**2.6 Di-***tert***-alcohol-functionalized dicationic ionic liquid**

The same research group developed another dicationic protic ionic liquid for substitution reactions. A task-specific hexaethylene glycol bridged bis-cationic ionic liquid (BFIL) such as bis(2-hydroxy-2-methyl-n-propylimidazolium) dimesylate (hexaehtylene glycol chain-Dt OHIM) was prepared, and its role in nucleophilic substitution reactions using an alkali metal nucleophiles was investigated [13]. They also compared their activities with a variety of mono-cationic ILs and found that the hexaehtylene glycol chain-functionalized IL more effectively enhanced the reactivity of KX compared with the *tert*-alcohol-functionalized IL hexaehtylene glycol chain-Dt OHIM (**Figure 9**).

The use of bis-functionalized ionic liquid (BFIL) enhances the substitution reaction rate compared to conventional ionic liquid as well as mono-functionalized protic ionic liquid due to the higher activity of BFIL by the additional dicationic moieties compared with the mono-cationic ionic liquid methods. The author found that the hexaethylene glycol moiety of these hexaehtylene glycol chain-functionalized ILs enhances the reactivity of alkali metal fluorides by two effects; one is chelation effect with alkali metal cations, allowing the fluoride to become necked, and the other is the flexible fluoride influence by flexible H-bonding between the hydroxyl groups of BFIL, t-alcohol medium and nucleophile. In the case of t-alcohol-functionalized BFIL, the t-alcohol moiety showed selectively flexible H-bonding in the process. Subsequently,

**Figure 6.**

*Synthesis of polar-aprotic glycol substituted imidazolium ionic liquids. A) mono-glycol chain substituted IL, B) bis-glycol chain substituted IL.*

**Figure 7.**

*Di-functional polyether chain-substituted imidazolium IL.*

#### **Figure 8.**

*Fluorination reaction by using bis-glycol substituted ILs catalyst with various leaving groups. A) acyl bromide B) tosylate C) mesylate substrates.*

bi-alcohol-functionalized BFIL, having two imidazolium cations functionalized by ethylene glycol chain, showed the excellent catalytic increases in the reactivity of metal fluoride in the nucleophilic substitution among the monocationic convention ionic liquids. *Tert*-alcohol-funtionlaized ionic liquid not only enhances the nucleophilicity of ion but also reduces the formation of by-products alkene and ether.

The reaction of fluorination on another base-sensitive substrate of secondary alkyl tosylate using hexaehtylene glycol chain-DHIM with KF in *t*-amyl alcohol at 80°C got a better yield of the secondary fluoro-product (**Figure 10**).

**213**

**Figure 11.**

*Synthesis of various* tert*-butanol amines.*

*Protic Reaction Media for Nucleophilic Substitution Reactions*

*Tert*-butanol-functionalized amines were prepared as shown in **Figure 11**. The easy synthesis of this amine was solvent-free reaction of isobutylene oxide with respective

*Synthesis of novel bis-functionalized protic ionic liquids: (A) bis(3-hexaehtylene glycol chainyl imidazolium) dimesylate (hexaethylene glycol-DHIM) and (B) bis(2-hydroxy-2-methyl-n-propylimidazolium) dimesylate* 

as promoters with alkali metal salts in the nucleophilic fluorination of alkylsulfonates. It significantly enhances the reactivity of alkali metal salts with the minimum formation of side products (alkene, ether and alcohol) compared to conventional phase-transfer catalyst. The synergism of *tert*-alcohol and amine moiety plays a pivotal role in fluorination. Fluorination reactions on the secondary leaving group of natural steroid substrate, cholesterol that was successfully converted into 2-fluoro-cholesterol in

The reaction of OTf-containing substrate in the presence of promoter *t*-butanolamine was much faster in giving the desired fluoro-product. It gave good substitution reactions with other leaving groups such as O-tosylate and O-nosylate as shown in **Figure 13**. Substitution reactions with reactive substrate such as bromoacetophenone to fluoro acetophenone gave poor conversion of corresponding fluorinated product, **Figure 14**. It may be due to the *tert*-butanolamine that may react with acyl bromide

The reaction could be conducted in acetonitrile on a wide variety of substrates with little alkene formation observed. Further, Lee et al. studied the quantum chemical calculations of these substitution reactions and suggested that tris-*tert*-buntenolamine complexed the fluoride ion through multiple

BuOH)A, 1-[Ethyl(2-

BuOH)EtA) and

BuOH)EtA]. These protic amines act

amines to afford corresponding tri-*tert*-butanolamine [(tri-*<sup>t</sup>*

1-(diethylamino)-2-methyl-2-propanol [(mono-*<sup>t</sup>*

and form the corresponding quaternary salts.

reasonable good yield (**Figure 12**).

hydroxy-2-methylpropyl)amino]-2-methylpropan-2-ol [(di-*<sup>t</sup>*

*Fluorination on secondary tosylate using KF with hexaehtylene glycol chain-DHIM.*

*DOI: http://dx.doi.org/10.5772/intechopen.91395*

*OHIM).*

**Figure 9.**

**Figure 10.**

*(hexaethylene glycol-D<sup>t</sup>*

#### **2.7 Protic amine tri-***tert***-butanolamine**

Shinde et al. developed novel series of protic amines, i.e. tri-*tert*-butanol amine, which can be used as catalyst or media for substitution reactions [14].

#### **Figure 9.**

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

*Di-functional polyether chain-substituted imidazolium IL.*

bi-alcohol-functionalized BFIL, having two imidazolium cations functionalized by ethylene glycol chain, showed the excellent catalytic increases in the reactivity of metal fluoride in the nucleophilic substitution among the monocationic convention ionic liquids. *Tert*-alcohol-funtionlaized ionic liquid not only enhances the nucleophilicity of ion but also reduces the formation of

*Fluorination reaction by using bis-glycol substituted ILs catalyst with various leaving groups. A) acyl bromide* 

The reaction of fluorination on another base-sensitive substrate of secondary alkyl tosylate using hexaehtylene glycol chain-DHIM with KF in *t*-amyl alcohol at

80°C got a better yield of the secondary fluoro-product (**Figure 10**).

Shinde et al. developed novel series of protic amines, i.e. tri-*tert*-butanol amine, which can be used as catalyst or media for substitution reactions [14].

**212**

**Figure 8.**

**Figure 7.**

by-products alkene and ether.

*B) tosylate C) mesylate substrates.*

**2.7 Protic amine tri-***tert***-butanolamine**

*Synthesis of novel bis-functionalized protic ionic liquids: (A) bis(3-hexaehtylene glycol chainyl imidazolium) dimesylate (hexaethylene glycol-DHIM) and (B) bis(2-hydroxy-2-methyl-n-propylimidazolium) dimesylate (hexaethylene glycol-D<sup>t</sup> OHIM).*

**Figure 10.**

*Fluorination on secondary tosylate using KF with hexaehtylene glycol chain-DHIM.*

*Tert*-butanol-functionalized amines were prepared as shown in **Figure 11**. The easy synthesis of this amine was solvent-free reaction of isobutylene oxide with respective amines to afford corresponding tri-*tert*-butanolamine [(tri-*<sup>t</sup>* BuOH)A, 1-[Ethyl(2 hydroxy-2-methylpropyl)amino]-2-methylpropan-2-ol [(di-*<sup>t</sup>* BuOH)EtA) and 1-(diethylamino)-2-methyl-2-propanol [(mono-*<sup>t</sup>* BuOH)EtA]. These protic amines act as promoters with alkali metal salts in the nucleophilic fluorination of alkylsulfonates. It significantly enhances the reactivity of alkali metal salts with the minimum formation of side products (alkene, ether and alcohol) compared to conventional phase-transfer catalyst. The synergism of *tert*-alcohol and amine moiety plays a pivotal role in fluorination.

Fluorination reactions on the secondary leaving group of natural steroid substrate, cholesterol that was successfully converted into 2-fluoro-cholesterol in reasonable good yield (**Figure 12**).

The reaction of OTf-containing substrate in the presence of promoter *t*-butanolamine was much faster in giving the desired fluoro-product. It gave good substitution reactions with other leaving groups such as O-tosylate and O-nosylate as shown in **Figure 13**.

Substitution reactions with reactive substrate such as bromoacetophenone to fluoro acetophenone gave poor conversion of corresponding fluorinated product, **Figure 14**. It may be due to the *tert*-butanolamine that may react with acyl bromide and form the corresponding quaternary salts.

The reaction could be conducted in acetonitrile on a wide variety of substrates with little alkene formation observed. Further, Lee et al. studied the quantum chemical calculations of these substitution reactions and suggested that tris-*tert*-buntenolamine complexed the fluoride ion through multiple

**Figure 11.** *Synthesis of various* tert*-butanol amines.*

### *Photophysics, Photochemical and Substitution Reactions - Recent Advances*

**Figure 12.**

*Nucleophilic fluorination on secondary substrate with metal salts using* t*-butanolamine.*

*Fluorination on primary substrate in the presence of* t*-BuOH-amine.*

**Figure 14.** *Acyl bromide substitution reactions in presence of* tert*-butanol amine.*

O▬H⋯nucleophile▬hydrogen bonds during the nucleophilic substitution reaction [15]. The formation of such complex did not have an effect on the reactivity of nucleophilicity and gave a selective substituted product.
