Factors Influencing the Course of the Macrocyclization of α,ω‐Diamines with Esters of α,ω‐Dicarboxylic Acids

Abstract

The efficient synthesis of eight new macrocyclic amides (lactams) via reaction of diesters with diamines under normal dilution conditions is described. The role of intermolecular H-bond formation and steric hindrance is discussed based on 1 H-and 15 N-NMR studies of appropriate model compounds. Principles for the optimal choice of esters that can be efficiently transformed into diamides have been developed.Introduction. ± The architecture of naturally occurring macrocycles has long provided the stimulus for the development of new methods for the synthesis of cyclic polyaza and polyoxa compounds [1]. The synthesis of macrocycles possessing both Nand O-atoms to produce receptors with distinct properties has been pursued by many research groups due to the potential application of these compounds in medicine, catalysis, and sensor technology, etc. [9], were successfully used, whereas esters of simple aliphatic diacids (e.g., adipinate) were found to be unreactive unless high pressure was applied [7b]. Recently, we have optimized the reaction conditions for macrocyclizations [11], using MeONa as a catalyst, which speeds up the reaction, improves the yields, and broadens the scope of the reaction by including less-reactive esters like dimethyl phthalate. Our results showed that there is no template effect operating in these reactions. Others have also made use of these (or similar) conditions for the synthesis of a wide scope of macrocyclic amides [12] [13].Our interest in the reaction of diesters and diamines has been motivated not only by its broad scope, but also by the amazing observation that standard dilution of reagents is enough to obtain high yields of macrocyclization. For this reason and keeping with our long-standing interest in diazacoronands, we undertook detailed studies to gain

Complex formation of pyridine‐azacrown ether amide macrocycles with proton and heavy metal ions in aqueous solution

“…[6][7][8] The protonation constants of 1-4 and stability constants of its complexes with Cu 2+ , Cd 2+ , Pb 2+ , Zn 2+ , Ni 2+ , and Fe 2+ were determined by potentiometric methods. The values of the stability constants for the metal complexes of 1-4 studied in this work, determined in water, are compiled in Table 1.…”

“…[6,7] Amide macrocycles 2-4 can be easily prepared with high yields by a reaction of the corresponding diamine and dimethyl pyridine-2,6-dicarboxylate. [8] From a structural point of view, these receptors derive from the α,ω-diamine containing oxygen or nitrogen heteroatoms able for metal ion binding and pyridine residue as additional coordination center. The presence of the crown-ether moieties in the composition of receptors confers them a certain degree of flexibility that is however limited by the presence of a relatively rigid chelate subunit containing a pyridine group.…”

Tri-n-butyltin Hydride-Mediated radical reactions of ortho-and meta-Iodobenzamides to synthesize benzomacrolactams: surprising formation of biphenyl compounds from meta-regioisomers

“…In view of the numerous biological activities of macrolactams [1][2][3][4] and the synthetic challenge they present, 3,5 we have studied the Bu 3 SnH-mediated radical cyclization reactions using unsaturated iodides as precursors of macrolactams, [6][7][8][9][10][11][12] mainly allyloxy-ortho-iodobenzamides derived from carbohydrates to give benzomacrolactams. [6][7][8][9][10][11] These precursors furnished benzomacrolactams with 11-, 12-and 20-membered ring by regioselective endo aryl radical carbocyclization.…”

“…Considering that (i) we have been stimulated to study the Bu 3 SnH-mediated radical reactions to construct Vol. 20, No.…”

“…20, No. 8, 2009 macrocycles, since there is a limited number of protocols available for the synthesis of large rings using free radical-mediated macrocyclizations, 13 (ii) the endomacrocyclization mode is favoured over the exo, [6][7][8][9]12,[14][15][16][17][18][19][20] (iii) the carbohydrate moiety impose conformational restriction to favour cyclization, [6][7][8][9]12 and (iv) although the majority of fused aromatic macrocycles have been obtained from ortho-halogenobenzene derivatives bearing an unsaturation in the side chain, [6][7][8][9][14][15][16][17][18][19] 3-halogenobenzene compounds have also been used as precursors of benzomacrolactams, 13 we selected to apply the Bu 3 (Figure 2), the respective meta-isomers of 1 and 2 ( Figure 1), in an attempt to form the benzomacrolactams 7 and 8 ( Figure 2) by 12-endo carbocyclization. In view of the results of these radical reactions, we also carried out the Bu 3 SnH-mediated reaction with methyl 2, (10) to synthesize the respectively 14-and 13-membered lactams 11 and 12 ( Figure 2).…”