Synlett 2013; 24(18): 2393-2396
DOI: 10.1055/s-0033-1339839
letter
© Georg Thieme Verlag Stuttgart · New York

Phase-Transfer Catalysis: Mixing Effects in Continuous-Flow Liquid/Liquid O- and S-Alkylation Processes

Benedikt Reichart, C. Oliver Kappe*, Toma N. Glasnov*
  • Christian Doppler Laboratory for Flow Chemistry (CDLFC) and Institute of Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria   Fax: +43(316)3809840   eMail: toma.glasnov@uni-graz.at   eMail: oliver.kappe@uni-graz.at
Weitere Informationen

Publikationsverlauf

Received: 05. August 2013

Accepted after revision: 22. August 2013

Publikationsdatum:
13.September 2013 (eFirst)

Abstract

This article describes detailed studies on the importance of mixing effects in the O- and S-alkylation of selected phenol and thiophenol substrates. Direct comparison between various continuous-flow reactors and a batch microwave reactor demonstrates the excellent mixing properties of the flow devices, which improve the reaction outcome.

Supporting Information

 
  • References and Notes

  • 1 Starks CM, Liotta CL, Halpern M In Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives. Chapman & Hall; New York; 1994. and references herein
  • 2 DeZani D, Colombo M. J. Flow. Chem. 2012; 1: 5
  • 3 Ji J, Zhao Y, Guo L, Liu B, Ji C, Yang P. Lab Chip 2012; 12: 1373
    • 4a McKillop A, Fiaud J.-C, Hug RP. Tetrahedron 1974; 30: 1379
    • 4b Branko J. Tetrahedron 1988; 44: 6677
    • 4c Jin G, Ido T, Goto S. Catal. Today 2001; 64: 279
    • 4d Yadav G. Top. Catal. 2004; 29: 145
    • 4e Coleman MT, LeBlanc G. Org. Process Res. Dev. 2010; 14: 732
  • 5 Aljbour S, Yamada H, Tagawa T. Chem. Eng. Process. 2009; 48: 1167
  • 6 Aljbour S, Yamada H, Tagawa T. Top. Catal. 2010; 53: 694
    • 7a Herriot AW, Picker D. J. Am. Chem. Soc. 1975; 97: 2345
    • 7b Reeves WP, Bothwell TC, Rudis JA, McClusky JV. Synth. Commun. 1982; 12: 1071
    • 7c Waghmode TW, Pathre GS, Pai NR. J. Chem. Pharm. Res. 2012; 4: 1589
    • 8a Denmark SE, Weintraub RC, Gould ND. J. Am. Chem. Soc. 2012; 134: 13415
    • 8b Yadav GD, Badure OV. Clean Technol. Environ. Policy 2009; 11: 163
    • 8c Yadav GD, Desai NM. J. Mol. Catal. A: Chem. 2006; 243: 278
    • 8d Yadav GD, Lande SV. Appl. Catal. A: Gen. 2005; 287: 267
    • 8e Herriot AW, Picker D. Tetrahedron Lett. 1972; 4521
    • 8f Yadav GD, Bisht PM. J. Mol. Catal. A: Chem. 2004; 223: 93
  • 10 Ueno M, Hisamoto H, Kitamori T, Kobayashi S. Chem. Commun. 2003; 8: 936
  • 11 de Bellefon C, Tanchoux N, Caravielhes S, Grenouillet P, Hessel V. Angew. Chem. Int. Ed. 2010; 39: 3442
  • 12 Ahmed B, Barrow D, Wirth T. Adv. Synth. Catal. 2006; 348: 1043
  • 13 Reichart B, Tekautz G, Kappe CO. Org. Process Res. Dev. 2013; 17: 152
  • 14 For information about the Biotage Initiator, see: http://www.biotage.com.
    • 15a Damm M, Gutmann B, Kappe CO. ChemSusChem 2013; 6: 978
    • 15b Hessel V, Kralisch D, Kockmann N, Noël T, Wang Q. ChemSusChem 2013; 6: 746
  • 16 Kockmann N, Roberge DM. Chem. Eng. Process. 2011; 50: 1017
  • 17 For information about the Syrris Asia system, see: http://syrris.com.
  • 18 For a recent review, see: Glasnov TN, Kappe CO. Chem. Eur. J. 2011; 17: 11956
  • 19 Synthesis of 1,3,5-Trimethyl-2-[(phenylmethyl)thio]-benzene: A: Batch Microwave Conditions: Into a 5-mL microwave Pyrex process vial equipped with a magnetic stir bar organic stock solution A (2 mL; 0.2 M 2,4,6-trimethylthiophenol and 0.24 M benzyl bromide in CH2Cl2) and aq stock solution D [2 mL; 0.6 M K2CO3 and 0–2 mM (0–1 mol%) TBAB] were placed. The vial was sealed with a Teflon septum fitted in an aluminum crimp top and heated in the microwave reactor for 1–10 min (fixed hold time) at 70–100 °C (3–18 bar). After cooling to 45 °C, the reaction mixture was immediately quenched with 2 M aq HCl to reach pH <2. After 2 min of vigorous stirring the aqueous phase was separated via syringe and 10 μL aliquots of the organic phase were subjected to HPLC analysis (λ = 215 nm). 1,3,5-Trimethyl-2-[(phenylmethyl)thio]benzene was isolated by phase separation from the basic aqueous phase, followed by H2O extraction (3 ×). The obtained organic phases were combined, dried over MgSO4, filtrated and concentrated under vacuum to provide the S-benzyl ether (88 mg, 91% yield, yellowish plates); mp 35–36 °C (lit.3: mp 36 °C). MS (APCI, –): m/z = 242.1 [M+], 241.1 [M+ – 1], 151.1 [M+ – 91]. 1H NMR (300 MHz, CDCl3): δ = 2.28 (s, 3 H), 2.37 (s, 6 H), 3.78 (s, 2 H), 6.92 (s, 2 H), 7.08–7.11 (m, 2 H), 7.22–7.25 (m, 3 H). B: Continuous Flow Conditions: For details please see the provided Supporting Information.