Solubility of thiophene

A notable exploitation of this reaction has been used for the preparation of potential anticancer agents. In an attempt to control the water solubility of thiophene analogs, a series of sodium salts of 2,5-dicarboethoxy-3,4-dihydroxythiophene have been produced by condensation between thiodiglycolate esters and diethyloxalate. These condensation reactions consistently proceeded in good yield. 

In SDS micelles, we show, that (i) the solubility of thiophene derivatives in water increases, (ii) their oxidation potentials are lower than those found in organic media, (iii) the thienyl rascal-cations formed are stabilized by electrostatic interactions with the dodec l anions, (iv) the synthesis of thin, electroactive and conductive polymers films having well-defined structures (practically no defects) with a relatively hi conjugation chain length has been realized. In addition, the resulting PEDOT films have a "columnar" structure. 

Solubility of thiophene and various hydrocarbons in various ionic liquids (unpublished data obtained in our laboratory)... 

As with PPy, polythiophene can be produced using a chemical oxidant. However, due to the limited solubility of thiophene, this reaction must be carried out in nonaqueous media. Copper (II) perchlorate has been used as an oxidizing agent in acetonitrile to yield a simultaneous polymeriza-tion/doping process. This results in polymer materials with conductivities of approximately 8 S cm T Alternatively, a Grignard reaction can be used (Figure 6.3) to produce polythiophene which is the first time conventional synthesis techniques have been used. 

By treatment with anhydrous aluminium chloride (Holmes and Beeman, 1934). Ordinary commercial, water-white benzene contains about 0 05 per cent, of thiophene. It is first dried with anhydrous calcium chloride. One litre of the dry crude benzene is shaken vigorously (preferably in a mechanical shaking machine) with 12 g. of anhydrous aluminium chloride for half an hour the temperature should preferably be 25-35°. The benzene is then decanted from the red liquid formed, washed with 10 per cent, sodium hydroxide solution (to remove soluble sulphur compounds), then with water, and finally dried over anhydrous calcium chloride. It is then distilled and the fraction, b.p. 79-5-80-5°, is collected. The latter is again vigorously shaken with 24 g. of anhydrous aluminium chloride for 30 minutes, decanted from the red liquid, washed with 10 per cent, sodium hydroxide solution, water, dried, and distilled. The resulting benzene is free from thiophene. 

Progress and prospects in hydrogenation, hydrogenolysis, and desulfurization of thiophenes with soluble metal complexes 98ACR109. 

The first example of microwave-promoted solid-phase methodology in heterocyclic chemistry was the arylation of thiophene and indole via Suzuki couplings on TentaGel S RAM resin, as demonstrated by Hallberg and coworkers in 1996, before temperature- and pressure-controlled microwave instruments were even available [189]. Three years later Schotten and coworkers presented analogous but aqueous Suzuki couplings of 5-bromo-thiophene anchored to PEG soluble support via a carboxylic function at its C-2 position [116]. Unfortunately, this work was performed in a do-... 

IkB kinase-p is a key regulatory enzyme in the NF-kB pathway, and inhibition of this enzyme has the potential for yielding treatments for inflammatory and autoimmune diseases. Morwick et al. [53] report on the optimization of a pM IKKp inhibitor with low aqueous solubility, moderate human liver microsome stability, and inhibition of several CYPs (3A4, 2C9, 1A2) with pM potencies. Modulation of the thiophene core (other thiophene isomer, pyrimidine and oxazole) produces compounds of similar potency to the hit. Fusing the 5-phenyl moiety to the thiophene to form a thieno[2,3-b]pyridine core increases aqueous solubility of the series as well as reduces the CYP liability. While the optimized compound still shows pM IKK(S potency, the aqueous solubility, HLM stability and CYP profiles are much improved. A pharmacophore model was generated that enabled scaffold hopping to yield this new chemotype (Scheme 7). 

The use of water-soluble metal catalysts for the hydrogenation of thiophenes in aqueous biphasic systems has been primarily introduced by Sanchez-Delgado and coworkers at INTEVEP S.A. [61]. The precursors RuHC1(TPPTS)2(L2) (TPPTS=triphenylphosphine trisulfonate L=aniline, 1,2,3,4-tetrahydroquinoline) and RuHC1(TPPMS)2(L2) (TPPMS=triphenylphosphine monosulfonate) were... 

The observed catalytic effect of the crown ether appears to be dependent on the nucleophile employed in both polymerization and corresponding model reactions. Not surprisingly, it appears that the stronger the nucleophile employed, the smaller the catalytic influence of the crown ether. For example, with potassium thiophen-oxide yields of polymer or model products were almost quantitative with or without catalyst. By contrast, the reaction of PFB with potassium phthalimide, a considerably weaker nucleophile, affords 6 in 50% with catalyst and in 2-3% without catalyst under identical conditions. However, it may be that this qualitative difference in rates is, in fact, an artifact of different solubilities of the crown complexed nucleophiles in the organic liquid phase. A careful kinetic study of nucleophilicity in catalyzed versus non-catalyzed reactions study is presently underway. 

Seymour. D.T., Verbeek, A.G., Hrudey, S.E.,and Fedorak, P.M. Acutetoxicity and aqueous solubility of some thiophenes and their microbial metabolites. Environ. Toxicol. Chem., 16(4) 658-665,1997. 

In order to quantify the transition metal ion concentration, Jones et al. [107] developed a highly sensitive fluorescent chemosensor in the form of dialkoxy-phenyleneethynylene-thiophene copolymers 68/69. The PAEs were functionalized on the thiophene unit with terpyridine (68), and included 2,2 -bipyridine (69) as a Lewis acid receptor. The terpyridine polymers [108] were found to respond quantitatively to transition metal ions at concentrations as low as 4x10 M (NP, Hg, Cr ", and Co " ). The additionally used bpy-PAE demonstrates that variation in the chelation at the receptor site is an important variable in tuning selectivity. The observed dynamic quenching mechanism, combined with the solubility of this material, provides the opportunity to extend these initial investigations to thin solid films for use in real-time monitoring applications. 

The solubilities of aromatic compounds in the ionic liquid are dramatically higher than those of saturated compounds. Benzene has a solubility of 4.9mol/mol of ionic liquid, and thiophene has a solubility of 6.7mol/mol of ionic liquid. A dramatic steric effect was observed on the solubility of aromatics the alkyl-substituted aromatics showed reduced solubility. Although the solubility of hexene in the ionic liquid is considerably lower than that of the aromatics, it is still measurably higher than that of hexane. Similar structure-solubility relationships characteristic of organic molecules were observed with the ionic liquids [BMIM]BF4, [BMIM]PFg, and [EMIM]BF4 (Fig. 10) (27). 

An increase in the number of alkyl substituents on an aromatic ring markedly reduces the solubility of the aromatic compound in [BMIM]BF4, [BMIMJPFg, and chloroaluminate-containing ionic liquids 27). For example, the solubility of trimethyl-benzene in [BMIMJPFg is 10-fold less than that of toluene. Similarly, the solubility of 2-methylthiophene in this ionic liquid is three times less than that of thiophene. 

Polymers of thiophene carboxylic acids (9) undergo different chromatic transitions upon the addition of a variety of cations (McCullough et al. 1997). Although the acid form of the polymer was not water soluble, addition of various ammonium or metal... 

Many of these studies utilized noble metals such as Ir, Os, Rh, Ru, or Re, whereas others used more conventional metals such as Mn, Fe, Mo, or Co. The particular metal on which the observations were made is not important at this point. What is important is that all of the important steps required for direct sulfur removal and hydrogenation of thiophene and more condensed derivatives have been shown to occur with soluble metal complexes. Thus, organometallic complex chemistry can be of great value in elucidating the mechanisms involved in conventional HDS processes and perhaps can point the way to improved catalyst formulations. 

Pyrrole, furan and thiophene have only limited solubility in water, decreasing in the order cited (6, 3 and 0.1%). The hydrogen donor property of the NH site of pyrrole and the hydrogen acceptor property of the oxygen atom of furan probably account for the much greater solubility of the first two over that of thiophene. 

The polymerization of thiophene, to yield intractable polythiophene 48, was first carried out in a controlled manner in the early 1980s [185-188]. Even in such an unyielding form, this polymer displayed many promising optical and electronic properties. Unfortunately, its lack of processibility precluded further exploration of these attractive attributes. Since then, the synthesis of soluble pol-... 

Comparable to thiophene, pyrrole is a five-membered heterocycle, yet the ring nitrogen results in a molecule with distinctly different behavior and a far greater tendency to polymerize oxidatively. The first report of the synthesis of polypyrrole (PPy) 62 that alluded to its electrically conductive nature was published in 1968 [263]. This early material was obtained via electrochemical polymerization and was carried out in 0.1 N sulfuric acid to produce a black film. Since then, a number of improvements, which have resulted from in-depth solvent and electrolyte studies, have made the electrochemical synthesis of PPy the most widely employed method [264-266]. The properties of electrosynthesized PPy are quite sensitive to the electrochemical environment in which it is obtained. The use of various electrolytes yield materials with pronounced differences in conductivity, film morphology, and overall performance [267-270]. Furthermore, the water solubility of pyrrole allows aqueous electrochemistry [271], which is of prime importance for biological applications [272]. 

The synthesis, characterization, electrical conductivity, and field effect mobility of a series of novel soluble N-alkyl dithieno[3,2-b 2, 3 -d]pyrrole (DTP) and thiophene (TH)-based copolymers (DTP-co-THs) were reported (06MM1771 08JA13167). The incorporation of DTP units extends n conjugation, and the introduction of thiophene subunits imparts good solubility, high conductivity, and high charge carrier mobility. Therefore, the incorporation of DTP units and various substituted thiophenes into the polymer backbone affords the ability to enhance the solubility, lower the band gap, and achieve the enhanced electronic properties. 

A mixture of 10.3 g of thiophene-2a-methylacetic acid [prepared by process of Bercot-Vatteroni, et al., Bull. Soc. Chim. (1961) pp. 1820-21], 11.10 g of benzoyl chloride and a suspension of 23.73 g of aluminum chloride in 110 cc of chloroform was allowed to stand for 15 minutes and was then poured into a mixture of ice and hydrochloric acid. The chloroform phase was extracted with a 10% aqueous potassium carbonate solution and the aqueous alkaline phase was acidified with N hydrochloric acid and was then extracted with ether. The ether was evaporated off and the residue was crystallized from carbon tetrachloride to obtain a 54% yield of 5-benzoyl-thiophene-2a-methylacetic acid melting at 83°C to 85°C. The product occurred in the form of colorless crystals soluble in dilute alkaline solutions, alcohol and ether and insoluble in water. 

Another type of noncovalent interaction, namely electrostatic ones, has recently been exploited by Wang et al. in the fabrication of a hybrid film containing a water-soluble poly(thiophene) derivative and CdSe NCs.141 In this case CdSe NCs were functionalized with 11-mercaptoundecanonic acid (MUA) molecules prior to their self-assembly with side chain-functionalized poly(thiophene), that is, poly(3-(3 -thienyloxy)propyltrimethylammonium bromide) (P3TOPA). 

The oligothiophenes 27 bear phenyl groups in the 3 -position of the thiophene cores that are para-substituted with electronically diverse functional groups (R = CF3, H, CH3, OCH3). Here, the phenyl spacers enhance the solubility of the oligomers and warrant the electronic communication between the elements of diver-... 

One of the reasons that polyalkylthiophenes have been investigated is the limited solubilities of unsubstituted thiophenes. The synthetic methods used for the preparation of both types of compounds are very similar. For example, both the parent thiophene and alkylthiophenes can be polymerized by reaction with FeCh in chloroform. Other synthetic approaches involve the reaction of dihalogen precursors in the presence of magnesium, zinc or nickel. Some examples of these approaches are shown in Figure 4.22. In all of these methods, the monomers are linked through the C2 and C5 carbon atoms rather than via 2,4 linkages. 

BR with narrow MMDs (Mw/Mn > 3.5) and a low solution viscosity can also be obtained by the use of a multi-component catalyst system which comprises the following six components (1) Nd-salt, (2) additive for the improvement of Nd-solubility, (3) aluminum-based halide donor, (4) alumoxane, (5) aluminum (hydrido) alkyl, and (6) diene. The solubility of the Nd-salt is improved by acetylacetone, tetrahydrofuran, pyridine, N,N-dimethylformamide, thiophene, diphenylether, triethylamine, organo-phosphoric compounds and mono- or bivalent alcohols (component 2). The catalyst components are prereacted for at least 30 seconds at 20 - 80 °C. Catalyst aging is preferably performed in the presence of a small amount of diene [397,398 ]. As the additives employed for the increase of the solubility of Nd salts exhibit electron-donating properties it can be equally well speculated that poisoning of selective catalyst sites favors the formation of polymers with a low PDI. 

The solubility of neodymium carboxylates in organic solvents is also improved by the addition of electron donors such as acetylacetone, tetrahy-drofuran, N,N -dimethylformamide, thiophene, diphenylether, triethylamine, pyridine, organic phosphorus compounds etc. Also the storage stability of neodymium carboxylates in organic solutions (reduction of sediment formation) is increased by these additives. Mixtures of the Nd-precursor and the respective additives are reacted in the temperature range 0-80 °C. The sequential addition of Al-compound and halide donor yield the active polymerization catalysts [409,410]. 

The harmala alkaloids harmaline (368 X = NH) and harmine (369 X = NH) are active reversible inhibitors of monoamine oxidase (MAO). Benzo[Z> ]thiophene analogs of harmaline (368 X = S) and harmine (369 X = S), when tested in vitro as inhibitors of rat liver MAO, showed that (368 X = S) was 50 times more potent than harmaline, but (369 X = NH or S) were equivalent in potency. The replacement of the indolic nitrogen by sulfur greatly increased the lipid solubility of the molecule, which was reflected in the physiological disposition of the two analogs. 

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