Synthesis of aspirin catalyzed by supramolecular compound based on Keggin-Type phosphomolybates with flexible 1,3-bis(4-pyridyl)propane

• Preparing an unreported supramolecular compound as catalyst in synthesis of aspirin; • Exploring PMo 12 O 40 -Bpp catalyzing activities in optimal conditions; • Indicating catalytic properties and recycle of PMo 12 O 40 -Bpp; • Providing inspiration to supramolecular compounds in pharmaceutical esterification; • Charactering structures and exploring weak interactions of hydrogen bonds. With an aim to catalyze the synthesis of aspirin in a green approach, an unreported supramolecular compound [H 3 (C 13 H 14 N 2 ) 2 ][PMo 12 O 40 ] (PMo 12 O 40 -Bpp) based on Keggin-type has been regarded as catalyst in synthesis of aspirin, which is prepared with flexible 1,3-bis(4-pyridyl)propane (C 13 H 14 N 2 , Bpp) and characterized structurally. Structural analysis of X-ray single crystal diffraction reveals that charge-assisted hydrogen bonds (CAHBs) N + -H … O - is formed between N + of protonated Bpp molecule in PMo 12 O 40 -Bpp as hydrogen bond donor and molybdenum phosphate oxide cluster anion [PMo 12 O 40 ] 3- , and 3D supramolecular framework with porous is connected by intermolecular hydrogen bonds C9-H9 … O3, C11- H 11 … O3 and C6-H6 … O7 alternatively. When reactants of pharmaceutical esterification are salicylic acid and acetic anhydride, by screening dose of catalyst PMo 12 O 40 -Bpp, temperature and reaction time, the optimal conditions are determined as follows: 0.15 g PMo 12 O 40 -Bpp (mass fraction 5%), 90 °C and 55 min. Under these conditions, the yield of aspirin, the conversion rate of salycilic acid and the selectivity of catalyst can reach up to 69.24%, 98.02% and 70.64%, which indicating that catalytic activity is similar to that of concentrated sulfuric acid (85%) under the same reaction conditions. The kinetic results of pharmaceutical esterification of aspirin catalyzed by PMo 12 O 40 -Bpp show that reaction order is 1.37, rate constant is 1.13 × 10 -3 k/L·(mol·s) -1 , and apparent activation energy is 64.39 kJ·mol −1 . After PMo 12 O 40 -Bpp catalyzes pharmaceutical esterification of aspirin repeatedly, PXRD, IR and lifetime of catalyst show that structure of PMo 12 O 40 -Bpp is unchanged and catalytic activity does not decrease significantly, indicating that PMo 12 O 40 -Bpp can be recycled for multiple times. Above experimental results may be due to specific “pseudo-liquid phase” phenomenon of POM-based supramolecular compounds to make full contact with reactants in the catalytic process, further stabilizing carbocation intermediates effectively through [PMo 12 O 40 ] 3- with greater surface electronegativity, which is more conducive to attack of hydroxyl oxygen atom on salicylic acid to promote pharmaceutical esterification reaction of aspirin catalyzed by PMo 12 O 40 -Bpp. This successful work implies that POM-based supramolecular compounds as catalysts in pharmaceutical synthetic process have potential to reduce environmental pollution and provide newfangled inspirations for green pharmaceutical chemistry.