Article
Inorganic Chemistry, Vol. 49, No. 11, 2010 5077
carbonate (5 equiv), and a catalytic amount of 18-crown-6 (0.1
equiv) in 50 mL of dry acetone was added either 4-bromomethyl-
benzoic acid tert-butyl ester (5, 2.2 equiv) to prepare 7, G1-OMs-
benzoic acid tert-butyl ester (OMs = mesylate) (10, 2.4 equiv) to
prepare 8, or G2-OMs-benzoic acid tert-butyl ester (12, 3 equiv) to
prepare 9. The mixture was refluxed for 12-72 h and stirred
vigorously under N2. At the end of reaction, the suspension was
cooled to room temperature and filtered. The filtrate was then
evaporated to remove the solvent under reduced pressure. The
crude product was purified by column chromatography, eluting
with the solvent system of 30% ethyl acetate in hexane.
(CDCl3): δ (ppm) 25.2, 28.2, 28.4, 37.5, 38.6, 44.8, 45.0, 68.5, 69.5,
70.9, 81.2, 114.1, 114.4, 127.1, 128.4, 128.6, 129.9, 131.7, 141.3,
142.1, 142.4, 156.6, 157.1, 157.2, 165.7. MALDI (TOF): calcd for
[M þ Naþ] C100H114O17SNa 1643.0, found 1644.6 (HABA matrix,
positive ion mode).
G3-OMs-Benzoic Acid tert-Butyl Ester (12). Yield: 51%
(1.12 g). IR: cm-1 1292, 1710, 2773. 1H NMR (CDCl3): δ (ppm)
1.20-1.82 (m, 107H), 2.15 (m, 14H), 2.9(s,3H), 3.85 (m, 12H), 4.1
(t, 2H, J = 5.5 Hz), 5.04 (s, 16H), 6.76 (d, 12H, J = 8.6 Hz), 6.85
(d, 16H, J = 8.6 Hz), 7.03 (m, 28H), 7.45 (d, 16H, J = 8.1 Hz),
8.00 (d, 16H, J = 8.0 Hz). 13C NMR (CDCl3): δ (ppm) 25.2, 28.2,
28.4, 37.5, 38.6, 44.8, 45.1, 68.5, 69.5, 81.2, 114.1, 114.5, 127.1,
128.5, 128.6, 129.9, 131.7, 141.3, 142.2, 142.5, 156.7, 157.2, 165.7.
MALDI (TOF): calcd for [M þ Naþ] C216H242O33SNa 3421.3,
found 3424.1 (HABA matrix, positive ion mode).
G1-OH-Benzoic Acid tert-Butyl Ester (7). Yield: 67% (1.69 g).
IR: 1292, 1710, 2975, 3409 cm-1. 1H NMR (CDCl3): δ (ppm) 1.35
(m, 2H), 1.50 (s, 3H), 1.53 (s, 18H), 2.00 (m, 2H), 3.53 (t, 2H, J =
6.5 Hz), 5.12 (s, 4H), 6.79 (d, 4H, J = 8.7 Hz), 7.00 (d, 4H,
J = 8.9 Hz), 7.40 (d, 4H, J = 8.0 Hz), 7.93 (d, 4H, J = 6.7 Hz). 13
C
General Procedure for Synthesis of Gn-N(CH3)COC6H4SCO-
CH3-Benzoic Acid tert-Butyl Esters (17-19, n = 1-3). Into a
sealed tube with a solution of Gn-OMs-benzoic acid tert-butyl ester
(10-12), ca. 0.5-1.0 g in 6 mL of THF, was added methyl amine
(40 wt % solution in H2O) (6 mL). The reaction mixture was then
heated to 60-70 °C for 5 h. At the end of the reaction as shown by
TLC the mixture was cooled to room temperature, and 20 mL of
water was added to quench the reaction. The solution was
extracted with 2 ꢀ 20 mL of dichloromethane. The combined
organic layers were dried over Na2SO4. Dichloromethane was
removed under reduced pressure to furnish the amines (13-15),
which were pure enough to be used in the next step without further
purification, with the exception of the third-generation amine (19);
see below. To a solution of amine (1 equiv) in dichloromethane
(7 mL) was added the activated ester prepared by mixing dicyclo-
hexyl carbodiimide (1 equiv) with carboxylic acid (1 equiv) in
dichloromethane (5 mL). The reaction mixture was then stirred at
room temperature for 12 h. At the end of the reaction the solvent
was removed under reduced pressure, and the residue was dis-
solved in ethyl acetate (5 mL) in which the solubility of cyclohexyl
urea byproduct was found to be less than in dichloromethane. The
suspension was then filtered, and the filtrate, on concentration
under reduced pressure and further on column purification using
20% ethyl acetate as eluent, furnished the desired amides.
NMR (CDCl3): δ (ppm) 28.1, 28.4, 38.2, 44.9, 63.6, 69.5, 81.3,
114.4, 127.0, 128.5, 129.9, 131.6, 142.1, 142.5, 156.5, 165.7. HRMS
(ESI): calcd for [M þ Naþ] C42H50O9SNa 675.3298, found
675.3293.
G2-OH-Benzoic Acid tert-Butyl Ester (8). Yield: 65%
(10.95 g). IR: 1291, 1711, 2973, 3515 cm-1. 1H NMR (CDCl3):
δ (ppm) 1.35 (m, 2H), 1.40-1.80 (m, 49H), 2.09 (m, 2H), 2.19 (m,
4H), 3.59 (t, 2H, J = 6.1 Hz), 3.86 (t, 4H, J = 6.1 Hz), 5.15 (s, 8H),
6.73 (d, 4H, J = 8.5 Hz), 6.91 (d, 8H, J = 8.4 Hz), 7.06 (d, 4H, J =
8.4 Hz), 7.11 (d, 8H, J = 8.6 Hz), 7.42 (d, 8H, J = 8.2 Hz), 7.95 (d,
8H, J=8.0Hz). 13CNMR(CDCl3):δ(ppm) 25.2, 28.2, 28.4, 38.5,
44.9, 45.0, 63.6, 68.4, 69.5, 81.3, 113.9, 114.4, 127.0, 128.4, 128.5,
129.9, 131.7, 142.0, 142.1, 142.4, 156.6, 157.00, 165.8. MALDI
(TOF): calcd for [M þ Naþ] C99H112O15Na 1564.9, found 1565.2
(HABA matrix, positive ion mode).
G3-OH-Benzoic Acid tert-Butyl Ester (9). Yield: 35% (1.49 g).
1
IR: 1294, 1710, 2973, 3411 cm-1. H NMR (CDCl3): δ (ppm)
1.35-1.80 (m, 107H), 2.14 (m, 14H), 3.53 (t, 2H, J = 6.2 Hz), 3.82
(t, 12H, J = 6.0 Hz), 5.04 (s, 16H), 6.72 (d, 12H, J = 8.8 Hz), 6.82
(d, 16H, J = 8.7 Hz), 7.03 (m, 28H), 7.43 (d, 16H, J = 8.4 Hz), 7.96
(d, 16H, J = 8.1 Hz). 13C NMR (CDCl3): δ (ppm) 25.2, 28.2, 28.4,
38.6, 44.9, 45.0, 63.5, 68.5, 69.5, 81.2, 113.9, 114.4, 127.0, 127.2,
128.4, 128.5, 129.9, 130.0, 130.2, 131.7, 141.9, 142.0, 142.1, 142.4,
156.6, 157.0, 165.7. MALDI (TOF): calcd for [M þ Naþ]
C215H240O31Na 3343.2, found 3344.8 (HABA matrix, positive ion
mode).
G1-N(CH3)COC6H4SCOCH3-Benzoic Acid tert-Butyl Ester
(17). Yield: 70% (0.372 g). IR: 1295, 1631, 1710, 2976, 3400,
3583 cm-1. 1H NMR (CDCl3): δ (ppm) 1.35 (m, 2H), 1.50 (m,
21H), 1.87 (m, 1H), 2.06 (m, 1H), 2.35 (s, 3H), 2.65 (s, 1.5H),
2.87 (s, 1.5H), 3.03 (m, 1H), 3.44 (m, 1H), 5.15 (s, 4H), 6.8 (d, 4H,
J = 8.1 Hz), 6.9 (d, 2H, J = 8.1 Hz), 7.05 (d, 2H, J = 7.9 Hz)
7.36 (d, 4H, J = 8 Hz), 7.40 (d, 4H, J = 8.3 Hz), 7.93 (d, 4H, J =
8.1 Hz). 13C NMR (CDCl3): δ (ppm) 22.5, 24.0, 28.0, 28.4, 30.5,
32.9, 37.4, 38.5, 38.9, 45.0, 47.7, 51.8, 69.5, 81.2, 114.5, 127.0,
128.4, 128.5, 129.6, 129.9, 131.7, 134.4, 137.9, 142.0, 142.4,
156.6, 165.7, 170.6, 171.2, 193.3. HRMS (ESI): calcd for [M þ
Hþ] C51H58NO8S 844.3805, found 844.3869.
General Procedure for the Synthesis of Gn-OMs-Benzoic Acid
tert-Butyl Esters (10-12, n = 1-3). To a solution of Gn-OH-
benzoic acid tert-butyl ester (7-9, 1 equiv), triethylamine (3 equiv),
and a catalytic amount of 4-dimethylaminopyridine (0.02 equiv) in
50 mL of dichloromethane at 0 °C was added dropwise methane
sulfonyl chloride (2 equiv). The reaction mixture was allowed to
warm to room temperature and stirred for 12 h. Then 50 mL of
water was added to quench the reaction. The solution was extracted
with 2 ꢀ 50 mL of dichloromethane. The combined organic layers
were dried over Na2SO4, and the solvents were removed under
reduced pressure. The crude product was purified by column
chromatography using ethyl acetate/hexane (1:6) as eluent.
G1-OMs-Benzoic Acid tert-Butyl Ester (10). Yield: 95% (1.95 g).
IR: 1294, 1709, 2975 cm-1. 1H NMR (CDCl3): δ (ppm) 1.35 (m,
2H), 1.50 (m, 21H), 2.06 (m, 2H), 2.89 (s, 3H), 4.10 (t, 2H, J = 6.3
Hz), 5.03 (s, 4H), 6.79(d, 4H, J= 8.2 Hz), 7.02 (d, 4H, J =8.4 Hz),
7.40 (d, 4H, J = 8.0 Hz), 7.93 (d, 4H, J = 8.1 Hz). 13C NMR
(CDCl3): δ (ppm) 25.1, 28.1, 28.4, 37.5, 37.9, 44.9, 69.5, 70.8, 81.2,
114.5, 127.0, 128.4, 129.9, 131.7, 141.9, 142.0, 156.7, 165.7. HRMS
(ESI): calcd for [M þ Naþ] C42H50O9SNa 753.3073, found
753.3062.
G2-N(CH3)COC6H4SCOCH3-Benzoic Acid tert-Butyl Ester
(18). Yield: 52% (0.248 g). IR: 1295, 1710, 2933, 2973, 3402,
3582 cm-1. 1H NMR (CDCl3): δ (ppm) 1.20-2.0 (m, 53H), 2.15
(m, 4H), 2.37 (s, 3H), 2.65 (s, 1.5H), 2.87 (s, 1.5H), 3.03 (m, 1H),
3.44 (m, 1H), 3.82 (t, 4H, J = 5.7 Hz), 5.03 (s, 8H), 6.70 (d, 4H,
J = 8.4 Hz), 6.86 (d, 10H, J = 8.6 Hz), 6.95 (d, 2H, J = 8.4 Hz),
7.02 (d, 8H, J = 8.6 Hz), 7.40 (d, 12H, J = 8.2 Hz), 7.93 (d, 8H,
J = 8.5 Hz). 13C NMR (CDCl3): δ (ppm) 24.5, 28.4, 28.4, 30.5,
38.9, 45.0, 68.5, 69.5, 81.2, 114.0, 114.4, 127.0, 128.5, 129.9,
131.7, 134.6, 138.1, 142.1, 142.4, 156.6, 165.7, 193.3. MALDI
(TOF): calcd for [M þ Naþ] C109H121NO16SNa 1754.8, found
1755.6 (DHB matrix, positive ion mode)
G2-OMs-Benzoic Acid tert-Butyl Ester (11). Yield: 65% (0.58 g).
IR: 1293, 1711, 2973 cm-1. 1H NMR (CDCl3): δ (ppm) 1.20 -1.82
(m, 51H), 2.15 (m, 6H), 2.88 (s, 3H), 3.83 (t, 4H, J = 5.4 Hz), 4.10
(t, 2H, J = 6.2 Hz), 5.08 (s, 8H), 6.70 (d, 4H, J = 8.5 Hz), 6.86 (d,
8H, J = 8.6 Hz), 7.01 (d, 4H, J = 8.4 Hz), 7.07 (d, 8H, J = 8.6 Hz).
7.40 (d, 8H, J = 8.2 Hz), 7.93 (d, 8H, J = 8.7 Hz). 13C NMR
G3-N(CH3)COC6H4SCOCH3-Benzoic Acid tert-Butyl Ester
(19). After cooling the reaction mixture of the amine, the solution
was extracted with 2 ꢀ 10 mL of dichloromethane. The combined
organic layers were dried over Na2SO4. Dichloromethane was
removed under reduced pressure to furnish crude amine, which on
column purification using a 10% MeOH/EtOAc system provided