N-bromoacetamide Research Articles

Bromocyclization of Alkenoic Thioester and Access to Functionalized Sulfur-Heterocycles.

Although oxygen, nitrogen, and carbon have been extensively studied as nucleophilic elements in the halocyclization of alkenes, sulfur-based nucleophiles are relatively unexplored. Herein, we investigated bromocyclization chemistry involving unsaturated thioesters, with a focus on their use as potential S-nucleophiles. We developed a bromocyclization method that uses alkenoic thioesters and N-bromoacetamide (NBA) to form cyclic bromosulfides. The resulting 5-exo products are labile and can be used in various nucleophilic substitution reactions.

Bromination of codeine and its derivatives: Revisiting a 95 year old process

A safe and practical methodology was developed for the bromination of codeine and its derivatives using NBA (N-bromoacetamide) in the presence of TFAA (trifluoroacetic anhydride). The described protocol provides a viable alternative to the commonly used approach developed about a century ago, which requires hydrogen bromide gas as a reagent. In contrast, this facile and safe bromination occurs under mild conditions, has a broad scope, and provides the desired products in good to excellent yields.

Catalytic asymmetric brominative dearomatization reaction of benzofurans

A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [(DHQ)2PHAL] as the catalyst and N-bromoacetamide (NBAc) as the brominating reagent. A series of brominated spiro[benzofuran-2,5'-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 97% ee).

Structural analysis and antitumor potential of novel 5,6-disubstituted-17a-homo-17-oxa-androstane derivatives

Starting from 3β-acetoxy-17a-homo-17-oxa-androst-5-en-16-one (1) and in the reaction with N-bromoacetamide (NBA) and perchloric acid, the 5α-bromo-6β-hydroxy (2), 5β,6β-epoxy (3) and 5α,6β-dibromo (4) derivatives were obtained. The structure of compounds 2–4, particularly stereochemistry at C5 and C6, is established by detailed NMR and X-ray analysis. The in vitro antiproliferative activity of newly synthesized compounds 2–4 against six human tumor cell lines was evaluated. All three compounds showed a significant toxicity toward hormone-independent breast adenocarcinoma MDA-MB-231 and cervical carcinoma cells HeLa, while dibromo derivative 4 was active toward five human cancer cell lines. These new 5,6-disubstituted-D-homolactone steroidal compounds have also displayed selectivity toward cancerous cell lines against inactivity found for noncancerous control cell line. This selectivity was not found for control compound, well-known chemotherapy drug cisplatin.

K3PO4-catalyzed regiospecific bromoamidation of β, β-dicyanostyrene derivatives with N-bromoacetamide(NBA)

An efficient method for the bromoamidation of β,β-dicyanostyrene derivatives with N-bromoacetamide (NBA) was developed. This protocol provides a convenient process to convert β,β-dicyanostyrene derivatives into the vicinal haloamines in excellent yields(up to 99%) at room temperature in the presence of anhydrous K3PO4 as a catalyst without the protection of the inert gaseous in CH2Cl2. A total of 11 examples were investigated and all the products showed the regionspecific feature. Based on the observation of different activities for the different substrates involving the electron-rich or electron-deficient β,β-dicyanostyrenes, a possible Michael addition mechanism was proposed.

Kinetic and mechanistic studies of Rh(III)-catalysed oxidation of D-xylose and L-sorbose by N-bromoacetamide in perchloric acid medium

The kinetic and mechanistic studies of homogeneously Rh(III)-catalysed oxidation of D-xylose and L-sorbose by Nbromoacetamide (NBA) in perchloric acid medium were carried out at 40 °C. The reactions were first-order with respect to each of [NBA], [Rh(III)] and [H+] and zero-order in [sugar]. Variation of [Cl−] showed positive effect while variation of [Hg(OAc)2] showed negative effect on the rate of the reactions. Addition of acetamide (NHA) had a negative effect on the rate of the reaction. The rate of the reaction was unaffected by the change in ionic strength (μ) of the medium. Various activation parameters were calculated with the help of pseudo-first-order rate constant, k1, obtained at four different temperatures. The mechanisms involving RhCl4(H2O)2−, as reactive species of rhodium(III), and H2OBr+, as reactive species of NBA, are proposed which find support from the spectrophotometric evidence and activation parameters, especially the entropy of activation.

Kinetics of Oxidation of 3‐Benzoylpropionic Acid by N‐Bromoacetamide in Aqueous Acetic Acid Medium

The kinetics of oxidation of 3‐benzoylpropionic acid (KA) with N‐bromoacetamide (NBA) have been studied potentiometrically in 50:50 (v/v) aqueous acetic acid medium at 298 K The reaction was first order each with respect to [KA], [NBA] and [H+]. The main product of the oxidation is the corresponding carboxylic acid. The rate decreases with the addition of acetamide, one of the products of the reaction. Variation in ionic strength of the reaction medium has no significant effect on the rate of oxidation. But the rate of the reaction is enhanced by lowering the dielectric constant of the reaction medium. A mechanism consistent with observed results have been proposed and the related rate law was deduced.

Kinetic and mechanistic investigation of Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of d(+)melibiose by N-bromoacetamide in acidic medium

The kinetic and mechanistic study of homogeneously Pd(II)-catalysed and Hg(II)- co-catalysed oxidation of d(+)melibiose (mel) by N-bromoacetamide (NBA) in perchloric acid medium have been made at temperature 40 °C ± 0.1 °C. Kinetic results show first-order kinetics with respect to NBA at its low concentrations, tending to zero-order at its high concentrations. The oxidation rate is directly proportional to [Pd(II)] and [sugar], indicating first-order kinetics with respect to Pd(II) and sugar. Zero effect of Cl − and H + ions throughout their variation have been noted. First-order kinetics with respect to Hg(II) at its low concentration tends to zero-order at its higher concentration. Addition of acetamide (NHA) decreases the first-order rate constant ( k 1) while the rate of reaction is not influenced by the change in ionic strength (μ) of the medium. The first-order rate constant decreases with an increase in dielectric constant of the medium. Arabinonic acid, lyxonic acid and formic acid were identified as oxidation products of the reaction. Various activation parameters including the entropy of activation were also calculated. A plausible mechanism conforming to kinetic data, spectrophotometric observations, reaction stoichiometry and product analysis has been proposed.

K3PO4-Catalyzed Regiospecific Aminobromination of β-Nitrostyrene Derivatives with N-Bromoacetamide as Aminobrominating Agent

A very simple, efficient, and regiospecific protocol for aminobromination of a wide scope of beta-nitrostyrene derivatives with N-bromoacetamide (NBA) as nitrogen/bromine sources has been developed by using K(3)PO(4) as catalyst. The reaction proceeded smoothly and cleanly to give the bromoamines in good to excellent yields (78-99%) within 24 h in CH(2)Cl(2) at room temperature without protection of inert gases. A possible mechanism involving a nucleophilic conjugate addition was proposed.

Kinetics of oxidation of d(+)melibiose and cellobiose by N-bromoacetamide using a rhodium(III) chloride catalyst

The kinetics of oxidation of the sugars d(+)Melibiose (mel) and Cellobiose (cel) by N-bromoacetamide (NBA) in the presence of Rh(III) chloride as homogeneous catalyst in acidic medium at 45 °C have been investigated. The reactions are first-order with respect to [NBA], [Rh(III)] and [substrate]. The rate is proportional to [H+]. No effects of [Hg(II)], [NHA] or [Cl−] on the rates were observed. Ionic strength and dielectric constant also have little effect. The observed kinetic data, available literature and spectroscopic evidence lead us to conclude that NBAH+ and [RhCl5(H2O)]2− are the reactive species of NBA and Rh(III) chloride, respectively. The rate-determining step of the proposed reaction path common for both sugars gives an activated complex by the interaction of a charged complex species and neutral sugar molecule, which in the subsequent steps disproportionates into the reaction products with the regeneration of catalyst. The reactions have been studied at four different temperatures and with the help of first-order rate constant values, various activation parameters have been calculated. The main oxidation products of the reactions were identified as arabinonic acid, formic acid and lyxonic acid in the case of mel and arabinonic acid and formic acid in the case of cel.

Kinetics of the Oxidation of D‐Glucose and Cellobiose by Acidic Solution of N‐Bromoacetamide Using Transition Metal Complex Species, [RuCl3(H2O)2OH] −, as Catalyst

AbstractThe kinetics of Ru(III)‐catalyzed and Hg(II)‐co‐catalyzed oxidation of D‐glucose (Glc) and cellobiose (Cel) by N‐bromoacetamide (NBA) in the presence of perchloric acid at 40 °C have been investigated. The reactions exhibit the first order kinetics with respect to NBA, but tend towards the zeroth order to higher NBA. The reactions are the first order with respect to Ru(III) and are fractional positive order with respect to [reducing sugar]. Positive effect of Cl− and Hg(OAc)2 on the rate of reaction is also evident in the oxidation of both reducing sugars. A negative effect of variation of H+ and acetamide was observed whereas the ionic strength (µ) of the medium had no influence on the oxidation rate. The rate of reaction decreased with the increase in dielectric constant and this enabled the computation of dAB, the size of the activated complex. Various activation parameters have been evaluated and suitable explanation for the formation of the most reactive activated complex has been given. The main products of the oxidation are the corresponding arabinonic acid and formic acid. HOBr and [RuCl3(H2O)2OH]− were postulated as the reactive species of oxidant and catalyst respectively. A common mechanism, consistent with the kinetic data and supported by the observed effect of ionic strength, dielectric constant and multiple regression analysis, has been proposed. Formation of complex species such as [RuCl3·S·(H2O)OH]− and RuCl3·S·OHgBr·OH during the course of reaction was fully supported by kinetic and spectral evidences.

Mechanistic studies of oxidation of maltose and lactose by [H 2OBr] + in presence of chloro-complex of Rh(III) as homogeneous catalyst

Kinetic studies in homogeneously Rh(III)-catalyzed oxidation of reducing sugars, i.e. maltose and lactose, by N-bromoacetamide (NBA) in the presence of perchloric acid have been made at 40 °C using mercuric acetate as Br − ion scavenger. The results obtained for the oxidation of both reducing sugars show first-order dependence of the reactions on NBA at its low concentrations, which shifts towards zero-order at its higher concentrations. First-order kinetics in [Rh(III)] and zero-order kinetics in [reducing sugar] were observed. Positive effect of [Cl −] was observed in the oxidation of both maltose and lactose. Order of reaction was found to be one and half (1.5) throughout the variation of [H +] in the oxidation of both maltose and lactose. An increase in the rate of reaction with the decrease in [Hg(OAc) 2] and [NHA] was observed for both the redox systems. The rate of oxidation is unaffected by the change in ionic strength ( μ) of the medium. The main oxidation products of the reactions were identified as formic acid and arabinonic acid in the case of maltose and formic acid, arabinonic acid and lyxonic acid in the case of lactose. A common mechanism for the oxidation of both maltose and lactose, showing the formation of most reactive activated complex, [RhCl 4(H 3O)H 2OBr] +, and an unreactive complex, [RhCl 4(H 2O)(H 2OBrHg)] 2+, has been proposed. Various activation parameters have also been calculated and on the basis of these parameters, a suitable explanation for the reaction mechanism has been given.

Mechanistic studies of oxidation of d-arabinose and d-mannose by acidic solution of N-bromoacetamide in presence of chloro-complex of Ru(III) as homogeneous catalyst

The present paper deals with the kinetics and mechanism of Ru(III)-catalyzed and Hg(II)- co-catalyzed oxidation of d-arabinose(ara) and d-mannose(man) by acidic solution of N-bromoacetamide(NBA). First-order dependence of the reaction on both NBA and sugar at low concentrations shifts to zero-order at their higher concentrations. First-order kinetics with respect to [Ru(III)] throughout its variation was observed in the oxidation of both arabinose and mannose. A positive effect on the oxidation rate is observed for [Hg(II)] and [Cl −] whereas a negative effect is observed for [H +] and [acetamide]. Ionic strength does not influence the oxidation rate. The decrease in the rate of reaction with the increase in dielectric constant ( D) of the medium was observed in the oxidation of both reducing sugars and the kinetic data thus obtained were utilized to calculate d AB, the size of activated complex. Various activation parameters have also been calculated. Formic acid and erythronic acid for arabinose and formic acid and arabinonic acid for mannose were identified as main oxidation products of the reactions. Kinetic and equivalence studies together with spectral information, observed effect of dielectric constant on the rate of reaction, activation parameters and multiple regression analysis were made a basis for the formation of a common reaction mechanism for the catalyzed oxidation of both, arabinose and mannose.

1,3-Dibromo-5,5-dimethylhydantoin as a New Imidazolidine Dehydrogenating Agent: Synthesis of 4,5-Dihydro-1H-imidazolium Salts

A study about the scope of the method for the attainment of 4,5-dihydro-1H-imidazolium salts by dehydrogenation of N,N'-dibenzyl- and N-aryl-N'-benzylimidazolidines is presented. Employed dehydrogenating agents were N-bromoacetamide (NBA), N-bromosuccinimide (NBS), carbon tetrachloride and 1,3-dibromo-5,5-dimethylhydantoin (DBDMH). DBDMH was the choice reagent due to the purity of the attained products, lowest reaction times and highest yields.

Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of d-glucose and d-fructose by N-bromoacetamide in the presence of perchloric acid: a kinetic and mechanistic study

The kinetics of Pd(II)-catalysed and Hg(II)-co-catalysed oxidation of d-glucose (Glc) and d-fructose (Fru) by N-bromoacetamide (NBA) in the presence of perchloric acid using mercury(II) acetate as a scavenger for Br − ions have been studied. The results show first-order kinetics with respect to NBA at low concentrations, tending to zero order at high concentrations. First-order kinetics with respect to Pd(II) and inverse fractional order in Cl − ions throughout their variation have also been noted. The observed direct proportionality between the first-order rate constant ( k 1) and the reducing sugar concentration shows departure from the straight line only at very higher concentration of sugar. Addition of acetamide (NHA) decreases the first-order rate constant while the oxidation rate is not influenced by the change in the ionic strength ( μ) of the medium. Variation of [Hg(OAc) 2] shows a positive effect on the rate of reaction. The observed negative effect in H + at lower concentrations tends to an insignificant effect at its higher concentrations. The first-order rate constant decreases with an increase in the dielectric constant of the medium. The various activation parameters have also been evaluated. The products of the reactions were identified as arabinonic acid and formic acid for both the hexoses. A plausible mechanism involving HOBr as the reactive oxidising species, Hg(II) as co-catalyst, and [PdCl 3·S] −1 as the reactive Pd(II)–sugar complex in the rate-controlling step is proposed.

Ruthenium(III)‐catalyzed oxidation of cyclopentanol and cyclohexanol by N‐bromoacetamide

AbstractKinetic investigations on Ru(III)‐catalyzed oxidation of cyclopentanol and cyclohexanol by acidic solution of N‐bromoacetamide (NBA) in the presence of mercury(II) acetate as a scavenger have been carried out in the temperature range of 30–45°C. Similar kinetics was followed by both the cyclic alcohols. First‐order kinetics in the lower concentration range of NBA was observed to tend to zero order at its higher concentrations. The reaction exhibits a zero‐order rate dependence with respect to each cyclic alcohol, while it is first order in RuIII. Increase in [H+] and [Cl−] showed positive effect, while successive addition of acetamide exhibited negative effect on the reaction rate. Insignificant effect of sodium perchlorate, D2O, and mercury(II) acetate on the reaction velocity was observed. Cationic bromine has been proposed as the real oxidizing species. Various thermodynamic parameters have been computed. A suitable mechanism in agreement with the kinetic observations has been proposed. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 275–281, 2005

Kinetics of N‐bromination of 2‐oxazolidinone

AbstractThe kinetics of N‐bromination of 2‐oxazolidinone by transfer of Br from sodium hypobromite, N‐bromosuccinimide (NBS), or N‐bromoacetamide (NBA) were determined spectrophotometrically, at pH between 4.6 and 12.45 (depending on the brominating agent). The reaction with hypobromite was of first order with respect to both the hypobromite and the substrate. The bromination of oxazolidinone with NBS (or NBA) has been found to be a reversible process of order one with respect to both NBA (or NBA) and oxazolidinone in the forward direction, and order one with respect to SI (or ACAM) and the resulting N‐bromo‐oxazolidinone in the other. The pH dependence of the reaction rate was in keeping with a mechanism in which all the brominating agents (HOBr, BrO−, NBS and NBA) react predominantly with the anion of the substrate. Bimolecular bromination rate constants increased in the order BrO− < NBA < NBS < HOBr. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 642–649, 2004

Mechanism of Ir(III)‐catalysed and Hg(II)‐co‐catalysed oxidation of reducing sugars by N‐bromoacetamide in acidic medium

AbstractThe kinetics of Ir(III)‐catalysed and Hg(II)‐co‐catalysed oxidation of D‐glucose (Glu) and D‐fructose (Fru) by N‐bromoacetamide (NBA) were studied in acidic medium. The reactions follow identical kinetics, being zero order in each sugar concentration. The experimental results show a first‐order dependence on NBA and Ir(III) at low concentrations, but tending towards zeroth order at higher concentrations. A negative effect of variation of [H+], [Cl−] and [NHA] was observed whereas the ionic strength (I) of the medium has no influence on oxidation rate. The important feature of the reaction is that it follows a second‐order dependence on mercury(II) ion concentration at low concentrations, but it tends towards first order at higher concentrations. Various activation parameters were calculated and recorded. The corresponding acids were identified as the main oxidation products of the reaction. On the basis of the experimental findings, a suitable mechanism consistent with the observed kinetics was proposed. A comparative study was also made between the kinetic results of the present investigation and those of Ru(III)‐ and Pd(II)‐catalysed oxidations of reducing sugars. Copyright © 2004 John Wiley & Sons, Ltd.

Mechanism of Pd(II) and Hg(II) co-catalyzed oxidation of d-mannose and maltose by acidic solution of N-bromoacetamide

Abstract The kinetics of the homogeneously Pd(II) catalyzed oxidation of d -mannose (Man) and maltose (Mal) by N -bromoacetamide (NBA) in perchloric acid medium, using mercuric acetate as scavenger for Br − ions as well as co-catalyst, have been studied in the temperature range 35–50 °C. The reactions exhibit first-order kinetics at low concentrations of sugars (Man and Mal) and NBA, tending to zero-order at high sugar and NBA concentrations. The oxidation rate is directly proportional to [Pd(II)], while inverse fractional order in each of [H + ], [Cl − ] and [acetamide] was found. A positive effect on the rate of the reaction was observed on successive addition of [Hg(OAc) 2 ], whereas change in ionic strength ( μ ) of the medium has no effect on the reaction velocity. Formic acid and arabinonic acid (for both reducing sugars, i.e. Man and Mal) were identified as main oxidation products of reactions. The various activation parameters have also been evaluated. A plausible mechanism from the results of kinetic studies, reaction stoichiometry and product analysis is proposed.

Kinetics and mechanism of Ru(III) and Hg(II) co-catalyzed oxidation of d-galactose and d-ribose by N-bromoacetamide in perchloric acid

Kinetics of oxidation of reducing sugars d-galactose (Gal) and d-ribose (Rib) by N-bromoacetamide (NBA) in the presence of ruthenium(III) chloride as a homogeneous catalyst and in perchloric acid medium, using mercuric acetate as a scavenger for Br − ions, as well as a co-catalyst, have been investigated. The kinetic results indicate that the first-order kinetics in NBA at lower concentrations tend towards zero order at its higher concentrations. The reactions follow identical kinetics, being first order in the [sugar] and [Ru(III)]. Inverse fractional order in [H +] and [acetamide] were observed. A positive effect of [Hg(OAc) 2] and [Cl −] was found, whereas a change in ionic strength ( μ) has no effect on oxidation velocity. Formic acid and d-lyxonic acid (for Gal) and formic acid and l-erythronic acid (for Rib) were identified as main oxidation products of reactions. The various activation parameters have been computed and recorded. A suitable mechanism consistent with experimental findings has been proposed.