NoVel Folding Patterns in a Family of Oligoanthranilamides
J. Am. Chem. Soc., Vol. 119, No. 44, 1997 10593
(150 mL) and hexane (100 mL) to obtain the desired compound as a
yellow solid (340 mg, 73%): mp 237-239 °C; H NMR (DMSO-d6)
mmol) and oxalyl chloride (102 mg, 0.8 mmol) in dry CH2Cl2 (3 mL)
was added DMF (25 µL) through a silica gel filter, and the mixture
was stirred at room temperature for 5 min. The reaction mixture was
evaporated in vacuo to obtain the acid chloride. To the acid chloride
was added a solution of 7 (101 mg, 0.2 mmol) and DIPEA (129 mg,
1.0 mmol) in dry CH2Cl2 (5 mL), and the mixture was stirred at room
temperature overnight. The reaction mixture was charged with CH2-
Cl2 (30 mL) and washed with saturated aqueous NaHCO3 (20 mL)
and brine (20 mL). The organic layer was separated, evaporated, and
triturated with hexanes. The crude product was purified by column
chromatography (SiO2, first 1/20 ) MeOH/CH2Cl2, later 1/3 ) MeOH/
CH2Cl2) to obtain the desired compound (137 mg, 89%): mp 150-
1
δ 9.89 (s, 2H, amide), 8.14 (s, 1H), 8.10 (d, J ) 8.1 Hz, 2H), 7.83 (t,
J ) 7.5 Hz, 2H), 7.72 (m, 4H), 6.83 (s, 1H), 3.85 (s, 6H); 13C NMR
(DMSO-d6) δ 164.4, 150.1, 146.8, 133.9, 132.9, 130.7, 129.4, 124.1,
121.0, 118.6, 97.2, 56.2; HRMS m/e calcd for C22H18N4O8 (M+)
466.1125, found 466.1106.
1,3-Bis(2-aminobenzoylamino)-4,6-dimethoxybenzene (7). A so-
lution of 6 (533 mg, 1.0 mmol) and 5% Pd/C (50 mg) in dry THF (30
mL) and MeOH (5 mL) was prepared in a 100-mL round-bottomed
flask containing a magnetic stirrer. H2 was introduced after removal
of air by an aspirator, and the solution was stirred vigorously at room
temperature for 5 h. The catalyst was removed by filtration through
Celite, and the filtrate evaporated in vacuo to give the desired compound
as a yellow solid (465 mg, 100%): 1H NMR (DMSO-d6) δ 9.17 (s,
2H, amide), 7.83 (s, 1H), 7.64 (d, J ) 7.8 Hz, 2H), 7.18 (t, J ) 7.5
Hz, 2H), 6.81 (s, 1H), 6.72 (d, J ) 8.1 Hz, 2H), 6.56 (t, J ) 7.5 Hz,
2H), 6.39 (s, 4H, amine), 3.85 (s, 6H).
1,3-Bis((6-(2-(2-methoxycarbonylphenylcarbamoyl)phen-
ylcarbamoyl)pyridine-2-carbonylamino)phenylcarbamoyl)-4,6-
dimethoxybenzene (8a). To a solution of 4a (168 mg, 0.4 mmol)
and TEA (40 mg, 0.4 mmol) in dry THF (10 mL) was added
trimethylacetyl chloride (96 mg, 0.8 mmol), and the reaction mixture
was stirred at room temperature for 30 min. The reaction mixture was
evaporated to give the mixed anhydride. The evaporated residue was
dissolved in dry THF (20 mL) and then added to 7 (81 mg, 0.2 mmol).
The mixture was refluxed for 5 h, and then the reaction mixture was
evaporated in vacuo. CH2Cl2 (50 mL) was added to the mixture which
was then washed with 5% citric acid (50 mL), saturated aqueous
NaHCO3 (50 mL), and brine (50 mL). The organic layer was dried
over MgSO4 and evaporated in vacuo to give the crude product. The
crude product was purified by preparative thin layer chromatography
(silica gel, 1/20 ) MeOH/CHCl3) to obtain the desired product as a
pale yellow powder (147 mg, 61%): mp 291-193 °C; 1H NMR
(CDCl3) δ 12.89 (s, 2H, amide), 12.42 (s, 2H, amide), 11.34 (s, 2H,
amide), 8.82 (m, 3H), 8.45 (d, J ) 7.5 Hz, 2H), 8.29 (d, J ) 8.1 Hz,
4H), 8.00 (m, 4H), 7.77 (d, J ) 7.8 Hz, 2H), 7.61 (t, 2H), 7.29 (m,
8H), 6.97 (t, 2H), 6.79 (m, 4H), 6.65 (t, J ) 8.1 Hz, 2H), 5.99 (s, 1H),
3.65 (s, 6H), 3.44 (s, 6H); 13C NMR (CDCl3) δ 168.3, 166.1, 164.1,
162.3, 161.3, 149.3, 149.0, 144.9, 141.2, 138.8, 138.7, 138.6, 134.0,
132.1, 131.7, 130.3, 127.4, 127.0, 124.8, 124.7, 123.3, 123.1, 122.9,
122.2, 122.1, 121.9, 120.2, 119.6, 114.5, 113.4, 93.4, 55.3, 52.1; HRMS
(FAB, MNBA) m/e calcd for C66H52N10O14Na (M + Na+) 1231.3562,
found 1231.3546.
1
152 °C; H NMR (CDCl3) δ 12.77 (s, 2H), 9.04 (s, 1H), 8.85 (d, J )
8.1 Hz, 2H), 8.62 (d, J ) 4.5 Hz, 2H), 8.23 (m, 4H), 7.78 (m, 4H),
7.54 (7.8, 2H), 7.30 (m, 2H), 7.16 (t, J ) 7.5 Hz, 2H), 6.45 (s, 1H),
3.80 (s, 3H); 13C NMR (CDCl3) δ 166.4, 163.5, 150.4, 148.9, 147.5,
138.9, 137.2, 127.5, 126.2, 123.3, 122.9, 122.4 (2C), 121.5, 119.3,
117.1, 94.9, 56.0; IR (2 mM in CH2Cl2) 3420, 3255, 1682, 1583, 1538,
1515, 1460, 1244, 1205 cm-1; HRMS m/e calcd for C34H28N6O6 (M+)
616.2070, found 616.2062.
Computational Approach for Calculating Ring Current Induced
Shifts. A program that can calculate the anisotropic effect of nearby
aromatic rings on individual protons was written in QuickBasic using
the equivalent dipole model of the ring current22 and the X-ray structural
coordinates of the molecule in question. First, the program reads the
coordinates of atoms that form the aromatic ring system. Second, the
program calculates the geometrical relationship of the proton relative
to all of the aromatic rings in the molecule (i.e., values of r and θ as
defined in eq 1, Figure 4). Third, individual values of ∆δ for the effect
of all aromatic rings on the proton are calculated using eq 1 and the
geometrical coordinates. The overall predicted ring current induced
shift for a given proton is obtained from the sum of all individual ∆δ
values, except those from the ring to which the proton is attached and
its directly linked neighbor. The ∆δ values from these two rings were
ignored because their effect will be cancelled when the experimental
∆δobs values are obtained by the comparison of the helical structures
(e.g., 10) with their control molecules (e.g., 12). The procedure was
repeated for all protons of interest. The source file for this program
can be found in the Supporting Information.
Note Added in Review. While this manuscript was under review
Seebach,23 Gellman,24 Lehn,25 and Moore26 reported the formation of
extended helical oligomers based on â-alanine, trans-2-aminocyclo-
hexanecarboxylic acid, pyridine-pyrimidine, and phenylacetylene units,
respectively.
1,3-Bis((6-(2-(2-(1-Hexoxycarbonyl)phenylcarbamoyl)phen-
ylcarbamoyl)-pyridine-2-carbonylamino)phenylcarbamoyl)-4,6-
dimethoxybenzene (8b). This was prepared by a method analogous
to 8a from 4b (98 mg, 0.2 mmol), TEA (26 mg, 0.25 mmol) in dry
THF (5 mL), trimethylacetyl chloride (27 mg, 0.23 mmol), and 7 (38
mg, 0.094 mmol) in dry THF (5 mL). The crude product was purified
by preparative thin layer chromatography (silica gel, 1/20 ) MeOH/
CHCl3) to obtain the desired product as a yellow foam (70 mg, 55%):
Acknowledgment. We thank the National Science Founda-
tion (CHE 9213937) for support of this work. We also thank
the Kureha Chemical Industry for a fellowship to Y.H.
Supporting Information Available: Crystallographic details
for the two polymorphs of 8a (Figure 2) and (Figure 3) including
tables of atomic coordinates, thermal parameters, bond angles
and bond lengths, and also an example of the use of the ring
current calculation program to predict the aromatic induced shifts
in 10 (23 pages). See any current masthead page for ordering
and Internet access instructions.
1
mp 229-231 °C; H NMR (CDCl3) δ 12.70 (s, 2H, amide), 12.54 (s,
2H, amide), 11.48 (s, 2H, amide), 8.78 (m, 3H), 8.46 (dd, J ) 7.7, 0.8
Hz, 2H), 8.30 (d, J ) 8.4 Hz, 4H), 8.14 (d, J ) 7.8 Hz, 2H), 8.02 (t,
J ) 7.7 Hz, 2H), 7.84 (dd, J ) 7.8, 1.5 Hz, 2H), 7.63 (t, J ) 7.7 Hz,
2H), 7.43 (m, 6H, 2H amide + 4H aromatic), 7.26 (t, 2H), 7.07 (t, J
) 7.8 Hz, 2H), 6.86 (m, 4H), 6.69 (t, J ) 7.2 Hz, 2H), 5.99 (s, 1H),
4.08 (t, J ) 6.6 Hz, 4H), 3.41 (s, 6H), 1.64 (m, 4H), 1.31 (m, 12H),
0.88 (t, J ) 6.8 Hz, 6H); 13C NMR (CDCl3) δ 168.0, 166.3, 164.2,
162.3, 161.4, 149.2, 149.1, 145.1, 141.2, 138.9, 138.7, 138.3, 134.0,
132.1, 131.8, 130.3, 127.7, 127.2, 124.9, 124.8, 123.8, 123.6, 123.0,
122.3, 121.9, 120.4, 119.7, 115.0, 113.7, 93.4, 65.4, 55.2, 31.4, 28.4,
25.6, 22.5, 14.0; IR (2 mM in CH2Cl2) 3424, 3325, 3261, 1688, 1600,
1586, 1535, 1458, 1274, 1234 cm-1; HRMS (FAB, MNBA) m/e calcd
for C76H72N10O14 (M+) 1348.5229, found 1348.5243.
JA963449U
(23) Seebach, D.; Overhand, M.; Ku¨hnle, F. N. M.; Martinoni, B.; Oberer,
L.; Hommel, U.; Widmer, H. HelV. Chim. Acta 1996, 79, 913. Seebach,
D.; Ciceri, P. E.; Overhand, M.; Jaun, B.; Rigo, D.; Oberer, L.; Hommel,
U.; Amstutz, R.; Widmer, H. HelV. Chim. Acta 1996, 79, 2043.
(24) Apella, D. H.; Christianson, L. A.; Karle, I. L.; Powell, D. R.;
Gellman, S. H. J. Am. Chem. Soc. 1996, 118, 13071-13072.
(25) Bassani, D. M.; Lehn, J. M.; Baum, G.; Fenske, D. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1845-1847.
1,3-Bis(2-((pyridine-2-carbonyl)amino)phenylcarbamoyl)-4,6-
dimethoxybenzene (11). To a solution of picolinic acid (74 mg, 0.6
(26) Nelson, J. C.; Saver, J. G.; Moore, J. S.; Wolynes, P. G. Science
1997, 277, 1793-1796.