1.2.4- Triazole-3,5 dione, formation

Cyclization of the 5-(A -arylcarboxamido)-4-hydrazino-6methylpyrim-idin-2-ones 104 with two molar equivalents of formaldehyde in the presence of pyridine caused the concomittant triazole and pyrimidine ring formation to yield the 4-aryl-l,3,4,10-tetrahydro-6-methyl-l,2,4-tria-zolo-[2,3,4-c,d]pyrimido[4,5-d]pyrimidine-5,8-diones 105 (89AP599)... 

Occasionally, addition products of 4//-l,2,4-triazole-3,5-diones or diazenedicarboxylic esters and oxepins have been obtained whose formation can be rationalized by an addition to the 2,4-diene system in the oxepin, e.g. formation of 10.190191 In these cases, the primary adduct usually cannot be isolated, because it undergoes a hetero-Cope rearrangement to a tricyclic or bicyclic structure in which the oxepin oxygen has become part of a carbonyl function.190 191,227... 

Several relevant papers and review articles have appeared recently. These contain reports on the mechanism and kinetics of the ene reaction of ADC compounds,243-245 examples of four-membered ring formation,246-247 other cycloadditions of ADC compounds,248-252 the synthesis of azoalkanes,253 the use of chiral l,2,4-triazole-3,5-diones,254 and the use of the DEAZD/PI13P reagent in organic synthesis.255... 

Dienes. (+ )-Camphor-derived 1 H-, 2,4-triazole-3,5(2//,4//)-dione 24 was used to determine the absolute configuration of chiral cyclooctatetraenes of type 23 and ent-23 by cycloadduct formation (compare with 25 and 26) and X-ray analysis (see also p 446)166. 

Another interesting synthesis of spiro[2.3]hexan-4-one (16) comprised of dipolar attack of 4-phenyl-l,2-dihydro-4//-l,2,4-triazole-3,5-dione on bicyclopropylidcnc to give a zwitterion 17, which underwent ring enlargement to 18 before ring closure to diaziridine 19 took place. Accordingly, in the presence of water, 18 was trapped with formation of spiro[2.3]hexan-4-one (16) which was also obtained from 19 by saponification.118... 

As l,2,4-triazole-3,5-dione (PTAD) is a stronger dienophile than acetylenic esters, more facile formation of the Diels-Alder cycloadducts was expected. But because it cannot behave as a diene in a reaction with alkynes such as diethyl azodicarboxylate, the formation of dihydrooxadia-zines is excluded. In spite of these characteristics, no Diels-Alder adducts were obtained in the reaction of l-phenyl-4-vinylpyrazole with PTAD in acetone at -80°C and 2,2-dimethyl-4(l-phenylpyrazol-4-yl)-8-phenyl-l,6,8-triaza-3-oxabicyclo[4.3.0]nona-7,9-dione 277 was obtained as a major product. The isolation of the tetrahydrooxadiazine 277 indicates that the 1,4-dipole 278 was formed and trapped with acetone. 

Another field of research is concerned with the one-pot synthesis of this system from readily available starting materials. In Scheme 12, reaction of phenyl azide and malononitrile in the presence of sodium ethoxide leads, via the intermediate triazole (139), to the self-condensation product (140), itself a triazolopyrimidine. In the presence of other nitriles the preferred formation of the more useful compounds (141) occurs in low to moderate yields with small amounts of dimer <87JHC997>. Direct synthesis of the 5,7-dione derivatives (143) (60-90%) is achieved by the reaction of the readily available aminopyrimidinedione (142) with an azide iminium salt in dichloromethane at moderately high dilution <87JHC1493>. 

Dipolar cycloaddition of 3//-1.2.4-triazole-3,5(4// )-diones to strained bicyclic alkenes generally leads to the formation of rearranged 1,2,4-triazolidines (Section7.2.10.1.), although bicyclo[2.2.2]-octene does not react and cyclopentadiene dimer gives exclusively the cne reaction product24. 

The cycloadditions of diethyl diazenedicarboxylate and 3//-1,2,4-triazole-3,5(47/)-diones to 1,3-dienes where one only double bond is part of a fused or bridged bicyclic structure occurs with complete diastcrcoselectivity, since the diazene approaches the diene from the least hindered side, e.g., formation of 22 and 33. 

The cycloaddition of 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione to 2-ex0-3-exo-bis(chloromethyl)-5-[( )-methoxymethylidene]-6-methylidene-7-oxabicyclo[2.2.1]heptane occurs exclusively, within the limit of detectability by H NMR, on the e.vo-face, i.e., from above the plane of the molecule, to give ll6. This is in contrast to the endo-face selectivity reported for a large number of cycloadditions of dienes grafted on to the bicyclo[2.2.1] skeleton (see also Section 7.2.10.3.1). The formation of 7-oxabicyclo[2.2.1]heptane-diazene charge transfer complexes, i.e., the assistance of the ethereal bridge in the cycloaddition, has been invoked to explain the exo-face selectivity. 

Formation of a C-N bond at the expense of a C-H bond a to a cyclopropane ring was also observed for the cycloadduct of 4-phenyl-4ET-l,2,4-triazole-3,5-dione and methyl bicyclo[4.1.0]hept-2,4-diene-ex o-7-carboxylate which was treated with base followed by iodomethane and rearranged to give a triazine derivative in low yield. 

The reaction of 3-substituted 1,2-diphenylcyclopropenes with 4-phenyl-4//-l,2,4-triazole-3,5-dione gave urazoles, possibly via the formation of a spiro[2-azabicyclo[1.1.0]butane-2,T-l,2,4-triazole] and subsequent ring opening. 

This procedure uses readily available reagents and provides a simple and efficient method for nitrile synthesis. The entire sequence of four steps can be performed in a single day. Although product formation in the second step is presumably thermodynamically controlled, the cyanohydrazine is favored in all cases studied except with aryl ketones. A water-methanol solution of ammonium chloride and potassium cyanide can also be employed for the cyanohydrazine formation, but lower yields (ca. 60%) are obtained. The third step, a conveniently performed titration procedure with bromine as oxidant, can be effected with other oxidizing reagents such as 4-phenyl-4H-l,2,4-triazole-3,5-dione, ferl-butyl hypochlorite, and Jones reagent.12 The final diazene-... 

Bargamov GG, Bargamova MD (1994) Formation of 1-amino-l,2,3-triazole by the oxidation of l,l,l,5,5,5-hexafluoro-4-(trifluoromethyl)pentane-2,3-dione dihydrazone. Izv Akad Nauk Ser Khim 1838-1839... 

Since vinyl azides like 34 are electron-rich olefins, [2 + 2] cycloaddition with electron-deficient alkenes such as diphenylketene could lead to azidocyclobutanes. " The stability of the cycloadducts 211, prepared from 34 or 52 and tetracyanoethene (TCNE), allowed characterization in solution but not isolation of these products because rapid ring-expansion regioselectively afforded the dihydropyrroles 212 already at room temperature (Scheme 5.25). "" A similar mechanism via [2 + 2] cycloaddition and quick ring-enlargement may perhaps explain the formation of 213 from 52 and 4-phenyl-l,2,4-triazole-3,5-dione (PTAD). In this " " and other " " cases, however, different interpretations were offered. The 2-azidobuta-l,3-dienes 92a,b underwent [4 + 2] cycloaddition in the... 

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