Assessing Solid Phase Reaction Yields

Though the reaction progress was monitored by both IR and gel-phase NMR, these spectroscopic tools are of relatively low sensitivity when used for resin analysis. Yield estimation by these methods was difficult, especially for the longer oligomers. For these reasons, the approaches used for the calculation of yield are described. 

The yield can be determined based on the weight difference of the resin. The weight increase caused by chemical modification of the resin (AW) is related to the yield (Y) by the following relation  

The molar concentrations of the products in the final resins were also monitored for compounds 50-58. The molar concentration decreases as the resin s mass increases due to modification of the reactive moiety. The actual concentration (mol/g) of the product in the final resin (Npf) is given by 

The theoretical and experimentally determined values for Npf are listed in Table 3.1. In both cases the concentration of 50 in the final resin was determined via elemental analysis using a method that will be described later. This initial value of 0.61 nunol/g was then used as the basis for the remainder of the calculations. The errors of the weight measurement caused significant discrepancies in the calculated concentrations. As a result, the moles of reagent needed in the polymer-supported reactions were determined assuming quantitative yields for all previous steps other than the formation of 50. 

The yield of these reactions was also derived from the elemental analysis data. The caleulations assumed that no side reactions were taking place and that unreacted functionality did not participate in any subsequent reactions. The element used for the calculations was unique either to the moiety being added to the resin or to the starting functionalized resin. Three distinct situations were encountered which required different methods of yield determination (1) The tag element was added to the resin over the course of the reaction. (2) The tag element was removed from the resin. (3) The tag element was unique to the resin and present before and after the reaction. The derivations of the equations used for each case are outlined here. 

---

The optimized reaction conditions to make the same library in solution or on SP differ significantly in most examples because of the influence exerted by the heterogeneous support (see Chapter 1), which may lead to different purities and yields of the final compounds. When the chemistry assessment, either in solution or on solid phase, does not give satisfactory results after having exploited all the reasonable experimental conditions, the other phase should at least be considered before abandoning the library synthesis. 

For the determination of standard Gibbs energies of reaction, a wide variety of experimental methods have been devised. These may be subdivided into e.m.f. measurements, equilibria with a gaseous phase, and distribution equilibria. From the temperature coefficients of the Gibbs energies, enthalpies and entropies of reaction can be deduced, but experience has shown that these cannot be relied upon when one or more solid phase takes part in the reaction, and errors are very difficult to assess. In such cases, it is recommended that the enthalpies of reaction are measured caloriraetrically and combined with the standard Gibbs energies to yield standard entropies of reaction. Calorimetric methods are also used to determine heat capacities, enthalpies of transformation, and enthalpies of fusion. Only for the determination of enthalpies of evaporation may... 

It should be noted that the exact cation stoichiometry of the product is highly sensitive to the exact metal concentration of the ruthenium source solution and temperature and pH of the reaction medium (inadvertent increases in both of these parameters lead to increased solubility of lead in the alkaline reaction medium and consequently yield solid products of lower lead ruthenium ratios). While synthesis of a pure lead ruthenium oxide pyrochlore is relatively easy, the precise cation stoichiometry of the product is a property that is not always easy to control. A relatively quick check on the cation stoichiometry of the lead ruthenium oxide product can be obtained, however, by using the correlation between lattice parameter and composition that is displayed in Fig. 1. When lattice parameter and cation stoichiometry are independently determined, the relationship shown in Fig. 1 also provides an assessment of product purity since data points that show significant departures from the displayed linear correlation indicate the presence of impurity phases. The thermal stability of the lead ruthenium oxides decreases with increasing occupancy of tetravalent lead on the octahedrally coordinated site, but all of the ruthenium oxide pyro-chlores described are stable to at least 350° in oxygen. 

---