| 100% |
With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; |
2-(4-Chlorophenoxy)acetyl chloride (56a). To a suspension of 4-chlorophenoxy acetic acid (9.32 g, 0.05 mol) in CH2CI2 (150 ml_) was added oxalyl chloride (32.5 ml_, of 2M in CH2CI2) and DMF (0.2 ml_). The resulting mixture was stirred at rt overnight under Ar. The mixture was concentrated in vacuo to give 10.3 g (100%) of 56a as colorless oil. 1 H NMR (60 MHz, CDCI3): delta 7.0-6.7 (m, 4H), 4.8 (s, 2H) ppm |
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With thionyl chloride; for 4h;Reflux; |
General procedure: Phenoxyaceticacids (50 mmol) was added to thionylchloride (50 mL) at room temperature under a calcium chloride tube.The mixture was then heated under reflux for 4 h. After cooling to roomtemperature, the mixture was evaporated in vacuo. The residue was dissolved in50 mL of dichloromethaneand aluminium chloride (13 g, 98 mmol) was addedslowly to the solution at 0C. After stirring at 0C for 15min, the reactionstirred at room temperature for 30min. The mixture was then poured into icewater, extracted with portions of ethyl acetate (3×50 mL). The organic layerwas washed with brine, dried over anhydrous sodium sulfate and the solventremoved in vacuo. The residue was purified by column chromatography to get theproduct. |
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With thionyl chloride;Reflux; |
General procedure: The 2-amino-5-mercapto-1,3,4-thiadiazole 1 (5 mmol) was dissolved in NaOH(5 mmol, 15 mL) at room temperature. Ethyl 2-bromopropionate (5 mmol) was addedto the solution obtained and the mixture was stirred for 20 min. After that, the solid precipitatewas filtered off, washed with cold water, air dried, and then recrystallized from ethanolto give 2-(5-amino-1,3,4-thiadiazol-2-ylthio) propanoate 2 in 78% yield as pale yellowsolid. Mp 79-80C; 1H NMR(CDCl3, 400 MHz) deltaH: 1.25-1.28 (t, 3H, CH3, J = 6.0 Hz),1.57-1.59 (d, 3H, CH3, J = 8.0 Hz), 4.03-4.08 (q, 1H, SCH, J = 12.0 Hz), 4.16-4.22(q, 2H, OCH2, J = 16.0 Hz).4.35 (s, 2H, NH2); 13C NMR (CDCl3, 400 MHz) deltaC: 14.0,17.5, 46.0, 61.8, 150.0, 170.9, 171.4; IR (KBr) nu: 3266 (NH2), 1736 (OC O), 1501,1449, 1321, 1094 (C N N C S) cm-1; Anal. calcd for C7H11N3O2S2: C36.04, H 4.75,N 18.01; found C 36.10, H 4.77, N 17.93.To a 50 mL round-bottom flask was added phenoxyalkanoic acid 4 (5 mmol) andSOCl2 (5 mL). The mixture was refluxed for 4 h, and the excess SOCl2 was removedunder vacuum. The crude diacyl chloride was dissolved in CH3CN (5 mL) and addeddropwise through a dropping funnel to themixture of 2-(5-amino-1,3,4-thiadiazol-2-ylthio)propanoate 2 (4.5 mmol) and Et3N (4.2 mL, 30 mmol) in CH3CN (15 mL) on an ice bath.This mixture was vigorously stirred at room temperature for an additional 12 h aftercompletion of the addition. The product was evaporated under reduced pressure washedwith water and brine, dried and recrystallized from ethanol to give the title compounds 6. |
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