L,2,4-Triazoline-3,5-diones, reactions

The values of X = NH, OH, F, Cl, and CH3 are smaller than that of X = H, in accordance with the observed selectivity. Excellent correlation was found for all other cyclopentadienes described above. Syn rr-facial selectivity in the reactions between 4-phenyl-l,2,4-triazoline-3,5-dione and cyclopentadiene having simple alkyl group at 5 positions are reported by Burnell and coworkers [46] (Scheme 37). 

The low temperature ene reactions of 4-substituted-l,2,4-triazoline-3,5-diones (RTD) were used to modify polydiene surfaces. Hydrophilic surfaces (contact angles with water of 30-50°) were obtained on polybutadiene, poly-isoprene and styrene-butadiene copolymers by first treating the polymer at room temperature with RTD (R=Ph,... 

Of particular interest to us was to find a method to surface modify elastomers. G. B. Butler and co-workers have demonstrated that 4-substituted-l,2,4-triazoline-3,5-diones, RTDs, readily undergo ene reactions with polydienes at ambient temperatures (13). They found that the solubility and solution properties of the modified... 

Electrocyclic reactions have been performed with three of the bridged [ 11 Jan-nulenones. Both 11 and 13, which both contain a cycloheptatriene unit, undergo Diels-Alder additions with dienophiles via their norcaradiene valence tautomers 41 and 43 and yield adducts of the type 42 and 44. Annulenone 13 was found to react only with 4-phenyl-l,2,4-triazoline-3,5-dione whilst 11 underwent reaction with a variety of dienophiles. 3,8-Methano[ 11 Jannulenone 12 contains a tetraene system and undergoes addition reactions, apparently of the (8 + 2)-type, at the termini of the tetraene system. Thus with maleic anhydride the adduct 46, the valence tautomer of the initial adduct 45, was isolated. 

The reaction of 4-methyl-l,2,4-triazoline-3,5-dione 428 with tetracyclopropylethylene gives 5,5,6,6-tetracyclopropyl-3-methyl-5,6-dihydro-oxazolo[3,2-A][l,2,4]triazolium-2-olate 140 (unreported yield) (Equation 89) <2004JA700>. 

The most powerful azo dienophile is the cisoid 4-phenyl-l,2,4-triazoline-3,5-dione 264, which is surpassed in reactivity only by singlet oxygen. The dione adds rapidly to all types of dienes and the process can be followed visually since the bright-red color of the reagent is discharged when the reaction is complete136. 

Scheme 18 Separation of zingiberene from ginger oil using a selective and reversible Diels-Alder reaction with phenyl l,2,4-triazoline-3,5-dione (PTAD) [105]...

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... 

In common with other azodicarboxylic acid derivatives, the uses of 4-phenyl-l,2,4-triazoline-3,5-dione are many. It undergoes a Diels-Alder reaction with most dienes11-14 and is, in fact, the most reactive dienophile so far reported.15 16 As with the formation of all Diels-Alder adducts the reaction is reversible, and in the case of the adduct with 3-j3-acetoxy-17-cyano-5,14,16-androstatriene, the reverse reaction can be made to proceed under especially mild conditions.14 An instance has also been reported of the dione photochemically catalyzing other retro Diels-Alder reactions.17 Along with the proven use of azodicarboxylic ester,18-18 the dione should be potentially important in the preparation of strained ring compounds. 

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. 

New examples involve the reaction of 5-vinyl-17/-imidazole 293 with 4-phenyl-l,2,4-triazoline-3,5-dione 294. In this way, the imidazo[4,5-i ]pyridazine skeleton was smoothly constructed (Equation 72) <1998TL4561>. Another example using in situ formed 294 can be found in Section 8.01.6.5. 

The following types of dipolarophiles have been used successfully to synthesize five-membered heterocycles containing three heteroatoms by [3 + 2]-cycloaddition of thiocarbonyl ylides azo compounds, nitroso compounds, sulfur dioxide, and Al-sulfiny-lamines. As was reported by Huisgen and co-workers (91), azodicarboxylates were noted to be superior dipolarophiles in reactions with thiocarbonyl ylides. Differently substituted l,3,4-thiadiazolidine-3,4-dicarboxylates of type 132 have been prepared using aromatic and aliphatic thioketone (5)-methylides (172). Bicyclic products (133) were also obtained using A-phenyl l,2,4-triazoline-3,5-dione (173,174). 

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). 

Several cycloaddition reactions of vinylthiophene and vinylbenzo[6]thiophene are known. 2-Vinylthiophene easily adds 4-phenyI-l,2,4-triazoline-3,5-dione to give (308) (74JA5591). 2-Vinyl-thiophenes also undergo stereospecific cycloaddition with singlet oxygen to produce the corresponding endoperoxides (Scheme 87) (75TL4471). 

Photolysis and thermolysis of 4-aryl-l,2,4-triazoline-3,5-diones (70, R = aryl) have been studied by Wamhoff and Wald (77CB1699). Photolysis produces the same products as were found in FVP. The thermal conversion of 70, R = Ph, into the corresponding s-triazolo[l,2-a]-s-triazole derivative, which takes place below the decomposition temperature of the educt, is assumed to proceed via a radical chain reaction (Scheme 8). 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

A 1,4-dipolar cycloaddition between tetrahydropyrido[l,2-a]pyrimidi-none 114 (R = Me) and 4-methyl-l, 2,4-triazoline-3,5-dione 666gave stable adduct 667 in acetonitrile or in acetic acid at room temperature for 1 hour (Scheme 44) (85CB4567). When ethyl cyanoformate was used as dienophile in boiling toluene for 20 hours, ethyl 3-methyl-4-oxo-6,7,8,9-tetrahydro-4//-pyrido[ 1,2-a]pyrimidine-2-carboxylate 669 was obtained (86CB1445). Pyrido[l,2-a]pyrimidine-2-carboxylate 669 was formed from the initial adduct 668 by elimination of phenyl isocyanate. Reaction of tetrahydropyr-ido[l,2-a]pyrimidinone 114 (R = Me) with l-(diethylamino)-l-propyne in... 

Phenyl-l,2,4-triazoline-3,5-dione acts as a dienophile by in situ reaction with butadiene, cyclopentadiene, cycloheptatriene, and bicyclohepta-diene (62TL615). Thus, it is possible to compare the reactivity of the cis-azo dienophile (110) with trans-azo dienophiles, such as ethyl azodicar-boxylate, which has been observed to undergo alternate modes of reaction when used with less reactive or hindered dienes. Treatment of (110) with several dienes resulted in exclusively Diels-Alder addition. The results are summarized in Table III. 

The aziridinofullerenes and azafulleroids obtained by Mattay et al. were subjected to further reactions to yield fullerene adducts of the second generation. As a model compound 4-methyl-l,2,4-triazoline-3,5-dione (NMTAD) 187, which is one of the most reactive dienophiles for Diels-Alder reactions, was selected. Sheridan et al. studied the photoinduced [4 + 2] cycloadditions of NMTAD to arenes [295], With alkenes, however, NMTAD reacts in photoinduced cycloadditions in a [2 + 2] fashion under formation of diazetidines [296], Both the sulfonyl-azafulleroids (185) and aziridinofullerene (186) were irradiated at 420 nm to give both the same [2 + 2] cycloadduct 186 (Scheme 71) [291], This indicates that at a certain stage rearrangements must be involved. 

Oxidation of hydrazines to diazines. Propargylic hydrazines are oxidized rapidly and efficiently in CH3OH at 0° by 4-methyl-l,2,4-triazoline-3,5-dione (MTAD) or diethyl azodicarboxylate (DEAD) with evolution of nitrogen to provide the corresponding allenes in 50-70% yield. The reaction occurs with high stereospecificity, and can be used to obtain optically active allenes (equation I).1... 

Diels-Alder reaction of 93 with dimethyl acetylenedicarboxylate (DMAD), maleic anhydride, or 4-phenyl-l,2,4-triazoline-3,5-dione gives the tri- and polycyclic products 94-97 in 57-95% yield (Scheme 3) <2004S2665>. 

Kim and O Shea have reported highly electrophilic additions of 4-substituted l,2,4-triazoline-3,5-diones with substituted alkenes by [2+2] cycloaddition reactions (Equation 33) <2004JA700>. A possible mechanism is depicted in Scheme 38. 

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