Macrocyclic malonate esters

Reaction of selected metal ion complexes of multidentate amines with formaldehyde and a variety of activated carbon compounds (such as nitro-methane or diethyl malonate) have led to ring closure to yield polyaza macrocycles (Comba et al., 1986 Lawrance and O Leary, 1987). Reaction with the malonate ester gave less than a 2% yield. Another approach for the... 

The first example shows the synthesis of a C-C-bridged bis-macrocycle (Figure 2) [7]. The preparation of 1 is a condensation of a polyamine with a malonic ester derivative, in analogy to the procedure developed by Tabushi et al [8]. The tetraamide 1 is so insoluble that it precipitates and can be obtained practically pure from the reaction mixture. Its reduction to the octaamine takes place if the reaction with is done in diglyme (bis-(2-methoxyethyl)ether), in which 1 is partially soluble. The product 2 is an ideal ditopic ligand,since it has all the typical properties of 1,4,8,11-tetraazacyclotetradecane (cyclam), i. e. the thermodynamic and kinetical stability of its complexes and the C-C linkage between the two macrocyclic subunits does not reduce the coordination tendency of the amine nitrogens. 

Based on malonic ester synthesis, a bifunctional derivative of 1,4,7,10-tetraazacyclotridecane-N,N, N",N" -tetraacetic acid (TRITA) has been developed as well (Ruser et aL 1990). Again, an intermolecular reaction between a diamine and a diester leads to the macrocycle forming peptide bonds (O Fig. 45.11). The final BFCs have been studied as complexation agents for in and have shown fast chelate formation, high radiochemical yield, and high stability. 

High-dilution conditions for the intramolecular application of the malonic ester synthesis to the preparation of macrocyclic diesters have been reported yields between 9 and 50% are obtained. Dialklacyl phosphonates provide a new method for the acetylation of enolates including the sodium enolate of diethyl malonate. An alternative method for the generation of diester enolates involves the reductive a-deacetoxylation of an a-acetoxy diester (Scheme 30). The... 

Diethyl malonate derivatives have been used to prepare peraza macrocycles that are smaller and larger than the cyclams. A [HJN, macrocycle was prepared in a low yield from cyanobenzylmalonic ester and a triamine (Craig et al., 1989b Helps et al., 1989b). A [19)Nf, ligand was prepared in a 17% yield... 

Transesterification in the presence of a templating metal cation has been used to prepare some tetra-ester polyether macrocycles from dimethyl malonate [equation (16)], and intramolecular transesterification of (75) is one of the... 

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