1- Methylimidazole, ionic liquid processing

In the BASF BASIL process that utilizes A-methylimidazole to scavenge HCl byproduct, the acidic ionic liquid A-methylimidazolium chloride [HMIMJCl was formed, with a melting point of 75°C (13,102). Recently, the group of Bronsted acidic ionic liquids with the same cation was extended to include other anions, such as BFF, TfO , and TsO . The melting point of the salt is between 30 and 109°C. Strong hydrogen bonding in the tosylate salt was characterized by IR spectroscopy. 

BASF s original acid scavenger, triethylamine, created viscosity and work-up problems because of the need to maintain anhydrous conditions. BASF s use of 1-methylimidazole instead of triethylamine, at their reaction temperature of 80°C, led to the formation of two liquid phases, an upper diethoxyphenylphosphine phase, and a lower methylimidazolium chloride phase (fortuitously, this ionic liquid melts at 75°C ). Moreover, methylimidazolium chloride proved to be a nucleophilic catalyst. The processing revolution generated by these discoveries enabled creation of a high-productivity continuous process for diethoxyphenylphosphine manufacture and created a whole new business in acid scavenging technology. 

One large scale application of an ionic liquid is as a base to remove HCl during the preparation of alkoxyphenylphosphines. BASF use V-methylimidazole which forms the ionic liquid [Hmim]Cl and forms a second liquid layer that may easily be removed from the system and recycled via phase separation. Although the ionic liquid is not employed as a solvent, the process makes use of biphasic technology to give a more efficient process which avoids an inconvenient filtration step. 

In March 2003, the use was reported of ionic liquids in a commercial process by BASF. The reaction of phenylchlorophosphines and ethanol forms alkoxyphenylphosphines 109 along with HCl, which is scavenged by A-methylimidazole (Scheme 48). The [hmim][Cl] salt 110 formed is an ionic liquid with a melting point of 75°C this leads to a biphasic mixture, which can be more easily stirred than a solution containing a suspension. This ionic liquid also acts as catalyst for this process of biphasic acid scavenging utilizing ionic liquids... 

Compared to amines, which have traditionally been used as HQ-scavengers in this type of readion, the BASF process based on 1-methylimidazole circumvents the problematic, time-consuming and expensive filtration of a solid ammonium hydrochloride cake by yielding an ionic liquid, the 1-methylimidazolinium... 

Ionic liquid synthesis is usually performed solvent-free by means of the Menschut-kin reaction, i.e. the two reactants (typically abase and an alkyl derivative with leaving group) are mixed and react in the liquid state and yield the liquid product, with almost complete conversion. The challenge for some of these reactions, such as the conversion of methylimidazole and diethyl sulfate (adiabatic temperature rise 173 K) is the high exothermicity under the high reaction rate [25]. This leads to considerable hot-spot formation with sudden temperature jumps of 100 °C and more. This adversely affects the product quality, as is easily visible by a coloring to yellowish or even brown, and places restrictions on safe process optimization. For these reasons, the reactions may be carried out more slowly than kinetically possible to allow for sufEcient heat transfer. 

After the reaction, there are two clear liquid phases that can easily be worked up by a simple phase separation. The upper phase is the pure product and no reaction solvent is needed. The lower phase is the pure Ionic Liquid and can be deprotonated with sodium hydroxide, regenerating the methylimidazole (Fig. 20.13). Comparing to the conventional method (Fig. 20.14a), BASIL process uses a much smaller reactor (Fig. 20.14b). 

The first industrial process to involve ionic liquids was introduced by BASF in 2002. Called BASIL", this technology addresses the problem of HCl formed as a byproduct in the synthesis of alkoxyphenylphosphanes (eq. 9.86). Before the advent of ionic liquids, HCl was scavenged by a tertiary amine, forming a solid [RsNHJCl salt which was separated by filtration. On a commercial scale, this operation is expensive. BASF now uses 1-methylimidazole to scavenge HCl (eq. 9.87). 1-Methylimidazolium chloride is an ionic liquid (mp 348 K) which is immiscible with the reaction solvent. Separation of the two liquid phases is achieved at a lower cost than the filtration previously needed. Deprotonation of the 1-methylimidazolium cation regenerates imidazole which is recycled. 

Ionic liquid matrices (ILMs) introduced by Armstrong et at. were repwrted to have not only the property to make a homogeneous spot surface of analyte-matrix mixture but also the suitable properties for ionization of analytes (Anderson, J. L. et al., 2002 Armstrong, D. W. et al., 1999, 2001 Carda-Broch, S. et al., 2003). The essential point is that the ILMs consist of a conventional solid MALDI matrix, e.g., CHCA, DHB or SA and an organic base, e.g., tributylamine, pyridine or 1-methylimidazole which enables a relative state of liquidity under vacuum conditions (Tholey, A. Heinzle, E., 2006). The constituent solid matrices probably contribute to the ionization process. Several ILMs have been described and increased sensitivity analyses at the fmol or amol level have been reported for peptides and carbohydrates (Bungert, D. et al., 2004 Cramer, R. Corless, S., 2005 Crank, J. A. Armstrong, D. W., 2009 Fukuyama, Y. et al., 2008a Kaneshiro, K et al., 2011 Laremore, T. N. et al, 2006, 2007 Mank, M. et al., 2004). 

A new electrochemical method was proposed for the determination of thymine by Sim et al. [33]. The method was relied on the oxidation of thymine at a carbon ionic liquid electrode (CILE) which was fabricated by using ionic liquid l-(3-chloro-2-hydroxy-propyl)-3-methylimidazole acetate as the binder. The electrochemical oxidation of thymine on the CILE was an adsorption-controlled irreversible process with one electron and one proton involved. 

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