Phosphoryl transfer from phenyl and 4-nitrophenyl phosphates in aprotic and protic solvents : Amine catalysis and formation of oxyphosphorane and metaphosphate intermediates

The behavior of 4-nitrophenyl dihydrogen phosphate, ArOPO₃H₂, and of its tetra-n-butylammonium and tetramethylammonium salts, ArOPO₃H^?R₄N⁺, ArOPO₃^2?2(R₄N⁺), was studied in aprotic solvents, in the absence and in the presence of increasing amounts of alcohols or water. The reactions were investigated in the absence of amines, and in the presence of hindered and unhindered amines, diisopropylethylamine and quinuclidine. The course of the reactions was followed at 35° or at 70° by ³¹P and ¹H NMR spectrometry. Values for the approximate half-times of the reactions were estimated (± 25 %) from the times at which reactant signal intensity becomes equal to product signal intensity. The mononitrophenyl ester transfers its phosphoryl group to alcohols and water from the diprotonated acid by the addition-elimination mechanism via oxyphosphorane intermediates, and from the monoanion and dianion by the elimination-addition mechanism via the monomeric metaphosphate intermediate, PO₃^?. Formation of PO₃^? is faster from dianion than from monoanion in acetonitrile and in alcohol solutions. Conversely, PO₃^? is generated at a faster rate from monoanion than from dianion in aqueous solution. This effect results from a decrease in the rate of formation of PO₃^? in the solvent series: acetonitrile > alcohols > water. The rate depression as a function of the medium is greater for the dianion than for the monoanion, and is attributed to greater solvation of the more polar phosphate ground state than of the less polar transition state in the more polar protic solvents. Unhindered amines add to 4-nitrophenyl phosphate monoanion, but not to the dianion. The oxyphosphorane intermediate thus formed collapses to aroxide ion and a protonated dipolar phosphoramide which is rapidly deprotonated by the relatively basic 4-nitrophenoxide: ArOPO₃H^? + CH(CH₂CH₂)₃N(acetonitrile ? CH(CH₂CH₂)₃N⁺P(O)(OH)O^? + ArO^?? CH(CH₂ CH₂)₃N⁺PO₃^2?+ ArOH → CH(CH₂CH₂)₃N + PO₃^?. The postulated formation of PO₃^? by this route explains why the addition of quinuclidine to an acetonitrile solution containing the monoanion salt, ArOPO₃H^?R₄N⁺, and t?BuOH produces t-butyl phosphate at a faster rate than the addition of diisopropylethylamine to the same solution. 2,4-Dinitrophenyl phosphate, which was previously studied by the same techniques, reacts via oxyphosphorane intermediates from the diprotonated and the monoanion forms, and via monomeric metaphosphate, from the dianion form.     

Steric hindrance in the amine–epoxide reaction

The effect of steric hindrance on the reaction of silicon-containing aliphatic amines with phenylglycidyl ether (PGE) has been studied using ¹³C-NMR, a technique described by Sojka and Moniz [J. Appl. Polym. Sci., 20 , 1977 (1976)]. It was found that steric hindrance produced a large change in the reaction rate of the primary and secondary amine hydrogens, thus leading to a separation of the polymerization and cross-linking reactions.     

A DFT study on proton transfers in hydrolysis reactions of phosphate dianion and sulfate monoanion

B3LYP calculations were carried out on hydrolysis reactions of monosubstituted(R) phosphate dianion and sulfate monoanion. In the reacting system, water clusters (H₂O)₂₂ and (H₂O)₃₅ are included to trace reaction paths. For both P and S substrates with R = methyl group, elementary processes were calculated. While the phosphate undergoes the substitution at the phosphorus, the sulfate does at the methyl carbon. For the S substrate with R = neopentyl group, the product tert‐amyl alcohol was found to be formed via a dyotropic rearrangement from the neopentyl alcohol intermediate. For R = aryl groups, transition‐state geometries were calculated to be similar between P and S substrates. Calculated activation energies are in good agreement with experimental values. After the rate‐determining transition state of the substitution, the hydronium ion H₃O⁺ is formed at the third water molecule. It was suggested that alkyl and aryl substrates are of the different reactivity of the hydrolysis. © 2014 Wiley Periodicals, Inc.     

STEADY-STATE FLUORESCENCE METHOD FOR EVALUATING EXCITED STATE PROTON REACTIONS: APPLICATION TO FLUORESCEIN

Abstract Fluorescein is a complex fluorophore in the sense that it displays four prototropic forms (cation, neutral, monoanion and dianion) in the pH range 1–9. In experiments with fluorescein-labeled proteins we have sometimes observed complex nanosecond emission kinetics, which could be due to conversion of the excited monoanion into the excited dianion through an excited state proton exchange with a proton acceptor in the labeled protein. However, the literature is ambiguous on whether this possible excited state proton reaction of fluorescein does occur in practice. In this article we describe a general steady-state fluorescence method for evaluating excited state proton reactions of simple as well as complex pH-sensitive fluorophores and apply it to evaluate excited state proton reactions of fluorescein. The method depends on finding a buffer that can serve as an excited state proton donor-acceptor but does not significantly perturb ground state proton equilibrium and especially does not form ground (or excited state complexes) with the fluorophore. Our results show that the excited monoanion-dianion proton reaction of fluorescein does occur in the presence of phosphate buffer, which serves as a proton donor-acceptor that does not significantly perturb ground state proton equilibria. The reaction becomes detectable at phosphate buffer concentrations greater than 20 mM and the reaction efficiency increases with increase in phosphate buffer concentrations. The reaction is most clearly demonstrated by adding phosphate buffer to a solution of fluorescein at constant pH 5.9 with preferential excitation of the monoanion. Under these conditions, the excited monoanion converts to the dianion during its lifetime. The conversion is detected experimentally as an increase in dianion and decrease in monoanion fluorescence intensities with increase in phosphate buffer concentration. The absorption spectrum is not significantly perturbed by the increase in phosphate buffer concentration. To quantitate the reaction, we have recorded titration graphs of fluorescence intensity versus pH for fluorescein solutions at low (5 mM) and high buffer (1 M) concentrations with preferential excitation of the monoanion and preferential detection of the dianion emission. We have also developed theoretical expressions that relate fluorescence intensity to pH in terms of the concentration of the four prototrophic forms of fluorescein, extinction coefficients, fluorescence efficiencies and ground and excited state pK_a. The theoretical expressions give very good fits to the experimental data and allow evaluation of fundamental parameters such as pK_a and fluorescence efficiencies. The analysis of the experimental data shows that the excited monoanion-dianion reaction does not significantly occur at 5 mM phosphate buffer concentration. However, at 1 M buffer concentration the reaction is sufficiently fast that it practically achieves equilibrium during the lifetimes of the excited fluorescein monoanion and dianion. The pK_a* of the excited monoanion-dianion proton reaction is around 6.3. The results and methods presented here should be useful in the development and testing of pH-sensitive labeling fluorophores and fluorescent indicators.     

Intercalation of Cyclic Amines into α-Titanium Phosphate

The intercalation of some amines (aniline, benzylamine, cyclohexylamine,piperidine, pyridine, pyrazine and piperazine) into -titaniumphosphate, Ti(HPO₄)_2×H₂O,has been investigated by the batch method and/or by exposing the host to thevapour of the amines. The changes in the interlayer distance of the solidduring the intercalation process was followed by X-ray powder diffraction.The new intercalates were characterised by chemical and thermal analysis.Materials with a monolaminar and/or bilaminar arrangement of amine moleculesin the phosphate interlayer region are obtained depending on the nature ofthe amine. Due to steric hindrance, saturated phases are not obtained forall amines studied. The thermal decomposition of the intercalates (nitrogenatmosphere), takes place in three stages: dehydration, removal of amines andcondensation of the hydrogenphosphate to pyrophosphate groups.     

Studies on interactions of excited cadmium and mercury atoms with secondary and tertiary alkyl- and silylamines in gas phase

The Cd(³P₁)- and Hg(³P₁)-photosensitized emissions of some secondary and tertiary alkyl- and silylamines have been investigated under conditions of steady illumination at 493 and 298 K, respectively. The emission bands were observed at around 440 nm in the cadmium-photosensitized reactions of these amines. In contrast, no appreciable emission bands were observed in the mercury-photosensitized reactions of these amines. However, upon addition of tert-butyl alcohol to the amine-mercury system, an emission band evolved at around 350 nm in the mercury-photosensitization. The peak-wavelengths for secondary and tertiary alkyl- and silylamines are slightly shorter than the values predicted from the correlations between the peak wavelength and the first ionization energy obtained in the cadmium- and mercury-photosensitized luminescence of ammonia and primary amines. The quenching efficiencies of the cadmium and mercury resonance lines by secondary alkyl- and silylamines are higher than those by tertiary alkyl- and silylamines. These observations suggest that the steric hindrance by the alkyl and silyl groups to the approach of the nitrogen atom in the amines to excited cadmium and mercury atoms seems to be an important factor for the stabilization of the exciplexes and the quenching of the resonance lines. The behavior of silylamines is similar to that of alkylamines in cadmium- and mercury-photosensitized reactions.     

Röntgenstrukturanalytische Untersuchungen von Diazadiphosphetidinen

X‐Ray Structure Analysis of Diazadiphosphetidines Various diazadiphosphetidines are synthesized by a modified Kirsanov reaction and subjected to X‐ray crystal structure analysis, the results of which show steric hindrance in the cyclohexyl‐substituted compound 4 . A comparison of its structure to that of the fluorine compound 12 shows that the steric hindrance occurs only in the case of chlorophosphoranes. During the Kirsanov reaction with aliphatic amines branched at the α‐position, a further reaction is observed if the amine is added in excess. The phosphonium salt 11 is characterized by ¹H‐, ¹³C‐ and ³¹P‐NMR‐spectra, FAB‐mass spectrum, elemental analysis and X‐ray crystal structure analysis.     

Polymerisation anionique du methacrylate de methyle par les organoalcalins—II. Polymerisation en milieu solvant protonique et influence de la temperature sur les tacticites des polymeres

Anionic polymerization of methylmethacrylate, initiated by fluorenyl-alkali metals in amine media, gives syndiotactic polymers.With amines having high dielectric constant (NH₃ and MeA) Li⁺, Na⁺ and K⁺ give approximately the same values of differential enthalpies and entropies of activation for iso- and syndiotactic placements.With primary amines having moderate dielectric constant (5 < ? < 7), influence of the nature of the counter-ion has been observed. The syndiotacticity increases with increasing alkali cation radius.For the same ion pair, the syndiotacticity of the propagation depends on the nature of the primary amine. From the absorption peak shifts detected by u.v. spectroscopy, it has been suggested that the living carbanion is solvated by amines. Because of this solvation, the coordination bond between the carboxy group of the living chain-end and the counter-ion is weakened; the syndiotactic placement is thus favoured.The strength of the solvation phenomenon depends on the steric hindrance of the amine molecule. Differences between the stereoconfiguration propagations have been observed for the bulky cyclohexylamine and the smaller and less rigid n-butylamine and ethylamine. With iso-propylamine, the behaviour of the anionic propagation is intermediate.Finally, with free ions or loose ion pairs, the anionic propagation is not affected by solvation of the living carbanion.     

Phosphorylation of Amine Compounds with Sodium Cyclo-triphosphate

Abstract

Among inorganic linear and cyclic phosphates, cyclo-triphosphate has drawn special attention for its high reactivity with various amine compounds. A ring opening reaction to produce N-alkylamidotriphosphate derivatives proceeds under moderate conditions, e.g., at room temperature in aqueous solution. In spite of its potentiality as a phosphorylating agent for amino groups, a systematic investigation on the reaction mechanism has not fully carried out. This may be due to the lack of analytical methods which allow the quantitative examination of the reactions. In this work, HPLC with an anion-exchanger column developed for phosphate compounds together with ³¹P-NMR were applied to a kinetic study. It has been clarified that; 1) the reactivity of amine compounds is primarily correlated with the basisity of the amino groups, i.e., pKa values of its conjugate acids, though, branching at α carbon of the amino group greatry retards the reaction rate because of steric hindrance, and 2) some bifunctional reagents, such as ethylenediamine, propanediamine, ethanol-amine, and some α-amino acids produce heterocycles which contain P-N bond through an intramolecular reaction following the ring opening of cyclo-triphosphate. Ba or Mg salts of N-alkylamidotriphosphate derivatives have been prepared from mono amines, diamines, aminoalcohols, and aminoacids.     

Reactivity of amines toward tert-butoxy radicals: Effect of solvent and amine structure

The reactivity of amines towards tert-butoxy radicals depends upon the amine ionization potential and the solvent, indicating that polar structures contribute to the reactivity of these compounds. Nevertheless, the dependence with the amine potential is smaller than the one obtained for the quenching of carbonyl excited states by amines and other factors as the strength of the broken hydrogen bond and steric hindrance are also significant in determining the rate of the process.     

Heterometallic “butterfly” cluster [Fe3(CO)9(μ3-OBut)Au(PPh3)]

Alkylation of the [Fe₃(μ₃-O)(CO)₉]²⁻ dianion withtert-butyl iodide afforded the [Fe₃(μ₃OBu¹)(CO)₉]⁻ monoanion. The reaction of the latter with Au(PPh₃)Cl in the presence of TIBF₄ yielded the new heterometallic “butterfly” cluster [Fe₃(CO)₉(μ₃-OBu^t)Au(PPh₃)]. According to the X-ray data, both clusters synthesized contain the unchanged Fe₃(μ₃-O) fragment of the initial dianion. The addition of the Au(PPh₃) fragment to the monoanion occurred in such a way as to minimize steric changes. As a result, a “turned inside out” heterometallic “butterfly”, which contains the μ₃-O ligand on the outside rather than on the inside, was obtained. The dihedral angle characterizing the “butterfly” is 151°. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1779–1783, September, 1999.     

Hydrogen bonding by alcohols and amines

The pure base calorimetric method has been used to determine the enthalpies of hydrogen bond complex formation between aliphatic amines and alcohols. The enthalpies of complexation for the series methanol-n-butanol bonding with triethylamine increase with decreasing alkyl chain length in accordance with the electron donating properties of alkyl groups. Unexpectedly, the enthalpies for the complexes of n-butanol with tributylamine, tripropylamine, and triethylamine increase with decreasing alkyl chain length.Primary and secondary amines form hydrogen bonded complexes with n-butanol in which the amine protons form an NH···O bond with the alcohol and the alcohol hydroxyl proton donates a proton to the amine nitrogen. The difference in enthalpy of complex formation between tertiary amines and secondary amines is largely accounted for by the involvement of the amine proton of the secondary amine. Primary amines, like secondary amines, donate only one proton to the complex with n-butanol but have a larger complex enthalpy than secondary amines probably because of steric hindrance and differences in basicity.     

Nucleophilic 1,2-Shifts of Alkoxycarbonyl and Carboxylate Groups in the Benzilic-Acid Type Rearrangement of α,β-Dioxobutyric Esters

tert-Butyl α,β-dioxobutyrate (hydrate; 1d ) undergoes, at medium or high pH, the benzilic-acid rearrangement with exclusive 1,2-shift of the COO(t-Bu) group; the same is true for the corresponding isopropyl ester 1c and ethyl ester 1b at high pH, whereas at lower pH, the overall picture of these reactions is complicated by concurrent hydrolysis of the ester, followed by a 1,2-shift of the COO ^? group. Consequently, the shift of these electron-attracting groups cannot be considered to be systematically disfavoured (compared, e.g., with alkyl-group shifts). Kinetic measurements of the rearrangement show for both esters (as well as for the analogous ethyl ester 1b , and also for ethyl 3-cyclopropyl-α,β-dioxopropionate ( 4 )) a characteristic rate profile: at relatively low pH, k is proportional to [HO^?], approaching saturation with increasing [HO^?] (interpreted as complete transformation of the substrate into the hydrate monoanion), which is followed at higher pH by another rate increase with k proportional to [HO^?] (probably due to the reaction of the hydrate dianion). The similarity of k values for 1b-d shows that in the shift of COOR steric hindrance caused by R is negligible.     

A Modular Phosphorylated Glycoluril-Derived Molecular Tweezer for Potent Binding of Aliphatic Diamines

A molecular tweezer based on a glycoluril-derived framework bearing four phosphate groups was synthesized and shown to be capable of binding organic amines in aqueous solution. This work reports the K_a values for 30 complexes of this molecular tweezer and amine guests, determined by means of ¹H NMR titrations. Both the hydrophobic cavity and the phosphate groups contribute to the binding. Bulkier molecules and molecules bearing negatively charged groups like carboxylates in amino acids bind less tightly due to a steric clash and coulombic repulsion. The narrow cavity and the strong ionic interactions of the phosphate groups with ammonium guests favor binding of aliphatic diamines. These binding properties clearly distinguish this system from structurally related molecular clips and tweezers.     

Synthesis and Physicochemical Investigation of Nickel (II). Complexes with salicylaldehyde S-methylthiosemicarbazone

Salicylaldehyde S-methylthiosemicarbazone (H₂L) in the presence of ClO₄– forms with Ni^II the paramagnetic octahedral bis(ligand) chelate complexes while in the presence of NCS^?, CH₃COO^?, Py and γ-Pic it gives diamagnetic square planar mono(ligand) chelate complexes. In the paramagnetic complexes H₂L is coordinated as a neutral molecule (H₂L) and monoanion (HL^?), and in diamagnetic ones only as a monoanion, except the complex obtained in the presence of CH₃COO^?, where it is coordinated as a dianion (L^2?). The last form of the ligand is the result of deprotonation, besides OH-, the NH₂-group. The complexes have been characterized by elemental analysis, magnetic measurements, i.r. and diffuse-reflection spectra, molar conductivity and TG analysis.     

Pt-Sn/γ-Al2O3-catalyzed highly efficient direct synthesis of secondary and tertiary amines and imines

Versatile syntheses of secondary and tertiary amines by highly efficient direct N‐alkylation of primary and secondary amines with alcohols or by deaminative self‐coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt–Sn/γ‐Al₂O₃ catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing‐hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH‐imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH‐imine intermediate with another molecule of amine forms an N‐substituted imine which is then reduced to a new amine product by the in‐situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt–Sn/γ‐Al₂O₃ catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N‐substituted imines.     

Steric hindrance as a key factor on proton transfer in the σ-adduct forming reactions of o -substituted anilines with 1,3,5-trinitrobenzene in dimethylsulfoxide

Kinetic and equilibrium studies are reported of the reactions of 1,3,5-trinitrobenzene (TNB) with a series of o-substituted anilines in dimethyl sulfoxide (DMSO) in the presence of 1,4-diazabicyclo[2.2.2.]octane (DABCO). The pK _a values in DMSO for the aniline derivatives were measured using the proton-transfer equilibrium with 2,4-dinitrophenol. Kinetic studies are compatible with a two-step process involving initial nucleophilic attack on TNB by amine to give a zwitterionic intermediate which may transfer an acidic proton to DABCO to yield the anionic product. The results indicate steric hindrance to proton transfer in reactions involving 2,6-disubstituted anilines.     

Derivatizat Ion of Primary Aromatic Amines with Fluorescamine

Abstract

Fluorescamine forms stable, fluorescent derivatives with sterically-unhindered primary aromatic amines in both aqueous (borate buffer, pH 9/acetonitrile) and nonaqueous (pyridine/-acetonitrile) media. Aromatic amines with a substituent such as a methyl group or an aromatic ring ortho to the amine functionality either derivatized poorly or not at all because of steric hindrance.     

‘Reductive ozonolysis’ via a new fragmentation of carbonyl oxides

This account describes the development of methodologies for ‘reductive’ ozonolysis, the direct ozonolytic conversion of alkenes into carbonyl groups without the intermediacy of 1,2,4-trioxolanes (ozonides). Ozonolysis of alkenes in the presence of DMSO produces a mixture of aldehyde and ozonide. The combination of DMSO and Et₃N results in improved yields of carbonyls but still leaves unacceptable levels of residual ozonides; similar results are obtained using secondary or tertiary amines in the absence of DMSO. The influence of amines is believed to result from conversion to the corresponding N-oxides; ozonolysis in the presence of amine N-oxides efficiently suppresses ozonide formation, generating high yields of aldehydes. The reactions with amine oxides are hypothesized to involve an unprecedented trapping of carbonyl oxides to generate a zwitterionic adduct, which fragments to produce the desired carbonyl group, an amine, and ¹O₂.     

Steric effects in the reaction of alkyl-phenyl and dialkyl-sulphides with chloramine-T

The rate of the reaction of dialkyl- and alkyl-phenyl-sulphides with TsNHCl increases with the increasing +I effect of the S-substituents, while the steric effect is only of minor importance. Rate constants of the reaction of dialkyl sulphides can be correlated with the Taft equation (?^* = ?1.96, δ = 0.285). The effect of ring size of cyclic sulphides on the reaction is discussed. The change of the rate constants with varying S-alkyl substituents is in agreement with a sterically unhindered electrophilic addition of Cl⁺ on bivalent sulphur, leading to chlorosulphonium ion. Sulphimides and sulphoxides are formed from the chlorosulphonium intermediates in the subsequent S_N-type reactions with different steric control.