Highly Efficient Synthesis of 1-Thioamidoalkyl-2-naphthols and 14-Aryl-14 H-dibenzo [ a , j ] xanthenes using a Novel Ionic Liquid : Catalyst Preparation , Characterization and Performing the Reactions

In this work, a novel Brønsted acidic ionic liquid namely triethylaminium-N-sulfonic acid trifluoroacetate {[TEASA][TFA]} has been synthesized by the reaction of NEt3 with ClSO3H, and then with CF3CO2H. The ionic liquid has been characterized by studying its spectroscopic data (1H and 13C NMR, FT-IR, and mass spectra). Afterward, it has been utilized as a highly effective and general catalyst to promote the following organic reactions in solvent-free conditions: (i) the production of 1thioamidoalkyl-2-naphthols from arylaldehydes, 2-naphthol and thioacetamide, and (ii) the preparation of 14-aryl-14H-dibenzo[a,j]xanthenes from arylaldehydes and 2-naphthol. It is noteworthy that [TEASA][TFA] has catalyzed the reactions under milder conditions relative to most of the reported methods. Moreover, it afforded the both products in higher yields with respect to most of the previous works. Copyright © 2018 BCREC Group. All rights reserved

Performing chemical reactions under solventfree conditions is an important technique in green chemistry in which many compounds could be synthesized in an effective and environ-ment friendly manner.Solvent-free synthesis has several benefits compared with the classical synthetic methods; these advantages include: (i) safer reaction profile, (ii) higher yield of product, (iii) shorter reaction time, (iv) higher selectivity in many reactions, (v) easier workup, (vi) maximum incorporation of the reactants into the aim product, (vii) fewer energy requirement to promote reaction, (viii) prevention of using harmful solvents, and (ix) prevention or minimization of waste/by-products [11][12][13].
The 1-thioamidoalkyl-2-naphthol derivatives are of significance as they can be readily converted to biologically important compounds namely γ-amino alcohols which show hypotensive, bradycardia, antipain, antibacterial, secretase inhibitory and notch-sparing activities [14][15][16][17].The general method for synthesis of 1-thioamidoalkyl-2-naphthols involves the condensation reaction of arylaldehydes with 2-naphthol and thioacetamide in the presence of a catalyst [18][19][20][21][22][23][24][25].In spite of high importance of this class of compounds, their production has been scarcely studied in the literature.Moreover, in most of the works, only a few numbers of these compounds have been prepared.
In this research, first of all, preparation and characterization of a novel Brønsted acidic ionic liquid (triethylaminium-N-sulfonic acid trifluoroacetate {[TEASA][TFA]}) using 1 H and 13 C NMR, FT-IR, and mass spectra have been reported.Then, application of the ionic liquid as a highly effective and general catalyst for the production of 1-thioamidoalkyl-2-naphthols and 14-aryl-14H-dibenzo[a,j]xanthenes has been reported.
It should be mentioned that we have previously used [TEASA][Cl] for the production of 1-thioamidoalkyl-2-naphthols (only three compounds) [21] and 14-aryl-14H-dibenzo[a,j] xanthenes [8].Novelties of this work relative to our previous works [8,21] including: (i) introducing [TEASA][TFA] as a novel ionic liquid, and testing its catalytic performance for organic synthesis, (ii) performing the reactions in milder conditions (in our previous works, the synthesis of 1-thioamidoalkyl-2-naphthols and xanthenes has been carried out at 110 and 120 °C, respectively; however, in this work, 1-thioamidoalkyl-2-naphthols and xanthenes have been prepared at 80 and 100 °C, correspondingly), (iii) application of fewer catalyst amount for the 1-thioamidoalkyl-2-naphthols synthesis, (iv) obtaining excellent yields and shorter reaction times for 1-thioamidoalkyl-2naphthols, (v) systematic study for the 1-thioamidoalkyl-2-naphthols production (in o u r p r e v i o u s w o r k , o n l y t h r e e 1-thioamidoalkyl-2-naphthols have been prepared; but, in the presented work, twelve 1-thioamidoalkyl-2-naphthols have been synthesized, and effect of various electronattracting, halogens and electron-releasing groups on different positions of arylaldehydes on the reaction has been studied).

Materials and measurements
All chemicals were purchased from Merck or Fluka Chemical Companies.Dichloromethane was dried over sodium sulfate, distilled and stored over molecular sieves.All known compounds were identified by comparison of their melting points and spectral data with those reported in the literature.The melting points were recorded on a Büchi B-545 apparatus in open capillary tubes.Progress of the reactions was monitored by thin layer chromatography (TLC) using silica gel SIL G/UV 254 plates.The 1 H NMR (300, 400 or 500 MHz) and 13 C NMR (75, 100 or 125 MHz) were run on a Bruker Avance DPX, FT-NMR spectrometers.Mass spectra were obtained with Shimadzu GC-MS-QP 1100 EX model.

Production and characterization of the catalyst
In continuation of our previous studies on the production of acidic ionic-liquid catalysts in which a SO3H group bonded to a tertiary amine or heterocyclic nitrogen [7][8][9][10], we prepared a novel member of this attractive class of ionic liquids namely triethylaminium-Nsulfonic acid trifluoroacetate {[TEASA][TFA]}, according to Scheme 1.
The novel ionic liquid was characterized by studying its 1 H and 13 C NMR, FT-IR, and mass spectroscopic data.In the 1 H NMR spectrum of [TEASA][TFA] (Figure 1), the peaks related to 9 hydrogens of the three CH3 groups, and 6 hydrogens of the three CH2 groups have appeared at 1.19 (as triplet) and 3.11 (as quartet) ppm, respectively.The acidic hydrogen of SO3H has appeared at 10.00 (as broad) ppm.The 13 C NMR spectrum of the ionic liquid (Figure 2) showed 4 peaks.The peaks observed at 8.  quartet peaks observed at 115.4 and 158.8 ppm as quartet, are related to the CF3 and C=O groups of anion moiety, respectively.The FT-IR spectrum is shown in Figure 3, and the relevant data are summarized in Table 1.As it can be seen in Figure 3 and Table 1, the peaks related to expected functional groups and bonds in [TEASA][TFA] have presented in the spectrum.The mass spectrum of triethylaminium-N-sulfonic acid trifluoroacetate showed the molecular mass (M + ) and (M + +1) at m/z 295 and 296, correspondingly.

Testing catalytic activity of [TEASA] [TFA] for the synthesis of 1thioamidoalkyl-2-naphthols
To show the efficient catalytic activity of [TEASA][TFA] to promote organic transformations, at first, the production of 1-thioamidoalkyl-2-naphthols was examined in the presence of this catalyst.Thus, the solventless condensation of 3-nitrobenzaldehyde (1 mmol) with 2-naphthol (1 mmol) and thioacetamide (1.2 mmol) was chosen as a model reaction (Scheme 2), and influence of the catalyst amount and temperature on it was studied.The main results are summarized in Table 2.As the data in this table indicate, the best results were observed when 15 mol% of the catalyst was used at 80 °C (entry 2).
After the reaction was optimized in terms of the catalyst amount and temperature, various arylaldehydes were reacted with 2-naphthol and thioacetamide; the corresponding results are shown in Table 3.As it is shown in this Table, the catalyst was highly effective and general for the reaction; all functional groups on different positions of the arylaldehydes afforded the respective of 1-thioamidoalkyl-2naphthols in excellent yields and in short reaction times.

Testing catalytic activity of [TEASA] [TFA] for the synthesis of 14-aryl-14Hdibenzo[a,j]xanthenes
After the successful application of [TEASA][TFA] for the production of 1-thioamidoalkyl-2-naphthols, its catalytic activity was checked for the synthesis of 14-aryl-14H-dibenzo[a,j]xanthenes.For this purpose, 3-nitrobenzaldehyde (1 mmol) was reacted with 2-naphthol (2 mmol) (Scheme 4) in the presence of various mol percentages of the ionic liquid at different temperatures.The main results are displayed in Table 4.According to the reported results in this Table, the most suitable catalyst amount and temperature were 15 mol% and 100 °C, respectively (entry 2).
After that, various arylaldehydes (bearing electron-attracting, electron-releasing and halogen substituents) were reacted with 2-naphthol in the optimized conditions.The respective results are summarized in Table 5.As it can be seen in this Table, [TEASA][TFA] has successfully catalyzed the reactions, and gave 14-aryl-14H-dibenzo[a,j]xanthenes in high yields and in short reaction times.Thus, [TEASA][TFA] was also highly effective and general catalyst for the production of 14-aryl-14H-dibenzo[a,j]xanthenes.According to the   above results, we think that the ionic liquid can catalyze organic reactions which need to acidic catalyst.
In a proposed mechanism (Scheme 5), which supported by the literature [33,39]
The benefits of application of [TEASA][TFA] to promote these reactions consist of: effectiveness, generality, higher yields and milder reaction conditions compared with most of the reported methods, short reaction times, simple preparation and operation of the catalyst, production of the catalyst from available and inexpensive starting materials, clean procedure, easy workup, and achieving the reactions in solvent-free conditions.

Figure 1 .
Figure 1.The 1 H NMR spectrum of [TEASA][TFA] 2-naphthol is added to the activated aldehyde by the acidic hydrogen of [TEASA][TFA] to give I; trifluoroacetate anion of the catalyst also helps to the nucleophilic addition.Removing a molecule of H2O from intermediate I, by helping the catalyst, affords II.Intermediate II is activated by the catalyst, and then, acetamide

Figure 2 .Figure 3 .
Figure 2. The 13 C NMR spectrum of the catalyst

Table 2 .
Influence of the catalyst amount and

Table 4 .
Effect of the catalyst amount and tem- b TLC showed completing the reaction.
, initially 2-naphthol is added to the activated aldehyde by the acidic catalyst to afford III.Removing a H2O molecule from III, by helping [TEASA][TFA], gives II.Then, intermediate II is activated by the catalyst, and another molecule of 2-naphthol is added to it to afford IV.