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DOI: 10.1055/a-2118-6813
Synthesis of Halogen-Bond-Donor-Site-Introduced Functional Monomers through Wittig Reaction of Perfluorohalogenated Benzaldehydes: Toward Digitalization as Reliable Strategy in Small-Molecule Synthesis
This work was partially supported by the ASAHI GLASS Foundation, the NAGAI Foundation for Science and Technology, a Grant-in-Aid for Precise Formation of a Catalyst Having a Specified Field for Use in Extremely Difficult Substrate Conversion Reactions (KAKENHI Grant No. 18H04275), and the Grant-in-Aid for Transformative Organic Synthesis (Digi-TOS) (KAKENHI Grant No. 21H05218) from the Ministry of Education, Culture, Sports, Science and Technology, Japan. N.M. and T.F. gratefully acknowledge JST-ACCEL for their financial support.
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This paper is dedicated to Professor Hisashi Yamamoto in celebration of his 80th birthday.
Abstract
The Wittig reaction of perfluoromonohalobenzaldehydes was systematically studied to synthesize 2,3,5,6-tetrafluoro-4-halostyrene (TFXSs) as functional monomers bearing halogen-bond donor sites. The reaction proceeded efficiently in tetrahydrofuran using 1,1,3,3-tetramethylguanidine as an organic base. Correlation analysis quantitatively identified three key factors required to obtain TFXSs in reasonable yields. The present approach not only contributes to the study of halogen-bond-based functional molecules, but also presents digitalization as a potential strategy in small-molecule synthesis.
Key words
perfluorohalo styrenes - halogen bond - functional monomers - digitalization of organic synthesis - Wittig reactionSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2118-6813.
- Supporting Information
Publication History
Received: 17 May 2023
Accepted after revision: 26 June 2023
Accepted Manuscript online:
27 June 2023
Article published online:
17 August 2023
© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
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References and Notes
- 1a Halogen Bonding: Impact on Materials Chemistry and Life Sciences, Vols. I and II. Metrangolo P, Resnati G. Springer; Cham: 2015
- 1b Gilday LC, Robinson SW, Barendt TA, Langton MJ, Mullaney BR, Beer PD. Chem. Rev. 2015; 115: 7118
- 1c Cavallo G, Metrangolo P, Milani R, Pilati T, Priimagi A, Resnati G, Terraneo G. Chem. Rev. 2016; 116: 2478
- 1d Costa PJ. Phys. Sci. Rev. 2017; 2: 20170136
- 2a Biswas S, Das A. ChemNanoMat 2021; 7: 748
- 2b Kampes R, Zechel S, Hager MD, Schubert US. Chem. Sci. 2021; 12: 9275
- 3a Bertani R, Metrangolo P, Moiana A, Perez E, Pilati T, Resnati G, Rico-Lattes I, Sassi A. Adv. Mater. (Weinheim, Ger.) 2002; 14: 1197
- 3b Houbenov N, Milani R, Poutanen M, Haataja J, Dichiarante V, Sainio J, Ruokolainen J, Resnati G, Metrangolo P, Ikkala O. Nat. Commun. 2014; 5: 4043
- 3c Vanderkooy A, Taylor MS. J. Am. Chem. Soc. 2015; 137: 5080
- 3d Kumar V, Pilati T, Terraneo G, Meyer F, Metrangolo P, Resnati G. Chem. Sci. 2017; 8: 1801
- 4 Takeuchi T, Minato Y, Takase M, Shinmori H. Tetrahedron Lett. 2005; 46: 9025
- 5 Okuma K, Sakai O, Shioji K. Bull. Chem. Soc. Jpn. 2003; 76: 1675
- 6 Tshepelevitsh S, Kütt A, Lõkov M, Kaljurand I, Saame J, Heering A, Plieger PG, Vianello R, Leito I. Eur. J. Org. Chem. 2019; 6735
- 7 Rodima T, Kaljurand I, Pihl A, Mäemets V, Leito I, Koppel IA. J. Org. Chem. 2002; 67: 1873
- 8 Vazdar K, Margetić D, Kovačević B, Sundermeyer J, Leito I, Jahn U. Acc. Chem. Res. 2021; 54: 3108
- 9a Präsang C, Whitwood AC. Bruce D. W. Cryst. Growth. Des. 2009; 9: 5319
- 9b Lu W, Gao J, Yang J.-K, Liu L, Zhao Y, Wu H.-C. Chem. Sci. 2014; 5: 1934
- 10 2,3,5,6-Tetrafluoro-4-iodostyrene (2a); Typical Procedure 1,1,3,3-Tetramethylguanidine (282 μL, 2.25 mmol, 4.5 equiv) was added to a solution of methyl(triphenyl)phosphonium bromide (0.643 g, 1.80 mmol, 3.6 equiv) in THF (5 mL) was added, and the resulting mixture was stirred at 80 °C for 30 min. A solution of 2,3,5,6-tetrafluoro-4-iodobenzaldehyde 1a (0.152 g, 0.50 mmol, 1.0 equiv) in THF (1.5 mL) was added, and the resulting mixture was stirred for 6 h. Subsequently, H2O (10 mL) was added to the mixture and the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (3 × 10 mL), and the combined organic layers were washed with brine (10 mL) and dried (MgSO4). Small aliquots from the organic layers were analyzed by 19F NMR with PhCF3 as a standard (NMR yield: 53%). The organic layers were concentrated under a reduced pressure to afford a colorless oil. Due to its instability, the product was characterized as a mixture, and full data could not be collected. Rf = 0.53 (hexane). IR (ATR): 1471, 1416, 1259, 1101, 983, 953, 794 cm–1. 1H NMR (400 MHz, CDCl3): δ = 6.69 (dd, J = 11.9, 6.2 Hz, 1 H), 6.15 (d, J = 18.1 Hz, 1 H), 5.76 (d, J = 11.9 Hz, 1 H). 19F NMR (376 MHz, CDCl3): δ = –121.65 to –121.74 (m, 2 F), –141.56 to –141.66 (m, 2 F). 13C NMR{19F} (100 MHz, CDCl3): δ = 147.2, 144.0 (d, J = 4.9 Hz), 124.3 (t, J = 160 Hz), 122.3 (dd, J = 163, 2.9 Hz), 117.6–117.3 (m), 70.3.
- 11 Datachemical LAB (accessed July 31, 2023): https://www.datachemicallab.com
- 12 May’s Database of Reactivity Parameters (accessed July 31, 2023): https://www.cup.lmu.de/oc/mayr/reaktionsdatenbank2/
- 13 Solvent Selection Tool, Version 1.0.0, 2018 (accessed July 31, 2023): https://www.acs.org/greenchemistry/research-innovation/tools-for-green-chemistry/solvent-selection-tool.html
- 14 Diorazio LJ, Hose DR. J, Adlington NK. Org. Process Res. Dev. 2016; 20: 760
- 15 Saito N, Nawachi A, Kondo Y, Choi J, Morimoto H, Ohshima T. Bull. Chem. Soc. Jpn. 2023; 96: 465