How flow chemistry can make processes greener.. Case study 1 Methylation with DMC.

Figure . Flow chart carboxylate system (B = vessel, V = valve).

Alkylation of N methylimidazole (MIM) with dimethyl carbonate (DMC) is investigated. Dimethyl carbonate is known as a clean methylation agent which can be used as safe alternative to conventional reagents such as methyl halides, dimethyl sulfate and phosgene. With the system shown in Figure 4, which is operated continuously, it is possible to synthesize the zwitterion 1,3-dimethyl-1H-imidazol-3-ium-2-carboxylate ([MMIM][CO2]) by alkylation of MIM with DMC. Similarly, the synthesis of ionic liquids based on N methylpiperidine and N methylpyrrolidine is possible. These ionic liquids represent versatile precursors for the synthesis of halogen free ionic liquids.

How flow chemistry can make processes greener

Case study 1 Methylation with DMC.

Increasing reaction efficiency through access to a wider range of reaction conditions

Efficient utilization of energy and time is fundamental to green chemistry and engineering. These factors are directly related to the rate of a chemical reaction, as a fast reaction will require less operating time. Economical use of space is also important, and fast reactions may allow for a smaller reactor to be utilized, particularly in continuous processes. The most straightforward way to increase reaction rate is with an increase in temperature; however, in a batch reactor, this is generally limited to the atmospheric boiling point of the solvent or reagents. In a flow reactor, pressure and temperature can be safely manipulated far beyond atmospheric conditions. Analogous to microwaves synthesis,1 reactions done in flow are often faster than in the corresponding batch reactions, which gives improved energy, time, and space efficiency.1 In contrast to typical microwave reactors, a closed system is not required, greatly facilitating scale-up.

Methylation reactions of nitrogen and oxygen nucleophiles such as indoles and phenols are important transformations often carried out on a large scale using hazardous reagents such as methyl iodideor dimethyl sulfate . Dimethylcarbonate (DMC) has been recognized as a green, albeit less reactive alternative. Due to the relatively low boiling point (90 °C) and reduced reactivity of this reagent, methylation reactions with DMC are generally slow.3 The use of an autoclave or microwave may allow higher temperatures to be used, accessing faster rates; however, this makes scale-up challenging. To access fast reaction rates and improve scalability, Tilstam used a flow reactor to do phenol and N-heterocycle methylations with DMC.4 A simple set-up was used consisting of a high pressure syringe pump, stainless steel tubing, a GC oven, and a back pressure regulator to ensure that the DMC stayed in solution. At 220 °C, yields up to 97% could be obtained with reaction times as short as ten minutes. A report by the Kappe and Holbrey group found similar results using an ionic liquid catalyst.5 While more energy may be required to reach these elevated temperatures, the use of insulation to prevent heat loss, and recycling of the energy given off from exothermic reactions all contribute greatly to energy efficiency on a commercial scale.6 Perhaps most importantly, the reduction in size and operating time of the vessel offers great improvements in sustainability. Indeed, the output of a reactor with respect to its size and operating time was identified as the most impactful component of a good process by researchers at Boehringer Ingelheim.7

 

Methylation with DMC.
Scheme 1 Methylation with DMC.
  1. Microwaves in Organic Synthesis, ed. A. Loupy, Wiley-VCH, Weinheim, 2006 Search PubMed.
  2. T. Razzaq and C. O. Kappe, Chem.–Asian. J., 2010, 5, 1274–1289 CAS.
  3. W.-C. Shieh, S. Dell and O. Repič, Org. Lett., 2001, 3, 4279–4281 CrossRef CAS.
  4. U. Tilstam, Org. Process Res. Dev., 2012, 16, 1974–1978 Search PubMed.
  5. T. N. Glasnov, J. D. Holbrey, C. O. Kappe, K. R. Seddon and T. Yan, Green Chem., 2012, 14, 3071–3076 RSC.
  6. S. Heubschmann, D. Kralisch, V. Hessel, U. Krtschil and C. Kompter, Chem. Eng. Technol., 2009, 32, 1757–1765 CrossRef CAS.
  7. R. Dach, J. J. Song, F. Roschanger, W. Samstag and C. H. Senanayake, Org. Process Res. Dev., 2012, 16, 1697–1706 Search PubMed.

 

Carbon dioxide (CO2) is an easily available, renewable carbon resource, which has the advantages of being non-toxic, abundant and economical. CO2 is also attractive as an environmentally friendly chemical reagent, and is especially useful as a phosgene substitute.CO2 is an “anhydrous carbonic acid” that rapidly reacts with basic compounds. Nucleophilicattack at CO2 conveniently produces carboxyl and carbamoyl groups. Further reactions of these species with electrophiles lead to the formation of organic carbonates and carbamates. The present article deals with the synthetic technologies leading to organic carbonates using CO2 as a raw material.

 

Graphical abstract: The synthesis of organic carbonates from carbon dioxide

The synthesis of organic carbonates from carbon dioxide

*Corresponding authors
aNational Institute of Advanced Industrial Science and Technology (AIST), AIST Central 5, 1-1-1 Higashi, Japan
E-mail: t-sakakura@aist.go.jp
Fax: +81 29-861-4719
bGraduate School of Pure and Applied Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki 305-8571, Japan
Chem. Commun., 2009, 1312-1330

DOI: 10.1039/B819997C

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