Chapter 2
Electrophilic Chemistry in Ionic Liquids Kenneth K. Laali
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Department of Chemistry, Kent State University, Kent, OH 44242
Room temperature ionic liquids (ILs), with low nucleophilicity counterions (OTf, FSO , PF , BF etc) constitute unique environments for exploring ionic reactions involving electrondeficient intermediates, in particular carbocations and onium ions. Lewis acids that typically show limited or no solubility in regular organic solvents can in many cases be dissolved/immobilized in imidazolium-based ILs. Moreover, these "designer solvents" appear to be ideal media for utilizing onium salts (i.e. diazonium, selectfluor™ etc) as reagents for synthesis because of their increased solubility in ILs as compared to regular organic solvents (onium salt reagents dissolved in onium salt solvents!). Current interest and activity of this laboratory in the ionic liquids area center around their potential application as solvents and as catalysts in fundamentally important electrophilic transformations, specially those that are carried out on large scale in industry such as nitration, alkylation, acylation and fluorination. The present review summarizes our survey studies in aromatic nitration, aromatic fluorination using NF reagents, fluorodediazoniation (Balz-Schiemann reaction), transacylation and deacylation of aromatic ketones, and in adamantylation of aromatics. -
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© 2007 American Chemical Society
In Ionic Liquids in Organic Synthesis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.
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Electrophilic Nitration of Aromatics in IL Solvents: A search for "greener", more environmentally acceptable, methods to carry out acid-catalyzed electrophilic aromatic nitration is certainly worthwhile, given the importance of the process and the demand for nitroaromatics as key organic intermediates. Despite the fact that aromatic nitration is a very extensively studied area in preparative and mechanistic organic chemistry, there is plenty of room for improvement, in particular with respect to environmental aspects (acid neutralization, aqueous work-up, disposal etc). In this frame of mind, we conducted a survey study to determine the efficacy of arene nitration in various IL solvents (1).
Figure 1. Electrophilic Nitration in imidazolium ILs (Adaptedfrom reference I.)
The RTILs employed were [EMIM][OTf], [EMIM][CF COO], as well as [HNEtPr ][CF COO]. Nitration reactions with nitronium salts, isoamyl nitrate/TfOH (or isoamyl nitrate/BF .Et 0), NH N0 /TFAA, as well as AgN0 /Tf 0 were examined. The most promising systems for nitration in IL solvents are sketched in Scheme 1. As part of the survey study, viable recycling/regeneration protocols were investigated for the identified optimal processes (1). Table 1 gives a condensed summary together with the yields and isomer distributions. More recently, Handy and Egrie (2) reported on some other methods for nitration in IL solvents. For example, they used Yb(OTf) with HN0 and Cu(OTf) with HN0 as nitrating system, employing N-butyl-Nmethylpyrrolidinium triflimide as the ionic liquid. Qiao and Yokoyama (3) used the Bronsted acidic ionic liquid Nmethylimidazolium-N-(CH )n-S0 H in combination with HN0 to nitrate benzene, toluene, chlorobenzene and bromobenzene. Earle et al (4) discovered that in reaction of toluene with HN0 employing [bmim][X] ILs the choice of the counterion greatly influenced the reaction outcome. With [bmim][OTf], ring nitration was observed whereas with [bmim][halide] the outcome was ring halogenation and with [BMIM][OMs] side chain oxidation was observed. 3
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In Ionic Liquids in Organic Synthesis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.
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Scheme 1. Most promising nitrating systems for IL nitration of arenes (Adapted from reference 1.) Electrophilic Fluorination of Arenes with Selectfluor™ (F-TEDA-BF ) in Ionic Liquids 4
As was pointed out earlier in the chapter, one of the promising aspects of IL chemistry from our perpective is to increase the synthetic utility of onium salts in preparative chemistry. The NF-fluorinating agent F-TEDA-BF dication salt dissolves in [EMIM][OTf], [EMIM][BF ], [BMIM][PF ] and [BMIM][BF ] (assisted by sonication). The resulting systems are convenient media for electrophilic fluorination of arenes under essentially acid-free conditions in a simple set-up which avoids the use of volative organic solvents. The process requires a simple extractions procedure and no aqueous work-up, and it offers the possibility to recycle and reuse the IL (5). Representative examples are gathered in Tables 2-4. For comparison, anisole was fluorinated with Selectfluor™ in recycled [EMM][OTf] (see Table 2). 4
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Figure 2. Fluorination of aromatics with Selectfluor (Adapted from reference 5.)
In Ionic Liquids in Organic Synthesis; Malhotra, S.; ACS Symposium Series; American Chemical Society: Washington, DC, 2007.
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Table 1. Nitration of Arenes in Ionic Liquids (Adaptedfrom reference 1.) R-Ar
Ionic Liquid.
OMe
[emin][OTf] [emim][CF COO] [HNEtPr^fCFsCOO] [emim][OTf] [emin][CF COO] [HNEtPr^JtCFsCOO] [emin][OTfj [emin][CF COO] [HNEtPr^JiCFsCOO] [emin][OTfj [emin][CF COO] [HNEtPr^JtCFaCOO] [emin][OTfj [emin][CF COO] [HNEtPr'iltCFsCOO] [emim][CF COO] [emin][OTf| [HNEtPr^HCF^OO] [emim][CF COO] [emim][OTf] [HNEtPr ][CF COO] [emim][CF COO] [emim][OTf] [emim][OTf] [emim][CF COO] 42-62 (GC) [emin][CF COO] [emim][OTf] [emin][CF COO]
Yield(%)
e
l-MeO/4-Me
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tBu
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1,3,5-tri-Me
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F
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Me
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Η
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CF
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4-F/l-Me
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[HNEtPr'zliCFsCOO] N0 2
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naphthalene
3
8
Isomer distribution (%
95 (GC) 75 (NMR) 99 (NMR) 90 (GC) 70 (GC) 88 (GC) 80 (GC) 81 (GC) 64 (GC) 80 (NMR) >66 (NMR) 53 (NMR) 90 (GC) 54 (GC) 97 (GC) 65 60 58 (NMR) 50 (GC) 84 (GC) 56 (GC) ~3 (GC) 24 (GC) 57 (NMR)
