Subscribe to RSS
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.
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/)
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
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