Acetylacetone 2a

We began our research by treating chalcone 1a (??) with acetylacetone 2a (??) in the presence of morpholine as the base (??) in CH3CN at 80 ºC for 12 h. The reaction was monitored by TLC until the disappearance of the starting material and the formation of 1-(5-benzoyl-2-methyl-4-phenyl-2,3-dihydrofuran-3-yl)ethanone 3a. this reaction mixture, containing the 2,3-dihydrofuran 3a generated in situ, was treated with sulfur element (??) in the presence of base of morpholine (??) at 80°C and the desired thiophene 4a was obtained in ?? % yield, after 5 h (Table 1). In order to find out the best reaction conditions for the synthesis of thiophene 4a, the reaction of 1a (??mmol) and 2a (?? mmol) have been screened by various parameters such as type and amount of base, reaction solvents and reaction temperatur.
So, we were investigated effect of different of bases on the improvement reaction.
We were employed (used from) other organic or inorganic bases such as piperidine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), NEt3, KHCO3, NaHCO3, K2CO3 and Na2CO3, in instead of morpholine for the first step of reaction, followed by ??equivalent of morpholine in acetonitrile (entries 2-8). We observed the best yield of thiophene 4a was obtained, when NEt3 used as the base of the first step of reaction (entry 4). Thus, we chose NEt3 as the suitable base for the first step of reaction (for this step).
We then attempted to increase (improve) the yield of thiophene 4a by using different base including piperidine, NEt3, KHCO3, NaHCO3, K2CO3 and Na2CO3 for the second step reaction and among them NEt3 was found to be the most effective base (entries 9–14). After having identified NEt3 as the best base for the both step, we examined several different solvents like EtOH, MeOH, acetone, PEG-300 and H2O the results revealed that CH3CN is the optimal solvent for this reaction (entries 10 and 15–19). Also, we evaluated the amount of NEt3 required. The results showed that ?? mol % NEt3 effective in promoting this reaction; the addition of larger amounts of the base did not improve the yields (entries 20–22). Without Base of NEt3 in the second step, TLC analysis indicated formation of thiophene 4a in the low yield (entry 23). Finally, the one-pot reaction between 1a, 2a and element sulfur (all 1 mmol) under the optimum conditions:, ?? mol% Et3N, ?? mol% NEt3, in CH3CN at 80 °C for 17 hours provided 3a in ??% yield (entry 21).

After determining the optimal reaction conditions, we then tested the scope of the reaction for the construction (synthesis) of various polysubstituted thiophenes. The results are summarized in Table 1. First, differently substituted chalcones 1 were reacted with acetylacetone/ethyl acetoacetate 2 under the optimal conditions. Pleasingly, the results indicated that a range of chalcones with electron-neutral (H), electron-donating (3-Me, 4-Me, 3-OMe, 4-Ph), and halogen-substituted (4-Cl) groups attached to the (on the) aryl ring reacted smoothly with the acetylacetone/ethyl acetoacetate 2 to generate the polysubstituted thiophenes (3a-e and 3g-n) in good to excellent yields. Notably, 2-furyl-substituted chalcone reacted with acetylacetone under the optimal conditions, and the corresponding products 3f was obtained in ??% yields. In addition, we investigated the reaction between cyclic 1,3-diketones such as 1,3-cyclohexanedione and dimedone in instead of aliphatic chain 1,3-diketone with various substituted chalcones under these conditions that led to formation the desired thiophenes??-?? in ??–?? yields.
The result encouraged us to carry out the reaction of various chalcones with 4-hydroxycoumarin as the another 1,3-dicarbonyl compound (Table 4). Accordingly, 4-hydroxycoumarin 2 reacted with chalcones including electron-donating groups (such as methyl, methoxy, isopropyl, and phenyl groups) or electron-withdrawing groups (such as chloro group) on the benzenes ring under optimized conditions and afforded the desired products 3aa–ak in satisfactory yields.