Oxirane Formation Research Articles

The Mechanism of Frabot Test for Uric Acid

Uric acid is an Analyte. Excess uric acid ─ hyperuricemia ─ leads to gout and renal stones. Frabot noted that uric acid added to an alkaline tungstate solution developed an intense blue colour. A colorimetric method widely utilized to quantify uric acid depends on the reduction of the chromogen sodium tungstate by uric acid to produce a measurable colour change. The reaction route from the initial products to the coloured compounds and the oxido-degradation of the organic substance has not been advanced. In this communication the electron flow is given in each step of the series of reactions that take place. These are isomerization to imidol, Michael addition to enone, oxirane formation in a redox step, hydrolysis of imido group, oxirane ring opening, ring contraction to five- member ring, ring opening via alkoxide, and finally assisted decarboxylation to the end product, 5-ureido hydantoin (allantoin).

Epoxidation of melon seed (Citrullus colocynthis L) oil: A kinetic and thermodynamic approach for industrial applications

Unsaturated melon seed oil had its epoxidation process studied at varied temperatures (30OC -70OC) within a three hours reaction time, for possible oxirane formation because of its industrial significance. Oil was extracted from melon seeds and characterized for its physicochemical properties using standard methods. The specific gravity (30OC), iodine value, acid value, saponification value, peroxide value and percentage oil content were found as 0.931, 118.69 gI2/100g, 5.08 mg KOH/g, 165.7 mg KOH/g, 4.75 meq/kg and 60% respectively. Physicochemical characteristic of the oil reveals it is semi-drying oil which is rich in high molecular weight fatty acids, with good stability against rancidity. The epoxidation process which was monitored by its oxirane content is seen to proceed faster at the highest studied temperature of 70OC, giving the highest oxirane content of 5.87%. Optimization of the epoxidation process showed that optimum epoxidation of melon seed oil can be achieved at 70OC within one hour; as compared to other temperatures studied. Process kinetics evaluated in terms of its oxirane yield showed that the epoxidation process followed pseudo-zero order kinetics with respect to oxirane formation. Their rate constants were found to be 0.032 hr-1, 0.041 hr-1, 0.059 hr-1 and 0.24 hr-1 for the epoxidation process at 30OC, 50OC, 60OC and 70OC respectively; which shows that the epoxidation rate increases with increasing temperature. Thermodynamic parameters such as activation energy (Ea), activation enthalpy (∆H≠), activation entropy (∆S≠) and Gibb’s free energy (ΔG≠) were determined to be 133.11 kJmol-1, 18.22 kJmol-1, -0.21 kJmol-1 K-1 and 87.95 kJmol-1 respectively. The observed thermodynamic properties indicated strong temperature dependence of the epoxidation reaction rate, endothermicity and non-spontaneity of the process. The findings of this study will guide in maximizing oxirane yield and save cost significantly in the production of epoxidized melon seed oil employed for large scale industrial applications.

A review of fatty epoxide ring opening reactions: Chemistry, recent advances, and applications

AbstractFatty epoxides are produced from the corresponding alkenes by oxidation in the presence of peracids or other oxidants. The classic method is the Prilezhaev epoxidation in which peracids are generated by in situ oxidation of formic or acetic acids with hydrogen peroxide. Epoxidized vegetable oils and esters are used directly as biobased plasticizers and stabilizers for poly(vinyl chloride) or as important platform chemicals for the oleochemical industry. Nucleophilic attack at the oxirane moiety affords a variety of ring opened monomeric or polymeric products, which in many cases undergo further synthetic modification to yield finished products. The most common nucleophiles include water, alcohols, carboxylic acids, acid anhydrides, and amines, although numerous others can also lead to valuable functionalized fatty derivatives. This review summarizes the chemistry of fatty epoxide ring opening reactions as well as applications of the resultant products. Literature from the last 20 years will be emphasized, although older publications of particular significance will be included. Important applications include biobased lubricants as well as polyols for subsequent production of polyurethanes. In addition, ring‐opening reactions hitherto unreported on fatty oxiranes will be suggested to facilitate further advancements in the chemistry and utility of fatty epoxides. Finally, interest in fatty epoxides and their consequent products will continue to grow due to the simplicity, efficiency, and versatility of oxirane formation and ring opening as well as the continued societal transition away from petroleum to a sustainable, circular, low‐carbon, and biobased economy.

Diphenoxytriphenylphosphorane: A potent carbohydrate cyclodehydration reagent

Methyl α(and β)-D-3,4-anhydro-tagatofuranosides are important synthetic building blocks as they undergo regioselective ring-opening to afford exclusively products with the D-fructo configuration. Previous attempts to prepare these compounds from the corresponding methyl D-fructofuranosides under standard Mitsunobu conditions have led to an undesired 9:1 mixture of tagato and psico oxiranes. We now report that in the presence of added phenol, the tagato product is formed exclusively and in quantitative yield under extremely mild conditions. Similarly, both D- and L-methyl arabinofuranosides, gave the corresponding methyl 2,3-anhydro-D-lyxofuranosides and methyl 2,3-anhydro-L-lyxofuranosides in quantitative yields using this modified Mitsunobu protocol. The mechanism of this reaction appears to involve the intermediate formation of diphenoxytriphenylphosphorane, which acts as a selective Mitsunobu reagent for oxirane formation from fructo and arabino furanosides as well as trans-diaxial pyranoside diols such as those in levoglucosan. An unusual Mitsunobu-induced anomerisation reaction is also reported.

Kinetics and Mechanism of Oxirane Formation by Darzens Condensation of Ketones: Quantification of the Electrophilicities of Ketones

The kinetics of epoxide formation by Darzens condensation of aliphatic ketones 1 with arylsulfonyl-substituted chloromethyl anions 2 (ArSO2CHCl-) have been determined photometrically in DMSO solution at 20 °C. The reactions proceed via nucleophilic attack of the carbanions at the carbonyl group to give intermediate halohydrin anions 4, which subsequently cyclize with formation of the oxiranes 3. Protonation of the reaction mixture obtained in THF solution at low temperature allowed the intermediates to be trapped and the corresponding halohydrins 4-H to be isolated. Crossover experiments, i.e., deprotonation of the halohydrins 4-H in the presence of a trapping reagent for the regenerated arylsulfonyl-substituted chloromethyl anions 2, provided the relative rates of backward ( k-CC) and ring closure ( krc) reactions of the intermediates. Combination of the kinetic data ( k2exptl) with the splitting ratio ( k-CC/ krc) gave the second-order rate constants kCC for the attack of the carbanions 2 at the ketones 1. These kCC values and the previously reported reactivity parameters N and sN for the arylsulfonyl-substituted chloromethyl anions 2 allowed us to use the linear free energy relationship log k2(20 °C) = sN( N + E) for deriving the electrophilicity parameters E of the ketones 1 and thus predict potential nucleophilic reaction partners. Density functional theory calculations of the intrinsic reaction pathways showed that the reactions of the ketones 1 with the chloromethyl anions 2 yield two rotational isomers of the intermediate halohydrin anions 4, only one of which can cyclize while the other undergoes retroaddition because the barrier for rotation is higher than that for reversal to the reactants 1 and 2. The electrophilicity parameters E correlate moderately with the lowest unoccupied molecular orbital energies of the carbonyl groups, very poorly with Parr's electrophilicity indices, and best with the methyl anion affinities calculated for DMSO solution.

Ultrasonic and solvent free Synthesis of Regioselective Diastereomeric Adducts and Heterocyclic Products as antibacterial agent

Oxirane ring containing the carboxylic group in the α,β-position are useful intermediates in the synthesis of biologically active compounds. Epoxidation of 4-(4-acetylamino and/or bromophenyl)-4-oxo-but-2-enoic acids via ultrasound condition afforded α-oxirane carboxylic acid followed by regioselective diastereomeric adducts of camphor. The steric factor plays an important role in regioselectivity. Formation of oxirane and furan derivatives via ultrasonic condition was considered as key steps for synthesis of some important heterocyclic compounds. The structure of new synthesized compounds 2-9a,b were elucidated by elemental analysis and spectroscopic data. The antibacterial activity for the synthesized compounds was evaluated.

A stereoselective approach for the total synthesis of (−)-tadanalactam from acetonide-d-glucose

A stereoselective and realistic approach for the total synthesis of naturally occurring δ-lactam (−)-tadanalactam, has been accomplished from the commercially existing acetonide-d-glucose involving Birch reduction, Pinnick oxidation, Staudinger reaction, and hydroboration reactions. Finally benzyl ether deprotection and subsequent oxirane formation using Birch reduction completed the total synthesis of (−)-tadanalactam.

Synthesis of Bio‐based Polyurethane from Modified Prosopis juliflora Oil

AbstractStudies on the epoxidation of Prosopis juliflora seed oil were carried out to evaluate the optimum level of oxirane formation. On optimization of epoxidation of Prosopis juliflora oil (PJO), it was observed that at 60 °C and the mole ratio of double bond to the hydrogen peroxide to the acetic acid was 1:1.1:0.5 and at 2 wt% catalyst loading gave the maximum oxirane conversion. Further, epoxidized Prosopis juliflora oil (EPJO) was reacted with aminopropyltrimethoxysilane. Aminopropyltrimethoxysilanated Prosopis juliflora oil (ASPJO) was used as a polyol and was allowed to react with varying concentrations of isophorone diisocyanate resulting in polyurethane. The polyurethane films biodegradability was studied using phosphate buffer and proteinase K. The epoxidized oil was characterized by its epoxy value and FT‐IR spectroscopy. Similarly, ASPJO was characterized by its amine value, FT‐IR and 1H‐NMR spectroscopy. Whereas the polyurethane coating was characterized by gel content, FT‐IR spectroscopy, scanning electron microscopic analysis and also evaluated for its chemical resistance, optical and mechanical properties.

Distinguishing Alternative Reaction Pathways by Single‐Molecule Fluorescence Spectroscopy

Focus on chemical transitions: Epoxidation of a double bond in conjugation to a fluorescent dye was studied at single-molecule level. Direct observation of oxirane formation, indicated as a spectral shift from substrate to product state, revealed an alternative reaction pathway for the epoxidation reaction. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Abstract 5549: Formation of propylamine during peroxidation of the tobacco alkaloid Myosmine

Abstract The alkaloid myosmine is widespread in the biosphere including food materials and tobacco. Its activation in vitro and in vivo, especially in biological systems, is documented by per-oxidation, CYP 450 systems and N-nitrosation procedure. As reported, activation of tobacco specific N-nitrosamines (TSNA) N’-nitroso-nornicotine (NNN) and 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanole (NNAL) leads to hydroxypyridylbutanone (HPB) which is also generated in case of myosmine by N-nitrosation, peroxidation and in rat experiments. The precursor of HPB is the highly reactive intermediate species POB which is assumed to be responsible for DNA-adducts causing tumorigenesis and cancer. Additionally, during peroxidation procedure from myosmine and in metabolic studies with rats compound 3-carbinol was detected. Activation via peroxidation of the alkaloid is performed at the C=N pyrrolidine-ring position preferentially leading to unstable oxirane formation. Subsequently decay between 2’-and 3’position takes place yielding 3-carbinol. Further degradation products of the pyrrolidine-oxirane decay were not known till now, but could be high-reactive intermediates. In our investigations we detected the amino propyl-moiety as additional fragment from pyrrolidine oxirane ring decay. Therefore, during myosmine peroxidation generation of two high-reactive species appear to be plausible. Either 3-picolyl derivative could lead to 3-carbinol and subsequently to nicotinic acid, or other fragment, the propylamino-intermediate reacts to the corresponding amine. Existence of 3-carbinol was reported by myosmine-peroxidation, but elucidating the postulated new propyl-amino pathway is in focus of our current interest. Myosmine was peroxidated by hydro-genperoxide as reported earlier and the formed propylamine amount could be directly de-rivatized by dansylchloride. The derivatised amine (dansylated propylamine) was analysed with high pressure liquid chromatography (HPLC) instrumentation using fluorescence detection with excitation at 320 nm and emission at 500 nm. Retention times were compared by analysis of reference substances. Possibility of myosmine activation to high-reactive amine derivatives with peroxides allows conversion of the substance under influence of ROS (reactive oxygen species). This new activation pathway may result in interaction of the propylamino-mojety with proteins, cell-receptors or DNA. A possible carcinogenic risk of myosmine uptake by humans could not be excluded. Further experiments are demanded to elucidate the new pathway in view of a possible carcinogenic risk of myosmine. Acknowledgement: This work was supported by DFG grant Zwi59/2-2, and TY 81/1-2 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5549. doi:10.1158/1538-7445.AM2011-5549

Switching on the Electrocatalytic Ethene Epoxidation on Nanocrystalline RuO2

Ruthenium-based oxides with rutile structure were examined regarding their properties in electrocatalytic ethene oxidation in acid media. A possible promoting effect of chloride ions toward oxirane formation was explored. Online differential electrochemical mass spectrometry combined with electrochemical polarization techniques were used to monitor the potential dependence of organic products resulting from ethene oxidation as well as the reaction solution decomposition products. Quantum chemical modeling by means of density functional theory was employed to study key reaction steps. The ethene oxidation in acid media led to CO(2), whereas oxirane was formed in the presence of 0.3 M Cl(-). In the Cl(-) promoted oxidation on RuO(2), oxirane and a small amount of CO(2) were the only detected electro-oxidation products at potentials below the onset of Cl(2) and O(2) evolution, resulting from Cl(-) and water oxidation. It is demonstrated here that the epoxidation is a surface-related electrocatalytic process that depends on the surface properties. Cl acts as the epoxidation promoter that switches off the combustion pathway toward CO(2) and enables the epoxidation reaction channel by surface reactive sites blocking. The proposed epoxidation mechanism implies binuclear (recombination) mechanism for O(2) evolution reaction on considered surfaces.

Thorpe-Ingold acceleration of oxirane formation is mostly a solvent effect.

The Thorpe-Ingold hypothesis for the gem-dimethyl effect in the cyclization reactions of 2-chloroethoxide derivatives has been investigated computationally in the gas phase and in aqueous solution. Ab initio MP2/6-311+G(d,p) and CBS-Q calculations reveal little intrinsic difference in reactivity with increasing alpha-methylation for the series of reactants 1-3. However, inclusion of continuum hydration or of explicit hydration through mixed quantum and statistical mechanics (MC/FEP) simulations does reproduce the substantial, experimentally observed rate increases with increasing alpha-methylation. Analysis of the MC/FEP results provides clear evidence that the rate increases stem primarily from increased steric hindrance to hydration of the nucleophilic oxygen atom with increasing alpha-methylation. Thus, the gem-dimethyl acceleration of oxirane formation for 1-3 is found to be predominantly a solvent effect.

Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors.

A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways.

Studies on the ketone‐catalyzed decomposition of caroate in aqueous alkaline medium

AbstractThe kinetics of ketone‐catalyzed decomposition of caroate (peroxomonosulfate) was studied in aqueous alkaline medium at 25°C. The rate follows simple second‐order kinetics, first order in each [Ketone] and [PMS]. The rate constant values are independent of hydroxide ion concentrations over the range from 0.05 M to 0.15 M. The experimental results suggest that the nucleophilic addition of SO ion at the carbonyl carbon leads to the formation of oxirane intermediate in the rate‐determining step. Oxirane reacts rapidly with another SO to give the parent ketone, oxygen, and SO. The observed substituent effect on the activation energy EA and Arrhenius (A) factor suggests that the electron‐donating substituents stabilize the activated state and make the entropy of activation more negative. This can be explained by the fact that the mechanism of oxirane formation shifts from concentric to nonconcentric process as we go from acetone to 3‐hexanone. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 483–488, 2005

Biochemical and spectroscopic studies on (S)-2-hydroxypropylphosphonic acid epoxidase: a novel mononuclear non-heme iron enzyme.

The last step of the biosynthesis of fosfomycin, a clinically useful antibiotic, is the conversion of (S)-2-hydroxypropylphosphonic acid (HPP) to fosfomycin. Since the ring oxygen in fosfomycin has been shown in earlier feeding experiments to be derived from the hydroxyl group of HPP, this oxirane formation reaction is effectively a dehydrogenation process. To study this unique C-O bond formation step, we have overexpressed and purified the desired HPP epoxidase. Results reported herein provided initial biochemical evidence revealing that HPP epoxidase is an iron-dependent enzyme and that both NAD(P)H and a flavin or flavoprotein reductase are required for its activity. The 2 K EPR spectrum of oxidized iron-reconstituted fosfomycin epoxidase reveals resonances typical of S = (5)/(2) Fe(III) centers in at least two environments. Addition of HPP causes a redistribution with the appearance of at least two additional species, showing that the iron environment is perturbed. Exposure of this sample to NO elicits no changes, showing that the iron is nearly all in the Fe(III) state. However, addition of NO to the Fe(II) reconstituted enzyme that has not been exposed to O(2) yields an intense EPR spectrum typical of an S = (3)/(2) Fe(II)-NO complex. This complex is also heterogeneous, but addition of substrate converts it to a single, homogeneous S = (3)/(2) species with a new EPR spectrum, suggesting that substrate binds to or near the iron, thereby organizing the center. The fact that NO binds to the ferrous center suggests O(2) can also bind at this site as part of the catalytic cycle. Using purified epoxidase and (18)O isotopic labeled HPP, the retention of the hydroxyl oxygen of HPP in fosfomycin was demonstrated. While ether ring formation as a result of dehydrogenation of a secondary alcohol has precedence in the literature, these catalyses require alpha-ketoglutarate for activity. In contrast, HPP epoxidase is alpha-ketoglutarate independent. Thus, the cyclization of HPP to fosfomycin clearly represents an intriguing conversion beyond the scope entailed by common biological epoxidation and C-O bond formation.

Chemical Modification of a Highly Functionalized Taxane. The Consequences of an Absent Bridgehead Double Bond on Oxetane D‐Ring Construction.

An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular SN2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.

Fluorinated epoxides: 6. Chemoselectivity in the preparation of 2-[(heptafluoroisopropyl)methyl]oxirane from iodoacetate and iodohydrin precursors

Fluorinated iodoacetate (CF 3) 2CFCH 2CHICH 2OAc ( 1) (prepared by radical addition of perfluoroisopropyl iodide to allyl acetate) and fluorinated iodohydrin (CF 3) 2CFCH 2CHICH 2OH ( 2) (prepared from 1) were converted to the corresponding perfluoroalkylated oxirane (CF 3) 2CFCH 2CH(O)CH 2 ( 3) in the yield of 62%. The chemoselectivity of the oxirane formation appeared to be strongly dependent on the starting compound 1 or 2 and solvent used. Byproducts (CF 3) 2CFCHCHCH 2OH ( 4) and (CF 3) 2CFCHCHCH 2OAc ( 5) can form a major part of the products in the formation of epoxide 3.

Chemical modification of a highly functionalized taxane. The consequences of an absent bridgehead double bond on oxetane D-ring construction.

An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular S(N)2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.

Functionalization of poly(oxyethylene phosphonate) under phase-transfer catalyst conditions

The feasibility of the reaction of poly(oxyethylene phosphonate) 1 with chloroacetone under phase-transfer catalysis conditions for the preparation of poly(oxyethylene phosphonate)s bearing α-hydroxyl and oxirane groups in the side chains has been investigated. It has been established that the first stage of the reaction involves addition of the P–H to the carbonyl bond of chloroacetone resulting in poly(oxyethylene α-hydroxy phosphonate). During the second stage of the reaction, the oxirane formation proceeds via elimination of chloride ion. It is possible to direct the reaction to produce poly(oxyethylene phosphonate) 2, bearing 86.2% α-hydroxyl groups, or to poly(oxyethylene phosphonate) 3, bearing 91% oxirane groups. The structure of the products has been proved by means of 1H, 13C and 31P NMR spectroscopy. Thus design poly(oxyethylene phosphonate)s bearing α-hydroxyl and oxirane groups are of interest as polymer-carriers of drugs and polymers with their own bioactivity. The cytotoxicity of poly(oxyethylene phosphonate), poly(oxyethylene phosphonate)s bearing α-hydroxyl and oxirane groups has been studied.

Epoxide of a ketene acetal. The first 2,2-dialkoxyoxirane to be isolated

Dimethoxycarbene, generated at 110°C in benzene by thermolysis of 2,2-dimethoxy-5,5-dimethyl-Δ3-1,3,4-oxadiazoline, reacted with cyclohexanone to afford 2,2-dimethoxyspiro[2.5]-1-oxaoctane. It is the first oxirane of a ketene acetal that could be isolated and characterized by 1H NMR-, 13C NMR-, and IR spectroscopy. The identical oxirane might be expected from conrotatory cyclization of the appropriate carbonyl ylide. That ylide was generated under identical conditions by thermolysis of an oxadiazoline precursor (3,4-diaza-2,2-dimethoxy-1-oxaspiro[4.5]dec-3-ene) (14). The ylide could either cyclize or fragment to dimethoxycarbene and cyclohexanone. Addition of 4-tert-butylcyclohexanone, to trap dimethoxycarbene in competition with the cyclohexanone generated from 14 and, to leave the ylide closure pathway as the only route to the oxirane, showed that the carbonyl ylide does cyclize. However, fragmentation of the carbonyl ylide is relatively fast compared to its cyclization and most of it fragments to dimethoxycarbene and cyclohexanone. Oxirane formation from the carbene and ketone is probably either a concerted cycloaddition or it occurs in two steps, by nucleophilic attack at the carbonyl carbon to form the C—C bond first, prior to ring closure. If the carbene is bonded first to O of the carbonyl group, as it is in the carbonyl ylide, subsequent formation of the C—C bond is too slow, relative to fragmentation of the ylide, to afford the oxirane ring efficiently.Key words: carbonyl ylide, dialkoxyoxirane, dimethoxycarbene, oxadiazoline, oxirane.