Structural Assignment of Isomeric S‐ and S,N‐1‐Alkoxycarbonylalkylated 6‐Amino‐2‐thiouracil Derivatives by Means of 1H and 13C NMR Spectroscopy

Abstract

The structures of new isomeric 2‐alkoxycarbonylalkylthio‐ and 2‐alkoxy‐ carbonylalkylthio‐1‐alkoxycarbonylalkyl‐6‐aminouracils (1–21) have been established on the basis of the ¹H NMR and ¹³C NMR spectroscopic data. The ¹H NMR and ¹³C NMR spectra of 1–21 have been fully assigned by a combination of two‐dimensional experiments [heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond correlation (HMBC)]. The ¹³C NMR spectra have been shown to be able to differentiate between isomers.     

1H, 13C and 19F NMR Studies of the Diels-Alder Adduct of p-Fluoranil with Phencyclone. II. Hindered Phenyl Rotations and Anisotropic Effects in a Model Compound for Drugs

Abstract

The Diels-Alder adduct of phencyclone, compound 1, with p-fluoranil, compound 3, has been prepared in refluxing toluene. The adduct, compound 2, has been examined by ¹H, ¹³C and ¹⁹F NMR spectroscopy at 300, 75 and 282 MHz, respectively. At ambient temperature, the unsubstituted bridgehead phenyl groups in adduct 2 are found to exhibit hindered rotation, resulting in slow exchange limit (SEL) ¹H NMR spectra. Full aryl proton assignments are made based on 1D and 2D (COSY45) NMR. The ¹⁹F NMR (proton coupled) reveals one of the two ¹⁹F signals to be a triplet. This resonance collapses to a singlet in the proton decoupled ¹⁹F spectrum, implying an unexpected long range ¹H-¹⁹F coupling. For the ¹³C NMR spectrum, tentative assignments are presented. Data for compound 2 as a model compound for drugs are discussed in terms of the hindered aryl rotation and evidence of magnetic anisotrppic effects.     

NMR Studies of Hindered Rotation. The Diels-Alder Adduct of Phencyclone with N-n-Propylmaleimide: Restricted Motion of Bridgehead Phenyls

The Diels-Alder adduct of phencyclone and N-n-propylmaleimide has been studied in CDCl₃ solution at ambient temperatures by one-and two-dimensional ¹H NMR (300 MHz) and ¹³C NMR (75 MHz) techniques. Clear evidence is presented from slow exchange limit (SEL) spectra for hindered rotation of the bridgehead phenyls in the adduct. Full ¹H spectral assignments have been made via selective homonuclear decoupling and high resolution COSY experiments. The number of signals in the aryl region of ¹³C NMR spectra also indicated slow rotation about the C(sp²)-C(sp³) bond to the unsubstantiated bridgehead phenyls. Striking evidence of magnetic anisotropic effects, seen from ¹H NMR, permits stereochemical assignment of the adduct as endo.     

1H and 13C NMR Studies of Etidocaine Free Base and Hydrochloride Salt. Solvent and Temperature Dependence

The ¹H and ¹³C NMR spectra of etidocaine free base, 1, and its hydrochloride salt, 2, have been examined at 200 MHz in a variety of solvents. Variable temperature ¹H NMR spectra of 2 were measured between 0° and 90°C at 500 MHz. Both ¹H and ¹³C spectra of the salt were strongly dependent on temperature, solvent and spectrometer frequency. Results are interpreted primarily as a consequence of acid-induced chirality at the amine nitrogen, resulting in solvent-dependent diastereoisomerism. Spectral complexity is explained as the result not only of diastereotopic nuclei due to the fixed “natural” chiral center at carbon, but also, in 2, to the presence of diastereomeric racemates resulting from the second chiral center (at nitrogen).     

NMR Spectroscopic Study of Camphanic Acid,Rh2[Camphanate]4, and its Adducts with 1,4-Benzodiazepines

The H and ¹³C NMR spectra of chiral camphanic acid, lactonc of (1S,3R)-1-hydroxy-2,2,3-trimethyl-cyclopentan-1,3-dicarboxylic acid (1), and dirhodium tetracamphanate complex (2) were completely assigned on the basis of one- and two-dimensional NMR experiments. The NMR spectra of the adducts of dirhodium tetracamphanate 2 with 5-pyrido-1, 4-benzodiazepin-2-ones 3 and 4, complexes with catalytic activity, support the assignation and also revealed two different types of axial complexation of these nitrogen ligands.     

NMR Studies of Hindered Rotation. The Diels-Alder Adduct of N-n-Butylmaleimide With Phencyclone: Restricted Motion of Bridgehead Phenyls

The Diels-Alder adduct of phencyclone and N-n-butylmaleimide has been prepared, and NMR studies have been carried out in CDCl₃ solution at ambient temperatures by one-and two-dimensional ¹H NMR (300 MHz) and ¹³C NMR (75 MHz) techniques. The resulting spectra appear to be consistent with slow rotation about the hindered C(sp²)-C(sp³) bonds to the bridgehead unsubstituted phenyls, i.e., slow exchange limit (SEL) spectra. Full rigorous ¹H spectral assignments have been made via high-resolution COSY experiments. The number of signals in the ¹³C NMR aryl region were also consistent with hindered phenyl rotations; preliminary ¹³C assignments are given. Striking evidence for magnetic anisotropic effects due to the phenanthrene moiety, bridging ketone carbonyl, and bridgehead phenyls are discussed, supporting endo stereochemical assignment of the adduct.     

Determination of the Stereochemistry of Substituted 5-Methylenehydantoins and Thiohydantoins by 13C NMR and Homonuclear NOE Experiments

Basically the aim of this work is to define the accurate configuration of the exocyclic double bond of substituted 5-methylenehydantoins and thiohydantoins which have been conceived as potential Aldose Reductase inhibitors. A previsional survey based upon the chemical shifts analysis from ¹H and decoupled ¹³C NMR spectra discloses, for a part of the family of compounds, the assignment of the Zconfiguration for unsubstituted (2,3) and N-3 substituted (6,7,9) derivatives, and the E-configuration for the N-1 substituted (8,11) ones. The qualitative study with Homonuclear NOE (8,11) and the coupling constant measuring ^{3 J}C4-C=C-H6 from coupled ¹³C NMR (1–11), lead to the assignment of the accurate configuration of the whole family's compounds in agreement with the previsional study.     

NMR Studies of Drugs. Methaqualone. Approaches to Rigorous 1H and 13C Assignments with Applications of Achiral and Chiral Shift Reagents

The ¹H and ¹³C NMR spectra of methaqualone, 1, have been extensively studied using one and two-dimensional techniques. These 300 MHz ¹H and 75 MHz ¹³C studies have allowed rigorous assignments to be made for the methyl groups and the quinazolinone nucleus. The 60 MHz ¹H spectra for 1 in CDCl₃ have been examined with     

Spectroscopic (FT‐IR,FT‐Raman,UV, 1H,and 13C NMR) and theoretical studies of m‐anisic acid and lithium,sodium, potassium,rubidium, and caesium m‐anisates

In order to understand the nature of the interactions of biologically important ligands, it is necessary to carry out the physico‐chemical studies of these compounds with their biological targets (e.g., receptors in the cell or important cell components). Results of this study make it possible to predict some properties of a molecule, such as its reactivity, durability of complex compounds, and kinship to enzymes. In this paper the effect of alkali metal cations (Li, Na, K, Rb, and Cs) on the electronic structure of m‐methoxybenzoic acid (m‐anisic acid) was studied. The experimental IR (in solid state and solution), Raman, UV (in solid state and solution), ¹H, and ¹³C NMR spectra of m‐methoxybenzoic acid, and its salts were registered, assigned, and analyzed. Some of the obtained results were compared with published data for o‐anisic acid and o‐anisates. The structures of anisic acid and Li, Na, and K m‐anisates were optimized at the B3LYP/6‐311++G** level. The IR, ¹H, and ¹³C NMR spectra and NPA, ChelpG, and MK atomic charges were calculated. The change of metal along with the series: Li → Na → K → Rb → Cs caused: (1) the change in the electronic charge distribution in anisate anion that is seen via the occurrence of the systematic shifts of several bands in the experimental and theoretical IR and Raman spectra of anisates; (2) systematic ¹H and ¹³C NMR chemical shifts; (3) hypsochromic shifts in UV spectra of salts as compared to ligands. Copyright © 2009 John Wiley & Sons, Ltd.     

NMR Studies of Hindered Rotation and Magnetic Anisotropy: The Diels–Alder Adducts of Phencyclone with N‐Phenylmaleimide and N‐(2‐Trifluoromethylphenyl)maleimide. Ab Initio Calculations for Optimized Structures

Abstract

N‐Phenylmaleimide, 2, and N‐(2‐trifluoromethylphenyl)maleimide, 3, were separately added to phencyclone, 1, to yield the corresponding phencyclone Diels–Alder adducts, 4 and 5. The resulting adducts (and some precursors) have been characterized by one‐ and two‐dimensional ¹H and ¹³C NMR at 300 and 75 MHz, and by ¹⁹F NMR at 282 MHz, at ambient temperatures. The NMR data are consistent, for both adducts, with: (a) hindered rotation of the bridgehead unsubstituted phenyl groups about the C(sp²)–C(sp³) bonds, based on slow exchange limit (SEL) spectra and (b) endo adduct configuration based on magnetic anisotropic effects in the ¹H NMR. The NMR spectra of the phencyclone adduct, 4, of N‐phenylmaleimide, indicate free rotation on the NMR timescales (fast exchange limit, FEL spectra) about the N‐phenyl bond. The spectra for the adduct, 5, of N‐(2‐trifluoromethylphenyl)maleimide are interpreted as consistent with SEL regimes, for the N‐aryl rotations, with a single rotamer present in which the trifluoromethyl group is directed “out of” the adduct cavity, and away from the phenanthrenoid moiety. This conclusion is based, in part, on NMR data suggesting the apparent slow N‐aryl bond rotation in a pair of atropisomers corresponding to the acetic acid addition products from the N‐(2‐trifluoromethylphenyl)maleimide. Evidence of magnetic anisotropic effects due to the phenanthrenoid moiety and proximal carbonyls is discussed. ¹H, ¹³C, and ¹⁹F assignments are presented and interpreted. Molecular modeling calculations at the Hartree–Fock level, 6‐31G* basis set, were performed to provide geometry optimizations for energy‐minimized structures of selected compounds.     

Complete Analysis of the 1H and 13C NMR Spectra of 5-Isopropylsulfonyl-2-Norbornenes Through the Application of Two-Dimensional NMR Techniques

Total assignment of ¹³C and ¹H NMR spectra of the 5-isopropylsulfonyl-2-norbornenes 2 was achieved using the concerted application of two-dimensional homonuclear and heteronuclear chemical shift correlations. The stereochemistry of both the diastereoisomers endo 2a and exo 2b have been established using the magnitude of the proton coupling constants.     

Synthesis and Chiral Recognition Properties of Novel Fluorescent Chemosensors for Amino Acid

The charge neutral chiral optical sensors 1a∼d containing thiourea and amide groups were synthesized by simple steps in good yields and their structures were characterized by IR, ¹H NMR, ¹³C NMR, MS spectra and elemental analysis. The enantioselective recognition for α-phenylglycine and phenylglycinol was examined by fluorescence emission and UV-vis spectra. The fluorescence and UV-vis spectra changes of 1a were obvious when the enantiomers of α-phenylglycine anion were added, which exhibited that 1a has good enantioselective recognition ability towards α-phenylglycine. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

NMR Studies in the Heterocyclic Series. XXIII. - 13C Spectra of Indazole and 3-Azido-Indazole in Acidified Dimethylsulfoxid Solutions

We reported previously the ¹³C NMR spectra of indazole 1 ² and 3-azido-indazole 2 ³.     

Molecular structure of alkali metal 4‐nitrobenzoates

The influence of lithium, sodium, potassium, rubidium, and cesium on the electronic system of the 4‐nitrobenzoic acid molecule was studied. The vibrational (FT‐IR, FT‐Raman) and NMR (¹H and ¹³C) spectra for 4‐nitrobenzoic acid salts of alkali metals were recorded. The assignment of vibrational spectra was done. Characteristic shifts of band wavenumbers and change in band intensities along the metal series were observed. Good correlation between the wavenumbers of the vibrational bands in the IR and Raman spectra for 4‐nitrobenzoates and ionic potential, electronegativity, atomic mass, and affinity of metals were found. The chemical shifts of protons and carbons (¹H, ¹³C NMR) in the series of studied alkali metal 4‐nitrobenzoates were observed too. Optimized geometrical structures of studied compounds were calculated by HF, B3PW91, B3LYP methods using 6‐311++G** basis set. The theoretical IR, Raman, and NMR spectra were obtained. The theoretical vibrational spectra were interpreted by means of potential energy distributions (PEDs) using VEDA 3 program. The calculated parameters were compared to experimental characteristic of studied compounds. Copyright © 2007 John Wiley & Sons, Ltd.     

An Example of Crossed Ship Conformation: The Tetrahydropyran Ring in Trioxa-bis-Spirocital Series

Abstract

The three ³J_HH coupling constants observed in the ¹H NMR spectra (500 MHz) of trioxa-bis-spirocital 1 and 2 serve to calculate the dihedral angles Ψ(8,9) and Ψ(9,10) of these two molecules. The values obtained, 54° for 1, 25° for 2, reflect the change in conformation: chair → crossed ship when passing from 1 to 2. This change in conformation corresponds in ¹³C NMR to strong shielding (?3.6 to ?5.5 ppm) of the lines of the carbons C₈, C₉ and C_10.     

Structural Assignment of Stilbenethiols and Chalconethiols and Differentiation of Their Isomeric Derivatives by Means of 1H‐ and 13C‐NMR Spectroscopy

Abstract

The ¹H‐ and ¹³C‐NMR spectra of some substituted stilbenes and chalcones were assigned unambiguously on the basis of a combination of homo‐ (COSY) and heteronuclear (HETCOR) two‐dimensional methods, the chemical shifts, as well as spin‐coupling constants. The A_ik empirical parameters of the –O–C(S)–N(CH₃)₂, –S–C(O)–N(CH₃)₂, and –SH group were calculated to help predict the chemical shifts of substituted stilbenes, 4′‐nitrostilbenes, and chalcones. The ¹H‐ and ¹³C‐NMR spectra have been shown to be able to differentiate between the isomers of O‐stilbenyl (4, 5) and S‐stilbenyl N,N‐dimethylthiocarbamates (7, 8) as well as O‐chalconyl (6) and S‐chalconyl N,N‐dimethylthiocarbamates (9).     

1H and 13C NMR Spectral Study of Some 2r-Aryl-6c-phenylthian-4-ones,Their 1-Oxides and 1,1-Dioxides

ABSTRACT

Four 2r-aryl-6c-phenylthian-4-ones 1b?1e and their 1-oxides 2b?2e and 1,1-dioxides 3b?3e have been newly synthesized. ¹H and ¹³C NMR spectra have been recorded for all these compounds and 2r,6c-diphenylthian-4-one 1-oxide 2a. ¹³C NMR spectrum has been recorded for the sulfone 3a of 1a. For selected compounds ¹H-¹H COSY, HSQC, HMBC, and NOESY spectra have been recorded. The vicinal proton–proton coupling constants suggest that in all these compounds, the heterocyclic ring adopts chair conformation with equatorial orientations of the aryl and phenyl groups. Proton and carbon chemical shifts suggest that in the sulfoxides, the S=O bond is axial and enhances the J _aa value by some special effect. The S = O bond causes a significant upfield shift even on carbons without hydrogens. Significant solvent shifts also were observed.     

Assignments of the 13C NMR Spectra of Enhydrin and 2′,3′-Dehydromelnerin A and the Molecular Structure of Enhydrin

Abstract

Two melampolide-type sesquiterpene lactones, enhydrin and 2,′ 3′-dehydromelnerin A, were isolated from a Louisiana population of Polymnia uvedalia. Their ¹³C NMR spectra were assigned using ¹³C-¹H correlation, DEPT and COLOC experiments. The molecular structure of enhydrin was established by single crystal X-ray diffraction.     

Structural Assignments of 1‐(β‐d‐Glucopyranosyl)‐1,2,3‐triazoles by 1H‐ and 13C‐NMR Study

The ¹H‐ and ¹³C‐NMR spectra of 1‐β‐d‐glucopyranosyl‐1,2,3‐triazole‐4,5‐dimethyl carboxylate, 1‐β‐d‐glucopyranosyl‐1,2,3‐triazole‐4,5‐dicarboxamide, ‐dialkylcarboxamide‐N‐nucleosides 4–18, and 6‐amino‐4H‐1‐(1‐β‐d‐glucopyranosyl)‐8‐hydroxy‐1,2,3‐triazolo[4,5‐e][1,3]‐diazepin‐4‐one 19 had been studied. Resonance signals and anomeric configurations were assigned by homo‐ and heteronuclear two dimensional methods (DQF‐COSY, HSQC, HMBC, HMQC, ROESY).     

17O and 13C NMR Studies of Isobenzopyrylium Salts

¹³C and ¹⁷O NMR chemical shifts for a series of isobenzopyrylium salts are reported. The oxygen signal range from 300 to 270 ppm as a double bonded carboxylic oxygen, From the ¹⁷O and ¹³C data valuable informations on the conjugative and substituent effects of isobenzopyrylium salts were obtained.