Synthesis of 3-(Piperidin-4-yl)-6,7-dihydro-5H-pyrrolo-[2,1-c][1,2,4]triazole and Theoretical Study of the Hydrazone-Hydrazine Tautomerism of the Intermediate Hydrazonation Product

Russian Journal of Organic Chemistry - 3-(Piperidin-4-yl)-6,7-dihydro-5H-pyrrolo[2,1-c][1,2,4]triazole was synthesized through a four-step process including etherification, hydrazonation,...     

Highly diastereoselective synthesis of C6-functionalized dihydroimidazotriazines

[reaction: see text] The first examples of C(6)-substituted 7-hydroxy-6,7-dihydro-5H-imidazo[1,2-b][1,2,4]triazines have been prepared by ring closure of different 5(2H)-1,2,4-triazin-3-ones 1a-c with 40% aqueous glyoxal and various nucleophiles (alcohols, thiols, or amines). The structure and exact stereochemistry of 2a was established by a single X-ray diffraction study and (1)H and (13)C NMR spectra analysis. The process was shown to be totally regio- and diastereoselective. A mechanism involving an imine intermediate was proposed.     

Reaction of Hetareno[e]pyrrolediones with 1,3-C,N-Binucleophiles. Isolation of Intermediate Product of Spiro Heterocyclization

Russian Journal of Organic Chemistry - Ethyl 1,2,4-trioxo-2,4-dihydro-1H-pyrrolo[2,1-c][1,4]benzoxazine-3-carboxylates reacted with ethyl (2Z)-[2-oxo-2H-1,4-benzoxazin-3(4H)-ylidene]acetates to...     

Synthesis of isoindolo[2,1-a]quinoline derivatives and their effects on N2-induced hypoxia

A variety of isoindolo[2,1-a]quinoline derivatives as well as the following related heterocycles have been prepared: 11b,12-dihydro-5H-isoindolo[2,1-b][2]benzazepine-7,13-dione (8a), 7,8,14,14a-tetrahydroisoindolo[2,1-c][3]benzazocine-5, 13-dione (8b), 6a,7-dihydroisoquinolino[2,3-a]quinoline-5,12-dione (12), 2,3,3a-4-tetrahydropyrrolo[1,2-a]quinoline-1,5-dione (14), and pyrido[2',3':3,4]pyrrolo[1,2-a]quinoline-5,11(5H)-dione (17). The key synthetic step involves an intramolecular Friedel-Crafts reaction of acid chlorides such as isoindole-1-acetyl chlorides (4), the acids (3) of which were prepared starting with 2-arylisoindole-1,3(2H)-diones (2-arylphthalimides) (1). The protective effects of isoindolo[2,1-a]quinoline derivatives (19 and 20) against N2-induced hypoxia were examined. Among them, 6-(diethylaminomethyl)isoindolo[2,1-a]quinoline-5,11(5H)-dio ne (19b) showed the most potency.     

NOVEL SYNTHESIS OF CONDENSED HETEROCYCLIC SYSTEMS CONTAINING 1,2,4-TRIAZOLE RING

3-Aryl-6,7-dihydro-s-triazolo[3,4-b][1,3]thiazines and 3-aryl-5,6-dihydro-thiazolo[2,3-c]-s-triazoles were synthesized by nucleophilic substitution of 3-aryl-5-mercapto-1,2,4-triazoles with 1,3-dibromopropane and 1,2-dichloroethane. And the bis-Mannich reaction of 3-aryl-5-mercapto-1,2,4-triazoles with formaldehyde has been studied.     

Practical synthesis of regioisomeric 5(7)-amino-6,7(4,5)-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazines

A convenient and efficient synthesis of new 5-azapurine derivatives was developed. The regioisomeric 5-amino-6,7-dihydro- and 7-amino-4,5-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazines were prepared in 3–4 steps from benzhydrazide via complementary and regiospecific routes as a part of our lead finding program. The molecular structures and tautomeric preferences of the compounds obtained were investigated using NMR spectral data and X-ray crystallography.     

Preparation of aminotriazole-thione derivatives from n-aryl-n-carboxyethyl-β-alanines

Depending on the substituents in the aryl moiety, the fusion of N-aryl-N-ethoxycarbonyl-β-alanines with thiocarbohydrazide gives di- or monotriazole derivatives, namely, 4-amino-(2-{[2-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]anilino}ethyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones, 1-[2-(4-amino- 5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)ethyl]-2,3-dihydroquinolin-4(1H)-ones, 4-amino-3-[2-(4-methylanilino))ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione and 4-amino-3-[2-(4-ethoxyanilino)-ethyl]-4,5-dihydro-1H-1,2,4-triazole-5-thione. A ditriazolethione derivative was also obtained from the diethyl ester of N-ethoxycarbonyl-N-(4-ethoxyphenyl)- β-alanine.     

Synthesis of (1H)-3,4-Dihydropyrrolo[2,1-c][1,4]oxazin-1-one Derivatives

It has been found that some acyl derivatives of 1,2,3,4-tetrahydro-1-indolizin-1-one 1and (1H)-3,4-dihydropyrrolo[1,2-a]pyrazin-1-one 2 show remarkable anti-inflammatory and analgesic activities1,2. The interest in extending the study of structure-activity relationships and search of new potent anti-inflammatory and analgesic agents led us to design and synthesize (1H)-3,4-dihydropyrrolo[2,1-c][1,4]oxazin-1-one 3 derivatives. NO 1 NNHO2 87654321ONO3 A few examples of the p…     

Reaction of Diethyl Chloroethynylphosphonate with 3-Amino-1,2,4-triazoles

Russian Journal of General Chemistry - A series of new 6-phosphonylated 1H-imidazo[2,1-c][1,2,4]triazoles was synthesized by the reaction of diethyl chloroethynylphosphonate with 2-substituted...     

Electron impact mass spectral fragmentation of 2a,4-disubstituted 2-chloro/2,2-dichloro-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]benzothia zepin-1-ones

The mass spectrometric behaviour of nine 2a,4-disubstituted 2-chloro/2,2-dichloro-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]b enzothiazepin-1-ones has been studied with the aid of mass-analysed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a neutral chlorine atom, or a chloroketene, or neutral propene, or styrene or substituted styrene molecule, plus Cl and/or H (or Cl) atom(s), to yield [M-Cl]+ ions, 2,3-dihydro-1,5-benzothiazepine derivative ions, 4,5-dihydro-5H-1,5-benzothiazepin-4-one ions which can further lose CO to give 1,4-benzothiazine ions. Both molecular ions and [M-Cl]+ ions show a tendency to eliminate an ethyl or benzyl/substituted benzyl radical to produce 2,2a-dihydro-1H-azeto[2,1-c][1,4]benzothiazin-1-one ions. The [M-Cl]+ ions could undergo rearrangement to yield 2,2a-dihydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-one ions, 2,2a,3,4-tetrahydro-1H-azeto[1,2-a]quinoline ions or 1,1a,2,3-tetrahydro-azirino[2,1-d][1,5]benzothiazepine ions by loss of an ethane or a benzene/substituted benzene, a SH radical or a CO molecule. The molecular ions could also undergo rearrangement reactions to form other small fragment ions.     

Synthesis and antimicrobial activity of some new pyrazoles, fused pyrazolo[3,4-d]-pyrimidine and 1,2-dihydroimidazo-[2,1-c][1,2,4]triazin-6-one derivatives

A novel series of 7,7-diphenyl-1,2-dihydroimidazo[2,1-c][1,2,4]triazin-6(7H)-one 6a-h, were easily prepared via reactions of novel 2-hydrazinyl-4,4-diphenyl-1H-imidazol-5(4H)-one (2) with hydrazonoyl halides 3a-h. In addition, we also examined the reaction of compound 2 with commercially available active methylene compounds to afford new pyrazoles containing an imidazolone moiety, expected to be biologically active. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, 1H-NMR and mass spectral data. The antifungal and antibacterial activities of the newly synthesized compounds were evaluated.     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Reactions of fused dihydro-1,2,4-thiadiazoles with isoselenocyanates giving 6aλ4-thia-1,3,4,6-tetraazapentalene derivatives and 5,10-dihydro-1,2,4-thiaselenazolo[4,5-b][2,4]benzodiazepines

3-Methyl-6,7-dihydro-5H-1,2,4-thiadiazolo[4,5-a]pyrimidine (1) reacted with isoselenocyanates with elimination of acetonitrile and concomitant addition of two molecules of the isoselenocyanate to give 2,3-di-substituted-6,7-dihydro-5H-2aλ⁴-thia-2,3,4a,7a-tetraazacyclopent[cd]indene-1(2H),4(3H)-diselones (6a)–(6j). 3-Methyl-5,10-dihydrobenzo[e]-1,2,4-thiadiazolo[4,5-a][1,3]diazepine (3) likewise reacted with alkyl isoselenocyanates to give the 2,3-dialkyl-5-10-dihydro-2aλ⁴-thia-2,3,4a,10a-tetraazapentaleno[3,3a,4-gh]benzocycloheptene-1,4-diselones (9a)–(9h), but reaction of (3) with aryl isoselenocyanates took place with elimination of acetonitrile and incorporation of one molecule of the aryl isoselenocyanate in the product to give 3-arylimino-5,10-dihydro-1,2,4-thiaselenazolo[4,5-b][2,4]benzodiazepines (10a)–(10h). Structure (10) is a new heterocyclic system. The pyrimidine (1) and the diazepine (3) reacted with aryl isoselenocyanates at room temperature in solvents of low polarity to give zwitterion 1:1 addition compounds (7) and (12), respectively. NMR studies reveal that the thiaselenazoles (10) react in solution with aryl isoselenocyanates to give diaryl diselones (11) in a reversible process involving a Dimroth rearrangement. © 1996 John Wiley & Sons, Inc.     

Some cyclization reactions of 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one: preparation and computational analysis of non symmetrical zwitterionic biscyanines

Regioselective nucleophilic addition of bisnucleophiles 1,2-benzenediamine, 2-amino-benzenethiol, and N-phenyl-1,2-benzenediamine to 1,3-diphenylbenzo[e][1,2,4]triazin-7(1H)-one (1) at C6 followed by intramolecular cyclocondensation at the C7 carbonyl afforded highly coloured tetracenes 1,3-diphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-4-ium 4-methylbenzenesulfonate (12), 1,3-diphenyl-1H-[1,2,4]triazino[6,5-b]phenothiazine (14) and 1,3,11-triphenyl-1,6-dihydro-[1,2,4]triazino[5,6-b]phenazin-11-ium 4-methylbenzenesulfonate (15), respectively. Neutralization of the latter with alkali gave the free base 1,3,11-triphenyl-1H-[1,2,4]triazino[5,6-b]phenazin-11-ium-6-ide (16). Furthermore, the benzotriazinone 1 reacts with dimethyl malonate to give 6-(methoxycarbonyl)-7-oxo-1,3-diphenyl-7H-benzofuro[5,6-e][1,2,4]triazin-1-ium-4-ide (17) in 74% yield, while with S(4)N(4) [5,6-c]-thiadiazolo-7-oxo-1,3-diphenyl-1,2,4-benzotriazine (22) was formed in 15% yield. The free bases 16 and 17 display negative solvatochromism, which supports charge separated ground states similar to those of zwitterionic biscyanines, and DFT calculations at the UB3LYP/6-31G(d) level afford ΔE(ST) values of -13.6 and -18.7 kcal mol(-1), respectively that strongly favour the singlet ground state. All ring systems described are new and fully characterized.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.     

Copper(I)-catalyzed cascade sulfonimidate to sulfonamide rearrangement: synthesis of imidazo[1,2-a][1,4]diazepin-7(6H)-one

A novel strategy of copper(I)-catalyzed cascade intramolecular nucleophilic attack on N-sulfonylketenimine followed by rearrangement of sulfonimidates to sulfonamides resulting in a library of substituted 8,9-dihydro-5H-imidazo[1,2-a][1,4]diazepin-7(6H)-ones has been developed.     

Palladium-catalyzed cyclization reactions of 3-propargylthio 1,2,4-triazin-5(2h)-ones to thiazolo-1,2,4-triazinones

Selective transformation of 3-propargylthio-1,2,4-triazin-5(2H)-ones ($\text{1}$) to 6-methylene-6,7-dihydro-4H-thiazolo[2,3-c][1,2,4]-triazin-4-ones ($\text{2}$) and 3-methylene-2,3-dihydro-7H-thiazolo[3,2-b]-[1,2,4]triazin-7-ones ($\text{3}$) is performed under the conditions of Pd(II) salt or sodium hydroxide catalysis, respectively.     

1,2,4-Triazines – products of reaction of thiocarbohydrazide and its alkyl(aryl)-substituted derivatives with 1,2-dicarbonyl compounds

The reaction of a series of 1,2-dicarbonyl compounds with thiocarbohydrazide and its 1- and 1,4-alkyl-(aryl)-substituted analogs has been studied. Treatment of diacetyl with the polynucleophiles indicated gives monohydrazones and/or 5-methylene-4,5-dihydro-2H-[1,2,4]triazine-3-thiones. Reaction of phenylglyoxal and benzil with thiocarbohydrazide yields 5-hydroxy- or 5-alkoxy-4,5-dihydro-2H-[1,2,4]triazine-3-thiones depending on the nature of the solvent. The products of condensation with 1,1-dimethylthiocarbohydrazide showed a thiocarbonohydrazone – 5-hydroxy-4,5-dihydro-2H-[1,2,4]tri-azine-3-thione ring-chain type equilibrium.     

First nucleophilic aromatic substitution of annelated pyrazole.

3-Chloropyrazolo[3,4-c]quinoline 5, 3-chloropyrazolo[3,4-c]isoquinoline 6, 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]quinolin-3-one 8, and 1,2-dihydro-1,2-dimethylpyrazolo[3,4-c]isoquinolin-3-one 10 were obtained by acid-induced nucleophilic aromatic substitution (S(N)H) of H-3 in N-hydroxypyrazolo[3,4-c]quinoline 1b and in N-hydroxy pyrazolo[3,4-c]isoquinoline 3b. In the acid-induced chlorination, 3b was far more reactive than 1b, whereas the related N-hydroxypyrazolo[4,3-c]quinoline 2b and N-hydroxypyrazolo[4,3-c]isoquinoline 4b were completely unreactive toward S(N)H under identical conditions.