Journal of Undergraduate Chemistry Research, 2013, 12(3),75

SYNTHESIS OF N,N-BUTYL-D9-METHYLPYRROLIDINIUM BIS(TRIFLUORO-

METHANESULFONYL)IMIDEt

Duane E. Weisshaar]", icole J. Altena*, Rachel S. Anderson*, Riley P. McManus*, Austin R. Letcher*, Mathew E.Amundson*, and Gary W. Earl

Abstract

Chemistry Department, Augustana College, Sioux Falls, SD 57197, duane.weisshaar@augie.edu

The production of N,N-butyl-d.-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide (BMP Tf2N, an ionic liquid) was desired tostudy the quenching of lanthanide fluorescence in this ionic liquid. Three steps to the ionic liquid were optimized with non-deuteratedreactants. First, 1-methylpyrrolidine was quaternized with 1-bromobutane by an SN2reaction. Cation HPLC was used to determinepercent conversion with yields >93%. Second, BMP Br was recrystallized using acetonitrile/ethyl acetate with yields >95%. Third,the anion was exchanged by mixing aqueous Li Tf2N and aqueous BMP Br producing the colorless BMP Tf2N as a separate layerwith yields >95%. 'H and 13CNMR verified production of the ionic liquid. Nine extractions with 10:1 (v/v) water:ionic liquid wererequired to reduce bromide concentration in the aqueous phase below the anion HPLC detection limit of 1.6 ppm. A similar synthesisusing perdeuterobutyl bromide proceeded smoothly producing a colorless ionic liquid with an overall 80% yield.

Keywords: Deuterated ionic liquid, Synthesis, Butylmethypyrrolidinium

Scheme 2.

:j: This work was previously presented as a poster at the 47thACS Midwest Regional Meeting, October 24-27, 2012, Omaha, NE.

Introduction

May et al. (I) have been studying the fluorescence oflanthanides in the non-coordinating ionic liquid N,N-butylmethylpyrrolidinium bis(trifluoromerhanesulfonyl)imide (BMP Tf2 ). To investigate the quenching effects ofthe solvent, that group desired deuterated analogs ofthe ionicliquid and asked our group to synthesize them. (Changingvibrational frequencies of the solvent molecules changes theefficiency of fluorescence quenching.) It was decided thatthe perdeuterobutyl analog would have sufficient deuterationfor the quenching study, so that became the primary target.The initial effort was optimization of each step in the synthesisusing non-deuterated reactants to establish conditions thatmaximized yield and purity.

The method of MacFarlane et at. (2) served as the startingpoint for the synthesis. This method begins with an SN2reaction of an alkyl halide with a tertiary amine (Scheme 1),followed by an anion exchange reaction to produce the ionicliquid (Scheme 2). BMP Tf2N should be a colorlesscompound, but typically this synthesis produces a productwith varying degrees of color from a yellow to red liquid.The most common strategy for removing the color is to heatthe ionic liquid with activated charcoal and filter (3).

Experimental

ReagentsThe reagents from Sigma-Aldrich (St. Louis, MO) were:

acetonitrile (99.8%), I-bromobutane (99%), I-bromobutane-d9 (98%), lithium bis(trifluoromethanesulfonyl)imide

-Scheme 1.

-o 0.e II ..•• II

+ Ll F3C-S-N-S-CF3II €> IIo 0

(Li Tf2N) (99.95%), ammonium acetate (99.99%), and aceticacid (99.99%). Additional reagents included: disodium 1,5-naphthalenedisulfonate dihydrate (98%, Acros Organics, NJ),l-methylpyrrolidine (99%, Fluka Analytical, St. Louis, MO),methanol (99.99%, Pharmco-Aaper, Brookfield CT), ethylacetate (ACS Reagent, Pharmco-Aaper, Brookfield CT),NMR solvent acetonitrile-d. (99.8%, Cambridge IsotopeLaboratories, Inc., Andover, MA), and compressed nitrogengas (Linweld, Sioux Falls, SD). All reagents were used asreceived. HPLC water was produced by a 3-cartridgeBarnstead anopure II water purification system (ThermoFisher Scientific).

Safety

Lithium bis(trifluoromethanesulfonyl)imide is flammableand corrosive. The l-brornobutane and l-methylpyrrolidineare toxic, corrosive, and flammable. The 1,5-disodiumnaphthalenedisulfonate (solid) is toxic and an irritant. Thesewere handled with gloves; goggles were worn at all times.

instrumentation'H- and I3C-NMR spectra were obtained on a JEOL ECS-

400 (400 MHz) Spectrometer (Peabody, MA). UV-Vis spectrawere obtained on a Shimadzu Model UV-2450 UV-VisSpectrometer (Columbia, MD) using quartz cuvettes. Bromidesalts were - 0.2 M in acetonitrile and the ionic liquid wasneat.

The HPLC for cation analysis was constructed fromindividual components that included the following: Series IIIpump, SSI LP-21 pulse dampener, Rheodyne Model 7125injector with 20 ~L sample loop, Model VD-4101 in-linedegasser (all from Chrom Tech, Inc., Minneapolis, MN), andWaters Model 410 differential refractometer (Milford, CT).A 150 x 4.6 mm, 5 urn Spherisorb SCX strong cation exchangecolumn (Waters Corp., Milford, CT) was used with an eluentof 50 mM ammonium acetate and 100 mM acetic acid in

o 0II .... II $ e

F3C-S-N-S-CF3 + u XII e IIo 0

Journal of Undergraduate Chemistry Research, 2013, 12(3),76

Figure 1. Mini-reactor.

methanol at a flow rate of I mLiminute.

Anion analysis employed an Agilent LCI 100 HPLC withphotodiode array detector and Rheodyne Model 7125 injectorwith 20 mL sample loop (Wilmington, DE) and a 150 x 4.1mm, Sum Hamilton PRP-X100 strong anion exchange column(Hamilton Co., Reno, NY). Indirect detection at 275 nm wasused with an aqueous 0.5 mM disodium 1,5-naphthalenedisulfonate (NDS) mobile phase at a flow rate of1 mL/min.

All mobile phases were filtered through Whatman GF/F(0.7 mm) filters (Thermo Fisher Scientific) and the sampleswere filtered through 0.2 mm polypropylene syringe filters(Chrom Tech).

Step J - BMP Br SynthesisPast experience synthesizing a variety of ionic liquids in

this lab has shown that removal of oxygen from thequatemization reaction is critical for minimizing color in thefinal product, but complete elimination of color is difficult.To facilitate oxygen exclusion a small, stainless steel, high-pressure reactor (mini-reactor, Figure I) was constructed froma Hoke 30 mL sampling cylinder (part number 4HDY30, JEMTechnical, Long Lake, MN), a street T (Swagelok, OmahaValve & Fitting Co., La Vista, NE), and a Hoke 300-450 psipressure relief valve (part number 6711L4YC). A brass togglevalve (Swage\ok) and straight-through quick disconnect body(CPC, Cole-Parmer Instrument Co., Vernon Hills, IL) wereadded to facilitate the 2flush. A Lollipop digital thermometer(Control Company, Fischer Scientific, Hanover Park, IL)wired to the outside of the mini-reactor tube monitored theonset and subsidence of the exothermic reaction.

The liquid reagents were massed in a syringe and transferredto the mini-reactor. In a typical synthesis, 1.7 g (0.02 mole,-2 mL) I-methylpyrrolidine, 2.7 g (0.02 mole, -2 mL) 1-bromo butane, and 10 mL acetonitrile were sealed in the mini-reactor. Oxygen was removed from the vessel by executingthe following procedure at least 10 times: the vessel waspressurized to 100 psi with N2, agitated for 15 seconds usinga test tube vortexer (CMS Super-Mixer, Morris Plains, J),and then pressure was released. The tubes were immersed ina constant temperature oil bath maintained at 70°C with a125 W immersion heater (Cenco 1655 I -1, Fischer Scientific,Hanover Park IL) controlled by a JKEM Model 150Temperature Controller (St. Louis, MO). When the rate oftemperature increase monitored by the external thermometer

Cation HPLC BMP Br Reaction Mixture

BMP

0.00 10.00 15.00 20.00 25.00 30.00

Time (mln)

5.00

Figure 2. Cation HPLC of the quaternization reaction productshowing complete conversion to BMP: expected retention timeof 1-methylpyrrolidine (arrow) 12.5 min, retention time BMP 20.5min.

indicated the exothermic reaction had begun (initiated around40°C), the tube was removed from the heating bath) until theexothermic reaction subsided (-10 minutes). The tube wasagain immersed in the heating bath and maintained at 70°Cfor 22 hours. After removing solvent and excess reactants byby rotary evaporation, a pale yellow solid was collected withgreater than 93% yield. Sometimes yields were greater than100% due to the hygroscopic nature of the material (deuteratedand non-deuterated).

Step 2- PurificationEarly in this work, it was discovered that the non-deuterated

BMP Br recrystallized from an acetonitrile/ethyl acetatemixture produced white, needle crystals, which could be anionexchanged (next step) to produce a colorless ionic liquid. Therecrystallization approach proved to be more efficient thanthe activated charcoal decolorizing process (3).

To recrystallize, the BMP Br was first dissolved inacetonitrile (- 0.3 g/rnl.) and vacuum filtered to removeinsoluble components. To establish the appropriate solventmixture, ethyl acetate was added to the hot acetonitrilesolution until crystals just began to form, and then acetonitrilewas added drop-wise until the crystals just dissolved. Thesolution was allowed to cool to room temperature and thencooled further in an ice bath. (Cooling in two steps producedlarger crystals). The crystals were removed by vacuumfiltration and washed with ethyl acetate. A second crop ofcrystals was recovered by a similar procedure after removingsolvent by rotary evaporation. A third crop of white crystalscould be harvested if the initial BMP Br was not too colored.Deuteration on the butyl group did not affect therecrystallization.

Step 3- Anion Exchange to Produce BMP TfJVThe recrystallized BMP Br was anion exchanged using

MacFarlane's (2) method with no modifications. Typically1.3 g (5.6 mmol) BMP Br was dissolved in 2 mL of deionizedwater, and 1.6 g (5.6 mmol) Li Tf2N was dissolved in aseparate 2 mL aliquot of deionized water. These two solutionswere then combined in a 10 mL Erlenmeyer flask and stirredon a magnetic stirrer for three hours. The aqueous (upper)layer was removed by pipet. To remove residual bromide,

Crude BMP Br Spectrum

0.8

0.6 ~~ \=01.c!s 0.4.c <,< -

0.2~

0250 350 450 550 650

Wavelength (nm)

Figure 3. UV-Vis spectrum of 0.2 M crude BMP Br in acetonitrile.The solution had a pale yellow color.

nine extractions with deionized H20 (10: I v/v H20:BMPTf2N) were required to reduce the bromide concentration inthe aqueous layer below the detection limit of the anion HPLC(20 11M, 1.6 ppm). Yields for this step were typically above95%. !he ionic ~iquid.appeared cloudy, presumably due toemulsion formation with water. Rotary evaporation at roomtemperature for -12 hours removed the cloudy appearance.IH NMR (400 MHz, CD3CN) 8 3.36 (m, 4 H), 3.17 (m, 2 H),2.90 (s, 1 H), 2.11 (m, 4 H), 1.68 (m, 2 H), 1.33 (hextet, J =7.33 Hz, 2 H), 0.93 (t, J = 7.33 Hz, 3 H). l3C NMR (400MHz, CD3CN) 8119.1 (q, J= 320 Hz, 2 C), 64.4 (2 C), 64.3,48.2,25.3,21.3 (2 C), 19.4, 12.8.

NMR spec~a for the ionic liquid with the deuterated butylgroup were similar except the deuterium peaks on the butylgroup were absent from the NMR, and the butyl carbon peakswere also attenuated as expected (4). The l3C peak for theTf2.N.carbons (119.1 ppm) appeared as a quartet due tosplitting by the three 19Fnuclei, not the usual singlet.

Results and Discussion

Halide SynthesisThe yields for BMP Br from the mini-reactor, based on

recovered masses, were greater than 93% with someexceeding 100%. The yield for the deuterated BMP Br was120%. Variable rotary evaporating efficiency and absorptionof water were the likely causes for yields greater than 100%.Sinc~ the anion exchange step was carried out in aqueoussolution, the water was not an issue. HPLC analyses showedno detectable amine left in the reaction mixture (Figure 2).

The crude BMP Br was a pale yellow color due to thepresence of unknown impurities, a typical result for thissynthesis (2,3). A UV- Vis spectrum of 0.2 M BMP Br inacetonitrile (Figure 3) exhibited a peak at 280 nm and twoshoulders at 350 nm and 470 nm. The band at 470 nmaccounted for the pale yellow color ofthe product.

RecrystallizationRecrystallization ofthe deuterated and non-deuterated BMP

Br from ethyl acetate/acetonitrile produced white needles. The470 nm band in the UV-Vis spectrum of 0.2 M BMP Br wasvirtually absent, the absorbance at 280 nm was reduced to0.04 and the absorbance at 350 nm bands was 0.02.

Journal of Undergraduate Chemistry Research, 2013, 12(3),77

Anion HPLC ofBMPTf2N Extractions

c

d------------------------~

O+------,-----r------.------I2.5 3 3.5

Time (min)

Figure 4. Anion HPLC of the aqueous layer after IL extractionwith water: extraction number a) 2, b) 3, c) 7, and d) 9.

4 4.5

Due to t~e hygroscopic nature of the crystals, an accuratemelting pomt could not be determined. A crystal sealed in amelting point tube was not melted at 200°C when heatingwas stopped to prevent bursting ofthe tube.

The overall yield from a single recrystallization was - 50%but after optimizing the procedure and employing threerecrystallizations, overall yields of >95% were routinelyachieved.

Anion Exchange SynthesisAnion ex.change with Li Tf2N yielded a colorless liquid

with a density of 1.45 ± 0.023 g/mL. Yields for the perfectedanion exchange step were - 90%. IH and l3C NMR verifiedthat BMP Tf2N formed with no evident impurities.

The spectrum of the neat deuterated BMP Tf2N did notshow the shoulder at 470 nm in the visible region, but didexhibit the bands at 280 nm and 350 nm with absorbances of1.0 and 0.4 respectively. This indicated that the impurities inthe crude BMP Br had not been completely removed.However, their absence in the NMR suggested that theirconcentrations were quite I?w. The deuterated BMP Tf2NNMR, before rotary evaporation (to remove water), displayedtrace amounts of ethanol. The source of the ethanol impurityis unknown, but due to the high cost of the deuteratedbromobutane, the synthesis was only executed once, thereforethe source of the impurity could not be investigated. Rotaryevaporation removed the ethanol.

The solubility of the ionic liquid was estimated throughcation HPLC. A chromatogram of the aqueous layer fromone of the ionic liquid extractions produced a peak heightapproximately the same as an 18.4 roM standard BMP Brindicating the solubility was - 20 mM. '

The aqueous layers from a series of extractions with 10: I(v/v) water:ionic liquid were analyzed for residual bromideby anion HPLC (Fig. 4). After the ninth extraction, thebromide concentration was below the detection limit of -2011Mbromide (1.6 ppm).

Journal of Undergraduate Chemistry Research, 2013, 12(3),78

Conclusion

The synthesis of N,N-butyl-d9-methylpyrrolidiniumbis(trifluoromethanesulfonyl)imide is described here, webelieve, for the first time. The May group reported thatfluorescence experiments using the non-deuterated BMP Tf2Nsynthesized here matched results using the commercial ionicliquid, so the synthesis method meets their requirements. Thedeuterated ionic liquid also fulfilled the purpose the Maygroup was hoping to accomplish. Details of their fluorescencestudy will be published elsewhere.

Acknowledgements

This material is based upon work supported by the NationalScience FoundationiEPSCoR Grant No. 0903804 and by theState of South Dakota and by the National Science Foundation-Undergraduate Research Center program: CHE-0532242"The Northern Plains Undergraduate Research Center(NPURC). The NIH Grant Number 2 P20 RR016479 madethis publication possible from the INBRE Program of theNational Center for Research Resources. Its contents aresolely the responsibility of the authors and do not necessarilyrepresent the official views of NIH. Further thanks go toAugustana's Roland Wright Chemistry EquipmentEndowment and Augustana College. Augustana's BrandonGustafson's patient assistance obtaining NMR spectra isgratefully acknowledged.

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