Green synthesis of 7-fluoro-6'-hydroxy-5'-(thiophene-2-carbonyl)-6'-trifluoroomethyl-5',6'- dihydro-1'H-spiroindole-3,4'-pyrimidine-2,2'(3'H)-dione and X-ray analysis

Objective To develop a green, simple and efficient method to construct pyrimidine-2-ketone skeleton molecules, so as to provide evidence for investigating antitumor activity of these molecules. Methods 7-Fluoroindoline-2,3-dione, urea and 4,4,4-trifluoro-1-(thiophene-2-yl) butane-1,3-dione were used as raw materials, while p-methylbenzene sulfonic acid as the catalyst.The target compound was synthesized through Biginelli reaction using a multi-component one pot method without solvent.The crystal structure was verified by ¹H NMR, ¹³C NMR, IR, HRMS and X-ray diffraction. Results The target compound, 7-fluoro-6'-hydroxy-5'-(thiophene-2-carbonyl)-6'-(trifluoroomethyl)-5',6'-dihydro-1'H-spiroindole-3,4'-pyrimidine-2,2'(3' H)-dione was obtained through Biginelli reaction under solvent free conditions, with a yield of 92%.The resultant product was characterized by NMR, IR and HRMS, and further confirmed by X-ray diffraction.According to X-ray diffraction, the crystal structure belonged to the orthorhombic system , and the space group was P2₁/n.Lattice parameters: a=18.691, b=6.052, c=20.084, α=90.00°,β=108.8570(10)°, γ=90.00°.According to atomic parameters corrected by the full matrix least square method, the final deviation factor was R=0.3967,wR₂=0.8133. Conclusions Pyrimidine-2-one skeleton molecule is successfully constructed via a multi-component Biginelli reaction under solvent-free conditions.The method is green and environment-friendly and the pure product can be obtained only by recrystallization.