Structure oxadiazines

Hexahydropyiido[ 1,2-d -1,3,4-oxadiazines 212 may formally exist in three con-formers (Scheme 138) [99ACSA213]. However, according to simple Hartree-Fock calculations, the trans conformer 212c is the energetically preferred structure. 

The reaction of acyclic ADC compounds with monoenes has already been discussed in Sections III,B and IV,B. In certain cases the major reaction pathway involves addition of the ADC compound as a 47r component, to the monoene to give 1,3,4-oxadiazines (Scheme 1). 1,3,4-Oxadiazines are the major or sole products from the reactions of ADC compounds with indene,80 and 4-nitrophenyl vinyl ether,90 and from the reaction of azodibenzoyl with enamines and enol ethers.91 93 Norbornadiene also gives a 1,3,4-oxadiazine (42) with ADC compounds.82 However, benzonorbornadiene behaves differently, and the major product from the reaction with PTAD has the structure 119.205 Other bicyclic monoenes react similarly.206 1,3,4-... 

The compilation of ring systems in Scheme 1 consists of all the ring systems discussed in this chapter. The first three lines of structures are fused oxadiazines, dithiazines, and thiadiazines, these ring systems are followed by various fused... 

Carbonyl-substituted isocyanates have been reported to add [2 + 2] to carbodiimides, although in one case the reported 4-imino-l,3-diazetidin-2-one (64AP623) was reassigned an oxadiazine structure (72BCJ1534). It is clear that the initially formed [2 + 2] kinetically favored adducts are thermally unstable and ultimately form more stable [4 + 2] products, oxadiazines (Scheme 13) (79BSF(2)499). 

Pyrimido[l,2-a][l,8]naphthyridines synthesis, 2, 599 Pyrimido[5,4-c]oxadiazine purine synthesis from, 5, 591 Pyrimido[4,5-6][ l,4]oxazine synthesis, 3, 312 Pyrimido[2,1 -6]pteridine structure, 3, 284 Pyrimido[5,4-g]pteridine structure, 3, 284 Pyrimidopurines, 5, 566 Pyrimido[4,5-c]pyridazine, aryl- H NMR, 3, 335... 

Table 3) are described in the literature although the rarer 1,3,2- and 1,5,2-isomers are only known as the fully oxidized tetraoxides. Oxadiazines (Table 4) of all six types are reported, four of the isomers having an extensive and well established chemistry. The 1,2,3-and 1,2,6-isomers have been reported, but there is no spectroscopic evidence to support either structure. All the six isomeric thiadiazines (Table 5) are known with only the 1,5,2-isomer being poorly described. In line with the oxadiazines and thiadiazines being the most well known ring systems containing three heteroatoms, they are also the most well reviewed to date. 

In the reactions of dimethyl and diethyl diazenedicarboxylate with electron-rich alkenes the diazetidine/oxadiazine ratio is dependent on the structure (cyclic, acyclic), the substitution pattern (1,1- or 1,2-disubstituted) and the geometry of the alkene. 

Diazetidines and/or 5,6-dihydro-4//-l,3,4-oxadiazines are produced by cycloaddition reactions of alkenes and acyl or diacyldiazenes, depending on the structure of both the reaction partners, but the synthetic application of this cycloaddition is seriously limited by the occurrence of the ene reaction (Section 7.2.10.1.). 

Diazetidines and/or oxadiazines are obtained from cnol ethers and acyclic diacyldiazenes depending on the structure and the substitution pattern of the alkene (Section 7.2.10.1.). For 3,4-dihydro-2//-pyran (12) and certain glycals it has been found that the cycloaddition of dibenzyl di-azenedicarboxylate 13 to give oxadiazines is favored over the ene products by carrying out the reactions at lower concentration of dihydropyran and under irradiation, which converts ( )-13 to (Z)-1312. 

Unexpectedly, the cw-azetidine 18 is predominantly obtained from (Z)-l-(ethylthio)propene, together with cis- and frarw-oxadiazines 1914, apparently produced through a nonconcerted cycloaddition mechanism. However, published information on the three compounds is scant and the basis for the structural and stereochemical assignments is not clear. 

The corresponding reactions of enamine with dialkyl diazenedicarboxylates19 and asymmetric diazenes20-23 are more complex and can lead initially to either the oxadiazines 21 (cis ring junction)21 or the substituted enamines 22 and 23. An equilibrium is then attained between the different products, depending on the structure (n.X) of the enamine and on the nature of the substituents (Y,Z) of the diazene. Further reaction of the primary products with a second diazene molecule can occur. The corresponding ketones arc then produced by acidic hydrolysis. 

On the other hand, the [4 +- 2] cycloaddition of diethyl diazenedicarboxylate and cyclic enol ethers is performed efficiently under UV irradiation. Without irradiation and by increasing concentration, the ene reaction product can be obtained from the substrates. The oxadiazine structure, as well as the stereochemistry of the cycloadduct 13 obtained from a cyclopropane-fused dihydrofuran and diethyl diazenedicarboxylate, was established by X-ray29. 

The diazabicycloheptane 14 obtained from cyclopentadiene and dibenzoyldiazene isomer-izes slowly to c/.s-bicyclic oxadiazine 15 when heated in a polar solvent48 50 or treated with an acid catalyst51. The structure and stereochemistry of the product 15 was confirmed by conversion to c/.v-2-amino- and c/.v-2-hydrazinocyclopentanol derivatives and comparison with authentic samples48,50. 

The reactions of the structurally related M-allyl acethydrazides 185 gave similar results [100]. As indicated in Scheme 28, at - 30 °C the cyclization afforded the six-membered 1,3,4-oxadiazines 186 and at 20 °C gave the five-membered M-acetyl pyrazolidines 187. 

Quinazoline 3-oxides 30 are conveniently prepared when oximes of 2-(acylamino)benzaldehyde or 2-(acylamino)phenyl ketones 29 are treated, generally, with concentrated sulfuric acid at room temperature, with diluted hydrochloric acid under reflux,or with polyphosphoric acid at 85 °C for a short period.The structure of quinazoline 3-oxides has been known only since 1960whereas in the older literature both the 1-acylindazole structure and the 3,1,4-benzoxadiazepine (4,5-benzo[hept-l,2,6-oxadiazine]) structurewere assigned to these products (cf Houben-Weyl, Vol. E8b, p 776). 

The IR spectra of l,2,4-oxadiazin-6-ones show NH and carbonyl bands at ca. 3250 and 1760 cm"1, respectively. In the II NMR spectra of compounds lacking substituents at nitrogen and at C5 the protons attached to C5 resonate as doublets, which confirms the 477-structure. 

Oxadiazine-3,5-diones are acidic the parent compound has pKa 7.6.5 These compounds arc included in this section because of formal tautomerism with unsaturatcd dihydroxy forms such as 5. However, there is no evidence for the existence of such tautomers. The oxadiazinediones exhibit two NH absorptions in the region 3200 3100 and two carbonyl bands, one at ca. 1750 and the other at 1710-1670 cm 1. The, 3C NMR spectra of oxadiazine-dione and its 2-substituted derivatives are informative C3 resonates at ca. 5 = 150, C5 at ca. 5 = 169 and C6 at ca. <5 = 70 ppm. An X-ray analysis of the parent compound confirmed its dione structure the structure shown gives bond lengths (pm) and angles of 2//-l,2,4-oxadi-azine-3,5(4/7,6//)-dione.6... 

Oxadiazine-3,5-dione and its 2-alkyl derivatives react with phosphorus pentasulfide in boiling dioxane to yield 5-thioxo-5,6-dihydro-2//-l, 2,4-oxadiazin-3(4//)-ones 2, whose structures follow from their l3C NMR spectra, which show that the chemical shift of C5 changes from <5 = 169 to 6 = 203 while those of C3 and C6 are virtually unaltered.5... 

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