5-CHLOROTHIOPHENE-2-CARBONYL CHLORIDE

Colorless to light yellow liquid

To a mixture of 2-acetyl-5-chlorothiophene (0.161 mg, 1.0 mmol), pyridine (0.012 ml, 0.15 mmol), and chlorobenzene (0.35 ml) was added SA mixture of 2-acetyl-5-chlorothiophene (161 mg, 1.00 mmol), pyridine (0.008 ml, 0.10 mmol), and thionyl chloride (0.435 ml, 6.00 mmol) was stirred at 70°C for 3 h 15 min, and then at 137°C for 14.5 h. Then the mixture was diluted with CDCIA mixture of 2-acetyl-5-chloro-thiophene (0.163 g, 1.0 mmol), pyridine (0.008 ml, 0.1 mmol), and disulfur dichloride (0.240 ml, 3.0 mmol) was stirred at 137 °C for 20 h. The mixture wasdiluted with CDC13 (2 ml), an internal standard was added (iBu3PO4, 0.0552 ml, 0.20 mmol), and the mixture was analyzed. 1H NMR indicated that 5-chloro-2-thiophene carbonyl chloride(68percent yield) had been formed.1H NMR (CDC13, 400 MHz) delta = 7.80 (d, J = 4 Hz, 1H), 7.06 (d, J = 4 Hz, 1H).13C NMR (CDC13, 100 MHz) delta = 158.5, 143.1, 137.5, 134.9, 128.3.32.0 g (0.20 mmol) 5-chloro-thiophene-2-carboxylic acid are 150 ml dichloromethane refluxed for 16 h with stirring with 100 ml of thionyl chloride and 250 μl DMF. The reaction mixture is evaporated down i. vac., the residue in each case is mixed 5 times with toluene and twice with dichloromethane and evaporated down completely. The residue is further reacted directly without any further purification.Yield: quant.CIntermediate 11A; 5-Chlorothiophene-2-carbonyl chloride 480 mg (2.95 mmol) of 5-chlorothiophene-2-carboxylic acid are dissolved in 24 ml of dichloromethane, and 2.4 ml (27.5 mmol) of oxalyl chloride are added. The mixture is heated under reflux for 16 h. It is then concentrated in vacuo, and the residue is again mixed with dichloromethane and concentrated once again. A viscous oil remains and is dried under high vacuum. 534 mg (quant.) of the target compound are obtained and are reacted further without further purification and characterization.(1) Passing the material through each module of the microchannel reactor system (including preheating module, reaction module and cooling module) replace the air with nitrogen; In a suitable reactor (for example 250 ml three-necked bottle) in 100 ml toluene, 30g5 - chloro -2 - carboxylic acid thiophene, a catalytic amount of N, N - dimethyl formamide, stirring under cooling to 5 °C following, slowly dropping 30g thionyl chloride, temperature control _AOMARKENCODELTX0AO _ 30 °C. Then completing, system heating to 80 °C, thermal insulation reaction 5.0h, TLC tracking after the reaction is complete, lowering the temperature to 50 - 60 °C, concentrated under reduced pressure, the concentrated residue by vacuum distillation, collecting 82 - 85 °C/4 - 5mmHg distill share 34g colorless transparent liquid, yield: 95percent, GC purity: _AOMARKENCODEGTX0AO _ 99.6percent, single hetero _AOMARKENCODELTX0AO _ 0.15percent.5-Chlorothiophene-2-carboxylic acid (500 g) was added to toluene (2500 mL) andthe reaction mixture was heated to 70°C to 80°C. Thionyl chloride (275 mL) was added to the reaction mixture over 90 minutes, and the reaction mixture was stirred for 1 hour at 70°C to 80°C. The reaction mixture was heated at 100°C to 105°C for 4 hours to S hours. The reaction mixture was cooled to 60°C to 65°C, and the solvent was completely recovered at 60°C to 65°C under vacuum to obtain 5-chlorothiophene-2-carbonylchloride.Yield: 89.78percent137 ml (1.57 mol) of oxalyl dichloride are added to a suspension of 51.2 g (0.315 mmol) of 5-chlorothiophene-2-carboxylic acid in 307 ml of dichloromethane. Example 1A5-Chlorothiophene-2-carbonyl chloride 137 ml (1.57 mol) of oxalyl chloride were added to a suspension of 51.2 g (0.315 mmol) of 5-chlorothiophene-2-carboxylic acid in 307 ml of dichloromethane. After addition of 2 drops of DMF the mixture was stirred at room temperature for 15 hours. The solvent and excess oxalyl chloride were then removed on a rotary evaporator. The residue was distilled under reduced pressure. The product boiled at 74-78° C. and a pressure of 4-5 mbar. This gave 50.5 g (87percent of theory) of an oil which solidified on storage in the fridge.Oxalyl chloride (14.0 g, 0.11 mol) is added dropwise to a suspension of 5-chloro-thiophene-2-carboxylic acid (5, 15 g, 0.09 mol) and catalytic amounts of N, N-dimethylformamide in 150 ml of dichloromethane. The reaction mixture is stirred for 1 h at room temperature, then heated to reflux for 1 h. After cooling to room temperature, the reaction mixture is evaporated under reduced pressure to deliver the intermediate 5-chloro-thiophene-2-carboxylic acid chloride (16.7 g, 0.09 mol) as residue. This yellow oil was dissolved in 180 ml of dichloromethane and N, O-dimethylamine hydrochloride (9.9 g, 0.10 mol) was added at 5 °C. Subsequently triethylamine (20.5 g, 0.20 mol) was added dropwise at 5 °C. The resulting thick yellow suspension was diluted with 80 ml of dichloromethane and stirred for 16 h at room temperature. It was washed with water, the organic phase washed with brine, dried over sodium sulfate and concentrated under reduced pressure to give 5-chloro-thiophene-2-carboxylic acid methoxy-methyl-amide (6, 18.8 g, 0.09 mol, 98percent) as a yellow oil. 62 gm (0.3827 moles) 5-Chloro thiophene-2 -carboxylic acid was charged in 310 ml toluene. To it was charged 67 gm (0.5630 moles) of thionyl chloride at room temperature. The reaction mixture was heated to reflux temperature for about 10- 12 hours. Toluene was distilled out completely to get an oil of 5-chloro thiophene-2 -carbonyl chloride (68 gm).To a solution of 5-chlorothiophene-2-carboxylic acid (VI) (6.51 g, 40 mmol) in toluene, Slowly drop the thionyl chloride(9.52 g, 80 mmol), And then heated to 105 ° C for 8 hours, The reaction solution was cooled to room temperature and dissolved under reduced pressureTo give oily substance 7.36 g of 5-chlorothiophene-2-carboxylic acid chloride (VII) without the need for purification directly for the next step.Add 1.9 g of the compound 5-chlorothiophene-2-carboxylic acid to a 50 mL two-necked flask equipped with a rotor and a thermometer.A drop of pyridine was added, 1.8 g of thionyl chloride was slowly added, and the mixture was heated to 80 ° C with stirring, and the solid was gradually dissolved, and the reaction was kept for 3 hours.After cooling to room temperature, excess thionyl chloride was distilled off under reduced pressure.2.1 g of 5-chlorothiophene-2-carbonyl chloride was obtained as a light yellow oily liquid.A mixture of oxalyl chloride, 2-chlorothiophene and sulfolane (3 : 1: 0.33, molar ratio) was heated in a closed vessel to 165 °C for 17.5 h. Analysis of the reaction mixture by 1H NMR indicated a conversion of 2-chlorothiophene of 100percent and a yield of 5-chlorothiophene-2- carbonyl chloride of 100percent.

Molecular Weight:181.04
XLogP3:3.4
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:179.9203412
Monoisotopic Mass:179.9203412
Topological Polar Surface Area:45.3
Heavy Atom Count:9
Complexity:128
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes