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6Циклические полиамины МаКрОГЭТЭрОЦМКЛЬ] Cyc|ic Polyamines http://macroheterocycles.isuct.ru
Статья Paper
Facile Synthesis of New Polyazamacrocycles by the Pd-Catalyzed Amination of 3,3'-Dibromobiphenyl
Alexei D. Averin,a@ Alexei N. Uglov,a Alexei K. Buryak,b and Irina P. Beletskayaab
aLomonosov Moscow State University, Department of Chemistry, Leninskie Gory, Moscow, 119991 Russia. bA. N. Frumkin Institute of Physical and Electrochemistry, 31 Leninskii prosp., Moscow, 119991, Russia. Corresponding author E-mail: averin@org.chem.msu.ru
Pd-Catalyzed amination of 3,3'-dibromobiphenyl using various polyamines and oxadiamines was studied. Target macrocycles were obtained in yields from moderate to good with a variety of polyamines and oxadiamines, cyclic oligomers were isolated in the majority of cases as by-products. Synthesis of the macrocycles containing two 3,3'-disubstituted biphenyls and twopolyamine fragments (cyclodimers) was elaborated using intermediate di(bromo-biphenyl)substitutedpolaymines or bis(polyamine)substituted biphenyls.
Keywords: Macrocycles, amination, catalysis, polyamines, biphenyl.
Introduction
Macrocycles containing biphenyl units attract a constant interest of researchers due to interesting coordination possibilities arising from attaching flexible and tunable polyoxa- and polyazacycles to a rigid non-planar aryl moiety. The most of reported macrocycles based on biphenyls were synthesized using non-catalytic approaches. Cyclic polyethers were formed starting from 2,2'-dihydroxybiphenyl,[1-3] and their coordination with cations like tert-butylammonium was studied.[2] Transport of Li, Na, K cations[4,5] and of Hg(CF3)2[6,7] through a liquid membrane was investigated using macrocycles of similar structure, in which one or two polyoxaethylene chains were attached to one biphenyl unit. Polyoxadiaminomacrocycles were also synthesized on the basis of 2,2'-disubstituted biphenyl and their complexation of primary alkylammonium salts, including chiral ones, was studied.[8] Polyazamacrocycles with 3, 4 and 8 nitrogen atoms were investigated as complexing agents for Cu2+, Zn2+ and [PdCl4]2- ions.[9] More sophisticated macrocycles like peptide-biphenyl hybrid[10] and hemispherand macrocycle[11] with bi- and quaterphenyl moieites have been recently reported. Cyclic triamides[12] as well as cyclic Schiff bases (trianglimines)[13,14] comprise three 3,3'-disubstituted biphenyls, the latter can be aslo built on the basis of 4,4'-disubstituted biphenyls. In some cases biphenyl fragment was built using Pd-catalyzed coupling of two benzene moieties at the step of macrocyclization, as it was in the case of the compound with diazacrown, dipeptide and biphenyl fragments.[15] It is to be mentioned that biphenyls are incorporated in some biologically active macrocycles, e.g. tricyclic glucopeptides of vancomicine group.[16] To the moment, there are no literature data on the synthesis of biphenyl-based macrocycles which employs catalytic bond formation between aromatic and aliphatic parts of the molecule. In recent years we have accumulated experience on the application of the Buchwald-Hartwig amination[17] in the synthesis of polyazamacrocycles starting from various
dihaloarenes[18-21] and we investigated this approach for the construction of biphenyl-based macrocycles.
Experimental
NMR spectra were registered using Bruker Avance 400 spectrometer, MALDI-TOF spectra were obtained with Bruker Ultraflex spectrometer using 1,8,9-trihydroxyanthracene as matrix and PEGs as standards. 2-Bromonitrobenzene, oxadiamines, polyamines, 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene
(BINAP), 2-dimethylamino-2'-dicyclohexylphosphinobiphenyl (DavePHOS), sodium tert-butoxide were purchased from Aldrich and Acros and used without further purification, Pd(dba)2 was synthesized according to the method described earlier.[22] 3,3'-Dibromobiphenyl was synthesized in 3 steps from 2-bromonitrobenzene according to the procedure.[23] Dioxane was distilled over NaOH followed by the distillation over sodium under argon, dichloromethane and methanol were distilled.
Typical procedure for the synthesis of macrocycles 3.
A two-neck flask equipped with a magnetic stirrer and a condenser, flushed with dry argon, was charged with 3,3'-dibromobiphenyl (1) (0.5 mmol, 156 mg), absolute dioxane (25 ml), Pd(dba)2 (24 mg, 8 mol%) and BINAP (28 mg, 9 mol%). The mixture was stirred for 2 min, then appropriate polyamine 2 (0.5 mmol) and tBuONa (1.5 mmol) were added, and the reaction mixture was refluxed for 24 h. After cooling to the ambient temperature and filtration of the precipitate dioxane was evaporated in vacuo and the residue was chromatographed on silica gel using a sequence of eluents: CH2Cl2, CH2Cl2-MeOH 500:1 - 3:1, CH2Cl2-MeOH-aq. NH3 100:20:1 - 10:4:1.
11,22,26-Tetraazapentacyclo[25.3.1.126.11216.117'21 ] tetratriaconta-1(31),2(34),3,5,12(33),13,15,17(32),18,20,27,29-dodecaene, 4a (n=1). Obtained from 37 mg of propane-1,3-diamine 2a. Eluent: CH2Cl2-MeOH 200:1. Yield 27 mg (24%). Pale-yellow crystals, m.p. 224-225oC (decomp.) m/z (MALDI-TOF) found: 448.2593. C30H32N4 requires 448.2627 [M+]. XH NMR (CDCl3, 297 K) 8H ppm: 1.943 (413, quintet, 3J = 6.1 Hz), 3.37 (8H, t,3J = 6.1 Hz), 3.91 (4H, br.s), 6.60 (4H, dd, 3J = 7.6 Hz, 4J = 1.8 Hz), 6.78 (4H, br.s), 6.91 (4H, d, 3J = 7.7 Hz), 7.21 (4H, t, 3J = 7.9 Hz). 13C NMR (CDCl3, 297 K) 8c ppm: 28.6 (2C), 42.4 (4C), 111.6 (4C), 112.1 (4C), 116.5 (4C), 129.6 (4C), 142.9 (4C), 148.3 (4C).
7,10,13,24,27,30-Hexaazapentacyclo[29.3.1.12 6.11418 A19'23] octatriaconta-1(35) , 2(38), 3,5,14(37), 15,17,19(36), 20,22,31,33-dodecaene, 4b (n=1). Obtained from 52 mg of triamine 2b. Eluent: CH2Cl2-MeOH/NH3-aq 100:20:1. Yield 29 mg (23%). Pale-yellow glassy solid. Contains admixtures of cyclotrimer 4b (n=2) and cyclotetramer 4b (n=3). m/z (MALDI-TOF) 507.39 (4b (n=1) [(M+H)+]), 760.44 (4b (n=2) [(M+H)+]), 1012.72 (4b (n=3) [M+]). 1H NMR (CDCl3, 297 K) 8H ppm: 2.85 (8H, br.s), 3.12-3.30 (8H, m), 6.50-6.58 (4H, m), 6.82-6.94 (8H, m), 7.11-7.21 (4H, m), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 43.0 (4C), 48.0 (4C), 111.7 (4C), 111.8 (4C), 116.4 (4C), 129.4 (4C), 142.3 (4C), 148.4 (4C).
7,11,15-Triazatricyclo[14.3.1.12,6]henicosa-1(20),2(21),3,5,16,18-hexaene, 3c. Obtained from 66 mg of triamine 2c. Eluent: CH2Cl2-MeOH 3:1. Yield 35 mg (25%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 281.1930. C18H23N3 requires 281.1892 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.82 (4H, quintet, 3J = 6.7 Hz), 2.71 (4H, t, 3J = 6.0 Hz), 3.37 (4H, t, 3J = 7.3 Hz), 4.06 (2H, br.s), 6.54 (2H, dd, 3J = 8.0 Hz, 4J = 0.8 Hz), 7.03 (2H, d, 3J = 7.5 Hz), 7.17 (2H, t, 3J = 7.8 Hz), 7.29 (2H, br.s), NH proton of the dialkylamino group was not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 29.7 (2C), 41.3 (2C), 47.0 (2C), 109.6 (2C),114.0 (2C), 114.8 (2C), 129.3 (2C), 142.1 (2C), 147.9 (2C).
7,11,15,26,30,34-Hexaazapentacyclo[33.3.1.126.11620.12125] dotetraconta-1(39),2(42),3,5,16(41),17,19,21(40),22,24,35,37-dodecaene, 4c (n=1). Obtained as by-product in the synthesis of macrocycle 3c. Eluent: CH2Cl2-MeOH-NH3-aq 100:20:1. Yield 30 mg (21%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 562.3701. C36H46N6 requires 562.3784 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.80 (8H, quintet, 3J = 6.7 Hz), 2.68 (8H, t, 3J = 5.9 Hz), 3.29 (8H, t, 3J = 5.1 Hz), 3.90 (4H, br.s), 6.53 (4H, d, 3J = 8.0), 7.02 (4H, d, 3J = 7.4 Hz), 7.16 (4H, t, 3J = 7.7 Hz), 7.17 (4H, br.s), NH proton of the dialkylamino group was not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 28.4 (4C), 41.1 (4C), 48.0 (4C), 109.8 (4C), 114.0 (4C), 114.8c (4C), 129.3 (4C), 142.3 (4C), 147.7 (4C).
7.10.13.16-Tetraazatricyclo[15.3.1.126]docosa-1(21),2(22),3,5,17,19-hexaene, 3d. Obtained from 73 mg of tetraamine 2d. Eluent: CH2Cl2-MeOH-NH3-aq 100:20:3. Yield 23 mg (16%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 296.1959. C18H24N4 requires 296.2001 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 2.82 (4H, s), 2.87 (4H, t, 3J = 6.6 Hz), 3.29 (4H, 3,3J = 6.6 Hz), 6.54 (2H, dd, 3J = 8.0 Hz, 4J = 2.0 Hz), 7.02 (2H, d, 3J = 7.7 Hz), 7.06 (2H, br.s), 7.16 (2H, t, 3J = 7.7 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 44.27 (2C), 48.5 (2C), 49.3 (2C), 108.9 (2C), 114.2 (2C), 115.7 (2C), 129.3 (2C), 142.2 (2C), 148.9(2C).
7,10,13,16,27,30,33,36-0ctaazapentacyclo[35.3.1.126.11721. 12226]tetratetraconta-1(41),2(44),3,5,17(43),18,20,22(42), 23,25,37,39-dodecaene, 4d (n=1). Obtained as by-product in the synthesis of macrocycle 3d. Eluent: CH2Cl2-MeOH-NH3-aq 100:25:5. Yield 27 mg (18%). Pale-yellow glassy solid. Contains admixture of cyclotrimer 4d (n=2). m/z (MALDI-TOF) 592.33 (4d (n=2) [M+]), 888.38 (4d (n=2) [M+]). 1H NMR (CDCl3, 297 K) 8H ppm: 2.74 (8H, s), 2.85 (8H, t, 3J = 5.8 Hz), 3.21 (8H, t, 3J = 5.2 Hz), 6.56 (4H, dd, 3J = 7.8 Hz, 4J = 1.9 Hz), 6.80 (4H, s), 6.89 (4H, d, 3J = 7.2 Hz), 7.15 (4H, t, 3J = 7.8 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 43.5 (4C), 48.4 (4C), 48.8 (4C), 111.7 (4C), 111.8 (4C), 116c.6 (4C), 129.5 (4C), 142.8 (4C), 148.6 (4C).
7.10.14.17-Tetraazatricyclo[16.3.1.126]tricosa-1(22),2(23),3,5,18,20-hexaene, 3e. Obtained from 80 mg of tetraamine 2e. Eluent: CH2Cl2-MeOH-NH3-aq 100:20:2. Yield 41 mg (26%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 310.2190. C19H26N4 requires 310.2157 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.(57 (2H, quintet, 3J = 6.4 Hz), 2.80 (4H, t, 3J = 6.4 Hz), 2.83 (4H, t, 3J = 6.9 Hz), 3.36 (4H, t, 3J = 6.9 Hz), 4.10 (2H, br.s), 6.57 (2H, dd, 3J = 8.0 Hz, 4J = 1.4 Hz), 6.96-7.00 (4H, m),
7.17 (2H, t, 3J = 7.7 Hz), NH protons of the dialkylamino groups were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 29.5 (1C), 44.3 (2C), 48.0 (2C), 49.2 (2C), 110.1 (2C), 114.2 (2C), 116.1 (2C), 129.3 (2C), 142.7 (2C), 148.7 (2C).
7,10,14,17,28,31,35,38-0ctaazapentacyclo[37.3.1.126.11822. 12327]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-NH3-aq 100:20:3. Yield 12 mg (8%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 620.4307. C38H52N8 requires 620.4314 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.669 (4H, quintet, 3J = 5.6 Hz), 2.77 (8H, t, 3J = 4.6 Hz), 2.83 (8H, t, 3J = 6.4 Hz), 3.24 (8H, br.s), 6.57 (4H, d, 3J = 7.8 Hz), 6.72 (4H, br.s), 6.85 (4H, d, 3J = 7.6 Hz), 7.14 (4H, t, 3J = 7.7 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 28.9-29.7 (m, 2C), 42.6-43.0 (m, 4C), 47.8-49.3 (m, 8C), 111.2-111.8 (m, 8C), 116.3+116.4 (4C), 129.5 (4C), 142.6 (4C), 148.4+148.5 (4C).
7.11.14.18-Tetraazatricyclo[17.3.1.126]tetracosa-1(23),2(24),3,5,19,21-hexaene, 3f. Obtained from 87 mg of tetraamine 2f. Eluent: CH2Cl2-MeOH 3:1 - CHp^MeOH-NH^aq 100:20:2. Yield 71 mg (44%). Pale-yellow crystals, m.p. 115-116oC. m/z (MALDI-TOF) found: 324.2264. C^H^N, requires 324.2314 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.92 (4H, quintet, 3J = 6.6 Hz), 2.82 (4H, t, 3J = 6.0 Hz), 2.88 (4H, s), 3.32 (4H, t, 3J = 7.2 Hz), 3.72 (2H, br.s), 6.53 (2H, d, 3J = 7.6 Hz), 6.93 (2H, s), 6.94 (2H, d, 3J = 7.8 Hz), 7.15 (2H, t, 3J = 7.7 Hz), NH protons of the dialkylamino groups were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 28.1 (2C), 42.4 (2C), 47.5 (4C), 110.9 (2C), 113.3 (2C), 115.7 (2C), 129.5 (2C), 142.5 (2C), 148.3 (2C).
7,11,14,18,29,33,36,40-0ctaazapentacyclo[39.3.1.126.11923. 12428]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-NH3-aq 100:20:3. Yield 41 mg (25%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 648.4612. C40H56N8 requires 648.4628 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.773 (8H, quintet, 3J = 6.3 Hz), 2.71 (8H, t, 3J = 6.3 Hz), 2.72 (8H, s), 3.15 (8H, t, 3J = 6.3 Hz), 6.53 (4H, dd, 3J = 7.8 Hz, 3J = 1.7 Hz), 6.76 (4H, t, 4J = 1.7 Hz), 6.87 (4H, d, 3J =7.5 Hz), 7.17 (4H, t, 3J = 7.7 Hz), NH protons of the dialkylamino groups were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 29.1 (4C), 42.9 (4C), 48.1 (4C), 48.9 (4C), 111.3 (4C), 111.9 (4C), 116.2 (4C), 129.3 (4C), 142.9 (4C), 148.8 (4C).
7.11.15.19-Tetraazatricyclo[18.3.1.126]pentacosa-1(24),2(25),3,5,20,22-hexaene, 3g. Obtained from 94 mg of tetraamine 2g. Eluent: CH2Cl2-MeOH-NH3-aq 100:20:1. Yield 69 mg (41%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 338.2410. C21H30N4 requires 338.2470 [M+]. 1H NMR (CDCl3, 297 K) 8H ppm: 1.70 (2H, quintet, 3J = 6.2 Hz), 1.83 (4H, quintet, 3J = 6.6 Hz), 2.74 (8H, t, 3J = 6.4 Hz), 3.22 (4H, t, 3J = 6.9 Hz), 6.53 (2H, d, 3J = 8.0 Hz), 6.85 (2H, br.s), 6.94 (2H, d, 3J = 7.6 Hz), 7.19 (2H, t, 3J = 7.8 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 28.5 (2C), 29.8 (1C), 43.1 (2C), 48.4 (2C), 48.5 (2C), 110c.7 (2C), 112.2 (2C), 115.4 (2C), 129.2 (2C), 142.5 (2C), 148.6 (2C).
7,11,15,19,30,34,38,42-0ctaazapentacyclo[41.3.1.126. 12024.12529]pentaconta-1(47),2(50),3,5,20(49),21,23,25(48),26,28, 43,45-dodecaene, 4g (n=1). Obtained as by-product in the synthesis of macrocycle 3g. Eluent: CH2Cl2-MeOH-NH3-aq 100:4:1. Yield 32 mg (19%). Contains admixtures of cyclotrimer 4g (n=2) and cyclotetramer 4g (n=3). Pale-yellow glassy solid. m/z (MALDI-TOF) 676.48 (4g (n=1) [M+]), 1014.57 (4g (n=2) [M+]), 1362.40 (4g (n=3) [M+]). 1H NMR (CDCl3, 297 K) 8H ppm: 1.72 (12H, br.s), 2.67 (16H, br.s), 3.11 (8H, br.s), (5.51 (4H, d, 3J = 5.4 Hz), 6.76 (4H, br.s), 6.86 (4H, d, 3J = 6.9 Hz), 7.15 (4H, t, 3J = 6.5 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 28.8 (4C), 29.1 (2C), 42.7 (4C), 48.0-48.6 (8C, m), 111.3-111.7 (8C, m), 116.0 (4C), 129.3 (4C), 142.7 (4C), 148.7 (4C).
7,10,13,16,19-Pentaazatricyclo[18.3.1.126]pentacosa-1(24),2(25),3,5,20,22-hexaene, 3h. Obtained from 94 mg of pentaamine 2h. Eluent: CH2Cl2-MeOH-NH3-aq 100:20:3. Yield 32 mg (19%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 339.2373. C20H29N5 requires 339.2423 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 21.742 (4Н, t, 3J = 4.7 Hz), 2.83 (4Н, t, 3J = 4.8 Hz), 2.90 (4Н, t, 3J = 6.1 Hz), 3.34 (4Н, t, 3J = 6.1 Hz), 6.60 (2Н, d, 3J = 7.3 Hz), 6.98 (2Н, s), 6.99 (2Н, d, 3J = 6.7 Hz), 7.22 (2Н, t, 3J = 8.0 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) Sc ppm: 43.7 (2С), 48.6 (2С), 49.1 (2С), 49.5 (2С), 111.6 (2С), 112.SÎ (2С), 116.2 (2С), 129.5 (2С), 142.6 (2С), 148.8 (2С).
7,10,13,16,19,30,33,36,39,42-Decaazapentacyclo [41.3.1.12 6.120,24.125 29]pentaconta-1(47),2(50),3,5,20(49),21, 23,25(48),26,28,43,45-dodecaene, 4h (n=1). Obtained as byproduct in the synthesis of macrocycle 3g. Eluent: CH2Cl2-MeOH-NH3-aq 100:25:5. Yield 5 mg (3%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 678.58. C40H58N10 requires 678.48 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 2.73 (16H, br.s), 2.86 (8H, br.s), 3.22 (8H, br.s), 6.59 (4H, d, 3J = 7.7 Hz), 6.82 (4H, br.s), 6.90 (4H, d, 3J = 6.7 Hz), 7.20 (4Н, t, 3J = 7.7 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) Sc ppm: 43.5 (4C), 48.6 (4C), 49.0 (4C), 49.2 (4C), 111.9 (8C), 11*6.5 (4C), 129.5 (4C), 142.8 (4C), 148.7 (4C).
10,13-Dioxa-7,16-diazatricyclo[15.3.1.126]docosa-1(21),2(22),3,5,17,19-hexaene, 3i. Obtained from 74 mg of dioxadiamine 2i in the presence of Pd(dba)2 (46 mg, 16 mol%) and BINAP (56 mg, 18 mol%). Eluent: CH2Cl2-MeOH 100:1. Yield 60 mg (40%). Pale-yellow crystals, m.p. 211-212oC. m/z (MALDI-TOF) found: 298.1681. C18H22N202 requires 298.1706 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 3.49 (4Н, t, 3J =5.5 Hz), 3.70 (4Н, s), 3.71 (4Н, t, 3J = 5.6 Hz), 4.09 (2Н, br.s), 6.59 (2Н, ddd, 3J = 8.0 Hz, 4J = 1.5 Hz, 4J = 0.8 Hz), 7.06 (2Н, d, 3J = 7.7 Hz), 7.19 (2Н, t, 3J = 7.7 Hz), 7.39 (2Н, t, 4J = 1.9 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 45.2 (2С), 70.9 (2С), 72.6 (2С), 110.9 (2С), 114.2 (2С), 1163 (2С), 128.9 (2С), 142.7 (2С), 148.9 (2С).
10,13,30,33-Tetraoxa-7,16,27,36-tetraazapenta-cyclo[35.3.1.126.11721.12226]tetratetraconta-1(41),2(44),3,5,17(43), 18,20,22(42),23,25,37,39-dodecaene, 4i (n=1). Obtained as byproduct in the synthesis of macrocycle 3i. Eluent: CH2Cl2-MeOH 75:1. Yield 22 mg (15%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 596.3409. C36H44N404 requires 596.3362 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 3.3 4 (8Н, t, 3J = 4.7 Hz), 3.68 (8Н, s), 3.73 (8Н, t, 3J = 4.8 Hz), 4.23 (4Н, br.s), 6.60 (4Н, d, 3J = 7.7 Hz), 6.79 (4Н, br.s), 6.91 (4Н, d, 3J = 7.1 Hz), 7.18 (4Н, t, 3J = 7.5 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 43.7 (4С), 69.6 (4С), 70.3 (4С), 111.8 (4С), 11235 (4С), 116.8 (4С), 129.5 (4С), 142.9 (4С), 148.5 (4С).
10,13,3 0,33,50,53-Hexaoxa-7,16,2 7,3 6,47,56-hexaazaheptacyclo[55.3.1.126.117-21.1 22-26.1 37 41.1 42-46] 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, 4i (n=2). Obtained as by-product in the synthesis of macrocycle 3i. Eluent: CH2Cl2-MeOH 20:1. Yield 24 mg (16%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 894.56. С54Н6Д.О6 requires 894.50 [M+]. 1H NMR (CDCl3, 297 K) SH ppm : 3.36 (12Н, br.s), 3.67 (12Н, s), 3.72 (12Н, br.s), 4.06 (6Н br.s), 6.62 (6Н, d, 3J = 7.5 Hz), 6.84 (6Н, br.s), 6.94 (6Н, d, 3J = 6.8 Hz), 7.22 (6Н, t, 3J = 7.4 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 43.6 (6С), 69.7 (6С), 70.3 (6С), 112.0 (6С), 112.1 (6С), 116c.8 (6С), 129.5 (6С), 142.9 (6С), 148.5 (6С).
11,16-Dioxa-7,20-diazatricyclo[19.3.1.12,6]hexacosa-1(25),2(26),3,5,21,23-hexaene, 3j. Obtained from 102 mg of dioxadiamine 2j. Eluent: CH2Cl2-MeOH 100:1. Yield 78 mg (44%). Pale-yellow crystals, m.p. 111-112oC. m/z (MALDI-TOF) found: 354.2279. C22H30N2O2 requires 354.2307 [M+]. 1H NMR (CDCl3, 297 K) SH ppm : 1.7 6 (4Н, quintet, 3J = 2.8 Hz), 1.90 (4Н, quintet, 3J = 5.8 Hz), 3.36 (4Н, t, 3J = 6.5 Hz), 3.47 (4Н, br.s), 3.61 (4Н, t,
3J = 5.3 Hz), 6.57 (2Н, ddd, 3J = 8.0 Hz, 4J = 2.2 Hz, 4J = 0.7 Hz), 6.99 (2Н, t, 4J = 2.1 Hz), 7.01 (2Н, d, 3J = 7.7 Hz), 7.24 (2Н, t, 3J = 7.8 Hz).13C NMR (CDCl3, 297 K) Sc ppm: 27.2 (2С), 29.3 (2С), 43.2 (2С), 70.3 (2С), 71.2 (2С), 111.5 (4С), 115.8 (2С), 129.3 (2С), 142.2 (2С), 149.1 (2С).
11,16,35,40-Tetraoxa-7,20,31,44-tetraazapenta-cyclo[43.3.1.126.12125.126,30]dopentaconta-1(49),2(52),3,5,21(51), 22,24,26(50),27,29,45,47-dodecaene, 4j (n=1). Obtained as byproduct in the synthesis of macrocycle 3j. Eluent: CH2Cl2-MeOH 75:1. Yield 20 mg (12%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 708.42. C44H60N4O4 requires 708.46 [M+]. 1H NMR (CDCl3, 297 K) SH ppm4 1.66 (8Н, quintet, 3J = 2.1 Hz), 1.85 (8Н, quintet, 3J = 6.1 Hz), 3.23 (8Н, t, 3J = 6.4 Hz), 3.43 (8Н, quintet, 3J = 2.1 Hz), 3.52 (8Н, t, 3J = 5.7 Hz), 4.13 (4Н, br.s), 6.54 (4Н, dd, 3J = 7.9 Hz, 4 J = 1.5 Hz), 6.77 (4Н, t, 4 J = 1.8 Hz), 6.87 (4Н, d, 3J = 7.6 Hz), 7.18 (4Н, t, 3J = 7.8 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 26.6 (4С), 29.3 (4С), 42.2 (4С), 69.5 (4С), 70.8 (4С), 1114 (4С), 111.7 (4С), 116.3 (4С), 129.3 (4С), 143.0 (4С), 148.8 (4С).
11,14,17-Trioxa-7,21-diazatricyclo[20.3.1.12,6]heptacosa-1(26),2(27),3,5,22,24-hexaene, 3k. Obtained from 110 mg of trioxadiamine 2k. Eluent CH2Cl2-MeOH 100:1. Yield 71 mg (38%). Pale-yellow crystals, m.p. 74-75oC. m/z (MALDI-TOF) found: 370.2240. C22H30N2O3 requires 370.2256 [M+]. SH (CDCl3, 297 K) 1.91 (4Н, quintet, 3J = 5.9 Hz), 3.35 (4Н, t, 3J = 6.5 Hz^ 3.60-3.66 (8Н, m), 3.73-3.77 (4Н, m), 4.26 (2Н, br.s), 6.57 (2Н, d, 3J = 7.9 Hz), 6.94 (2Н, br.s), 6.97 (2Н, d, 3J = 7.7 Hz), 7.21 (2Н, t, 3J = 7.8 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 29.3 (2С), 42.5 (2С), 70.1 (2С), 70.7 (2С), 71.0 (2 С), 111.1 (2С), 111.9 (2С), 115.9 (2С), 129.2 (2С), 142.5 (2С), 149.0 (2С).
11,14,17,36,39,42-Hexaoxa-7,21,32,46-tetraaza-pentacyclo[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, 4k (n=1). Obtained as by-product in the synthesis of macrocycle 3k. Eluent: CH2Cl2-MeOH 50:1. Yield 22 mg (12%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 740.4473. C44H60N4O6 requires 740.4512 [M+]. 1H NMR (CDCl3, 297 K) SH ppm : 1.84 (8Н, quintet, 3J = 6.0 Hz), 3.23 (8Н, t, 3J = 6.4 Hz), 3.55 (8Н, t, 3J = 5.8 Hz), 3.55-3.60 (8Н, m), 3.63-3.67 (8Н, m), 4.18 (4Н, br.s), 6.54 (4Н, dd, 3J = 7.7 Hz, 4 J = 1.9 Hz), 6.73 (4Н, br.s), 6.85 (4Н, d, 3J = 7.4 Hz), 7.17 (4Н, t, 3J = 8.0 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 29.0 (4С), 41.7 (4С), 69.7 (4С), 70.2 (4С), 70.6 (4С), 111.3 (4С ), 111.8 (4С), 116.1 (4С), 129.3 (4С), 143.0 (4С), 148.8 (4С).
Synthesis of N,N'-(2,2'-(ethane-1,2-diylbis(oxy))bis(ethane-2,1-diyl))bis(5'-bromobiphenyl-3-amine), 5i, is analogous to the procedure described for the preparation of macrocycles 3, from 3,3'-dibromobiphenyl (1) (1.5 mmol, 468 mg) and dioxadiamine 2i (0.5 mmol, 74 mg), in absolute dioxane (5 ml), in the presence of Pd(dba)2 (12 mg, 4 mol%), Xanthphos (13 mg, 5 mol%) and tBuONa (1.5 mmol). Reflux time: 8 h. Eluent; CH2Cl2-MeOH 200:1. Yield 82 mg (27%). Pale-yellow glassy solid. m/z (MALDI-TOF) found: 608.0713. C30H30Br2N2O2 requires 608.0674 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 3.36 (4H, t, 3J = 5.2 Hz), 3.68 (4H, s), 3.74 (4H, t, 3J = 5.2 Hz), 4.20 (2H, br.s), 6.63 (2H, dd, 3J = 8.1 Hz, 4J = 1.4 Hz), 6.77 (2H, t, 4J = 1.4 Hz), 6.88 (2H, d, 3J = 7.7 Hz), 7.22 (2H, t, 3J = 7.9 Hz), 7.25 (2H, d, 3J = 7.8 Hz), 7.42-7.47 (4H, m), 7.69 (2H, t, 4J = 1.6 Hz). 13C NMR (CDCl3, 297 K) Sc ppm: 43.5 (2C), 69.6 (2C), 70.2 (2C), 111.6 (2C), 112.6 (2C), 116.6> (2C), 122.7 (2C), 125.7 (2C), 129.7 (2C), 129.9 (2C), 130.0 (2C), 130.1 (2C), 140.8 (2C), 143.8 (2C), 148.6 (2C).
Synthesis of N3,N3'-bis(2-(2-(2-aminoethoxy)ethoxy)ethyl) biphenyl-3,3'-diamine, 6i, is analogous to the procedure described for the preparation of compound 5i, from 3,3'-dibromobiphenyl 1 (0.5 mmol, 156 mg) and dioxadiamine 2i (2 mmol, 296 mg), in absolute dioxane (5 ml), in the presence of Pd(dba)2 (12 mg, 4 mol%), BINAP (14 mg, 4.5 mol%) and tBuONa (1.5 mmol). Reflux time: 8 h. m/z (MALDI-TOF) found: 446.42. C24H38N4O4 requires 446.29 [M+]. 1H NMR (CDCl3, 297 K) SH ppm: 2.83 (4H, t, 3J =
5.3 Hz), 3.32 (4H, t, 3J = 5.3 Hz), 3.49 (4H, t, 3J = 5.2 Hz), 3.603.66 (8H, m), 3.71 (4H, t, 3J = 5.2 Hz), 6.59 (2H, ddd, 3J = 8.1 Hz, 4 J = 2.4 Hz, 4 J = 0.7 Hz), 6.80 (2H, t, 4J = 2.1 Hz), 6.89 (2H, d, 3J = 7.6 Hz), 7.19 (2H, t, 3J = 7.8 Hz), NH protons were not assigned. 13C NMR (CDCl3, 297 K) 8c ppm: 41.5 (2C), 43.4 (2C), 69.6 (2C), 70.2 (4C), 73.4 (2C), 112.0 (4C), 116.7 (2C), 129.3 (2C), 142.8 (2C), 148.4 (2C).
Synthesis of cyclodimer 4i (n=1) from compound 5i is analogous to the procedure described for the preparation of macrocycles 3, from compound 5i (0.135 mmol, 82 mg) and dioxadiamine 2i (0.135 mmol, 20 mg), in absolute dioxane (7 ml), in the presence of Pd(dba)2 (6.5 mg, 8 mol%), BINAP (7.5 mg, 9 mol%) and tBuONa (0.4 mmol, 39 mg). Reflux time: 24 h. Eluent; CH2Cl2-MeOH 20:1. Yield 33 mg (27%).
Synthesis of cyclodimer 4i (n=1) from compound 6i is analogous to the procedure described for the preparation of macrocycles 3, from the mixture of compound 6i (ca 0.25 mmol) with dioxadiamine 2i (ca 0.5 mmol) and 3,3'-dibromobiphenyl (1) (0.75 mmol, 234 mg), in absolute dioxane (12 ml), in the presence of Pd(dba)2 (36 mg, 8 mol%), BINAP (42 mg, 9 mol%) and tBuONa (2.25 mmo l, 216 mg). Reflux time: 24 h. Eluent; CH2Cl2-MeOH 20:1. Yield 98 mg (44%).
Results and Discussion
The reactions of equimolar amounts of 3,3'-dibromobiphenyl 1 with a variety of di- and polyamines 2a-k (Figure 1) were run in enough dilute dioxane solutions (c = 0.02 M) using Pd(dba)2/BINAP (8/9 mol%) catalytic system[24] which was found to be almost universal for the synthesis of polyazamacrocycles, the products were isolated by column chromatography on silica gel. The results are given in Table 1.
As expected, propane-1,3-diamine 2a was too short to give a desired mono-cycle 3, and it produced
cyclodimer 4a (n=1) in 24% yield as well as a mixture of higher mass oligomers 4a (n=2-7) (37%) (Table 1, entry 1). Diethylenetriamine 2b (7 atoms in the chain) also gave only cyclooligomers 4b (n=1-5) (entry 2), but beginning from triamine 2c (9 atoms) target macrocycles 6 were formed successfully in yields from moderate to good (entries 3-13). The best yields (44%, entries 6, 11) were achieved with tetraamine 2f and dioxadiamine 2j, also enough high yields for the macrocyclization reaction (ca 40%) were afforded by tetraamine 2g and trioxadiamine 2k (entries 7, 12). We increased the yield of the macrocycle 3k to 45% by the application of 2-dicyclohexylphosphino-2'-dimethylamino-biphenyl (DavePHOS) ligand instead of BINAP (entry 13), however, this approach did not work in the case of dioxadiamine 2i, but the use of 16% mol catalyst gave corresponding macrocycle 3i in 40% yield (entry 10). In many cases cyclodimers 4 (n=1) were isolated from oligomeric mixtures in 8-25% yields, and in the reactions with dioxadiamine 2i even cyclotrimer 4i (n=2) was obtained separately in 16% yield. It is to be mentioned that 40% yields of polyazamacrocycles are among the highest ever achieved by the Pd-catalyzed amination of dihaloarenes, e.g. they notably surpass those obtained recently with 2,7-dibromonaphthalene.[25] Mono-cycles 3 contain from 15 (3c) to 21 atoms (3k) in the cycle, cyclodimers 4 possess from 22 (4a, n=1) to 42 atoms (4k, n=1), while cyclotrimer 4i (n=2) has a cavity formed by 48 atoms.
Cyclodimers which possess two biphenyl units and two polyamine chains and thus have a larger cavity size are of interest for the coordination studies with big cations and anions and organic molecules. We elaborated two approaches to such compounds. According to the first route, we synthesized N,N'-di(bromobiphenyl) substituted dioxadiamine 5i which was
H2N X NH2 2a-k
Pd(dbafe/BINAP fBuONa, dioxane Br reflux
Figure 1.
Table 1. Pd-Catalyzed amination of 3,3'-dibromobiphenyl (1).
Entry Amine Pd(dba)2/BINAP, mol% Isolated yields of 3, % Yields of 4, %
1 2a 8/9 3a, 0 4a (n=1), 24 4a (n=2-7), 37 (mixture)
2 2b 8/9 3b, 0 4b (n=1), 23 4b (n=2-5), 38 (mixture)
3 2c 8/9 3c, 25 4c (n=1), 21 4c (n=2-5), 23 (mixture)
4 2d 8/9 3d, 16 4d (n=1,2), 18 (mixture)
5 2e 8/9 3e, 26 4e (n=1), 8 4e (n=1-3), 27 (mixture)
6 2f 8/9 3f, 44 4f (n=1), 25 4f (n=1,2), 17 (mixture)
7 2g 8/9 3g, 41 4g (n=1-3), 19 (mixture)
8 2h 8/9 3h, 19 4h (n=1), 3 4h (n=1,2), 12 (mixture)
9 2i 8/9 3i, 19 4i (n=1), 12
10 2i 16/18 3i, 40 4i (n=1), 15 4i (n=2), 16
11 2j 8/9 3j, 44 4j (n=1), 12 4j (n=1-4), 18 (mixture)
12 2k 8/9 3k, 38 4k (n=1), 12 4k (n=1-4), 17 (mixture)
13a) 2k 8/10 3k, 45 4k (n=1), 21 4k (n=1-3), 9 (mixture)
a) DavePHOS was used instead of BINAP
H2N 0 0 NH2 2i
_0.33 equiv.
Pd(dba)2/Xanthphos 4/4.5 mol% Br fBuONa, dioxane reflux
H,N
0 0 2i
4 equiv. Pd(dba)2/BINAP
8/9 mol% fBuONa, dioxane reflux
NH,
5i, 27%
H2N 0 0 NH2 2i
Pd(dba)2/BINAP
8/9 mol% fBuONa, dioxane reflux
Pd(dba)2/BINAP
8/9 mol% fBuONa, dioxane reflux
4i, 44%
c
NH 0 0
4i, 27%
HN 0 0 HN
Figure 2.
taken as an exemplary amine (Figure 2). Three equivalents of 3,3'-dibromobiphenyl 1 were employed in the presence of 4 mol% catalyst to give 5i in 27% yield. The reaction was severely complicated by A,A-diarylation and diamination processes, thus the application of Xanthphos ligand instead of BINAP was helpful. The cyclization into cyclodimers with dioxadiamine 2i was carried out under the conditions similar to those used for the macrocycles 3. As a result, 4i (n=1) was isolated in 27% yield. The attempts to introduce diaryl derivative 5i in situ were totally unsuccessful. Alternative approach included the synthesis of bis(dioxadiamine) substituted biphenyl 6i using 4 equivalents of dioxadiamine 2i. The yield of this compounds in the reaction mixtures was very high according to NMR data, and 6i was used in situ in the further reaction with 3,3'-dibromobiphenyl (Scheme 2). Target macrocycle 4i (n=1) was obtained in 44% yield. This approach to cyclodimers was found to be much more efficient because it is carried out as a one-pot procedure and provides higher overall yield of the target compound.
Conclusions
To sum up, we have investigated 3,3'-dibromobiphenyl in the Pd-catalyzed amination reactions with polyamines and oxadiamines, demonstrated the possibilitites to obtain polyazamacrocycles in enough high yields, elaborated two approaches to the corresponding cyclodimers and found out the advantage of the route through bis(polyamine) derivatives.
Acknowledgements. This work was supported by RFBR grants 09-03-00735, 08-03-00628 and by the Russian Academy of Sciences program P-8 "Development of the methods for the synthesis of new chemicals and creation of new materials".
References
1. Kohama H., Yoshinaga M., Ishizu K. Bull. Chem. Soc. Jpn.
1980, 53, 3707-3708.
2. Reinhoudt D.N., de Jong F., van de Vondervoort E.M.
Tetrahedron 1981, 37, 1753-1762.
3. Reinhoudt D.N., de Jong F., van de Vondervoort E.M. Tetrahedron 1981, 37, 1985-1990.
4. Rebek Jr. J. Acc. Chem. Res. 1984, 17, 258-264.
5. Rebek Jr.J. Costello T., Marshall L., Wattley R., Gadwood R.C., Onan K. J. Am. Chem. Soc. 1985, 107, 7481-7487.
6. Rebek Jr.J., Wattley R.V., Costello T., Gadwood R., Marshall L. J. Am. Chem. Soc. 1980, 102, 7398-7400.
7. Gavina F., Luis S.V., Costero A.M., Burguete M.I., Rebek Jr., J. J. Am. Chem. Soc. 1988, 110, 7140-7143.
8. Burguete M.I., Diaz P., Garcia-Espana E., Luis S.V., Miravet J.F., Querol M., Ramirez J.A. Chem. Commun. 1999, 649650.
9. Pearson D.P.J., Leigh S.J., Sutherland I.O. J. Chem. Soc., Perkin Trans. 1979, 1, 3113-3126.
10. Montero A., Albericio F., Royo M., Herradön B. Eur. J. Org. Chem. 2007, 1301-1308.
11. Artz S.P., Cram D.J. J. Am. Chem. Soc. 1984, 106, 2160-2171.
12. Choi K., Hamilton A.D. J. Am. Chem. Soc. 2003, 125, 1024110249.
13. Kuhnert N., Straßnig K., Lopez-Periago A.M. Tetrahedron: Asymmetry 2002, 13, 123-128.
14. Kuhnert N., Rossignolo G.M., Lopez-Periago A.M. Org. Biomol. Chem, 2003, 1, 1157-1170.
15. Patel H.K., Kilburn J.D., Langley G.J., Edwards P.D., Mitchell T., Southgate R. Tetrahedron Lett. 1994, 35, 481-484.
16. Lloyd-Williams P., Giralt E. Chem. Soc. Rev. 2001, 30, 145157.
17. Yang B.H., Buchwald S.L. J. Organomet. Chem. 1999, 576, 125-146.
18. Beletskaya I.P., Bessmertnykh A.G., Averin A.D., Denat F., Guilard R. Eur. J. Org. Chem. 2005, 281-305.
19. Averin A.D., Ulanovskaya O.A., Fedotenko I.A., Borisenko A.A., Serebryakova M.V., Beletskaya I.P. Helv. Chim. Acta 2005, 88, 1983-2002.
20. Averin A.D., Ulanovskaya O.A., Pleshkova N.A., Borisenko A.A., Beletskaya I.P. Coll. Czech. Chem. Comm. 2007, 72, 785-819.
21. Averin A.D., Shukhaev A.V., Golub S.L., Buryak A.K., Beletskaya I.P. Synthesis 2007, 2995-3012.
22. Ukai T., Kawazura H., Ishii Y., Bonnet J.J., Ibers J.A. J. Organomet. Chem. 1974, 65, 253-266.
23. Snyder H.R., Weaver C., Marshall C.D. J. Am. Chem. Soc. 1949, 71, 289-291.
24. Wolfe J.P., Buchwald S.L. J. Org. Chem. 2000, 65, 1147-1157.
25. Averin A.D., Uglov A. N., Beletskaya I.P. Chem. Lett. 2008, 37, 1074-1075.
Received 09.07.2009 Accepted 11.08.2009
