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Synlett 2014; 25(17): 2447-2450
DOI: 10.1055/s-0034-1379018
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© Georg Thieme Verlag Stuttgart · New York

When Chlorides are the Most Reactive: A Simple Route towards Diverse Mono- and Dicationic Dimethyl Phosphate Ionic Liquids

Elina Priede*
University of Latvia, Faculty of Chemistry, 19, Rainis Blvd., Riga, LV1586, Latvia   Fax: +37167378736   Email: priede_elina@inbox.lv
,
Eduards Bakis
University of Latvia, Faculty of Chemistry, 19, Rainis Blvd., Riga, LV1586, Latvia   Fax: +37167378736   Email: priede_elina@inbox.lv
,
Andris Zicmanis
University of Latvia, Faculty of Chemistry, 19, Rainis Blvd., Riga, LV1586, Latvia   Fax: +37167378736   Email: priede_elina@inbox.lv
› Author Affiliations
Further Information

Publication History

Received: 10 June 2014

Accepted after revision: 03 August 2014

Publication Date:
09 September 2014 (online)

 
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Abstract

Structurally diverse aromatic and aliphatic ionic liquids have been prepared via anion metathesis utilizing alkylammonium chlorides and trimethyl phosphate. Excellent oxygen-containing functional-group tolerance in preparation of potentially greener dimethyl phosphate ionic liquids has been demonstrated. For the first time, this method has been employed in the synthesis of dicationic imidazolium-based ionic liquids possessing a dimethyl phosphate counterion, providing a simple, direct route towards structurally novel products of high purity.


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Key words

monocationic ionic liquids - dicationic ionic liquids - anion metathesis - dimethyl phosphate

Over recent decades, ionic liquids (IL) have become compounds of interest in a range of fields. The extensive application of IL is based on their versatile and beneficial properties, fine tunability, and structural diversity.[1] As a result, a series of novel dicationic and functionalized IL have recently been prepared and have attracted interest due to their distinct chemical and physical properties in comparison with their monocationic and nonfunctionalized analogues.[2]

Another readily available group of IL that has attracted attention is that of the alkylammonium dialkyl phosphates, which have been mainly exploited for the dissolution of cellulose and other carbohydrates.[3] In addition to this, several imidazolium-based dimethyl phosphate derived (DMP) IL have been successfully applied as solvents in various reactions.[4] These hydrophilic IL, with their superior enhanced thermal and hydrolytic stability, are usually prepared via alkylation of tertiary amines with esters of phosphoric acid.[5] However, elevated temperatures (80 °C and higher) and long reaction times (24 h or more) are necessary for these chemical transformations to proceed efficiently, thereby often causing yellow to brown coloration in the products.[6] However, completely colorless IL are normally required in fundamental studies, usually for acquisition of exact UV-vis spectroscopic data in order to calculate polarity characteristics[6a] [7] or for studies of reaction kinetics in IL media.[8]

The growing demand for halide-free DMP IL[5] has become a driving force for the development of new synthetic routes yielding products of high purity. Several methods for the preparation of halide-free IL are known, mostly based on either anion metathesis or acid–base neutralization reactions. A wide range of hydrophobic IL with [BF4]–, [PF6]–, and [NTf2]– anions has been obtained by such means.[1a] Unfortunately, both organic and inorganic oxoanions are too basic to be exchanged in this way, thus barring access to dialkyl phosphate, trifluoroacetate, tosylate, mesylate, and many other IL by such protocols. One approach overcomes these limitations by reacting different onium halides with esters of phosphorus oxoacids.[9] Bielawski et al. have developed an efficient protocol for obtaining phosphonium-, pyridinium-, and imidazolium-based IL via anion metathesis between organic halide salts and methyl sulfates, sulfonates, phosphates, and oxonium salts.[10] Schottenberger et al. have successfully applied a similar strategy for the synthesis of methyl phosphonate IL.[11]

These previously reported approaches encouraged us to adapt this anion metathesis for the synthesis of several functionalized and nonfunctionalized monocationic and dicationic IL with a DMP counterion, thereby broadening the scope of the methodology. Furthermore, the possibility to design the cation has led us to novel IL. Based on the results of preliminary studies,[9] [10] [11] chloride-containing IL were selected as the most reactive and thereby promising starting materials for efficient synthesis of halide-free DMP IL.

Primarily, we focused on the anion metathesis between some imidazolium-based IL and trimethyl phosphate (Scheme [1]). Treatment of alkylimidazolium chlorides 1a–d and 3a–c with alkylating agent resulted in vigorous gas evolution at elevated temperature and formation of the desired compounds 2a–d and 4a–c. The excess of TMP was removed by washing the crude products with toluene. The DMP IL were obtained as colorless, viscous liquids or white solids in quantitative yields (Table [1]). The time and the amount of TMP required for completion of the reaction, as determined by AgNO3 analysis, varied according to the nature of the respective chlorides. Dicationic IL and hydroxyl functional group containing IL tended to exchange chloride to DMP anion slower than their monocationic and nonfunctionalized analogues resulting in extended reaction times. This can be rationalized by the increased chloride ion content in the precursor dicationic IL, as well as the reduced mobility of chloride, owing to the possible hydrogen bonding to the hydroxyl functionality of the cation. In order to overcome such limitation, increased amounts of TMP (2.0–4.0 equiv) were used to ensure a rapid formation of the desired products. The residual chloride anion content in all DMP IL prepared was confirmed to be below 0.5 ppm, as certified by AgNO3 analysis [Ksp 25 °C(AgCl)=1.8·10–10 mol2·L–2].

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Scheme 1 Synthesis of imidazolium-based monocationic and dicationic IL 2a–d and 4a–c via anion metathesis with trimethyl phosphate TMP

Table 1 Dimethyl Phosphate (DMP) IL

Entry

DMP ILa (CAS)

Cation

TMP (equiv)

Temp (°C)c

Time (h)

Appearance

1

2a
(1320340-91-7)

2.0

80/110

2

colorless, viscous liquid

2

2b
(1006063-31-5)

2.0

80/110

4

colorless, viscous liquid

3

2c b

2.0

82d

2

colorless, viscous liquid

4

2d
(945611-42-7)

1.5

75/100

2

white solid (mp 93 °C)e

5

4a

3.0

90/120

4

colorless, viscous liquid

6

4b

4.0

85/100

8

colorless, viscous liquid

7

4c

4.0

100/120

2

colorless, viscous liquid

8

5
(118978-98-6)

2.0

90/110

2

white solid (mp 55 °C)e

9

6
(1323125-78-5)

1.5

80/110

2

white solidf

a The structure of IL was confirmed by NMR spectroscopy and ESI-HRMS. The residual moisture after drying (0.6 mbar, 100 °C, 8 h) was below 1000 ppm (determined by Karl Fischer titration).

b The residual moisture after drying (0.6 mbar, r.t., 24 h) was 2300 ppm (determined by Karl Fischer titration). Drying at higher temperature caused discoloration of IL 2c.

c Temperature at which the evolution of gas started/temperature at which the reaction was carried out.

d Synthesis of IL 2c was carried out in refluxing MeCN. Performance of the reaction under neat conditions required high temperature and prolonged reaction time and led to intensely colored product.

e The melting points of IL were determined via differential thermal analysis/thermogravimetry (DTA/TG) as the onset temperatures of the melting peaks.

f The melting point of IL 6 could not be determined due to its extremely hygroscopic character.

According to the approach depicted in Scheme [1, a] facile synthesis of dicationic imidazolium IL with DMP anion has been demonstrated for the very first time (Table [1], entries 5–7). Our initial attempts to obtain the above-mentioned IL were based on preparation of the respective α,ω-bis(imidazol-1-yl)alkanes[12] and their subsequent alkylation with TMP. However, the moderate yields of intermediates, need for inert conditions and long reaction times, and frequently resultant coloration of the target IL prompted us to seek an alternative route. In addition, direct alkylation of 1,6-bis(imidazol-1-yl)hexane in the case of IL 4c would be restricted by the scarce availability of the respective trialkyl phosphate. The alternative approach, employing anion metathesis with TMP, avoids long synthetic pathways and tedious workup, as well as provides colorless products. Similar considerations, based on evaluation of the methods reported previously,[13] were also applied to the synthesis of monocationic imidazolium-based and aliphatic DMP IL (Table [1], entries 1–4, 8, and 9). The diversity, simple preparation, and low cost of alkylammonium chlorides that can be used within the scope of this method are particularly advantageous in applying them to the synthesis of functionalized monocationic or dicationic IL.

In addition to studies concerning application of the DMP IL, the toxicity of these salts has become a divisive subject of discussion.[14] However, the toxicity and biodegradability of IL often strongly depend on the structure of the cation.[15] As reported,[16] introduction of oxygen-containing functional groups in the side chain of imidazolium cation may significantly reduce the toxicity of IL and increase their biodegradability. Herein, several examples on the synthesis of IL with 2-hydroxyethyl-, 2-methoxyethyl-, and 2-methoxy-2-oxoethyl groups within the cation moiety (Table [1], entries 1–3, 7, and 8) have been disclosed in order to highlight both the functional-group tolerance as an advantage of this method and an alternative route towards greener DMP IL. The preparation of choline DMP 5 (Table [1], entry 8) also demonstrates the benefit of using a readily available choline chloride instead of the hazardous N-(2-hydroxyethyl)dimethylamine.

In conclusion, we report a protocol that broadens the scope of chloride anion metathesis with TMP and have prepared structurally diverse aromatic and aliphatic DMP IL in high yields. Excellent oxygen-containing functional-group tolerance in the preparation of potentially green IL has been demonstrated. We have also applied this method to a novel, straightforward route towards dicationic imidazolium-based DMP IL of high purity, thus providing a new, advantageous approach for the synthesis of IL of this class.


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General Procedure for the Synthesis of Dimethyl Phosphate Ionic Liquids

The requisite monocationic alkylammonium chloride (10.0 mmol) or dicationic alkylammonium chloride (5.0 mmol) and TMP (1.5–4.0 equiv, see Table [1]) were added to a 25 mL round-bottomed flask equipped with a reflux condenser and CaCl2 drying tube, and the resulting mixture was stirred for 2–8 h at the temperature specified in Table [1]. Toluene (5 mL) was added to the crude product and the mixture vigorously stirred and heated to reflux for 5 min. The toluene layer was then decanted while hot, and the procedure was repeated a further four times. Any remaining solvent was removed by rotary evaporation (10 mbar, 70 °C, 4 h). The pure product was dried under vacuum (0.6 mbar, 100 °C, 8 h) and was subjected to AgNO3 analysis to confirm the absence of starting material.


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Procedure for the Synthesis of 1-(2-Methoxy-2-oxoethyl)-3-­methylimidazolium Dimethyl Phosphate (2c)

1-(2-Methoxy-2-oxoethyl)-3-methylimidazolium chloride (1c, 1.91 g, 10.0 mmol), TMP (2.80 g, 20.0 mmol), and MeCN (4 mL) were added to a 25 mL round-bottomed flask equipped with a reflux condenser and CaCl2 drying tube, and the resulting mixture was heated to reflux for 2 h. After completion of the reaction, the MeCN was removed by rotary evaporation (10 mbar, 60 °C, 4 h). Toluene (5 mL) was added to the residue, and the mixture vigorously stirred at r.t. for 5 min. The toluene layer was decanted, and this procedure was repeated a further four times. Any remaining solvent was removed by rotary evaporator (10 mbar, 60 °C, 4 h). The yellow oil was purified with activated charcoal in MeOH according to a known procedure.[17] The pure product was dried under vacuum (0.6 mbar, r.t., 24 h) over P2O5 and was subjected to AgNO3 analysis to confirm the absence of starting material. Colorless, viscous liquid 2c (2.76 g, 98%) was obtained.

All sealed flasks containing the synthesized IL were stored in a desiccator over P2O5.


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Selected Analytical Data


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1-(2-Methoxy-2-oxoethyl)-3-methylimidazolium Dimethyl Phosphate (2c)

1H NMR (400 MHz, DMSO-d 6): δ = 9.18 (s, 1 H), 7.73 (s, 2 H), 5.27 (s, 2 H), 3.91 (s, 3 H), 3.75 (s, 3 H), 3.24 (d, J = 10.3 Hz, 6 H). 13C NMR (100 MHz, DMSO-d 6): δ = 167.6, 138.3, 123.8, 123.4, 52.7, 51.3, 51.2, 49.3, 35.8. FTIR (ATR film): 2947, 1750, 1578, 1437, 1227, 1179, 1090, 1039, 775, 735, 707, 627 cm–1. ESI-HRMS: m/z calcd for C7H11N2O2 + [M+]: 155.0815; found: 155.0805.


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1,6-Bis(3-methylimidazolium-1-yl)hexane Bis(dimethyl Phosphate) (4a)

1H NMR (400 MHz, CDCl3): δ = 10.56 (s, 2 H), 7.74 (t, J = 1.8 Hz, 2 H), 7.37 (t, J = 1.7 Hz, 2 H), 4.31 (t, J = 7.2 Hz, 4 H), 4.00 (s, 6 H), 3.56 (d, J = 10.5 Hz, 12 H), 1.91 (t, J = 6.9 Hz, 4 H), 1.39 (t, J=  6.8 Hz, 4 H). 13C NMR (100 MHz, CDCl3): δ = 138.7, 123.3, 122.8, 52.8, 52.7, 49.2, 36.2, 29.3, 24.6. FTIR (ATR film): 2940, 2861, 2835, 1570, 1465, 1242, 1177, 1091, 1040, 769, 729, 656, 627 cm–1. ESI-HRMS: m/z calcd for C14H23N4 + [M+]: 247.1917; found: 247.1918.


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1,4-Bis(3-butylimidazolium-1-yl)butane Bis(dimethyl Phosphate) (4b)

1H NMR (400 MHz, D2O): δ = 8.79 (s, 2 H), 7.49 (d, J = 10.9 Hz, 4 H), 4.23 (s, 4 H), 4.18 (t, J = 7.1 Hz, 4 H), 3.55 (d, J = 10.1 Hz, 12 H), 1.87 (s, 4 H), 1.75–1.85 (m, 4 H), 1.27 (sext, J = 7.4 Hz, 4 H), 0.89 (t, J = 7.4 Hz, 6 H). 13C NMR (100 MHz, D2O): δ = 135.9, 123.2, 122.8, 53.4, 50.0, 49.3, 31.8, 26.9, 19.4, 13.2. FTIR (ATR film): 2940, 1565, 1465, 1241, 1172, 1091, 1043, 774, 732, 648 cm–1. ESI-HRMS: m/z calcd for C18H31N4 + [M+]: 303.2543; found: 303.2545.


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1,6-Bis[3-(2-hydroxyethyl)imidazolium-1-yl]hexane Bis(dimethyl Phosphate) (4c)

1H NMR (400 MHz, DMSO-d 6): δ = 9.37 (s, 2 H), 7.78 (dt, J = 9.9, 1.8 Hz, 4 H), 5.83 (s, 2 H), 4.23 (t, J = 5.0 Hz, 4 H), 4.17 (t, J = 7.2 Hz, 4 H), 3.71 (t, J = 5.1 Hz, 4 H), 3.28 (d, J = 10.4 Hz, 12 H), 1.79 (t, J = 6.8 Hz, 4 H), 1.26 (t, J = 6.9 Hz, 4 H). 13C NMR (100 MHz, DMSO-d 6): δ = 136.8, 122.8, 122.1, 59.3, 51.5, 48.5, 29.0, 24.7. FTIR (ATR film): 3080, 2944, 2840, 1565, 1460, 1233, 1172, 1088, 1038, 782, 735, 650 cm–1. ESI-HRMS: m/z calcd for C16H27N4O2 + [M+]: 307.2129; found: 307.2128.


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(2-Hydroxyethyl)trimethylammonium Dimethyl Phosphate (5)

1H NMR (400 MHz, DMSO-d 6): δ = 6.50 (s, 1 H), 3.77–3.84 (m, 2 H), 3.39–3.46 (m, 2 H), 3.29 (d, J = 10.4 Hz, 6 H), 3.13 (s, 9 H). 13C NMR (100 MHz, DMSO-d 6): δ = 67.0, 55.1, 53.1, 53.0, 51.4, 51.3. FTIR (ATR film): 3152, 2948, 2846, 1484, 1232, 1183, 1086, 1038, 1009, 952, 779, 736 cm–1. ESI-HRMS: m/z calcd for C5H14NO+ [M+]: 104.1070; found: 104.1077.


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Acknowledgment

This research was supported by the European Social Foundation (ESF), project Nr.1DP/1.1.1.2.0/13/APIA/VIAA/011. The authors gratefully acknowledge Dr. Ilva Nakurte (University of Latvia) for HRMS analyses, Mr. Toms Rekis and Mr. Agris Berzins (University of Latvia) for DTA/TG analyses, and Dr. Juris Popelis (Latvian Institute of Organic Synthesis) for NMR analyses.

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Zoom Image
Scheme 1 Synthesis of imidazolium-based monocationic and dicationic IL 2a–d and 4a–c via anion metathesis with trimethyl phosphate TMP