Preparation of nano SSA
The approach described previously with slight additional modification was used for the preparation of nano SiO2-SO3H (SSA)[28]. For this purpose, 1 g of nano SiO2 was sonicated and suspended in dry CH2Cl2 (25 mL) and ClSO3H (1 mL) was added slowly over a period of 15 min at 0 °C. A gas channel tube was connected for leading HCl gas into water during the reaction. In the following, the mixture was stirred at room temperature for 12 h. To complete the preparation of nano SiO2-SO3H, the mixture was filtered, washed with diethyl ether (2×10 mL) and dried at 70°C for 1 h, finally white powder of nano SSA was collected (1.25 g).
Preparation of organic zwitterions
1-benzyl-4-phenyl-1H-1,2,3-triazole and N-methyl imidazole were chosen as aromatic nucleophilic sources for the preparation of organic zwitterions. To reach this goal, n-methyl imidazole and 1-benzyl-4-phenyl-1H-1,2,3-triazole were reacted with 1,4-butane sultone in dry toluene at 75 ̊C for appropriate time (Scheme 1). During the reactions, 4-(1-benzyl-4-phenyl-1H-1,2,3-triazol-3-ium-3-yl)butane-1-sulfonate (TrAzBs) and 4-(1-methyl-1H-imidazol-3-ium-3-yl)butane-1-sulfonate (MImBs) zwitterions were obtained slowly as white precipitates. The synthesis of these organic zwitterions is clean, simple and straightforward, without any side-reaction. Their extraction was done with simple filtration, without the need for further tedious or expensive purification techniques. The prepared zwitterions were characterized using FTIR, 1H and 13C NMR spectroscopies. The 1H NMR spectrum of the prepared MImBs zwitterion is presented in Figure 1.
Preparation of nano SSA supported BAILs (SSA@BAILs)
TrAzBs or MImBs zwitterion was added to nano SSA in ethanol as the reaction media and the reaction mixture was refluxed with stirring for 12 h. Then the resulting slurry was filtered and washed several times with deionized water and dried at 80 °C for 10 h. Finally, SSA@TrAzB-SO3H (CAT-1) and SSA@MImB-SO3H (CAT-2) were obtained as white powders (Scheme 2).
Characterization of the catalysts
FT-IR spectroscopy
Successful preparation of SSA@BAILs could be confirmed by FT-IR spectroscopy. The FT-IR spectra of nano SiO2, nano SSA, MimBs zwitterion and SiO2-SO3@MImB-SO3H (CAT-2) are comparatively depicted in Figure 2. In the FT-IR spectrum of SiO2 the peaks at 3487 and 1640 cm-1 are referred to the hydroxyl groups of SiO2. Nano spherical particles of SiO2 also displays two peaks at 1093 and 820 cm-1 which are ascribed to the asymmetric and symmetric stretching vibration modes of Si-O-Si. Moreover, the peak at 459 cm-1 is attributed to the stretching vibrations of the Si-O band. Nano spherical particles of SSA (SiO2-SO3H) exhibits distinctive absorption peaks at 1170, 1109 and 540 cm-1 referred to asymmetric and symmetric stretching vibrations of S=O group respectively[29]. The stretching broad band of hydroxy groups is observed around 3400 cm-1. The FT-IR spectrum of MImBs zwitterion shows asymmetric stretching absorptions of aromatic and aliphatic C-H at above and below 3000 cm-1. The asymmetric and symmetric stretching vibrations of aromatic C=C are appeared at 1648 and 1461 cm-1 respectively. The stretching mode of C=N is observed at 1569 cm-1. Furthermore, the sulfonate group represents its asymmetric and symmetric stretching vibrations at 1195, 1141 and 594 cm-1 [30]. The FT-IR of the novel CAT-2 shows all characteristic absorption bands of its constituents when is compared individually with each of them and strongly confirms the successful synthesis of the targeted catalyst.
FESEM and EDS
Field-emission scanning electron microscopies (FESEM) of nano SiO2-SO3H@TaAzB-SO3H (CAT-1) is presented in Figure 3. It can be seen from the FESEM image that morphology change is happened in the catalyst structure when is compared with the structure of pure nano SSA. Although nano catalyst has kept its nanostructure, some aggregations are formed for SSA nano particles. The morphology of the prepared organic-inorganic hybrid obviously shows a two-phase structure which organic zwitterion moieties occupied the distances between nearly spherical nano SSA particles.
Energy dispersive spectrometer (EDS) analysis of the prepared CAT-1 is shown in Figure 4. This analysis approves the existence of silicon, oxygen, carbon, nitrogen and sulfur elements as constituent of the introduced nanohybrid which is a further reason for the successful loading of the zwitterion on nano SSA support in the structure of CAT-1.
TEM
The TEM image of CAT-1 is presented in Figure 5. Two distinguishable phases are observed which on the them is spherical and is referred to SSA nano particles and another one is non-spherical that most probably belong to the organic zwitterion moiety. The particle size from FESEM and TEM analysis was calculated to be between 20-30 nm.
TG and DSC
The thermal stability of the synthesized nanomaterials was investigated using TGA. As shown in Figure 6, the TGA curves of nano SiO2 shows 9% weight loss below 200 ℃ which is most possibly attributed to the evaporation of adsorbed water and other organic solvents that were utilized during catalyst synthesis. However, when the temperature is increased, the TGA curve of nano SiO2 shows weight stability without extraordinary weight decreasing up to 600°C. The TGA of CAT-2 catalyst (Figure 7), shows small (5%) weight loss at <200°C which is caused from the loss of the adsorbed moisture. Against nano SiO2, the CAT-2 nano hybrid catalyst shows the major weight loss (20%) between 230°C and 450°C that is ascribed to the decomposition of organic moieties and sulfonic groups that are anchored onto the SiO2 support. This observation indicates that the synthesized CAT-2 is thermally stable up to 230°C which is acceptable thermal stability for using in chemical transformations.
N2 adsorption–desorption determination of catalyst pore structures and surface areas
N2 adsorption–desorption tests were applied to evaluate the surface characteristics of CAT-1 and CAT-2 using the BET and BJH analyses. The prepared catalysts as well as SSA display type-IV isotherms, approving the mesoporous nature of the synthesized catalysts, (Figures 8 and 9). This kind of isotherm demonstrates the adsorption progress. “Ink-bottle” form pores are proved by the existence of H2 hysteresis loops containing adsorption and desorption divisions at relative pressures of 0.8 and 0.4, respectively[31]. From table 1, it can be seen that both catalysts have lower surface pore volumes and surface areas than SSA support. However, mesopore blocking raised from anchoring TrAzBs or MImBs zwitterions to SSA support leads to decrease in the specific surface area[32]. Moreover, the BET data for CAT-1 and CAT-2 represents their lower surface area than SSA. The mean pore diameter and surface area of SSA mesoporous support are 70.32 °A and 430.4 m2 g-1, respectively. By anchoring the organic zwitterions to SSA, the pore diameters growth to 110.64 °A (CAT-1) and 115.21 °A (CAT-2) and surface areas decrease to 95. 5 m2 g-1 (CAT-1) and 133.2 m2 g-1 (CAT-2). Additionally, in the case of SSA support, the pore volume of 0.390 for SSA decreases to 0.066 for CAT-1 and 0.223 for CAT-2. The anchoring effect of large TrAzBs and MImBs moieties on the framework of SSA support is an increased strain on the meso structured which has positive effect on catalytic activity of the catalysts[33]. All these observations verify the successful immobilization of organic zwitterions on SSA support.
Table 1 Obtained data of N2 adsorption measurements of SSA and organic-inorganic nanohybrid catalysts
Sample
|
BET surface
area [m2 g-1]
|
Single desorption
pore volume [cm3 g-1]
|
BJH desorption
average pore diameter [°A]
|
SSA
|
430.4
|
0.390
|
70.32
|
CAT-1
|
95.5
|
0.066
|
110.64
|
CAT-2
|
133.2
|
0.223
|
115.21
|
Catalytic activity of the synthesized nanohybrid catalysts for the preparation of tetrazolopyrimidines
The preparation of biologically active tetrazolopyrimidines, can be accomplished form multicomponent reactions of aldehydes, 5-aminotetrazole, and dimedone or acetoacetate as active methylene compounds the by using an effective catalyst. To assess the catalytic ability of the introduced catalysts, organic-inorganic acidic nanohybrid were used as heterogenous catalysts in the three-component reaction involving benzaldehyde, 5-aminotetrazole and acetoacetate ester as the typical reaction. The progress of the reaction was examined in various solvent even under solvent free condition at different temperatures. The reaction was not progressed without catalyst after prolong time at room temperature even thermal condition (Table 2, entries 1, 2). By using 10 mg of the introduced organic-inorganic nanohybrids as catalyst, the desired tetrazolopyrimidine product was gained which indicated the catalytic role of the prepared catalysts (entries 3-10). However, the most satisfied isolated yields were gained when the reaction was performed under solvent free condition (entries 3-5).
The best condition for the typical reaction was achieved by using 20 mg of CAT-1 and CAT-2 nanohybrids as catalyst under solvent free condition at 120 ℃. Any further improvement in the reaction times and yield of the product was not detected by using larger amount of the catalysts (entries 13, 14).
Table 2 Synthesis of tetrazolopyrimidine in the presence of introduced organic-inorganic hybrids under different reaction condition
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Byh6OeVq1apevxg5IWOM6Q72YEbcbg2DEpYfl980M4/KVydBV3oX2oHZmNmegf79e1DeOOcex6cxf2XNyDjq92oOn5JuxL34ff7PoNVn1sFRLrEoN2ge3gCr7a2iQw0ly86P6t7CsvvACcO+f749KcuruB5GTg2jXAYpFUifBw2dffL1dxgGwrL5fXXLsm7/FVcvzoqPSdlZXyvKNDRsBWrJCAKy5OFkPYvFluiAXkuiAx0XvMbrVKkOZZE6y3N/CDN8d9B94ceRM7frIDf3fy7/zShvt/uY9R2ygyGzOR2ZgJ26QN9/5yzy9tMVJcXBzy8vJw4MABOFz+uLQ6XFoOVXFxMa5cuTKV42W1WnHlyhUUFxfP6zzaSNfvHwz/LrWOWP6DSsVvvfXW1DYtH8w1yT+gbd7sLNxt8Ifcc8agowN4EKcDAKIiotD0fBMqNlVge/t27Hpzl8+XBZv88yQOXzmMzMZMbPj4BnQVd+GZTz0ztX/dynWoebYGrS+04uDlg8g7l4dR26hP2+B3KpjcuKHUnTvyu9WqVFSUfueKipJzkCGsVqUKCpQymZTq6/P+mhs3lMrKksfAgPu+vj6lMjKUys2V1y3GnTtKlZcrlZCgVGvr9P1jY0r19Mhjpvbl5ko7XP8NZrMsCur5Pm2x0EB098O76tAvDqmY2hh14NIBpZRSVrtVZZ7OVEknkpTlhsWQdjT9pkl9suaT6oX/eEHd/fCuuvvhXfX8uefVupp1quk3TYa0wZ/sdrtKT09XsbGxymw2q6qqKhUbG6tiY2PV0NCQUkqpoaEhBWDqNdr+sbExpZRSPT09CoAym81uz/Py8qbOAWDqNbGxsW77lVJen8fGxqqqqqpp+7U2A1BVVVUqLy9PAVAWi2XW4wXE11lPj3yozWalhobk9/R0pfLyvHcCcx3L8/VaJ/Tg/52n+nrpvw4dUuru3fmdpv5qvUowJ6hDvzik7n44zzfNonWgVSWYE1T5z8vVnbt3fPYe+z276hnrUT1jPcp+zz5t/9Afhqb2ez68vV5vAfDX6kVVlfyxuv7hDQ3JtgcfZnX3rlJdXfq1YedO+UsmXd29q1RFhVIxMUo1zfO7sqNDOpjSUmcsrmltlX3l5dP3zWYxndZMLBalkpLkp1LBF3zN1VH2WftUxukMlducq27cWWQkPIeuW13KdNKkCn5UoKz26RdJVrtVFfyoQGWczlB91hmi+SBisViU2WxWZrPZLYjR2O121d7ersxms2pvb1d2u/PLaGxsTJnNZtXz4A9Ue97e3u72/jNnzqgzZ86ooaGhafs9n2uvOXPmjNf9rm0+c+bMVCA40/G0f9uy5xp8KaVUWZnzg77Q4Mvbe7TOxOO/hdbn7Ny5uDGDO3fvqPKfl6sEc4LqGOlY+AGUUgO3B5b0udcu6BLMCar+qvt3b9XbVQqVUOk/SFd5zXkKlVBVb1e5BVXa9rzmvGmPoT8MuR3PiGAsALt25bxKSE93btP+qF2uhnRlscgQBummqUmCroqKxQU8NTUSMHnGyHfvShCVkDB3QLfUTms+giX4Grg9oLLOZs27c9WCtApLhU+uqJVyBlWmkybVdWvuiy/LDYtKOpGkdv50p9cgjcinPIOvsbGZg6+iIhkqb2jwfqWovSc21rnNS/DV0DB9tH2xbty5obLOZqmss1lq4PbA3G9QEriVXihVCeYEn4x4W+1WtfOnO5XppEnduXtnKvBqH3QJ7v8wpFAJVfafZVPbtOBrNpYbFhV7PFb1jC0gCF6kAOraXWjBF6CUdvVjdPClFKceddLXJ9OLBQVL/89rtUrg5DrS5LpPm8r0HCTV9vmq05qN1l+eOeOcSdD+nAMh+HLtXBd6VXz3w7uqwlKhYmpjljQNuNTjuE6teDL/2qxij8cqVEKhEqq4vXjalbLWsXt7GNGRU4DwDL6UcnYA3q7AWlslCIuMlEDMNd/BNWjTvgdnGPnytY6RDpVgTlClF0pnnTqs6apRMbUxqqarxudtGLg9oMbsY1OjWZ7K/rNMoRJTn9W5gq8x+5hK/0G6QiXUmWtn1Jjd+9StrwRA1+6Fa/AVG6uU3e6f4ItTjz7lGij5esZ4tpyvri5nsDc6uvBpzqXS+kst9UN7BELw5avOdaEjVq58NYLmOrWiXaFrHfiZazI9Zr9nn9apKzW/q+qesR6vXxIUQrT0GNcpVrvd+aEfGpr5va2tMpyv0ToNraOw2w0LvjQzff7nG5wtleWGRaESyvzr6f9ez33aZ9Qz30v7HLcPtk9dMKX/IN1tJE0Py7xrn4H2zeT6h2ZE8NXVJdncmhCdevSWn7FUd+4otWqV/rHsbDlfTU1KffSjSr366tLzuhYiEKcdLTcsunSuWq5WUVvRnNOAeuWODdweUBWWCtUz1jNt6kIpCcBQCRV73DndM5/gS+vYiXxC+75z/R40OPhSyjnynXQiSZ27fk7lNucuaFpyKcy/Ns8YfGmfX8/gyzPfq+rtqqn3uAZoegvsUhOFhfKzpETWxdJTba3cn1tT49xmMgG//CWwd6+zxsF89fYCYWHu63sBUqsgLMx5+3FdnftzTViYPPxgrqVCFsNmAx55BNi506eHnSY3V+qCeasBVlAgi2Hv3OksXxFM6urqpqqSL9aobRR55/Jw8PJBtL7QippnaxAZHumjFgKmx03oKu7CpnWbkNmYicNXDk+ruK3VBtrevh0VmyrQ+kIrYiJjfNaGhEcTUJlRie73ugEABevdV02PeDgCZZ8rw8gHI/OuG5Z/Ln/q97CDYei1BngNEVqcSR2qxxcWArGx8j04anw5hsjwSNQ8W4OGnAYUtRchJz4HHV/tQMKjCXO/eYlWfnThdTxbXmhxe+zfuF+Hls0tsIOviAigvV1+97KemE/YbFIQ5eZN94Iog4Py7f3P/wysXi2V6v76r+W1tbVSdGo+RkYkwFrment7UVdXh7oHbb1+/frUc6sOVZorK/VbtNqzBpieq1EtJ0sJmm2TNuy7tA9bfrgFhRsKYSm06Nq5FiUVoau4CxP3JpD8ejLaBtum1Qbq29GHjJilVVOfzaV3L824Twv27PfdL/rCDoa5PbSgq+WFlqnXqAqFlOggqVe1zNmW0zq8tbXy8LWICKmWDzh/Gki7OEqKSsLH/9vHdf1Mekp8LBEAMDE5vZDwwO0BAMDaR+a30oPRHvJ3A5YsO1ui/pER3x+7sxPYtUtGu1yLtZ44Abz+OtDU5AzGysvlqqazU4q7bt8ulTWzsoBNm+RnVJT385SUyNULV7OfcvOm/hdxUVFAfb2+5/C33t5edHd3Tz3XgmZAillqS8rMZtwxjszGTBRuKETfjj6EP2TMsGBkeCQObT6EHSk78NKFl7DzpzuxPXk7uoq7fDra5kuqQvm7CfTA+Pg41q1bh0cffRQ5OTnIzs5Glh5Ft+eju1sGCjo69Dm+ttTGlSv6HH8GbYNtuPi7i6j/on860pToFMSuisWBtw7gpc++hIiHnd+h37r8LQDA0088PdPb/Srwgy9AgiBfr3BcWQlcvizDI1rQZLNJMBYZKevXeM5NhYdLkKV9wMfHZTry8mWZsoyMBHbsAEpLne/RAsfjx4H9/hn+nI+UlJSp6tIlJSUzLopLC7d2rRS7XrHCfftyWbouKiLKrwFPTGQMzhecx/uO9/HxiI8bdt7Nn9qM1sFWr/u0atsrHl7hdT/5X1RUFJ555hn87Gc/Q319PZqamuBwOLBx40ZkZ2fDZDLBZDIZ05hjx+RKT/vO2LNHLspdV2RZqtpa338PzsE2afPrQtwA8NP/8VPEm+Ox5Ydb8O3MbwMAjv/qOEY+GIGl0OIWkAHwOuUfvzoeEQ9HIHVNKloHWzFwewArHl6BuNVx017rK8ERfKWkOJdqWKrJSSAzE3j2WQm8NN3dEni9+qokB81HVBRQVCQPQKYqPRfkfvll+WAeOCCjZTMx+EM1G7PZPO9Fe2lu2dny8NTSMn3bQvkqaF4OI01GBl6A5J8BQPP1ZrdpQsd9B6rfqUbsqlhdO+eF6O/vx549e/zdjGXnvffew0c+8hF8+OGHU1OQFosFlgd9e0NDw9Si3Yt2/rzkLuTnA1/7mnP7g2WS0NIiAwSatjYZ1nfNH16MvDz374WUFFlk9ne/kyu6EBG3Og5j/zCGloEWHP/VcQBA6ppU1H2xDtERzpH91DXy36rq7appxzj8zGHErY7DS599Ce/eeRctAy14/JHH9f18657Sr4ehoZmXVXC9VXdgQGoXLKSUuVLTaxEcOiR3NS52XRpvXOu9WCzye3Hx9GUmAvFWuEW4cUPKO2iKiqQ4oNFiYnz7v3k50eMu1WDnWWpizD6mituLp90RNZ+7HbVaYUoZU0GblMrMzFQA1Mc+9jH1yCOPqEceeUQ999xzqr6+Xg14rkG2WK51ulwr8Xvro+/elbo2C/1OWqYa+hpUUVvR1POY2hjdVq0INoE58uV5hyAgt6l55q8kJACf/ayMZNXXy92JgDPB3XUEoLdXRrdMJudqyDYbsHUrkJQkc/V63QKXkSFXMadOLe79Dgfw9a87R/7a270PpVBI4zTxwh35whHERMbg9d7Xsa11GwCgOLkYQyVDXq+Kww5OvwO558UepESnoPq/VyOnOQdhB8NmfD/5zujoKK5evYrnnnsOX/7yl5GRkYGEBJ3vwDt6FDhyZOb94eGSskIhLzCDr4UoKpLgZtcuGfqNjJQEd0DqDWjDxN3dst1sdgZfeXkyzWhEkuaBA4ufNj1+HLh+XcpttLUBOTlyzUVES7b7qd3Y/dTsgavr3YwzyY7PZkK+gWJiYmDXuwSRp+pq4Jvf9D5AoCebTb6vXFNlaFkL7FIT8xUTIyNXkR55K9u2yajRTCwWYwIvwDlfvxj79wPDw3K35MT0W26JiEhnZrP8LC83/tw2m19qfNHihUbwNZvGRn+3wOmVV5b2/vPnZfSuanpCIRER6chkct745VkUm8hD6AZfeXnOqsA6FAmdU0qKTA265uFERzuXStWmPnfvdn+u0V6nOX9ephvz8oCXXtK//URE5E7LJ9661b/toGUvdIMvwFkN+OhR/7ZjqYaHJfAqLpbbmlmslYjIeNHRkj6iR9FvCiqhHXxlZ8tIUXU1cGnmpUSWvX/7N/l56pRf13wkIgp5FRX+bgEFgNAOvgC5yxDwTYFWfzlyxDkN6TkdSURExomIcCbfE82AwVdKikzXERERLVR+PtDTA8THO7cVFsq2nh7/tYuWNQZfAPDtb/u7BUREFIiio+Ui3jXXNiJCtnneKEX0QPAXWfXGbHZf+yo6WqrC37rlrIJPfhUePr0smx5qa+U8S13ejYhoRrW1slJKRoZvjjc+LgW1s7KkjiUFnNAMvrwts8LleJaVmhr9VnMCgAsXgD17pO9i4EVEuiooALZskWLfUVGLO4YWcJ07BwwOArm5clw/Sng0AeOOcb+2IVCFZvBFy054uCw2oC2vqVfgNTgoQRcg91i4LvXW3y9t0DPoI6IQFBUlV5Tbt0sANl+joxJwNTZK8JWbK3dT+moEbYlMj5tgepyzRYvBnC9aFqKigB//WAKjXbukn/Elmw3Yt09qH778svR/WuBls8k5t2+XNiz2wpSIaEYZGZLy0tsrtRldDQ/Ldm25u9OngeRkIDMTuHkTaGiQYuD19e6B1/g4cOKELJU3Pg4cPmzcv8fDiZ4TGHeM419/+a+wTdr81o5AweCLlo3Pfx7o6gI2bJA+5/BhYHJy6cc9cQJIS5N11Lu63JfrrK2VPm7DBqCvT9pARKQLmw1ITZU7I13XFS4vl+1DQ85tDQ3AjRsyYpaU5Nw+OiodV1qadF7XrslNY1arrO2bmCh5FQbpHO1E8uvJuPb+NVj/wYq41XFIO5WGEz0nDGtDIGLwRcvOzp0SJE1MSN/S1ra443R2Ovsmi0X6N21K8cIF6aNu3pSga+dO37WfiGhOBw/OvK+oyHvA5ToaVlPjPhoWGQkcOiT5FMeOSW+sEHcAAAQwSURBVI7Z4KBuzR+1jSLvXB4OXj6IhpwG1H+xHpHhkSg1lcJSaMG1968h+fVkdI526taGQBamFCty0vI1OipTkTab9DGuOVrzeY/nRaNrzldNzfyOR0TkE729MsKlGRuTu+3z8yVo6ulxlqdwzfey2STfq7DQvUObzYULkmuRlQW8+qrPbh+f/PMkDl85jHO/PYdDmw8hNyF3xtf2j/djz8U9iAyPRM2zNYiJ5J2ZGo580bIWEyN9UkWFrASlBVXeTE5KX7Nli/RRFouzn7LZ5L15edNzvoiIDJWXJz+93XmvOXbMme/lbfpxLllZMoWwcqVMUZ7wmAYcHpagb+9e9+3f+Y5s98xLA9B8vRmJdYkAgL4dfbMGXgCQFJUES6EFhRsKseWHW1DZWYnJP/sglyQIMPiigJCRAQwMAOvWych7be301/T3Sz/T1ycXiRpttH7dOjmGa84XEZHhNm+WAKy1VUbDvKmpWXjA5Sk8XPItLBbJv0hOlo4SAOx2OX91teRoaHp6ZLvdPrWpf7wfaafS0D7Ujq7iLlRmVCL8ofnfFp6bkIu+HX0AgMS6RDRfb178vylIMPiigFJaKsHVzZvT80pNJve8Li3nS8vrKi31T5uJiKbR7kw0omOKipK8jYYGmc709OKLs7792K+OoebZGjQ934SoiMXdDh7+UDgqMyrRVdyF9qF2pJ1KQ/d73Ys6VjBgnS8KOJGRckG4Y4dMJb7+ujzXCj275nw1NCztwpGISBdxcUBZmYw8GSUpyXuHODICnD0LfO1rXt/WkNPgsyZERUSh6fkmdL/XjT0X9yAmMgY1z9YsOqgLVBz5ooCVkCC5W4WFkue1d688vOV8EREtO6+84u8WAFVV8nPbNvfyFzozPW5CV3EXcuJzkNmYicNXDodUPhiDLwp4ubkyrfinP8nDM+eLiGhZio6Wwqv+tHKlsw2NjYafvmB9AbqKuzBxbwLJryejf7zf8Db4A6cdKSiEhwPf/76/W0FENIsVKyTRfu1a57bCQuDSJed+f9i9W+6uLCkBYmMNP31keCQObT6EHSk7QqY6PoMvIiIiI8TFAS0t7tsiIqZv84fqaiAnR/K//CSU6oBx2pGIiCjUZWc764+R7hh8EREREXDggL9bEDK4vBAREVGocThkIe81ayTxX6MVfY2PlylR0gVHvoiIiELN2JiUmbh61X37xYuyfWzMP+0KEQy+iIiIQo22vNCtW+7bvSwvRL7H4IuIiIjIQAy+iIiIiAzEOl9ERESh6tgxZ5FXQKYcSXcMvoiIiEJVTg5QUOB8fvs2cOWK/9oTIhh8ERERhaqYGCAlxfn8scf815YQwpwvIiIiIgMx+CIiIiIyEIMvIiIiIgNxeSEiIqJQM9PyQsPDUmCVywvpisEXERERkYE47UhERERkIAZfRERERAb6/wG72jfHQuLsAAAAAElFTkSuQmCC)
Entry
|
Catalyst (mg)
|
Solvent
|
T ( ̊C)
|
Time(min)
|
Yield (%)a
|
1
|
-
|
-
|
120
|
240
|
-
|
2
|
-
|
-
|
120
|
240
|
-
|
3
|
CAT-1 (10)
|
-
|
80
|
40
|
40
|
4
|
CAT-1 (10)
|
-
|
120
|
40
|
75
|
5
|
CAT-2 (10)
|
-
|
120
|
40
|
79
|
6
|
CAT-1 (10)
|
EtOH
|
78
|
40
|
30
|
7
|
CAT-1 (10)
|
H2O
|
100
|
40
|
40
|
8
|
CAT-2 (10)
|
THF
|
60
|
40
|
35
|
9
|
CAT-1 (10)
|
CH3CN
|
80
|
40
|
45
|
10
|
CAT-2 (10)
|
DMF
|
120
|
40
|
66
|
11
|
CAT-1 (20)
|
-
|
120
|
20
|
90
|
12
|
CAT-2 (20)
|
-
|
120
|
20
|
89
|
13
|
CAT-1 (30)
|
-
|
120
|
20
|
88
|
14
|
CAT-2 (30)
|
-
|
120
|
20
|
90
|
a Isolated yield
After finding the optimized reaction condition, to show the generality and effectiveness of the presented method in a wide range, the protocol was explored with different types of aromatic aldehyde (A), dimedone (B) or acetoacetate ester (C) and 5-aminotetrazole under determined reaction condition to provide corresponding methyl-7-aryl-4,7-
dihydrotetrazolo[1,5-a]pyrimidine-6-carboxylate (D) and 6,6-dimethyl-9-aryl-5,6,7,9-tetrahydrotetrazolo[5,1-b]quinazolin-8(4H)-one (E) products. The results are tabulated in Table 3. Generally, the target products (E) using dimedone as active methylene reagent are obtained during shorter times than products (D) which are prepared using acetoacetate ester (table 3 and scheme 3). Under optimized reaction condition, various aromatic aldehydes with different electron-releasing or electron-withdrawing groups were successfully reacted. It was detected that aldehydes bearing electron-withdrawing groups gave the corresponding tetrazolopyrimidines during shorter reaction times than their electron-donating aldehyde counterparts.
Table 3 Preparation of tetrazolopyrimidines under optimized condition using CAT-1 and CAT-2 catalysts
Product
|
A
|
Active methylene
|
T (min)
|
Yield (%)a
|
Catalyst
|
Mp (̊C)
|
D1
|
C6H5CHO
|
B
|
20
|
90
|
CAT-1
|
202-204[23]
|
D1
|
C6H5CHO
|
B
|
20
|
89
|
CAT-2
|
202-204[23]
|
D2
|
4-MeOC6H4CHO
|
B
|
30
|
88
|
CAT-1
|
194-196[3]
|
D2
|
4-MeOC6H4CHO
|
B
|
30
|
91
|
CAT-2
|
194-196[3]
|
D3
|
2,4-DiCl-C6H3CHO
|
B
|
20
|
90
|
CAT-1
|
252-255[3]
|
D3
|
2,4-DiCl-C6H3CHO
|
B
|
20
|
87
|
CAT-2
|
252-255[3]
|
D4
|
2-NO2C6H4CHO
|
B
|
20
|
89
|
CAT-1
|
241-243[3]
|
D4
|
2-NO2C6H4CHO
|
B
|
20
|
90
|
CAT-2
|
241-243[3]
|
E1
|
C6H5CHO
|
C
|
15
|
89
|
CAT-1
|
273-275[23]
|
E1
|
C6H5CHO
|
C
|
15
|
88
|
CAT-2
|
270-273[23]
|
E2
|
4-MeOC6H4CHO
|
C
|
25
|
90
|
CAT-1
|
224-226[3]
|
E2
|
4-MeOC6H4CHO
|
C
|
25
|
92
|
CAT-2
|
224-226[3]
|
E3
|
2-NO2C6H4CHO
|
C
|
15
|
88
|
CAT-1
|
262-264[23]
|
E3
|
2-NO2C6H4CHO
|
C
|
15
|
87
|
CAT-2
|
262-264[23]
|
E4
|
2,4-DiCl-C6H3CHO
|
C
|
20
|
86
|
CAT-1
|
>270 [34]
|
E4
|
2,4-DiCl-C6H3CHO
|
C
|
20
|
89
|
CAT-2
|
>270 [34]
|
E5
|
4-BrC6H4CHO
|
C
|
15
|
86
|
CAT-1
|
248-250[23]
|
E5
|
4-BrC6H4CHO
|
C
|
15
|
85
|
CAT-2
|
248-250[23]
|
a Isolated Yield
Recycling study of the introduced catalysts
The reusability of the catalyst is an important benefit particularly for commercial applications. To investigate the catalytic stability of the presented nano heterogeneous acidic hybrid catalysts over recycling process, the typical reaction from table 1 was selected. The reactions were performed in the presence of optimized amount (20 mg) of CAT-1 or CAT-2 at 12 ̊ C under solvent free condition. Upon completion of the reaction as monitored by TLC, 10 ml of hot EtOH was added and the mixture was stirred for 5 min. Afterward, then the reaction mixture was filtered and the filtrate recovered catalyst was washed with acetone and dried at 80 ̊C for using in the next 4 consecutive tests. Simple filtration and washing with acetone make the catalyst ready for repeating runs and it can be observed that the yield deference between the first and fifth runs for both catalysts is negligible demonstrating high catalytic stability of the presented nano hybrid catalysts.
A recommended and probable mechanism to reveal the catalytic activity of the presented nano hybrid catalysts for the preparation of tetrazolopyrimidines (D and E) is described (scheme 4). Initially, aromatic aldehyde (A) is activated by the acidic nano hybrid, and in the following, an aldol condensation type reaction is occurred among activated aldehyde and enolic form of activated methylene compound (B or C). Subsequently, 5-aminotetrazole makes a Michel type addition to the activated Michel acceptor under catalytic activation by nano hybrid catalyst afterward cyclization and then dehydration give the desired tetrazolopyrimidines (D or E).