A new strategy for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines

A series of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of aldehyde N-(1,3-diphenylpyrazolo[3,4-d]pyrimidin-4-yl)hydrazones. Dimroth rearrangement of such a series yielded pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.     

Flash vacuum pyrolysis (fvp) of some hexahydroquinazolin-4(1H)-ones

Some cis/trans-2-thioquinazolin-4-ones and their 2,4-dione analogs were subjected to flash vacuum pyrolysis. The cis- and trans-thio compounds reacted at lower temperatures than the cis- and trans-dioxo analogs, showing a lower thermal stability. All of these compounds afforded similar reactions: ring opening to the corresponding iso(thio)cyanate, the loss of H and NCS to form three isomeric cyclohexadienes and then aromatization to form the corresponding benzamide. The cis-dioxo compound also underwent a competitive retro Diels-Alder (RDA) reaction to form 3-phenylpyrimidine-2,4(1H,3H-dione(3-phenyluracil)) and butadiene. Kinetic measurements of the ring opening reaction supported a concerted β-elimination as the most probable mechanism.     

Synthesis of 5-arylpyrrolo[2,1-c][1,4]benzodiazepines under mild cyclodehydration conditions

The efficiency of a cyclodehydration reaction leading to benzodiazepinones is markedly improved by N-methylation of the amide link connecting the nucleophile and the electrophile, which is attributed to its favouring both the more reactive E-rotamer and the exit of the leaving group.     

Rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones to furo[3,4-c]quinoline-3,4(1H,5H)-diones

Thermally assisted base-catalyzed rearrangement of furo[2,3-c]quinoline-2,4(3aH,5H)-diones 1 to the corresponding furo[3,4-c]quinoline-3,4(1H,5H)-diones 2 is reported, and a mechanism of the transformation is proposed.     

Anodic formation of 3,6-diaryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and 2(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles

3,6-Disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles together with the unknown systems 2-(3-aryl-5-methyl-1H-[1,2,4]triazol-1-yl)-5-aryl-1,3,4-thiadiazoles were obtained by anodic oxidation, under aprotic conditions, of aryl aldehyde N-(5-aryl-1,3,4-thiadiazol-2-yl) hydrazones. Mechanistic proposals are given.     

Flash vacuum pyrolysis of 2,2-dioxo-1H,3H-pyrrolo[1,2-c]thiazoles and 2-vinyl-1H-pyrroles

The flash vacuum pyrolysis of new 1,1-dimethyl- and 1-methyl-1H,3H-pyrrolo[1,2-c]thiazole-2,2-dioxides gave penta-substituted 2-vinyl-1H-pyrroles via sigmatropic [1,8]-H shift of the corresponding azafulvenium methide intermediates. In some cases these 1H-pyrroles underwent rearrangement to 2-allyl-1H-pyrroles. Di-substituted 2-vinylpyrroles have also been prepared and their reactivity studied. Under FVP N-benzyl-pyrrol-2-ylpropenoates were converted into 3H-pyrrolizin-3-ones. On the other hand, microwave-assisted reaction of 1-benzyl-2-vinyl-1H-pyrrole gave a 4,5,6,7-tetrahydro-1H-indole derivative.     

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.     

One-pot synthesis of novel 1,2,6,7-tetrahydro-3H-pyrazolo[4,3-c]pyridine-3,4(5H)-diones

A facile synthesis of novel 1,2,6,7-tetrahydro-3H-pyrazolo[4,3-c]pyridine-3,4(5H)-diones has been achieved. The operationally simple procedure, using readily available intermediates, allows for rapid derivatisation of the pharmacophore with alkyl, aryl and heteroaryl substituents.     

Azo-coupling of pyrazole-3(5)-diazonium chlorides with cyanothioacetamide: a convenient synthesis of pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides

Cyanothioacetamide reacts with pyrazole-3(5)-diazonium chlorides to afford pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides 5. The latter can be oxidized with H₂O₂ to give either pyrazolo[5,1-c][1,2,4]triazine-3-carboxamides or 1,2,4-thiadiazole derivatives, depending on the reaction conditions. The Hantzsch-type reaction of thioamides 5 with α-bromo ketones leads to 3-(thiazol-2-yl)pyrazolo[5,1-c][1,2,4]triazines.     

An efficient one-pot synthesis of pyrazolyl-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-6-yl)-2H-pyran-2-one derivatives via multicomponent approach and their potential antimicrobial and nematicidal activities

A series of simple or/and aryl, heteryl hydrazono pyrazolyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl)-2H-pyran-2-one derivatives have been efficiently synthesized in excellent yields via one-pot, multi-component approach. The importance of this methodology is that in a one-pot operation four new bonds (3C–N and 1C–S) are generated. The structure of compound 5a was confirmed by single-crystal X-ray diffraction. The newly synthesized compounds were evaluated for their in vitro antimicrobial activity against gram-positive bacteria (Staphylococcusaureus and Bacillussubtilis), gram-negative bacteria (Escherichiacoli andKlebsiellapneumoniae), antifungal activity against Candida albicans, and nematicidal activity against Meloidogyneincognita. Among all the compounds 6f showed excellent antimicrobial and nematicidal activity against tested bacteria, fungi, and nematodes.     

Regioselective synthesis of the 3,4-dihydrofuro[3,2-d]pyrimidin-2(1H)-one skeleton: a new class of compound

We hereby report the first preparation of the 3,4-dihydrofuro[3,2-d]pyrimidin-2(1H)-one skeleton formed by two controlled Curtius rearrangements of the corresponding acyl azides, prepared from 2-(2-methoxy-2-oxoethyl)furan-3-carboxylate via the hydrazide. Rearrangement of the acyl azides followed by trapping by nucleophiles and intramolecular trapping provided the target compounds.     

Microwave-assisted one-pot synthesis of benzo[b][1,4]thiazin-3(4H)-ones via Smiles rearrangement

The synthesis of benzo[b][1,4]thiazin-3(4H)-one derivatives in a simple and efficient method from the one-pot reaction of substituted 2-chlorobenzenthiols, chloroacetyl chloride, and primary amines via Smiles rearrangement under microwave irradiation gave high yields (65-92%) of the products with short reaction time (15-20 min).     

Proton transfer process in synthesis of 3-acetyl-4-(substituted ethylenyl)coumarins and chromeno[3,4-c]pyridines

The triphenylphosphine mediated reactions of electron-deficient carbon-carbon triple bonds with 3-acetylcoumarins in dichloromethane afford functionalized 3-acetyl-4-(substituted ethylenyl)coumarins. Also, triphenylphosphine-catalyzed three-component cascade annulation reactions of 3-acetylcoumarins, activated acetylenic compounds, and hydrazines or amines provide a straightforward access to 3,5-dihydro-2H-chromeno[3,4-c]pyridine-1,2-dicarboxylates. In these strategies, the main step to the target products is proton transfer process. All products were obtained in good to high yields.     

A novel class of compounds: synthesis of 5,5′-carbonyl-bis(5,6-dihydro-4H-furo- and thieno-[2,3-c]pyrrol-4-ones)

We hereby report the first synthesis of novel class of compounds, 5,5′-carbonyl-bis(5,6-dihydro-4H-thieno- and furo-[2,3-c]pyrrol-4-one starting from methyl 2-(2-methoxy-2-oxoethyl) thiophene- and furan-3-carboxylate, respectively. The ester functionalities connected to methylene group were regiospecifically converted to the desired monoacyl azides. Curtius rearrangement of acyl azides followed by hydrolysis of the formed isocyanates gave the symmetrical urea derivatives. Cyclization of the ester groups provided the target compounds.     

Synthesis of ethyl 4,5-disubstituted 2-azido-3-thiophenecarboxylates and use in the synthesis of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-ones

New heterocyclic azides, ethyl 2-azido-4-R¹-5-R²-3-thiophenecarboxylates, were synthesized by diazotization of 2-aminothiophenes and subsequent treatment with sodium azide. The reactions of these heterocyclic azides with β-ketoesters and activated acetonitriles were studied. The derivatives of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine, a new ring system, were prepared in high yields via an anionic hetero-domino reaction.     

6,8-Dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione: new heterocyclizations based on SN-methodology. Unexpected formation of the first iso-π-electronic analogue of the still unknown dibenzo[a,o]pycene

N₍₂₎-Oxide and 3-amino derivatives of 6,8-dimethylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-dione have been shown to react with primary alkylamines in the presence of an oxidant to produce condensed imidazolines or imidazoles. Both conversions based on S_N^H-strategy represent a new approach to imidazoline-(imidazole-)ring annulation. Heterocyclic analogues of the still unknown dibenzo[a,o]pycene were obtained as a by-products of the above transformations upon using of cyclohexylamine.     

On the mechanism of conversion of 4-carboxy-3,4-dihydro-3-phenyl-1(2H)-isoquinolones to indeno[1,2-c]isoquinolines by thionyl chloride

It has been known for a long time that thionyl chloride can effectively mediate the transformation of 4-carboxy-3,4-dihydro-3-phenyl-1(2H)-isoquinolones to indeno[1,2-c]isoquinolines. The mechanism of this unique transformation, however, remains to be established. Evidence is presented to demonstrate that (1) the two-electron dehydrogenation precedes Friedel-Crafts cyclization and (2) the two-electron dehydrogenation occurs via H-4 deprotonation and subsequent O-sulfinylation of the lactam moiety instead of C-sulfinylation of the carbon α to the carboxyl group.     

Photochemical synthesis of triazolo[3,4-b]-1,3(4H)-benzothiazines: a detailed mechanistic study on photocyclization/photodesulfurisation of triazole-3-thiones

Irradiation of 4-(2-halobenzyl)-5-substituted-1,2,4-triazole-3-thiones under base mediated (CH₃CN/2 M NaOH) condition afforded triazolo[3,4-b]-1,3(4H)-benzothiazines and desulfurized triazoles. Benzophenone sensitized photolysis of triazole-3-thiones gave desulfurized triazoles exclusively. The mechanism of the photocyclization/photodesulfurization and the involvement of singlet and triplet energy levels are discussed.     

Unexpected behavior of 6H,13H-5:12,7:14-dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) toward phenols

A new 20-membered octaazamacrocyclic compound named 1:4,6:9,11:14,16:19-tetramethylentetrabenzo[b,g,l,q][1,4,6,9,11,14,16,19]octaazaeicocine (TTBOE) (9) has been prepared by means of in situ one-pot synthesis between the aminal 6H,13H-5:12,7:14-dimethanedibenzo[d,i][1,3,6,8]tetraazecine (DMDBTA) (3) and electron-deficient phenols. Otherwise, electron-rich phenols such as 4-chloro-3,5-dimethylphenol or 2-naphthol produce an ortho-regioselective aminomethylation resulting in 2-(1H-benzimidazol-1-ylmethyl)-4-chloro-3,5-dimethylphenol (7) and 1-(1H-benzimidazol-1-ylmethyl)-2-naphthol (8) in a Mannich type reaction in a basic medium. Moreover, obtainment of 1,1′-methylenbis(1H-benzimidazole) (15) from TTBOE is discussed.     

Construction of furo[3,4-c]pyran skeleton starting from the Baylis-Hillman adducts via the ring-closing metathesis (RCM) reaction of exo-methylene tetrahydrofuran

Construction of furo[3,4-c]pyran ring skeleton was achieved starting from the Baylis-Hillman adducts. The synthesis was carried out by the successive introduction of propargyl alcohol, radical cyclization, reduction, allylation, and finally ring-closing metathesis reaction.