1,3,5-trioxane, protonation

Both reaction kinetics and chemical equilibria of the formation/decomposition of 1,3,5-trioxane in aqueous formaldehyde solutions were studied by quantitative H NMR spectroscopy <2006MI910> a virtual reference signal of high stability was generated electronically and employed for the quantification of the small 1,3,5-trioxane proton signal. 

DFT molecular dynamics simulations were used to investigate the kinetics of the chemical reactions that occur during the induction phase of acid-catalyzed polymerization of 205 [97JA7218]. These calculations support the experimental finding that the induction phase is characterized by the protolysis of 205 followed by a rapid decomposition into two formaldehyde molecules plus a methylenic carbocation (Scheme 135). For the second phase of the polymerization process, a reaction of the protonated 1,3,5-trioxane 208 with formaldehyde yielding 1,3,5,7-tetroxane 209 is discussed (Scheme 136). 

Curioni et al.148 studied the protonation of 1,3-dioxane and 1,3,5-trioxane by means of CP molecular dynamics similations. The dynamics of both molecules was continued for few ps following protonation. The simulation provided a detailed picture the evolution of both the geometry and the electronic structure, which helped to rationalize some experimental observations. CP molecular dynamics simulations were applied by Tuckerman et al.149,150 to study the dynamics of hydronium (H30+) and hydroxyl (OH-) ions in liquid water. These ions are involved in charge transfer processes in liquid water H20 H+. .. OH2 - H20. .. H+-OH2, and HOH. . . OH- -> HO-. . . HOH. For the solvatetd H30+ ion, a picture consistent with experiment emerged from the simulation. The simulation showed that the HsO+ ion forms a complex with water molecules, the structure of which oscillates between the ones of H502 and I L/ij clusters as a result of frequent proton transfers. During a consid-... 

This consists of protonation in a fast pre-equilibrium process followed by ratedetermining reaction of the protonated substrate SH +, equation (30) a typical example is the much-studied acid-catalyzed depolymerization of trioxane, shown in equation (31).144... 

If the substrate is predominantly unprotonated in the acidity range covered, the protonation correction term (second on the left in equation (35)) will be zero, and if the activity coefficient term on the right cancels to zero, log values will be linear in —Ho with unit slope (the Zucker-Hammett hypothesis).146 In practice, linearity is usually observed,23 e.g. for the trioxane depolymerization in equation (31),144 although the slopes are seldom exactly unity. For more strongly basic substrates that are predominantly protonated in the acidity range covered, equation (36) is easily derived this is acidity independent and should have zero slope against — H0 if the substrate is fully protonated and the last term cancels.145... 

The next structural study of polydioxolans of DP ranging from 7 to 70 by Plesch and Westermann [6] confirmed the regular structure of the polymer. It was also shown that when a polydioxolan was formed and then depolymerised in solution by perchloric acid, the only product was monomer. This is apparently in conflict with the findings of Miki, Higashimura, and Okamura [7] who reported that a reaction mixture, in which dioxolan had been polymerised for 3 hours at 35 °C by BF3-Et20, contained 1,3,5-trioxepan, 1,4-dioxane, trioxane, and other compounds. Most probably the difference is at least partly due to the long reaction time and the use of boronfluoride, which is well known to produce more side-reactions than protonic acids. 

Also for 1,2,4-trioxane, from MM3 calculations, a structure close to a chair with the protons and substituents in axial and equatorial positions, respectively, was suggested [92JCS(CC)1689]. The substituted derivatives 63 (Scheme 25) have substituents R [Me, iPr, CH2HgBr, CH(HgBr)Me] in an equatorial position (all in agreement with standard conformational principles), and only in 64-66 were axial methyl substituents reported, based on NOE measurements and 7c-h coupling constants [92JCS(CC)1689]. 

It should be noted that, in addition to the product shown in Scheme 3, the ring-contracted THF product 21 was also observed. Indeed, significant quantities of both 21 and deoxyartemisinin 3 (using iron(II) bromide in THF) were observed in a ratio 13 21 3 of 1 6 3, determined from the proton NMR spectrum. A second pathway (in which SET occurs from iron(II) to Ol the 01 route ) leading to formation of a similar THF product was suggested in 1992 when investigating the degradation of an 0-labelled trioxane (Scheme 1). ... 

Fig. 9.10. Mechanism of the proton-catalyzed polymerization of monomeric formaldehyde (top), formalin (middle) and 1,3,5-trioxane (F bottom) to give polyformaldehyde ("paraformaldehyde" H), respectively. The carboxonium ions A, B, C, E etc. play a central role. They are transformed into each other through the nucleophilic reaction of a formaldehyde monomer on the respective carboxonium carbon atom. Analogously, E and formaldehyde continue to react to yield a high-molecular carboxonium ion that is intercepted by (traces of) water to furnish the final neutral product H.

Table I. Assignment o New Proton Signals During the Copolymerization of Trioxane and Ethylene Oxide ...

Radical nucleophile oxidation based on one-electron oxidation, known as the Minisci reaction, is employed for the functionalization of /V-heterocycles with acidic hydrogen peroxide in the presence of iron(II) salts (Figure 3.112).472 A range of A-heterocycles (pyridines, pyrazines, quinolines, etc.) which are activated towards attack by nucleophilic radicals when protonated are suited to this chemistry. The Minisci reaction is suitable for the preparation of carboxylic amides (from formamide), carboxylic esters (from pyruvic esters via a hydroxyhydroperoxide), aldehydes (from 1,3,5-trioxane) and alkylated pyridines (either from carboxylic acids or from alkyl iodides in dimethyl sulfoxide).473 The latter reaction uses dimethyl sulfoxide as the source of methyl radical (Figure 3.112). 

Indeed, at least in one case (polymerization of 1,3,5-trioxane), it has been shown that BF3 does not initiate the polymerization of rigorously purified monomer, although polymerization proceeds in less thoroughly dried systems [38], Also in the presence of proton trap, BF3 does not initiate the polymerization of 1,3,5-trioxane [39]. 

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