Madelungs method

The title compound, mapindolol 198, a potent /7-adrenoceptor blocking (antihypertensive) agent, has been synthesized200 by the Madelungs method of indole synthesis using [l-14C]acetyl chloride as starting material (equation 80). 

Two of these reactions are, in the most general terms, examples of intramolecular aldol condensations. Path A, which includes the Madelung method and its variants, uses o-substituted anilides as starting materials. Path B reverses the electrophilic and nucleophilic components for C2—C3 bond formation. Among the classic indole syntheses corresponding to the first pattern is the Madelung synthesis, exemplified by the preparation of 2-methylindole from iV-acetyl-o-toluidine (Equation (16)) <550SC597>. 

A variation of the Madelung cyclization involves installing a functional group at the o-methyl group which can facilitate cyclization. For example, a triphenylphosphonio substituent converts the reaction into an intramolecular Wittig condensation. The required phosphonium salts can be prepared by starting with o-nitrobenzyl chloride or bromide[9]. The method has been applied to preparation of 2-alkyl and 2-arylindoles as well as to several 2-alkenylindoles. Tabic 3.2 provides examples. 

In our case there are six different sites in the considered cluster. So, to apply the method described previously (system of equations (1)), we need seven shells to reproduce the Madelung potential on these six sites. There are various possibilities to define seven shells by considering various grouping of the 218 charges located on the exterior surface of the complete array. As an example consider the following definition of shells which we used in our calculation SI contains 32 yttrium ions located on the upper and lower faces of the array S2 contains 24 yttrium ions on the lateral faces S3... 

The constant A in this expression is called the Madelung constant. It can be evaluat ed by straightforward mathematical methods.3 Values of... 

Based upon the method of calculation adopted, a complete computer programme consisting of three main parts can easily be written for support of such calculations. The three parts are as follows (a) the CNDO part or EHMO part with Madelung correction for calculation of the localized electron orbitals in the anionic group (b) the transition matrix element calculation part and (c) the second-order susceptibility part for the calculation of the microscopic susceptibility of the anionic group followed by the calculation of the macroscopic SHG coefficients of the crystal. 

The theorem has the important implication that intramolecular interactions can be calculated by the methods of classical electrostatics if the electronic wave function (or charge distribution) is correctly known. The one instance where it can be applied immediately is in the calculation of cohesive energies in ionic crystals. Taking NaCl as an example, the assumed complete ionization that defines a (Na+Cl-) crystal, also defines the charge distribution and the correct cohesive energy is calculated directly by the Madelung procedure. 

For crystals containing unequal numbers of multiple cations and anions, the definition of a Madelung constant becomes more complicated, but the Madelung (or lattice) energy can always be calculated by simple computerized methods [76]. In principle, a dimensionless interaction curve can be derived for any structure type. 

For many of the compounds described in this chapter, there is not sufficient commercial interest in the materials for the development of reasonable synthetic routes. Exceptions are the pyr-rolopyridines, furopyridines, and thienopyridines. Even for these compounds, most of the classical literature routes (Madelung and Fischer methods, for example, for the pyrrolopyridines) lead to... 

As a solution to this problem we have tried the application of Madelung potential [2] to the semiconductor crystals. Till now, the trial has not been carried out in the semiconductor crystals to our knowledge except our presentation at the fourth international conference on DV-Xa method (2006) [3]. The difficulty in the application to the semiconductor crystals might be related with a kind of a sea with + electronic charges used in the Madelung potential technique. This is partly so because the semiconductor crystals such as Si and diamond are of covalent bond structure and these crystals are composed of a single element. These two difficulties make the application of a Madelung potential to the semiconductor crystals difficult. 

---