Correspondence
Correspondence on Microwave Effects in Organic Synthesis
Prof. Dr. Gregory B. Dudley,
Prof. Dr. Albert E. Stiegman,
Michael R. Rosana,
Corresponding Author
Prof. Dr. Gregory B. Dudley
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)Search for more papers by this authorProf. Dr. Albert E. Stiegman
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Search for more papers by this authorMichael R. Rosana
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Search for more papers by this authorProf. Dr. Gregory B. Dudley,
Prof. Dr. Albert E. Stiegman,
Michael R. Rosana,
Corresponding Author
Prof. Dr. Gregory B. Dudley
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)Search for more papers by this authorProf. Dr. Albert E. Stiegman
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Search for more papers by this authorMichael R. Rosana
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390 (USA)
Search for more papers by this authorGraphical Abstract
They're real. Microwave effects in organic synthesis remain controversial, but there is no longer any room for doubt that they exist. The question of whether the organic synthesis community should try to harness microwave effects strategically is the focus of this Correspondence.
References
- 1C. O. Kappe, B. Pieber, D. Dallinger, Angew. Chem. 2013, 125, 1124–1130;
10.1002/ange.201204103 Google ScholarAngew. Chem. Int. Ed. 2013, 52, 1088–1094.
- 2M. R. Rosana, Y. Tao, A. E. Stiegman, G. B. Dudley, Chem. Sci. 2012, 3, 1240–1244.
- 3According to the Angewandte Chemie's Author Guidelines on writing an Essay: “Use of unpublished results from original research should be extremely limited.”
- 4Our system featured a dilute homogeneous solution comprising an ionic substrate and nonpolar solvent in a quartz (not Pyrex) vial. Only one component of this system—the reaction substrate—interacts with MW radiation, so any heat generated within the system arises from the MW-actuated reactant.
- 5
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- 6
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- 6bE. Van der Eycken, P. Appukkuttan, W. De Borggraeve, W. Dehaen, D. Dallinger, C. O. Kappe, J. Org. Chem. 2002, 67, 7904–7907.
- 7According to Prof. Kappe, “The formation of ‘molecular radiators’ by direct coupling of microwave energy to specific reagents in homogeneous solution” is a specific MW effect.
- 8The same descriptor is simultaneously attached to nonthermal effects. As we note below (see Ref. [10]), there is a clear distinction between so-called nonthermal effects and specific microwave effects, and any attempt to associate them will result in confusion.
- 9This Essay better meets the criteria for an Angewandte Correspondence, except that our article was published in a different journal. The Author Guidelines state: “Manuscripts that critically comment on publications in Angewandte Chemie can be published as Correspondences if they make an important contribution to the scientific discussion. The author of the publication to which the Correspondence pertains will have the opportunity to reply.”
- 10We contend that it is not appropriate to discuss nonthermal effects in the same context as specific MW effects, much as no one discusses vitalism in the context of drug design. The nonthermal effects discussed in the Essay were postulated early in MW chemistry, but less so now as the field has matured and understanding of the underlying physics has improved. Specific MW effects may be rare and difficult to design successfully into experiments at this time, but there is no reason to doubt at this point that they are possible.
- 11For an excellent theoretical discussion, see:
- 11aD. Stuerga, J. Microw. Power Electromagn. Energy 1996, 31, 87–100;
- 11bD. Stuerga, J. Microw. Power Electromagn. Energy 1996, 31, 101–113.
- 12
- 12a“The straw man fallacy”: D. Walton in Logic and Argumentation (Eds.: ), Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1996, pp. 115–128;
- 12bSee also http://en.wikipedia.org/wiki/Straw_man (accessed 5 April 2013).
- 13The Supporting Information (p. S15) includes an explicit example of the attempt to paint our research as a misguided quest for nonexistent, nonthermal microwave effects: “reflux…︁ should ensure a consistent internal temperature and therefore present more or less ideal conditions to verify/falsify a nonthermal microwave effect. For this reason, the Dudley group has performed the reaction of BnOP-BArF 1 in refluxing toluene” (italics added). This is their reasoning, not ours. We have no interest in the quest to verify/falsify so-called nonthermal effects, as we see no physical rationale for their existence.
- 14We repeat the use of the term “superheating” here to be consistent with the Essay. However, we and others prefer the terms “superheated boiling”, “superboiling”, or “nucleation-limited boiling”, because the term “superheating” has already been applied to a different physical phenomenon that is not microwave-specific. These effects are discussed in more detail below and in references [27–30].
- 15Also, neither claim is supported by the data. As discussed herein, we contend that microwave superheated boiling is neither well understood nor relevant to the observed effects in our vigorously stirred system. Moreover, the existence of one effect does not negate the possibility of other effects.
- 16The authors may be confusing thermal effects with temperature effects. Heat and temperature are different, just like mass and weight are different. We note the distinction between heat and temperature in our manuscript, and we will elaborate on this important point in the context of microwave heating in a forthcoming publication.
- 17Nonthermal effects are inconsistent with the current understanding of microwave heating, so it is not clear what Prof. Kappe and co-workers would consider to constitute evidence of a nonthermal effect. We make no mention of nonthermal effects in our paper, as noted above.
- 18We used a noninvasive external IR sensor to monitor system temperature, with repeated multipoint calibration to ensure correlation with solution temperature. Our manuscript includes a discussion of the strengths and limitations of this technology and why it was the appropriate choice for our experiments, and a control experiment showing that the IR sensor is sufficiently reliable to support our conclusions. The Essay authors acknowledge that our discussion is correct, but they insist that we should have used an internal fiber-optic probe anyway. They are entitled to their opinions here, and we do not wish to belabor a moot point. As we discuss in more detail later, what they describe as the “genuine reaction temperature” is not physically defined for multicomponent solutions under steady-state MW irradiation.
- 19They attribute the different behavior of our respective systems to “a serious hardware or temperature measurement problem in the Dudley experiments.” (p. 29 in the Supporting Information) We contend that other explanations, like differential release of heat to the surroundings, should be considered here, perhaps resulting from a seemingly trivial change in the experiment setup. The shape, size, and thickness of the vials used and any other physical impediments between the system and surroundings will impact heat transfer, and we spent considerable time optimizing our specific system to achieve the heat-transfer profile we needed to conduct the experiments. We offered and would have been more than happy to advise them on a similar optimization of their system, but they repeatedly declined these offers.
- 20We also suggested that they lower the concentration of the solute (such that less heat is generated), rather than reduce the incident MW power, to remain faithful to the design principles that we set forth in our publication.
- 21The reflux experiments described below are easier to compare, and in these experiments their data aligned very closely with ours.
- 22This control experiment also demonstrates the ability of the properly calibrated external IR sensor to regulate system temperature, despite the fact that this system is more prone to rapid temperature fluctuations; cf. reference [18].
- 23We did not use boiling chips in our experiments. The new data in the Essay table in the column labeled “MW with boiling chips” is discussed below.
- 24No citation was provided here, and we cannot find relevant literature to connect this effect to our experiments. Such a 40 °C temperature differential in an unstirred liquid is reported in a 2001 Chemat paper entitled, “Microwave Super-Heated Boiling of Organic Liquids: Origin, Effect, and Application.” See reference [28]. We discuss this and related papers on superheated boiling in the following section.
- 25In fact, the heterogeneous systems described in the main text of the Essay are not comparable to our homogeneous system. Changes in homogeneity impact the transfer of energy and heat, and surface effects of the additives must also be considered. The heterogeneous additives cannot be assumed to be inert. We have begun to examine systems like the ones they describe. Preliminary indications are that crushed glass, for example, accelerates benzylation under conventional heating. For leading references on heterogeneous and surface catalysis (e.g., of Friedel–Crafts reactions), see:
- 25a Fine Chemicals through Heterogeneous Catalysis (Eds.: ), Wiley-VCH, 2008;
- 25bM. A. Keane, J. Mater. Sci. 2003, 38, 4661–4675.
- 26A related claim by Prof. Kappe and co-workers in the main text that “it is not possible to superheat the solvent above its boiling point” is also undermined by their data and cited literature, although it is true that solvent superheating is minimal at best with proper stirring.
- 27“Bumping” of unstirred liquids during distillation is a common manifestation of this effect. For discussions on superheated liquids with leading references, see:
- 27aV. G. Baidakov, Explosive Boiling of Superheated Cryogenic Liquids, Wiley-VCH, 2009;
- 27bP. G. Debenedetti, Metastable Liquids, Princeton University Press, 1996.
- 28F. Chemat, E. Esveld, Chem. Eng. Technol. 2001, 24, 735–744.
- 29R. Saillard, M. Poux, J. Berlan, M. Audhuy-Peaudecerf, Tetrahedron 1995, 51, 4033–4042.
- 30D. R. Baghurst, M. P. Mingos, J. Chem. Soc. Chem. Commun. 1992, 674–677.
- 31We thank Jacob Hunt and Anthony Ferrari (Stiegman lab) for assisting with these temperature measurements.
- 32We used ceramic boiling chips made from crushed Büchner funnels as the Essay authors describe, as well as the same amounts of reagent and solvent as they report.
- 33Our measured reflux temperatures fall within a few degrees at most of the boiling point, so what could explain “an extremely fluctuating temperature profile” in their experiments? Superheated boiling of unstirred systems depends on myriad factors (reference [28]), and their experimental setup differed from ours in several ways: less reagent, less solvent, smaller flask, and probably a smaller reflux condenser. Perhaps the parameters of their smaller system enabled them to produce unprecedented levels of stirred superheated boiling, although our data (cf. Figure 3) suggest otherwise. Alternatively, perhaps their reflux condenser was too small for the task at hand, and the solvent they report seeing trapped in the condenser created “an extremely fluctuating” pressure profile; see also reference [19].
- 34“Temperature” is only defined for a system at thermal equilibrium. Strictly speaking, temperature cannot be measured for a multicomponent system under ssMWi, because thermal equilibrium between individual components is perturbed as a function of differential interactions with the incident MW energy. The “measured temperature” data provided by the thermometer has empirical value but requires a nuanced interpretation.
- 35Our central design hypothesis was based on the premise that ssMWi at high power results in differential average kinetic molecular energy between the solute and solvent. A more detailed discussion of the underlying physics will be included in future manuscripts; our initial study was focused on securing experimental support for the hypothesis.
- 36Specific MW effects are unequivocally observed in this system. However, the nature of the effects and opportunity to exploit them remain as open questions.
- 37
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- 38As we discovered during the course of our studies, however, Pyrex is not MW-transparent, so the systematic comparison of reactions conducted in silicon carbide and Pyrex vials would have more appropriately featured quartz vials:
- 38aD. Obermayer, B. Gutmann, C. O. Kappe, Angew. Chem. 2009, 121, 8471–8474;
10.1002/ange.200904185 Google ScholarAngew. Chem. Int. Ed. 2009, 48, 8321–8324;
- 38bB. Gutmann, D. Obermayer, B. Reichart, B. Prekodravac, M. Irfan, J. M. Kremsner, C. O. Kappe, Chem. Eur. J. 2010, 16, 12182–12194.
- 39It is also my opinion that the Kappe lab should have offered to work with us to resolve our experimental differences before submitting the Essay. The interests of science would have been better served by cooperation here.
