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P. Wang et al. / European Journal of Medicinal Chemistry 74 (2014) 199e215
Elemental Anal. Calcd for C7H8NO5ClSRu: C, 23.70; H, 2.27; N, 3.95%.
Found: C, 24.33; H, 2.75; N, 3.71%.
13C NMR (CDCl3, TMS, ppm):
d 196.8 (RueCO), 195.5 (RueCO), 171.2
(COO), 168.3 (CON), 157.1, 145.1, 143.6, 135.3, 134.4, 128.0, 127.6,
122.9, 117.8, 116.8, 116.6, 21.3. ESI-MS: calcd for C17H13O6Cl2N2Ru
[M þ H]þ 512.9194, found 512.9106. Elemental Anal. Calcd for
4.10.16. Preparation of Ru(CO)3Cl-Acac (8)
509.5 mg orange solid was obtained after recrystallization in
81.1% yield. IR (KBr, cmꢀ1): 2925.5 (w, CH), 2134.4 (w, CO), 2067.4 (s,
CO), 1998.6 (s, CO), 1627.2 (m, C]O), 1523.1 (w, C]C). 1H NMR
C17H12N2O6Cl2Ru: C, 39.86; H, 2.36; N, 5.47%. Found: C, 40.03; H,
2.68; N, 5.35%.
(DMSO-d6, TMS, ppm):
d
5.578 (s, 1H, CH]C), 3.346 (s, 6H, 2CH3).
197.0 (RueCO), 186.8 (RueCO), 99.4
4.10.20. Preparation of [Ru(CO)3Cl2-L5] (12)
13C NMR (CDCl3, TMS, ppm):
d
A 228.9 mg portion of pale yellow solid was isolated with yield
89.4%. IR (KBr, cmꢀ1): 3324.6 (w, NH), 2137.5 (s, CO), 2064.9 (s, CO),
1996.0 (s, CO), 1715.6 (m, COO), 1616.4 (s, CONH), 1593.1 (m, pyri-
dine, C]C), 1513.2 (s, Ar C]C). 1H NMR (DMSO-d6, TMS, ppm):
(CH3CO), 46.8 (CH), 28.1 (CH3). ESI-MS: calcd for C8H7O5ClRuNa
[M þ Na]þ 342.8923, found 342.8801. Elemental Anal. Calcd for
C8H7O5ClRu: C, 30.06; H, 2.21%. Found: C, 30.21; H, 2.38%.
d
11.275 (s, 1H, NH), 8.805 (m, 2H, pyridine H2,6), 8.644 (d, 1H,
4.10.17. Preparation of [Ru(bpy)(CO)3Cl]þ [Cl]ꢀ(H5O2)þClꢀ (9) [61]
[Ru(CO)3Cl2]2 (500 mg) and 625 mg of 2,20-bipyridine were
dissolved separately in 5 ml of ethylene glycol. Solutions were
gently heated until reagents were completely dissolved. Solutions
were combined and stirred for 2 h at room temperature. Pale yel-
low started to precipitate almost immediately after combining of
the solutions. The solid product was washed with 2-propanol and
hexane and dried under vacuum. The complex obtained above was
dissolved in a little amount of concentrated HCl under air. After a
few minutes, nearly colorless solid started to crystallize. The solu-
tion was allowed to evaporate to dryness at room temperature. The
total yield was 46%. IR (KBr, cmꢀ1): 2112.4 (s, CO), 2060.7 (v, CO),
1993.3 (v, CO), 1602.8 (s, pyridine C]C). 1H NMR (CDCl3, ppm):
J ¼ 5.2 Hz, AreH6), 8.463 (d, 1H, J ¼ 6.0 Hz, AreH3), 7.972 (d, 1H,
J ¼ 5.2 Hz, AreH4), 7.781 (m, 2H, pyridine H3,5), 7.715 (d, 1H,
J ¼ 6.0 Hz, AreH5), 2.201 (s, CH3). 13C NMR (DMSO-d6, TMS, ppm):
d
195.9 (RueCO), 194.3 (RueCO), 174.1 (COO), 167.0 (CON), 157.1,
149.0,143.3,134.1,129.8,121.5,120.1,118.9,116.7, 21.4. ESI-MS: calcd
for C17H13O6Cl2N2Ru [M þ H]þ 512.9194, found 512.9114. Elemental
Anal. Calcd for C17H12N2O6Cl2Ru: C, 39.86; H, 2.36; N, 5.47%. Found:
C, 40.06; H, 2.49; N, 5.66%.
4.10.21. Preparation of [Ru(CO)3Cl2-L6] (13)
A 273.9 mg portion of yellow solid was isolated with yield 92.9%.
IR (KBr, cmꢀ1): 3069.2 (w, NH2), 2132.2 (v, CO), 2059.7 (v, CO),
1994.2 (s, CO), 1746.9 (m, COO), 1611.4 (s, CONH), 1543.6 (m, pyri-
d
9.202 (d, 2H, J ¼ 7.2 Hz), 8.814 (d, 2H, J ¼ 8.0 Hz), 8.210 (t, 2H,
dine, C]C), 1486.2 (s, Ar C]C). 1H NMR (CDCl3, TMS, ppm):
d 9.313
J ¼ 7.6 Hz), 7.879 (t, 2H, J ¼ 6.4 Hz). 13C NMR (CDCl3, ppm):
d
188.1
(s, NH), 8.222 (s, AreH), 8.084 (s, AreH), 7.949 (s, AreH), 7.857 (t,
J ¼ 6.8 Hz, AreH), 7.545 (m, AreH), 7.130 (t, J ¼ 8.4 Hz, AreH), 6.998
(s, AreH), 6.926 (d, J ¼ 7.6 Hz, AreH), 5.251 (t, 1H, BpeCH), 4.644 (t,
(RueCO), 184.5 (RueCO), 157.2, 156.3, 143.5, 130.0, 126.6. Elemental
Anal. Calcd for C13H13N2O5Cl3Ru: C, 32.21; H, 2.70; N, 5.78%. Found:
C, 32.41; H, 2.92; N, 5.63%.
1H, BpeCH), 2.337 (s, CH3). 13C NMR (CDCl3, TMS, ppm):
d 197.3
(RueCO), 194.5 (RueCO), 173.9 (COO), 170.6 (CON), 160.3, 158.7,
157.9, 148.1, 135.7, 134.3, 127.1, 125.6, 123.4, 122.1, 119.0, 45.1, 22.1.
ESI-MS: calcd for C18H15O6Cl2N2Ru [M þ H]þ 526.9351, found
526.9256. Elemental Anal. Calcd for C18H14N2O6Cl2Ru: C, 41.08; H,
2.68; N, 5.32%. Found: C, 41.71; H, 2.95; N, 5.43%.
4.10.18. Preparation of [Ru(CO)3Cl2-L3] (10) [56]
[Ru(CO)3Cl2]2 (256.1 mg, 0.50 mmol) was added to the solution
of 256.0 mg (1.00 mmol) L3 in 15 ml of deoxygenated 1,2-
dimethoxyethane. Then the solution was heated at 60 ꢁC, and the
mixture was stirred for 6 h in the presence of nitrogen atmosphere.
After filtering, the solvent was removed under vacuum, the residue
was extracted by minimum amount of THF. After removing solvent
under vacuum 473.02 mg pale yellow solid was obtained with yield
92.4%. IR (KBr, cmꢀ1): 3079.9 (w, NH), 2134.3 (s, CO), 2065.6 (s, CO),
1955.8 (s, CO), 1765.8 (m, COO), 1641.0 (s, CONH), 1615.8 (s, pyridine
4.10.22. Preparation of [Ru(CO)3-L7]þClꢀ (14)
[Ru(CO)3Cl2]2 (256.0 mg, 0.50 mmol) was added to the solution
of 164.1 mg (1.00 mmol) L7 and 200 ml (1.43 mmol) Et3N in 15 ml of
deoxygenated 1,2-dimethoxyethane. Then the solution was heated
at 60 ꢁC, and the mixture was stirred for 5 h in the presence of
nitrogen atmosphere. The solvent was removed under vacuum, and
the residue was extracted by minimum amount of THF. After
filtering, the THF was removed and 322.6 mg golden yellow solid
was obtained with yield 92.7%. IR (KBr, cmꢀ1) 2981.8 (w, NH2),
2047.1 (v, CO),1971.1 (v, CO), 1930.7 (m, CO),1618.4 (s, C]N), 1448.0
C]C), 1478.6 (s, Ar C]C). 1H NMR (DMSO-d6, TMS, ppm):
d 12.889
(s, 1H, NH), 8.793 (d, 1H, J ¼ 5.6 Hz, AreH), 8.253 (t, 1H, J ¼ 7.6 Hz,
AreH), 7.863 (d,1H, J ¼ 6.8 Hz, AreH), 7.772 (t,1H, J ¼ 7.2 Hz, AreH),
7.642 (d, 1H, J ¼ 8.4 Hz, AreH), 7.588 (t, 1H, J ¼ 6.4 Hz, AreH), 7.523
(t, 1H, J ¼ 7.2 Hz, AreH), 7.413 (d, 1H, J ¼ 7.6 Hz, AreH), 2.331 (s, 3H,
CH3). 13C NMR (DMSO-d6, TMS, ppm):
d
196.6 (RueCO), 195.1 (Rue
(m, Ar C]C). 1H NMR (CDCl3, TMS, ppm):
d 9.099 (bs, 2H, NH2),
CO), 168.8 (CON, COO), 148.7, 148.1, 142.2, 134.1, 130.0, 126.0, 125.8,
8.346 (s, 1H, AreCH), 7.234e6.337 (m, AreH), 4.891 (d, 1H,
J ¼ 9.6 Hz, NCH), 4.512 (d, 1H, J ¼ 6.4 Hz, NCH), 4.310 (d, 1H,
J ¼ 6.8 Hz, NCH), 4.066 (d, 1H, J ¼ 9.6 Hz, N-CH). 13C NMR (CDCl3,
124.2, 122.9, 117.9, 20.9. ESI-MS: calcd for
C17H13O6Cl2N2Ru
[M þ H]þ 512.9194, found 512.9097. Elemental Anal. Calcd for
C
17H12N2O6Cl2Ru: C, 39.86; H, 2.36; N, 5.47%. Found: C, 40.26; H,
TMS, ppm): d 195.0 (RueCO), 188.3 (RueCO), 185.4 (RueCO), 161.9,
2.72; N, 5.62%.
157.4, 133.2, 131.6, 125.3, 120.4, 115.2, 54.1, 39.61. Elemental Anal.
Calcd for C12H11N2O4RuCl: C, 37.56; H, 2.89; N, 7.30%. Found: C,
37.98; H, 3.02; N, 7.46%.
4.10.19. Preparation of [Ru(CO)3Cl2-L4] (11)
Complexes 11e13 were synthesized following the same proce-
dure as for complexes 10, but changing the ligand from L4eL6. A
233.7 mg portion of pale yellow solid was isolated with yield 91.2%.
IR (KBr, cmꢀ1): 3079.8 (w, NH), 2136.4 (s, CO), 2071.5 (s, CO), 2005.2
(m, CO),1759.9 (m, COO),1683.4 (m, CONH),1608.7 (m, pyridine C]
4.10.23. Preparation of [Ru(CO)3-L8]þClꢀ (15)
Complex 15 was synthesized following the same procedure as
for complex 14, but changing the ligand L8, 336.4 mg scarlet red
solid was obtained with yield 90.9%. IR (KBr, cmꢀ1): 2049.3 (s, CO),
2022.2 (s, CO), 1973.8 (s, CO), 1935.1 (s, CO), 1611.9 (s, C]N), 1522.5
(m, pyridine C]C), 1466.8 (m, pyridine C]C), 1440.1 (m, Ar C]C).
C), 1541.5 (m, Ar C]C). 1H NMR (CDCl3, TMS, ppm):
d 9.184 (s, 1H,
NH), 8.831 (s, 1H, AreH), 8.575 (d, 1H, J ¼ 8.0 Hz, AreH), 8.517 (d,
1H, J ¼ 5.2 Hz, AreH), 7.884 (d, 1H, J ¼ 7.2 Hz, AreH), 7.564 (t, 1H,
J ¼ 7.6 Hz, AreH), 7.478 (t, 1H, J ¼ 6.8 Hz, AreH), 7.376 (t, 1H,
J ¼ 7.6 Hz, AreH), 7.208 (d, 1H, J ¼ 8.4 Hz, AreH), 2.418 (s, 3H, CH3).
1H NMR (CDCl3, TMS, ppm):
aromatic H). 13C NMR (CDCl3, TMS, ppm):
(RueCO),186.1 (RueCO),173.1,166.2,156.8,150.3,139.2,133.1,131.8,
d
9.202 (s, AreCH), 7.346e6.557 (m,
195.2 (RueCO), 188.0
d