Nucleophilic Agents Research Articles

SYNTHESIS OF POLYMERS WITH AMINO END GROUPS BY ATOM TRANSFER RADICAL POLYMERIZATION

Atom Transfer Radical Polymerization (ATRP) is a controlled radical polymerization process that produces polymers with predictable molecular weights, narrow polydispersities, and well-defined halogen end groups. The key factor in the control of the polymerization process is the presence of a metal/ligand complex that provides a fast, reversible activation and deactivation of the growing polymer chains. The ligands, used to complex the metal are mostly tertiary amino compounds. However, amines can interact with the halogen end groups of the initiator molecules or of the growing chains. Our investigations concern-ing this issue indicate that under the experimental conditions used during the polymerization process, interactions of end groups with tertiary amines are negligible. Ammonia and primary amines, e.g., n-butylamine, however can react with the halogen end groups. Moreover, after the polymerization reaction they can be used as nucleophilic agents to replace the halogens by other functional end groups. The use of difunctional molecules such as ethanolamine leads to the incorporation of alcohol end groups at the chain ends.

Detoxification of methylglyoxal by the nucleophilic bidentate, phenylacylthiazolium bromide.

Dicarbonyl-containing compounds such as methylglyoxal (MG) are toxic to cells since they can interact with the nucleophilic centers of macromolecules. MG has been found to accumulate during hyperglycemia, and it has been suggested that this reactive dicarbonyl may contribute to the tissue damage and long-term complications of diabetes. A sensitive bacterial assay for investigating the ability of nucleophilic agents to interact with and detoxify MG has been developed. This assay utilizes the sensitivity of exponential phase cells of an Escherichia coli double mutant lacking the KefB and KefC potassium channels toward MG. The bidentate nucleophile, phenylacylthiazolium bromide (PTB), was found to protect and allow the growth of E. coli cells in the presence of either externally added or endogenously produced MG. In the absence of PTB, growth was completely inhibited and rapid cell death occurred under these conditions. PTB protected E. coli against MG almost as well as aminoguanidine, a compound shown previously to be involved in detoxification. The level of protection by PTB against MG was much greater than for the endogenous nucleophile, glutathione. These data suggested that PTB could interact with and detoxify MG. The mechanism of this interaction was characterized by NMR and mass spectroscopy.

TiCl 4 promoted three component coupling reaction: A new method for the synthesis of functionalized tetrahydrofurans and tetrahydropyrans

TiCl 4 promoted coupling of ethyl glyoxylate and dihydrofuran or dihydropyran provided oxonium ion intermediates which upon reaction with a nucleophilic trapping agent such as allyltrimethylsilane provided 2,3-disubstituted tetrahydrofurans and pyrans in good yields. The overall protocol constitutes an efficient three component coupling reaction in one pot.

Chemistry of puupehenone: 1,6-conjugate addition to its quinone-methide system.

The marine natural product puupehenone (1), isolated in good yields from sponges of the genus Hyrtios, has been shown to undergo stereospecific 1,6-conjugate addition to its quinone-methide system. Several nucleophilic agents such as hydrogen cyanide, Grignard reagents, and nitroalkanes were studied, producing structurally diverse compounds. This lead optimization study was initiated due to the bioactivity of puupehenone and its natural analogues, which includes numerous previous reports of potential anticancer and antiinfective activity.

Catalytic competence of O-acetylserine sulfhydrylase in the crystal probed by polarized absorption microspectrophotometry

The reactions of the pyridoxal 5′-phosphate-dependent enzyme O-acetylserine sulfhydrylase with the substrate O-acetyl- l-serine and substrate analogs have been investigated in the crystalline state by single-crystal polarized absorption microspectrophotometry. This approach has allowed us to examine the catalytic competence of the enzyme in different crystalline states, one of which was used to determine the three-dimensional structure; experimental conditions were defined for the accumulation of catalytic intermediates in the crystal suitable for crystallographic analyses. O-Acetyl- l-serine reacts with the enzyme in one of the crystal forms leading via a β-elimination reaction to the accumulation of the α-aminoacrylate Schiff base, absorbing maximally at 320 and 470 nm, as in solution. The dissociation constant for the α-aminoacrylate Schiff base is in the millimolar range, 500-fold higher than in solution, suggesting that crystal lattice interactions may oppose functionally relevant conformational changes. The dissociation constant exhibits a bell-shaped dependence on pH centered at pH 7. At this pH the α-aminoacrylate species slowly decays with time (30% decrease in 24 hours). The α-aminoacrylate intermediate readily reacts with sodium azide, an analog of sulfide, the natural nucleophilic agent, to give a new amino acid and the native enzyme, indicating that the crystalline enzyme catalyzes the overall β-replacement reaction as in solution. In other crystal forms, including that used for the X-ray investigation, O-acetyl- l-serine either has an even higher dissociation constant or causes crystal damage upon binding. When the crystalline enzyme reacts with either l-cysteine or l-serine, the external aldimine intermediate is formed. The dissociation constants for both substrate analogs are closer to those observed in solution and are modulated by pH as in solution. Findings demonstrate that O-acetylserine sulfhydrylase is catalytically competent in the crystal although some regions of the molecule, likely involved in an open-closed transition induced by O-acetyl- l-serine binding, may have a limited flexibility. The accumulation in the crystal of both the external aldimine and the α-aminoacrylate intermediate makes feasible their structural determination and, therefore, the elucidation of the catalytic pathway at the molecular level.

Studies of reactions of dimethylphosphoramidic difluoride withtrans-2-(N,N-dialkylamino)cycloalkanols in the presence of various sulfur-containing nucleophiles

The reactions of dimethylphosphoramidic difluoride (1) withtrans-2-(N,N-dialkylamino)cycloalkanols were studied in the presence of various sulfur-containing nucleophiles and Et3N. WhenO,O-diisopropyl thiophosphoric acid was used as a nucleophile, the correspondingO,O-diisopropylS-[2-(N,N-dialkylamino)cycloalkyl] thiophosphates were obtained in satisfactory yields. The direction of this reaction in the presence ofO-isopropyl toluenephosphonothioic acid depends on the pKa of aminoalcohol, namely, the amount ofO-isopropyl tolylphosphonofluoridate that was formed along withO-isopropylS-[2-(N,N-dialkylamino)cycloalkyl] tolylphosphonothioates was increased as the pKa increased. The reactions of compound1 withtrans-2-(N,N-dialkylamino)cycloalkanols and thioacetic acid afforded 2-(N,N-dialkylamino)cycloalkanethiols, certain of which were readily oxidized to the corresponding disulfides. In the case of potassium ethyl xanthate, the composition of the reaction products depends on the nature of aminoalcohol. X-ray diffraction analysis ofS-(2-piperidinocyclohexyl)N,N-dimethyldithiocarbamate demonstrated that this compound exists as thetrans isomer. This fact supports the reaction mechanism, which we have suggested previously and which involves the formation of aziridinium cations followed by their opening under the action of nucleophilic agents.

Mechanism-based inactivation of cytochrome P450 2B1 by 8-methoxypsoralen and several other furanocoumarins.

Of several furanocoumarins [5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), 5-hydroxypsoralen (5-OH-P), 8-hydroxypsoralen (8-OH-P), 4',5'-dihydro-8-MOP (DH-8-MOP), and psoralen (P)] tested as mechanism-based inactivators (MBIs) of purified reconstituted cytochrome P450 (P450) 2B1, 8-MOP was found to be the most potent (KI, kinact, and partition ratio of 2.9 microM, 0.34 min-1, and 1.3, respectively). The inactivation was not prevented by reactive oxygen species scavengers or nucleophilic trapping agents and proceeded with a decrease in P450 spectral content. Liquid chromatography (LC) separation of the reconstituted enzyme mixture, followed by liquid scintillation counting, indicated that [14C]-8-MOP binding was specific to the apoprotein of P450 2B1 with a binding stoichiometry of 0.7:1. The major metabolites formed by P450 2B1 from the furanocoumarins that were MBIs were characterized by LC electrospray ionization tandem mass spectrometry (ESI-MS/MS) as dihydro diols. Results from H218O incorporation experiments supported initial oxidation of 8-MOP and P to an epoxide which can react with some nucleophilic active site residue and inactivate the enzyme or partition to a dihydro diol metabolite by hydrolytic ring opening. On the other hand, 5-MOP was converted to an epoxide or gamma-keto enal intermediate prior to inactivation or dihydro diol formation. Comparison of the ESI mass spectra of P450 2B1 and furanocoumarin exposed P450 2B1, indicated a mass difference consistent with the covalent addition of a furanoepoxide to P450 2B1.

Brominated Polyethylene. Synthesis, Photooxidation and Use as the Intermediate for the Preparation of New Polymeric Stabilizers

The hydrobromination of polyoctenamer was performed using concentrated hydrogen bromide chloroform solutions. The conditions for the total hydrobromination of polyoctenamer were established. The photoageing of the resulting brominated polyethylene was analyzed and compared with those of pure polyethylene and chlorinated homologues. The brominated polyethylene has been used as an intermediate for the synthesis of a new polymeric hindered amine stabilizer. Nucleophilic substitution of bromine atoms was performed by 4-amino-2,2,6,6-tetramethylpiperidine and resulted in a partial grafting of 2,2,6,6-tetramethylpiperidine groups on the polymer chain. Using 2,2,6,6-tetramethyl and 1,2,2,6,6-penta-methyl-4-piperidinol in the presence of NaH or their sodium salts as the nucleophilic agents did not lead to any grafting under the experimental conditions used. This new additive resulted in good stabilizing properties upon the photo-and the thermooxidation of elastomers as EPDM and polyoctenamer.

The influence of an acetyl group on the cyclopentadienyl ring in the formation of Sn-Mo(W) complexes by nucleophilic displacement reactions, crystal and molecular structure of CH3COC5H4(CO)3MoSnPh2Cl

Sodium tricarbonylacetylcyclopentadienylmolybde-num (tungsten) reacted with Ph2SnL2 (L=Cl, Br) in a 1:1 ratio or even a 4:1 ratio only to afford bimetallic complexes CH3CO-C5H4(CO)3MSnPh2L (M=Mo. W; L=Cl or Br), which have been characterized by elemental analyses, IR and 1H NMR spectroscopy. The acetyl group on the Cp ring exerts an electron-withdrawing effect that makes the organomolybdenum anion a less effective nucleophilic agent in displacing the remaining halogen from the CH3COC5H4Mo-(CO)3.SnPh2L. The bimetallic complex could be isolated, and the crystal structure of the titled complex is orthorhombic, a = 16.271, b = 10.247(2), c = 14.450(2) Å, Z = 4, space group Pna21, and the Mo atom has a 3:4 piano stool structure with an Sn-Mo bond length of 2.7683(6) Å. © 1998 John Wiley & Sons, Inc. Heteroatom Chem 9:169–172, 1998

ChemInform Abstract: Reactions of 21‐Acetoxy‐16α,17α‐epoxypregn‐4‐ene‐3,20‐ dione with Nitrogen‐Containing Nucleophilic Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Novel aspects of carbonyl oxide chemistry

The structural and chemical properties of 1,3-dipolar peroxidic species (X—O—O) such as ozone (X=O) and carbonyl oxides (X=R2C) depend significantly on the nature of X. Although cyclic O3 is thermodynamically unstable, dioxiranes, cyclic isomers of carbonyl oxides, are isolable and have been fully characterized. In contrast to the well known electrophilic nature of ozone, carbonyl oxides usually act as a nucleophilic oxygen transfer agent, but their reactivity could be altered by substituents. It is expected that the chemistry of R2C—O2 species will provide a good starting point for a better understanding of dioxygen complexes (X—O2) with various Xs. Interesting aspects of carbonyl oxide chemistry are discussed, including methods of generation, cyclization to dioxiranes and the nature of their oxygen transfer activities. © 1997 John Wiley & Sons, Ltd.

Preparation of hyperbranched macromolecules with aryl fluoride and phenol terminal functionalities using new monomers and Cs2CO3 or Mg(OH)2 as the condensation agent

New A2B monomers were synthesized for preparation of hyperbranched aryl ether sulfone macromolecules with aryl fluoride and phenol terminal functionalities. The macromolecules, which possess high thermal stability, were prepared using the divergent approach. A masked phenol with two aryl fluoride groups and a bisphenol with an aryl fluoride group were the monomers used to synthesize these polymers. In both cases, the aryl fluoride group is activated by a sulfone moiety. The synthetic method used for the preparation of the hyperbranched macromolecules gave a fast reaction and a high yield. These methods include, e.g., the use of Cs2CO3 and Mg(OH)2 to generate the phenolate ion in situ. Use of the latter results in the formation of insoluble magnesium fluoride. The best conditions for the reaction utilized the more active nucleophilic polycondensation agent, Cs2CO3, and an aryl carbonate as a masked phenol. NMR, SEC, and MALDI-TOF-MS were used to characterize the samples. MALDI-TOF-MS allowed us to identify the different oligomeric species present, and it also indicated that an internal cyclization competes with the polymerization. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35: 2015–2033, 1997

Reversible blockade of gap junctional communication by 2,3-butanedione monoxime in rat cardiac myocytes.

2,3-Butanedione monoxime (BDM), a nucleophilic agent endowed with a "phosphatase-like" activity, is often used as a tool for investigating the effects of changes in phosphorylation level of protein constituents on membrane channel function. BDM produced a rapid, dosc-dependent, and reversible abolition of the cytosolic continuity existing between cells via gap junctional channels. The persistence of this effect when a nonhydrolyzable analogue of ATP [adenosine 5'-O-(3-thiotriphosphate) (ATP(gamma)S)] was introduced in the cytosol suggests that the acute suppressant effect of BDM was not due to dephosphorylation. However, the higher reversibility after BDM withdrawal in presence of ATP(gamma)S could signify that a protein-dephosphorylating activity gradually occurred during the oxime treatment. Junctional uncoupling took place even when the moderate increase in cytosolic Ca2+ concentration induced by BDM was prevented by ryanodine. These results are consistent with the model of dual mechanism of BDM action proposed for some other membrane channels, consisting of a quick channel block and a parallel slow inhibition, plausibly through dephosphorylation.

Oxidation of Ruthenium(II) to Ruthenium(IV) η4-Diene Complexes: Swing Mechanism and Diene−Allyl Conversion

This paper reports on the synthesis and reactivity of Ru(IV) η4-diene complexes of the type Ru(η5-C5Me5)(η4-diene)Br2+ obtained by oxidative bromine additions to Ru(II) η4-diene complexes. Mechanistic details are derived from the reaction products varying with the oxidizing agent and the leaving ligand and are backed up by extended Huckel molecular orbital calculations. The diene fragment in Ru(IV) is prone to gauche deformation and is therefore extremely susceptible to nucleophilic attack of even weak anionic bases generating the corresponding Ru(IV) η3-allyl complexes. Accordingly, Ru(IV) η4-diene complexes are stabilized either by using 2,3-disubstituted diene ligands in which case gauche deformation is highly unfavorable or else by excluding nucleophilic agents. For the latter method, two convenient routes to affording Ru(IV) η4-diene complexes are (i) the reaction of Br+CF3SO3- with Ru(η5-C5Me5)(η4-diene)Br and (ii) the reaction of dibromine with labile Ru(η5-C5Me5)(η4-diene)(CF3SO3). The conversion ...

New syntheses of 2,4-diaminopyrroles and aminopyrrolinones

Oxazolin-2-ylidene-malononitriles3a–d, obtainable from thioketenaminals and α-halogen-ketones, react with primary and secondary amines to afford 2,4-diamino-pyrroles5a–h. Mercaptobenzen as nucleophilic agent gives the 4-amino-2-phenylthio-pyrrole5j. Analogously, cyano-(3,5-diphenyl-3H-oxazol-2-ylidene)-acetic acid methyl esters were prepared as intermediates for the synthesis of 2-amino-4-oxo-pyrrolines10a–d. The isomeric 4-amino-2-oxo-pyrrolines13a–d can be obtained from 4-amino-2-methoxy-pyrroles, which serves as proof for the position of substituents. The structures were investigated by1H and13C NMR spectroscopy.

Reactions of 21-Acetoxy-16α,17α-epoxypregn-4-ene-3,20-dione with Nitrogen-Containing Nucleophilic Agents

21-Acetoxy-16α,17α-epoxypregn-4-ene-3,20-dione (1) enters a reaction with acetonitrile catalyzed by perchloric acid, giving unusual products with the furostane skeleton. In contrast to analogous reactions, the reaction with sodium azide results in the azido derivative possessing the non-rearranged ring D. The 1H NMR, 13C NMR, and mass spectra are discussed.

Reactions of polyhalogenopyridines. 12. Reactions of 4-pentafluoroethylthio-2,3, 5,6-tetrafluoropyridine with nucleophilic agents

The reactions of 4-perfluoroethylthio-2,3,5,6-tetrafluoropyridine with various nucleophilic agents were investigated. It was shown that the pentafluoroethylthio group is inert toward N- and O-nucleophiles.

A challenging synthetic approach to phosphonium ylide-betaines of the pyrimidine series

Adducts of the available ylide Ph 3 P + -C̄HCN with acylisocyanates and their thio analogues undergo facile cyclization, promoted by hydrogen chloride in methanol, to give high yields of 2-alkyl(aryl)-4-hydroxy(mercapto)-6-oxo-1,6-dihydropyrimidin-5-yl-triphenyl-phosphonium chlorides suitable to prepare several types of phosphonium ylide-betaines of the pyrimidine series, the structure of which was established by chemical transformations and X-ray diffraction analysis. Despite the mesomeric character of these heterocyclic nucleophilic agents, they are alkylated in a regioselective manner, which proves this approach to be important for the synthesis of non-phosphorylated pyrimidine derivatives, which are otherwise difficult to obtain.

ChemInform Abstract: Reaction of 2‐Substituted 6‐Alkoxy‐4H‐1,3‐oxazin‐4‐ones with Some Electrophilic and Nucleophilic Agents.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Anodic oxidation of dimethyl sulfoxide based electrolyte solutions: Anin situ FTIR study

Anodic oxidation of dimethyl sulfoxide (DMSO) based electrolyte solutions, containing LiClO4, LiBF4 and KPF6, on platinum (Pt), glassy carbon (GC) andn-TiO2 (anatase), electrodes was studied usingin situ Fourier transform infrared spectroscopy (FTIR). All solutions contained small amounts of H2O. Regardless of the supporting electrolyte all systems were unstable at potentials above 1.0 V vs SCE. The major oxidation product is dimethyl sulfone, formation of which is initiated by the trace water breakdown. In contrast to acetonitrile based solutions there is no evidence of electrolyte involvement in the breakdown process. Photoanodic decomposition of dimethyl sulfoxide based solutions proceeds in the same way as the anodic oxidation in the dark. In the presence of nucleophilic agent (iodides) the prevailing redox process is iodide oxidation. Small amounts of, probably, methylsulfinyliodide are also formed. The irreversible consumption of charge mediator significantly restricts the possible practical use of DMSO in photoelectrochemical devices.