Synthesis of azacrown ethers and benzocryptands by macrocyclization of podands at high concentrations of reactants

Abstract

The reactions of 1,2 bis(2 Y ethoxy)benzenes, N,N bis(2 Y ethyl) N phenylamines, or 2,6 bis(Y methyl)pyridines (Y = I, Br, or OTs) with α,ω polyoxaalkanediamines or diazacrown ethers in the presence or absence of alkali carbonates in a concentrated acetonitrile solution of the reactants afforded the corresponding azacrown ethers or cryptands in high yields.The replacement of oxygen atoms in macroheterocy clic crown ether compounds by nitrogen atoms affords complexes capable of being coordinated to different types of metal cations (alkali, alkaline earth, heavy, and transi tion), 1-7 due to which this class of ligands has attracted interest. 8-12 Macrocyclic azapolyethers can be derivatized at the nitrogen atom, with the result that they can be used as intermediates in the synthesis of ion selective dyes, 13-17 biologically active compounds, 17-19 bicyclic analogs, and polymer bound reagents. 20,21There are various methods for the synthesis of azamac roheterocyclic compounds. 22-30 Nevertheless, the devel opment of new facile methods for the synthesis of ben zoazacrown compounds, particularly, of functionalized derivatives, is an important problem.Earlier, 31 we have developed a method for the synthe sis of formyl derivatives of benzodiazacrown ethers and benzocryptands based on the condensation of 3,4 bis(2 iodoethoxy)benzaldehyde with α,ω polyoxaalkanediamines and diazacrown ethers in the presence of alkali metal car bonates at high dilutions in different organic solvents and their mixtures with water. However, the reactions of un substituted terminal diamines with diazacrown ethers are accompanied by partial resinification of the starting reac tants and, consequently, the purification of the reaction products presents considerable difficulties.With the aim of preventing resinification and extend ing the range of the reactants, in the present study we developed a procedure for the synthesis of derivatives of benzoazacrown compounds by the condensation of acy clic precursors under mild conditions. The main differ ence between this method and the method described earli er 31 is that the reaction is performed at room temperature (as opposed to the refluxing of the starting compounds in acetonitrile) and in a concentrated acetonitrile solution of the reactants (as opposed to the high dilution technique used in the method developed earlier 31 ). The formation of azamacrocyclic compounds can occur even in the absence of alkali carbonates, which has not been observed earlier in the syntheses of azacrown ethers. The advantages of the new method are that the reaction products are formed in good or high yields and are characterized by higher purity.We studied the condensation of substituted 1,2 bis (2 iodoethoxy)benzenes 1a,b and related dielectrophiles de signed on diethylphenylamine 1c,d and 2,6 lutidine 1e,f with diamines 2a-f and diazacrown ethers 2g,h and 3d in the presence of alkali carbonates (Scheme 1).The condensation occurs with linear dielectrophiles 1a-f and dinucleophiles 2a-h or 3d in a concentrated acetonit...

Structural, Magnetic, and Redox Diversity of First-Row Transition Metal Complexes of a Pyridine-Based Macrocycle: Well-Marked Trends Supported by Theoretical DFT Calculations

“…The most common representatives of these ligands are in complexes whose X-ray crystal structures are the most abundant in the Cambridge Structural Database (CSD); they are shown in Figure . According to the decreasing number of references regarding each of the compounds, including the metal complexes, they can be ordered as follows: 15-pydienN 3 O 2 , − 3,12,18-triaza-6,9-dioxabicyclo[12.3.1]­octadeca-1(18),14,16-triene (15-pyN 3 O 2 , L ), − 15-pydionN 3 O 2 , − Me 2 -15pyN 3 O 2 , , (15-pydienN 3 O 2 ) 2 , L1 , and L2 . The above-mentioned ligands were used to complex different d-block transition metals as well as f-block lanthanides, and usually crystal structures and magnetic properties in the solid state were investigated, but also some experiments in solution regarding their redox properties, their thermodynamic/kinetic stabilities, or their efficiency as magnetic resonance imaging (MRI) contrast agents were performed …”

Analysis of benzodiaza‐15‐crown‐5 ether derivative binding properties by potentiometric and optical methods

“…4,10‐dimethyl‐2,3,4,5,6,8,9,10,11,12‐decahydrobenzo [b]trioxadiazacyclopenta‐decine‐15‐carbaldehyde ( 1 ) was prepared as described in …”

“…EXPERIMENTAL Materials 4,10-dimethyl-2, 3,4,5,6,8,9,10,11,12-decahydrobenzo [b] [1,4,10,7,13] trioxadiazacyclopenta-decine-15-carbaldehyde (1) was prepared as described in. [41] 2-[(E)-2-(4,10-dimethyl-3,4,5,6,9,10,11,12-octahydro-2H,8H-1,7,13,4,10benzotrioxadiazacyclopentadecin-15-yl)vinyl]-3-ethyl-1,3-benzothiazol-3-ium perchlorate (2) The benzothiazolium styryl dye (2) was prepared by heating 0.1 g (0.36 mmol) of heterocyclic salt and 0.13 g (0.04 mmol) of formyl derivative of benzoazacrown ether 1 in 7 ml dry ethanol for 6 h at 80-90 C under argon atmosphere. The reaction mixture was cooled, and the precipitate was filtered off, washed with 60 ml of acetone and dried to yield 0.113 g (58%) of the desired product as brick-red crystals.…”

Macrocyclization Reactions at High Concentration (≥0.2M): The Role of Catalysis

“…The use of templates is essential in the synthesis of (aza)crown ethers and cryptands, which necessarily occurs by macrocyclization reactions, and high concentration conditions have been claimed during the syntheses. 44 However, the number of examples found at high concentration (>0.2M) is extremely limited; the nature of the template can vary, and very few macrocycles rather than crown ethers can be prepared through template-mediated technologies. It is worthwhile to mention here that the effect of metal templates during reaction could include or be considered as catalytic effects, and more work may be necessary to study this issue.…”