1-Methyl-3-( 2-( sulfooxy ) ethyl )-1 H-imidazol-3-ium Chloride as a New and Green Ionic Liquid Catalyst for One-Pot Synthesis of Dihydropyrimidinones under Solvent-Free Condition

First reported for multicomponent reaction involves a threecomponent, one-pot condensation of an aldehyde, αα,ββketoester, and urea under strongly acidic conditions discovered by Biginelli in 1893 [10]. In the past few decades, interest in this reaction has increased dramatically since dihydropyrimidinones have a wide range of biological activities, acting as calcium channel antagonists, anti-hypertensive, anti-bacterial and anti-in�ammatory agents, while also possessing cytotoxic activity [11–17]. In order to improve the efficiency of Biginelli reaction, a variety of catalysts have been reported which of them H4PMo11VO40, [18], Dowex50W [19], H3PW12O40/SiO2 [20], MgBr2 [21], polymersupported 4-aminoformoyldiphenylammonium tri�ate [22], NaHSO4/SiO2 [23], FeCl3 [24], ZrCl4 [25], Cu(OTf)2 [26], Bi(OTf)3 [27], yutterbium tri�ate [28], NH2SO3H [29], 12Molybdopho sphoric acid [30], naturalHEU type zeolite [31], Sr(OTf)2 [32], covalently anchored sulfonic acid onto silica [33], ZrOCl2⋅8H2O [34], silica tri�ate [35], Fe(HSO4)3 [36], TCICA [37], PPh3 [38], CaF2 [39], [bmim]BF4-immobilized Cu(II) acetylacetonate [40], [bmim][FeCl4] [7], ionic liquidsunder ultrasound irradiation [41], andmelamine trisulfonic acid [42] are examples. Ionic liquids (ILs), which have been widely promoted as green solvents, are attracting much attention for applications in many �elds of chemistry and industry due to their chemical and thermal stability, low vapor pressure, and high-ionic-conductivity properties. Over the last few years, ILs have been popularly used as solvents for organic synthesis, catalysis, and also been used as media for extraction processes [43, 44]. But some of the mentioned methods encounter drawbacks such as the requiring expensive reagents, long reaction times, low yields of the products and tedious workup.e advantages of the present procedure are simplicity of operation, short reaction times, inexpensive reagents, green condition, and the high yields of products. We synthesized the bronsted acidic ionic liquid 1-methyl3-(2-(sulfooxy)ethyl)-1H-imidazol-3-ium chloride [45] as an efficient and reusable catalyst for the synthesis of DHPMs derivatives.


General Procedure for the Preparation of DHPMs.
A mixture of an aromatic aldehyde (1 mmol), -dicarbonyl (1 mmol), urea/thiourea (1.5 mmol), and catalyst (50 mg) was �nely mixed together in a test tube at 80 ∘ C for the times reported in (Table 2).During the reaction process, a solid product spontaneously formed.e completion of the reaction was monitored by TLC.e reaction mixture was cooled to room temperature and then cold water (20 mL) was added to the reaction mixture and stirred for 10-15 min.During this time, crystals of the product formed which were collected by �ltration and dried and then recrystallized from ethanol to afford the pure product.e results are summarized in Table 2. e aqueous layer (including BAIL) was separated, and its solvent was evaporated to obtain pure BAIL.e recycled catalyst was used for the next run under identical reaction conditions.

Results and Discussion
e one-pot synthesis of 3,4-dihydropyrimidin-2(1H)-ones and -thiones was achieved by the three-component condensation of aldehydes, dicarbonyl, and urea or thiourea in presence of bronsted acidic ionic liquid is conducted at 80 ∘ C, and the results are summarized in Table 1.e procedure gives products in good yields, short reaction times and avoids the use of organic solvents (handling, cost, safety, pollution) (Table 4).Environmental friendly ionic liquid afforded a valuable alternative to promote a numerous efficient catalytic systems that have already been proposed for the achievement of DHPMs.As long as, the reaction rate and the yields are depending on electron donating/withdrawing effect of the groups on the benzene ring in benzaldehydes.Aryl aldehydes containing electron-donating substituent gave excellent yields of the products in a shorter reaction time.e mechanism of the Biginelli reaction established by Kappe [6] proposed that the key step in this cyclocondensation process should involve the formation of N-acyliminium ion intermediate (Scheme 3).
According at Table 2 the using of thiourea and ethylacetoacetate increased reaction time, and also the using of thiourea reduces the efficiency of Biginelli reaction.iourea stability of negatively charged than urea and low nucleophiles property of thiourea than urea at intermediate State.e catalyst is reusable and can be applied several times without any decrease in the yield of the reaction.As it can be seen from Table 3, (MSEI)Cl as a catalyst afforded the good results with respect to the another ionic liquid catalysts.

Conclusions
In summary, we have developed the use of bronsted acidic ionic liquid 1-methyl-3-(2-(sulfooxy)ethyl)-1H-imidazol-3ium chloride as an inexpensive, easy to handle, noncorrosive and environmentally benign catalyst for the Biginelli reaction from an aldehyde, a -dicarbonyl, and urea or thiourea.e advantages of the present procedure are simplicity of operation, very short reaction times compared with other procedures for the preparation of dihydropyrimidinones derivatives, and the high yields of products.In this reaction the catalyst can be were easily recyclable aer removing starting materials and water (Table 5).

T
1: Temperature and time effect on dihydropyrimidinones synthesis.Formation of DHMP in different solvents and comparison with solvent-free condition.
a s.f.: solvent free condition.