Polyaza-crowns

Polyaza-crown compounds, N-alkyl-substituted, 70,135 Polyaza-crowns, 70, 135,136... 

General Synthetic Methods for the Polyaza-crown Macrocycles... 

The 1 1 cyclization process has been used extensively for the synthesis of the polyaza-crowns. A typical example of the first type of 1 1 cycloaddition is the reactions of an a,w-diacid chloride with an a,o)-diamine to form a cyclic diamide. A second molecule of the diamine is generally used to trap the released hydrogen chloride (Dietrich et al., 1973). The preparation of N,N -... 

Greene observed that the formation of 18-crown-6 from a ditosylate and a diol in the presence of f-butoxide salts was enhanced when a potassium cation was used (Greene, 1972). This template effect was operative for the synthesis of other polyether crown compounds using alkali or alkaline-earth metal cations. Template effects have also been observed for the preparation of aza-crown ethers, although the effect is less pronounced because the softer A-donor atoms form weaker complexes with the alkali metal cations (Frens-dorff, 1971). Richman and Atkins reported that high-dilution techniques were not required for the cyclization reaction of the disodium salt of a pertosylated oligoethylenepolyamine with sulfonated diols to form medium and large polyaza-crown compounds (Richman and Atkins, 1974 Atkins et al., 1978). 

The case for template assistance in the cyclization step in the formation of polyaza-crown compounds has not been proved for many cyclization reactions. Certainly, other factors such as base strength and intramolecular hydrogen bonding need to be considered. 

The simultaneous addition of the two starting materials over an extended time period is not convenient. Tabushi and coworkers found that high-dilution techniques were not required for the reaction of diesters (including malonates) with diamines to form the cyclic bis-amides (Tabushi et al., 1976, 1977). The cyclic diamides were reduced to form the polyaza-crowns. This method, along with the yV-tosyl method for ring closure, are the most common procedures for the preparation of peraza-crowns. The yields for these ester plus amine... 

Richman and Atkins (1974) reported the generality of the sulfonamide method to prepare the polyaza-crowns. They used a ditosylate ester starting material rather than a dihalide. A similar reaction was reported at the same time by Cram (1977) in a patent filed in 1974. The so-called Richman-Atkins cyclization reaction is the reaction of the polysulfonamide or its disodium or dipotassium salt with a ditosylate or a dimesylate. The interior sulfonamide... 

The diester (or methylacrylate) cyclization reactions give the cyclic mono-, di-, or tetraamides. These materials must be reduced to provide the polyaza-crown compounds. The reduction process is usually carried out using diborane-THF or lithium aluminum hydride. The best results were obtained with a large excess of borane, however, a stable boron complex with the macrocycle often results. It is difficult to separate the macrocycle from the complex. Reduction of [12]N3 diamide with borane-THF always gave the stable complex. This problem was avoided by first forming N-tosyl[12]N,-diamide using the ester cyclization method followed by reduction with borane-THF and detosylation with HBr/phenol (Helps et al., 1989b). 

The crab-like cyclization reaction was used to prepare polyaza-crowns with one or two unsubstituted ring nitrogen atoms (Bradshaw et al., 1989a, 1990b Krakowiak et al., 1990b). The amide nitrogen atoms are not effective nu-... 

From these comments, it is evident that the crab-like cyclization reaction is a convenient method for preparation of a great variety of aza-crowns in good yields. Some of the polyaza products included /V-pivot lariat polyaza-crowns, polyaza-crowns and cyclams with one or two unsubstituted ring nitrogen atoms, peraza-cage compounds, and polyaza-crowns containing sulfur atoms. This new method could become the method of choice for preparation of the functionalized polyaza- and peraza-crowns. 

---