Qualitative Analyses Molecular Structure Determination

While some features of the proton NMR spectrum have been discussed earlier, we will go through some examples of how to use a proton NMR spectrum to work out the structure of some simple organic molecules. We need to understand a few more aspects of the NMR spectrum first. 

The primary use of NMR spectroscopy is for the determination of the molecular structure of compounds. These may be organic compounds synthesized or separated by organic chemists, pharmaceutical chemists, and polymer chemists organic compounds isolated by biologists, biochemists, and medicinal chemists and organometallic and inorganic compounds synthesized by chemists and materials scientists. The importance of NMR spectroscopy in deducing molecular structure cannot be overstated. 

Relationship Between the Area of a Peak and Molecular Structure As we learned in Section 3.4, the multiplicity of a given peak tells us the number of adjacent equivalent protons. The multiplicity tells us nothing about the number of protons that give rise to the peak itself. That information comes from the peak area. The total area of an absorption peak is directly proportional to the number of protons that resonate at the frequency. By total area, we mean the area of all the peaks in the multi-plet, if the peak is a multiplet, or the total area of the peak if the peak is a singlet. 

From this relative area calculation, we can state that there are twice as many protons in the group giving rise to peak B as there are in the group giving rise to peak C and that there are 3 x as many protons in the peak A group as in the peak C group. We cannot say that peak C is due to one proton and peak A due to three protons without more information. The empirical formula can be determined if we have elemental analyses information and the molecular formula can be calculated if the molecular weight is known from another measurement, such as MS. 

It is also important to keep in mind that the smallest peak may be equal to more than one proton. You can deduce this if your ratios look like 1.9 1.5 1, for example. Clearly, you cannot have a molecule with 1.5 protons on a carbon atom. Now, you need to multiply everything through by the same common factor, until you get whole number values. If you multiply 1.9, 1.5, and 1 by 2, you get 4, 3, and 2 protons, respectively, which is a reasonable set of whole numbers to work with in building a stmcture. A good practice example of this type is the spectmm of butylamine (Fig. 3.37). 

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Raman spectroscopy is by no means a new technique, although it is not as widely known or used by chemists as the related technique of infrared spectroscopy. However, following developments in the instrumentation over the last 20 years or so Raman spectroscopy appears to be having something of a rebirth. Raman, like infrared, may be employed for qualitative analysis, molecular structure determination, functional group identification, comparison of various physical properties such as crystallinity, studies of molecular interaction and determination of thermodynamic properties. 

An unknown substance, X, was isolated from rabbit muscle. Its structure was determined from the following observations and experiments. Qualitative analysis showed that X was composed entirely of C, H, and 0. A weighed sample of X was completely oxidized, and the H20 and C02 produced were measured this quantitative analysis revealed that X contained 40.00% C, 6.71% H, and 53.29% O by weight. The molecular mass of X, determined by mass spectrometry, was 90.00 u (atomic mass units see Box 1-1). Infrared spectroscopy showed that X contained one double bond. X dissolved readily in water to give an acidic solution the solution demonstrated optical activity when tested in a polarimeter. 

X-Ray methods are used for qualitative and quantitative elemental analysis, and for determination of crystal and molecular structure, by measurement of the absorption, emission, fluorescence, and scattering of... 

A number of low molecular weight products, for example, benzaldehyde, formic acid, formaldehyde, phenylglyoxal, phenylglyoxalic acid, and carbon dioxide, were identified among the products of thermal decomposition of the ozonides. A determination of the detailed structure of the polymer is possible from the qualitative analysis of these decomposition products. 

There are many reasons that one might want to record, assign, and interpret the electronic spectrum of a diatomic molecule. These include qualitative (which molecular species are present) and quantitative (what is the number density of a known quantum state of a known molecule) analysis, detection of trace constituents (wanted, as in analysis of ore samples for a precious metal, or unwanted, as in process diagnostics where specific impurities are known to corrupt an industrial process), detection of atmospheric pollutants, monitoring of transient species to optimize a combustion process by enhancing efficiency or minimizing unwanted byproducts, laboratory determinations of transition frequencies and linestrengths of interstellar molecules, and last but certainly not least, fundamental studies of molecular structure and dynamics. 

These two structures are two different compounds with the same molecular formula. They are called isomers. Elemental analysis cannot distinguish between these isomers, but NMR and MS usually can distinguish isomers. Another example of a more difficult qualitative analysis problem is the case of the simple sugar, erythrose. The empirical formula determined by elemental analysis is CH2O. The molecular formula, C4Hg04, and some of the structure can be obtained from IR, NMR, and MS, but we cannot tell from these techniques which of the two possible isomers shown in Eig. 1.1 is our sample. 

Qualitative analysis MS can be used to identify the molecular weight of organic and inorganic compounds, from very small molecules to large polymers and biological molecules (> 100,000 Da). MS is a powerful tool in the determination of the structure of organic compounds. Fragmentation patterns can reveal the presence of substructure units within the molecule. 

MS is a useful analytical technique to analyze and determine the molecular structure of an organic compound by observing its fragmentation pattern. This can be applied to qualitative or quantitative analysis. 

Molecular orbital calculations have been widely used both for the investigation of the structure and the aromaticity of these seven-membered heterocycles as well as for the determination of the reaction pathways. A qualitative analysis based on MNDO and ab initio molecular orbital calculations has been reported <87JCS(P1)1579,87JCS(P2)i669> for the cycloaddition of several alkynes to tetrasulfur tetranitride with the formation of trithiadiazepines and 1,2,5-thiadiazoles (see heme 28). 

Identification is primarily based on molecular-mass determination, while for an actual structure elucidation LC-MS must be used in combination with tandem mass spectrometry (MS-MS). ESI and APCI are soft-ionization techniques, generating only intact molecule-derived ions, but no fragment ions for most molecules. Therefore, it is frequently applied in combination with MS-MS to achieve more structural information. With respect to qualitative analysis, the use of electrospray LC-MS-MS for peptide sequencing as part of proteomics research is currently an important area. 

While X-ray diffraction at present provides the ultimate method for the complete determination of the three-dimensional structure of a solid compound, the organic chemist requires a more rapid method for the determination of the molecular constitution of materials, which are often liquids. Infrared spectroscopy still provides a valuable method of qualitative analysis, but more powerful methods of structure determination have been widely employed since the early 1960s. The two most important are nuclear magnetic resonance and mass spectroscopy. 

In connection with the identification of an organic compound, time will usually not permit a quantitative analysis for the elements (step three, above), since it is desired to identify a compound not in a few days time, but during a few hours. For the same reason, molecular weight determinations are applied only in exceptional instances. Step five, the assignment of structure, often involves years of investigational work. Fortunately, this work has already been accomplished for an enormous number of organic compounds, and the path has thus been cleared in the direction of qualitative identification when these compounds are again met. 

This chapter is concerned with quantitative equilibrium constants obtained for proton transfer equilibria at near room temperatures. There have been numerous reports of qualitative orders of base and acid strengths [10, 17, 26-33, 52, 53] which have been valuable as guide-lines for subsequent quantitative studies as well as for isolating a number of important structural features. The quantitative results are required, however, for analysis and separation of molecular structural effects. The first report of equilibrium constant determinations for gaseous proton-transfer reactions is due to Bowers, Aue, Webb, and Mclver [14]. 

W. Brugel, Introduction to Infrared Spectroscopy, Wiss. Forschungsber. Naiurw. Reihe 62, 1-366, 1954. A review, with 595 references, on the theory of infrared spectra, on apparatus and methods of study, and on the application to determination of molecular structure and chemical constitution, and to qualitative and quantitative analysis. 

Relative contribution of each of these structures differs significantly and is determined by internal structural characteristics of the nitrones and by the influence of external factors, such as changes in polarity of solvent, formation of a hydrogen bond, and complexation and protonation. Changes in the electronic stmcture of nitrones, effected by any of these factors, which are manifested in the changes of physicochemical properties and spectral characteristics, can be explained, qualitatively, by analyzing the relative contribution of A-G structures. On the basis of a vector analysis of dipole moments of two series of nitrones (355), a quantum-chemical computation of ab initio molecular orbitals of the model nitrone CH2=N(H)0 and its tautomers, and methyl derivatives (356), it has been established that the bond in nitrones between C and N atoms is almost... 

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