The influence of salt additives on the macrocyclic product distributions in double-amidation reactions

Abstract

We present an improvement of our own method for synthesising macrocyclic compounds via doubleamidation reactions of aromatic dimethyl esters with five oxa-aliphatic α,ω-diamines of different lengths, leading to a large library of potential ion receptors. We studied the influence of various inorganic salts (NaCl, KCl, CsCl, NH4Cl, MgSO4, CaCl2, CuSO4) on the macrocyclization reaction. The results were analyzed in terms of substrate conversion and distribution of products, using high performance liquid chromatography (HPLC).

Static Combinatorial Chemistry: A High-Pressure Approach to the Synthesis of Macrocyclic Benzoamide Libraries

“…We recently demonstrated that inorganic salts have a great impact on the formation of macrocyclic benzoamides via the double-amidation reaction of methyl dicarboxylic esters with α,ω-diamines. 52 On the basis of these results, herein we investigate the distribution of the macrocyclic products of this reaction, namely, macrocyclic diamides and tetraamides, in two-, three-, and four-substrate CLs formed under atmospheric and high-pressure conditions. To study these processes, we chose two chemsets of substrates, i.e., methyl dicarboxylic esters (chemset 1 ) and α,ω-diamino ethers (chemset 2 ) ( Figure 1 ).…”

“…The composition of each library was analyzed by reversed-phase HPLC utilizing a recently reported procedure and the collection of macrocyclic products shown in Figure 4 . 52 …”

“…The composition of each library was analyzed by reversed-phase HPLC utilizing a recently reported procedure and the collection of macrocyclic products shown in Figure 4. 52 The molar ratios of macrocyclic products observed in twosubstrate libraries under atmospheric and high-pressure conditions are shown in Table 1. Analyzing the composition of libraries under atmospheric pressure, one can observe that the structure of the substrates strongly affects the distribution of macrocyclic products.…”

“…The influence of rising pressure on the yield and distribution of products was investigated in two-, three-, and four-substrate CLs created from variously mixed members from chemsets 1 and 2 . The composition of each library was analyzed by reversed-phase HPLC utilizing a recently reported procedure and the collection of macrocyclic products shown in Figure …”

“…The referenced benzoamides (chemsets 3 and 4 ) were synthesized as previously described, and the libraries were analyzed by HPLC on a Bionacom Velocity C18-2 column (4.6 mm × 250 mm, grain size 5 μm) at 25 °C at a flow rate of 1 mL/min with gradient elution (25% → 50% acetonitrile in water in 30 min). 52 To identify all of the macrocyclic hybrid tetraamides (chemset 4 hyb ), the UPLC–MS method was used (MALDI SYNAPT G2-S HDMS (Waters) connected with an Acquity UPLC (Waters) at 25 °C at a flow rate of 1.5 mL/min with gradient elution (25% → 50% acetonitrile in water in 30 min).…”