HETEROCYCLES

Paper | Special issue | Vol. 80, No. 2, 2010, pp. 957-975
Received, 23rd July, 2009, Accepted, 11th September, 2009, Published online, 14th September, 2009.
DOI: 10.3987/COM-09-S(S)68

■ Synthesis of Polyazamacrocycles Comprising 6,6’-Diamino-2,2’-bipyridine Moieties via Pd-Catalyzed Amination

Alexei D. Averin,* Alexei N. Uglov, Alexei K. Buryak, Alla G. Bessmertnykh, Roger Guilard, and Irina P. Beletskaya*

Department of Chemistry, Moscow State University, Leninskie Gory 1/3, 119991, Moscow, Russia

Abstract

Pd-catalyzed amination of 6,6’-dibromo-2,2’-bipyridine with a variety of di-, tri-, tetraamines and oxadiamines was carried out for the synthesis of a new class of polyazamacrocycles comprising a 6,6’-diamino-2,2’-bipyridine unit. The obtained results of the catalytic amination reaction were shown to be dramatically dependent on the nature of the amines, mainly on the length of the amine chain. The shortest propane-1,3-diamine and butane-1,4-diamine derivatives provided only cyclic dimers whereas the longest di- and trioxadiamines gave desired macrocycles in very good yields. The formation of cyclic oligomers was observed in all cases. Different reaction conditions leading to cyclic dimers were explored.

INTRODUCTION
2,2’-Bipyridine (bipy) and its derivatives are well known as chelating ligands and serve as basic building blocks for various transition metal complexes. For example, bipy-ruthenium(II) complexes showed characteristic emission spectra and have been the subject of intense studies.1-3 Different 2,2’-bipyridine derivatives were synthesized to evaluate the influence of the substituents upon the metal ion affinity of ligands and physical properties of the complexes.4-17 Among these compounds, 6,6’-diamino-2,2’- bipyridine derivatives are of special interest due to their steric hindrance and original optical properties.
Contrary to most of the non-fluorescent derivatives, bipyridines bearing an amino-group at C-6 position exhibit oxygen-independent fluorescence with high quantum yield.18 On the other hand, 6,6’-disubstituted bipyridines give almost exclusively mono- and bis-bipy complexes with transition metals,19-22 while many other derivatives usually form stable tris-bipy complexes. Therefore, 6,6’-diamino-2,2’-bipyridines and their complexes were extensively studied as models to mimic biological systems,23-28 to extract or transport transition metal cations and anions,29-32 in catalysis33-36 or sensoring.37, 38 However, chemical modification of parent 6,6’-diamino-2,2’-bipyridine is not a simple task. The acylation of the amino groups was often used to prepare tetradentate (N2O2) ligands.19, 24-26, 32, 33, 35 The alkylation of the amino groups can be achieved after their deprotonation under harsh conditions.18 The search of new synthetic routes to these derivatives may allow to develop a new strategy for designing pyridine-based fluorescent sensors or biomimetic models. The catalytic amination reaction of 6,6’-dibromo-2,2’-bipyridine can be an efficient method to prepare these derivatives. This reaction was used to obtain bismacrocyclic derivatives possessing 6,6’-diaminobipyridine moiety as a rigid spacer. Both azacrown ethers and tetraazamacrocycles can be linked by this fragment using Pd-catalyzed amination reactions.39, 40 Moreover, Cu(I)-mediated amination was applied in the synthesis of camphor sultam based chiral bipyridines.36 Here we report the synthesis of a new family of macrocyclic ligands incorporating one or two fluorescent 6,6’-diaminobipyridine moieties using Buchwald-Hartwig amination reaction.41


RESULTS AND DISCUSSION
We have decided to apply Pd-catalyzed amination of aryl halides for the synthesis of polyazamacrocycles which contain a 6,6’-diamino-2,2’-bipyridine moiety. Based on our knowledge in the synthesis of a great variety of macrocycles using this approach,42-45 the conditions of the synthesis of the pyridine-based macrocycles starting from 2,6- and 3,5-dibromopyridines46-49 was a priori the most relevant way to synthesize the aimed derivatives. The reaction of equimolar amounts of 6,6’-dibromo-2,2’-bipyridine 1 and polyamines 2a-j (Scheme 1) was carried out in the presence of the catalytic system Pd(dba)2/BINAP (8/9 mol%) which was found to be the most convenient and universal system for the arylation of mono- and polyamines.50 Diluted solutions (c = 0.02 M) of starting compounds in dioxane and sodium tert-butoxide as a base were used and the completion of the reactions were obtained after 15 h of reflux. Reaction mixtures were analyzed using 1H NMR spectroscopy and target macrocycles 3 were purified by chromatography on silica gel. The experimental data are given in Table 1.
It was obvious that diamines 2a,b would not give the corresponding monocycles, but rather the cyclic dimers 4. Indeed, the shortest propane-1,3-diamine derivative (2a) afforded cyclodimer 4a in 21% yield (Table 1, entry 1), and its analogue 2b gave 4b (n = 1) in a better yield (35% yield) (entry 2) while in parallel a mixture of cyclotrimer and cyclotetramer was isolated.

Much longer decane-1,10-diamine (2c) produced target macrocycle 3c in a good yield of 30% (entry 3), because the chain length was quite sufficient to favor the ring closure. We have also studied the reactivity of triamine 2d using the same experimental conditions. According the length of the molecule (9 atoms), the yield of the monocycle 3d was very poor (entry 4) and a notable amount of cyclooligomers 4d (n=1-3) was produced as well as linear oligomers. Surprisingly, the reaction of the tetraamine 2e afforded the corresponding macrocycle 3e, but in a low 10% yield (entry 5). To improve the process a double amount of the catalyst was used (entry 6) but no significant change was observed. Another electron donor 2-dicyclohexylphosphino-2'-dimethylamino-1,1'-biphenyl ligand which could stimulate diamination of dihaloarenes was also studied without success. It has to be noted that the yield of cyclodimer 4e (n=1) was also low, while the formation of cyclic and acyclic oligomers of higher mass were observed. The presence of cyclooligomers 4e (n = 2-4) was established by MALDI-TOF spectroscopy, and acyclic oligomers were observed as admixtures by NMR. We suggest that the low yield observed for compound 3e is due to the presence of two ethylenediamine fragments in the tetraamine 2e. These fragments may form 5-membered chelate complexes with Pd which cannot be intermediates in the amination catalytic cycle. The same low reactivity of polyamines comprising repeating ethylenediamine units in the reaction with dihalopyridines was already observed by our groups.46, 48 This is in good agreement with the best yields observed with tetraamines 2f,g: macrocycle 3f was synthesized in 20% yield (entry 7), while compound 3g was obtained in 29% yield (entry 8).

Finally, we have also studied the reaction of various oxygen-containing diamines with dibromide derivative 1. The length of dioxadiamine 2h was not sufficient to obtain the corresponding macrocycle 3h in a good yield (entry 9), and we have observed mainly the formation of cyclodimer and higher mass oligomers. The evolution of the reaction changed dramatically when the long dioxadiamine 2i was used since the macrocycle 3i was obtained in a very good yield (47%, entry 10). The same high yield was also observed with trioxadiamine 2j (48%, entry 11), and it is remarkable to note that these yields of the cyclisation reaction obtained via catalytic amination of dihaloarenes are among the highest ever observed in such a cyclization reaction.42-49 For example, they surpass substantially the yields obtained for the pyridine-based macrocycles described previously by our groups.47, 49 One possible interpretation of such variations of the monocycle yields can be due to the template effect of sodium cations present in the reaction mixtures which form more stable complexes with oxadiamines compared to polyamines. Chromatographic purification of the macrocycles 3c,h-j – derivatives of diamines was more easy than for the macrocycles 3d-g – derivatives of tri- and tetraamines, this is evidenced by the comparison of the reaction before and after chromatography.
Macrocycles 3 can be easily discriminated in the reaction mixtures from cyclic oligomers 4 by 1H NMR spectra. H3,3’ protons of the bipyridine moiety in the macrocycles were observed in the region 7.0-7.1 ppm, whereas the same protons of cyclic dimers are downfield shifted (7.4-7.5 ppm). The chemical shift of these protons depends on the size of the cycle: the larger is the cavity, the more downfield shifted the signal of these protons. These data might be due to the s-cis configuration (which is the only possible one) of the bipyridine moiety in monocycles and to s-trans configuration in the case of cyclic and linear oligomers. The ring current and the electrostatic effect of the nitrogen lone pair are responsible for the anomalous downfield shift of H3,3’ protons of the bypiridine moiety of cyclic and linear oligomers, while for monocycles 3 the second parameter does not act.37
UV spectra of the macrocycles 3 are similar to the parent 6,6’-diaminopyridine and characterized by a broad absorption band in the region 340-350 nm which corresponds to a π-π* transfer.51 The starting dibromide 1 possesses two close absorption bands centered at 295 and 308 nm. Thus, as expected, the substitution of the halogen atoms by the amino groups induces a significant bathochrome shift of the absorption band.
Cyclodimers of type 4 are of great interest due to the presence of two 2,2’-bipyridine moieties and two polyamine chains which can be suitable for the coordination of metal cations or polar organic molecules. In our previous works we have elaborated two different approaches to cyclic dimers possessing two aromatic moieties in the macrocycle: via N,N’-di(haloaryl)susbtituted polyamines and via bis(polyamine)substituted arenes.43, 47, 49 We have studied these two routes for the synthesis of cyclodimers 4 to determine the best way of synthesis. The first approach proved to be totally useless for the synthesis of desired N,N’-di(bromobipyridine)susbtituted diamines which were not obtained even in trace amounts. We tried other conditions for the synthesis of cyclodimers by reacting 1 equivalent of dibromide 1 with 3 equivalents of di- and triamines 2d,h-j, and the resulting bis(amino)bipyridines 5d,h-j were further reacted in situ with two equivalents of dibromide 1 (Scheme 2). The experimental data are detailed in Table 2. Intermediate compounds 5 were synthesized in enough high yields according to NMR and MALDI-TOF spectra of the reaction mixtures (ca 50%), but the yields of the target cyclodimers 4 were lower than those obtained in the above detailed data by reacting equimolar amounts of 6,6'-dibromo-2,2'-bipyridine with polyamines (Table 1). Cyclic oligomers of higher masses 4 (n = 2, 3) were also formed by cyclization of oligomeric by-products 6 obtained during the first step of the reaction as observed on MALDI-TOF spectra.

It has to be noted that the main products in all syntheses were linear oligomers detected on NMR spectra as complex mixtures. This is the proof that the cyclization of compounds 5 and 6 with dibromide 1 proceeds reluctantly due to the unfavorable s-trans configuration of compound 5 and 6. Surprisingly, mono-cycles 3 were also isolated in quite reasonable yields due to the reaction of an excess of polyamine formed in the reaction mixture with dibromide 1 added at the second step of the synthesis. In the case of

short triamine 2d and dioxadiamine 2h we have obtained monocycles 3d,h in substantially higher yields (19% and 44% respectively) than for the cyclization reactions carried out with equimolar amounts of starting compounds (Table 1, entries 4, 9). This result may be due to the higher concentration of dibromobipyridine at the second step of the synthesis of cyclodimers. Indeed, we carried out the reaction of equimolar amounts of dibromide 1 with triamine 2d at higher concentration (c = 0.05 M instead of 0.02 M) and obtained corresponding macrocycle 3d in 10% yield. The same reaction gave 11% yield of the cyclodimers 4d.
In conclusion, we have elaborated an efficient one-step synthesis of the nitrogen- and oxygen-containing macrocycles comprising 6,6'-diamino-2,2'-bipyridine moiety. The yields of the target compounds depend on the nature of polyamines employed. We have studied the formation of cyclooligomeric by-products and proposed the synthesis of cyclic dimers using N,N'-di(bromobipyridyl)substituted polyamines.

EXPERIMENTAL
All chemicals were purchased from Aldrich and Acros companies and used without further purification. Pd(dba)2 was synthesized according to a procedure already described.52 Commercial dioxane was distilled over NaOH and sodium under argon, dichloromethane and methanol were distilled prior to use. Column chromatography was carried out using silica gel (40-60 µm) purchased from Fluka. 1H and 13C NMR spectra were registered in CDCl3 using Bruker Avance 400 spectrometer at 400 and 100.6 MHz respectively. Chemical shift values δ are given in ppm and coupling constants J in Hz. MALDI-TOF spectra were recorded with Bruker Ultraflex spectrometer using 1,8,9-trihydroxyanthracene as matrix and PEGs as internal standards. UV spectra were registered on Perkin-Elmer Lambda-40 spectrometer in CH2Cl2.

Typical procedure for the synthesis of macrocycles 3c-k and cyclodimers 4a,b (n=1).
A two-neck flask (25 mL) flushed with dry argon, equipped with a magnetic stirrer and condenser was charged with 6,6'-dibromo-2,2'-bipyridine (1) (0.25 mmol, 79 mg), Pd(dba)2 (11 mg, 8 mol%), BINAP (14 mg, 9 mol%) and absolute dioxane (12 mL). The mixture was stirred for 2 min, then appropriate amine 2a-k (0.25 mmol) was added followed by sodium tert-butoxide (0.75 mmol, 72 mg). The reaction mixture was refluxed for 15 h, after cooling down to ambient temperature the residue was filtered off, dioxane evaporated in vacuo, and the residue was analyzed by NMR spectroscopy. Column chromatography was carried out using a sequence of eluents: CH2Cl2, CH2Cl2-MeOH 50:1 – 3:1, CH2Cl2-MeOH-NH3aq 100:20:1 – 10:4:1.

7,11,22,26,31,32,33,34-Octaazapentacyclo[25.3.1.12,6.112,16.117,21]tetratriaconta-1(31),2(34),3,5,12(33),13,15,17(32),18,20,27,29-dodecaene (4a) (n = 1). Synthesized from 19 mg (0.25 mmol) of diamine 2a. Eluent CH2Cl2-MeOH 3:1. Yield 12 mg (21%). Pale-yellow solid. Mp 214-215 oC. UV λmax (CH2Cl2) 352 (ε 11000). 1H NMR (CDCl3): δ 1.80-1.85 (m, 4H), 3.29-3.34 (m, 8H), 6.35 (d, J = 8.1 Hz, 4H), 6.88 (d, J = 7.5 Hz, 4H), 7.35 (t, J = 7.8 Hz, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 29.3 (2C), 38.2 (4C), 108. 5 (4C), 110.7 (4C), 138.0 (4C), quaternary carbons were not observed due to broad signals of aromatic carbons (25-100 Hz). HRMS (MALDI-TOF) m/z calcd for C26H28N8 [M+] 452.2437, found 452.2451.

7,12,23,28,33,34,35,36-Octaazapentacyclo[27.3.1.12,6.113,17.118,22]hexatriaconta-1(33),2(36),3,5,13(35),14,16,18(34),19,21,29,31-dodecaene (4b) (n = 1). Synthesized from 22 mg (0.25 mmol) of diamine 2b. Eluent CH2Cl2-MeOH 3:1. Yield 21 mg (35%). Pale-yellow solid. Mp 208-210 oC. UV λmax (CH2Cl2) 347 (ε 8900). 1H NMR (CDCl3): δ 1.86-1.91 (m, 8H), 3.32-3.37 (m, 8H), 6.58 (d, J = 8.1 Hz, 4H), 7.16 (d, J = 7.4 Hz, 4H), 7.56-5.61 (m, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 25.5 (4C), 41.0 (4C), 108.5 (4C), 108.9 (4C), 138.4 (4C), quaternary carbons were not observed due to broad signals of aromatic carbons (30-40 Hz). HRMS (MALDI-TOF) m/z calcd for C28H32N8 [M+] 480.2750, found 480.2717.

Mixture of cyclotrimer 4b (n = 2) and cyclotetramer 4b (n = 3). Obtained as by-products in the synthesis of cyclodimer 4b (n = 1). Eluent CH2Cl2-MeOH 20:1-10:1. Yield 30 mg (50%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.73-1.78 (m, 4(n+1)H), 3.33-3.38 (m, 4(n+1)H), 6.34-6.38 (m, 2(n+1)H), 7.38-7.42 (m, 2(n+1)H), 7.45-7.50 (m, 2(n+1)H), NH protons were not observed. 13C NMR (CDCl3): δ 26.3-26.7 (m, 2(n+1)C), 41.5 (2(n+1)C), 106.6 (2(n+1)C), 107.0 (2(n+1)C), 138.3 (2(n+1)C), quaternary carbons were not observed due to broad signals of aromatic carbons (20-35 Hz). MS (MALDI-TOF) m/z calcd for C42H48N12 [M+] 720.41, found 720.55 (4b (n = 2)); calcd for C56H64N16 [M+] 960.55, found 960.63 (4b (n = 3)). In this work the composition of the mixtures of cyclic oligomers was not determined precisely.

7,18,23,24-Tetraazatricyclo[17.3.1.12,6]tetracosa-1(23),2(24),3,5,19,21-hexaene (3c). Synthesized from 43 mg (0.25 mmol) of diamine 2c. Eluent CH2Cl2-MeOH 20:1-10:1. Yield 24 mg (30%). Pale-yellow solid. Mp 123-124 oC. UV λmax (CH2Cl2) 344 (ε 9700). 1H NMR (CDCl3): δ 1.30-1.34 (m, 4H), 1.38-1.42 (m, 8H), 1.70-1.75 (m, 4H), 3.52 (t, J = 7.6 Hz, 4H), 6.59 (bs, 2H), 7.05 (d, J = 7.4 Hz, 2H), 7.45 (t, J = 7.9 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 26.1 (2C), 26.4 (2C), 27.3 (2C), 28.4 (2C), 41.6 (2C), 109.9 (4C), 138.1 (2C), 156.3 (2C), 158.2 (2C). HRMS (MALDI-TOF) m/z calcd for C20H28N4 [M+] 324.2314, found 324.2343.

7,18,29,40,45,46,47,48-Octaazapentacyclo[39.3.1.12,6.119,23.124,28]octatetraconta-1(45),2(48),3,5,19(47),20,22,24(46),25,27,41,43-dodecaene (4c) (n =1 ). Obtained as the second product in the synthesis of macrocycle 3c. Eluent CH2Cl2-MeOH 3:1. Yield 26 mg (32%). Pale-yellow solid. Mp 109-111 oC. UV λmax (CH2Cl2) 345 (ε 14000). 1H NMR (CDCl3): δ 1.26-1.31 (m, 16H), 1.34-1.39 (m, 8H), 1.59-1.63 (m, 8H), 3.31 (t, J = 6.6 Hz, 8H), 6.39 (d, J = 7.7 Hz, 4H), 7.43 (bs, 4H), 7.51 (t, J = 7.5 Hz, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 27.0 (4C), 28.7 (4C), 29.3 (4C), 29.6 (4C), 42.3 (4C), 106.5 (4C), 112.9 (4C), 138.7 (4C), 152.4 (4C), 158.0 (4C). HRMS (MALDI-TOF) m/z calcd for C40H56N8 [M+] 648.4628, found 648.4620.

Mixture of cyclotrimer 4с (n = 2) and cyclotetramer 4с (n = 3). Obtained as by-products in the synthesis of macrocycle 3с. Eluent CH2Cl2-MeOH-NH3aq 100:20:1. Yield 12 mg (15%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.26-1.40 (m, 12(n+1)H), 1.61 (t, J = 7.5 Hz, 4(n+1)H), 3.29 (t, J = 5.8 Hz, 4(n+1)H), 4.57 (bs, 2(n+1)H), 6.35 (d, J = 6.0 Hz, 2(n+1)H), 7.47-7.53 (m, 4(n+1)H). 13C NMR (CDCl3): δ 27.1 (2(n+1)C), 28.7-29.6 (m, 6(n+1)C), 42.4 (2(n+1)C), 106.1 (2(n+1)C), 110.0 (2(n+1)C), 138.0 (2(n+1)C), 155.1 (2(n+1)C), 158.4 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C60H84N12 [M+] 972.69, found 972.34 (4c (n = 2)); calcd for C80H112N16 [M+] 1296.93, found 1296.78 (4c (n = 3)).
7,11,15,20,21-Pentaazatricyclo[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaene (3d). Synthesized from 33 mg (0.25 mmol) of triamine 2d when running the reaction in 5 mL dioxane. Eluent CH2Cl2-MeOH-NH3aq 100:20:3. Yield 7 mg (10%). Pale-yellow solid. Mp 135-137 oC. UV λmax (CH2Cl2) 351 (ε 6600). 1H NMR (CDCl3): δ 1.95-2.00 (m, 4H), 3.03 (t, J = 5.6 Hz, 4H), 3.49 (t, J = 5.3 Hz, 4H), 6.38 (d, J = 8.2 Hz, 2H), 7.05 (d, J = 7.6 Hz, 2H), 7.33 (t, J = 7.9 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 29.2 (2C), 36.5 (2C), 46.2 (2C), 109.6 (2C), 110.8 (2C), 137.8 (2C), 153.8 (2C), 159.2 (2C). HRMS (MALDI-TOF) m/z calcd for C16H21N5 [M+] 283.1797, found 283.1819. Spectral data for cyclic oligomers 4d (n = 1-3) are given below.

7,10,14,17,22,23-Hexaazatricyclo[16.3.1.12,6]tricosa-1(22),2(23),3,5,18,20-hexaene (3e). Synthesized from 40 mg (0.25 mmol) of tetraamine 2e. Eluent CH2Cl2-MeOH-NH3aq 100:25:5. Yield 8 mg (10%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.57 (quintet, J = 6.0 Hz, 2H), 2.79 (t, J = 5.8 Hz, 4H), 2.90 (t, J = 5.9 Hz, 4H), 3.56 (q, J = 5.9 Hz, 4H), 5.13 (bs, 2H), 6.40 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 7.4 Hz, 2H), 7.40 (t, J = 7.9 Hz, 2H), NH protons of dialkylamino groups were not observed. 13C NMR (CDCl3): δ 28.7 (1C), 41.9 (2C), 48.2 (2C), 49.2 (2C), 108.2 (2C), 111.1 (2C), 137.6 (2C), 155.3 (2C), 158.4 (2C). HRMS (MALDI-TOF) m/z calcd for C17H24N6 [M+] 312.2062, found 312.2093.

7,10,14,17,28,31,35,38,43,44,45,46-Dodecaazapentacyclo[37.3.1.12,6.118,22.123,27]hexatetraconta-1(43),2(46),3,5,18(45),19,21,23(44),24,26,39,41-dodecaene (4e) (n = 1). Obtained as by-product in the synthesis of macrocycle 3e. Eluent CH2Cl2-MeOH-NH3aq 100:25:5. Yield 4 mg (5%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.58 (quintet, J = 5.7 Hz, 4H), 2.64 (t, J = 7.0 Hz, 8H), 2.85 (t, J = 5.7 Hz, 8H), 3.49 (t, J = 5.0 Hz, 8H), 6.28 (d, J = 8.2 Hz, 4H), 7.14 (d, J = 7.6 Hz, 4H), 7.47 (t, J = 7.6 Hz, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 29.3 (2C), 41.6 (4C), 47.9 (4C), 48.2 (4C), 107.2 (4C), 110.1 (4C), 137.8 (4C), 155.3 (4C), 159.0 (4C). HRMS (MALDI-TOF) m/z calcd for C34H48N12 [M+] 624.4125, found 624.4103.

Mixture of cyclotrimer 4e (n = 2), cyclotetramer 4e (n = 3) and cyclopentamer 4e (n = 4). Obtained as by-products in the synthesis of macrocycle 3e. Eluent CH2Cl2-MeOH-NH3aq 100:25:5. Yield 12 mg (15%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.61-1.66 (m, 2(n+1)H), 2.58-2.74 (m, 8(n+1)H), 3.38-3.47 (m, 4(n+1)H), 6.31-6.45 (m, 2(n+1)H), 7.44-7.65 (m, 4(n+1)H), NH protons were not observed. 13C NMR (CDCl3): δ 28.1 ((n+1)C), 41.6 (2(n+1)C), 48.1 (2(n+1)C), 48.9 (2(n+1)C), 109.9-110.2 (m, 4(n+1)C), 137.8-138.0 (m, 2(n+1)C), 155.3 (2(n+1)C), 158.3 + 158.4 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C51H72N18 [M+] 936.62, found 936.31 (4e (n = 2)); calcd for C68H96N24 [M+] 1248.82, found 1248.64 (4e (n = 3)); calcd for C85H120N30 [M+] 1561.03, found 1561.27 (4e (n = 4)).

7,11,14,18,23,24-Hexaazatricyclo[17.3.1.12,6]tetracosa-1(23),2(24),3,5,19,21-hexaene (3f). Synthesized from 44 mg (0.25 mmol) of tetraamine 2f. Eluent CH2Cl2-MeOH-NH3aq 100:20:3. Yield 16 mg (20%). Pale-yellow solid. Mp 108-110 oC. UV λmax (CH2Cl2) 348 (ε 9200). 1H NMR (CDCl3): δ 1.83 (quintet, J = 5.5 Hz, 4H), 2.56 (s, 4H), 2.72 (t, J = 5.3 Hz, 4H), 3.61 (t, J = 6.4 Hz, 4H), 5.21 (bs, 2H), 6.36 (d, J = 8.2 Hz, 2H), 7.06 (d, J = 7.4 Hz, 2H), 7.41 (t, J = 7.8 Hz, 2H), NH protons of dialkylamino groups were not observed. 13C NMR (CDCl3): δ 29.3 (2C), 40.0 (2C), 47.5 (2C), 49.1 (2C), 107.3 (2C), 110.7 (2C), 137.6 (2C), 155.2 (2C), 159.1 (2C). HRMS (MALDI-TOF) m/z calcd for C18H26N6 [M+] 326.2219, found 326.2262.

7,11,14,18,29,33,36,40,45,46,47,48-Dodecaazapentacyclo[39.3.1.12,6.119,23.124,28]octatetraconta-1(45),2(48),3,5,19(47),20,22,24(46),25,27,41,43-dodecaene (4f) (n = 1). Obtained as by-product in the synthesis of macrocycle 3f. Eluent CH2Cl2-MeOH-NH3aq 100:25:5. Yield 12 mg (15%). Pale-yellow glassy solid. UV λmax (CH2Cl2) 348 (ε 21000). 1H NMR (CDCl3): δ 1.69 (quintet, J = 6.3 Hz, 8H), 2.58 (s, 8H), 2.61 (t, J = 6.3 Hz, 8H), 3.37 (t, J = 6.0 Hz, 8H), 5.06 (bs, 4H), 6.29 (J = 8.2 Hz, 4H), 7.44 (t, J = 7.8 Hz, 4H), 7.52 (d, J = 7.4 Hz, 4H), NH protons of dialkylamino groups were not observed. 13C NMR (CDCl3): δ 29.7 (4C), 40.1 (4C), 47.2 (4C), 49.0 (4C), 106.7 (4C), 110.0 (4C), 138.0 (4C), 154.9 (4C), 158.5 (4C). HRMS (MALDI-TOF) m/z calcd for C36H52N12 [M+] 652.4438, found 652.4417.

7,11,15,19,24,25-Hexaazatricyclo[18.3.1.12,6]pentacosa-1(24),2(25),3,5,20,22-hexaene (3g). Synthesized from 47 mg (0.25 mmol) of tetraamine 2g. Eluent CH2Cl2-MeOH-NH3aq 100:20:3-100:25:5. Yield 25 mg (29%). Pale-yellow solid. Mp 112-113 oC. UV λmax (CH2Cl2) 347 (ε 8600). 1H NMR (CDCl3): δ 1.39 (quintet, J = 5.7 Hz, 2H), 1.85 (bs, 4H), 2.52 (t, J = 5.9 Hz, 4H), 2.68 (t, J = 4.8 Hz, 4H), 3.58 (bs, 4H), 5.20 (bs, 2H), 6.36 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 7.4 Hz, 2H), 7.43 (t, J = 7.8 Hz, 2H), NH protons of dialkylamino groups were not observed. 13C NMR (CDCl3): δ 28.7 (1C), 29.4 (2C), 39.7 (2C), 46.6 (2C), 47.3 (2C), 107.9 (2C), 110.7 (2C), 137.9 (2C), 155.5 (2C), 159.0 (2C). HRMS (MALDI-TOF) m/z calcd for C19H28N6 [M+] 340.2375, found 340.2395.

10,13-Dioxa-7,16,21,22-tetraazatricyclo[15.3.1.12,6]docosa-1(21),2(22),3,5,17,19-hexaene (3h). Synthesized from 37 mg (0.25 mmol) of dioxadiamine 2h. Eluent CH2Cl2-MeOH-NH3aq 100:20:1. Yield 10 mg (13%). Pale-yellow solid. Mp 114-115 oC. 1H NMR (CDCl3): δ 3.46-3.51 (m, 4H), 3.74 (s, 4H), 3.85 (t, J = 7.2 Hz, 4H), 5.00 (bs, 2H), 6.37 (d, J = 8.2 Hz, 2H), 7.01 (d, J = 7.4 Hz, 2H), 7.38 (t, J = 7.8 Hz, 2H). 13C NMR (CDCl3): δ 41.5 (2C), 69.2 (2C), 69.7 (2C), 108.7 (2C), 111.2 (2C), 137.2 (2C), 154.7 (2C), 158.3 (2C). HRMS (MALDI-TOF) m/z calcd for C16H20N4O2 [M+] 300.1586, found 300.1528.

10,13,30,33-Tetraoxa-7,16,27,36,41,42,43,44-octaazapentacyclo[35.3.1.12,6.117,21.122,26]tetratetra-conta-1(41),2(44),3,5,17(43),18,20,22(42),23,25,37,39-dodecaene (4h) (n = 1). Obtained as by-product in the synthesis of macrocycle 3h. Eluent CH2Cl2-MeOH 10:1. Yield 15 mg (20%). Pale-yellow solid. Mp 91-93oC. UV λmax (CH2Cl2) 342 (ε 20000). 1H NMR (CDCl3): δ 3.53 (t, J = 5.2 Hz, 8H), 3.64 (s, 8H), 3.69 (t, J = 5.5 Hz, 8H), 5.00 (bs, 4H), 6.26 (d, J = 8.1 Hz, 4H), 7.29 (t, J = 7.8 Hz, 4H), 7.44 (t, J = 7.9 Hz, 4H). 13C NMR (CDCl3): δ 41.8 (4C), 69.9 (4C), 70.3 (4C), 107.5 (4C), 110.3 (4C), 137.8 (4C), 154.6 (4C), 157.9 (4C). HRMS (MALDI-TOF) m/z calcd for C32H40N8O4 [M+] 600.3173, found 600.3153.

Mixture of cyclotrimer 4h (n = 2), cyclotetramer 4h (n = 3), cyclopentamer 4h (n = 4) and cyclohexamer 4h (n = 5). Obtained as by-products in the synthesis of macrocycle 3h. Eluent CH2Cl2-MeOH-NH3aq 100:20:1. Yield 20 mg (26%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 3.57-3.62 (m, 4(n+1)H), 3.64 (s, 4(n+1)H), 3.68-3.73 (m, 4(n+1)H), 6.35 (d, J = 8.2 Hz, 2(n+1)H), 7.42 (t, J = 7.6 Hz, 2(n+1)H), 7.59 (d, J = 7.2 Hz, 2(n+1)H), NH protons were not observed. 13C NMR (CDCl3): δ 41.6 (2(n+1)C), 70.0 (2(n+1)C), 70.2 (2(n+1)C), 107.5 (2(n+1)C), 110.1 (2(n+1)C), 137.8 (2(n+1)C), 154.7 (2(n+1)C), 158.0 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C64H80N16O8 [M+] 1200.63, found 1200.55 (4h (n = 3)); calcd for C80H100N20O10 [M+] 1500.76, found 1500.72 (4h (n = 4)); calcd for C96H120N24O12 [M+] 1800.96, found 1800.78 (4h (n = 5)), data for cyclotrimer 4h (n = 2) vide infra.

11,16-Dioxa-7,20,25,26-tetraazatricyclo[19.3.1.12,6]hexacosa-1(25),2(26),3,5,21,23-hexaene (3i). Synthesized from 51 mg (0.25 mmol) of dioxadiamine 2i. Eluent CH2Cl2-MeOH 10:1. Yield 42 mg (47%). Pale-yellow solid. Mp 93-95 oC. UV λmax (CH2Cl2) 345 (ε 7100). 1H NMR (CDCl3): δ 1.71-1.73 (m, 4H), 1.97 (quintet, J = 5.4 Hz, 4H), 3.40-3.45 (m, 8H), 3.59 (t, J = 5.2 Hz, 4H), 6.61 (bs, 2H), 7.06 (d, J = 7.4 Hz, 2H), 7.51 (t, J = 7.9 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 27.0 (2C), 28.7 (2C), 42.0 (2C), 70.5 (2C), 71.4 (2C), 107.2 (2C, line width 70 Hz), 109.8 (2C), 138.7 (2C), 157.9 (2C), one quaternary carbon was not observed due to broad signal. HRMS (MALDI-TOF) m/z calcd for C20H28N4O2 [M+] 356.2212, found 356.2222.

11,16,35,40-Tetraoxa-7,20,31,44,49,50,51,52-octaazapentacyclo[43.3.1.12,6.121,25.126,30]dopentaconta-1(49),2(52),3,5,21(51),22,24,26(50),27,29,45,47-dodecaene (4i) (n = 1). Obtained as by-product in the synthesis of macrocycle 3i. Eluent CH2Cl2-MeOH 20:1. Yield 15 mg (17%). Pale-yellow solid. Mp 78-80 oC. UV λmax (CH2Cl2) 345 (ε 22000). 1H NMR (CDCl3): δ 1.65-1.68 (m, 8H), 1.87 (quintet, J = 6.0 Hz, 8H), 3.41 (t, J = 6.5 Hz, 8H), 3.42-3.45 (m, 8H), 3.52 (t, J = 5.2 Hz, 8H), 6.34 (d, J = 7.6 Hz, 4H), 7.44 (t, J = 7.4 Hz, 4H), 7.47 (d, J = 7.8 Hz, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 26.5 (4C), 29.5 (4C), 40.0 (4C), 68.9 (4C), 70.7 (4C), 106.7 (4C), 109.6 (4C), 138.2 (4C), 153.0 (4C), 158.0 (4C). HRMS (MALDI-TOF) m/z calcd for C40H56N8O4 [M+] 712.4425, found 714.4471.

Mixture of cyclotrimer 4i (n = 2), cyclotetramer 4i (n = 3), cyclopentamer 4i (n = 4) and cyclohexamer 4i (n = 5). Obtained as by-products in the synthesis of macrocycle 3i. Eluent CH2Cl2-MeOH-NH3aq 100:20:1. Yield 20 mg (22%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.65-1.68 (m, 4(n+1)H), 1.87-1.92 (m, 4(n+1)H), 3.41-3.45 (m, 8(n+1)H), 3.51-3.55 (m, 4(n+1)H), 4.85 (bs, 2(n+1)H), 6.35 (d, J = 8.1 Hz, 2(n+1)H), 7.47 (t, J = 7.7 Hz, 2(n+1)H), 7.57 (d, J = 7.3 Hz, 2(n+1)H). 13C NMR (CDCl3): δ 26.5 (2(n+1)C), 29.5 (2(n+1)C), 40.0 (2(n+1)C), 69.1 (2(n+1)C), 70.8 (2(n+1)C), 106.4 (2(n+1)C), 109.9 (2(n+1)C), 137.9 (2(n+1)C), 154.9 (2(n+1)C), 158.3 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C60H84N12O6 [M+] 1068.66, found 1068.57 (4i (n = 2)); calcd for C80H112N16O8 [M+] 1424.89, found 1424.80 (4i (n = 3)); calcd for C100H140N20O10 [M+] 1781.11, found 1781.27 (4i (n = 4)); calcd for C120H168N24O12 [M+] 2137.33, found 2137.43 (4i (n = 5)).

11,14,17-Trioxa-7,21,26,27-tetraazatricyclo[20.3.1.12,6]heptacosa-1(26),2(27),3,5,22,24-hexaene (3j). Synthesized from 55 mg (0.25 mmol) of dioxadiamine 2j. Eluent CH2Cl2-MeOH 10:1-3:1. Yield 45 mg (48%). Pale-yellow viscous oil. UV λmax (CH2Cl2) 345 (ε 9900). 1H NMR (CDCl3): δ 1.99 (quintet, J = 5.8 Hz, 4H), 3.53 (t, J = 6.2 Hz, 4H), 3.56-3.60 (m, 4H), 3.63-3.68 (m, 8H), 6.80 (bs, 2H), 7.10 (d, J = 7.4 Hz, 2H), 7.54 (t, J = 7.9 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 28.6 (2C), 39.3 (2C), 68.9 (2C), 70.5 (4C), 108.6 (2C), 110.7 (2C, line width 50 Hz), 139.7 (2C), 156.1 (2C), one quaternary carbon was not observed due to broad signal. HRMS (MALDI-TOF) m/z calcd for C20H28N4O3 [M+] 372.2161, found 372.2185.

11,14,17,36,39,42-Hexaoxa-7,21,32,46,51,52,53,54-octaazapentacyclo[45.3.1.12,6.122,26.127,31]-tetrapentaconta-1(51),2(54),3,5,22(53),23,25,27(52),28,30,47,49-dodecaene (4j) (n = 1). Obtained as by-product in the synthesis of macrocycle 3j. Eluent CH2Cl2-MeOH 25:1-10:1. Yield 14 mg (15%). Pale-yellow solid. Mp 78-80 oC. UV λmax (CH2Cl2) 345 (ε 19000). 1H NMR (CDCl3): δ 1.87 (quintet, J = 6.1 Hz, 8H), 3.41 (t, J = 6.2 Hz, 8H), 3.53-3.58 (16H), 3.61-3.66 (m, 8H), 6.36 (d, J = 8.0 Hz, 4H), 7.39-7.45 (m, 8H), NH protons were not observed. 13C NMR (CDCl3): δ 29.3 (4C), 39.7 (4C), 69.2 (4C), 70.2 (4C), 70.6 (4C), 107.0 (4C), 109.5 (4C), 138.2 (4C), 151.6 (4C), 158.0 (4C). HRMS (MALDI-TOF) m/z calcd for C40H56N8O6 [M+] 744.4323, found 744.4302.

Typical procedure for the synthesis of cyclodimers 4d, h-j (n = 1).
A two-neck flask (25 mL) flushed with dry argon, equipped with a magnetic stirrer and condenser was charged with 6,6'-dibromo-2,2'-bipyridine (1) (0.2 mmol, 63 mg), Pd(dba)2 (4.5 mg, 4 mol%), BINAP (5.5 mg, 4.5 mol%) and absolute dioxane (2 mL). The mixture was stirred for 2 min, then appropriate amine 2d, h-j (0.6 mmol) was added followed by sodium tert-butoxide (0.6 mmol, 58 mg). The reaction mixture was refluxed for 8 h, after cooling down to ambient temperature 0.5 mL (25%) of the solution was taken, evaporated in vacuo, and analyzed with NMR and MALDI-TOF spectroscopy. Then 6,6'-dibromo-2,2'-bipyridine (1) (0.3 mmol, 94 mg), Pd(dba)2 (14 mg, 8 mol%), BINAP (17 mg, 9 mol%), absolute dioxane (8 mL) and sodium tert-butoxide (0.9 mmol, 87 mg) were added, the reaction was then refluxed for 15 h. After cooling down to ambient temperature, the residue was filtered off, dioxane evaporated in vacuo, and the residue was analyzed by NMR spectroscopy. Column chromatography was carried out using a sequence of eluents: CH2Cl2, CH2Cl2-MeOH 50:1 – 3:1, CH2Cl2-MeOH-NH3aq 100:20:1 – 10:4:1.

N1,N1'-(2,2'-Bipyridine-6,6'-diyl)bis(N3-(3-aminopropyl)propane-1,3-diamine) (5d). Obtained in situ from triamine 2d (0.6 mmol, 79 mg). 1H NMR (CDCl3): δ 1.57 (quintet, J = 6.9 Hz, 4H), 1.75 (quintet, J = 6.7 Hz, 4H), 2.60 (t, J = 7.0 Hz, 4H), 2.69 (t, J = 6.6 Hz, 8H), 3.38 (t, J = 6.3 Hz, 4H), 6.32 (d, J = 8.1 Hz, 2H), 7.45 (t, J = 7.9 Hz, 2H), 7.54 (d, J = 7.1 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 29.6 (2C), 33.7 (2C), 40.2 (2C), 40.3 (2C), 47.7 (2C), 47.8 (2C), 106.5 (2C), 109.8 (2C), 137.8 (2C), 154.8 (2C), 158.2 (2C). MS (MALDI-TOF) m/z calcd for C22H38N8 [M+] 414.32, found 414.38. Following by-products were registered in the reaction mixture: m/z calcd for C38H59N13 [M+] 697.50, found 697.48 (6d (n = 1)); calcd for C54H80N18 [M+] 980.68, found 980.52 (6d (n = 2)). Compound 5d was introduced in the reaction with 6,6’-dibromo-2,2’-bipyridine (1) in situ to produce cyclodimer 4d (n = 1) (eluent CH2Cl2-MeOH-NH3aq 100:25:5-10:4:1, yield 16 mg (19%)), macrocycle 3d (eluent CH2Cl2-MeOH-NH3aq 100:20:3-100:25:5, yield 10 mg (23%)), a mixture of cyclotrimer 4d (n = 2) and cyclotetramer 4d (n = 3) (eluent CH2Cl2-MeOH-NH3aq 100:20:3, yield 26 mg (31%)), a mixture of linear oligomers (CH2Cl2-MeOH-NH3aq 10:4:1, yield 30 mg (35%)).

7,11,15,26,30,34,39,40,41,42-Decaazapentacyclo[33.3.1.12,6.116,20.121,25]dotetraconta-1(39),2(42),3,5,16(41),17,19,21(40),22,24,35,37-dodecaene (4d) (n = 1). Eluent CH2Cl2-MeOH-NH3aq 100:25:5-10:4:1. Yield 16 mg (19%). Pale-yellow solid. Mp 118-120 oC. UV λmax (CH2Cl2) 347 (ε 20000). 1H NMR (CDCl3): δ 1.45 (quintet, J = 6.4 Hz, 8H), 2.36 (t, J = 6.4 Hz, 8H), 3.15-3.20 (m, 8H), 6.23 (d, J = 8.2 Hz, 4H), 7.27 (d, J = 7.4 Hz, 4H), 7.37 (t, J = 7.8 Hz, 4H), NH protons were not observed. 13C NMR (CDCl3): δ 29.3 (4C), 38.7 (4C), 46.4 (4C), 107.0 (4C), 110.0 (4C), 137.9 (4C), 154.9 (4C), 158.4 (4C). HRMS (MALDI-TOF) m/z calcd for C32H42N10 [M+] 566.3594, found 566.3651.

Mixture of cyclotrimer 4d (n = 2) and cyclotetramer 4d (n = 3). Eluent CH2Cl2-MeOH-NH3aq 100:25:5. Yield 26 mg (31%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.50-1.60 (m, 4(n+1)H), 2.40-2.52 (m, 4(n+1)H), 3.24 (bs, 4(n+1)H), 6.28 (d, J = 8.2 Hz, 6H, cyclotrimer), 6.34 (d, J = 5.2 Hz, 8H, cyclotetramer), 7.32 (d, 6H, J = 7.9 Hz, 6H, cyclotrimer), 7.34-7.43 (m, 16H, cyclotetramer), 7.39 (d, 6H, J = 7.6 Hz, 6H, cyclotrimer), NH protons were not observed. 13C NMR (CDCl3): δ 28.1-29.0 (m, 2(n+1)C), 39.1-39.7 (m, 2(n+1)C), 46.3-47.3 (m, 2(n+1)C), 107.0 (2(n+1)C), 109.9 (2(n+1)C), 138.0 (2(n+1)C), 154.5 (2(n+1)C), 158.4 + 158.5 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C48H63N15 [M+] 849.54, found 849.38 (4d (n = 2)); calcd for C64H84N20 [M+] 1132.72, found 1132.41 (4d (n = 3)).

N6,N6'-Bis(2-(2-(2-aminoethoxy)ethoxy)ethyl)-2,2'-bipyridine-6,6'-diamine (5h). Obtained in situ from diamine 2h (0.6 mmol, 89 mg). 1H NMR (CDCl3): δ 2.80 (t, J = 4.2 Hz, 4H), 3.46 (t, J = 4.5 Hz, 4H), 3.58 (s, 8H), 3.59-3.62 (m, 4H), 3.66-3.69 (m, 4H), 6.36 (d, J = 8.1 Hz, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.57 (d, J = 7.3 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 41.4 (4C), 69.9 (2C), 70.2 (4C), 73.3 (2C), 107.4 (2C), 110.0 (2C), 137.7 (2C), 154.7 (2C), 157.9 (2C). MS (MALDI-TOF) m/z calcd for C22H36N6O4 [M+] 448.28, found 448.24. Following by-products were registered in the reaction mixture: m/z calcd for C38H56N10O6 [M+] 748.44, found 748.56 (6h (n = 1)); calcd for C54H76N14O8 [M+] 1048.60, found 1048.57 (6h (n = 2)); calcd for C70H96N18O10 [M+] 1348.76, found 1348.55 (6h (n = 3)). Compound 5h was introduced in the reaction with 6,6’-dibromo-2,2’-bipyridine (1) in situ to produce cyclodimer 4h (n = 1) (eluent CH2Cl2-MeOH 20:1, yield 7 mg (8%)), cyclotrimer 4h (n = 2) (eluent CH2Cl2-MeOH 20:1, yield 4 mg (4%)), macrocycle 3h (eluent CH2Cl2-MeOH 10:1-3:1, yield 20 mg (44%)), a mixture of linear oligomers (CH2Cl2-MeOH 3:1, CH2Cl2-MeOH-NH3aq 100:20:1, yield 78 mg (86%)). The spectral data for the cyclodimer 4h (n = 1) are given above.

10,13,30,33,50,53-Hexaoxa-7,16,27,36,47,56,61,62,63,64,65,66-dodecaazaheptacyclo- [55.3.1.12,6.117,21.122,26.137,41.142,46]hexahexaconta-1(61),2(66),3,5,17(65),18,20,22(64),23,25,37(63),38,40,42(62),43,45,57,59-octadecaene (4h) (n = 2). Obtained as by-product in the synthesis of cyclodimer 4h (n = 1). Eluent CH2Cl2-MeOH 20:1. Yield 4 mg (4%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 3.57 (t, J = 5.0 Hz, 12H), 3.65 (s, 12H), 3.72 (t, J = 5.1 Hz, 12H), 4.57 (bs, 6H), 6.31 (d, J = 8.2 Hz, 6H), 7.37 (t, J = 7.8 Hz, 6H), 7.56 (d, J = 7.4 Hz, 6H). 13C NMR (CDCl3): δ 41.8 (6C), 69.9 (6C), 70.3 (6C), 107.4 (6C), 110.1 (6C), 137.9 (6C), 154.7 (6C), 158.0 (6C). HRMS (MALDI-TOF) m/z calcd for C48H60N12O6 [M+] 900.4759, found 900.4819.

N6,N6'-Bis(3-(4-(3-aminopropoxy)butoxy)propyl)-2,2'-bipyridine-6,6'-diamine (5i). Obtained in situ from diamine 2i (0.6 mmol, 121 mg). 1H NMR (CDCl3): δ 1.58-1.60 (m, 4H), 1.61-1.63 (m, 4H), 1.67 (quintet, J = 6.5 Hz, 4H), 1.88 (quintet, J = 6.2 Hz, 4H), 2.73 (t, J = 6.5 Hz, 4H), 3.36-3.42 (m, 12H), 3.45 (t, J = 6.3 Hz, 4H), 3.52 (t, J = 5.9 Hz, 4H), 6.33 (d, J = 8.1 Hz, 2H), 7.46 (t, J = 7.7 Hz, 2H), 7.56 (d, J = 7.3 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 26.4 (4C), 29.5 (2C), 33.4 (2C), 39.4 (2C), 39.9 (2C), 68.9 (2C), 69.0 (2C), 70.6 (2C), 70.7 (2C), 106.4 (2C), 109.8 (2C), 137.8 (2C), 154.9 (2C), 158.2 (2C). MS (MALDI-TOF) m/z calcd for C30H52N6O4 [M+] 560.41, found 560.39. Following by-products were registered in the reaction mixture: m/z calcd for C50H80N10O6 [M+] 916.63, found 916.86 (6i (n = 1)); calcd for C70H108N14O8 [M+] 1272.85, found 1272.59 (6i (n = 2)). Compound 5i was introduced in the reaction with 6,6’-dibromo-2,2’-bipyridine (1) in situ to produce cyclodimer 4i (n = 1) (eluent CH2Cl2-MeOH 20:1, yield 10 mg (9%)), a mixture of cyclotimer 4i (n = 2) and cyclotetramer 4i (n = 3) (eluent CH2Cl2-MeOH 20:1, yield 9 mg (8%)), macrocycle 3i (eluent CH2Cl2-MeOH 20:1-10:1, yield 23 mg (43%)), a mixture of linear oligomers (CH2Cl2-MeOH 10:1-3:1, yield 43 mg (40%)). The spectral data for the cyclodimer 4i (n = 1) are given above.

N6,N6'-Bis(3-(2-(2-(3-aminopropoxy)ethoxy)ethoxy)propyl)-2,2'-bipyridine-6,6'-diamine (5j). Obtained in situ from diamine 2j (0.6 mmol, 132 mg). 1H NMR (CDCl3): δ 1.64 (quintet, J = 6.5 Hz, 4H), 1.83 (quintet, J = 6.1 Hz, 4H), 2.70 (t, J = 6.7 Hz, 4H), 3.47 (t, J = 6.2 Hz, 4H), 3.49-3.59 (m, 24H), 6.30 (d, J = 8.2 Hz, 2H), 7.40 (t, J = 7.6 Hz, 2H), 7.51 (d, J = 7.3 Hz, 2H), NH protons were not observed. 13C NMR (CDCl3): δ 29.2 (2C), 33.2 (2C), 39.4 (2C), 39.6 (2C), 69.2 (2C), 69.3 (2C), 70.0 (2C), 70.1 (2C), 70.4 (4C), 106.5 (2C), 109.6 (2C), 137.6 (2C), 154.8 (2C), 158.0 (2C). MS (MALDI-TOF) m/z calcd for C30H52N6O6 [M+] 592.39, found 592.45. Compound 5j was introduced in the reaction with 6,6’-dibromo-2,2’-bipyridine (1) in situ to produce cyclodimer 4j (n = 1) (eluent CH2Cl2-MeOH 20:1, yield 13 mg (12%)), a mixture of cyclotimer 4j (n = 2) and cyclotetramer 4j (n = 3) (eluent CH2Cl2-MeOH 20:1, yield 12 mg (11%)), macrocycle 3j (eluent CH2Cl2-MeOH 20:1-10:1, yield 22 mg (39%)), a mixture of linear oligomers (CH2Cl2-MeOH 10:1-3:1, yield 64 mg (57%)). The spectral data for the cyclodimer 4j (n = 1) are given above.

Mixture of cyclotrimer 4j (n = 2) and cyclotetramer 4j (n = 3). Obtained as by-products in the synthesis of cyclodimer 4j (n = 1). Eluent CH2Cl2-MeOH 20:1. Yield 12 mg (11%). Pale-yellow glassy solid. 1H NMR (CDCl3): δ 1.87 (quintet, J = 6.1 Hz, 4(n+1)H), 3.41 (t, J = 6.2 Hz, 4(n+1)H), 3.53-3.58 (8(n+1)H), 3.61-3.66 (m, 4(n+1)H), 6.36 (d, J = 8.0 Hz, 2(n+1)H), 7.39-7.45 (m, 4(n+1)H), NH protons were not observed. 13C NMR (CDCl3): δ 29.4 (2(n+1)C), 39.7 (2(n+1)C), 69.2 (2(n+1)C), 70.3 (2(n+1)C), 70.7 (2(n+1)C), 107.0 (2(n+1)C), 109.5 (2(n+1)C), 138.2 (2(n+1)C), 151.5 (2(n+1)C), 157.8 (2(n+1)C). MS (MALDI-TOF) m/z calcd for C60H84N12O9 [M+] 1116.65, found 1116.63 (4j (n = 2)); calcd for C80H112N16O12 [M+] 1488.86, found 1488.89 (4j (n = 3)).

ACKNOWLEDGMENTS
This work was supported by the RFBR grants N 09-03-00735 and 08-03-00628, by the Russian Academy of Sciences program "Elaboration of the methods for the synthesis of chemical compounds and construction of new materials" and by the program ARCUS / Bourgogne / Russie, N 079210AAO153582.

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