Probing the mechanism of direct Mannich‐type α‐methylenation of ketoesters via electrospray ionization mass spectrometry

Milagre, Cíntia D. F.; Milagre, Humberto M. S.; Santos, Leonardo S.; Lopes, Marcelo L. A.; Moran, Paulo J. S.; Eberlin, Marcos N.; Rodrigues, J. Augusto R.

doi:10.1002/jms.1173

Cited by 37 publications

(24 citation statements)

References 72 publications

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“…[46,47] Recently, direct infusion electrospray ionization mass spectrometry (ESI-MS) has been incorporated to the set of major techniques for mechanistic studies of organic and inorganic reactions. [48,49] Owing to its outstanding ability to "fish" ionic or ionized intermediates directly from reaction solutions into the gas phase, with high sensitivity, speed and gentleness, ESI-MS and its tandem version ESI-MS/MS have provided continuous snapshots of the ionic composition of reaction solutions with on-line MS and MS/MS characterization of the intercepted intermediates. We rationalized therefore that ESI-MS and ESI-MS/ MS, by its outstanding ability to intercept intermediates (even transient species) could provide a detailed picture of the Biginelli mechanism in light of its three alternative mechanisms (Scheme 3).…”

Section: Introductionmentioning

confidence: 99%

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

Souza

Penha

Milagre³

et al. 2009

Chemistry A European J

112

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Biginelli reactions have been monitored by direct infusion electrospray ionization mass spectrometry (ESI-MS) and key cationic intermediates involved in this three-component reaction have been intercepted and further characterized by tandem MS experiments (ESI-MS/MS). Density functional theory calculations were also used to investigate the feasibility of the major competing mechanisms proposed for the Biginelli reaction. The experimental and theoretical results were found to corroborate the iminium mechanism proposed by Folkers and Johnson, whereas no intermediates directly associated with either the more energy demanding Knoevenagel or enamine mechanisms could be intercepted.

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Section: Introductionmentioning

confidence: 99%

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

Souza

Penha

Milagre³

et al. 2009

Chemistry A European J

112

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“…We investigated via ESI(+)-MS monitoring the reaction of ketoesters with p-formaldehyde catalyzed by morpholine in acetic acid:acetonitrile solution (Scheme 6). 30 As the key players of the catalytic cycle of the reaction could be either ionic or neutral species, the neutral species were intercept as protonated molecules from the acetic acid solutions. Few examples of disfavored proton-transfer equilibrium are described, however, it could be useful in intercepting neutral species because of the high sensitivity of ESI-MS in transferring ionic intermediates from solution to the gas phase.…”

Section: A-methylenation Of Ketoestersmentioning

confidence: 99%

What do we know about reaction mechanism? the electrospray ionization mass spectrometry approach

Santos¹

2011

J. Braz. Chem. Soc.

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O fascínio do homem por reações químicas remonta aos tempos antigos. Com a introdução de técnicas espectroscópicas, a arte de explorar as reações se tornou uma ciência intrigante. Portanto, não é surpreendente que uma das fronteiras mais prósperas e gratificantes na Química moderna é o estudo de mecanismo de reações em processos químicos e biológicos. Como a imaginação do homem não termina nas fronteiras definidas pela natureza, e com o poder crescente da catálise, o químico orgânico sintético está pronto para contribuir de uma maneira importante no invento e desenvolvimento de novas tecnologias que permitam a geração de novos catalisadores e metodologias. Neste account uma nova ferramenta para acelerar o desenvolvimento na descoberta de novas reações é revisada através do monitoramento por espectrometria de massa com ionização eletrospray (ESI-MS).Man's fascination with chemical reactions goes back to ancient times. With the introduction of spectroscopic techniques, the art of exploiting reactions became an intriguing science. It is, therefore, not surprising that one of the most flourishing and rewarding frontiers in modern Chemistry is the study of reaction mechanisms in chemical and biological processes. As man's imagination does not stop at the frontiers defined by nature, and with the ever increasing power of catalysis, the synthetic organic chemist is poised to make important contributions by inventing and developing new enabling technologies for the generation of new catalysts and methodologies. In this account is offered a new tool for accelerating the development through electrospray ionizationmass spectrometric (ESI-MS) monitoring in new reaction discovering.

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“…Direct infusion ESI( þ )-MS(/MS) was used to monitor Mannich-type a-methylenation of a-, b-, and g-ketoesters, and the results guided development of a convenient one-pot method for the efficient preparation of their a-methylene derivatives [17]. More specifically, we monitored the reaction of a ketoester with paraformaldehyde catalyzed by morpholine in an acetic acid/acetonitrile solution (Scheme 3.8).…”

Section: A-methylenation Of Ketoestersmentioning

confidence: 99%

“…Scheme 3 17. Catalytic cycle for Suzuki-type cross-coupling.3.2 Reaction Mechanisms j81reaction is based on three reaction steps: (i) oxidative addition, (ii) transmetalation, and (iii) reductive elimination (Scheme 3 19)…”

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confidence: 99%

Organic Reaction Studies by ESI‐MS

Nachtigall

Eberlin

2009

Reactive Intermediates

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IntroductionReactions are the heart and soul of chemistry. Therefore chemists, to effectively control and improve their chemical reactions, need to know the mechanistic details by which these usually sophisticated, multistep and multicomponent processes with many intermediates and transient species proceed. The tremendous success and rapid broad use of electrospray ionization mass spectrometry (ESI-MS) [1] results mainly from its ability to transfer, in a gentle and efficient way, ions of many types, charge states and nearly unlimited masses from the real-world environment of reaction solutions directly to the diluted gas phase and to characterize these intact and isolated gaseous ions according to their masses and connectivities with the outstanding speed, sensitivity and selectivity that only mass spectrometry is able to provide. ESI-MS (for ion detection and mass and isotopic pattern determination) as well as its tandem version ESI-MS(/MS) (for structural investigation) has therefore established itself as the principal technique to study reaction mechanisms of organic reactions in solution. ESI can fish, rapidly and efficiently, reactants, intermediates and products (either ionic species or molecules in ionic forms) and transfer them to mass spectrometers (leaving behind the solvent molecules and counter ions) to measure their masses and access their structures and intrinsic reactivities using tandem MS/MS experiments. Continuous on-line monitoring of organic reactions of many types by ESI-MS(/MS) ion fishing (Figure 3.1) provides instantaneous and comprehensive snapshots of the ionic composition and thus permits organic chemists to follow how these reactions progress as a function of time and reaction conditions, whereas the high sensitivity and speed of ESI-MS allow even transient (low concentrations for short times) intermediates to be detected and characterized. The intrinsic reactivity of each key gaseous species fished by ESI can also be further investigated via ESI-MS(/MS) experiments in the search for the most intrinsically active species via gas-phase ion/ molecule reactions in which solvent and counter-ion effects are absent. Therefore, the ability to fish ions (or neutral, zwitterionic, or radical species in ionic forms such as protonated, deprotonated, or cationized or anionized molecules) provides a detailed j63 64j 3 Organic Reaction Studies by ESI-MS R 1 OH Scheme 3.2 Currently accepted catalytic cycle for the MBH reaction. 3.2 Reaction Mechanisms j65 66j 3 Organic Reaction Studies by ESI-MS À , CF 3 CO 2 À ). 68j 3 Organic Reaction Studies by ESI-MS 70j 3 Organic Reaction Studies by ESI-MS 98j 3 Organic Reaction Studies by ESI-MS

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Probing the mechanism of direct Mannich‐type α‐methylenation of ketoesters via electrospray ionization mass spectrometry

Cited by 37 publications

References 72 publications

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

The Three‐Component Biginelli Reaction: A Combined Experimental and Theoretical Mechanistic Investigation

What do we know about reaction mechanism? the electrospray ionization mass spectrometry approach

Organic Reaction Studies by ESI‐MS

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