4,7-Bis(thiophen-2-yl)benzo[c][1,2,5]thiadiazole

To a mixture of 4, 7-dibromobenzo[cJ{1, 2, 5]thiadiazole (147 mg, 0.50 mmol, 1 equiv), thiophen-2-ylboronic acid (192 mg, 1.50 mmol, 3 equiv), and K3P045H20 (0.90 g, 3.0 mmol, 6 equiv) was added THF (900 jiL) then a THF stock solution of 3 and PAd3 (100 iL, 0.25 jtmol ofPd/PAds). The mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate then extracted with water. The combine organic layers were evaporated andthe crude product was purified by flash chromatography. After drying, 143 mg (95percent) of 40 was obtained as an orange solid. NMR spectroscopic data agreed with literature values.I) 4, 7-dibromo-2, 1, 3-benzothiadiazole (2.01 g, 6.84 mmol), 2-thiopheneBoric acid (1.42 g, 11 mmol) was dissolved in 20 mL of toluene and 15 mL of 2M potassium carbonate solution was injected.(Tetraphenylphosphine) palladium (150 mg, 0.14 mmol) was added and heated to 75 ° C for 2-8 h. Natural cold to room temperature, dichloromethaneHexane extraction, drying, concentration and column chromatography to obtain red crystals of 4, 7-dithiophene-2, 1, 3-benzothiadiazole 1.73 g, yield84.3percent.Preparation of bis-4, 7-(thien-2-yl)-2, 1, 3-benzothiadiazole Preparation of 4 , 7-di-2-thienyl-2 , 1 , 3-benzothiadiazole having formula (a) 4, 7-dibromo-2, 1, 3-benzothiadiazole (0.294 g, 1.0 mmoles), potassium acetate (0.295 g, 3.0 mmoles), N, N- dimethylacetamide (5 ml), thiophene (0.842 g, 10 mmoles) and palladium (II) acetate [Pd(OAc)2] (1.2 mg, 0.005 mmoles), were charged into a 10 ml Pyrex glass reactor equipped with a screw stopper. The reactor was placed in an oil bath preheated to 130°C and left under vigorous stirring, for 4 hours. After cooling to room temperature (25°C) , the reaction mixture was put into a saturated solution of sodium chloride (25 ml) and extracted with ethyl acetate (3 x 25 ml) . The organic phase obtained was dried on anhydrous sodium sulfate and evaporated. The residue obtained (brown solid) was purified by flash chromatography on silica gel using a mixture of n- heptane/ethyl acetate (1/1, vol/vol), as eluent, obtaining 240 mg of pure 4 , 7 -di-2-thienyl-2 , 1 , 3-benzo- thiadiazole as a red solid (yield 80percent) . Said , 7-di-2-thienyl-2 , 1 , 3-benzothiadiazole was characterized by means of 4, 7-dibromo-2, 1, 3-benzothiadiazole (0.294 g, 1.0 mmoles), potassium acetate (0.295 g, 3.0 mmoles), N, N-dimethylacetamide (5 ml), thiophene (0.842 g, 10 mmoles) and palladium (II) acetate [Pd(OAc)4, 7-Dibromo-2, 1, 3-benzothiadiazole (0.2 g, 0.68 mmol) andthiophene (0.272 mL, 3.4 mmol) were dissolved in 40 mL dry DMF.The solution was purged with nitrogen for 10 min followed byaddition of pivalic acid (0.104 g, 1.02 mmol), K2CO3 (0.47 g, 3.4 mmol) and catalyst Pd(OAc)2 (0.076 g, 0.34 mmol). The reactionwas conducted for 4 h at 80 °C under nitrogen atmosphere. Theproduct was extracted with ethyl acetate and the solvent wasevaporated to obtain crude product which was purified by silica gelcolumn chromatography using 3percent ethyl acetate/hexane as eluent toobtain M4, a bright orange colour solid (81.7 g, 40percent). Meltingpoint=128 °C. 1HNMR (300 MHz, CDCl3) δ: 8.13(d, 2H), 7.90(s, 2H), 7.46(d, 2H), 7.23(m, 2H) [29].The thien-2-yl-zinc chloride was prepared by adding n-butyllithium (2.5 M in hexane, 30 mL, 75.0 mmol) dropwise to a stirred solution of thiophene (6.5 g, 77.0 mmol) in THF (50 mL) at 0° C. under nitrogen over 15 minutes. Upon completion of addition, the solution was allowed to warm to room temperature with stirring. After stirring for 3 hours at room temperature, the mixture was cooled to 0° C. again and anhydrous zinc chloride (10.05 g, 75 mmol) was added in one portion. The resultant mixture was allowed to warm to room temperature and was stirred for an additional 1 hour. [0029] This resulting thien-2-yl-zinc chloride solution was added via a cannula to a stirred mixture of 4, 7-dibromo-2, 1, 3-benzothiadiazole (10.28 g, 35 mmol), Pd(OAc)2 (39.2 mg, 0.175 mmol) and Ph3P (91.7 mg, 0.35 mmol) in THF (50 mL) at room temperature under nitrogen over 1 hour 15 minutes. The mixture was stirred for an additional 20 minutes at room temperature and quenched with aqueous HCl (3 N, 80 mL). After stirring for 30 minutes, the crude product was collected by filtration, rinsed with water (100 mL) and ethanol (50 mL) and dried. Crude product 9.47 g (98percent purity by GC area) was obtained, which was recrystallized from toluene/ethanol (40 mL/120 mL) to pure product (9.04 g, 86percent yield).4, 7-dibromobenzo[c][1, 2, 5]thiadiazole (1.32 g, 4.5 mmol), 2-(thiophen-2-yl)-1, 3, 2-dioxaborinane (1.68 g, 10 mmol) and 23.1 mg Pd(PPh4, 7-Dithienyl-2, 1, 3-benzothiadiazole (3) As reported in [2], a solution of 4, 7-dibromo-2, 1, 3-benzothiadiazole (2, 200 mg, 0.680 mmol)and 2-(tributylstannyl)thiophene (558.27 mg, 1.492 mmol) in 4 mL toluene was taken undernitrogen atmosphere. The reaction mixture was purged with N2 for 15 min andtris(dibenzylideneacetone)palladium(0) (12 mg, 0.014 mmol) and tri(o-tolyl)phosphine(21.2 mg, 0.05 mmol) were added. After flushing nitrogen for 15 min the mixture wasrefluxed 110 °C for 24 h under inert atmosphere. The resultant mixture was cooled andprecipitated from methanol. Yield 90percent1.00 g (3.4 mmoles) of 4 , 7-dibromo-2 , 1 , 3 -benzo- thiadiazole and 18 ml of a solution in anhydrous DMSO containing palladium (II) acetate and triphenylphosphine in concentrations of 9.44 x 104, 7-dibromo-2, 1, 3-benzothiadiazole of example 1.1 (2.026 g; 6.89 mmole) was placed in a tri-necked flask and the flask was subsequently filled with dried nitrogen, then anhydrous tetrahydrofuran (50 ml) and tributyl (2-thienyl) stannate of example 1.2 (6.7358 g; 20.7 mmole) were added. A catalyst solution was prepared by dispersing Pd(PPhA solution with reaction mixture of 4, 7-dibromobenzo[c]-1 , 2, 5-thiadiazole (compound 11 , 2.00 g, 0.0068 mol), 2-(tributylstannyl)thiophene (5.59 g, 0.0150 mol) and toluene (30 ml) was bubbled through with nitrogen to deoxygenate the solvent. Under a nitrogen atmosphere Pd(PPh4, 7-Dibromo-2, 1, 3-benzothiadiazole (1 g, 3.4 mmol) is taken in dry THF (25 mL). Add to this 2-tributylstannylthiophene (2.37 mL, 7.48 mmol) and PdCl2 (PPh3)2 (0.11924 g, 0.17 mmol) and reflux for 10–12 h under nitrogen atmosphere. After cooling the reaction mixture, quench with water and extract in EtOAc. Purify using column chromatography on alumina using EtOAc / petroleum ether (1:20) as eluent and further recrystallize in petroleum ether.M4 (0.07 g, 0.233 mmol) was dissolved in 3.3 mLdry CHCl3 followed by addition of NBS (0.87 g, 0.489 mmol) at 0 C.The reaction was conducted in dark by covering the flask withaluminium foil. The product was extracted with CHCl3 and thesolvent was evaporated to obtain crude product which was purifiedby silica gel column chromatography using 5% ethyl acetate/hexaneas eluent to obtain M5 as bright orange solid (0.101 g, 95%). Meltingpoint = 258 C. 1HNMR (300 MHz, CDCl3) d: 7.85(s, 2H), 7.80(d, 2H), 7.13(d, 2H) [29] (see Scheme 5).Preparation of bis-4, 7-(2'-bromo-5'-thienyl)-2, 1, 3-benzothiadiazole (N2S-1)-T2-Br2 9.51 g (54 mmol) of N-bromosuccinimide were added to a solution of 7.72 g (25.7 mmol) of bis-4, 7-(thien-2-yl)-2, 1, 3-benzothiadiazoline in 770 ml of chloroform over a period of 15 minutes at RT in a protective gas atmosphere and with exclusion of light. The mixture was stirred for 6 hours, and 80 ml of saturated Na2CO3 solution were subsequently added, the organic phase was separated off and dried over Na2SO4. After removal of the solvent, the residue was recrystallized from DMF/EtOH. Dying at 50 C. under reduced pressure gave the product in the form of yellow-orange crystals which according to HPLC had a purity of about 99.6%. The yield was 10 g (85%). 1H NMR (DMSO-d6, 500 MHz): [ppm]=8.17 (s, 2H), 7.95 (d, 3JHH=4.2 Hz, 2H), 7.40 (d, 3JHH=4.2 Hz, 2H).A 5-liter reactor equipped with agitator, condenser and thermometer, were charged with o-dichlorobenzene (3L), 4, 7-bis(thien-2-yl)-2, 1, 3-benzothiadiazole (150.0 g, 0.5 mol) and NBS (170.0 g, 0.95 mol). The mixture was heated slowly to 55 C. After stirring at 55 C. for 3 hours, the resulting slurry was heated to 150 C. to dissolve the solids. When all solids disappeared, the mixture was allowed to cool to room temperature. Stirring was stopped and the supernatant liquid was drawn off by vacuum (aspirator) using a glass fritted sparge tube (removing as much liquid as possible). The remaining wet cake was slurried/stirred with water (2×2, 500 mL) and ethanol (500 mL), and each time the supernatant liquid was drawn off by vacuum as described above. The wet cake was dried by passing a nitrogen stream over the solids, followed by pulling vacuum on the vessel. The crude product which had 98.4% purity by GC area, was recrystallized from o-dichlorobenzene as follows: 1, 200 mL of o-dichlorobenzene was added to the reactor. The mixture was heated with stirring to 150 C. until all solids were dissolved, then allowed to cool to room temperature. The liquid was drawn off in vacuo using a glass fritted sparge tube, the reactor was recharged with 1, 200 mL of o-dichlorobenzene and the above recrystallization process repeated. The wet cake was washed with o-dichlorobenzene (100 mL) and ethanol (400 mL) and dried at 50 C./2-3mmHg overnight. Pure product (194.2 g) was obtained in 84.8% yield, which was of 99.7% of purity as measured by GC area. M.p.247-248 C., 1H NMR spectroscopic analysis:(300 MHz/DMSO-d6) 8.16 (s, 2H), 7.97(m, 2H), 7.39 (m, 2H).4, 7-Di(thiophen-2-yl)benzo[c][1, 2, 5]thiadiazole (4.0 g, 13.3 mmol) was dissolved in CHCl3 (100 mL) and a catalyticamount of acetic acid. Then, N-bromosuccinimide(NBS) (5.5 g, 30.6 mmol) was added portion wise, andthe mixture was stirred for 36 h at room temperature withlight protection. The precipitate was filtered through aBuechner funnel, and then washed with copious amountsof MeOH, water, and acetone. The product was collectedas a red solid (4.6 g, 76%). 1H NMR (400 MHz, CDCl3: 7.80 (dd, 4 H), 7.13 (d, 2 H). 13C NMR (400 MHz, CDCl3: 154.2, 140.8, 131.1, 129.6, 129.1, 128.0, 111.6.4, 7-Bis(5-bromothiophen-2-yl)benzo(1, 2, 5)thiadiazole (M1) Compound 3 (100 mg, 0.332 mmol) and 1.5 mL acetic acid and 3 mL of CHCl3 were stirredat 0 C under nitrogen purging for 10 min. NBS (130 mg, 0.732 mmol) was added in portionsat the same temperature and the reaction mixture stirred for 24 h at rt under inert atmosphere.Then it was poured into water and extracted with dichloromethane. The organic phase wasdried over anhydrous sodium sulfate and concentrated in a rotary evaporator under reducedpressure. Further purification of the monomer M1 was carried out by columnchromatography with hexane as the eluent. Yield: 60%Add the product from Step 1 (0.50g, 1.6m mol) to a 100mL three-necked flask, And add 70mL of anhydrous tetrahydrofuran to dissolve;0 -5 under dark conditions and nitrogen blanket, Slowly add NBS (0.66g, 3.6mmol);Then, react at room temperature, and monitor the progress of the reaction by thin chromatography;After 15 hours, 10 mL of deionized water was added to quench the reaction;After that, chloroform was selected to extract the organic layer (3 × 120 mL), and the organic layers were combined.Wash the organic layer with saturated saline (3 × 120mL).After drying and removing solvents, a red crude product is obtained.After the crude product was separated by column chromatography and recrystallized, 0.4 g of a solid powder was obtained with a yield of 52%.Intermediate B '(0.8 g, 2.67 mmol) was added to the reaction flask and dissolved in anhydrous THF.Cooled to -78 C with acetone and dry ice.In another reaction flask, 2, 2, 6, 6-Tetramethylpiperidine (1.19 mL, 7 mmol) and anhydrous THF were added and stirred, Cooled to -78 C with acetone and dry ice.Next, n-BuLi (1.6M in hexane, 4.53 mL, 7.25 mmol) was added dropwise to a 2, 2, 6, 6-Tetramethylpiperidine solution, The solution was kept at -78 C for 15 minutes.Lithium 2, 2, 6, 6-tetramethylpiperidide (LTMP) was added dropwise to the solution of intermediate B ', Acetonitrile and dry ice were used for 1 hour at -40 C.Again lower the temperature to -78 , 2-Isopropoxy-4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane (1.41 mL, 6.92 mmol) was slowly added using a syringe.The reaction temperature was raised to room temperature and stirred for 20 minutes.After the reaction, the reaction mixture was extracted with ether and brine.Dry the organic layer with anhydrous MgSO 4 and evaporate the solvent.Purification with acetonitrile gave a red solid.(0.57 g, 41% yield).The compound BrDPPT2 (0.178 g, 22 mmol), TBT (0.033 g, 11 mmol) was added to a 25 mL slick tube.Anhydrous K2CO3 (373 mg, 0.27 mmol), PivOH (29.2 mg, 0.032 mmol) and Pd (OAc) 2 (4.5 mg, 0.022 mmol).After stirring in an anhydrous state, dimethylacetamide (DMA, 5 mL) was added, and the mixture was reacted at 110 C for 10 hours under a nitrogen atmosphere.The reaction was quenched and cooled to rt.The organic phase was purified by column chromatography, the solid phase was silica gel, and the eluent was petroleum ether / dichloromethane.After separation, it was washed with methanol and dried to give a white solid (160 mg, 81%).

Molecular Weight:300.4
XLogP3:4.5
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:2
Exact Mass:299.98496178
Monoisotopic Mass:299.98496178
Topological Polar Surface Area:111
Heavy Atom Count:19
Complexity:298
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes