67.3%, based on the hydrogen fluoride employed) of 1-trichloromethyl-3-trifluoromethyl-benzene are obtained by fractional distillation of the reaction mixture.
Stage #1: 1,3-bis(trifluoromethyl)benzene With potassium <i>tert</i>-butylate; methyllithium In tetrahydrofuran at -78℃; for 3h; Inert atmosphere; Schlenk technique; Glovebox;
Stage #2: With iodine at 20℃; Inert atmosphere; Schlenk technique;
78%
With n-butyllithium; potassium <i>tert</i>-butylate; iodine In tetrahydrofuran at -75℃; for 2h;
50%
Stage #1: 1,3-bis(trifluoromethyl)benzene With n-butyllithium In tetrahydrofuran; hexane at -40℃; for 1h;
Stage #2: With zirconocene dichloride; 1,2-Diiodoethane In tetrahydrofuran; hexane at -80℃; for 2.5h; regioselective reaction;
General procedure: [RuCl2(p-cymene)]2 (2.3 mg, 3.8 mumol) and TpMe2K (2.5 mg, 7.5 mumol)were placed in a resealable Schlenk tube. The tube was evacuated,backfilled with dinitrogen and then charged with the arene 2 (5 mmol).After stirring the mixture at room temperature for 1 h, pinacolborane(1; 36 muL, 0.25 mmol) was added. The reaction mixture was thenstirred at 120 C for 16 h. After the reaction, the mixture was analysedby GC and GC-MS. The volatile material was removed in vacuo, andthe residue was purified by Kugelrohr distillation.
1,2-bis(dimethylphosphanyl)ethane; at 150℃; for 3.5h;
3,5-Bis(trifluoromethyl)phenol was synthesiszed as follows. The general process was applied to 1,3-bis(trifluoromethyl)benzene (214 mg, 1.0 mmol). The borylation step was carried out neat with HBPin (200 mg, 1.55 mmol, 1.55 equiv.) and dmpe (3.0 mg, 0.02 mmol, 2 mol %) at 150 C. for 3.5 hours. The oxidation step was then performed as described above, afterwhich the crude material was dissolved in CH2Cl2 and passed through a plug of silica gel. Evaporation of solvent gave 218 mg material containing 189 mg of the phenol (82%), 4 mg CH2Cl2 and 25 mg acetone. Passing through prepGC at 120 C. afforded the analytically pure product as a colorless oil. 1HNMR (300 MHz, CDCl3): delta7.44 (brs, 1 H), 7.25 (brs, 2 H), 5.23 (s, 1 H); 13CNMR (125 MHz, CDCl3): delta156.2, 133.2 (q, J=33 Hz), 123.0 (q, J=273 Hz), 115.9, 114.7 (sept, J=34 Hz); IR (neat): 3613, 3443, 1464, 1387, 1281, 1177, 1134, 939 cm-1. LRMS: m/e 230 (M+), 211, 210, 180, 161, 132, 113; HRMS: anal. calcd for C8H4F6O: 230.0166; found 230.0165. Previous preparation was two steps from 1,3-bis(trifluoromethyl)benzene in 45% yield, (Porwisiak and Schlosser, Chem. Ber. 129: 233-5 (1996).
[3,5-bis(trifluoromethyl)phenyl]triethylsilane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; tert-butylethylene; 3,4,7,8-Tetramethyl-o-phenanthrolin In cyclohexane at 100℃; for 4h; Inert atmosphere; Sealed tube; chemoselective reaction;
38 % Chromat.
With (hydridotris(3,5-dimethylpyrazolyl)borate)PtMe2H at 200℃; for 48h;
> 98 %Spectr.
With bis(norbornadiene)rhodium(l)tetrafluoroborate; 1,2-bis((2R,5R)-2,5-diisopropylphospholano)ethane; cyclohexene In neat (no solvent) at 80℃; for 20h; Inert atmosphere; regioselective reaction;
With hydrogenchloride; sodium hydroxide; iodine; sodium sulfite; In methanol; hexane; dichloromethane;
3-Iodo-5-Trifluoromethylbenzoic Acid The title product was prepared according to the literature procedure (Fujiki, Kanji; Kashiwagi, Mitsuyoshi; Miyamoto, Hideyuki; Sonoda, Akinari; Ichikawa, Junji; et al J. Fluorine Chem. 1992, 57, 307-321) from 3,5-bis(trifluoromethyl)benzene (7.3 mL, 47 mmol) and iodine (11.95 g, 47 mmol) in 30% oleum (30 mL) at 55 degrees for 15h. Quenching with ice was followed by extraction of the crude product into ether, sequential washing of the aqueous layer with sodium sulfite (1M) and water. Sodium hydroxide (!N, ~150 mL) was added to the crude ether solution until pH basic, the layers were separated and the aqueous layer was then acidified using HCl (12N, ~10 mL, pH acidic). Extraction into ether followed by drying over magnesium sulfate yielded the crude acid (4.3 g, 29%). The material was insufficiently pure for use, so the product was esterified using acetyl chloride in methanol, purified using flash chromatography (silica gel, 20% dichloromethane in hexane) and hydrolyzed with sodium hydroxide in methanol yielding 2.95 g (69%) of pure 3-iodo-5-Trifluoromethylbenzoic acid.
49 EXAMPLE 49
EXAMPLE 49 In this example a two-step, one-pot protocol for the synthesis of a biaryl from an arene, a borane, and a halogenated aromatic is demonstrated. An arylboronate ester is first generated using an Ir catalyst, and is then subsequently coupled to the halogenated aromatic using a palladium catalyst. To a small Schlenk tube equipped with a stir bar, in a glove box, was added HBPin (224 mg, 1.75 mmol) to mixture of 1,3-bis(trifluoromethyl)benzene (250 mg, 1.17 mmol), Ir(COD)(Indenyl) (9.7 mg, 0.023 mmol), and dppe (9.3 mg, 0.23 mmol). The tube was sealed and heated at 100° C. for 6 h. The reaction solution was allowed to cool to room temperature and Pd(PPh3)4 (27.0 mg, 0.234 mmol), iodobenzene (217 mg, 1.06 mmol), Ba(OH)2.8H2O (552 mg, 1.75 mmol), and toluene (10 mL) were added. The mixture was stirred at 90-95° C. for 16.5h. The mixture was allowed to cool, additional Ba(OH)2.8H2O (200 mg, 0.634 mmol) was added, and the solution stirred for 2 h at 90-95° C. Solvent was removed by rotary evaporation and the crude material subjected to column chromatography eluding with hexanes. 3,5-Bis(Trifluoromethyl)biphenyl was obtained (46 mg, 15%) as a colorless oil.
With hydrogen sulfide;palladium; In quinoline; water; toluene;
Example 1 60 g of freshly distilled quinoline and 10 g of sulfur were refluxed for 5 hours with stirring. The cooled mixture was diluted with 700 ml of toluene. This gave a solution of a quinoline-sulfur complex containing 100 mg of the complex per ml. 2.5 g of 5percent palladium on barium sulfate, 0.25 ml of the solution of the complex and 250 g of 3,5-bis(trifluoromethyl)benzoyl chloride were placed in a reaction vessel at room temperature with exclusion of water. A gentle stream of hydrogen gas was then passed through the mixture at atmospheric pressure. The mixture was subsequently heated to 100-110° C. and hydrogen gas was continuously introduced at atmospheric pressure. After liberation of acidic offgases had ceased (12 hours), the mixture was cooled, the catalyst was separated off by filtration, and the filtrate was distilled at 27 mbar. A yield of 190.0 g of 3,5-bis(trifluoromethyl)benzaldehyde having a boiling point of 79° C. was obtained. This corresponds to a yield of 86percent of theory. A small amount of a mixture of toluene and 3,5-bis(trifluoromethyl)benzene was obtained as first fraction during the distillation.
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; N,N-dimethyl-formamide;
EXAMPLE 2 With Temperature Variation A solution of y mol of 2,2,6,6-tetramethylpiperidine in 400 ml of anhydrous tetrahydrofuran is cooled under a stream of argon to to and there is added dropwise thereto at this temperature within 30 minutes 100*y/0.16 ml of a 1.6M solution of n-butyllithium in hexane. Subsequently, 20.2 ml (0.13 mol) of 1,3-bis(trifluoromethyl)benzene are added dropwise thereto at to within 15 minutes, the wine-red solution obtained is stirred for a further*minutes at to and then at this temperature 20 ml (0.26 mol) of N,N-dimethylformamide are allowed to flow in rapidly from a dropping funnel. The internal temperature t rises by about 15° as a consequence of the exothermic reaction. The dark red solution obtained is then slowly added dropwise and while stirring and cooling to 500 ml of cold 3M hydrochloric acid (strongly exothermic). The emulsion obtained is diluted with 300 ml of hexane, the aqueous phase is separated, the organic phase is extracted with 500 ml of cold 3M hydrochloric acid, washed neutral twice with 250 ml of saturated sodium chloride solution each time, dried over sodium sulphate and the organic solvent is largely distilled off at 40° bath temperature/20 kPa. The residue is distilled over a column having a length of 20 cm, whereby firstly residual solvent is removed at 50° bath temperature/20 kPa and then the bath temperature is increased to 80° and the vacuum is increased to 1.4 kPa. During the increase in the internal temperature a forerun of about 1 g is removed and then the 2,4-bis(trifluoromethyl)benzaldehyde obtained distils over at 56°./1.4 kPa as a colourless liquid.
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane; N,N-dimethyl-formamide;
a) A solution of 68 ml (0.4 mol) of 2,2,6,6-tetramethyl- piperidine in 1 l of tetrahydrofuran is cooled under argon to -10° and at this temperature there are added dropwise thereto while stirring 250 ml of a 1.6M solution of n-butyllithium in hexane. Subsequently, 62 ml (0.4 mol) of 1,3-bis(trifluoromethyl)-benzene are added dropwise thereto at -10° within 5 minutes. The resulting wine-red solution is stirred at -10° for a further 5 minutes and then 62 ml (0.8 mol) of N,N-dimethylformamide are allowed to flow in rapidly. The internal temperature rises by 15° as a consequence of the exothermic reaction. The dark brown solution obtained is then added slowly and under a slight argon pressure to 1.2 l of stirred, ice-cold 1M hydrochloric acid. The internal temperature rises to 10° as a consequence of the stongly exothermic reaction in spite of constant cooling. The resulting emulsion is diluted with 750 ml of hexane, the aqueous phase (1.5 l) is separated and stored for the recovery of 2,2,6,6-tetra- methylpiperidine. The organic phase (1.9 l) is extracted twice with 1 l of water each time, dried over sodium sulphate, filtered and the organic solvent is distilled off at 40° under a vacuum (20 kPa). The residue (about 100 ml) is distilled over a column having a length of 20 cm, firstly at 50° bath temperature under a vacuum of 20 kPa in order to remove the residual solvent, then the bath temperature is increased to 80° and the vacuum is increased to 1.4 kPa. A forerun is removed until the constant internal temperature of 57° has been reached and then the residue distils over as a fraction at 57°/1.4 kPa. There are obtained 68 g (70percent) of 2,4-bis(trifluoromethyl)benzaldehyde with a purity (GC) of 96-98percent.
With lithium diisopropyl amide; In tetrahydrofuran; N,N-dimethyl-formamide;
EXAMPLE 4 A solution of 100 ml (0.21 mol) of lithium diisopropylamide in tetrahydrofuran is cooled under argon to -70° and at this temperature there are added dropwise thereto while stirring 31 ml (0.2 mol) of 1,3-bis(trifluoromethyl)benzene. The resulting dark red, viscous suspension is stirred at -70° for a further 30 minutes and then 31 ml (0.4 mol) of N,N-dimethylformamide are allowed to flow in rapidly. The internal temperature rises to -20° as a consequence of the exothermic reaction in spite of continuous cooling. The violet solution obtained is then processed further as described in Example 3a). 2,4-Bis(trifluoromethyl)-benzaldehyde is obtained.
With n-butyllithium; In diethyl ether; hexane; n-heptane;
EXAMPLE 1 Preparation of 2,4-bis-trifluoromethylbenzoic acid. A solution of dibutylmagnesium in heptane (0.9 M, 10 mmoles, 11 ml) is dropped, under vacuum and at room temperature, into a solution of 1,3-bis-trifluoromethyl benzene (2.14 g, 10 mmoles) in ethyl ether (10 ml). The solution thus obtained is cooled to 0C and a solution of n-butyllithium in hexane (2.5 M, 10 mmoles, 4 ml) is added. The reaction mixture is kept at 20C for 4 hours, and is then poured onto solid carbon dioxide in fine powder form, and kept under vigorous stirring. The mixture is then left to reach room temperature and acidified to pH 1-2 with 0.1 M HCl. The resulting reaction mixture is extracted with dichloromethane and the phases are separated. The organic phase is extracted with 10% aqueous NaOH and the basic water extract is acidified with HCl to pH 1.2, whereafter said water extract is extracted with dichloromethane and the resulting organic extract is washed with water and dried over sodium sulphate. Upon evaporation of the solvent under vacuum, 2,4-bis-trifluoromethylbenzoic acid (1.8 g), b.p. 107-109C, is obtained. 1H-NMR (CDCl3) delta (ppm): 7.95 (m, 1H), 8.06 (m, 1H), 8.12 (m, 1H), 11.8 (broad, 1H).
Stage #1: 1,3-bis(trifluoromethyl)benzene With potassium <i>tert</i>-butylate In tetrahydrofuran at -70℃; for 0.5h;
Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 1.5h;
Stage #3: formaldehyd In tetrahydrofuran; hexane at -70 - 20℃; for 3.5h;
23 (2,6-bis(trifluoromethyl)phenyl)methanol (JM3-1352-2)
To a solution of KOtBt (1.3 g, 11.62 mmol) in THF at -70° C. was added 2,6-bis(trifluoromethyl)benzene (2.0 g, 9.3 mmol) dropwise over a period of 30 min. To this solution was added n-BuLi (18.6 mmol, 2.5 M in hexanes) dropwise for 30 min, stirring continued at -70° C. for 60 min. To this mixture was added Paraformaldehyde (61.2 g, 37.2 mmol) and stirring continued at -70° C. for 30 min, then allowed to room temperature for 3 h. The reaction mixture was poured into conc. HCl (2 mL) and ice water (60 mL) and stirred for 1 h, extracted with hexanes (3*10 mL) and washed with brine, dried over Na2SO4, and concentrated in vacuo to get final compound as dark brown oil (40%). ESI-MS (M)+ 244.03.
Stage #1: 1,3-bis(trifluoromethyl)benzene With potassium <i>tert</i>-butylate In tetrahydrofuran at -70℃; for 0.5h;
Stage #2: With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 1h;
Stage #3: formaldehyd With hydrogenchloride; water more than 3 stages;
47
2,6-Bis(trifluoromethyl)benzyl alcohol; A mixture of 80 mL of THF and t-BuOK (7. 0 g, 62. 5 mmol) is added to a 250 mL four-neck flask equipped with a mechanical stirrer, a thermometer, a gas inlet tube and a 100 mL dropping funnel with a gas outlet tube. Cool down to-70 °C. and 2, 6- bis (trifluoromethyl) benzene (8. 0 mL, 10. 7g, 50. 0 mmol) is added dropwise and keep agitating ~-70 °C for 30 min. Add n-BuLi (0. 10 mol, 2. 87 M in hexanes 35. 0 mL, 100. 0 mmol) dropwise over 30 min with agitation at--70 °C for 60 min. Paraformaldehyde (6. 0g, 0. 20 mol) is added and keep agitating ~70 °C for 30 min, then gradually warm to room temperature for 3 h. Pour mixture into cons cl (10 mL) and ice water (300 mL), and stir for 1 h. Extract with hexanes (3 x 50 mL). Wash the combined organic layers with 50 mL of brine, dry over anhydrous Na2S04, filter and concentrate. The crude product is vacuum distilled (72-76 °C at 4-5 mm Hg) to give the desired compound (5 g). MS m/z = 244 (M+).
With bis(tricyclohexylphosphine)nickel(II) dichloride; lithium triethylborohydride; nickel dichloride In tetrahydrofuran at 20℃; Inert atmosphere; Reflux;
54 %Chromat.
With bis(tricyclohexylphosphine)nickel(II) dichloride; lithium tri-t-butoxyaluminum hydride In tetrahydrofuran for 5h; Inert atmosphere; Reflux;
NiCl2(PCy3)2-catalyzed hydrodefluorination
General procedure: NiCl2(PCy3)2 (17 mg, 0.025 mmol) was added to a substrate (0.5 mmol) in dry THF (4 mL - 10 mL) and then LiAl(O-t-Bu)3H (2 mmol - 8 mmol, ) was added to this solution slowly under argon atmosphere. The mixture was then heated to reflux and left to stir while being periodically monitored by GC and GC/MS. All products were identified by GC/MS and GC.
With triphenylgermane; trityl tetrakis(pentafluorophenyl)borate In neat (no solvent) at 20℃; for 18h; Glovebox; Schlenk technique; Inert atmosphere;
With silver(I) acetate; palladium diacetate; cesium pivalate; Trimethylacetic acid for 12h; Inert atmosphere; Reflux; regioselective reaction;
Typical procedure for the synthesis of 2a: A stirred mixture of chromone (1a, 73 mg, 0.5 mmol), Pd(OAc)2 (6 mg, 5 mol %), AgOAc (251 mg, 1.5 mmol), PivOH (306 mg, 3.0 mmol), and CsOPiv (23 mg, 0.1 mmol) in benzene (2.7 mL, 60 equiv) was heated to reflux for 12 h under nitrogen atmosphere. After cooling to room temperature, the crude reaction mixture was filtered over a pad of Celite and washed with CH2Cl2. The solvent was removed and the residue was dissolved in EtOAc (150 mL) and washed with a saturated solution of NaHCO3 (20 mL × 3). The combined organic layers were dried over MgSO4 and concentrated under vacuum. The residue was purified by column chromatography (hexanes/EtOAc, 10:1) to afford 2a (76 mg, 68%) as a pale yellow solid along with a trace amount of 3a (4 mg, 4%).3e Other compounds were synthesized similarly, and the selected spectroscopic data of unknown compounds 2b-d, 2f, 2g, 2i and 2j are as follows. The compounds 2a,2c2e,2a2f',2l2h1b are known, and the spectroscopic data are same with the reported.
With phenylsulphur trifluoride at 100℃; for 2h; Inert atmosphere; Neat (no solvent);
4.7.1. Fluorination of carboxylic acids in a sealed reactor
A typical procedure: 132 mg (1.08 mmol) of benzoic acid was added portion by portion to 448 g (2.7 mmol) of 2a in a fluoropolymer (PTFE or FEP) tube (i.d. 5/16''; o.d. 3/8''), the end of which was sealed, at room temperature. Immediately after the addition, the other end of the tube was sealed. When the two reactants were mixed, a mild exothermic reaction occurred. The sealed tube was heated for 2 h in an oil bath of 100 °C. After that, the tube was cooled to room temperature and opened. 19F NMR analysis of the reaction mixture showed that benzotrifluoride was produced in 90% yield.
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Inert atmosphere;
Stage #2: diphenyldisulfane With [2,2]bipyridinyl; copper(l) chloride In water; dimethyl sulfoxide at 80℃; for 24h; Inert atmosphere; regioselective reaction;
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Inert atmosphere;
Stage #2: diphenyl diselenide With [2,2]bipyridinyl; copper(l) chloride In water; dimethyl sulfoxide at 80℃; for 24h; Inert atmosphere; regioselective reaction;
63%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Schlenk technique; Inert atmosphere;
Stage #2: diphenyl diselenide With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 24h; Schlenk technique; Inert atmosphere; regioselective reaction;
3'-methyl-3,5-bis(trifluoromethyl)-1,1'-biphenyl[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With palladium diacetate; potassium carbonate; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
65%
With (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; C24H29Cl2N3Pd; potassium carbonate In N,N-dimethyl acetamide at 80℃; for 48h; Inert atmosphere; Schlenk technique;
2-methyl-3',5'-bis(trifluoromethyl)biphenyl[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
With rubidium carbonate; 2,2-dimetyl-3-(adamantan-1-yl)propanoic acid; palladium dichloride In N,N-dimethyl acetamide at 55℃; for 40h; Inert atmosphere; Schlenk technique;
59%
With palladium diacetate; potassium carbonate; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
56%
With C24H29Cl2N3Pd; potassium carbonate; trimethylpyruvic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
3,5-bis(trifluoromethyl)-4’-methoxybiphenyl[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
91%
With (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; C24H29Cl2N3Pd; potassium carbonate In N,N-dimethyl acetamide at 80℃; for 72h; Inert atmosphere; Schlenk technique;
68%
With palladium diacetate; potassium carbonate; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
With palladium diacetate; potassium carbonate; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
67%
With (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; C24H29Cl2N3Pd; potassium carbonate In N,N-dimethyl acetamide at 80℃; for 72h; Inert atmosphere; Schlenk technique;
With palladium diacetate; potassium carbonate; Trimethylacetic acid In N,N-dimethyl acetamide at 110℃; for 24h; Inert atmosphere; Schlenk technique;
85%
With (2S,3S)-N-acetyl-2-amino-3-methylpentanoic acid; C24H29Cl2N3Pd; potassium carbonate In N,N-dimethyl acetamide at 80℃; for 48h; Inert atmosphere; Schlenk technique;
3,5-bis(trifluoromethyl)phenyl dodecyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
60%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: 1-dodecylthiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction mixture was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. This flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, alkyl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 120 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 3.
59%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Schlenk technique; Inert atmosphere;
Stage #2: 1-dodecylthiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 24h; Schlenk technique; Inert atmosphere; regioselective reaction;
3,5-bis(trifluoromethyl)phenyl 2-methyl-1-butyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: 2-methyl-1-butanethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction mixture was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. This flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, alkyl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 120 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 3.
53%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Schlenk technique; Inert atmosphere;
Stage #2: 2-methyl-1-butanethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 24h; Schlenk technique; Inert atmosphere; regioselective reaction;
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: phenylmethanethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction mixture was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. This flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, alkyl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 120 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 3.
47%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tetrahydrofuran at 80℃; for 24h; Schlenk technique; Inert atmosphere;
Stage #2: phenylmethanethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 24h; Schlenk technique; Inert atmosphere; regioselective reaction;
General procedure: To a flame dried 100mL flask were added 1,3-disustituted benzene (3.0mmol), TMEDA (1.1equiv, 3.3mmol), DIPA (5percentequiv, 0.16mmol), and THF (10.0mL). The solution was cooled to ?78°C for 10min and then n-BuLi (1.1equiv, 3.3mmol) was added dropwise. The mixture was kept at this temperature for 1h; DMF (1.5equiv, 4.5mmol) was added and the mixture was further stirred for another half an hour at ?78°C. The mixture was allowed to warm up to room temperature and quenched by the addition of saturated NH4Cl?H2O solution (5mL); extracted three times with ethyl acetate (10mL×3). The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The regioselectivity of the crude product was ascertained by 19F NMR (for fluorinated products) or by GC/MS (for nonfluorinated ones) and then subjected to flash chromatography to obtain the desired products which were characterized by 1H NMR, 19F NMR, and 13C NMR spectral data and GC?MS analyses.
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: thiophenol With pyridine; copper diacetate In N,N-dimethyl-formamide at 135℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction vessel was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. The flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, aryl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 135 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 2.
3,5-bis(trifluoromethyl)phenyl 3-trifluoromethylphenyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
70%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: 3-trifluoromethyl-thiophenol With pyridine; copper diacetate In N,N-dimethyl-formamide at 135℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction vessel was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. The flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, aryl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 135 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 2.
3,5-bis(trifluoromethyl)phenyl 1-naphthyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: 1-Naphthalenethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 135℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction vessel was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. The flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, aryl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 135 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 2.
3,5-bis(trifluoromethyl)phenyl cyclohexyl sulfide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55%
Stage #1: 1,3-bis(trifluoromethyl)benzene With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; bis(pinacol)diborane; 4,4'-di-tert-butyl-2,2'-bipyridine In tert-butyl methyl ether at 80℃; for 1h; Inert atmosphere; Glovebox; Microwave irradiation;
Stage #2: Cyclohexanethiol With pyridine; copper diacetate In N,N-dimethyl-formamide at 120℃; for 1.5h; Inert atmosphere; Microwave irradiation; regioselective reaction;
General procedure: A flask equipped with a magnetic stirrer bar was charged with [Ir(OCH3)(C8H12)]2 (99.0 mg, 0.015mmol), 4,4′-di-tert-butyl-2,2′-dipyridyl (82.0 mg, 0.03 mmol) and pin2B2 (254 mg, 1.0 mmol) in anitrogen-filled glove box. This flask was then covered with a rubber septum and removed from theglove box. Under a nitrogen atmosphere, arene (1.0 mmol) and MTBE (2.0 mL) were added viasyringe, and the reaction mixture was placed under microwave irradiation at 80 °C. After stirring at thistemperature for 1 h, the heterogeneous mixture was cooled to room temperature, after removed thevolatile components under vacuum. This flask was returned to the glove box, Cu(OAc)2 (136 mg, 0.75mmol) was added, the flask was then covered with a rubber septum and removed from the glove box.Under an argon atmosphere, alkyl thiol (0.5 mmol), pyridine (0.123 mL, 1.5 mmol) and DMF (2.0 mL)were added via syringe, and the reaction vessel was placed under microwave irradiation at 120 °C.After stirring at this temperature for 1.5 h, the heterogeneous mixture was cooled to room temperatureand diluted with ethyl acetate (20 mL). The resulting solution was directly filtered through a pad ofsilica gel then washed with ethyl acetate (20 mL) and concentrated to give the crude material whichwas then purified by column chromatography (SiO2, hexane) to yield 3.
Stage #1: 1,3-bis(trifluoromethyl)benzene With n-butyllithium In diethyl ether at -78℃; Inert atmosphere;
Stage #2: With phosphorus trichloride In diethyl ether at -78 - 20℃; Inert atmosphere;
4.3 Synthesis of Ar″PCl2 (3)
Ar″PCl2 (3) was prepared in a mixture with Ar′PCl2 (4), which could not be separated by distillation in vacuo. A solution of Ar′Li/Ar″Li (96 mmol) was added dropwise over 20 min to a solution of PCl3 (25.2 g, 16 ml, 183 mmol) in diethyl ether (100 ml) at -78 °C. The mixture was allowed to warm to room temperature and stirred for 4 h. The white solid (LiCl) which appeared was removed by filtration, and solvent and any excess PCl3 removed in vacuo, giving a brown oil. The product was purified by distillation under vacuum (Bp 86 °C, 0.01 Torr). The components were identified by 19F and 31P solution-state NMR spectroscopy (Table 1).
2,4-bis-trifluoromethylbenzene-2,5-bis-trifluoromethylbenzene arsenic chloride[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Stage #1: 1,3-bis(trifluoromethyl)benzene With n-butyllithium In diethyl ether at -78℃; Inert atmosphere;
Stage #2: With arsenic trichloride In diethyl ether; hexane at -78 - 20℃; Inert atmosphere;
4.4 Synthesis of Ar′AsCl2 (13)/Ar″AsCl2 (14)/Ar′Ar″AsCl (17)/Ar″2AsCl (16)
A solution of Ar′Li/Ar″Li (100 ml, 94 mmol) in diethyl ether was added dropwise to a solution of AsCl3 (13.5 ml, 160 mmol) in hexanes (100 ml) over a period of 20 min at -78 °C. The mixture was allowed to warm to room temperature and stirred for 4 h. A precipitate of LiCl formed. This was filtered off and the solvents and excess AsCl3 removed in vacuo, leaving a brown oil. This was distilled under reduced pressure (0.01 Torr), and fractions were collected at 115 °C (a mixture of all four products) and 145 °C (mainly Ar′Ar″AsCl (17)). Some solid appeared in the first fraction. This was separated, redissolved in CH2Cl2 and left in the freezer, producing a white microcrystalline product unsuitable for X-ray diffraction. 19F solution-state NMR spectroscopy showed that this product was Ar″2AsCl (16). The solid isolated from the higher-boiling fraction was successfully recrystallized from hexane, and has been fully characterised as Ar′Ar″AsCl (17) by single-crystal X-ray diffraction [37].
With N,N,N,N,-tetramethylethylenediamine; C39H46IrN4 In acetonitrile at 45℃; for 48h; Sealed tube; Glovebox; Inert atmosphere;
74%
With [2-(di-tert-butylphosphinomethyl)-6-(diethylaminomethyl)pyridine]ruthenium(II) chlorocarbonyl hydride; isopropyl alcohol; sodium t-butanolate at 100℃; for 18h; Inert atmosphere; Sealed tube; Green chemistry;
99 %Spectr.
With 1,3-dimethyl-2-phenyl-2,3-dihydro-1H-benzo[d]imidazole; C39H45IrN4 In N,N-dimethyl-formamide at 45℃; for 24h; Irradiation; Glovebox;
(4,4-difluoro-4-(3-(trifluoromethyl)phenyl)butyl)trimethylsilane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
83%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
79%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
1-(3-ethoxy-1,1-difluoropropyl)-3-(trifluoromethyl)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
81%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
1-(4,4-diethoxy-1,1-difluorobutyl)-3-(trifluoromethyl)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
78%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
75%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
5,5-difluoro-5-(3-(trifluoromethyl)phenyl)pentan-1-ol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
85%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
56%
With (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; sodium formate; mesna In dimethyl sulfoxide for 16h; Sealed tube; Inert atmosphere; Irradiation;
6,6-difluoro-6-(3-(trifluoromethyl)phenyl)hexanoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
68%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
1-(1,1-difluorononyl)-3-(trifluoromethyl)benzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
With Cyclohexanethiol; 10-phenyl-10H-phenothiazine; sodium formate In water; dimethyl sulfoxide at 23℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Schlenk technique;
80%
With Cyclohexanethiol; sodium formate In water; dimethyl sulfoxide at 60℃; Irradiation; Inert atmosphere;
B-chloro-9,10-dihydro-9-aza-10-boraanthracene[ No CAS ]
C20H12BF6N[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
43%
Stage #1: 1,3-bis(trifluoromethyl)benzene With n-butyllithium; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; hexane at -78℃; for 2h;
Stage #2: B-chloro-9,10-dihydro-9-aza-10-boraanthracene In tetrahydrofuran; hexane at -78 - 20℃; for 10h;
S-glutathione-(4-azidobut-1-ynyl)-1,2-vinylbenziodoxolone[ No CAS ]
C22H24F6N6O6S[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 2C6H7N3O2(2-)*4Li(1+)*Pd(2+)*2C2H3O2(1-) In aq. phosphate buffer; dimethyl sulfoxide at 37 - 50℃; for 0.5h;
General procedure J:
General procedure: A 1.5 mL Eppendorf Safe-Lock microcentrifuge tube was charged with phenyl boronic acid (10.0 μmol,10.0 equiv.), phosphate buffer (63 mM, pH 8.2, 290 μL) and DMSO (10 μL). The resulting mixture washeat up to 50 °C in order to obtain a clear solution (except (para-hydroxyphenyl)boronic acid (30c) andfuran-2-ylboronic acid (30l), dissolved at room temperature). After cooling down to 37 °C, a 10.0 mMsolution of 3a in 63 mM phosphate buffer pH 8.2 (100 μL, 1.00 μmol) was added to the 33.3 mM solutionof phenyl boronic acid. The resulting solution was vortexed few seconds to ensure proper reagent mixingand incubated at 37 °C over 10 minutes. Then, a 10.0 mM solution of 31a in water (100 μL, 1.00 μmol,1.00 equiv.) was added in one portion. The resulting solution was vortexed few seconds to ensure properreagent mixing and incubated 30 minutes at 37 °C. The reaction was quenched with a 570 mM solutionof 3-mercaptopropionic acid in water (10.0 μL, 5.70 μmol, 5.70 equiv. per equiv. of palladium) andshaken at room temperature for 10 minutes. No effort was made to exclude oxygen. The reaction wasanalyzed by HPLC-MS. For the (para-methoxyphenyl)boronic acid (30a), the yield was determined bycomparing the integration area of absorption peak at 214 nm of the product in the mixture to that of astandard curve.
4-(3-(benzyloxy)propyl)-2-(2,6-bis(trifluoromethyl)phenyl)-1,3,2-dioxaborinane[ No CAS ]
[ 402-31-3 ]
6-(benzyloxy)hexane-1,3-diol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 0.2h; Reflux;
General Procedure for the Deprotection of the Boronic Esterswith TBAF; Method A (Catalytic Conditions, Table 1, Entry 8)
General procedure: TBAF (0.20 M in THF, 100 L, 0.0200 mmol, 10 mol%) and H2O (6.0 M in THF, 100 L, 0.600 mmol, 3.0 equiv) were added to a solution of 1a (89.2 mg, 0.200 mmol, 1.0 equiv) in dry THF (1.8mL, total 0.10 M) at room temperature. After stirring for 2 hunder reflux and cooling to room temperature, the reaction mixture was filtered through a short pad of amino silica gel(800 mg) eluting with EtOAc (20 mL), and the filtrate was concentrated under reduced pressure to give 2a (46.8 mg, 0.200 mmol, >99% yield) as a colorless oil. Analytical Data for 2a Rf = 0.13 (n-hexane/EtOAc, 4:1). 1H NMR (400 MHz, CDCl3): = δ 7.38-7.27 (m, 5 H), 4.53 (s, 2 H), 3.90-3.79 (m, 3 H), 3.57-3.49 (m, 2 H), 2.34 (br s, 2 H), 1.79-1.52 (m, 6 H). 13C NMR (100 MHz,CDCl3): = δ 137.9, 128.4, 127.8, 127.7, 73.1, 71.9, 70.5, 61.7, 38.3, 35.2, 26.2. IR (neat): = ν 3372, 2942, 2865, 1278, 1099 cm-1. HRMS (ESI): m/z calcd for C13H20O3Na [M + Na]+: 247.1310; found: 247.1311.
Stage #1: 1,3-bis(trifluoromethyl)benzene With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere;
Stage #2: 2-(3',3'-dimethyl-6-nitro-3'H-spiro[chromene-2,2'-indol]-1'-yl)-ethanol In dichloromethane at 20℃; for 24h; Inert atmosphere;
With lithium 2,2,6,6‐tetramethylpiperidide at -60 - 20℃; for 7h; Acidic conditions;
2.2; 3.2; 4.2 The second step boronation reaction:
1,3-ditrifluorotoluene (107g, 0.5mol) was slowly added dropwise to Intermediate A, and the temperature was controlled from -60°C to -40°C. After the dropwise addition, the reaction was carried out for 2 hours; Triisopropyl borate (113g, 0.6mol) was added, and after the reaction was incubated for 2 hours, the temperature was naturally raised to room temperature and stirred for 3 hours; the reaction solution was rotary evaporated to obtain a viscous oil, which was placed in a four-necked round-bottomed flask, 500 g of methyl tert-butyl ether was added, the temperature was controlled at 0--10° C., 470 g of 10% hydrochloric acid was added dropwise, the pH was adjusted to 2-3, and the aqueous layer was separated. The aqueous layer was extracted once with 100 ml of ethyl acetate. The oil layers were combined and washed twice with 100 g of 3% hydrochloric acid. Wash once with 100 g of saturated brine. Rotary evaporated to dryness, added 300 g of heptane, beating for 1 hour, suction filtered, rinsed to obtain 103 g of an off-white solid with a yield of 79.8%. The liquid content was measured to be 98.1%.
With lithium 2,2,6,6‐tetramethylpiperidide at -60 - 20℃; for 5h; Acidic conditions;
1.2 The second step boronation reaction:
slowly drop 1,3-ditrifluorotoluene (107g, 0.5mol) into Intermediate A, control the temperature from -60°C to -40°C, and react for 1 hour after dropping; Trimethyl borate (62.4g, 0.6mol) was added, and after the reaction was incubated for 1 hour, the temperature was naturally raised to room temperature, and stirred for 3 hours; the reaction solution was rotary-evaporated to obtain a viscous oil, which was placed in a four-necked round-bottomed flask, 500 g of ethyl acetate was added, the temperature was controlled at 0--10° C., 470 g of 10% hydrochloric acid was added dropwise, the pH was adjusted to 2-3, and the aqueous layer was separated. The aqueous layer was extracted once with 100 ml of ethyl acetate. The oil layers were combined and washed twice with 100 g of 5% hydrochloric acid. Wash once with 100 g of saturated brine. Rotary-evaporated to dryness, added 300 g of petroleum ether, beating for 1 hour, suction filtered, rinsed to obtain 91 g of off-white solid with a yield of 70.6%. The liquid content was measured to be 98.1%,
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