Novel Conversions of Benzotriazol-1-ylmethyl Derivatives.

Azolyacetones as Precursors to Indoles and Naphthofurans Facilitated by Microwave Irradiation with Simultaneous Cooling

“…Heating of 4 or 7a with zinc chloride and a few drops of acetic acid under microwave irradiation at 160 °C for 30 minutes afforded compounds 8 or 9 in 72% and 88% yields, respectively. Despite Katritzky’s reports [ 13 , 14 ] that benzotriazole substituents are masked halides, we failed to replace the benzotriazolyl moiety in the formed indole under a variety of conditions. It is of value to report that compound 8 has been previously obtained via pyrolysis of 4,5-disubstituted 1-phthalimido-1,2,3-triazoles [ 15 ].…”

Synthesis and NMR Analysis of a Conformationally Controlled β-Turn Mimetic Torsion Balance

“…24 The Katritzky conditions were modified by employing a separate preliminary condensation of 1-hydroxymethylbenzotriazole (21) with 19 (Scheme 3). 25 This modification removed the uncertainty of the formalin reaction and related equilibria. Treatment of 19 with 21, followed by reduction with NaBH 4 ,afforded the methylated biaryl 20 in 53% yield.…”

“…The oil was purified by flash chromatography (SiO 2 , hexanes/ethyl acetate/methanol elution gradient 1:1:0/2:3:0/0:1:0/0:9:1) to give 0.007 g (76%) of 4 as a white foam: R f 0.34 (100% ethyl acetate); IR (thin film, cm −1 ) 3338, 2932,1751,1723,1655,1580,1423,1393,1369,1329,1235,1193,1135,1029,996,844,806,733; 1 H NMR (700 MHz, CDCl 3 ) δ 7.34− 7.27 (m, 8H), 7.22−7.19 (m, 4H), 7.14−7.13 (m, 1H), 6.26 (broad s, 1H), 5.07 (s, 2H), 5.02 (s, 2H), four protons of conformers: [4. 25,3.96 (qAB, J = 15 Hz), 4.20, 4.15 (qAB, J = 15 Hz)], 4.02 (s, 3H), two protons of conformers: [3.65 (qd, J = 4.9 Hz), 3.35 (s)], 3.15 (s, 3H), 2.01 (s, 3H), 1.95 (s, 3H); 13 C NMR (500 MHz, CDCl 3 ) δ 170.0, 169.0, 167.2, 167.1, 166.1, 153.5, 141.6, 139.6, 136.4, 135.6, 135.3, 133.9, 131.4, 131.3, 127.8, 111.7, 111.3, 69.5, 67.4, 67.1, 53.7, 42.2, 36.3, 23.4, 15.3 5). In a round-bottom flask, 0.49 g (1.36 mmol) of benzoate 10, 0.26 mL (1.63 mmol) of benzyl bromoacetate, 0.22 g (1.63 mmol) of K 2 CO 3 , and 0.08 g (0.33 mmol) of 18-crown-6 were dissolved in acetone (35.4 mL), and the reaction mixture was refluxed for 24 h. The volatile components were removed under reduced pressure, and the residue was diluted with DCM (25 mL) and water (25 mL); the organic layer was extracted, and the aqueous layer was washed with additional DCM (3 × 25 mL).…”

Click-based synthesis of triazolobithiazole ΔF508-CFTR correctors for cystic fibrosis

“…After some experimentation, we found that bromination of 3a proceeded most effectively by treatment with elemental bromine in dioxane at 60 °C. 8 Workup, consisting of quenching with 10% NaHSO 3 and EtOAc extraction, delivered 2-bromo-1-(thiazol-5-yl)-2-(1H-1,2,3-triazol-1-yl)ethanone 8a in 45% yield (Scheme 3). While the yield for 3a → 8a was modest, product isolation was straightforward and 8a was stable to manipulation.…”