Azomethine bond oxidation

Some papers are devoted to the modification of 2,3-dihydrodiazepines with respect to the C = N bond. The oxidation reaction involving the azomethine bond and leading to the formation of epoxide [107] was referred to earlier. The interaction of 2,2,4-trimethyl-2,3-dihydrobenzodiazepine 76 with 2-(oxyphenylimino)-1-phenylethanone 119 is described in [112] (Scheme 4.38). The reaction is carried out in benzene at room temperature and apart from the C = N bond involves the 4-methyl group (compound 120). 

Azides, reaction with thiols 752 Azodkarboxylic acid, diethyl ester, oxidation of thiols by 799 Azomethine bond, addition of thiols 765... 

C led to metallation in the 2-position and not addition to the azomethine bond. Reaction with DMF gave the 2-formyl-derivative. The 3-lithio-derivative was obtained by halogen-metal exchange with 3-bromothieno[2,3-6]pyridine. Further studies of the chlorination and 5-oxidation of thieno[2,3-6]pyridine have been reported. The mass-spectral fragmentation patterns of a series of thieno-pyridine A -oxides, 5-oxides, and 55-dioxides have been elaborated. The reductive acetylation of nitro-thieno-pyridines has been studied. Polymethine... 

Iron(III) complexes of 2-acetylpyridine Af-oxide iV-methyl- and 3-azabicyclo[3.2.2.]nonylthiosemicarbazone, 24 and 25, respectively, have been isolated from both iron(III) perchlorate and chloride [117], The perchlorate salt yields low spin, octahedral, monovalent, cationic complexes involving two deprotonated, tridentate thiosemicarbazone ligands coordinated via the N-oxide oxygen, azomethine nitrogen and thiol sulfur based on infrared spectral studies. Their powder ESR g-values are included in Table 1 and indicate that bonding is less covalent than for the analogous thiosemicarbazones prepared from 2-acetylpyridine, 3a and 4. Starting with iron (III) chloride, compounds with the same cations, but with tetrachloroferrate(III) anions, were isolated. 

Copper(II) complexes have been prepared with the 2-acetylpyridine N-oxide 3-azabicyclo[3.2.2.]nonylthiosemicarbazone, 25, and bonding occurs via the pyridine N-oxide oxygen, azomethine nitrogen and thiol sulfur [128]. Based on electronic and ESR spectra, bonding to copper(II) of uninegative, tridentate 25-H is considerably weaker than the related 2-acetylpyridine thiosemicarbazone, 4-H. The other copper(II) complexes reported to date have been prepared... 

This chapter deals mainly with the 1,3-dipolar cycloaddition reactions of three 1,3-dipoles azomethine ylides, nitrile oxides, and nitrones. These three have been relatively well investigated, and examples of external reagent-mediated stereocontrolled cycloadditions of other 1,3-dipoles are quite limited. Both nitrile oxides and nitrones are 1,3-dipoles whose cycloaddition reactions with alkene dipolarophiles produce 2-isoxazolines and isoxazolidines, their dihydro derivatives. These two heterocycles have long been used as intermediates in a variety of synthetic applications because their rich functionality. When subjected to reductive cleavage of the N—O bonds of these heterocycles, for example, important building blocks such as p-hydroxy ketones (aldols), a,p-unsaturated ketones, y-amino alcohols, and so on are produced (7-12). Stereocontrolled and/or enantiocontrolled cycloadditions of nitrones are the most widely developed (6,13). Examples of enantioselective Lewis acid catalyzed 1,3-dipolar cycloadditions are summarized by J0rgensen in Chapter 12 of this book, and will not be discussed further here. 

Oxidative ring closure by formation of a nitrogen-nitrogen bond may be obtained, using suitable heterocyclic hydrazones, formazans, and certain other azomethine functions as substrates. 

Pyrazolines have also been incorporated as modifying groups by 1,3-addition of azomethine ylides to the carbon-carbon double bond of unsaturated poly(esters) (186 Scheme 89) (68MI11100). Poly(isoxazolines) were prepared in similar fashion by reaction of an unsaturated polymer with a nitrile oxide (75MI11106). 

The 1,7-electrocyclization of azomethine imines 106 and 109, with an a,13-aromatic bond and the N—O bond of a nitro group as the y,8-bond, has been proposed as a key step in the conversion of azomethine imines 106 (Scheme 33) [62AG(E)158] or diaziridines 108 (Scheme 34) to benzotri-azole- 1-oxides 107 and 110, respectively (72JOC2980). 

The authors believe that the formation of the (3-adduct 170 (instead of azomethine 168) at the first stage of the reaction is caused by higher polarization of the C = C bond of mesityl oxide in comparison with chalcones. 

Similarly, the enamine salt 15 is obtained by lithiation of 14 (equation 5). In both cases the lower steric hindrance leads to higher stability of the enaminic system33 where the double bond is formed on the less substituted carbon. The Af-metalated enamines 11 and 15 are enolate analogs and their contribution to the respective tautomer mixture of the lithium salts of azomethine derivatives will be discussed below. Normant and coworkers34 also reported complete regioselectivity in alkylations of ketimines that are derived from methyl ketones. The base for this lithiation is an active dialkylamide—the product of reaction of metallic lithium with dialkylamine in benzene/HMPA. Under these conditions ( hyperbasic media ), the imine compound of methyl ketones 14 loses a proton from the methyl group and the lithium salt 15 reacts with various electrophiles or is oxidized with iodine to yield, after hydrolysis, 16 and 17, respectively (equation 5). 

Similarly small rate factors were obtained for 1,3-dipolar cycloadditions between diphenyl diazomethane and dimethyl fumarate [131], 2,4,6-trimethylbenzenecarbonitrile oxide and tetracyanoethene or acrylonitrile [811], phenyl azide and enamines [133], diazomethane and aromatic anils [134], azomethine imines and dimethyl acetylenedi-carboxylate [134a], diazo dimethyl malonate and diethylaminopropyne [544] or N-(l-cyclohexenyl)pyrrolidine [545], and A-methyl-C-phenylnitrone and thioketones [812]. Huisgen has written comprehensive reviews on solvent polarity and rates of 1,3-dipolar cycloaddition reactions [541, 542]. The observed small solvent effects can be easily explained by the fact that the concerted, but non-synchronous, bond formation in the activated complex may lead to the destruction or creation of partial charges, connected... 

Achiwa reported a short synthesis of pyrrolizidine derivatives by the cycloadditions using a nonstabilized azomethine ylide 23 (m = 1) (82CPB3167). When the trimer of 1-pyrroline is treated with a silylmethyl triflate, N-alkylation of the 1-pyrroline takes place. Then the resulting iminium salt is desilylated with fluoride ion in the presence of ethyl acrylate to give ethyl pyrrolizidine-l-carboxylate 295 as a mixture of stereoisomers (28%). After the epimerization of 295 with LDA, the ester moiety is reduced with lithium aluminum hydride in ether to provide (+ )-trachelanthamidine (296). A double bond can be introduced into 295 by a sequence of phenyl-selenylation at the 1-position, oxidation with hydrogen peroxide, and elimination of the selenyl moiety. The 1,2-dehydropyrrolizidine-l-carboxylate 297 is an excellent precursor of (+ )-supinidine (298) and (+)-isoretronecanol (299). Though in poor yield, 297 is directly available by the reaction of 23 with ethyl 3-chloropropenoate. 

---