Elusive intermediates

The anhydride of thiophene-2,3-dlcarboxylic acid is of interest as a precursor of 2,3-didehydrothiophene. Evidence for the generation of this elusive intermediate is obtained by the isolation of [4-1-2] and [2-1-2] cycloaddition products with dienes (81T4151). 

Since the corresponding endoperoxide precursors are all too unstable for isolation, the diimide reduction constitutes an important chemical structure confirmation of these elusive intermediates that are obtained in the singlet oxygenation of the respective 1,3-dienes. However, the aza-derivative 14 and the keto-derivative 15 could not be prepared,17> because the respective endoperoxides of the pyrroles 18) and cyclopentadienones suffered complex transformations even at —50 °C, so that the trapping by the diimide reagent was ineffective. 

The only notable exception is regarding the very strained alkylidenecyclopropanes 21, which are believed to be formed in situ as elusive intermediates and cannot be either isolated or even detected (Scheme 62) [121,122,11a]. 

Intramolecular Lewis base complexation of the germanium atom also did not appear to be a valuable alternative to overcome the lability of these elusive intermediates, since the germanones expected from oxidation of the base-stabilized germylenes 140131 (with Me3NO) and 141132 (with 02, DMSO, or pyridine oxide) either rearrange as already mentioned [Section VI,A,4, Eq. (33)]131 or dimerize to digermadioxetane 160132 [Eq. (35)]. 

Only with less efficient catalysts and at low temperature, have p-chelate intermediates been intercepted by P H HP NMR spectroscopy in the course of copolymerisations in MeOH-d4 [5g]. The unambiguous detection of p-chelates has been observed in a reaction catalysed by the l,r-bis(diphenylphosphino)ferro-cene complex [Pd(H20)2(dppf)](0Ts)2 (3) at room temperature (Scheme 7.7) [5g]. As shown in the sequence of P H NMR spectra reported in Figure 7.8, the P-chelate intermediates 4- disappeared already at 50 °C. A parallel model study confirmed the formation and the structure of the dppf P-chelates and also provided information of more elusive intermediates (see Section 7.2.1.8) [19]. 

Aryl and acyl isothiocyanates were also found to react with alkyl azides, but yield thiatriazoline-5-imines only as elusive intermediates which are transformed in situ into a series of bisadducts after loss of nitrogen. Interestingly, L abbe et al. have found that picryl isothiocyanate is an exception to this and reacts smoothly with alkyl azides to yield 4-alkyl-5-picrylimino-l,2,3,4-thiatriazolines (177) which are stable below 100°C <90JHC1059>. Kinetic experiments indicate that the reaction between picryl isothiocyanate and alkyl azides most likely is concerted as no significant solvent effect was observed. 

While both the primary and secondary ozonides have been isolated and characterized, the pair formed by the carbonyl oxide (CO) and the carbonyl compound (CC) has never been directly put into evidence. This elusive intermediate, called also Criegee intermediate zwitterion (CZ), according to this AMI study which did not take into account solvent effects, forms a tight pair or a dipolar complex (DC). The primary ozonide has an O-envelope halfchair conformation and as such two conformers are possible from a rfr-alkene 11 and 12 and only one 13 from the trans-alkene. The splitting of the primary ozonide can lead either to an anti 14 or syn 15 CO and has a determining role for the stereochemical outcome of the reaction <1997JOC2757>. 

Fully conjugated 1,2,3,5-thiatriazoles have been described in the form of the mesoionic aminides 9 <1988ACB63>, as thiatriazolium salts 10 <1990J(P2)1619> and as compounds with hexavalent sulfur 11 <1997CJC1188>. The parent 1,2,3,5-thiatriazoles of type 12 are described as elusive intermediates in the reaction of amidrazones with thionyl chloride leading to benzonitrile formation <2004H01J833>. 

The first step of peroxidase catalysis involves binding of the peroxide, usually H2C>2, to the heme iron atom to produce a ferric hydroperoxide intermediate [Fe(IE)-OOH]. Kinetic data identify an intermediate prior to Compound I whose formation can be saturated at higher peroxide concentrations. This elusive intermediate, labeled Compound 0, was first observed by Back and Van Wart in the reaction of HRP with H2O2 [14]. They reported that it had absorption maxima at 330 and 410 nm and assigned these spectral properties to the ferric hydroperoxide species [Fe(III)-OOH]. They subsequently detected transient intermediates with similar spectra in the reactions of HRP with alkyl and acyl peroxides [15]. However, other studies questioned whether the species with a split Soret absorption detected by Back and Van Wart was actually the ferric hydroperoxide [16-18], Computational prediction of the spectrum expected for Compound 0 supported the structure proposed by Baek and Van Wart for their intermediate, whereas intermediates observed by others with a conventional, unsplit Soret band may be complexes of ferric HRP with undeprotonated H2O2, that is [Fe(III)-HOOH] [19]. Furthermore, computational analysis of the peroxidase catalytic sequence suggests that the formation of Compound 0 is preceded by formation of an intermediate in which the undeprotonated peroxide is coordinated to the heme iron [20], Indeed, formation of the [Fe(III)-HOOH] complex may be required to make the peroxide sufficiently acidic to be deprotonated by the distal histidine residue in the peroxidase active site [21],... 

Notwithstanding the relatively limited time resolution of the conventional fast FTIR technique, it will be demonstrated here that the number of catalytic systems that can be characterized successfully in dynamic investigations can be increased by adopting suitable temperature and pressure conditions, which permit the observation of otherwise elusive intermediates. 

To combine an impeccably systematic account with imaginitive presentation is not the least merit of this book, which may be studied with profit by chemists who pursue elusive intermediates in any field. 

However, by analogy with the reactions of alkenes, an alternative mechanism via the formation of a pentacoordinate cyclic periodinane (145) is also plausible. Oxidative addition of HTIB or its analogs to the enol affords the periodinane. Ligand coupling yields a new elusive intermediate, an a-hydroxy-iodinane (146), which undergoes elimination of iodobenzene. (Scheme 5.21)... 

Jenkins DC, Sylvester ID, Pinheiro TJT (2008) The elusive intermediate on the folding pathway of the prion protein. FEBS J 275 1323-1335... 

Dihydrodioxins may undergo various oxidation reactions. Thus, the m-chloroperbenzoic acid oxidation of dihydrodioxins affords, in high yields, ethylene glycol dibenzoates (95) via unstable epoxy diethers (96). These elusive intermediates have been characterized chemically and by H NMR spectroscopy <85JCS(pi)457>. 

We and others have demonstrated that association of short strands containing a single guanine-repeat seems to obey a fourth-order kinetics model. Third or fourth-order reactions are not common in biochemistry, and the practical consequences of this reaction order are important. A fourth-order reaction does not imply that an elementary kinetic step involves a four-body collision. Such mechanism is extremely unlikely and other processes could lead to this fourth order. The structure of these elusive intermediates remains unknown Stefl et have recently demonstrated that a Hoogsteen G-G duplex is an improbable intermediate. Its identification will be experimentally difficult, as numerical simulations indicate that it may not be present at detectable levels. 

One way to identify these elusive intermediates is mass spectrometry. Electrospray allows the isolation of species of various molecular weights, (Figure 7) (Rosu et al., in preparation). These dimeric and trimeric species might be intermediates leading to the formation of the tetrameric structure. However, we cannot exclude yet that they represent dead ends in the pathway towards quadruplexes their progressive disappearance at long incubation times do not unambiguously demonstrate they are true intermediates. 

JosHi, A. P., U. R. Nayak, and Sukh Dev Studies in Sesquiterpenes. L. 3-Hydroxy-longifolaldehyde, the Elusive Intermediate in the Abnormal Perbenzoic Acid Oxidation of Longifolene. Tetrahedron 32, 1423 (1976). 

Thioketone 5-oxides with pronounced steric hindrance such as the thiopivalophenone Soxide (139) are thionated with LR to yield the corresponding Ssulfides (140) as elusive intermediates, which further react with a thione to afford the 1,2,4-trithiolane (141) (eq 47). ... 

The potential for introduction of chiral centres using a Diels-Alder approach makes this a particularly attractive route to benzo-fused cyclohexanes. However, the chemistry of orthoxylylenes is relatively unexplored as previous routes to this elusive intermediate involved the use of reagents such as disodium tetracarbonylferrate. This reagent is extremely intolerant of other functional groups, mainly as a result of its high basicity and the yields obtained are only a fraction of those available using the zinc/ultrasound route. 

One of the most promising applications of mass spectrometry to the chemistry of metal compounds is in the investigation of the reactivity of metal-containing ions and molecules in the gas phase. Information about transformations of molecules on metal centres can be provided by these experiments. This is especially profitable in the study of mechanisms of reactions involving elusive intermediates (catalytic processes, interstellar chemistry, etc.) that cannot be isolated or characterized by traditional spectral methods. 

One final example within this context is discussed here and this chemistry was reported by the Minakata group [86]. The synthesis starts with the use of butynyl or butenyl alcohols, which can be converted in situ to carbonic acid monoesters by treatment with CO2 (Figure 10). Although being elusive intermediates and supposed to be highly... 

Minkin VI, Metelitsa AV, Dorogan IV, Lukyanov BS, Besugjiy SO, Micheau J-C (2005) Spectroscopic and theoretical evidence for the elusive intermediate of the photoinitiated and thermal rearrangements of photochromic spiropyrans. J Phys Chem A 109 9605-9616... 

An elusive intermediate of atmospheric reactions of HONO may be nitrosyl O-hydroxide, HOON. Electronic structure calculations seem to indicate that HOON is best represented by a combination of three... 

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