反応 #87298

反応方程式

(2E)-3-(2-thienyl)acrylic acid

piperidine

NaOH

oxalyl chloride

ammonia water

2-thiophene carboxaldehyde

malonic acid

→

(2E)-3-(2-thienyl)acrylamide

溶媒

water

dichloromethane

DMF

pyridine

反応条件

後処理

1. 1
   その他reacted at 80° C. for 6 h
2. 2
   抽出extracted with ethyl acetate
3. 3
   その他a large amount of yellow solid (2E)-3-(2-thienyl)acrylic acid was precipitated
4. 4
   ろ過filtered
5. 5
   洗浄washed with water
6. 6
   その他to obtain 1.12 g
7. 7
   workup.ADDITIONafter adding dropwise
8. 8
   workup.ADDITIONthe reaction solution was added dropwise into 0° C
9. 9
   その他the layers were separated
10. 10
    その他evaporated
11. 11
    その他to remove solvent

実験手順

1.12 g of 2-thiophene carboxaldehyde and 3.12 g of malonic acid were dissolved in 15 ml of pyridine, added with a catalytically effective amount of piperidine, reacted at 80° C. for 6 h, the reaction solution was poured into 20 ml of water, regulated with 10% NaOH aqueous solution to reach PH 12, extracted with ethyl acetate, the water layer was taken and regulated with 2N hydrochloric acid to reach PH3, a large amount of yellow solid (2E)-3-(2-thienyl)acrylic acid was precipitated, filtered and washed with water to obtain 1.12 g. The (2E)-3-(2-thienyl)acrylic acid was dissolved in 10 ml of anhydrous dichloromethane, added with a catalytically amount of DMF, added dropwise with 1.5 ml of oxalyl chloride under ice-water bath, after adding dropwise, heated to room temperature, stirred for 2 h, the reaction solution was added dropwise into 0° C. 10 ml concentrated ammonia water, stirred for 30 min, the layers were separated, the dichloromethane layer was taken, evaporated to remove solvent and obtain white needle crystal (2E)-3-(2-thienyl)acrylamide 0.7 g. It together with 1.20 g of trichloroacetaldehyde hydrate was added to 30 ml of toluene, refluxed at 110° C. for 8 h, cooled to room temperature to precipitate a large amount of yellow lamellar crystal (2E)-3-(2-thienyl)-N-(1-hydroxy-2,2,2-trichloroethyl)acrylamide 1.20 g. It was dissolved in 20 ml anhydrous THF, added with DMF for catalysis, added dropwise with SOCl2 1.2 ml at room temperature, heated to 60° C. and reacted for 2 h. After solvent was evaporated, it was dissolved in anhydrous acetone, added with 0.3 g of KSCN, stirred and reacted at 40° C. for 2 h, filtered with diatomite, the filtrate was eluted with developing solvent system of petroleum ether:ethyl acetate=20:1, to obtain yellow needle crystal (2E)-3-(2-thienyl)-N-(1-isothiocyano-2,2,2-trichloroethyl)acrylamide 0.81 g. It was dissolved in 10 ml of THF, added with 0.30 g of 8-aminoquinoline, heated to 60° C. and reacted for 2 h, cooled to room temperature to precipitate a large amount of white flocculent solid (2E)-3-(2-thienyl)-N-[1-(8-quinolylamino)thioformylamino-2,2,2-trichloroethyl]-2-acrylamide, which was recrystallized with THF to obtain a pure product of 0.92 g. 1H-NMR(400 MHz, DMSO-d6)δ6.63-6.67(d,1H); δ7.12-7.14(q,1H); δ7.42-7.43(d,1H); δ7.53-7.73(m, 6H); δ8.42-8.44(dd,1H); δ8.95-9.03(m,3H); δ9.54-9.56(d,1H); δ11.03(s,1H). MS(TOF) 487.0 (M+).

出典