The case for the intermediacy of monomeric metaphosphate analogues during oxidation of H-phosphonothioate, H-phosphonodithioate, and H-phosphonoselenoate monoesters: mechanistic and synthetic studies

Studies on the reaction of H-phosphonothioate, H-phosphonodithioate, and H-phosphonoselenoate monoesters with iodine in the presence of a base led to identification of a unique oxidation pathway, which consists of the initial oxidation of the sulfur or selenium atom in these compounds, followed by oxidative elimination of hydrogen iodide to generate the corresponding metaphosphate analogues. The intermediacy of the latter species during oxidation of the investigated H-phosphonate monoester derivatives with iodine was supported by various diagnostic experiments. The scope and limitation of these oxidative transformations for the purpose of the synthesis of nucleoside phosphorothioate, nucleoside phosphorodithioate, and nucleoside phosphoroselenoate diesters was also investigated.     

Aryl H-phosphonates. 12. Synthetic and (31)P NMR studies on the preparation of nucleoside H-phosphonothioate and nucleoside H-phosphonodithioate monoesters

Transformation of nucleoside H-phosphonate monoesters into the corresponding H-phosphonothioate and H-phosphonodithioate derivatives and possible side-reactions that may accompany this process were studied using (31)P NMR spectroscopy. These provided new insight into a possible mechanism involved in this transformation and constituted the basis for development of efficient methods for the preparation of nucleoside H-phosphonothioate and nucleoside H-phosphonodithioate monoesters using readily available H-phosphonate monoesters as starting materials.     

Synthesis of polyesters from active diesters

Ester-exchange and polycondensation reactions of active diesters such as diphenyl, dithiophenyl, or dipyridinyl esters of adipic or terephthalic acids with glycols were carried out in order to investigate the reactivity of these active diesters toward nucleophilic replacement. Catalysts such as potassium carbonate were required for the esterexchange of these active diesters. Comparison of the reactivity of these active diesters with that of ordinary diesters in the presence of potassium carbonate as a catalyst indicates the rates or the equilibrium constants of the exchange reactions of these active diesters were much larger than those of ordinary diesters, indicating that polyesterification reactions favorably occur. Polyesters were obtained in good yield either by solution or bulk methods in mild conditions.     

Reactive intermediates in the H-phosphonate synthesis of oligonucleotides

The formation of H-phosphonate diesters is an important step in the synthesis of oligonucleotides. Using diphenylchlorophosphate as the activator for the coupling step is often accompanied by side reactions as a result of self 'capping' and other reactions of the reactive intermediate. In the absence of base, the activation of ethyl H-phosphonate with diphenylchlorophosphate probably occurs through the intermediate formation of bis diethyl pyro-di-H-phosphonate rather than the expected diphenyl ethyl pyro-H-phosphonate. Pyridine acts as a nucleophilic catalyst converting diphenylchlorophosphate to its pyridinium adduct. Several side and unwanted reactions are quantified so that conditions to minimise these can be identified.     

Computational study of the mechanism and selectivity of palladium-catalyzed propargylic substitution with phosphorus nucleophiles

The mechanism and sources of selectivity in the palladium-catalyzed propargylic substitution reaction that involves phosphorus nucleophiles, and which yields predominantly allenylphosphonates and related compounds, have been studied computationally by means of density functional theory. Full free-energy profiles are computed for both H-phosphonate and H-phosphonothioate substrates. The calculations show that the special behavior of H-phosphonates among other heteroatom nucleophiles is indeed reflected in higher energy barriers for the attack on the central carbon atom of the allenyl/propargyl ligand relative to the ligand-exchange pathway, which leads to the experimentally observed products. It is argued that, to explain the preference of allenyl- versus propargyl-phosphonate/phosphonothioate formation in reactions that involve H-phosphonates and H-phosphonothioates, analysis of the complete free-energy surfaces is necessary, because the product ratio is determined by different transition states in the respective branches of the catalytic cycle. In addition, these transition states change in going from a H-phosphonate to a H-phosphonothioate nucleophile.     

Studies on Pyrazine Derivatives. 38. Synthesis, Reactions, and Tuberculostatic Activity of Pyrazinyl-substituted Derivatives of Hydrazinocarbodithioic Acid

The synthesis of N'-[amino(6-chloro- and 6-cycloaminopyrazin-2-yl)methylene]carbodithioic acid mono- and diesters and their reactions are described. Cyclization of monoesters with secondary amines in acidic media gave the 1,3,4-thiadiazole derivatives, while the cyclization of diesters with amines yielded 1,2,4-triazoles with the amine substituent in position 3. The in vitro tuberculostatic activity of the prepared compounds was tested.     

Chemoselective synthesis of novel aminoindolizines using aminopyridines,acetylenic diesters and α-halo ketones

A chemoselective synthesis of novel indolizine derivatives were reported via three-component reactions of aminopyridines, acetylenic diesters and a-halo ketones. In these reactions, the zwitterion generated from aminopyridines and acetylenic diesters reacted with a-halo ketones to produce indolizine skeleton in good to high yields under mild reaction conditions.     

Catalysis and acceleration of acyl transfer by aminocyclodextrins: a biomimetic system of use in enzyme modeling and drug design

[formula: see text] Aminocyclodextrins (ACDs), perfunctionalized at the 6-position with amino groups, bind phosphonoformate (PFA) diesters and accelerate acyl transfer reactions with high efficiency at neutral pH. Aminolysis and esterolysis are accelerated and hydrolysis of PFA diesters is catalyzed by ACDs. PFA diesters have significant antiviral activity. The rapid reactions observed with ACDs show that biological nucleophiles may undergo facile covalent modification by PFA esters at physiological pH, which has significant implications for prodrug and drug design strategies.     

Synthesis of polyamides through active diesters

Polycondensation reactions of active diesters including several aromatic or heterocyclic nuclei with hexamethylenediamine were carried out in order to investigate the enhancement of reactivity of active diesters for nucleophilic replacement to form polyamide for synthesis of polyamides under moderate condition. These active diesters easily induce polycondensation reaction in solutions, forming polyamides at room temperature. Solvents have a considerable influence on the rate of the polycondensation. The reactivity of these active diesters toward aminolysis is strongly controlled by the structure of the alcohol formed. The reactivity enhancement of active ester group toward amine could be attributed either to the polarization of carbonyl group or to the resonance effect of the alkoxy group.     

Practical selective monohydrolysis of bulky symmetric diesters: Comparing with sonochemistry

The conditions of the practical selective monohydrolysis of symmetric diesters we previously reported have been modified and applied to selective monohydrolysis of bulky symmetric diesters. While ultrasound is generally considered effective for two-phase reactions, its effect actually turned out to be rather marginal. Instead, use of a larger proportion of a polar aprotic co-solvent, DMSO, and aqueous KOH helped enhance the reaction rates and improve the yields of the half-esters. The reactions are simple, mild and practical without special devices.     

Cyclopentannulation of 3-alkylindoles: a synthesis of a tetracyclic subunit of the kopsane alkaloids.

Indoles which bear an alkyl substituent in the 3-position undergo a [3 + 2] annulation reaction when treated with 1,1-cyclopropane diesters in the presence of Yb(OTf)(3) resulting in 2,3-cyclopentanoindolines. Typically, the reactions are performed at elevated temperatures or at ultrahigh pressures. In cases where steric crowding is an issue, ultrahigh pressures are required. In reactions involving substituted cyclopropanes, significant regio- and diastereocontrol was observed. When the substituent was aromatic or olefinic, the reactions took place at ambient temperature and pressure. The applicability of this methodology to the preparation of a key tetracyclic subunit of the kopsane alkaloids was demonstrated.     

Synthesis of perfluoro(polyether) difunctional compounds

Omega-iodoperfluoro(polyether) esters IR_fOR_fCO₂R have been synthesized by two procedures. These iodoesters have been reacted via zinc coupling reactions to yield alpha, omega-perfluoro(polyether) diesters. The diesters serve as convenient starting materials for the synthesis of a variety of other difunctional compounds of high molecular weight and exhibiting a variation of oxygen-carbon ratio.     

Agents for the treatment of overactive detrusor. II. Synthesis and inhibitory activity on detrusor contraction of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function.

A series of 1,1'-biphenyl-2,6-dicarboxylic acid diesters with an aminoalkyl group in the ester function were synthesized and examined for their inhibitory activity on detrusor contraction in vitro and in vivo. In the in vivo test, arrhythmia was observed as a side effect. Among those compounds synthesized, 2-methyl 6-[4-(1-methylpiperidinyl)] 3-hydroxy-5-methyl-2'-nitro-1,1'-biphenyl-2,6-dicarboxylate (18) showed strong inhibitory activity on detrusor contractions in vivo (ED50 = 0.54 mg/kg i.v., ED50 = 7.2mg/kg i.d.) and good separation from the side effect. Compound 18 was chosen for further pharmacological evaluation as an agent for the treatment of overactive detrusor.     

A mechanistic study of the alkaline hydrolysis of diaryl sulfate diesters

Nearly all of the reported studies of reactions of sulfate diesters are for dialkyl or alkyl aryl diesters, which undergo reaction by carbon-oxygen bond fission. Sulfuryl transfer reactions of sulfate diesters (RO-SO(2)-OR') proceeding by attack at sulfur have been little explored. When both ester groups are aryl groups the hydrolysis reaction (sulfuryl transfer to water) occurs by way of attack at sulfur. The alkaline hydrolysis of diaryl sulfate diesters was shown to obey first-order kinetics with respect to [(-)OH] and proceed through S-O bond fission, in a mechanism that is most likely concerted. Activation parameters for 4-chloro-3-nitrophenyl phenyl sulfate and 4-nitrophenyl phenyl sulfate gave the following respective values: Delta H(++) = 88.0 +/- 0.1 and 84.83 +/- 0.06 kJ mol(-)(1) and Delta S(++) = -37 +/- 1 and -50.2 +/- 0.5 J mol(-)(1) deg(-)(1). The dependence of the second-order rate constant for hydrolysis on leaving group pK(a) was analyzed giving a beta(lg) slope of -0.7 +/- 0.2 and a Leffler alpha parameter value of 0.36. A (15)k kinetic isotope effect (KIE) for the hydroxide attack on 4-nitrophenyl phenyl sulfate of 1.0000 +/-0.0005 and an (18)k(lg) KIE value of 1.003+/-0.002 were obtained.     

Reaktionen von Glutaminsäuredimethylester im Massenspektrometer. 21. Mitteilung über das massenspektrometrische Verhalten von Stickstoffverbindungen

The mass spectral fragmentation of dimethyl glutamate ( 1 ) and its deuterated derivatives 1a , 1b and 1c has been investigated. By loss of a methoxycarbonyl group from the molecular ion an ion of m/e 116 is generated. The latter splits off methanol (m*), the resulting fragment of m/e 84 giving raise to the base peak of the spectrum. Only part of the hydrogen transferred to the leaving group originates from thc amino group, as was suggested earlier [2] [3]. Basing on experiments with deuterated compounds we propose an additional mechanism for the reaction, i.e. hydrogen transfer from C(3) to methoxyl. The fragment generated by both processes is most likely to be a pyrrolinonium ion. Thermal side reactions in the mass spectrometer (formation of pyroglutamic acid ester) followed by fragmentation may lead to the same ion. – The mechanisms discussed are supported by the mass spectral fragmentation of N-acetyl-glutamic acid diesters 3 , 3a , 3b and 3d and of the N, N-dimethyl derivatives 4 and 4a . – The fragmentation reactions investigated are similar to some of 1,3-trimethylenediamine derivatives [7]. This means that there are parallels in the mass spectral fragmentation of difunctional compounds irrespective of the nature of the functional groups.     

Stereoselective oligomerizations catalyzed by lipases in organic solvents

Lipases have been found to act as stereoselective catalysts in polycondensation reactions between racemic diesters and achiral diols (or vice versa) in organic solvents. Optically active trimers andpentamers have been formed as a result.     

HYDROLYSE DE SPIROPHOSPHORANES II. Derives de l'Octamethyl-2,2,3,3,7,7,8,8 Tetraoxa 1,4,6,9 Phospha V-5 Spiro 4,4 Nonane

Abstract

L'étude de l'hydrolyse de tetraoxaspirophosphoranes dérivés du pinacol et [sgrave] liaison P–C extracyclique a permis de mettre en évidence des équilibres esters cycliques–esters acycliques dépendant de différents facteurs (substituants, solvant, température, nature du milieu etc….). Les réactions d'hydrolyse peuvent ětre orientées sélectivement vers la formation soit de diesters soit de monoesters phosphoniques, cycliques ou acycliques.

Cyclic-acyclic esters equilibria have been found in the study of pinacol derivated tetraoxaspirophosphorans hydrolysis. These equilibria depend on different factors (substituents, solvent, temperature, basicity etc….). Hydrolysis reactions can be directed towards the formation of either diesters or cyclic and acyclic phosphonic monoesters.     

Thermochemical Reactions of H Complexes

Thermal reactions of H complexes formed by methyl and ethyl diesters of aromatic tetracarboxylic acids with diamines were studied by thermal analysis. Some kinetic parameters of formation and degradation of polyimides during thermolysis in the self-generated atmosphere were determined.     

Organische Carbonate. Grüne Lösungsmittel für Synthese und Katalyse

Organic carbonates (cyclic and acyclic diesters of carbonic acid) are highly boiling, polar and non‐toxic solvents. By selection of suitable mono‐ and di‐alcohols as ester components their physical properties can be influenced dramatically. Their use has been proven in lithium batteries, natural gas purification and in cosmetics. Especially propylene carbonate (PC) owns perfect properties as solvent in biphasic transition metal catalyzed reactions. This is a main issue for the use in continuous processes to minimize the amount of catalysts.     

Synthesis of unsaturated esters of m- and p-carboranedicarboxylic acids

Conclusions Some unsaturated diesters of the m- and p-carboranedicarboxylic acids, which can be used in polymerization and copolymerization reactions, were synthesized and characterized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, p. 1904, August, 1982.