Structure and protonation study of the imidazo [1,2-a]-pyrimidine system in 1H nuclear magnetic resonance

The ¹H NMR spectra of imidazo [1,2-a]pyrimidine derivatives have been analysed to study the aromatic character and protonation behaviour of this system. By employing the ‘ring currentn’ model and calculations based on the coupled Hartree-Fock method it can be deduced that a large π-electron delocalisation exists in this heterocyclic system and affects the screening constant of the protons. Charge density schemes obtained by SCF techniques agree with the reactivity behaviour of these molecules. A detailed study of protonation carried out by following the ¹H NMR spectra both in trifluoroacetic acid and in aqueous hydrochloric acid shows that the most probable site of protonation is N-1, but leaves open the possibility of a rapid exchange of one proton between N-1 and N-8.     

19F nuclear magnetic resonance spectra of some trisubstituted metal trifluorophosphine complexes. Examples of [AX3]3 nuclear spin systems

The ¹⁹F NMR spectra of π-allyl-tris(trifluorophosphine)rhodium(I), [A], benzene-tris(trifluorophosphine)chromium(0), [B], and nitrosyl-tris(trifluorophosphine) rhodium(-I), [C], are presented. These are examples of [AX₃]₃ nuclear spin systems (A = phosphorus, X = fluorine). The spectra of [A] and [B] have been completely analysed to afford values of ¹J(PF), ²J(PP′), ³J(PF′) and ⁴J(FF′).     

19F substituent chemical shifts (SCS) of 4-substituted bicyclo[2.2.2]oct-1-yl flourides

The results of a linear multiple regression analysis indicate that the ¹⁹F SCS of 4-substituted bicyclo[2.2.2]oct-1-yl fluorides are essentially a manifestation of electric field and electronegativity effects.     

Synthesis of 13c-labelled [s]-proline and its conformational analysis by nuclear magnetic resonance

In order to analyze completely the ring conformation of [S]-Proline (l-thiazolidine-4-carboxylic acid) this compound has been synthesized with its C_δ atom enriched at 90% in ¹³C. The ¹H-¹H, ¹³C-¹H, ¹³C-¹³C vicinal coupling constants measured at several pH values describe well the geometry of the thiazolidine ring. The results suggest that the ring has an average planar conformation only in a narrow range of pH close to the pK of the amine group. Above and below this pH the ring tends to adopt preferentially the S_γendo and S_γexo puckered conformations respectively. It is concluded that a good correlation exists between the value of the dihedral angle ø and the character S_γendo or S_γexo of the ring.     

Synthetic approaches towards [18F]fluoro-DOG1, a potential radiotracer for the imaging of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) can currently only be identified by invasive biopsy sampling followed by immunohistochemical analysis. It would however be highly advantageous to have a radioligand able to bind the calcium-activated chloride channel DOG1, which is specific for GIST, and thus enable the sensitive, non-invasive and specific functional imaging of the disease by Positron Emission Tomography (PET). For this purpose, we developed different synthetic strategies towards a 4-phenylthiazole-2-amine-based labeling precursor that can be directly reacted with ¹⁸F-fluoride to yield a radiotracer intended to bind DOG1. Of these, a boronic acid pinacol ester radiolabeling precursor could be efficiently reacted with ¹⁸F in a one-step reaction, and the target radioligand [¹⁸F]fluoro-DOG1 be obtained in radiochemical yields of 34.0?±?11.1% within 85?min overall synthesis time.     

Studies on the structure of olivomycin a and mithramycin by 1H and 13C nuclear magnetic resonance spectroscopy

Extensive ¹H and ¹³CNMR studies confirmed the gross structure of olivomycin A except for a revision with respect to a saccharide linkage. The structure of mithramycin was elucidated similarly, resulting in a substantial revision of structure for its carbohydrate moiety including interglycosidic bonds.     

Polar field-inductive parameters of some group IVB metalloidal substitutents: a 13C and 19F NMR study in the phenylbicyclo[2.2.2]octane ring system

A number of bridgehead metalloidal-substituted phenylbicyclo[2.2.2]octyl and (m- and p-)fluorophenylbicyclo[2.2.2]octyl derivatives have been synthesized and their ¹³C and ¹⁹F NMR spectra have been recorded. The appropriate ¹³C and ¹⁹F substituent chemical shifts of these stereochemically well-defined model systems, together with the known polar susceptibility parameters, provide a definitive scale of polar field-inductive parameters (σ₁ values) for a representative array of metalloidal substituents attached to an sp³ hybridized carbon center. The implication of these results with respect to the physical interpretation of σ₁ parameters is discussed. In addition, the previously reported results for alkyl groups in these systems have been re-evaluated in terms of possible through-bond effects involving orbitals of π symmetry of the bicyclo[2.2.2]- octane ring system. Factors determining α, β, γ and δ effects are briefly alluded to.     

Qualitative and quantitative characterization of a complex mixture of hexylbenzenes by 13C nuclear magnetic resonance and gas chromatography-mass spectrometry

Summary A considerable amount of byproducts is formed in the production of isopropylbenzene (cumene). Recently, a distillation fraction of these byproducts became commercially attractive which justified its compositional analysis. All the signals in the complex ¹³C nuclear magnetic resonance (NMR) spectrum of this material have been assigned. The mass spectra of the individual constituents were recorded by the application of capillary gas chromatography-mass spectrometry. The data obtained with both analytical techniques revealed that the product is composed of a complex mixture of 3 isomeric diisopropylbenzenes and 10 different hexyl-substituted benzenes. The mass spectra and carbon-13 NMR chemical shift data of most of the compounds presented here have not been previously reported. NMR data of all possible butyl- and a number of pentyl-substituted benzenes are included in this report for assignment purposes. Quantitative studies on this material and some of its distillation fractions by ¹³C NMR and gas chromatography enabled the assignment of individual peaks in the gas chromatogram.

---

Qualitative und quantitative Charakterisierung eines komplexen Gemisches von Hexylbenzolen durch ¹³C-NMR und GC/MS

     

Simultaneous assay of organic fluorine compounds in biological fluids by fluorine-19 nuclear magnetic resonance spectrometry over a large spectral width: Application to Fluoropyrimidines

¹⁹F-n.m.r. spectrometry is used as a direct method to assay simultaneously in body fluids (urine, plasma) all the fluorinated metabolites of a new antineoplastic drug fluoropyrimidine, 5′-deoxy-5-fluorouridine. The resonances of these metabolites are spread over a large spectral width (about 100 ppm). The calibration graphs for 5′-deoxy-5-fluorouridine and its major metabolite, α-fluoro-β-alanine, are linear over the range 10^?5–10^?1 M; the accuracy is 3–5% for urine samples and 5–7% for plasma samples. The method is applied to the determination of all the metabolites in urine from a patient.     

A study of some imidazo[l,5-a]benzodiazepin-6-ones by electron impact mass spectrometry. characterization by tandem mass spectrometry of a distonic fragment ion

The mass spectra of several imidazo[l,5-a]benzodiazepin-6-one derivatives of neuropharmacological significance were determined in order to establish their decomposition paths under electron impact. A novel distonic fragment ion was observed and it was possible to demonstrate by consideration of metastable ions and by tandem mass spectrometry that it undergoes isomerization to the corresponding classical structure.     

Pyrazolo[1,5-a]pyrimidines. A combined multinuclear magnetic resonance (1H, 13C, 15N, 19F) and DFT approach to their structural assignment

Multinuclear magnetic resonance spectroscopy together with GIAO-DFT calculations allowed establishment of the structure of the products obtained by condensation of 3(5)-amino-4-phenyl-1H-pyrazole and beta-dicarbonyl compounds bearing a trifluoromethyl group. They are 3-phenyl-5-(R)-7-trifluoromethylpyrazolo[1,5-a]pyrimidines.     

Proton magnetic resonance studies of compounds with bridgehead nitrogen. 37–a comparison of the positions of conformational equilibria in 1-methylperhydro-oxazolo[3,4-a]pyridines and in 1-methylperhydrothiazolo [3,4-a]pyridines

cis(1-H, 8a-H)-1-Methylperhydro-oxazolo[3,4-a]pyridine and cis(1-H, 8a-H)-1-methylperhydrothiazolo[3,4-a]pyridine both adopt exclusively the trans-fused conformation in carbon tetrachloride solution at room temperature. Both parent unsubstituted systems exist under similar conditions as equilibria containing c. 67% (oxazolo compound) and 64% (thiazolo compound) of the trans-fused conformation. In marked contrast to these similar positions of conformational equilibria in both systems the trans(1-H,8a-H)-1-methylperhydrooxazolo[3,4-a]pyridine exists as c. 73% trans-fused in equilibrium with a cis-fused conformation whereas the trans(1-H, 8a-H)-1-methylperhydrothiazolo[3,4-a]pyridine exists almost exclusively in a cis-fused ring conformation. These differences in conformational equilibria are explained in terms of changes in non-bonded interactions.     

Synthesis of imidazo[1, 2-a]pyridines via the silver acetate-catalyzed Groebke-Blackburn-Bienayme reaction with ethylene glycol as a biodegradable and sustainable solvent

An efficient, silver-based catalytic system has been designed for the synthesis of biologically important 3-aminoimidazo-fused heterocycles via the Groebke-Blackburn-Bienayme reaction, in which AgOAc was used as a catalyst and ethylene glycol as a solvent from isocyanides, various aryl aldehydes and an 2-amino heterocycle were also used. Good to excellent yields, high atomic economy and environmentally friendly conditions are the potential features of this one-pot process.     

On the estimation of the field constant of 35Cl nuclear quadrupole resonance frequency in the series of [R1R2R3AsCl]+M? compounds

The field constant of the NQR frequency of a chlorine atom (³⁵Cl) in a series of arsenic derivatives [R¹R²R³AsCl]⁺M⁻ was estimated from correlations. The field frequency is ∼41.5±3.5 Hz cm kV⁻¹, which is nearly twice as much as that in analogous phosphorus compounds. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1758–1760, August, 2005.     

[O9,24] [2.1.2.1] metacyclophane-9-ene,a “twin cyclophane”, and its dehydrogenation products - synthesis structure determination and 1H-NMR-spectroscopy

The synthesis of [O⁹,24] [2.1.2.1]metacyclophane-9-ene and of its dehydrogenation products^the new pyrenocyclophanes $\text{8}$, $\text{10}$, $\text{11}$, and $\text{12}$, is described; their structures are discussed in connection with their ¹H-NMR-spectra.