* 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 the Chemical Society, 1940, p. 305,308
[2] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 2697 - 2717
8
[ 251-41-2 ]
[ 25121-87-3 ]
Yield
Reaction Conditions
Operation in experiment
99%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃;
Thienothiophene(2.01 g of Tokyo Chemical Industry Co., Ltd.) and 30 mL of dimethylformamide (DMF) were placed in a reaction vessel.After stirring at room temperature to confirm dissolution,6.10 g (2.4 eq) of N-bromosuccinimide (NBS) was put in a powder state.After confirming the disappearance of the raw materials, n-hexane and ion-exchanged water were added to the reaction solution.Perform liquid separation.After washing the organic layer with ion-exchanged water and saturated saline once,Drying was carried out using Na2SO4.Distilling off the solvent under reduced pressure and dryingThiophenethiophene dibromide4.21g (99percent yield).
95%
With N-Bromosuccinimide In N,N-dimethyl-formamide at 0℃; for 12 h;
Added to the reactor 30 mlDMF, thieno [3, 2 - b] thiophene (2.31 g, 16.5 mmol), followed by cooling to 0 °C, adding NBS (8.81 g, 49.5 mmol), light reaction 12 h, NaHSO reaction after the conclusion3Washing, removing the upper layer solvent, congeals the organic phase concentration, over silica gel column purification to obtain compound C - 21 - 1 (4.67 g, 95percent).
88%
With N-Bromosuccinimide In DMF (N,N-dimethyl-formamide) at 20℃; for 3 h;
N-bromosuccinimide (1.24 g, 6.94 mmol) was added to a solution of thieno [3,2-b]thiophene (1.0 g, 6.94 mmol) in DMF (30 ml) at room temperature and this mixture was stirred for 3h. After this water ( 100 ml) was added and the precipitate formed was filtrated off, washed with water and dried to give 2 as a white solid (1.87 g, 88 percent). 1H NMR (300 MHz, CDCl3): 8 (ppm) 7.14 (s, 2H, Ar-H); 13C NMR (75 MHz, CDC13): 8 (ppm) 138.3 (quat.), 121.8 (CH), 113.7 (quat.)
85%
at 20℃; Inert atmosphere
A solution of 1.55 g (8.7 mmol) of N-bromosuccinimide (NBS) in 1 ml of DMF was slowly added in a stirred solution of 0.61 g (4.35 mmol) of thieno[3,2-b]thiophene in 9 ml of DMF. The reaction mixture was stirred overnight. The product was extracted with dichloromethane and the organic phase was washed 3 times with water, dried with MgSO4 and the organic solvent was removed with roto-evaporation. The resulting crude residue was purified by column chromatography on silica gel with hexane/dichloromethane 9/1 to give a white solid (1 g, 85percent yield). (m.p. 116.4-118.6 °C) δH (200 MHz, CDCl3) 7.19 (1H, s, 1-H), δC (50 MHz, CDCl3) 128.6, 122.2, 114.4.
68%
With N-Bromosuccinimide In tetrahydrofuran at 10℃; for 80 h; Inert atmosphere
In a 150 mL 3-neckedflask, a solution of thienothiophene(TT) (11.2 g, 80 mmol) in dry THF (100 mL) was cooled to 10 °C under a nitrogenatmosphere. NBS (35.6 g, 200 mmol) was addedslowly in portions and allowed to stir for 8 h at approximately 10 °C. Thereaction mixture was then poured into dichloromethane (DCM).The organic layer was washed with water and dried over anhydrous MgSO4. After removing thesolvent, the crude product was recrystallized from petroleum ether (PE, boiling range: 60-90 C) to give a colorless solid(16.2 g, 68percent yield). 1H NMR (300 MHz, CDCl3):δ (ppm) 7.14 (s, 2H). 13C NMR (75 MHz, CDCl3):δ (ppm) 138.31, 121.75, 113.64. GC-MS (EI, m/z) calcd for (C6H2Br2S2):297.79, found: 297.77.
Reference：
[1] Patent: TWI630193, 2018, B, . Location in patent: Paragraph 0104; 0105
[2] Chemistry - A European Journal, 2011, vol. 17, # 3, p. 866 - 872
[3] Angewandte Chemie - International Edition, 2013, vol. 52, # 10, p. 2920 - 2924[4] Angew. Chem., 2013, vol. 125, # 10, p. 2992 - 2996,5
[5] Tetrahedron Letters, 2009, vol. 50, # 51, p. 7148 - 7151
[6] Patent: CN107056798, 2017, A, . Location in patent: Paragraph 0061; 0062; 0063; 0064
[7] Journal of Nanoscience and Nanotechnology, 2010, vol. 10, # 10, p. 6800 - 6804
[8] Journal of Organic Chemistry, 2015, vol. 80, # 20, p. 10127 - 10133
[9] Macromolecules, 2013, vol. 46, # 3, p. 727 - 735
[10] Patent: WO2005/121150, 2005, A1, . Location in patent: Page/Page column 33
[11] Organic Electronics: physics, materials, applications, 2014, vol. 15, # 4, p. 943 - 953
[12] Dyes and Pigments, 2015, vol. 116, p. 146 - 154
[13] Polymer, 2012, vol. 53, # 12, p. 2334 - 2346
[14] Journal of the Institute of Petroleum, 1948, vol. 34, p. 226,229
[15] Dalton Transactions, 2005, # 5, p. 874 - 883
[16] Molecules, 2012, vol. 17, # 10, p. 12163 - 12171
[17] Journal of the American Chemical Society, 2013, vol. 135, # 6, p. 2040 - 2043
[18] Patent: US8779204, 2014, B2, . Location in patent: Page/Page column 13; 14
[19] Patent: KR101540066, 2015, B1, . Location in patent: Paragraph 0021; 0022; 0023
9
[ 251-41-2 ]
[ 124638-53-5 ]
Yield
Reaction Conditions
Operation in experiment
95%
With bromine; acetic acid In chloroform at 20 - 78℃;
S1,willAnd thiophenethienothiophene(5 g, 35.7 mmol)Soluble in glacial acetic acid (36ml)And chloroform (10 ml)Of the mixed solvent,Br2 is added dropwise at room temperature(28.5 g, 180.56 mmol),Continue to stir for half an hour,And then heated to reflux at room temperature of 78 ° C overnight; Ling to room temperature, washed with water, precipitation of white solid compounds, and then washed with water and methanol 3 times, vacuum drying at room temperature,To give white solid compound 1, [M +] = 455.0 (yield: 95percent);
93%
Stage #1: With acetic acid In chloroform for 1 h; Inert atmosphere Stage #2: With bromine In chloroform for 1 h; Reflux
In the reactor into the thieno [3, 2 - b] thiophene (4.21 g, 30 mmol), under the protection of nitrogen, acetic acid is added into the reactor 30 ml, chloroform 50 ml, will be 20 mmol of Br2Solution is dripped slowly into the reaction in the reactor, stirring after 1 h, then gradually adding 15 mmol of Br2, Stirring 1 h, reflux overnight, cooled to the room temperature, to obtain the solid precipitation, successively de-ionized water and methanol washing, drying, the obtained crude product over silica gel column, to obtain compound C - 1 - 1 (12.72 g, 93percent).
91%
With bromine In chloroform at 60℃; for 24 h; Inert atmosphere
In an inert atmosphere, the bromine (9.2 ml; 28.5 g; 178.2 mmoles) diluted in 40 ml of chloroform is added to a solution of thienothiophene (5g; 35.7 mmoles) in 40 ml of chloroform, by slow dripping. The temperature is brought to 60°C. After 24 hours, it is brought to 20°C and a 1 M aqueous solution of sodium thiosulfate is added until the excess bromine is completely destroyed. The precipitate is filtered and washed first with water and then with chloroform. 14.6 g of 2,3,5,6-tetrabromothieno[3,2-b]thiophene of formula (VI) are obtained with a 91 percent yield:
Reference：
[1] Patent: CN106188090, 2016, A, . Location in patent: Paragraph 0086
[2] Patent: CN107056798, 2017, A, . Location in patent: Paragraph 0055; 0056; 0057
[3] Patent: WO2016/92065, 2016, A1, . Location in patent: Page/Page column 21
[4] Journal of Materials Chemistry C, 2018, vol. 6, # 16, p. 4471 - 4478
[5] Bulletin of the Chemical Society of Japan, 1989, vol. 62, # 5, p. 1547 - 1555
[6] J. Inst. Petr. Technol., 1935, vol. 21, p. 135,148
[7] Chemical Communications, 2005, # 9, p. 1161 - 1163
[8] Patent: US2009/43113, 2009, A1, . Location in patent: Page/Page column 6
[9] Chemistry - An Asian Journal, 2010, vol. 5, # 7, p. 1550 - 1554
[10] New Journal of Chemistry, 2013, vol. 37, # 4, p. 1189 - 1194
[11] Chemical Communications, 2015, vol. 51, # 60, p. 11961 - 11963
10
[ 251-41-2 ]
[ 68-12-2 ]
[ 31486-86-9 ]
Yield
Reaction Conditions
Operation in experiment
75%
With trichlorophosphate In 1,2-dichloro-ethane at 0 - 20℃;
Thieno[3,2-b]thiophene (3.00g, 21.4mmol) was taken in a 100mL round bottom flask in ethylene dichloride (75.0mL) and dimethylformamide (1.65mL, 21.4mmol) was added at room temperature. The resulting reaction solution was cooled to 0°C and POCl3 (5.87mL, 64.3mmol) was added drop-wise. The reaction mixture was allowed to warm to room temperature and heated at reflux overnight. The reaction mixture was treated with a saturated solution of sodium acetate and the organic layer was separated. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulphate and the solvent was evaporated in vacuo to give a crude dark yellow oil, which was purified by column chromatography on silica (hexane:ethyl acetate 9:1) to give the title compoundS1 (2.70g, 75percent) as a light yellow oil. Rf (10percent ethyl acetate/hexane) 0.45; 1H NMR (400MHz, CD3COCD3, 25°C, ppm) δ 10.05 (s, 1H), 8.33 (s, 1H), 8.00–7.99 (m, 1H), 7.57–7.55 (m, 1H); 13C NMR (100.6MHz, CDCl3, 25°C, ppm) δ 183.7, 145.9, 145.6, 139.4, 134.1, 129.3, 120.3; HRMS (APCI): calcd for C7H5OS2 (M+H)+ 168.9775; found 168.9776.
74.98%
With trichlorophosphate In 1,2-dichloro-ethane at 0℃; Reflux
Compound Example 4.; Step 1 . Synthesis of thieno[3,2-blthiophene-2-carbaldehyde; Thieno[3,2-b]thiophene (3 g, 21.43 mmol) was taken in ethylene dichloride (75 ml) in a 250 ml round bottom flask followed by the addition of dimethylformamide (1.65 ml, 21 .43 mmol) at RT. The resulting reaction solution was cooled to 0°C and POCI3 (5.87 ml, 64.29 mmol) was added to it. The reaction mixture was allowed to warm to RT and refluxed for overnight. Reaction mix was allowed to cool down, worked up with saturated sodium acetate solution and product was extracted in ethyl acetate. The organic layer was washed twice with water followed by brine and dried over Na2S04 and recovered to afford crude yellow oil which was subjected to column chromatography on silica (Hexane:Ethyl acetate (9:1 )) to afford 2.7 g (74.98percent) of thieno[3,2-b]thiophene-2-carbaldehyde as light yellow oil.1H NMR (200MHz, DMSO) δ 9.97 (s, IH), 8.39 (m, 1 H), 8.07 (m, 1 H), 7.55 (m, 1 H)
67%
With trichlorophosphate In 1,2-dichloro-ethane at 0 - 80℃; for 5 h; Inert atmosphere
In a 250 mL 3-necked flask, asolution of DMF (21.9 g, 300 mmol) in dry 1,2-dichloroethane (50 mL) was cooled to 0 °C under a nitrogen atmosphere. Following this, POCl3 (23.0 g, 150mmol) was added dropwise with stirring. When all the POCl3 had been added, and the heat of the reaction had subsided, a solution of thienothiophene (TT) (14.0 g, 100 mmol) in 1,2-dichloroethane (50 mL) was added dropwise. The reaction mixture was stirred for 5 h at 80 °C and then poured into cold saturated solution of sodium bicarbonate (200 mL) and extracted with DCM. The organic layer was washed with water and dried over anhydrous MgSO4. After removing the solvent, the crude product obtained was purified by column chromatography (PE/EA = 15/1, v/v) to give a light yellow solid (11.3 g, 67percentyield). 1H NMR (300 MHz, CDCl3): δ (ppm) 9.96 (s, 1H),7.93 (s, 1H), 7.69 (d, J = 5.1 Hz, 1H), 7.33 (d, J = 5.4 Hz, 1H).13C NMR (75 MHz, CDCl3): δ (ppm) 183.54, 145.73, 145.47,139.23, 133.90, 129.06, 120.16. GC-MS (EI,m/z) calcd. for (C7H4OS2): 167.97. Found:168.03.
Reference：
[1] Journal of Materials Chemistry C, 2015, vol. 3, # 2, p. 370 - 381
[2] Chemistry - A European Journal, 2014, vol. 20, # 34, p. 10685 - 10694
[3] Dyes and Pigments, 2015, vol. 119, p. 122 - 132
[4] Patent: WO2011/137487, 2011, A1, . Location in patent: Page/Page column 31
[5] Dyes and Pigments, 2015, vol. 120, p. 85 - 92
[6] Journal of Materials Chemistry A, 2016, vol. 4, # 22, p. 8784 - 8792
[7] Journal of Medicinal Chemistry, 2017, vol. 60, # 7, p. 2697 - 2717
[8] Journal of Organic Chemistry, 2008, vol. 73, # 12, p. 4608 - 4614
[9] Patent: US6642237, 2003, B1, . Location in patent: Page/Page column 125-126
[10] Journal of Materials Chemistry A, 2013, vol. 1, # 37, p. 11295 - 11305
[11] RSC Advances, 2013, vol. 3, # 44, p. 22544 - 22553
Reference：
[1] Synlett, 2011, # 15, p. 2151 - 2156
13
[ 251-41-2 ]
[ 392662-65-6 ]
Reference：
[1] Chemical Communications, 2005, # 9, p. 1161 - 1163
[2] Macromolecules, 2013, vol. 46, # 3, p. 727 - 735
[3] Patent: WO2016/92065, 2016, A1,
[4] Patent: CN107056798, 2017, A,
14
[ 251-41-2 ]
[ 61676-62-8 ]
[ 924894-85-9 ]
Yield
Reaction Conditions
Operation in experiment
61.25%
Stage #1: With n-butyllithium In tetrahydrofuran; hexanes at -78℃; for 1.16667 h; Inert atmosphere; Cooling with ice Stage #3: With ammonium chloride In tetrahydrofuran; hexanes; water
To a solution of thieno[3,2-b]thiophene (1 .5 g, 10.70 mmol) in THF (25.5 mL) at -78 °C under N 2 is added dropwise a solution of BuLi in hexanes (8.988 mL of 2.5 M, 22.47 mmol), stirred for 20 min, cooling bath is replaced with ice bath and stirred for 50 min. The resultant thick suspension is quenched with 2- isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (4.181 g, 4.584 mL, 22.47 mmol). The reaction mixture is kept for overnight and then quenched with saturated aq. NH4Cl solution. After extraction with CH2Cl2 (2 x 100 mL), the combined extracts are washed with brine and dried (Na2S04). Organic solution is diluted with -20 mL of ethyl acetate, concentrated slowly on rotary evaporator until CH2Cl2 is removed. The resultant white fine crystals are collected by filtration. The solid is washed with heptanes and dried under high vacuum to afford 4,4,5,5-tetramethyl-2-[5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)thieno[3,2-b]thiophen-2-yl]-1 ,3,2-dioxaborolane (2.57 g, 6.554 mmol, 61.25percent) as half-white solid. 1H NMR (400 MHz, CDCl3) δ 7.75 (s, 2H), 1.343 (s, 12H).
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃;
Thienothiophene(2.01 g of Tokyo Chemical Industry Co., Ltd.) and 30 mL of dimethylformamide (DMF) were placed in a reaction vessel.After stirring at room temperature to confirm dissolution,6.10 g (2.4 eq) of N-bromosuccinimide (NBS) was put in a powder state.After confirming the disappearance of the raw materials, n-hexane and ion-exchanged water were added to the reaction solution.Perform liquid separation.After washing the organic layer with ion-exchanged water and saturated saline once,Drying was carried out using Na2SO4.Distilling off the solvent under reduced pressure and dryingThiophenethiophene dibromide4.21g (99% yield).
99%
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃;
2.00 g of thienothiophene (manufactured by Tokyo Chemical Industry Co., Ltd.) and 30 mL of dimethylformamide (DMF) were placed in a reaction vessel, and after stirring at room temperature to confirm dissolution, N-bromosuccinimide was added. (Bromosuccinimide: NBS) 6.10 g (2.4 eq) was put in a powder state.After confirming that the raw materials disappear,N-hexane and ion-exchanged water are added to the reaction solution.Perform liquid separation.The organic layer was washed once with ion-exchanged water and saturated brine, and dried using Na 2 SO 4 .Distilling off the solvent under reduced pressure and drying4.21 g (yield 99%) of the desired thienothiophene dibromide was obtained.
99%
With N-Bromosuccinimide; In chloroform; for 18h;Reflux;
To a solution of thieno[3,2-b]thiophene (10.3 g, 73.5 mmol) in chloroform (200 mL) was added N-bromosuccinimide (32.7 g, 183.8 mmol). The mixture was heated at reflux for 18 hours. The reaction mixture was allowed to cool to room temperature before being diluted with dichloromethane (50 mL) and washed with distilled water (2*100 mL), sodium hydrogen carbonate saturated solution (100 mL), and ammonium chloride saturated solution (100 mL) and brine (100 mL). The organic layer was passed through a phase separator and concentrated in vacuo, yielding 2,5-dibromothieno[3,2-b]thiophene (21.8 g, 99%) as a grey solid. 1H NMR (400 MHz, CDCl3): delta 7.16 (s, 2H).
98%
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 3h;Inert atmosphere;
A 500 ml double neck round bottom flask was placed and placed in a stir bar, and dried and filled with nitrogen; 14.022 g of thieno[3,2-b]thiophene (0.1 mol, 1 eq) and 36.488 g of N-bromosuccinyl group were separately added. (0.205 mol, 2.05 eq),Then, 250 mL of N,N-dimethylformamide was added at 0 C and the reaction was continued for 3 hours; the reaction was terminated with 200 mL of a saturated aqueous solution of sodium hydrogencarbonate.Then extract with 200 mL of diethyl ether and repeat the extraction 3 times.The obtained extract is sequentially added with magnesium sulfate to dry, filtered and spin-dried;The crude product was purified by hexane as a solvent.29.205 g of compound P01 were obtained (yield: 98%).
95%
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 0℃; for 12h;
Added to the reactor 30 mlDMF, thieno [3, 2 - b] thiophene (2.31 g, 16.5 mmol), followed by cooling to 0 C, adding NBS (8.81 g, 49.5 mmol), light reaction 12 h, NaHSO reaction after the conclusion3Washing, removing the upper layer solvent, congeals the organic phase concentration, over silica gel column purification to obtain compound C - 21 - 1 (4.67 g, 95%).
88%
With N-Bromosuccinimide; In DMF (N,N-dimethyl-formamide); at 20℃; for 3h;
N-bromosuccinimide (1.24 g, 6.94 mmol) was added to a solution of thieno [3,2-b]thiophene (1.0 g, 6.94 mmol) in DMF (30 ml) at room temperature and this mixture was stirred for 3h. After this water ( 100 ml) was added and the precipitate formed was filtrated off, washed with water and dried to give 2 as a white solid (1.87 g, 88 %). ¹H NMR (300 MHz, CDCl3): 8 (ppm) 7.14 (s, 2H, Ar-H); ¹³C NMR (75 MHz, CDC13): 8 (ppm) 138.3 (quat.), 121.8 (CH), 113.7 (quat.)
85%
With N-Bromosuccinimide; at 20℃;Inert atmosphere;
A solution of 1.55 g (8.7 mmol) of N-bromosuccinimide (NBS) in 1 ml of DMF was slowly added in a stirred solution of 0.61 g (4.35 mmol) of thieno[3,2-b]thiophene in 9 ml of DMF. The reaction mixture was stirred overnight. The product was extracted with dichloromethane and the organic phase was washed 3 times with water, dried with MgSO4 and the organic solvent was removed with roto-evaporation. The resulting crude residue was purified by column chromatography on silica gel with hexane/dichloromethane 9/1 to give a white solid (1 g, 85% yield). (m.p. 116.4-118.6 C) deltaH (200 MHz, CDCl3) 7.19 (1H, s, 1-H), deltaC (50 MHz, CDCl3) 128.6, 122.2, 114.4.
68%
With N-Bromosuccinimide; In tetrahydrofuran; at 10℃; for 80h;Inert atmosphere;
In a 150 mL 3-neckedflask, a solution of thienothiophene(TT) (11.2 g, 80 mmol) in dry THF (100 mL) was cooled to 10 C under a nitrogenatmosphere. NBS (35.6 g, 200 mmol) was addedslowly in portions and allowed to stir for 8 h at approximately 10 C. Thereaction mixture was then poured into dichloromethane (DCM).The organic layer was washed with water and dried over anhydrous MgSO4. After removing thesolvent, the crude product was recrystallized from petroleum ether (PE, boiling range: 60-90 C) to give a colorless solid(16.2 g, 68% yield). 1H NMR (300 MHz, CDCl3):delta (ppm) 7.14 (s, 2H). 13C NMR (75 MHz, CDCl3):delta (ppm) 138.31, 121.75, 113.64. GC-MS (EI, m/z) calcd for (C6H2Br2S2):297.79, found: 297.77.
With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 12h;Cooling;
Specific preparation process is described as follows: under the conditions of ice-bath and keeping out of the sun, adding 7.83 g NBS in batches into reactor containing 2.80 g thieno[3,2-b]thiophene and 60 mE DMF, stirring for i2 hours at room temperature. After the reaction, quenching reaction solution by pouring into ice water, extracting with dichloromethane, drying with anhydrous magnesium sulfate, rotary evaporating, separating by column chromatography to obtain solid products. The test result is: MAEDI-TOF-MS (mlz):298.0 (M).
With bromine; acetic acid; In chloroform; at 20 - 78℃;
S1,willAnd thiophenethienothiophene(5 g, 35.7 mmol)Soluble in glacial acetic acid (36ml)And chloroform (10 ml)Of the mixed solvent,Br2 is added dropwise at room temperature(28.5 g, 180.56 mmol),Continue to stir for half an hour,And then heated to reflux at room temperature of 78 C overnight; Ling to room temperature, washed with water, precipitation of white solid compounds, and then washed with water and methanol 3 times, vacuum drying at room temperature,To give white solid compound 1, [M +] = 455.0 (yield: 95%);
93%
In the reactor into the thieno [3, 2 - b] thiophene (4.21 g, 30 mmol), under the protection of nitrogen, acetic acid is added into the reactor 30 ml, chloroform 50 ml, will be 20 mmol of Br2Solution is dripped slowly into the reaction in the reactor, stirring after 1 h, then gradually adding 15 mmol of Br2, Stirring 1 h, reflux overnight, cooled to the room temperature, to obtain the solid precipitation, successively de-ionized water and methanol washing, drying, the obtained crude product over silica gel column, to obtain compound C - 1 - 1 (12.72 g, 93%).
91%
With bromine; In chloroform; at 60℃; for 24h;Inert atmosphere;
In an inert atmosphere, the bromine (9.2 ml; 28.5 g; 178.2 mmoles) diluted in 40 ml of chloroform is added to a solution of thienothiophene (5g; 35.7 mmoles) in 40 ml of chloroform, by slow dripping. The temperature is brought to 60C. After 24 hours, it is brought to 20C and a 1 M aqueous solution of sodium thiosulfate is added until the excess bromine is completely destroyed. The precipitate is filtered and washed first with water and then with chloroform. 14.6 g of 2,3,5,6-tetrabromo<strong>[251-41-2]thieno[3,2-b]thiophene</strong> of formula (VI) are obtained with a 91 % yield:
Synthesis of Compound 2Tetrabromothienothiophene was obtained by brominating thienothiophene using techniques developed by Iddon et al. (Lance S. Fuller, Brian Iddon, Kevin A. Smith J. Chem. Soc., Perkin Trans. 1, 1997, 34653470).Tetrabromo-<strong>[251-41-2]thieno[3,2-b]thiophene</strong> (2.0 g, 4.39 mmol) was dissolved in 50 ml of dry tetrahydrofuran (THF). The solution was cooled to -78 C. The cooled solution was slowly added with butyllithium (4 ml of 2.5 M in a hexane solution) and stirred for 30 min. Benzaldehyde (0.94 ml, 9.22 mmol) was slowly added in droplets. The solution was stirred overnight, allowing the temperature to gradually increase to room temperature. The solution was added with 50 ml of a saturated ammonium chloride solution and diluted with ethyl acetate. The organic layer was separated, dried and concentrated under reduced pressure, yielding compound 2 (a white solid). Compound 2 was used directly in the following reaction without additional purification or separation.
[Preparation of Heteroacene Compound]; PREPARATIVE EXAMPLE 1; (1) Synthesis of Compound 2; Thienothiophene 1 could be synthesized using a process developed by Iddon et al (Lance S. Fuller, Brian Iddon, Kevin A. Smith J. Chem. Soc., Perkin Trans. 1, 1997, 3465-3470). The thienothiophene (about 3.35 g, about 24 mmol) was dissolved in about 50 ml of dry ether, and the solution was added in droplets to about 100 ml of a dry ether solution containing butyl lithium (about 21 ml of about 2.5 M in a hexane solution) cooled to about 0 C., after which the temperature was gradually increased and a stirring process was performed at about room temperature for about 2 hours. To the turbid solution, dimethylformamide (DMF, about 4.6 ml) was slowly added in droplets and then the mixture was stirred overnight. About 50 ml of a saturated solution of ammonium chloride was added thereto, and a precipitate was filtered and then washed several times with water and ether, thus obtaining a desired compound 2 (yield about 75%).1NMR (CDCl3) d 10.1 (s, 2H), 8.05 (s, 2H).
~ 75%
(1) Synthesis of Compound 2; Thienothiophene 1 could be synthesized using a process developed by Iddon et al (Lance S. Fuller, Brian Iddon, Kevin A. Smith J. Chem. Soc., Perkin Trans. 1, 1997, 3465-3470). The thienothiophene (about 3.35 g, about 24 mmol) was dissolved in about 50 ml of dry ether, and the solution was added in droplets to about 100 ml of a dry ether solution containing butyl lithium (about 21 ml of about 2.5 M in a hexane solution) cooled to about 0C, after which the temperature was gradually increased and a stirring process was performed at about room temperature for about 2 hours. To the turbid solution, dimethylformamide (DMF, about 4.6 ml) was slowly added in droplets and then the mixture was stirred overnight. About 50 ml of a saturated solution of ammonium chloride was added thereto, and a precipitate was filtered and then washed several times with water and ether, thus obtaining a desired compound 2 (yield about 75%). 1NMR (CDCl3) d 10. 1 (s, 2H), 8.05 (s, 2H) .
75%
Thienothiophene 1 is synthesized in a method developed by Iddon and the like (Reference: Lance S. Fuller, Brian Iddon, Kevin A. Smith J. Chem. Soc., Perkin Trans. 1, 1997, 3465-3470). Thienothiophene (3.35 g, 24 mmol) is dissolved in 50 mL of dry ether, and the solution is added in a dropwise fashion to 100 mL of a dry ether solution including butyl lithium (2.5 M in 21 mL of a hexane solution) cooled down to 0 C., and the mixture is slowly heated up to room temperature and stirred for 2 hours. Subsequently, dimethyl formamide (DMF; 4.6 mL) is added in a dropwise fashion to the opaque solution, and the obtained mixture is stirred overnight. Then, 50 mL of an ammonium chloride-saturated solution is added thereto, and a precipitate therein is filtered and several times washed with water and ether to obtain desired Compound 2 (A yield: 75%). (0246) 1NMR (CDCl3) d 10.1 (s, 2H), 8.05 (s, 2H).
45%
The synthetic route of CNP2V2TT molecule is shown as Scheme 1 . To a solution of <strong>[251-41-2]thieno[3, 2-b]thiophene</strong> 1 (0.56 g, 4 mmol) and in dry Et2O 50 ml, n-butyl lithium in n-hexane (6 ml, 10 mmol, 1.6 M) was added dropwise under an argon atmosphere at 0 C. The stirring was continued for 2 h and subsequently DMF (?1 ml, 13 mmol) was added and stirred for additional 1 day at ambient temperature. The solution was quenched with diluted aqueous HCl under vigorous stirring. The precipitate was filtered and dried to give a yellow solid 2 (354 mg, 1.8 mmol, yield 45%), which was practically pure and can be used to the next reaction. 1H NMR (500 MHz, CDCl3) delta8.01 (s, 2H, Ar-H), 10.05 (s, 2H, CHO);
17%
General procedure: To a solution of <strong>[251-41-2]thieno[3,2-b]thiophene</strong> 7 (0.5 g, 3.56 mmol) in THF (10 ml) an n-butyllithiumsolution (2.5 in hexanes, 3.1 ml, 7.84 mmol, 2.2 equiv.) was carefully added at -78 C under argon and thereaction mixture was slowly allowed to warm to 0 C within 2 h. Anhydrousdimethylformamide (1 ml, excess) was then added and the reaction was stirred room temperature overnight. The solutionwas poured into aq HCl (1N, 10 ml) and stirred for 20 min. After neutralisationby aq NaHCO3 (1N, 10 ml), the water phase was extracted withdichloromethane (3 x 30 ml). The combined organic portions were dried overanhydrous MgSO4 and the solvent was removed in vacuo. Thechromatography of the crude mixture on silicagel (hexane-ethyl acetate 6:1) yielded to dicarbaldehyde 8d (115mg, 17%) as a white amorphous solid
2,5-Bis-trimethylsilanyl-thieno[3,2-b]thiophene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85.95%
Thieno[3,2-b]thiophene (5 g, 35.7 mmol), dissolved in 100 mL of anhydrous tetrahydrofuran,Under ice protection, the ice water bath was cooled to 0 C and stirred for 30 minutes.Slowly add n-butyllithium (35.7mL, 2.5M), the solution gradually changed from light yellow to orange yellow.Wine red, purple, dark brown, brown eventually turned grayish pink, after stirring for 1 hour,Further, trimethylsilyl chloride (11.57 mL, 0.11 mol) was slowly added dropwise.The solution changed from gray-green turbid to brown to dark green, and after stirring for 10 minutes in an ice bath,Remove and leave at room temperature for 4 hours, the system gradually fades from dark green,It is transparent yellow green and finally transparent yellow.After quenching with water, the mixture was extracted with methylene chloride.Filter, collect the filtrate, and remove the solvent. The mixture was separated and purified on a silica gel column and rinsed with petroleum ether.8.7 g of a white solid were obtained in a yield of 85.95%.
Its synthesis was referenced the four step method according to previous reports by us and Fuller et al.[22,23]. Lithium diisopropylamide (LDA) (27.4 mL 218.9 mmol) was added in the 100 mL of dry THF solution with 3-bromothiophene (7.9 g, 48.5 mmol) and N-formylpiperidine (6.1 mL 54.8 mmol) was added after stirred 30 min at 0 C. After simple purification, the crude product was add to the N,N-dimethylformamide (100 mL) solution containing ethyl 2-sulfanylacetate (4.12g 34.3 mmol) and K2CO3 (8.6 g 62.2 mmol) for stirring 97 h. The crude product was added to the mixture solution of LiOH (1 mol L-1 50 mL) and THF (150 mL) (1/3 v/v) and added 0.1M HCl (15 mL) solution after reflux for 6 h to get the solid powder. The solid powder was added to quinolone (4 mL) solution with Cu powder (0.1 g) stirring at 260 C for 1 h. The crude product was purified by column chromatography (petroleum ether (PE)) and dried in vacuoto give pure TT as white solid. (1.9 g 28%). 1H NMR (400 MHz, CDCl3)delta 7.37 (d, J=4.9 Hz, 2H), 7.26-7.24 (m, 2H). Anal. Calcd for C6H4S2:C, 51.34, H, 2.85 and S, 44.21. Found: C, 51.36, H, 2.56 and S, 44.23.
With trichlorophosphate; In 1,2-dichloro-ethane; at 0 - 20℃;
Thieno[3,2-b]thiophene (3.00g, 21.4mmol) was taken in a 100mL round bottom flask in ethylene dichloride (75.0mL) and dimethylformamide (1.65mL, 21.4mmol) was added at room temperature. The resulting reaction solution was cooled to 0C and POCl3 (5.87mL, 64.3mmol) was added drop-wise. The reaction mixture was allowed to warm to room temperature and heated at reflux overnight. The reaction mixture was treated with a saturated solution of sodium acetate and the organic layer was separated. The organic layer was washed with water followed by brine, dried over anhydrous sodium sulphate and the solvent was evaporated in vacuo to give a crude dark yellow oil, which was purified by column chromatography on silica (hexane:ethyl acetate 9:1) to give the title compoundS1 (2.70g, 75%) as a light yellow oil. Rf (10% ethyl acetate/hexane) 0.45; 1H NMR (400MHz, CD3COCD3, 25C, ppm) delta 10.05 (s, 1H), 8.33 (s, 1H), 8.00-7.99 (m, 1H), 7.57-7.55 (m, 1H); 13C NMR (100.6MHz, CDCl3, 25C, ppm) delta 183.7, 145.9, 145.6, 139.4, 134.1, 129.3, 120.3; HRMS (APCI): calcd for C7H5OS2 (M+H)+ 168.9775; found 168.9776.
74.98%
With trichlorophosphate; In 1,2-dichloro-ethane; at 0℃;Reflux;
Compound Example 4.; Step 1 . Synthesis of thieno[3,2-blthiophene-2-carbaldehyde; Thieno[3,2-b]thiophene (3 g, 21.43 mmol) was taken in ethylene dichloride (75 ml) in a 250 ml round bottom flask followed by the addition of dimethylformamide (1.65 ml, 21 .43 mmol) at RT. The resulting reaction solution was cooled to 0C and POCI3 (5.87 ml, 64.29 mmol) was added to it. The reaction mixture was allowed to warm to RT and refluxed for overnight. Reaction mix was allowed to cool down, worked up with saturated sodium acetate solution and product was extracted in ethyl acetate. The organic layer was washed twice with water followed by brine and dried over Na2S04 and recovered to afford crude yellow oil which was subjected to column chromatography on silica (Hexane:Ethyl acetate (9:1 )) to afford 2.7 g (74.98%) of <strong>[251-41-2]thieno[3,2-b]thiophene</strong>-2-carbaldehyde as light yellow oil.1H NMR (200MHz, DMSO) delta 9.97 (s, IH), 8.39 (m, 1 H), 8.07 (m, 1 H), 7.55 (m, 1 H)
67%
With trichlorophosphate; In 1,2-dichloro-ethane; at 0 - 80℃; for 5h;Inert atmosphere;
In a 250 mL 3-necked flask, asolution of DMF (21.9 g, 300 mmol) in dry 1,2-dichloroethane (50 mL) was cooled to 0 C under a nitrogen atmosphere. Following this, POCl3 (23.0 g, 150mmol) was added dropwise with stirring. When all the POCl3 had been added, and the heat of the reaction had subsided, a solution of thienothiophene (TT) (14.0 g, 100 mmol) in 1,2-dichloroethane (50 mL) was added dropwise. The reaction mixture was stirred for 5 h at 80 C and then poured into cold saturated solution of sodium bicarbonate (200 mL) and extracted with DCM. The organic layer was washed with water and dried over anhydrous MgSO4. After removing the solvent, the crude product obtained was purified by column chromatography (PE/EA = 15/1, v/v) to give a light yellow solid (11.3 g, 67%yield). 1H NMR (300 MHz, CDCl3): delta (ppm) 9.96 (s, 1H),7.93 (s, 1H), 7.69 (d, J = 5.1 Hz, 1H), 7.33 (d, J = 5.4 Hz, 1H).13C NMR (75 MHz, CDCl3): delta (ppm) 183.54, 145.73, 145.47,139.23, 133.90, 129.06, 120.16. GC-MS (EI,m/z) calcd. for (C7H4OS2): 167.97. Found:168.03.
With trichlorophosphate; at 0 - 100℃; for 4h;
EXAMPLE 27; (alphaR,gammaS,2S)-N-((3S,4S)-3,4-dihydro-3-hydroxy-2H-1-benzopyran-4-yl)-gamma-hydroxy-alpha-(3-pyridinylmethyl)-4-(thieno[3,2-b]thien-2-ylmethyl)-2-[[(2,2,2-trifluoroethyl)amino]carbonyl]-1-piperazinepentanamide; To a solution of thieno[3,2-B]thiophene (100 mg, 0.700 mmol) in DMF (5 mL) at 0 C. was added POCl3 (110 mg, 0.700 mmol). The mixture was slowly heated to 100 C. over 1 hour and stirred at that temperature for 3 hours. The mixture was then cooled to ambient temperature and poured onto cold water (100 mL). The pH was adjusted to 6 with solid sodium acetate, and the mixture was extracted with diethyl ether (100 mL). The organic layer was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), dried (MgSO4) and concentrated in vacuo. Purification by flash chromatography (10% ethyl acetate in hexane) afforded the title compound as a yellow solid.
To a stirred solution of <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (10.7 mmol) in anhydrous CH2Cl2 (200 mL) was added octanoyl chloride (11.0 mmol). The mixture was stirred for 30 min at room temperature, cooled to 0 C., and AlCl3 (12.0 mmol) was added portionwise. The mixture was then warmed to 25 C. and stirred overnight. The reaction was quenched by the addition of water and acidified with a 2 M HCl aqueous solution. The mixture was extracted with CH2Cl2. The organic layers were washed with water and dried over MgSO4. After the removal of solvent, the crude product was purified by column chromatography (CH2Cl2/n-hexane: 1/1) on silica gel to afford 1-(thieno[3,2-b]thiophen-2-yl)octan-1-one (2.08 g) as milk white solid. Yield: 72%. 1H NMR (400 MHz, CDCl3, TMH): 7.90 (s, 1H), 7.61 (d, 1H), 7.30 (d, 1H), 2.92 (t, 2H), 1.81 1.74 (m, 2H), 1.37 1.30 (m, 8H), 0.88 (t, 3H)
tert-butyldimethyl-(6-thieno[3,2-b]thiophen-2-yl-hexyloxy)-silane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
84%
To a stirred solution of thieno(3,2-b)thiophene (3.15 g, 22.50 mmol) in dry THF (70 ml) was added n-butyllithium (2.5 M in hexanes, 7.50 ml, 18.75 mmol) dropwise at -78 C under nitrogen. After complete addition, the mixture was allowed to warm to room temperature, with stirring, over 2 h, followed by the addition of 6-bromohexyloxy-tert- butyldimethylsilane (5.53 g, 18.75 mmol). The resultant mixture was stirred overnight at room temperature. The reaction was quenched with sat. aq. ammonium chloride, and the reaction mixture was extracted with ethyl acetate (3 x 70 ml). The combined organic extracts were washed with water, brine, and dried over magnesium sulphate. The solvent was removed under reduced pressure and the residue was purified by chromatography (silica gel, petroleum/ethyl acetate from 100: 0 to 20:1 ), to give the product as an brown oil ( 5.61 g, 84 %). ¹H NMR (300 MHz, CDCl3) : No. (ppm) 7.23 (d, J = 5.2 Hz, 1 H, Ar-H), 7.15 (d, J = 5.2 Hz, 1 H, Ar-H), 6.93 (s, 1 H, Ar-H), 3.60 (t, J = 6.4 Hz, 2H, OCH@), 2.86 (t, J = 7.9 Hz, 2H, ArCH2), 1.35-1.90 (m, 8 H, CH2), 0.90 (s, 9 H, CH3), 0.05 (s, 6 H, CH3); ¹³C NMR (75 MHz, CDCl3) : No. (ppm) 148.4 (quat.), 138.7 (quat.), 137.4 (quat.), 125.3 (CH), 119.4 (CH), 116.2 (CH), 63.2 (OCH@), 32.8 (CH@), 31.6 (CH2), 31.2 (CH2), 28.9 (CH@), 26.0 (CH3) 25.6 (CH2), 18.4 (quat. ), - 5.2 (CH3); MS (m/e): 354 (M+ 2 %), 297 (50), 179 (14), 153 (100), 75 (56)
With n-butyllithium; In tetrahydrofuran; hexane; at 0 - 20℃;Inert atmosphere;
In a dry flask n-butyllithium (2.4 M in n-hexane, 1.25 mL, 3.0 mmol) was added dropwise to a solution of the <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (1, 420 mg, 3.0 mmol) in tetrahydrofuran (THF, 20 mL) at 0 C under nitrogen atmosphere ( Scheme 2 ). After 1 h of stirring at this temperature, neat triisopropyl chlorosilane (0.74 mL, 3.45 mmol) was added dropwise. The solution was stirred for another 3 h and allowed to warm to room temperature, followed by dilution with hexane and washing with water and brine. The organic layer was collected and dried over anhydrous Na2SO4. After the solvent was removed in vacuo, the residue was purified by column chromatography on silica gel, eluting with hexane to yield silyl compound 2 (774 mg, 87%) as a white solid. 1H NMR (600 MHz, CDCl3) delta 7.39 (d, J = 5.4 Hz, 1H), 7.37 (s, 1H), 7.25 (d, J = 5.4 Hz, 1H), 1.37 (m, 3H), 1.13 (d, J = 7.8 Hz, 18H); 13C NMR (150 MHz, CDCl3) delta 144.6, 141.2, 138.0, 127.9, 126.9, 119.1, 18.6, 11.8.
[0602] To a solution of 148 (5 g, 35.65 mmol) in THF (70 mL) was added n-BuLi (1.6 M in hexanes, 23.4 mL, 37.4 mmol) at -70 C dropwise for 30 min with stirring under N2 atmosphere. After addition, the reaction was stirred at the same temperature for 30 min, followed by the addition of 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.29 g, 39.2 mmol). The reaction was allowed to warm to room temperature and stirred for 16 hrs. After quenched with saturated aq. NH4Cl solution at 0 oC, the mixture was extracted with EtOAc twice. The combined organic layers are washed with brine, dried over anhydrous Na2SO4 and concentrated to dryness to give the title compound (8.1 g, 85.4% yield) as light green solid.
85.4%
To a solution of S1 (5 g, 35.65 mmol) in THE (70 mL) was added n-BuLi (1.6 M in hexanes, 23.4 mL, 37.4 mmol) at -70 dropwise for 30 min with stirring under N2atmosphere. After addition, the reaction was stirred at the same temperature for 30 min and 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7.29 g, 392 mmol) was added The reaction mixture was allowed to warm to room temperature and stirred for 16 hrs. After quenched with saturated aq. NH4Cl solution at 0 C., the mixture was extracted with EtOAc twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4and to give the title compound (8.1 g, 85.40% yield) as light green solid.
73%
To a solution of thieno[3,2-jb]thiophene (4.08 g, 29.1 mmol) in THF (70 ml) is added BuLi (2.5 M in hexanes, 10.5 ml, 26.3 mmol) at -78 0C dropwise, with stirring, under N2. After complete addition, the mixture is stirred for 30 min at the same temperature, followed by the addition of 2-isopropoxy-4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolane (4.89 g, 26.3 mmol). The mixture is allowed to warm to room <n="59"/>temperature and stired overnight (~ 15h), then poured to a sat.aq. ammonium chloride solution. The product is extracted with ethyl actate (3 x 70 ml). The extracts are combined and washed with brine, then dried (Na2SO4). The solvent is removed under reduced pressure the residue is recrystallised with acetonitrile, to give deep blue crystals (5.14 g, 73%). 1H NMR (300 Hz1 CDCI3): delta (ppm) 7.76 (s, 1H1 Ar-H)1 7.42 (d, J = 5.3 Hz, 1 H, Ar-H), 7.21 (d, J = 5.3 Hz, 1 H, Ar- H)1 1.32 (s, 12H1 CH3); 13C NMR (75 Hz, CDCI3): delta (ppm) 145.7,140.9, 130.2, 129.1 , 119.5, 84.3, 24.8.
0.982 g thieno[3,2-b}thiophene (7.0 mmol) was dissolved in 40 mL THF under N2 and cooled to -78C. 7 ml BuLi (1.6 M in hexanes, 7.0 mmol) was added and the mixture wasstirred at -78C for 1 hour. Then 1.6 mL 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2- dioxaborolane (7.7 mmol) was added and after 10 minutes stirring the mixture was allowed to warm up to room temperature. It was quenched with saturated aq. NH4CI solution, then extracted with THF, dried over Na2SO4, filtered and concentrated and purified via flash chromatography using heptane and EtOAc as eluents to give Preparation BA2.MS (El, 70 eV) m/z (% relative intensity, [ion]): 120 (19), 165 (25), 166 (100), 167 (44),180 (17), 206 (22), 223 (60), 266 (68, [Mt]).
With N-chloro-succinimide; In N,N-dimethyl-formamide; at 25℃;
Take a single-necked round-bottomed flask, add N-chlorosuccinimide to the N, N-dimethylformamide solution of thiophene and stir at room temperature for several hours. Monitor by TLC. After the reaction is completed, quench with water and quench The liquid was transferred to a separatory funnel and extracted with ether. The organic phase was dried over anhydrous sodium sulfate. After spinning, it was passed through the column with petroleum ether eluent to obtain a white solid, namely bilateral chlorothiophene product 1; of which, N-chloro The ratio of succinimide, thiophene, and N, N-dimethylformamide is 10-20 mmol: 20-50 mmol: 40-100 mL; the yield is 90.4%
Commercially available <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (4 g, 32 mmol) in THF (100 mL) was cooled to -78 C and n-butyllithium solution (1.6 M, 42 mL, 66 mmol) was added drop wise over 60 minutes using a dropping funnel. The reaction mixture was gradually warmed to room temperature and stirred for 3 hrs. The resultant suspension was again cooled to -78 C and a solution of trimethyltin chloride (13.15 g, 66 mmol) in THF (50 mL) was added drop wise over 30 minutes using a dropping funnel. The resultant mixture was gradually warmed to room tem-perature and stirred for 16 hrs. The reaction mixture was quenched with water (150 mL) and extracted with Et.20 (2 x 100 mL). Combined organic layers were washed with brine and concentrated to give brown solids, which were triturated with ethanol (4 x 20 mL). The solids were collected by filtration and washed thoroughly with ethanol (2 x 20 mL) to yield compound 8a as a white solid (10 g, 68%), which was used directly in the next step without further purification. H NMR (400 MHz, CDCI3) delta 7.26 (s, 2H), 0.37 (s, 18H).
54.1%
Synthesis Example 2Synthesis 2 of Intermediate of Specific CompoundSynthesis of Compound 8A 200 mL-round bottom flask, which had been sufficiently dried, was charged with <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (2.81 g, 20.0 mmol), and purged with argon. The flask was further charged with anhydrous tetrahydrofuran, (hereinafter referred to as THF) (50 mL), and cooled down to -78C by using an acetone-dry ice bath. Into the flask, n-butyllithium (2.2 eq, 28.1 mL (1.6 M hexane solution), 44 mmol) was added dropwise for 15 minutes, and the temperature of the reaction system was increased to room temperature, followed by stirring at room temperature for 16 hours. The reaction system was cooled down to -78C again, and trimethyltin chloride (2.5 eq, 50 mL (1.0 M hexane solution), 50 mmol) was added at one time to the reaction system. The temperature of the reaction system was increased to room temperature, followed by stirring for 24 hours.Water (80 mL) was added to the reaction system, followed by quenching. Then ethyl acetate was further added to the reaction system, so as to separate the organic layer. The organic layer was washed with a saturated aqueous potassium fluoride solution, and washed with saturated brine, and dried with sodium sulfate. After filtration, the filtrate wascondensed to thereby obtain a brown solid. The brown solid was recrystallized from acetonitrile consecutively three times, to thereby obtain Compound 8 as colorless crystals. The amount of Compound 8 was 5.0 g, and the yield was 54.1%.The analysis result of the compound 8 is as follows.NMR (500 MHz, CDC13, TMS, delta) : 0.38 (s, 18H), 7.23 (s,2H) Mass spectrometry: GC-MS m/z = 466 (M+)From the above analysis result, it was confirmed that a structure of the synthesized product did not contradict that ofCompound 8.
54.1%
[Synthesis Example 2- Synthesis 2 of compound intermediate] <Synthesis of Compound (8)> According to the following reaction formula (scheme), Compound (8) was synthesized.A 200 mL round-bottom flask was thoroughly dried and charged with thieno [3,2"b]thiophene (2.81 g, 20.0 mmol). The flask was purged with argon, followed by addition of anhydrous tetrahydrofuran (hereinafter abbreviated as "THF") (50 mL). The mixture was cooled to -78C in an acetone-dry ice bath. Then, n-butyllithium (2.2 eq., 28.1 mL (1.6M hexane solution), 44 mmol) was added dropwise to the mixture for 15 min. The reaction system was increased to room temperature, followed by stirring at the same temperature for 16 hours. Then, the mixture was cooled again to -78C, and trimethyltin chloride (2.5 eq., 50 mL (1.0M hexane solution), 50 mmol) was added thereto at one time. The reaction system was increased to room temperature, followed by stirring for 24 hours. Water (80 mL) was added to quench the mixture, and ethyl acetate was added thereto to separate an organic layer. The organic layer was washed sequentially with saturated aqueous potassium fluoride solution and saturated brine and dried with sodium sulfate, followed by filtration. The filtrate was concentrated to obtain a brown solid, which was then recrystallized from acetonitrile (repeatedly three times) to obtain Compound (8) as colorless crystals (yield amount: 5.0 g, yield rate: 54.1%). The analysis results of Compound (8) are shown below..H NMR (500 MHz, CDC13, TMS, 5) : 0.38 (s, 18H), 7.23 (s,2H) Mass spectrometry: GC-MS m/z = 466(M+) From the above analysis results, it was confirmed that a structure of the synthesized product did not contradict that ofCompound (8).
53%
In a 3 -neck round bottom flask equipped with an argon inlet and an addition funnel, <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (7.5 g, 54 mmol) was dissolved in tetrahydrofuran (1 L). After the solution was cooled to -78C using an isopropanol/dry ice bath, t-BuLi (100 mL, 170 mmol) was transferred by cannula to the addition funnel. The organolithium reagent was then added dropwise. After completion of the addition, the mixture was stirred for 20 min at -78C then warmed up with an isopropanol bath at room temperature for 30 minutes during which a yellow precipitate formed. The solution was cooled back at -78C, and after cannula transfer to the addition funnel, trimethyltin chloride (200 mL of 1 M solution in THF, 200 mmol) was added dropwise. During addition of trimethyltin chloride, the precipitate disappeared and the solution turned light brown. After warming to room temperature the solution was stirred for 30 minutes then was poured into ice-cold water. The aqueous phase was further extracted with hexane. The combined organic phase were washed with cold water then dried with magnesium sulfate. After filtration, the solvent is evaporated under vacuum to yield a grey- brown solid. The product was purified by precipitation of a chloroform solution into methanol followed by filtration (13.2 g, 53%).Spectral data: 1H NMR (CDC13, 300 MHz): deltaH0.41 (s, 18H), 7.26 (s, 2H).13C (CDCI3, 75 MHz): delta 7.99, 126.29, 141.4, 147.62.
To a solution of thieno[3,2-b]thiophene (1 .5 g, 10.70 mmol) in THF (25.5 mL) at -78 C under N 2 is added dropwise a solution of BuLi in hexanes (8.988 mL of 2.5 M, 22.47 mmol), stirred for 20 min, cooling bath is replaced with ice bath and stirred for 50 min. The resultant thick suspension is quenched with 2- isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (4.181 g, 4.584 mL, 22.47 mmol). The reaction mixture is kept for overnight and then quenched with saturated aq. NH4Cl solution. After extraction with CH2Cl2 (2 x 100 mL), the combined extracts are washed with brine and dried (Na2S04). Organic solution is diluted with -20 mL of ethyl acetate, concentrated slowly on rotary evaporator until CH2Cl2 is removed. The resultant white fine crystals are collected by filtration. The solid is washed with heptanes and dried under high vacuum to afford 4,4,5,5-tetramethyl-2-[5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)thieno[3,2-b]thiophen-2-yl]-1 ,3,2-dioxaborolane (2.57 g, 6.554 mmol, 61.25%) as half-white solid. 1H NMR (400 MHz, CDCl3) delta 7.75 (s, 2H), 1.343 (s, 12H).
Example 1 , 2, 5-Bis(4,4, 5, 5-tetramethyl- 1 , 3, 2-dioxaborolan-2-yl)thieno[ 3, 2- 6]thiophene (Compound 52)To a solution of thieno[3,2-b]thiophene (3.0 g, 21.39 mmol) in tetrahydrofuran (50 mL) at -78C under N2 was added n-butyl lithium (17.97 mL of 2.5 M in hexanes, 44.92 mmol). Let stir for 30 minutes at -78 C, then warmed to 0C for 1 hour. Cooled reaction to -78 C and added 2-isopropoxy-4,4,5,5-tetramethyl-1 ,3,2-dioxaborolane (8.358 g, 9.164 mL, 44.92 mmol). Let warm to room temperature overnight. Added saturated ammonium chloride and extracted with ethyl acetate (2x). Combined organic extracts and washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was then triturated with hexanes and filtered. 5.996 g 1H NMR (300 MHz, DMSO) delta 7.84 (s, 2H), 1.31 (s, 24H)
Stage #1: thieno[3,2-b]thiophene With aluminum (III) chloride; boron trichloride; Dimethyl-p-toluidine In dichloromethane at 20℃; for 0.166667h;
Stage #2: 2,3-dimethyl-2,3-butane diol With triethylamine In dichloromethane at 20℃; for 0.5h;
23
Example 23 - Preparation of 5-(4 A5,5-tetramethyl-1 ,3,2-dioxaborolan-2-ylHhieno- r3.2-b1-thiophen-2-yl1. 1eq. BCI3, 1.2 eq.pinacol20°C, 30 mins[00126] BCI3 (1 M in dichloromethane) (0.2ml_, 1 eq, 0.2 mmol), Λ/,/V-dimethyl p- toluidine (31 μΙ_, 1 .2eq, 0.24mmol) and dry dichloromethane (0.2 mL) were added by syringe to a J. Youngs NMR tube. AICI3 (25mg, 1 eq. 0.2mmol) and thieno[3,2-b]thiophene (26mg, 1 eq. 0.2mmol) were added consecutively as solids. After 10 minutes, the NMR tube was charged with triethylamine (0.4ml_, 15eq 3mmol) followed by addition of pinacol (55mg, 2.5eq, 0.5mmol). The suspension was extracted into a Schlenk, the NMR tube was washed with dichloromethane (2ml_) and the resulting mixture was evaporated under vacuum. To the resulting solid, hexane (3ml_) was added and the mixture was sonicated for 1 minute. The solids were removed by filtration, upon washing with further hexane (3ml_), the extracts were combined and the volatiles removed in vacuum to give the crude product which was purified by flash chromatography through a short plug of neutral alumina using hexane as solvent to give a colourless crystalline solid. Isolated Yield: 81 %1 H-NMR (400MHz, CDCI3): 7.76 (s, 1 H), 7.48 (d, J= 5.2Hz, 1 H), 7.28 (d, J= 5.2 Hz, 1 H), 1 .36 (s, 12H).13C-NMR (100MHz, CDCI3): 145.6, 140.1 , 130.0, 129.0, 128.9, 1 19.5, 84.3, 24.9, 24.8. 1 1 B-NMR: 29.1
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere;
Stage #2: With trimethyltin(IV)chloride In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere;
Stage #3: 4,7-dibromo-5,6-bis(octyloxy)benzo-[c][1,2,5]-thiadiazole With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran; hexane for 24h; Inert atmosphere; Reflux;
tributyl(thieno[3,2-b]thiophen-2-yl)stannane[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
To the solution of <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (17.529 g; 125.00 mmol) in THF anhydrous ( 50 cm3) was added at -78 C n-BuLi (50.0 cm3; 25.00 mmol) over 20 minutes. The mixture was stirred with cooling for 1 hour to yield a milky white suspension. The flask was lifted out of the cooling bath and was stirred without cooling for 30 min then cooled back to -78 C again. Tributyltin chloride (35.3 cm3; 125.00 mmol) was syringed into the solution in one portion and the mixture was stirred with the cooling bath for 16 hours then at 22C for 1 hour to yield a white suspension. The solid of diethyl 2,5-dibromo-terephthalate (19.00 g; 50.00 mmol), Pd(PPh3)2CI2 (1.0 g; 1.42 mmol; 2.84 mol%) and DMF anhydrous (50.0 cm3) were added sequentially and the mixture was heated to boiling for 0.5 hour. A distillation head was installed on the flask and 100 cm3 of the solvents were removed by distillation. The residue was then stirred at reflux for an additional 20 hours. The mixture was evaporated under vacuum to remove the low boiling solvents until a solid started crashing out. Methanol (200 cm3) was added to the residue and the precipitate was suction filtered off to yield a green-yellow crystalline solid. The solid was dissolved in hot chloroform (250 cm3) then filtered through a short silica plug (15 cm) which was washed with chloroform. The filtrate was concentrated to almost dryness and the solid was triturated with methanol followed by a suction filtration to yield the product as bright yellow crystals (19.40 g, 78%). 1H- NMR (CDC , 300 MHz): delta= 1.13 (t, J = 7.2 Hz, 3H), 4.25 (q, J = 7.2 Hz, 2H), 7.28 (dd, J1 = 5.2 Hz, J2 = 0.6 Hz, 1H), 7.30 (d, J = 0.6 Hz, 1 H), 7.40 (d, J = 5.2 Hz, 1 H), 7.89 (s, 1H). 13C-NMR (CDCI3, 75 MHz): delta= 13.8, 61.8, 119.3, 119.4, 127.4, 132.0, 133.8, 134.1 , 139.3, 139.9, 142.0, 167.4.
Add thieno [3,2-b] thiophene (4.2 g, 30 mmol) to a 500 mL reaction flask under nitrogen atmosphere and dry THF (100 mL).The reaction was cooled to -78 C and then slowly added dropwise 2.5 M n-BuLi in hexane solution (12 mL, 30 mmol) to the reaction.Stir at the same temperature (-78 C) for 30 minutes, then warm the reaction at some temperature (-35 C) and then stir for a further 20 minutes.In another reaction vessel, add anhydrous zinc chloride (4.1 g, 30 mmol) to anhydrous THF (100 mL), and slowly add to the reaction.The reaction is warmed to 0 C and then stirred for 1 hour.Remove the bath and add compound 5-1 (4.6 g, 12 mmol) and Pd (PPh3) 4 (0.7 g, 0.6 mmol). The reaction is stirred at reflux overnight.After confirmation of the reaction, the reaction product was filtered using celite-pad, extracted with EA, and dried over anhydrous Na 2 SO 4.The dried reaction mixture was filtered, the filtrate was reduced under reduced pressure and purified by column chromatography to obtain a yellow solid compound 5-1 (4.8 g, 79%).
[0142] Synthesis of Compound 2-1 [0143] 4.22 g (30 mmol) of thieno[3,2:b]thiophene is dissolved in 50 mL of dry ether, and the resultant is added in dropwise fashion to 100 mL of dry ether solution in which 25 mL of 2.5M butyl lithium solution dissolved in hexane is contained and is cooled to 0 C. The temperature is slowly increased to room temperature (24 C.) and agitation for two hours is performed at room temperature. 10 g (62 mmol) of benzothiophene-3-aldehyde is slowly added in a dropwise fashion to the resultant haze solution and is agitated overnight. 100 mL of ammonium chloride saturated solution is added. Precipitated materials are filtered and the filtered product is washed with water and ether to a Compound 2-1 (yield 70%). [0144] 1H NMR (300 MHz, CDCl3): delta ppm 7.89 (m, 2H), 7.77 (m, 2H), 7.59 (s, 2H), 7.35 (m, 4H), 7.13 (s, 2H), 6.44 (d, 2H), 2.56 (d, 2H).
Compound T2 of Preparation Example 5 was prepared according to the method described in J. Mater. Chem. C, 2013, 1, 3686-3694. In a dried reaction flask, <strong>[251-41-2]thieno [3,2-b] thiophene</strong> (1 g, 7.13 mmol) was dissolved in THF (tetrahydrofuran) (20 mL)N-BuLi (1.6 M in hexanes, 4 mL, 6.42 mmol) was slowly added dropwise under argon charging conditions at -78 [deg.] C,The reaction solution was stirred for about 1 hour, and 1-bromooctane (1.2 mL, 7.13 mmol) was added thereto at the same temperatureIt fell down. The reaction solution was stirred at -78 C for 30 minutes, the temperature was raised to room temperature, and the mixture was stirred for 12 hours.The reaction solution was poured into ice water, extracted with dichloromethane,Water was removed with Na2SO4.The reaction solution was concentrated, and 610 mg (64% yield) of compound T2 (2-octyl-<strong>[251-41-2]thieno [3,2-b] thiophene</strong>) was obtained by flash column chromatography (hexane) on silica gel.
64%
Compound T2 is prepared according to J. Mater. Chem. C, 2013, 1, 3686-3694.2-octyl<strong>[251-41-2]thieno [3,2-b] thiophene</strong> (T2) was synthesized by the following reaction scheme (Scheme 1)A dried reaction flask was charged with <strong>[251-41-2]thieno [3,2-b] thiophene</strong>(1.6 M in hexane, 4 mL, 6.42 mmol) was slowly added dropwise at -78 & lt; 0 & gt; C and argon charging conditions to a solution of the enoin in THF (20 mL) After stirring for about 1 hour, at the same temperature,1-Bromooctane (1.2 mL, 7.13 mmol) was slowly added dropwise. Then, the solution was stirred at -78 C for 30 minutes, then the temperature was raised to room temperature, stirred for 12 hours,The ice water was poured out, extracted with dichloromethane, and water was removed using Na2SO4. The reaction solution was concentrated and the compound T2 (610 mg, 64%) was obtained by silica gel column chromatography (hexane)
64%
Compound T2 is J. Mater. Chem. C, 2013, 1, 3686 - 3694 products on the copiers. (Thieno [3,2 b] thiophene) dried reaction cap to in mote looking old five pen (1 g, 7. 13 mmol) of THF (tetrahydrofuran) (20 ml) solution obtained by dissolving a solutionn- BuLi (1. 6 M in hexane, 4 ml, 6. 42 mmol) -78 C a, a charging condition enemyit is under, slowly under argon, said reaction solution after stirring 1 temporal extent such as temperatures 1 - bromo octane (1 a-bromooctane) (1. 2 ml, 7. 13 mmol) slowly enemy a-gate. After stirring 30 minutes at room temperature the reaction solution in said -78 C it makes, meat and mixing 12 raised to a given temperature, a size slightly larger than said ice water biocatalytic reaction solution then methane extraction, Na2SO4Been number with a water stand-alone. Silica gel flash column chromatography (hexane) T2 said reaction the polymer solution is concentrated compounds (2 a-octyl-a thieno [3,2 b] thiophene) obtained a 610 mg (64% yield) (compound 7).
44%
To the solution of <strong>[251-41-2]thieno[3,2-b]thiophene</strong> (1 g, 7.13 mmol) in tetrahydrofuran (50 mL), n-butyllithium (1.6 M in hexane, 4.46 mL,7.13 mmol) was added dropwise at 78?C under N2 atmosphere. The mixture was stirred for 1 h, following which 1-bromooctane(1.23 mL, 7.13 mmol) was added dropwise at 78?C. After stirring overnight at room temperature, the solution was poured into water, extracted with ethyl acetate, and dried over anhydrous MgSO4. The solvent was removed via rotary evaporation and thecrude liquid was purified by column chromatography on silica gel(hexane) to yield colorless oil. (0.8 g, 44%) 1H NMR (300 MHz,CDCl3, delta): 7.29 (d, J 5.4 Hz, 1H), 7.21 (d, J 5.4 Hz, 1H), 6.97 (s, 1H),2.90 (t, J 7.5 Hz, 2H), 1.74 (m, 2H), 1.59e1.26 (m, 10H), 0.92 (t, J 7.2 Hz, 3H) 13C NMR (300 MHz, CDCl3, delta): 148.60, 138.71, 137.30,125.26, 119.47, 116.16, 31.89, 31.63, 31.22, 29.36, 29.26, 29.10, 22.70,14.15 Elem. Anal. Calcd. for C14H20S2: C, 66.6; H, 8.0; S, 25.4, found,C, 66.6; H, 8.1; S, 23.6. FTIR (KBr, neat, cm-1): 3082 (sp2 C-H stretch,w), 2954, 2925, 2853 (sp3 C-H stretch, s), 1522 (aromatic C=Cstretch, w), 1464, 1349, 1076, 912, 810.
42.5%
n-Butyllithium (51 ml, 0.14 mol, 2.5M in hexanes) was added drop wise to a solution of thienothiophene (20 g, 0.14 mol) in THF (310 ml) at -78 C. under nitrogen. After stirring at this temperature for 1 hr, octyl bromide (24.9 ml, 0.14 mol) was added drop wise and the reaction mixture allowed to warm to room temperature over night. The mixture was then poured into water, extracted with diethyl ether, dried (MgSO4), filtered and concentrated under reduced pressure. The crude residue was distilled to remove excess bromide and the residue purified by column chromatography (silica gel, hexane) to give the product as a clear oil (15 g, 42.5% )
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran at -78℃; for 1.5h; Inert atmosphere;
Stage #2: 3-bromomethylheptane at -78 - 20℃; for 12h;
2-(2- Ethylhexyl)thieno[3,2-b]thiophene(A2)
Under the protection of argon, n-butyllithium (2.5 M, 14.26 mL, 35.6 mmol)was dropwise added tothieno[2,3-b]thiophene (5.00g, 35.60 mmol) in dry THF (20 mL) at -78 °C over 1 h. and then stirredfor another 0.5 h. 3-(bromomethyl)heptane (5.50 g, 28.48 mmol), then was added into the mixture at-78 °C in one portion, and the mixture was warmed to room temperature and stirred for 12 h. therest procedures was following to A1, with the yield of 60%.
80%
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1.33333h; Inert atmosphere;
Stage #2: 3-bromomethylheptane In tetrahydrofuran; hexane at 20℃; for 12h; Inert atmosphere;
80%
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran; hexane at -78 - 20℃; for 1.33333h; Inert atmosphere;
Stage #2: 3-bromomethylheptane In tetrahydrofuran; hexane at -78 - 20℃; Inert atmosphere;
cyclohexyl (E)-3-(thieno[3,2-b]thiophen-2-yl)acrylate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
63%
With copper(II) 2-ethylhexanoate; chlorobis(ethylene)rhodium(I) dimer; silver sulfate In cyclohexane at 140℃; for 24h; Inert atmosphere;
2-1. General procedure for Rh-catalyzed non-directed alkenylation (Scheme 1 and 2)
General procedure: A screw-top glass tube was charged with aromatic compound 1 (1.25 mmol, 5.0 eq.), alkene 2 (0.25 mmol, 1.0 eq.), [RhCl(C2H2)2]2 (2.5 mol %), Cu(eh)2 (0.5 mmol, 2.0 eq.), and Ag2SO4 (0.5mmol, 2.0 eq.). Cyclohexane (3.0 mL) was added via syringe, and the resulting mixture was stirred at 140 °C for 24 h. After cooling to room temperature, the reaction mixture was extracted with EtOAc several times. The combined organic layers was washed with H2O containing ethylenediamine (ca. 1.0 mL), dried over Na2SO4, and concentrated in vacuo. The residue was subjected to silica gel column chromatography to give the corresponding product 3.
60%
With palladium diacetate; silver trifluoroacetate In propionic acid at 50℃; for 24h; Inert atmosphere; regioselective reaction;
2-((2-ethylhexyl)thio)thieno[3,2-b]thiophene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1.5h; Inert atmosphere;
Stage #2: With sulfur In tetrahydrofuran; hexane at 0℃; for 2h; Inert atmosphere;
Stage #3: 3-bromomethylheptane In tetrahydrofuran; hexan-1-ol at 20℃; Inert atmosphere;
41%
Stage #1: thieno[3,2-b]thiophene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere;
Stage #2: With sulfur In tetrahydrofuran at -78 - 20℃; for 1.5h;
Stage #3: 3-bromomethylheptane In tetrahydrofuran at -78 - 20℃; for 12h;
2-((2-Ethylhexyl)thio)thieno[3,2-b]thiophene (A1)
Under the protection of argon, n-butyllithium (n-BuLi) (2.5 M, 14.26 mL, 35.6 mmol) was dropwiseadded to thieno[2,3-b]thiophene (5.00g, 35.60 mmol) in dry tetrahydrofuran THF ( 20 mL ) at -78 °Cover 1 h. The Sulphur Powder ( 0.92 , 28.48mmol ) was added. After being stirred for 1 h, themixture was warmed to room temperature and stirred for another 0.5 h.3-(bromomethyl)heptane(5.50 g, 28.48 mmol), then was added into the mixture at -78 °C in one portion, and the mixture waswarmed to room temperature and stirred for 12 h. Subsequently, the mixture was poured into waterand extracted with petroleum ether (20 mL × 2). The organic layer was washed with water and dried over anhydrous Na2SO4 for 3 h. After removal of solvent, the crude product was purified by silicagel using petroleum ether as eluent to afford compound 2a as a colorless liquid (2.40 g, 41%).
With N-Bromosuccinimide; acetic acid; at 20℃; for 2h;
Thieno[3,2-b]thiophene (1.0 g, 7.13 mmol) was dissolved in acetic acid(10 mL). N-bromosuccinimide (1.27 g, 7.13 mmol) was added and the reaction mixture was stirred atroom temperature for 2 h. Solvent was removed and the residue was dissolved in diethyl ether (80 mL)and washed with NaOH (1 M, 100 mL x 3), H2O (100 mL x 3) and brine (100 mL). The resultingsolution was dried over Na2SO4, and the solvent was removed by rotary evaporation to obtain pure 4as a light yellow liquid (1.3 g, 81% yield). 1H-NMR (500 MHz, CDCl3) delta 7.40 (ddd, J = 5.7, 3.0, 1.5 Hz,1H), 7.28 (d, J = 4.1 Hz, 1H), 7.20-7.14 (m, 1H). 13C-NMR (126 MHz, CDCl3) delta 127.57, 126.78, 122.32,121.98, 119.60, 119.24. HRMS-ESI m/z 217.8837 ([M]+, C6H3BrS2+, calc. 217.8860).
With N-Bromosuccinimide; In dichloromethane; for 5h;
NBS (2 g, 11.2 mmol) was added to a solution of compound 53 (1.57 g, 11.2 mmol) in dichloromethane (10 mL)Stirring for 5 hours, the lamellar detection reaction is complete, with sodium thiosulfate solution and salt water washing, and concentrated to obtain crude 2.6g.
The flask was charged with thieno [3,2-b] thiophene (13.4 mmol) Tetrahydrofuran (hereinafter referred to as "THF") (180 mL) was added, The reaction system was cooled to 0 C. under a nitrogen atmosphere. Then, n-Butyllithium (28.1 mmol) was slowly added dropwise, After stirring for 30 minutes, 3,4-Dibutoxy-3-cyclobutene-1,2-dione (26.8 mmol) was added. The reaction system was returned to room temperature, And the mixture was further stirred for 2 hours. Dilute hydrochloric acid and water were added to the reaction system, followed by filtration, The filtrate was washed with ethanol to obtain a yellow powder compound 11. (4.1 mmol, yield: 31%).
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In o-xylene; at 140℃; for 24h;Schlenk technique;
General procedure: In a Schlenk tube, a mixture of thiophene-based fused compound(0.5 mmol), aryl bromide 2 (1.5 mmol), NaOt-Bu (1.5mmol), Pd2(dba)3 (0.005 mmol), and SPhos (0.01 mmol) in oxylene(2.0 mL) was heated at 140 C for 24 h. The resulting mixture was poured into H2O and extracted with EtOAc threetimes. Combined organic layers were dried over Na2SO4 andconcentrated in vacuo. The residue was subjected to silica gelchromatography and/or GPC.
With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; In o-xylene; at 140℃; for 24h;Schlenk technique;
General procedure: In a Schlenk tube, a mixture of thiophene-based fused compound(0.5 mmol), aryl bromide 2 (1.5 mmol), NaOt-Bu (1.5mmol), Pd2(dba)3 (0.005 mmol), and SPhos (0.01 mmol) in oxylene(2.0 mL) was heated at 140 C for 24 h. The resulting mixture was poured into H2O and extracted with EtOAc threetimes. Combined organic layers were dried over Na2SO4 andconcentrated in vacuo. The residue was subjected to silica gelchromatography and/or GPC. 2,5-Bis(2-methylthiophenyl)thieno[3,2-b]thiophene (5)Purified by GPC, 69% yield, white solid, mp 198-199 C. 1H NMR(400 MHz, CDCl3): delta = 2.45 (s, 6 H), 7.20 (dt, J = 1.6, 7.3 Hz, 2 H),7.32-7.35 (m, 4 H), 7.44 (s, 2 H), 7.44 (dd, J = 1.4, 7.4 Hz, 2 H).13C NMR (100 MHz, CDCl3):delta = 16.20, 119.93, 124.80, 125.70,128.65, 131.01, 133.36, 138.21, 139.37, 142.62. HRMS (APCI):m/z [M + H]+ calcd for C20H17S4: 385.0208; found: 385.0201. Forother compounds, see the Supporting Information.
Multi-step reaction with 2 steps
1: lithium hydroxide; water / tetrahydrofuran / 4 h / 100 °C
2: copper(l) iodide; N,N,N,N,-tetramethylethylenediamine / 1-methyl-pyrrolidin-2-one / 1 h / 220 °C
With 2,3,6,7-tetramethoxy-9(10H)-anthracenone; caesium carbonate In dimethyl sulfoxide at 25℃; for 18h; Irradiation; Sealed tube; regioselective reaction;
General Procedure for the Carboxylation of Hetero(arenes) and Styrenes- GP2a
General procedure: To a dry flat-bottomed crimp vial (5 mL) equipped with stirring bar, was added the arene (if solid)(0.1 mmol) and 2,3,6,7-tetramethoxyanthracen-9(10H)-one (6.3 mg, 0.02 mmol, 20 mol %). Cs2CO3 (98 mg,3 equiv.) was quickly added and the vial was sealed with a Supelco aluminium crimp seal with septum(PTFE/butyl). The vial was then evacuated and refilled with CO2 (5×) via syringe needle. The reactionmixture was dissolved in DMSO (1 mL, dry and degassed by bubbling with N2) and the arene (0.1 mmol) (ifliquid) was added via syringe. The vial was sealed with two layers of Parafilm and then had gaseous CO2added via a Luer Lock Monoject (20 ccm) syringe, into the head space. The vial was then irradiated fromthe bottom side with blue LED light and a constant reaction temperature (25°C) was maintained byemploying a water-cooling circuit connected to a thermostat. After 18 hrs of reaction time the pressure wasreleased. For product isolation, the reaction mixtures of 4 reactions run in parallel were combined andtransferred with water and Et2O into a separating funnel. The ether layer was extracted with water (3×) andthe combined aqueous layers were acidified with aq. HCl (2M) to adjust to an acidic pH. The aqueous layerwas extracted with EtOAc (3×) and the combined EtOAc layers were dried over Na2SO4, filtered andconcentrated in vacuo. The crude material was purified by silica flash column chromatography usingmixtures of hexanes and ethyl acetate with 0.5% HOAc (v/v) as eluents.
2-(thieno[3,2-b]thiophen-2-yl)-3-(thiophen-2-yl)quinoxaline[ No CAS ]
2-(thieno[3,2-b]thiophen-2-yl)-3-(5-(3-(thiophen-2-yl)quinoxalin-2-yl)thiophen-2-yl)quinoxaline[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
1: 35%
2: 15%
Stage #1: thieno[3,2-b]thiophene With 2,2,6,6-tetramethyl-piperidine; n-butyllithium In tetrahydrofuran; hexane at -78 - -10℃; for 1h; Inert atmosphere;
Stage #2: 2-(thiophen-2-yl)quinoxaline In tetrahydrofuran; hexane at -78 - 20℃; for 12h; Inert atmosphere;
Stage #3: With iodine In tetrahydrofuran; hexane at 20℃; for 5h; Inert atmosphere;
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