Carbonates spectra

Two-dimensional nmr spectroscopy has led to a much better understanding of biopolymers and their function (151). This technique has been apphed to polyacrylamide for absolute assignments of proton and carbon spectra at the tetrad level (152). 

This bond is clearly visible in both the proton and carbon spectra. We recommend making a table of the information these give the tables can be added to as the structure elucidation continues. 

If one wishes to obtain a fluorine NMR spectrum, one must of course first have access to a spectrometer with a probe that will allow observation of fluorine nuclei. Fortunately, most modern high field NMR spectrometers that are available in industrial and academic research laboratories today have this capability. Probably the most common NMR spectrometers in use today for taking routine NMR spectra are 300 MHz instruments, which measure proton spectra at 300 MHz, carbon spectra at 75.5 MHz and fluorine spectra at 282 MHz. Before obtaining and attempting to interpret fluorine NMR spectra, it would be advisable to become familiar with some of the fundamental concepts related to fluorine chemical shifts and spin-spin coupling constants that are presented in this book. There is also a very nice introduction to fluorine NMR by W. S. and M. L. Brey in the Encyclopedia of Nuclear Magnetic Resonance.1... 

The proton and carbon spectra for /-butyl fluoride are provided in Figs. 3.9 and 3.10. 

Proton and Carbon Spectra. Proton and carbon NMR data, including 31P chemical shift and P—C coupling constants for the above compounds are given in Scheme 3.27. 

Proton and Carbon NMR Data. Some selected chemical shift and coupling constant data from proton and carbon spectra of chloro- and bromofluoroethylenes are presented in Scheme 3.46. 

The isomeric 1- and 2-fluoronaphthalenes have fluorine chemical shifts of -124 and -116 ppm, respectively. A full analysis of the proton and carbon spectra of 1-fluoronaphthalene is given in Scheme 3.56. NMR data for a number of other fluoropolycyclic aromatic compounds are available.7... 

There do not appear to be proton or carbon spectra available for these compounds, but note the relatively small 2/FH coupling constants of these compounds. 

Regarding carbon spectra, an alcohol, ether, or ester function on the adjacent carbon shields the carbons of a CF3 group (Scheme 5.13). 

Some proton and carbon data for trifluoroethyl compounds are given in Scheme 5.27, with the proton and carbon spectra of 4,4,4-trifluoro-... 

Proton and carbon spectra of 3,3,3-trifluoropropene are provided in Figs. 5.12 and 5.13 as specific examples of such spectra. The proton spectrum is more complicated than one would have expected based on a first-order analysis. However, a fluorine-decoupled spectrum becomes first order, as was depicted and discussed in Chapter 2, Section 2.3.5, Figs. 2.9 and 2.10. 

The proton and carbon NMR spectra of both of these trifluoroethyl systems are marked by the usual large two-bond F—H coupling constants, with the 1,2,2-trifluoro system exhibiting individual coupling constants from the A and B fluorines to the CHF2 carbon. Data for the proton and carbon spectra of both types of trifluoroethyl compounds are provided in Scheme 6.3. 

Hexafluoro-wo-propanol has become a popular solvent. Its fluorine, proton, and carbon spectra are provided in Figs. 6.15-6.17. The doublet in the fluorine spectrum centered at -77.1 ppm exhibits a three-bond... 

D-correlation spectra were collected. This information was used with empirical spectral simulations of proton and carbon spectra to elucidate the structures. The necessary information was thus provided to demonstrate that multiple dimer-like structures were formed through bonding of residual synthetic precursor to each of the hydroxyl sites of the drug substance itself. Three distinct dimers were identified. These species were tracked by LC-NMR, and two were shown to interconvert over time. Analogous trimer structures were also evident at lower levels. 

A comparison of the carbon SSNMR spectra of the manufactured formulation to that of the equivalent physical mixture, both shown on the left of Fig. 10.25, shows no significant differences. The chemical shift and line shape differences between the top and bottom carbon spectra in the figure are minor and thus do not themselves prove an interaction between the API and excipients. Small spectral differences such as these may arise from minor fluctuations in sample temperature, for instance. One may, albeit incorrectly, conclude at this point that no drug-excipi-ent interactions exist. However, as we shall soon see, it is risky to make such conclusions based on the lack of an observed change. 

To continue the investigation, carbon detected proton T relaxation data were also collected and were used to calculate proton T relaxation times. Similarly, 19F T measurements were also made. The calculated relaxation values are shown above each peak of interest in Fig. 10.25. A substantial difference is evident in the proton T relaxation times across the API peaks in both carbon spectra. Due to spin diffusion, the protons can exchange their signals with each other even when separated by as much as tens of nanometers. Since a potential API-excipient interaction would act on the molecular scale, spin diffusion occurs between the API and excipient molecules, and the protons therefore show a single, uniform relaxation time regardless of whether they are on the API or the excipients. On the other hand, in the case of a physical mixture, the molecules of API and excipients are well separated spatially, and so no bulk spin diffusion can occur. Two unique proton relaxation rates are then expected, one for the API and another for the excipients. This is evident in the carbon spectrum of the physical mixture shown on the bottom of Fig. 10.25. Comparing this reference to the relaxation data for the formulation, it is readily apparent that the formulation exhibits essentially one proton T1 relaxation time across the carbon spectrum. This therefore demonstrates that there is indeed an interaction between the drug substance and the excipients in the formulation. 

Fortuitously for this project, the drug substance, and not the excipients, contained a fluorine moiety. Fluorine-19 MAS spectra were therefore also acquired at 500 MHz on the two samples, and they are shown to the right of the corresponding carbon spectra for each sample in Fig. 10.25. The fluorine-19 chemical shifts are sensitive enough in this example to show the API-excipients interaction directly. This is evident from the dramatic change in spectral line shape. 

In this case study, it was demonstrated that conclusions based on the lack of observations, such as no change observed for the carbon spectra, could be misleading. It is much more compelling to identify an... 

XPS Spectrum of Surface. Figure 2 shows XPS spectra of CDC nickel-plated sheets with various pretreatment. Carbon, oxygen, chromium and nickel are observed in the surface of CDC nickel-plated sheets oiled with DOS and ATBC. The carbon spectra show ester carbonyl carbon and hydrocarbon species on both samples. The ester carbonyl carbon reflects the ester bond of DOS (C8Hi7C00C8Hi60C0C8Hi7) and ATBC ((C3H7COO)3C(CH2)OCOCH3). 

In Fig. 8 are shown the olefin carbon spectra of four copolymers as a function of temperature, including that shown in Fig. 6. As we have seen, eight groups of resonances are recognizable. 

Carbon-13 NMR spectroscopy has also been utilized to probe the structure, isomers, and conformational aspects of 1,2,5-oxadiazole chemistry. The dc values for monocyclic furazans vary from 140 to 160 ppm depending on the substituent, and C- H couplings of ca. 200 Hz are observed for the parent furazan and monosubstituted derivatives (92KGS1 lOl >. For furoxans the most noteworthy feature of their carbon spectra is the large displacement of the C(3) resonance to lower chemical shift. While the C(4) peak remains in the range 140-160 ppm that for C(3) is shifted to 100-125 ppm. At low temperatures benzofuroxan shows two peaks at 113.7 (C(3)) and 152.2 (C(4)) which coalesce on warming. The parent furoxan has C- H couplings of 211 Hz for C(3) and 202 Hz for... 

Carbon-13 NMR spectra were obtained using a JEOL FX90Q operating at 22.5 MHz for carbon. Spectra were obtained using 75° pulses and a 4 sec. delay between pulses with complete proton decoupling. The samples were analyzed in 10 mm tubes. 

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