Issue in Honor of Prof. Cheng-Ye Yuan ARKIVOC 2004 (ix) 4-8
The optimized reaction time for the microwave-irradiated solvent-free Knoevenagel condensations of 1a-c with 2 with NH4OAc and silica gel as the catalyst is 2 min and 20 min respectively. In contrast, conventional liquid-phase Knoevenagel reaction took much longer time. For example, ß-alanine-catalyzed reaction of 1a with 2 took 16 hr in refluxing benzene under a water separator,14 while the NH4OAc-catalyzed reaction of 1c with 2 required about 12 hr in refluxing benzene with continuous removal of water.15 The much shorter reaction time under our reaction conditions clearly indicates the advantage of the application of microwave irradiation to the solvent-free reaction. Among the studied ketones, 1a was the most reactive one and afforded arylidenemalononitrile 3a in the highest yield, meanwhile 1b and 1c gave arylidenemalononitriles 3b and 3c in moderate yields due to some side reactions for the former ketone and poor reactivity for the latter ketone.
Different irradiation powers varied between 80 W and 700 W and various catalysts were examined for the Knoevenagel condensation to find the optimal reaction conditions. It was found that the use of very low irradiation power required long reaction times and afforded the condensation products in low yields, while the application of very high irradiation power decreased the product yields due to the occurrence of side reactions even only after short microwave irradiation. Irradiation at 300 W gave the highest yields of products 3a-c. Compared with NH4OAc and silica gel, the use of Na2CO3, K2CO3, NaHCO3, NaOH, NH4Cl and piperidine as the catalyst for the Knoevenagel reactions of 1a-c with 2 was ineffective. It should be noted that in the absence of any catalyst the condensation reaction failed to give the desired arylidenemalononitriles 3a-c.
The Knoevenagel condensations of 1a-c with 2 catalyzed by NH4OAc could take place in the absence of any solvent by conventional thermal heating. The yields and reaction conditions for the neat Knoevenagel condensations are listed in Table 3. It was found that the reaction of 1a with 2 occurred very fast and at lower temperature, reflecting its higher reactivity. The reason for the low yield in the case of 1b is that more by-products were produced in the condensation reaction between 1b and 2.
Table 3. Yield of neat Knoevenagel condensations of 1a-c with 2 catalyzed by NH4OAc under thermal conditions
Product 3a 3b 3c Reaction time 1 hr 1 hr 1 hr Reaction temp 70 °C 100 °C 150 °C Yield 91% 13% 52%
Since the solvent-free Knoevenagel condensation between ketones 1a-c and 2 under microwave irradiation and thermal heating conditions afforded satisfactory results, we became interested in alternative method for the clean synthesis of arylidenemalononitriles. Inspired by the efficient uncatalyzed Knoevenagel condensation of aldehydes with 2 in water10, we investigated the Knoevenagel condensation of ketones 1a-c with 2 in water in the absence of any catalyst. To our delight, the uncatalyzed condensation of 1a-c with 2 indeed occurred in
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