15N chemical shifts and one bond 15N?1H coupling constants in simple amides

An indirect method is employed for determining the ¹⁵N parameters at the natural abundance level in a series of simple acyclic and cyclic amides. The one bond coupling constant, ¹J(¹⁵N¹H), and the ¹⁵N chemical shift are measured as a function of the carbonyl substituent group or the ring size and the nature of the solvent (CCl₄ or H₂O). These ¹⁵N parameters are related to the amide bond structure, the nitrogen configuration and possible intermolecular hydrogen bonding (amide-amide or amide-water).     

Structural Characterization of N‐Alkylated Twisted Amides: Consequences for Amide Bond Resonance and N−C Cleavage

Herein, we describe the first structural characterization of N‐alkylated twisted amides prepared directly by N‐alkylation of the corresponding non‐planar lactams. This study provides the first experimental evidence that N‐alkylation results in a dramatic increase of non‐planarity around the amide N?C(O) bond. Moreover, we report a rare example of a molecular wire supported by the same amide C=O‐Ag bonds. Reactivity studies demonstrate rapid nucleophilic addition to the N?C(O) moiety of N‐alkylated amides, indicating the lack of n_N to π^*_C=O conjugation. Most crucially, we demonstrate that N‐alkylation activates the otherwise unreactive amide bond towards σ N?C cleavage by switchable coordination.     

Physicochemical Properties of Solutions of Amides in H2O and in D2O

Excess volume, partial molar volumes, viscosity, and ultrasound velocity in H₂O and D₂O solutions of formamide (FM), acetamide (AM), dimethylformamide (DMF), and dimethylacetamide (DMA) were studied at 20°C. The change in the excess volume of the various amide solutions on substitution of D₂O for H₂O varies both in magnitude and direction. On the other hand, the isotope effect on the ultrasound velocity behaves similarly in all cases. Its magnitude is greatest for pure water and then decreases monotonically with increasing amide concentration. Although the behavior of the concentration dependence of viscosity is similar to that for ultrasound velocity, the isotope effect on the viscosity behaves in a different way. For methyl-substitued amides, a maximum isotope effect is observed at amide mole fraction 0.2, but the isotope effect for FM and AM increases monotonically with increasing amide concentration. The differences in the behavior of amides in aqueous solution are discussed in terms of their interactions with water.     

The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides

Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods for amide bond formation, including those that are catalyzed by enzymes, is therefore of significant interest. The ATP‐dependent amide bond synthetase (ABS) enzyme McbA, from Marinactinospora thermotolerans, catalyzes the formation of amides as part of the biosynthetic pathway towards the marinacarboline secondary metabolites. The reaction proceeds via an adenylate intermediate, with both adenylation and amidation steps catalyzed within one active site. In this study, McbA was applied to the synthesis of pharmaceutical‐type amides from a range of aryl carboxylic acids with partner amines provided at 1–5 molar equivalents. The structure of McbA revealed the structural determinants of aryl acid substrate tolerance and differences in conformation associated with the two half reactions catalyzed. The catalytic performance of McbA, coupled with the structure, suggest that this and other ABS enzymes may be engineered for applications in the sustainable synthesis of pharmaceutically relevant (chiral) amides.     

Efficient Synthesis of Novel Thiazol‐2‐ylidene‐amides Using Carbonylthiourea Building Blocks

In this work, an efficient and versatile synthesis of novel thiazol‐2‐ylidene‐amides from various carbonylthiourea derivatives is described. A sequential alkylation–cyclization reaction between thioureas and propargyl bromide in the presence of DABCO in refluxing ethanol afforded 4‐methylthiazol‐2(3H)‐ylidene‐amide derivatives in good yields.     

Apparent molar volumes and compressibilities of selected electrolytes in dimethylsulfoxide

Densities at T = (293.15, 298.15, 303.15, 313.15, 323.15, and 333.15) K and sound velocities at T = 298.15 K of tetraphenylphosphonium bromide, sodium tetraphenylborate, sodium bromide, and sodium perchlorate in dimethylsulfoxide have been measured over the composition range from (0 to 0.3) mol · kg⁻¹. From these data, apparent molar volumes and apparent molar isentropic compressibilities at infinite dilution as well as the expansibilities have been evaluated. The results have been discussed in terms of employing tetraphenylphosphonium tetraphenylborate as a reference electrolyte in splitting the limiting apparent molar volumes and apparent molar isentropic compressibilities into ionic contributions.     

Synthesis and X-ray single crystal structure of a bivalent glycocluster

The crystal structure of a bivalent glycocluster containing aromatic amides reveals that alkylation of secondary amides alters amide configuration and thus carbohydrate presentation. This also facilitates non covalent interactions (azide-azide, carbonyl-pyranose and aromatic-pyranose) and thus carbohydrate-carbohydrate stacking.     

Partial molar volumes and adiabatic compressibilities ofN-acetyl-DL-serinamide andN-acetyl-L-threonmamide in dilute aqueous solutions

Densities and sound velocities in dilute aqueous solutions ofN-acetyl-DL-serinamide andN-acetyl-L-threoninamide were measured at 5, 15, 25, 35, and 45°C. Partial molar volumes and partial molar adiabatic compressibilities of these amino acid derivatives at infinite dilution were determined. The partial molar quantities for the parent amino acids, serine and threonine, were also determined and compared with the acetyl amide derivatives. The contribution of the side chain of theN-acetyl amino acid amide or amino acid to the partial molar quantities were estimated from the difference between the partial molar quantities for the solute studied and those for the corresponding species,N-acetyl-glycinamide or glycine, without the side chain.     

Partial molar volumes of tetraalkylammonium hydroxides in aqueous solution at 25°C

The densities of aqueous solutions of tetramethylammonium, tetraethylammonium, tetra-n-propylammonium and tetra-n-butylammonium hydroxide have been measured at 25°C in the concentration range 0.1–1.0 mol-kg^-1 . The apparent and partial molar volumes are calculated from the density measurements. The apparent molar volumes of the solutes show considerable deviation from the Debye-Hülckel limiting law, even at high dilution. The relation for the concentration dependence of the apparent molar volume is given in an analytical form. The limiting apparent molar volumes of the solutes are split into their ionic components by an extrathermodynamic approach and are discussed in terms of ion-solvent interactions. In this way, the limiting partial molar ionic volume for the hydroxide ion is found to be 2 cm³-mol^-1.     

Volumetric Properties of Binary Mixtures of Glycerol + <Emphasis Type="Italic">tert</Emphasis>-Butanol over the Temperature Range 293.15 to 348.15 K at Atmospheric Pressure

Densities of glycerol (1) + tert-butanol (2) mixtures were measured over the temperature range 293.15 to 348.15 K at atmospheric pressure, over the entire composition range, with a vibrating tube densimeter. Excess molar volumes, apparent and partial molar volumes of glycerol and tert-butanol, thermal isobaric expansivities of the mixture and partial molar expansivities of the components were calculated. The excess molar volumes of the mixtures are negative at all temperatures, and deviations from ideality increase with increasing temperature. Excess molar volumes were fitted to the Redlich–Kister equation. Partial molar volumes of glycerol decrease with increasing tert-butanol concentration. The temperature dependence of the partial molar volumes of glycerol is characterized by an inversion at x ₂≈0.7. “Negative expansion” of the limiting partial volumes of glycerol was observed.     

Densities,Refractive Indices and Excess Properties of N-<Emphasis Type="Italic">p</Emphasis>-Tolylbenzohydroxamic Acid in Dimethyl Sulfoxide at 298.15 to 313.15 K

Densities and refractive indices have been measured for N-p-tolylbenzohydroxamic acid (p-TBHA) in dimethyl sulfoxide (DMSO) as a function of concentration at (298.15, 303.15, 308.15, 313.15 and 318.15) K. The apparent molar volumes and partial molar volumes were obtained from these density data. The limited partial molar expansivities have been calculated from the temperature dependence of the limiting partial molar volume. The molar refractions were calculated from the experimental refractive index values for p-TBHA in DMSO. The excess volumes, deviations of the refractive indices, and molar refractions were also calculated. The results are discussed in terms of molecular interactions.     

Application of the Bjerrum association model to volumes of electrolytes in water and acetonitrile

The Bjerrum association model has been extended to partial and apparent molar volumes. It was tested for electrolytes in water and in acetonitrile using literature or new (n-propylammonium bromide) data to cover systems having association constants between 0 and 10⁵. The association constants and apparent distances of closest approach were obtained from conductivities. The volumes at low concentration can be fitted quantitatively to obtain by extrapolation the standard infinite dilution partial molar volume. Deviations at higher concentrations can be accounted for with a second virial coefficient.     

Apparent Molar Volume and Apparent Molar Expansibility of Rubidium, Cesium, and Ammonium Cyclohexylsulfamate in Aqueous Solution

Summary. The apparent molar volume of rubidium, caesium, and ammonium cyclohexylsulfamate was determined from the density data of their aqueous solutions at 293.15, 298.15, 303.15, 313.15, 323.15, and 333.15 K. From the apparent molar volume, determined at various temperatures, the apparent molar expansibility was calculated. The limiting apparent molar volume and apparent molar expansibility were evaluated and apportioned into their ionic components. The limiting partial molar ionic volumes and expansibilities are discussed in terms of the various effects of the ion in solution on the structure of water. It was shown that the limiting partial molar ionic expansibilities of the alkali-metal cations increase with their ionic radii. The coefficients of thermal expansion of the investigated solutions at 298.15 K were calculated and are presented graphically together with some alkali-metal cyclohexylsulfamates and tetramethylammonium cyclohexylsulfamate. The densities of the investigated solutions can be adequately represented by an equation derived by Redlich.     

Densities and Apparent Molar Volumes of Aqueous NaNO3 Solutions at Temperatures from 292 to 573 K and at Pressures Up to 30 MPa

Densities of four aqueous NaNO₃ solutions (0.100, 0.303, 0.580, 0.892 mol-kg^–1 H₂O) have been measured in the liquid phase with a constant-volume piezometer immersed in a precision liquid thermostat. Measurements were made at ten isotherms between 292 and 573 K. The range of pressure was 0.1–30 MPa. The total uncertainty of density, pressure, temperature, and concentration measurements were estimated to be less than 0.06%, 0.05%, 10 mK, and 0.014%, respectively. Values of saturated densities were determined by extrapolating experimental P- data to the vapor pressure at fixed temperature and composition. Apparent molar volumes were derived using measured values of density for the solutions and for pure water. The apparent molar volumes were extrapolated to zero concentration to yield partial molar volumes at infinite dilution. The temperature, pressure, and concentration dependence of partial and apparent molar volumes were studied. The measured values of density and apparent and partial molar volume were compared with data reported in the literature.     

Apparent Molar Volume and Apparent Molar Expansibility of Rubidium, Cesium, and Ammonium Cyclohexylsulfamate in Aqueous Solution

The apparent molar volume of rubidium, caesium, and ammonium cyclohexylsulfamate was determined from the density data of their aqueous solutions at 293.15, 298.15, 303.15, 313.15, 323.15, and 333.15 K. From the apparent molar volume, determined at various temperatures, the apparent molar expansibility was calculated. The limiting apparent molar volume and apparent molar expansibility were evaluated and apportioned into their ionic components. The limiting partial molar ionic volumes and expansibilities are discussed in terms of the various effects of the ion in solution on the structure of water. It was shown that the limiting partial molar ionic expansibilities of the alkali-metal cations increase with their ionic radii. The coefficients of thermal expansion of the investigated solutions at 298.15 K were calculated and are presented graphically together with some alkali-metal cyclohexylsulfamates and tetramethylammonium cyclohexylsulfamate. The densities of the investigated solutions can be adequately represented by an equation derived by Redlich.     

Stereocontrolled alkylative construction of quaternary carbon centers

Protocols for the stereodefined formation of alpha,alpha-disubstituted enolates of pseudoephedrine amides are presented followed by the implementation of these in diastereoselective alkylation reactions. Direct alkylation of alpha,alpha-disubstituted pseudoephedrine amide substrates is demonstrated to be both efficient and diastereoselective across a range of substrates, as exemplified by alkylation of the diastereomeric pseudoephedrine alpha-methylbutyramides, where both substrates are found to undergo stereospecific replacement of the alpha-C-H bond with alpha-C-alkyl, with retention of stereochemistry. This is shown to arise by sequential stereospecific enolization and alkylation reactions, with the alkyl halide attacking a common pi-face of the E- and Z-enolates, proposed to be opposite the pseudoephedrine alkoxide side chain. Pseudoephedrine alpha-phenylbutyramides are found to undergo highly stereoselective but not stereospecific alpha-alkylation reactions, which evidence suggests is due to facile enolate isomerization. Also, we show that alpha,alpha-disubstituted pseudoephedrine amide enolates can be generated in a highly stereocontrolled fashion by conjugate addition of an alkyllithium reagent to the s-cis-conformer of an alpha-alkyl-alpha,beta-unsaturated pseudoephedrine amide, providing alpha,alpha-disubstituted enolate substrates that undergo alkylation in the same sense as those formed by direct deprotonation. Methods are presented to transform the alpha-quaternary pseudoephedrine amide products into optically active carboxylic acids, ketones, primary alcohols, and aldehydes.     

Apparent and partial molar volumes of quaternary phosphonium halides in aqueous solutions

The apparent and partial molar volumes in aqueous solution were obtained for (n-Bu)₄PBr and (n-Bu)_4-n Ph _n PCl (n=1–4) at six temperatures from 1 to 55°C. The apparent molar expansibilities were also obtained. The hydrophobic character of the cations is reduced by replacing butyl groups with phenyl groups, as evidenced by the decrease in the magnitudes of the B _v -coefficient (negative for all n) and of the temperature dependent extrema found in the apparent molar volumes and expansibilities as a function of concentration. However, the extrema exist even with BuPh₃PCl at low temperatures. The result suggests that the phenyl groups weakly affect the butyl cospheres and cation-cation interactions.     

A rapid,simple, and mild procedure for alkylation of phenols,alcohols, amides and acids

A general, rapid method is described for alkylation of phenols and alcohols to give ethers, for amides to give N-substituted amides, and for acids to give esters. Differences in optimum reaction times suggest that where two or more such groups as phenol, alcohol, amide, and acid occur in the same molecule, differential alkylation could be effected with suitable substrates. Alkylation with primary alkyl halides was very effective but secondary halides showed evidence for competitive dehydrohalogenation before alkylation was complete and tertiary halides were rapidly dehydrohalogenated with no formation of alkylated derivatives. The method has been applied successfully to N,O-alkylation of peptides for mass spectrometric sequence determination. C-Methylation of peptidic amino-acid residues was observed only on carbon α to a carboxylic ester.     

Volumetric behavior of a bolaamphiphile in different amides-water and ethylene glycol-water mixtures

The effect of binary aqueous mixtures of ethylene glycol (EG), formamide (FA), N-methylformamide (NMF), dimethylformamide (DMF), and their pure phase on the apparent molar volume phi(V) of the bolaamphiphile decamethonium bromide (C10Me6) has been investigated at 298.15 K. The behavior of standard molar volumes V2(0) and transfer volumes Delta(t)phi(V) of C10Me6 from water to solvent/water (S/W) binary mixtures, shows different minima and maxima depending on the composition of the solvent. This behavior is influenced by the nature of the cosolvent and on the type of the solute and more or less corresponds to volumetric changes in the S/W mixture. The investigation of the transfer volumes in different fixed concentrations reveals an inversion of Delta(t)phi(V) values between the compositions, which suggests a differentiation of the effects of different volume contributions on the partial molar volume of ions. The correlation of Delta(t)phi(V) with the dielectric constant of the aqueous amide mixtures shows that the behavior of Delta(t)phi(V) vs x(amide) reflects the changes of epsilon(E) vs x(amide).     

Ion association in N-methylpyrrolidone and the N-methylpyrrolidone-water mixed solvent from data on heat capacity and density of solutions

Association constants for solutions of electrolytes in N-methylpyrrolidone (MP) and the MP-water mixed solvent at 298.15 K are calculated. It is shown that, over a wide range of concentrations, concentration dependences of apparent molar heat capacities and apparent molar volumes of the electrolytes in MP and MP-water mixtures are described adequately in terms of equilibria between ions and ion pairs of a single type in the solution.