Amines In Aprotic Solvents Research Articles

A Method for the Preparation of β-Amino-α,β-unsaturated Carbonyl Compounds: Study of Solvent Effect and Mechanism.

An efficient method for the preparation of β-amino-α,β-unsaturated carbonyl compounds is demonstrated. Bench-stable sodium 3-oxo-enolates were prepared from carbonyl compounds, and reacted with amines in the presence of an acid and a desiccant. DFT studies revealed contrasting mechanisms toward the reactivity of aliphatic amines in protic solvents and aromatic amines in aprotic solvents. While the former proceeds through the formation of an imine, the latter passes through the Michael addition-elimination mechanism.

The “dimer nucleophile mechanism” for reactions with rate‐determining first step: Derivation of the whole kinetic law and further treatment of kinetic results

AbstractOverwhelming evidence has been previously reported for the existence of the so‐called “dimer nucleophile mechanism” in aromatic nucleophilic substitutions by amines in aprotic solvents, for which the most prominent feature is the fourth‐order kinetics (third order in amine) that has been observed with many different substrate–nucleophile systems, especially those in which departure of the nucleofuge is the rate‐determining step. The mechanism has been confirmed by several other features, although other alternative mechanisms were suggested to explain the fourth‐order kinetics, no one has been able to explain the other above‐mentioned features. The present paper affords additional experimental evidence and derivation of the kinetic expressions for reactions with good nucleofugues, where the first step is rate determining. The work involves studies of the reactions of 2,4‐dinitrofluorobenzene and 2,4‐dinitrochlorobenzene with aniline and with alkyldiamines in toluene. The novelty of this work lies in the selection of substrate–nucleophile systems exhibiting kinetic behavior that allows estimations of the different k's involved. The satisfactory agreement between the quotients of k's calculated from sets of data obtained under different reaction conditions hereby reported indicates that the assumptions made are correct and that the whole treatment applied to the kinetic data is justified. All together, the results fit well with the reaction scheme involving the dimer nucleophile mechanism, adding new evidence to this mechanism that it is well established in the current literature. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 735–742, 2010

Hydrogen bonding in aromatic polyamine 2-guanidinobenzimidazole: Study based on density functional theory calculations

The role of inter- and intramolecular hydrogen bonding is very important for defining the reactivity of a great diversity of structures. In aromatic nucleophilic substitutions (S NAr) with amines in aprotic solvents, the attendance of hydrogen bond interactions (solute–solute and solute–solvent) has been proposed to understand kinetic results. In order to hold up recently reported experimental results on S NAr, in this paper we study structural and electronic properties of the aromatic polyamine 2-guanidinobenzimidazole, the aprotic polar solvent molecule dimethylsulphoxide and their interactions. Semi-empirical and ab-initio density functional theory calculations were performed to investigate, in particular, the possibility of hydrogen bond formation. It is found that 2-guanidinobenzimidazole presents intra- and intermolecular hydrogen bond formation leading to homo 2-GB and mixed solute–solvent dimers; being the latter energetically slightly more favorable than the former one.

Cyclic tetramers from 3,5-disubstituted 4-hydroxybenzenesulfonyl chlorides. A conformational study

Temperature-dependent 1 H- NMR experiments on the cyclic tetramers 1a, 1b, and 1c, obtained through reaction of the appropriate 3,5-disubstituted 4-hydroxybenzenesulfonyl chlorides and aliphatic tertiary amines in aprotic solvents, indicate that these cyclic compounds retain conformational flexibility. Free energies for the intra-annular rotation of the substituted benzene rings have been determined from the rate constants at the coalescence temperature. The influence of the nature of the ring substituents on the conformational barrier has been evaluated.

The synthesis of alkylamino-N-alkylnaphthalic-1,8-imides from 2- and 4-nitronaphthalic anhydrides by nitro group displacement

4-Alkylamino-N-alkylnaphthalic-1,8-imides and 2-alkylamino isomers have been synthesised by the reaction of 4-nitro- and 2-nitronaphthalic anhydrides respectively with primary amines in aprotic solvents in which reaction the nitro group in 3-nitronaphthalic anhydride is unreactive. Unsymmetrical compounds in the 2- and 4-series are derived from either the appropriate 4-nitro-N-alkylnaphthalic-1,8-imide or for 4-dialkylamino compounds from 4-nitronaphthalic anhydride by reaction with a secondary amine and then the 4-dialkylaminonaphthalic anhydride with a primary amine.

Effects of the Nucleophile Structure on the Mechanisms of Reaction of 1-Chloro-2,4-dinitrobenzene with Aromatic Amines in Aprotic Solvents

The kinetics of reactions of 1-chloro-2,4-dinitrobenzene with aniline and several substituted aromatic amines, B, in toluene shows a quadratic dependence of the second-order rate constant, kA, on [B], which is preserved even in the presence of increasing amounts of dimethylaniline, while the reaction with N-methylaniline shows a linear dependence of kA vs [B]. All these results are interpreted by the "dimer nucleophile" mechanism, and confirmed by the effects of a non-nucleophilic hydrogen bond acceptor tertiary amine which show the relevance of the structure of the nucleophile and the role of mixed aggregates in defining the mechanisms of aromatic nucleophilic substitutions with amines in aprotic solvents.

Mechanisms of aromatic nucleophilic substitution reactions by amines in solvents of low relative permittivity

AbstractThe evidence for the mechanisms proposed for aromatic nucleophilic substitution reactions by primary and secondary amines in aprotic solvents of low relative permittivity is reviewed.

Cyclic tetramers from 3,5- disubstituted 4-hydroxybenzenesulfonyl chlorides. Their synthesis and characterization.

The reaction of 3,5-dimethyl- ( 1a) and 3,5-dichloro-4-hydroxybenzenesutfonyl chloride ( 1c) with aliphatic tertiary amines in aprotic solvents affords the uncommon cyclic tetramers 3a and 3b, respectively.

The Ullmann Condensation Reaction of Haloanthraquinone Derivatives with Amines in Aprotic Solvents. VI. The Combination of Cu(I) and Hydroxo or Alkoxo Cu(II) as Effective Catalyst System

Abstract The reaction rate of the Ullmann condensation reaction of haloanthraquinone with ethylenediamine (EN) by copper(I) halide catalyst decreased along with the formation of inactive Cu(II) species [Cu(EN)2X2] by one-electron transfer from Cu(I) to haloanthraquinone. However, the combination of Cu(I) and Cu(II) salts, having an OH, OCH3, or OCOR group, enhanced the reaction rate in the following order: CuCl<CuCl–CuCl(OCH3)<CuCl–Cu(OCH3)2<CuCl–Cu(OH)2. In condensation using Cu(OR)2 or CuCl(OCH3) alone, the Cu(II) species was reduced to Cu(I) to form an active catalyst system [Cu(I)+Cu(II)]. On the other hand, CuBr2 or CuCl2 was not reduced and was ineffective for the reaction. These were confirmed by ESR measurements and the presence of a dehalogenation product. Mixed valence species bridged by the alkoxo or hydroxo group was proposed as an active species.

The ‘dimer mechanism’ in aromatic nucleophilic substitution by amines in aprotic solvents

AbstractThe mechanism of aromatic nucleophilic substitutions by amines in protic solvents is well established; on the contrary the mechanism/s of the reactions in aprotic solvents is/are still subject of controversy. The present paper describes several systems for which fourth‐order kinetics (third‐order in amine) were observed. A mechanism is proposed to account for this as well as other observation such as: overall negative energies of activation, quadratic dependence of kA with non‐nucleophilic tertiary bases, spectacular effects of hydrogen‐bond donor (HBD) and hydrogen‐bond acceptor (HBA) catalysts, etc. Other alternative mechanisms are also discussed.

Kinetische untersuchungen zur deprotonierung von Fe 3(CO) 9(μ 2-H)(μ 3-S-t-Bu) durch amine

Fe 3(CO) 9(μ 2-H)(μ 3-S-t-Bu) reacts with amines in aprotic solvents to give salts [Fe 3(CO) 9(μ 3-S-t-Bu)] −[AminH] + under deprotonation. The association of cluster and amine under formation of a solvated ion pair follows a second order rate law. The isotope effects k H/ k D as well as the rate constants are strongly correlated with the steric demand of the individual bases used: The largest rate constants and the largest isotope effects (up to k H/ k D = 13) are observed for bases with the least steric hindrance.

High-pressure kinetics of the reactions of p-benzoquinone with aliphatic amines in aprotic solvents

The rates of substitution reaction between p-benzoquinone and dibutylamine and of the electron-transfer reaction between chloranil and tripropylamine were examined spectrophotometrically, under pressure, in dichloromethane, 1,2-dichloroethane, chloroform, and acetonitrile. For the substitution to produce 2-dibutylamino-p-benzoquinone the reaction rate obeyed a third-order kinetic equation: first order with respect to p-benzoquinone and second order with respect to dibutylamine. The activation volume was as large as ca.–60 cm3 mol–1 in the solvents used, and a negative activation energy of –31 kJ mol–1 was observed in acetonitrile. A reaction scheme has been proposed where an electron-transfer reaction to form the p-benzoquinone anion radical occurs prior to the rate-determining step, which is the second attack by the amine. By taking into account the result that the electron transfer from chloranil to tripropylamine accompanied the activation volume of ca.–30 to –45 cm3 mol–1, the reaction volume of this process was estimated to be ca.–45 cm3 mol–1. Thus, in the p-benzoquinone–dibutylamine system we may reasonably assign the activation volume of –10 to –15 cm3 mol–1 to the second bimolecular attack by the amine.

The Ullmann Condensation Reaction of Haloanthraquinone Derivatives with Amines in Aprotic Solvents. V. The Formation of Active Catalyst by the Partial Oxidation of Copper(I) with Molecular Oxygen

Abstract Although copper(I) is a more effective catalyst than copper(II) in the Ullmann condensation reaction of haloanthraquinones with ethylenediamine in aprotic solvents under a nitrogen atmosphere, the oxidation products of copper(I) by molecular oxygen enhanced the reaction rate compared to copper(I) catalyst. From the studies on the effect of Cu(II) salt addition to Cu(I) salt, solvent effects, and ESR spectra, it was concluded that alkoxycopper(II) species, formed by the oxidation of Cu(I) with molecular oxygen in alcohol–ethylenediamine solution, acted cooperatively with Cu(I) to increase the catalytic activity. The idea was also supported by the fact that the condensation was remarkably accelerated by the combination of Cu(I) and chloromethoxycopper(II). Reaction pathways including the alkoxo and halogen bridged Cu(I)···Cu(II) mixed valence complex are proposed and discussed.

Complex formation by phenols with tertiary amines in aprotic media

1. The equilibrium constants (Kg) and the enthalpies of formation of H-bonds in complex-formating reactions of phenols with tertiary amines in aprotic solvents fall with a rise in the polarity of the medium and in its capacity for specific solvation with the phenols. 2. The introduction of the electron-accepting substituent chlorine into the para position of phenol leads to a considerable rise in Ke, but in the case of o-chlorophenol, because of the strong intramolecular H-bond the value of Ke is somewhat lower than for unsubstituted phenol. 3. With an increase in the steric accessibility of the N-atom of a tertiary amine and a rise in its basicity, Ke increases. The tertiary amines studied form the following sequence of decreasing Ke values: (C2H5)3N > (C4H9)3N > (CH2=CHCH2)3N.

The Ullmann Condensation Reaction of Haloanthraquinone Derivatives with Amines in Aprotic Solvents. IV. Kinetic Studies of the Condensation with Ethylenediamine

Abstract In the Ullmann condensation of bromoanthraquinones (AQBr) with ethylenediamine using copper(I) bromide as a catalyst, the reaction rate decreased with time which has been interpreted in terms of the formation of the ineffective copper(II) species. The kinetic investigation showed the reaction rate to be first order both for the copper(I) species and AQBr. After prolonged reaction the copper(I) species was quantitatively converted to the copper(II) species, the copper(II) species appearing to have little catalytic activity due to strong coordination with ethylenediamine. The reactivities of the haloanthraquinones were dependent on the ease of coordination with Cu(I) and the rate of Cu(II) formation. The mechanism, including the reaction between CuI(AQBr) and ethylenediamine, has been proposed and discussed.

The Ullmann Condensation Reaction of Haloanthraquinoiie Derivatives with Amines in Aprotic Solvents. III. The Formation and Role of Copper(II) Species in the Condensation with 2-Aminoethanol by Copper(I) Catalyst

Abstract The ESR spectra of the Ullmann condensation reaction system of 1-bromoanthraquinone-2-aminoethanol-CuBr showed that copper(II) species and 1-bromoanthraquinone radical anion were formed by an electron transfer from copper(I) species to 1-bromoanthraquinone. Although copper(II) species alone had little catalytic activity, the resulting copper(II) species increased the catalytic activity of the copper(I) species, and a pseudo-first order rate constant could be expressed as follows: k=k1[CuI]+k2[CuI][CuII]. According to the magnitude of k1 and k2C0, where C0 is the initial concentration of copper(I) catalyst, the reaction of haloanthraquinone with 2-aminoethanol by copper(I) catalyst can be classified into three modes. When k1<k2C0, an induction period is present. The possible mechanisms of the cooperation between copper(I) and copper(II) species have been proposed. It has been also found that 1-bromoanthraquinone radical anion was responsible for the debromination.

The Ullmann Condensation Reaction of Haloanthraquinone Derivatives with Amines in Aprotic Solvents. II. The Presence of an Induction Period in the Condensation with 2-Aminoethanol

Abstract An induction period was present in the Ullmann condensation reactions of 1-bromoanthraquinone(AQBr) with 2-aminoethanol(AE) in the presence of CuBr or CuI in aprotic solvents under a nitrogen atmosphere, while there was no induction period in the reaction systems of 1-iodoanthraquinone(AQI)–AE–CuBr, AQI–AE–CuI, and AQBr–AE–[Cu(CH3CN)4]ClO4. In the condensation system with a copper(I) catalyst, the Cu(I) species was oxidized to the Cu(II) species by means of an electron transfer from Cu(I) to haloanthraquinone as the reaction proceeded. By adding copper(II) bromide, the induction period vanished in the reaction system of AQBr–AE–CuBr. The copper(II) species increased the catalytic activity of the copper(I) species. The formation of the copper(II) species was responsible for the presence of an induction period and played an important role in the Ullmann condensation reaction of haloanthraquinones with amines in the presence of copper(I) salt as a catalyst.

Ullmann Condensation Reaction of Haloanthraquinone Derivatives with Amines in Aprotic Solvents

Abstract Cuprous catalysts were more effective than cupric ones in the Ullmann condensation of haloanthraquinones with amines in aprotic media. In the presence of Cu(I) catalyst, amines with a hydroxyl group (3-amino-1-propanol and 2-aminoethanol) were more reactive than the higher basic butylamine.

Studies on the pyridoxal phosphate site in glycogen phosphorylase b.

It is usually accepted that the adduct formed by reaction of pyridoxal phosphate with amines in aprotic solvents is a good model to stimulate some properties of the pyridoxal phosphate site in glycogen phosphorylase. The chemical structure of this adduct was not very well established. An aldimine structure is supported by the infrared, electronic absorption and nuclear magnetic resonance spectra given in this work. Therefore, we conclude that, at neutral pH, the pyridoxal phosphate is bound to the glycogen phosphorylase through a Schiff base structure and embedded in a hydrophobic environment. The polarographic measurements reported in this paper could explain the fact that, at neutral pH, the pyridoxal phosphate can not be reduced onto phosphorylase by NaBH4.

Kinetic isotope effects and tunnelling corrections in the proton-transfer reactions between 4-nitrophenylnitromethane and some tertiary amines in aprotic solvents

Kinetic isotope effects for the proton-transfer reaction between 4-nitrophenylnitromethane and the tertiary amine bases tri-n-butylamine, triethylamine and quinuclidine, in toluene, have been determined at temperatures between –15°C and +35°C by the stopped-flow technique. The rate ratios kH/kD for these bases at 25°C are respectively 14 ± 1, 11.0 ± 0.7 and 15.6 ± 0.6. The ratios of the pre-exponential factors AD/AH are respectively 1, 4 and 9. These values are interpreted in terms of tunnelling. Bell's equations for an unsymmetrical parabolic barrier give almost the same barrier width for all three bases. Earlier results for such reactions in acetonitrile are interpreted in terms of coupling of the motions of solvent molecules with that of the proton.