Ortho-substituent effect promoted rapid cleavage of amide C–N bond under mild conditions

This article reports the ortho-substituent effect on the cleavage of the amide C–N bond. In the structure of N ^α -Phth-N-pyridinyl-amide, when the hydrogen atom in the 3-position of pyridine ring was replaced by alkoxy group, the amide C–N cleavage can take place in the 2-position of the pyridine ring. This transformation can proceed rapidly in methylamine ethanol solution under mild conditions to afford 2-amino-3-alkoxy pyridines.     

1,3-Thiazepines. 6. UV Spectroscopic and Theoretical Study of the Electronic Structures of 2-Aminotetrahydro- and 2-Iminotetrahydro-1,3-thiazepines

On the basis of studies of the electronic absorption spectra and quantum-chemical calculations of the energies and bond orders of a series of N-acetyl-N-aryl substituted 2-amino-4,5,6,7-tetrahydro-1,3-thiazepines and N-aryl substituted 2-iminohexahydro-1,3-thiazepines it has been concluded that the reason for the weak basicity of the ring nitrogen atom of the former is the acceptor properties of the amide carbonyl which obstructs the interaction of the unshared pair (USP) of this atom with the phenyl ring; in the case of the derivatives of hexahydroazepine the strengthening of the basic properties of the exocyclic nitrogen atom is associated with the conjugation of its USP with the -electrons of the benzene ring, which is strengthening by delocalisation of the USP of the sp³-hybridized ring nitrogen atom into the azomethine bond.     

Spectroscopic Identification of Cyclic Imide b2-Ions from Peptides Containing Gln and Asn Residues

In mass-spectrometry based peptide sequencing, formation of b- and y-type fragments by cleavage of the amide C–N bond constitutes the main dissociation pathway of protonated peptides under low-energy collision induced dissociation (CID). The structure of the b ₂ fragment ion from peptides containing glutamine (Gln) and asparagine (Asn) residues is investigated here by infrared ion spectroscopy using the free electron laser FELIX. The spectra are compared with theoretical spectra calculated using density functional theory for different possible isomeric structures as well as to experimental spectra of synthesized model systems. The spectra unambiguously show that the b₂-ions do not possess the common oxazolone structure, nor do they possess the alternative diketopiperazine structure. Instead, cyclic imide structures are formed through nucleophilic attack by the amide nitrogen atom of the Gln and Asn side chains. The alternative pathway involving nucleophilic attack from the side-chain amide oxygen atom leading to cyclic isoimide structures, which had been suggested by several authors, can clearly be excluded based on the present IR spectra. This mechanism is perhaps surprising as the amide oxygen atom is considered to be the better nucleophile; however, computations show that the products formed via attack by the amide nitrogen are considerably lower in energy. Hence, b₂-ions with Asn or Gln in the second position form structures with a five-membered succinimide or a six-membered glutarimide ring, respectively. b₂-Ions formed from peptides with Asn in the first position are spectroscopically shown to possess the classical oxazolone structure.      

N‐Benzylnicotinamide and N‐benzyl‐1,4‐dihydronicotinamide: useful models for NAD+ and NADH

3‐Aminocarbonyl‐1‐benzylpyridinium bromide (N‐benzylnicotinamide, BNA), C₁₃H₁₃N₂O⁺·Br⁻, (I), and 1‐benzyl‐1,4‐dihydropyridine‐3‐carboxamide (N‐benzyl‐1,4‐dihydronicotinamide, rBNA), C₁₃H₁₄N₂O, (II), are valuable model compounds used to study the enzymatic cofactors NAD(P)⁺ and NAD(P)H. BNA was crystallized successfully and its structure determined for the first time, while a low‐temperature high‐resolution structure of rBNA was obtained. Together, these structures provide the most detailed view of the reactive portions of NAD(P)⁺ and NAD(P)H. The amide group in BNA is rotated 8.4 (4)° out of the plane of the pyridine ring, while the two rings display a dihedral angle of 70.48 (17)°. In the rBNA structure, the dihydropyridine ring is essentially planar, indicating significant delocalization of the formal double bonds, and the amide group is coplanar with the ring [dihedral angle = 4.35 (9)°]. This rBNA conformation may lower the transition‐state energy of an ene reaction between a substrate double bond and the dihydropyridine ring. The transition state would involve one atom of the double bond binding to the carbon ortho to both the ring N atom and the amide substituent of the dihydropyridine ring, while the other end of the double bond accepts an H atom from the methylene group para to the N atom.     

How Strong is Hydrogen Bonding to Amide Nitrogen?

The protonation of the carboxamide nitrogen atom is an essential part of in vivo and in vitro processes (cis-trans isomerization, amides hydrolysis etc). This phenomenon is well studied in geometrically strongly distorted amides, although there is little data concerning the protonation of undistorted amides. In the latter case, the participation of amide nitrogen in hydrogen bonding (which can be regarded as the incipient state of a proton transfer process) is less well-studied. Thus, it would be a worthy goal to investigate the enthalpy of this interaction. We prepared and investigated a set of peri-substituted naphthalenes containing the protonated dimethylamino group next to the amide nitrogen atom (“amide proton sponges”), which could serve as models for the study of an intramolecular hydrogen bond with the amide nitrogen atom. X-Ray analysis, NMR spectra, basicity values as well as quantum chemical calculations revealed the existence of a hydrogen bond with the amide nitrogen, that should be attributed to the borderline between moderate and weak intramolecular hydrogen bonds (2–7 kcal ⋅ mol⁻¹).     

Etude des composés d'addition des acides de Lewis - XXXV. Note sur les composés d'addition entre amides et,respectivement, PdCl2 et PtCl2

The adducts of dimethylformamide, diethylformamide, dimethylacetamide and diethylacetamide with PdCl₂ and PtCl₂ have been prepared and the IR. spectra of the compounds in nujol mull or in CH₂Cl · CH₂Cl solution are studied. The lowering of the carbonyl frequency (amide I) shows that the metal is linked by a dative bond to the amide oxygen atom acting as a donor; the lowering is about 33 to 59 cm^?1. The decrease of the frequency of the carbonyl group vibration, observed in these cases as for other addition compounds of Lewis acids, is due to an intramolecular electronic displacement in the direction of the amid oxygen atom.     

4,5‐Di­hydro‐3‐methyl‐5‐(4‐methyl­phenyl)‐1H‐pyrazole‐1‐carbox­amide

The reaction between 4‐(4‐methyl­phenyl)­but‐3‐en‐2‐one and amino­guanidine produced an unexpected product of formula C₁₂H₁₅N₃O, consisting of a carbox­amide moiety joined to a substituted pyrazoline ring at one of the N atoms. The pyrazoline ring adopts a flat‐envelope conformation and the substituted phenyl ring is oriented almost perpendicular to the heterocycle. The carbonyl O atom has partial anionic character as a result of the transfer of π density from the two adjacent sp² N atoms and is involved in an intermolecular hydrogen bond with the amide group.     

Dinicotinamidium squarate

The crystal structure determination of the dinicotinamidium squarate salt, 2C₆H₇N₂O⁺·C₄O₄²⁻, is reported, with the squarate dianion residing on an inversion centre and the unique cation in a general position. Salt formation occurs by donation of two H atoms from squaric acid to the nicotin­amide base. The crystal packing is derived from three types of hydrogen bonding. The primary hydrogen bond involves a squarate anion O atom and an H atom of the protonated pyridine group of the nicotin­amide, with an N⋯O distance of 2.5760 (13) Å. The second hydrogen bond involves a second anion O atom and an amide H atom, with an N⋯O distance of 2.8374 (14) Å. Thirdly, an intermolecular interaction between two coplanar nicotin­amide moieties occurs between an amide O atom and a symmetry‐related amide H atom, with an N1⋯O3 distance of 2.8911 (15) Å. These hydrogen bonds are also responsible for the planarity of the nicotin­amide moiety in the salt.     

Spectroscopic,X-ray Diffraction and Density Functional Theory Study of Intra- and Intermolecular Hydrogen Bonds in Ortho-(4-tolylsulfonamido)benzamides

The conformations of the title compounds were determined in solution (NMR and UV-Vis spectroscopy) and in the solid state (FT-IR and XRD), complemented with density functional theory (DFT) in the gas phase. The nonequivalence of the amide protons of these compounds due to the hindered rotation of the C(O)–NH₂ single bond resulted in two distinct resonances of different chemical shift values in the aromatic region of their ¹H-NMR spectra. Intramolecular hydrogen bonding interactions between the carbonyl oxygen and the sulfonamide hydrogen atom were observed in the solution phase and solid state. XRD confirmed the ability of the amide moiety of this class of compounds to function as a hydrogen bond acceptor to form a six-membered hydrogen bonded ring and a donor simultaneously to form intermolecular hydrogen bonded complexes of the type N–H···O=S. The distorted tetrahedral geometry of the sulfur atom resulted in a deviation of the sulfonamide moiety from co-planarity of the anthranilamide scaffold, and this geometry enabled oxygen atoms to form hydrogen bonds in higher dimensions.     

Geminal proton non-equivalences and internal rotation in 2-amino-thiophen derivatives.

3-Substituted N-acetyl, N-ethoxycarbonylmethyl-2-aminothiophen derivatives are shown to exist in the endo (the amide carbonyl cis to the thiophen ring) and exo forms, the latter in predominant amount (92 to 98%). Proton nonequivalence reveals the absence of coplanarity between the thiophen and amide planes and the presence of two biphenyl-like enantiomers d and l. The barriers to rotation about the amide bond (R_x) and the aryl-to-nitrogen bond (R_N) have been measured in three solvents: ΔG^≠ (25°C) ～ 71 and 54 kJ. mole^?1, respectively. Competitive delocalisation of the nitrogen doublet to the amide group or to the thiophen ring is shown to account for structural and solvent effects upon the endo to exo molar ratio, the degree of chemical shift nonequivalence and the kinetic parameters of processes R_x and R_N.     

Ab initio study of mechanism of forming a spiro-ge-heterocyclic ring compound

The mechanism of cycloaddition reaction between singlet state dichloromethylenegermene (Cl₂C=Ge:) and ethene has been investigated with the CCSD(T)//B3LYP/6-31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction channel. The reaction rule presented is that the 4p unoccupied orbital of Ge in dichloromethylenegermene and the π orbital of ethene forming a π → p donor–acceptor bond resulting in the formation of a three-membered ring intermediate. Ring-enlargement effect make the three-membered ring intermediate isomerizes to a four-membered ring germylidene. Because the 4p unoccupied orbital of Ge atom in the four-membered ring germylidene and the π orbital of ethene form a π → p donor–acceptor bond, the four-membered ring germylidene further combines with ethene to form another intermediate. Because the Ge atom in the intermediate happens sp ³ hybridization after transition state, the intermediate isomerizes to a spiro-Ge-heterocyclic ring compound.     

Hindered rotation around the aryl-to-nitrogen bond of n-acetyl,n-ethoxycarbonylmethyl-2-amino, 5-nitrothiophen

Two stereoisomers of the title compound are observed by H NMR at 10°. Their spectra coalesce at higher temperature (10°-90°). The equilibrium and rate constants K and k, strongly dependent on the solvent used (1,4-dioxane, tetrahydrofuran, acetone, chloroform); typical values for these parameters and the related thermodynamic functions are: K(25°)= 0.170; k(25°)=23.2s^?1; ΔH_R and ΔH^≠=4.94 and 17.9 kcal.mol.^?1; ΔS_R and ΔS^≠ =13.1 and 7.7 e.u, in a 0.2 molar solution in 1,4-dioxane. The two isomers are shown to result from a hindered rotation around the aryl-to-nitrogen bond, presumably due to a direct resonance effect between the amide and nitro groups. The more abundant isomer was assigned a planar molecular structure in which the O atom of the amide group is close to the S atom of the thiophen ring, presumably on account of an electrostatic interaction between these two atoms which bear partial electrical charges of opposite sign.     

Molekül- und Kristallstruktur des Dimeren Magnesium-bis[bis(trimethylsilyl)amids]

Molecular and Crystal Structure of the dimeric Magnesium bis[bis(trimethylsilyl)-amide] The magnesium bis[bis(trimethylsilyl)amide] crystallizes as a dimeric molecule in the space group C2/c with {a = 1821.0(4); b = 1494.4(4); c = 1859.6(6) pm; β = 121.10(2)°; Z = 4 dimers}. The cyclic planar Mg₂N₂ moiety shows endocyclic NMgN angles of 95.8°. The bond lengths within this ring system to the four-coordinate, bridging nitrogen atoms N^b are 215 pm, whereas the distances between the magnesium atom and the terminal, three-coordinate nitrogen atom N^t display values of approximately 198 pm. These different coordination numbers of the nitrogen atoms affect the NSi bond length (N^tSi 171, N^bSi 177 pm).     

Fast atom bombardment mass spectra of iodonium salts

Positive-ion fast atom bombardment mass spectra and linked-scan tandem mass spectra were measured for aromatic iodonium salts. The mass spectra usually contain the intact cation of the iodonium salt as the base peak, fragment ions of lower abundance resulting from simple cleavages or rearrangements, and a characteristic loss of atomic iodine. High-level semi-empirical calculations suggest that an obtuse ring? I⁺? ring angle facilitates loss of atomic iodine through concomitant ring? to? ring bond formation.     

Intrinsic Folding Proclivities in Cyclic β‐Peptide Building Blocks: Configuration and Heteroatom Effects Analyzed by Conformer‐Selective Spectroscopy and Quantum Chemistry

This work describes the use of conformer‐selective laser spectroscopy following supersonic expansion to probe the local folding proclivities of four‐membered ring cyclic β‐amino acid building blocks. Emphasis is placed on stereochemical effects as well as on the structural changes induced by the replacement of a carbon atom of the cycle by a nitrogen atom. The amide A IR spectra are obtained and interpreted with the help of quantum chemistry structure calculations. Results provide evidence that the building block with a trans‐substituted cyclobutane ring has a predilection to form strong C8 hydrogen bonds. Nitrogen‐atom substitution in the ring induces the formation of the hydrazino turn, with a related but distinct hydrogen‐bonding network: the structure is best viewed as a bifurcated C8/C5 bond with the N heteroatom lone electron pair playing a significant acceptor role, which supports recent observations on the hydrazino turn structure in solution. Surprisingly, this study shows that the cis‐substituted cyclobutane ring derivative also gives rise predominantly to a C8 hydrogen bond, although weaker than in the two former cases, a feature that is not often encountered for this building block.     

Etude par Résonance Magnétique Nucléaire de dioxaphosphorinanes-1,3,2 à liaison P?N extracyclique. Exemple de changement d'orientation de la liaison P?N

The ¹H NMR spectra of several 1,3,2-dioxaphosphorinanes bearing an extracyclic P? N bond have been analysed. The ³J(POCH) couplings are strongly dependent upon the orientation of the bond around the phosphorus atom. Depending upon the nature of the bonds attached to the nitrogen atom, the dioxaphosphorinane ring may adopt either a fixed chair conformation with the P? N bond in the axial or equatorial orientation, or it may be in equilibrium between two chair conformations where the P? N bond is alternately axial or equatorial. The equilibrium is fast on the NMR time scale.     

Ab initio study of mechanism of forming a spiro-heterocyclic ring compound involving Si from dichlorosilylenesilylene (Cl2Si=Si:)→Cl2Si=Si: and aldehyde

The mechanism of the cycloaddition reaction between singlet dichlorosilylenesilylene (Cl₂Si=Si:)→Cl₂Si=Si: and aldehyde has been investigated with the CCSD(T)//MP2/6-31G* method. From the potential energy profile, it could be predicted that the reaction has one dominant reaction pathway. The reaction rules presented is that the two reactants firstly form a four-membered ring silylene through the [2+2] cycloaddition reaction. Because of the 3p unoccupied orbital of Si: atom in the four-membered ring silylene and the π orbital of aldehyde forming a π → p donor–acceptor bond, the four-membered ring silylene further combines with aldehyde to form an intermediate. Because the Si: atom in the intermediate happens sp ³ hybridization after transition state, then the intermediate isomerizes to a spiro-heterocyclic ring compound involving Si via a transition state.     

NMR study of cis3̄trans isomerism in N-methylated lactams with 11- and 13-membered rings

From ¹H-NMR spectra of 1-methyl-azacyclo-undeca-2-one and 1-methyl-azacyclo-trideca-2-one, the bands corresponding to the cis and trans forms have been assigned and analyzed; based on this analysis, conformational structures about the C-C bond next to nitrogen are proposed. By analysis of the relative areas and shapes of the N-methyl bands measured for the two lactams in 1,1,2,2-tetrachloroethane-d₂, over a broad temperature range, the equilibrium and thermodynamic parameters characterizing the cis—trans isomerism of the amide bond in these lactams have been determined. Peaks corresponding to the cis and trans forms in the ¹³C-NMR spectra of these lactams have also been assigned.     

Matrix isolation study of the photochemical reaction of cyclohexane and cyclohexene with CrCl2O2

The matrix isolation technique, combined with infrared spectroscopy, has been used to characterize the products of the photochemical reactions of cyclohexane and cyclohexene with CrCl₂O₂. While initial twin jet deposition of the reagents led to no visible changes in the recorded spectra, strong product bands were noted following irradiation with light of λ > 300 nm. The irradiation was shown to lead to oxygen atom transfer, forming complexes between cyclic alcohol derivatives and CrCl₂O, although complexes between ring expansion products and CrCl₂O could not be ruled out. This latter result could arise from C-C bond activation and oxygen atom insertion into a C-C bond. For the cyclohexene system, the cyclohexanone-CrCl₂O complex was also observed. The identification of the complexes was further supported by isotopic labeling (²H) and by density functional calculations at the B3LYP/6-311G++(d,2p) level.     

Conformational analysis of N-aryl-N-(2-azulenyl)acetamides

Aromatic amides bearing 2-azulenyl group on the amide nitrogen were synthesized and their structures were investigated. The π-electron density of the N-aryl group was found to influence the cis-trans conformational preferences of these compounds in solution. X-ray crystallography revealed that the plane of the 2-azulenyl ring has a strong tendency to lie coplanar with the amide plane when the azulene group is located on the same side as the amide oxygen atom.