DFT Study of Benzofuroxan Synthesis Mechanism from 2-Nitroaniline via Sodium Hypochlorite

The oxidative cyclization reaction of 2-nitroaniline via sodium hypochlorite to yield benzo-furoxan is investigated by the hybrid density functional theory B3LYP/6-31G(d,p) method. Solvent effects are estimated with the polarizable continuum model to optimize structures. The title reaction is predicted to undergo two pathways, each of which is a stepwise process.Path A includes four steps, namely oxidization, H-attack, hydrolysis, and cyclization. Path B involves the nucleophilic attack of OH^- to the H atom of the N-H bond and the proton transfer to the N atom of amino group leading to the cleavage of the N-H single bond in the amino group. The calculated results indicate that path A is favored mechanism for the title reaction. Furthermore, it is rational for one water molecule serving as a bridge to assist in the hydrolysis step of Path A and our calculations exhibit that this process is the rate-determining step.     

[1-Hydroxy-1-(2-hydroxyphenyl)ethyl]phosphonates and -phosphinates: convenient synthesis through intramolecular Abramov reaction and protective activity against influenza A

A combination of intramolecularization and tandem reaction methodologies has been applied to the synthesis of diethylammonium[1-hydroxy-1-(2-hydroxyphenyl)ethyl]phosphonates and -phosphinates, which were found to be unavailable through a standard intermolecular hydrophosphonylation/hydrolysis sequence. A mild hydrolysis of amidophosphites and -phosphonites, bearing 2-acetylphenoxy-fragment and a hydrolytically labile diethylamino-group at the same trivalent phosphorus atom, directly afforded the title compounds. The overall process probably consists of three steps: (i) selective hydrolysis of the P(III)–N bond to generate the hydrophosphoryl-type intermediates; (ii) formation of the strained 2-substituted 3-hydroxy-2-oxo-2,3-dihydro-1,2-benzoxaphospholes through intramolecular Abramov reaction; (iii) hydrolysis of the endocyclic P(IV)–O bond in the 1,2-benzoxaphospholes to give the acyclic products. Being only modestly active in vitro, at high dosage non-toxic water-soluble title α,γ-dihydroxyphosphonates and -phosphinates exhibited beneficial, but short-lasting effect against experimental influenza A infection (H3N2) in mice.     

An MNDO study of the reaction of methanol with fulminic acid and acetonitrile oxide

The reaction pathway of fulminic acid (HCNO) and acetonitrile oxide (CH₃CNO) with methanol as a nucleophile (RCNO + CH₃OH → RC(OCH₃)?NOH) and the formation of H-bonded complex with methanol have been studied using the MNDO method. MNDO-SCF calculations were performed with complete geometry optimization using the Davidon–Fletcher–Powell method. The reaction pathways were studied by varying all the bond lengths, the bond angles and the twist angles, using the distance C₃? O₂(R) between the carbon of the 1,3-dipoles and the oxygen of the methanol molecule as the reaction coordinate. The reaction is exothermic and proceeds in two steps. The first step is the formation of a five-centered hydrogen-bonded complex (INT ) and is the rate-determining step of the reaction. The second step involves the rearrangement of the H-bonded complex to the product, and this step requires a very small amount of activation energy. Thus, there is an intermediate on the reaction pathway, and therefore, the reaction is stepwise. Acetonitrile oxide is less reactive (activation energy 34.59 kcal/mol) relative to fulminic acid (activation energy 28.91 kcal/mol).     

Water solubility in calcium aluminosilicate glasses investigated by first principles techniques

First-principles techniques have been employed to study the reactivity of water into a calcium aluminosilicate glass. In addition to the well known hydrolysis reactions Si-O-Si+H₂O→Si-OH+Si-OH and Si-O-Al+H₂O→Si-OH+Al-OH, a peculiar mechanism is found, leading to the formation of an AlO₃-H₂O entity and the breaking of Al-O-Si bond. In the glass bulk, most of the hydrolysis reactions are endothermic. Only a few regular sites are found reactive (i.e. in association with an exothermic reaction), and in that case, the hydrolysis reaction leads to a decrease of the local disorder in the amorphous vitreous network. Afterwards, we suggest that ionic charge compensators transform into network modifiers when hydrolysis occurs, according to a global process firstly suggested by Burnham in 1975. Our theoretical computations provide a more general model of the first hydrolysis steps that could help to understand experimental data and water speciation in glasses.     

An investigation into the mechanism of the imidazolidinone catalyzed cascade reaction

The cascade reaction of α,β-unsaturated butyric aldehydes with 2-methyl furan and chlorinated quinone catalyzed by a (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidin-4-one·TFA was investigated by using density functional theory (DFT) calculations at the PCM(EtOAc)/B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level to (a) confirm the detailed reaction mechanism and key factors controlling the enantioselectivity; and (b) check the models of the iminium ion formation and hydrolysis process that were carried out in another reaction. Two favorable reaction channels, corresponding to the enantioselectivity of the (2R,3S)-product and (2S,3S)-product, have been characterized. The enantioselectivity is controlled by the steps involved in the formation of the C–C bond and the C–Cl bond in the iminium catalysis and the enamine catalysis, respectively. The calculated results explain the reaction mechanism and the enantioselectivity, which are in agreement with experimental observations, and may be helpful for understanding the reaction mechanism of similar cascade reactions.     

Theoretical study on the reactions of Zr<Superscript>+</Superscript> and Zr with CO<Subscript>2</Subscript> in gas phase

Density functional theory (DFT) calculations have been performed to explore the potential energy surfaces of C-O bond activation in CO₂ molecule by gas-phase Zr⁺ cation and Zr atom, for better understanding the mechanism of second-row transition metal reacting with CO₂. The minimum energy reaction path is found to involve the spin inversion in the different reaction steps. This potential energy curvecrossing dramatically affects reaction energetics. The present results show that the reaction mechanism is insertion-elimination mechanism along the C-O bond activation. All theoretical results not only support the existing conclusions inferred from early experiment, but also complement the pathway and mechanism for this reaction.     

Hydrolysis of hydro(pyrrolyl-1)borates

The hydrolysis of hydro(pyrrolyl-l)borates ([BH_n(NC₄H₄)_4-n]⁻, n = 1,2,3) can be treated as a kinetically one-step reaction outside of the mildly acidic region. In strongly acidic medium the hydrolysis takes place in a stepwise manner; the intermediates (boranes and the cationic boron compounds) being hydrolyzed more slowly than the borate anion. In the first step of the hydrolysis of [BH₃(NC₄H₄)]⁻ the B---H bond, while in case of [BH₂(NC₄H₄)₂]⁻ and [BH(NC₄H₄)₃]⁻ the B---N bond is breaking.In neutral and mildly alkaline medium, the hydrolysis is a general acid catalyzed reaction (A---S_E2 mechanism). It becomes to a special H⁺-ion catalyzed reaction (A-1 mechanism) in strongly alkaline region since the protonated intermediate can be reversed to the original borate upon reaction with the OH⁻ ion. The hydrolysis presumably takes place through an intermediate which is protonated on the pyrrolyl nitrogen. Concomitant to the hydrolysis an isotopic exchange reaction was observed on the C_α and C_β atoms of the pyrrolyl group in heavy water. In the hydrolysis of the [BH₃(NC₄H₄)]⁻-anion the N-protonated intermediate is assumed to be able to reverse to the original borate even in acidic or neutral region, at least in part.     

Etude cinetique de l'hydrolyse du paranitrophenylphosphate dans l'acetonitrile faiblement aqueux. Processus dissociatif.

Basic hydrolysis of paranitrophenylphosphate in acetonitrile of low water content (0.02 to 0.5 M) is an unimolecular process, with likely a phosphenium cation as intermediate. Comparison with reaction in water - also occuring through an unimolecular process - indicates that the large rate enhancement in CH₃ CN (3.10⁶ for [H₂O] 0.02 M) is entropy controlled.     

Reactions of Thorium Oxide Clusters with Water: The Effects of Oxygen Content

Thorium oxide has many important applications in industry. In this article, theoretical calculations have been carried out to explore the hydrolysis reactions of the ThO_n (n=1–3) clusters. The reaction mechanisms of the O-deficient ThO and the O-rich ThO₃ are compared with the stoichiometric ThO₂. The theoretical results show good agreement with the prior experiments. It is shown that the hydrolysis mainly occurred on the singlet potential surface. The overall reactions consist of two hydrolysis steps which are all favourable in energy. The effects of oxygen content on the hydrolysis are elucidated. Interestingly, among them, the peroxo group O₂²⁻ in ThO₃ is converted to the HOO− ligand, behaving like the terminal O²⁻ in the hydrolysis which is transformed into the HO− groups. In addition, natural bond orbital (NBO) analyses were employed to further understand the bonding of the pertinent species and to interpret the differences in hydrolysis.     

Highly active Fe36Co44 bimetallic nanoclusters catalysts for hydrolysis of ammonia borane: The first-principles study

In this paper, Fe₃₆Co₄₄ nanocluster structure is used to catalyze the hydrolysis reaction of ammonia borane to produce H₂. Firstly, we complete the construction of Fe₃₆Co₄₄ cluster structure and calculate the electronic properties of the cluster. By comparing the adsorption process of Ammonia Borane (AB) in active sites of the cluster, which have different Effective Coordination Number (ECN), the qualitative relationship between ECN and the catalytic activation of AB is clarified, and the optimal catalytic active site is obtained. Then, from the perspective of different reaction paths, we study the hydrolysis reaction of AB in multiple paths, and obtain 5 different reaction paths and energy profiles. The calculation results show that in the case of NH bond priority break (path 5), the reaction has the minimum rate-determining step (RDS) barrier (about 1.02 eV) and the entire reaction is exothermic (about 0.40 eV). So, path 5 is an optimal catalytic reaction path. This study will have an important guiding significance for the study of the AB hydrolysis reaction mechanism.     

Kinetics and mechanism of the defluorination of 8-fluoropurine nucleosides in basic and acidic media

For investigating the stability of C(8)-fluorine bond in 8-fluoropurine nucleosides some protected 8-fluoroguanosine, 8-fluoroinosine and 8-fluoroadenosine derivatives were prepared by direct fluorination of acetyl-protected purine nucleosides with elemental fluorine in solvents such as chloroform, acetonitrile and nitromethane. Fluorination reactions conducted in chloroform medium gave better yields of 8-fluoropurines. The fluorination yields were slightly lower when acetonitrile or nitromethane was used as solvent, but the product purification was found to be much easier. When the synthesized, protected fluoronucleosides were subjected to standard basic (NH₃ in methanol or 2-propanol) and acidic (HCl in methanol) deprotection conditions relevant to nucleoside chemistry, an efficient defluorination reaction took place. The kinetics of these defluorination reactions were conveniently followed, under pseudo-first-order reaction conditions, using ¹⁹F NMR spectroscopy. ¹H NMR, LC-MS and mass spectroscopy identified the products of the kinetic reaction mixtures. The defluorination reaction rate constants (k_obs) in basic media depended upon the electron density at C(8) while the k_obs data in acidic medium were determined by the pK_a of N⁷. An addition-elimination based mechanism (S_NAr) has been proposed for the defluorination reactions of these 8-fluoropurine nucleosides.     

A comprehensive theoretical study on the hydrolysis of carbonyl sulfide in the neutral water

The detailed hydration mechanism of carbonyl sulfide (COS) in the presence of up to five water molecules has been investigated at the level of HF and MP2 with the basis set of 6-311++G(d, p). The nucleophilic addition of water molecule occurs in a concerted way across the C==S bond of COS rather than across the C==O bond. This preferential reaction mechanism could be rationalized in terms of Fukui functions for the both nucleophilic and electrophilic attacks. The activation barriers, DeltaH( not equal) (298), for the rate-determining steps of one up to five-water hydrolyses of COS across the C==S bond are 199.4, 144.4, 123.0, 115.5, and 107.9 kJ/mol in the gas phase, respectively. The most favorable hydrolysis path of COS involves a sort of eight-membered ring transition structure and other two water molecules near to the nonreactive oxygen atom but not involved in the proton transfer, suggesting that the hydrolysis of COS can be significantly mediated by the water molecule(s) and the cooperative effects of the water molecule(s) in the nonreactive region. The catalytic effect of water molecule(s) due to the alleviation of ring strain in the proton transfer process may result from the synergistic effects of rehybridization and charge reorganization from the precoordination complex to the rate-determining transition state structure induced by water molecule. The studies on the effect of temperature on the hydrolysis of COS show that the higher temperature is unfavorable for the hydrolysis of COS. PCM solvation models almost do not modify the calculated energy barriers in a significant way.     

Analogs of pyrimidine mono- and polynucleotides

The phosphorylation of N₁-(l,4-dihydroxy-2-butyl) thymlne with β-cyanoethyl phosphate in the presence of dicyclohexylcarbodiimide was investigated. The optimum conditions for the specific synthesis of the diphosphate, the isomeric monophosphates, and the cyclophosphate of N₁-(l,4-dihydroxy-2-butyl)thyimine were found. A number of side products were identified, and the fundamental ideas regarding the reaction mechanism are given. It is shown that the “pseudoglycoside” bond in the synthesized compounds is more resistant to acid hydrolysis than the analogous bond in the natural prototypes.     

The substituent effects of the leaving groups on the aminolysis of phenyl acetates: DFT studies

The density functional theory B3LYP/6-31G(d, p) method is employed to study the mechanism of aminolysis reaction of p-substituted phenyl acetates (CH₃C(O)OC₆H₄X, X = H, NH₂, and NO₂) with ammonia in the gas phase. Two reaction pathways are considered: the concerted process and the stepwise pathway through neutral intermediates. The substituent effects of the leaving groups on the reactivity of phenyl acetates are discussed. The solvent effect of acetonitrile on the title reaction is also assessed by the polarizable continuum model (CPCM model) at B3LYP/6-31++G(d, p) level of theory. The calculated results show that the activation barriers of the concerted pathways are lower than those of the rate-controlling steps of the stepwise processes for all the three aminolysis reactions. This aminolysis of phenyl acetates is more favorable for X = NO₂ than for X = H and NH₂ in the gas phase and in acetonitrile.     

DFT Study of the BH4− Hydrolysis on Au(111) Surface

The mechanism of the catalytic hydrolysis of BH₄⁻ on Au(111) as studied by DFT is reported. The results are compared to the analogous process on Ag(111) that was recently reported. It is found that the borohydride species are adsorbed stronger on the Au⁰-NP surface than on the Ag⁰-NP surface. The electron affinity of the Au is larger than that of Ag. The results indicate that only two steps of hydrolysis are happening on the Au(111) surface and the reaction mechanism differs significantly from that on the Ag(111) surface. These remarkable results were experimentally verified. Upon hydrolysis, only three hydrogens of BH₄⁻ are transferred to the Au surface, not all four, and H₂ generation is enhanced in the presence of surface H atoms. Thus, it is proposed that the BH₄⁻ hydrolysis and reduction mechanisms catalyzed by M⁰-NPs depend considerably on the nature of the metal.     

A DFT Study on the Conversion of Aryl Iodides to Alkyl Iodides: Reductive Elimination of R−I from Alkylpalladium Iodide Complexes with Accessible β‐Hydrogens

DFT calculations have been performed on the palladium‐catalyzed carboiodination reaction. The reaction involves oxidative addition, alkyne insertion, C?N bond cleavage, and reductive elimination. For the alkylpalladium iodide intermediate, LiOtBu stabilizes the intermediate in non‐polar solvents, thus promoting reductive elimination and preventing β‐hydride elimination. The C?N bond cleavage process was explored and the computations show that PPh₃ is not bound to the Pd center during this step. Experimentally, it was demonstrated that LiOtBu is not necessary for the oxidative addition, alkyne insertion, or C?N bond cleavage steps, lending support to the conclusions from the DFT calculations. The turnover‐limiting steps were found to be C?N bond cleavage and reductive elimination, whereas oxidative addition, alkyne insertion, and formation of the indole ring provide the driving force for the reaction.     

A quantum chemical study of the mechanism of manganese catalase

The catalytic mechanism of manganese catalase has been studied using the Becke's three parameter hybrid method with the Lee, Yang and Parr correlation functional. On the basis of available experimental information on the geometric and electronic structure of the active manganese dimer complex, different possibilities were investigated. The mechanism finally suggested consists of eight steps. In the first steps, the first hydrogen peroxide becomes bound and its O–O bond is activated. This occurs in a spin-forbidden process found to be common in many biological processes where the O–O bond is cleaved, and two general rules are formulated for the requirements for a low activation energy in this type of reaction. As the O–O bond is cleaved a hydroxyl radical is initially formed in the overall rate-limiting step of the catalytic cycle. This radical is then immediately and irreversibly quenched in a strongly exothermic step. In the subsequent steps, the second hydrogen peroxide becomes bound and its two O–H bonds are broken, leading to the formation of an O₂ molecule, which is released. Parallels between the reversal of the present O–O cleavage mechanism in manganese catalase and the recently suggested O–O bond formation in photosystem II are drawn. Received: 12 July 2000 / Accepted: 12 July 2000 / Published online: 21 December 2000     

Density functional study of the l-proline-catalyzed α-aminoxylation of aldehydes reaction: The reaction mechanism and selectivity

The reaction mechanism of the l-proline-catalyzed α-aminoxylation reaction between aldehyde and nitrosobenzene has been investigated using density functional theory (DFT) calculation. Our calculation results reveal following conclusions [1]. The first step that corresponds to the formation of C–O bond, is the stereocontrolling and rate-determining step [2]. Among four reaction channels, the syn-attack reaction channel is more favorable than that of the anti one, and the TS-ss channel dominates among the four channels for this reaction in the step of C–O bond formation [3]. The intermolecular hydrogen bond between the acidic hydrogen of l-proline and the N atom of the nitrosobenzene in an early stage of the process catalyzes very effectively the C–O bond formation by a large stabilization of the negative charge that is developing at the O atom along the electrophilic attack [4]. The effect of solvent decreases the activation energy, and also, the calculated energy barriers are decrease with the enhancement of dielectric constants for C–O bond formation step. These results are in good agreement with experiment, and allow us to explain the origin of the catalysis and stereoselectivity for l-proline-catalyzed α-aminoxylation of aldehyde reaction. The addition of H₂O to substituted imine proline, intermolecular proton-transfer steps, and the l-proline elimination process were also studied in this paper.     

Tandem cleavage of 2,3,5-trimethyl 7-trifluoroacetyl-1,2,3,4-tetrahydro-pyrrolo[1,2-<Emphasis Type="Italic">c</Emphasis>]pyrimidine by activated alkynes,caused by Michael addition of a tertiary nitrogen atom to a triple bond

The interaction of 7-trifluoroacetyltetrahydropyrrolo[1,2-c]pyrimidine with acetylenedicarboxylic ester (DMAD) and ethyl propiolate in acetonitrile and alcohols has been studied. It was established that DMAD splits pyrrolopyrimidine at the aminal fragment in acetonitrile and methanol with the formation of 1-H-and 2-(N-dimethoxycarbonylvinyl-N-methyl)aminoethyl-1-methoxymethyl-3-methyl-5-trifluoroacetylpyrroles. In acetonitrile ethyl propiolate splits pyrrolopyrimidine both at the aminal fragment and at the C₍₃₎-N₍₂₎ bond (Hofmann reaction), but in ethanol only at the C₍₃₎-N₍₂₎ bond with the formation of 2-propenylpyrroles. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1082–1087, July, 2007.