Structurally diagnostic ion-molecule reactions: acylium ions with alpha-, beta- and gamma-hydroxy ketones

Gas-phase reactions of four acylium ions and a thioacylium ion with three isomeric alpha-, beta- and gamma-hydroxy ketones are performed by pentaquadrupole mass spectrometric experiments. Novel structurally diagnostic reactions are observed, and found to correlate directly with interfunctional group separation. All five ions tested (CH(3)CO(+), CH(2)(double bond)CHCO(+), PhCO(+), (CH(3))(2)NCO(+) and (CH(3))(2)NCS(+)) react with the gamma-hydroxy ketone (5-hydroxy-2-pentanone) to form nearly exclusively a cyclic oxonium ion of m/z 85 that formally arises from hydroxy anion abstraction. With the beta-hydroxy ketone (4-hydroxy-2-pentanone), CH(2)(double bond)CHCO(+), PhCO(+) and (CH(3))(2)NCO(+) form adducts that undergo fast cyclization via intramolecular water displacement, yielding resonance-stabilized cyclic dioxinylium ions. With the alpha-hydroxy ketone (3-hydroxy-3-methyl-2-butanone), PhCO(+), (CH(3))(2)NCO(+) and (CH(3))(2)NCS(+) form stable adducts. Evidence that these adducts display cyclic structures is provided by the triple-stage mass spectra of the (CH(3))(2)NCS(+) adduct; it dissociates to (CH(3))(2)NCO(+) via a characteristic reaction-dissociation pathway that promotes sulfur-by-oxygen replacement. If cyclizations are assumed to occur with intramolecular anchimeric assistance, relationships between structure and reactivity are easily recognized.     

Gas-phase polar [4+ + 2] cycloaddition with ethyl vinyl ether: a structurally diagnostic ion-molecule reaction for 2-azabutadienyl cations

The intrinsic reactivity of eight gaseous, mass-selected 2-azabutadienyl cations toward polar [4(+) + 2] cycloaddition with ethyl vinyl ether has been investigated by pentaquadrupole mass spectrometric experiments. Cycloaddition occurs readily for all the ions and, with the only exception of those from the N-acyl 2-azabutadienyl cations (N-acyliminium ions), the cycloadducts are found to dissociate readily upon collision activation (CID) both by retro-Diels-Alder reaction and by a characteristic loss of an ethanol (46u) neutral molecule. Ethanol loss from the intact polar [4(+) + 2] cycloadduct functions therefore as a structurally diagnostic test: 72 u neutral gain followed by 46 u neutral loss, i.e., as a combined ion-molecule reaction plus CID 'signature' for N-H, N-alkyl and N-aryl 2-azabutadienyl cations. The two N-acyliminium ions tested are exceptional as they form intact cycloadducts with ethyl vinyl ether which dissociate exclusively by the retro-Diels-Alder pathway.     

Unexpected synthesis of conformationally restricted analogues of gamma-amino butyric acid (GABA): mechanism elucidation by electrospray ionization mass spectrometry

From previous results with lower homologues, dehydroiodination of the three alkenyl-beta-enamino esters 3a-c was expected to provide six-membered N-heterocyclic products. The reactions of 3a-c with triethylamine are found to lead, however, to the unexpected stereoselective synthesis of the trisubstituted cyclopentane derivatives 4a-c, as confirmed by IR and NMR spectroscopy. Cyclopentanes 4a-c bear two chiral centers and a gamma-amino ester moiety, and are therefore conformationally restricted analogues of gamma-amino butyric acid (GABA), which is the major inhibitory neurotransmitter in the central nervous system. Use of electrospray ionization mass (ESI-MS) and tandem mass spectrometry (ESI-MS/MS) allowed the key iminium ion intermediates 5a-c(+), as well as the protonated molecules of both the reactant and final products, [3a-c + H](+) and [4a-c + H](+), to be intercepted and structurally characterized. From these findings a mechanism for this unexpected but synthetically attractive and efficient stereoselective reaction is proposed.     

Determination of phthalates in water using fiber introduction mass spectrometry

Fiber introduction mass spectrometry (FIMS)-a direct coupling of SPME and MS-using selective ion monitoring (SIM) was used to detect and quantify dimethylphthalate (DMP), diethylphthalate (DEP) and dipropylphthalate (DPP) in mineral water. In FIMS, a chromatographic silicone septum is the only barrier between ambient and the high-vacuum mass spectrometer, permitting direct introduction of the SPME fiber into the ionization region of the equipment. After their thermal desorption and ionization and dissociation, the extracted phthalates are detected and quantitated by MS. Three types of SPME fibers were screened for best analyte sorption/desorption behaviors: 100 microm polydimethylsiloxane (PDMS), 65 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) and 65 microm Carbowax/divinylbenzene (CW/DVB). The PDMS/DVB and CW/DVB fibers were then evaluated for precision, and quantitative figures of merit were assessed for extractions using the PDMS/DVB fiber, which displayed the best overall performance. FIMS with the PDMS/DVB fiber allows simple extraction and MS detection and quantitation of DMP in water with good linearity and precision, and at concentrations as low as 3.6 microg L(-1). The LD and LQ of FIMS are below the maximum phthalate concentration allowed by the USEPA for drinking water (6 microg L(-1)).     

Mechanisms of nucleophilic substitution reactions of methylated hydroxylamines with bis(2,4-dinitrophenyl)phosphate. Mass spectrometric identification of key intermediates

Mono- and dimethylation of hydroxylamine on nitrogen does not significantly affect rates of initial attack of NHMeOH and NMe(2)OH on bis(2,4-dinitrophenyl)phosphate (BDNPP), which is largely by oxygen phosphorylation. O-Methylation, however, blocks this reaction and NH(2)OMe then slowly reacts with BDNPP via N-attack at phosphorus and at the aryl group. With NHMeOH, the initial product of O-attack at phosphorus reacts further, either by reaction with a second NHMeOH or by a spontaneous shift of NHMe to the aryl group via a transient cyclic intermediate. There is a minor N-attack of NHMeOH on BDNPP in an S(N)2(Ar) reaction. Reactions occurring via N-attack are blocked by N-dimethylation, and reaction of NMe(2)OH with BDNPP occurs via O-attack, generating a long-lived product. Reaction mechanisms have been probed, and intermediates identified, by using both NMR and MS spectroscopy, with the novel interception of key reaction intermediates in the course of reaction by electrospray ionization mass and tandem mass spectrometry.     

In Melting Points We Trust: A Review on the Misguiding Characterization of Multicomponent Reactions Adducts and Intermediates

We discuss herein the problems associated with using melting points to characterize multicomponent reactions’ (MCRs) products and intermediates. Although surprising, it is not rare to find articles in which these MCRs final adducts (or their intermediates) are characterized solely by comparing melting points with those available from other reports. A brief survey among specialized articles highlights serious and obvious problems with this practice since, for instance, cases are found in which as many as 25 quite contrasting melting points have been attributed to the very same MCR adduct. Indeed, it seems logical to assume that the inherent non-confirmatory nature of melting points could be vastly misleading as a protocol for structural confirmation, but still many publications (also in the Q1 and Q2 quartiles) insist on using it. This procedure contradicts best practices in organic synthesis, and articles fraught with limitations and misleading conclusions have been published in the MCRs field. The drawbacks inherent to this practice are indeed serious and have misguided MCRs advances. We therefore suggest some precautions aimed at avoiding future confusions.     

Mass spectrometry molecular fingerprinting of mineral and synthetic lubricant oils

The molecular composition of lubricating oils has a strong impact on how automotive engines function, but the techniques used to monitor the quality parameters of these oils only inspect their gross physical–chemical properties such as viscosity, color, and bulk spectroscopy profiles; hence, bad-quality, adulterated, or counterfeit oils are hard to detect. Herein, we investigated the ability of direct infusion electrospray ionization mass spectrometry (ESI-MS) to provide simple, rapid but characteristic fingerprint profiles for such oils of the mineral and synthetic types. After a simple aqueous extraction, ESI-MS analyses, particularly in the positive ion mode, did indeed show characteristic molecular markers with unique profiles, which were confirmed and more clearly visualized by partial least squares-discriminant analysis (PLS-DA). Nuclear magnetic resonance and Fourier transform infrared-attenuated total reflection spectroscopy were also tested for the bulk samples but showed nearly identical spectra, thus failing to reveal their distinct molecular composition and to differentiate the oil samples. To simulate adulteration, mixtures of mineral and synthetic oils were also analyzed by ESI(+)-MS, and additions as low as 1% of mineral oil to synthetic oil could be detected. The technique therefore offers a simple and fast but powerful tool to monitor the molecular composition of lubricant oils, particularly vias their more polar constituents.     

Cyclam kappa4 to kappa3 ligand denticity change upon mono-n-substitution with a carboxypropyl pendant arm in a ruthenium nitrosyl complex

The complex fac-[Ru(NO)Cl2(kappa(3)N(4),N(8),N(11)(1-carboxypropyl)cyclam)]Cl.H2O (1-carboxypropyl)cyclam=3-(1,4,8,11-tetraazacyclotetradecan-1-yl)propionic acid) was prepared in a one pot reaction by mixing equimolar amounts of RuNOCl 3 and (1-carboxypropyl)cyclam and was characterized by X-ray crystallography, electrospray ionization tandem mass spectrometry (ESI-MS/MS), elemental analysis, NMR, and electronic and vibrational (IR) spectroscopies. fac-[Ru(NO)Cl 2(kappa(3)N(4),N(8),N(11)(1-carboxypropyl)cyclam)]Cl.H2O crystallizes in the triclinic, space group P1, No. 2, with unit cell parameters of a=8.501(1) A, b=9.157(1) A, c=14.200(1) A, alpha=72.564(5) degrees , beta=82.512(5) degrees , gamma=80.308(5) degrees , and Z=2. The Ru-N interatomic distance and bond angle in the [Ru-NO] unit are 1.739(2) A and 167.7(2) degrees , respectively. ESI-MS/MS shows characteristic dissociation chemistry that initiates by HCl or NO loss. The IR spectrum displays a nu(NO) at 1881 cm(-1) indicating a nitrosonium character. The electronic spectrum shows absorptions bands at 264 nm (log epsilon=3.27), 404 nm (log epsilon=2.53), and 532 nm (log epsilon=1.88). (1)H and (13)C NMR are in agreement with the proposed molecular structure, which shows a very singular architecture where the cyclam ring N (with the carboxypropyl pendant arm) is not coordinated to the ruthenium resulting in a kappa(3) instead of the expected kappa(4) denticity.     

The mechanism of Tröger's base formation probed by electrospray ionization mass spectrometry

Using direct infusion electrospray ionization mass and tandem mass spectrometric experiments [ESI-MS(/MS)], we have performed on-line monitoring of some reactions used to form Tr?ger's bases. Key intermediates, either as cationic species or as protonated forms of neutral species, have been intercepted and characterized. The role of urotropine as the methylene source in these reactions has also been accessed. Reaction pathways shown by ESI-MS(/MS) have been probed by gas-phase ion/molecule reactions, and an expanded mechanism for Tr?ger's base formation based on the mass spectrometric data has been elaborated.