1.2.4- Trioxan-5-ones

To distinguish between dioxane and trioxane, one can decyclize trioxane back into formaldehydes by adding acid and heating and then perform the Tollen s test or Schiff test. 

Lespiau s [23] synthesis (in the same period) of 3-buten-l-ol (in 30% yield) by a Barbier reaction with allyl bromide, magnesium and trioxane - one of the earliest reports of Barbier reactions with allylic halides - has been mentioned in Sect. 2.3 (p. 20)... 

The details of the commercial preparation of acetal homo- and copolymers are discussed later. One aspect of the polymerisation so pervades the chemistry of the resulting polymers that familiarity with it is a prerequisite for understanding the chemistry of the polymers, the often subde differences between homo- and copolymers, and the difficulties which had to be overcome to make the polymers commercially useful. The ionic polymerisations of formaldehyde and trioxane are equiUbrium reactions. Unless suitable measures are taken, polymer will begin to revert to monomeric formaldehyde at processing temperatures by depolymerisation (called unsipping) which begins at chain ends. 

One variation of rearrangement polymerisation is ring-opening polymerisation. Important examples include the polymerisation of trioxane, ethylene oxide and e-caprolactam Figure 2.8 (a) to (c) respectively). It is to be noted that... 

Obtain the energies of formaldehyde and 1,3,5-trioxane. What is AH n for trioxane cracking Is the process endothermic or exothermic Is ASrxn for the cracking reaction likely to be positive or negative Explain. Given the direction of the change in entropy, should one crack trioxane at higher or lower temperatures Explain (use equation 1). 

Even with the limitation on yield implied by the statistical process, cross-dimerization is still useful when one of the reactants is an alkane, because the products are easy to separate, and because of the few other ways to functionalize an alkane. The cross-coupling of an alkane with trioxane is especially valuable, because hydrolysis of the product (10-6) gives an aldehyde, thus achieving the conversion RH RCHO. The mechanism probably involves abstraction of H by the excited Hg atom, and coupling of the resulting radicals. 

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-... 

The mechanism of oxetane formation is similar to the one discussed for cyclobutane formation in chapter 4.3.3. The 1,4-diradicals can be efficiently trapped with molecular oxygen. The resulting 1,2,4-trioxanes are interesting synthetic intermediates (4.81) 495>. 

Both end groups can be determined quantitatively. A second side reaction is the transacetalization. Here a poly(oxymethylene) cation attacks an oxygen of a poly(oxymethylene) chain with formation of an oxonium ion that decomposes. Through continued cleavage and recombination of poly(oxymethylene) chains one obtains polymers which are chemically and molecularly largely homogeneous. For the case of a trioxane/ethylene oxide copolymer the following reaction scheme can be formulated ... 

In addition to artemisinin, other synthetic trioxanes and endoperoxides (fenozan BO-7 4 and arteflene 5 " ) have enjoyed some success arteflene reached Phase II pre-clinical trials. More recently, Vennerstrom and coworkers have reported on the outstanding antimalarial properties of several 1,2,4-trioxolanes, one of which, OZ 277 (6), has entered clinical trials in man . These exciting, easily prepared drugs will be discussed in detail later in this chapter. In order to determine the parasiticidal action of this class of antimalarial, many research groups have focused their efforts on artemisinin and its semi-synthetic derivatives (artemether, arteether and artesunate Ic, Id and le), and this is the point where our discussion will begin. 

Aerobic Co(II) catalysed hydroperoxysiiyiation of allylic alcohols provides silyl peroxides that can be condensed with ketones to produce 1,2,4-trioxanes or 1,2,4-trioxepanes by a simple one-pot procedure (Scheme 35A). A recent improvement in the use of Co(acac)2 is the use of Co(thd)2 (thd = bis (2,2,6,6-tetramethyl-3,5-heptanedionato)). This more reactive catalyst allows cyclic allylic alcohols to be oxygenated and the resulting peroxysilyl alcohol can be transformed to spiro trioxanes, some of which have potent in vitro antimalarial activity (Scheme 35B). For example, compound 87 expresses activity around 20 nM (artemisinin = 10 nM). 

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