Spectroscopy proton NMR

Proton NMR spectroscopy has found wide applications in the investigation and structure determination of A,B-diheteropentalenes. The results of earlier studies have been reviewed 84CHEC-1(4)1037). This chapter introduces the chemical shifts and coupling constants of the previously known parent compounds (Table 3). 

The similarity of the H NMR spectra of l//,4//-pyrrolo[3,2-6]pyrrole (10) and of pyrrole suggests that both ring systems possess similar ring currents and aromaticity. The observed upfield shift (0.17 ppm) of the /f-proton seems to reflect the influence of the fused pyrrole ring on the electron density of this system. 

Proton nuclear magnetic resonance (NMR) data of parent A,B-diheteropentalenes have been reviewed 1984CHEC(4)1037, 1984CHEC(6)1027, 1996CHEC-II(7)1 . 

On the basis of their 13C NMR assignments (see below), 111—111 correlation spectroscopy (COSY) and H-13C COSY experiments allowed to assign the H NMR data of a series of sparteine analogues and derivatives (compounds 24-27). These data are collected in Table 2 2003JST275 . Detailed 111 NMR assignments for other sparteine derivatives are also available in the literature (see, for instance, 2005JST75 ). 

Nuclear Overhauser enhancement spectroscopy (NOESY) experiments play a very important role in structural studies in quinolizidine derivatives. For instance, the endo-type structure of compound 28 was proven by the steric proximity of the H-3a and H-12a protons according to the NOESY cross peak, while the spatial proximity of the H-6f3 and H-8/3 protons reveals that tha A/B ring junction has a /ra t-stereochemistry. Similarly, compound 28 could be distinguished from its regioisomer 29 on the basis of the NOESY behavior of its H-13 atom 1999JST153 . 

Hydrogen atoms on the a-carbon atoms of primary and secondary alcohols as well as the related ethers have chemical shifts in the 3.0—4.1 Sregion. The deshielding effect of the electronegative oxygen atom falls off with distance, as shown by the following examples. 

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Intimate information about the nature of the H bond has come from vibrational spectro.scopy (infrared and Raman), proton nmr spectroscopy, and diffraction techniques (X-ray and neutron). In vibrational spectroscopy the presence of a hydrogen bond A-H B is manifest by the following effects ... 

Proton nmr spectroscopy has also proved valuable in studying H-bonded systems. As might be expected, substantial chemical. shifts are observed and information can be obtained... 

The possibility that the allyl group CH2=CH-CHi- can act as an ligand was recogni2ed independently by several groups in I960 and since then the held bas flourished, partly because of its importance in homogeneous catalysts and partly because of the novel sleric possibilities and inferconversions that can be studied by proton nmr spectroscopy. Many synthetic routes are available of which the following are representative. 

Evidence for the reactive intermediate in Eq. (20) is strictly of a kinetic nature. Since attempts at its detection by proton NMR spectroscopy starting with RMn(CO)j or CpMo(CO)jR were not successful (80, 81, 97), such a species must be present in low concentrations. 

Grootveld, M., Henderson, E.B., Farrell, A.J., Blake, D.R, Parkes, H.G. and Haycock, P. (1991). Oxidative damage to hyaluronate and gjucose in synovial fluid during exercise of the inflamed rheumatoid joint detection of abnormal low-molecular-mass metabolites by proton NMR spectroscopy. Biochem. J. 273, 459-467. 

Those of the readers who are already quite familiar with proton NMR spectroscopy are aware that, as the most electronegative element, fluorine substituents deshield proximate hydrogens more than any other atomic substituent because of their unique inductive influence. This fact is exemplified below in Scheme 2.11. 

This book is an up-to-date follow-up to the original Laboratory Guide to Proton NMR Spectroscopy (Blackwell Scientific Publications, 1988). It follows the same informal approach and is hopefully fun to read as well as a useful guide. Whilst still concentrating on proton NMR, it includes 2-D approaches and some heteronuclear examples (specifically 13C and 19F plus a little 15N). The greater coverage is devoted to the techniques that you will be likely to make most use of. 

Molecular Motions and Dynamic Structures. Molecular motions are of quite general occurrence in the solid state for molecules of high symmetry (22,23). If the motion does not introduce disorder into the crystal lattice (as, for example, the in-plane reorientation of benzene which occurs by 60° jumps between equivalent sites) it is not detected by diffraction measurements which will find a seemingly static lattice. Such molecular motions may be detected by wide-line proton NMR spectroscopy and quantified by relaxation-time measurements which yield activation barriers for the reorientation process. In addition, in some cases, the molecular reorientation may be coupled with a chemical exchange process as, for example, in the case of many fluxional organometallic molecules. ... 

Proton and 13C NMR spectral data of 33 derivatives of 64 have been tabulated and assigned <1996MRC409>. Several 3-oxo derivatives of 64 have been studied by proton and 13C NMR spectroscopy as part of a comprehensive investigation of their structural and spectroscopic properties <2003BCJ2361>. The regioselectivity of the formation of the six-membered ring in derivatives of 67 from 1,3-diketones has been established by proton NMR spectroscopy and nuclear Overhauser effects <1997CHE535>. 

C NMR spectroscopy has been used to establish the structures of intermediates formed during the photooxygenation of 13C-labeled derivatives of 64 related to bioluminescent luciferins <1996T12061>. The mechanism of the formation of 3-oxo derivatives of 64 related to the chemistry of bioluminescence has been studied by low-temperature 13C (together with variable temperature proton) NMR spectroscopy <1997J(P2)1831>. The 13C and 1SN... 

Pontanen and Morris [8] compared the structure of humic acids from marine sediments and degraded diatoms by infrared and C13 and proton NMR spectroscopy. Samples of marine sediments taken from the Peru continental shelf were extracted with water, sodium hydroxide (0.05mol 1 J) and sodium pyrophosphate (0.05mol l-1) under an atmosphere of nitrogen and fractionated by ultrafiltration. Humic acids of molecular weight 300000 and above were examined. Diatoms were collected from... 

Apart from fluorescence, several other methods may be used to obtain time-resolved information. In the case of proteins containing an iron atom, Mossbauer spectroscopy allows the determination, in the iron binding site, of not only root-mean-square shifts of atoms but also the times over which such shifts occur. Detailed investigations of myoglobin have yielded relaxation times on the order of 10 8 Proton NMR spectroscopy can be used to... 

J. Thomas and G. N. LaMar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton NMR spectroscopy, Biochem, Biophys. Res. Commun. 119, 640-654 (1984). 

One-dimensional proton NMR spectroscopy is the most straightforward method for process validation and development. It can be used as a limit test, i.e., to demonstrate that a particular analyte is below the detection limit. It can also be used to accurately quantify an analyte by comparing the NMR peak area from a test sample against a standard curve. To get accurate quantitation, it is important to keep the acquisition parameters and conditions constant for both standard and test samples. For example, the receiver gain, power level, and duration of all pulses must stay the same within an assay. In addition, the probe should remain tuned for all samples. 

Proton NMR spectroscopy ( H MRS) has shown to offer excellent possibilities for evaluation of biochemistry in vivo. Due to its non-invasive character it is of increasing interest not only for the study of human brain diseases, which describe the majority of clinical applications, but also for metabolic characterization of organs outside the brain, as prostate, liver, heart or skeletal muscle. Studies on skeletal muscle have been of increasing interest during the last years, since it was shown that MRS enables the differentiation between two muscular lipid compartments the bulk fat components along the fasciae and muscular boundaries, which are called extramyocellular lipids (EMCL), and the metabolically highly active intramyocellular lipids (IMCL). The latter are stored in spherical droplets in the cytoplasm of muscle... 

An increasing number of studies on lipid metabolism in human skeletal muscle using localized MR proton spectroscopy have been performed since the first description of the phenomenon that proton NMR spectroscopy allows the differentiation of two distinct lipid compartments and the experimental confirmation that one of these compartments is attributed to the IMCL pool. The non-invasiveness and the high sensitivity even to low lipid concentrations under physiological conditions denote the uniqueness of this modality and allow examinations of large numbers of healthy volunteers and follow-up metabolic intervention studies. 

Since GR is contaminated with wax and other hydrocarbons it must be purified before chlorination. In our case purification was monitored by proton NMR spectroscopy (Figure 1). The peak assignments representing satisfactory purification are as follows ... 

For NMR, the intensity of the signal (which may be measured by electronically measuring the area under individual resonance signals) is directly proportional to the number of nuclei undergoing a spin-flip and proton NMR spectroscopy is a quantitative method. 

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