6222 Journal of Medicinal Chemistry, 2007, Vol. 50, No. 24
Kalinowski et al.
atoms were refined with anisotropic thermal parameters. Aryl and
amino H-atoms were included at estimated positions using a riding
model. Water and amide H-atoms (if any) were first located from
difference maps then restrained at these positions in a manner
similar to that employed for the remaining H-atoms. Molecular
structure diagrams were produced with ORTEP3.74 The data in CIF
format has been deposited at the Cambridge Crystallographic Data
Centre.
577 m. 1H NMR (DMSO-d6) δ 9.29 (s, 1H, NH), 8.51 (d, 1H, ArH),
7.82-7.89 (m, 4H, ArH), 7.60 (dd, 2H, ArH), 7.41 (m, 3H, ArH),
7.31 (qd, 2H, ArH). 13C NMR (DMSO-d6) δ 91.2, 120.8, 122.8,
126.0, 128.8, 129.4, 131.1, 137.1, 142.9, 148.6, 161.3. MS (ESI)
m/z 319 (M + H+).
2-Benzoylpyridine Thiobenzoyl Hydrazone (HBPTBH), HBPT-
BH was collected as orange needles. Yield 63%. Crystals suitable
for X-ray work were obtained from CH2Cl2/hexane solution. Anal.
(C19H15N3S) C, H, N, S. IR (cm-1) 3040w, 2840w, 1475s, 1459m,
1447m, 1417m, 1315m, 1286w, 1243s, 1152w, 1126s, 1004m, 966s,
797m, 779s, 738s, 702s, 643s, 617 m. 1H NMR (DMSO-d6) δ 9.32
(s, 1H, NH), 8.57 (d, 1H, ArH), 7.90 (td, 1H, ArH), 7.76 (d, 1H,
ArH), 7.59 (d, 2H, ArH) 7.25-7.50 (m, 9H, ArH). 13C NMR
(DMSO-d6) δ 91.1, 120.2, 122.8, 126.0, 126.2, 127.7, 128.2, 128.8,
129.2, 131.3, 137.2, 143.5, 148.9, 161.7. MS (ESI) m/z 318 (M +
H+).
Synthesis of Thiobenzhydrazide. Thiobenzhydrazide was pre-
pared using standard procedures.75-77 Briefly, S-(thiobenzoyl)-
thioglycolic acid (2.0 g, 9.4 mmol) was dissolved in 1 M NaOH
(10 mL, 1 equiv). Water (10 mL) was then added, and this orange
solution was cooled in an ice bath. Upon the addition of hydrazine
hydrate (1.7 g, 55%, 18.8 mmol), the orange color disappeared.
Dilute HCl was added to bring the reaction pH to 5-6 and was
allowed to stir for 1 h while cooled in an ice bath. The product
was collected by vacuum filtration, washed with chilled water, and
air-dried. This crude product was subsequently recrystallized from
tepid water to yield thiobenzhydrazide as white crystals, which were
General Synthesis of the Fe Complexes (Using FeII(ClO4)2‚
6H2O). The appropriate sulfur ligand (1.1 mmol) was dissolved in
20 mL of acetonitrile, and the nonvolatile base, 1,6-diazabicyclo-
[5.4.0]undec-7-ene (0.17 g, 1.1 mmol), was added while purging
with nitrogen. Fe(ClO4)2‚6H2O (0.2 g, 0.55 mmol) was dissolved
in 6 mL of nitrogen-purged acetonitrile and was added with stirring
to the ligand solution. The mixture was then gently refluxed under
nitrogen for 30 min. After cooling, the green product was collected
by filtration and washed with acetonitrile.
stored at 4 °C. Yield 69%. Anal. (C7H8N2S) C, H, N. IR (cm-1
)
3264m, 3081s, 1589s, 1563s, 1493m, 1449m, 1388w, 1322w,
1309w, 1218m, 1109s, 1074w, 1035w, 1000w, 965m, 904m, 760m,
1
686s, 638w, 603w. H NMR (DMSO-d6) δ 7.72 (dd, 2H, ArH),
7.49 (m, 3H, ArH). MS (ESI) m/z 153 (M + H+).
Pyridoxal Thiobenzoyl Hydrazone (H2PTBH). Equimolar
amounts of pyridoxal hydrochloride (0.47 g, 2.3 mmol) and
thiobenzhydrazide (0.35 g, 2.3 mmol) were dissolved in ethanol
(100 mL) and refluxed for 30 min with stirring. Upon cooling, the
bright orange precipitate was collected by vacuum filtration to yield
pure H2PTBH‚0.5H2O as an orange powder. Yield 70%. Anal. calcd
for C15H16N3O2.5S: C, 58.04; H, 5.20; N, 13.54; S, 10.33%.
Found: C, 58.14; H, 4.74; N, 12.33; S, 9.60%. IR (cm-1) 3312m,
2692s, 1540m, 1472w, 1453w, 1393w, 1375w, 1320m, 1252s,
1230s, 1155m, 1089m, 1050m, 995m, 960m, 940w, 862w, 813m,
FeII(PKTBH)2. Yield 85%. Anal. (C36H26FeN8S2) C, H, N, S.
IR (cm-1) 3051w, 1582m, 1564w, 1510w, 1488w, 1452s, 1414s,
1345s, 1292w, 1279m, 1254w, 1234m, 1201w, 1172w, 1156w,
1116w, 1078m, 1029w, 1016w, 989m, 967m, 944w, 924w, 788m,
764s, 741s, 688s, 662w, 614m, 582s. 1H NMR (DMSO-d6) δ 8.98
(d, 1H, ArH), 8.59 (d, 1H, ArH), 8.30 (t, 1H, ArH), 8.09 (d, 2H,
ArH), 7.87 (d, 1H, ArH) 7.73 (t, 2H, ArH), 7.63 (t, 1H, ArH), 7.48
(t, 1H, ArH), 7.41 (t, 2H, ArH), 7.24 (t, 1H, ArH). Electronic
spectrum (MeOH): λmax (nm) (ꢀ L mol-1 cm-1) 272 (33000), 313
(29500), 372 (22500), 466 (8900), 724 (9500). MS (ESI-positive)
m/z 691 (Fe(PKTBH)2 + H+). Crystals suitable for X-ray work
were obtained by slow evaporation of a 1:1 CH2Cl2/MeOH solution.
FeII(BPTBH)2. Yield 72%. Anal. (C38H28FeN6S2) C, H, N, S.
IR (cm-1) 3055w, 1589w, 1506w, 1445w, 1417s, 1337s, 1300w,
1254w, 1172w, 1069m, 1014m, 999w, 962m, 911w, 781w, 766s,
743s, 721w, 691s, 656 m 625w, 580s. 1H NMR (DMSO-d6) δ 8.05
(d, 2H, ArH), 8.01 (d, 2H, ArH), 7.88 (d, 1H, ArH), 7.80 (t, 2H,
ArH), 7.69 (t, 1H, ArH) 7.61 (t, 1H, ArH), 7.43 (d, 2H, ArH), 7.37
(t, 2H, ArH), 7.23 (t, 1H, ArH). Electronic spectrum (MeOH): λmax
(nm) (ꢀ L mol-1 cm-1) 283 (34100), 368 (20800), 467 (9700), 727
(8100). MS (ESI-positive) m/z 688 (Fe(BPTBH)2 + H+).
General Synthesis of the Fe Complexes (Using FeIII(ClO4)3‚
6H2O). The appropriate ligand (0.87 mmol) was dissolved in 20
mL of acetonitrile, and the nonvolatile base, 1,6-diazabicyclo[5.4.0]-
undec-7-ene (0.26 g, 1.73 mmol), was added. Fe(ClO4)3‚6H2O (0.2
g, 0.43 mmol) was dissolved in 6 mL of acetonitrile and added
with stirring to the ligand solution. The mixture was then gently
refluxed for 30 min. After cooling, the dark product was collected
by filtration and washed with acetonitrile.
1
768m, 748m, 689s, 668s, 628w. H NMR (DMSO-d6) δ 13.03 (s,
1H), 9.45 (s, 1H, HCdN), 8.25 (s, 1H, ArH), 8.00 (d, 2H, ArH),
7.65 (d, 1H, ArH), 7.54 (dd, 2H, ArH), 4.81 (s, 2H, CH2), 2.68 (s,
3H, CH3). 13C NMR (DMSO-d6) δ 14.6, 57.9, 127.5, 127.8, 128.2,
129.3, 131.8, 137.2, 138.2, 143.8, 148.6, 152.4, 195.0. MS (ESI)
m/z 302 (M + H+). All other sulfur analogues were prepared in a
similar manner with the appropriate aldehyde or ketone.
Salicylaldehyde Thiobenzoyl Hydrazone (H2STBH). The
H2STBH monomer was isolated by direct crystallization from the
reaction mixture. Yield 88%. Anal. (C14H12N2OS) C, H, N, S. IR
(cm-1) 3194m, 3022w, 1606m, 1566w, 1518w, 1480m, 1444m,
1362w, 1331m, 1308w, 1288w, 1264w, 1231w, 1198w, 1152w,
1031w, 952s, 792m, 744s, 683s, 665m, 631m, 577s. 1H NMR
(DMSO-d6) δ 13.61 (s, NH, Z isomer), 11.56 (s, OH, Z isomer),
10.60 (s, OH, E isomer), 9.96 (s, HCdN), 8.89 (s, NH, E isomer),
7.86 (d, ArH), 7.34-7.64 (m, ArH), 7.15 (td, ArH), 6.97-7.02
(m, ArH), 6.79-6.87 (m, ArH). MS (ESI) m/z 257 (M + H+). The
azine disulfide was isolated by further recrystallization of the
monomer in hot EtOH.
2-Hydroxy-1-Naphthaldehyde Thiobenzoyl Hydrazone
(H2NTBH). H2NTBH was collected as small orange crystals, which
were suitable for crystallography. Yield 40%. Anal. calcd for
C18H14N2OS: C, 70.56; H, 4.61; N, 9.14; S, 10.46%. Found: C,
69.58; H, 4.77; N, 9.22; S, 11.75%. IR (cm-1) 3095w, 2952w,
2870w, 1619m, 1596m, 1564s, 1461m, 1410w, 1340m, 1306w,
1230m, 1182s, 1083m, 974m 939s, 860w, 823s, 774s, 744s, 691s,
[FeIII(HPTBH)(PTBH)]‚2.75H2O. The H2PTBH Fe complex
was obtained in the ferric form. Yield 87%. Anal. calcd. for C30H32.5
-
FeN6O6.75S2: C, 51.10; H, 4.65, N, 11.92; S, 9.09%. Found: C,
51.01; H, 4.13; N, 12.02; S, 8.77%. IR (cm-1) 3462m, 2782m,
2642s, 1621m, 1559w, 1473s, 1421s, 1372s, 1311m, 1221s, 1175w,
1088w, 1037m, 994s, 933s, 827m, 757s, 687s, 645w, 612s, 586w,
1
664m, 637s. H NMR (DMSO-d6) δ 11.26 (s, 1H), 8.58 (d, 1H,
556w. Electronic spectrum (MeOH): λmax (nm) (ꢀ L mol-1 cm-1
)
ArH), 8.08-8.14 (m, 2H, ArH), 8.04 (d, 1H, ArH), 7.93 (d, 1H,
ArH), 7.54-7.64 (m, 4H, ArH), 7.38-7.45 (m, 2H, ArH). 13C NMR
(DMSO-d6) δ 118.9, 120.3, 123.5, 127.5, 127.8, 127.8, 128.1, 128.9,
131.0, 131.7, 133.7, 139.1, 151.2, 158.4, 191.8. MS (ESI) m/z 307
(M + H+).
Di-2-pyridylketone Thiobenzoyl Hydrazone (HPKTBH).
HPKTBH was isolated as the cyclic dihydrothiadiazole form. Yield
50%. Anal. (C18H14N4S) C, H, N, S. IR (cm-1) 3253m, 3057w,
1584s, 1567m, 1461m, 1429s, 1295w, 1270m, 1112w, 1100w,
1053m, 979m, 966m, 909m, 756s, 745s, 691s, 673s, 648m, 616m,
253 (44100), 418 (14400). MS (ESI-positive) m/z 656 (Fe(HPTBH)-
(PTBH) + H+). Crystals of the complex [Fe(HPTBH)2]Cl‚2H2O
were grown from slow evaporation of a 1:1 DMF/MeOH solution
of the complex in the presence of a slight excess of NaCl.
(NMe4)2[FeII(STBH)2]‚0.5NMe4ClO4‚0.5CH3CN. NMe4ClO4
(75 mg, 0.43 mmol) was added to assist the crystallization of the
complex. The H2STBH Fe complex was obtained in the ferrous
form. Yield 67%. Anal. calcd. for C39H51.5Cl0.5FeN7O4S2: C, 57.12;
H, 6.33, N, 11.96; S, 7.82%. Found: C, 56.72; H, 5.55; N, 11.66;
S, 6.57%. IR (cm-1) 3225w, 3110w, 2936w, 1637s, 1579s, 1533m,