1.2.4.5- Tetrazines, 1,2-dihydro-, structure

Further reports on 1,4-dihydro-1,2,4,5-tetrazine structures by x-ray diffraction are found for the 3-(p-chlorophenyl)-6-trifluoromethyl derivative <85JHC643>, l,3,6-triphenyl-l,4-dihydro-l,2,4,5-tetrazine <90JCS(Pl)2527>, 6-bromo-l,4-dihydro-l,4-di(o-tolyl)-l,2,4,5-tetrazin-3(27/)-one, and 3,6-dibromo-1,4-dihydro-l,4-bis(p-methoxyphenyl)-1,2,4,5-tetrazine <94AX(C)l78l>. Finally, there are reports on the crystal structures of the heterocyclic betaine l,4-dimethyl-6-oxo-1,2,4,5-tetrazin-l-ium-3-olate (17) <84TL629> and tetramethyl-p-urazine (18), from which cation radicals could be formed <9UOC1045>. 

There are manifold possibilities for tautomerism in partially saturated derivatives. As an example, dihydro-1,2,4,5-tetrazines have been formulated in the 1,2-, 1,4-, 1,6- and 3,6-dihydro structures, but the 1,4-dihydro structure is probably the most stable (see also Section 3.2.2.3.2). 

Dihydro-1,2,4,5-tetrazines have been formulated as 1,2-dihydro- (40), 1,4-dihydro- (41), 1,6-dihydro- (42) and 3,6-dihydro-l,2,4,5-tetrazines (43). It seems to us that there is still a great confusion over the structure of these substances, especially the 1,2-dihydro- and... 

A [3 + 3] atom fragment method for the preparation of dihydro-1,2,4,5-tetrazines is the dimerization of diazo compounds under the influence of bases. In 1900 Hantzsch and Lehmann observed the formation of a new compound when ethyl diazoacetate (312) was treated with sodium hydroxide (00CB3668). The structure which they proposed originally was incorrect it was shown later that the product isolated was the disodium salt of l,2-dihydro-l,2,4,5-tetrazine-3,6-dicarboxylic acid (313) (or the 1,4-dihydro compound) <78HC(33)1075, p. 1078). 

The reaction of ethyl diazoacetate (312) with sodium or potassium ethoxide was studied by Curtius and his coworkers (08CB3140). They isolated a compound for which they proposed structure (316), which is a metal salt of diethyl l,6-dihydro-l,2,4,5-tetrazine-3,6-dicarboxy-late complexed with one mole of the ethoxide used. 

Cyclooctatetraene reacts as a dienophile with 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine to form, upon loss of N2, a cycloocta[4]pyridazine and a tetracyclic bis-Diels-Alder cycloadduct [95LA661]. In a nonpolar solvent, the former produced a dihydrobarrelenofrflpyridazine that could be oxidized (with 4-phenyltriazolinedione) to the barreleno[d]pyridazine, but in a polar solvent it gave a dihydrocycloocta[d]pyridazine in a multistep process. X-ray crystal structures of some of these compounds have been obtained. The attempted dehydrogenation of 4,4a-dihydro-5//[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones with m-CgH NC SOjNa unexpectedly led to new 5-hydroxy[ 1 ]benzopyrano[4,3-c]pyridazin-3(2//)-ones [95JHC79]. 

Oxidation of a solution of 3-alkyl(aryl)-l,2,4,5-tetrazines in liquid ammonia with permanganate proved to be an excellent route for preparing 6-amino-l,2,4,5-tetrazines (Scheme 30) (81JHC123). The covalent a-adduct, i.e., amino-dihydro-1,2,4,5-tetrazine, is intermediate, as proved by NMR spectroscopy. Based on model studies of 3-phenyl-1,6-dihydro-1,2,4,5-tetrazine, this non-isolable amino-dihydro-1,2,4,5-tetrazine has been characterized as having a homotetrazole structure A (Scheme 30) (81JOC3805). 

There are many possibilities for tautomerism in partially-saturated derivatives. Dihydropyridines can exist in several tautomeric forms, e.g., 37 and 38, of which the 1,4-dihydro isomers are usually the most stable. Similarly, dihydro-1,2,4,5-tetrazines have been formulated as the 1,2-, 1,4-, 1,6- and 3,6-dihydro structures but the 1,4-dihydro structure is probably the most stable. In contrast, 2/7-pyrans, e.g., 67, are more stable than 4/7-pyrans, e.g., 68. Of the five possible dihydropyrimidines most known derivatives have 1,2-, 1,4-, or 1,6-dihydro structures of which the 1,2-structure is calculated to be the most stable <1985AHC(38)1>. 

Dihydropyridazines are obtained from 1,4-dicarbonyl compounds and hydrazine (Section III,B) or from the reaction of sym-tetrazines and simple ethylenic compounds (Section III,H). There are also a few special reactions, such as that between a tetrahydrofuran and phenylhydrazine, or from a 1,4,5,6-tetrahydropyridazine derivative. The 1,4-dihydro structure has been found to be correct, rather than the 1,6-dihydro structure, postulated earlier for some of these reduced pyridazines (Section III,H). 1,4-Dihydropyridazines can be reduced or oxidized easily and acid treatment of l-tosyl-1,4-dihydropyridazine causes rearrangement to 1-tosylaminopyrrole. ... 

No mass spectra of 1,2,3-triazoles were described prior to 1968, when a series of highly substituted triazoles, the oxidation products of 1,2-dicarbonyl-bis-benzoylhydrazones, were investigated. The previously assigned structure of a dihydro-1,2,3,4-tetrazine could be excluded in favor of the 1,2,3-triazole-isoimide (52), which showed a low intensity molecular ion Mt, but a prominent [M-28] ion corresponding to loss of N2 giving (53) (68TL231). The [Af-28] ion underwent further fragmentations as shown in Scheme 1. 

Trifluoroacetaldehyde azine, prepared from trifluoroacetaldehyde hydrate and hydrazine monohydrate, reacts with triethylamine in methanol to give the 1,4-dihydro-1,2,4,5-tetrazine derivatives 28, whose structure is confirmed by X-ray analysis (95BCJ2085) (Scheme 28). 

Much more is known about tetrahydro-l,2,4-tetrazines which can form tautomeric structures with more than one double bond in the ring. These include the tetrahydro-oxo(thioxo)-1,2,4-triazines and tetrahydro-dioxo(thioxo)-l,2,4-triazines, which, in the absence of a principal group of higher priority, are more usually named as dihydro-1,2,4-triazinones and dihydro-1,2,4-tri-azinethiones. Still better known are the tetrahydro-dioxo-l,2,4-triazines and their mono- and di-thiooxo analogues, because the 3,5-isomers [l,2,4-triazine-3,5(2//,4//)-diones, 1,2,4-triazine-3,5(2/7,4//)-dithiones, and dihydro-3/5-thioxo-l,2,4-triazin-5/3-ones] are aza-uracil derivatives. 

In addition to the aromatic tetrazine system (1), dihydro-1,2,4,5-tetrazines, tetrahydro-1,2,4,5-tetrazines, and hexahydro-1,2,4,5-tetrazines are known. In almost all the cases which have been studied by x-ray diffraction the dihydro derivatives are best described as 1,4-dihydro isomers (2) structures such as 1,2- and 1,6-dihydro isomers, (3) and (4) respectively, are very rare. Tetrahydro and hexahydro tetrazines, such as (5) and (6), are also known. 

This chapter will mainly describe new developments in the area of theoretical methods and experimental structural methods, and in the rapidly growing field of inter- and intramolecular Diels-Alder reactions of these electron-poor azadienes. Quantitative data for the reactivity of dienes and dienophiles in these (4 -1- 2) cycloadditions with inverse electron demand will be discussed. The synthesis and reactions of dihydro, tetrahydro, and hexahydro tetrazines cannot be discussed broadly beyond the scope of <84CHEC-I(3)53l>. Verdazyls, a well-known class of compound, cannot be treated in detail within the frame of this contribution (see Section 6.21.5.9). 

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