Solution-Phase Organic Chemistry

Standard quantum chemical computations are performed on a single molecule or complex. This isolated species represents a molecule in the gas phase. While gas-phase chemistry comprises an important chemical subdiscipline, the vast majority of chemical reactions occur in solution. Perhaps most critical is that aU of biochemistry takes place in an aqueous environment, and so if computational chemistry is to be relevant for biochemical apphcations, treatment of the solvent is imperative. 

Neglecting solvent effects is extremely hazardous. Equilibria and kinetics can be dramatically altered by the nature of the solvent For example, the rate of nucleophilic substitution reactions spans 20 orders of magnitude in going from the gas phase to polar and nonpolar solvents. A classical example of a dramatic solvent effect on equilibrium is the tautomerism between 1 and 2. In the gas phase, the equilibrium lies far to the left, while in the solution phase, 2 dominates because of its much larger dipole moment. Another classical example is that the trend in gas-phase acidity of aliphatic alcohols is reverse of the well-known trend in the solution phase in other words, in the solution phase, the relative acidity trend is R3COH R2CHOH RCH2OH, but the opposite is true in the gas phase.  

Computational Organic Chemistry, Second Edition. Steven M. Bachrach 2014 John Wiley Sons, Inc. Published 2014 by John Wiley Sons, Inc. 

Over the past 25 years, a number of significant theoretical and algorithmic advances have been proposed towards incorporating solvent effects into quantum chemical computations. These methodologies were presented in Section 1.4. Interested readers looking for further computational details are referred to the monographs by Cramer and Jensen and comprehensive reviews by Tomasi, ° Cramer and Truhlar, and Mennucci. This chapter presents representative case studies of aqueous-phase chemistry analyzed using quantum mechanical computations. 

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A host of analytical techniques, including thin-layer chromatography and NMR spectroscopy, are available to the researcher in the field of solution-phase organic chemistry. These methods enable rapid assessment of the progress of the reaction in question. 

Nucleophilic/electrophilic reactions are frequently observed in solution phase organic chemistry and have thus been subjected to detailed study [42]. In the majority... 

The further development of these methods will allow chemists to select an appropriate method on the basis of the specific SP synthetic problem in hand and the instmmentation available in their laboratory. Eventually, analytical monitoring will become a routine element of SPS, as it is in classical solution-phase organic chemistry, and one of the major bottlenecks for the further development of SPS will disappear. 

While the majority of attention in combinatorial syntheses has been on solid phase analysis, the use of traditional solution phase organic chemistry to form compound collections should not be disregarded. MS techniques are widely used for evaluation of mixtures produced by combinatorial chemistry (4). However, a potential problem with the MS methodology involves a situation when isomolecular weight compounds are present. The compounds can be stereoisomers, positional isomers or by chance identical molecular weight materials. In these cases, the identity of the substance as determined by MS can be ambiguous. 

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