A series of Betti bases from 4‐(3‐pyridyl)azo‐1‐naphthol dye, possessing flexible  methylene or more constrained aryl‐methyne spaced NH‐containing side‐chains, were  obtained and characterized. It was shown by NMR spectroscopy that the ligands exist  in keto form. The products’ structure was confirmed by single crystal XRD of a  selected sample. A study on the coordination ability of the ligands with silver(I) was  performed, leading to an unexpected substitution reaction

Fromm, Katharina M.

Kurteva, Vanya B.

Lubenov, Lubomir A.

Nikolova, Rositsa P.

Shivachev, Boris L.

RERO DOC Digital Library

Betti Bases from 4-(3-Pyridazo)-1-naphthol: Synthesis,Coordination Behaviour and Unusual SubstitutionReactionsVanya B. Kurteva,*[a] Lubomir A. Lubenov,[a] Boris L. Shivachev,[b] Rositsa P. Nikolova,[b] andKatharina M. Fromm[c]A series of Betti bases from 4-(3-pyridyl)azo-1-naphthol dye,possessing flexible methylene or more constrained aryl-methyne spaced NH-containing side-chains, were obtained andcharacterized. It was shown by NMR spectroscopy that theligands exist in keto form. The products’ structure wasconfirmed by single crystal XRD of a selected sample. A studyon the coordination ability of the ligands with silver(I) wasperformed, leading to an unexpected substitution reaction.IntroductionCoordination compounds are of great importance both inindustry and academy.[1] They find applications in medicine[2]and play a fundamental role in synthetic organic chemistry ascatalysts for various transformations.[3] Silver(I) complexes inparticular are widely studied because of their remarkablemedicinal applications.[4] The antibacterial activity of Ag(I)complexes, well known for many centuries, is among theirmost attractive biological profiles. Numerous examples ofamazingly active complexes with negligible toxicity werereported and summarized in a number of articles.[5] The flexiblecoordination sphere of silver ions allows the generation ofvarious supramolecular structures with ligands containingnitrogen, oxygen, and/or sulphur donor atoms.[6] Therefore,enormous efforts are devoted to the development of newefficient organic ligands.[7]Azo colorants represent the largest and most importantgroup of synthetic dyes[8] with broad industrial applications,[9]mainly due to their intense colour, chemical stability and lowprice. Azo-naphthol dyes[10] in particular, are among the mostexamined dyestuffs due to their optical stability. They play animportant role in analytical chemistry as organic complexingreagents[11] due to their capacity to form mostly neutral andhydrophobic complexes with the vast majority of transitionmetal ions. Several members of this class have also displayed avariety of biological activity profiles with medicinal applica-tions.[12]Multicomponent reactions have been approved recently asa powerful tool for waste-free atom efficient synthesis ofcomplex molecules.[13] In particular, the three componentMannich and Betti condensations represent key protocols forthe construction of amino alcohols. The Betti reaction,[14] similarto the Mannich reaction, using aldehydes instead offormaldehyde, is typically carried out with 2-naphthol, whilethe number of examples using 1-naphtol is limited.[15]As a part of our study on the synthesis of new polydentateligands with potential coordination properties, a series of Bettibases from azo-naphthol dyes were designed. The generalconcept is to combine both fascinating fragments in a commonmolecule and to tune the ligands’ coordination ability byvarying the number and type of heteroatoms in the azo-dyeunit and the side-chain. Herein, we present the synthesis of aseries of 4-(pyridin-3-yldiazenyl)naphthalen-1-ol ligands pos-sessing a 3-pyridyl Betti type substituent at the 2-position ofthe naphthyl unit and the examination of their complexationability towards Ag(I).Results and DiscussionTwo types of molecules were designed, possessing a flexiblemethylene or a more constrained aryl-methyne bridged 3-pyridyl unit, in an attempt to analyse the influence of sterichindrance and the type and number of heterocyclic fragmentson the complexation behaviour of the ligands. The generalformula of the ligands is depicted in Figure 1.The starting 4-(pyridin-3-yldiazenyl)naphthalen-1-ol (1)[16]was obtained by classical diazo-coupling and was further usedwithout purification. A sample for analyses was purified by flashchromatography on silica gel. The NMR spectra in DMSO-d6(Figures S1-S6) showed a mixture of two compounds in 83%and 17% population of the enol and keto tautomer, respec-tively. To confirm this assignment, the signals in the spectra[a] Prof. Dr. V. B. Kurteva, Dr. L. A. LubenovInstitute of Organic Chemistry with Centre of PhytochemistryBulgarian Academy of SciencesAcad. G. Bonchev street, bl. 9, 1113 Sofia, BulgariaE-mail: vkurteva@orgchm.bas.bg[b] Prof. Dr. B. L. Shivachev, Prof. Dr. R. P. NikolovaInstitute of Mineralogy and Crystallography “Acad. Ivan Kostov”Bulgarian Academy of SciencesAcad. G. Bonchev street, bl. 107, 1113 Sofia, Bulgaria[c] Prof. Dr. K. M. FrommDepartment of ChemistryUniversity of FribourgChemin du Musée 9, CH-1700 Fribourg, Switzerland1http://doc.rero.chPublished in "ChemistrySelect 3(43): 12017–12021, 2018" which should be cited to refer to this work.123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657were compared with those of a series of model compounds.The enol and keto forms were fixed as OMe and NMederivatives by methylation of 1. Additionally, compound 2,which was expected to exist in the enol form,[17] was obtainedby Mannich condensation (Scheme 1). As seen on Figures S19and S20, the signals of the major component in the spectra of1 are fully congruent with those of the model enol compounds1-OMe and 2.The starting naphthol 1 was submitted to a Mannichreaction with 3-aminopyridine using standard conditions inrefluxing benzene. Surprisingly, the bis-substituted product 3was isolated instead of the desired ligand 4 (Scheme 1). Thisproblem was solved by performing the reaction in a two-stepone-pot protocol with first the formation of the imine at 85 °Cin DMSO, then the condensation reaction at room temperature.The products were characterized by 1D and 2DNMR spectro-scopy and turbo spray mass spectrometry. Compound 4possesses very limited solubility even in DMSO-d6, and13C and2D spectra could not be recorded in a reasonable time scale atroom temperature. Unfortunately, the 1H spectra at variabletemperature (Figure S34) showed that at 300 K and 328 K, thepattern is similar, while at 358 K the product is partiallydecomposed. The signals in the proton spectrum of 4 wereassigned by comparison with those of the better soluble side-product 3 (Figures S27–S32). The latter is possible because thespectra of both compounds show identical chemical shifts andpatterns, e.g. broad signals for azo-bridged 3-pyridyl and a partof the naphthyl ring protons (Figure 2).As compound 3 is an example of a pure keto tautomer, andcomparting the signals in the spectra of 4 with those of themodel compounds, we can assume that the product 4 exists inDMSO solution in the keto form. The structure of the ligand 4was confirmed by single crystal XRD of the correspondingperchlorate (Figure 3 and Table S1).[18] The free bases howevercould not be crystallized in our hands from numerous testedsolvents and solvent systems.The aryl-methyne spaced compound group 5 (Scheme 1)was designed with the idea to restrict partially the flexibility ofthe side-chain. The ligands were obtained by a three-component Betti condensation between crude 1, 3-amino-pyridine and aromatic aldehyde in good overall yields of up to56% in two steps. Ligands 5a-5c were synthesised in order tostudy the influence of an additional heteroatom on thecomplexation properties, in particular phenyl vs 3-thiophenylvs 3-pyridyl, while 5d and 5e were designed in an attempt toimprove the ligands’ solubility. Unfortunately, all compoundspossess only limited solubility. The NMR spectra of the productsat room temperature showed broad signals for a significantpart of the protons due to slow exchange between two sides,which assignment was not reliable. For that reason, 1D and 2Dspectra of ligand 5a were recorded at 343 K. The protonresonances were fully assigned based on the interactions inCOSY and NOESY experiments and on the effects in selectiveNOE spectra at 298 K (Figures S41-S56). The carbon resonanceswere partially assigned from HSQC and HMBS spectra (Figur-Figure 1. General formula and numbering scheme of the current studyobjects.Scheme 1. i) piperidine or 3-aminopyridine, (HCHO)n, p-TSA, benzene, reflux,3 h; ii) a) 3-aminopyridine, (HCHO)n, DMSO, 85 °C, 1.5 h, b) 1, rt, 3 h; iii) 3-aminopyridine, ArCHO, DMSO, rt, 4–6 days.Figure 2. 1HNMR spectra of 3 (brown) and 4 (green) in DMSO-d6 at roomtemperature.2http://doc.rero.ch123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657es S39 and S40). Some of the quaternary carbon atoms couldnot be explicitly assigned and are not given.A comparison between proton resonances of 5a and itsmethylene bridged analogue 4 (Figure 4) showed that only CH-6’’ and CH-3 signals are slightly shifted downfield and upfield,respectively, and are more broadened in the Betti base withrespect to methylene bridged compound.The structures of the ligands 5b-5e were assigned bycomparison of the NMR spectra with those of 5a. As illustratedon Fig. 5 on the example of 5b, the signals for the skeletonprotons have identical chemical shifts as those of 5a. Thispattern is valid for all ligands 5.The coordination ability of compounds 5 towards Ag(I) wasstudied using different anions, solvents, and dilutions, whilemaintaining a ratio of 1:1 between the ligand and the metalion. In all cases a black solid phase was formed upon mixing,either immediately or after several hours or days dependingmainly on the dilution. The amount of solid always exceededthe expected mass of Ag(0), which led to the assumption thatcoordination took place. Unfortunately, the residues werecompletely insoluble in any solvent or solvent system to recordNMR spectra and/or to be recrystallized.Only in one case did we obtain a crystal appropriate forXRD analyses using slow evaporation of an extremely dilutedethanol solution (103 M, 0.05 mmol in 50 ml) of ligand 5b andsilver(I) nitrate. Surprisingly, the analysis showed that instead ofdesired silver complex, compound 6 was formed in which theside-chain pyridyl group was unexpectedly replaced by anethyl group (Scheme 2, Figure 6, and Table S1).[18]The observed transformation could be explained by areaction between 5b and acetaldehyde, obtained by oxidationof a part of ethanol, going most probably via an iminium state.To confirm this suggestion, the same ligand was submitted to areaction with acetaldehyde in DMF, which was used as asolvent in order to reach a sufficient concentration of 3x102 MFigure 3. ORTEP view of 4 perchlorate with the atomic numbering scheme;ellipsoids are drawn at 50% probability, hydrogen atoms are shown as smallspheres with arbitrary radii. The solvate acetonitrile molecule is disorderedover two positions with major orientation at 70% (minor component isshown as dashed lines).Figure 4. 1H spectra of 3 (brown) and 5a (green) in DMSO-d6 at roomtemperature.Figure 5. 1H spectra of 5a (green) and 5b (brown) in DMSO-d6 at roomtemperature.Scheme 2. i) AgNO3, EtOH, rt; ii) CH3CHO, DMF, rt; iii) CH3CHO, EtOH, rt.3http://doc.rero.ch123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657for the reaction. The isolated product was however identifiedby NMR and XRD as compound 7 (Scheme 2, Figures S65-S69,Figure 7, and Table S1).[18] In order to avoid this, the experimentwas then performed in ethanol suspension. Among a series ofethanol-acetaldehyde condensation products, which were iso-lated by chromatography, compound 6 could be unambigu-ously attributed in the NMR spectrum of the reaction mixture,confirming thus the proposed pathway (Fig. S70–74).ConclusionsA series of Betti bases from 4-pyridylazo-1-naphthol wereefficiently synthesised and characterized in solution and in thesolid state. The compounds can be divided into two groups,e.g. the ones possessing i) a flexible methylene or ii) a moreconstrained arylmethyne bridged 3-pyridyl side-chain. It wasdemonstrated that the ligands exist in keto tautomeric formindependently of the type of the spacer group. The study onthe complexation ability of the ligands was unsuccessful due tothe lack of solubility of the formed products. An unexpectedresult with side-chain pyridyl group replacement was obtainedand the product was analysed by XRD. A possible pathway wassuggested and synthetically confirmed.Supporting Information SummarySupporting Information includes experimental details, charac-terization and crystallography data of all synthesised com-pounds and Appendix, containing original NMR and UVspectra.AcknowledgementsThe financial support by Swiss National Science Found, project160515“SupraMedChem@Balkans.eu” under SCOPES 2015–2018,by The Bulgarian Science Fund, project DCOST-01-23 and infra-structure projects UNA-17/2005, DRNF-02-13/2009 and DRNF-02/01, and by The EU, COST Action CA15106 “C–H Activation inOrganic Synthesis” (CHAOS), is gratefully acknowledged.Conflict of InterestThe authors declare no conflict of interest.Keywords: 4-(3-pyridylazo)-1-naphthol · Betti condensation · 3-aminopyridine · NMR · XRD[1] a) S. Jurisson, D. Berning, W. Jia, D. Ma, Chem. Rev. 1993, 93, 1137–1156;b) K. L. Haas, K. J. Franz, Chem. Rev. 2009, 109, 4921–4960; c) H. Willms,W. Frank, C. Ganter, Organometallics 2009, 28, 3049–3058; d) H. C.Aspinall, Chem. Rev. 2002, 102, 1807–1850.[2] a) C. W. Schwietert, J. P. McCue, Coord. Chem. Rev. 1999, 184, 67–89; b) J.Reedijk, Macromolec. Symp. 2008, 270, 193–201.[3] a) P. B. Weisz, Annual Rev. Phys. Chem. 1970, 21, 175–196; b) J. Halpern,Annual Rev. Phys. Chem. 1965, 16, 103–124.[4] a) E. M. Hetrick, M. H. Schoenfisch, Chem. Soc. Rev. 2006, 35, 780–789;b) A. Kascatan-Nebioglu, M. J. Panzner, C. A. Tessier, C. L. Cannon, W. J.Youngs, Coord. Chem. Rev. 2007, 251, 884–895; c) S. I. M. Rafique, A.Nasim, H. Akbar, A. Athar, Biotechnol. Mol. Biol. Rev. 2010, 5, 38–45; d) K.Fromm, Nature Chem. 2011, 3, 178; e) S. Eckhardt, P. S. Brunetto, J.Gagnon, M. Priebe, B. Giese, K. M. Fromm, Chem. Rev. 2013, 113, 4708–4754.Figure 6. ORTEP view of 6 with the atomic numbering scheme; ADP aredrawn at 50% probability, hydrogen atoms are shown as small spheres witharbitrary radii. The thiophene ring sulphur (S33) and C43 atom are disorderedover two positions with major orientation at 53% (minor component notshown on the drawing).Figure 7. ORTEP view of 7 with the atomic numbering scheme; ADP aredrawn at 40% probability, hydrogen atoms are shown as small spheres witharbitrary radii. The thiophene ring sulphur (S33) and C43 atoms aredisordered over two positions with major orientation at 73% (minorcomponent is shown as dashed lines).4http://doc.rero.ch123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657[5] a) S. Djokić, Bioinorg. Chem. Appl. 2008, Article ID 436458, 7 pp.; b) K.Vasilev, J. Cook, H. J. Griesser, Expert Rev. Med. Dev. 2009, 6, 553–567;c) O. Gordon, T. Vig Slenters, P. S. Brunetto, A. E. Villaruz, D. E.Sturdevant, M. Otto, R. Landmann, K. M. Fromm, Antimicrob. AgentsChemother. 2010, 54, 4208–4218; d) N. Loginova, A. Chernyavskaya, G.Polozov, N. Osipovich, T. Koval’chuk, A. Gres, Y. Halauko, A. Halauko, R.Zheldakova, Y. Faletrov, I. Azarko, Mini-Rev. Org. Chem. 2013, 10, 227–240; e) P. Pallavicini, G. Dacarro, Y. A. Diaz-Fernandez, A. Taglietti, Coord.Chem. Rev. 2014, 275, 37–53.[6] H. W. Roesky, M. Andruh, Coord. Chem. Rev. 2003, 236, 91–119.[7] C. Copéret, A. Comas-Vives, M. P. Conley, D. P. Estes, A. Fedorov, V.Mougel, H. Nagae, F. Núñez-Zarur, P. A. Zhizhko, Chem. Rev. 2016, 116,323–421.[8] a) K. Venkataraman, The chemistry of synthetic dyes, Academic Press,New-York and London, 1970; b) H. Zollinger, Color Chemistry, Synthesis,Propertiesand Application of Organic Dyes and Pigments, Wiley-VCH,Weinheim, 2003; c) R. M. Christie, Azo dyes and pigments, RSC Publish-ing, 2001.[9] a) P. Gregory, High-Technology Applications of Organic Colorants, PlenumPress, New York, 1991; b) Industrial Dyes. Chemistry, Properties, Applica-tions, Hunger, K. (Ed.), Wiley-VCH Verlag GmbH & Co. KGaA, 2003.[10] A. D. Towns, Dyes Pigm. 1999, 42, 3–28.[11] a) T. M. Florence, Y. Farrar, Anal. Chem. 1963, 35, 1613–1616; b) K. L.Cheng, R. H. Bray, Anal. Chem. 1955, 27, 782–785; c) R. G. Anderson, G.Nickless, Analyst 1967, 92, 207–238; d) K. Pytlakowska, V. Kozik, M.Dabioch, Talanta 2013, 110, 202–228.[12] a) C. Huggins, J. Pataki, PNAS 1965, 53, 791–796; b) E. Węglarz-Tomczak,Ł. Górecki, Chemik 2012, 66, 1298–1307.[13] a) T. J. J. Müller, Multicomponent reactions, McGraw-Hill Education, 2016;b) I. Ugi, A. Dömling, W. Hörl, Endeavour 1994, 18, 115–122; c) C. deGraaff, E. Ruijter, R. V. A. Orru, Chem. Soc. Rev. 2012, 41, 3969–4009; d) A.Dömling, W. Wang, K. Wang, Chem. Rev. 2012, 112, 3083–3135.[14] a) Z. Wang, Comprehensive Organic Name Reactions and Reagents, JohnWiley & Sons, Inc., 2010; b) C. Cardellicchio, M. A. M. Capozzi, F. Naso,Tetrahedron: Asymm. 2010, 21, 507–517.[15] I. Szatmári, F. Fülöp, Tetrahedron 2013, 69, 1255–1278.[16] S. H. Etaiw, Y. M. Issa, Kolorisztikai Ertesito 1978, 20, 37–41.[17] a) L. Antonov, V. Deneva, S. Simeonov, V. Kurteva, D. Nedeltcheva, J.Wirz, Angew. Chem. Int. Ed. 2009, 48, 7875–7878; b) L. M. Antonov, V. B.Kurteva, S. P. Simeonov, V. V. Deneva, A. Crochet, K. Fromm, Tetrahedron2010, 66, 4292–4297; c) L. Antonov, V. Deneva, V. Kurteva, D. Nedeltch-eva, A. Crochet, K. M. Fromm, RSC Adv. 2013, 3, 25410–25416; d) V. B.Kurteva, L. M. Antonov, D. V. Nedeltcheva, A. Crochet, K. M. Fromm, R. P.Nikolova, B. L. Shivachev, M. S. Nikiforova, Dyes Pigm. 2012, 92, 1266–1277.[18] Crystallographic data (with structure factors) for the structural analysishave been deposited with the Cambridge Crystallographic Data Centre,Nos. CCDC - 1854785 (4 perchlorate), 1873276 (6) and 1873277 (7).Copies of this information may be obtained free of charge from: TheDirector, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK. Fax:+44(1223)336-033, e-mail:deposit@ccdc.cam.ac.uk, or www:www.ccdc.cam.ac.uk.5http://doc.rero.ch

Betti bases from 4-(3-pyridazo)-1-naphthol: synthesis, coordination behaviour and unusual substitution reactions

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Betti bases from 4-(3-pyridazo)-1-naphthol: synthesis, coordination behaviour and unusual substitution reactions

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