Synthesis of Heterocyclic Compounds Using Amidines as Their Ene-1,1-diamine Tautomers,IV: Synthesis of N-Bridged Heterocycles 1,2,3,4-Tetrahydropyrido[1,2-a]pyrimidin-6-ones and Methyl 1,2,3,4-Tetrahydropyrrolo[1,2-a]pyrimidin-7-ylideneacetates

2-Benzyl-1,4,5,6-tetrahydropyrimidines 1 (as ene-1,1-diamine N,C-tautomers) in diglyme reacted with ethyl benzoylacetate at 160 °C in an oil bath to give 1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-6-ones 3 and with dimethyl acetylenedicarboxylate in methanol at room temperature, leading to methyl 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidin-7-ylideneacetates 5, respectively.      

Copper(I)-Catalyzed Tandem Cyclization/Condensation Reaction to Novel 4,5-Dihydropyrazolo[1,5-a]quinolines and Pyrazolo[1,5-a]indoles

A facile copper(I)-catalyzed tandem reaction for the synthesis of 4,5-dihydropyrazolo[1,5-a]quinolines and pyrazolo[1,5-a]indoles is reported here. High efficiency and good yields are displayed in this transformation under mild reaction conditions.      

Elegant One-Pot Synthesis of Quinolino[2′,3′:7,6]-cyclohept[1,2-b]indole Through Friedländer and Pfitzinger Annulation Reaction

A rapid, simple, and efficient method for the preparation of various quinolino[2′,3′:7,6]cyclohept[1,2-b]indoles has been developed through the Friedländer and Pfitzinger condensations of 1-oxo-cyclohept[b]indole with o-amino benzophenone and isatin respectively. Reactions were performed by under different reaction conditions.     

Synthesis of new condensed heterocyclic systems

Two new diamines — [1,3-bis(5-phenyl-1,2,4-triazol-3-yl)-4,6-diamino]benzene and [1,3-di-(2-benzimldazolyl)-4,6-diamino]benzene — were synthesized from 4,6-dinitroisophthalic acid. Newheterocyclic systems — 3,5,9,11-tetraphenyl[benzo[1,2-a; 4,5-a]bis(1,2,4-triazolo[4,3-c]pyrimidine)] and 2,16-diphenyl[benzo[1,2-a;4,5-a']bis(pyrimido[1,6-a]benzimidazole)]—were obtained by reaction of the diamines with benzoyl chloride and subsequent cyclization.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1274–1277, September, 1977.     

Fused Polycyclic Nitrogen-Containing Heterocycles: VI. Pyrrolo[1,2-a]quinoxalines

3-(-Chlorobenzyl)-1,2-dihydroquinoxalin-2-one reacts with anions derived from acetylacetone, benzoylacetone, dibenzoylmethane, malononitrile, ethyl acetoacetate, and ethyl cyanoacetate to give the corresponding 3-(-R,R'CH-benzyl)-1,2-dihydroquinoxalin-2-ones which undergo intramolecular cyclocondensation to functionally substituted pyrrolo[1,2-a]quinoxalines on heating in boiling acetic acid. The reaction of 3-(-chloro-p-nitrobenzyl)-1,2-dihydroquinoxalin-2-one with acetylacetone anion directly leads to the corresponding pyrrolo[1,2-a]quinoxaline, without heating in acetic acid.     

Iodine-Catalyzed,Multicomponent, One-Pot Synthesis of 5-Aryl-5,8-dihydrotetrazolo[1,5-a]pyrimidine-7-carboxylic Acids

A series of 5-aryl-5,8-dihydrotetrazolo[1,5-a]pyrimidine-7-carboxylic acids (4) were synthesized from 5-aminotetrazole, pyruvic acid, and aromatic aldehydes in one pot in the presence of I₂ with moderate to good yields. Operational simplicity, mild reaction conditions, and ecofriendly procedure make this novel protocol a promising alternative for the fusion of tetrazolopyrimidines. The structures of the products were proved by ¹H and ¹³C NMR spectroscopy, liquid chromatography–mass spectrometry, and elemental analysis.      

Palladium-Catalyzed N-Arylation of 3-Functionalized 2-Amino-4,5-dimethylpyrroles

A versatile class of 2-aminopyrroles containing various electron-withdrawing substituents at the 3-position have been N-arylated on the amine using a palladium-catalyzed cross-coupling reaction. Using this methodology, a pyrimidone-based tricyclic system has been prepared in just one step from a starting 2-aminopyrrole.

Stereoselective Synthesis and Characterization of (Z)-(−)-4-(1′-Alkoxyl-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones

Abstract

A series of enantiomerically pure (Z)-(?)-4-(1′-alkyloxy-1′-alkyloxycarbonyl-methylidene)-5(R)-[(1R)-menthyloxy]-γ-butyrolactones were synthesized and characterized in good to excellent yields via O-alkylation of (4R,5R)-(?)-4-ethoxyoxalyl-5-[(1R)-menthyloxy]-γ-butyrolactone with alkyl halides in the presence of K₂CO₃ in acetone at room temperature.     

Synthesis and properties of cyanomethyl derivatives of imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine,imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine,and imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazole

2-Cyanomethyl derivatives were obtained of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole, and their reactivity was investigated by an example of imidazo[1,2-a]pyridine: It was subjected to nitration, bromination, azo coupling and nitrosation. Acylation of the methylene group effected by amino acids esters with a subsequent addition of the amino group to the cyano group resulted in the formation of 5-amino-4-imidazo[1,2-a]-pyridin-2-yl-1-phenyl-1,2-dihydro-3H-pyrrol-3-one and 2-amino-1-ethyl-3-imidazol[1,2-a]pyridin-2-yl-4(1H)-quinolinone.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Sigmatropic Rearrangement of Ammonium Ylides—Key Step in the Synthesis of Methyl 2-Formylphenyl Acetate

N-Cyanomethyl-N,N-dimethyl-N-(α-methoxycarbonyl)benzylammonium salts 5 were synthesized and treated with different base/solvent systems, giving the products of sigmatropic rearrangements [2,3] 7 and [1,2] 8. In reactions carried out in liquid ammonia, [2,3] rearrangement definitively prevailed. Pure 7(or mixture of 7 and 8) were deprotected to afford methyl 2-formylphenyl acetate (9) in good yield.      

Synthesis and regiospecificity in methylation of pyrido[1,2-a]pyrazinium-1- and 3-olates and pyrido[1,2-b]pyridazinium-2- and 4-olates

New methods have been developed for the synthesis of pyrido[1,2-a]pyrazinium-1- and 3-olates 5a-f, 9 and 1-thiolate 24 as well as of pyrido[1,2-b]pyridazinium-4- and 2-olates 14, 20 . The methylation of these new compounds was studied by soft and hard methylating agents. Depending on the nature of the reagent used, the pyrido[1,2-a]pyrazinium-1-olates 5a-f gave NMe 22a-f and/or OMe 23a-f products, whereas the 3-olate 9 and both the 4- and 2-pyridazinium-olates 14, 20 afforded solely OMe compounds 10, 15, 21 . A selectivity rule for methylation is proposed.     

Cyclocondensation of <Emphasis Type="Italic">N</Emphasis>-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole

Cyclization of N-aryl-3-oxobutanethioamides with 2-aminoimidazole and 2-aminobenzimidazole gave 7-methyl-5,8-dihydroimidazo[1,2-a]pyrimidine-5-thione or 2-methylpyrimido[1,2-a]benzimidazole-4(1H)-thione and 4-(arylamino)-2-methylpyrimido[1,2-a]benzimidazoles whose ratio depends on the nature of aryl substituents in the initial butanethioamides and on the presence of a protic solvent.     

Efficient Methods for the Synthesis of Benzopyrano[3,4-c]pyrrolidines by Catalyzed 1,3-Dipolar Cycloaddition of Azomethine Ylides with 3-Substituted Coumarins

With triethylamine as a catalyst, the 1,3-dipolar cycloaddition of azomethine ylides with 3-substituted coumarins proceeded smoothly under mild conditions to afford the desired products benzopyrano[3,4-c]pyrrolidines in good to excellent yields.      

Synthesis of sulfonamide derivatives of pyrido-[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazolin-11-one and pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6-one

Methods were developed of indirect introduction of sulfonamide group in the structures of pyrido-[2,1-b]quinazolin-11-one and pyrido[1,2-a]quinazolin-6-one underlain by cyclocondensation of 2-halo-5-(Rsulfamoyl) benzoyl chlorides with derivatives of 2-aminopyridine. The fact of thermal rearrangement of 8-(morpholin-4-ylsulfonyl)pyrido[1,2-a]quinazolin-6-one into isomeric 2-(morpholine-4-ylsulfonyl)pyrido[2,1-b]-quinazolin-11-one was experimentally registered.     

Synthesis of unsymmetrically tetrasubstituted pyrroles and studies of AIEE in pyrrolo[1,2-a]pyrimidine derivatives

Pyrroles are among the most important heterocycles in pharmaceuticals and agrochemicals. Construction of pyrrole scaffolds with different substituents and a free NH group, however, is challenging. Herein, a metal-free method for the synthesis of unsymmetrically tetrasubstituted NH-pyrroles using a consecutive chemoselective double cyanation is reported. The desired pyrroles were obtained with yields up to 99% and good functional group tolerance. Mechanistic studies identified a reaction mechanism that features a subtle sequence of first cyano-addition and migration, followed by cyano-addition and aromatization to afford the pyrrole skeleton. Pyrrolo[1,2-a]pyrimidines are synthesized as the synthetic applications of NH-pyrroles, and these pyrrolo[1,2-a]pyrimidines exhibit unpredicted time-dependent aggregation-induced emission enhancement (AIEE) properties.

A novel method for the challenging synthesis of unsymmetrically tetrasubstituted NH-pyrroles from chalcone derivatives is reported. The pyrrolo[1,2-a]pyrimidine derivatives that were synthesized from NH-pyrroles exhibit AIE and AIEE property.     

Reactions of heterocyclic cations with N-containing nucleophiles. 17. Synthesis of pyrylium salts with three-ring azole substituents

2,6-Diphenylpyrylium perchlorate was hetarylated with imidazo- and pyrrolo-[1,2-a]benzimidazoles, and deeply colored 4-azolylpyrylium perchlorates were obtained.See [1] for communication 16.Communication 24 from the series Research on imidazo[1,2-a]benzimidazole derivatives. See [2] for communication 23.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 309–313, March, 1987.     

Novel Synthesis of Some New Pyridazine and Pyridazino[4,5-d]pyridazine Derivatives

Phenacyl-malononitrile derivatives 1a and b react with dimethylformamide dimethylacetal (DMFDMA) in refluxing toluene to afford the enaminones 2a and b respectively. Compounds 2a and 2b react with the hydrazine hydrate 3a and phenyl hydrazine 3b in refluxing ethanol to afford the pyridazine derivatives 5a–d, presumably via the intermediates 4. Compounds 5a–d, react with hydrazine hydrate 3a to afford the pyridazino[4,5-d]pyridazines 6a–d respectively. The pyridazines 5a and b and the pyridazino[4,5-d] pyridazines 6a and b could be oxidized into the full aromatic systems 7a and b and 8a and b respectively. Compounds 7a and b react also with hydrazine hydrate 3a to afford 8a and b respectively.

Synthesis of Novel Poly(ethyleneglycol)-400 Ionic Liquid and Its Application in Morita–Baylis–Hillman Reaction

Novel Poly(ethyleneglycol)-400 ionic liquid containing imidazolium cations have been synthesized by the atom-efficient reaction of 1,2-dimethylimidazole with p-toluenesulfonate; the p-toluenesulfonate provides the anionic component of the resultant ionic liquid. It have been used for the first time as a new solvent for the Morita–Baylis–Hillman reaction under ambient conditions. A wide variety of aldehydes and active olefins participate very efficiently, resulting in good to excellent yields of products.