Trioxanes, formation

The 1,2-dioxetanes of 2-(phenoxymethylidene)adamantanes (206) when mixed with excess acetaldehyde in methylene chloride containing a catalytic amount of Amberlyst-15 give the erythro and threo diastereomers (220) and (221) in a ratio of ca. 2 1 and yields of 45-75% (Equation (33)) <83HCA2615>. p-Chloro- and p-methoxyphenoxy-substituted dioxetanes give the highest yields. Trioxane formation is less efficient with propanal and the p-chloro and p-nitro derivatives of... 

The conventional electrochemical reduction of carbon dioxide tends to give formic acid as the major product, which can be obtained with a 90% current efficiency using, for example, indium, tin, or mercury cathodes. Being able to convert CO2 initially to formates or formaldehyde is in itself significant. In our direct oxidation liquid feed fuel cell, varied oxygenates such as formaldehyde, formic acid and methyl formate, dimethoxymethane, trimethoxymethane, trioxane, and dimethyl carbonate are all useful fuels. At the same time, they can also be readily reduced further to methyl alcohol by varied chemical or enzymatic processes. 

Trioxane and Tetraoxane. The cycHc symmetrical trimer of formaldehyde, trioxane [110-88-3] is prepared by acid-catalyzed Hquid- or vapor-phase processes (147—151). It is a colorless crystalline soHd that bods at 114.5°C and melts at 61—62°C (17,152). The heats of formation are — 176.9 kJ/mol (—42.28 kcal/mol) from monomeric formaldehyde and —88.7 kJ/mol (—21.19 kcal/mol) from 60% aqueous formaldehyde. It can be produced by continuous distillation of 60% aqueous formaldehyde containing 2—5% sulfuric acid. Trioxane is extracted from the distillate with benzene or methylene chloride and recovered by distillation (153) or crystallization (154). It is mainly used for the production of acetal resins (qv). 

Formaldehyde is a gas with a boiling point of -21 °C. It is usually supplied as a stabilised aqueous solution ( 40% formaldehyde) known as formalin. When formalin is used as the source of the aldehyde, impurities present generally include water, methanol, formic acid, methylal, methyl formate and carbon dioxide. The first three of these impurities interfere with polymerisation reactions and need to be removed as much as possible. In commercial polymerisation the low polymers trioxane and paraformaldehyde are convenient sources of formaldehyde since they can be obtained in a greater state of purity. 

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>. 

From gas-phase ion-molecule reactions we obtain54 the necessary enthalpy of formation of 34, 44 8 kJmol-1, and so derive A//f(33, g) as equal to ca —46 kJmol-1. Is this number plausible We start with the trimerization enthalpy. Intuitively, this number for C=N bonded species should interpolate the trimerization enthalpy of species with C=C and C=0 bonds. More precisely, since it is N and not C that is methylated, the trimerization enthalpy of 34 should be close to that of CH2NH. As such, this reaction enthalpy should interpolate that of CH20 and CH2CH2. Our thermochemical archive includes the enthalpies of formation of these latter two substances and of their trimers, 1,3,5-trioxane (33, X = O), and cyclohexane (alternatively identified as 33, X = CH2 and 2, n = 6), from which derive the desired reaction enthalpies —140.1 and —276.0 kJmol-1 respectively. The reaction enthalpy for the X = NMe case interpolates that of X = CH2 and X = O as expected from size and electronegativity reasoning. 

PROPYLENE OXIDE ETHYL FORMATE METHYL ACETATE PROPIONIC ACID 3-MERCAPTOPROPIONIC ACID LACTIC ACID METHOXYACETIC ACID TRIOXANE THIACYCLOBUTANE 1-BROMOPROPANE... 

Formaldehyde, in aqueous acidic solution, undergoes cyclotrimerization to trioxane (1,3,5-trioxacyclohexane), and also disproportionation to methanol and formic acid, with some resultant formation of methyl formate. The kinetic behaviour observed suggests a significant autocatalysis by formic acid. 

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 ... 

Using various derivatives of artemisinic acid, the methodology onthned in Scheme 184 was extended to the synthesis of a nnmber of modified artemisinin-type tetracychc trioxanes. For example, the syntheses of 6,9-desdimethylartemisinin 586a , A-fi-hydroxyartemisinin , and C9-alkylated artemisinin analognes were reported . In some cases it is possible to avoid the lactonization step while preserving the ester fnnctionality and interrnpting the cychzation of aldehyde-peroxyhemiacetals of type 652, at the step of formation of tricyclic 5-hydroxy-1,2,4-trioxane . ... 

Treatment of compound 222, containing a 1,2,4-trioxane ring fused to a cyclopentene ring, with O2 leads to formation of a hydroperoxide (223) with ene displacement, as shown in equation 76. The structure of 223 was determined by single-crystal XRD analysis. A contact of the hydroperoxy group with the endocyclic ether O atom of a neighboring molecule (287.4 pm) points to weak H-bonding. ... 

Posner and Oh, and later Jefford and coworkers led the earliest investigations by synthetic chemists into the mechanism of action of 1,2,4-trioxane antimalarials. Both proposed that formation of a C-centred radical was essential for activity but the nature of the radical (primary or secondary) and the mechanistic pathways put forward were not identical. The iron degradation studies of Posner and coworkers implicated a role for the... 

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). ... 

The concept of a (bound) formaldehyde intermediate in CO hydrogenation is supported by the work of Feder and Rathke (36) and Fahey (43). Experiments under H2/CO pressure at 182-220°C showed that paraformaldehyde and trioxane (which depolymerize to formaldehyde at reaction temperatures) are converted by the cobalt catalyst to the same products as those formed from H2/CO alone. The rate of product formation is faster than in comparable H2/CO-only experiments, and product distributions are different, apparently because secondary reactions are now less competitive. However, Rathke and Feder note that the formate/alcohol ratio is similar to that found in H2/CO-only reactions (36). Roth and Orchin have reported that monomeric formaldehyde reacts with HCo(CO)4 under 1 atm of CO at 0°C to form glycolaldehyde, an ethylene glycol precursor (75). The postulated steps in this process are shown in (19)—(21), in which complexes not observed but... 

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