Synthesis of a New Imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione Heterocyclic System

A novel imidazo[4′,5′:3,4]pyrazolo[5,1‐c][1,2,4]triazine‐4,8‐dione heterocyclic system was synthesized starting from available 4‐amino‐6‐tert‐butyl‐3‐methylthio‐1,2,4‐triazin‐5(4H)‐one in four steps with 28% overall yield.     

Facile synthesis of pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer

Efficient synthesis of biological important pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione dimer linked through the C‐2 positions by fumarate group is described.     

Synthesis of Imidazo[2,1‐b][2H‐1,3,4]thiadiazines and 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines

Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.     

Design,Synthesis, and Characterization of (2‐Alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone

The important therapeutic properties of imidazole‐related drugs have encouraged the medicinal chemists to synthesize and test a large number of novel molecules. In this investigation, it was of interest to synthesize (2‐alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone by short reaction times of N‐triazol‐3‐yl imidate with phenacyl bromides under basic conditions. All compounds were elucidated by spectroscopic methods including IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectral analysis.     

C‐phosphorylation of 1,2,4‐triazoles with phosphorus(III) halides. Synthesis of 4,5‐dihydrobenzo[e][1,2,4]triazolo[5,1‐c][1,4,2]diazaphosphinine derivatives

Phosphorylation of 4‐ and 1‐substituted 1,2,4‐triazoles with PCl₃, PhPCl₂, Ph₂PCl, and (Et₂N)₂ PCl was carried out. A novel phosphorus‐containing condensed heterocyclic system ( 18, 23 ) was constructed by the reactions of 2‐(1H‐1,2,4‐triazol‐1‐yl)‐1‐(4‐chlorophenylcarboxamido)‐5‐trifluoromethylbenzene with PBr₃ and PhPBr₂. Treatment of the bromophosphonite 18 with an excess of morpholine in the presence of sulfur resulted in a diazaphosphinine ring opening and provided functionalized 1H‐1,2,4‐triazol‐5‐ylphosphonic acid derivatives 21 and 22 . © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:146–152, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10010     

8‐Fluoro‐4‐hydroxy‐1H‐[1,2,4]triazino[4,5‐a]quinoline‐1,6(2H)‐dione: Synthesis and reactivity

A simple and versatile methodology to synthesise 4‐hydroxy‐1H‐[1,2,4]triazino[4,5‐a]quinoline‐1,6(2H)‐dione from methyl 6‐fluoro‐4‐oxo‐1,4‐dihydro‐2‐quinolinecarboxylate has been developed. It involves car‐bohydrazide formation followed by a condensation with triphosgene to form the fused [1,2,4]triazino ring. In addition, the reactivity of the [1,2,4]triazino ring has been studied.     

A Convenient and Facile Synthesis of Isoxazolyl‐chromeno[4,3,2‐de]pyrimido[4,5‐h][1,6]napthyridinones

The ceric ammonium nitrate‐catalyzed synthesis of (E)‐5‐amino‐N‐(3‐methyl‐5‐styrylisoxazol‐4‐yl)‐2‐arylchromeno[4,3,2‐de][1,6]napthyridin‐4‐carboxamides 5 was simply achieved upon the one‐pot four‐component reaction of isoxazolyl cyanoacetamide 1 with malononitrile 2 , 2‐hydroxy acetophenone 3 , and aromatic aldehydes 4 in ethanol. Compounds 5 on heating with acetic anhydride underwent tandem N‐acetylation and cyclocondensation involving intramolecular cyclization to afford the title compounds (E)‐11‐methyl‐12‐(3‐methyl‐5‐styrylisoxazol‐4‐yl)‐2‐arylchromeno[4,3,2‐de][1,6]napthyridin‐13(12H)‐ones 6 in good yields. The chemical structures have been confirmed by analytical and spectral analyses.     

Synthesis and properties of 4,5‐dihydrobenzo[e]imidazo[2,1‐c][1,4,2]diazaphosphinine derivatives

A number of 4,5‐dihydrobenzo[e]imidazo[2,1‐c][1,4,2]diazaphosphinine derivatives were prepared by the direct phosphorylation of 1‐(4‐Chlorophenylcarboxamido)‐2‐(1H‐1‐imidazolyl)‐5‐trifluoromethylbenzene in basic medium with phosphorus(III) bromide and dibromophenylphosphine. The tricyclic compounds 6a, 6b , and 9 having a trivalent phosphorus atom undergo the diazaphosphinine ring opening upon treatment with secondary amines in the presence of sulfur. © 2002 John Wiley & Sons, Inc. Heteroatom Chem 13:84–92, 2002; DOI 10.1002/hc.10000     

Synthesis of 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones

In an attempt to discover bicyclic compounds containing the 1,2,4‐triazine moiety, 1,2,4‐triazolo[1,5‐d]‐1,2,4‐triazine‐5‐thiones from one pot reaction of arylnitriles with 4‐amino‐1,2,4‐triazine‐3‐thione‐5‐one in the presence of potassium tert‐butoxide were synthesized.     

Synthesis and antifungal activity of novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazepines

5‐Aryl‐3,4‐diamino‐1,2,4‐triazoles 5 on treatment with β‐chlorocinnamaldehydes 7 in the presence of catalytic amount of p‐TsOH and N,N‐dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil‐bath heating at 80 °C affords novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b]‐1,2,4]triazepines 8 . The structures of the synthesized compounds were established on the basis of ¹H NMR, IR, mass spectral data and elemental analysis.     

A Convenient Approach to 4,7‐Dihydrotetrazolo [5,1‐c][1,2,4]triazine Synthesis

Azo coupling of 1,3‐dicarbonyl compounds with tetrazolyl‐5‐diazonium chloride is used to develop a convenient one‐step procedure for the synthesis of 4,7‐dihydrotetrazolo[5,1‐c][1,2,4]triazines. In contrast to nonfluorinated analogs, 7‐hydroxy‐7‐polyfluoroalkyl‐4,7‐dihydrotetrazolo[5,1‐c][1,2,4]triazines undergo a ring‐chain isomerism resulting from the cleavage at the C7―N7a bond. A distinctive feature of nonfluorinated 4,7‐dihydrotetrazolo[5,1‐c][1,2,4]triazines is the possibility to dehydration, which is accompanied by an azide rearrangement due to the tetrazole ring cleavage with the formation of tetrazolo[1,5‐b][1,2,4]triazines.     

A new site‐selective route for synthesis of functionalized imidazo[2,1‐c][1,2,4]triazoles

Reactions of 4‐arylhydrazono‐2‐methylthio‐imidazolin‐5(1H)‐one 3 with various hydrazonoyl halides 1 proved to be site‐selective and yielded the respective imidazo[2,1‐c][1,2,4]triazole derivatives 8 . The structure of the latter was elucidated by X‐ray analysis and the mechanism of the studied reactions was discussed.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 22 Dibenzo[f,h]benzothieno[2,3‐c]quinoline,dibenzo[f,h]benzothieno[2,3‐c][1,2,4]triazolo[4,3‐a]quinoline and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinoline

Photocyclization of 3‐chloro‐N‐(9‐phenanthryl)benzo[b]‐thiophene‐2‐carboxamide ( 3 ) and 3‐chloro‐N‐(9‐phenanthryl)‐naphtho[1,2‐b]thiophene‐2‐carboxamide ( 10 ) yielded dibenzo[f,h]benzothieno[2,3‐c]‐quinolin‐10(9H)‐one ( 4 ) and dibenzo[f,h]naphtho[2′,1′:4,5]thieno[2,3‐c]quinolin‐10(9H)‐one ( 11 ), respectively. Further elaboration of the lactams provided three novel unsubstituted new ring systems.     

New Regioselective Synthesis and Biological Activity of Substituted 1H‐[1,2,4]Triazolo[3,4‐c][1,2,4]Triazoles

Two regioselective synthetic approaches for the title compounds 7 via reaction of hydrazonoyl halides 1 with 3‐methylthio‐5‐phenyl‐1,2,4‐triazole 3 and base‐catalyzed cyclization of N‐phenyl‐N‐(5‐phenyl‐s‐triazol‐3‐yl)thiohydrazides 6 are described. The mechanisms of the reactions studied and the biological activity of the isolated products 6 and 7 are pointed out.     

Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.     

A new series of non‐classical type C heteropentalenes: 2H‐pyrrolo[2,1‐c][1,2,4]triazoles

7‐Functionalized title compounds 5 are obtained by cyclization of 3‐acetonyl‐ or 3‐[(alkoxycarbonyl)‐methyl]‐4‐phenacyl‐1,2,4‐triazolium salts 2 having methyl at C(5) the process can be effected in an acetate buffer or by base, irrespective of the function at C(3). 5‐Unsubstituted salts 2 do not react unless the side chain at C(3) is an acetonyl group. Cyclization of 2 with acetic anhydride‐base gives rise to 5,7‐difunctionalized compounds 8 ; again methyl at C(5) of 2 is compulsory, but here the reaction can be extended to salts having an (alkoxycarbonyl)methyl group at C(4). Regarding defunctionalization, acetyl groups can be split from C(5) only, whereas ester functions are removable also from C(7). Title compounds devoid of acceptor groups ( XIII ) are unstable but can be trapped by electrophilic reagents (DMAD, acetic anhydride, and phenyl isocyanate) to give the derivatives 10 and 12 . The 7‐functionalized products 5 are likewise susceptible to S_E‐reactions. By comparison, all title compounds appear to be more reactive toward this kind of reagents than the isomeric 1H‐pyrrolotriazoles ( 13 ) including 2H‐pyrrolotetrazoles ( III ). This is consistent with B3LYP‐DFT calculations using appropriate models.     

An irreversible phase transition in 1‐n‐butylindeno[2,1‐c]pyran‐3,9‐dione

At ambient temperature, the title compound, C₁₆H₁₄O₃, is triclinic, with the n‐butyl side chain disordered in an out‐of‐plane orientation. On cooling below 240 K, it converts into a different triclinic phase with an ordered planar conformation and denser packing, which is retained on warming to room temperature. The transition (occasionally) proceeds from single crystal to single crystal.