The Journal of Organic Chemistry
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1H, COOH); 11.27 (bs, 1H, NH-12); 11.26 (bs, 1H, NH-11); 8.34
(dd, JHH = 1.5 Hz, JHH = 0.7 Hz, 1H, CH-1); 8.24 (ddd, JHH = 8.2
(CH-5 or CH-6); 111.7 (CH-10); 64.8 (CH2). 15N NMR (40.6 MHz,
DMSO-d6, +25 °C): δ 115.14 (NH-12); 114.45 (NH-11). IR (ATR-
4
5
3
5
3
Hz, 5JHH = 0.7 Hz, JHH = 0.5 Hz, 1H, CH-4); 8.18 (dddd, JHH = 7.8
Hz, 4JHH = 1.2 Hz, 5JHH = 0.9 Hz, 5JHH = 0.6 Hz, 1H, CH-7); 7.97 (bs,
2H, CH-5,6); 7.82 (dd, 3JHH = 8.2 Hz, 4JHH = 1.5 Hz, 1H, CH-3); 7.70
FT-IRS) ν
̃
: 3384, 3349, 1678, 1277 cm−1. ESI-ICR (m/z): solvent
∼0.1% DMSO/MeOH, calcd for C26H16N3O4 [M − H]− 434.11463,
found 434.11457.
3
4
5
(ddd, JHH = 8.1 Hz, JHH = 1.0 Hz, JHH = 0.9 Hz, 1H, CH-10); 7.41
(ddd, JHH = 8.1 Hz, JHH = 7.1 Hz, JHH = 1.2 Hz, 1H, CH-9); 7.22
Data for 17: Yield: 120.0 mg, 0.28 mmol, 85.7%. Light-yellow solid.
3
3
4
1
Mp: decomposed above 350 °C. Rf = 0.53 (50% THF in hexane). H
(ddd, JHH = 7.8 Hz, JHH = 7.1 Hz, JHH = 1.0 Hz, 1H, CH-8). 13C
NMR (100.6 MHz, DMSO-d6, +25 °C): δ 168.1 (COO); 139.1 (C-
10′); 138.3 (C-12′); 127.3 (C-11″); 127.2 (C-4′); 126.5 (C-2); 125.4
(C-11′); 124.8 (CH-9); 123.6 (C-7′); 120.9 (C-6′); 119.9 (CH-3);
119.8 (CH-7); 119.4 (C-5′); 119.3 (CH-4); 119.0 (CH-8); 113.3 (CH-
1); 112.2 (CH-5 or CH-6); 112.0 (CH-5 or CH-6); 111.7 (CH-10).
15N NMR (40.6 MHz, DMSO-d6, +25 °C): δ: 114.78 (NH-12);
3
3
4
NMR (400.1 MHz, DMSO-d6, +25 °C): δ 11.34 (bs, 1H, NH-11);
4
5
11.28 (bs, 1H, NH-12); 8.37 (dd, JHH = 1.5 Hz, JHH = 0.6 Hz, 1H,
3
5
5
CH-1); 8.26 (ddd, JHH = 8.2 Hz, JHH = 0.7 Hz, JHH = 0.6 Hz, 1H,
CH-4); 8.18 (dddd, 3JHH = 7.9 Hz, 4JHH = 1.2 Hz, 5JHH = 0.7 Hz, 5JHH
= 0.6 Hz, 1H, CH-7); 7.97 (bs, 2H, CH-5,6); 7.83 (dd, 3JHH = 8.2 Hz,
4JHH = 1.5 Hz, 1H, CH-3); 7.70 (ddd, JHH = 8.1 Hz, JHH = 1.0 Hz,
3
4
5JHH = 0.7 Hz, 1H, CH-10); 7.48 (AA′ of AA′XX′, 2H, CH-2,6Ph);
114.14 (NH-11). IR (ATR-FT-IRS) ν
̃
: 3410, 2951, 2831, 1679 cm−1.
3
3
4
7.41 (ddd, JHH = 8.1 Hz, JHH = 7.1 Hz, JHH = 1.2 Hz, 1H, CH-9);
3
3
4
ESI-ICR (m/z): solvent ∼0.1% DMSO/MeOH, calcd for C19H11O2N2
7.22 (ddd, JHH = 7.9 Hz, JHH = 7.1 Hz, JHH = 1.0 Hz, 1H, CH-8);
6.99 (XX′ of AA′XX′, 2H, CH-3,5Ph); 5.34 (s, 2H, CH2); 3.78 (s, 3H,
OCH3). 13C NMR (100.6 MHz, DMSO-d6, +25 °C): δ 166.4 (COO);
159.2 (CH-4Ph); 139.1 (C-10′); 138.3 (C-12′); 130.0 (CH-2,6Ph);
128.3 (C-1Ph); 127.5 (C-4′); 127.5 (C-11″); 125.3 (C-2); 125.3 (C-
11′); 124.9 (CH-9); 123.5 (C-7′); 121.0 (C-6′); 119.9 (CH-7); 119.7
(CH-3); 119.5 (CH-4); 119.3 (C-5′); 119.1 (CH-8); 113.9 (C-3,5Ph);
113.3 (CH-1); 112.4 (CH-5 or CH-6); 112.1 (CH-5 or CH-6); 111.7
(CH-10); 65.9 (CH2); 55.1 (OCH3). 15N NMR (40.6 MHz, DMSO-
d6, +25 °C): δ 114.98 (NH-12); 114.37 (NH-11). IR (ATR-FT-IRS)
[M − H]− 299.08260, found 299.08281.
General Procedure for Compounds 15−18, 20, and 21.
Compound 14 (0.16 or 0.32 mmol) and K2CO3 (2 equiv) were
dissolved in dry DMF (2−3 mL), and then the respective reactant (1.3
equiv) was added dropwise. The reactants were the following:
bromomethylbenzene, 1-bromomethyl-4-nitrobenzene, 1-chlorometh-
yl-4-methoxybenzene, 1-chloromethyl-3-methylbenzene, iodoethane,
and 2-iodopropane. The reaction mixture was stirred for 3 h at 80 °C
under an atmosphere of N2. After disappearance of the starting
material (as monitored by TLC), the reaction mixture was cooled to
room temperature and quenched in water, and the product was
extracted with ethyl acetate. The ethyl acetate solution was washed
with water and saturated aqueous NaCl solution, dried over MaSO4,
filtered, and concentrated under reduced pressure. The crude product
was washed with diethyl ether to get the pure compound 15−18, 20,
or 21 as a solid.
ν
̃
: 3372, 3336, 1669, 1245 cm−1. ESI-ICR (m/z): solvent ∼0.1%
DMSO/MeOH, calcd for C27H19N2O3 [M − H]− 419.14012, found
419.14024.
Data for 18: Yield: 100.0 mg, 0.24 mmol, 74.6%. Light-yellow solid.
Mp: decomposed above 324.5−326.5 °C. Rf = 0.55 (50% THF in
hexane). 1H NMR (400.1 MHz, DMSO-d6, +25 °C): δ 11.38 (bs, 1H,
4
5
NH-11); 11.34 (bs, 1H, NH-12); 8.40 (dd, JHH = 1.5 Hz, JHH = 0.6
Data for 15: Yield: 60.0 mg, 0.15 mmol, 92.3%. Light-yellow solid.
3
5
5
Hz, 1H, CH-1); 8.27 (ddd, JHH = 8.2 Hz, JHH = 0.6 Hz, JHH = 0.6
1
Mp: decomposed above 350 °C. Rf = 0.59 (50% THF in hexane). H
3
4
Hz, 1H, CH-4); 8.18 (dddd, JHH = 7.8 Hz, JHH = 1.2 Hz, 5JHH = 0.7
NMR (400.1 MHz, DMSO-d6, +25 °C): δ 11.36 (bs, 2H, NH-11,12);
5
3
Hz, JHH = 0.6 Hz, 1H, CH-7); 7.97 (bs, 2H, CH-5,6); 7.86 (dd, JHH
4
5
3
8.41 (dd, JHH = 1.5 Hz, JHH = 0.6 Hz, 1H, CH-1); 8.27 (dd, JHH
=
= 8.2 Hz, 4JHH = 1.5 Hz, 1H, CH-3); 7.70 (ddd, 3JHH = 8.1 Hz, 4JHH
=
=
8.2 Hz, 5JHH = 0.6 Hz, 1H, CH-4); 8.18 (ddd, 3JHH = 7.8 Hz, 4JHH = 1.2
Hz, JHH = 0.7 Hz, 1H, CH-7); 7.98 (bs, 2H, CH-5 or CH-6); 7.87
(dd, JHH = 8.2 Hz, JHH = 1.5 Hz, 1H, CH-3); 7.70 (ddd, JHH = 8.1
Hz, JHH = 1.0 Hz, JHH = 0.7 Hz, 1H, CH-10); 7.54 (m, 2H, CH-
5
3
3
1.0 Hz, JHH = 0.7 Hz, 1H, CH-10); 7.41 (ddd, JHH = 8.1 Hz, JHH
5
4
7.1 Hz, JHH = 1.2 Hz, 1H, CH-9); 7.34 (m, 1H, CH-2Ph); 7.33 (m,
1H, CH-5Ph); 7.32 (m, 1H, CH-6Ph); 7.22 (ddd, 3JHH = 7.8 Hz, 3JHH
7.1 Hz, 4JHH = 1.0 Hz, 1H, CH-8); 7.19 (m, 1H, CH-4Ph); 5.38 (s, 2H,
3
4
3
=
4
5
3
3
2,6Ph); 7.45 (m, 2H, CH-3,5Ph); 7.41 (ddd, JHH = 8.1 Hz, JHH = 7.1
Hz, 4JHH = 1.2 Hz, 1H, CH-9); 7.38 (m, 1H, CH-4Ph); 7.22 (ddd, 3JHH
= 7.8 Hz, 3JHH = 7.1 Hz, 4JHH = 1.0 Hz, 1H, CH-8); 5.43 (s, 2H, CH2).
13C NMR (100.6 MHz, DMSO-d6, +25 °C): δ 166.4 (COO); 139.1
(C-10′); 138.3 (C-12′); 136.5 (C-1Ph); 128.5 (C-3,5Ph); 128.1 (CH-
4Ph); 128.0 (CH-2,6Ph); 127.6 (C-4′); 127.5 (C-11″); 125.3 (C-11′);
125.1 (C-2); 124.9 (CH-9); 123.5 (C-7′); 121.0 (C-6′); 119.9 (CH-7);
119.7 (CH-3); 119.5 (CH-4); 119.3 (C-5′); 119.0 (CH-8); 113.3 (CH-
1); 112.4 (CH-5 or CH-6); 112.1 (CH-5 or CH-6); 111.7 (CH-10);
66.0 (CH2). 15N NMR (40.6 MHz, DMSO-d6, +25 °C): δ 115.14
CH2); 2.35 (dd, JHH = 1.0 Hz, JHH = 0.6 Hz, 3H, CH3). 13C NMR
(100.6 MHz, DMSO-d6, +25 °C): δ 166.4 (COO); 139.2 (C-10′);
138.3 (C-12′); 137.7 (C-3Ph); 136.3 (C-1Ph); 128.7 (CH-4Ph); 128.6
(CH-2Ph); 128.4 (CH-5Ph); 127.6 (C-4′); 127.5 (C-11″); 125.4 (C-
11′); 125.15 (C-2); 125.12 (CH-6Ph); 124.9 (CH-9); 123.5 (C-7′);
121.0 (C-6′); 119.9 (CH-7); 119.7 (CH-3); 119.5 (CH-4); 119.3 (C-
5′); 119.0 (CH-8); 113.3 (CH-1); 112.4 (CH-5 or CH-6); 112.1 (CH-
5 or CH-6); 111.7 (CH-10); 66.0 (CH2); 21.0 (CH3). 15N NMR (40.6
MHz, DMSO-d6, +25 °C): δ 115.17 (NH-12); 114.49 (NH-11). IR
4
4
(ATR-FT-IRS) ν
̃
: 3377, 3335, 1671, 1282 cm−1. ESI-ICR (m/z):
̃
(NH-12); 114.45 (NH-11). IR (ATR-FT-IRS) ν: 3387, 3343, 1675,
solvent ∼0.1% DMSO/MeOH, calcd for C27H19N2O2 [M − H]−
403.14520, found 403.14556.
1282 cm−1. ESI-ICR (m/z): solvent ∼0.1% DMSO/MeOH, calcd for
C26H17N2O2 [M − H]− 389.12955, found 389.12955.
Data for 20: Yield: 40.0 mg, 0.12 mmol, 73.2%. Light-yellow solid.
Data for 16: Yield: 59.7 mg, 0.13 mmol, 59.7%. Yellow solid. Mp:
decomposed above 350 °C. Rf = 0.46 (50% THF in hexane). 1H NMR
(400.1 MHz, DMSO-d6, +25 °C): δ 11.34 (bs, 1H, NH-11); 11.32 (bs,
1H, NH-12); 8.44 (dd, 4JHH = 1.5 Hz, 5JHH = 0.6 Hz, 1H, CH-1); 8.30
(XX′ of AA′XX′, 2H, CH-3,5Ph); 8.29 (ddd, 3JHH = 8.2 Hz, 5JHH = 0.6
1
Mp: decomposed above 350 °C. Rf = 0.58 (50% THF in hexane). H
NMR (400.1 MHz, DMSO-d6, +25 °C): δ 11.33 (bs, 1H, NH-11);
4
5
11.29 (bs, 1H, NH-12); 8.37 (dd, JHH = 1.5 Hz, JHH = 0.7 Hz, 1H,
3
5
5
CH-1); 8.26 (ddd, JHH = 8.2 Hz, JHH = 0.7 Hz, JHH = 0.6 Hz, 1H,
CH-4); 8.18 (dddd, 3JHH = 7.8 Hz, 4JHH = 1.2 Hz, 5JHH = 0.8 Hz, 5JHH
= 0.6 Hz, 1H, CH-7); 7.97 (bs, 2H, CH-5,6); 7.83 (dd, 3JHH = 8.2 Hz,
3
4
Hz, 5JHH = 0.6 Hz, 1H, CH-4); 8.18 (dddd, JHH = 7.8 Hz, JHH = 1.2
Hz, 5JHH = 0.8 Hz, 5JHH = 0.6 Hz, 1H, CH-7); 7.98 (bs, 2H, CH-5,6);
4JHH = 1.5 Hz, 1H, CH-3); 7.70 (ddd, JHH = 8.1 Hz, JHH = 1.0 Hz,
3
4
3
4
7.90 (dd, JHH = 8.2 Hz, JHH = 1.5 Hz, 1H, CH-3); 7.81 (AA′ of
AA′XX′, 2H, CH-2,6Ph); 7.71 (ddd, 3JHH = 8.1 Hz, 4JHH = 1.0 Hz, 5JHH
5JHH = 0.8 Hz, 1H, CH-10); 7.42 (ddd, JHH = 8.1 Hz, JHH = 7.1 Hz,
3
3
4JHH = 1.2 Hz, 1H, CH-9); 7.22 (ddd, JHH = 7.8 Hz, JHH = 7.1 Hz,
4JHH = 1.0 Hz, 1H, CH-8); 4.38 (q, 3JHH = 7.1 Hz, 2H, CH2); 1.39 (t,
3JHH = 7.1 Hz, 3H, CH3). 13C NMR (100.6 MHz, DMSO-d6, +25 °C):
δ 166.5 (COO); 139.1 (C-10′); 138.3 (C-12′); 127.4 (C-4′,11″); 125.5
(C-2); 125.4 (C-11′); 124.8 (CH-9); 123.6 (C-7′); 121.0 (C-6′); 119.9
(CH-7); 119.7 (CH-3); 119.4 (CH-4); 119.3 (C-5′); 119.0 (CH-8);
113.1 (CH-1); 112.3 (CH-5 or CH-6); 112.0 (CH-5 or CH-6); 111.7
(CH-10); 60.5 (CH2); 14.3 (CH3). 15N NMR (40.6 MHz, DMSO-d6,
3
3
= 0.8 Hz, 1H, CH-10); 7.42 (ddd, 3JHH = 8.1 Hz, 3JHH = 7.1 Hz, 4JHH
=
1.2 Hz, 1H, CH-9); 7.23 (ddd, 3JHH = 7.8 Hz, 3JHH = 7.1 Hz, 4JHH = 1.0
Hz, 1H, CH-8); 5.57 (s, 2H, CH2). 13C NMR (100.6 MHz, DMSO-d6,
+25 °C): δ 166.2 (COO); 147.1 (C-4Ph); 144.3 (C-1Ph); 139.1 (C-
10′); 138.3 (C-12′); 128.6 (CH-2,6Ph); 127.8 (C-4′); 127.6 (C-11″);
125.3 (C-11′); 124.9 (CH-9); 124.7 (C-2); 123.7 (C-3,5Ph); 123.5 (C-
7′); 121.1 (C-6′); 119.9 (CH-7); 119.8 (CH-3); 119.6 (CH-4); 119.3
(C-5′); 119.1 (CH-8); 113.4 (CH-1); 112.4 (CH-5 or CH-6); 112.1
2511
dx.doi.org/10.1021/jo4027963 | J. Org. Chem. 2014, 79, 2501−2513