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Anushree Mondal ; Pronay Roy ; Jaclyn Carrannatto , et al. DOI: PubMed ID:

Abstract: The prenylated-flavin mononucleotide-dependent decarboxylases (also known as UbiD-like enzymes) are the most recently discovered family of decarboxylases. The modified flavin facilitates the decarboxylation of unsaturated carboxylic acids through a novel mechanism involving 1,3-dipolar cyclo-addition chemistry. UbiD-like enzymes have attracted considerable interest for biocatalysis applications due to their ability to catalyse (de)carboxylation reactions on a broad range of aromatic substrates at otherwise unreactive carbon centres. There are now ∼35[thin space (1/6-em)]000 protein sequences annotated as hypothetical UbiD-like enzymes. Sequence similarity network analyses of the UbiD protein family suggests that there are likely dozens of distinct decarboxylase enzymes represented within this family. Furthermore, many of the enzymes so far characterized can decarboxylate a broad range of substrates. Here we describe a strategy to identify potential substrates of UbiD-like enzymes based on detecting enzyme-catalysed solvent deuterium exchange into potential substrates. Using ferulic acid decarboxylase (FDC) as a model system, we tested a diverse range of aromatic and heterocyclic molecules for their ability to undergo enzyme-catalysed H/D exchange in deuterated buffer. We found that FDC catalyses H/D exchange, albeit at generally very low levels, into a wide range of small, aromatic molecules that have little resemblance to its physiological substrate. In contrast, the sub-set of aromatic carboxylic acids that are substrates for FDC-catalysed decarboxylation is much smaller. We discuss the implications of these findings for screening uncharacterized UbiD-like enzymes for novel (de)carboxylase activity.

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Product Details of [ 95-15-8 ]

CAS No. :95-15-8 MDL No. :MFCD00005864
Formula : C8H6S Boiling Point : -
Linear Structure Formula :- InChI Key :FCEHBMOGCRZNNI-UHFFFAOYSA-N
M.W : 134.20 Pubchem ID :7221
Synonyms :

Calculated chemistry of [ 95-15-8 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 0.0
Num. H-bond donors : 0.0
Molar Refractivity : 41.83
TPSA : 28.24 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -4.9 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.03
Log Po/w (XLOGP3) : 3.12
Log Po/w (WLOGP) : 2.9
Log Po/w (MLOGP) : 2.64
Log Po/w (SILICOS-IT) : 3.78
Consensus Log Po/w : 2.89

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.38
Solubility : 0.0562 mg/ml ; 0.000419 mol/l
Class : Soluble
Log S (Ali) : -3.38
Solubility : 0.0557 mg/ml ; 0.000415 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.31
Solubility : 0.0659 mg/ml ; 0.000491 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.61

Safety of [ 95-15-8 ]

Signal Word:Danger Class:9
Precautionary Statements:P501-P273-P260-P270-P264-P280-P391-P314-P337+P313-P305+P351+P338-P301+P312+P330 UN#:3077
Hazard Statements:H302-H319-H372-H410 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 95-15-8 ]

* 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.

  • Upstream synthesis route of [ 95-15-8 ]
  • Downstream synthetic route of [ 95-15-8 ]

[ 95-15-8 ] Synthesis Path-Upstream   1~43

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Reference: [1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 963 - 968
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Reference: [1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 963 - 968
[2] Patent: EP2336107, 2015, B1,
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Reference: [1] Russian Chemical Bulletin, 1996, vol. 45, # 3, p. 662 - 666
[2] Russian Chemical Bulletin, 1996, vol. 45, # 3, p. 662 - 666
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Reference: [1] Russian Journal of Organic Chemistry, 1993, vol. 29, # 11.2, p. 1863 - 1867[2] Zhurnal Organicheskoi Khimii, 1993, vol. 29, # 11, p. 2246 - 2250
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Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 4, p. 782 - 790
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Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 36, p. 7292 - 7304
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Reference: [1] Journal of Physical Chemistry, 1981, vol. 85, # 14, p. 2098 - 2103
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Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 4, p. 782 - 790
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YieldReaction ConditionsOperation in experiment
16%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -70℃; for 0.5 h;
Stage #2: With N-Bromosuccinimide In tetrahydrofuran; hexane at -70 - 20℃; for 1 h;
j00275j To a solution of benzo[blthiophene (2.0 g, 15 mmol) in tetrahydrofuran (20 mL) at -70 °C under nitrogen was added dropwise n-butyllithium (2.5 M in hexane, 12 mL, 30 mmol). The reaction mixture was stirred at this temperature for 30 mm. Then N-bromosuccinimide (5.3 g, 30 mmol) was added, and the resulting solution was allowed to warm from -70 °C to room temperature over 1 hour. On completion, the mixture was quenched with saturated aqueous ammonium chloride (20 mL) and extracted with ethyl acetate (3 x 30 mL). The combined organic phases were concentrated in vacuo, and the residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 100:11 to give compound B-i (0.50 g, 16percent yield) as a white solid.
76% With n-butyllithium; bromine In diethyl ether; hexane a
2-Bromobenzothiophene
94.0 g (0.7 mol) of benzothiophene in 940 ml of absolute diethyl ether are initially taken at 20°-30° C., and 332 g (0.77 mol) of a 15percent strength solution of n-butyllithium in n-hexane are added dropwise in the course of 2 hours.
After one hour, 127 g (0.799 mol) of bromine are added dropwise, also at 0° C., and stirring is continued for 2 hours.
After working up was carried out in a conventional manner, 2-bromobenzothiophene is distilled off, finally at 1-1.2 mmHg and 84°-86° C. Yield: 240 g (76percent).
Reference: [1] Patent: WO2006/56418, 2006, A2, . Location in patent: Page/Page column 68-69
[2] Chemistry - An Asian Journal, 2014, vol. 9, # 9, p. 2542 - 2547,6
[3] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 11, p. 3034 - 3038
[4] Patent: WO2017/69980, 2017, A1, . Location in patent: Paragraph 00274; 00275
[5] Journal of the American Chemical Society, 1952, vol. 74, p. 664
[6] Patent: US5110829, 1992, A,
[7] Patent: WO2013/119895, 2013, A1, . Location in patent: Paragraph 00271
[8] Canadian Journal of Chemistry, 2013, vol. 91, # 8, p. 679 - 683
  • 10
  • [ 5312-73-2 ]
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  • [ 5381-20-4 ]
Reference: [1] Patent: US2002/161237, 2002, A1,
  • 11
  • [ 4885-02-3 ]
  • [ 95-15-8 ]
  • [ 5381-20-4 ]
Reference: [1] Tetrahedron Letters, 2012, vol. 53, # 25, p. 3165 - 3168
[2] European Journal of Organic Chemistry, 2007, # 12, p. 1891 - 1904
  • 12
  • [ 50-00-0 ]
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  • [ 3541-37-5 ]
Reference: [1] Synlett, 2004, # 9, p. 1575 - 1576
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Reference: [1] Chemistry - A European Journal, 2006, vol. 12, # 10, p. 2739 - 2744
[2] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
[3] Journal of Organic Chemistry, 1948, vol. 13, p. 635,637
[4] Patent: CN108250058, 2018, A,
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YieldReaction ConditionsOperation in experiment
100% With N-Bromosuccinimide; acetic acid In chloroform at 0 - 20℃; for 52 h; To a solution of benzo[b]thiophene (10 g, 74.5 16 mmol) in chloroform (75 mL) and acetic acid (75 mL), was stepwise added NBS (16.6 g, 93.268 mmol) for 4 hr at 0°C and the mixture allowed to stir at room temperature for 48 hr. The progress of the reaction was monitored by TLC and, after completion of reaction, the reaction mass was diluted with chloroform (200 mL) and the resulting mixture was successively washed with a saturated solution of sodium thiosulfate (200 mL), sodium carbonate (200 mL) and brine (150 mL). The extracted organic layer was then dried over sodium sulfate, filtered and evaporated under reduced pressure. The resulting red liquid was then filtered of a pad of silica gel, eluting with hexane to afford 3-bromo-1-benzothiophene (15.87 g, 74.474 mmol, 100percent) as yellow oil. The ‘H NMR and mass was confirmed by reported literature.
95% With N-Bromosuccinimide; acetic acid In chloroform for 3 h; Reflux Benzo [b] thiophene 30 g (0.224 mol)225 mL of CHCl3 and 225 mL of AcOH were added at room temperature. 43.8 g (0.246 mol) of N-Bromosuccinimide was added to the reaction solution, and the mixture was heated to reflux for 3 hours. The reaction mixture was cooled to 0 [deg.] C and neutralized with a saturated aqueous solution of NaHCO3 to terminate the reaction. The organic layer was separated with 500 mL of CH3Cl and washed with distilled water and brine. The obtained organic layer was dried over anhydrous MgSO4, distilled under reduced pressure, and then purified by silica gel column chromatography to obtain the aimed compound (45.3 g, yield 95percent).
94% With bromine In acetic acid at 0 - 20℃; for 16 h; Benzothiophene (2.68 g, 20.0 mmol) was dissolved in glacial acetic acid (100 mL) and cooled to 0° C. The resulting solution was treated by dropwise addition of bromine (1.08 mL, 21.0 mmol). The reaction mixture was allowed to warm to room temperature and was stirred for 16 hours. The crude mixture was concentrated to an oil. The residue was purified by silica gel chromatography eluting with hexane to obtain 4.02 g (94percent) 3-bromobenzothiophene.
90% With N-Bromosuccinimide In tetrachloromethane at 20℃; for 2 h; Irradiation Weigh benzothiophene (1.34 g, 10 mmol),N-bromosuccinimide (1.78 g, 10 mmol) was added to a three-necked flask and 20 mL of carbon tetrachloride was added.Irradiate with a 200w incandescent bulb and react at room temperature for 2 hours.The white solid was filtered off and the liquid was concentrated.1.9 g (90percent) of a colorless transparent liquid were obtained.
88% With bromine; sodium acetate In dichloromethane at 0℃; for 4 h; A 2 L round bottom flask was charged with benzo[b]thiophene (50 g, 373.13 mmol), CH2Cl2 (800 mL), and NaOAc (62 g, 756.10 mmol). To this was added a solution of Br2 (34 g, 212.50 mmol) and CH2Cl2 (700 mL), dropwise at 0° C. over 3 hours. The resulting solution was stirred for 1 hour while the temperature was maintained at 0° C. Reaction progress was monitored by TLC (EtOAc/petroleum ether=1:100). Work up: the resulting mixture was washed three times with saturated NaHSO3(200 mL). The organic layers were combined, dried over MgSO4, concentrated, and purified by flash chromatography with a 1:1000 EtOAc/petroleum ether. This resulted in 70 g (88percent) of product as a colorless oil.
84% With N-Bromosuccinimide In N,N-dimethyl-formamide at 0 - 25℃; for 9 h; Inert atmosphere To a solution of benzo[b]thiophene (6.91 g, 51.5 mmol) in DMF (100 mL) was addedN-bromosuccinimide (8.71 g, 48.9 mmol) at 0 °C, and the mixture was allowed to warm up to25 °C and stirred for 9 h. Into the reaction mixture was added saturated aq. Na2SO3 (50 mL).The resulting mixture was extracted with hexane (3 × 100 mL) and the combined organic phasewas washed with water (3 × 100 mL) and brine (100 mL). The organic phase was dried overMgSO4, filtered, and concentrated under reduced pressure. The crude product was purified bycolumn chromatography on silica gel (hexane) to afford the title compound as colorless liquid(9.23 g, 43.3 mmol, 84percent).
83.3% With N-Bromosuccinimide; acetic acid In chloroform at 20℃; Benzo[b]-thiophene (10 g, 74.5 mmol) was dissolved in AcOH/CHCl3 (100 mL/100 mL), and then NBS (14.6 g, 82.0 mmol) was added in portions with 2 h at room temperature, the resulting solution was stirred overnight. The reaction was quenched by the addition of brine (200 mL) and extracted with hexane (100 mL × 3). The combined organic fraction was washed with brine (100 mL × 3), dried over anhydrous Na2SO4, and filtered. Removing the solvent under vacuum, the residue was purified by column chromatography over silica gel using (DCM/hexane) as the eluent, yielding 1 as colorless oil (13.2 g, 83.3percent). 1H NMR (400 MHz, CDCl3) d: 7.87-7.84 (m, 2H), 7.48 (td, J = 7.2 Hz, J = 1.0 Hz, 1H), 7.45-7.39 (m, 2H). 13C NMR (100 MHz, CDCl3) d: 138.6, 137.5, 125.3, 125.0, 123.5, 123.1, 122.7, 107.7.
63.4% With N-Bromosuccinimide In tetrahydrofuran at 0 - 20℃; for 13 h; Benzo on L reactor thiophene 35 g (261 mmol), was stirred into 350 mL of tetrahydrofuran. 0 And cooled to ° C, were introduced into N-bromo-succinimide 55.7 g (313 mmol) and stirred for 1 hour. After the temperature was raised to roomtemperature and stirred for 12 hours, into a sodium sulfite aqueous solution and then Imohsel using ethyl acetate and distilled water and the organic layer was extracted. Theorganic layer was concentrated under reduced pressure to give the intermediate 14-b43 g (yield: 63.4percent).
48% With bromine; sodium thiosulfate In tetrachloromethane EXAMPLE 5
4-[(Benzo[b ]thiophene-3-yl)carbonyl]-1-piperidinecarboxylic acid, 1,1-dimethylethyl ester STR13
Dissolve benzo[b]thiophene (23 g, 0,170 mmol) in carbon tetrachloride (80 mL).
Add, by dropwise addition, a solution of bromine (26.85 g, 0,168 mmol) in carbon tetrachloride (30 mL) and stir at room temperature for 2 days.
Quench with a 1M solution of sodium thiosulfate and separate the organic phase.
Extract the aqueous phase with carbon tetrachloride, combine the organic phases and dry (MgSO4).
Evaporate the solvent in vacuo and purify by distillation to give 3-bromobenzo[b]thiophene as a pale yellow liquid (17.33 g, 48percent); bp 64°-72° C. at; 0.02 mm Hg.

Reference: [1] Tetrahedron, 2004, vol. 60, # 14, p. 3221 - 3230
[2] Patent: WO2014/186035, 2014, A1, . Location in patent: Page/Page column 186; 187
[3] Journal of the American Chemical Society, 2018, vol. 140, # 20, p. 6432 - 6440
[4] Tetrahedron Letters, 2004, vol. 45, # 42, p. 7943 - 7946
[5] Chemistry of Materials, 2010, vol. 22, # 17, p. 5031 - 5041
[6] Patent: KR2015/27443, 2015, A, . Location in patent: Paragraph 0069-0072
[7] Patent: US6828332, 2004, B1, . Location in patent: Page column 53
[8] Journal of Organic Chemistry, 2015, vol. 80, # 15, p. 7530 - 7535
[9] Patent: CN108250058, 2018, A, . Location in patent: Paragraph 0381; 0384-0386
[10] Patent: US2008/21026, 2008, A1, . Location in patent: Page/Page column 16; 25
[11] Chemical Communications, 2017, vol. 53, # 36, p. 5044 - 5047
[12] Journal of Organic Chemistry, 2014, vol. 79, # 3, p. 1138 - 1144
[13] Chemistry Letters, 2018, vol. 47, # 8, p. 1044 - 1047
[14] Tetrahedron Letters, 2018, vol. 59, # 28, p. 2717 - 2721
[15] Chemical Communications, 2008, # 46, p. 6227 - 6229
[16] Synlett, 2004, # 3, p. 461 - 464
[17] Tetrahedron, 1989, vol. 45, # 24, p. 7869 - 7878
[18] Chemical Communications, 2009, # 42, p. 6460 - 6462
[19] Patent: KR2016/2328, 2016, A, . Location in patent: Paragraph 0592-0594
[20] Tetrahedron, 1994, vol. 50, # 41, p. 11893 - 11902
[21] Patent: US5371093, 1994, A,
[22] European Journal of Organic Chemistry, 2006, # 9, p. 2100 - 2109
[23] Zeitschrift fuer Physikalische Chemie (Muenchen, Germany), 1981, vol. 127, p. 13 - 22
[24] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1980, vol. 19, # 12, p. 1183 - 1187
[25] Journal fuer Praktische Chemie (Leipzig), 1929, vol. <2> 122, p. 329
[26] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1946, vol. 222, p. 1441
[27] Journal of the American Chemical Society, 1950, vol. 72, p. 571,575
[28] Synlett, 2002, # 12, p. 2083 - 2085
[29] Journal of Medicinal Chemistry, 2000, vol. 43, # 7, p. 1293 - 1310
[30] Patent: US4659717, 1987, A,
[31] Patent: US4548948, 1985, A,
[32] Angewandte Chemie - International Edition, 2012, vol. 51, # 8, p. 1934 - 1937
[33] Russian Chemical Bulletin, 2012, vol. 61, # 7, p. 1456 - 1462[34] Izv. Akad. Nauk, Ser. Khim., 2012, # 7, p. 1441 - 1447,7
[35] Patent: WO2015/188790, 2015, A1,
[36] Angewandte Chemie - International Edition, 2016, vol. 55, # 27, p. 7737 - 7741[37] Angew. Chem., 2016, vol. 128, p. 7868 - 7872,5
[38] Chem, 2017, vol. 3, # 3, p. 428 - 436
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Reference: [1] Indian Journal of Chemistry, Section A: Inorganic, Physical, Theoretical & Analytical, 1988, vol. 27, # 6, p. 538 - 539
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YieldReaction ConditionsOperation in experiment
100% With tert.-butylhydroperoxide; [Mo2(O)4[2,2'-(1,3-phenylene)bis(4,5-dihydrooxazole-4,2-diyl)]dimethanol}(acac)2] In 1,2-dichloro-ethane for 1 h; Reflux General procedure: In a 25 mL round-bottom flask equipped with a magnetic stirring bar, a solution of sulfide (1 mmol), catalyst (6 mg, 0.008 mmol, 0.016 mmol Mo) in 1,2-dichloroethane (4 mL) was prepared. TBHP (2 mmol) was added to this solution and the reaction mixture was stirred under reflux conditions. The reaction progress was monitoredby TLC. After the reaction was completed, the isolation and purification of the products were done as described above.
99% With formic acid; dihydrogen peroxide In dichloromethane at 20℃; To a solution of benzothiophene (0501-36) (2.0 g, 15 mmol, 1.0 eq.) in dichloromethane (20 ml) was added 30percent hydrogen peroxide solution (6 ml) and formic acid (4 ml).The reaction was stirred at room temperature overnight.Add sodium bicarbonate solution (100 ml), extract with dichloromethane (100 ml × 3), and combine organic phases.Dry over anhydrous sodium sulfate, filter, and spin dry.The white solid product benzo[b]thiophene 1,1-dioxide (4.0 g, yield: 99percent) was obtained.
98% With dihydrogen peroxide In ethanol; n-heptane; water at 60℃; for 2.16667 h; General procedure: Solid sulfides were oxidized to the corresponding sulfonesby stirring a solution of the sulfide (1 mmol) and the catalyst(0.15 g) in n-heptane-ethanol (v/v, 4:2). Then a certain amountof H2O2 (30percent aq.) was added as the oxidant. The mixture wasstirred for a specified time at 60 °C, and the reaction was monitoredusing thin-layer chromatography. After completion ofthe reaction, the catalyst was separated from the reaction solutionusing an external magnet. The corresponding sulfoneproducts were separated from the reaction mixture. The solventwas evaporated to generate the crude product. The crude product was purified by column chromatography on silica gelusing hexane/ethyl acetate as the eluent (method b).
94% With dihydrogen peroxide In water at 20℃; for 0.5 h; General procedure: To a mixture of sulfide (1 mmol) and catalyst (0.04 g), H2O2 30percent(v/v) (0.28 g, 2.5 equiv.) was added and stirred at room temperature for a specified time. After completion of the reaction, as indicated on thin-layer chromatography (TLC), ethyl acetate (20 mL) was added and the mixture was centrifuged to separate the catalyst. The filtrate was washed with brine and dried over anhydrous Na2SO4. Purification of the combined organics by preparative TLC (hexane-ethyl acetate, 10:1) provided pure products. The recycled catalyst was washed with ethyl acetate and acetone. After being dried at 60 °C, it can be reused without further purification. All of the products were known and identified by comparison of their melting points and spectral data with those reported in the literature 2.4.
90% With dihydrogen peroxide In ethanol; hexane; water at 80℃; for 1.08333 h; General procedure: A mixture of 0.03 g of the catalyst and 30percent H2O2 (10 mmol)aq. was added to a solution of the sulfide (1 mmol) in a mixedsolvent of EtOH and hexane (1:1; 2 mL), and the resulting mixture was stirred at 80 °C. The reaction mixture was cooled toroom temperature and the catalyst was separated using anexternal magnetic field. The corresponding sulfones were extractedwith EtOH from the reaction mixture (Method c, Table2, entries 8–11).
87% With dihydrogen peroxide In octane; acetonitrile at 20℃; for 0.25 h; Sonication; Green chemistry General procedure: The UAOD generally carry out in biphasic system that consistsof a polar solvent and model fuel. The UAOD studies wereperformed with model oil, with refractory sulfur compoundscommonly found in fuels (BT, DBT or 4,6-DMDBT), was preparedby dissolving in n-octane (500 mg.L1 for each compound). TheUAOD reactions were carried out in a biphasic medium that formedby the model fuel and different polar solvent such as water,acetonitrile (MeCN), isopropanol and dimethylformamide (DMF).In a generic experiment, 15 mg of PTATMU-17-NH2 (containing 20 wtpercent of PTA) was placed in the vessel then a mixture of MeCN (5 mL) and model fuel (5 mL, 2.5 mgr of DBT) was added to it andthe catalytic process was started with addition of H2O2 30percent(1:1 oxidant/S-contain compound molar ratio (O/S)) as oxidant inreaction medium. In next step, the resulting mixture was exposedultrasound waves for 5 min in an ultrasonic bath at ambient temperature(100W and 37 kHz). In order to stop the reaction, theflask was put into an ice bath. Supernatant layer that is model oilwas decanted, then catalyst was separated from the lower layerwith centrifuge. The reaction progress was quantified periodicallyby GC and tetradecane as a standard. PTATMU-17-NH2 could berecycled by centrifuge the catalyst after each UAOD cycle, then,soaking MeCN at room temperature. The UAOD system was optimizedusing PTATMU-17-NH2 as catalyst (5–30 mg), differentextraction solvent and various O/S molar ratio (1:1, 2:1, 3:1) indifferent time (5–20 min) under various powers of ultrasonicirradiation (50–150 W, 37 kHz) at ambient temperature.
85% With 1,2-diphenyl-1,1,2,2-tetrahydroperoxyethane In tetrahydrofuran at 20℃; for 2.33333 h; Green chemistry General procedure: To a stirred solution of sulfde (1 mmol) and THF (4 mL),THPDPE (1 up to 5.5 mmol (0.310 up to 1.70 g) dependingon the substrates and products) was added and the mixture wasstirred at room temperature for an appropriate time. After completion of the reaction, as monitored by TLC, a saturated aqueous solution of Na2SO3 (2 mL of 1 M solution) was added toquench the excessive oxidant that was remained in the mixture.Water (10 mL) was added to the mixture and extracted usingchloroform (3 × 5 mL) and dried over anhydrous MgSO4. Afterevaporation of solvent under reduced pressure chromatographyon silica gel was used to give pure products.
84% With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 16 h; m-Chloroperbenzoic acid (77percent, 6.35 g, 27.9 mmol) was added portion wise to a solution of benzo[£>]thiophene (1 .50 g, 1 1 .1 mmol) in anhydrous dichloromethane (100 ml_) at room temperature with vigorous stirring, the resulting reaction mixture was stirred for 16 h at the same temperature. A saturated aqueous NaHC03 solution (250 mL) was added and aqueous layer was extracted with dichloromethane (2 x 100 m L), organic layer was separated, combined organic layers dried (MgS04) and concentrated in vacuo. Crystallization from ethanol afforded benzo[b]thiophene 1 , 1 -dioxide (1 .56 g, 84percent) as an off-white solid. 1 H NMR (600 MHz, CDCI3): δ = 7.73 (d, J = 6 Hz, 1 H), 7.58-7.53 (m, 2H), 7.38 (d, J = 12 Hz, 1 H), 7.23 (d, J= 6 Hz, 1 H), 6.73 (d, J = 6 Hz, 1 H). LCMS (m/z): 167 [M +H] +
81% With tert.-butylhydroperoxide In hexane; toluene at 40℃; for 6 h; 0.15 g (0.0011 mol) benzothiophene (BT) was placed in a 25 mL round bottom flask containing 10 mL mixture of toluene/hexane (1:4) and 0.015 g (0.0135 mmol) of oxidation catalyst. The mixture was heated to 40 °C with continuous stirring at 500 rpm in an oil bath. An oxidant-to-substrate ratio of 6.8 was then added to the mixture. The oxidation reaction was allowed to proceed for 6 h under continuous stirring after the addition of tert-butylhydroperoxide. A white precipitate of benzothiophene sulfone (BTO2) observed was collected through filtration and washed with hexane to remove unreacted benzothiophene. Yield = 81percent. 1H NMR (δ, ppm in DMSO) δ 7.83 (d, J = 7.2, 1H), 7.69 (t, J = 7.4, 1H), 7.62 (t, J = 9.1, 3H), 7.34 (d, J = 6.8, 1H). Anal. Calcd(found) for C8H6O2S (percent): C, 57.81(57.49); H, 3.64(3.89); S 19.29(19.02).
74% With 3-chloro-benzenecarboperoxoic acid In tetrahydrofuran at 0 - 35℃; for 2 h; Reference Example 117
1-Benzothiophene 1,1-dioxide
To a solution (120 mL) of 1-benzothiophene (11.2 g) in tetrahydrofuran was added m-chloroperbenzoic acid (70percent containing, 43.1 g) at 0°C and the mixture was stirred at the same temperature for 1 hr, further stirred at room temperature for 1 hr.
An aqueous sodium thiosulfate solution (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate.
The extract was washed with 1 mol/L aqueous sodium hydroxide solution, saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.
The residue was recrystallized from ethyl acetate to give the title compound as a white solid (yield 10.3 g, 74percent).
1H-NMR (CDCl3)δ: 6.72 (1H, d, J=7.0 Hz), 7.20-7.24 (1H, m), 7.34-7.38 (1H, m), 7.52-7.60 (2H, m), 7.70-7.74 (1H, m).

Reference: [1] Petroleum Chemistry, 2007, vol. 47, # 3, p. 225 - 225
[2] Polyhedron, 2014, vol. 72, p. 19 - 26
[3] RSC Advances, 2014, vol. 4, # 61, p. 32054 - 32062
[4] Patent: CN108658908, 2018, A, . Location in patent: Paragraph 0204; 0205
[5] Journal of Organic Chemistry, 1997, vol. 62, # 5, p. 1457 - 1462
[6] Chemical Communications, 2010, vol. 46, # 13, p. 2289 - 2291
[7] Chemical Communications (Cambridge, United Kingdom), 2012, vol. 48, # 95, p. 11632 - 11634,3
[8] Chinese Journal of Catalysis, 2015, vol. 36, # 8, p. 1342 - 1349
[9] RSC Advances, 2015, vol. 5, # 122, p. 101013 - 101022
[10] Tetrahedron, 1989, vol. 45, # 11, p. 3299 - 3306
[11] Bulletin of the Korean Chemical Society, 2010, vol. 31, # 3, p. 547 - 548
[12] Journal of the Chilean Chemical Society, 2018, vol. 63, # 1, p. 3829 - 3833
[13] European Journal of Organic Chemistry, 2005, # 3, p. 552 - 557
[14] Chinese Journal of Catalysis, 2017, vol. 38, # 3, p. 458 - 468
[15] Journal of Chemical Research, 2008, # 2, p. 109 - 114
[16] Chemical & Pharmaceutical Bulletin, 1985, vol. 33, # 11, p. 5071 - 5074
[17] Ultrasonics Sonochemistry, 2017, vol. 34, p. 713 - 720
[18] Tetrahedron Letters, 1998, vol. 39, # 39, p. 7055 - 7058
[19] Tetrahedron Letters, 2008, vol. 49, # 32, p. 4708 - 4712
[20] Phosphorus, Sulfur and Silicon and the Related Elements, 2017, vol. 192, # 3, p. 316 - 321
[21] Patent: WO2016/131098, 2016, A1, . Location in patent: Page/Page column 115; 116
[22] Tetrahedron Letters, 1991, vol. 32, # 30, p. 3699 - 3700
[23] Reactive and Functional Polymers, 2014, vol. 81, # 1, p. 61 - 76
[24] Organic Letters, 2015, vol. 17, # 20, p. 5100 - 5103
[25] Tetrahedron: Asymmetry, 1993, vol. 4, # 3, p. 479 - 490
[26] Patent: WO2006/36024, 2006, A1, . Location in patent: Page/Page column 154
[27] Patent: EP2336107, 2015, B1, . Location in patent: Paragraph 0291
[28] Green Chemistry, 2015, vol. 17, # 2, p. 817 - 820
[29] Journal of Organic Chemistry, 1982, vol. 47, # 19, p. 3773 - 3774
[30] Catalysis Science and Technology, 2015, vol. 5, # 1, p. 320 - 324
[31] Green Chemistry, 2012, vol. 14, # 11, p. 3047 - 3052,6
[32] Green Chemistry, 2012, vol. 14, # 11, p. 3047 - 3052
[33] Tetrahedron, 1985, vol. 41, # 4, p. 781 - 784
[34] Comptes Rendus Hebdomadaires des Seances de l'Academie des Sciences, 1912, vol. 154, p. 519
[35] Journal of the American Chemical Society, 1949, vol. 71, p. 1702,1704
[36] Chemische Berichte, 1956, vol. 89, p. 2115,2118, 2122
[37] Journal of the Chemical Society, Chemical Communications, 1994, # 17, p. 1959 - 1960
[38] Environmental Science and Technology, 2000, vol. 34, # 13, p. 2804 - 2809
[39] Journal of Chemical Thermodynamics, 2003, vol. 35, # 8, p. 1253 - 1276
[40] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 5, p. 963 - 968
[41] Chemistry - A European Journal, 2005, vol. 11, # 13, p. 3899 - 3914
[42] Chemistry - A European Journal, 2003, vol. 9, # 12, p. 2685 - 2695
[43] Journal of Molecular Catalysis A: Chemical, 2010, vol. 332, # 1-2, p. 59 - 64
[44] Catalysis Today, 2010, vol. 157, # 1-4, p. 270 - 274
[45] Catalysis Today, 2010, vol. 157, # 1-4, p. 390 - 396
[46] Green Chemistry, 2010, vol. 12, # 11, p. 1954 - 1958
[47] Journal of Catalysis, 2011, vol. 282, # 1, p. 201 - 208
[48] Journal of Catalysis, 2012, vol. 287, p. 5 - 12
[49] Chemistry - A European Journal, 2012, vol. 18, # 15, p. 4775 - 4781
[50] Asian Journal of Chemistry, 2012, vol. 24, # 3, p. 1199 - 1202
[51] Applied Catalysis A: General, 2012, vol. 439-440, p. 51 - 56
[52] Catalysis Communications, 2012, vol. 29, p. 73 - 76
[53] Chemical Communications, 2013, vol. 49, # 35, p. 3673 - 3675
[54] Applied Catalysis A: General, 2013, vol. 466, p. 307 - 314
[55] Journal of Molecular Catalysis A: Chemical, 2014, vol. 382, p. 8 - 14
[56] European Journal of Inorganic Chemistry, 2014, # 5, p. 812 - 817
[57] Molecules, 2013, vol. 18, # 11, p. 13691 - 13704
[58] European Journal of Inorganic Chemistry, 2014, # 17, p. 2779 - 2786
[59] Journal of Molecular Catalysis A: Chemical, 2014, vol. 392, p. 188 - 193
[60] Dalton Transactions, 2014, vol. 43, # 31, p. 11950 - 11958
[61] Organic Letters, 2014, vol. 16, # 22, p. 5980 - 5983
[62] Journal of the Iranian Chemical Society, 2015, vol. 12, # 3, p. 477 - 485
[63] RSC Advances, 2014, vol. 4, # 104, p. 59885 - 59889
[64] Materials Research Bulletin, 2015, vol. 63, p. 181 - 186
[65] European Journal of Inorganic Chemistry, 2014, vol. 2014, # 17, p. 2779 - 2786
[66] Green Chemistry, 2015, vol. 17, # 9, p. 4552 - 4559
[67] ChemCatChem, 2016, vol. 8, # 1, p. 200 - 208
[68] Asian Journal of Chemistry, 2016, vol. 28, # 3, p. 617 - 621
[69] Catalysis Science and Technology, 2016, vol. 6, # 9, p. 3271 - 3278
[70] RSC Advances, 2016, vol. 6, # 58, p. 53069 - 53079
[71] RSC Advances, 2016, vol. 6, # 41, p. 35071 - 35075
[72] Inorganic Chemistry Communications, 2016, vol. 69, p. 47 - 51
[73] Catalysis Today, 2016, vol. 271, p. 102 - 113
[74] Journal of Nanoscience and Nanotechnology, 2016, vol. 16, # 8, p. 8387 - 8395
[75] Journal of Catalysis, 2016, vol. 340, p. 354 - 367
[76] RSC Advances, 2016, vol. 6, # 71, p. 66841 - 66846
[77] RSC Advances, 2016, vol. 6, # 83, p. 79520 - 79525
[78] Chemistry - A European Journal, 2017, vol. 23, # 8, p. 1920 - 1929
[79] Inorganica Chimica Acta, 2016, vol. 446, p. 13 - 18
[80] Chinese Journal of Catalysis, 2016, vol. 37, # 12, p. 2098 - 2105
[81] Kinetics and Catalysis, 2017, vol. 58, # 1, p. 28 - 33[82] Kinet. Katal., 2017, vol. 58, # 1, p. 30 - 35,6
[83] Australian Journal of Chemistry, 2017, vol. 70, # 3, p. 271 - 279
[84] Green Chemistry, 2017, vol. 19, # 4, p. 1175 - 1181
[85] RSC Advances, 2017, vol. 7, # 8, p. 4681 - 4687
[86] RSC Advances, 2017, vol. 7, # 21, p. 12805 - 12811
[87] ChemCatChem, 2017, vol. 9, # 6, p. 971 - 979
[88] RSC Advances, 2017, vol. 7, # 76, p. 48208 - 48213
[89] Dalton Transactions, 2014, vol. 43, # 39, p. 14570 - 14576
[90] Asian Journal of Chemistry, 2017, vol. 29, # 8, p. 1723 - 1727
[91] Inorganic Chemistry, 2017, vol. 56, # 22, p. 14053 - 14059
[92] Journal of Materials Chemistry A, 2018, vol. 6, # 7, p. 2914 - 2921
[93] Inorganic Chemistry, 2018, vol. 57, # 4, p. 1796 - 1805
[94] Catalysis Letters, 2018, vol. 148, # 8, p. 2501 - 2509
[95] Russian Journal of Applied Chemistry, 2018, vol. 91, # 6, p. 981 - 989[96] Zh. Prikl. Khim. (S.-Peterburg, Russ. Fed.), 2018, vol. 91, # 6, p. 850 - 858,9
[97] Chemistry - A European Journal, 2018, vol. 24, # 43, p. 11059 - 11066
[98] Dalton Transactions, 2018, vol. 47, # 29, p. 9677 - 9684
  • 17
  • [ 95-15-8 ]
  • [ 825-44-5 ]
  • [ 51500-42-6 ]
YieldReaction ConditionsOperation in experiment
75% With tert.-butylhydroperoxide; [Mo2(O)4[2,2'-(1,3-phenylene)bis(4,5-dihydrooxazole-4,2-diyl)]dimethanol}(acac)2] In 1,2-dichloro-ethane for 0.5 h; Reflux General procedure: In a 25 mL round-bottom flask equipped with a magnetic stirring bar, a solution of sulfide (1 mmol), catalyst (6 mg, 0.008 mmol, 0.016 mmol Mo) in 1,2-dichloroethane (4 mL) was prepared. TBHP (2 mmol) was added to this solution and the reaction mixture was stirred under reflux conditions. The reaction progress was monitoredby TLC. After the reaction was completed, the isolation and purification of the products were done as described above.
Reference: [1] Polyhedron, 2014, vol. 72, p. 19 - 26
[2] Catalysis Today, 2013, vol. 211, p. 84 - 89
[3] Journal of the Iranian Chemical Society, 2015, vol. 12, # 3, p. 477 - 485
[4] RSC Advances, 2014, vol. 4, # 102, p. 58800 - 58804
[5] Inorganic Chemistry, 2017, vol. 56, # 10, p. 5748 - 5756
[6] Inorganic Chemistry, 2017, vol. 56, # 19, p. 11710 - 11720
[7] ChemCatChem, 2017, vol. 9, # 19, p. 3714 - 3724
[8] Dalton Transactions, 2018, vol. 47, # 29, p. 9677 - 9684
  • 18
  • [ 95-15-8 ]
  • [ 825-44-5 ]
Reference: [1] Patent: EP1803709, 2007, A1,
  • 19
  • [ 95-15-8 ]
  • [ 825-44-5 ]
  • [ 121823-04-9 ]
  • [ 239-35-0 ]
Reference: [1] Organic and Biomolecular Chemistry, 2012, vol. 10, # 4, p. 782 - 790
  • 20
  • [ 7722-84-1 ]
  • [ 64-19-7 ]
  • [ 95-15-8 ]
  • [ 825-44-5 ]
  • [ 20841-53-6 ]
Reference: [1] Journal of the Chemical Society, 1952, p. 4678,4681
  • 21
  • [ 50-00-0 ]
  • [ 95-15-8 ]
  • [ 17890-56-1 ]
Reference: [1] Journal of the American Chemical Society, 1949, vol. 71, p. 2856,2858
[2] Journal of Organic Chemistry, 1999, vol. 64, # 12, p. 4324 - 4338
[3] Patent: WO2003/101994, 2003, A1, . Location in patent: Page 79
  • 22
  • [ 95-15-8 ]
  • [ 17890-56-1 ]
Reference: [1] Chemistry - A European Journal, 2006, vol. 12, # 10, p. 2739 - 2744
[2] Journal of Medicinal Chemistry, 2002, vol. 45, # 20, p. 4559 - 4570
[3] Acta Chemica Scandinavica, 1996, vol. 50, # 1, p. 71 - 76
[4] Patent: US2004/2488, 2004, A1,
  • 23
  • [ 68-12-2 ]
  • [ 95-15-8 ]
  • [ 17890-56-1 ]
Reference: [1] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1211 - 1214
  • 24
  • [ 93-61-8 ]
  • [ 95-15-8 ]
  • [ 24434-84-2 ]
  • [ 55219-11-9 ]
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4588 - 4595
  • 25
  • [ 4885-02-3 ]
  • [ 95-15-8 ]
  • [ 24434-84-2 ]
Reference: [1] European Journal of Organic Chemistry, 2015, vol. 2015, # 9, p. 2023 - 2029
  • 26
  • [ 95-15-8 ]
  • [ 24434-84-2 ]
  • [ 55219-11-9 ]
Reference: [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 8, p. 2186 - 2189[2] Angew. Chem., 2014, vol. 53, # 8, p. 2218 - 2221,4
  • 27
  • [ 143-33-9 ]
  • [ 95-15-8 ]
  • [ 24434-84-2 ]
  • [ 55219-11-9 ]
Reference: [1] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1992, # 3, p. 333 - 336
  • 28
  • [ 95-15-8 ]
  • [ 10243-15-9 ]
Reference: [1] Chemistry - A European Journal, 2015, vol. 21, # 8, p. 3174 - 3177
[2] Chemistry - A European Journal, 2015, vol. 21, # 23, p. 8471 - 8482
[3] Chemistry - A European Journal, 2016, vol. 22, # 3, p. 1070 - 1075
[4] Synlett, 2017, vol. 28, # 12, p. 1422 - 1426
[5] Patent: CN106905312, 2017, A,
[6] Journal of the American Chemical Society, 2018, vol. 140, # 20, p. 6432 - 6440
  • 29
  • [ 95-15-8 ]
  • [ 6287-82-7 ]
YieldReaction ConditionsOperation in experiment
100% With bromine; potassium acetate In dichloromethane In the DCM solvent, in the presence of potassium acetate, benzothiophene (11) was brominated using bromine the benzothiophene. A white solid of compound (12) was obtained in a yield of 100percent. In addition, equation (1) when manufacturing the compound shown, compound (11) gives the desired compound X can be replaced.
99% With bromine In chloroform at 20℃; for 19.5 h; A solution of 18 g (134 mmol) of benzo[b]thiophene in 200 mL of chloroform was stirred and to this mixture was added 42.9 g (13.7 mL, 268 mmol) of bromine in 100 mL of chloroform dropwise at RT over 1.5 h. After stirring for 18 h, solid NaHCO3 was added to neutralize the hydrobromic acid. The organic layer was washed with water and Na2S2O8 and dried (MgSO4). On evaporation of the solvent solid was obtained which was crystallized from methanol to give 38.8 g (99percent) of 2,3-dibromobenzo[b]thiophene.
90% With bromine In chloroform at 0℃; for 12 h; Benzo[b]thiophene (10 g, 74.5 mmol) was dissolved in 250 ml of chloroform. The resulting solution was cooled down to 0°C and bromine (7.87 ml, 152.8 mmol) was added. The mixture was stirred for 12h. The reaction mixture was poured into water and extracted with chloroform. The organic layer was separated, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure to afford (3) as a white solid, yield 90percent. 1H NMR (CDCl3, 400MHz) 7.76–7.74 (d, J=8.8Hz, 1H), 7.73–7.71 (d, J=8Hz, 1H), 7.45–7.41 (t, J=7.6Hz, 1H), 7.41–7.36 (t, J=8Hz, 1H) ppm.
84% With bromine; potassium acetate In dichloromethane at 20℃; Reflux To a CH2Cl2 solution (50 mL) of benzo[b]thiophene (14, 5.00 g, 37.3 mmol) and KOAc (7.30 g, 74.6 mmol) was added Br2 (3.8 mL, 74.6 mmol) at 20 °C, and the solution was heated under reflux for 24 h.
To the solution was added a satd solution of Na2S2O3 and NaHCO3.
The organic and the aqueous layer were separated, and the latter was extracted with CH2Cl2 (3*30 mL).
The combined organic layers were dried (Na2SO4), filtered, and concentrated in vacuo.
The residue was purified by flash silica column chromatography (pure heptanes) to yield 15a as a white solid (9.1 g, 84percent).
The spectroscopic data were identical with those reported.<ce-sup primary_key="ce-sup-35854493-none">17,18
57 mmol, 28% With bromine In chloroform A.
2,3-Dibromobenzo[b]thiophene STR16
Benzothiophene (26.8 g, 0.2 mol) was dissolved in 150 mL CHCl3 and treated with a solution of bromine (64 g, 0.4 mol) in 75 mL CHCl3 dropwise over an hour.
The reaction was allowed to stir overnight then cautiously quenched with saturated aqueous Na2 CO3 until no gas evolution was evident.
The layers were separated and the organic layer was first washed with saturated aqueous Na2 CO3 then with water.
It was dried over MgSO4 and concentrated under vacuum to a solid.
Recrystallized from MeOH to obtain 16.5 g (57 mmol, 28percent) of a white fluffy solid.
1 H NMR (CDCl3) δ7.77-7.71 (m, 2H), 7.46-7.38 (m, 2H).
57 mmol, 28% With bromine In CHCl3and; CHCl3dropwise A.
2,3-Dibromobenzo[b]thiophene.
Benzothiophene (26.8 g, 0.2 mol) was dissolved in 150 mL CHCl3and treated with a solution of bromine (64 g, 0.4 mol) in 75 mL CHCl3dropwise over an hour.
The reaction was allowed to stir overnight then cautiously quenched with saturated aqueous Na2CO3until no gas evolution was evident.
The layers were separated and the organic layer was first washed with saturated aqueous Na2CO3then with water.
It was dried over MgSO4and concentrated under vacuum to a solid.
Recrystallized from MeOH to obtain 16.5 g (57 mmol, 28percent) of a white fluffy solid.
1H NMR (CDCl3) δ 7.77-7.71 (m, 2H), 7.46-7.38 (m, 2H).

Reference: [1] Patent: JP2017/160159, 2017, A, . Location in patent: Paragraph 0049
[2] Patent: US2014/256936, 2014, A1, . Location in patent: Paragraph 0229
[3] Organic Letters, 2017, vol. 19, # 10, p. 2564 - 2567
[4] Chemistry - A European Journal, 2014, vol. 20, # 49, p. 16266 - 16272
[5] Chemistry - An Asian Journal, 2015, vol. 10, # 8, p. 1725 - 1730
[6] Journal of Organic Chemistry, 1993, vol. 58, # 16, p. 4360 - 4369
[7] Tetrahedron, 1997, vol. 53, # 45, p. 15515 - 15534
[8] Journal of the American Chemical Society, 2018, vol. 140, # 20, p. 6432 - 6440
[9] Chemistry - A European Journal, 2013, vol. 19, # 11, p. 3721 - 3728
[10] Dyes and Pigments, 2014, vol. 111, p. 116 - 123
[11] Tetrahedron, 2013, vol. 69, # 1, p. 160 - 173
[12] Tetrahedron Letters, 2006, vol. 47, # 17, p. 2887 - 2891
[13] Inorganic Chemistry, 2011, vol. 50, # 17, p. 8516 - 8523
[14] Synlett, 2009, # 16, p. 2691 - 2695
[15] Chemische Berichte, 1955, vol. 88, p. 34,36
[16] Synlett, 2002, # 12, p. 2083 - 2085
[17] Patent: US6133262, 2000, A,
[18] Patent: US4659717, 1987, A,
[19] Patent: EP997460, 2000, A1,
[20] Heterocyclic Communications, 2010, vol. 16, # 4-6, p. 241 - 244
[21] New Journal of Chemistry, 2014, vol. 38, # 12, p. 5754 - 5760
[22] Patent: WO2015/188790, 2015, A1, . Location in patent: Page/Page column 22
  • 30
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  • [ 6287-82-7 ]
YieldReaction ConditionsOperation in experiment
90% With sodium hydroxide; bromine In chloroform Synthesis of (R,R) [3,4-bis(2',5'-dimethylphospholanyl)]-benzo[b]thiophene
Stage a:
Synthesis of 2,3-dibromo-benzo[b]thiophene
A solution of Br2(21.1 mL) in CHCl3 (65 mL) was dropped into a solution of benzo[b]thiophene (26.4 g) in CHCl3 (120 mL), under stirring, at a temperature of 0° C.
The progress of the reaction was controlled in TLC (hexane) up to the disappearance of the starting product: Rf (thianaphthene): 0.33, Rf (2,3-dibromobenzothiophene): 0.5.
The mixture was then poured into aqueous, NaOH; the organic phase was separated, washed twice with a solution of 10percent NaOH and once with water, and then dehydrated on Na2SO4.
The solvent was evaporated to yield the 2,3-dibromo-benzo[b]thiophene as a white solid (52 g) (yield 90percent).
Reference: [1] Patent: US2005/107248, 2005, A1,
  • 31
  • [ 95-15-8 ]
  • [ 26167-45-3 ]
Reference: [1] Journal of Chemical Research, Miniprint, 1994, # 5, p. 1042 - 1059
  • 32
  • [ 67-56-1 ]
  • [ 68-12-2 ]
  • [ 95-15-8 ]
  • [ 3541-37-5 ]
  • [ 22913-24-2 ]
YieldReaction ConditionsOperation in experiment
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5 h;
Stage #2: at -78 - 20℃; for 2 h;
General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 °C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3.x.20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82percent yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil.
Reference: [1] Tetrahedron, 2012, vol. 68, # 24, p. 4701 - 4709
  • 33
  • [ 95-15-8 ]
  • [ 22913-24-2 ]
Reference: [1] Chemische Berichte, 1933, vol. 66, p. 245,249
  • 34
  • [ 95-15-8 ]
  • [ 75894-07-4 ]
Reference: [1] Journal of the American Chemical Society, 1949, vol. 71, p. 2856,2858
  • 35
  • [ 105-36-2 ]
  • [ 95-15-8 ]
  • [ 75894-07-4 ]
Reference: [1] Journal of the Chemical Society, 1937, p. 1697
  • 36
  • [ 95-15-8 ]
  • [ 4521-30-6 ]
Reference: [1] Journal of Organic Chemistry, 1993, vol. 58, # 21, p. 5620 - 5623
[2] Angewandte Chemie - International Edition, 2006, vol. 45, # 46, p. 7838 - 7842
  • 37
  • [ 121-43-7 ]
  • [ 95-15-8 ]
  • [ 98437-23-1 ]
YieldReaction ConditionsOperation in experiment
87.3%
Stage #1: With n-butyllithium In tetrahydrofuran at -78 - 20℃; for 13 h;
Stage #2: at -78 - 20℃; for 2 h;
Benzothiophene into a 144 g (554 mmol) and 1000 mL of tetrahydrofuran in the 2L reactor and stirred. After cooling to -78 ° C, was added dropwise 415 mL of nbutyllithium(1.6M hexane solution) and stirred for 1 hour. After stirring thetemperature was raised to room temperature for 12 hours, cooled to -78 ° C andwarming up to room temperature and then added dropwise trimethylborate 80.3 mL(664 mmol) was stirred for 2 hours. After cooling to -0 ° C, into a 2N aqueoushydrochloric acid solution and extracted using ethyl acetate and distilled water. Wasstirred into the formed organic layer was concentrated under reduced pressure and hexane and then filtered to give the intermediate 1-e 86 g (yield 87.3percent).
Reference: [1] Patent: KR2016/2328, 2016, A, . Location in patent: Paragraph 0413-0415
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Reference: [1] Patent: US6342610, 2002, B2, . Location in patent: Page column 112
[2] Organic Letters, 2008, vol. 10, # 13, p. 2697 - 2700
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  • [ 72932-82-2 ]
  • [ 5018-30-4 ]
  • [ 108-59-8 ]
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Reference: [1] Journal of the American Chemical Society, 2007, vol. 129, # 51, p. 15746 - 15747
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  • [ 761423-87-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[2] Patent: CN108276396, 2018, A,
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  • [ 951382-34-6 ]
Reference: [1] Patent: CN108276396, 2018, A,
  • 42
  • [ 95-15-8 ]
  • [ 1034305-17-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
[2] Patent: CN108276396, 2018, A,
  • 43
  • [ 93777-26-5 ]
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  • [ 1034305-11-7 ]
YieldReaction ConditionsOperation in experiment
89%
Stage #1: With n-butyllithium In tetrahydrofuran at -78℃; for 1.5 h;
Stage #2: at -78℃; for 2 h;
At -78 ° C,16.6 g (124 mmol) of benzothiophene (compound of formula 2) was dissolved in 200 mL of tetrahydrofuran.Add 78.5 mL (937 mmol) of n-butyllithium,The mixture was stirred at -78 ° C for 1.5 hours.Will be 23.95g (118mmol)5-bromo-2-fluorobenzaldehyde (formula 1 compound) is solubleIn 300 mL of tetrahydrofuran,And mixing it with the above benzothiophene solution,Stirring was continued for 2 hours at -78 °C.Water and diethyl ether were added to the reaction mixture.Separating the organic phase,And dried with magnesium sulfate,It is then filtered and dried under vacuum.The obtained crude product was purified by column chromatography (ethyl acetate-hexane).Obtaining benzo[b]thiophene-2-methanol,Α-(5-bromo-2-fluorophenyl) (compound of formula 3) 35.4 g;Purity 99.5percent; yield 89percent;
84.8%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -24.2 - -13.5℃; Inert atmosphere
Stage #2: at -23.5 - -11.8℃; Inert atmosphere
Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane; toluene
EXAMPLE; (Example); First step: Synthesis of 1-benzothien-2-yl(5-bromo-2-fluorophenyl)methanol; Into a tetrahydrofuran (100 liters) solution of benzo[b]thiophene (17.4 kg ) was dropwise added a n-hexane solution (56.2 kg) of n-butyl lithium (15.08percent) in an argon atmosphere at -24.2 to -13.5°C, followed by stirring at -22.1 to -13.5°C for 40 minutes. Into this solution was dropwise added a tetrahydrofuran (18 liters) solution of 5-bromo-2-fluorobenzaldehyde (25.5 kg) at -22.1 to -11.8°C, followed by stirring at -23.5 to -16.1°C for 2 hours. To the reaction mixture were added water (100 liters), toluene (130 liters) and 38percent hydrochloric acid (12.3 kg), and extraction was conducted. The organic layer was washed with water (130 liters) and then subjected to distillation at normal pressure to distill off the solvent until the residue became 100 liters. Toluene (130 liters) was added to the residue and the mixture was subjected to distillation at normal pressure to distil off the solvent until the residue became 100 liters. The operation of adding toluene to the residue and subjecting the mixture to distillation under reduced pressure to distill off the solvent, was repeated twice: Then, n-heptane (310 liters) was added to the residue, followed by heating to dissolve the residue. To the solution was added, as a seed crystal, about 26 g of the 1-benzothien-2-yl(5-bromo-2-fluorophenyl)methanol produced in the same manner as that shown in the first step of Reference Example 1, followed by stirring at 1.2 to 5.0°C for 13 hours. The separated-out crystals were collected by filtration, washed twice with a toluene-n-heptane (1:6) mixed solvent (26 liters), and subjected to vacuum drying to obtain, as white crystals, 1-benzothien-2-yl(5-bromo-2-fluorophenyl)methanol [35.91 kg, yield: 84.8percent, purity: 99percent (HPLC)]. 1H-NMR (CDCl3): δ 2.74 (1H, d), 6.35 (1H, d), 6.93 (1H, dd), 7.14 (1H, s), 7.27-7.38 (2H, m), 7.39 (1H, m), 7.68 (1H, dd), 7.74 (2H, m)
Reference: [1] Patent: CN108276396, 2018, A, . Location in patent: Paragraph 0041; 0046; 0047; 0062; 0077
[2] Patent: EP2105442, 2009, A1, . Location in patent: Page/Page column 13
[3] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3263 - 3279
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