Solvent-Free Synthesis of 5-Alkenyl-2 , 2-butylidene-1 , 3-dioxane-4 , 6-diones under Ultrasonic Irradiation with o-Phthalimide-N-Sulfonic Acid as Catalyst

5-Alkenyl-2,2-butylidene-1,3-dioxane-4,6-diones were synthesized by the Knoevenagel condensation reaction of aromatic aldehydes with 2,2-butylidene-1,3-dioxane-4,6-dione using o-phthalimide-N-sulfonic acid as catalyst, without solvent under ultrasonic irradiation. The present method has some notable advantages such as mild reaction conditions, short reaction times, less catalyst dosage and high yields with the green aspects by avoiding toxic catalysts and solvents. Further, the catalyst can be reused for five times without any noticeable decrease in the catalytic activity.

More recently, lots of methods for the synthesis of 5alkenyl-1,3-dioxane-4,6-diones have been reported in the literature.Generally, they were synthesized by the Knoevenagel condensation reaction of 1,3-dioxane-4,6diones and aromatic aldehydes in the presence of bases such as pyridine [9,10], piperidine/glacial acetic acid [11,12], or hexamethyldisilazane [13] and Lewis acids, such as anhydrous zinc chloride [14], TiCl 4 /pyridine [15] and CePW 12 O 40 [16].However, many of these methodologies have not been entirely satisfactory, owing to such drawbacks as low yields, long reaction time, more catalyst dosage, environmentally unfavorable solvents, emerging the problems of tedious work-up and effluent pollution.Uncatalyzed reaction was also reported in the literature using DMF or DMSO as solvent, which is toxic, teratogenic and suspected carcinogen.Those methods gave mixtures of unsaturated and Michael addition products [17].Thus, a mild, efficient, and environmentally friendly method using economical catalyst is desirable.
Recently, the solvent-free condition and the use of heterogeneous catalysts have emerged as an eco-friendly alternative of great importance within organic synthesis, as they reduce environmental pollution and bring down handling costs due to simplification of work-up technique [18].

Results and Discussion
To optimize the reaction conditions, a selected model reaction was carried out with 2,2-butylidene-1,3-dioxane-4,6-dione 1 (0.01 mol, 1.7 g), benzaldehyde 2 (0.01 mol) and different sets of reaction conditions.The results are summarized in Table 1.The results clearly show that the catalyst is essential, the catalytic activity of o-phthalimide-N-sulfonic acid (OPNSA) is high, giving 3a in high yield in a short reaction time.Using OPNSA as the catalyst, we evaluated the reaction in various solvents and under solvent-free conditions.The product yield in a polar solvent was higher than the one in non-polar solvent, but under solvent-free conditions the highest yield was obtained (Table 1, Entries 1-8).The catalyst (OPNSA) plays a crucial role in the success of the reaction in terms of the yields.The presence of 0 mol% OPNSA gave the product 3a in quantitative yield (35%) at 60˚C.Increasing the catalyst to 1, 3, and 5 mol% results in improved reaction yields to 76%, 89% and 87% respectively (Table 1, Entries 8-11).Use of just 3 mol% OPNSA is sufficient to push the reaction forward.Higher amounts of the catalyst did not improve the results to a great extent.Thus, 3 mol% OPNSA was chosen as a quantitative catalyst for these reactions.
To find the optimum reaction time, the reaction was carried out in the presence of OPNSA for 20, 30, 40 and 60 minutes, resulting in the isolation of 3a in 90%, 91%, 90% and 89% yield, respectively.Similarly, the optimum reaction temperature was 30˚C.In addition, it must be pointed out that all of these reactions were carried out without solvent under ultrasonic irradiation.Under mechanical agitation conditions the product yield for 68% and with ultrasonic irradiation the product yield for 91%, which indicated the ultrasonic radiation to promote the reaction effectively (Table 1, Entries 16, 17).The best results was obtained when was conducted at 30˚C, for 30 minutes in the presence of 3 mol% OPNSA (Table 1

, Entry 16).
To determine the generality of this method, the scope of the reaction was investigated using a number of aromatic aldehydes under the optimized reaction conditions.The results are presented in Table 2.The results show benzaldehyde and aromatic aldehydes with electron with drawing groups (-Cl, -NO 2 , -F) and electron-donating groups (-OCH 3 , -OH, -N(CH 3 ) 2 ) have all provided high yields of the products.
The principle advantages of the use of o-phthalimide-N-sulfonic acid (OPNSA) in organic transformations are their reusability.The catalyst was readily recovered from  the reaction mixture using the procedure outlined in the experimental section.The separated catalyst was washed with 2-methoxy-2-methylpropane (10 mL), it was directly used in a similar reaction.From Table 3 we found that the catalyst could be used at least five times with only a slight reduction in activity (91% yield for first use, 91% for second use, 90% for third use, 89% for fourth time and 86% for fifth time).A plausible mechanism for the formation of the 5-alkenyl-2,2-butylidene-1,3-dioxane-4,6-diones products using o-phthalimide-N-sulfonic acid (OPNSA) as a catalyst has been depicted in Scheme 2.

Conclusion
The catalyst of o-phthalimide-N-sulfonic acid (OPNSA), showed high catalytic activity in the synthesis of 5-alkenyl-2,2-butylidene-1,3-dioxane-4,6-diones synthesized by the Knoevenagel condensation reaction of aromatic aldehydes with 2,2-butylidene-1,3-dioxane-4,6-dione without solvent under ultrasonic irradiation.This procedure offers several advantages over the other techniques available in the literature, including much shorter reaction times, higher yields, milder conditions, and the absence of any hazardous organic solvents, which makes it a useful and attractive protocol for the synthesis of these compounds.Furthermore, the catalyst could be recycled after a simple work-up, and used at least five times without significant reduction in its catalytic activity.

Preparation of o-Phthalimide-N-Sulfonic Acid (OPNSA)
A solution of chlorosulfonic acid (11.6 g, 0.1 mol) in CH 2 Cl 2 (20 ml) was added to o-Phthalimide (14.7 g, 0.1 mol) in CH 2 Cl 2 (20 ml) solution at 0˚C.Then the mixture was stirred at room temperature for 24 h.The solvent was evaporated at reduced pressure and the remaining solid was washed with 2-methoxy-2-methylpropane (3 × 10 mL) and filtered to give the desired product as a yellow solid material in 97% yield.1), the reaction mixture was diluted with 20 mL ethanol.The catalyst was collected from the filtrate, which was concentrated on reduced pressure.After the remaining catalyst was washed with 2-methoxy-2-methylpropane (10 mL), it was directly used for the next reaction.The crude solid product was filtered and then purified by recrytallization from ethanol to afford the pure product 3 (3a-3h).The physical data (mp, IR, NMR) of known compounds were identical to the corresponding literature data.

4. 1 .
Reagents and InstrumentsAll chemicals were purchased from Aladdin, Aldrich and Fluka Chemical Companies and without further purification.The melting points of the various compounds were measured by XT-4 digital micro melting point instrument and are uncorrected.Reaction monitoring was accompanied by TLC using silica gelSIL G/UV 254 plates.KQ-250E-machine ultrasonic instrument is made in Kunshan Co., LTD.IR spectra were taken on a Nicolet-360 FT-IR spectrometer by incorporating samples in KBr disks. 1 HNMR spectra were recorded with Bruker Avance 400 MHz spectrometer with CDCl 3 as the solvent and TMS as the internal standard.The 13 CNMR data were collected on Bruker Avance 100 MHz instrument with CDCl 3 as the solvent and TMS as the internal standard.

Table 3 . The recycling of OPNSA in synthesis of 3a under the reaction optimized conditions.
a Isolated yields.