Oxadiazine derivatives

Malenfisch etal, US Patent 6,627,753 (September 30, 2003) Assignee Syngenta Investment Corporation Utility Pesticides 

A reactor was charged with paraformaldehyde (30.5 g), N-methyl-N -nitroguanidine (20 g), triethylamine (17 g) and 100 ml apiece toluene and dioxane, and the mixture refluxed 16 hours. Thereafter, the solvent was evaporated, the residue purified by column chromatography on silica using CH2Cl2/methyl alcohol, 95 5, and the product isolated, mp= 137-139 °C. 

The product from Step 1 (1.44 g), 2-chloro-5-chloromethylpyridine (2.2 g), K2CO3 (3.7 g) and 20 ml DMF were heated to 50 °C 4 hours. The mixture was filtered, purified as in Step 1, and the product isolated, mp = 116-118°C. 

Other methods have also been used to prepare nitroguanidine precursors are as illustrated in Eq. 1 and discussed (1). 

In a subsequent investigation by the author, the Step 3 analogue, 3-(2 chloropyrid-5-yl-methyl)-2-nitromethylidene-pyrrolidine, (I), and derivatives were prepared and are described (2). 

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Cyclopentanone (403) and cyclohexanone enamines react with symmetric and non-symmetric diimides of type Et02CN=NAr, ArCON=NCOAr and ArN=NCOAr (404) to give 1,3,4-oxadiazine derivatives 405 or open-chain Michael-type compounds 406 (equation 85)243-245. The formation of the former products seems to be favored by the presence of acceptor substituents on the aromatic ring of the diazene, and their stability is highly dependent on the ring size of the enamine employed. 

Ghlorobenzaldehyde 232 reacts with ammonium acetate and acetic acid in nitromethane under ultrasonic irradiation to give the 1,3,4-oxadiazine derivate 239 <2000JOC4750>. From chromatographic investigations the formation of the intermediates 233 and 234 was indicated. A reaction mechanism is proposed in Scheme 30. 

Oxadiazine derivatives are widely used in agrochemistry as insecticides, herbicides, fungicides, and pesticides. For example, 2-aryl-4-alkyl-5,6-dihydro-l,3,4-oxadiazines are useful insecticidal and acaricidal compounds... 

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>. 

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. 

The NMR spectrum of oxadiazine derivative 129 shows (84ZOR717) only one signal for the acetyl group probably only the -conformer is present. 

A molecular mechanics force field based on ab initio calculations developed for systems containing the N—C—O unit has been applied to fully saturated 1,3,5-oxadiazine derivatives <90JST(206)29, 91MI 618-01 >. Results indicate that for perhydro-1,3,5-oxadiazine (6 R = R = R = R = H) the conformer with the NH hydrogens in the axial positions (AA) is more stable than the (AE) and... 

Naphthoquinone[2,3 ]oxadiazine derivative 191 reacts with triethyl orthoformate in the presence of acetic anhydride to give compound 192. Further reaction with active methyl compounds (a-picoline, 7-picoline, quinaldine) affords the corresponding cyanine dyes 193 (Scheme 27) <1996IJH305>. 

Some 4-substituted-2-aryl-5,6-dihydro-l,3,4-oxadiazines 351 <1996DEP4444865>, 2-heterocyclic-substituted 4-fluor-oethyl-5,6-dihydro-l,3,4-oxadiazines 352 <2000USP6083942>, 2-aryl-5,6-dihydro-l,3,4-oxadiazin -yl-carboxamides 353 <1998W09833794>, and 7-chloro-3/7-indano[l,2-< ]l,3,4-oxadiazine derivatives 354 <1999USP5869657, 1995W09529171> exhibit pesticidal activity. Benzo[4,2,l]oxadiazines are used as herbicides 355 <1998USP5739326>. 

The reaction of 3,5-dimethyl-l-thia-3,5-diazacyclohexane 41c with 1 or 2equiv of BHa-THF initially gives the monoadduct 63, which further disproportionates to the bis-adduct 45 as shown by their NMR spectra. In both adducts, the N-BH3 groups are in the equatorial positions, as indicated by the NMR chemical shifts of the N-CH3 groups <1999EJ12069>. The nitroimino[l,3,5]oxadiazinane 119 reacts with 2-chloromethyl-5-aryl-l,3,4-oxadiazoles 120 in DMSO in the presence of NaH to give oxadiazine derivatives 121 in 26-43% yield (Equation 21) <2002HC0601>. 

Oxadiazine derivatives of diphenylglycouril 134, 169, generally referred to as cyclic ethers in the literature, are obtained by the treatment of diphenylglycouril 367 with paraformaldehyde in the presence of PTSA (Equation 51) <1989JOC3710>. In addition, the same reaction can be carried out under anhydrous conditions <2003T1961>. The anhydrous TEA used in this latter reaction is sufficiently acidic, easy to remove, and an excellent solvent for 367. 

Substituted 4-(nitroimino)perhydro-l,3,5-oxadiazine derivatives 394 have been used as pesticides <1997WO9806710> and substituted iminooxadiazine dione derivatives have been utilized for the manufacture of... 

Arylcarbonyl isothiocyanates react with A,A-disubstituted hydrazones 188 to give 1,3,5-oxadiazine derivatives 189 . 

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). 

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). 

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... 

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>. 

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) . 

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. 

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