With oxadiazine

The reaction of 2-aminothiazole derivatives with the 1,3,5-oxadiazine 2,4.6-trione shown leads to biuret derivatives (126) (Scheme 83) (287). 

Oxadiazines herbicidal activity, 3, 1085 reactions with bases, 3, 1060 ring contraction, 3, 1065 ring opening, 3, 1061... 

Dehydrogenation of piperidine derivative 329 with Hg(II)-EDTA reagent afforded a mixture of perhydropyrido[l,2-n]pyrimidin-2-one 330 and pyrido[],2-c][],2,5]oxadiazine 331 (99ZN(B)632). 

Early studies on tautomerism of benzo-fused 1,3,4-oxadiazines (70CB331 76AHCS1, p. 79) suggested the predominance of the 2H tautomer 119a, which, however, easily tautomerizes to the 4H isomer 119b on treatment with sodium alkoxide (Scheme 31). 

Similarly to the oxadiazine system 158, reaction of 162 with a series of amines was performed. Nucleophilic displacement of fluorine atom only at 10-position occurred when the 9,10-difluoro derivative 162a was treated with various amines (such as pyrrolidine, 4-methylpiperazine, morpholine, 4-ethoxycarbonylpiperazine) in the presence of a catalytic amount of DBU in refluxing acetonitrile or pyridine to give compounds 163. When the... 

Pyrazolo[l,2-r-][l,3,4]oxadiazine derivative 188 is converted to the corresponding (V-oxide 189 by oxidation with magnesium monoperoxyphthalate (MMPP) or -chloroperbenzoic acid (MCPBA) (Equation 23) <2004CEJ737>. 

PTAD spontaneously reacts with various olefins to give the corresponding ene adducts, for example, the reaction with 2-methylbut-2-ene gives a nearly quantitative yield of 645 <1980JOC3467>. When the reaction is run in acetone in the presence of various salts, for example, magnesium perchlorate, in addition to 645, triazolol l, 2-r oxadiazine 646 is formed in 10-30% yield, depending on the reaction conditions (Scheme 105) <1994T1821>. 

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 benzofurazans can be oxidized or form the quaternary salts. For example, phenantro-l,2,5-oxadiazine 32 was readily quarternized to iV-methylazolium salt on being heated in dimethyl sulfate. Anion exchange with sodium perchlorate gave high yields of the phenanthroazolium perchlorate salts 33 (Equation 7) <1997J(P1)1047>. 

Selective reduction of the 7-oxo group in pyrido[23-synthetic approach to 5,10-dideazatetrahydrofolic acid <00H(53)1207>. Cycloaddition of pyrimido[4,5-c][l,2,5]oxadiazine 96 with 2,3-dihydrofuran affords a new synthesis of dimethyllumazine derivative 97 which undergoes a ring-opening reaction to give pyrazine derivative 98 <00JHC419>. 

Two other synthetic routes to derivatives of this ring system should be mentioned here, and the transformations are shown in Scheme 54. The phenanthrene-fused fV-aryldihydro[1.2.4]triazine 274 was found to undergo 1,3-dipolar cycloaddition with diarylnitrilimine to give the cycloadduct 275 <1997J(P1)1047. This transformation is entirely analogous to that taking place with a fused oxadiazine derivative, as discussed in Section 11.19.6.1. 

Abderrahim etal. <1997SC3039> found that treatment of the ethylidenaminobenzimidazole compound 177 with a Grignard reagent is a convenient tool for the synthesis of the partially saturated benzimidazo[2,3- 7][l,3,5]oxadiazine... 

The synthetic route to 1,3,4-oxadiazines and 1,3,4-thiadiazines (Scheme 105) begins with the iminophosphorane of imidazolone 294, which is converted with isocyanate or isothiocyanate to carbodiimide 295. A second addition of the heterocumulenes occurs to the CH acid at the 5-position,... 

The reaction of a-halogenoximes 126 with amidines in the presence of iron carbonyls gives imidazoles 127 in 31-79% yields. The reaction occurred via deoxygenation of 4H-1,2,5-oxadiazines by iron carbonyls (equation 55). Efficiency of carbonyls decreased in the following order Fe3(CO)i2 > Fe2(CO)9 > Fe(Co)5 . ... 

Oxadiazine 370 was obtained from aziridinooxime 369 and concentrated HCl in 51% yield (equation 161) . CycUzation of acylated amidoxime 371 in the presence of K2CO3 in DMF also leads to formation of oxadiazine ring 372 (yield 12%), along with quinohne derivative 373 (equation 162) . 

Reaction of a-aminoketoximes 374 with l,l -carbonyldiimidazole (GDI) in THE afforded l,2,5-oxadiazin-6-ones 375 in 41-65% yields (equation 163) °. 

However, with liquid ammonia or anhydrous methylamine 1,2,4-oxadiazines (88) are formed. 5-(Chloromethyl)-l,2,4-oxadiazoles (e.g., (86) react with urotropin to form salts, which are hydrolyzed with hydrochloric acid to 5-(aminomethyl) compounds (the Delepine reaction). Alternatively, 5-(aminomethyl)-l,2,4-oxadiazoles have been prepared by condensation of amidoximes with a-amino-acids <72JHC435>. 

Thermal condensation of a-chlorocarboxylic chlorides with amidoximes affords 1,2,4-oxadiazoles. However, in the presence of a strong base (NaH) l,2,4-oxadiazin-5-ones were isolated (Scheme 41) <87H(26)163>. 

Of particular note is the report by Butler et al. of the generation of 3,4-diarylfurazan 7V-methanides (92) <95JCS(P1)1083>. These were formed (Scheme 15) as transient intermediates by desilylation of 7V-trimethylsilylmethyl-l,2,5-oxadiazolium salts (93) using caesium fluoride, and subsequently underwent rapid ring expansion to 6//-1,2,4-oxadiazines. Methanide (92) also resulted from treatment of A-methylfurazan salt (94) with base. 

The l,3,4-oxadiazin-6-one (240) undergoes cycloaddition followed by a remarkable rearrangement to give the triazole A(-imine 241 and an open-chain product (136). Cycloadditions have also been carried out with the following ring systems 1,2-dihydroisoquinoline (242) (137) dihydro-1,3-oxazine (243) (138,139), 2H-, 3-benzothiazine (244) (140,141), and 27/-l-pyran-2-thione (245) (142). 

The addition of hydrazine to diphenylvinylene carbonate 92 quantitatively affords a 1 1 mixture of perhydro-l,3,4-oxadiazin-2-one 93 and 2-oxazolidinone 94 derivatives, both of which are smoothly dehydrated with P2O5 to afford 1,3,4-oxadiazin-2-one 95 and 3-amino-2(3//)-oxazolone 96 (Fig. 5.24), respectively. Addition of primary amines to diphenylvinylene carbonate results in exclusive formation of 3-aIkyl-2(3//)-oxazolones, previously investigated as amino protecting groups in peptide synthesis. 

A novel approach to the formation of the fused [l,3,4]oxadiazine ring in this heterocyclic system involved treatment of pyrazol-3-one 77 with acetic anhydride and hydrazine hydrate to give oxadiazine 78 in high yield (Scheme 55) <2002IJB664>. 

Pyrazolo[4,3- ][l,3,4]oxadiazine 78, whose preparation is given in Section 10.13.9.1.2(iv), was condensed with various amines to give pyrazolo[3,4- ][l,2,4]triazines 101 (Scheme 78 Table 9) <2002IJB664>. This ring system was earlier reported by synthesis of the fused six-membered ring, through condensation onto pyrazolediones <1996CHEC-II(7)489>. 

A review on the synthesis of 1,3,4-thiadiazines and 1,3,4-oxadiazines shows the formation of the diones 105 and 106 (Equation 57) <1998H(49)557>. TPHA3 was preparedby treatment of 107 with DBU in air (Scheme 10) <1998JA2989,... 

Recently, a variable-temperature study of the 13C-NMR of 3,4-dimethyl-hexahydro-l,3,4-oxadiazine and of the trans-fixed derivative 434 have completely clarified the conformational equilibria and allowed a rather complete energy contour to be constructed for the monocyclic oxadiazine (Fig. 17).344 The conformational analysis of other methyl-substituted tetrahydro-1,3,4-oxadiazines345,346 is consonant with these results. 

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