Milled Dry Ice as a C1 Source for the Carboxylation of Aryl Halides

Abstract

The use of carbon dioxide as a C1 chemical feedstock remains an active field of research. Here we showcase the use of milled dry ice as a method to promote the availability of CO₂ in a reaction solution, permitting practical synthesis of arylcarboxylic acids. Notably, the use of milled dry ice produces marked increases in yields relative to those obtained with gaseous CO₂, as previously reported in the literature.

Key words

carboxylation - carbon dioxide - C1 source - dry ice - arylcarboxylic acids

• References and Notes

• 1 Ruzi R, Liu K, Zhu C, Xie J. Nat. Commun. 2020; 11: 3312
• 2 Lassalas P, Gay B, Lasfargeas C, James MJ, Tran V, Vijayendran KG, Brunden KR, Kozlowski MC, Thomas CJ, Smith AB. III, Huryn DM, Ballatore C. J. Med. Chem. 2016; 59: 3183
• 3 Ballatore C, Huryn DM, Smith AB. III. ChemMedChem 2013; 8: 385
• 4 Sheldon RA. Green Chem. 2014; 16: 950
• 5 Vechorkin O, Hirt N, Hu X. Org. Lett. 2010; 12: 3567
• 6 Fujihara T, Tsuji Y. Front. Chem. 2019; 7: 430
• 7 Liu Q, Wu L, Jackstell R, Beller M. Nat. Commun. 2015; 6: 5933
• 8 Gilman H, Beel JA. J. Am. Chem. Soc. 1949; 71: 2328
• 9 Hussey AS. J. Am. Chem. Soc. 1951; 73: 1364
• 10 Zhang Z, Roisnel T, Dixneuf PH, Soulé JF. Angew. Chem. Int. Ed. 2019; 58: 14110
• 11 Luo J, Larrosa I. ChemSusChem 2017; 10: 3317
• 12 White AR, Wang L, Nicewicz DA. Synlett 2019; 30: 827
• 13 Wiberg E, Holleman AF, Wiberg N. Inorganic Chemistry . Academic Press; 2001
• 14 Miller MB, Chen D.-L, Luebke DR, Johnson JK, Enick RM. J. Chem. Eng. Data 2011; 56: 1565
• 15 Kunerth W. Phys. Rev. 1922; 19: 512
• 16 4-Fluoro-2,6-dimethylbenzoic Acid (1); Typical Procedure Under a positive pressure of N₂, 2-bromo-5-fluoro-1,3-dimethylbenzene (3.040 g, 1.0 equiv, 14.97 mmol) was added to a flame-dried 100 mL round-bottomed flask and then diluted with anhyd THF (20 mL). The solution was cooled to –78 °C and a 1.6 M solution of n-BuLi (1.055 g, 1.1 equiv, 16.47 mmol) in hexanes (10.29 mL) was added dropwise. The resulting solution was then stirred at –78 °C for 1 h. Separately, under a constant stream of N₂, anhyd THF (~50 mL) was added to a flame-dried, 250 mL Erlenmeyer flask and cooled to –78 °C. Freshly milled dry ice (~75 g) was slowly added to the flask from a powder funnel. The flask was vigorously swirled, ensuring that the milled dry ice remained completely submerged in the solvent. The resulting slurry was filtered by vacuum filtration under a constant stream of N₂. After complete removal of the solvent, the resulting milled dry ice was quickly transferred to the original round-bottomed reaction flask by using a powder funnel (see the Supporting Information for additional details). The resulting reaction mixture was removed from the cooling bath and stirred at r.t. until complete sublimation of the dry ice was observed. (Safety Note: Sublimation of dry ice produces a large amount of gas. To prevent a dangerous buildup of pressure, the reaction flask was left open to the atmosphere after dry ice addition.) The solution was then concentrated in vacuo, and the residue was dissolved in H₂O (25 mL) and CH₂Cl₂ (25 mL). The resulting bilayer mixture was transferred to a separatory funnel, and the organic layer was removed. The aqueous layer was washed with CH₂Cl₂ (3 × 25 mL) and acidified to pH 2–3 with 1 M aq HCl. The resulting aqueous solution was then extracted with CH₂Cl₂ (4 × 25 mL), and the organic layers were collected, dried (MgSO₄), filtered, and concentrated in vacuo to give a white solid; yield: 2.409 g (14.32 mmol, 95.68%, n = 4). ¹H NMR (400 MHz, CDCl₃): δ = 6.81 (d, J = 9.3 Hz, 2 H), 2.47 (s, 6 H). The spectral data agreed with those previously reported.
• 17 Wu J, Yang X, He Z, Mao X, Hatton TA, Jamison TF. Angew. Chem. Int. Ed. 2014; 53: 8416
• 18 Shiina I, Miyao R. Heterocycles 2008; 76: 1313
• 19 Zhang Q, Zhang FM, Zhang CS, Liu SZ, Tian JM, Wang SH, Zhang XM, Tu YQ. Nat. Commun. 2019; 10: 2507
• 20 Paridala K, Lu S.-M, Wang M.-M, Li C. Chem. Commun. 2018; 54: 11574
• 21 Schlosser M, Cottet F, Heiss C, Lefebvre O, Marull M, Masson E, Scopelliti R. Eur. J. Org. Chem. 2006; 729
• 22 Correa A, Martín R. J. Am. Chem. Soc. 2009; 131: 15974
• 23 Screttas CG, Steele BR. J. Org. Chem. 1989; 54: 1013
• 24 Nagaraj HK. M, Bandodkar BS, Ravilla L, Yellapu S, Rudresha AS, Singh JK. ; G, V. WO 2016027285, 2016
• 25 Gschwend HW, Rodriguez HR. Org. React. 1979; 26: 1