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Chemical Structure| 19432-69-0 Chemical Structure| 19432-69-0

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Chemical Structure| 19432-69-0

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Product Details of [ 19432-69-0 ]

CAS No. :19432-69-0
Formula : C7H8O2S
M.W : 156.20
SMILES Code : O=C(C1=CC=C(C)S1)OC
MDL No. :MFCD06203669
InChI Key :NEPZGUGQLAOODR-UHFFFAOYSA-N
Pubchem ID :580756

Safety of [ 19432-69-0 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501

Application In Synthesis of [ 19432-69-0 ]

* 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.

  • Downstream synthetic route of [ 19432-69-0 ]

[ 19432-69-0 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 19432-69-0 ]
  • [ 56921-01-8 ]
YieldReaction ConditionsOperation in experiment
67% With sulfuric acid; nitric acid; at 0 - 5℃; for 0.5h; Step 2: Production of methyl 4-nitro-5-methylthiophene-2-carboxylate To a solution of methyl 5-methylthiophene-2-carboxylate (40.8 g, 260 mmol) in conc. sulfuric acid (400 ml) was added dropwise under ice-cooling a solution of fuming nitric acid (16.5 ml, 391 mmol) in conc. sulfuric acid (100 ml) at an inside temperature not exceeding 5C. After the completion of the dropwise addition, the mixture was stirred under ice-cooling for 30 min and gradually poured into ice (1 kg). The precipitated solid was washed with water (500 ml x 6) and dried under reduced pressure to give methyl 4-nitro-5-methylthiophene-2-carboxylate (35.1 g, yield 67%). 1H-NMR(300MHz, δppm, CDCl3): 8.20(1H, s), 3.91 (3H, s), 2. 84 (3H, s).
44 - 67% With sulfuric acid; nitric acid; at 0 - 5℃; for 0.5h;Product distribution / selectivity; To a solution of methyl 5-methylthiophene-2-carboxylate (40.8 g, 260 mmol) in conc. sulfuric acid (400 ml) was added dropwise a solution of fuming nitric acid (16.5 ml, 391 mmol) in conc. sulfuric acid (100 ml) under ice-cooling in such a manner that the inside temperature did not exceed 5 C. After the completion of the dropwise addition, the mixture was stirred under ice-cooling for 30 min, and poured slowly into ice (1 kg). The precipitated solid was washed with water (500 ml×6) and dried under reduced pressure to give methyl 4-nitro-5-methylthiophene-2-carboxylate (35.1 g, yield 67%). 1H-NMR (300 MHz, δppm, CDCl3) 8.20(1H, s), 3.91(3H, s), 2.84(3H, s).; To a solution of methyl 5-methylthiophene-2-carboxylate (109 g, 700 mmol) in conc. sulfuric acid (850 ml) was added dropwise a solution of fuming nitric acid (31 ml, 738 mmol) in conc. sulfuric acid (150 ml) under ice-cooling in such a manner that an inside temperature did not exceed 5 C. After the completion of the dropwise addition, the mixture was stirred under ice-cooling for 30 min, and slowly poured into ice (2 kg). The precipitated solid was collected by filtration, washed with water (500 ml×6) and dried under reduced pressure to give methyl 4-nitro-5-methylthiophene-2-carboxylate (62 g, yield 44%). 1H-NMR (400 MHz, δppm, CDCl3) 8.20(1H, s), 3.91(3H, s), 2.84(3H, s).
With sulfuric acid; nitric acid; at 0℃; for 0.5h; A solution of concentrated HN03 (7.2 mL, 1 1 1.5 mmol) in concentrated H2S04 (20 mL) was added dropwise to the solution of methyl 5-methylthiophene-2-carboxylate (F-2) (13.4 g, 86.0 mmol) in concentrated H2S04 (30 mL) at 0C. The reaction mixture was stirred at 0C for 30 mins and poured into ice-water. The precipitate was filtered and washed with water. A solid was collected as the product (14.8 g).
With sulfuric acid; nitric acid; In sulfuric acid; at 0℃; for 0.5h; Methyl 5-methyl-4-nitrothiophene-2-carboxylate (F-3) A solution of concentrated HNO3 (7.2 mL, 111.5 mmol) in concentrated H2SO4 (20 mL) was added dropwise to the solution of methyl 5-methylthiophene-2-carboxylate (F-2) (13.4 g, 86.0 mmol) in concentrated H2SO4 (30 mL) at 0 C. The reaction mixture was stirred at 0 C. for 30 mins and poured into ice-water. The precipitate was filtered and washed with water. A solid was collected as the product (14.8 g).
2.90 g With sulfuric acid; nitric acid; at 0℃; for 0.5h; To a stirred and cooled (0 C) solution of methyl 5-methylthiophene-2-carboxylate (5.0 g, 32.010 mmol) in conc. H2504 (30 ml) was added fuming nitric acid (1.41 ml,33.616 mmol) and the reaction mixture was stirred at the same temperature for 30 minutes. The reaction mixture was poured slowly on crushed ice and precipitate thusobtained was filtered and washed with water. The compound obtained after drying was purified by silica gel column chromatography to yield 2.90 g of the title product as white solid. ESI-MS (m/z) 200 (M-H).
24.3 g With sulfuric acid; nitric acid; at 0℃; for 0.25h; [0511] Methyl 5-methylthiophene-2-carboxylate (25.8 g) was dissolved in 50 mL of cold concentrated sulfuric acid and the mixture was kept cooling in an ice bath. To this solution, a prepared solution of fuming nitric acid (14 mL) and concentrated sulfuric acid (40 mL) was added dropwise. After completion of the addition, the mixture was kept stirring for an additional 15 mm at 0 C. The reaction mixture was poured carefully into crushed ice and the solid was collected by filtration, then washed with water, and dried. The desired product (24.3 g) was used directly in the next synthetic step. ‘H NIVIR (400 MHz, CDCL3): (major isomer) ö: 2.84 (s, 3H), 3.91 (s, 3H), 8.20 (s, 1H) ppm. LC (method A): tR = 1.73 mi LC/MS (El) m/z. [M + H] 202.3.
243 g With sulfuric acid; nitric acid; at 0℃; for 0.25h; Methyl 5-methylthiophene-2-carboxylate (25.8 g) was dissolved in 50 mL of cold concentrated sulfuric acid and the mixture was kept cood in an ice bath. To this solution, a prepared solution of fuming nitric acid (14 mL) and concentrated sulfuric acid (40 mL) was added dropwise. After completion of the addition, the mixture was stirred for an additional 15 min at 0 C. The reaction mixture was poured carefully into crushed ice and the solid was collected by filtration, washed with water, and dried. The desired product (24.3 g) was used directly in the next synthetic step. NMR (400 MHz, CDCh): (major isomer) δ: 2.84 (s, 3H), 3.91 (s, 3H), 8.20 (s, 1H) ppm. LC (method A): = 1.73 min. LC/MS (EI) mlz: [M + H]+ 202.3.

  • 2
  • [ 19432-69-0 ]
  • [ 108499-32-7 ]
YieldReaction ConditionsOperation in experiment
100% With N-Bromosuccinimide; dibenzoyl peroxide; In chloroform; for 7h;Reflux; Add freshly recrystallised NBS (323.8 g, 1.81 mol) to a solution of methyl-5- methylthiophene-2-carboxylate (258 g, 1.65 mol) in chloroform (2.6 L) at room temperature, and stir. Add benzoyl peroxide (3.99 g, 0.016 mol) and heat the reaction mixture to reflux for 7 hours. Cool the reaction mixture to ambient temperature and filter through diatomaceous earth. Wash the filter cake with chloroform (250 ml). Collect the organic layers and remove the solvent to give the title compound (388 g, 100%), which is used without further purification. ESI (m/z) 236(M+H).
90% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 2h; A mixture of compound 26.1, NBS (6.26 g, 35.2 mmol) and AIBN (0.03 g, 0.18 mmol) in CCl4 (20 mL) was heated to 8O0C for 2 hours, then cooled to room temperature, filtered, washed with cold CH2Cl2 / CCl4 (1 :1). The filtrate was concentrated to provide compound 26.2 as major product (90%) and was used in the next step without purification.
85% With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); In tetrachloromethane; at 80℃; for 2h; To a stirred solution of compound 20 (2.50 g, 17.58 mmol) in MeOH (30.00 mL) cooled to 0 C, SOCl2 (5.11 mL, 7.32 mmol) was added and the reaction was stirred at 25 C for 12 h. A 2 N solution of NaOH was added and volatiles were removed under reduced pressure. The aqueous phase was extracted with DCM (3 x 25.00 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. Methyl 5-methylthiophene-2-carboxylate was obtained in quantitative yield without any further purification. ESI-MS m/z 179 [M+Na]+; 1H NMR (300 MHz, CDCl3) delta 2.51 (s, 3H), 3.84 (s, 3H), 6.75 (d, J =3.1 Hz, 1H), 7.60 (d, J = 3.1 Hz, 1H). To a solution of the previously synthesized ester (3.00 g, 16.85 mmol) in CCl4 (15.00 mL), N-bromosuccinimide (2.70 g, 15.17 mmol)and azobisisobutyronitrile (catalytic amount) were added, and the reaction was stirred at 80 C for 2 h. The reaction was cooled to 25 C and filtered on asmall plug of Celite. Volatiles were removed under reduced pressure and the crude was purified by means of chromatography on silica gel (5 % diethyl ether in petroleum ether) to afford title compound (85 % yield) as a transparent oil. ESI-MS m/z 233-235 [M+H]+; 1H NMR (300 MHz, CDCl3) delta 3.87 (s, 3H), 4.66 (s, 2H), 7.08 (d, J = 3.8Hz, 1H), 7.62 (d, J = 3.8 Hz, 1H).
82% With N-Bromosuccinimide; dibenzoyl peroxide; In tetrachloromethane; for 12h;Reflux; The methyl ester 13, (2.4 g, 15.5 mmol) was refluxed in CC1< in the presence of NBS (3 g, 17 mmol) and benzoyl peroxide (121 mg, 0.03 equiv) for 12 h. The reaction was cooled to 0 C and filtered. Organics was filtered, dried over Na2S04 and evaporated in vacuo. Crude material was purified on silica gel column (EtOAc: Hexanes = 1:5) to give the titled compound 14. (2.9 g, 82%). XH NMR (CHCI3, 400 MHz): delta 7.64 (d, J=3.6, 1H) , 7.10 (m, 1H) , 3.90 (s, 3H) , 3.89 (s, 3H) ; 13C NMR (CHCI3, 100 MHz): 5 162.4, 149.8, 135.5, 130.2, 124.8, 52.4, 23.4; [M+H]+ = 235.1 (APCI+) .
With N-Bromosuccinimide; dibenzoyl peroxide; In chloroform; at 60℃; for 3h;Heating / reflux; N-Bromosuccinimide (Aldrich; 1.70 g, 9.6 mmol) and a catalytic amount of benzoyl peroxide were added to a solution of 5-methyl-thiophene-2-carboxylic acid methyl ester (1.40 g, 9.0 mmol) in chloroform (15 mL). The rection mixture was stirred under argon at reflux (60 C.) for 3 h, then filtered through Celite and evaporated under reduced pressure to give 5-bromomethyl-thiophene-2-carboxylic acid methyl ester (2 g) as a yellow oil which was used directly in the next step without further purification

  • 3
  • [ 19432-69-0 ]
  • [ 108499-32-7 ]
  • [ 1001200-44-7 ]
YieldReaction ConditionsOperation in experiment
28% Preparation 20 Methyl 5-(bromomethyl)-2-thiophene carboxylate The title compound of Preparation 19 (1.9 g, 12.2 mmol), N-bromosuccinimide (NBS, 2.2 g, 12.4 mmol), and benzoyl peroxide (20 mg, 0.08 mmol) were combined with 125 ml CCl4 under an inert atmosphere at room temperature. The reaction mixture was heated to 87 for 4 hrs. An additional 540 mg of NBS (3.0 mmol) and 75 mg of benzoyl peroxide (0.3 mmol) were then added and the reaction mixture was stirred for another hour at 87. The reaction mixture was filtered while hot and the filtrate was stripped to provide the title compound of this Preparation (811 mg, 28% yield) as a brown oil. 1 H NMR (CDCl3): delta 7.63 (1H, d, J=4), 7.09 (1H, d, J=4), 4.68 (2H, s), 3.89 (3H, s).
  • 5
  • [ 19432-69-0 ]
  • hexanes-ethyl acetate [ No CAS ]
  • 2,2'-aza-bis-isobutyronitrile [ No CAS ]
  • [ 108499-32-7 ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide; In tetrachloromethane; Preparation of 5-Bromomethyl-thiophene-2-carboxylic acid methyl ester (T-1). 5-Methyl-thiophene-2-carboxylic acid methyl ester (20.0 g, 0.13 mol) was dissolved in a suspension of N-bromosuccinimide (45.4 g, 0.26 mol) and 2,2'-aza-bis-isobutyronitrile (0.1 g, 0.61 mmol) in 1 L of carbon tetrachloride. The suspension was refluxed for 48 hours then cooled and the precipitate was filtered off. The filtrate was concentrated and the residue was purified on silica gel (100% hexanes then 9:1 Hexanes-Ethyl acetate) to provide a 26 g fraction containing mainly the di-brominated compound 5-dibromomethyl-thiophene-2-carboxylic acid methyl ester as a yellow oil and a more polar fraction (7.5 g) containing mainly compound T-1 (25% yield) as a yellow oil (70% purity).
 

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