Synthesis and characterisation of main‐chain hydrogen‐bonded supramolecular liquid crystalline complexes formed by azo‐containing compounds

A series of azopyridine‐containing hydrogen bonding acceptors (4a–c) with flexible spacers of oligo(methylene) were synthesised. Hydrogen‐bonded polymeric complexes 4/5 and trimeric complexes 4/6₂ , where 5 and 6 are aromatic dicarboxylic acids and monocarboxylic acids, respectively, were prepared and their liquid crystallinity was examined using differential scanning calorimetry and polarising optical microscopy. The study showed that most of the complexes displayed reversible thermotropic nematic phase. The isotropic to nematic phase transition temperatures of polymeric complexes 4/5 and trimeric complexes 4/6₂ in general decreased with the increase in length of spacers and terminal groups in the corresponding proton acceptors 4 and the proton donors 5 and 6, respectively. Hydrogen bonding interactions in complexes 4/5 and 4/6₂ were studied by X‐ray photoelectron spectroscopy and Fourier transform infrared spectroscopy.     

In quest of reversibility of Friedel-Crafts acyl rearrangements in the pyrene series

Friedel-Crafts acyl rearrangements in PPA of diacetylpyrenes (80–120 °C), dibenzoylpyrenes (80–200 °C), and bis(4-flurobenzoyl)pyrenes (80–120 °C) and Scholl reactions in AlCl₃/NaCl of dibenzoylpyrenes (140–200 °C) have been studied. The substrates were 1-AcPY, 2-AcPY, 1,3-Ac₂PY, 1,6-Ac₂PY, 1,8-Ac₂PY, 2,7-Ac₂PY, 1-BzPY, 1,6-Bz₂PY, 1,8-Bz₂PY, 1-4FBzPY, 1,6-4FBz₂PY, 1,8-4FBz₂PY. The mixtures of pyrene, 1-AcPY, 2-AcPY, 1,3-Ac₂PY, 1,6-Ac₂PY, 1,8-Ac₂PY, and 2,7-Ac₂PY were separated by HPLC. The following reversible intermolecular isomerizations were established: 1,6-Ac₂PY ? 1,8-Ac₂PY, 1,6-Bz₂PY ? 1,8-Bz₂PY, and 1,6-4'FBz₂PY ? 1,8-4'FBz₂PY, albeit not in high yields. The results substantiate Gore’s 1955 proposition that “The Friedel–Crafts acylation reaction of reactive aromatic hydrocarbons is a reversible process.” The isomerizations reported here differ from the few previously reported completely reversible intramolecular Friedel-Crafts acyl rearrangements. At ≥ 140 °C, in PPA and in AlCl₃/NaCl, 1,6-Bz₂PY and 1,8-Bz₂PY underwent a highly regioselective double Scholl reaction to give pyranthrone (3) and deacylations to 1-BzPy (and pyrene), followed by mono-Scholl reactions to give 8H-dibenzo[def,qr]chrysen-8-one (1), and 11H-indeno[2,1-a]pyren-11-one (2). The formation of 3 and not the expected tribenzo[a,ghi,o]perylene-7,16-dione (4) from 1,8-Bz₂PY indicates that 1,8-Bz₂PY has first undergone isomerization to 1,6-Bz₂PY. The present study confirms the linkage between Friedel-Crafts acyl rearrangements and the Scholl reaction.

     

Secoiridoids and other chemotaxonomically relevant compounds in Pedicularis: phytochemical analysis and comparison of Pedicularis rostratocapitata Crantz and Pedicularis verticillata L. from Dolomites

We compared the respective metabolite patterns of two Pedicularis species from Dolomites. Seven phenylethanoid glycosides, i.e., verbascoside (1), echinacoside (2), angoroside A (3), cistantubuloside B1 (4), wiedemannioside C (5), campneoside II (11) and cistantubuloside C1 (12), together with several iridoid glucosides as aucubin (6), euphroside (7), monomelittoside (8), mussaenosidic acid (9) and 8-epiloganic acid (13) were identified. Pedicularis verticillata showed also the presence of greatly unexpected secoiridoids, ligustroside (14) and excelside B (15), very rare compounds in Lamiales. Both PhGs and iridoids are considered of taxonomical relevance in the Asteridae and their occurrence in Pedicularis was discussed. In particular, the exclusive presence of several compounds such as 8-epiloganic acid (13), campneoside II (11), cistantubuloside C1 (12), ligustroside (14) and excelside B (15) in Pedicularis rostratocapitata, and angoroside A (3), cistantubuloside B1 (4) and wiedemannioside C (5) in P. verticillata could be considered specific markers for the two botanical entities.     

Electronic states of XC<Subscript>3</Subscript>H<Subscript>3</Subscript>Si five-membered rings (X = CH,N, P,and As)

Stable configurations of XC₃H₃Si five-membered rings, 1 _X and 2 _X (X = CH, N, P, and As) in the singlet and triplet states are found at B3LYP/6-311++G** level of theory. All the singlet states of 1 _X and 2 _X have lower potential energy than the triplet state. The ΔG _s−t differences between the singlet and triplet states of 1 _X and 2 _X changes at the B3LYP/6-311++G** level in the order (in kcal/mol): 1 _N (−17.56) > 1 _CH (−15.26) > 1 _P (−4.96) > 1 _As (−3.45) and 2 _CH (−15.26) > 2 _N (−9.21) > 2 _P (−7.39) > 2 _As (−6.15), respectively.     

Solution structure and equilibrium of new calix[4]resorcinarene complexes—prototype of molecular machines. NMR data

Association properties and molecular machine application of water soluble calix[4]resorcinarene (1) with two aromatic guests (2-naphthol (2) and 1,5-naphthalenediamine (3)) have been investigated by various NMR methods (chemical shift, nOe and diffusion measurements) in aqueous solution at different concentrations and pH range. In neutral solution 1 strongly associates with 2, while only moderately associating with 3. Increase in concentration causes an increase in the stability of 1 + 3 and 1 + 2 + 3 complexes and produces high order complexes. The decrease of pH does not have an influence on 1 + 2 association, but disrupts 1 + 3 assembly. 1 can be used for the separation of 2 + 3 mixture in aqueous solution at moderate concentrations. The pH dependency of the association properties of the 1 + 3 system makes these compounds prime candidates for pH-responsive molecular machines applications.     

Cyanothioacetanilide Intermediates in Heterocyclic Synthesis,Part 1: Synthesis and Biological Evaluation of Some Novel Thiazole,Thiophene, Pyrazole,and Pyrazolo[1,5-a]Pyrimidine Derivatives

Some novel thiophenes (4a,b, 5, and 9a,b) were obtained from the cycloalkylation of the thiocarbamoyl group in the cyanothioacetanilide derivative (1) with α-halocarbonyl compounds. Also, the reaction of cyanothioacetanilide derivative with phenyl isothiocyanate in the presence of potassium hydroxide followed by in situ heterocyclization of the resulting adduct with α-halocarbonyl compounds furnished the corresponding thiazole (12, 14, and 15), pyrazole (19), and pyraozlo[1,5-a]pyrimidine (22, 25, and 26) derivatives. Compounds (4b, 5, 9a, 12, 13, 18, 22, 25, and 26) were tested to evaluate their antimicrobial activity.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

New N,S-Derivatives of Nitrodienes from Thioallyl-and Thiodibromopropyl Nitrodienes

Compound 3 and 5a, b were obtained from the reaction of 1,3,4,4-tetrachloro-1-thioallyl-2-nitro-1,3-butadiene (1) with thiomorpholine (2) and piperazine derivatives 4a, b in dichloromethane. The reaction of compound 1 and bromine gave compound 6. Compounds 8 and 10 were obtained from the reaction of 6 with 1-(diphenylmethyl)piperazine (7) and piperidine (9) in dichloromethane. The derivative 13 was synthesized from the reaction of 4-bromo-1,1,3,4-tetrachloro-2-nitro-1,3-butadiene (11) and allylmercaptane (12). Compounds 15 and 16a, b were obtained from the reaction of 1-allyl-4-bromo-1,3,4-trichloro-2-nitro-1,3-butadiene (13) with morpholine (14) and the piperazine derivatives 16a, b, in dichloromethane, respectively.     

Synthesis of Phosphonodithioate,Oxathiaphosphinin, Oxathiaphosphole,and Dithiaphosphole Derivatives from the Reaction of Lawesson's Reagent with Phenolic Mannich Bases and Oxime Derivatives

The reaction of Lawesson's reagent 1a, with niclosamide 2 proceeded by thionation and formation of carbothioamide 3 and the zwitterionic oxathiaphosphinin 4a. LR reacted with 8-hydroxyquinoline (5), 2-methylquinoline-4-ol (7), and β-naphthol (9) to give the phosphonodithioates 6, 8, or 10. The reaction of LR with the Mannich bases 11 and 14 afforded the oxathiaphosphinins 13 and 15, whereas the phosphonodithioates 17 and 19 were isolated in the case of Mannich bases 16 and 18. LR reacted with phthalimide Mannich base 20 to give the dithione 21 and N-methylphthalimide (22). Reaction of ketone monoxime 23 with LR resulted in the formation of the oxathiaphosphole 24 and the dithiaphosphole 25, whereas the monoxime 26 afforded the thioxoethanone thioxime 27. Ketone dioximes 28 and 34 afforded the phosphonodithioates 29 and 36, respectively, when they were allowed to react with LR, whereas the dioxime 30 gave compounds 32 and 33. Moreover, the molluscicidal potency of the newly synthesized compounds against Biomphalaria glabrata snails was studied, too.     

N,S-, S-, S,S-, <S═O-, and < SO2-Substituted Dienes from Halo-1,3-Butadienes

Mono(thio)substituted dienes 1 gave 3a–g , 5 , and 7 with piperazine derivatives in dichloromethane. Hexachlorobutadiene 14 in a water-ethanol mixture in the presence of sodium hydroxide reacted with thiol 15 to give the mono(thio)substituted thioether 16 and di(thio)substituted thioether 17 . 18 was obtained from the reaction of 16 with m-CPBA in chloroform. 9 was obtained from the reaction of l,2,3,4,4-pentachloro-(1-2-hydroxyethylthio)-1,3- butadiene 8 with 47% HI, and 11 was synthesized from the reaction of 8 with concentrated H₂SO₄ and KBr. Compounds 9 and 11 gave in the reaction with m-CPBA in chloroform 10 , 12 , and 13 , respectively.     

Synthesis,Characterization, and Thermal and Antibacterial Studies of Diorganotin(Iv) Derivatives of Amino Acids

Abstract

Six diorganotin(IV) derivatives of α-aminoacids with general formulae [(CH₃)₂ SnAACl]₂ and [(CH₃CH₂CH₂CH₂)₂SnAACl]₂, where AA = L-alaninate, L-phenylalaninate, and L-isoleucinate, have been synthesized by reacting dimethyltin(IV) dichloride (M) and dibutyltin(IV) dichloride (B) with L-alanine (A) or L-phenylalanine (PA) or L-isoleucine (I) using acetonitrile as the solvent and designated as MA, MPA, MI, BA, BPA, and BI. These complexes have been characterized by elemental analysis, infrared (IR), ¹H NMR, ¹³C NMR, and ¹¹⁹Sn NMR spectroscopy. Thermal studies of all of the synthesized complexes were also carried out using thermogravimetric (TG) and differential scanning calorimetry (DSC) techniques. The thermal decomposition mechanisms were similar for MA, BA, MI, and BI and occurred in one step, while in compounds MPA and BPA, it occurred in two consecutive steps. The TG curves of MPA and BPA suggest the loss of the ligand (AA) in the first step, with probable formation of a tin oxide R₂SnO as an intermediate, and in the second step, free tin is obtained, similar to MA, BA, MI, and BI, in accordance with the stoichiometry of the related derivatives. The diorganotin(IV) complexes have also been screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa. The minimum inhibitory concentration values of these complexes show enhanced activity.     

Synthesis and Biological Activities of Novel 1,4-Bridged Bis-1,2,4-Triazoles,Bis-1,3,4-Thiadiazoles and Bis-1,3,4-Oxadiazoles

Abstract

The terephthalic acid hydrazide(1) reacted with phenyl/benzyl isothiocyanate2a,bto yield the corresponding bis-thiosemicarbazides4a,b,viaacid hydrolysis of the intermediate 3whereas cyclization of4gave the bis-1,2,4-triazoles 5,6and bis-1,3,4-thiadiazoles7,8. Similarly, compound 1reacted with phenyl isocyanate9to give the bis-semicarbazide10, which was cyclized to the bis-oxadiazole 11and/or bis-1,2,4-triazole12in POCl_ti3and NaOH respectively.     

Polymerizations of methyl methacrylate and rac-lactide by zinc(II) precatalyst containing N-substituted 2-iminomethylpyridine and 2-iminomethylquinoline

The reaction of [ZnCl₂] with N-cyclopentyl-1-(quinolin-2-yl)methanimine (L_A), N-cyclohexyl-1-(quinolin-2-yl)methanimine (L_B), N-cyclohexyl-1-(pyridin-2-yl)methanimine (L_C), 2,6-diethyl-N-(pyridin-2-ylmethylene)aniline (L_D), N-cyclopentyl-1-(pyridin-2-yl)methanimine (L_E), and N-phenyl-(pyridin-2-yl)methanimine (L_F) in ethanol produced the bidentate [(NN′)ZnCl₂] complexes, [L_AZnCl₂], [L_BZnCl₂], [L_CZnCl₂], [L_DZnCl₂], [L_EZnCl₂] and [L_FZnCl₂], respectively. The molecular structures revealed that the zinc in [L_nZnCl₂] (L_n = L_A ? L_D) showed a distorted tetrahedral geometry involving two nitrogens of N,N’-bidentate ligands and two chloride ligands. Most of these initiators were effective for polymerization of methyl methacrylate (MMA) and polymerization of rac-lactide (rac-LA). [L_CZnCl₂] (with N-cyclohexyl substituted at imine-pyridine moiety) exhibited the highest catalytic activity for MMA polymerization in the presence of modified methylaluminoxane (MMAO) with an activity of 3.33 × 10⁴ g PMMA/mol·Zn·h at 60 °C, giving moderate syndiotactic poly methyl methacrylate (PMMA) with high molecular weight (9.62 × 10⁵ g/mol). The dimethyl derivatives [L_nZnMe₂] (L_n = L_A ? L_F), generated in situ, polymerized rac-LA with moderate activity and yielded a polylactide (PLA) with good number-average molecular weights and narrower polydispersity indices (PDIs). [L_AZnMe₂] effectively initiates the ring-opening polymerization (ROP) of rac-LA to attain heterotactic PLA (P_r = 0.91).     

X-ray structures of cobalt(III) complexes with bio-relevant pyrazolyl thiosemicarbazone: Indication of structural changes on the increasing bulkiness of the alkyl substituents on thiosemicarbazone moiety

X-ray crystallographic studies of cobalt(III) complexes of 5-methyl-3-formylpyrazole-N(4)-diethylthiosemicarbazone (HMP_zNEt₂), [Co(MP _z NEt ₂ ) ₂ ]Br·2H ₂ O, 5-methyl-3-formylpyrazole-N(4)-dipropylthiosemicarbazone (HMP_zNPr ₂ ), [Co(MP _z NPr ₂ ) ₂ ]Br·2H ₂ O and 5-methyl-3formylpyrazole-N(4)-dibutylthiosemicarbazone (HMP_zNBu ₂ ), [Co(MP _z NBu ₂ ) ₂ ]Br·H ₂ O, have been reported. In all the three complex species, X-ray crystallography has authenticated a CoN₄S₂ octahedral coordination with the pair of orthogonally coordinated NNS tridentate ligands in the monodeprotonated form of the ligand. The two azomethine nitrogen atoms are trans to each other, while the pyrazolyl ring nitrogens and the thiolato sulfurs are in cis positions. A gradual decrease in the dihedral angle between the coordinating ligands has been observed with increase in the bulkiness of the aliphatic side chains of the substituent on the thiosemicarbazone moieties. In all the three complexes, intraligand C–H···S contacts appear to arrest the free rotation of the side chains about the C(6)–N(5) single bond. ^†Deceased     

MECHANISM OF THE REACTION OF SOME STABLE HEMIMERCAPTALS WITH Secondary-AMINES: EVIDENCE AGAINST THE INTERMEDIACY OF A METHYLENESULFONIUM ION

Abstract

The reaction of the arenethiols 4a-b with formaldehyde and the sec-amines 5a-c gave the aminomethyl aryl sulfides 6a-d. The reaction of the hemimercaptals 3a-b with 5a in methanol gave 6a-b in high yield. In acetonitrile reaction media, 6b was obtained by the reaction of 3b with 5a which suggested that 7b was not an intermediate in the formation of 6b in methanolic media. The absence of 7b in methanolic media suggests that the methylenesulfonium ion 8b is not an reaction intermediate. The formation of 7b was observed in the reaction of 3b with methanol when catalyzed by the Lewis acid tetrafluoroboric acid diethyl ether complex. The experimental observations are best explained by a mechanism whereby 3a-b are in rapid equilibrium with 4a-b under the basic reaction conditions. Rapid reaction of the liberated formaldehyde with 5a leads to the normal Mannich reaction pathway. Consistent with this mechanism, the reaction of a mixture of 3a-b and 12 with 5a gave both 6a-b and 13.     

Supramolecular dyad derived from a buckybowl series of O2N2-donor naphthodiaza-crowns coordinated to C60: photophysical,NMR and theoretical studies

Supramolecular complexation of C₆₀ with L¹-L⁵ were studied in toluene, chloroform and 1,2-dichlorobenzene solvents using UV–vis, fluorescence, ¹H, ¹³C NMR spectroscopy as well as density functional theory (DFT) calculations. The Job’s plot of continuous variation method established 1:1 stoichiometry for L¹-L⁵/C₆₀. Binding constants (K) calculated for L¹-L⁵/C₆₀ were also determined employing UV–vis and fluorescence spectroscopy. Both steady-state and time-resolved fluorescence spectroscopic surveys showed remarkable fluorescence quenching phenomenon for L¹-L⁵ in the presence of C₆₀ which was primarily attributed to involvement of a static process. The observed fluorescence quenching in L¹–L⁵ was described in terms of both π–π and n–π interactions of the naphthalene moieties and the nitrogen donor groups on the aza-crown macrocyclic ligands with C₆₀, respectively. Moreover, DFT calculations using B₃LYP/6-31G* basis set confirmed on the aforesaid π–π interaction of naphthalene groups on the aza-crowns with C₆₀. The DFT calculations also established significant distributions of charge between C₆₀ and L¹-L⁵ in according to the electronic structure and geometry of L¹-L⁵/C₆₀, very similar to phthalocycnine/C₆₀ systems.     

Synthesis and Tuberculostatic Activity of Some 1,1-Bis-methylthio-2-nitro-ethene Derivatives

1,1-bis-methylthio-2-nitro-ethene was used as a substrate to the syntheses of new heterocyclic compounds. In the reactions, with 1-phenylpiperazine—the corresponding diaminonitroethane 1 , 1,3-diaminonitropropane, and 1,3-diaminonitropropanol—the nitromethylenotetrahydropyrimidine derivatives 2 and 3 were prepared, whereas, with o-phenylenediamine—2-nitromethyleno-benzimidazole 4 were obtained. In the condensation reactions of compounds 2 , 3 , and 4 with benzoyl isothiocyanate, the products 5 , 6 , and 7 were obtained, and afterwards two of them, 5 and 6 , were transformed into the isothiazolines 8 and 9 .

1,1-bis-(4-phenylpiperazino)-2-nitroethane ( 1 ) was exposed to the action of phenyl isothiocyanate and the derivative obtained ( 10 ) was transformed, in the reaction with phenacylbromide, in to benzoylonitrothiophene 11 . The diazo compounds 12 , 13 , and 14 were obtained in the reactions of nitromethylenotetrahydropyrimidines 2 and 3 and of 2-nitromethylenobenzimidazole 4 with benzenediazonium chloride. The derivatives obtained were tested in vitro for their tuberculostatic activity. The compounds 7 (MIC 8–32 μg/mL) and 14 (MIC 16–63 μg/mL) appeared to be the most active compounds.     

Anti-inflammatory activities of the chemical constituents isolated from Trametes versicolor

Twenty-seven compounds including nine triterpenoids (1–9), eight sterols (10–17), two ribonucleotides (18, 19), four phenols (20–23), three glycosides (24–26), and one furan (27) were isolated from the fruiting bodies of Trametes versicolor (L.) Lloyd. This study is the first confirmation of the presence of the 11 compounds (3, 5, 6, 8, 18, 20, 21, 23–25, and 27) isolated from the Polyporaceae family, with six of these (2 and 12–16) from the genus Trametes. Compounds 3, 4, 10, 11, 16 and 17 were found to significantly inhibit the production of NO, TNF-α and IL-6 in a dose-dependent manner.     

SYNTHESIS OF NEW ANTHRACYCLINE DERIVATIVES CONTAINING PYRUVIC,ASPARTIC, OR N-ACETYLASPARTIC ACID MOLECULE

ABSTRACT

The new anthracycline analogues (2–10) as potential anticancer agents were synthesized from daunomycin (1a) and doxorubicin (1b). Compounds 2, 6, and 7 were prepared by the nucleophilic displacement type esterification of a 14-bromodaunomycin (1c) with a sodium pyruvate, aspartate, and N-acetylaspartic acid, respectively. Whereas compounds (3, 8) and (4, 9) were prepared by the reaction of daunomycin (1a) or doxorubicin (1b) with one equivalent of the corresponding acids in the presence of EDCI/PP, compounds (5, 10) were obtained from 1b by reaction with two equivalents of the corresponding acids in the same manner.     

Synthesis and Reactions of Some New Heterocyclic Compounds Related to Pyrrolylthieno[2,3-d]pyrimidines and Thieno[2,3-d][4,5-d]dipyrimidines

Abstract

Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxylate (3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-pyrrolyl derivative4, which in turn could be easily reacted with hydrazine hydrate in ethanol yielding the carbohydrazide derivative5. Reaction of5 with aromatic aldehydes, acetylacetone, carbon disulfide or phenylisothiocyanate gave pyrrolyl derivatives6,7,8,9 respectively. On the other hand, condensation of 5-(1-pyrrolyl)-6-acetyl-2,4-diphenylthieno[2,3-d]pyrimidine11 with benzaldehyde afforded the corresponding chalcone12, which on treatment with hydrazine hydrate, phenyl hydrazine, or thiourea gave the pyrazolinyl derivatives13,14 and pyrimidinyl derivative15, respectively. Furthermore some new pyrimidothienopyrimidne16,17a–d,19,20a–c were obtained using 5-amino-carboxamide3c as starting material.     

A New Approach to the Synthesis of Etoposide (VP 16)

ABSTRACT

The synthesis of the glycosyl donors 2,3-di-O-acetyl- and 2,3-di-O-chloroacetyl- 4,6-O-ethylidene-ß-D-glucopyranose (10β) and (11β) and their use for the glycosidation of 4'-O-benzyloxycarbonyl- and 4'-O-chloroacetyl-4'-O-demethyl-4-epi-podophyllotoxins (12) and (13) is described. Starting from benzyl β-D-glucopyranoside (6), benzyl 2,3-di-O-acetyl- and 2,3-di-O-chloroacetyl-4,6-O-ethylidene-ß-D-glucopyranoside (8) and (9) were prepared. Hydrogenolysis of the benzyl group in 8 or 9 afforded the β-hydroxy glucopyranose donors 10β and 11β. Condensation of 10β or 11β with 4'-O-Z-epi-podophyllotoxin 12 in the presence of BF₃-etherate gave selectively the 4-O-(2,3-di-O-acetyl- or -2,3-di-O-chloroacetyl-4,6-O-ethylidene-β-D-glucopyranosyl)-epi-podophyllotoxins 14β and 15β, respectively. The β-glycoside 16 was prepared in the same manner starting from 11β and 4'-O-chloroacetyl-epi-podophyllotoxin 13. By deblocking (Dowex 1X8, 3:2 methanol-chloroform) of the chloroacetyl groups in 15β and the following hydrogenolysis of the benzyloxycarbonyl group in 17 etoposide 1 was obtained. The deacylation of 16 afforded 1 in a one step procedure.