Aminomethylene derivatives

Aminomethylene derivatives may be prepared by reacting the pyrido [1,2-a]pyrimidines (63 R = H) with aminomethanols in ethereal hydrogen chloride solution or with amines and paraformaldehyde.295... 

Depending on the work-up conditions, Vilsmeier-Haack formylation of 4-oxo-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidines gave various 9-sub-stituted pyrido[l,2-a]pyrimidines (240 -242).284,319 The 9-aminomethylene derivatives (240) were transformed by hydrolysis in 0.5 N hydrochloric acid to the 9-formyl compounds (241 R3 = H), by ethanolic hydrogen chloride to... 

The pyrolysis of aminomethylene derivatives of Meldrum s acid has also been studied extensively. The parent compound 395 loses acetone and CO2 at 400 °C to give 396, which at higher temperatures isomerizes to 397 which loses CO to give ethynylamine (398)159. A range of cycloalkylamino compounds such as 399 reacts similarly on FVP at 500-600 °C to give the methyleneketene 400, but under the conditions this undergoes... 

Method E, which assumes the N(7)-C(7a) bond formation in the cyclization step, is also rarely used in the synthesis of thienopyridines. For example, the method (1997H255, 1998JMC(E)33, 1998PS21) for the preparation of 4-oxo-4,7-di-hydrothieno[2,3-Z>]pyridine-5-carboxylic acid esters 54 is based on intramolecular /V-nucleophilic substitution of (E/Z)-aminomethylene derivatives of (2,5-dichloro-3-thenoyl)acetic acid esters 52 in the presence of a strong base. Esters 52 and products of their alkaline hydrolysis 56 have an antibacterial action the influence of the substituents on the biological activity of the resulting compounds was studied. 

Many examples of ICC of the examined type are known amongst complexes of ligands of heterocyclic series [269]. Thus, nickel [886] and copper [887] complexes 496 of aminomethylene derivatives of 5-selenopyrazolone 471 (X — Se) have been obtained and structurally characterized. A series of coordination compounds has been synthesized on the basis of 2-selenohydrido derivatives of azines 497 [8,13,888-894] ... 

Synthesis of Metal Chelates of 4-Aminomethylenic Derivatives of 5-Thio(seleno)pyrazoles (2.13), (3.57) [68,73a]... 

Complexes were prepared by refluxing (5-10 min) equimolecular quantities of nickel acetate with the respective 4-aminomethylene derivatives of 1,3-substituted 5-thio(seleno)-N-pyrazoles in ethanol solution. All the complexes thus obtained were purified by repeated crystallization... 

The ICC, synthesized on the basis of 4-aminomethylene derivatives of 5-imine-, oxo-, thio-, and selenoderivatives of pyrazole, are represented most widely. The coordination units MN4, MN202, MN2S2, and MN2Se2, respectively, are found in them [100,134,176-186], Thus, the methods A and B (4.49) were used for obtaining ICC of type 868 (X = NR, R-Het, compound 222) [187] ... 

The low-temperature, Mn(III)-oxidation of unsaturated derivatives of Meldrum s acid provides a route to cyclohexenes <02T25> and the readily available 5-substituted Meldrum s acids are a convenient source of a-substituted acrylate esters <02JOC7365>. Flash vacuum thermolysis of 5-aminomethylene derivatives of Meldrum s acid 26 generates imino-propadienones, RN=C=C=C=0 <02JOC8558>. 

We have studied the reaction of similar cyclic -substituted enaminones which yielded indolones when the reaction was carried out in acetic acid and the quinones had lower oxidation potential, thus preventing prior oxidation of the enaminones. Secondary aminomethylene derivatives of cyclopentanone, cyclohexanone and cycloheptanone reacted with the quinones to presumably form intermediate spiro compounds, as a consequence of normal enaminone chemistry. However, this was unexpectedly followed by rearrangement with ring expansion to indolones (equation 158). In this way carba-zoles, cycloheptindoles and cyclooctindoles can be obtained by a simple entry to this class of indoles, although partially in low yields222-224. Due to their bifunction-ality the produced indol-2-ones are versatile synthons for fused heterocycles (e.g. triazepino- and pyrazino-carbazoles) which become easily accessible225,226. 

Junek and coworkers reacted tertiary aminomethylene derivatives of rvri u, , with malonodinitrile to yield cycloalkenopyridone derivatives248,249 (equation 180) The reaction of acyclic enaminones and cyanoacetamide was also studied 9... 

A similar reaction is observed252 when tertiary aminomethylene derivatives of 0-hydroxyacetophenones are treated with acid. Chromones are formed in high yields according to a method of Fohlisch253 (equation 183). 

N-monosubstituted aminomethylene derivatives of 1,3-dicarbonyls are accessible from trialkyl orthoformates, aromatic amines and 1,3-diketones. They are useful synthons for formation of hexahydroquinolinediones by treatment with KOH and malonodinitrile299. Depending on the substituents of the aniline derivative, replacement of the amine results from 1,4-addition-elimination of malonodinitrile or alkyl cyanoacetate to the en-aminedione and lead to quinolones300. The yields are not high but acceptable, since the starting materials are easily accessible (equation 223). 

Aminomethylene derivatives of ketones and 1,3-dicarbonyls are used in order to incorporate a formyl group into CH-acidic heterocycles via initial reaction with ethyl orthoformate and aniline followed by hydrolytic cleavage, as is shown e.g. with barbituric acid301 (equation 224). 

A study of aminomethylene derivatives of ketones, thiones and selenones including pyrrole, furan or pyrazole as the heterocyclic ring showed them to form intermolecular hydrogen bonds with phenol76. 

Shakhidoyatov and co-workers obtained the 3-bromo-3-formyl-tetrahydropyrrolo[2,1 - )]quinazolinone 382 when they treated the dimethyl-aminomethylene derivative 381 with bromine in refluxing chloroform. 

The five-membered homolog of 390 (R = R = H, = 0) gave the dimethylaminomethylene derivative 381 upon treatment with dimethyl-amine. The formyl compounds 390 = 0,1) and the dimethylaminomethylene derivatives 392 were transformed by amines, hydrazines, and hydroxylamine into the corresponding 3-aminomethylene derivatives of type 394. - ° The dimethylaminomethylene compound 381 and the formyl derivative 390 (R = R = H, = 0) afforded cyano derivatives 395 on treatment with acetone cyanohydrin. - Compound 395 (R = NMe2) was hydrolyzed to the acetic acid derivative 396 in concentrated hydrochloric acid. Treatment of the (dimethylaminomethylene) pyrrolo-[2,l-i ]quinazoline 381 with formic acid furnished the bis derivative 397. The formyl and dimethylaminomethylene groups of compounds... 

Those 3(2//)-furanones with a methylene group at the 2-position condense with ethyl formate and amines to give aminomethylene derivatives of type 46. In such compounds the heterocyclic ring is easily opened by nucleophiles because the functional grouping is that of a vinylogous ester with amines,... 

Junek and coworkers reacted tertiary aminomethylene derivatives of with malonodinitrile to yield cycloalkenopyridone derivatives gm xu ... 

FIGURE 9.16 Ammonia derivatization process involving benzene sulfonylation with benzenesulfonyl chloride and subsequent reaction with dimethylformamide dimethyl acetal to form benzesulfonyldimethyl-aminomethylene derivative. 

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