A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability

Aschenbrenner

Balczewski

Biedron

Bradaric

Cassity

Chen

Dake

Ding

Dzygiel

Fraser

Hyang

Jiangou Yu

Kuchenbuch

Liaw

Mark A. Honey

Nazira Karodia

Olivier-Bourbigou

Richard T. Wheelhouse

Singh

Sowmiah

Welton

Wilkes

Journal of Molecular Liquids

Crossref

Synthesis and characterisation of novel nopyl-derived phosphonium ionic liquids

Yu, Jiangou

Wheelhouse, Richard T.

Honey, Mark A.

Karodia, Nazira

Greenwich Academic Literature Archive

Synthesis and Characterization of Novel Nopyl-Derived Phosphonium Ionic Liquids Jiangou Yu,a Richard T. Wheelhouse,a Mark A. Honeyb* and Nazira Karodiac* a) Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, University of Bradford, BRADFORD, BD7 1DP, UK. b) School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Kent, ME4 4TB, UK c) Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, United Kingdom Email: m.a.honey@gre.ac.uk; Nazira.Karodia@wlv.ac.uk  Abstract A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.  Key Words Ionic liquid; phosphonium; chiral; nopyl-derivative Introduction The use of ionic liquids (ILs) as both reagents and solvents has seen significant interest in recent years and has been the subject of a recent review.1 ILs offer a number of advantages in comparison with conventional organic solvents, advantages including: chemical and thermal stability,2 no measurable vapour pressure,3 low-combustibility4 and catalytic ability.5 Moreover, studies of the involvement of ILs in catalytic transformations have demonstrated their ability to exert unique thermodynamic and kinetic effects within a reaction system, with some ILs increasing the efficiency and selectivity of known transformations in comparison with the same transformations conducted in conventional solvents.5 As such, the use of ILs as alternative media for organic chemistry, as well as other applications such as chemical separations, analytical chemistry amongst others is increasing.1  Chiral ionic liquids (CILs), where chirality is built into the IL itself, have facilitated chiral induction in a range of chemical transformations.6 The use of CILs as a medium for asymmetric synthesis is one example of their many uses – others include chiral separation of racemates,7 stereoselective polymerizations8 and gas chromatography.9  The preparation of CILs has historically proven difficult, but their potential utility across a range of applications has driven  the development of more reliable and reproducible syntheses.1 CILs are typically synthesised from chiral building blocks from a natural chiral pool (e.g. amino acids, amines, amino alcohols and alkaloids etc.)10 or via asymmetric synthesis, depending on the component of the IL that contains the chiral centre.11 As CILs have two components (the cation and anion), there are three possible combinations for introducing chirality, which can be classified as:   chiral cation, chiral anion, and [chiral cation + chiral anion] diastereomeric salt. One of the most widely investigated classes of ILs is the  imidazolium anion family  which has found wide-spread utility since their initial development in 1982.12,13 Although widely applied, including use in asymmetric synthesis, they can sometimes display undesirable behaviour, being unstable under harsh conditions and having relatively high decomposition rates with each reaction cycle.14 Phosphonium salt ILs offer advantages over their imidazolium counterparts as they generally show greater thermal stability (due to a lack of the acidic hydrogen found on imidazolium variants) and as such, show less decomposition per reaction cycle.15,16   The relative stability of phosphonium ionic liquids (PILs) makes them an attractive alternative for numerous synthetic applications, and yet they remain under-explored.   The core component of PILs is the phosphonium cation, containing phosphorous bonded to four substituents. This phosphonium cation is associated with a counter anion and these salts can be represented by the generic formula [PR1R2R3R4][X].  There are two main strategies to include chirality at the phosphonium cation; the chirality can be at the phosphorus centre [PR1R2R3R4]+ [X]– (where R1,R2,R3,R4 are not equivalent), or can be located on one or more of the phosphorous-bound substituents, see Figure 1.    Figure 1: Chirality residing on substituent (left) and inherent chirality due to inequivalent substituents (right)  Chiral PILs (CPILs) with chirality located on a phosphorous-bound substituent offer several advantages over chiral phosphorus centres - phosphines such as Ph3P, n-Bu3P, i-Bu3P, n-Oct3P, which are low cost and commercially available, can be used, avoiding the need to selectively substitute four separate alkyl groups at the phosphorus centre, a potentially complicated and costly process.  The synthesis of tetraalkylphosphonium ILs [R*PR3][X] would proceed via nucleophilic substitution an appropriate electrophile by a tertiary phosphine. Derivatives of (R)-nopol (Figure 2) have previously been utilized as the electrophile - these studies have shown that this low-cost terpineol, available as a single enantiomer,  can be incorporated into imidazolium ILs with the leaving group, which will form the counter anion, being easily manipulated.17 (R)-Nopol has also demonstrated an ability to interact stereospecifically with (S)--pinene when incorporated into a chiral membrane, which gives promise for its potential application in asymmetric synthesis when utilised in an ionic liquid.18 With the above in mind, and the knowledge that there are no previous reports of the synthesis of phosphonium ionic liquids derived from (R)-nopol, and as such we report herein the synthesis and characterisation of 16 novel nopyl-derived PILs.   Figure 2: (1R)-(-)-Nopol  Results and Discussion Novel nopyl-PILs were prepared as shown in Scheme 1 A-D. Depending on the desired counter anion, the alcohol on (R)-nopol was converted to the appropriate precursor functional group. In order to synthesise the mesylate or esylate ILs, (R)-nopol was reacted with either mesyl chloride or esyl chloride respectively, followed by treatment with the appropriate trialkyl phosphine, producing the target ILs in good yields (79-85%, Scheme 1A). Phosphonium chlorides were synthesised by an initial Appel reaction to convert the alcohol to the alkyl chloride, followed by nucleophilic substitution with the corresponding phosphine (Scheme 1B). Bromides were synthesised by treatment of the alcohol with SOBr2 followed by displacement with a phosphine to produce these ILs in up to 55% yield (Scheme 1C). The approach to tetrafluoroborate and hexafluorophosphate ILs was slightly different – an initial reaction of the iodo-nopol derivative was reacted with the appropriate alkyl phosphine to give the intermediates approximately 84% yield, followed by successful ion exchange with sodium tetrafluoroborate or hexafluorophosphate salts to form the desired ILs in excellent yield (70-95%, Scheme 1D).  Scheme 1. A-D Synthesis of nopyl-phosphonium ionic liquids  Characterisation and Stability Studies   IL R X Yield (%) Form at 25 oC δp δF P-C stretch / cm–1 Anion stretch  / cm–1 Measured mass Calculated mass 1 Bu Cl 37 oil 34.17 - 1463 - 387.2968 387.2955 2 Oct Cl 19 oil 33.75 - 1464 - 555.4787 555.4763 3 Bu Br 36 oil 33.95 - 1465 - 431.2456 431.2450 4 Oct Br 55 oil 33.87 - 1465 - 599.4244 599.4238 5 Bu I 83 oil 33.87 - 1466 - 479.2311 479.2298 6 Oct I 84 oil 33.68 - 1467 - 647.4211 647.4176 7 Bu OTs 91 oil 33.95 - 1470 1131 (S=O) 523.3403 523.3369 8 Oct OTs 71 oil 33.84 - 1470 1131 (S=O) 691.5238 691.5247 9 Bu OMs 79 oil 34.02 - 1464 1125 (S=O) 447.3077 447.3056 10 Oct OMs 80 oil 33.86 - 1465 1123 (S=O) 615.4921 615.4934 11 Bu OEs 79 oil 34.04 - 1464 1124 (S=O) 461.3255 461.3213 12 Oct OEs 85 oil 33.89 - 1465 1123 (S=O) 629.5125 629.5091 13 Bu PF6 90 wax 34.00 –71.92 1465 849 (P–F) - - 14 Oct PF6 70 wax 33.94 –71.73 1466 848 (P–F) 627.4737 627.4751 15 Bu BF4 94 oil 34.06 –150 1464 1227 (B–F) 439.3245 439.3240 16 Oct BF4 95 oil 33.87 –150 1465 1226 (B–F) 607.5155 607.5164  Table 1: Collated physical data for the new ionic liquids.  Form, 31P and 19F NMR Most of the nopyl PILs are oils at room temperature, with the exception of the PF6- salts, which are waxes, and as such can potentially be used as solvents for processes requiring elevated reaction temperatures. 31P NMR spectroscopy was employed to monitor the quaternarization of the tertiary phosphine as formation of the phosphonium salt was a key diagnostic indicator for successful synthesis; the 31P NMR resonances of the starting alkyl and aryl phosphines typically displayed a single peak between -30 ppm and -5 ppm, with the quaternary phosphonium salts appearing at around +34 ppm. The presence of a single peak in the 31P NMR spectra of the newly synthesised compounds showed that the liquids contained phosphonium ions only. New ILs containing fluorine counterions, clear fluorine resonances could be seen by 19F NMR spectroscopy, and so confirmed that ionic exchange had successfully occurred.   1H and 13C NMR Spectroscopy The 1H and 13C NMR data detailed in the supporting information fully agree with the structures of each synthesised IL.   Infrared Spectroscopy Analysis of the IR spectra of all PILs (Table 1) showed characteristic strong absorption bands for P—C bond stretching at approximately 1460 cm–1. The phosphonium liquids containing mesyl and esyl anions showed the appropriate S=O stretch at approximately 1125 cm–1, and S—H stretching at approximately 985 cm–1. B—F and P—F stretches are visible at 1225 cm–1 and 850 cm–1 respectively for the liquids containing BF4- and PF6- counterions respectively.  Mass Spectrometry High resolution mass-spectrometry measurements are presented in Table 3. Often phosphonium ionic liquids exhibit both the naked cation and the undissociated ion pair, for example, the characteristic fragmentation pattern of NopylPBu3OMs is: [NopylPBu3] at m/e=351 and [NopylPBu3]·[OMs] at m/e=447. The figures quoted in Table 1 correspond to the observed masses for the cation-anion pair, with each example showing the correct mass for the corresponding IL.  Thermogravimetric Analysis  To establish the suitability of the ILs for use at elevated temperatures, their thermal stability was studied by thermogravimetric analysis (TGA). In common with other ILs, PILs do not boil at high temperatures but do show upper limits to thermal stability. TGA data for each of the new ILs are presented in in Figures 3 and 4. Each graph shows the percentage mass loss as a function of temperature with the test material being heated at a rate of 5 °C min–1, to a maximum temperature of 450 °C. The collated data indicate that the majority of the new ILs are stable to approximately 300 °C for the PBu3 series, and to approximately 200 - 250 °C for the POct3 derivatives. For both sets of compounds, initial weight loss around 110 °C was the result of volatile material such as residual toluene evaporating and thus does not represent true decomposition. Within the two series, stability dependence on the nature of the anion followed similar overall trends with PF6- and  BF4- being the most stable (50% mass loss at approx. 400 °C for the PBu3 series and up to 420 °C for NopylPOct3BF4); the bromide and iodide salts were the least stable (50% mass loss around 360 °C for the PBu3 and 340 °C for the POct3 series), with the sulfonate salts displaying varying stabilities.    Figure 3. TGA data for the tributylphosphonium series of ILs. The graph shows (%) mass change with increasing temperature (5 °C min-1) for NopylPBu3PF6, NopylPBu3BF4, NopylPBu3Br, NopylPBu3OEs, NopylPBu3I, NopylPBu3OMs and NopylPBu3OTs.   Figure 4. TGA data for the trioctylphosphonium series of ILs. The graph shows (%) mass change with increasing temperature (5 °C min-1) for NopylPOct3PF6, NopylPOct3BF4, NopylPOct3Br, NopylPOct3OEs, NopylPOct3I, NopylPOct3OMs, NopylPOct3OTs.    Differential Scanning Calorimetry  The nopyltributyl and nopyltrioctyl PILs showed no freezing point or melting point. Large heat flow changes were observed for the BF4 nopyl PILs; the smallest changes were noticed for the PF6 nopyl PILs.   Figure 5: DSC profiles (wg-1 vs T (C)) of tributyl nopyl PILs (NopylPBu3PF6, NopylPBu3BF4, NopylPBu3Br, NopylPBu3OEs, NopylPBu3I, NopylPBu3OMs, NopylPBu3OTs).    Figure 6: DSC profiles (wg-1 vs T (C) of PILs trioctyl Nopyl PILs (NopylPOct3PF6, NopylPOct3BF4, NopylPOct3Br, NopylPOct3OEs, NopylPOct3I, NopylPOct3OMs, NopylPOct3OTs).  Conclusions The synthesis and physical characteristics of 16 novel nopol-derived, chiral phosphonium ionic liquids has been reported. These ionic liquids were isolated in good yields, in high purity with each showing good thermal stability and desirable physical properties. Overall, the Bu3P series is more stable than the POct3 by approx. 30 °C; both series appear suitable for applications up to 300 °C, with the PF6– salts offering scope to extend the working temperature towards 400 °C. The application of these ionic liquids in catalysis and chiral induction, as well as their biological effects on multidrug-resistant bacterial cell lines is currently being investigated within our laboratories and will be reported in due course. Funding This work was funded by the University of Bradford (UK) Notes and references 1 T. Welton, Biophys. Rev., 2018, 10, 691-706. 2 (a) S. Sowmiah, V. Srinivasadesikan, M.-C. Tseng and Y.-H. Chu, Molecules, 2009, 14, 3780-3813; (b) C. G. Cassity, A. Mirjafari, N. Mobarrez, K. Strickland, R. A. O’Brien and J. H. Davis Jr, Chem. Commun., 2013, 49, 7590-7592. 3 O. Aschenbrenner, S. Supasitmongkol, M. Taylor and P. Styring, Green Chem., 2009, 11, 1217-1221. 4 H.-J. Liaw, C.-C. Chen, Y.-C. Chen, J.-R. Chen, S.-K. Huang and S.-N. Liu, Green Chem., 2012, 14, 2001-2008. 5 H. Olivier-Bourbigou, L. Magna and D. Morvan, Applied Catalysis A: General, 2010, 373, 1-56. 6 A. Kuchenbuch and R. Giernoth, ChemistryOpen, 2015, 4, 677-681. 7 S. He, Y. He, L. Cheng, Y. Wu and Y. Ke, Chirality, 2018, 30, 670-679. 8 T. Biedron and P. Kubisa, J. Polym. Sci. Part A: Polym. Chem., 2005, 43, 3454-3459. 9 J. Ding, T. Welton and D. W. Armstrong, Anal. Chem., 2004, 76, 6819-6822. 10 X. Chen, X. Li, A. Hu and F. Wang, Tetrahedron: Asymmetry, 2008, 19, 1-14. 11 A. Singh and H. K. Chopra, Current Organic Synthesis, 2017, 14, 488-510. 12 J. S. Wilkes, J. A. Levisky, R. A. Wilson and C. L. Hussey, Inorg. Chem., 1982, 21, 1263-1264. 13 S. A. Dake, S. R. Sarda, R. P. Marathe, R. B. Nawale, U. A. Deokate, A. A. Khadabadi and R. P. Pawar, Imidazolium Ionic Liquids: An Environment-Friendly Medium for Various Applications, ed. K. Ameta and A. Dandia, Springer, New Delhi, 2014, 201-230. 14 G. Hyang, W.-C. Lin, P. He, Y. Pan and C.-M. Shu, Journal of Molecular Liquids, 2018, 272, 37-42. 15 K. J. Fraser and D. R. MacFarlane, Aust. J. Chem., 2009, 62, 309-321. 16 C. J. Bradaric, A. Downard, C. Kennedy, A. J. Robertson and Y. Zhou, Green Chem., 2003, 5, 143-152. 17 P. Balczewski, B. Bachowska, T. Bialas, R. Biczak, W. M. Wieczorek and A. Balinska, J. Agric. Food Chem., 2007, 55, 1881-1892. 18 P. Dzygiel, P. Wieczorek and P. Kafarski, J. Sep. Sci., 2003, 26, 1050-1056. 

Synthesis and characterisation of novel nopyl-derived phosphonium

ionic liquids

This is an accepted manuscript of an article published by Elsevier in Journal of Molecular Liquids on 18/07/2020, available online: https://doi.org/10.1016/j.molliq.2020.113857 
The accepted version of the publication may differ from the final published version.A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.Published versio

Wheelhouse, Richard T

Honey, Mark A

Wolverhampton Intellectual Repository and E-theses

YesA series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.The full-text of this article will be released for public view at the end of the publisher embargo on 19 Jul 2021

Honey, M.A.

Karodia, N.

Bradford Scholars

Synthesis and Characterization of Novel Nopyl-Derived Phosphonium Ionic Liquids Jiangou Yu,a Richard T. Wheelhouse,a Mark A. Honeyb* and Nazira Karodiac* a) Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, University of Bradford, BRADFORD, BD7 1DP, UK. b) School of Science, Faculty of Engineering and Science, University of Greenwich, Chatham, Kent, ME4 4TB, UK c) Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, United Kingdom Email: m.a.honey@gre.ac.uk; Nazira.Karodia@wlv.ac.uk  Abstract A series of novel nopyl-derived chiral phosphonium ionic liquids have been successfully synthesised and characterised. Analysis of each novel ionic liquid was conducted in order to confirm structure, purity and thermal stability.  Key Words Ionic liquid; phosphonium; chiral; nopyl-derivative Introduction The use of ionic liquids (ILs) as both reagents and solvents has seen significant interest in recent years and has been the subject of a recent review.1 ILs offer a number of advantages in comparison with conventional organic solvents, advantages including: chemical and thermal stability,2 no measurable vapour pressure,3 low-combustibility4 and catalytic ability.5 Moreover, studies of the involvement of ILs in catalytic transformations have demonstrated their ability to exert unique thermodynamic and kinetic effects within a reaction system, with some ILs increasing the efficiency and selectivity of known transformations in comparison with the same transformations conducted in conventional solvents.5 As such, the use of ILs as alternative media for organic chemistry, as well as other applications such as chemical separations, analytical chemistry amongst others is increasing.1  Chiral ionic liquids (CILs), where chirality is built into the IL itself, have facilitated chiral induction in a range of chemical transformations.6 The use of CILs as a medium for asymmetric synthesis is one example of their many uses – others include chiral separation of racemates,7 stereoselective polymerizations8 and gas chromatography.9  The preparation of CILs has historically proven difficult, but their potential utility across a range of applications has driven  the development of more reliable and reproducible syntheses.1 CILs are typically synthesised from chiral building blocks from a natural chiral pool (e.g. amino acids, amines, amino alcohols and alkaloids etc.)10 or via asymmetric synthesis, depending on the component of the IL that contains the chiral centre.11 As CILs have two components (the cation and anion), there are three possible combinations for introducing chirality, which can be classified as:   chiral cation, chiral anion, and [chiral cation + chiral anion] diastereomeric salt. One of the most widely investigated classes of ILs is the  imidazolium anion family  which has found wide-spread utility since their initial development in 1982.12,13 Although widely applied, including use in asymmetric synthesis, they can sometimes display undesirable behaviour, being unstable under harsh conditions and having relatively high decomposition rates with each reaction cycle.14 Phosphonium salt ILs offer advantages over their imidazolium counterparts as they generally show greater thermal stability (due to a lack of the acidic hydrogen found on imidazolium variants) and as such, show less decomposition per reaction cycle.15,16   The relative stability of phosphonium ionic liquids (PILs) makes them an attractive alternative for numerous synthetic applications, and yet they remain under-explored.   The core component of PILs is the phosphonium cation, containing phosphorous bonded to four substituents. This phosphonium cation is associated with a counter anion and these salts can be represented by the generic formula [PR1R2R3R4][X].  There are two main strategies to include chirality at the phosphonium cation; the chirality can be at the phosphorus centre [PR1R2R3R4]+ [X]– (where R1,R2,R3,R4 are not equivalent), or can be located on one or more of the phosphorous-bound substituents, see Figure 1.    Figure 1: Chirality residing on substituent (left) and inherent chirality due to inequivalent substituents (right)  Chiral PILs (CPILs) with chirality located on a phosphorous-bound substituent offer several advantages over chiral phosphorus centres - phosphines such as Ph3P, n-Bu3P, i-Bu3P, n-Oct3P, which are low cost and commercially available, can be used, avoiding the need to selectively substitute four separate alkyl groups at the phosphorus centre, a potentially complicated and costly process.  The synthesis of tetraalkylphosphonium ILs [R*PR3][X] would proceed via nucleophilic substitution an appropriate electrophile by a tertiary phosphine. Derivatives of (R)-nopol (Figure 2) have previously been utilized as the electrophile - these studies have shown that this low-cost terpineol, available as a single enantiomer,  can be incorporated into imidazolium ILs with the leaving group, which will form the counter anion, being easily manipulated.17 (R)-Nopol has also demonstrated an ability to interact stereospecifically with (S)--pinene when incorporated into a chiral membrane, which gives promise for its potential application in asymmetric synthesis when utilised in an ionic liquid.18 With the above in mind, and the knowledge that there are no previous reports of the synthesis of phosphonium ionic liquids derived from (R)-nopol, and as such we report herein the synthesis and characterisation of 16 novel nopyl-derived PILs.   Figure 2: (1R)-(-)-Nopol  Results and Discussion Novel nopyl-PILs were prepared as shown in Scheme 1 A-D. Depending on the desired counter anion, the alcohol on (R)-nopol was converted to the appropriate precursor functional group. In order to synthesise the mesylate or esylate ILs, (R)-nopol was reacted with either mesyl chloride or esyl chloride respectively, followed by treatment with the appropriate trialkyl phosphine, producing the target ILs in good yields (79-85%, Scheme 1A). Phosphonium chlorides were synthesised by an initial Appel reaction to convert the alcohol to the alkyl chloride, followed by nucleophilic substitution with the corresponding phosphine (Scheme 1B). Bromides were synthesised by treatment of the alcohol with SOBr2 followed by displacement with a phosphine to produce these ILs in up to 55% yield (Scheme 1C). The approach to tetrafluoroborate and hexafluorophosphate ILs was slightly different – an initial reaction of the iodo-nopol derivative was reacted with the appropriate alkyl phosphine to give the intermediates approximately 84% yield, followed by successful ion exchange with sodium tetrafluoroborate or hexafluorophosphate salts to form the desired ILs in excellent yield (70-95%, Scheme 1D).  Scheme 1. A-D Synthesis of nopyl-phosphonium ionic liquids  Characterisation and Stability Studies   IL R X Yield (%) Form at 25 oC δp δF P-C stretch / cm–1 Anion stretch  / cm–1 Measured mass Calculated mass 1 Bu Cl 37 oil 34.17 - 1463 - 387.2968 387.2955 2 Oct Cl 19 oil 33.75 - 1464 - 555.4787 555.4763 3 Bu Br 36 oil 33.95 - 1465 - 431.2456 431.2450 4 Oct Br 55 oil 33.87 - 1465 - 599.4244 599.4238 5 Bu I 83 oil 33.87 - 1466 - 479.2311 479.2298 6 Oct I 84 oil 33.68 - 1467 - 647.4211 647.4176 7 Bu OTs 91 oil 33.95 - 1470 1131 (S=O) 523.3403 523.3369 8 Oct OTs 71 oil 33.84 - 1470 1131 (S=O) 691.5238 691.5247 9 Bu OMs 79 oil 34.02 - 1464 1125 (S=O) 447.3077 447.3056 10 Oct OMs 80 oil 33.86 - 1465 1123 (S=O) 615.4921 615.4934 11 Bu OEs 79 oil 34.04 - 1464 1124 (S=O) 461.3255 461.3213 12 Oct OEs 85 oil 33.89 - 1465 1123 (S=O) 629.5125 629.5091 13 Bu PF6 90 wax 34.00 –71.92 1465 849 (P–F) - - 14 Oct PF6 70 wax 33.94 –71.73 1466 848 (P–F) 627.4737 627.4751 15 Bu BF4 94 oil 34.06 –150 1464 1227 (B–F) 439.3245 439.3240 16 Oct BF4 95 oil 33.87 –150 1465 1226 (B–F) 607.5155 607.5164  Table 1: Collated physical data for the new ionic liquids.  Form, 31P and 19F NMR Most of the nopyl PILs are oils at room temperature, with the exception of the PF6- salts, which are waxes, and as such can potentially be used as solvents for processes requiring elevated reaction temperatures. 31P NMR spectroscopy was employed to monitor the quaternarization of the tertiary phosphine as formation of the phosphonium salt was a key diagnostic indicator for successful synthesis; the 31P NMR resonances of the starting alkyl and aryl phosphines typically displayed a single peak between -30 ppm and -5 ppm, with the quaternary phosphonium salts appearing at around +34 ppm. The presence of a single peak in the 31P NMR spectra of the newly synthesised compounds showed that the liquids contained phosphonium ions only. New ILs containing fluorine counterions, clear fluorine resonances could be seen by 19F NMR spectroscopy, and so confirmed that ionic exchange had successfully occurred.   1H and 13C NMR Spectroscopy The 1H and 13C NMR data detailed in the supporting information fully agree with the structures of each synthesised IL.   Infrared Spectroscopy Analysis of the IR spectra of all PILs (Table 1) showed characteristic strong absorption bands for P—C bond stretching at approximately 1460 cm–1. The phosphonium liquids containing mesyl and esyl anions showed the appropriate S=O stretch at approximately 1125 cm–1, and S—H stretching at approximately 985 cm–1. B—F and P—F stretches are visible at 1225 cm–1 and 850 cm–1 respectively for the liquids containing BF4- and PF6- counterions respectively.  Mass Spectrometry High resolution mass-spectrometry measurements are presented in Table 3. Often phosphonium ionic liquids exhibit both the naked cation and the undissociated ion pair, for example, the characteristic fragmentation pattern of NopylPBu3OMs is: [NopylPBu3] at m/e=351 and [NopylPBu3]·[OMs] at m/e=447. The figures quoted in Table 1 correspond to the observed masses for the cation-anion pair, with each example showing the correct mass for the corresponding IL.  Thermogravimetric Analysis  To establish the suitability of the ILs for use at elevated temperatures, their thermal stability was studied by thermogravimetric analysis (TGA). In common with other ILs, PILs do not boil at high temperatures but do show upper limits to thermal stability. TGA data for each of the new ILs are presented in in Figures 3 and 4. Each graph shows the percentage mass loss as a function of temperature with the test material being heated at a rate of 5 °C min–1, to a maximum temperature of 450 °C. The collated data indicate that the majority of the new ILs are stable to approximately 300 °C for the PBu3 series, and to approximately 200 - 250 °C for the POct3 derivatives. For both sets of compounds, initial weight loss around 110 °C was the result of volatile material such as residual toluene evaporating and thus does not represent true decomposition. Within the two series, stability dependence on the nature of the anion followed similar overall trends with PF6- and  BF4- being the most stable (50% mass loss at approx. 400 °C for the PBu3 series and up to 420 °C for NopylPOct3BF4); the bromide and iodide salts were the least stable (50% mass loss around 360 °C for the PBu3 and 340 °C for the POct3 series), with the sulfonate salts displaying varying stabilities.    Figure 3. TGA data for the tributylphosphonium series of ILs. The graph shows (%) mass change with increasing temperature (5 °C min-1) for NopylPBu3PF6, NopylPBu3BF4, NopylPBu3Br, NopylPBu3OEs, NopylPBu3I, NopylPBu3OMs and NopylPBu3OTs.   Figure 4. TGA data for the trioctylphosphonium series of ILs. The graph shows (%) mass change with increasing temperature (5 °C min-1) for NopylPOct3PF6, NopylPOct3BF4, NopylPOct3Br, NopylPOct3OEs, NopylPOct3I, NopylPOct3OMs, NopylPOct3OTs.  Differential Scanning Calorimetry  The nopyltributyl and nopyltrioctyl PILs showed no freezing point or melting point. Large heat flow changes were observed for the BF4 nopyl PILs; the smallest changes were noticed for the PF6 nopyl PILs.   Figure 5: DSC profiles (wg-1 vs T (C)) of tributyl nopyl PILs (NopylPBu3PF6, NopylPBu3BF4, NopylPBu3Br, NopylPBu3OEs, NopylPBu3I, NopylPBu3OMs, NopylPBu3OTs).    Figure 6: DSC profiles (wg-1 vs T (C) of PILs trioctyl Nopyl PILs (NopylPOct3PF6, NopylPOct3BF4, NopylPOct3Br, NopylPOct3OEs, NopylPOct3I, NopylPOct3OMs, NopylPOct3OTs). Conclusions The synthesis and physical characteristics of 16 novel nopol-derived, chiral phosphonium ionic liquids has been reported. These ionic liquids were isolated in good yields, in high purity with each showing good thermal stability and desirable physical properties. Overall, the Bu3P series is more stable than the POct3 by approx. 30 °C; both series appear suitable for applications up to 300 °C, with the PF6– salts offering scope to extend the working temperature towards 400 °C. The application of these ionic liquids in catalysis and chiral induction, as well as their biological effects on multidrug-resistant bacterial cell lines is currently being investigated within our laboratories and will be reported in due course. Funding This work was funded by the University of Bradford (UK) Notes and references 1 T. Welton, Biophys. Rev., 2018, 10, 691-706. 2 (a) S. Sowmiah, V. Srinivasadesikan, M.-C. Tseng and Y.-H. Chu, Molecules, 2009, 14, 3780-3813; (b) C. G. Cassity, A. 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Synthesis and Characterization of Novel Nopyl-Derived Phosphonium Ionic Liquids

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Synthesis and characterisation of novel nopyl-derived phosphonium ionic liquids

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