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mL, three times). The organic phase dried over sodium sulfate
and concentrated. Compound 9 was obtained as a white solid;
1
2
2
.8 g (80%). H NMR (400 MHz, DMSO) d 6.92 (s, 2H), 5.41 (s,
H), 4.90 (d, J ¼ 2.4 Hz, 2H), 4.48 (s, 4H), 3.66 (t, J ¼ 2.4 Hz, 1H).
Synthesis of 2,6-bis (chloromethyl)-4-(prop-2-yn-1-yloxy)
pyridine (10). Compound 9 (2.5 g, 13 mmol) was slowly added
ꢁ
in 20 mL of SOCl
2
at 0 C. The reaction mixture was stirred at
room temperature for 1 h and heated to reux for another 2 h.
The crude mixture was removed solvent under vacuum and
2
0 mL of H O was added. The solution was ltrated and satu-
2
rated aqueous solution of sodium bicarbonate was added in
drops into the ltrate. The precipitate was isolated by ltration
1
to afford compound 10; 2.4 g, (80%). H NMR (400 MHz, CDCl
3
)
d 7.05 (s, 2H), 4.81 (d, J ¼ 2.4 Hz, 2H), 4.64 (s, 4H), 2.61 (s, 1H).
1
3
3
C NMR (101 MHz, CDCl ) d 166.49 (s), 157.20 (s), 109.51 (s),
Fig. 8 Synthesis scheme of rigid ligand (L). (a) SOCl
2
, MeOH, reflux for
ꢁ
ꢁ
77.59 (s), 77.23 (s), 56.34 (s), 44.87 (s). ESI-MS: m/z ¼ 230.01 (M +
1
2 3 3
h; (b) KI, K CO , CH CN, 45 C, 12 h; (c) NaOH, H
h.
2
O/MeOH, 45 C,
+
2
H ).
Synthesis and characterization of ligand with alkynyl group
(
1
K
L-Alkynyl, 11). Compound 2 (2.65 g, 16 mmol) and compound
0 (2.1 g, 8 mmol) were dissolved in 30 mL dry acetonitrile,
ꢀ1
solution (MnL concentration: 10 mg mL ). MnL complexes in
the following experiments were further puried through
Sephadex LH-20 column before use.
2
CO
3
(11 g, 80 mmol) and KI (30 mg) were added. The mixture
ꢁ
was stirred at 45 C for 12 h. Filtered inorganic salt from solu-
tion, solvent was evaporated off. The product was puried by
silica gel column chromatography (methylene dichloride/ethyl
Synthesis of the ligand with alkynyl group
1
acetate ¼ 2/1). H NMR (400 MHz, CDCl
3
) d 6.98 (s, 2H), 4.75
Synthesis of dimethyl 4-hydroxypyridine-2,6-dicarboxylate (d, J ¼ 1.6 Hz, 2H), 3.97 (t, J ¼ 15.7 Hz, 2H), 3.76 (d, J ¼ 14.2 Hz,
(
7). Chelidamic acid 6 (10.0 g, 54.6 mmol) was suspended in 2H), 3.67 (s, 6H), 3.49–3.37 (m, 2H), 3.18–3.04 (m, 2H), 2.54 (q, J
1
50 mL absolute methanol (MeOH). Then, 2,2-dimethoxy- ¼ 8.2 Hz, 3H), 2.25–1.70 (m, 8H). Then, the product (830 mg, 2
propane (DMP, 60 mL, 75 mmol) and concentrated HCl (7.5 mL, mmol) was dissolved in 20 mL methanol, NaOH (320 mg, 8
7
5 mmol) were slowly added in with magnetic stirring. The mmol) was dissolved in 2 mL MilliQ water and added in. Stirring
ꢁ
result mixture was heated to reux for 4 h under a CaCl drying at 40 C for 5 h, methanol and water was evaporated off. The
2
tube. Following, cooling to room temperature and evaporating light-yellow solid was dissolved in 5 mL water, added concen-
off the solvents. Anhydrous ether (100 mL) was added in to stir, trated HCl to adjust pH to 6.5, and water was evaporated off.
the insoluble hydrochloride (compound 7) was ltered to be Ethanol added to dissolve the product, ltered resulting salt.
1
1
collected (11.9 g, yield 88%). H NMR (400 MHz, DMSO) d 7.65 Solvent was evaporated off to get the ligand (765 mg, 99%). H
s, 2H), 3.89 (s, 6H).
NMR (400 MHz, D
O) d 7.16 (s, 2H), 4.93 (s, 2H), 4.52 (d, J ¼
Synthesis of dimethyl 4-(prop-2-yn-1-yloxy)pyridine-2,6- 13.8 Hz, 2H), 4.40 (d, J ¼ 12.4 Hz, 2H), 3.94 (m, 2H), 3.82–3.63 (m,
(
2
1
3
dicarboxylate (8). Compound 7 (5.0 g, 20 mmol) was dissolved 2H), 3.21 (m, 2H), 2.58–2.39 (m, 2H), 2.26–1.96 (m, 7H). C NMR
in 150 mL acetonitrile, anhydrous K CO (27.6 g, 200 mmol) was (101 MHz, D O) d 165.21 (s), 141.91 (s), 129.68 (s), 110.63 (s),
2
3
2
added in. The solution was stirred for 30 min at room temper- 77.70 (s), 76.77 (s), 69.07 (s), 58.89 (s), 57.38 (s), 56.13 (s), 28.96
+
ature. Then, 3-bromo-1-propyne solution in toluene (3.4 mL, (s), 22.61 (s). HRMS (ESI): m/z ¼ 410.1647 (M + Na ) (Fig. 9).
30 mmol) was added, and heated to reux for 12 h. Filtered the
insoluble from solution, acetonitrile was evaporated off to
obtain crude product. 50 mL chloroform added to dissolve the
product, washed three times with 20 mL water in a separatory
2
+
Synthesis of PEGylated Mn complex (MnL-PEG-MnL)
Synthesis of PEG with terminal azide group (N -PEG-N ).
3
3
funnel. Chloroform layer was dried with anhydrous magnesium PEG2k (Mw 2000 Da) or PEG4.6k (Mw 4600 Da) (1 mmol) and
sulfate. Filtered and evaporated off chloroform to get the triethylamine (1 mL) were dissolved in 100 mL of methylene
1
product 8 (4.5 g, 90%). H NMR (400 MHz, CDCl
4
3
) d 7.91 (s, 2H), chloride. P-Toluenesulfonyl chloride (0.95 g, 5 mmol) dissolved
ꢁ
.88 (d, J ¼ 1.4 Hz, 2H), 4.02 (s, 6H), 2.63 (s, 1H).
Synthesis of
dimethanol (9). Compound 8 (4.5 g, 18 mmol) was dissolved was washed three times with 50 mL water in a separatory fun-
in 20 mL methylene chloride was added in slowly at 0 C. The
(4-(prop-2-yn-1-yloxy)pyridine-2,6-diyl) solution was stirred at room temperature for 24 h. The mixture
in 80 mL ethanol, NaBH
4
(2.7 g, 72 mmol) was added in slowly at nel. Methylene chloride layer was dried with anhydrous
ꢁ
0
2
C. The reaction mixture was stirred at room temperature for magnesium sulfate and concentrated to 30 mL. The products
h and heated to reux for another 5 h. The crude mixture was were precipitated in cold diethyl ether, and dried in vacuo to give
concentrated under vacuum and 100 mL saturated aqueous a white powder. Then, the product was dissolved in 50 mL DMF,
solution of potassium carbonate was added. Aer stirred at NaN (325 mg) was added in slowly. The mixture was heat to
0 C for 2 h, products were extracted out with chloroform (100 60 C and stirred for 24 hours. DMF was evaporated off via
3
ꢁ
ꢁ
6
This journal is © The Royal Society of Chemistry 2017
RSC Adv., 2017, 7, 54603–54609 | 54607
Wu, Changqiang
