Phenanthroline-derived ratiometric chemosensor for ureas

Article abstract of DOI:10.1021/jo062130h

The syntheses of 1,10-phenanthroline fluorophore-based chemosensor 7 and its truncated analog 9 are reported. Interactions of these compounds with urea, thiourea, 1,3-dimethylurea, tetrahydropyrimidin-2(lH)-one, imidazolidin-2-one, and selected uronium sa

Full text of DOI:10.1021/jo062130h

Supporting Information.
Tweezer-Type Ratiometric Chemosensor for Ureas and
Uronium Salts
Yoni Engel, Adi Dahan, Emily Rozenshine-Kemelmakher and Michael Gozin*
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel Aviv University,
Tel Aviv 69978, Israel.
cogozin@mgchem.tau.ac.il
Content
Theoretical calculations………………….……………………………….S2
Synthetic Procedures for 1-3……………………………………………...S3-S6
NMR spectra of 1-10……………………………………………………...S7-S17
IR spectra of 1-10…………………………………………………………S18-S22
MS spectra of 1-10………………………………………………………..S23-S27
UV-Vis spectra of 1-9……………………………………………….……S28-S32
Titrations data..…………………………....………………………………S33-S35
Calculations results………………………………….…………………….S36-S40
S1

Theoretical calculations.
Calculated geometries were optimized by the Gaussian 03 package at the DFT level of theory
by using the B3LYP functional and the 3-21g(**) basis set.
S2

1,10-Phenanthroline-N-oxide (1). To a solution of 1,10-phenanthroline monohydrate (4.87 g,
24.57 mmol) in acetic acid (30 mL) was added 30% H2O2 (3.2 mL). The temperature was
carefully maintained at 70 oC for 3 h, after which an additional portion of H2O2 (3.2 mL) was
added and the heating was continued for an additional 3 h. After cooling to rt, a third portion of
H2O2 (2 mL) was added and the reaction mixture was stirred for 10 h. Then, the solution was
concentrated under vacuum to a total volume of approximately 10 mL, which was followed by
addition of water (35 mL) and re-concentration back to a volume of 10 ml. To the resulting
dark-brown oil a solid K2CO3 (50.0 g) was added and the mixture was extracted (Soxhlet
apparatus) by CHCl3 (500 mL) for 3 h. To the CHCl3 solution a charcoal and MgSO4 were
added. Subsequently, solids were filtered of and the solvent was removed to afford 1 as a
greenish powder (3.43 g, 71%). M.p 170-175 oC (lit. 180-181 oC). 1H NMR (400 MHz, CDCl3)
δ: 9.31 (dd, J = 1.8, 4.3 Hz, 1H), 8.73 (dd, J = 1.2, 6.3 Hz, 1H), 8.23 (dd, J = 1.8, 8.0Hz, 1H),
7.80 (d, J = 8.8 Hz, 1H), 7.74 (d, J = 8.9 Hz, 1H), 7.74 (d, J = 8.0, 1.0 Hz, 1H), 7.66 (dd, J =
4.4, 8.1 Hz, 1H,), 7.45 (dd, J = 6.3, 8.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 150.0, 142.7,
140.8, 138.5, 135.8, 133.3, 129.02, 128.89, 126.5, 124.26, 123.12, 122.8. IR (KBr): 3410,
1627, 1600, 1432, 1413, 1256, 1204, 1069 cm-1. MS (CI+): m/z 197.1 (MH+). λmax (MeOH):
241, 268, 325 nm.
S3

2-Chloro-1,10-phenanthroline (2). To a mixture of 1 (495 mg, 2.52 mmol) and NaCl (3.0 g,
51.0 mmol) in DMF (9.0 mL), a neat POCl3 (0.7 ml, 7.53 mmol) was added by syringe at 0 ºC.
Then, the reaction mixture was heated to 100 oC for 6 h. After cooling to rt, water (20 mL) was
added and the mixture was basified with aqueous ammonia and saturated with NaCl. Solids
were filtered and solution was extracted with CHCl3 (3 × 15 mL). The combined extracts were
washed with brine (3 × 15 mL), dried over MgSO4 and evaporated. The crude residue was
purified by column chromatography (SiO2; 3:2, EtOAc/hexanes; Rf = 0.3) to afford 2 as a
yellow solid (279 mg, 52%). M.p. 129-130 ºC (lit. 129-130 °C ). 1H NMR (400 MHz, CDCl3)
δ: 9.22 (dd, J = 1.4, 4.1 Hz, 1H), 8.25 (dd, J = 1.7, 8.1 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 7.81
(d, J = 8.8 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.65 (dd, J = 4.3, 8.1 Hz, 1H), 7.62 (d, J = 8.4 Hz,
1H). 13C NMR (125 MHz, CDCl3) δ: 151.5, 150.8, 146.1, 145.1, 138.6, 136.0, 129.0, 127.25,
126.91, 125.69, 124.3, 123.4. IR (KBr): 3464, 3049, 2358, 1580, 1491, 1402, 1124, 1072, 841,
728, 615 cm-1. MS (EI+): m/z 214.1 (M+). λmax(MeOH): 227, 268 nm.
S4

2-Amino-1,10-phenanthroline (3). A mixture of 2 (1.75 g, 8.15 mmol), acetamide (9.63 g,
163.0 mmol) and K2CO3 (7.9 g, 57.0 mmol) was heated to 200 oC and stirred for 1.5 h. After
cooling to rt, water (50 mL) was added and resulting mixture was extracted with CH2Cl2 (4 × 80
mL). The combined organic extracts were washed with brine (3 × 40 ml), dried over MgSO4 and
evaporated. The crude residue was purified by flash chromatography (SiO2; 3:7:90, NH4OH
(25%)/MeOH/EtOAc; Rf = 0.3) to afford 3 as a yellow powder (886 mg, 56% yield). M.p. 200-
203 oC (lit. 204-206 ºC). 1H NMR (500 MHz, CDCl3) δ: 9.09 (dd, J = 1.7, 4.3 Hz, 1H), 8.15 (dd,
J = 1.7, 8.1 Hz, 1H), 7.95 (d, J = 8.6 Hz, 1H), 7.62 (d, J = 8.6 Hz, 1H), 7.51 (dd, J = 4.3, 8.1 Hz,
1H), 7.51 (d, J = 8.6 Hz, 1H), 6.90 (d, J = 8.6 Hz, 1H), 5.23 (br s, 2H). 13C NMR (125 MHz,
CDCl3) δ: 157.8, 149.5, 145.85, 145.22, 138.0, 135.8, 129.3, 126.4, 122.88, 122.34, 121.89,
111.8. IR (KBr): 3482, 3199, 2923, 1658, 1464, 1394, 844 cm-1. MS (EI+): m/z 195.1 (M+),
λmax(CHCl3): 241, 286 nm.
S5

2,5,8,11-Tetraoxatridecan-13-yl 4-methylbenzenesulfonate. To a solution of tetraethylene-
glycol monomethyl ether (10.0 g, 48.02 mmol) and pyridine (84 mL) in CH2Cl2 (170 mL) solid
p-toluenesulfonyl chloride (22.0 g, 115.39 mmol) was added portion-wise at -20 ºC under inert
atmosphere and the resulting reaction mixture was stirred for 10 h. Then, the reaction mixture
was allowed to warm up to rt and water (200 mL) was added. with and the aqueous layer was
extracted with CH2Cl2 (3 × 150 mL). The combined organic layers were dried over MgSO4 and
evaporated. The crude product was purified by flash chromatography (SiO2; step gradient from
1:1, EtOAc/hexanes to EtOAc; Rf = 0.3 in EtOAc) to afford 2,5,8,11-tetraoxatridecan-13-yl-4-
1
methylbenzenesulfonate as a colorless oil (15.3 g, 88 %). HNMR (200 MHz, CDCl3) δ: 7.78
(d, J = 8.4Hz, 2H), 7.33 (d, J = 8.5 Hz, 2H), 4.16 (m, 2H), 3.59 (m, 14H), 3.36 (s, 3H), 2.43 (s,
3H). 13C NMR (125 MHz, CDCl3) δ: 144.7, 132.9, 129.7, 127.9, 71.8, 70.61, 70.48, 70.44,
70.40, 69.17, 68.58, 58.9, 21.5. IR (CH2Cl2): 2887, 1726, 1599, 1545, 1359, 1276, 1246, 1179,
1100, 1018, 924 cm-1. MS (CI+): m/z 363.2 (MH+), λmax(CHCl3): 225 nm.
S6

N
O
N
1
10.0
5.0
0.0
ppm (t1)
Figure S(1):1H NMR of compound 1 in CDCl3 at 400 MHZ.
N
O
N
1
150
100
50
0
ppm (t1)
Figure S(2):13C NMR of compound 1 in CDCl3 at 100 MHZ.
S7

Cl
N
N
2
10.0
5.0
0.0
ppm (t1)
Figure S(3):1H NMR of compound 2 in CDCl3 at 400 MHZ.
Cl
N
N
2
150
ppm (t1)
100
50
0
Figure S(4):13C NMR of compound 2 in CDCl3 at 125 MHZ.
S8

NH2
N
N
3
10.0
5.0
0.0
ppm (t1)
Figure S(5):1H NMR of compound 3 in CDCl3 at 500 MHZ.
NH2
N
N
3
150
125
100
75
50
25
0
Figure S(6):13C NMR of compound 3 in CDCl3 at 125 MHZ.
S9

O
O
O
S
O
O
O
O
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
ppm (f1)
Figure S(7):1H NMR of 2,5,8,11-tetraoxatridecan-13-yl 4-methylbenzenesulfonate
in CDCl3 at 200 MHZ.
O
O
O
S
O
O
O
O
100
50
0
ppm (f1)
Figure S(8):13C NMR of 2,5,8,11-tetraoxatridecan-13-yl 4-methylbenzenesulfonate
in CDCl3 at 125 MHZ.
S10

O
O
O
O
O
O
O
OMe
OMe
4
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
ppm (t1)
Figure S(9):1H NMR of compound 4 in CD3CN at 500 MHZ.
O
O
O
O
O
O
O
OMe
OMe
4
150
100
50
0
ppm (t1)
Figure S(10):13C NMR of compound 4 in CD3CN at 125 MHZ.
S11

O
O
O
O
O
O
O
OH
OH
5
10.0
ppm (t1)
5.0
0.0
Figure S(11):1H NMR of compound 5 in CDCl3 at 400 MHZ.
O
O
O
O
O
O
O
OH
OH
5
150
100
50
0
ppm (t1)
Figure S(12):13C NMR of compound 5 in CDCl3 at 100 MHZ.
S12

O
O
O
O
O
O
O
Cl
Cl
6
8.0
7.0
6.0
5.0
4.0
3.0
2.0
1.0
0.0
ppm (t1)
Figure S(13):1H NMR of compound 6 in CDCl3 at 500 MHZ.
O
O
O
O
O
O
O
Cl
Cl
6
150
100
50
0
ppm (t1)
Figure S(14):13C NMR of compound 6 in CDCl3 at 125 MHZ.
S13

O
O
O
O
O
O
O
NH
HN
N
N
N
N
7
10.0
5.0
0.0
ppm (t1)
Figure S(15):1H NMR of compound 7 in CD2Cl2 at 500 MHZ.
O
O
O
O
O
O
O
NH
N
HN
N
N
N
7
150
100
50
0
ppm (f1)
Figure S(16):13C NMR of compound 7 in CD2Cl2 at 100 MHZ.
S14

O
O
O
O
O
O
O
NH
HN
O
N
N
N
N
H2N
NH2
10
10.0
7.5
5.0
2.5
0.0
Figure S(17):1H NMR of compound 7 complex with urea in CD2Cl2 at 500 MHZ.
O
O
O
O
O
O
O
NH
HN
O
N
N
N
N
H2N
NH2
10
150
100
50
0
ppm (t1)
Figure S(18):13C NMR of host 7 complex with urea in CD2Cl2 at 100 MHZ.
S15

O
O
O
O
O
O
O
O
OH
8
8.50
8.00
7.50
7.00
6.50
6.00
5.50
5.00
4.50
4.00
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
Figure S(19):1H NMR of compound 8 in CD3CN at 400 MHZ.
O
O
O
O
O
O
O
O
OH
8
150
100
50
0
ppm (f1)
Figure S(20):13C NMR of compound 8 in CD3CN at 100 MHZ.
S16

O
O
O
O
O
O
O
O
HN
N
N
9
10.0
5.0
0.0
ppm (t1)
Figure S(21):1H NMR of compound 9 in CDCl3 at 500 MHZ.
O
O
O
O
O
O
O
O
HN
N
N
9
150
100
50
0
ppm (t1)
Figure S(22):13C NMR of compound 9 in CDCl3 at 125 MHZ.
S17

N
O
N
1
3500
3000
2500
2000
Wavenumber cm-1
1500
1000
Figure S(23): IR Spectrum of compound 1 IN KBr.
Cl
N
N
2
3000
2000
1000
Wavenumbers (cm-1)
Figure S(24): IR Spectrum of compound 2 IN KBr
S18

NH2
N
N
3
4000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Figure S(25): IR Spectrum of compound 3 IN KBr
O
O
O
S
O
O
O
O
3500
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure S(26): IR Spectrum of compound 2,5,8,11-tetraoxatridecan-13-yl 4-
methylbenzenesulfonate in CH2Cl2
S19

O
O
O
O
O
O
O
OMe
OMe
4
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure S(27): IR Spectrum of compound 4 IN CH2Cl2
O
O
O
O
O
O
O
OH
OH
5
3500
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure S(28): IR Spectrum of compound 5 IN KBr.
S20

O
O
O
O
O
O
O
NH
HN
N
N
N
N
7
3500
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure S(29): IR Spectrum of compound 7 in KBr.
O
O
O
O
O
O
O
NH
HN
O
N
N
N
N
H2N
NH2
10
3500
3000
2500
2000
Wavenumber cm-1
1500
1000
Figure S(30): IR Spectrum of complex 10 in KBr.
S21

O
O
O
O
O
O
O
O
OH
8
3500
3000
2500
2000
Wavenumber cm-1
1500
1000
Figure S(31): IR Spectrum of compound 8 IN CH2Cl2
O
O
O
O
O
O
O
O
HN
N
N
9
3500
3000
2500
2000
1500
1000
Wavenumber cm-1
Figure S(32): IR Spectrum of compound 9 IN CH2Cl2
S22

N
O
N
1
Figure S(33): CI-MS Spectrum of compound 1.
Cl
N
N
2
Figure S(34): EI-MS Spectrum of compound 2.
S23

NH2
N
N
3
Figure S(35): EI-MS Spectrum of compound 3 .
O
O
O
O
S
O
O
O
Figure S(36): CI-MS Spectrum of 2,5,8,11-tetraoxatridecan-13-yl-
4-methylbenzenesulfonate.
S24

O
O
O
O
O
O
O
OMe
OMe
4
Figure S(37): CI-MS Spectrum of compound 4.
+TOF MS: 12 MCA scans from 050726_Gozin_034_1.wiff
Max. 2.0e4 counts.
a=3.55121541078045830e-004, t0=4.84736862130303050e+001, Smoothed
2.0e4
1.9e4
1.8e4
1.7e4
1.6e4
1.5e4
1.4e4
1.3e4
1.2e4
1.1e4
1.0e4
9000.0
8000.0
7000.0
6000.0
5000.0
4000.0
3000.0
2000.0
1000.0
0.0
395.1281
373.1512
O
O
O
O
O
O
355.1449
O
390.1853
OH
OH
5
396.1394
374.1571
337.1333
330
340
350
360
370
380
390
400
410
420
430
440
450
460
470
480
490
500
m/z, amu
Figure S(38): MALDI-TOF HRMS Spectrum of compound 5.
S25

Voyager Spec #1=>MC[BP = 727.3, 50585]
727.2883
728.2878
729.2899
100
90
80
70
60
50
40
30
20
10
0
5.1E+
O
O
O
O
O
O
O
NH
N
HN
N
N
N
749.2720
750.2716
7
765.2344
789.2036
791.2069
751.2750
766.2379
730.2873
731.8858
767.2368
752.2760
753.4
793.2159
781.2259
712.0
794.8
836.2
877.6
919.0
Mass (m/z)
Figure S(39): MALDI-TOF HRMS Spectrum of compound 7.
O
O
O
O
O
O
O
O
OH
8
Figure S(40): MALDI-TOF HRMS Spectrum of compound 8.
S26

586.337
587.223
100
90
80
70
60
50
40
30
20
10
1.5E+4
O
O
O
O
O
564.230
565.221
O
O
602.173
588.169
O
HN
N
N
9
603.173
604.174
589.165
587.772
566.217
567.217
608.175
605.181
578.237
579.256
600.214
601.4
626.128
614.224
609.181
591.561
562.217
571.236
0
554.0
569.8
585.6
Mass (m/z)
617.2
633.0
Figure S(41): MALDI-TOF HRMS Spectrum of compound 9.
S27

1.2
1
N
O
268
N
241
1
0.8
0.6
0.4
0.2
0
325
220
240
260
280
300
320
340
λ [nm]
Figure S(42): UV-Vis Spectrum of compound 1 IN MeOH.
1.4
227
1.2
268
1
Cl
N
N
0.8
0.6
0.4
0.2
0
2
220
240
260
280
300
320
340
λ [nm]
Figure S(43): UV-Vis Spectrum of compound 2 IN MeOH.
S28

3
2.5
2
286
241
NH2
N
N
1.5
1
3
0.5
0
220
240
260
280
300
320
340
λ [nm]
Figure S(44): UV-Vis Spectrum of compound 3 IN CHCl3.
1.2
225
O
O
O
S
1
O
O
O
O
0.8
0.6
0.4
0.2
0
220
240
260
280
300
320
340
λ [nm]
Figure S(45): UV-Vis Spectrum of compound 2,5,8,11-Tetraoxatridecan-13-yl-
4-methylbenzenesulfonate IN CH3CN.
S29

O
O
O
O
2
1.8
1.6
1.4
1.2
1
O
O
O
305
OMe
OMe
4
247
0.8
0.6
0.4
0.2
0
220
240
260
280
300
320
340
λ [nm]
Figure S(46): UV-Vis Spectrum of compound 4 IN CHCl3.
O
1.4
O
O
O
O
309
1.2
1
248
O
O
OH
OH
5
0.8
0.6
0.4
0.2
0
220
240
260
280
λ [nm]
300
320
340
Figure S(47): UV-Vis Spectrum of compound 5 IN CHCl3.
S30