High-dilution synthesis methods

The synthesis of podand hosts is conceptually relatively straightforward and is generally achieved using conventional synthetic methods such as ether, sulfide or amide bond formation however, the synthesis of macrocycles is a little more challenging and is accomplished by one or both of two general procedures, i.e. high-dilution synthesis and template synthesis. 

The intramolecular version for synthesizing cyclic and polycyclic compounds offers a powerful synthetic method for naturally occurring macrocyclic and polycyclic compounds, and novel total syntheses of many naturally occurring complex molecules have been achieved by synthetic designs based on this methodology. Cyclization by the coupling of an enone and alkenyl iodide has been applied to the synthesis of a model compound of l6-membered car-bomycin B 162 in 55% yield. A stoichiometric amount of the catalyst was used because the reaction was carried out under high dilution conditions[132]. 

Synthesis. Iminoboranes, thermodynamically unstable with respect to oligomerization can be isolated under laboratory conditions by making the oligomerization kineticaHy unfavorable. This is faciUtated by bulky substituents, high dilution, and low temperatures. The vacuum gas-phase pyrolysis of (trimethylsilylarnino)(aLkyl)haloboranes has been utilized as an effective method of generating iminoboranes RB=NR as shown in equation 19 for X = F,... 

In the course of experiments directed at the synthesis of open-chained equivalents of macrocyclic polyethers (see Chap. 7), Rasshofer and Vogtle found that 9 or its derivatives were formed rather than the desired compounds . Although the yields obtained by this method are modest, the facts that the reaction is conducted without the use of high dilution and in one-pot recommend it. 

Shortly after their first report of all-oxygen bridged cryptands, Dietrich, Lehn and Sauvage reported incorporation of sulfur in the strands. The experimental methods used were essentially similar to those applied in the syntheses of the parent cryptands. As in previous cases, a diacyl chloride was condensed with a diamine under high dilution conditions. In this case, however, the diamine contained sulfur atoms rather than oxygen. The synthesis of compound 5 was accomplished in two stages as illustrated below in Eq. (8.3). The first cyclization step affords the macrocyclic amine in 55% yield. The macrobicyclic product (5) is formed in 25% yield from the monocyclic diamine and the acid chloride. 

Trost and coworkers137 have reported the polymer-supported palladium catalyzed cyclization of 1, l-bis(phenylsulfonyl)epoxyalkene 235 which gives cycloalkanes 236 and 237 in a 2 1 ratio (equation 143). This method has proven useful for the synthesis of macrocyclic compounds under neutral conditions without using high dilution technique. Temperature and concentrations are critical. The best results are achieved if a reaction mixture of 0.1-0.5 m is added to a preheated (at 65 °C) suspension of the catalyst. 

The high-dilution and template methods are frequently used in the synthesis of cyclic compounds with the aim of increasing the yield. The former method is carried out at substrate concentrations lower than 1 mM [18-20]. This reaction condition decreases the contact of the substrate molecules in the solution. The linear intermediate produced prefers the intramolecular cyclization reaction rather than the intermolecular reaction. Therefore, this reaction condition is useful for the intramolecular reaction, method B (Fig. 2). 

Recently, Dolbie2"21 reported a new, nonpyrolytic method for the synthesis of PA-F dimer [Eq. (4)]. This method allows easy laboratory preparation of gram quantities of PA-F dimer but still presents difficulties with regard to commercialization because of the high-dilution methodology that is required for a good yield of high-purity product. 

The following synthesis of OBISTREN is carried out by the coupling of two tripodal subunits, by triple C—N bond formation without the use of high-dilution conditions. The procedure was first described by Dietrich et al.14 and was later modified by Motekaitis et al.3 It had previously been synthesized by a stepwise procedure requiring a high-dilution step.10 The tripodal synthetic method has been used to synthesize several analogs of OBISTREN.14 The procedure used here is described in detail by Chen et al.15... 

Spinel oxides are important industrial catalysts, possessing good thermal and chemical stability and an ability to maintain catalytic activity at high temperatures. The study reported here is concerned with the properties ofZn(II)-Cr(III) spinel oxides prepared from a carbonate containing LDH precursor. For this study the spinel oxide was separated, by treatment with dilute mineral acid, from the oxide mixture (ZnO and ZnC O, ) obtained by the thermal decomposition of LDH. For comparison, Zn(II)-Cr(lII) spinel oxides were also prepared by more standard synthesis methods. Structural and textural properties were evaluated, using PXRD, TG/MS, FT-IR and N2 adsorption. 

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