Synthesis of new heteroaromatic nitrogen ligands: Pyrimido‐[4″,5″:4′,5′]‐thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidines and 1,2,3‐triazine[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]‐1,2,3‐triazines

An efficient one‐pot access for the synthesis of the previously unreported tetracyclic fused pyrimido‐[4″,5″:4′,5′]thieno[3′,2′:4,5]thieno[3,2‐d]pyrimidine ( 3 ) and 1,2,3‐triazine[4″,5″:4′,5′]thieno‐[3′,2′:4,5]thieno‐[3,2‐d]‐1,2,3‐triazine ( 5 ) heteroaromatic nitrogen ligands is described. The title compounds 3 and 5 were obtained from 3,4‐diaminothieno[2,3‐b]thiophene‐2,5‐dicarbonitrile and phosgeniminium chloride and sodium nitrite/HCl, respectively. Substituted condensed thieno[2,3‐b]thiophene derivatives 4 and 6 were synthesized by nucleophilic displacement of the chloroderivatives 3 and 5 .     

Chemistry of the phenoxathiins VIII. Synthesis of 7-chlorobenzo[1″.2″:5,6:3″,4″:5′,6′] bis[1,4] oxathiino[3,2-b:3′.2′-b′]dipyridine

As a continuation of recent study on the synthesis of a bis[1,4]oxathiinodipyridine ring system, we would now like to report the preparation of 7-chlorobenzo[1″,2″:5,6:3″,4″:5′,6′]-bis[1,4]oxathiino[3,2-b: 3′,2′-b]dipyridine. Although a potentially complex reaction with several products possible, the title compound was formed exclusively, suggesting considerable mechanistic selectivity. The characterization of the product by FT-¹H-nmr as well as its mass spectral fragmentation pathways are also reported.     

Partial Synthesis of 3′-Hydroxy-2′-deoxy-2″,3″,4″,5″-tetrahydroverrucarin A. Verrucarins and roridins, 38th Communication [1]

The macrocyclic trichothecene triester 3′-hydroxy-2′-deoxy-2",3",4",5"-tetrahydroverrucarin A ( 37 ), has been synthesized starting from the sesquiterpene alcohol verrucarol ( 3 ), adipic acid and a derivative of mevalonic acid ( 14 ). The latter has been prepared from 4-(tetrahydro-2-pyranyloxy)-2-butanone ( 9 ).     

Synthesis of novel pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidines,pyrido[3″,2″:4′,5′]thieno[3′,2′:4,5]pyrimido[l,6‐a]benzimidazoles and related fused systems

3‐Amino‐4‐aryl‐5‐ethoxycarbonyl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides 3a‐c were prepared from ethyl 4‐aryl‐3‐cyano‐6‐methyl‐2‐thioxo‐1,2‐dihydropyridine‐5‐carbonylates 1a‐c and reacted with some carbonyl compounds to give tetrahydropyridothienopyrimidine derivatives 6a‐c, 7a‐c and 8a‐c , respectively. Treatment of compound 3c with chloroacetyl chloride led to the formation of a next key compound, ethyl 2‐chloromethyl‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 9 . Also, 3‐amino‐2‐benzimidazolylthieno[2,3‐b]pyridine‐5‐carboxylate 5 and 2‐(3′‐aminothieno [2,3‐b]pyridin‐2′‐yl)‐4‐oxo‐3,4‐dihydropyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐8‐carboxylate 17 were prepared from 1c. The compounds 5, 9 and 17 were used as good synthons for other pyridothienopyrimidines and pyridothienopyrimidobenzimidazoles as well as for related fused polyheterocyclic systems.     

Synthesis and characterization of soluble polyimides derived from [1,1′;4′,1″]terphenyl‐2′,5′‐diol and biphenyl‐2,5‐diol

Two series of polyimides based on laterally attached p‐terphenyl and biphenyl groups were synthesized. The solubility and thermal properties were studied using DSC, thermogravimetric analysis, and the solubility test. These polymers exhibited good thermal stability and excellent solubility. The high solubility for both polymer series was attributed to the non‐coplanarity of diamine monomers and the use of fluorinated dianhydride, whereas the slightly better solubility for polymers based on p‐terphenyl was attributed to further weakening of interchain interaction of the polymers. Both polymer series exhibited glass‐transition temperatures (T_g's) in the range of 244–272 °C. The T_g's of polymers containing laterally attached p‐terphenyls were higher than those of their counterparts containing biphenyls by 5–17 °C. This was attributed to the formation of an interdigitated structure that hinders the segmental movement of polymer chains. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2998–3007, 2001     

Synthesis,structure and some reactions of 4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]‐quinazolines]

2′‐Substituted 5′,6′,7′,8′‐tetrahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 3a‐d were synthesized by condensation of 3‐substituted 5‐amino‐1,2,4‐triazoles 1a‐d with 2‐cyclohexylidene cyclohexanone 2 in DMF. The compounds 3 were hydrogenated with sodium borohydride in ethanol to give 2′‐substituted cis‐4a',5′,6′,7′,8′,8a'‐hexahydro‐4′H‐spiro[cyclohexane‐1,9′‐[1,2,4]triazolo[5,1‐b]quinazolines] 4a‐d in high yields. The reactions of alkylation, acylation and sulfonylation of the compounds 4 were studied. The structure of the synthesized compounds was determined on the basis of NMR measurements including HSQC, HMBC, NOESY techniques and confirmed by the X‐ray analysis of 6 and 11b . The described synthetic protocols provide rapid access to novel and diversely substituted hydrogenated [1,2,4]triazolo[5,1‐b]quinazolines.     

Chemistry of the phenoxathiins. III. Synthesis of benzo[1″,2″:5,6:5″,4″:5′,6′]bis[1,4]oxathiino[3,2-b:3′,2′-b']dipyridine

As a result of studies dealing with the synthesis of 1-azaphenoxathiins, the synthesis of benzo[1″,2″:5,6:5″,4″:5′,6′]bis[1,4]oxathiino[3,2-b:3′,2′-b']dipyridine was examined. Unique evidence of solvent participation in the synthesis of these compounds by the structure elucidation of a novel minor by-product formed during the synthesis of the title compound is also reported.     

First synthesis of novel pentaheterocyclic ring system of 1,2,4‐triazolo[2″,3″:6′,1′]pyrimido[4′,5′:2,3]pyrido[1,2‐a]benzimidazole

Reaction of 1‐amino‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (1) with dimethylformamide‐dimethylacetal (DMF‐DMA) gave 1 ‐[N,N‐(dimethylaminomethylene)amino]‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (2). Compounds (1) reacted with triethylorthoformate yielding 1‐[N‐(ethoxymethylene)amino]‐3‐arylpyrido[1,2‐a]benzimidazole‐2,4‐dicarbonitrile (3). 3‐Amino‐4‐imino‐5‐aryl‐6‐cyanopyrimido[5′,4′:5,6]pyrido[1,2‐α] benzimidazole (4) was synthesized via condensation of either (2) or (3) with hydrazine hydrate. Reactions of (4) with acetic anhydride, ethyl chloroformate or aryl isothiocyanate yielded the respective derivative of the new ring system namely 1,2,4‐triazolo[2″,3″:6′,1′]pyrimido[4′,5′:2,3]pyrido[1,2‐a]benzimidazole (5–7).     

4,4′′′′‐Azobis[2,2′: 6′,2″‐terpyridine] and its Metal Complexes

By two different routes, 4,4′′′′‐azobis[2,2′: 6′,2″‐terpyridine] was synthesized. Its ruthenium complexes show interesting metal‐to‐ligand charge transfer (MLCT) absorption maxima in the electronic spectra. They represent the first ruthenium complexes of terpyridine units to give blue solutions.     

Naphtho[1′,2′:5,6] pyrano[2,3-c] pyrazole derivatives

Reaction of 1-oxo-3-dialkylamino-1 H-naphtho[2,1-b]pyrans with N,N-dimethylformamide in the presence of phosphorus oxychloride afforded the corresponding 1-oxo-2-formyl-3-dialkyl-amino-1H-naphtho[2,1-b]pyrans. Condensation of 1-oxo-2-formyl-3-dimethylamino-1H-naphtho[2,1-b]pyran with hydrazine or monosubstituted hydrazines was found to lead to the formation of 8-alkyl(aryl)-1 1-oxo-8H,1 1H-naplitho[1′,2′:5,6] pyrano[2,3-c]pyrazoles through the intermediate hydrazones and subsequent cyclization. The same result was achieved starting from other 3-dialkylamino derivatives but in a lower yield.     

The synthesis of novel polycyclic heterocyclic ring systems. 3. Synthesis and NMR spectroscopy of 15-chloro[1]benzo-thieno[2″,3″:3′,4′]naphtho[1′,2′:4,5]thieno[2,3-c]quinoline

The polycyclic heterocyclic compound with a novel ring system, 15-chloro[1]benzothieno[2″,3″:3′,4′]-naphtho[1′,2′:4,5]thieno[2,3-c]quinoline was synthesized via photocyclization of 3-chloro-N-phenyl[1]-benzothieno[2′,3′:3,4]naphtho[2,1-b]fhiophene-2-carboxamide followed by chlorination with phosphorus oxychloride. The assignment of its ¹H and ¹³C nmr spectra was accomplished by utilizing two-dimensional nmr methods.     

Synthesis of Some Novel Phenyl Substituted Oxothiazolidin- 1’’,3’’,4’’-thiadiazolo-[3’,4’-b]thiazoline of 3β-Substituted Cholestane

Three title compounds 4a—4c have been synthesized by the cyclodehydration of 1’-benzylidine-4’-(3β-substituted-5α-cholestane-6-yl)thiosemicarbazones 2a—2c with thioglycolic acid followed by the treatment with cold conc. H2SO4 in dioxane. The compounds 2a—2c were prepared by condensation of 3β-substituted-5α-cholestan- 6-one-thiosemicarbazones 1a—1c with benzaldehyde. These thiosemicarbazones 1a—1c were obtained by the reaction of corresponding 3β-substituted-5α-cholestan-6-ones with thiosemicarbazide in the presence of few drops of conc. HCl in methanol. The structures of the products have been established on the basis of their elemental, analytical and spectral data.     

Structural and Photophysical Properties of Lanthanide Nitrate 1:1 Complexes with planar tridentate nitrogen ligands analogous to 2,2′:6′,2′-terpyridine

The ligand 2,6-bis(1-methylbenzimidazol-2-yl)pyridine (mbzimpy, 1 ) reacts with Eu^III to give [Eu(mbzimpy)(NO₃)₃(CH₃OH)] [ 4 ] whose crystal structure (EuC₂₂H₂₁N₈O₁₀, a = 7.658(3) Å, b = 19.136(2) Å, c = 8.882 Å, β = 104.07(1)°, monoclinic, P2₁, Z = 2) shows a mononuclear structure where Eu^III is ten-coordinate by a meridional tridentate mbzimpy ligand, three bidentate nitrates, and one CH₃OH molecule, leading to a low-symmetry coordination sphere around the metalion. Essentially the same coordination is found in the crystal structure of [Eu(obzimpy)(NO₃)₃] ( 8 ) (EuC₃₅H₄₅N₈O₉, a = 9.095(2) Å, b = 16.624(2) Å, c = 26.198(6) Å, β = 95.85(1)°, monoclinic, P2₁/c, Z = 4) obtained by reaction of 2,6-bis(1-octylbenzimidazol-2-yl)pyridine (obzimpy, 2 ) with Eu^III. Detailed photophysical studies of crystalline [Ln(mbzimpy)(NO₃)₃(CH₃OH)] and [Ln(obzimpy)(NO₃)₃] complexes (Ln = Eu, Gd, Tb, Lu) show that 1 and 2 display ¹ππ* and ³ππ* excited states very similar to those observed in 2,2′:6′,2″-terpyridine, leading to efficient ligand to Ln^III intramolecular energy transfer. Spectroscopic results show that an extremely efficient mbzimpy-to-Eu^III transfer occurs in [Ln(mbzimpy)(NO₃)₃(CH₃OH)] and in the case of Tb^III, a Tb^III-to-mbzimpy back transfer is also implied in the deactivation process. The origin of these peculiar effects and the influence of ligand design by going from mbzimpy to obzimpy are discussed. ¹H-NMR and luminescence data indicate that the structure found in the crystal is essentially maintained in solution.     

Synthesis and photovoltaic properties of thieno[3,4‐b]pyrazine or dithieno[3′,2′:3,4;2″,3″:5,6]benzo[1,2‐d]imidazole‐containing conjugated polymers

Novel conjugated polymers composed of benzo[1,2‐b:4,5‐b′]dithiophene and thieno[3,4‐b]pyrazine or dithieno[3′,2′:3,4;2″,3″:5,6]benzo[1,2‐d]imidazole units are synthesized by Stille polycondensation. The resulting polymers display a longer wavelength absorption and well‐defined redox activities. The effective intramolecular charge‐transfer and energy levels of all polymers are elucidated by computational calculations. Bulk‐heterojunction solar cells based on these polymers as p‐type semiconductors and [6,6]‐phenyl‐C₆₁‐butyric acid methyl ester (PC₆₁BM) as an n‐type semiconductor are fabricated, and their photovoltaic performances are for the first time evaluated. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1067–1075     

Synthesis,Configuration, and Antimicrobial Properties of Novel Substituted and Cyclized ‘2′,3″‐Thiazachalcones’

Nine new thiazachalcone‐based drugs, compounds 1 – 9 , were prepared and fully characterized. The configurations of the photochemical‐dimerization products 7 – 9 were rationalized by semi‐empirical calculations. Both the experimental data and the theoretical calculations showed that the δ‐truxinic acid type dimer is the most stable isomer of all. All compounds were tested for their antibacterial and antifungal activities. The N‐alkylated congeners 4 – 6 showed strong antimicrobial activities against various bacteria and a yeast‐like fungus. The MIC and MBC values were as low as 0.1 μg/ml. All the compounds were active against the Gram‐positive bacterium Staphylococcus aureus.     

Dispiro[adamantane‐2,2′‐1′,3′,6′,9′,11′,14′‐hexathiacyclohexadecane‐10′,2′′‐adamantane]

The conformational features of the title compound, C₂₈H₄₄S₆, are compared with previously reported analogous macrocycles. The type of substituent affects considerably the conformation of the macrocycle. A ¹H NMR titration of the title compound with AgBF₄ indicated the formation of the 1:1 complex, which was not crystallized.     

Synthesis of nitrogen‐containing heterocycles 9. Preparation and carbon‐carbon bond cleavage of spiro[cycloalkane[1′,2′,4′]‐triazolo[1′,5′‐a][1′,3′,5′]triazine] derivatives and related compounds

Diaminomethylenehydrazones of cyclic ketones 1–5 reacted with ethyl N‐cyanoimidate (I) at room temperature or with bis(methylthio)methylenecyanamide (II) under brief heating to give directly the corresponding spiro[cycloalkane[1′,2′,4′]triazolo[1′,5′,‐a][1′,3′‐5′]triazine] derivatives 7–12 in moderate to high yields. Ring‐opening reaction of the spiro[cycloalkanetriazolotriazine] derivatives occurred at the cycloalkane moiety upon heating in solution to give 2‐alkyl‐5‐amino[1,2,4]triazolotriazines 13–16. Diaminomethylenehydrazones 17–19, of hindered acyclic ketones, gave 2‐methyl‐7‐methylthio[1,2,4]‐triazolo[1,5‐a][1,3,5]triazines 21–23 by the reaction with II as the main products with apparent loss of 2‐methylpropane from the potential precursor, 2‐tert‐butyl‐2‐methyl‐7‐methylthio[1,2,4]triazolo[1,5‐a]‐[1,3,5]triazines 20, in good yields. In general, bis(methylthio)methylenecyanamide II was found to be a favorable reagent to the one‐step synthesis of the spiro[cycloalkanetriazolotriazine] derivatives from the diaminomethylenehydrazones. The spectral data and structural assignments of the fused triazine products are discussed.     

Synthesis and Tautomeric Structure of Tris(arylazo) Derivatives of Novel 1H‐Bis‐imidazo[1,2‐b:2′,1′‐e]pyrazole Ring System

An efficient and convenient synthesis of tris(arylazo) derivatives of novel heterocyclic ring system, namely, 1H‐bis‐imidazo[1,2‐b:2′,1′‐e]pyrazole, is described. The structures of the compounds prepared and their tautomeric structure were elucidated on the basis of their elemental analyses and spectral data in addition to correlation of their acidity constants by Hammett equation. The mechanism of the studied reactions and their site selectivity are discussed.     

Complexation Properties of N,N′,N″,N′′′‐[1,4,7,10‐Tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H4dotagl). Equilibrium,Kinetic, and Relaxation Behavior of the Lanthanide(III) Complexes

Eu³⁺, Dy³⁺, and Yb³⁺ complexes of the dota‐derived tetramide N,N′,N″,N′′′‐[1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetrayltetrakis(1‐oxoethane‐2,1‐diyl)]tetrakis[glycine] (H₄dotagl) are potential CEST contrast agents in MRI. In the [Ln(dotagl)] complexes, the Ln³⁺ ion is in the cage formed by the four ring N‐atoms and the amide O‐atom donor atoms, and a H₂O molecule occupies the ninth coordination site. The stability constants of the [Ln(dotagl)] complexes are ca. 10 orders of magnitude lower than those of the [Ln(dota)] analogues (H₄dota=1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid). The free carboxylate groups in [Ln(dotagl)] are protonated in the pH range 1–5, resulting in mono‐, di‐, tri‐, and tetraprotonated species. Complexes with divalent metals (Mg²⁺, Ca²⁺, and Cu²⁺) are also of relatively low stability. At pH>8, Cu²⁺ forms a hydroxo complex; however, the amide H‐atom(s) does not dissociate due to the absence of anchor N‐atom(s), which is the result of the rigid structure of the ring. The relaxivities of [Gd(dotagl)] decrease from 10 to 25°, then increase between 30–50°. This unusual trend is interpreted with the low H₂O‐exchange rate. The [Ln(dotagl)] complexes form slowly, via the equilibrium formation of a monoprotonated intermediate, which deprotonates and rearranges to the product in a slow, OH^?‐catalyzed reaction. The formation rates are lower than those for the corresponding Ln(dota) complexes. The dissociation rate of [Eu(dotagl)] is directly proportional to [H⁺] (0.1–1.0M HClO₄); the proton‐assisted dissociation rate is lower for [Eu(H₄dotagl)] (k₁=8.1?10^?6 M ^?1 s^?1) than for [Eu(dota)] (k₁=1.4?10^?5 M ^?1 s^?1).     

Synthesis,Characterization, and Antimicrobial Screening of 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole Derivatives

A series of novel 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole ( 8a‐p ) derivatives has been synthesized and screened for antibacterial activity against four pathogenic bacteria, Escherichia coli, Pseudomonas flurescence, Staphylococcus aureus, and Bacillus subtilis. Among them, compounds 8a and 8j exhibited excellent antibacterial activity with minimum inhibitory concentration range of 1.0 to 5.3 μg/mL and compounds 8m and 8p exhibited moderate to good antibacterial activity with minimum inhibitory concentration range of 16.9 to 29.7 μg/mL against all tested strains. All the synthesized compounds were screened for their in vitro antifungal activity against Cocinida candida. Most of the compounds reported moderate antifungal activity. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimicrobial agent.