Uses of 13C NMR Spectroscopy

The information derived from l3C NMR spectroscopy is extraordinarily useful for structure determination. Not only can we count the number of non-equivalent carbon atoms in a molecule, we can also get information about the electronic environment of each and can even find how many protons each is attached to. As a result, we are able to answer many structural questions that go unanswered by infrared spectroscopy or mass spectrometry. 

Let s take an example. How might we prove that E2 elimination of an alkyl halide gives the more highly substituted alkene (Zaitsev s rule, Section 11.10) Does reaction of 1-chloro-l-methylcyclohexane with strong base lead predominantly to 1-methylcyclohexene or to methylenecyclo-hexane  

The 1 C NMR spectrum of 1-methykydohexene, the E2 reaction product from 1 -chloro-1 -methylcydohexane. 

Problem 13,12 We saw in Section 8.4 that addition of HBr to terminal alkynes leads to tl Markovnikov addition product, with the Br bonding to the more highly substitute carbon. How could you use 13C NMR to identify the product of the addition of 1 

Problem 13.11 Propose a structure for an aromatic hydrocarbon, CnH16, that has the following 

1-Methylcyclohexene will have five sp3-carbon resonances in the 20 to 50 6 range and two s/ -carbon resonances in the 100 to 150 6 range. Methylenecyclohexane, however, because of its symmetry, will have only three sp3-carbon 

454 CHAPTER 13 Structure Determination Nuclear Magnetic Resonance Spectroscopy 

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The use of 13C-NMR spectroscopy in stereochemical assignment of disubstituted cyclopentanes has been investigated using dimethylcyclopentanes and mcthylcyclopentanols495. In 1,2-disubstituted derivatives the chemical shifts of the substituted and the methyl carbons are significantly smaller (2 to 5 ppm) in the cis than in the trans series. In 1,3-disubstituted cyclopentanes the sequence is the same, but the differences are often so small that a reliable assignment is possible only if both isomers are available. 

Use of 13C nmr spectroscopy to determine whether a substituent is in an axial or equatorial position is well illustrated with cis- and trans-4-tert-bntylcyclo-hexanols, 5 and 6 ... 

The review aims to highlight some recent studies that involve liquid crystals and show the utility of newer pulse NMR techniques in LC. They may involve solutes dissolved in ordered phases and their applications, or may involve the molecular ordering, rotational and/or translational diffusion of solvent molecules. Deuterium NMR spectroscopy has demonstrated many advantages over other nuclei like H and 13C, but the need to specifically deuteriate mesogens is sometimes a major drawback. 13C NMR spectroscopy seems to be useful since non-enriched samples can often be used. However, the use of 13C NMR in semi-solids like LC often requires more sophisticated NMR techniques and instrumentation. There are indeed many uncharted... 

Application of 13C NMR spectroscopy to heterocyclic chemistry has developed very rapidly during the past 15 years, and the technique is now used almost as routinely as 1H NMR spectroscopy. There are four main areas of application of interest to the heterocyclic chemist (i) elucidation of structure, where the method can be particularly valuable for complex natural products such as alkaloids and carbohydrate antibiotics (ii) stereochemical studies, especially conformational analysis of saturated heterocyclic systems (iii) the correlation of various theoretical aspects of structure and electronic distribution with chemical shifts, coupling constants and other NMR derived parameters and (iv) the unravelling of biosynthetic pathways to natural products, where, in contrast to related studies with 14C-labelled precursors, stepwise degradation of the secondary metabolite is usually unnecessary. 

For the synthesis of peptides, amino acid derivatives with protected amino or carboxy groups are used as starting materials. The application of 13C NMR spectroscopy for the control of the synthesis of those protected amino acids has ben reported in the literature [791, 792, 794]. 

The tacticity of anionically prepared polystyrenes has been the subject of extensive study by a number of groups of workers, mostly by means of 13C-NMR spectroscopy. From a study of the aromatic Cl resonances, Matsuzaki and coworkers found 234) that there is a tendency towards syndiotacticity when using -butyl-Iithium in toluene as initiator. From the sensitivity of the CMR spectrum to the nature of the solvent employed it was concluded that the polymerization did not conform to Bernoullian statistics. Randall examined the methylene resonances in the CMR spectrum and concluded that butyllithium initiated polystyrene is essentially atactic 235) and that propagation is Bernouillian. Uryu et al.236) examined polystyrene... 

Compared with spectrophotometry, the NMR method has a number of advantages (i) The procedure is very rapid, and it can be used by observing the variation of chemical shifts of diverse nuclei such as 3H, 13C, 19F, and nO. (ii) It is insensitive to colored impurities and slight decomposition of the indicator, (iii) In principle, it can be used over the whole range of known acidity. The medium effect, which may be important in 1H NMR, becomes negligible in the case of 13C NMR spectroscopy. The method can be used with a wide variety of weak bases having a lone-pair containing heteroatoms as well as simple aromatic hydrocarbons. 

Notwithstanding all its advantages, the principle of solid-phase synthesis cannot be applied to all kinds of chemical reactions. Although reactants are used in excess, reaction is not always quantitative. The resulting impurities cannot be separated on the solid phase, giving rise to separation problems particularly in multi-step systems. Moreover, only limited use can often be made of conventional analytical methods (NMR, MS). Recent methods of 13C-NMR spectroscopy on solid phases [21] or in gel phases [22] are ideally suited for solid-phase synthesis, but are not universally available owing to the expensive instrumentation. 

A final example of the application of 13C NMR spectroscopy is taken from our work9 on copolymers of methacrylates and vinyl phenol which were synthesized using similar chemistry to that shown previously for the styrene-co-vinyl phenol copolymers. In Figure 7-48 are typical 13C NMR spectra of an ethyl methacrylate (EMA) copolymer containing 52 mole % EMA before (top) and after (bottom) deprotection. The absence of the NMR peaks at around 0 ppm (the two methyl carbons attached to silicon), 19 ppm (the tertiary carbon of the f-butyl group), and 26 ppm (the three methyl carbons on the f-butyl group) after desilylation, clearly indicates the absence of any residual f-butyldi-methylsilyl groups. 

The structure of a 3-0- p -D-glucopyranoside of calystegine B, was determined by the use of 2D NMR spectroscopy [32], The linkage site was established by a correlation peak in the HMBC spectrum between the anomeric proton and the aglycone C(3) carbon. A downfield shift fix the C(3) resonance and upfield shifts for the C(2) and C(4) resonances in the 13C NMR spectrum, relative to the aglycone, provided additional confirmation for the structure. 

The samples used for NMR spectroscopy were freeze-dried to prevent any reaction during the drying process. Adamantane and the trimethylsilyl ester of double four-ring octameric silicate, Q8M8 were used to optimize experimental parameters and as external secondary (relative to TMS) chemical-shift references for 13C and 29Si, respectively. Both the Ti measurements and a discussion on the use of 29Si NMR spectroscopy for quantitative measurements will be described elsewhere (47). 

In 1972, Jones and Benn (100, 101) made a significant contribution in the application of 13CNMR spectroscopy by demonstrating the use of 13C NMR studies in elucidating the structures of two new Ci9-diterpenoid alkaloids. The 13C NMR spectra of the several aconitine- and lycoctonine-... 

H-NMR spectroscopy can be used to determine alkenesulfonates in mixtures [115]. Under normal conditions, 1-alkenesulfonate shows a signal separated from the other positional isomers [122]. Moreover, the utilization of a lanthanide shift reagent makes possible even the separation of the signals of isomeric alkenesulfonic acids and hydroxyalkanesulfonic acids as their methyl esters [124]. 13C-NMR spectroscopy, which is not as quantitative, simply gives the cis/trans ratio of the main positional isomer. 

Because this diketene acetal is so susceptible to cationic polymerization, acids cannot be used to catalyze its condensation with diols because the competing cationic polymerization of the diketene acetal double bonds leads to a crosslinked product. Linear polymers can, however, be prepared by using iodine in pyridine (11). Polymer structure was verified by 13c nmR spectroscopy as shown in Fig. 

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