Synthesis of new allylidene amino phenol-containing Schiff bases and metal complex formation using trimethinium salts

An efficient route for the synthesis of novel Schiff bases from the condensation reaction of 2-substituted 1,3-bis(dimethylamino)-trimethinium salts with diverse aminophenols in the presence of triethylamine in EtOH at reflux is described. Complexes of transition metals with Schiff base ligand (L) 3c, having the donor atom set N2O2, were studied. The ultraviolet spectral behavior of the complexes in DMSO was investigated and the λmax of these compounds was examined. The structure of the new compounds was confirmed based on their spectral data from IR, 1H NMR and 13C NMR, mass spectra, and elemental analysis.


Introduction
Schiff bases are some organic compounds that are highly used. They are used as pigments and dyes, intermediates in organic synthesis, catalysts, and polymer stabilizers. Schiff bases exhibit a wide range of biological activities, including antifungal, antiviral, antimalarial, antibacterial, anti-inammatory, antiproliferative, and antipyretic properties. [1][2][3][4][5][6] Schiff base ligands have the capability of coordinating metals through imine nitrogen and another group. Nowadays active and well-designed Schiff base ligands are considered "privileged ligands". Schiff bases are able to stabilize many different metals in various oxidation states, controlling the performance of metals in a wide variety of useful catalytic transformations. [7][8][9] Metal complexes of Schiff bases play a central role in the development of coordination chemistry. This situation is manifested by the huge number of publications ranging from purely synthetic to modern physicochemical to biochemically relevant studies of these complexes. A wide variety of stable chemical species have been synthesized containing both transition and nontransition metals and multifarious ligand systems. 10,11 The vinamidines, with saturated nitrogen as the p-donor and the imino group as the p-acceptor, are of particular interest to us. Vinamidinium salts have long found practical use as versatile three-carbon building blocks in the synthesis of heterocyclic benzenoid and nonbenzenoid aromatic rings, from cyclic and acyclic precursors alike. One of the useful attributes of many vinamidinium salts is their ease of preparation from substituted acetic acids under Vilsmeier-Haack conditions. [12][13][14][15][16][17][18][19][20][21][22][23] "In this study, our research group was able to prepare bsubstituted trimethinium salts with different R groups (including aryls and heteroaryls) from correspondingly substituted acetic acids, R-CH 2 CO 2 H, with good yields". 24,25 In continuation of this research on applications of trimethinium salts in organic synthesis (Scheme 1), [26][27][28][29][30][31] in this study, we report a new and highly efficient method for the synthesis of a novel class of allylidene amino phenol-containing Schiff bases from the reaction of trimethinium salts and diverse aminophenols in the presence of triethylamine, under catalyst-free conditions in EtOH at reux (Scheme 2). and various trimethinium salts in the presence of triethylamine in ethanol as a solvent at reux. Initially, N-(2-(4-bromophenyl)-3-(dimethylamino)-allylidene)-N-methylmethanaminium perchlorate (1e) and 2-amino-4-chlorophenol (2b) were chosen as the model substrates to optimize the reaction conditions, (the reason for this choice is the good TLC of these two reactants for observations), such as various reagent sources and solvents. The results are summarized in Table 1. In this study, various reagents such as NaH and NaOCH 3 were examined and it became clear that they cannot continue this reaction ( Table 1, entries 1 and 2). The bases such as Et 3 N and i-Pr 2 NEt were examined in EtOH, in which resulted higher yield and shorter reaction time when the reaction was carried out in the presence of (1 eq.) of the Et 3 N ( Table 1, entries 3 and 4). The effect of solvents were also investigated and it was observed that the desired product was not obtained in the solvents CH 3 CN and DMF. However, the reaction was obtained highly effective with solvents such as EtOH and MeOH (Table 1, entries 4-7). The control experiment conrmed that the reaction has not occur in the absence of the base and acid conditions ( Table 1, entries 8 and 9).
In the next stage, the efficiency of the process under optimized conditions was explored. For this purpose, trimethinium salts 1a-f were condensed with aminophenol derivatives 2a-c in the presence of Et 3 N (1 eq.) to afford the corresponding products 3a-i in high yields.
The synthetic pathway to synthesis the titled compounds is consisting of two steps. At rst, compounds 1 were prepared similar to the previous studies. [18][19][20][21][22][23][24][25] Then the results were treated with aminophenol derivatives to afford the related Schiff base ligands as the desired products. As Table 2 indicates, a variety of trimethinium salts were successfully applied in this process to afford the corresponding Schiff base ligands derivatives as novel compounds with excellent yields.
As shown in Table 2, compound 3a unlike the other compounds, creates the 1,4-oxazpine salt as a product, probably due to the lack of electrons of the unsubstituted pyridine ring, which causes an intramolecular reaction. In the other molecules, the electron deciency is less and there is enough time to perform the intermolecular reaction.

The complexation steps
The complexation of a series of new allylidene amino ortho hydroxy-containing Schiff bases as ligand with different metal ions was studied by means of the ultraviolet-visible spectrophotometry technique in DMSO as a solvent. Copper, zinc, cobalt, and nickel Schiff bases were prepared using the corresponding acetate M(OAc) 2 (M $ Cu, Zn, Co, Ni). For this purpose, compound 3c was chosen; then, UV-Vis absorption spectrum of the ligand 3c and its complexes were investigated in range of 190-840 nm in DMSO solvent (Scheme 3). The ultraviolet-visible electronic spectrum of ligand 3c shows the absorption peak at (370) nm, which can be attributed to n / p* electronic transitions. As shown in Scheme 3, for all complexes, maximum absorption wavelengths shied to longer values (bathochromic effect) compared to the ligand 3c indicating the complex formation.
The proposed mechanism for the formation of Schiff bases

Experimental
All chemicals were purchased from Merck or Fluka chemical companies. The 1 H NMR (300 and 400 MHz) and 13 C NMR spectra (75 and 100 MHz) were run on a Bruker Avance 400. Tetramethylsilane (TMS) was used as the internal standard for the NMR analysis. IR spectra were recorded using an FTIR apparatus. Melting points were recorded on a Stuart Scientic Apparatus SMP3 (UK) in open capillary tubes. Elemental C, H and N analyses, were performed using a Costech CHNS-O Scheme 2 Synthesis of Schiff bases 3 via the reaction between trimethinium salts 1 and diverse aminophenols 2 in the presence of Et 3 N in EtOH at reflux.   General procedure for the synthesis of Schiff base derivatives 3 A mixture of trimethinium salts 1a-f (1 mmol) and trimethylamine (1.0 mL) were dissolved in boiling ethanol (8 mL).
Aminophenols 2a-c (2 mmol) in EtOH (7 mL) were added dropwise to the stirred mixture at reux ethanol for 12 h. (2-Amino-4chlorophenol and 2-amino-4-nitrophenol in ethanol (7 mL) and other aminophenols in methanol (7 mL) was dissolved). Aer completion of the reaction conrmed by TLC, the reaction mixture was set aside in a refrigerator for 12 h. Then the solvent  Scheme 4 Proposed mechanism for the synthesis product 3a-i.
was evaporated under vacuum, and a small amount of dichloromethane (10 mL) was added, and the precipitate formed was collected by ltration, recrystallized from 2-propanol, and dried in vacuum at 80 C to afford the pure product 3a-i.

General procedure for the synthesis metal complexes of Schiff base 3c
A solution of Schiff base 3c (1 mmol) and acetate salt of transition metals copper(II), zinc(II), cobalt(II) or nickel(II) (1 mmol) in DMSO (3 mL) was heated at 100 C for 6 h. Aer completion of the reaction conrmed by TLC, the reaction mixture was cooled to room temperature, then a small amount of water (3 mL) was added and the precipitate formed was collected by ltration, recrystallized from distilled water (5 mL) to get pure products in excellent yield.

Conclusions
In conclusion, we have reported a highly efficient method for the synthesis of important Schiff base derivatives via a condensation reaction between 2-substituted trimethinium salts as starting compounds with aminophenol in presence of triethylamine in ethanol at reux. A simple procedure in the excellent yields, mild reaction conditions, and metal-catalyst free are the main advantages of this method. Metal complexes of Schiff base can be used as catalysts and to advance a number of reactions such as carbon-carbon or carbon-nitrogen coupling reactions, which are separately planned for future works.

Conflicts of interest
There are no conicts to declare.