Purity target compounds

Because of the instability of many of the compounds involved, it is necessary to determine the chemical recoveries in all cases. This requires the use of macro quantities (10 mg up to several hundred mg) of carriers and target compounds. This, in turn, makes it impractical to use the various thin-layer methods, such as paper and thin-layer chromatography and paper electrophoresis, although such methods have proved useful in identifying products and in checking the purity of fractions. The separation methods now most commonly used are column chromatography and sublimation. 

As CH-acids in the MCRs with aldehydes and aminoazoles, other classes of organic compounds were used as well. Cyanoacetic acid derivatives, acetoyl(aroyl) acetonitriles, ketosulfones, acetophenones, and other reagents were successfully introduced into these three-component heterocyclizations. For example, synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles 40 was carried out as the multicomponent treatment of 5-aminopyrazole, aldehyde, and benzoylacetonitriles solvent-free by fusion either in ammonium acetate at 120°C or in boiling ethanol with EtsN (Scheme 17) [69]. The second approach gave the worst results from the viewpoint of yields and purity of the target compounds. 

An important criteria in solid-phase synthesis is product purities immediately after cleavage from the support. Ideally, the target compound should be cleaved into a solvent-reagent system that can be easily removed, usually by evaporation. Solvents/cleavage reagents that are difficult to remove may compromise subsequent biological screening of the libraries. Consequently,... 

An equimolar amount of a resolving agent is reacted with a several mmol amount of a target racemate. The crystallizing condition is adjusted so as to crystallize out about a half-molar amount of the diastereomeric salt. After the target compound is recovered by decomposing the salt, the optical purity of the obtained enantiomer is measured. 

In certain cases, the enantiomer of high purity is usually obtained by recrystallizing the enantiomer mixture which is recovered by decomposing the diastereomeric salt. In such a case, it is favorable to know the crystallizing characteristic of the target compound. For instance, the crystallizing characteristic of an enantiomer mixture can be outlined by its binary phase diagram. 

Compared to batch protocols, the flow reaction afforded the target compound 128 in quantitative yield and purity, with no sign of the competing ketal 129 formation. Although the flow reactions proceeded to near quantitative conversion in all cases, should the 1,3-dithiane or 1,3-dithiolane be used in subsequent reaction steps where Pd catalysts are employed for example, it is crucial than no dithiol residues are present. With this in mind, the authors packed a plug of silica gel impregnated... 

Sheng and co-workers [113] described an efficient Hantzsch reaction for the synthesis of polyhydroquinolines 67 applying a solvent-free microwave-assisted one-pot four-component reaction of PEG-bound acetoacetate, 1,3-cyclohexane-dione, an aromatic aldehyde and ammonium acetate in the presence of a catalytic amount of PPA. The target compounds 67 were obtained in excellent yields and purities, after cleavage from the PEG support using NaOEt in EtOH. The reactions were carried out in domestic microwave oven (Scheme 51). 

The reaction of metal hydrides MH2 with acidic hydrocarbons seems an attractive way to prepare the target compound since a commercially available metal source can be utilized. Moreover, the formation of only gaseous byproducts ensures a facile work-up (equation 13). However, only few compounds have been prepared using this route owing to the low reactivity of the hydrides caused by their polymeric, insoluble nature. Moreover, the unreliable purity of the commercial hydrides poses significant problems. As such, rather acidic ligands and enforced reaction conditions are required for the reaction to proceed. 

Normally, a report would give the chemist information about whether his target compound was present, what was the sample purity and identification of those impurities by virtue of the diode-array detection of all components present > Wc. An example of the report is given in Fig. 5.7 for a four-component test mix. 

The best results were obtained with aluminium hydroxide resulting from hydrolysis of aluminium(III) iso-propylate. A high sorption capacity (ca 10%) of compound 2, a high degree of desorption of complex 3, and the purity of the resulted clathrochelate 4 make aluminium(III) hydroxide the most suitable matrix for the synthesis of targeted compounds [64]. 

The determination of the purity of intermediates in a synthetic route to a target compound is more common in pharmaceutical analysis than organic or food analysis. This is because lengthy syntheses are more common in the preparation of drugs than foods or general organic compounds. 

There are certain requirements for purity of new compounds in most journals. This is especially so for samples which are shown to have biological activity. See instructions to authors for ACS journals especially in J. Med. Chem (see Guidelines for Authors under Purity Criteria for Target Compounds (i) ) which specify that elemental analysis (with an accuracy of 0.4%), homogeneity by HPLC, and spectral data (e.g. NMR, HRMS) as well as biological activity data should be stated in the paper or in supporting information. 

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