Synlett, Table of Contents Synlett 2024; 35(20): 2465-2470DOI: 10.1055/a-2422-1416 letter Special Issue to Celebrate the 75th Birthday of Prof. B. C. Ranu Sodium Metabisulfite Mediated Synthesis of Bis(pyrazolo[1,5-a] pyrimidin-3-yl)methanes from Pyrazolo[1,5-a]pyrimidines with Dimethyl Sulfoxide as a C1 Synthon Authors Paramita Pattanayak Appanapalli N. V. Satyanarayana Samiran Saha‡ Hariharasubramanian Sai Keerthana‡ Ainala Naresh‡ Yogesh K. Girase Tanmay Chatterjee ∗ Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) Dedicated to Professor Brindaban C. Ranu on the occasion of his 75th birthday. Abstract We report an unprecedented synthesis of bis(pyrazolo[1,5-a]pyrimidin-3-yl)methanes, a new class of di(hetaryl)methanes, from pyrazolo[1,5-a]pyrimidines by using DMSO as a C1 synthon (methylene source). The transformation is mediated by sodium metabisulfite (Na2S2O5), which plays a crucial role in the presence of acetic acid as a promoter. A wide variety of bis(pyrazolo[1,5-a]pyrimidin-3-yl)methanes were synthesized in moderate to good yields of up to 90%. Mechanistic studies suggested that the reaction follows an ionic pathway, probably involving a methyl(methylene)sulfonium ion as an active electrophilic species formed in situ by the reaction of DMSO with Na2S2O5. Key words Key wordssodium metabisulfite - pyrazolopyrimidines - bispyrazolopyrimidinylmethanes - C1 synthons - DMSO - metal-free reaction Full Text References References and Notes 1 Ma F, Li J, Zhang S, Gu Y, Tan T, Chen W, Wang S, Xu H, Yang G, Lerner RA. ACS Catal. 2022; 12: 1639 2 Rashidinia A, Dinari M. New J. Chem. 2023; 47: 17174 3a Dethe DH, Shukla M, Dherange BD. Org. Lett. 2020; 22: 5778 3b Moghaddam FM, Tavakoli G, Saeednia B. ChemistrySelect 2017; 2: 1316 4 Hammouda MM, Gaffer HE, Elattar KM. RSC Med. 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V, Chatterjee T. J. Org. Chem. 2024; 89: 12439 30 Paul TK, Sathpathy U, Konar RS. J. Appl. Polym. Sci. 1982; 27: 1501 31 3,3′-Methylenebis(2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine) (2c); Typical Procedure An oven-dried round-bottomed flask was charged with 2-methyl-7-phenylpyrazolo[1,5-a]pyrimidine (1c; 0.5 mmol, 105 mg), Na2S2O5 (284.7 mg, 1.5 mmol, 3 equiv), and AcOH (6 μL, 0.1 mmol, 0.2 equiv). DMSO (5 mL) was added, and the mixture was stirred at 120 °C for 16 h until the reaction was complete (TLC). The resulting solution was extracted with EtOAc (3 × 10 mL), and the combined organic layer was washed with ice-cold water (3 × 10 mL). The organic layer was dried (Na2SO4), and the solvent was evaporated under reduced pressure to afford a crude product that was purified by column chromatography (silica gel, 20% EtOAc–hexane) to give a yellow solid; yield: 0.092 g (85%); mp 190–192 °C. IR (neat): 2921.28, 2851.43 cm–1. 1H NMR (400 MHz, CDCl3): δ = 8.47 (d, J = 4.3 Hz, 2 H), 8.08–8.01 (m, 4 H), 7.56–7.50 (m, 6 H), 6.76 (d, J = 4.3 Hz, 2 H), 4.40 (s, 2 H), 2.40 (s, 6 H). 13C NMR (101 MHz, CDCl3): δ = 153.96, 147.83, 147.69, 145.77, 131.33, 130.80, 129.17, 128.59, 106.74, 106.17, 77.00, 15.63, 13.39. HRMS (ESI): m/z [M + H]+ calcd for C27H23N6: 431.1984; found: 431.2000. Supplementary Material Supplementary Material Supporting Information (PDF)
