A Bifunctional Chelator and its Coordination Chemistry with (O)ReV
FULL PAPER
[PPh4][ReO{(NH2)ON2S}] (6): [ReOCl3(PPh3)2] (324.5 mg,
0.39 mmol) was added to a mixture of 5 (149.1 mg, 0.3 mmol) and
sodium acetate (163.2 mg, 1.2 mmol) in dry methanol (40 mL). Af-
ter refluxing for 4 h, the solution was cooled, filtered, then evapo-
rated to dryness. The residue was dissolved in a mixture of MeOH
(15 mL) and CH2Cl2 (15 mL), then tetraphenylphosphonium chlo-
ride (122.7 mg, 0.33 mmol) was added. After stirring for 30 min the
solvent was removed and the crude product was purified by column
chromatography on silica gel (eluent: CH2Cl2/MeOH, 98:2 then
95:5 then 90:10) to yield complex 6 as a red powder (137.8 mg,
[Na][ReO{(β-ala)ON2S}]
(9):
[ReOCl3(PPh3)2]
(103.8 mg,
0.126 mmol) was added to 8 (63 mg, 0.096 mmol) and sodium ace-
tate (52.2 mg, 0.384 mmol) dissolved in dry methanol (20 mL). Af-
ter refluxing for 4 h, the solution turned brown. After cooling, the
solution was filtered and the solvents evaporated to dryness. The
residue was purified twice by column chromatography on silica gel
(eluent: CHCl3/MeOH: 95:15 then 85:15) to yield complex 9 as a
dark-red powder (37.0 mg, 60%). M.p. 172 °C. 1H NMR
(400 MHz, MeOD): δ = 1.21 (t, J = 7.2 Hz, 3 H, CH3), 2.66 (t, J
= 6.6 Hz, 2 H, CH2), 3.81 (d, J = 17.4 Hz, 1 H, CH2S), 3.84 (t, J
= 6.6 Hz, 2 H, CH2), 4.10 (q, J = 7.2 Hz, 2 H, OCH2), 4.15 (d, J
1
58%). M.p. 184 °C. H NMR (250 MHz, CDCl3): δ = 3.30 (m, 2
H, NH2), 3.63 (d, J = 17.1 Hz, 1 H, CH2S), 3.93 (d, J = 17.1 Hz, = 17.4 Hz, 1 H, CH2S), 4.53 (d, J = 18.3 Hz, 1 H, CH2N), 5.47 (d,
1 H, CH2S), 4.35 (d, J = 18.3 Hz, 1 H, CH2N), 5.29 (d, J = 18.3 Hz,
1 H, CH2N), 6.14 (dd, J = 8.2 and 2.4 Hz, 1 H, HAr), 6.72 (d, J =
J = 18.3 Hz, 1 H, CH2N), 6.83 (dd, J = 8.5 and 2.3 Hz, 1 H, HAr),
7.08 (d, J = 8.5 Hz, 1 H, HAr), 8.16 (d, J = 2.3 Hz, 1 H, HAr) ppm.
8.2 Hz, 1 H, HAr), 7.48 (m, 9 H, HAr + HAr PPh ), 7.67 (m, 8 H, 13C{1H} NMR (100.6 MHz, MeOD): δ = 14.2 (CH3), 34.0 (CH2),
4
HA r
), 7.81 (m, 4 H, HA r
) ppm. 1 3 C{1 H} NMR 40.8 (CH2S), 41.0 (CH2), 61.1 (OCH2), 61.7 (CH2N), 118.6, 119.4,
P P h 4
P P h 4
(100.6 MHz, CDCl3): δC(ppm) = 40.4 (CH2S), 61.2 (CH2N), 106.6,
122.3 (3 CHAr), 127.5, 131.4, 146.2 (3 CAr), 172.0 (CO), 179.6 (CS),
109.6, 114.6 (3 CHAr), 116.8, 118.0 (4 CAr PPh ), 130.9, 131.1, 134.3, 187.4, 193.1 (2 CO) ppm. MS (ES–): m/z (%) = 611 (60), 613 (100)
134.4, 135.7, 135.8 (20 CHAr
), 140.6, 164.47 (2 CAr), 186.9, 193.4 [M–]. IR (KBr): νRe=O = 968 cm–1. C16H18N4NaO6S2Re (636.67).
PPh4
(2 CO) ppm. MS (ES–): m/z (%) = 452 (60), 454 (100) [M–]. IR
(KBr): νRe=O = 950 cm–1. C34H29N3O4PReS (792.86): calcd. C
51.51, H 3.69, N 5.30; found C 51.08, H 3.43, N 5.14.
calcd. C 30.18, H 3.01, N 8.80; found C 31.00, H 3.05, N 9.00.
Stability vs. Cysteine: A freshly prepared 50 m buffered saline
solution of cysteine was added to a 1-m methanolic solution of
the rhenium complex (6 or 9). The vial was sealed with a Teflon-
lined cap and the solution was stirred and incubated at 37 °C for
various time intervals (1, 6 and 18 h). Aliquots were removed peri-
odically and analysed by HPLC.
N-(4-Isothiocyanato-2-hydroxyphenyl)-2-[(triphenylmethylthio)meth-
ylcarbonylamino]ethanamide (7): Thiophosgene (540 µL, 7.0 mmol)
was added to a solution of 5 (350 mg, 0.7 mmol) in THF (10 mL).
The solution was stirred for one hour at room temperature under
nitrogen, and the solvent was then removed under reduced pressure.
The residue was purified by column chromatography on silica gel
(eluent: CHCl3 then CHCl3/MeOH, 95:5) to give compound 7 as
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1
a white powder (330 mg, 87%). H NMR (250 MHz, [D6]DMSO):
δ = 2.86 (s, 2 H, CH2S), 3.85 (d, J = 5.6 Hz, 2 H, CH2N), 6.88 (d,
J = 8.6 Hz, 1 H, HAr), 7.01 (dd, J = 8.6 and 2.6 Hz, 1 H, HAr),
7.31 (m, 15 H, HAr Trt), 7.99 (d, J = 2.6 Hz, 1 H, HAr), 8.34 (s, 1
H, NH), 9.27 (s, 1 H, NH), 10.59 (s, 1 H, OH) ppm. 13C{1H} NMR
(100.6 MHz, [D6]DMSO): δ = 36.3 (CH2S), 43.7 (CH2N), 66.6
(CTrt), 116.0, 118.8 (2 CHAr), 120.9 (CS), 122.1 (CHAr), 127.4 (CAr),
127.3, 128.6, 129.6 (15 CHAr Trt), 132.6 (CAr), 144.5 (3 CAr Trt),
147.5 (CAr), 168.4 (2 CO) ppm. MS (DCI/NH3): m/z = 540 [M +
H+], 557 [M + NH4+]. IR (KBr): νC=O = 1657, 1698; νNCS
=
2124 cm–1. C30H25N3O3S2 (539.67): calcd. C 66.77, H 4.67, N 7.79;
found C 66.58, H 4.37, N 7.70.
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(β-ala)ON2S(Trt) (8): Compound 7 (301.8 mg, 0.56 mmol) was
added, under nitrogen, to a solution of β-alanine ethyl ester hydro-
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THF (10 mL). The mixture was stirred for three hours at room
temperature and the solvent was then removed under reduced pres-
sure. The residue was purified by column chromatography on silica
gel (eluent: CHCl3 then CHCl3/MeOH, 95:5) to give compound 8
1
as a white powder (334.2 mg, 91%). H NMR (400 MHz, CDCl3):
δ = 1.19 (t, J = 7.1 Hz, 3 H, CH3), 2.63 (t, J = 5.8 Hz, 2 H, CH2),
3.19 (s, 2 H, CH2S), 3.74 (d, J = 5.1 Hz, 2 H, CH2N), 3.83 (t, J =
5.8 Hz, 2 H, CH2), 4.06 (q, J = 7.1 Hz, 2 H, OCH2), 6.74 (s, 1 H,
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NH), 6.83 (m, 3 H, HAr), 6.95 (s, 1 H, NH), 7.28 (m, 9 H, HAr Trt), [11] a) S. G. Gouin, E. Benoist, J.-F. Gestin, J.-C. Meslin, D. De-
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Gestin, L. Morandeau, F. Segat-Dioury, J.-C. Meslin, D. De-
niaud, Org. Biomol. Chem. 2005, 3, 454–461.
7.41 (m, 6 H, HAr Trt), 8.09 (s, 1 H, NH), 8.75 (m, 2 H, OH + NH)
ppm. 13C{1H} NMR (100.6 MHz, CDCl3): δ = 14.3 (CH3), 33.8
(CH2), 35.7 (CH2S), 40.7 (CH2), 44.3 (CH2N), 61.1 (OCH2), 68.1
(CTrt), 118.3, 119.4, 123.5 (3 CHAr), 126.5 (CAr), 127.4, 128.5, 129.7
(15 CHAr Trt), 130.4 (CAr), 144.0 (3 CAr Trt), 146.5 (CAr), 167.9,
170.4, 172.9 (3 CO), 180.9 (CS) ppm. MS (DCI/NH3): m/z = 657
[M + H+]. IR (KBr): νC=O = 1720, 1654 cm–1. C35H36N4O5S2
(656.82): calcd. C 64.00, H 5.52, N 8.53; found C 63.18, H 5.40, N
8.12.
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