**4. Ionic liquids**

Ionic liquids (ILs), defined here as materials that are made up of cations and anions (salts) which melt at or below 100°C, evolved from the nineteenth century. This field started with a report by Paul Walden, in which he studied the physical properties of ethylammonium nitrate ([EtNH3][NO3]), a salt which melted at around 14°C [96]. Ionic liquids are commonly formed through the combination of an organic cation (usually heterocyclic), such as dialkylimidazolium, and either an inorganic or organic anion (such as halides or methanesulfonate) [97]. The advantage with ionic liquids is their low vapor pressure, meaning the risk of atmospheric contamination and related health issues are reduced by using these solvents. It is for this particular reason that they are viewed as green solvents [98]; however, low volatility alone is not the only property that makes ionic liquids green. For instance, toxic and non-biodegradable ionic liquids will not be referred to as a green solvent even though they have negligible volatility [97]. In this regard, ionic liquids composed of bio-derived components have the added advantage and are outstanding candidates as sustainable and green solvents.

### **4.1 Sugar-based ionic liquids**

Since the depolymerization of hard-to-dissolve carbohydrate polymers can be achieved using ILs, it would be beneficial to develop sugar-based ILs with the aim of employing these in a 'closed-loop' carbohydrate polymer depolymerization process [99]. Some sugar-based ionic liquids which have potential in this regard have already been synthesized, even though they have been used for various other processes. The glucose-linked 1,2,3-triazolium ionic liquids were synthesized by copper(I)-catalysed regioselective cycloaddition of a glucose azide to a glucose alkyne, followed by quaternization with methyl iodide (**Figure 6**) [100]. The ILs were used as reusable chiral solvents and ligands in copper(I)-catalysed amination of aryl halides with aqueous ammonia. The triazolium salt affords the compound in its liquid state at room temperature, and hence the compound can be used as a solvent, while the free hydroxyl groups of the glucose moiety aids in stabilizing the copper(I) species during the reaction.

Methyl-D-glucopyranoside has also been used to synthesize an ionic liquid with promising solvent potential [101]. The synthetic sequence involved uses thexyldimethylsilyl chloride (TDSCl) to protect the hydroxyl at the primary position. The other secondary hydroxyl groups were converted to methyl ethers followed by reduction of the anomeric position and further deprotection of the primary hydroxyl. After deprotection of the primary hydroxyl group, it was then converted to a triflate to form an intermediate. This triflate intermediate finally underwent a nucleophilic substitution reaction using diethyl sulphide to afford an ionic liquid, with a triflate anion and a sulfonium cation, which was a liquid at room temperature (**Figure 6**).

Handy et al. have used fructose to synthesize room temperature ionic liquids [102]. In their synthetic protocol, copper carbonate, ammonia and formaldehyde were used to ring-close fructose and form hydroxymethylene imidazole. This imidazole was then taken through a series of alkylation steps (with 1-bromobutane followed by iodomethane) to form an imidazolium cation. Anion metathesis was performed to give a series of room temperature ionic liquids (**Figure 7**), which were used as recyclable solvents for Mizoroki-Heck cross-coupling of aryl iodides with alkenes.

An arabinose-based imidazolium IL was synthesized in 2018 starting with 2,3,5-tri-*O*-benzyl-D-arabinofuranose [103]. The pentofuranoside starting material was prepared by benzylating all the hydroxyl groups of D-arabinose, except the hydroxyl group on the carbon adjacent the ring oxygen atom. The free hydroxyl group was then reacted with propane-1,3-diyldioxyphosphoryl chloride in the presence of 1-methylimidazole to form a mixture of anomeric phosphates. This was then reacted with 1-methylimidazolium chloride and trimethylsilyl triflate, in catalytic amounts, to give a pure anomeric ionic liquid with a chloride anion. Anion metathesis reactions gave two additional ionic liquids (**Figure 7**), which were used as co-solvents in the synthesis of alcohols from aromatic aldehydes.

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*Bio-Solvents: Synthesis, Industrial Production and Applications*

*DOI: http://dx.doi.org/10.5772/intechopen.86502*

**4.2 Alkaloid-based ionic liquids**

*ILs based on pentoses [(A) fructose-based ILs; (B) arabinose-based ILs].*

**Figure 6.**

**Figure 7.**

solvating agents (**Figure 8**) [106].

**4.3 Lipid-based ionic liquids**

Ionic liquids which contain ampicillin as active pharmaceutical ingredients

were developed by Ferraz et al., by neutralizing basic ammonia solutions of ampicillin with different organic cation hydroxides. These ampicillinbased ILs may be useful in the development of bioactive materials [104]. A chiral IL derived from ephedrine was synthesized by Wasserscheid et al. N-methylephedrine was synthesized from ephedrine and alkylated with dimethyl sulphate followed by ion exchange to form the IL, with a melting point of 54°C [105]. Heckel et al. reported the synthesis of ionic liquids derived from nicotine by the quaternization of the pyridine ring of nicotine with methyl iodide and ethyl bromide. The resulting chiral nicotine-based ILs were examined as chiral

*Glucose-based ionic liquids [(A and B) glucose-tagged triazolium ILs; (C) glucopyranoside-based IL].*

Linoleate and oleate were used in the syntheses of four ILs with melting points below −21°C (**Figure 9**). Unsaturated fatty acids were initially taken through neutralization reactions with NaOH followed by ion exchange with either *Bio-Solvents: Synthesis, Industrial Production and Applications DOI: http://dx.doi.org/10.5772/intechopen.86502*

**Figure 6.** *Glucose-based ionic liquids [(A and B) glucose-tagged triazolium ILs; (C) glucopyranoside-based IL].*

**Figure 7.**

*Solvents, Ionic Liquids and Solvent Effects*

candidates as sustainable and green solvents.

**4.1 Sugar-based ionic liquids**

copper(I) species during the reaction.

ture (**Figure 6**).

alkenes.

inorganic or organic anion (such as halides or methanesulfonate) [97]. The advantage with ionic liquids is their low vapor pressure, meaning the risk of atmospheric contamination and related health issues are reduced by using these solvents. It is for this particular reason that they are viewed as green solvents [98]; however, low volatility alone is not the only property that makes ionic liquids green. For instance, toxic and non-biodegradable ionic liquids will not be referred to as a green solvent even though they have negligible volatility [97]. In this regard, ionic liquids composed of bio-derived components have the added advantage and are outstanding

Since the depolymerization of hard-to-dissolve carbohydrate polymers can be achieved using ILs, it would be beneficial to develop sugar-based ILs with the aim of employing these in a 'closed-loop' carbohydrate polymer depolymerization process [99]. Some sugar-based ionic liquids which have potential in this regard have already been synthesized, even though they have been used for various other processes. The glucose-linked 1,2,3-triazolium ionic liquids were synthesized by copper(I)-catalysed regioselective cycloaddition of a glucose azide to a glucose alkyne, followed by quaternization with methyl iodide (**Figure 6**) [100]. The ILs were used as reusable chiral solvents and ligands in copper(I)-catalysed amination of aryl halides with aqueous ammonia. The triazolium salt affords the compound in its liquid state at room temperature, and hence the compound can be used as a solvent, while the free hydroxyl groups of the glucose moiety aids in stabilizing the

Methyl-D-glucopyranoside has also been used to synthesize an ionic liquid with

Handy et al. have used fructose to synthesize room temperature ionic liquids [102]. In their synthetic protocol, copper carbonate, ammonia and formaldehyde were used to ring-close fructose and form hydroxymethylene imidazole. This imidazole was then taken through a series of alkylation steps (with 1-bromobutane followed by iodomethane) to form an imidazolium cation. Anion metathesis was performed to give a series of room temperature ionic liquids (**Figure 7**), which were used as recyclable solvents for Mizoroki-Heck cross-coupling of aryl iodides with

An arabinose-based imidazolium IL was synthesized in 2018 starting with 2,3,5-tri-*O*-benzyl-D-arabinofuranose [103]. The pentofuranoside starting material was prepared by benzylating all the hydroxyl groups of D-arabinose, except the hydroxyl group on the carbon adjacent the ring oxygen atom. The free hydroxyl group was then reacted with propane-1,3-diyldioxyphosphoryl chloride in the presence of 1-methylimidazole to form a mixture of anomeric phosphates. This was then reacted with 1-methylimidazolium chloride and trimethylsilyl triflate, in catalytic amounts, to give a pure anomeric ionic liquid with a chloride anion. Anion metathesis reactions gave two additional ionic liquids (**Figure 7**), which were used

as co-solvents in the synthesis of alcohols from aromatic aldehydes.

promising solvent potential [101]. The synthetic sequence involved uses thexyldimethylsilyl chloride (TDSCl) to protect the hydroxyl at the primary position. The other secondary hydroxyl groups were converted to methyl ethers followed by reduction of the anomeric position and further deprotection of the primary hydroxyl. After deprotection of the primary hydroxyl group, it was then converted to a triflate to form an intermediate. This triflate intermediate finally underwent a nucleophilic substitution reaction using diethyl sulphide to afford an ionic liquid, with a triflate anion and a sulfonium cation, which was a liquid at room tempera-

**12**

*ILs based on pentoses [(A) fructose-based ILs; (B) arabinose-based ILs].*

### **4.2 Alkaloid-based ionic liquids**

Ionic liquids which contain ampicillin as active pharmaceutical ingredients were developed by Ferraz et al., by neutralizing basic ammonia solutions of ampicillin with different organic cation hydroxides. These ampicillinbased ILs may be useful in the development of bioactive materials [104]. A chiral IL derived from ephedrine was synthesized by Wasserscheid et al. N-methylephedrine was synthesized from ephedrine and alkylated with dimethyl sulphate followed by ion exchange to form the IL, with a melting point of 54°C [105]. Heckel et al. reported the synthesis of ionic liquids derived from nicotine by the quaternization of the pyridine ring of nicotine with methyl iodide and ethyl bromide. The resulting chiral nicotine-based ILs were examined as chiral solvating agents (**Figure 8**) [106].

## **4.3 Lipid-based ionic liquids**

Linoleate and oleate were used in the syntheses of four ILs with melting points below −21°C (**Figure 9**). Unsaturated fatty acids were initially taken through neutralization reactions with NaOH followed by ion exchange with either

**Figure 8.** *Alkaloid-based ILs [(A) ampicillin-based ILs; (B) ephedrine-based IL; (C) nicotine-based ILs].*

**Figure 9.**

*Anions and cations used in the syntheses of lipid-based ILs.*

**Figure 10.** *Lipid-based imidazolyl ILs.*

tetraoctylammonium or methyltrioctylammonium chloride. The ILs were then successfully used as solvents in the extraction of metal ions from aqueous solutions [107].

Kwan et al. also synthesized ILs using lipids through alkylating a tertiary amine (**Figure 10**). The lipids used in this instance were methyl oleate and methyl stearate. In a third instance, cyclopropanated oleic acid methyl ester synthesized the reaction of the double bond of the oleate with diiodomethane, and diethylzinc was used to alkylate the tertiary amine. After reacting the obtained alkyl iodide with the imidazoles, anion exchange of the iodide with bistriflimide gave imidazolium bistriflimide ILs [108].
