Synthesis of 2-(arylthio)-3'-(alkyl-or dialkylamino)diphenyl sulfides via 5-arylthianthrenium perchlorates and their complexations with silver(I) and lead(II) ions

Treatment of 5-arylthianthrenium perchlorates 2 with secondary alkylamines in the presence of LDA in THF at reflux gave 2-(arylthio)-3'-(dialkylamino)diphenyl sulfides 7 as major products along with 2-(arylthio)-2'-(dialkylamino)diphenyl sulfides 8 and thianthrene. The latter two compounds were formed depending on the structures of amines employed and the concentrations of LDA. It has been found that the methoxy groups of 7e , 7g , and 7h were displaced by amide ions in the presence of excess amounts of LDA to give the corresponding 2-(4-dialkylaminophenylthio)-3'-(dialkylamino)diphenyl sulfides ( 14a - c ). The reactions with aza-15-crown-5, aza-18-crown-6, and 7, 16-diaza-18-crown-6 gave analogous products via a benzyne intermediate. The affinity of selected metal cations for compounds 7a , 7e - f , 7h , 7j , 7m , 10 , 13a , and 18a was examined by an extraction method. The dialkylamino groups of 7a , 7e , 7f , and 7h increased somewhat the extractive abilities of Ag + ion (14 - 28%) compared with that of 10 (8%), whereas compound 13a having a diisopropylamino group showed low (9%) and high (67%) extractive abilities toward Ag + and Pb 2+ ions, respectively. Compounds 7j and 7m having an aza-18-crown-6 moiety showed 67% and 66% extractive abilities toward Pb 2+ but 40% and 24% extractive abilities towards Ag + ions, respectively. However, compound 18a with two identical lariats showed high (86%) and low (12%) extractive abilities toward Ag + and Pb 2+ ions, respectively.


Results and Discussion
To begin with, treatment of 2a with a primary alkylamine such as pentylamine (2.3 equiv.) in the presence of NaH (5.3 equiv.)for 3 h in THF at reflux gave 2-(4-methoxyphenylthio)-3'-(pentylamino)diphenyl sulfide (7b) (X = MeO, Y = H, R = pentylNH) (21%), 2-(4methoxyphenylthio)diphenyl sulfide (10) (31%), and 9 (18%) (entry 1, Table 1).No 8b (X = MeO, Y = H, R = pentylNH) was obtained.On the other hand, the same reaction was conducted by adding LDA (2 M, hexane) in place of NaH.LDA (0.3 mL, 0.6 mmol) was added six times at 40 min intervals during the reaction since LDA was expected to be deteriorated at reflux temperature.From the reaction were obtained 7b and 9 in 26 and 16% yields, respectively (entry 2, Table 1).No 8b was obtained.In order to identify the bonding position of the incoming H -ion leading to 10, 2a was treated with NaD in place of NaH under the same foregoing conditions to give deuterated 10 in 63% yield (Scheme 2).However, the assignment of each of the aromatic protons of deuterated 10 on the basis of the 1 H NMR spectrum was unsuccessful simply because of poor resolution.Accordingly, the deuterated 10 was oxidized with m-CPBA to give disulfone 11.

Scheme 2
The 2D NMR spectrum of 11 showed a multiplet at 7.94 ppm, assigned to two H4 protons and one H13 proton, whose intensity was compared with that obtained from the same compound not possessing a deuterium atom.Although we are aware of the deuterium atomic bonding position, further study is necessary to delineate the mechanism for the formation of 10.Similar reaction of 2a with p-toluidine (2.0 equiv.)and NaH (2.3 equiv.)gave 7c (X = MeO, Y = H, R = p-MeC 6 H 4 NH) and 9 in 28 and 41% yields, respectively (entry 3).No 10 was detected.Arylamine is more acidic than alkylamine which may account for decreased availability of NaH.No 10 was detected in both reactions.Interestingly, the reaction of 2a with ethylenediamine (4 equiv.)and LDA (0.3 mL x 4) gave 7d (X = MeO, Y = H, R = HNCH 2 CH 2 NH 2 ) in 45% yield (entry 4), whereas N,N-disubstituted ethylenediamine derivative 12 was obtained in 72% yield when 2a (5 equiv.) was treated with ethylenediamine and LDA (0.3 mL x 8) (entry 5).Since a large quantity of 9 was obtained from the reaction with primary arylamine and NaH (entry 3), coupled with a relatively high yield of 7a from the reaction with diethylamine and LDA (entry 6), we decided to study the reactions of 2 with secondary alkylamines in the presence of LDA.The yields of 7, 8, and 9 are summarized in Table 1.The structures of compounds 7a-n, 8a, 8f-h, 13a, 14a-c, 15a-b, 17, 18a-b were identified on the basis of spectroscopic ( 1 H and 13 C NMR, IR, MS) and analytical data.Reactions with dried amines (i.e., diethylamine (entry 7) and dipropylamine (entry 9)) were compared with reactions where the same amines had not been previously dried.When purchased Et 2 NH (5.7 equiv.)and LDA (0.3 mL x 2) were employed, 7a, 8a, and 9 were obtained (entry 6).In addition, a spot corresponding to 13a was observed on TLC (EtOAc : hexane = 1 : 3, R f = 0.45).By employing a dried excess amount of Et 2 NH (15 equiv.)and the same amount of LDA, only 7a, 8a, and 9 were obtained in 51, 19, and 18% yields, respectively (entry 7).Yields of 7a, 8a, and 9 seemed to be independent of the dryness of Et 2 NH.In addition, no spot corresponding to 13a was observed from the latter reaction presumably due to the low concentrations of diisopropylamide ion in the presence of excess Et 2 NH.
For the reactions with an excess amount of dried Pr 2 NH and LDA (0.3 mL x 2) (entry 9), 7e was obtained in 55% yield, whereas the reaction with purchased Pr 2 NH (4 equiv.)and LDA (0.3 mL x 8) gave 14a, 15a, and 9 in 49, 10, and 15% yields (entry 8) instead of 7e and 8e.This result indicates that the reactions depend strongly on the concentration of LDA rather than the dryness of purchased amines.The formation of 14a and 15a may be achieved via a nucleophilic displacement of the methoxy groups of 7e and 8e by dipropylamide ion.The displacement of the methoxy group in preference to the phenylthio group indicates that the first step corresponding to a nucleophilic attack of an amide ion is a rate determining step. 9However, the electronic (for 7e and 8e) and steric (for 8e) effects of dipropyl groups of 7e and 8e cannot be ruled out.

Complexations of some prepared sulfur-containing compounds. (a) Extractive ability
The affinity of selected metal cations to compounds 7a, 7e-f, 7h, 7j, 7m, 10, 13a, and 18a was examined by mixing a deionized aqueous solution of a metal picrate (5 x 10 -3 M, 2 mL), prepared by a reported procedure, 10 with each of the host compounds in CHCl 3 (1 x 10 -3 M, 2 mL).The mixture was vigorously stirred, followed by maintenance at constant temperature for 12 h.The extractive ability defined in equation 1 was calculated, where the subtraction of the picrate transferred into the plain CHCl 3 from the initial concentration of picrate in the aqueous phase is the [M aq ] value, and [M t ] is the concentration of picrate in the aqueous phase after extraction.[H o ] is the concentration of the host molecule.The results are tabulated in Table 2. Table 2 shows that the extractive abilities of 10 toward all metal cations employed are essentially zero.In contrast, the extractive abilities of 7a having a diethylamino group at the meta position toward Ag + and Pb 2+ ions increased somewhat to 28 and 18%, respectively.On the other hand, the extractive abilities of 7e and 7f having a dipropyl-and dibutylamino group, respectively, in place of a diethylamino group of 7a toward the same metal ions decreased to 18 and 5%, respectively, for 7e, and to 14 and 7%, respectively, for 7f.The results suggest that the nonbonding electrons on the amino group at the meta position are somehow involved in the complexations with both Ag + and Pb 2+ ions.However, bulky groups such as the dipropyl-and dibutylamino groups are envisaged to reduce the efficiency of the complexations, presumably due to the steric hindrance.Compound 7h, having a piperidine moiety at the same meta position showed almost the same extractive abilities as those of 7a toward Ag + and Pb 2+ ions.This may be ascribed to the similar electronic and steric effects of the piperidine ring and diethylamino group.In this regard, it is necessary to explain the observation in which compound 13a, having a diisopropylamino group at the same meta position, showed a very low extractive ability (9%) toward Ag + ion and a relatively high extractive ability (67%) toward Pb 2+ ion.One might explain the different tendencies in the extractive ability of 13a toward Ag + ion and Pb 2+ ions by presuming the involvement of two molecules of 13a in producing a cavity for complexing metal ions.The cavity may be suitable for accommodation of the smaller Pb 2+ ions (ionic radius = 1.20 Å) compared with Ag + ions (ionic radius = 1.26 Å). 11 Figure 2 shows molecular mechanics-calculated conformations (MN2 + force field, MC/SD conformational search) 12 of (a) 13a (parallel) -Pb 2+ , (b) 13a (parallel, T-shaped 13 ) -Pb 2+ , and (c) 13a (anti-parallel) -Pb 2+ picrate complexes.The non-bonded distances between the middle of the methoxyphenyl groups bonded to S1 and S3 atoms, and two diisopropylaminophenyl groups bonded to S2 and S4 atoms of the 13a (parallel) -Pb 2+ and the 13a (parallel, T-shaped) -Pb 2+ picrate complexes are calculated to be 3.69 and 5.65 Å, and 4.89 and 4.17 Å, respectively.Similarly, the non-bonded distances between two phenyl groups bonded to S1 and S4, and S2 and S3 atoms of the 13a (anti-parallel) -Pb 2+ are 3.99 and 4.94 Å , respectively.The distances over 4 Å are a little greater for π-π stacking interactions. 14It shows that a Pb 2+ ion interacts with four sulfur atoms whose geometry resembles a crushed tetrahedral (refer to the supporting information (SI) for non-bonded distance and bond angle).The interaction energies between the HOMO of 13a and the LUMO of Pb 2+ ion (refer to the SI for the energies of the HOMO and the LUMO), 15 and the thermodynamic energies of the complexes are summarized in Table 3.The data show that the 13a (parallel, T-shaped) -Pb 2+ picrate complex has a lower thermodynamic energy compared with other complexes by 1011 to 1029 kcal/mol.Furthermore, the smallest HOMO -LUMO interaction energy (1.9 eV) is involved in the formation of the complex.Consequently, not only the thermodynamic stability of the complex but also the HOMO -LUMO interaction energy are envisaged to play an important role leading to the formation of the 13a (parallel, T-shaped) -Pb 2+ picrate complex.

Extractive ability (%) = (([M aq
Figure 3 shows conformations of (a) 13a (parallel) -Ag + and (b) 13a (anti-parallel) -Ag + picrate complexes obtained by the same method as for 13a -Pb 2+ picrate complex.The 13a (parallel) -Ag + picrate complex shows that the Ag + ion forms a kind of tetrahedral geometry with four sulfur atoms.The non-bonded distances between two methoxyphenyl groups bonded to S1 and S3 atoms, and those of the two diisopropylaminophenyl groups bonded to S2 and S4 atoms of the 13a (parallel) -Ag + picrate complex, obtained by the same method as for the 13a -Pb 2+ picrate complexes, are 3.31 and 4.14 Å, respectively.A π-π stacking interaction may be possible only between two methoxyphenyl groups.The HOMO -LUMO interaction energies between 13a and Ag + ion and the thermodynamic energies of the 13a (parallel) -Ag + and the 13a (anti-parallel) -Ag + picrate complexes are summarized in Table 3.The data show that the latter has a smaller HOMO -LUMO interaction energy compared with that of the latter by 1.25 eV for α-spin and 1.31 eV for β−spin but it is less stable than the former by 14.33 kcal/mol.Accordingly, it may be difficult to predict a plausible conformation for the complex formed by 13a and Ag + picrate based on the thermodynamic energy and the HOMO -LUMO interaction energy.Nevertheless, it may be envisaged that the lower thermodynamic energy as well as a smaller HOMO -LUMO interaction energy of the 13a (parallel, T-shaped) -Pb 2+ picrate complex compared with corresponding value for the 13a -Ag + picrate complex may be responsible for a higher extractive ability of 13a toward Pb 2+ ion compared with Ag + ion.
Figure 4 shows conformation of (a) 7a (parallel) -Ag + and (b) 7a (anti-parallel) -Ag + picrate complexes obtained by the same method as for 13a -Ag + picrate complex.The non-bonded distances between two methoxyphenylgroups bonded to S1 and S3 atoms and two diethylaminophenyl groups bonded to S2 and S4 atoms of the 7a (parallel) -Ag + picrate complex, determined by the same method as before, are 3.45 and 3.82 Å, respectively, which suggests possible π-π stacking interactions between two pairs of the phenyl rings.Similar calculations conducted on the 7a (anti-parallel) -Ag + picrate complex show that the non-bonded distances between methoxyphenyl group bonded to S1 and diethylaminophenyl group bonded to S4, and diethylaminophenyl group bonded to S2 and methoxyphenyl group bonded to S3 atoms are 3.86 and 3.67 Å, respectively.The non-bonded distances between the phenyl groups of the 7a (anti-parallel) -Ag + picrate complex are reasonable distances for π-π stacking interactions as is the case for the 7a (parallel) -Ag + picrate complex.In the meantime, the calculated HOMO -LUMO interaction energies between 7a and Ag + picrate and the thermodynamic energies of the 7a -Ag + picrate complex are summarized in Table 4 (7a (parallel, T-stacking) -Ag + picrate complex is improbable).
Table 4.The energy differences between the HOMO of 7a and the LUMO of metal cations (Pb 2+ , Ag + ) and the thermodynamic energies of 7a -metal cation complexes at 25 o C complex energy 7a (P) -Ag + 7a (A P) -Ag + 7a (P) -Pb 2+ 7a (A P) -Pb 2+ The data show that the 7a (parallel) -Ag + picrate complex has a smaller HOMO -LUMO interaction energy than the 7a (anti-parallel) -Ag + picrate complex by 1.4 eV for α -spin and 0.68 eV for β -spin.In addition, the former has a lower thermodynamic energy than the latter by 270 kcal/mol.Accordingly, it is conceivable that the formation of 7a (parallel) -Ag + picrate complex is preferable to that of 7a (anti-parallel) -Ag + picrate complex.Figure 5 shows conformations of (a) 7a (parallel) -Pb 2+ and (b) 7a (anti-parallel) -Pb 2+ picrate complexes obtained by the same method as for 7a -Ag + picrate complex.Non-bonded distances between two methoxyphenyl groups and two diethylaminophenyl groups of 7a (parallel) -Pb 2+ picrate complex are 4.13 and 4.51 Å, respectively, whereas those between two groups bonded to S1 and S4, and S2 and S3 of 7a (anti-parallel) -Ag + picrate complex are 5.22 and 3.56 , respectively.The calculated HOMO -LUMO interaction energies between 7a and Pb 2+ picrate and the thermodynamic energies of the 7a and Pb 2+ picrate complexes are summarized in Table 4.The data show that the 7a (anti-parallel) -Pb 2+ picrate complex has smaller HOMO -LUMO interaction energies than the 7a (parallel) -Ag + picrate complex by 2.9 eV for α-spin and 2.2 eV for β-spin.The former also has a lower thermodynamic energy than the latter by 220 kcal/mol.Consequently, it is conceivable that the formation of 7a (anti-parallel) -Pb 2+ picrate complex is preferable to that of 7a (parallel) -Pb 2+ picrate complex.
Although the HOMO -LUMO interaction energy of the 7a (anti-parallel) -Pb 2+ picrate complex is smaller than that of the 7a (parallel) -Ag + picrate complex, the latter shows a lower thermodynamic energy compared with that of the former, which may be reflected in the higher extractive ability of 7a toward Ag + ion compared with Pb 2+ ion.The different tendencies of 7a and 13a with regard to complexing Ag + and Pb 2+ ions are envisaged to be due to the presence of the bulky diisopropylamino group as a substituent which makes two molecules of 13a interact with Pb 2+ ion to form a T-stacking complex so that the interaction energy between the HOMO of 13a and the LUMO of Pb 2+ ion becomes drastically smaller compared with those between the HOMO -LUMO of other host and guest pairs and the complex becomes remarkably stable.
Compounds 7j and 7m having an aza-18-crown-6 moiety, respectively showed almost the same extractive abilities (67 and 66%, respectively) as that of 13a toward Pb 2+ ion.Surprisingly, aza-15-crown-5 and aza-18-crown-6, tethered sulfur-containing lariats at nitrogen atoms, have been seldom reported 16 despite the existence of numerous studies of other types of lariats.Examination of the molecular mechanics calculations on 7j showed that a structure where the pendent arm is directed away from the azacrown has the lowest energy (E = 38.06kcal/mol) (Figure 6, (a)).In this regard, the conformation is similar to the X-ray crystal structure of 14b (Figure 1).The preparation of a single crystal for X-ray crystallography of 7j -Pb 2+ complex was unsuccessful.However, the molecular mechanics calculations indicate that the interactions of a Pb 2+ ion with two sulfur and three oxygen atoms of one molecule of aza-18-crown-6 leads to a bent-type complex, which is the most stable complex having E = 29.76kcal/mol (Figure 6, (b)).A sandwich-type complex in which two ligands accommodate a Pb 2+ ion between two lariats of 7j requires a higher energy by ca. 10 kcal/mol (E = 39.63 kcal/mol) (Figure 6, (c)).The increase in the extractive abilities of 7j and 7m toward Ag + ion (40 and 24%, respectively) compared with that of 13a (9%) may be ascribed to the oxygen atoms comprising aza-18-crown-6.Surprisingly, compound 18a showed a very high selectivity toward Ag + ion (86%), whereas its selectivity toward Pb 2+ ion was comparable with those of 7e-f.It is envisaged that two lariats, i.e.  Figure 6 shows that the highest absorbance was obtained when 1.6 x 10 -4 M of 7a was mixed with 8 x 10 -5 M of aqueous silver picrate.Furthermore, the complex obtained from the chloroform layer showed a mass number (m/z) of 899.82 on the MALDI-TOF spectrum, corresponding to the molecular weight of a complex consisting of two molecules of 7a and an Ag + ion.(c) 1 H NMR study of the complexation of 7m with Ag + and Pb 2+ ions The 1 H NMR spectrum (300 MHz, CDCl 3 ) of 7m was compared with those of the 7m -Ag + and the 7m -Pb 2+ complexes.The comparison of the intensities of the aromatic protons of picrate appearing at 8.72 ppm with those of the methyl protons of the isopropyl group appearing at 1.35 ppm indicates the efficiency of the formation of the complex under the conditions in which the extractability experiment was performed.The 1 H NMR spectroscopic data showed 33 and 79% complexations toward Ag + and Pb 2+ ions, respectively.These values are a little higher than 24 and 66%, respectively, which were obtained from the extractability experiments.
A noteworthy feature is that there is little difference in the shape of a multiplet appearing at 3.55 -3.67 ppm, assigned to 24 methylene protons of 7m and 7m -Ag + complex, but significantly different shapes were observed in the multiplets of the aromatic proton signals.In contrast, the 7m -Pb 2+ complex exhibited a multiplet in the range of 3.32 -3.85 ppm.The range observed from the latter complex is wider than that observed from the 7m -Ag + complex.Furthermore, the shape differed considerably from that of the 7m -Ag + complex but the shapes of the aromatic proton signals of the 7m -Ag + and 7m -Pb 2+ complexes appeared similar.The results indicate that Ag + ion does not interact strongly with aza-18-crown-6 ring but Pb 2+ interacts strongly with the same ring.This view is in good agreement with the similar extractabilities of 7a, 7h, and 7m toward Ag + ion (Table 2) and the large difference in the extractabilities between 7a or 7h and 7m toward Pb 2+ ion.

Experimental Section
General Procedures.The 1 H and 13 C NMR spectra were recorded 300 MHz and 75 MHz, respectively in CDCl 3 or DMSO-d 6 solution containing Me 4 Si as internal standard.IR spectra were recorded in KBr or film on KBr plates.Elemental analyses were determined by the Korea Basic Science Center.MALDI-TOF and FAB mass spectra were determined by National Center for Inter-University Research Facilities.Column chromatography was performed using silica gel (230-400 mesh, Merck).Melting points were measured on Fisher-Jones melting point apparatus and uncorrected.5-Arylthianthrenium perchlorates (2) were prepared by the literature methods. 2 Amines were dried as reported in the literature. 17neral procedure for the reactions of 2 with alkylamines (a) To a solution of alkylamine in THF (20 mL) was added NaH (1.64 mmol) under nitrogen atmosphere.The solution was stirred for 20 min at room temperature, followed by the addition of 2. The mixture was additionally stirred for an appropriate hour at reflux.Removal of the solvent in vacuo gave a residue, which was chromatographed on silica gel (7 x 1.5 cm).Elution with a mixture of EtOAc and hexane (1 : 9) gave thianthrene (9) and desired compounds 7 and 8. Quantities of 2 and NaH, and yields of 7, 8, and 9 are summarized in Table 1.(b) To a solution of alkylamine in THF (50 mL) was added 2. The mixture was heated at reflux under nitrogen atmosphere, followed by the addition of 0.3 mL (0.6 mmol) of LDA (2 M, hexane) six to eight times at the intervals of 40 min using a hypodermic syringe.Removal of the solvent in vacuo gave a residue, which was chromatographed on silica gel (7 x 1.5 cm) as described in (a).

Table 1 .
Quantities of 2 and amines, and yields of 7, 8, and 9 sCompound 18b was obtained in 33% yield.t sm : small amount.In the cases of entries 15 -23, a mixtures of small amounts of 9 and unidentifiable materials were obtained.

Table 2 .
Extractive ability of some compounds

Table 3 .
The energy differences between the HOMO of 13a and the LUMO of metal cations (Pb 2+ , Ag + ) and the thermodynamic energies of 13a -metal cation complexes at 25 o C P: parallel; A P: anti-parallel; T: T-shaped; α : α -spin; β: β -spin.