Mechanochemical Synthesis of Diarylethynes from Aryl Iodides and CaC₂

Abstract

A mechanochemical synthesis of diarylethynes from aryl iodides and calcium carbide as acetylene source is reported. The reaction is catalyzed by a palladium catalyst in the presence of copper salt, base, and ethanol as liquid assisting grinding (LAG) additive. Various aryl and heteroaryl iodides have been converted in up to excellent yields.

Key words

mechanochemistry - calcium carbide - ball milling - diaryl­ethyne - catalysis - palladium

Publication History

Received: 09 November 2021

Accepted after revision: 07 January 2022

Accepted Manuscript online:
07 January 2022

Article published online:
10 February 2022

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• 14 1,2-Di-p-tolylethyne (2a); Procedure: A stainless steel milling jar (volume: 5 mL) equipped with one stainless steel milling ball (diameter: 10 mm) was loaded with Pd(OAc)₂ (2.3 mg, 0.01 mmol, 5 mol%), PPh₃ (5.3 mg, 0.02 mmol, 10 mol%), CuI (3.8 mg, 0.02 mmol, 10 mol%), K₂CO₃ (55.3 mg, 0.4 mmol, 2.0 equiv) and iodo-4-methylbenzene (87.2 mg, 0.4 mmol, 2.0 equiv). The jar was brought inside a glovebox and CaC₂ [25.6 mg, 0.4 mmol, 2.0 equiv of technical grade CaC₂ (75.54% purity), real amount added 0.30 mmol] and ethanol (45 μL) were added. The jar was closed tightly under argon atmosphere using Teflon tape for the thread and additional Parafilm was wrapped around the closed jar. After 90 min at 30 Hz the jar was opened in air, the product was extracted with ethyl acetate (5 × 3 mL) and evaporated on silica. The product was purified by flash column chromatography on silica gel [n-pentane; R_f 0.39 (n-pentane)] to give 1,2-di-p-tolylethyne (40.1 mg, 0.194 mmol, 97%) as a pale-yellow solid. ¹H NMR (600 MHz, CDCl₃): δ = 7.43 (d, J = 8.1 Hz, 4 H), 7.16 (d, J = 7.8 Hz, 4 H), 2.38 (s, 6 H) ppm. ¹³C{¹H} NMR (151 MHz, CDCl₃): δ = 138.3, 131.6, 129.2, 120.5, 89.0, 21.6 ppm. The analytic data is consistent with reported data (ref. 11f).
• 15 When the typical procedure (see ref. 14) was modified by not using the glovebox and adding freshly ground CaC₂ and ethanol in air followed by flushing the jar with argon, 2a was obtained in only 80% yield (as determined by ¹H NMR spectroscopy). Most likely, the moisture sensitivity of CaC₂ and a partial evaporation of ethanol were responsible for this decrease in yield. Also in this case, 2a′ remained undetected.
• 16 Besides 2i (44% yield), 22% of aryl iodide 1i could be isolated. After the unsuccessful attempt to couple 1-iodonaphthalene, the starting material was recovered in 58%. Except when detailed, no mono-aryl alkynes were observed in any of the couplings.
• 17 After our submission, Ito, Kubota, and co-workers reported a mechanochemical Sonogashira cross-coupling of aryl bromides and chlorides with triisopropylsilyl acetylene and aryl acetylenes under high-temperature ball-milling conditions. The protocol expands the scope of the mechanochemical Sonogashira cross-couplings developed by Mack and Stolle and highlights the benefits of ball milling compared to solution-based reactions of poorly soluble substrates. See: Gao Y, Feng C, Seo T, Kubota K, Ito H. Chem. Sci. 2021; 13: 430