C-n coupling process with [cu2( µ-salben)2] complexes

Abstract

The invention relates to a process for the coupling of an aryl halogenide with an N- nucleophile compound which is characterized in that the coupling takes place in the presence of a dinuclear copper(II) complex bearing substituted salben-type ligands having the formula (I). Also described are novel dinuclear copper(II) complex bearing substituted salben-type ligands within the scope of formula (I).

Description

[0001] C-N coupling process with [Cu2( ^-salben)2] complexes The invention relates to a novel process for the coupling of aryl halogenides with an N- nucleophile compound in the presence of dinuclear copper(II) complexes bearing substituted salben-type ligands of the formula I wherein R1and R2are the same or different and are optionally substituted C1-12-alkyl, aryl or heteroaryl or hydrogen, and G1, G2, G3and G4are the same or different and stand for hydrogen or one or more substituents selected from C1-12-alkyl, C1-12-alkoxy, halogen C1-12-alkyl, halogen, mono- or di- C1-12-alkyl amino, carboxyl, C1-12 alkoxy carbonyl or nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6- alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro. The inventions also relates to novel dinuclear copper(II) complexes bearing substituted salben-type ligands of the formula I, wherein R1and R2are the same and are substituents of the formula IIa, IIb or IIc wherein R3, R4, R5, R6and R7are the same or different and are hydrogen, C1-12-alkyl, C1-12- alkoxy, halogen, halogen-C1-12-alkyl, mono- or di- C1-12-alkyl amino, nitro or R3and R4or R4and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6-alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro. X1, X2, X3, X4and X5are the same or different and represent at least one heteroatom selected from nitrogen, oxygen or sulphur; n is 0 or 1; R8, R9and R10are the same or different and are hydrogen, C1-12-alkyl, halogen C1-12- alkyl, hydroxy, hydroxy- C1-12-alkyl, halogen or R8and R9together form a saturated carbocycle or a heterocycle or R8, R9and R10together form an unsaturated carbocycle, with the proviso that compounds with R1and R2being hydrogen, or R1and R2having the formula IIa and wherein R3, R4, R6and R7are hydrogen, while R5is hydrogen, chlorine, methyl, or nitro, are excluded. The object of the present invention was to provide an alternative method for the C-N- coupling, i.e. the coupling of an aryl halogenide with an N-nucleophile with a dinuclear copper(II) complex bearing substituted salben-type ligands of the formula I and to provide novel dinuclear copper(II) complex bearing substituted salben-type ligands of the formula I capable to catalyse the coupling. The object could be reached with the process as outlined below, which comprises the coupling of an aryl halogenide with an N-nucleophile compound in the presence of a dinuclear copper(II) complex bearing substituted salben-type ligands having the formula I. The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. The term “C1-12-alkyl” relates to a branched or straight-chain monovalent saturated aliphatic hydrocarbon radical of one to twelve carbon atoms, preferably one to eight, more preferably one to four carbon atoms. This term is further exemplified by radicals as methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl or t-butyl, pentyl, or hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl and its isomers. The term “C1-12-alkoxy” refers to a C1-12-alkyl group as defined above to which an oxygen atom is attached. Typical representatives are methoxy or ethoxy. The term “mono- or di- C1-12-alkyl amino” refers to an amino group which is mono- or di-substituted by a C1-12-alkyl group as defined above. Typical examples are N-methylamino, N- ethylamino, N,N-dimethylamino or N,N-diethylamino. The term “halogen” refers to fluorine, chlorine, bromine or iodine, preferably to fluorine and chlorine, but in regard to the C-N coupling particularly to bromine and iodine. The term “halogen-C1-12-alkyl” refers to a C1-12-alkyl group as defined above which is substituted with one or more halogens, such as trichloromethyl, 1,1-dichloroethyl or 1,1-di- chlorooctyl. The term “aryl” relates to an aromatic carbon ring such as to the phenyl, naphthyl ring anthracenyl or phenanthrenyl ring, preferably the phenyl ring. The term “heteroaryl” refers to an aromatic 5 to 6 membered monocyclic ring or 9 to 10 membered bicyclic ring which can comprise 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and / or sulphur, such as pyridyl, pyridinyl, pyrazolyl, pyrimidinyl, benzoimidazolyl, quinolinyl and isoquinolinyl, thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, thiazolyl or imidazolyl. The term “optionally substituted” refers to one or more substituents selected from C1-12- alkyl, C1-12-alkoxy, halogen, halogen C1-12-alkyl, mono- or di- C1-12-alkyl amino or nitro. The spiral bond and thus indicating chirality of the molecule, but also for mixtures of the enantiomers. Whenever a chiral carbon is present in a chemical structure, it is intended that all stereoisomers associated with that chiral carbon are encompassed by the structure as pure stereoisomers as well as mixtures thereof. Process: As outlined above the invention relates to a novel process for the coupling of aryl halogenides with an N-nucleophile compound in the presence of dinuclear copper(II) complexes bearing substituted salben-type ligands of the formula I. Aryl halogenide: Suitable aryl halogenides can be defined with the formula III wherein X6, X7, X8, X9and X10are the same or different and represent carbon or at least one heteroatom selected from nitrogen, oxygen or sulphur; R19, R20, R21, R22and R23are the same or different and are hydrogen, C1-12-alkyl, C2-12- alkenyl, C2-12-alkynyl, C1-12-alkoxy, halogen, halogen-C1-12-alkyl, mono- or di- C1-12-alkyl amino or cyano, or R19and R20or R20and R21or R21and R22or R22and R23together with the ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-12-alkyl, C1-12-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro; n is 0 or 1 and Z is a halogen atom. In preferred aryl halogenides X6, X7, X8, X9and X10are the same or different and represent carbon or one nitrogen atom; R19, R20, R21, R22and R23are the same or different and are hydrogen, methyl, methoxy or cyano; n is 1 and Z is chlorine, bromine or iodine, preferably bromine or iodine. The aryl halogenides of the formula III are as a rule commercially available or they can be synthesized following procedures well known by the skilled in the art. N-nucleophile: Suitable N-nucleophile can be selected from compounds of the formulae

[0002] wherein R11, R12, R13, R14, R15, R16, R17and R18are the same or different and are hydrogen, C1-12- alkyl, C1-12-alkoxy, aryl, halogen, halogen-C1-12-alkyl, nitro, hydroxy, mono- or di- C1-12-alkyl amino or R15and R16together with the nitrogen they are attached to form a saturated 5-or 6- member heterocycle; X11, X12, X13and X14are the same or different and represent a carbon atom optionally substituted with C1-12-alkyl, aryl-C1-12-alkyl, C1-12-alkoxy, halogen, halogen-C1-12-alkyl and at least one further heteroatom selected from nitrogen, oxygen or sulphur. Preferred N-nucleophiles have the formula IVc, IVd, IVe, wherein R15, R16, R17and R18are the same or different and are hydrogen, C 15 1-6-alkyl, aryl, or R and R16together with the nitrogen they are attached to form a saturated heterocycle 5-or 6- member heterocycle; X11, X12, X13and X14are the same or different and represent a carbon atom optionally substituted with C1-12-alkyl, aryl-C1-12-alkyl, and at least one further heteroatom selected from nitrogen, oxygen or sulphur. Catalysts: The process of the present invention takes place in the presence of a dinuclear copper(II) complexes bearing substituted salben-type ligands having the formula I

[0003] wherein R1and R2are the same or different and are optionally substituted C1-12-alkyl, aryl or heteroaryl, or hydrogen and G1, G2, G3and G4are the same or different and stand for hydrogen or one or more substituents selected from C1-12-alkyl, C1-12-alkoxy, halogen, halogen C1-12-alkyl, mono- or di- C1-12-alkyl amino, carboxyl, C1-12-alkoxy carbonyl or nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6- alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro. In a preferred embodiment G1, G2, G3and G4are the same or different and stand for hydrogen or one or more substituents selected from methyl, ethyl, t-butyl, methoxy, ethoxy, fluorine, chlorine, bromine, trifluoromethyl, N.N-dimethylamino, N.N-diethylamino, carboxyl, methoxy carbonyl, ethoxy carbonyl, i-propoxy carbonyl, n-butoxy carbonyl, t-butoxy carbonyl, nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring. In a preferred embodiment R1and R2are the same and are substituents of the formula IIa, IIb or IIc

[0004] wherein R3, R4, R5, R6and R7are the same or different and are hydrogen, C1-12-alkyl, C1-12- alkoxy, halogen, halogen-C -alkyl, mono- or di- C -alkyl amino, nitro or R3and R4o 4 1-12 1-12 r R and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6-alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro, X1, X2, X3, X4and X5are the same or different and represent at least one heteroatom selected from nitrogen, oxygen or sulphur; n is 0 or 1; R8, R9and R10are the same or different and are hydrogen, C1-12-alkyl, halogen C1-12- alkyl, hydroxy, hydroxy-C1-12-alkyl, halogen or R8and R9together form a saturated carbocycle or a heterocycle or R8, R9and R10together form an unsaturated carbocycle. Preferred substituents of formula IIa are those wherein R3, R4, R5, R6and R7are the same or different and are hydrogen, methyl, ethyl, t-butyl, methoxy, ethoxy, chlorine, bromine, trifluoromethyl, N.N-dimethylamino, N.N-diethylamino, nitro or R3and R4or R4and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fused aryl ring selected from 2-naphthalene, anthracene or phenanthrene In particular, examples of formula IIa ● R3to R7are hydrogen, or ● R3is methyl, methoxy, chlorine or nitro and R4to R7are hydrogen, or ● R5is methyl, t-butyl, methoxy, chlorine, nitro or N,N-dimethylamino and R3and R4and R6and R7are hydrogen, or ● R3and R5are methoxy or chlorine and R4, R6and R7are hydrogen, or ● R3and R7are methoxy or chlorine and R4to R6are hydrogen, or ● R3, R5and R7are methoxy and R4to R6are hydrogen. Preferred substituents of formula IIb can be selected from Particularly preferred substituents are of the formula IIb1, IIb2, IIb14, IIb17. Preferred substituents of formula IIc are those wherein R8, R9and R10are the same or different and are hydrogen, hydroxy, hydroxy-C1-4-alkyl or R8and R9together form a heterocycle or R8, R9and R10together form an unsaturated carbocycle. Particular examples of substituents of formulas IIc are:

[0005] Preferably they are selected from formula IIc1 and IIc2 The substituents IIa and IIc are most preferred. Particularly preferred catalysts of the formula IIa are those wherein, R3, R4, R5, R6and R7are hydrogen, or R3is chlorine or methoxy and R4, R5, R6and R7are hydrogen, or R5is chlorine or methoxy and R3, R4, R6and R7are hydrogen, or R3and R7are methoxy and R4, R5and R6are hydrogen. Particularly preferred catalysts of the formula IIc are those with the formula IIc1. The most preferred catalysts are listed below.

[0006]

[0007] Dinuclear copper(II) complex bearing substituted salben-type ligands having the formula I wherein G1, G2, G3and G4are the same or different and stand for hydrogen or one or more substituents selected from C1-12-alkyl, C1126-alkoxy, halogen, halogen C1-12-alkyl, mono- or di- C1-12-alkyl amino, carboxyl, C1-12- alkoxy carbonyl or nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6- alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro; R1and R2are the same and are substituents of the formula IIa, IIb or IIc

[0008] R3, R4, R5, R6and R7are the same or different and are hydrogen, C1-12-alkyl, C1-12- alkoxy, halogen, halogen-C1-12-alkyl, mono- or di- C1-12-alkyl amino, nitro or R3and R4or R4and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6-alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro. X1, X2, X3, X4and X5are the same or different and represent at least one heteroatom selected from nitrogen, oxygen or sulphur; n is 0 or 1; R8, R9and R10are the same or different and are hydrogen, C1-12-alkyl, halogen C1-12- alkyl, hydroxy, hydroxy- C1-12-alkyl, halogen or R8and R9together form a saturated carbocycle or a heterocycle or R8, R9and R10together form an unsaturated carbocycle, with the proviso that compounds with R1and R2being hydrogen, or R1and R2having the formula IIa and wherein R3, R4, R6and R7are hydrogen while R5is hydrogen, chlorine, methyl, or nitro, are excluded. The excluded compounds have been disclosed by a) Alessandro Pasini, Francesco Demartin, Olivo Piovesana, Brunetto Chiari, Antonio Cinti and Ornella Crispu, J. Chem. Soc., Dalton Trans.2000, 3467–3472, DOI: 10.1039 / b003825n The novel dinuclear copper(II) complex bearing substituted salben-type ligands having the formula I are novel and therefore constitute a particular embodiment of the present invention. With the exception for the known compounds, the preferences and particular examples as outlined before likewise apply for the novel dinuclear copper(II) complex bearing substituted salben-type ligands. Preparation of catalysts: The preparation of the catalyst can be accomplished according to the scheme below: The H2salben-type derivatives of formula XII can be prepared by reacting an N,N’-bis- (salicylidene)-2-hydroxyphenylmethanediamine derivative of formula X with the appropriate aldehyde of formula XI in the presence of ammonium acetate a or ammonia and a polar protic solvent such as methanol or ethanol at temperatures from -10 °C to 40 °C under stirring for a period of time from 3 h to 120 h. The resulting ligand can be isolated by filtration, washing with polar protic solvent, and dried under vacuum. The formation of the dinuclear copper(II) complex bearing substituted salben-type ligands having the formula I can then happen by adding a copper(II) salt CuX2, preferably the acetate monohydrate, to the suspended H2salben-type ligand of formula XII in a polar protic solvent, preferably methanol or ethanol, in the presence of tertiary amine, preferably triethylamine at temperatures from -10 °C to 40 °C under stirring for a period of time from ½ h to 24 h. The resulting complex can be isolated by filtration, washing with polar protic solvent, and dried under vacuum. C-N coupling process: The C-N coupling process i.e. the coupling of aryl halogenides with an N-nucleophile compound in the presence of dinuclear copper(II) complexes bearing substituted salben-type ligands of the formula I is advantageously performed in the presence of a suitable base. The base can be selected from alkali salts of mineral acids or organic acids, such as caesium carbonate, potassium phosphate, potassium carbonate or sodium acetate, or from alkali alcoholates such as sodium- or potassium t-butylate. The preferred bases are caesium carbonate and potassium phosphate. As a rule the base is applied in equivalents: from 1 to 5, preferably from 1.5 to 4. Furthermore, the reaction takes place in the presence of an organic solvent which can be selected from aliphatic alcohols, such as methanol, ethanol, t-amylalcohol, N.N- dimethylformamide, tetrahydrofuran, acetonitrile, toluene or dimethylsulfoxide. Preferred organic solvents are acetonitrile, tetrahydrofuran and dimethylsulfoxide, The equivalent aryl halogenide in relation to1 equivalent of the N-nucleophile, may vary dependent on the halogenide, but typically ranges from 0.2 to 3.0: 1.0., preferably 0.3 to 2.5:1.0. The reaction temperature is as rule held between 20 °C and 200 °C, preferably between 50 °C and 100 °C, more preferably between 70 °C and 90 °C. The catalyst loading in mol %, referred to the limiting reagent, which can be the N- nucleophile or the aryl halogenide, can vary between 0.1 mol % and 5.0 mol %, preferably between 0.25 mol % and 3.0 mol %. After a reaction time of 4 h to 24 h, preferably of 8 h to 18 h, the resulting aryl amine can be isolated by filtering off the catalyst and by evaporating the organic phase. The resulting crude aryl amine can further be purified via chromatography. Examples: Abbreviations: RT = room temperature MeOH = methanol Et2O = diethyl ether iPr2O = diisopropyl ether Et3N = triethylamine EtOH = ethanol MeCN = acetonitrile DMSO = dimethylsulfoxide THF = tetrahydrofuran DCM = dichloromethane 1. Activity of copper(II) complexes as catalysts in C-N coupling reactions 1.1 Optimized conditions The coupling of aryl iodide and pyrazole can be achieved by reaction with 0.5 mol% [Cu2(μ-salben)2] catalyst in the presence of 2 equiv of Cs2CO3 in acetonitrile (MeCN) at 82°C. After 16 h full conversion is observed, and the product can be isolated in 83% yield. 1.2 Optimization studies Table 1. Optimization of temperature and catalyst loading.

[0009] General conditions: iodobenzene (215 µL, 1.93 mmol, 1.5 equiv), pyrrole (90 µL, 1.29 mmol, 1 equiv), Cs2CO3(839.2 mg, 2.58 mmol, 2 equiv), [Cu2(μ-salben)2] in 1 mL of MeCN.[a]The catalyst loading refers to the amount of pyrrole.[b] 1H NMR yield, isolated yields in brackets. Table 2. Screening of bases in MeCN. General conditions: iodobenzene (715 µL, 6.42 mmol, 1.5 equiv), pyrrole (300 µL, 4.29 mmol, 1 equiv), base (2 equiv) [Cu2(μ-salben)2] in 3.5 mL of MeCN.[a]The catalyst loading refers to the amount of pyrrole.[b] 1H NMR yield, isolated yields in brackets.[c]Tetrahydrofuran (THF) as solvent.[d]K3PO4(3.64 g, 17.18 mmol, 4 equiv). Table 3. Screening of solvent and bases. General conditions: iodobenzene (215 µL, 1.93 mmol, 1.5 equiv), pyrrole (90 µL, 1.29 mmol, 1 equiv), base (2.58 mmol, 2 equiv), [Cu2(μ-salben)2] (2.52 mg, 0.003 mmol, 0.0025 equiv) in 1 mL of solvent; T = 70-82°C, t = 16 h.[a]DMF = dimethylformamide, DMSO = dimethylsulfoxide, EtOH = ethanol. Table 4. Activity of the different copper (II) derivatives as catalysts. d General conditions: iodobenzene (215 µL, 1.93 mmol, 1.5 equiv), pyrrole (90 µL, 1.29 mmol, 1 equiv), base (2.58 mmol, 2 equiv), 1 mL of MeCN; T = 82 °C, t = 16 h.[a]LC / MS yield (%). Table 5. Influence of various equivalents of base and iodobenzene. Entry Iodobenzene (equiv) Base (equiv) NMR yield , , , , K3PO4, [Cu2(μ-salben)2] (0.006 mmol, 0.005 equiv) in 1 mL of MeCN; T = 82 °C, t = 16 h. 1.3. Substrate scope Table 6. Substrate scope with aryl iodides Aryl io e - uceop e ro uct Yield % (LC / MS)

[0010] General conditions: aryl iodide (1.5 equiv), N-nucleophile (1 eq), Cs2CO3 (2 equiv), [Cu2(μ- salben)2] (0.5 mol %) in MeCN, c = 1 mol L–1; T = 82 °C, t = 16 h. Table 7. Substrate scope with aryl bromides t yield (LC / MS) O 66% N 55% N 51% N 20% N 48% N 54% O 63% O 94% General conditions: aryl bromide (1 equiv), N-nuclephile (n equiv as reported in the table), base, [Cu2(μ-salben)2] (2.5 mol%), base (n equiv as reported in the table), solvent, c = 0.5 mol L–1; T = 85 °C, t = 16 h. 2. Synthesis of the novel salben-type ligands 2.1 Synthesis of H2sal(2,6-diOMe)ben H3salmp (0.499 g, 1.44 mmol) and 2,6-dimethoxybenzaldehyde (0.478 g, 2.87 mmol) were added to a solution of ammonium acetate (0.113 g, 1.46 mmol) in 5 mL of methanol (MeOH), obtaining a yellow suspension that was left under magnetic stirring for 24 h at room temperature (RT). The yellow product was then recovered by filtration, washed with MeOH (2 × 2 mL) and diethyl ether (Et2O) (2 × 2 mL) and dried under vacuum for several hours, yielding 0.645 g of a bright yellow powdery solid (76% yield). Elemental analysis for C23H22N2O4, MW = 390.44 g / mol, calculated: C 70.75%; H 5.68%; N 7.17%. Found: C 70.54%; H 5.79%, N 7.24%. IR spectrum, cm-1(ATR): 3050-2830, 1628, 1585, 1493-1474, 1397, 1276, 1250, 1110- 1067, 758.1H NMR, 298 K, CDCl3, 400 MHz: δ (ppm) 13.62 (2H, s), 8.55 (2H, d), 7.32-7.28 (4H, m), 7.26 (1H, t), 6.95 (2H, dd), 6.87 (2H, td), 6.77 (1H, s), 6.58 (2H, d), 3.85 (3H, s).13C NMR, 298 K, CDCl3, 101 MHz: δ (ppm) 163.4, 161.5, 158.5, 132.6, 132.0, 130.3, 119.1, 118.6, 117.3, 115.6, 104.7, 79.6, 56.0. 2.2 Synthesis of H2sal(2)thn H3salmp (3.012 g, 8.695 mmol) was added to a solution of ammonium acetate (2.024 g, 26.26 mmol) in EtOH (50 mL). Thiophene-2-carboxaldehyde (1.70 mL, 18.5 mmol) was then added to the suspension, and the reaction mixture was stirred at RT for 4 days. The formed pale- yellow solid was filtered, washed with EtOH and diisopropyl ether (iPr2O) and dried under vacuum for several hours, yielding 2.946 g of the title compound (67%). Elemental analysis for C19H16N2O2S, MW = 336.41, calculated: C 67.84%; H 4.79%; N 8.33%; S 9.53. Found: C 67.77%; H 4.84%; N 8.15%; S 10.05%. m.p.: 109-112 °C. IR spectrum, cm–1(ATR): 3109, 2853, 1618, 1575, 1497, 1456, 1422, 1372, 1357, 1272, 1040, 1025, 975, 897, 753, 712, 598.1H NMR, 298 K, acetone-d6, 400 MHz: δ (ppm) 6.44 (s, 1H), 6.94 (dd, 2H), 7.08 (dd, 2H), 7.24 (dt, 2H), 7.40 (ddd, 2H), 7.51 (dd, 2H), 7.52 (dd, 2H), 8.85 (s, 2H), 12.82 (s, 2H).13C NMR, 298 K, acetone-d6, 101 MHz: δ (ppm) 86.2, 116.8, 118.7, 119.0, 125.2, 126.8, 127.2, 132.8, 133.4, 144.4, 161.1, 166.5. Mass spectrum (ESI+) in MeOH, m / z (intensity %): calculated for [M + H]+: 337.1011; found: 337.1000 (100). 2.3 Synthesis of H2sal(3)thn H3salmp (3.011 g, 8.694 mmol) was added to a solution of ammonium acetate (2.017 g, 26.17 mmol) in EtOH (30 mL). Thiophene-3-carboxaldehyde (2.012 g, 17.94 mmol) was added to the suspension, and the reaction mixture was stirred at RT for 4 days. The formed pale-yellow title compound (75%). Elemental analysis for C19H16N2O2S, MW = 336.41, calculated: C 67.84%, H 4.79%, N 8.33%, S 9.53%. Found: C 67.18%, H 4.76%, N 8.55%, S 10.50%. m.p.: 94-96 °C. IR spectrum, cm1(ATR): 3107, 3054, 3000, 2858, 1618, 1576, 1500, 1456, 1424, 1368, 1273, 1043, 976, 779, 752, 733, 635. ‘H NMR, 298 K, acetone^,, 400 MHz: 5 (ppm) 6.26 (s, 1H), 6.94 (d, 2H), 6.96 (dd, 2H), 7.29 (dd, 2H), 7.39 (dd, 2H), 7.50 (dd, 2H), 7.54 (dd, 1H), 7.56 (m, 1H), 8.83 (s, 2H), 13.01 (s, 2H).13C NMR, 298 K, acetone^,, 101 MHz: 5 (ppm) 87.5, 117.6, 119.6, 119.7, 123.4, 127.0, 127.8, 133.5, 133.9, 143.0, 162.0, 167.0. Mass spectrum (ESI+) in MeOH, m / z (intensity %): calculated for [M + H]+: 337.1011; found: 337.1001 (100).

[0011] Hssalmp (0.30135 g, 0.870 mmol) was added to a solution of NH4OAC (0.20471 g, 2.66 mmol) in MeOH (10 mL). (A)-Myrtenal (0.25308 g, 1.68 mmol) was added to the yellow suspension, and it was stirred at RT for 1 d, during which Hssalmp completely dissolved in 6 h and the desired product precipitated after 12 h. The formed pale-yellow solid was filtered, washed with MeOH (3 x 3 mL) and / Pr2O (3 x 3 mL) and dried under vacuum for 1 h. Yield: 0.29610 g (61%). Elemental analysis calcd (%) for C24H26N2O2 (374.48): C 76.98, H 7.00, N 7.48. Found: C 76.78, H 7.04, N 7.51. Melting point: 184-187 °C. 'HNMR (400 MHz, 298 K, acetone-de) in ppm: 5 0.86 (3H, s), 1.43 (3H, s), 1.85 (1H, d, 10 Hz), 2.00 (1H, dd, 2 - 4 Hz), 2.14 - 2.19 (1H, m), 2.57 - 2.66 (2H, m), 3.45 (1H, t, 5 Hz), 4.40 (1H, d, 8 Hz), 6.83 (1H, s), 6.86 - 6.94 (4H, m, 1 - 7 Hz), 7.30 - 7.34 (2H, m, 2 Hz), 7.37 (1H, dd, 2 - 8 Hz), 7.43 (1H, dd, 2 - 8 Hz), 8.40 (1H, s), 8.61 (1, s), 13.15 (1H, s), 13.20 (1H, s).13C NMR (101 MHz, 298 K acetone-de) in ppm: 5 22.3, 26.4, 27.5, 34.9, 41.5, 42.0, 45.9, 64.2, 117.4, 117.4, 119.5, 119.8, 120.1, 120.4, 132.6, 132.7, 133.0, 133.3, 138.5, 144.8, 161.6, 161.9, 163.3, 164.2. IR-ATR (cm ): 2993, 2969, 2949, 2865, 1645, 1620, 1596, 1563, 1495, 1456, 1413, 1300, 1278, 1244, 1148, 1079, 971, 844, 753. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 375.2073; found: 375.2060 (100).

[0012]

[0013] ( / ?)-Myrtenal (0.1352 g, 0.900 mmol) was added to a solution of NH3 (750 μL of an aqueous solution 25% m / m, 10.0 mmol) in MeOH (2.5 mL). Salicylaldehyde (salH) (0.2001 g, 1.64 mmol) was added to the colourless solution, and the mixture was stirred at RT for 3 h with the formation of the desired product as precipitate. The formed pale-yellow solid was filtered, washed with MeOH (3 x 3 mL) and iPr2O (3 x 3 mL) and dried under vacuum overnight. Yield: 0.2112 g (69%). Elemental analysis calcd (%) for C24H26N2O2 O.2 H2O (382.08): C 76.24, H 7.04, N 7.41. Found: C 76.04, H 6.68, N 7.38. Melting point: 135-139 °C. 'H NMR (400 MHz, 298 K, aceton e-t / r,) in ppm: 5 0.79 (3H, s), 1.28 (3H, s), 1.85 (1H, d, 10 Hz), 2.09-2.14 (1H, m), 2.27-2.42 (2H, m, 6 Hz), 2.45-2.48 (2H, m), 5.49 (1H, s), 5.76 (1H, s), 6.91-6.95 (4H, m), 7.35- 7.40 (2H, m), 7.48 (2H, dd, 1 - 8 Hz), 8.71 (1H, s), 8.73 (1H, s), 13.04 (1H, s), 13.06 (1H, s).13C NMR (101 MHz, 298 K acetone-t / 6) in ppm: 5 21.6, 26.4, 32.0, 32.3, 38.6, 41.6, 43.1, 91.7, 117.6, 119.6, 121.4, 121.4, 133.3, 133.7, 148.2, 162.0, 166.6, 166.8. IR-ATR (cm '): 2989, 2969, 2927, 2877, 1620, 1574, 1494, 1457, 1413, 1365, 1274, 1212, 1150, 1039, 976, 897, 836, 751. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 375.2073; found: 335.2067 (100.

[0014] 2.6 Synthesis of H2(4-OMe)salben Benzaldehyde (0.1631 mg, 1.537 mmol) was added to a supersaturated solution of ammonium acetate (0.1631 g, 1.5368 mmol) in MeOH (2.5 mL) and stirred at RT for 5 min under inert atmosphere.4-OMe-salH (0.4175 g, 2.734 mmol) was then added to the colourless solution, and the reaction mixture was stirred at RT for 4 h. The formed pale-grey solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1 h. Yield 0.2615 g (49%). Elemental analysis calcd (%) for C23H22N2O4, (390.44): C 70.76, H 5.68, N 7.16. Found: C 70.70, H 5.80, N 6.85. Melting Point: 111 - 112 °C.1H NMR (400 MHz, 298 K, acetone-d6) in ppm: δ 13.44 (2H, s), 8.74 (2H, s), 7.56 (2H, d, 8 Hz), 7.47 – 7.43 (2H, m), 7.40 (2H, d, 8 Hz), 7.39 – 7.34 (1H, m), 6.51 (2H, dd, 8 – 2 Hz), 6.46 (2H, d, 2 Hz), 6.03 (1H, s), 3.84 (6H, s).13C NMR (151 MHz, 298 K, acetone- d6) δ 164.9, 163.9, 163.5, 141.8, 133.8, 128.8, 128.2, 127.0, 112.6, 106.4, 100.8, 90.4, 54.9. IR- ATR (cm−1): 1610, 1570, 1452, 1316, 1288, 1240, 1168, 764. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 391.1658; found: 391.1639 (100). 2.7 Synthesis of H2(5-OMe)salben Benzaldehyde (84.2 mg, 0.794 mmol) was added to a supersaturated solution of ammonium acetate (0.9672 g, 15.81 mmol) in MeOH (2.5 mL) and stirred at RT for 5 min under inert atmosphere.5-OMe-salH (201.3 mg, 1.332 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed pale-yellow solid was filtered, washed with MeOH (3 x 3 mL) and iPr2O (3 x 3 mL) and dried under vacuum for 1 h. Yield 0.1754 g (68%). Elemental analysis calcd (%) for C23H22N2O4, (390.44): C 70.76, H 5.68, N 7.16. Found: C 71.04, H 5.71, N 7.26. Melting Point: 137-141 °C.1H NMR (600 MHz, 298 K, acetone-d6) in ppm: δ 12.49 (2H, s), 8.82 (2H, s), 7.59 – 7.54 (2H, m), 7.47 – 7.42 (2H, m), 7.39 – 7.33 (1H, m), 7.08 (2H, d, 3 Hz), 7.00 (2H, dd, 9 – 3 Hz), 6.86 (2H, d, 9 Hz), 6.14 (1H, s), 3.76 (6H, s).13C NMR (151 MHz, 298 K, acetone-d6) δ 166.7, 156.1, 153.3, 129.8, 129.3, 127.8, 121.2, 119.3, 118.4, 116.3, 91.5, 56.1. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 391.1658; found: 391.1655 (100). 2.8 Synthesis of H2(5-F)salben Benzaldehyde (83.2 mg, 0.784 mmol) was added to a supersaturated solution of ammonium acetate (0.8828 g, 11.442 mmol) in MeOH (2.5 mL) and stirred at RT for 5 min.5-F- salH (206.1 mg, 1.4708 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and iPr2O (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.2295 g (85%). Elemental analysis calcd (%) for C21H16F2N2O2, (366.12): C 68.45, H 4.40, N 7.65. Found: C 68.19, H 4.32, N 7.54. Melting Point: 144 - 147 °C.1H NMR (600 MHz, 298 K, acetone-d6) δ 12.78 (2H, d, 4 Hz), 8.86 (2H, d, 3 Hz), 7.58 (2H, d, 8 Hz), 7.46 (2H, dd, 8 Hz), 7.43 – 7.35 (1H, m), 7.32 (2H, ddd, 9 – 3 – 2 Hz), 7.19 (2H, ddd, 9 – 3 Hz), 6.94 (2H, ddd, 9 – 4 – 2 Hz), 6.20 (, 2 Hz).13C NMR (151 MHz, 298 K, acetone-d6) δ 166.1, 158.3, 156.3 (d, JC-F=233 Hz), 141.7, 129.8, 129.4, 127.9, 120.8 (d, 23 Hz), 119.6 (d, 8 Hz) 118.9 (d, 8 Hz), 118.3 (d, 23 Hz), 91.4. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 367.1258; found: 367.1254 (100). 2.9 Synthesis of H2(5-Cl)salben Benzaldehyde (81.1 mg, 0.764 mmol) was added to a supersaturated solution of ammonium acetate (0.9869 g, 12.80 mmol) in MeOH (3 mL) and stirred at RT for 5 min.5-Cl- salH (200.6 mg, 1.281 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and iPr2O (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.1567 g (61%). Elemental analysis calcd (%) for C21H16Cl2N2O2·0.3 H2O (405.28): C 62.33, H 4.13, N 6.92. Found: C 62.33, H 3.96, N 6.82. Melting Point: 128 - 131 °C.1H NMR (600 MHz, 298 K acetone-d6) δ 13.05 (2H, s), 8.86 (2H, s), 7.60 – 7.54 (4H, m, 2 – 7 Hz), 7.49 – 7.40 (2H, m(dd), 7 Hz), 7.40 – 7.34 (3H, m, 2 - 9 Hz), 6.95 (2H, d, 9 Hz), 6.21 (1H, s).13C NMR (151 MHz, 298 K, acetone-d6) δ 166.1, 160.7, 141.6, 133.6, 132.5, 129.9, 129.5, 127.9, 123.8, 120.8, 119.5, 91.2. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + Na]+: 399.0667; found: 399.0661 (100). 2.10 Synthesis of H2(5-Me)salben Benzaldehyde (84.2 mg, 0.8015 mmol) was added to a supersaturated solution of ammonium acetate (0.8636 g, 11.20 mmol) in MeOH (2.5 mL) and stirred at RT for 5 min.5-Me- salH (214.5 mg, 1.5755 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.2041 g (72%). Elemental analysis calcd (%) for C23H22N2O2·0.05 NH4OAc (362.29): C 76.58, H 6.22, N 7.93. Found: C 76.38, H 5.98, N 7.80. Melting Point: 125 - 130 °C.1H NMR (400 MHz, 298 K, CDCl3) δ 12.72 (2H, s), 8.53 (2H, s), 7.49 – 7.29 (5H, m), 7.16 (2H, dd, 8 – 2 Hz), 7.11 (2H, d, 2 Hz), 6.89 (2H, d, 8 Hz), 5.99 (1H, s), 2.29 (6H, s). Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 359.1758; found: 359.1747 (100). 2.11 Synthesis of H2(3-OMe)sal(2-Cl)ben 2-Cl-benzaldehyde (92.2 mg, 0.657 mmol) was added to a solution of ammonium acetate (0.8808 g, 11.40 mmol) in MeOH (10 mL) and stirred at RT for 5 min. 3-OMe-salH (0.2085 g, 1.370 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.1431 g (51%). Elemental analysis calcd (%) for C23H21ClN2O4 (424.12): C 65.02, H 4.98, N 6.59. Found: C 64.56, H 4.91, N 6.54.1H NMR (400 MHz, 298 K, acetone-d6) δ 13.00 (2H, s), 8.91 (2H, s), 7.72 (1H, dd, 1 - 8 Hz), 7.53 (1H, dd, 1 - 8 Hz), 7.49 (1H, dd, 1 - 7 Hz), 7.43 (1H, dd, 2 - 7 H) 7.15 (2H, d, 8Hz), 7.11 (2H, d, 8 Hz), 6.89 (2H, dd, 8 Hz), 6.55 (1H, s), 3.85 (6H, s).13C NMR (101 MHz, 298 K, acetone-d6) δ 166.7, 151.5, 148.5, 138.1, 132.6, 130.0, 129.2, 127.2, 124.1, 118.8, 118.6, 118.5, 115.8, 86.3, 55.6. IR-ATR (cm−1): 1613, 1600, 1459, 1317, 1252, 1171, 764, 728. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 425.1268; found: 425.1248 (60). 2.12 Synthesis of H2(5-OMe)sal(2-Cl)ben 2-Cl-benzaldehyde (0.1322 g, 0.8689 mmol) was added to a solution of ammonium acetate (0.21665 g, 2.038 mmol) in MeOH (10 mL) and stirred at RT for 5 min.5-OMe-salH (0.2864 g, 2.038 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.1278 g (32%). Elemental analysis calcd (%) for C23H21ClN2O4 (424.12): C 65.02, H 4.98, N 6.59. Found: C 64.78, H 4.95, N 6.51.1H NMR (400 MHz, 298 K, acetone-d6) δ 12.34 (2H, s), 8.85 (2H, s), 7.71 (1H, dd, 8 – 2 Hz), 7.51 (1H, dd, 8 – 2 Hz), 7.47 (1H, dd, 8 – 2 Hz), 7.41 (1H, dd, 8 – 2 Hz), 7.12 (2H, d, 3 Hz), 7.02 (2H, dd, 9 – 3 Hz), 6.86 (2H, d, 9 Hz), 6.54 (1H, s), 3.76 (6H, s).13C NMR (101 MHz, 298 K, acetone-d6) δ 166.7, 155.2, 152.5, 138.1, 132.6, 130.0, 129.2, 127.9, 120.6, 118.4, 117.6, 115.5, 115.4, 86.5, 55.2. IR-ATR (cm−1): 1634, 1584, 1487, 1329, 1266, 1225, 1165, 770. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 425.1268; found: 425.1248 (60). 2.13 Synthesis of H2(5-OMe)sal(2-OMe)ben 2-OMe-benzaldehyde (0.1349 g, 0.9584 mmol) was added to a solution of ammonium acetate (0.2294 g, 2.977 mmol) in MeOH (10 mL) and stirred at RT for 5 min.5-OMe-salH (0.2883 g, 1.895 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.3028 g (76%). Elemental analysis calcd (%) for C24H24N2O5(420.47): C 68.75, H 5.75, N 6.62. Found: C 69.07, H 5.83, N 6.68.1H NMR (400 MHz, 298 K, acetone-d6) δ 12.60 (2H, s), 8.78 (2H, s), 7.49 (1H, dd, 8 – 2 Hz), 7.35 (1H, dd, 9 Hz), 7.10 – 7.07 (3H, m), 7.03 (1H, dd, 6 Hz), 7.00 (2H, dd, 9 – 3 Hz), 6.85 (2H, d, 9 Hz), 6.50 (1H, s), 3.96 (3H, s) 3.76 (6H, s).13C NMR (101 MHz, 298 K, acetone-d6) δ 165.7, 156.8, 154.9, 153.2, 152.8, 129.6, 128.6, 127.5, 120.8, 120.0, 118.6, 117.5, 115.4, 111.4, 84.2, 55.2. IR-ATR (cm−1): 1635, 1585, 1489, 1328, 1266, 1240, 1167, 760. Mass spectrum (ESI+) in MeCN,m / z (intensity %): calculated for [M + H]+: 421.1764; found: 421.2400 (40).

[0015] 2-OMe-benzaldehyde (0.1287 g, 0.9449 mmol) was added to a solution of ammonium acetate (0.2173 g, 2.819 mmol) in MeOH (10 mL) and stirred at RT for 5 min.5-Cl-salH (0.2918 g, 1.864 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.2996 g (76%). Elemental analysis calcd (%) for C22H18Cl2N2O3 (429.30): C 61.35, H 4.23, N 6.53. Found: C 61.05, H 4.26, N 6.55. Melting Point (°C): 152 – 154.1H NMR (400 MHz, 298 K, acetone-d6) δ 13.23 (2H, s), 8.90 (2H, s), 7.63 (2H, d, 3 Hz), 7.55 (1H, dd, 8 – 2 Hz), 7.36-7.30 (3H, m), 7.09 (1H, d, 9 Hz), 7.05 (1H, ddd, 8 – 1 Hz), 6.90 (2H, d, 9 Hz), 6.50 (1H, s), 3.90 (3H, s).13C NMR (101 MHz, 298 K, acetone-d6) δ 166.9, 162.2, 157.9, 133.8, 133.4, 130.7, 129.6, 128.5, 121.8, 119.9, 119.8, 117.7, 112.3, 85.2, 56.1. IR-ATR (cm−1): 1606, 1521, 1453, 1384, 1297, 1242, 1165, 748. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 429.0773; found: 429.0660 (40). 2-NO2-benzaldehyde (0.1390 g, 0.9199 mmol) was added to a solution of ammonium acetate (0.2212 g, 2.869 mmol) in MeOH (10 mL) and stirred at RT for 5 min. 5-OMe-salH (0.2796 g, 1.837 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 ^ 3 mL) and dried under vacuum for 1h. Yield 0.1957 g (49%). Elemental analysis calcd (%) for C23H21N3O6 (435.42): C 63.24, H (1H, dd, 7 - 1 Hz), 7.66 (1H, dd, 8 - 1 Hz), 7.11 (2H, d, 3 Hz), 7.01 (2H, dd, 9 - 3 Hz), 6.85 (2H, dd, 9 Hz), 6.66 (1H, s), 3.77 (6H, s).13C NMR (101 MHz, 298 K, acetone-t / 6) 8 166.9, 156.7, 154.8, 153.4, 134.7, 133.7, 129.7, 129.6, 124.5, 120.8, 118.3, 117.6, 115.6, 84.7, 55.9. IR-ATR (cm '): 1626, 1586, 1525, 1489, 1370, 1338, 1158, 767. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 436.1483; found: 436.1493 (60).

[0016] 2.16 Synthesis of H2(5-Cl)sal(2-NOi)ben

[0017] 2-NO2-benz H2(5-CI)sal(2-NO2)ben

[0018] 2-NO2-benzaldehyde (0.0976 g, 0.646 mmol) was added to a solution of ammonium acetate (0.1677 g, 2.175 mmol) in MeOH (10 mL) and stirred at RT for 5 min. 5-Cl-salH (0.2096 g, 1.339 mmol) was added to the colourless solution, and the reaction mixture was stirred at RT for 3 h. The formed yellow solid was filtered, washed with MeOH (3 x 3 mL) and dried under vacuum for Ih. Yield 0.477 g (50%). Elemental analysis calcd (%) for C22Hi5C12N3O4 (443.27): C 56.77, H 3.40, N 9.46. Found: C 57.26, H 3.42, N 9.61. Melting Point (°C): 148 - 151. *H NMR (400 MHz, 298 K, acetone-t / e) 6 12.73 (2H, s), 8.80 (2H, s), 8.04 (IH, dd, 8 - 2 Hz), 7.99 (IH, dd, 7.8 - 1.3 Hz), 7.87 (IH, dd, 7 Hz), 7.69 (IH, dd, 8 Hz), 7.60 (2H, d, 3 Hz), 7.40 (2H, dd, 9 - 3 Hz), 6.95 (2H, d, 9 Hz), 6.73 (IH, s).13C NMR (101 MHz, 298 K, aceton e-6 / 6) 6 167.7, 160.4, 150.3, 135.0, 134.9, 133.3, 132.5, 130.4, 129.6, 124.9, 124.0 120.06, 119.6, 84.5. IR-ATR (cm '): 1616, 1559, 1520, 1473, 1342, 1199, 792, 751. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 444.0417; found: 444.0505 (40). 3. Synthesis of the new copper(II) dinuclear complexes

[0019] 3.1 Synthesis of [Cu2(p-sal(4-tBu)ben)2] 2

[0020] [Cu2(p.-sal(4-tBu)ben)2]

[0021] EtsN (0.109 g, 1.08 mmol) was added to a yellow suspension of H2sal(4- / Bu)ben (0.2021 g, 0.5229 mmol) in 8 mL of EtOH. Solid Cu(OAc)2 H2O (0.1017 g, 0.5094 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 ^ 2 mL) and dried under vacuum for several hours. Yield: 0.1882 g of a brown solid (83%). Elemental analysis calcd (%) for C50H48CU2N4O4 0.8EtOH (932.91): C 66.43, H 5.70, N 6.01. Found: C 66.51, H 5.70, N 6.01. IR-ATR (cm -1): 3047, 2964, 1606, 1533, 1466, 1387, 1317, 1192, 1147, 1107, 981, 928, 827. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 895.2346; found: 895.2327 (100).

[0022] The ligand structure has been published in Rigamonti, L et al, Int. J. Mol. Sci. 2020, 21, 7882, DOI: : 10.3390 / ijms21217882.

[0023] 3.2 Synthesis of [Cu2(p-sal(2-OMe)ben)2]

[0024]

[0025] EtsN (0.185 g, 1.83 mmol) was added to a yellow suspension of H2sal(2-OMe)ben (0.329 g, 0.922 mmol) in 14 mL of EtOH. Copper acetate monohydrate (0.184 g, 0.912 mmol) was then added obtaining a colour change to brown / green in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL), Et2O (2 x 2 mL) and dried under vacuum for several hours, yielding 0.354 g of a brown solid (92% yield). Elemental analysis for C44H36CU2N4O6, MW = 843.9 g / mol calculated: C 62.62%; H 4.30%; N 6.64%. Found: C 61.85%; H 4.34%, N 6.74%. IR spectrum, cm’1(ATR): 3044-3010, 1601, 1586, 1531-1490, 1387, 1318, 1242, 1147-1026, 751. Mass spectrum (ESI+), m / z (intensity %): 843 [Cu2(sal(2-OMe)ben)2 + 1]+(100).

[0026] EtsN (0.150 g, 1.48 mmol) was added to a yellow suspension of H2sal(2,6-diOMe)ben (0.290 g, 0.743 mmol) in 7 mL of MeOH. Copper acetate monohydrate (0.148 g, 0.742 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 30 minutes at 0 °C, and then the precipitate was isolated by filtration, washed with cold MeOH (2 x 2 mL), Et2O (2 x 2 mL) and dried under vacuum for several hours, yielding 0.285 g of a brown solid (85% yield). Elemental analysis for C46H40CU2N4O8, MW = 903.94 g / mol calculated: C 61.12%; H 4.46%; N 6.20%. Found: C 60.82%; H 4.57%, N 6.19%. IR spectrum, cm’1(ATR): 3050-2840, 1604, 1528, 1470-1426, 1383, 1250, 1195, 1034-980, 758. Mass spectrum (ESI+), m / z (intensity %): 903 [Cu2(sal(2,6- diOMe)ben)2 + 1]+(100).

[0027] 3.4 Synthesis of [Cu2(p-sal(4-OMe)ben)2]

[0028] [Cu2(n-sal(4-OMe)ben)2]

[0029] EtsN (0.138 g, 1.36 mmol) was added to a yellow suspension of H2sal(4-OMe)ben (0.245 g, 0.680 mmol) in 10 mL of EtOH. Copper acetate monohydrate (0.138 g, 0.690 mmol) was then added obtaining a colour change to green / brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (3 mL), z'Pr2O (3 mL) and dried under vacuum for several hours, yielding 0.198 g of a brown solid (69% yield). Elemental analysis for C44H36CU2N4O6, MW = 843.89 g / mol calculated: C 62.62%; H 4.30%; N 6.64%. Found: C 63.02%; H 4.34%, N 6.83%. IR spectrum, cm’1(ATR): 3050-2835, 1607, 1534, 1467-1440, 1395, 1243, 1196, 1176, 1148, 1051-979, 750, 736.

[0030] 3.5 Synthesis of [Cu2(μ-sal(2-Cl)ben)2] H2sal(2-CI)ben

[0031] [Cu2(n-sal(2-CI)ben)2]

[0032] EtsN (0.156 g, 1.54 mmol) was added to a yellow suspension of H2sal(2-C1)ben (0.255 g, 0.699 mmol) in 10 mL of EtOH. Copper acetate monohydrate (0.154 g, 0.774 mmol) was then added obtaining a colour change to green-brown in a few minutes. After 3 h under stirring, further 5 mL of EtOH were added and then the reaction mixture was left under magnetic stirring overnight at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL), Et2O (2 x 2 mL) and dried under vacuum for several hours, yielding 0.285 g of a brown solid (96% yield). Elemental analysis for C42H30CI2CU2N4O4, MW = 852.72 g / mol calculated: C 59.16%; H 3.55%; N 6.57%. Found: C 59.23%; H 3.46%, N 6.80%. IR spectrum, cm’1(ATR): 3058-2903, 1605, 1530, 1464-1430, 1319, 1270, 1194, 1149, 1035-978, 744.

[0033] 3.6 Synthesis of [Cu2(p-sal(2)thn)i]

[0034] EtsN (2.11 g, 20.8 mmol) was added to a yellow suspension of H2sal(2)thn (1.699 g, 5.051 mmol) in 75 mL of EtOH. Copper acetate monohydrate (1.012 g, 5.070 mmol) was then added obtaining a colour change to brown in a few minutes. After 3 h under stirring at RT, the obtained dark brown solid was filtered, washed with EtOH (2 x 10 mL) and / Pr2O (2 x 10 mL) and dried under vacuum for several hours, yielding 1.398 g of the title compound (70%). Elemental analysis for C38H28CU2N4O4S2, MW = 795.88, calculated: C 57.35%, H 3.55%, N 7.04%, S 8.06%. Found: C 57.25%, H 3.54%, N 7.03%, S 8.19%. IR spectrum, cm1(ATR): 3084, 3016, 2894, 1602, 1531, 1465, 1437, 1393, 1344, 1320, 1241, 1190, 1145, 1123, 1033, 973, 750, 735, 707. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 795.0223; found: 795.0217 (100). 3.7 Synthesis of [Cu2(p-sal(3)thn)2]

[0035] EtsN (1.81 g, 17.9 mmol) was added to a yellow suspension of H2sal(2)thn (1.706 g, 5.073 mmol) in 75 mL of EtOH. Copper acetate monohydrate (1.012 g, 5.072 mmol) was then added obtaining a colour change to brown in a few minutes. After 3 h under stirring at RT, the obtained dark brown solid was filtered, washed with EtOH (2 x 10 mL) and iPr2O (2 x 10 mL) and dried under vacuum for several hours, yielding 1.695 g of the title compound (84%). Elemental analysis for C38H28CU2N4O4S2, MW = 795.88, calculated: C 57.35%, H 3.55%, N 7.04%, S 8.06%. Found: C 57.11%, H 3.52%, N 7.10%, S 8.06%. IR spectrum, cm1(ATR): 3088, 3017, 2898, 1604, 1532, 1465, 1439, 1393, 1343, 1320, 1192, 1145, 1123, 1033, 974, 845, 751, 732. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 795.0223; found: 795.0200 (100).

[0036] 3.8.1 Synthesis of [Cu2(p,-(l?)-salClmyr)2]

[0037] Solid Cu(OAc)2H2O (0.09931 g, 0.497 mmol) was added to a yellow suspension of (R )- H2salClmyr (0.20174 g, 0.539 mmol) in EtOH (8 mL) and NEts (0.11112 g, 1.10 mmol) and the resulting dark green / brown mixture was stirred at RT for 3 h. The formed dark brown solid was filtered, washed with EtOH (3 x 3 mL) and / Pr2O (3 x 3 mL) and dried under vacuum for 2 h. Yield: 0.10927 g (50%). Further title compound was isolated upon storing the reaction mixture in the fridge for 4 d (0.06016 g, 28%). Elemental analysis calcd (%) for C48H48CU2N4O4 (872.03): C 66.11, H 5.55, N 6.43. Found: C 66.22, H 5.90, N 6.30. IR-ATR (cm '): 2970, 2918, 2864, 1600, 1532, 1464, 1445, 1325, 1194, 1145, 1051, 979, 917, 849, 752. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 871.2346; found: 871.2319 (100).

[0038] 3.8.2 Synthesis of [Cu2(p,-(l?)-salClmyr)2]

[0039] Solid Cu(OAc)2H2O (0.0544 g, 0.273 mmol) was added to a yellow suspension of ( / ?)- EEsalClmyr (0.1023 g, 0.273 mmol) in EtOH (4 mL) and NEts (0.0566 g, 0.559 mmol) and the resulting dark green / brown mixture was stirred at RT for 3 h. The formed dark brown solid was filtered, washed with EtOH (3 x 3 mL) and / Pr2O (3 x 3 mL) and dried under vacuum for 2 h. Yield: 0.09696 g (82%). Elemental analysis calcd (%) for C48H48CU2N4O4 0.55H2O (881.94): C 65.37, H 5.61, N 6.35. Found: C 65.32, H 5.56, N 6.35. IR-ATR (cm '): 3015, 2974, 2926, 2827, 1608, 1533, 1464, 1440, 1348, 1318, 1246, 1194, 1147, 971, 925, 750.

[0040] 3.9 Synthesis of [Cu2(p-(4-OMe)salben)2]

[0041] [Cu2(p.-(4-OMe)salben)2]

[0042] EtsN (0.109 g, 1.08 mmol) was added to a yellow suspension of H2(4-OMe)salben (0.2333 g, 0.5974 mmol) in 8 mL of EtOH. Solid Cu(OAc)2 H2O (0.1216 g, 0.6090 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.1198 g of a light brown solid (44%). Elemental analysis calcd (%) for C46H40CU2N4O8 (903.94): C 61.12, H 4.46, N 6.20. Found: C 61.15, H 4.57, N 5.86. IR-ATR (cm '): 3002, 2936, 2839, 1592, 1520, 1485, 1439, 1314, 1217, 1117, 1025, 975, 832.

[0043] 3.10 Synthesis of [Cu2(p-(5-OMe)salben)2]

[0044] EtaN (54.5 mg, 0.538 mmol) was added to a yellow suspension of H2(5-OMe)salben (0.1005 g, 0.2575 mmol) in 4 mL of EtOH. Solid Cu(OAc)2 H2O (0.05171 g, 0.2590 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.08951 g of a brown solid (77%). Elemental analysis calcd (%) for C46H40CU2N4O8 (903.94): C 61.12, H 4.46, N 6.20. Found: C 60.97, H 4.43, N 6. 13. IR-ATR (cm '): 3062, 2928, 2827, 1623, 1592, 1532, 1456, 1307, 1215, 1157, 1026, 975, 813, 700. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 903.1517; found: 903.1331 (100).

[0045] 3.11 Synthesis of [Cu2(p-(5-F)salben)2] EtsN (57.4 mg, 0.57 mmol) was added to a yellow suspension of H2(5-F)salben (0.1004 g, 0.2742 mmol) in 4 mL of EtOH. Solid Cu(OAc)2 H2O (0.0564 g, 0.282 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 ^ 2 mL) and dried under vacuum for several hours. Yield: 0.0945 g of a brown solid (81%). Elemental analysis calcd (%) for C42H28CU2F4N4O4 (855.80): C 58.95, H 3.30, N 6.53. Found: C 58.91, H 3.17, N 6.53. IR-ATR (cm '): 3053, 3004, 2897, 1607, 1538, 1457, 1393, 1310, 1241, 1209, 1141, 1002, 925, 865, 812.

[0046] 3.12 Synthesis of [Cu2(p-(5-Cl)salben)2]

[0047] [Cu2(p.-(5-CI)salben)2]

[0048] EtsN (105.3 mg, 1.04 mmol) was added to a yellow suspension of H2(5-Cl)salben (0.2015 g, 0.5048 mmol) in 8 mL of EtOH. Solid Cu(OAc)2 H2O (0.10236 g, 0.5127 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.2074 g of a brown solid (89%). Elemental analysis calcd (%) for C42H28CU2CI4N4O4 (921.60): C 54.34, H 3.06, N 6.08. Found: C 54.37, H 3.03, N 5.99. IR-ATR (cm '): 3061, 2899, 1609, 1521, 1449, 1309, 1172, 1099, 976, 941, 876, 772. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 942.9325; found: 942.9382 (100). 3.13 Synthesis of [Cu2(p-(5-Me)salben)2]

[0049] [Cu2(p.-(5-Me)salben)2]

[0050] EtsN (61.7 mg, 0.609 mmol) was added to a yellow suspension of H2(5-Me)salben (0.1019 g, 0.2843 mmol) in 4 mL of EtOH. Solid Cu(OAc)2 H2O (0.0568 g, 0.284 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.1001 g of a brown solid (84%). Elemental analysis calcd (%) for C46H40CU2N4O4 (839.94): C 65.78, H 4.80, N 6.67. Found: C 65.78, H 4.75, N 6.64. IR-ATR (cm"1): 3059, 3004, 2911, 2853, 1619, 1529, 1468, 1382, 1313, 1251, 1137, 1045, 974, 824, 759. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + H]+: 839.1720; found: 839.1714 (100).

[0051] 3.14 Synthesis of [Cu2(p-(4-OMe)sal(2-Cl)ben)2]

[0052] [Cu2(|4-(4-OMe)sal(2-CI)ben)2] EtsN (54.5 mg, 0.538 mmol) was added to a yellow suspension of H2(4-OMe)sal(2-Cl)ben (0.1099 g, 0.2587 mmol) in 4 mL of EtOH. Solid Cu(OAc)2H2O (0.05256 g, 0.2633 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.0672 g of a brown solid (52%). Elemental analysis calcd (%) for C46H38C12CU2N4O8H2O (990.84): C 55.76, H 4.07, N 5.65. Found: C 55.85, H 3.85, N 5.45. IR-ATR (cm '): 3059, 3004, 2911, 2853, 1619, 1595, 1529, 1468, 1382, 1313, 1251, 1215, 1163,1137, 1045, 974, 824, 759.

[0053] 3.15 Synthesis of [Cu2(p-(5-OMe)sal(2-Cl)ben)2]

[0054] [Cu2(|4-(5-OMe)sal(2-CI)ben)2]

[0055] EtsN (36.4 mg, 0.359 mmol) was added to a yellow suspension of H2(5-OMe)sal(2-Cl)ben (0.7146 g, 0.1685 mmol) in 3 mL of EtOH. Solid Cu(OAc)2H2O (0.0330 g, 0.165 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.07628 g of a brown solid (95%). Elemental analysis calcd (%) for C46H38C12CU2N4O8(972.82): C 56.79, H 3.94, N 5.76. Found: C 56.85, H 4.00, N 5.73. IR-ATR (cm '): 2831, 1624, 1594, 1532, 1470, 1307, 1218, 1159, 1031, 973, 952, 824, 755. 3.16 Synthesis of [Cu2(p-(5-OMe)sal(2-OMe)ben)2]

[0056] [Cu2(n-(5-OMe)sal(2-OMe)ben)2]

[0057] EtsN (98.0 mg, 0.969 mmol) was added to a yellow suspension of H2(5-OMe)sal(2- OMe)ben (0.2004 g, 0.4763 mmol) in 8 mL of EtOH. Solid Cu(OAc)2H2O (0.0951 g, 0.0968 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.2091 g of a brown solid (91%). Elemental analysis calcd (%) for C48H44CU2N4O10 (963.99): C 59.81, H 4.60, N 5.81. Found: C 60.28, H 4.51, N 5.82. IR-ATR (cm '): 3053, 2832, 1622, 1597, 1533, 1459, 1392, 1306, 1246, 1219, 1158, 1207, 953, 824, 754. Mass spectrum (ESI ) in MeCN, m / z (intensity %): calculated for [M + H]+: 963.1728; found: 963.1677 (100).

[0058] 3.17 Synthesis of [Cu2(p-(5-Cl)sal(2-OMe)ben)2]

[0059] [Cu2(n-(5-CI)sal(2-OMe)ben)2] EtsN (98.0 mg, 0.969 mmol) was added to a yellow suspension of H2(5-Cl)sal(2-OMe)ben (0.1929 g, 0.1685 mmol) in 8 mL of EtOH. Solid Cu(OAc)2 H2O (0.0940 g, 0.471 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.2088 g of a brown solid (94%). Elemental analysis calcd (%) for C44H32CI4CU2N4O6 (981.65): C 53.84, H 3.29, N 5.71. Found: C 53.74, H 3.26, N 5.60. IR-ATR (cm"1): 2960, 2839, 1611, 1520, 1483, 1457, 1311, 1241, 1172, 1043, 982, 823, 740.

[0060] 3.18 Synthesis of [Cu2(p-(5-Cl)sal(2-NO2)ben)2]

[0061] [Cu2(g-(5-CI)sal(2-NO2)ben)2]

[0062] EtsN (94.4 mg, 0.933 mmol) was added to a yellow suspension of H2(5-Cl)sal(2-NO2)ben (0.2046 g, 0.460 mmol) in 8 mL of EtOH. Solid Cu(OAc)2 H2O (0.0898 g, 0.450 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.2123 g of a brown solid (93%). Elemental analysis calcd (%) for C42H26CI4CU2N6O8 (1011.60): C 49.87, H 2.59, N 8.31. Found: C 49.63, H 2.55, N 8.00. IR-ATR (cm-1): 1610, 1520, 1384, 1311, 1175, 1036, 978, 829, 765. 3.19 Synthesis of [Cu2(p-(5-OMe)sal(2-NO2)ben)2]

[0063] [Cu2(n-(5-OMe)sal(2-NO2)ben)2]

[0064] EtsN (69.0 mg, 0.682 mmol) was added to a yellow suspension of H2(5-OMe)sal(2- NO2)ben (0.1435 g, 0.330 mmol) in 5.5 mL of EtOH. Solid Cu(OAc)2H2O (0.0665 g, 0.333 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for several hours. Yield: 0.141 g of a brown solid (82%). Elemental analysis calcd (%) for C46H38CU2N6OI2EtOH (1040.00): C 55.44, H 4.29, N 8.08. Found: C 55.06, H 3.94, N 7.81. IR-ATR (cm"1): 2853, 1625, 1596, 1525, 1467, 1339, 1302, 1271, 1218, 1160, 1032, 954, 811, 766.

[0065] 3.20 Synthesis of [Cu2(p-(sal(2-NO2)ben)2]

[0066] H2sal(2-NO2)ben

[0067] [Cu2(n-sal(2-NO2)ben)2]

[0068] EtsN (58.1 mg, 0.574 mmol) was added to a yellow suspension of H2sal(2-NO2)ben (0.100 g, 0.266 mmol) in 4 mL of EtOH. Solid Cu(OAc)2H2O (0.050 g, 0.275 mmol) was then added obtaining a colour change to brown in a few minutes. The reaction mixture was left under magnetic stirring for 3 h at RT, and then the precipitate was isolated by filtration, washed with EtOH (2 x 2 mL) and dried under vacuum for 1 h. Yield: 0.1022 g of a brown solid (43.9%). Elemental analysis calcd (%) for C42H30CU2N6O8 (873.82): C 57.73, H 3.46, N 9.62, O 14.65. Found: C 57.5, H 3.6, N 9.6, O 14.7. IR-ATR (cm '): 3039, 3021, 2940, 2904, 1605, 1522, 1464, 1443, 1339, 1319, 1194, 1147, 1126, 1027, 979, 851, 751, 741, 713. Mass spectrum (ESI+) in MeCN, m / z (intensity %): calculated for [M + CH3CN + NH4+]+: 931.1327; found: 931.1322 (100).

[0069] 4. C-N coupling reactions

[0070] 4.1 Coupling of iodobenzene with pyrazole with CS2CO3 as base

[0071] Under inert atmosphere, iodobenzene (215 pL, 1.93 mmol, 1.5 equiv) and pyrrole (90 pL, 1.29 mmol, 1 equiv) were added to a suspension of CS2CO3 (839.2 mg, 2.58 mmol, 2 equiv) and [Cu2(p-salben)2] (5 mg, 6.45 x 10'3mmol, 0.005 equiv) in 1 mL of MeCN in a 10 mL tube with screw cap. The tube was closed and heated with an oil bath at 82°C and the reaction mixture was stirred for 16 h. The suspension was allowed to cool to RT and then the solvent was removed under reduced pressure. The obtained residue was treated with 10 mL of dichloromethane (DCM), the resulting suspension was filtered on a paper filter, and the remaining solid was washed with DCM (2 x 5 mL). The organic phase was concentrated under reduced pressure to obtain the crude product as a brown liquid that was purified via flash column chromatography on silica gel to afford 153 mg of the desired product (83% yield). The identity of the product was confirmed by comparison of theJH NMR spectrum with the commercially available sample. ‘H NMR, 298 K, CDCI3, 400 MHz: 5 (ppm) 7.45-7.38 (4H, m), 7.27-7.23 (1H, m), 7.09 (2H, t), 6.35 (2H, t).

[0072] 4.2 Coupling of iodobenzene with pyrazole with K3PO4 as base

[0073] Under inert atmosphere, iodobenzene (720 pL, 6.47 mmol, 1.5 equiv) and pyrrole (300 pL, 4.29 mmol. 1 equiv) were added to a suspension of K3PO4 (17.2 mmol, 3.65 g, 4 equiv) and [Cu2(p-salben)2] (0.0429 mmol, 33.6 mg, 0.010 equiv) in 3 mL of MeCN in a 50 mL tube with screw cap. The tube was closed and heated with an oil bath at 82°C and the reaction mixture was stirred for 16 h. The suspension was allowed to cool to RT and then the solvent was removed under reduced pressure. The obtained residue was treated with 10 mL of DCM, the obtained suspension was filtered on a paper filter, and the remaining solid was washed with DCM (2 x 5 mL). The organic phase was concentrated under reduced pressure to obtain the crude product as a brown liquid. The residual oil was purified via flash column chromatography on silica gel to afford 521 mg of the desired product (85% yield). The identity of the product was confirmed by comparison of the1H NMR spectrum with a commercially available sample.1H NMR, 298 K, CDC13, 400 MHz: 5 (ppm) 7.45-7.38 (4H, m), 7.27-7.23 (1H, m), 7.09 (2H, t), 6.35 (2H, t).

[0074] 4.3 General procedure for the screening of solvents and bases

[0075] Under inert atmosphere, a 10 mL tube was charged with the base and the catalyst. The solvent was added (1 mL), and iodobenzene and pyrrole were added to the resulting suspension. The tube was closed and heated at the indicated temperature. After the indicated time, the tube was allowed to cool to RT. The suspension was filtered with a syringe on a 0.45 pm PTFE filter. The solid on the filter was washed with the reaction solvent (3 x 3 mL). The filtrated was concentrated under reduced pressure to obtain the crude product. The external standard solution (1 mL of a 0.429 mol L“1CDCI3 solution of dimethyl sulfone) was added, 150 pL of the so- obtained solution were diluted to 700 pL with CDCI3 in an NMR tube, and the1H NMR spectrum was registered to calculate the yield.

[0076] 4.4 General procedure for the coupling of aryl halides with N-nucleophiles

[0077] Under inert atmosphere, a screw-cap glass tube equipped with a stirring bar was charged with the base, the catalyst and the solvent. To the suspension, the N-nucleophile and the aryl halide were added. The tube was closed and heated at the indicated temperature for the indicated time. The reaction mixture was filtered over 0.45 pm PTFE Syringe-Filter and the filter washed with MeCN (1-2 mL). LC-MS sample was prepared from resulting solution. Optionally, the solvent was evaporated, and the crude product purified by chromatography for additional characterization.

[0078] 4.5 Characterization data for product

Claims

Claims1. Process for the coupling of aryl halogenides with an N-nucleophile compound in the presence of dinuclear copper(II) complexes bearing substituted salben-type ligands of the formula Iwherein R1and R2are the same or different and are optionally substituted Ci-12-alkyl, aryl or heteroaryl, or hydrogen andG1, G2, G3and G4are the same or different and hydrogen or one or more substituents selected from Ci-12-alkyl, Ci-12-alkoxy, halogen Ci-12-alkyl, halogen, mono- or di- Ci-12-alkyl amino, carboxyl, C1-12 alkoxy carbonyl or nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from Ci-6-alkyl, Ci- 6-alkoxy, halogen, mono- or di- Ci-6-alkyl amino or nitro.

2. Process of claim 1, wherein R1and R2are the same and are substituents of the formula Ila, lib or liewhereinR3, R4, R5, R6and R7are the same or different and are hydrogen, Ci-12-alkyl, C1-12- alkoxy, halogen, halogen-Ci-12-alkyl, mono- or di- Ci-12-alkyl amino, nitro or R3and R4or R4and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from Ci-6-alkyl, Ci-6-alkoxy, halogen, mono- or di- Ci-6-alkyl amino or nitro,X1, X2, X3, X4and X5are the same or different and represent at least one heteroatom selected from nitrogen, oxygen or sulphur; n is 0 or 1;R8, R9and R10are the same or different and are hydrogen, Ci-12-alkyl, halogen C1-12- alkyl, hydroxy, hydroxy- Ci-12-alkyl, halogen or R8and R9together form a saturated carbocycle or a heterocycle or R8, R9and R10together form an unsaturated carbocycle.

3. Process of claim 1 or 2, wherein the aryl halogenide has the formula IIIwhereinX6, X7, X8, X9and X10are the same or different and represent carbon or at least one heteroatom selected from nitrogen, oxygen or sulphur;R19, R20, R21, R22and R23are the same or different and are hydrogen, Ci-12-alkyl, C2-12- alkenyl, C2-i2-alkinyl, Ci-12-alkoxy, halogen, halogen-Ci-12-alkyl, mono- or di- Ci-12-alkyl amino or cyano, or R19and R20or R20and R21or R21and R22or R22and R23together with the ringthey are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from Ci-6-alkyl, Ci-6-alkoxy, halogen, mono- or di- Ci-6-alkyl amino or nitro; n is 0 or 1 andZ is a halogen atom.

4. Process of any one of claims 1 to 3, wherein the N-nucleophile can be selected from compounds of the formulaewhereinR11, R12, R13, R14, R15, R16R17and R18are the same or different and are hydrogen, C1-12- alkyl, Ci-12-alkoxy, aryl, halogen, halogen-Ci-12-alkyl, nitro, hydroxy, mono- or di- Ci-12-alkyl amino or R15and R16together with the nitrogen they are attached to, form a saturated heterocycle 5-or 6-member heterocycle;X11, X12, X13and X14are the same or different and represent a carbon atom optionally substituted with Ci-12-alkyl, aryl-Ci-12-alkyl, Ci-6-alkoxy, halogen, halogen-Ci-12-alkyl and at least one further heteroatom selected from nitrogen, oxygen or sulphur.

5. Process of anyone of claims 1 to 4, wherein a base is present, which is selected from alkali salts of mineral acids or organic acids or from alkali alcoholates.

6. Process of anyone of claims 1 to 5, wherein the reaction takes place in the presence of an organic solvent at a reaction temperature between 20 °C and 200 °C.

7. Dinuclear copper(II) complex bearing substituted salben-type ligands having the formula IwhereinR1and R2are the same or different and are optionally substituted Ci-12-alkyl, aryl or heteroaryl, or hydrogen andG1, G2, G3and G4are the same or different and stand for hydrogen or one or more substituents selected from Ci-12-alkyl, Ci-12-alkoxy, halogen, halogen Ci-12-alkyl, mono- or di- Ci-12-alkyl amino, carboxyl, Ci-12-alkoxy carbonyl or nitro or G1, G2, G3and G4, independently of each other, together with the phenyl ring they are attached to form a fused aryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6- alkyl, Ci-6-alkoxy, halogen, mono- or di- Ci-6-alkyl amino or nitro;R1and R2are the same and are substituents of the formula Ila, lib or lieR3, R4, R5, R6and R7are the same or different and are hydrogen, C1-12-alkyl, C1-12- alkoxy, halogen, halogen- C1-12-alkyl, mono- or di- C1-12-alkyl amino, nitro or R3and R4or R4and R5or R5and R6or R6and R7together with the phenyl ring they are attached to form a fusedaryl ring with two or three rings, which are optionally substituted with one or more substituents selected from C1-6-alkyl, C1-6-alkoxy, halogen, mono- or di- C1-6-alkyl amino or nitro.X1, X2, X3, X4and X5are the same or different and represent at least one heteroatom selected from nitrogen, oxygen or sulphur; n is 0 or 1;R8, R9and R10are the same or different and are hydrogen, C1-12-alkyl, halogen C1-12- alkyl, hydroxy, hydroxy- Ci-12-alkyl, halogen or R8and R9together form a saturated carbocycle or a heterocycle or R8, R9and R10together form an unsaturated carbocycle, with the proviso that compounds with R1and R2being hydrogen, or R1and R2having the formula Ila and wherein R3, R4, R6and R7are hydrogen, while R5is hydrogen, chlorine, methyl, or nitro, are excluded.

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