Azomethine derivatives reactions

Aldimines, Ketimines, and Related Compounds as Dipolarophiles Reactions of aldimines with nitrile oxides proceed readily to give 1,2,4-oxadiazolines independently of the nature of substituents both in dipole and dipolarophile molecules. 1,2,4-Oxadiazolines were prepared by the regiospe-cihc 1,3-dipolar cycloaddition of nitrile oxides with fluoro-substituted aldimines (295). Phosphorylnitrile oxides gave with azomethines, PhCH NR, phosphory-lated 1,2,4-oxadiazolines 129 (296). Expected 1,2,4-oxadiazolines were also obtained from azomethines, derived from 4-formylcoumarine (179) and 1,3-diphenylpyrazole-4-carbaldehyde (297). 

The alkylation of caclohexanone has been studied as a model reaction in detail. Generally, enamino compounds (126) are allowed to react with alkyl halides or a, 3-unsaturated carbonyl compounds. The enamine (126a) is prepared directly from the ketone and a chiral secondary amine (route A). A metalloenamine (126b) can be synthesized from chiral azomethine, derived from the model ketone and a primary chiral amine (route B). The primary amine used for the formation of (126b) must possess an oxygen function. This oxygen function plays a key role in the coordination of the lithium ion in the complex (126b). 

A new route to mono- and dioxo derivatives of 1,3-oxazine was given by Martin et a/.96-97 addition of 2 moles of ketene to the C=N of azomethines. (This reaction was described by Staudinger98-100 in 1906, but piperidinedione structures were assigned to these compounds.) When the SchifFs base PhCH=NEt reacted with 2 moles of dimethyl-ketene a good yield of a derivative of 2-isopropylidenetetrahydro-l,3-... 

The success achieved with the Rh(II)-catalyzed transformations of -oximino diazo carbonyl compounds prompted our group to study some additional systems where the C-N 7i-bond was configurationally locked so that azomethine ylide formation would readily occur. Toward this end, we investigated the Rh(II)-catalyzed behavior of isoxazoline 186 in the presence of DMAD. This reaction afforded the azomethine-derived cycloadduct 187 as a 4 1 mixture of diastereomers in 65% yield. A similar transformation occurred using the a-diazoacetophenone derivative 188 which produced isoxazolo[3,2-a]isoquinoline 189 as a 2 1 mixture of diastereomers in 82% yield.84... 

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). 

The electrochemical behavior of azomethine derivatives, e.g., oximes, of heteroaromatic carbonyl compounds is much like that of the corresponding benzene derivatives.91 Pyridine aldoximes271-274 and ketoximes275 are reduced in acid solution by a four-electron reaction to the amine. The reaction mechanism is probably, as in other oximes,01 a reduction of the protonated compound with cleavage of the N-0 bond, followed by saturation of the C=N double bond. The amine is often further reducible at a more negative potential (Section VI, E). 

Another type of mechanism operates in the synthesis of amino acids by electrore-ductive coupling of alkyl halides with Schiff bases in DMF in these reactions the alkyl halide chosen is reduced at less negative potentials than the azomethine derivative of an a-ketoester, and the coupling is proposed to be a nucleophilic addition of an alkyl anion [Eq. (7)] to the azomethine compound, [Eq. (8)] the benzyl group is afterward reductively removed [32,33] ... 

As discussed in Section 3.06.5 aminothiazoles react with alkyl halides to give mainly the product of alkylation at the endocyclic nitrogen when the reaction is conducted in the absence of strong bases with acyl and sulfonyl halides, the exocyclic nitrogen becomes the main nucleophilic site. The reaction of 2-aminothiazoles with heterocyclic or aromatic aldehydes show ample differences depending on the various amine-aldehyde pairs <9lS62i>. In general the azomethine derivatives are obtained by a suitable procedure which has to be followed in each case. The increase of the amine/aldehyde ratio leads to bis-amines as the major products of the reaction. 

The ultimate goal of using an external, chiral Hgand in a chemical reaction is the potential for a catalytic, asymmetric synthetic transformation, [ 1 a, lb, 1 c]. Thus, the substoichiometric, asymmetric alkylation of aldehydes with organozinc reagents represents a major accompHshment [la, 15a, 15b, 15c, 15d], whereas a similar catalytic process for azomethine derivatives has only recently been achieved. 

Oxidation of heterocyclic amino derivatives yields various reaction products depending on the structure of the amine. 4-Benzylamino-3-methyl-4//-1,2,4-triazole is oxidized with DCT in chloroform to give the azomethine derivative 110 (69ZC325). l-Amino-4,5-diphenyl-l,2,3-triazole under the action of CBT forms diphenylacetylene 2-aminobenzotriazole yields cis, cw-l,4-dicyanobuta-l,3-diene and 1-aminobenzotriazole yields a mixture of chlorobenzene and o-dichlorobenzene. Oxidation of 1-aminobenzotriazole in the presence of tetraphenylcyclopentadienone leads to 1,2,3,4-tetraphenylnaphthalene via benzyne intermediate [68JCS(CC)1305 69JCS(C)1474] (Scheme 101). 

The azomethine derivative is generally prepared by the condensation of a substituted hydrazine with nitrofurfural in the presence of acid. For example, nitrofurazone(.E) is formed by the interaction of 5-nitrofurfural diacetate which is hydrolysed to the active 5-nitrofurfural and semicarbazide in the presence of sulphuric acid and water. This reaction proceeds by heating at about 100°C for 5 hours. 

This reaction is generally used in the preparation of azomethine derivatives, which are used in the dye and drug industry. 

Azomethines derived from formaldehyde are cyclic aminals, (RN=CH2)3, and in their reaction with alkyl isothiocyanate, [2+2+2] cycloadducts are obtained as result of an insertion into the C-N bond of the cyclic aminal. ... 

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... 

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

Aromatic nitro compounds are often strongly colored. They frequently produce characteristic, colored, quinoid derivatives on reaction with alkali or compounds with reactive methylene groups. Reduction to primary aryl amines followed by diazotization and coupling with phenols yields azo dyestuffs. Aryl amines can also react with aldehydes with formation of Schiff s bases to yield azomethines. 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utihzed to obtain highly substituted pyrroHdines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine yhdes 100,... 

Several variations and extensions of this HHT method have recently been reported. The mildness of this reaction was exemplified through the synthesis of glyphosate thiol ester derivatives 35. The requisite thioglycinate HHT 34 was prepared in high yield by a novel, methylene-transfer reaction between r-butyl azomethine and the ethyl thioglycinate... 

The "one-pot domino reaction" of A/-benzylaniline with benzaldehyde in refluxing toluene results in a mixture of oxazolidines via a transient azomethine ylide (Scheme 14) <96S367>. The 2-benzoyloxazolidine 69 rearranges spontaneously to the oxazine 70 <96JHC1271>. The ring-closure of derivatives 71 (R = H or Me) of (f )-phenylglycinol to oxazolidin-2-ones... 

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