Synthesis, properties, and redox behavior of di(1-azulenyl)(2- and 3-thienyl)methyl cations and dications composed of two di(1-azulenyl)methylium units connected with 2,5-thiophenediyl and 2,5-thienothiophenediyl spacers

The titled stable monocations, di(1-azulenyl)(2- and 3-thienyl)methyl cations 7a,b and 8a,b and dications composed of two di(1-azulenyl)methylium units connected with 2,5-thiophenediyl and 2,5-thieno[3,2-b]thiophenediyl spacers 9a,b and 10a,b were prepared by hydride abstraction of the corresponding methane derivatives. These mono- and dications 7a,b, 8a,b, 9a,b, and 10a,b showed high stability with large pK(R)+ values. The values of monocations 7a,b and 8a,b were 11.2-11.8 +/- 0.1 and 11.4-12.4 +/- 0.1, respectively. Two cation units in dications 9a,b and 10a,b were neutralized via one step at the pH of 11.1-11.7 +/- 0.1, which corresponds to the average of the pK(R)+ values of the dications and half-neutralized monocations. Electrochemical behavior of 7a,b, 8a,b, 9a,b, and 10a,b was examined by cyclic voltammetry (CV). Formation of the thienoquinoid products 18a,b and 19a,b from 9a,b and 10a,b was characterized by UV-vis spectroscopy under electrochemical reduction conditions. Chemical reduction of 9a,b and 10a,b with Zn powder in acetonitrile afforded 18a,b and 19a,b as deep-colored crystals, which exhibited rather high electron-donating ability.     

四氟乙烯齐聚体的反应 四氟乙烯四、五聚体和芳香胺的反应

前已报道四氟乙烯四聚体(全氟-3,4-甲基己烯-3)(1)、五聚体(全氟-3,4-二甲基-4-乙基己烯-2)(2)和脂肪烷氧以及脂肪胺的亲核反应.本文报道化合物1,2和芳香胺如苯胺、β-萘胺的反应.由于烯烃1、2双键处于分子中间,因而当亲核试剂进攻时,双键容易发生重排,生成的末端基烯烃更具反应性,故导致一取代、二取代、三取代以及环化降解等复杂产物.     

The Utility of Carbon Disulphide and Lawesson's Reagent for Synthesis of Different Fused Heterocycles for Antimicrobial Evaluation

Hexahydroquinolines 1a , 1b reacted with carbon disulphide in different conditions to yield the corresponding adducts 2a , 2b and 3a , 3b . Carrying out the same reactions in acetone as solvent produced the modified new products 4a , 4b . The interaction of pyrazolopyridine derivatives 5a , 5b , 5c , 5d with carbon disulphide under the same previous conditions furnished the isolated products 6a , 6b , 6c , 6d , 7a , 7b , 7c , 7d , and 8a , 8b , 8c , 8d . Studying the behavior of 1a , 1b or 5a , 5b , 5c , 5d toward Lawesson's reagent (LR) formed the final adducts 11a , 11b or 12a , 12b , 12c , 12d . The structure of synthesized compounds was confirmed with the spectroscopic and microanalytical data. The biological activities of 2a , 4a , 4b , 7a , 7c , 8d , 11a , 11b , 12b , and 12c were tested for antimicrobial evaluation.     

Highly Stereoselective Cationic Cyclization Assisted by a Sulfenyl Group. Scope, Limitation, and Mechanism

When 8-acetoxy-2-methyl-9-(phenylthio)-2-nonene (1a) was treated with an acid, followed by a base, alkylative cyclization proceeded to give a mixture of 1,2-disubstituted cyclohexanes: 2a, 3a, and 4a. The stereochemistry of the reaction was only slightly affected by the leaving group and the reaction conditions, such as the temperature, solvent, and acid. However, the bulkiness of the sulfenyl group had a great effect on the stereochemical course of the reaction. High trans selectivity was attained when 1c (a derivative of 1a with a bulkier sulfenyl group) was used as a substrate. On the other hand, the length and rigidity of the carbon chain of the substrate also had a major effect on the stereochemistry of the reaction; a high cis selectivity was observed when 10a (a one-carbon-fewer analog of 1a) or 15a (a derivative with one more double bond in the carbon chain than in 1a) was used as the substrate. The reaction proceeded via a 6,5- or 5,5-fused-ring intermediate. The sulfenyl-group-assisted reaction could be a useful method for the stereoselective cyclization of acetates of alpha-sulfenylated secondary alcohols.     

Refolding foldamers: triazene-arylene oligomers that change shape with chemical stimuli

We describe the preparation of five triazene-arylene oligomers (3, 4, 7, 8, and 11) and investigations of their folding properties in aqueous solution. These oligomers contain four 2-fold rotors and populate a conformational ensemble comprising at least 10 states. Extensive 1D and 2D NMR studies as well as X-ray crystallography establish that the presence of three members of the cucurbit[n]uril family (CB[n]), CB[10], CB[7], and CB[8], results in the selective population of the (a,a,a,a)-, (a,s,s,a)-, and (a,a,a,s)-conformers. As a result of the high affinity and highly selective binding properties of the CB[n] family, it is possible to fold a single foldamer strand (3) into the CB[8].(a,a,a,s)-3 conformer by the addition of CB[8], then unfold and refold it into the CB[7].(a,s,s,a)-3.CB[7] conformer by addition of CB[7] and 3,5-dimethylaminoadamantane (17), then unfold and refold it again into the CB[10].(a,a,a,a)-3 conformer by addition of CB[10].CB[5] and aminoadamantane (18). The transformation of CB[8].(a,a,a,s)-3 into CB[7].(a,s,s,a)-3.CB[7] proceeds through the intermediacy of CB [8].(a,a,s,a)-3.CB[7], which enhances the rate of dissociation of strand 3 from CB[8].     

Total synthesis of iejimalide B. An application of the Shiina macrolactonization

The potent anticancer compound iejimalide B (1) was prepared by a total synthesis through a strategy that features Julia olefinations, Wittig olefinations, a Carreira enantioselective alkynylation, a Heck reaction, a Marshall propargylation reaction, a Stille coupling, and a Shiina macrolactonization.     

Photochromism of mixed crystals containing bisthienyl-, bisthiazolyl-, and bisoxazolylethene derivatives

Single crystals composed of two or three different kinds of diarylethenes, having similar geometrical structures but different colors in the closed-ring isomers, 1,2-bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene (1a), 1,2-bis(5-methyl-2-phenyl- 4-thiazolyl)perfluorocyclopentene (2a), and 1,2-bis(5-methyl-2-phenyl-4-oxazolyl)perfluorocyclopentene (3a) have been prepared in an attempt to form single crystals which exhibit different colors, depending on illumination wavelengths. When 1a and 2a are mixed in ethanol and the content of 2a in the feed is higher than that of 1a, only a needle-shaped crystal is obtained. The crystal shape is similar to that of 2a. On the other hand, high content of 1a in the feed leads to formation of a block-shaped crystal, of which the shape is similar to that of 1a. At a feed ratio of 1:1 for 1a and 2a, two types of crystals such as needle- and block-shapes are obtained from the same batch. Mixed crystals composed of three kinds of derivatives 1a/2a/3a have also been prepared. A crystal composed of the three derivatives in the molar ratio of 32 (1a):53 (2a):15 (3a) was obtained. X-ray analysis proved that 1a and 3a are packed in the crystal lattice of 2a. The mixed crystal 1a/2a/3a changed color from colorless to yellow, red, and blue upon irradiation with light of appropriate wavelengths.     

Surface integration approach: a new technique for evaluating geometry dependent forces between objects of various geometry and a plate

We present a new approach, which can be considered as a generalization of the Derjaguin approximation, that provides exact means to determine the force acting between a three-dimensional body of any shape and a half-space mutually interacting via pairwise potentials. Using it, in the cases of the Lennard-Jones, standard and the retarded (Casimir) van der Waals interactions we derive exact expressions for the forces between a half-space or a slab of finite thickness and an ellipsoid in a general orientation, which in the simplest case reduces to a sphere, a tilted fully elliptic torus, and a body obtained via rotation of a single loop generalized Cassini oval, a particular example of which mimics the shape of a red blood cell. The results are obtained for the case when the object is separated from the plane via a non-polar continuous medium that can be gas, liquid or vacuum. Specific examples of biological objects of various shapes interacting with a plate like substrates are also considered.     

Synthesis of Some Novel Heterocyclic Xylidinyl Amines and Carboxamides

The xylidines 1a , 1b undergo condensation with ethyl cyanoacetate 2 and ethyl benzoyl acetate 15 to afford the cyano acetanilides 3a , 3b and the β‐diketones 16a , 16b , respectively. Compounds 3a , 3b react with hydrazine and phenyl hydrazine to afford the azine‐bis derivatives 5a , 5b and 7a , 7b , whereas 16a , 16b react with the same reagents to afford the pyrazolyl amine derivatives 17a , 17b and 18a , 18b , respectively. Compounds 3a , 3b react also with dimethylformamide dimethylacetal to afford the enaminonitriles 8a , 8b , whereas 16a , 16b react with the same reagent to afford only the enaminone 19b . The enaminonitriles 8a , 8b react with hydrazine and phenyl hydrazine to afford also the azine‐bis derivatives 11a , 11b and 14a , 14b , respectively.     

The Synthesis of New Spiro β-Lactam and Thiazolidinone Compounds Incorporating Quinones and Their Biological Activity

A series of some fused and spiro heterocyclic compounds such as pyrazolines, isoxazolines, pyrimidines, β-lactams, and thiazolidinone derivatives incorporating compounds 3, 6a–d, 7a–d, 9a–c, 10a–c, 11a–c, 12a–c, and 13a–c have been synthesized by a cycloaddition and cyclocondensation reaction of monochloroacetyl chloride, mercaptoacetic acid, hydrazines, hydroxylamine, urea, and thiourea with the prepared 5a–d and 8a–c.     

Photochromic reactions of diarylethenes in single crystals with intermolecular O--H...N hydrogen-bonding networks

The crystal structures and photochromic performance of a single crystal of a diarylethene derivative possessing carboxyl groups, 1,2-bis(5-carboxyl-2-methyl-3-thienyl)perfluorocyclopentene (1 a), and cocrystals of 1 a with 4,4'-, 2,4'-, and 2,2'-bipyridines were examined. In crystal 1 a, a discrete cyclic structure was observed, in which four 1 a molecules are linked through hydrogen bonds between the carboxyl groups. In the homocrystal, photoreactive and photoinactive conformers of 1 a exist in the ratio of 1:1. In the cocrystals of 1 a with bipyridines, O--HN-type hydrogen bonds between 1 a and pyridyl groups were formed, and all 1 a molecules are fixed in a photoreactive conformation. Both the homocrystal 1 a and the cocrystals showed photochromic performances, and color variation from bluish-violet to cyan was observed, depending on the conformation of the packed diarylethene molecules.     

When,in the context of drug design,can a fluorine atom successfully substitute a hydroxyl group?

In this article, we deal with the question of whether a fluorine atom can substitute a hydroxyl group in such a way that will lead to a compound showing a desired biologic activity, that is, a potential new drug. It is obvious that a fluorine atom differs from a hydroxyl group, as it cannot donate hydrogen bonds. However, it can accept them. Moreover, both fluorine and oxygen are of similar size and are the most electronegative elements. Therefore, a fluorine atom is thought to be a good substitute for a hydroxyl group. However, it was shown that for conformationally labile aliphatic compounds a replacement of a hydroxyl by a fluorine increases conformational diversity, so the fluorine‐containing aliphatic molecules are present in equilibrium at room temperature as a mixture of several different conformers. In contrast, for cyclic compounds the substitution of an OH group by an F atom does not much change shape and electrostatic potential around corresponding conformers. Moreover, these compounds are present in equilibrium at room temperature in aqueous solution as a mixture of the same most favored structures. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002     

One-pot synthesis of metalated pyridines from two acetylenes, a nitrile, and a titanium(II) alkoxide

Four-component coupling process involving two acetylenes, a nitrile, and a divalent titanium alkoxide reagent, Ti(O-i-Pr)(4)/2i-PrMgCl, directly yielded titanated pyridines in a highly selective manner. The reaction can be classified into four categories: (i) a combination of an internal acetylene, a terminal acetylene, sulfonylnitrile, and the titanium reagent to yield alpha-titanated pyridines, (ii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield alternative alpha-titanated pyridines, (iii) a combination of an internal acetylene, a (sulfonylamino)acetylene, a nitrile, and the titanium reagent to yield titanated aminopyridines, and (iv) a combination of an acetylenic amide, a terminal acetylene, a nitrile, and the titanium reagent to yield pyridineamides with their side chain titanated. Some of these reactions enabled virtually completely regioselective coupling of two different, unsymmetrical acetylenes and a nitrile to form a single pyridine. Synthetic applications of these reactions have been illustrated in the preparation of optically active pyridines and medicinally useful compounds.     

Synthesis of dihydrofuro[2,3‐b]pyridines by the reaction of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles with α,β‐unsaturated carbonyl compounds

The reactions of 2‐amino‐4,5‐dihydro‐3‐furancarbonitriles 1a‐d with α,β‐unsaturated carbonyl compounds in the presence of sodium ethoxide (0.1 equivalent) gave the corresponding Michael adducts 2a‐d , 3a‐d and 4a‐d. Compounds 2a‐d and 3a‐c reacted with sodium alkoxide (1 equivalent) to yield the corresponding 7a‐alkoxyhexahydrofuro[2,3‐b]pyridines 5a‐d, 6a‐d, 7a‐c and 8a‐c . Treatment of 5a‐d, 6a‐d, 7a‐c and 8a‐c with potassium tert‐butoxide produced the corresponding dihydrofuro[2,3‐b]pyridines 9a‐d and 10a‐c . The reaction of 4a‐c with sodium ethoxide (1 equivalent) afforded the corresponding dihydro‐furo[2,3‐b]pyridines 11a‐c .     

Tautomeric equilibrium between penta- and hexacoordinate silicon chelates. A chloride bridge between two pentacoordinate silicons.

The reaction of O-trimethylsilyl-1,1-dimethyl-2-trifluoroacetylhydrazine (1a) with chloromethyl(methyl)dichlorosilane affords an unexpected equilibrium mixture, 10a right arrow over left arrow 11a, between a neutral hexacoordinate silicon chelate with a covalent chloro ligand (10a) and an ionic pentacoordinate silicon complex (11a). The equilibrium reaction consists formally of a migration of the covalent chloro ligand from silicon to an adjacent ammonium nitrogen, as a chloride anion, and thus constitutes a novel type of tautomeric reaction. Crystallographic and NMR data provide evidence for the reaction. Temperature, solvent, substituent, and counterion effects on the tautomeric equilibrium are discussed: when the temperature of the mixture is raised, the equilibrium ratio 10a/11a increases. Formation of the mixture in toluene, a nonionizing solvent, shifts the equilibrium completely toward the neutral 10a. When the initial hydrazide has a phenyl (11c) or a hydrogen (11b) group as substituent, rather than CF3, the equilibrium is shifted to the ionic side. Replacement of the chloride counterion by triflate, using trimethylsilyl triflate, shifts the 10a/11a mixture to the ionic side. Low-temperature NMR monitoring of the stepwise formation of 10/11 was carried out and provided insight into the reaction mechanism. In an attempt to grow crystals of 11c, the pentacoordinate tautomer analogue, an unprecedented chloride-bridged disiloxane complex, with two pentacoordinate silicons sharing a common axial chloro ligand, crystallized and was characterized and described.     

Pyridoxylated Polymerized Hemoglobin Solution Processing

Glutaraldehyde hemoglobin polymerization gives too many high polymers, resulting in a too viscous solution. We describe here an alternate method leading to superior results, as compared to the classical one. This method includes a molecular fractionation step using a tangential flow ultrafiltration that secondarily lowers the unpolymerized tetramer’s content of a mildly polymerized, pyridoxylated hemoglobin solution (Pyr-Poly Hb). This leads to an adequately polymerized product with a lesser high polymer content, implying a lower viscosity. We thus obtain a pyridoxylated, polymerized molecular fractionated solution presenting suitable features as a blood substitute: A 7.5 g% hemoglobin 2 g% albumin solution had a 16% unpolymerized tetramer’s ratio, a 1.8 mPas viscosity, a P₅₀ of 2.8 kPa, a Hill coefficient of 2.1, a binding coefficient of 1.3 mL/g, a colloid osmotic pressure of 2.4 kPa, and a methemoglobin concentration of 3% Male Sprague-Dawley rats undergoing an isovolumic blood exchange with this Pyr-Poly Hb solution, down to a 2% hematocrit, present a mean survival time of 20 h.     

Gibbs free energy of liquid drops on conical fibers

Small drops can move spontaneously on conical fibers. As a drop moves along the cone, it must change shape to maintain a constant volume, and thus, it must change its surface energy. Simultaneously, the exposed surface area of the underlying cone must also change. The associated surface energies should balance each other, and the drop should stop moving when it reaches a location where the free energy is a minimum. In this paper, a minimum Gibbs free energy analysis has been performed to predict where a drop will stop on a conical fiber. To obtain the Gibbs free energies of a drop at different locations of a conical fiber, the theoretical expressions for the shape of a droplet on a conical fiber are derived by extending Carroll's equations for a drop on a cylindrical fiber. The predicted Gibbs free energy exhibits a minimum along the length of the cone. For a constant cone angle, as the contact angle between the liquid and the cone increases, the drop will move toward the apex of the cone. Likewise, for a constant contact angle, as the cone angle increases, the drop moves toward the apex. Experiments in which water and dodecane were placed on glass cones verify these dependencies. Thus, the final location of a drop on a conical fiber can be predicted on the basis of the geometry and surface energy of the cone, the surface tension and volume of the liquid, and the original location where the drop was deposited.     

Domino 6pi-electrocyclization/Diels-Alder reactions on 1,6-disubstituted (E,Z,E)-1,3,5-hexatrienes: versatile access to highly substituted tri- and tetracyclic systems

The (E,Z,E)-1,3,5-hexatrienes 1a, 2a,b and 3b undergo 6pi-electrocyclization within 15-30 min upon heating to 200-215 degrees C. While the cyclohexene-annelated products 8a,b were stable, the analogous cyclopentene- and cycloheptene-annelated derivatives 7a and 9b easily underwent dehydrogenation to the corresponding aromatic compounds 10a and 12b during the work-up. The cyclohexadiene derivatives 8a,b were employed in thermal Diels-Alder reactions with 4-phenyl-3H-1,2,4-triazoline-3,5-dione (PTAD) and tetracyanoethylene (TCNE) to give the expected [4+2] cycloadducts 13a and 14a in good yields (60 and 78%). The initially formed cycloadduct of 8a and dimethyl acetylenedicarboxylate (DMAD) underwent a subsequent retro-Diels-Alder reaction to give the tetrahydronaphthalene 11b (47%). Under high pressure (10 kbar), the cycloadduct 15a was formed at room temperature and could be isolated in 44% yield. TCNE and N-phenylmaleimide with 8a under high pressure also led to the [4+2] cycloadducts 14a and 16a in good yields (60 and 77%). The 6pi-electrocyclization and subsequent Diels-Alder reaction, when performed as a one-pot domino process, provided direct access to Diels-Alder products of intermediately formed 6pi-electrocyclization products, for example from the 1,3,5-hexatrienes 1a,b, 2a,b, 3b and TCNE to the corresponding tricyclic products 17a,b, 14a,b, 18b in moderate to good yields (27-80%) depending on the nature of the alkoxycarbonyl group. Such sequential reactions with N-phenylmaleimide, maleic anhydride, dimethyl maleate and fumarodinitrile, the latter two under high pressure (10 kbar), worked as well to yield 16b (70%), 19a,b (19, 32%) and 20b (39%) and 21b (76%), respectively. With PTAD, however, the hexatrienes 2a,b reacted at ambient temperature without 6pi-electrocyclization to give the formal [4+2] cycloadducts 27a,b (48 and 46%), most probably via zwitterionic intermediates 23a,b and 25a,b.     

Double-emulsion drops with ultra-thin shells for capsule templates

We introduce an emulsification technique that creates monodisperse double-emulsion drops with a core-shell geometry having an ultra-thin wall as a middle layer. We create a biphasic flow in a microfluidic capillary device by forming a sheath flow consisting of a thin layer of a fluid with high affinity to the capillary wall flowing along the inner wall of the capillary, surrounding the innermost fluid. This creates double-emulsion drops, using a single-step emulsification, having a very thin fluid shell. If the shell is solidified, its thickness can be small as a hundred nanometres or even less. Despite the small thickness of this shell, these structures are nevertheless very stable, giving them great potential for encapsulation. We demonstrate this by creating biodegradable microcapsules of poly(lactic acid) with a shell thickness of a few tens of nanometres, which are potentially useful for encapsulation and delivery of drugs, cosmetics, and nutrients.