* 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 Materials Chemistry C, 2017, vol. 5, # 30, p. 7527 - 7534
[2] RSC Advances, 2015, vol. 5, # 94, p. 77460 - 77468
[3] Patent: WO2008/127029, 2008, A1, . Location in patent: Page/Page column 15; 18-19
[4] Patent: US2010/99840, 2010, A1,
[5] Journal of the American Chemical Society, 2010, vol. 132, # 22, p. 7595 - 7597
[6] Organic Letters, 2004, vol. 6, # 19, p. 3381 - 3384
[7] Journal of the American Chemical Society, 1981, vol. 103, # 10, p. 2760 - 2769
[8] Journal of the American Chemical Society, 2011, vol. 133, # 34, p. 13685 - 13697
[9] Journal of the American Chemical Society, 2012, vol. 134, # 46, p. 19035 - 19042
[10] Dyes and Pigments, 2016, vol. 134, p. 129 - 138
[11] Chemistry - A European Journal, 2015, vol. 21, # 24, p. 8754 - 8757
[12] Journal of Organic Chemistry, 1954, vol. 19, p. 70,72
[13] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 2, p. 267 - 270
[14] Journal of Organic Chemistry, 2006, vol. 71, # 26, p. 9602 - 9608
[15] Patent: EP2083011, 2009, A1, . Location in patent: Page/Page column 10
[16] Patent: EP2093228, 2009, A1, . Location in patent: Page/Page column 12
[17] Patent: EP2431371, 2012, A1, . Location in patent: Page/Page column 26
[18] Journal of Polymer Science, Part A: Polymer Chemistry, 2012, vol. 50, # 18, p. 3758 - 3766
[19] Macromolecules, 2013, vol. 46, # 16, p. 6408 - 6418
[20] RSC Advances, 2014, vol. 4, # 68, p. 35868 - 35878
[21] Advanced Synthesis and Catalysis, 2014, vol. 356, # 18, p. 3761 - 3768
[22] Journal of Materials Chemistry A, 2017, vol. 5, # 34, p. 18088 - 18094
[23] Chinese Chemical Letters, 2018, vol. 29, # 3, p. 381 - 384
[24] Patent: US2008/176900, 2008, A1, . Location in patent: Page/Page column 13
[25] Patent: EP1964842, 2008, A1, . Location in patent: Page/Page column 26-27
3
[ 18853-32-2 ]
[ 4282-29-5 ]
Yield
Reaction Conditions
Operation in experiment
88%
Stage #1: With potassium hydroxide In ethylene glycol Stage #2: With hydrogenchloride; water In ethylene glycol
Thiophene-3,4-dicarbonitrile (13.4 g, 100 mmol) and KOH (56.1 g, 1 mol) were dissolved in ethylene glycol (167 ml), and heated under stirring overnight. The solution was cooled and put into distilled water, and washed with diethyl ether. The aqueous layer was oxidized with saturated hydrochloric acid, and organic materials were extracted with ethyl acetate. The organic layer was dried over MgSO and the4, solvent was evaporated Then, recrystallization was performed in distilled water to obtain thiophene-3,4-dicarboxylic acid (15.2 g, 88percent).
88%
With potassium hydroxide In water; ethylene glycol
2) Synthesis of thiophene-3,4-dicarboxylic acid Thiophene-3,4-dicarbonitrile (13.4 g, 100 mmol) and KOH (56.1 g, 1 mol) were dissolved in ethylene glycol (167 ml), and heated under stirring overnight. The solution was cooled and put into distilled water, and washed with diethyl ether. The aqueous layer was oxidized with saturated hydrochloric acid, and organic materials were extracted with ethyl acetate. The organic layer was dried over MgSO4 and the solvent was evaporated Then, recrystallization was performed in distilled water to obtain thiophene-3,4-dicarboxylic acid (15.2 g, 88percent).
Reference：
[1] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1993, # 9, p. 1589 - 1596
[2] Patent: WO2008/127029, 2008, A1, . Location in patent: Page/Page column 18
[3] Patent: US2010/99840, 2010, A1,
[4] Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 1103 - 1108
[5] Journal of the American Chemical Society, 2012, vol. 134, # 46, p. 19035 - 19042
[6] Organic Letters, 2004, vol. 6, # 19, p. 3381 - 3384
[7] Patent: EP2083011, 2009, A1, . Location in patent: Page/Page column 10
[8] Patent: EP2093228, 2009, A1, . Location in patent: Page/Page column 11
[9] Patent: EP2431371, 2012, A1, . Location in patent: Page/Page column 25
[10] Patent: US2008/176900, 2008, A1, . Location in patent: Page/Page column 12-13
[11] Patent: EP1964842, 2008, A1, . Location in patent: Page/Page column 26
4
[ 4282-35-3 ]
[ 4282-29-5 ]
Yield
Reaction Conditions
Operation in experiment
80%
With sodium hydroxide In water at 80℃;
Dimethyl thiophene-3,4-dicarboxylate was in round-bottom flask. To this 1M solution of NaOH was added and the mixture was stirred at 80 oC for overnight. The solution was the acidified with HCl to pH=3 and extracted with ethyl acetate, dried over sodium sulfate and concentrated to obtain the yellow solid compound. Yield 80percent.
Reference：
[1] Journal of Organic Chemistry, 1954, vol. 19, p. 1671,1677
15
[ 5472-38-8 ]
[ 4282-29-5 ]
Reference：
[1] Journal of Organic Chemistry, 1954, vol. 19, p. 1671,1677
16
[ 4282-30-8 ]
[ 4282-29-5 ]
Reference：
[1] Collection of Czechoslovak Chemical Communications, 1988, vol. 53, # 6, p. 1268 - 1273
17
[ 4282-29-5 ]
[ 190723-12-7 ]
Yield
Reaction Conditions
Operation in experiment
85.6%
at 20℃; for 12 h;
3,4-dicarboxylic acid thiophene (5 g, 29.04 mmol) and 40 mL of glacial acetic acid were sequentially added to a 100 mL single-mouth bottle.Stir at room temperature, add liquid bromine (8.9 mL, 174.24 mol) to a 25 mL constant pressure dropping funnel.Slowly drip into the reaction flask and react for 12 h. After the reaction is over,The reaction solution was poured into 500 mL of a saturated sodium hydrogensulfate solution and stirred until a beige solid precipitated.Filter under reduced pressure and dry to give a beige solid (8.2 g, 85.6percent).
60%
With bromine In acetic acid at 20℃; for 12 h;
A 500 mL one neck round bottom flask was charged with thiophene-3,4-dicarboxylic acid (29 g, 0.17 mol) and glacial acetic acid (280 mL). Bromine (52 mL, 1.0 mol) was added dropwise to the reaction flask and the mixture was stirred for 12 hours at RT. An aqueous solution of sodium bisulfate was added until the reddish color disappeared. The mixture was basified and filtered. The filtrate was acidified to give a gray solid which was filtered, washed with cold water, and dried to give the product. The crude product was recrystalized twice from water (60percent).Spectral data: 1H NMR (300 MHz, CDC13): 13.6 (br s, 2H).13C NMR (300 MHz, DMSO): δ 162.5, 135.0, 118.
Reference：
[1] Patent: CN108250222, 2018, A, . Location in patent: Paragraph 0059; 0062; 0063
[2] Journal of the American Chemical Society, 1997, vol. 119, # 41, p. 9624 - 9631
[3] Chemical Communications, 2011, vol. 47, # 40, p. 11345 - 11347
[4] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 14, p. 1929 - 1940
[5] Journal of Materials Chemistry C, 2018, vol. 6, # 3, p. 500 - 511
[6] Patent: WO2011/28827, 2011, A2, . Location in patent: Page/Page column 127
[7] Journal of the American Chemical Society, 2013, vol. 135, # 12, p. 4656 - 4659
[8] Journal of the American Chemical Society, 2014, vol. 136, # 27, p. 9608 - 9618
[9] Angewandte Chemie - International Edition, 2016, vol. 55, # 42, p. 12996 - 13000[10] Angew. Chem., 2016, vol. 128, p. 13190 - 13194,5
[11] Macromolecules, 2012, vol. 45, # 3, p. 1710 - 1714
[12] Chemistry of Materials, 2012, vol. 24, # 7, p. 1346 - 1356
[13] Macromolecules, 2012, vol. 45, # 24, p. 9611 - 9617
To a stirred solution of <strong>[4282-29-5]thiophene-3,4-dicarboxylic acid</strong> (24, 1.5 g, 8.71 mmol) in methanol (15 mL) was added conc. sulfuric acid (1 mL) dropwise. The reaction was heated to reflux and stirred under nitrogen overnight. The reaction mixture was allowed to cool to room temperature followed by concentration under vacuum. The resulting crude residue was then partitioned between saturated aqueous NaHCO3 and diethyl ether, and the aqueous layer was further extracted with diethyl ether (2 * 40 mL). The combined ether solutions were washed with brine (20 mL), dried (Na2SO4), and concentrated to dryness under reduced pressure to provide the desired product as a clear oil (1.46 g, 84%). 1H NMR (500 MHz, CDCl3) delta 7.88 (s, 2H), 3.88 (s, 6H). 13C NMR (126 MHz, CDCl3) delta 163.41, 133.11, 131.90, 52.33. HRMS (LC-TOF): Calcd for C8H8O4S 200.0143; found 200.0130.
<strong>[4282-29-5]Thiophene-3,4-dicarboxylic acid</strong> (10 g, 58 mmol) is placed in a 3 dry 3 -neck round bottom flask equipped with an argon inlet and a water condenser. Dry ethanol (100 mL) is added to the flask along with a catalytic amount of cc. sulfuric acid (1 mL). The reaction completion is determined by taking aliquot for NMR analysis. When complete, the reaction is cooled to room temperature. The ethanol is evaporated and the resulting product is purified via column chromatography, using a 100% hexane to 60% hexane/40% ethyl acetate gradient
Thiophene-3,4-dicarboxylic acid (15.0 g, 87 mmol) was dissolved in acetic acid <n="20"/>anhydride (218 ml), and heated under stirring overnight. After stirring, the solvent was evaporated, and recrystallization was performed in toluene to obtain thiophene- 3,4-dicarboxylic acid anhydride (12.5 g, 93%).[110] GC/MS : [M+H]+ = 155
93%
In acetic anhydride; toluene;
3) Synthesis of thiophene-3,4-dicarboxylic acid anhydride Thiophene-3,4dicarboxylic acid (15.0 g, 87 mmol) was dissolved in acetic acid anhydride (218 ml), and heated under stirring overnight. After stirring, the solvent was evaporated, and recrystallization was performed in toluene to obtain thiophene-3,4-dicarboxylic acid anhydride (12.5 g, 93%). GC/MS: [M+H]+=155
With acetic anhydride; for 3h;Heating / reflux;
To a 250 mL round bottom flask equipped with an electromagnetic stirrer, a reflux condenser and a drying tube, 15 g of thiophene-3,4-dicarboxylic acid and 120 mL of acetic anhydride were added. The mixture was refluxed for 3h, and evaporated to remove solvent. 13 g of deep brown solid was obtained.
With acetic anhydride; for 3h;Reflux;
To a 250 mL round bottom flask, equipped with an electromagnetic stirrer, a reflux condenser, and a dying tube, 15 g of thieno-3,4-dicarboxylic acid and 120 mL of acetic anhydride were added. The mixture was refluxed for 3 h, evaporated to remove solvent to give 13 g of deep brown solid.
With acetic anhydride; for 3h;Reflux;
Compound 7 thiophene[3,4-c]furan-1,3-diketone To a 250 ml of round-bottom flask equipped with an electromagnetic stirrer, a reflux-condenser and a drying tube were added 15 g of compound 6 and 120 ml of acetic anhydride. The mixture was refluxed for 3 hours. The solvent was evaporated to give 13 g of a brown solid.
With acetic anhydride; at 90℃; for 6.17h;Inert atmosphere; Sealed tube;
To an over-dried tube was charged with thiophene-3,4-dicarboxylic acid (1) (1.72 g, 10 mmol) and acetic anhydride (10 mL). After purged with Ar for10 minutes, the tube was sealed and heated in an oil bath at 90C for 6 hours. Then the excessivesolvent was evaporated under vacuum. The resultant solid of thieno[3,4-c]furan-1,3-dione was used immediately without purification.
With acetic anhydride; for 3h;Heating / reflux;
To a 250 mL round bottom flask under inert atmosphere, equipped with an electromagnetic stirrer, and a reflux condenser, 15 g of thieno-3,4-dicarboxylic acid and 120 mL of acetic anhydride were added. The mixture was refluxed for 3 h, evaporated to dryness to remove solvent. 13 g of deep brown solid were obtained.
With acetic anhydride; for 3h;Heating / reflux;
Thieno(3,4-c)furan-1,3-dione [Show Image] To a 250 mL round bottom flask under inert atmosphere, equipped with an electromagnetic stirrer, and a reflux condenser, 15 g of thieno-3,4-dicarboxylic acid and 120 mL of acetic anhydride were added. The mixture was refluxed for 3h, evaporated to dryness to remove solvent. 13 g of deep brown solid were obtained.
With acetic anhydride; at 110℃; for 16h;
A solution of thiophene-3,4-dicarboxylic acid (25.0 g, 145 mmol) in acetic anhydride (250 mL) was heated to 110 C. for 16 h.The mixture was then concentrated to give thieno[3,4-c]furan-1,3-dione (22.0 g crude) as a yellow solid and used for the next step without further purification.
General procedure: o-Dicarboxylic acids (4.14 mmol) were heated under reflux in SOCl2 (50 mL) for 18 h. The solution was evaporated to dryness to give the o-diacid dichlorides, as yellow oils, which were immediately used without purification. Benzimidazole (2.12 mmol) and o-diacid dichloride (4.14 mmol) in Ac2O (50 mL) were stirred at 90 C for 15 min. The precipitated p-dione adduct was filtered, washed with Ac2O, and dried under vacuum. Compounds did not require purification, unless otherwise stated.
<strong>[18853-32-2]Thiophene-3,4-dicarbonitrile</strong> (13.4 g, 100 mmol) and KOH (56.1 g, 1 mol) were dissolved in ethylene glycol (167 ml), and heated under stirring overnight. The solution was cooled and put into distilled water, and washed with diethyl ether. The aqueous layer was oxidized with saturated hydrochloric acid, and organic materials were extracted with ethyl acetate. The organic layer was dried over MgSO and the4, solvent was evaporated Then, recrystallization was performed in distilled water to obtain thiophene-3,4-dicarboxylic acid (15.2 g, 88%).
88%
With potassium hydroxide; In water; ethylene glycol;
2) Synthesis of thiophene-3,4-dicarboxylic acid <strong>[18853-32-2]Thiophene-3,4-dicarbonitrile</strong> (13.4 g, 100 mmol) and KOH (56.1 g, 1 mol) were dissolved in ethylene glycol (167 ml), and heated under stirring overnight. The solution was cooled and put into distilled water, and washed with diethyl ether. The aqueous layer was oxidized with saturated hydrochloric acid, and organic materials were extracted with ethyl acetate. The organic layer was dried over MgSO4 and the solvent was evaporated Then, recrystallization was performed in distilled water to obtain thiophene-3,4-dicarboxylic acid (15.2 g, 88%).
To a 500 mL round bottom flask equipped with an electromagnetic stirrer and a reflux condenser, 15.978 g of <strong>[18853-32-2]3,4-dicyanothiophene</strong>, 43.997 g of KOH, and 174 mL of ethylene glycol were added; and the mixture was refluxed for 4h. After the reaction mixture was cooled, 350 mL of water was added, and the aqueous layer was extracted with ether (2x100 mL). The ether layer was removed, the aqueous layer was cooled down in an ice bath, and an excess of strong hydrochloric acid was added until a white precipitate was formed. The solid was filtered and dissolved in 2000 mL of ether. The filtrate was extracted with ether (3x300 mL). The organic layers were combined, dried over anhydrous MgSO4, filtered, and evaporated to remove the solvent. 15 g of white solid was obtained and recrystallized from water. 1H NMR (DMSO-d6): delta 10.35 (brs, 2H), 8.17 (s, 2H); MS (m/z): 171 (M-1)+.
To a 500 mL round bottom flask equipped with an electromagnetic stirrer, and a reflux condenser, 15.978 g of <strong>[18853-32-2]3,4-dicyanothiophene</strong>, 43.997 g of KOH, and 174 mL of glycol were added; and the mixture was refluxed for 4h. After the reaction mixture was cooled, 350 mL of water was added, and the aqueous layer was extracted with diethyl ether (2×100 mL). The ether layer was removed, the aqueous layer was cooled down in an ice bath, and an excess of strong hydrochloric acid was added until a white precipitate appeared. The solid was filtered and dissolved in 2000 mL of ether. The filtrate was extracted with diethyl ether (3×300 mL). Organic layers were combined, dried over anhydrous MgSO4, filtered, and evaporated. 15 g of white solid was obtained and recrystallized from water. 1H NMR (DMSO-d6): delta 10.35 (brs, 2H), 8.17 (s, 2H); MS (m/z): 171 (M-1)+
Compound 6 thiophene-3,4-dicarboxylic acid To a 500 ml of round-bottom flask equipped with an electromagnetic stirrer and a reflux-condenser were added 15.978 g of compound 5, 43.997 g of potassium hydroxide and 174 ml of ethylene glycol. The mixture was refluxed for 4 hours. After cooling, 350 ml of water was added to the reaction mixture. The resultant mixture was extracted with diethyl ether (100 ml * 2). The diethyl ether layers were discarded. An excess amount of concentrated hydrochloric acid was added to the aqueous layer in an ice bath to give a white precipitate. The white precipitate was filtrated and the solid was dissolved in diethyl ether (about 2000 ml). The filtrate was extracted with diethyl ether (300 ml * 3). All diethyl ether layers were combined. The organic phase was dried over anhydrous MgSO4 and filtered. The solvent was evaporated to give 15 g of a white solid. The white solid was recrystallized with water. 1H NMR (DMSO-d6): delta 10.35 (brs, 2H), 8.17 (s, 2H); MS (m/z): 171 [M-1]+.
With potassium hydroxide; In ethylene glycol; for 4h;Heating / reflux;
To a 500 mL round bottom flask equipped with an electromagnetic stirrer and a reflux condenser, 15.978 g of <strong>[18853-32-2]3,4-dicyanothiophene</strong>, 43.997 g KOH, and 174 mL glycol were added; and the mixture was refluxed for 4 h. After the reaction mixture was cooled, 350 mL water was added, and the aqueous layer was extract with ether (2×100 mL). The layers were separated, the aqueous layer was cooled down in an ice bath, and excess strong hydrochloric acid was added until a white precipitate appeared. The solid was filtered and dissolved in 2000 mL of ether. The aqueous layer was extracted with ether (3×300 mL). Organic layers were combined, dried over anhydrous MgSO4, filtered, and evaporated to dryness. 15 g of white solid was obtained and recrystallized from water. 1H NMR (DMSO-d6): delta 10.35 (brs, 2H, COOH), 8.17 (s, 2H); MS (m/z): 171 (M-1)+.
Thiophene-3,4-dicarboxylic acid [Show Image] To a 500 mL round bottom flask equipped with an electromagnetic stirrer and a reflux condenser, 15.978 g of <strong>[18853-32-2]3,4-dicyanothiophene</strong>, 43.997 g KOH, and 174 mL glycol were added; and the mixture was refluxed for 4h. After the reaction mixture was cooled, 350 mL water was added, and the aqueous layer was extract with ether (2×100 mL). The layers were separated, the aqueous layer was cooled down in an ice bath, and excess strong hydrochloric acid was added until a white precipitate appeared. The solid was filtered and dissolved in 2000 mL of ether. The aqueous layer was extracted with ether (3×300 mL). Organic layers were combined, dried over anhydrous MgSO4, filtered, and evaporated to dryness. 15 g of white solid was obtained and recrystallized from water. 1H NMR (DMSO-d6): delta10.35 (brs, 2H, COOH), 8.17 (s, 2H); MS (m/z): 171 (M-1)+.
(1) Compound 1 (5g, 28.5 mmol),60 mL of glacial acetic acid was placed in a 500 mL three-necked flask, and the three-necked flask was placed in an ice water bath and stirred for 30 mins.A solution of bromine in acetic acid (1 mol / L, 172 mL, 172 mmol) was slowly added dropwise to the three-necked flask through a constant pressure dropping funnel. After the addition, the ice-water bath continued to be stirred for 15 mins.Then slowly raise the temperature to 85oC and stir overnight.After the mixture was cooled to room temperature, most of the solvent was removed under reduced pressure by a rotary evaporator, and saturated sodium thiosulfate aqueous solution was slowly added to the residueStir while adding until the reaction no longer generates gas and the system pH is close to 7. Filter, the filter cake was washed with a small amount of deionized water and absolute ethanol, and recrystallized in deionized water, filtered, and dried in vacuo to obtain 8.2 g of gray needle-like solid 2,5-dibromo-3,4-thiophenedicarboxylic acid (Compound 2), the yield was 87.2%.
85.6%
With bromine; acetic acid; at 20℃; for 12h;
3,4-dicarboxylic acid thiophene (5 g, 29.04 mmol) and 40 mL of glacial acetic acid were sequentially added to a 100 mL single-mouth bottle.Stir at room temperature, add liquid bromine (8.9 mL, 174.24 mol) to a 25 mL constant pressure dropping funnel.Slowly drip into the reaction flask and react for 12 h. After the reaction is over,The reaction solution was poured into 500 mL of a saturated sodium hydrogensulfate solution and stirred until a beige solid precipitated.Filter under reduced pressure and dry to give a beige solid (8.2 g, 85.6%).
60%
With bromine; In acetic acid; at 20℃; for 12h;
A 500 mL one neck round bottom flask was charged with thiophene-3,4-dicarboxylic acid (29 g, 0.17 mol) and glacial acetic acid (280 mL). Bromine (52 mL, 1.0 mol) was added dropwise to the reaction flask and the mixture was stirred for 12 hours at RT. An aqueous solution of sodium bisulfate was added until the reddish color disappeared. The mixture was basified and filtered. The filtrate was acidified to give a gray solid which was filtered, washed with cold water, and dried to give the product. The crude product was recrystalized twice from water (60%).Spectral data: 1H NMR (300 MHz, CDC13): 13.6 (br s, 2H).13C NMR (300 MHz, DMSO): delta 162.5, 135.0, 118.
Example 1 Thiophene-3,4-dicarboxylic anhydride <strong>[4282-29-5]Thiophene-3,4-dicarboxylic acid</strong> (12 g, 0.07 mol) is dissolved in acetic anhydride (60 ml) and boiled for 2.5 hours. The mixture is then concentrated to dryness. There is obtained 10.55 g (98%) of thiophene-3,4-dicarboxylic anhydride (m.p. 147-149 C.).
A solution of <strong>[4282-29-5]thiophene-3,4-dicarboxylic acid</strong> (3.00 g, 17.4 mmol) in acetic anhydride(62.8 mL) was stirred at 140C overnight. After removal of the solvent, the resulting brownsolid was dissolved in toluene (160 mL); 2-ethylhexylamine (3.37 g, 26.1 mmol) was thenadded and the mixture was refluxed for 24 h. After cooling the mixture and removing thesolvent, the crude solid was dissolved in thionyl chloride (136 mL) and the mixture wasrefluxed for 4 h. The white solid product was obtained by column chromatography using dichloromethane:hexane (2:1). Yield: 3.40 g (73.6%). 1H NMR (400 MHz, CDCl3): delta (ppm)7.80 (s, 2H), 3.60 (d, 2H), 1.37 (m, 9H), 0.90 (m, 6H).
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
110K+ Compounds
Competitive Price
1-2 Day Shipping
