The Initial Stage of the Reaction of Melamine with Formaldehyde

The concentration-time relationships of the individual active species in the oligocondensation stage of the reaction of melamine with formaldehyde have been investigated, mainly by electrochemical methods. Based on the reaction equations, a kinetic model of the overall reaction was established and the rate constants were calculated by numerical methods. The results suggest the hydroxy-methylamines are converted to methylene and dimethylene ether bridged compounds by acid- and base-catalyzed reactions, respectively. At pH 7-10 the formation of methylene bridges by base-catalyzed scission of dimethylene ether bridges may occur.     

Kinetics and mechanism of tetrahydrofuran synthesis via 1,4-butanediol dehydration in high-temperature water

We conducted an experimental investigation into the kinetics and mechanism of tetrahydrofuran synthesis from 1,4-butanediol via dehydration in high-temperature liquid water (HTW) without added catalyst at 200-350 degrees C. The reaction was reversible, with tetrahydrofuran being produced at an equilibrium yield of 84% (at 200 degrees C) to 94% (at 350 degrees C). The addition of CO2 to the reaction mixture increased the reaction rate by a factor of 1.9-2.9, because of the increase in acidity resulting from the formation and dissociation of carbonic acid. This increase was much less than that expected (factor of 37-60) from a previously suggested acid-catalyzed mechanism. This disagreement prompted experiments with added acid (HCl) and base (NaOH) to investigate the influence of pH on the reaction rate. These experiments revealed three distinct regions of pH dependence. At high and low pH, the dehydration rate increased with increasing acidity. At near-neutral pH, however, the rate was essentially insensitive to changes in pH. This behavior is consistent with a mechanism where H2O, in addition to H+, serves as a proton donor. This work indicates that the relatively high native concentration of + (large KW), which has commonly been thought to lead to the occurrence of acid-catalyzed reactions in HTW without added catalyst, does not explain the dehydration of 1,4-butanediol in HTW without catalyst. Rather, H2O serves directly as the proton donor for the reaction.     

The photokinetics of phenothiazine dyes with titanium trichloride in different solvents

The kinetic parameters of photoinduced electron transfer reaction of two phenothiazine dyes, methylene blue and methylene green with titanium trichloride, were determined in water and different aqueous-alcoholic solvents at different acidities by using a specially designed optical system. The rate of photoinduced electron transfer reaction was measured by determining the quantum yield of the reaction. The methylene green had a higher reactivity as compared to methylene blue with titanium trichloride. The graphical analysis showed that the reaction of dye with titanium trichloride follows pseudo–first-order kinetics. A reaction mechanism was proposed by considering the different excited states of dye and their possible interaction with the solvent and titanium trichloride. The different steps in the reaction mechanism were taken into consideration for deriving rate equations, which were used to determine the different rate constants in the reaction mechanism in different solvents.     

有机废弃物在水热-热解耦合过程中NOx前驱物的释放机制研究

以城市污泥(SS)、中药药渣(HTW)和硅藻(DT)为对象,在水平管式反应器上对比研究了水热处理前后样品在热解过程中NO_x前驱物的生成特征,并结合热重(TGA)和X射线光电子能谱(XPS)表征分析了该耦合过程对NO_x前驱物的影响机制。结果表明,在240℃下进行水热预处理能直接或间接地影响样品燃料N在不同热解阶段时的转化路径,从而在整体层面上降低NO_x前驱物的释放量,例如当热解温度为900℃时,源于水热焦燃料N的NO_x前驱物为55.0%(SS_(240))、48.1%(HTW_(240))和51.2%(DT_(240)),比未经处理样品的NO_x前驱物释放量分别少9.5%(SS)、6.0%(HTW)和15.4%(DT),但若以原料燃料N为基准,源于水热焦的NO_x前驱物则比未经处理样品的NO_x前驱物释放量分别少90.1%(SS)、41.9%(HTW)和59.8%(DT),并且对NH_3的抑制效果高于HCN。进一步根据热失重曲线及其半焦N官能团的演变规律可以推测,水热预处理对NO_x前驱物的两条影响机制,即含N官能团的脱除(对于初次反应的NH_3释放)与含N官能团的稳定化(对于二次反应的HCN释放),可为废弃物的清洁利用提供理论参考。     

An activated sulfonylating agent that undergoes general base-catalyzed hydrolysis by amines in preference to aminolysis

Activated sulfonyl derivatives, similar to acyl ones, usually undergo aminolysis with amines in water as nucleophilic attack by the amine is preferred to hydrolysis. However, despite being active sulfonyl derivatives, four-membered heterocyclic sulfonamides, beta-sultams, do not undergo aminolysis in aqueous solution but preferentially react to give hydrolysis products only. The rate of the reaction of beta-sultams in buffered solutions of simple primary amines shows a first-order dependence on amine concentrations attributed to general base-catalyzed hydrolysis by the amine. Even N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, which is both a beta-sultam and a beta-lactam, undergoes hydrolysis at the sulfonyl center rather than aminolysis at either the sulfonyl or acyl center. The solvent kinetic isotope effects (SKIE, k(H(2)O)/k(D(2)O)) for the amine-catalyzed hydrolyses are 1.4 and 1.9 for the hydrolysis of N-benzoyl-beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, respectively, compatible with a general base-catalyzed mechanism. The amine-catalyzed hydrolysis gives a Bronsted beta value of +0.9 for both N-benzoyl beta-sultam and N-benzyl-4,4-dimethyl-3-oxo-beta-sultam, indicating that the general base amine is almost fully protonated in the transition state. A general base-catalyzed mechanism for hydrolysis rather than nucleophilic attack was also deduced for the reaction of N-benzyl-4,4-dimethyl-3-oxo-beta-sultam with carboxylate anions based on a SKIE of 1.7-1.9 and rate constants which fit the Bronsted plot for amines. In contrast to acyl transfer reactions, those for sulfonyl transfer appear to show an inverse reactivity-selectivity relationshipthe most active compounds being the most selective. The lack of reactivity of beta-sultams toward amine nucleophiles appears to be related to the mechanism of ring opening of beta-sultams with a decreased reactivity toward amines relative to hydroxide ion, probably related to the expulsion of the relatively poor leaving group amide anion.     

Mechanism of intramolecular catalysis in the hydrolysis of alkyl monoesters of 1,8-naphthalic acid

Hydrolysis of alkyl 1,8-naphthalic acid monoesters 1a-d is subject to highly efficient intramolecular nucleophilic catalysis by the neighboring COOH group. The reactivity for the COOH reaction depends on the leaving group pK(a), with values of β(LG) of -0.50, consistent with a mechanism involving rate determining breakdown of tetrahedral addition intermediates. The release of the steric strain of the peri-substitiuents in the highly reactive alkyl 1,8-naphthalic acid monoesters is fundamental to understand the observed special reactivity in this intramolecular reaction. DFT calculations show how the proton transfers involved in the cleavage of the neutral ester can be catalyzed by solvent water, thus facilitating the departure of poor alkoxide leaving groups.     

Biomimetic monoacylation of diols in water. Lanthanide-promoted reactions of methyl benzoyl phosphate

The direct monoacylation of diols by acyl phosphate monoesters in water is a biomimetic analogy to the enzymic aminoacylation of tRNA by aminoacyl adenylates. Without catalysis, acyl phosphate monoesters react rapidly with amines but very slowly with water and alcohols. Lanthanide ions dramatically and selectively facilitate the base-catalyzed monoacylation of diols in water by methyl benzoyl phosphate (MBP), a typical acyl phosphate monoester, in neutral solutions where reactive amines are protonated and unreactive. The reaction patterns and reactivity of various diols with MBP in the presence of lanthanides are consistent with a mechanism that involves internal addition from the conjugate base of the bis-bidentate complex of the lanthanide with the diol and MBP. The method is also applicable to reactions of nucleosides as evidenced by the selective monoacylation of the 2'- or 3'-hydroxyl group of adenosine, without reaction of the 5'-hydroxyl group or the 6-amino group. Analogues of adenosine without the diol are unreactive. This suggests that the method will selectively monoacylate the hydroxyl groups at the unique diol in tRNA that forms the 3'-terminus.     

两类药渣的水热提质效果及其燃烧特性研究

以中药药渣（HTW）与抗生素药渣（PMW）为对象，采用X射线光电子能谱、热重分析仪、量热仪与傅里叶红外分光光度计等技术分析两类药渣的差异并探究水热处理对药渣的提质效果与作用机理。结果表明，HTW含有大量木质纤维类成分，而PMW则以蛋白质与多糖为主；尽管这两类组分在水热提质中的转化途径有所区别，但均能提高药渣的热值（HTW：从19.4到26.2 MJ/kg；PMW：从19.1到29.3 MJ/kg）。同时，药渣的煤化程度随温度的上升而增加，甚至能接近烟煤水平。此外，由于水热过程中的脱挥发分与芳构化作用使得药渣中低能量的碳氢键转变为高能量的碳碳双键，不仅改善了药渣的燃烧性能，还使药渣在燃烧过程更为稳定且充分。     

A highly efficient way to recycle inactive stereoisomers of Bedaquiline into two previous intermediates via base-catalyzed C_(sp3)–C_(sp3) bond cleavage

Bedaquiline is a new medicine for pulmonary multi-drug resistant tuberculosis(MDR-TB), which is a pure enantiomer with two chiral centers. The current industrial preparation process requires the separation of active Bedaquiline from a mixture of four isomers. Obviously, direct dispose of the other three undesired stereoisomers will cause significant waste and increase the unnecessary cost of production. Here, we developed an efficient, facile and scalable process for recycling the inactive stereoisomers of Bedaquiline. All these inactive stereoisomers could be recycled by their conversion to two important intermediates in the Bedaquiline synthesis via a base-catalyzed Csp3–Csp3 bond cleavage of a benzyl alcohol intermediate. And the precise conditions and mechanism of the base-catalyzed cleavage reaction were discussed.     

A new base-catalyzed cleavage reaction for the preparation of protected peptides

A new base-catalyzed elimination reaction employing the hindered, non-nucleophilic bases tetramethylguanidine or 1,8-diazabicyclo-[5.4.0.]undec-7-ene has been developed for the removal of protected peptides from a 2-[4-(hydroxymethyl)phenyl-acetoxy]propionyl-resin. The proposed reaction mechanism involved cleavage of the ester bond between the peptide and resin via a base-catalyzed elimination. The protected peptide-resin cleavage reaction is mild, rapid and proceeds in good yield with a very simple work- up procedure. Four protected peptide-resins varying in size from seven to sixteen residues were prepared using the 2-[4-(hydroxymethyl)phenyl-acetoxy]- propionyl-resin and then cleaved in the protected form to demonstrate the utility of the new cleavage technique. The protected peptide cleavage products can be used in the preparation of larger peptides by fragment condensation.     

Kinetics of synthesis of bis‐(benzoxazolyl‐2‐methyl) sulfide under phase‐transfer catalysis conditions

Kinetics of synthesis of bis‐(benzoxazolyl‐2‐methyl) sulfide (BBMS) is investigated under phase‐transfer catalysis conditions. Thus, the reaction of 2‐chloromethylbenzoxazole and sodium sulfide is carried out in a two‐phase (organic/water) medium, and quaternary ammonium salt and quaternary phosphonium salt are used as phase‐transfer catalyst (PTC) in the reaction. The conversion of 2‐chloromethylbenzoxazole is dramatically enhanced by adding a small quantity of PTC and is also greatly affected by the reaction conditions. The effects of various reaction variables on the kinetics are investigated, including the amount of catalyst, the temperature, the kinds of catalysts, the kinds of solvents, and the agitation speed. An interfacial reaction mechanism is proposed to explain the characteristics of the reaction. A pseudo‐first‐order rate model is established to describe the relationship between the fractional conversion and the reaction time. The kinetics data demonstrate that the model is suitable to the reaction of synthesis of BBMS. © 2009 Wiley Periodicals, Inc. Int J Chem Kinet 41: 296–302, 2009     

Vesicular catalysis of an S(N)2 reaction: toward understanding the influence of glycolipids on reactions proceeding at the interface of biological membranes

The kinetics of the S(N)2 reaction of a series of aromatic alkylsulfonates with water and bromide ions in membrane mimetic media have been investigated. These media include vesicles formed from only synthetic amphiphiles, vesicles composed only of phospholipids and mixtures of these components. Special focus is placed on the influence of the addition of n-dodecyl-beta-glucoside as a mimic for glycolipids. The kinetic data have been analyzed by using the pseudophase model for bimolecular reactions. Contrary to previous results on a base-catalyzed E2 reaction (Org. Biomol. Chem. 2004, 2, 1789-1799), the presence of n-dodecyl-beta-glucoside at the vesicular surface does not lead to large rate accelerations for the S(N)2 reaction. In fact, when present at 50 mol % (i.e., the additive covers 34% of the vesicular surface) these glycolipid mimics appear not to affect the bimolecular rate constants, but they only decrease the local water concentration by about 40%. The reactivity of water at the surface of vesicles that are formed from cationic amphiphiles appears to be increased about 10-fold relative to the reactivity of water in the bulk liquid, whereas in zwitterionic vesicles the reactivity is comparable to that in bulk water. The obtained rate constants are also compared to micellar rate constants.     

Mononuclear heterocyclic rearrangement. Note I. Kinetic study of the rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole

The rates of the mononuclear heterocyclic rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1) into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole (II) have heen measured in dioxane/water (50:50, v:v) in the range of pS⁺ 3.8–12.2 at various temperatures and the activation parameters determined. On the basis of the results obtained, we present evidence for the occurrence of two different types of reaction: the first, base-catalyzed; the second, pS⁺ -independent. In the base-catalyzed range the catalysis is of the general type.     

Changes in the relative contribution of specific and general base catalysis in cationic micelles. The cyclization of substituted ethyl hydantoates

The rate-surfactant profiles for the HO(-)- and AcO(-)-catalyzed ring closure of two ethyl hydantoates, E2 and E3, to hydantoins with three cetyltrimethylammonium salts (CTAX, X = Br(-), Cl(-), or AcO(-)) are measured in 0.02 and 0.2 M acetate buffers 50% base with starting pH 4.65. Marked accelerations associated with large pH increases are found in 0.02 M buffered CTAOAc. Smaller accelerations and smaller pH changes are observed in 0.2 M buffered CTAOAc and CTACl. From these profiles, the micellar rate constants for the specific base- and general base-catalyzed reactions, and, respectively, of E2 and E3 are obtained separately. The resulting values of k(2,m)/k(w), E2/E3 rate constant ratios, and kinetic solvent isotope effects, KSIEs, are consistent with a strong predominance of the HO(-) reaction in the dilute buffer, while in the more concentrated buffer, specific and general catalysis compete for the two substrates. This result is in sharp contrast with that observed in water in which the reaction of E2 is almost exclusively specifically catalyzed. The increase in the general base-catalyzed pathway for E2 is attributed not to an increase in the rate constant for this pathway in micelles but to a smaller decrease than that for the specific catalysis (k(2,m)/k(w) = 0.2 and 0.4 for the specific and general catalysis, respectively). The different responses of the rate constants to the micellar media are interpreted as a larger effect of the interfacial polarity on the specific than on the general catalysis. The apparent contradiction between the rate constant decreases and the marked accelerations in micellar media is discussed in terms of pH changes, i.e., [HO(-)] changes, and of acetate inclusion via ion exchanges at micellar interfaces.     

Modeling acid and cationic catalysis on the reactivity of duocarmycins

Several catalyzed alkylation reactions of 9-methyladenine by a model [CPI, cyclopropa[c]pyrrolo[3,2-e]indol-4(5H)-one (1)] of duocarmycin anticancer drugs have been compared to the uncatalyzed reaction in gas phase and in water solvent bulk, using density functional theory at the B3LYP level with the 6-31+G(d,p) basis set and C-PCM solvation model. The effect on the CPI reactivity induced by water, formic and phosphoric acids (general acid catalysis), H3O+ (specific acid catalysis), sodium, and ammonium cation complexation (cationic catalysis) has been investigated. The calculations indicate that the specific acid catalysis and the catalysis induced by sodium cation complexation are strong in the gas phase, but solvation reduces them dramatically by electrostatic effects. The specific acid catalysis is still operative, but strongly reduced in water solution, where the reaction barrier is reduced by 8.6 kcal mol(-1) in comparison to the uncatalyzed reaction. The general acid catalysis induced by phosphoric acid (-7.3 kcal mol(-1)) and the catalysis induced by Na+ and NH4+ complexation become competitive, with a catalytic effect of -3.6 and -4.1 kcal mol(-1) in water, respectively. With the specific acid catalysis, the high acidity (low pK(a) value) of the conjugated acid of CPI (CPIH+), computed in water solution using both C-PCM (pK(a) = +2.6) and PCM-B3LYP/6-31+G(d,p) (pK(a) = +2.4) solvation models, suggests that the catalytic effects induced by NH4+ complexation could become more important than the specific acid catalysis and the general catalysis by H3PO4 under physiological conditions, due to concentration effects of the catalysts.     

The DMAP-catalyzed acetylation of alcohols--a mechanistic study (DMAP = 4-(dimethylamino)pyridine)

The acetylation of tert-butanol with acetic anhydride catalyzed by 4-(dimethylamino)pyridine (DMAP) has been studied at the Becke3 LYP/6-311 + G(d,p)//Becke3 LYP/6-31G(d) level of theory. Solvent effects have been estimated through single-point calculations with the PCM/UAHF solvation model. The energetically most favorable pathway proceeds through nucleophilic attack of DMAP at the anhydride carbonyl group and subsequent formation of the corresponding acetylpyridinium/acetate ion pair. Reaction of this ion pair with the alcohol substrate yields the final product, tert-butylacetate. The competing base-catalyzed reaction pathway can either proceed in a concerted or in a stepwise manner. In both cases the reaction barrier far exceeds that of the nucleophilic catalysis mechanism. The reaction mechanism has also been studied experimentally in dichloromethane through analysis of the reaction kinetics for the acetylation of cyclohexanol with acetic anhydride, in the presence of DMAP as catalyst and triethylamine as the auxiliary base. The reaction is found to be first-order with respect to acetic anhydride, cyclohexanol, and DMAP, and zero-order with respect to triethyl amine. Both the theoretical as well as the experimental studies strongly support the nucleophilic catalysis pathway.     

Solvent structure and hammerhead ribozyme catalysis

Although the hammerhead ribozyme is regarded as a prototype for understanding RNA catalysis, the mechanistic roles of associated metal ions and water molecules in the cleavage reaction remain controversial. We have investigated the catalytic potential of observed divalent metal ions and water molecules bound to a 2 A structure of the full-length hammerhead ribozyme by using X-ray crystallography in combination with molecular dynamics simulations. A single Mn(2+) is observed to bind directly to the A9 phosphate in the active site, accompanying a hydrogen-bond network involving a well-ordered water molecule spanning N1 of G12 (the general base) and 2'-O of G8 (previously implicated in general acid catalysis) that we propose, based on molecular dynamics calculations, facilitates proton transfer in the cleavage reaction. Phosphate-bridging metal interactions and other mechanistic hypotheses are also tested with this approach.     

The role of fluorine in the stereoselective tandem aza-Michael addition to acrylamide acceptors: an experimental and theoretical mechanistic study

Aza-Michael additions of alpha-amino esters to fluorinated acceptors take place in a highly stereoselective manner, to give partially modified Psi[NHCH2]retropeptides incorporating a hydrolytically stable trifluoroalanine mimic. The reaction mechanism has been investigated experimentally and theoretically, in order to explain the effect of the trifluoromethyl group on the reactivity and the origins of the experimentally observed stereocontrol. The reaction is a two-step process, involving a tandem aza-Michael addition followed by a stereoselective hydrogen transfer. Both steps are base-catalyzed. The high level of stereocontrol is the result of a combination of electrostatic interactions and steric effects.     

A DFT study on the mechanism of phosphodiester cleavage mediated by monozinc complexes

Density functional theory (DFT), Tao-Perdew-Staroverov-Scuseria (TPSS), is employed to study the reaction mechanism for the zinc-mediated phosphodiester cleavage reaction. The calculations indicate a general base catalysis mechanism. The flexibility of Zn(II) ion's coordination number (5 and 6) as well as the formation of hydrogen bonds between the coordinating water and the ester are responsible for the trapping (namely, coordinating to the Zn complexes) of the phosphodiester. The hydrogen bonds, between the water, the ester, and the nitrogen-ligand, tris(6-amino-2-pyridylmethyl)amine, not only stabilize the key five-coordinated phosphorus intermediates with a trigonal pyramidal PO5 unit but also lower the energy barriers for the proton transfer within the complexes by gaining stronger solvation energies.     

Influence of the nucleobase and anchimeric assistance of the carboxyl acid groups in the hydrolysis of amino acid nucleoside phosphoramidates

Nucleoside phosphoramidates (NPs) are a class of nucleotide analogues that has been developed as potential antiviral/antitumor prodrugs. Recently, we have shown that some amino acid nucleoside phosphoramidates (aaNPs) can act as substrates for viral polymerases like HIV‐1 RT. Herein, we report the synthesis and hydrolysis of a series of new aaNPs, containing either natural or modified nucleobases to define the basis for their differential reactivity. Aqueous stability, kinetics, and hydrolysis pathways were studied by NMR spectroscopy at different solution pD values (5–7) and temperatures. It was observed that the kinetics and mechanism (P? N and/or P? O bond cleavage) of the hydrolysis reaction largely depend on the nature of the nucleobase and amino acid moieties. Aspartyl NPs were found to be more reactive than Gly or β‐Ala NPs. For aspartyl NPs, the order of reactivity of the nucleobase was 1‐deazaadenine>7‐deazaadenine>adenine>thymine≥3‐deazaadenine. Notably, neutral aqueous solutions of Asp‐1‐deaza‐dAMP degraded spontaneously even at 4 °C through exclusive P? O bond hydrolysis (a 50‐fold reactivity difference for Asp‐1‐deaza‐dAMP vs. Asp‐3‐deaza‐dAMP at pD 5 and 70 °C). Conformational studies by NMR spectroscopy and molecular modeling suggest the involvement of the protonated N3 atom in adenine and 1‐ and 7‐deazaadenine in the intramolecular catalysis of the hydrolysis reaction through the rare syn conformation.