Triazolines, oxidation

In azide addition to quinones, the triazoline adducts are spontaneously oxidized to the triazoles.1-8 9,279-281,317,392 393 Potassium permanganate32,155,286,288 and nickel peroxide394 also effect triazoline oxidation. Permanganate oxidation of 1,5-substituted triazolines in a two-phase system using a phase-transfer catalyst provides a convenient route to the synthesis of 1,5-disubstituted triazoles (Scheme 118).395,396 Triazoline 4-carboxylic esters32,287,288 and a 4-carboxamide397 are converted to triazoles by potassium permanganate and nickel peroxide, respectively. 

In many instances, however, the intermediate triazoline can be isolated and separately converted into the aziridine, often with poor stereoselectivity. The first practical modification to the original reaction conditions generated the (presumed) nitrenes by in situ oxidation of hydrazine derivatives. Thus, Atkinson and Rees prepared a range of N-amino aziridine derivatives by treatment of N-aminophthali-mides (and other N-aminoheterocydes) with alkenes in the presence of lead tetraacetate (Scheme 4.10) [7]. 

Triazoline imino sugar derivatives 297 that are prospective glycosidase inhibitors have been prepared as single diastereomers in high yield via an lAOC reaction of in situ generated azido alkene 296 (Eq. 32) [78]. m-CPBA oxidation of the dithioacetal groups in the 0-acetylated 5-azido-5-deoxydibenzyl dithio-acetal of o-xylose or D-ribose 294 to the bis-sulfone 295, followed by loss of HOAc between C-1 and C-2 provided the lAOC precursor 296. 

When a solution of phenacyl halide 258 and excess tosyl hydrazide in methanol is heated to reflux, l-(tosylamido)-4-aryltriazole 261 is formed. The reaction proceeds presumably via dihydrazide derivative 259 that subsequently undergoes intramolecular cyclocondensation to triazoline 260. In the following step, the triazoline must be oxidized to the final triazole product 261. Mechanism of the oxidation is not quite clear, but the probable oxidant is the starting phenacyl halide, as a half of it is converted to the corresponding acetophenone tosylhydrazone that is isolated as the main side product of the reaction (Scheme 37) <2004H(63)1175>. 

Dienophilic cyclic a-carbonylazo compounds (triazoline diones, indazolone, phthalazine dione) prepared in a flow cell, by anodic oxidation of the corresponding hydrazino compounds in acidic methanol or acetonitrile, react with dienes (Scheme 50) [72, 73]. 

The versatility of permanganate as an oxidant has been greatly enhanced in the past decade by the observation that it can be solubilized in nonaqueous solvents with the aid of phase transfer agents (1). The literature contains descriptions for the use of this procedure for the oxidation of alkenes (2-13), alkynes (13-18), aldehydes (19), alcohols (20), phenols (21,22), ethers (23), sulfides (24,25), and amines (20,26). The dehydrogenation of triazolines has also been achieved by the use of permanganate and a phase transfer agent (27). ... 

From Azides and x-Acylphosphorus ylids Addition of azides to a-acylphosphorus ylids takes place at room temperature in dichloromethane or at 80°C in benzene, giving triazolines from which a phosphine oxide is spontaneously eliminated. " The ylids exist almost exclusively in the cis-enolate configuration, and a mechanism involving concerted 1,3-dipolar addition has been proposed (Scheme 12) on the basis that there is a low entropy of activation for the reaction, and that the reaction rate is insensitive to changes in solvent polarity. ... 

Phenyl-l,2,4-triazoline-3,5-dione has been prepared by oxidizing 4-phenylurazole with lead dioxide,7 and with ammoni-acal silver nitrate followed by an ethereal solution of iodine.8 The yields are low for both methods. 4-Substituted triazoline-diones can also be made by oxidation of the corresponding urazole with fuming nitric acid9 or dinitrogen tetroxide.10 Oxidation by <-butyl hypochlorite in acetone solution has also been described 1112 it, however, yields an unstable product, even after sublimation. Either dioxane12 or ethyl acetate are preferred as solvents for the reaction, since the product is obtained in a stable form. The latter solvent is superior since... 

Phenyl-l,2,4-triazoline-3,5-dione also undergoes addition-abstraction reactions (e.g., with acetone17). As would be expected for such a species, it will oxidize alcohols to the corresponding aldehydes or ketones.20 This oxidation is especially mild (room temperature in benzene, chlorobenzene or ethyl acetate) and so is a valuable method of oxidizing, or preparing, compounds sensitive to acid, base, or heat. 

Table 16 Comparison of NiOj and KMn04 oxidation of 1,5-disubstituted 1,2,3-triazolines <90JOC5891>.

The synthetic applications of substituted 1,2,3-triazole 1-oxides and 1,2,3-triazolium-l-imides in the preparations of 1,2,3-triazines, 1,3,4,5-oxo- and -thia-triazines, and 1,2,3,5-tetrazines have been discussed in Section 4.01.4.12. Conversions of 1,2,3-triazolines into aziridines either thermally or photochemically were described in detail in CHEC-I <84CHEC-1(5)691 > and in a review <84AHC(37)217>. Some recent developments are discussed in Section 4.01.5. 

Substituted l,2,4-triazoline-3,5-diones are excellent dienophiles which react rapidly at room temperature with oxepins, but particularly with the arene oxide valence tautomer. A similar [4+2] cycloaddition reaction between the episulfide tautomer of thiepin (44) and 4-phenyl-l,2,4-triazoline-3,5-dione has been reported (74AG(E)736>. Benzene episulfide (the valence tautomer of thiepin 44) was generated in situ by thermal decomposition of the diepisulfide (151) at 20 °C and trapped as a cycloadduct at the same temperature (equation 34). A 1,3-dipolar cycloaddition reaction between thiepin (152) and diazomethane has been reported (56CB2608). Two possible cycloadduct products are shown since the final structure has not been unequivocally established (equation 35). 

Kabada268 has prepared heterocyclic 5-substituted 1,2,3-triazoles (172) by oxidation of 1,2,3-triazolines with KMn04 under PT conditions. 

Amino-3-hydrazino-l,2,4-triazoline-5-thione (122) and aldehydes form unstable products (123), which readily air-oxidize to deeply colored tetrazines (124). This is a sensitive method for determining aldehydes (70CC1719). 

Triazoline aromatization to triazoles can be achieved by oxidation, isomerization reactions, and elimination of stable molecular fragments, all of which require the presence of a free hydrogen at position 4 and/or 5 of the triazoline ring. The aromatization reaction affords a selective, synthetic route for the preparation of triazoles of definitive structure, inasmuch as azide addition to acetylenes is not regioselective.33... 

However, the possibility of equilibrium between triazoline 4-carboxylic esters and the ring-opened diazo compounds (Section II,A,4,a) poses a problem as to which entity is actually oxidized. In fact, the open-chain tautomers formed from the addition of phenyl azide to acrylic and cinnamic esters are oxidized in good yield to the triazoles by permanganate (Scheme 119).32-28" 398 When the diazo compound is formed with ease, the oxidation is very smooth284 thus the diazo compound from the addition of phenyl or methyl azide to benzylideneacetone is oxidized rapidly in air to a triazole-4-carboxylic ester.284 A similar mechanism may be proposed to... 

The triazoline diazo compound equilibrium may be considered to play a role in the cis-trans isomerization332 and oxidation (Scheme 119)284 of certain triazolines. Triazole formation by elimination of amine214 or alcohol405 is also postulated to involve intermediate diazo compounds (Scheme 123). Unlike normal triazolines, the inability of 1-fluorotriazolines to undergo thermolysis or photolysis reactions to yield aziridines is ascribed to the fact that the triazoline always exists in equilibrium with the diazo compound (Scheme 98).356 Spontaneous isomerizations of triazolines not... 

N-Methylindole acts like an enamine with sulfonyl azides and gives a diazoimino compound.443-445 So does dihydropyridine but only in the presence of 5% lithium hydroxide (Scheme 147).242 A triazole is postulated to be formed from the triazoline followed by a ring opening oxidation of diazoamino compounds to triazoles has been known to proceed via a diazoimino compound in equilibrium with the triazole (Scheme 1 19).285-3"-400... 

The A4-triazoline II showed a single proton at higher field than for diethyl maleate, indicating that the ester groups might be cis, an arrangement which would reduce steric congestion.23 Other possible structures for II were excluded based on the absence of NH, as shown by the NMR spectrum which was unaltered by addition of deuterium oxide.23... 

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