4-Phenyl-l ,2,4-triazoline-3,5-dione, 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). 

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 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. 

The N=N double bond of 4-phenyl-l,2,4-triazoline-3,5-dione (PTAD) (177) is undoubtedly the most studied heteroatom-heteroatom multiple bond involved in reactions with MCPs. 

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. 

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. 

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. 

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>. 

Some hetero double bond systems have been shown to enter [3 + 2] cycloaddition reactions with the mesoionic 1,3-dithiolones. Thus, the mesoionic 1,3-dithiolones (2) react with formaldehyde, prepared in situ by depolymerization of paraformaldehyde, with regiospecific formation of the 2-oxa-6,7-dithiabicyclo[2.2.1]heptanone derivatives (131). The corresponding reaction of (2) with the N=N double bond of dimethyl azodicarboxylate proceeds via cycloaddition yielding (132), and a similar reaction takes place between (2) and 4-phenyl-l,2,4-triazoline-3,5-dione (78CB3171). 

Reaction of a sulfonamide-protected 5-vinylimidazole 516 with 4-phenyl-l,2,4-triazoline-3,5-dione 517 in methanol gave the Diels-Alder adduct 518 in 85% yield, subequent aromatization to form the imidazole ring in 519 was achieved quantitatively by DBU treatment (Scheme 118) <1998TL4561, 20010L1319>. 

There have been only a few reports of reactions of this type including cycloaddition of dienes 157 with the powerful dienophile 4-phenyl-l,2,4-triazoline-3,5-dione <1996J(P1)2297> and stereoselective cycloaddition of the chiral nitrone 158 with a variety of dipolarophiles <2000JOC7000>. A rare example of intramolecular hetero-Diels-Alder reaction involving a 4-methylene-l,3-oxathiolan-5-one 3 -oxide is provided by the cycloaddition reaction of 159 to give 160 (Equation 42) <1998EJ02733>. 

DIELS-ALDER REACTIONS Bis(triphen-ylphosphine)dicyanonickel(O). 2-Chloro-acrylonitrile. 2-Chloroacrylyl chloride. Cyclopropene. Dichloromaleic anhydride. Dicyanoacetylene. Indanocyclone. Oxygen, singlet. 4-Phenyl-l,2,4-triazoline-3,5-dione. 

Whereas methylenecyclopropanes only react with highly electron-deficient dienophiles in a [ 2n + 2fT) + 2n] fashion, alkenylidenecyclopropanes 1 readily undergo this cycloaddition type. A number of comprehensive and elaborate investigations with various alkenylidenecyclopropanes and 4-phenyl-l,2,4-triazoline-3,5-dione indicate that these reactions are concerted and proceed via [( 2j+,25+ 2 J -I-, 2 J transition states, involving the terminal double bond in an eight-electron Mobius aromatic transition structure 4. 

The mechanism of this type of reaction has received some attention.It has been suggested that these reactions are pericyclic processes, and since N=N dienophiles have lower lying LUMOs than C=—C compounds, Aey are more reactive. Cyclic N N species have an even lower LUMO energy. However, a recent investigation of the cycloadditions of 4-phenyl-l,2,4-triazoline-3,5-dione (vide infra) indicates that in at least some cases the Diels-Alder reactions involve discrete intermediates.It would appear that a range of mechanisms may be available to azo dienophiles. 

Ergosta-5,7,22,24(28)-tetraen-3jS-ol has been synthesised from ergosterol by ozonolysis to the 22-aldehyde and construction of the appropriate side-chain using a Wittig reaction. During these reactions, the 5,7-diene system was protected as the Diels-Alder adduct (546) with 4-phenyl-l,2,4-triazolin-3,5-dione, from which the homoannular diene could be regenerated in 99 % yield by reduction with lithium aluminium hydride. 

Other Addition Reactions.—A review on the applications of retro-Diels-Alder reactions has appeared. Reformation of the steroidal 5,7-dienes from the 4-phenyl-l,2,4-triazoline-3,5-dione adducts was achieved by heating with K2CO3 in DMSO or DME. This provides a very useful alternative to the previously reported L1A1H4 cleavage. A cation-radical mechanism was proposed... 

Diels-Alder reactions. This butadiene dimer reacts with tetracyanoethyl-ene and maleic anhydride to give only 1 1 adducts, (2) and (3), even under forcing conditions. However, it does give the diadduct (4) with the highly reactive 4-phenyl-l, 2,4-triazoline-3,5-dione. 

The hydrolysis of 2,5-dimethoxythiophene leads to methyl 2-methoxythiocarbonylpropionate. The corresponding thiomaleate (541) has now been prepared <82CC1033>. Reaction of 4-phenyl-l,2,4-triazolin-3,5-dione with 2,5-dimethoxythiophene in wet methanol gives (541) in 87% yield (Scheme 112) this easily isomerizes to the thiofumarate (542). If the reaction is run in anhydrous methanol at — 15°C, the unstable adduct (540) can be isolated. This rapidly hydrolyzes to (541). The formation of (540) could have taken place via either the zwitter ion (543) or the Diels-Alder adduct (544). 

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