An Efficient Preparation of Macrocycles Bearing Vinamidine Moieties by the Cyclocondensation of Malonaldehyde Derivatives and 1,ω-Diaminoalkanes

Abstract

An efficient preparation of macrocycles 7 and 9 bearing vinamidine moieties is described. The key to the preparation is the (2:2) cyclocondensation of malonaldhyde derivatives 1 and 8 and 1,w-diaminoalkanes 6.Vinamidine (1,5-diazapentadiene) and vinamidinium salts are unique conjugate systems 1 because electron-donating and electron-withdrawing groups are separately attached to a carbon-carbon double bond. Vinamidinium salts have been used for the preparation of heterocycles, while vinamidine derivatives were rarely used for the synthetic purpose. 2 We have recently been studying an efficient preparation of N,N'-diaryl-3-cyanovinamidines 5a by the reaction of 3-butoxy-2-cyanoacrolein 1, a synthetic equivalent of cyanomalonaldehyde 2, with two molar equivalents of arylamine 3a via the initially formed product 4a. 3 Similar reaction of acrolein derivative 1 with aliphatic primary amines, such as benzyl-3b, cyclohexyl3c, and (R)-1-phenylethyl-amine 3d, also gave vinamidine derivatives 5b-d in good yields (Scheme 1). In our continuing study on the synthetic utility of malonaldehydes, we examined the reaction of acrolein derivative 1 and (methoxycarbonyl)malonaldehyde 8 4 with 1,w-diaminoalkanes 6 expecting to form cyclic products bearing vinamidine moieties. Scheme 1To a solution of 3-butoxy-2-cyanoacrolein 1, generated by the acid treatment of commercially available 1,3,3-tributoxy-2-cyanopropene, 5 in acetonitrile were added 1.2 equivalents of 1,6-diaminohexane (6e). The resultant mixture was refluxed for 8 hours and the solvent was evaporated to dryness, and the white solid was crystallized from methanol to give an unexpected (2:2) cyclic product 7e in 78% yield. The structure of 7e was confirmed on the basis of its analytical and spectroscopic data; in its IR spectrum characteristic absorption bands due to N-H and CN stretching were observed. The simple signal patterns in the 1 H and 13 C NMR spectra of product 7e implied that it has a symmetrical structure and, especially, its mass spectra showed the proposed molecular ion peaks [354 (M + ) for EI and 355 (MH + ) for CI]. Similar reaction of 1 with 1,2-diaminoethane (ethylenediamine) 6a, 1,4-diaminobutane 6c, 1,5-diaminopentane (gadaverine) 6d, and 1,12-diaminododecane 6f gave the corresponding (2:2) cyclic products 7a, 7c, 7d, and 7f in moderate to good yields (Scheme 2, Tables 1, 2). In addition, the reaction of 1 with 1,5-diaminopentane 6d gave another product 7d' along with product 7d. Product 7d' could not be isolated in its pure form; 7d' in deuteriochloroform and methanol was not stable and gradually converted to 7d within a few days on standing at room temperature. A prolonged reaction in refluxing acetonitrile (72 hours) gave only 7d (Table 1, run 4). The 1 H and 13 C NMR spectra of 7d' were almost consistent with those of 7d over the whole region. These findings suggest that product 7d' is a conformational isomer of 7d.(Methoxycarbonyl)malonaldehyde 8 was also reacted with diaminoalkanes 6a, 6c, 6e, and 6f; the same type of (2:2) cyclic products 9a, 9c...

Tuning the Properties of Neutral Tetraazamacrocyclic Complexes of Copper(II) and Nickel(II) for Use as Host–Guest Compounds with Bismacrocyclic Transition Metal Cations

“…The synthesis of the nickel(II) and copper(II) complexes 4Ni , 4Cu , 5Ni , 5Cu , 6Ni and 6Cu is summarised in Scheme . The 14‐membered ligand 4 was obtained by direct condensation of an equimolar mixture of 2‐formyl‐3‐hydroxypropenoic methyl ester3b and ethylenediamine 3a. Refluxing the ligand 4 with nickel(II) or copper(II) acetate in methanol solution gave the neutral complexes 4Ni and 4Cu , respectively.…”

“…These groups could then be used for the extension of the ligand superstructure. The synthesis of the 14‐membered tetraimine 4 (see Scheme ) was recently reported by Takamura,3a although the 15‐ ( 5 ) and 16‐membered ( 6 ) analogues were not accessible by this procedure. We have synthesised the 15‐ and 16‐membered derivatives following a template Jäger synthetic strategy4,5 from 2‐formyl‐3‐hydroxypropenoic methyl ester and the appropriate diamines.…”

Synthesis of Carbonyl‐substituted Tetracyanodihydrotetraaza[14]annulenes

“…Both non-substituted bis-carbonyl tetracyano DH-TAA units -aH and eH -can be synthesised according to the same procedure (Scheme 1) involving direct use of diaminomaleonitrile and β-dicarbonyl compound, which can be either triformylmethane [22] (a) or methyl diformylacetate [23] (e). Although the procedure leading to the synthesis of the 14membered cyclidene diester ligand was similar, [4,24] the cycli-dene dialdehyde substituted rings [25] could not be cyclised directly and the reaction required more than one step with a supporting role of a metal ion as a template. In fact, three steps are required: obtaining the linear tetradentate ligand, coordination of a metal ion and subsequent ring-closure with ethylenediamine.…”

“…Anal. Calcd for C 24 2,3,9,10-tetracyano-1,4,8,11-tetraazacyclotetrade-ca-2,4,6,9,11,13-hexaene (aH). 4 g (40.0 mmol) of triformylmethane as a dicarbonyl substrate and 4.375 g (40.5 mmol) of diaminomaleonitrile were dissolved in 250 mL of ethanol.…”

“…It should be noted that corresponding cyclidene diester ligands, that exhibit far less planar structures (Figure 1), need clearly more harsh conditions for the macrocyclisation to take place (8 h under reflux). [24] All tetracyano DH-TAA ligands can be coordinated into corresponding nickel(II), copper(II) and palladium(II) complexes. These particular metals were chosen in view of previously studied coordination abilities of cyclidenes, which nickel(II), copper(II) and palladium(II) complexes are most common and show very rich electrochemical properties.…”