Amidoximes formation

TW HNYAr V 0 H2N nh2 [178] One example using a carbamate linker has been decribed. The amidoxime formation is much slower on resin than in solution. The acid-labile linkers (Wang-type) gave higher yields than the photolabile linker. [178]... 

The first A/ -oxides of the 1,2,4-thiadiazole ring system have been reported and were prepared by condensation of benzamidoximes (86) with 4,5-dichloro-l,2,3-dithiazohum chloride (87). A -labelling showed the compounds to be 4-oxides (88) and a mechanism was proposed for their formation. Alkyl amidoximes and arylamidoximes with electron-withdrawing substituents did not give A/ -oxides, but only the dithiazolone (89) and the dithiazolthione (90) <96CC1273>. 

Table 6.4 Scope of selectivity of amidoxime addition to DMAD and hydroxypyri midi none formation via microwave-accelerated thermal rearrangement. 

In another example using the isomeric amidoxime substrate 61, the formation of the expected [3,3]-rearrangement product 63 was not observed (Scheme 6.22). Instead the Z-adduct 62Z cyclized to oxadiazoline 64. Interestingly, the E-adduct 62E rearranged to hydroxypyrimidinone 60 and imidazole 66 instead of 63. The rearrangement of the substrate 62E was proposed to occur via intermediate 65 via a [l,3]-sigmatropic rearrangement which, after cyclization, led to the observed products 60 and 66. 

The cyclization of the five-atom component O-acylated amidoximes 204 leads to 1,2,4-oxadiazoles via C-N bond formation as shown in Scheme 30. The requisite O-acylated amidoximes 204 are accessed via the reaction of an amidoxime with an activated carboxylic acid or a carboxylic acid derivative. Often the O-acylated amidoxime 204 is not isolated and the cyclization is either spontaneous or occurs in a one-pot process, and these approaches are dealt with in Section 5.04.9.1.2 as syntheses from a one-atom component and a four-atom component. In this section, only those methods in which the O-acylated amidoxime 204 is isolated and cyclized in a separate step are dealt with. 

The reaction of malonates 213 with 2equiv of an amidoxime in the presence of potassium carbonate results in the formation of the bis-l,2,4-oxadiazoles 214 (Equation 35), a process that also gives excellent yields of the mono-1,2,4-oxadiazoles when a 1 1 ratio is employed (see Table 5) <2006TL3629>. 

Addition of ammonia as a model nucleophile to nitrile oxides was studied by a semiempirical MNDO method, for fulminic acid and acetonitrile oxide (121). The reaction is exothermic and proceeds in two steps. The first (and rate-determining) step is the formation of a zwitterionic structure as intermediate. The second step, which involves transfer of a proton, is very fast and leads to the formation of Z-amidoximes in accordance with experimental data. Similar results were... 

Jousserandot, A., Boucher, J. L., Henry, Y., Niklaus, B., Clement, B., Mansuy, D., Microsomal cytochrome P450 dependent oxidation of N-hydroxyguanidines, amidoximes, and ket oximes mechanism of the oxidative cleavage of their C=N(OH) bond with formation of nitrogen oxides, Biochemistry 37 (1998),... 

Triazines 347 were obtained from amidoximes 346 and ethyl orthoacetate (equation 151). The mechanism of formation of products 347 includes Beckmann rearrangement of amidoximes to carbodiimides, followed by reaction with amidoxime and orthoester. ... 

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 oxidation of aldoximes and amidoximes (methods Q and R) is not a practical process but rather a way of formation. The reactions have been described because oxadiazoles have been isolated among a lot of other oxidation products. 

However, the dehydration of two N-acyl amidoximes is reported. In the first example, the dibenzoyl derivative of oxyguanidine (X) has been transformed by hydrolysis into 3-amino-5-phenyloxadiazole but the postulated intermediate, N-benzoylaminoformamidoxime (XI) was not isolated (2,121), and the formation of the O-benzoyl intermediate would be more probable. 

Even though N-acylated amidoximes have never been isolated, their existence as intermediates in some reactions involving the formation of the oxadiazole ring cannot be excluded. Indeed, the formation of N-acyl-amidoximes is postulated in the following methods of oxadiazole synthesis. 

The obtention of the oxadiazole cycle cannot be interpreted without assuming the formation of a N-acylated amidoxime as intermediate. 

In both reactions, the formation of oxadiazoles is interpreted by the immediate cydization of unstable N-acyl amidoximes. 

The two following reactions also yield oxadiazoles in one step and their mechanism involves the formation of intermediate N-acyl amidoximes. 

Generally, amidoxime hydrochlorides or formates, the latter having a lower melting point are used. Sometimes the condensation works in a solvent such as an excess of low melting amide, glacial acetic acid or carbitol. 

These compounds can be synthesized from amidoximes reacting with the anhydride of trichloracetic acid. In contrast to the 3-trichloro-methyl derivatives, the CCI3 group in this class is reactive. Under formation of chloroform the 5-amino, 5-hydrazino, or 5-hydroxy-compounds can be obtained under mild conditions (compare p. 841,843). 

This oxadiazole formation involves O-acylation of the amidoxime followed by a condensation. 

Amidoximes (155) may be made by heating a nitrile (154) with hydroxylamine in acid solution. The sulfone function does not interfere with subsequent ring formation (79JHC1197). Amidoximes (158) may also be of an aldoxime (156) followed by ammonolysis of the oximinochloride (157). 

When the (149b) fragment is a carbonic acid derivative (166), i.e. of oxidation state +4, a hydroxy or an amino group may be introduced at C-5. If chloroethyl formate is used with an amidoxime, a 5-hydroxyoxadiazole (167) is obtained. 

Amidines, N-(l,2,4-thiadiazol-5-yl)-, rearrangement, 56, 103 Amidoximes, 1,2,4-oxadiazol-3-yl-, rearrangements, 56, 55 Amidyl radicals, see Radicals, nitrogen Amination, asymmetric, of carboxylic acids by chiral nitroso compds, 57, 41 Amines, catalysis of 3-acyl-1,2,4-oxadiazole arylhydrazone rearrangement by, 56, 87 Amines, thionitroso-, formation, 55, 20 Aminium cation radicals, see Radicals, nitrogen... 

Amidinyl radicals 1166 are readily generated from amidoxime benzoates, for example, 1165, by treatment with a stannane-diazo initiator or with Ni-AcOH and captured by an internal olefin to give the corresponding imidazoline 1167. Interestingly, the use of allyl tri- -butylstannane in the case of substrate 1168 results in the clean formation of allyl imidazoline 1169. As expected, allylation occurs from the least hindered exo face to give the isomer shown (Scheme 284) <2003CC1870> (ACCN = l,l -azobis(cyclohexanecarbonitrile)). 

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