DOI: 10.1002/asia.201500889
Full Paper
N Ligands
Multicomponent One-pot Reactions Towards the Synthesis of Stereoisomers of Dipicolylamine Complexes Sakthi Raje,[a] Sureshbabu Gurusamy,[a] Abhishek Koner,[a] Sonam Mehrotra,[a] Samson Jegan Jennifer,[a] Prema G. Vasudev,[b] Ray J. Butcher,[c] and Raja Angamuthu*[a] Dedicated to Professor Stephen J. Lippard on the occasion of his 75th birthday
Abstract: Reported are multi-component one-pot syntheses of chiral complexes [M(LROR’)Cl2] or [M(LRSR’)Cl2] from the mixture of an N-substituted ethylenediamine, pyridine-2-carboxaldehyde, a primary alcohol or thiol and MCl2 utilizing insitu formed cyclized Schiff bases where a C¢O bond, two stereocenters, and three C¢N bonds are formed (M = Zn, Cu, Ni, Cd; R = Et, Ph; R’ = Me, Et, nPr, nBu). Tridentate ligands LROR’ and LRSR’ comprise two chiral centers and a hemiaminal ether or hemiaminal thioether moiety on the dipicolylamine skeleton. Syn-[Zn(LPhOMe)Cl2] precipitates out readily from the reaction mixture as a major product whereas anti[Zn(LPhOMe)Cl2] stays in solution as minor product. Both syn[Zn(LPhOMe)Cl2] and anti-[Zn(LPhOMe)Cl2] were characterized using NMR spectroscopy and mass spectrometry. Solid-state structures revealed that syn-[Zn(LPhOMe)Cl2] adopted a square pyramidal geometry while anti-[Zn(LPhOMe)Cl2] pos-
sesses a trigonal bipyramidal geometry around the Zn centers. The scope of this method was shown to be wide by varying the components of the dynamic coordination assembly, and the structures of the complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Syn complexes were isolated as major products with ZnII and CuII, and anti complexes were found to be major products with NiII and CdII. Hemiaminals and hemiaminal ethers are known to be unstable and are seldom observed as part of cyclic organic compounds or as coordinated ligands assembled around metals. It is now shown, with the support of experimental results, that linear hemiaminal ethers or thioethers can be assembled without the assistance of Lewis acidic metals in the multi-component assembly, and a possible pathway of the formation of hemiaminal ethers has been proposed.
Introduction
plexes based on the dipica scaffold appeared in more than 1000 reports including about 200 patents due to their importance in the context of fluorescent probes of the Zinpyr family,[4] dynamic multi-component covalent assemblies,[5] heterometallic complexes,[6] chiral discriminators,[7] unsymmetrical ligands,[8] optical fiber sensors,[9] magnetic nanoparticles,[10] anion receptors,[11] new peptides,[12] artificial enzymes,[13] catalysts,[14] etc. The main reason why the dipica moiety exhibits versatility in all the aforementioned areas is the strong chelating ability of its three N donors with a wide range of transition metals and the opportunity of incorporating modifications on the backbone through substitutions on the central N donor. Our laboratory is beginning to explore unconventional routes to prepare new forms of dipica and their transition metal complexes in order to utilize them as catalysts. Reported herein is our maiden effort in the synthesis of a new family of tridentate ligands comprising the 2,2’-dipicolylamine moiety (Figure 1). To synthesize these new ligands, we have taken advantage of a four-component dynamic covalent assembly comprising pyridine-2-carboxaldehyde, an N-substituted ethylenediamine, an aliphatic primary alcohol or thiol and a transition metal ion. The tridentate ligand scaffold presented in this report possesses two NPy donors (N1 and N3) and a tertiary amine nitrogen
Dipicolylamines (dipica) were introduced by Binieck and Kabzinska around fifty years ago[1] and served as coronary vasodilators (gapicomine, bicordin) for many decades.[2] Simultaneously, 2,2’-dipicolylamine was familiarized as a promising trisdentate ligand by various chemists.[3] Since then ligands and com[a] S. Raje, S. Gurusamy, A. Koner, S. Mehrotra, Dr. S. J. Jennifer, Dr. R. Angamuthu Laboratory of Inorganic Synthesis and Bioinspired Catalysis (LISBIC) Department of Chemistry Indian Institute of Technology Kanpur Kanpur 208016 (India) E-mail: [email protected] [b] Dr. P. G. Vasudev Metabolic and Structural Biology Division CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP) Lucknow 226015 (India) [c] Prof. R. J. Butcher Department of Chemistry Howard University Washington, D.C. 20059 (USA) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201500889. Chem. Asian J. 2016, 11, 128 – 135
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Full Paper plane while another nitrogen (N2) and chloride (Cl1) occupy the axial positions. The zinc ion is displaced by 0.358 æ from the N2Cl mean plane towards the axially coordinated chloride (Cl2). The angle of 70.518 between two pyridine planes (p) in the solid-state structure of the complex indicates that the dipicolylamine backbone adopted a wings-folded butterfly mode to bind with the ZnII ion. We then explored the nature of the precipitate obtained from the reaction; colorless crystals were obtained from an acetonitrile solution at 0 8C and single-crystal XRD analysis revealed the presence of syn forms (6R,7R and 6S,7S enantiomers) of [Zn(LPhOMe)Cl2] exclusively (Figure 3). In contrast to the anti forms, the ZnII ion was located in a distorted square pyramidal environment with a t value of 0.37.[15] However, the zinc ion is displaced by 0.586 æ from the N3Cl mean plane to-
Figure 1. The 2,2’-dipicolylamine-based, hemiaminal ether comprising ligands presented in this report with crystallographic numbering scheme. The carbon centers C6 and C7 are stereogenic (R = Ph, Et; R’ = Me, Et, nPr, nBu).
donor (N2), similar to the conventional 2,2’-dipicolylamine, in addition to a tertiary amine on the backbone (N4) that cannot participate in coordination with the same metal as other three N donors; N2 and N4 are part of the imidazolidinyl ring originating from ethylenediamine providing the humpback to these ligands and offering certain interesting steric restrictions upon complexation. Substituting an appropriate group on N4 can tune a complex, synthesized using a suitable metal ion, to have wide range of aforementioned applications.
Results and Discussion As a test reaction, we have treated two equivalents of pyridine-2-carboxaldehyde with N-phenylethylenediamine in methanol at room temperature to obtain the transient compound LROR’ (R = Ph; R’ = Me). The hemiaminal ether-appended ligand LPhOMe was then reacted in situ with an equivalent of anhydrous ZnCl2 that yielded a white precipitate immediately. Upon standing at 0 8C for one day, the filtrate of the reaction yielded colorless shiny needles of diffraction quality. Single-crystal Xray diffraction (XRD) exhibited the presence of anti forms (6R,7S and 6S,7R enantiomers) of [Zn(LPhOMe)Cl2] exclusively (Figure 2). The ZnII ion exhibited a pentacoordinated distorted trigonal-bipyramidal geometry with an Addison–Reedijk t parameter of 0.86.[15] Two pyridine nitrogens (N1, N3) of the ligand and a chloride (Cl2) occupy the corners of the triangular
Figure 3. Solid-state structures of syn-[Zn(LPhOMe)Cl2]·CH3CN showing 6R,7R and 6S,7S enantiomers (extracted from packing). Solvated acetonitrile and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn(1)-N(3) 2.128(5); Zn(1)–N(1) 2.128(5); Zn(1)–Cl(2) 2.2505(16); Zn(1)–Cl(1) 2.2706(17); Zn(1)– N(2) 2.281(4); N(3)-Zn(1)-N(1) 148.93(19) = b; N(3)-Zn(1)-Cl(2) 99.43(13); N(1)Zn(1)-Cl(2) 97.27(14); N(3)-Zn(1)-Cl(1) 97.41(14); N(1)-Zn(1)-Cl(1) 95.59(14); Cl(2)-Zn(1)-Cl(1) 122.11(6); N(3)-Zn(1)-N(2) 74.68(17); N(1)-Zn(1)-N(2) 74.95(17); Cl(2)-Zn(1)-N(2) 110.87(12); Cl(1)-Zn(1)-N(2) 126.98(12) = a. t = 0.37.[15] p = 11.168.
wards the axially coordinated chloride (Cl2).[15] Three nitrogens of the ligand and a chloride occupy the corners of the square plane while another chloride occupies the axial position. To our surprise, the angle between two pyridine planes is only 11.168 indicating that the dipicolylamine backbone adopted a planar flight mode as all the three N donors are almost on same plane. The folded facial (butterfly) binding mode observed in the anti complex and planar (flight) binding mode in the syn complex is enforced by the presence of the humpback created by the manifestation of the imidazolidinyl ring; a butterfly mode for syn and flight mode for anti might be impossible due to steric strain that may result from this arrangement. However, the classical 2,2’-dipicolylamine is flexible enough to adopt both modes depending on factors such as size of the metal ion, preferred coordination mode, etc. To check if this facial (anti) and planar (syn) orientation of the ligand LPhOMe is solvent-dependent, we have recrystallized the syn[Zn(LPhOMe)Cl2] in chloroform and found the similar planar binding mode as in the case of syn-[Zn(LPhOMe)Cl2]·CH3CN; however, few minor changes in the angles were observed (Figure S27).
Figure 2. Solid-state structures of anti-[Zn(LPhOMe)Cl2] showing 6R,7S and 6S,7R enantiomers (extracted from packing). Hydrogen atoms other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn–N(1), 2.070(2); Zn–N(2), 2.385(2); Zn–N(3), 2.065(2); Zn–Cl(1), 2.3500(8); Zn–Cl(2), 2.2420(8); N(3)-Zn-N(1), 113.10(8) = a; N(3)-Zn-Cl(2), 119.79(6); N(1)-Zn-Cl(2), 118.77(6); N(3)-Zn-Cl(1), 98.07(6); N(1)Zn-Cl(1), 96.67(6); Cl(2)-Zn-Cl(1), 104.00(3); N(3)-Zn-N(2), 75.39(8); N(1)-ZnN(2), 73.92(8); Cl(2)-Zn-N(2), 91.22(5); Cl(1)-Zn-N(2), 164.67(5) = b. t = 0.86.[15] Angle between two Py planes = p = 70.518. Chem. Asian J. 2016, 11, 128 – 135
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Full Paper In order to study the solution properties of these complexes, the 1H NMR spectrum of a crude product (Figure S1), obtained by evaporating the volatiles of the reaction mixture, was recorded in CDCl3 at room temperature. This revealed the presence of both syn and anti forms of [Zn(LPhOMe)Cl2], as confirmed by comparing with the 1H NMR spectra of isolated syn and anti forms independently (Figure 4 and Figures S2–S4). The singlets for the hydrogens attached to the chiral centers C6 and C7 of anti-[Zn(LPhOMe)Cl2] appear at 5.34 and Figure 5. Solid-state structures of anti-[Zn(LPhOH)Cl2]·CDCl3 showing 6R,7S and 6S,7R enantiomers (extracted from packing). Solvated CDCl3 and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn–N(1), 2.077(7); Zn–N(2), 2.378(7); Zn–N(3), 2.082(8); Zn–Cl(1), 2.378(3); Zn–Cl(2), 2.230(3); N(1)-ZnN(3), 116.8(3) = a; N(1)-Zn-Cl(2), 115.2(2); N(3)-Zn-Cl(2), 121.1(2); N(1)-Zn-N(2), 74.6(3); N(3)-Zn-N(2), 76.8(3); Cl(2)-Zn-N(2), 92.3(2); N(1)-Zn-Cl(1), 94.6(2); N(3)-Zn-Cl(1), 95.8(2); Cl(2)-Zn-Cl(1), 105.69(12); N(2)-Zn-Cl(1), 161.7(2) = b. t = 0.75.[15] p = 64.058.
metal in a planar fashion. 1H NMR spectra of crude reaction mixtures and of the white precipitates share all the main features in common with [Zn(LPhOMe)Cl2]. Further, to explore the ability of ethylenediamines with various substitutions to undergo this reaction, N-phenylethylenediamine was replaced by N-ethylethylenediamine and found to yield same type of zinc complex with the formula [Zn(LEtOMe)Cl2] (Figure S22). The single-crystal XRD analysis of the crystals of syn forms of [Zn(LEtOMe)Cl2], obtained from a methanolic solution, confirmed that the structural features indeed match those of syn-[Zn(LPhOMe)Cl2] (Figure S30). In order to examine the metal dependence of the formation of these hemiaminal ether complexes, ZnCl2 was replaced by CdCl2 and CuCl2·2 H2O, and found to yield [Cd(LPhOMe)Cl2]2 (Figure S23) and [Cu(LPhOMe)Cl2] (Figure S24). The 1H NMR spectrum of the precipitate formed by the reaction with CdCl2 showed two singlets at 5.09 and 6.02 ppm, corresponding to the protons attached to the chiral carbons, indicating the existence of the ligand in anti form (Figure S15), which was further confirmed by the XRD analysis of the crystals grown in a solution of dichloromethane (Figure 6). The structure shows a dimeric form of [Cd(LPhOMe)Cl2] with two m-Cl bridges such that each cadmium exists in a hexacoordinated octahedral geometry where one cadmium possesses the 6R,7S form while the other has the 6S,7R form of the hemiaminal ether ligand LPhOMe. On the other hand, CuCl2·2 H2O yielded a green precipitate, which showed the presence of an envelope corresponding to the [Cu(LPhOMe)Cl] + monocation in its ESI mass spectrum (m/z = 444.0807). Green crystals grown in methanol showed the presence of syn forms of [Cu(LPhOMe)Cl2] exclusively where the CuII ion is situated in a square pyramidal geometry (Figure 7). To find out if the formation of hemiaminal ether ligands demands the assistance of Lewis acidic metal ions,[5] we have performed the multicomponent reaction of aldehyde and amine in primary alcohol for 24 h, and all the volatiles were evaporated to obtain an oily substance that is presumably the hemiaminal ether. This oily substance was redissolved in acetonitrile and a batch of NiCl2·6 H2O was added as solid and stirred for
Figure 4. 1H NMR spectra of crude [Zn(LPhOMe)Cl2] showing the presence of both syn and anti complexes (bottom), isolated anti-[Zn(LPhOMe)Cl2] (middle), and syn-[Zn(LPhOMe)Cl2] (top).
5.57 ppm; the same for the syn-[Zn(LPhOMe)Cl2] appear at 6.06 and 6.31 ppm, respectively.[5] The 1H NMR spectrum of anti[Zn(LPhOMe)Cl2] as a CDCl3 solution shows the presence of trace amounts of free components as the complex tends to dissociate in solutions as observed by Anslyn and coworkers for similar complexes (Figure S3).[5] We have isolated colorless shiny crystals from the NMR tube containing anti-[Zn(LPhOMe)Cl2] in CDCl3 and the structure exhibited the formation of anti-[Zn(LPhOH)Cl2] with loss of alcohol (Figure 5). Repeating the same in CHCl3 also yielded the same result (Figure S31). However, the 1H NMR spectrum of syn[Zn(LPhOMe)Cl2] remained unchanged for days. In order to investigate the scope of the reaction, the reaction of two equivalents of pyridine-2-carboxaldehyde with Nphenylethylenediamine was carried out in other primary alcohols such as ethanol, 1-propanol, and 1-butanol. Complexes [Zn(LPhOEt)Cl2], [Zn(LPhOPr)Cl2], and [Zn(LPhOBu)Cl2] were obtained as precipitates from the corresponding alcohols and crystallized in the corresponding alcohol or in acetonitrile. Initial characterization using ESI mass spectrometry (Figures S19– S21) and 1H NMR spectroscopy (Figures S5–S13) confirmed the identity of the complexes formed as [Zn(LROR’)Cl2]. The solidstate structures of the crystals revealed the presence of syn[Zn(LPhOEt)Cl2] (Figure S28) and syn-[Zn(LPhOPr)Cl2] (Figure S29); they are indeed identical with syn-[Zn(LPhOMe)Cl2] and both feature a Zn(II) situated in a square pyramidal environment. As expected, these syn complexes have the ligand bound to the Chem. Asian J. 2016, 11, 128 – 135
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Figure 6. Solid-state structures of anti-[Cd(LPhOMe)Cl2]2·2 CH2Cl2 showing 6R,7S and 6S,7R enantiomers. Solvated dichloromethane and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cd–N(1), 2.400(3); Cd–N(2), 2.493(3); Cd–N(3), 2.385(3); Cd–Cl(1), 2.5948(9); Cd–Cl(2), 2.4830(8); Cd–Cl(1)#1, 2.6207(8); Cl(1)–Cd#1, 2.6207(8); N(3)-Cd-N(1), 89.86(10); N(3)-Cd-Cl(2), 95.31(8); N(1)-Cd-Cl(2), 92.79(7); N(3)-Cd-N(2), 70.13(10); N(1)-Cd-N(2), 69.24(9); Cl(2)-Cd-N(2), 156.24(7); N(3)-Cd-Cl(1), 164.10(8); N(1)-Cd-Cl(1), 89.98(7); Cl(2)-Cd-Cl(1), 100.58(3); N(2)-Cd-Cl(1), 95.01(7); N(3)-Cd-Cl(1)#1, 88.89(8); N(1)-Cd-Cl(1)#1, 160.01(7); Cl(2)-Cd-Cl(1)#1, 107.19(3); N(2)-CdCl(1)#1, 91.63(7); Cl(1)-Cd-Cl(1)#1, 85.85(3); Cd-Cl(1)-Cd#1, 94.14(3). p = 85.748.
Figure 8. Solid-state structures of anti-[Ni(LEtOMe)(H2O)Cl2] showing 6R,7S and 6S,7R enantiomers (extracted from packing). Hydrogens other than the two bound to the chiral centers and of coordinated H2O are omitted for clarity. Selected bond distances [æ] and angles [deg]: Ni–N(1), 2.0440(16); Ni– N(2), 2.1814(15); Ni–N(3), 2.0947(15); Ni–Cl(1), 2.4240(5); Ni–Cl(2), 2.4081(5); Ni–O(1W), 2.0831(14); N(1)-Ni-O(1W), 170.21(6); N(1)-Ni-N(3), 90.55(6); O(1W)Ni-N(3), 86.85(6); N(1)-Ni-N(2), 81.78(6); O(1W)-Ni-N(2), 88.46(6); N(3)-Ni-N(2), 79.19(6); N(1)-Ni-Cl(2), 91.40(4); O(1W)-Ni-Cl(2), 90.16(4); N(3)-Ni-Cl(2), 173.32(5); N(2)-Ni-Cl(2), 94.77(4); N(1)-Ni-Cl(1), 97.34(5); O(1W)-Ni-Cl(1), 92.23(4); N(3)-Ni-Cl(1), 92.94(5); N(2)-Ni-Cl(1), 172.06(4); Cl(2)-Ni-Cl(1), 93.140(18). p = 86.618.
best of our knowledge, is the first known metal complex of a hemiaminal thioether (Figure 9). Very few molecules are known in the literature comprising a hemiaminal thioether moiety as part of cyclic compounds;[16] the present LPhSEt serves as the first example of a linear hemiaminal thioether molecule. Interestingly, anti-LPhSEt is not bound to the CuII ion facially, whereas in the case of hemiaminal ether complexes reported above, the anti-LROR’ ligands are always bound to the metal ion facially as seen in the cases of anti-[Zn(LPhOMe)Cl2], anti-[Cd(LPhOMe)Cl2]2, and anti-[Ni(LEtOMe)(H2O)Cl2]. If the components were not assembled as hemiaminal thioether prior to the addition of CuCl2·2 H2O, the free thiol present in the mixture would have reduced the CuII to CuI with concurrent formation of diethyl disulphide, and eventually the formation of
Figure 7. Solid-state structures of syn-[Cu(LPhOMe)Cl2]·MeOH showing 6R,7R and 6S,7S enantiomers. Solvated methanol and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cu(1)–N(1), 2.006(3); Cu(1)–N(3), 2.007(3); Cu(1)– N(2), 2.073(3); Cu(1)–Cl(1), 2.2370(9); Cu(1)–Cl(2), 2.5509(9); N(1)-Cu(1)-N(3), 159.22(11) = a; N(1)-Cu(1)-N(2), 81.53(11); N(3)-Cu(1)-N(2), 80.79(11); N(1)Cu(1)-Cl(1), 96.73(8); N(3)-Cu(1)-Cl(1), 97.17(8); N(2)-Cu(1)-Cl(1), 163.73(8) = b; N(1)-Cu(1)-Cl(2), 94.50(8); N(3)-Cu(1)-Cl(2), 96.48(8); N(2)-Cu(1)-Cl(2), 90.47(8); Cl(1)-Cu(1)-Cl(2), 105.81(3). t = 0.08.[15] p = 20.578.
2 h at room temperature. The filtrate of this reaction yielded the NiII complex [Ni(LEtOMe)Cl2] after removing a small amount of insoluble precipitate (Figure S25). Single-crystal XRD analysis showed that the complex is of anti-LEtOMe coordinated to the NiII ion in a facial manner where the hexacoordinate nickel has two chlorides and an aqua ligand in addition to the tridentate LEtOMe (Figure 8). Successful isolation of the above complexes, especially anti-[Ni(LEtOMe)(H2O)Cl2], suggests that the assistance of Lewis acids is not necessary to assemble the hemiaminal ether when we use primary alcohols as solvent in these multicomponent reactions. To confirm this further, unequivocally, we set out a reaction using ethanethiol as alcohol component, evaporated all the volatiles after 24 h, redissolved the hemiaminal thioether residue in acetonitrile and then added CuCl2·2 H2O; a brownish green precipitate formed that was isolated and recrystallized in acetonitrile. Single-crystal XRD analysis displayed the presence of anti-[Cu(LPhSEt)Cl2], which, to the Chem. Asian J. 2016, 11, 128 – 135
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Figure 9. Solid-state structures of anti-[Cu(LPhSEt)Cl2]·CH3CN showing 6R,7S and 6S,7R enantiomers. Solvated CH3CN and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cu(1)–N(1A), 1.994(3); Cu(1)–N(2A), 2.066(3); Cu(1)– N(3A), 1.979(3); Cu(1)–Cl(1A), 2.2717(10); Cu(1)–Cl(2A), 2.4132(10); N(3A)Cu(1)-N(1A), 162.05(13) = b; N(3A)-Cu(1)-N(2A), 81.26(12); N(1A)-Cu(1)-N(2A), 80.80(12); N(3A)-Cu(1)-Cl(1A), 97.90(10); N(1A)-Cu(1)-Cl(1A), 96.55(9); N(2A)Cu(1)-Cl(1A), 146.45(8) = a; N(3A)-Cu(1)-Cl(2A), 92.64(10); N(1A)-Cu(1)-Cl(2A), 94.97(9); N(2A)-Cu(1)-Cl(2A), 112.39(8); Cl(1A)-Cu(1)-Cl(2A), 101.16(4). t = 0.26.[15] p = 23.778.
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Full Paper hemiaminal thioether and the CuII complex, [Cu(LPhSEt)Cl2], would have been impeded. Finally, the 1H NMR spectrum of a CD3OD solution composed of two equivalents of pyridine-2carboxaldehyde and one equivalent of N-phenylethylenediamine was recorded and found to contain sets of singlets in the range of 5.06 and 5.70 ppm, thereby indicating the formation of hemiaminal ether without the assistance of metal ions (Figure S16). From the observations of the aforementioned reactions and the mechanisms proposed for other multicomponent assemblies in the literature by Anslyn[5] and others,[17] we postulate the following mechanism for the formation of hemiaminal ether/thioether complexes presented in this report. In the four-component reaction mixture, the zwitterion 1, formed by the nucleophilic attack of N-substituted ethylenediamine on pyridine-2carboxaldehyde, converts into 2 by proton transfer (Scheme 1).[5f, 17b] Further protonation of 2 leads to 3, which undergoes 5-exo-tet-cyclization to generate 4. Another molecule of pyridine2-carboxaldehyde reacts with 4 and forms zwitterion 5. Once again, proton transfer, further protonation and elimination generate the iminium ion 8. Finally, combination of 8 with an alcohol forms the transient hemiaminal ether ligand 9 with two R chiral centers at carbons C6 and Scheme 1. Proposed pathway of the formation for dipicolylamine-based hemiaminal ether ligand (L OR’) with two stereocenters, which generates four possible stereoisomers of complexes with transition metals (R = Et, Ph; C7.[5, 17b] Hemiaminals and hemia- R’ = Me, Et, Pr, Bu; M = Ni, Cu, Zn, Cd). minal ethers are proven to be the Achilles’ heel of organic synConclusions thesis and are seldom observed[18] as discrete entities;[19] yet they are known to have been stable and isolated as a part of cyclic compounds[20] or coordination complexes.[5, 17a, 20d, 21] FurAccording to Anslyn and coworkers, the initial equilibrium lies thermore, ligands such as 9 are inaccessible by normal routes between the components and the Zn-hemiaminal complex, and demand tedious multistep synthetic process.[22] Only which loses a molecule of water to yield the iminium ion that a handful of chiral ligands based on the dipicolylamine moiety forms a hemiaminal ether (after the reaction with alcohol) and are known in the literature[23] as synthesizing them necessitates eventually its zinc complex.[5a, e, f] Formation of the Zn-hemiami[23c, f] [23d, g] chiral precursors, multiple steps and/or special medianal ether complex can be driven by adding excess alcohol; tors such as lipase.[23b, g] however, Zn-hemiaminal ether complexes have not been isolated though they have been observed in solution by NMR spectroscopy, which could be due to the bulkiness of the secChem. Asian J. 2016, 11, 128 – 135
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Full Paper ondary alcohols used in Anslyn’s multicomponent assembly.[5c, d] We have used primary alcohols in large excess and isolated M-hemiaminal ether/thioether complexes in a number of cases (M = Ni, Cu, Zn, Cd). Under the conditions reported herein, we have observed that 1) the hemiaminal ether/thioether can also be assembled without the assistance of Lewis acids, 2) adding metal chloride solution to the multicomponent mixture drives the final equilibrium towards the formation of the most stable M-hemiaminal ether/thioether complexes, 3) only less stable stereoisomers are involved in the equilibrium to form the more stable counterparts, 4) less stable isomers of M-hemiaminal ether complexes tend to lose the alcohol to form a M-hemiaminal ether complex upon dissolution in chloroform, as observed in the formation of anti-[Zn(LPhOH)Cl2] from anti-[Zn(LPhOMe)Cl2], 5) ZnII and CuII ions prefer to bind with LROR’ with all the three N donors in one plane afforded by 6R,7R and 6S,7S-LROR’, and 6) NiII and CdII ions prefer to have the ligand bound in facial manner afforded by 6R,7S and 6S,7R-LROR’ whereas anti-LRSR’ binds to copper with all the three N donors in a plane which could be due to the orientation of S-Et in LRSR’. Post-modification of metal-bound chiral hemiaminal ethers/thioethers, which might yield rationally designed chiral ligands and complexes that are otherwise synthesized through multistep processes, is currently considered.
least-squares technique using the SHELXL-97 program package. The lattice parameters and structural data are listed at the end of the Supporting Information. CCDC 1060136–1060146 and 1060974 contain the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre.
Syn-[Zn(LPhOMe)Cl2] In a 100 mL round-bottom flask, pyridine-2-carboxaldehyde (0.214 g, 2 mmol) was dissolved in 10 mL of methanol under stirring for 5 min. A methanolic solution (10 mL) of N-phenylethylenediamine (0.141 g, 1 mmol) was then added dropwise to the stirred aldehyde solution. The resulting yellow solution was stirred at room temperature for 24 h. Then a methanolic solution (5 mL) of anhydrous zinc chloride (0.137 g, 1 mmol) was added dropwise to the solution of hemiaminal ether LPhOMe. A white precipitate started to appear within 5 min after adding the solution of metal salt. The reaction mixture was continued to stir for 3 h at room temperature. The white precipitate was filtered off and the pale-yellow filtrate was left at 0 8C. The white precipitate was recrystallized in acetonitrile. Yield: 0.31 g (64 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.24 (d, 1 H, J = 5.1 Hz, Py), 9.21 (d, 1 H, J = 5.2 Hz, Py), 7.99 (t, 1 H, J = 7.7 Hz, Py), 7.87 (t, 1 H, J = 7.7 Hz, Py), 7.77 (d, 1 H, J = 8.0 Hz, Py), 7.60–7.53 (m, 3 H, Py), 7.37 (t, 2 H, J = 7.9 Hz, Ph), 6.90 (t, 1 H, J = 7.3 Hz, Ph), 6.81 (d, 2 H, J = 8.1 Hz, Ph), 6.31 (s, 1 H, C*H), 6.06 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.49 (d, 3 H, J = 4.7 Hz, CH3 of H-bonded MeOH), 3.35 (s, 3 H, OCH3), 3.28 (t, 1 H, J = 7.6 Hz, CH2-Im), 3.08–2.93 (m, 2 H, CH2-Im), 0.94 ppm (q, 1 H, J = 5.4 Hz, OH of H-bonded MeOH). ESI-MS: m/z = 445.0779 (calcd. 445.0774) = [M¢Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OZn·CH3OH: C, 51.33; H, 5.09; N, 10.88. Found: C, 51.01; H, 5.02; N, 10.88. The elemental analysis is consistent with the Xray and NMR data, as the hydrogen-bonded methanol molecule has been observed in both cases.
Experimental Section Materials Pyridine-2-carboxaldehyde (Sigma Aldrich), N-ethylethylenediamine (Alfa Aesar), N-phenylethylenediamine (TCI), anhydrous ZnCl2 (NICE), CuCl2·2 H2O (Merck), NiCl2·6 H2O (Rankem), and CdCl2 (SDFCL) were used as received from commercial sources. Solvents were distilled under dry nitrogen atmosphere using conventional methods.
Anti-[Zn(LPhOMe)Cl2] Colorless needles of anti-[Zn(LPhOMe)Cl2] isolated from the filtrate which was left at 0 8C overnight. Yield: 0.053 g (11%). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.54 (d, 1 H, J = 5.3 Hz, Py), 9.39 (d, 1 H, J = 4.6 Hz, Py), 8.01 (t, 1 H, J = 7.8 Hz, Py), 7.85 (t, 1 H, J = 7.8 Hz, Py), 7.64 (d, 1 H, J = 7.5 Hz, Py), 7.58 (t, 1 H, J = 6.9 Hz, Py), 7.51 (m, 2 H, Py), 7.28 (t, 2 H, J = 4.3 Hz, Ph), 6.85 (t, 1 H, J = 7.3 Hz, Ph), 6.57 (d, 2 H, J = 8.0 Hz, Ph), 5.57 (s, 1 H, C*H), 5.34 (s, 1 H, C*H), 3.71–3.43 (m, 4 H, CH2-Im), 3.62 (s, 3 H, OCH3), 3.47 (d, 3 H, J = 5.5 Hz, CH3 of H-bonded MeOH), 1.05 ppm (q, 1 H, J = 5.5 Hz, OH of H-bonded MeOH).
Methods Elemental analyses were carried out on a PerkinElmer CHNS/O analyzer. NMR spectra were recorded on JEOL 500 MHz and JEOL 400 MHz spectrometers. The temperature was kept constant using a variable-temperature unit within the error limit of 1 K. The software MestReNova was used for the processing of the NMR spectra. Tetramethylsilane (TMS) or the deuterated solvent residual peaks were used for calibration. Mass spectrometry measurements were performed on a Waters-Q-ToF-Premier-HAB213 system equipped with an electrospray interface. Spectra were collected by constant infusion of the sample dissolved in methanol or acetonitrile with 0.1 % formic acid.
Syn-[Zn(LPhOEt)Cl2] Yield: 0.286 g (57 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.21 (d, 1 H, J = 6.1 Hz, Py), 9.18 (d, 1 H, J = 5.2 Hz, Py), 7.97 (t, 1 H, J = 8.4 Hz, Py), 7.86 (t, 1 H, J = 6.2 Hz, Py), 7.75 (d, 1 H, J = 8.0 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 7.5 Hz, Ph), 6.88 (t, 1 H, J = 7.4 Hz, Ph), 6.80 (d, 2 H, J = 8.1 Hz, Ph), 6.26 (s, 1 H, C*H), 6.10 (s, 1 H, C*H), 3.75 (dd, 1 H, J = 7.9 Hz, CH2-Im), 3.59 (m, 1 H, CH2CH3), 3.47 (m, 1 H, CH2CH3), 3.27 (m, 1 H, CH2-Im), 3.0 (m, 2 H, CH2-Im), 0.93 ppm (t, 3 H, J = 7.0 Hz, CH3). ESI-MS: m/z = 459.0926 (calcd. 459.0930) = [M¢Cl] + . Elemental anal. calcd. (%) for C22H24Cl2N4OZn·1.2 EtOH·0.2 H2O: C, 52.74; H, 5.73; N, 10.08. Found: C, 52.53; H, 5.42; N, 9.78.
Crystal Structure Determinations Single-crystal X-ray data were collected on a Bruker SMART APEX CCD diffractometer using graphite-monochromated MoKa radiation (l = 0.71069 æ). The linear absorption coefficients, the scattering factors for the atoms, and the anomalous dispersion corrections were taken from the International Tables for X-ray Crystallography. Data integration and reduction were conducted with SAINT. An empirical absorption correction was applied to the collected reflections with SADABS using XPREP. Structures were determined by the direct method using SHELXTL and refined on F2 by a full-matrix Chem. Asian J. 2016, 11, 128 – 135
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Full Paper Anti-[Zn(LPhOEt)Cl2]
9.8 Hz, Py), 7.94 (t, 1 H, J = 7.7 Hz, Py), 7.73 (d, 1 H, J = 8.3 Hz, Py), 7.65 (d, 1 H, J = 7.8 Hz, Py), 7.53 (m, 2 H, Py), 5.59 (s, 1 H, C*H), 5.16 (s, 1 H, C*H), 3.80 (s, 3 H, OCH3), 3.1 (m, 2 H, CH2-Im), 2.96 (m, 2 H, NCH2CH3), 2.86 (m, 2 H, CH2-Im), 1.28 ppm (t, 3 H, J = 7.2 Hz, NCH2CH3). ESI-MS: m/z = 397.0786 (calcd. 397.0774) = [M¢Cl] + . Elemental anal. calcd. (%) for C17H22Cl2N4OZn·0.1 CH3OH·0.1 CH3CN: C, 47.01; H, 5.18; N, 12.99. Found: C, 47.18; H, 5.22; N, 12.46.
1
Yield: 0.045 g (9 %). H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.59 (d, 1 H, J = 7.8 Hz, Py), 9.43 (d, 1 H, J = 4.3 Hz, Py), 8.01 (t, 1 H, J = 7.8 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.64 (d, 1 H, J = 7.8 Hz, Py), 7.57–7.49 (m, 3 H, Py), 7.27 (t, 2 H, J = 4.4 Hz, Ph), 6.84 (t, 1 H, J = 7.3 Hz, Ph), 6.55 (d, 2 H, J = 7.9 Hz, Ph), 5.66 (s, 1 H, C*H), 5.33 (s, 1 H, C*H), 3.85–3.40 (m, 6 H, 4 H for 2xCH2-Im and 2 H for CH2CH3), 1.13 ppm (t, 3 H, J = 7.0 Hz, CH3).
Anti-[Cd(LPhOMe)Cl2]
Syn-[Zn(LPhOPr)Cl2]
Yield: 0.345 g (65 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.27 (d, 1 H, J = 5.0 Hz, Py), 9.09 (d, 1 H, J = 5.1 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.67 (t, 1 H, J = 7.7 Hz, Py), 7.55 (d, 1 H, J = 7.9 Hz, Py), 7.41 (t, 1 H, J = 6.3 Hz, Py), 7.35 (m, 2 H, Py), 7.25 (t, 2 H, J = 7.9 Hz, Ph), 6.81 (t, 1 H, J = 7.3 Hz, Ph), 6.50 (d, 2 H, J = 8.1 Hz, Ph), 6.02 (s, 1 H, C*H), 5.09 (s, 1 H, C*H), 4.21 (m, 1 H, CH2-Im), 4.03 (m, 1 H, CH2Im), 3.78 (m, 1 H, CH2-Im), 3.66 (s, 3 H, OCH3), 3.59 ppm (m, 1 H, CH2-Im). ESI-MS: m/z = 495.0524 (calcd. 495.0512) = [M-Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OCd: C, 47.61; H, 4.19; N, 10.58. Found: C, 47.42; H, 4.08; N, 9.86.
Yield: 0.291 g (57 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.22 (d, 1 H, J = 5.5 Hz, Py), 9.19 (d, 1 H, J = 5.0 Hz, Py), 7.98 (t, 1 H, J = 7.8 Hz, Py), 7.86 (t, 1 H, J = 7.7 Hz, Py), 7.77 (d, 1 H, J = 7.8 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 8.0 Hz, Ph), 6.88 (t, 1 H, J = 7.3 Hz, Ph), 6.79 (d, 2 H, J = 7.9 Hz, Ph), 6.27 (s, 1 H, C*H), 6.12 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.51–3.33 (m, 2 H, O-CH2), 3.28 (dd, 1 H, J = 7.5 Hz, CH2-Im), 3.03 (m, 2 H, CH2-Im), 1.37 (m, 1 H, CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.63 ppm (t, 3 H, J = 7.4 Hz, CH3). ESI-MS: m/z = 473.1096 (calcd. 473.1087) = [M¢Cl] + . Elemental anal. calcd. (%) for C23H26Cl2N4OZn·0.5 PrOH·0.5 H2O: C, 53.52; H, 5.68; N, 10.19. Found: C, 53.56; H, 5.13; N, 9.82.
Syn-[Cu(LPhOMe)Cl2] To pyridine-2-carboxaldhyde (0.428 g, 4 mmol) dissolved in 17 mL methanol was added N-phenylethylenediamine (0.272 g, 2 mmol), and the resulting yellow solution was stirred at room temperature for 24 h. Subsequently, CuCl2·2H2O (0.341 g, 2 mmol) dissolved in 3 mL methanol was added dropwise to the above stirred yellow solution. A greenish brown precipitate appeared after 15 min of stirring after introducing the CuCl2 solution. The reaction mixture was stirred for further 12 h at room temperature and the volume was reduced to 5 mL. Slow addition of diethyl ether (15 mL) resulted in complete precipitation of Cu(LPhOMe)Cl2 ; the greenish brown precipitate was filtered, washed once with 5 mL of diethyl ether, and recrystallized in methanol at 0 8C. Yield: 0.972 g (65 %). ESI-MS: m/z = 444.0807 (calcd. 444.0778) = [M¢Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OCu·CH3OH: C, 51.52; H, 5.11; N, 10.92. Found: C, 51.49; H, 5.13; N, 10.96.
Anti-[Zn(LPhOPr)Cl2] Yield: 0.051 g (10 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.58 (d, 1 H, J = 6.1 Hz, Py), 9.42 (d, 1 H, J = 5.4 Hz, Py), 8.0 (t, 1 H, J = 7.8 Hz, Py), 7.84 (t, 1 H, J = 7.8 Hz, Py), 7.63 (d, 1 H, J = 7.9 Hz, Py), 7.58–7.48 (m, 3 H, Py), 7.25 (t, 2 H, J = 4.4 Hz, Ph), 6.83 (t, 1 H, J = 7.3 Hz, Ph), 6.56 (d, 2 H, J = 7.9 Hz, Ph), 5.65 (s, 1 H, C*H), 5.32 (s, 1 H, C*H), 3.75–3.41 (m, 6 H, 4 H for 2xCH2-Im and 2 H for O-CH2), 1.54 (m, 1 H, CH2-Me), 0.74 ppm (t, 3 H, J = 7.4 Hz, CH3).
Syn-[Zn(LPhOBu)Cl2] Yield: 0.278 g (53 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.21 (d, 1 H, J = 5.0 Hz, Py), 9.17 (d, 1 H, J = 5.3 Hz, Py), 7.98 (t, 1 H, J = 7.7 Hz, Py), 7.86 (t, 1 H, J = 7.7 Hz, Py), 7.75 (d, 1 H, J = 7.9 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 8.0 Hz, Ph), 6.88 (t, 1 H, J = 7.4 Hz, Ph), 6.79 (d, 2 H, J = 8.2 Hz, Ph), 6.27 (s, 1 H, C*H), 6.11 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.56–3.37 (m, 2 H, O-CH2), 3.28 (dd, 1 H, J = 6.9 Hz, CH2-Im), 3.03 (m, 2 H, CH2-Im), 1.4–0.93 (m, 4 H, -CH2-CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.70 ppm (t, 3 H, J = 7.3 Hz, CH3). ESI-MS: m/z = 487.1245 (calcd. 487.1243) = [M¢Cl] + . Elemental anal. calcd. (%) for C24H28Cl2N4OZn·0.1 BuOH·0.1 CH2Cl2 : C, 54.42; H, 5.44; N, 10.36. Found: C, 54.40; H, 5.32; N, 10.07.
Anti-[Ni(LEtOMe)(H2O)Cl2]
Yield: 0.037 g (7 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.58 (d, 1 H, J = 4.4 Hz, Py), 9.42 (d, 1 H, J = 4.5 Hz, Py), 8.00 (t, 1 H, J = 7.7 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.61 (d, 1 H, J = 7.9 Hz, Py), 7.56–7.48 (m, 3 H, Py), 7.26 (t, 2 H, J = 4.4 Hz, Ph), 6.83 (t, 1 H, J = 7.3 Hz, Ph), 6.55 (d, 2 H, J = 7.9 Hz, Ph), 5.64 (s, 1 H, C*H), 5.32 (s, 1 H, C*H), 3.79–3.41 (many peaks, 4 H, CH2-Im and 2 H, O-CH2), 1.4– 0.93 (m, 4 H, -CH2-CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.70 ppm (t, 3 H, J = 7.4 Hz, CH3). This spectrum contains resonances of the starting materials as impurities; most probably they arise due to the dissociation of the components in solution.
In a 100 mL round-bottom flask, pyridine-2-carboxaldehyde (0.214 g, 2 mmol) was dissolved in 10 mL methanol. A methanolic solution (10 mL) of N-ethylethylenediamine (0.088 g, 1 mmol) was then added dropwise to the stirred aldehyde solution. The light yellow solution was left to stir at room temperature for 24 h. Excess methanol was removed under reduced pressure to yield a brownish yellow oily compound, which was dissolved in 10 mL of acetonitrile. Next, activated 3 æ molecular sieves (8–10 mesh) and NiCl2·6 H2O (0.236 g, 1 mmol) were added to the ligand solution. After stirring for 2 h at room temperature, a green precipitate was obtained and filtered off. The volume of the filtrate was reduced, and 30 mL of diethylether was added to precipitate the compound. The obtained green precipitate was dissolved in acetonitrile and left at 0 8C to obtain crystals suitable for single-crystal XRD. Yield: 0.217 g (52 %). ESI-MS: m/z = 401.1110 (calcd. 401.1124) = [M¢2Cl + formate] + . Elemental anal. calcd. for C17H24Cl2N4O2Ni·0.1 H2O: C, 45.6; H, 5.45; N, 12.51. Found: C, 45.62; H, 5.56; N, 12.35.
Syn-[Zn(LEtOMe)Cl2]
Anti-[Cu(LPhSEt)Cl2]
Yield: 0.165 g (38 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.18 (d, 1 H, J = 5.3 Hz, Py), 9.14 (d, 1 H, J = 4.4 Hz, Py), 7.98 (t, 1 H, J =
To pyridine-2-carboxaldhyde (0.428 g, 4 mmol) dissolved in acetonitrile (5 mL) was added N-phenylethylenediamine (0.272 g, 2 mmol)
Anti-[Zn(LPhOBu)Cl2]
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Full Paper and ethanethiol (2 mL), and the resulting yellow solution was stirred for 24 h. Subsequently, excess ethanethiol along with acetonitrile were evaporated in vacuo, and the resulting yellow oily residue was redissolved in acetonitrile (20 mL). Next, CuCl2·2 H2O (0.341 g, 2 mmol) was added to the yellow acetonitrile solution, and the mixture was stirred for 12 h. A greenish brown precipitate formed, which was filtered, dried, and recrystallized from acetonitrile. Yield: 0.123 g (12 %). ESI-MS: m/z = 474.0701 (calcd. 474.0706) = [M¢Cl] + . Elemental anal. calcd. (%) for C22H24Cl2N4SCu·0.5CH3CN·0.2 H2O: C, 51.63; H, 4.88; N, 11.78. Found: C, 51.23; H, 4.79; N, 11.99.
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Acknowledgements This work was supported by Board of Research in Nuclear Sciences (Department of Atomic Energy, India) through “Young Scientist Research Award” to RA (2012/20/37C/BRNS). RA is grateful for the generous funding through the “New Faculty Initiation Grant” (IITK/CHM/20120078) of Indian Institute of Technology Kanpur (IITK, India). SR, SG and SM gratefully acknowledge the Council of Scientific and Industrial Research (CSIR, India) and University Grants Commission (UGC, India) for their Research Fellowships. We are grateful to Professors Jan Reedijk, Veejendra Kumar Yadav, Anand Singh and Dr. Logesh Mathivathanan for stimulating discussions. We thank Professors Ramanathan Gurunath, Ramesh Ramapanicker and Mr. Hansaraj for allowing us to use the laboratory facilities for the initial experiments. Authors thank one of the reviewers for fruitful suggestions. Keywords: chiral complexes · dipicolylamine · nitrogen ligands · one-pot synthesis · zinc complexes [1] S. Biniecki, Z. Kabzinska, Ann. Pharm. Fr. 1964, 22, 685 – 687. [2] L. Samochowiec, J. Wûjcicki, K. Gregorczyk, E. Szmatloch, Mater. Med. Pol. 1974, 6, 298 – 300. [3] a) J. K. Romary, J. E. Bunds, J. D. Barger, J. Chem. Eng. Data 1967, 12, 224 – 226; b) D. W. Gruenwedel, Inorg. Chem. 1968, 7, 495 – 501; c) S. M. Nelson, J. Rodgers, J. Chem. Soc. A 1968, 272 – 276; d) J. K. Romary, R. D. Zachariasen, J. D. Barger, H. Schiesser, J. Chem. Soc. C 1968, 2884 – 2887; e) J. K. Romary, J. D. Barger, J. E. Bunds, Inorg. Chem. 1968, 7, 1142 – 1145. [4] a) G. K. Walkup, S. C. Burdette, S. J. Lippard, R. Y. Tsien, J. Am. Chem. Soc. 2000, 122, 5644 – 5645; b) W. Lin, D. Buccella, S. J. Lippard, J. Am. Chem. Soc. 2013, 135, 13512 – 13520; c) K. P. Carter, A. M. Young, A. E. Palmer, Chem. Rev. 2014, 114, 4564 – 4601; d) P. Rivera-Fuentes, S. J. Lippard, ChemMedChem 2014, 9, 1238 – 1243. [5] a) L. You, J. S. Berman, E. V. Anslyn, Nat. Chem. 2011, 3, 943 – 948; b) L. You, J. S. Berman, A. Lucksanawichien, E. V. Anslyn, J. Am. Chem. Soc. 2012, 134, 7126 – 7134; c) L. You, S. R. Long, V. M. Lynch, E. V. Anslyn, Chem. Eur. J. 2011, 17, 11017 – 11023; d) L. You, G. Pescitelli, E. V. Anslyn, L. Di Bari, J. Am. Chem. Soc. 2012, 134, 7117 – 7125; e) Y. Zhou, Y. Yuan, L. You, E. V. Anslyn, Chem. Eur. J. 2015, 21, 8207 – 8213; f) H. H. Jo, R. Edupuganti, L. You, K. N. Dalby, E. V. Anslyn, Chem. Sci. 2015, 6, 158 – 164. [6] a) D. L. M. Suess, J. C. Peters, Chem. Commun. 2010, 46, 6554 – 6556; b) S. K. Goforth, R. C. Walroth, L. McElwee-White, Inorg. Chem. 2013, 52, 5692 – 5701; c) S. K. Goforth, R. C. Walroth, J. A. Brannaka, A. Angerhofer, L. McElwee-White, Inorg. Chem. 2013, 52, 14116 – 14123; d) W.-Z. Lee, T.L. Wang, H.-C. Chang, Y.-T. Chen, T.-S. Kuo, Organometallics 2012, 31, 4106 – 4109. [7] a) J. W. Canary, C. S. Allen, J. M. Castagnetto, Y. Wang, J. Am. Chem. Soc. 1995, 117, 8484 – 8485; b) A. E. Holmes, S. Zahn, J. W. Canary, Chirality 2002, 14, 471 – 477. Chem. Asian J. 2016, 11, 128 – 135
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Manuscript received: August 24, 2015 Accepted Article published: September 29, 2015 Final Article published: October 16, 2015
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N Ligands
Multicomponent One-pot Reactions Towards the Synthesis of Stereoisomers of Dipicolylamine Complexes Sakthi Raje,[a] Sureshbabu Gurusamy,[a] Abhishek Koner,[a] Sonam Mehrotra,[a] Samson Jegan Jennifer,[a] Prema G. Vasudev,[b] Ray J. Butcher,[c] and Raja Angamuthu*[a] Dedicated to Professor Stephen J. Lippard on the occasion of his 75th birthday
Abstract: Reported are multi-component one-pot syntheses of chiral complexes [M(LROR’)Cl2] or [M(LRSR’)Cl2] from the mixture of an N-substituted ethylenediamine, pyridine-2-carboxaldehyde, a primary alcohol or thiol and MCl2 utilizing insitu formed cyclized Schiff bases where a C¢O bond, two stereocenters, and three C¢N bonds are formed (M = Zn, Cu, Ni, Cd; R = Et, Ph; R’ = Me, Et, nPr, nBu). Tridentate ligands LROR’ and LRSR’ comprise two chiral centers and a hemiaminal ether or hemiaminal thioether moiety on the dipicolylamine skeleton. Syn-[Zn(LPhOMe)Cl2] precipitates out readily from the reaction mixture as a major product whereas anti[Zn(LPhOMe)Cl2] stays in solution as minor product. Both syn[Zn(LPhOMe)Cl2] and anti-[Zn(LPhOMe)Cl2] were characterized using NMR spectroscopy and mass spectrometry. Solid-state structures revealed that syn-[Zn(LPhOMe)Cl2] adopted a square pyramidal geometry while anti-[Zn(LPhOMe)Cl2] pos-
sesses a trigonal bipyramidal geometry around the Zn centers. The scope of this method was shown to be wide by varying the components of the dynamic coordination assembly, and the structures of the complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Syn complexes were isolated as major products with ZnII and CuII, and anti complexes were found to be major products with NiII and CdII. Hemiaminals and hemiaminal ethers are known to be unstable and are seldom observed as part of cyclic organic compounds or as coordinated ligands assembled around metals. It is now shown, with the support of experimental results, that linear hemiaminal ethers or thioethers can be assembled without the assistance of Lewis acidic metals in the multi-component assembly, and a possible pathway of the formation of hemiaminal ethers has been proposed.
Introduction
plexes based on the dipica scaffold appeared in more than 1000 reports including about 200 patents due to their importance in the context of fluorescent probes of the Zinpyr family,[4] dynamic multi-component covalent assemblies,[5] heterometallic complexes,[6] chiral discriminators,[7] unsymmetrical ligands,[8] optical fiber sensors,[9] magnetic nanoparticles,[10] anion receptors,[11] new peptides,[12] artificial enzymes,[13] catalysts,[14] etc. The main reason why the dipica moiety exhibits versatility in all the aforementioned areas is the strong chelating ability of its three N donors with a wide range of transition metals and the opportunity of incorporating modifications on the backbone through substitutions on the central N donor. Our laboratory is beginning to explore unconventional routes to prepare new forms of dipica and their transition metal complexes in order to utilize them as catalysts. Reported herein is our maiden effort in the synthesis of a new family of tridentate ligands comprising the 2,2’-dipicolylamine moiety (Figure 1). To synthesize these new ligands, we have taken advantage of a four-component dynamic covalent assembly comprising pyridine-2-carboxaldehyde, an N-substituted ethylenediamine, an aliphatic primary alcohol or thiol and a transition metal ion. The tridentate ligand scaffold presented in this report possesses two NPy donors (N1 and N3) and a tertiary amine nitrogen
Dipicolylamines (dipica) were introduced by Binieck and Kabzinska around fifty years ago[1] and served as coronary vasodilators (gapicomine, bicordin) for many decades.[2] Simultaneously, 2,2’-dipicolylamine was familiarized as a promising trisdentate ligand by various chemists.[3] Since then ligands and com[a] S. Raje, S. Gurusamy, A. Koner, S. Mehrotra, Dr. S. J. Jennifer, Dr. R. Angamuthu Laboratory of Inorganic Synthesis and Bioinspired Catalysis (LISBIC) Department of Chemistry Indian Institute of Technology Kanpur Kanpur 208016 (India) E-mail: [email protected] [b] Dr. P. G. Vasudev Metabolic and Structural Biology Division CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP) Lucknow 226015 (India) [c] Prof. R. J. Butcher Department of Chemistry Howard University Washington, D.C. 20059 (USA) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.201500889. Chem. Asian J. 2016, 11, 128 – 135
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Full Paper plane while another nitrogen (N2) and chloride (Cl1) occupy the axial positions. The zinc ion is displaced by 0.358 æ from the N2Cl mean plane towards the axially coordinated chloride (Cl2). The angle of 70.518 between two pyridine planes (p) in the solid-state structure of the complex indicates that the dipicolylamine backbone adopted a wings-folded butterfly mode to bind with the ZnII ion. We then explored the nature of the precipitate obtained from the reaction; colorless crystals were obtained from an acetonitrile solution at 0 8C and single-crystal XRD analysis revealed the presence of syn forms (6R,7R and 6S,7S enantiomers) of [Zn(LPhOMe)Cl2] exclusively (Figure 3). In contrast to the anti forms, the ZnII ion was located in a distorted square pyramidal environment with a t value of 0.37.[15] However, the zinc ion is displaced by 0.586 æ from the N3Cl mean plane to-
Figure 1. The 2,2’-dipicolylamine-based, hemiaminal ether comprising ligands presented in this report with crystallographic numbering scheme. The carbon centers C6 and C7 are stereogenic (R = Ph, Et; R’ = Me, Et, nPr, nBu).
donor (N2), similar to the conventional 2,2’-dipicolylamine, in addition to a tertiary amine on the backbone (N4) that cannot participate in coordination with the same metal as other three N donors; N2 and N4 are part of the imidazolidinyl ring originating from ethylenediamine providing the humpback to these ligands and offering certain interesting steric restrictions upon complexation. Substituting an appropriate group on N4 can tune a complex, synthesized using a suitable metal ion, to have wide range of aforementioned applications.
Results and Discussion As a test reaction, we have treated two equivalents of pyridine-2-carboxaldehyde with N-phenylethylenediamine in methanol at room temperature to obtain the transient compound LROR’ (R = Ph; R’ = Me). The hemiaminal ether-appended ligand LPhOMe was then reacted in situ with an equivalent of anhydrous ZnCl2 that yielded a white precipitate immediately. Upon standing at 0 8C for one day, the filtrate of the reaction yielded colorless shiny needles of diffraction quality. Single-crystal Xray diffraction (XRD) exhibited the presence of anti forms (6R,7S and 6S,7R enantiomers) of [Zn(LPhOMe)Cl2] exclusively (Figure 2). The ZnII ion exhibited a pentacoordinated distorted trigonal-bipyramidal geometry with an Addison–Reedijk t parameter of 0.86.[15] Two pyridine nitrogens (N1, N3) of the ligand and a chloride (Cl2) occupy the corners of the triangular
Figure 3. Solid-state structures of syn-[Zn(LPhOMe)Cl2]·CH3CN showing 6R,7R and 6S,7S enantiomers (extracted from packing). Solvated acetonitrile and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn(1)-N(3) 2.128(5); Zn(1)–N(1) 2.128(5); Zn(1)–Cl(2) 2.2505(16); Zn(1)–Cl(1) 2.2706(17); Zn(1)– N(2) 2.281(4); N(3)-Zn(1)-N(1) 148.93(19) = b; N(3)-Zn(1)-Cl(2) 99.43(13); N(1)Zn(1)-Cl(2) 97.27(14); N(3)-Zn(1)-Cl(1) 97.41(14); N(1)-Zn(1)-Cl(1) 95.59(14); Cl(2)-Zn(1)-Cl(1) 122.11(6); N(3)-Zn(1)-N(2) 74.68(17); N(1)-Zn(1)-N(2) 74.95(17); Cl(2)-Zn(1)-N(2) 110.87(12); Cl(1)-Zn(1)-N(2) 126.98(12) = a. t = 0.37.[15] p = 11.168.
wards the axially coordinated chloride (Cl2).[15] Three nitrogens of the ligand and a chloride occupy the corners of the square plane while another chloride occupies the axial position. To our surprise, the angle between two pyridine planes is only 11.168 indicating that the dipicolylamine backbone adopted a planar flight mode as all the three N donors are almost on same plane. The folded facial (butterfly) binding mode observed in the anti complex and planar (flight) binding mode in the syn complex is enforced by the presence of the humpback created by the manifestation of the imidazolidinyl ring; a butterfly mode for syn and flight mode for anti might be impossible due to steric strain that may result from this arrangement. However, the classical 2,2’-dipicolylamine is flexible enough to adopt both modes depending on factors such as size of the metal ion, preferred coordination mode, etc. To check if this facial (anti) and planar (syn) orientation of the ligand LPhOMe is solvent-dependent, we have recrystallized the syn[Zn(LPhOMe)Cl2] in chloroform and found the similar planar binding mode as in the case of syn-[Zn(LPhOMe)Cl2]·CH3CN; however, few minor changes in the angles were observed (Figure S27).
Figure 2. Solid-state structures of anti-[Zn(LPhOMe)Cl2] showing 6R,7S and 6S,7R enantiomers (extracted from packing). Hydrogen atoms other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn–N(1), 2.070(2); Zn–N(2), 2.385(2); Zn–N(3), 2.065(2); Zn–Cl(1), 2.3500(8); Zn–Cl(2), 2.2420(8); N(3)-Zn-N(1), 113.10(8) = a; N(3)-Zn-Cl(2), 119.79(6); N(1)-Zn-Cl(2), 118.77(6); N(3)-Zn-Cl(1), 98.07(6); N(1)Zn-Cl(1), 96.67(6); Cl(2)-Zn-Cl(1), 104.00(3); N(3)-Zn-N(2), 75.39(8); N(1)-ZnN(2), 73.92(8); Cl(2)-Zn-N(2), 91.22(5); Cl(1)-Zn-N(2), 164.67(5) = b. t = 0.86.[15] Angle between two Py planes = p = 70.518. Chem. Asian J. 2016, 11, 128 – 135
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Full Paper In order to study the solution properties of these complexes, the 1H NMR spectrum of a crude product (Figure S1), obtained by evaporating the volatiles of the reaction mixture, was recorded in CDCl3 at room temperature. This revealed the presence of both syn and anti forms of [Zn(LPhOMe)Cl2], as confirmed by comparing with the 1H NMR spectra of isolated syn and anti forms independently (Figure 4 and Figures S2–S4). The singlets for the hydrogens attached to the chiral centers C6 and C7 of anti-[Zn(LPhOMe)Cl2] appear at 5.34 and Figure 5. Solid-state structures of anti-[Zn(LPhOH)Cl2]·CDCl3 showing 6R,7S and 6S,7R enantiomers (extracted from packing). Solvated CDCl3 and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Zn–N(1), 2.077(7); Zn–N(2), 2.378(7); Zn–N(3), 2.082(8); Zn–Cl(1), 2.378(3); Zn–Cl(2), 2.230(3); N(1)-ZnN(3), 116.8(3) = a; N(1)-Zn-Cl(2), 115.2(2); N(3)-Zn-Cl(2), 121.1(2); N(1)-Zn-N(2), 74.6(3); N(3)-Zn-N(2), 76.8(3); Cl(2)-Zn-N(2), 92.3(2); N(1)-Zn-Cl(1), 94.6(2); N(3)-Zn-Cl(1), 95.8(2); Cl(2)-Zn-Cl(1), 105.69(12); N(2)-Zn-Cl(1), 161.7(2) = b. t = 0.75.[15] p = 64.058.
metal in a planar fashion. 1H NMR spectra of crude reaction mixtures and of the white precipitates share all the main features in common with [Zn(LPhOMe)Cl2]. Further, to explore the ability of ethylenediamines with various substitutions to undergo this reaction, N-phenylethylenediamine was replaced by N-ethylethylenediamine and found to yield same type of zinc complex with the formula [Zn(LEtOMe)Cl2] (Figure S22). The single-crystal XRD analysis of the crystals of syn forms of [Zn(LEtOMe)Cl2], obtained from a methanolic solution, confirmed that the structural features indeed match those of syn-[Zn(LPhOMe)Cl2] (Figure S30). In order to examine the metal dependence of the formation of these hemiaminal ether complexes, ZnCl2 was replaced by CdCl2 and CuCl2·2 H2O, and found to yield [Cd(LPhOMe)Cl2]2 (Figure S23) and [Cu(LPhOMe)Cl2] (Figure S24). The 1H NMR spectrum of the precipitate formed by the reaction with CdCl2 showed two singlets at 5.09 and 6.02 ppm, corresponding to the protons attached to the chiral carbons, indicating the existence of the ligand in anti form (Figure S15), which was further confirmed by the XRD analysis of the crystals grown in a solution of dichloromethane (Figure 6). The structure shows a dimeric form of [Cd(LPhOMe)Cl2] with two m-Cl bridges such that each cadmium exists in a hexacoordinated octahedral geometry where one cadmium possesses the 6R,7S form while the other has the 6S,7R form of the hemiaminal ether ligand LPhOMe. On the other hand, CuCl2·2 H2O yielded a green precipitate, which showed the presence of an envelope corresponding to the [Cu(LPhOMe)Cl] + monocation in its ESI mass spectrum (m/z = 444.0807). Green crystals grown in methanol showed the presence of syn forms of [Cu(LPhOMe)Cl2] exclusively where the CuII ion is situated in a square pyramidal geometry (Figure 7). To find out if the formation of hemiaminal ether ligands demands the assistance of Lewis acidic metal ions,[5] we have performed the multicomponent reaction of aldehyde and amine in primary alcohol for 24 h, and all the volatiles were evaporated to obtain an oily substance that is presumably the hemiaminal ether. This oily substance was redissolved in acetonitrile and a batch of NiCl2·6 H2O was added as solid and stirred for
Figure 4. 1H NMR spectra of crude [Zn(LPhOMe)Cl2] showing the presence of both syn and anti complexes (bottom), isolated anti-[Zn(LPhOMe)Cl2] (middle), and syn-[Zn(LPhOMe)Cl2] (top).
5.57 ppm; the same for the syn-[Zn(LPhOMe)Cl2] appear at 6.06 and 6.31 ppm, respectively.[5] The 1H NMR spectrum of anti[Zn(LPhOMe)Cl2] as a CDCl3 solution shows the presence of trace amounts of free components as the complex tends to dissociate in solutions as observed by Anslyn and coworkers for similar complexes (Figure S3).[5] We have isolated colorless shiny crystals from the NMR tube containing anti-[Zn(LPhOMe)Cl2] in CDCl3 and the structure exhibited the formation of anti-[Zn(LPhOH)Cl2] with loss of alcohol (Figure 5). Repeating the same in CHCl3 also yielded the same result (Figure S31). However, the 1H NMR spectrum of syn[Zn(LPhOMe)Cl2] remained unchanged for days. In order to investigate the scope of the reaction, the reaction of two equivalents of pyridine-2-carboxaldehyde with Nphenylethylenediamine was carried out in other primary alcohols such as ethanol, 1-propanol, and 1-butanol. Complexes [Zn(LPhOEt)Cl2], [Zn(LPhOPr)Cl2], and [Zn(LPhOBu)Cl2] were obtained as precipitates from the corresponding alcohols and crystallized in the corresponding alcohol or in acetonitrile. Initial characterization using ESI mass spectrometry (Figures S19– S21) and 1H NMR spectroscopy (Figures S5–S13) confirmed the identity of the complexes formed as [Zn(LROR’)Cl2]. The solidstate structures of the crystals revealed the presence of syn[Zn(LPhOEt)Cl2] (Figure S28) and syn-[Zn(LPhOPr)Cl2] (Figure S29); they are indeed identical with syn-[Zn(LPhOMe)Cl2] and both feature a Zn(II) situated in a square pyramidal environment. As expected, these syn complexes have the ligand bound to the Chem. Asian J. 2016, 11, 128 – 135
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Figure 6. Solid-state structures of anti-[Cd(LPhOMe)Cl2]2·2 CH2Cl2 showing 6R,7S and 6S,7R enantiomers. Solvated dichloromethane and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cd–N(1), 2.400(3); Cd–N(2), 2.493(3); Cd–N(3), 2.385(3); Cd–Cl(1), 2.5948(9); Cd–Cl(2), 2.4830(8); Cd–Cl(1)#1, 2.6207(8); Cl(1)–Cd#1, 2.6207(8); N(3)-Cd-N(1), 89.86(10); N(3)-Cd-Cl(2), 95.31(8); N(1)-Cd-Cl(2), 92.79(7); N(3)-Cd-N(2), 70.13(10); N(1)-Cd-N(2), 69.24(9); Cl(2)-Cd-N(2), 156.24(7); N(3)-Cd-Cl(1), 164.10(8); N(1)-Cd-Cl(1), 89.98(7); Cl(2)-Cd-Cl(1), 100.58(3); N(2)-Cd-Cl(1), 95.01(7); N(3)-Cd-Cl(1)#1, 88.89(8); N(1)-Cd-Cl(1)#1, 160.01(7); Cl(2)-Cd-Cl(1)#1, 107.19(3); N(2)-CdCl(1)#1, 91.63(7); Cl(1)-Cd-Cl(1)#1, 85.85(3); Cd-Cl(1)-Cd#1, 94.14(3). p = 85.748.
Figure 8. Solid-state structures of anti-[Ni(LEtOMe)(H2O)Cl2] showing 6R,7S and 6S,7R enantiomers (extracted from packing). Hydrogens other than the two bound to the chiral centers and of coordinated H2O are omitted for clarity. Selected bond distances [æ] and angles [deg]: Ni–N(1), 2.0440(16); Ni– N(2), 2.1814(15); Ni–N(3), 2.0947(15); Ni–Cl(1), 2.4240(5); Ni–Cl(2), 2.4081(5); Ni–O(1W), 2.0831(14); N(1)-Ni-O(1W), 170.21(6); N(1)-Ni-N(3), 90.55(6); O(1W)Ni-N(3), 86.85(6); N(1)-Ni-N(2), 81.78(6); O(1W)-Ni-N(2), 88.46(6); N(3)-Ni-N(2), 79.19(6); N(1)-Ni-Cl(2), 91.40(4); O(1W)-Ni-Cl(2), 90.16(4); N(3)-Ni-Cl(2), 173.32(5); N(2)-Ni-Cl(2), 94.77(4); N(1)-Ni-Cl(1), 97.34(5); O(1W)-Ni-Cl(1), 92.23(4); N(3)-Ni-Cl(1), 92.94(5); N(2)-Ni-Cl(1), 172.06(4); Cl(2)-Ni-Cl(1), 93.140(18). p = 86.618.
best of our knowledge, is the first known metal complex of a hemiaminal thioether (Figure 9). Very few molecules are known in the literature comprising a hemiaminal thioether moiety as part of cyclic compounds;[16] the present LPhSEt serves as the first example of a linear hemiaminal thioether molecule. Interestingly, anti-LPhSEt is not bound to the CuII ion facially, whereas in the case of hemiaminal ether complexes reported above, the anti-LROR’ ligands are always bound to the metal ion facially as seen in the cases of anti-[Zn(LPhOMe)Cl2], anti-[Cd(LPhOMe)Cl2]2, and anti-[Ni(LEtOMe)(H2O)Cl2]. If the components were not assembled as hemiaminal thioether prior to the addition of CuCl2·2 H2O, the free thiol present in the mixture would have reduced the CuII to CuI with concurrent formation of diethyl disulphide, and eventually the formation of
Figure 7. Solid-state structures of syn-[Cu(LPhOMe)Cl2]·MeOH showing 6R,7R and 6S,7S enantiomers. Solvated methanol and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cu(1)–N(1), 2.006(3); Cu(1)–N(3), 2.007(3); Cu(1)– N(2), 2.073(3); Cu(1)–Cl(1), 2.2370(9); Cu(1)–Cl(2), 2.5509(9); N(1)-Cu(1)-N(3), 159.22(11) = a; N(1)-Cu(1)-N(2), 81.53(11); N(3)-Cu(1)-N(2), 80.79(11); N(1)Cu(1)-Cl(1), 96.73(8); N(3)-Cu(1)-Cl(1), 97.17(8); N(2)-Cu(1)-Cl(1), 163.73(8) = b; N(1)-Cu(1)-Cl(2), 94.50(8); N(3)-Cu(1)-Cl(2), 96.48(8); N(2)-Cu(1)-Cl(2), 90.47(8); Cl(1)-Cu(1)-Cl(2), 105.81(3). t = 0.08.[15] p = 20.578.
2 h at room temperature. The filtrate of this reaction yielded the NiII complex [Ni(LEtOMe)Cl2] after removing a small amount of insoluble precipitate (Figure S25). Single-crystal XRD analysis showed that the complex is of anti-LEtOMe coordinated to the NiII ion in a facial manner where the hexacoordinate nickel has two chlorides and an aqua ligand in addition to the tridentate LEtOMe (Figure 8). Successful isolation of the above complexes, especially anti-[Ni(LEtOMe)(H2O)Cl2], suggests that the assistance of Lewis acids is not necessary to assemble the hemiaminal ether when we use primary alcohols as solvent in these multicomponent reactions. To confirm this further, unequivocally, we set out a reaction using ethanethiol as alcohol component, evaporated all the volatiles after 24 h, redissolved the hemiaminal thioether residue in acetonitrile and then added CuCl2·2 H2O; a brownish green precipitate formed that was isolated and recrystallized in acetonitrile. Single-crystal XRD analysis displayed the presence of anti-[Cu(LPhSEt)Cl2], which, to the Chem. Asian J. 2016, 11, 128 – 135
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Figure 9. Solid-state structures of anti-[Cu(LPhSEt)Cl2]·CH3CN showing 6R,7S and 6S,7R enantiomers. Solvated CH3CN and hydrogens other than the two bound to the chiral centers are omitted for clarity. Selected bond distances [æ] and angles [deg]: Cu(1)–N(1A), 1.994(3); Cu(1)–N(2A), 2.066(3); Cu(1)– N(3A), 1.979(3); Cu(1)–Cl(1A), 2.2717(10); Cu(1)–Cl(2A), 2.4132(10); N(3A)Cu(1)-N(1A), 162.05(13) = b; N(3A)-Cu(1)-N(2A), 81.26(12); N(1A)-Cu(1)-N(2A), 80.80(12); N(3A)-Cu(1)-Cl(1A), 97.90(10); N(1A)-Cu(1)-Cl(1A), 96.55(9); N(2A)Cu(1)-Cl(1A), 146.45(8) = a; N(3A)-Cu(1)-Cl(2A), 92.64(10); N(1A)-Cu(1)-Cl(2A), 94.97(9); N(2A)-Cu(1)-Cl(2A), 112.39(8); Cl(1A)-Cu(1)-Cl(2A), 101.16(4). t = 0.26.[15] p = 23.778.
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Full Paper hemiaminal thioether and the CuII complex, [Cu(LPhSEt)Cl2], would have been impeded. Finally, the 1H NMR spectrum of a CD3OD solution composed of two equivalents of pyridine-2carboxaldehyde and one equivalent of N-phenylethylenediamine was recorded and found to contain sets of singlets in the range of 5.06 and 5.70 ppm, thereby indicating the formation of hemiaminal ether without the assistance of metal ions (Figure S16). From the observations of the aforementioned reactions and the mechanisms proposed for other multicomponent assemblies in the literature by Anslyn[5] and others,[17] we postulate the following mechanism for the formation of hemiaminal ether/thioether complexes presented in this report. In the four-component reaction mixture, the zwitterion 1, formed by the nucleophilic attack of N-substituted ethylenediamine on pyridine-2carboxaldehyde, converts into 2 by proton transfer (Scheme 1).[5f, 17b] Further protonation of 2 leads to 3, which undergoes 5-exo-tet-cyclization to generate 4. Another molecule of pyridine2-carboxaldehyde reacts with 4 and forms zwitterion 5. Once again, proton transfer, further protonation and elimination generate the iminium ion 8. Finally, combination of 8 with an alcohol forms the transient hemiaminal ether ligand 9 with two R chiral centers at carbons C6 and Scheme 1. Proposed pathway of the formation for dipicolylamine-based hemiaminal ether ligand (L OR’) with two stereocenters, which generates four possible stereoisomers of complexes with transition metals (R = Et, Ph; C7.[5, 17b] Hemiaminals and hemia- R’ = Me, Et, Pr, Bu; M = Ni, Cu, Zn, Cd). minal ethers are proven to be the Achilles’ heel of organic synConclusions thesis and are seldom observed[18] as discrete entities;[19] yet they are known to have been stable and isolated as a part of cyclic compounds[20] or coordination complexes.[5, 17a, 20d, 21] FurAccording to Anslyn and coworkers, the initial equilibrium lies thermore, ligands such as 9 are inaccessible by normal routes between the components and the Zn-hemiaminal complex, and demand tedious multistep synthetic process.[22] Only which loses a molecule of water to yield the iminium ion that a handful of chiral ligands based on the dipicolylamine moiety forms a hemiaminal ether (after the reaction with alcohol) and are known in the literature[23] as synthesizing them necessitates eventually its zinc complex.[5a, e, f] Formation of the Zn-hemiami[23c, f] [23d, g] chiral precursors, multiple steps and/or special medianal ether complex can be driven by adding excess alcohol; tors such as lipase.[23b, g] however, Zn-hemiaminal ether complexes have not been isolated though they have been observed in solution by NMR spectroscopy, which could be due to the bulkiness of the secChem. Asian J. 2016, 11, 128 – 135
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Full Paper ondary alcohols used in Anslyn’s multicomponent assembly.[5c, d] We have used primary alcohols in large excess and isolated M-hemiaminal ether/thioether complexes in a number of cases (M = Ni, Cu, Zn, Cd). Under the conditions reported herein, we have observed that 1) the hemiaminal ether/thioether can also be assembled without the assistance of Lewis acids, 2) adding metal chloride solution to the multicomponent mixture drives the final equilibrium towards the formation of the most stable M-hemiaminal ether/thioether complexes, 3) only less stable stereoisomers are involved in the equilibrium to form the more stable counterparts, 4) less stable isomers of M-hemiaminal ether complexes tend to lose the alcohol to form a M-hemiaminal ether complex upon dissolution in chloroform, as observed in the formation of anti-[Zn(LPhOH)Cl2] from anti-[Zn(LPhOMe)Cl2], 5) ZnII and CuII ions prefer to bind with LROR’ with all the three N donors in one plane afforded by 6R,7R and 6S,7S-LROR’, and 6) NiII and CdII ions prefer to have the ligand bound in facial manner afforded by 6R,7S and 6S,7R-LROR’ whereas anti-LRSR’ binds to copper with all the three N donors in a plane which could be due to the orientation of S-Et in LRSR’. Post-modification of metal-bound chiral hemiaminal ethers/thioethers, which might yield rationally designed chiral ligands and complexes that are otherwise synthesized through multistep processes, is currently considered.
least-squares technique using the SHELXL-97 program package. The lattice parameters and structural data are listed at the end of the Supporting Information. CCDC 1060136–1060146 and 1060974 contain the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre.
Syn-[Zn(LPhOMe)Cl2] In a 100 mL round-bottom flask, pyridine-2-carboxaldehyde (0.214 g, 2 mmol) was dissolved in 10 mL of methanol under stirring for 5 min. A methanolic solution (10 mL) of N-phenylethylenediamine (0.141 g, 1 mmol) was then added dropwise to the stirred aldehyde solution. The resulting yellow solution was stirred at room temperature for 24 h. Then a methanolic solution (5 mL) of anhydrous zinc chloride (0.137 g, 1 mmol) was added dropwise to the solution of hemiaminal ether LPhOMe. A white precipitate started to appear within 5 min after adding the solution of metal salt. The reaction mixture was continued to stir for 3 h at room temperature. The white precipitate was filtered off and the pale-yellow filtrate was left at 0 8C. The white precipitate was recrystallized in acetonitrile. Yield: 0.31 g (64 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.24 (d, 1 H, J = 5.1 Hz, Py), 9.21 (d, 1 H, J = 5.2 Hz, Py), 7.99 (t, 1 H, J = 7.7 Hz, Py), 7.87 (t, 1 H, J = 7.7 Hz, Py), 7.77 (d, 1 H, J = 8.0 Hz, Py), 7.60–7.53 (m, 3 H, Py), 7.37 (t, 2 H, J = 7.9 Hz, Ph), 6.90 (t, 1 H, J = 7.3 Hz, Ph), 6.81 (d, 2 H, J = 8.1 Hz, Ph), 6.31 (s, 1 H, C*H), 6.06 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.49 (d, 3 H, J = 4.7 Hz, CH3 of H-bonded MeOH), 3.35 (s, 3 H, OCH3), 3.28 (t, 1 H, J = 7.6 Hz, CH2-Im), 3.08–2.93 (m, 2 H, CH2-Im), 0.94 ppm (q, 1 H, J = 5.4 Hz, OH of H-bonded MeOH). ESI-MS: m/z = 445.0779 (calcd. 445.0774) = [M¢Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OZn·CH3OH: C, 51.33; H, 5.09; N, 10.88. Found: C, 51.01; H, 5.02; N, 10.88. The elemental analysis is consistent with the Xray and NMR data, as the hydrogen-bonded methanol molecule has been observed in both cases.
Experimental Section Materials Pyridine-2-carboxaldehyde (Sigma Aldrich), N-ethylethylenediamine (Alfa Aesar), N-phenylethylenediamine (TCI), anhydrous ZnCl2 (NICE), CuCl2·2 H2O (Merck), NiCl2·6 H2O (Rankem), and CdCl2 (SDFCL) were used as received from commercial sources. Solvents were distilled under dry nitrogen atmosphere using conventional methods.
Anti-[Zn(LPhOMe)Cl2] Colorless needles of anti-[Zn(LPhOMe)Cl2] isolated from the filtrate which was left at 0 8C overnight. Yield: 0.053 g (11%). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.54 (d, 1 H, J = 5.3 Hz, Py), 9.39 (d, 1 H, J = 4.6 Hz, Py), 8.01 (t, 1 H, J = 7.8 Hz, Py), 7.85 (t, 1 H, J = 7.8 Hz, Py), 7.64 (d, 1 H, J = 7.5 Hz, Py), 7.58 (t, 1 H, J = 6.9 Hz, Py), 7.51 (m, 2 H, Py), 7.28 (t, 2 H, J = 4.3 Hz, Ph), 6.85 (t, 1 H, J = 7.3 Hz, Ph), 6.57 (d, 2 H, J = 8.0 Hz, Ph), 5.57 (s, 1 H, C*H), 5.34 (s, 1 H, C*H), 3.71–3.43 (m, 4 H, CH2-Im), 3.62 (s, 3 H, OCH3), 3.47 (d, 3 H, J = 5.5 Hz, CH3 of H-bonded MeOH), 1.05 ppm (q, 1 H, J = 5.5 Hz, OH of H-bonded MeOH).
Methods Elemental analyses were carried out on a PerkinElmer CHNS/O analyzer. NMR spectra were recorded on JEOL 500 MHz and JEOL 400 MHz spectrometers. The temperature was kept constant using a variable-temperature unit within the error limit of 1 K. The software MestReNova was used for the processing of the NMR spectra. Tetramethylsilane (TMS) or the deuterated solvent residual peaks were used for calibration. Mass spectrometry measurements were performed on a Waters-Q-ToF-Premier-HAB213 system equipped with an electrospray interface. Spectra were collected by constant infusion of the sample dissolved in methanol or acetonitrile with 0.1 % formic acid.
Syn-[Zn(LPhOEt)Cl2] Yield: 0.286 g (57 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.21 (d, 1 H, J = 6.1 Hz, Py), 9.18 (d, 1 H, J = 5.2 Hz, Py), 7.97 (t, 1 H, J = 8.4 Hz, Py), 7.86 (t, 1 H, J = 6.2 Hz, Py), 7.75 (d, 1 H, J = 8.0 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 7.5 Hz, Ph), 6.88 (t, 1 H, J = 7.4 Hz, Ph), 6.80 (d, 2 H, J = 8.1 Hz, Ph), 6.26 (s, 1 H, C*H), 6.10 (s, 1 H, C*H), 3.75 (dd, 1 H, J = 7.9 Hz, CH2-Im), 3.59 (m, 1 H, CH2CH3), 3.47 (m, 1 H, CH2CH3), 3.27 (m, 1 H, CH2-Im), 3.0 (m, 2 H, CH2-Im), 0.93 ppm (t, 3 H, J = 7.0 Hz, CH3). ESI-MS: m/z = 459.0926 (calcd. 459.0930) = [M¢Cl] + . Elemental anal. calcd. (%) for C22H24Cl2N4OZn·1.2 EtOH·0.2 H2O: C, 52.74; H, 5.73; N, 10.08. Found: C, 52.53; H, 5.42; N, 9.78.
Crystal Structure Determinations Single-crystal X-ray data were collected on a Bruker SMART APEX CCD diffractometer using graphite-monochromated MoKa radiation (l = 0.71069 æ). The linear absorption coefficients, the scattering factors for the atoms, and the anomalous dispersion corrections were taken from the International Tables for X-ray Crystallography. Data integration and reduction were conducted with SAINT. An empirical absorption correction was applied to the collected reflections with SADABS using XPREP. Structures were determined by the direct method using SHELXTL and refined on F2 by a full-matrix Chem. Asian J. 2016, 11, 128 – 135
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Full Paper Anti-[Zn(LPhOEt)Cl2]
9.8 Hz, Py), 7.94 (t, 1 H, J = 7.7 Hz, Py), 7.73 (d, 1 H, J = 8.3 Hz, Py), 7.65 (d, 1 H, J = 7.8 Hz, Py), 7.53 (m, 2 H, Py), 5.59 (s, 1 H, C*H), 5.16 (s, 1 H, C*H), 3.80 (s, 3 H, OCH3), 3.1 (m, 2 H, CH2-Im), 2.96 (m, 2 H, NCH2CH3), 2.86 (m, 2 H, CH2-Im), 1.28 ppm (t, 3 H, J = 7.2 Hz, NCH2CH3). ESI-MS: m/z = 397.0786 (calcd. 397.0774) = [M¢Cl] + . Elemental anal. calcd. (%) for C17H22Cl2N4OZn·0.1 CH3OH·0.1 CH3CN: C, 47.01; H, 5.18; N, 12.99. Found: C, 47.18; H, 5.22; N, 12.46.
1
Yield: 0.045 g (9 %). H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.59 (d, 1 H, J = 7.8 Hz, Py), 9.43 (d, 1 H, J = 4.3 Hz, Py), 8.01 (t, 1 H, J = 7.8 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.64 (d, 1 H, J = 7.8 Hz, Py), 7.57–7.49 (m, 3 H, Py), 7.27 (t, 2 H, J = 4.4 Hz, Ph), 6.84 (t, 1 H, J = 7.3 Hz, Ph), 6.55 (d, 2 H, J = 7.9 Hz, Ph), 5.66 (s, 1 H, C*H), 5.33 (s, 1 H, C*H), 3.85–3.40 (m, 6 H, 4 H for 2xCH2-Im and 2 H for CH2CH3), 1.13 ppm (t, 3 H, J = 7.0 Hz, CH3).
Anti-[Cd(LPhOMe)Cl2]
Syn-[Zn(LPhOPr)Cl2]
Yield: 0.345 g (65 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.27 (d, 1 H, J = 5.0 Hz, Py), 9.09 (d, 1 H, J = 5.1 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.67 (t, 1 H, J = 7.7 Hz, Py), 7.55 (d, 1 H, J = 7.9 Hz, Py), 7.41 (t, 1 H, J = 6.3 Hz, Py), 7.35 (m, 2 H, Py), 7.25 (t, 2 H, J = 7.9 Hz, Ph), 6.81 (t, 1 H, J = 7.3 Hz, Ph), 6.50 (d, 2 H, J = 8.1 Hz, Ph), 6.02 (s, 1 H, C*H), 5.09 (s, 1 H, C*H), 4.21 (m, 1 H, CH2-Im), 4.03 (m, 1 H, CH2Im), 3.78 (m, 1 H, CH2-Im), 3.66 (s, 3 H, OCH3), 3.59 ppm (m, 1 H, CH2-Im). ESI-MS: m/z = 495.0524 (calcd. 495.0512) = [M-Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OCd: C, 47.61; H, 4.19; N, 10.58. Found: C, 47.42; H, 4.08; N, 9.86.
Yield: 0.291 g (57 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.22 (d, 1 H, J = 5.5 Hz, Py), 9.19 (d, 1 H, J = 5.0 Hz, Py), 7.98 (t, 1 H, J = 7.8 Hz, Py), 7.86 (t, 1 H, J = 7.7 Hz, Py), 7.77 (d, 1 H, J = 7.8 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 8.0 Hz, Ph), 6.88 (t, 1 H, J = 7.3 Hz, Ph), 6.79 (d, 2 H, J = 7.9 Hz, Ph), 6.27 (s, 1 H, C*H), 6.12 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.51–3.33 (m, 2 H, O-CH2), 3.28 (dd, 1 H, J = 7.5 Hz, CH2-Im), 3.03 (m, 2 H, CH2-Im), 1.37 (m, 1 H, CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.63 ppm (t, 3 H, J = 7.4 Hz, CH3). ESI-MS: m/z = 473.1096 (calcd. 473.1087) = [M¢Cl] + . Elemental anal. calcd. (%) for C23H26Cl2N4OZn·0.5 PrOH·0.5 H2O: C, 53.52; H, 5.68; N, 10.19. Found: C, 53.56; H, 5.13; N, 9.82.
Syn-[Cu(LPhOMe)Cl2] To pyridine-2-carboxaldhyde (0.428 g, 4 mmol) dissolved in 17 mL methanol was added N-phenylethylenediamine (0.272 g, 2 mmol), and the resulting yellow solution was stirred at room temperature for 24 h. Subsequently, CuCl2·2H2O (0.341 g, 2 mmol) dissolved in 3 mL methanol was added dropwise to the above stirred yellow solution. A greenish brown precipitate appeared after 15 min of stirring after introducing the CuCl2 solution. The reaction mixture was stirred for further 12 h at room temperature and the volume was reduced to 5 mL. Slow addition of diethyl ether (15 mL) resulted in complete precipitation of Cu(LPhOMe)Cl2 ; the greenish brown precipitate was filtered, washed once with 5 mL of diethyl ether, and recrystallized in methanol at 0 8C. Yield: 0.972 g (65 %). ESI-MS: m/z = 444.0807 (calcd. 444.0778) = [M¢Cl] + . Elemental anal. calcd. (%) for C21H22Cl2N4OCu·CH3OH: C, 51.52; H, 5.11; N, 10.92. Found: C, 51.49; H, 5.13; N, 10.96.
Anti-[Zn(LPhOPr)Cl2] Yield: 0.051 g (10 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.58 (d, 1 H, J = 6.1 Hz, Py), 9.42 (d, 1 H, J = 5.4 Hz, Py), 8.0 (t, 1 H, J = 7.8 Hz, Py), 7.84 (t, 1 H, J = 7.8 Hz, Py), 7.63 (d, 1 H, J = 7.9 Hz, Py), 7.58–7.48 (m, 3 H, Py), 7.25 (t, 2 H, J = 4.4 Hz, Ph), 6.83 (t, 1 H, J = 7.3 Hz, Ph), 6.56 (d, 2 H, J = 7.9 Hz, Ph), 5.65 (s, 1 H, C*H), 5.32 (s, 1 H, C*H), 3.75–3.41 (m, 6 H, 4 H for 2xCH2-Im and 2 H for O-CH2), 1.54 (m, 1 H, CH2-Me), 0.74 ppm (t, 3 H, J = 7.4 Hz, CH3).
Syn-[Zn(LPhOBu)Cl2] Yield: 0.278 g (53 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.21 (d, 1 H, J = 5.0 Hz, Py), 9.17 (d, 1 H, J = 5.3 Hz, Py), 7.98 (t, 1 H, J = 7.7 Hz, Py), 7.86 (t, 1 H, J = 7.7 Hz, Py), 7.75 (d, 1 H, J = 7.9 Hz, Py), 7.55 (m, 3 H, Py), 7.35 (t, 2 H, J = 8.0 Hz, Ph), 6.88 (t, 1 H, J = 7.4 Hz, Ph), 6.79 (d, 2 H, J = 8.2 Hz, Ph), 6.27 (s, 1 H, C*H), 6.11 (s, 1 H, C*H), 3.73 (dd, 1 H, J = 8.0 Hz, CH2-Im), 3.56–3.37 (m, 2 H, O-CH2), 3.28 (dd, 1 H, J = 6.9 Hz, CH2-Im), 3.03 (m, 2 H, CH2-Im), 1.4–0.93 (m, 4 H, -CH2-CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.70 ppm (t, 3 H, J = 7.3 Hz, CH3). ESI-MS: m/z = 487.1245 (calcd. 487.1243) = [M¢Cl] + . Elemental anal. calcd. (%) for C24H28Cl2N4OZn·0.1 BuOH·0.1 CH2Cl2 : C, 54.42; H, 5.44; N, 10.36. Found: C, 54.40; H, 5.32; N, 10.07.
Anti-[Ni(LEtOMe)(H2O)Cl2]
Yield: 0.037 g (7 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.58 (d, 1 H, J = 4.4 Hz, Py), 9.42 (d, 1 H, J = 4.5 Hz, Py), 8.00 (t, 1 H, J = 7.7 Hz, Py), 7.84 (t, 1 H, J = 7.7 Hz, Py), 7.61 (d, 1 H, J = 7.9 Hz, Py), 7.56–7.48 (m, 3 H, Py), 7.26 (t, 2 H, J = 4.4 Hz, Ph), 6.83 (t, 1 H, J = 7.3 Hz, Ph), 6.55 (d, 2 H, J = 7.9 Hz, Ph), 5.64 (s, 1 H, C*H), 5.32 (s, 1 H, C*H), 3.79–3.41 (many peaks, 4 H, CH2-Im and 2 H, O-CH2), 1.4– 0.93 (m, 4 H, -CH2-CH2-Me), 1.28 (m, 1 H, CH2-Me), 0.70 ppm (t, 3 H, J = 7.4 Hz, CH3). This spectrum contains resonances of the starting materials as impurities; most probably they arise due to the dissociation of the components in solution.
In a 100 mL round-bottom flask, pyridine-2-carboxaldehyde (0.214 g, 2 mmol) was dissolved in 10 mL methanol. A methanolic solution (10 mL) of N-ethylethylenediamine (0.088 g, 1 mmol) was then added dropwise to the stirred aldehyde solution. The light yellow solution was left to stir at room temperature for 24 h. Excess methanol was removed under reduced pressure to yield a brownish yellow oily compound, which was dissolved in 10 mL of acetonitrile. Next, activated 3 æ molecular sieves (8–10 mesh) and NiCl2·6 H2O (0.236 g, 1 mmol) were added to the ligand solution. After stirring for 2 h at room temperature, a green precipitate was obtained and filtered off. The volume of the filtrate was reduced, and 30 mL of diethylether was added to precipitate the compound. The obtained green precipitate was dissolved in acetonitrile and left at 0 8C to obtain crystals suitable for single-crystal XRD. Yield: 0.217 g (52 %). ESI-MS: m/z = 401.1110 (calcd. 401.1124) = [M¢2Cl + formate] + . Elemental anal. calcd. for C17H24Cl2N4O2Ni·0.1 H2O: C, 45.6; H, 5.45; N, 12.51. Found: C, 45.62; H, 5.56; N, 12.35.
Syn-[Zn(LEtOMe)Cl2]
Anti-[Cu(LPhSEt)Cl2]
Yield: 0.165 g (38 %). 1H NMR (400.16 MHz, 25 8C, CDCl3): d = 9.18 (d, 1 H, J = 5.3 Hz, Py), 9.14 (d, 1 H, J = 4.4 Hz, Py), 7.98 (t, 1 H, J =
To pyridine-2-carboxaldhyde (0.428 g, 4 mmol) dissolved in acetonitrile (5 mL) was added N-phenylethylenediamine (0.272 g, 2 mmol)
Anti-[Zn(LPhOBu)Cl2]
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Full Paper and ethanethiol (2 mL), and the resulting yellow solution was stirred for 24 h. Subsequently, excess ethanethiol along with acetonitrile were evaporated in vacuo, and the resulting yellow oily residue was redissolved in acetonitrile (20 mL). Next, CuCl2·2 H2O (0.341 g, 2 mmol) was added to the yellow acetonitrile solution, and the mixture was stirred for 12 h. A greenish brown precipitate formed, which was filtered, dried, and recrystallized from acetonitrile. Yield: 0.123 g (12 %). ESI-MS: m/z = 474.0701 (calcd. 474.0706) = [M¢Cl] + . Elemental anal. calcd. (%) for C22H24Cl2N4SCu·0.5CH3CN·0.2 H2O: C, 51.63; H, 4.88; N, 11.78. Found: C, 51.23; H, 4.79; N, 11.99.
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Acknowledgements This work was supported by Board of Research in Nuclear Sciences (Department of Atomic Energy, India) through “Young Scientist Research Award” to RA (2012/20/37C/BRNS). RA is grateful for the generous funding through the “New Faculty Initiation Grant” (IITK/CHM/20120078) of Indian Institute of Technology Kanpur (IITK, India). SR, SG and SM gratefully acknowledge the Council of Scientific and Industrial Research (CSIR, India) and University Grants Commission (UGC, India) for their Research Fellowships. We are grateful to Professors Jan Reedijk, Veejendra Kumar Yadav, Anand Singh and Dr. Logesh Mathivathanan for stimulating discussions. We thank Professors Ramanathan Gurunath, Ramesh Ramapanicker and Mr. Hansaraj for allowing us to use the laboratory facilities for the initial experiments. Authors thank one of the reviewers for fruitful suggestions. Keywords: chiral complexes · dipicolylamine · nitrogen ligands · one-pot synthesis · zinc complexes [1] S. Biniecki, Z. Kabzinska, Ann. Pharm. Fr. 1964, 22, 685 – 687. [2] L. Samochowiec, J. Wûjcicki, K. Gregorczyk, E. Szmatloch, Mater. Med. Pol. 1974, 6, 298 – 300. [3] a) J. K. Romary, J. E. Bunds, J. D. Barger, J. Chem. Eng. Data 1967, 12, 224 – 226; b) D. W. Gruenwedel, Inorg. Chem. 1968, 7, 495 – 501; c) S. M. Nelson, J. Rodgers, J. Chem. Soc. A 1968, 272 – 276; d) J. K. Romary, R. D. Zachariasen, J. D. Barger, H. Schiesser, J. Chem. Soc. C 1968, 2884 – 2887; e) J. K. Romary, J. D. Barger, J. E. Bunds, Inorg. Chem. 1968, 7, 1142 – 1145. [4] a) G. K. Walkup, S. C. Burdette, S. J. Lippard, R. Y. Tsien, J. Am. Chem. Soc. 2000, 122, 5644 – 5645; b) W. Lin, D. Buccella, S. J. Lippard, J. Am. Chem. Soc. 2013, 135, 13512 – 13520; c) K. P. Carter, A. M. Young, A. E. Palmer, Chem. Rev. 2014, 114, 4564 – 4601; d) P. Rivera-Fuentes, S. J. Lippard, ChemMedChem 2014, 9, 1238 – 1243. [5] a) L. You, J. S. Berman, E. V. Anslyn, Nat. Chem. 2011, 3, 943 – 948; b) L. You, J. S. Berman, A. Lucksanawichien, E. V. Anslyn, J. Am. Chem. Soc. 2012, 134, 7126 – 7134; c) L. You, S. R. Long, V. M. Lynch, E. V. Anslyn, Chem. Eur. J. 2011, 17, 11017 – 11023; d) L. You, G. Pescitelli, E. V. Anslyn, L. Di Bari, J. Am. Chem. Soc. 2012, 134, 7117 – 7125; e) Y. Zhou, Y. Yuan, L. You, E. V. Anslyn, Chem. Eur. J. 2015, 21, 8207 – 8213; f) H. H. Jo, R. Edupuganti, L. You, K. N. Dalby, E. V. Anslyn, Chem. Sci. 2015, 6, 158 – 164. [6] a) D. L. M. Suess, J. C. Peters, Chem. Commun. 2010, 46, 6554 – 6556; b) S. K. Goforth, R. C. Walroth, L. McElwee-White, Inorg. Chem. 2013, 52, 5692 – 5701; c) S. K. Goforth, R. C. Walroth, J. A. Brannaka, A. Angerhofer, L. McElwee-White, Inorg. Chem. 2013, 52, 14116 – 14123; d) W.-Z. Lee, T.L. Wang, H.-C. Chang, Y.-T. Chen, T.-S. Kuo, Organometallics 2012, 31, 4106 – 4109. [7] a) J. W. Canary, C. S. Allen, J. M. Castagnetto, Y. Wang, J. Am. Chem. Soc. 1995, 117, 8484 – 8485; b) A. E. Holmes, S. Zahn, J. W. Canary, Chirality 2002, 14, 471 – 477. Chem. Asian J. 2016, 11, 128 – 135
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Manuscript received: August 24, 2015 Accepted Article published: September 29, 2015 Final Article published: October 16, 2015
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