High-Dilution Methods

Template and high dilution methods are vital to produce reasonable yields of macrocycles, which are generally much more preorganised for cation binding than comparable podands... 

The high-dilution method (for technical details see for example Ref. 21) has been used not only to form simple cryptands, but also in the syntheses of more complex systems — cylindrical macrotricyclic molecules24), lateral macrobicycles 25), spherical macrotetracyclic systems 26), and speleands 27). Nevertheless, the important drawback of the method is the last step, e.g. reduction with diborane. That means only compounds which do not interfere with this reagent can be formed in this manner. Also, even a small contamination of the solvents and reactants with water has a significant influence on the yield. 

Diaza[12]coronand-4 (21) was condensed with diethylene glycol bismesylate 22 in the presence of butyllithium. Precipitation, occuring during the reaction course, afforded the proton cryptate 24 H+ c= [1.1.1] in 40% yield. It should be noted that [1.1.1] was obtained only in 10% yield via the high-dilution method 23). Lithium promoted cyclization was excluded (as an alternative mechanism) by an additional experiment in which KH served as a base instead of BuLi. Identical yield was achieved, indicating that intramolecular hydrogen bonding was responsible of the cyclization. 

All the methods presented in this Chapter have their merits and drawbacks. The most important factor in the synthesis of cryptands is the yield. As it was shown, the high-dilution technique is superior to all remaining methods in this respect (except for the [1.1.1] cryptand case). Furthermore, the high-dilution method has been applied... 

The oxa-thiacrown ether having bicyclo[2.2.2]octane units was prepared from a mixture of dichloro sulfides 28 and 29 <2002CHE261>. The reaction of the mixture with diethylene glycol by a high-dilution method led to the formation of only one stereoisomer of 30 in 40% yield (Scheme 3). 

The procedure described here is an example of the use of the dithiane method for the preparation of ketones. The reactions appear to be general, and the yields are satisfactory. The dithiane method can be successfully applied to the synthesis of rings containing up to seven carbon atoms with a slight modi-fication of the procedure above. The synthesis of larger rings may require high dilution methods. ... 

The TACN analog (248) is accessible from the open chain starting compound by standard high dilution methods.114 An alternative procedure starting from facially Mo(CO)3 coordinated PhP(C2H5S)2 has also been reported.115... 

Diimide = diimine = N2H . See Diazene Diisopropylamine etc. See 2-Propaneamine,... etc. Diketones. See Dioxo compounds Diketopiperazines = 2 -piperazinediones, 237 Dilution. See High-dilution methods 1,4 5,8-Dimethanonaphthalene, 1,2,3,4,10,10-hexachloro-l,4,4a,5,8,8a-hexahydro-,... 

Hexen-l-yn-3-one, 1-methoxy spiroanellation with, 74 Hexonamides, TV-alkyl- aqueous suspensions various micellar aggregates, 352-353 L-Hexoses total synthesis, 264-265 2-Hexulosides by redox glycosylation , 272 High-dilution methods macrocycle syntheses by, 145-146, 240-241, 329, 338 Hindrance, steric. See Steric hindrance Hippuric acid See Glycine, iV-bcnzoyl-HMDS. See Silanamine,. .. 

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