Carbamate C-N Rotamer Equilibria
J . Org. Chem., Vol. 63, No. 21, 1998 7261
standard regression methods,13 which resulted in a Ka
7.2 (s, 2 H), 7.70 (t, 1 H, J ) 8.0 Hz), 7.90 (d, 2 H, J ) 7.5 Hz);
13C NMR (125 MHz, CDCl3) δ 14.3, 22.8, 25.6, 29.2, 29.4, 31.9,
38.1, 109.6, 141.1, 149.6, 171.8; FAB MS m/z 362 (MH)+; FAB
HRMS (calcd for C21H35N3O2) 362.2808, found 362.2797. Anal.
Calcd for C21H35N3O2: C, 69.77; H, 9.76; N, 11.62. Found: C,
69.92; H, 9.85; N, 11.70.
of ∼0.1 M-1
.
While the uncertainties associated with the van’t Hoff
and titration analyses are probably quite large, they both
agree that the Ka for syn-3a :1 is 103-104 times higher
than the Ka for anti-3a :1. This implies that the tert-
butoxy oxygen in anti-3a is a much poorer hydrogen bond
acceptor than the carbonyl oxygen in syn-3a , most likely
because of a combination of steric and electrostatic factors
(Figure 3).14
As expected, the cholesteryl derivative, 3b , behaves
much like the tert-butyl analogue except the values for
Ks/a are slightly lower (compare Figure 6 with Table 1).
Cholesterol carbamates are used as building blocks for
a range of supramolecular assemblies such as DNA-
containing lipoplexes, liquid crystals, gels, and Lang-
muir-Blodgett films.15,16 In each case the macroscopic
properties of the assembly are controlled by apparently
subtle changes in the shape of the cholesteric component.
The next goal of this research is to prepare liquid
crystalline films that incorporate cholesterol carbamates
such as 3b and to determine if the films’ optical proper-
ties change when exposed to compounds such as bis-
(amide) 1.17
N,N′-Dim eth yl-2,6-bis(octyla m id o)p yr id in e, 2. Com-
pound 1 (500 mg, 1.38 mmol) was dissolved in dry THF (9-10
mL) and placed under N2 atmosphere. The reaction flask was
cooled to -78 °C, and NaN(Si(CH3)3)2 (3.04 mL, 2.2 equiv) was
added dropwise. Methyl iodide (430 µL, 6.88 mmol, 5 equiv)
was added dropwise and the mixture allowed to warm to room
temperature. After stirring overnight, the solvent was evapo-
rated to give a yellow precipitate which turned blue-green after
sitting for a day. Purification by column chromatography
(silica gel, 5:1 chloroform/methanol) yielded a brownish oil.
Yield: 84%. Rf (5:1 chloroform/methanol) ) 0.55; 1H NMR (300
MHz, CDCl3) δ 0.81 (t, 6 H, J ) 6.0 Hz), 1.20 (s, 16 H), 1.63
(m, 4 H), 2.39 (t, 4 H, J ) 7.5 Hz), 3.38 (s, 6 H), 7.24 (s, 2 H),
7.78 (t, 1 H, J ) 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ 14.4,
22.8, 25.5, 29.3, 29.4, 31.8, 35.2, 35.6, 118.4, 139.9, 155.0, 173.9;
FAB MS m/z 390 (MH)+; FAB HRMS (calcd for C23H39N3O2)
390.3121, found 390.3112.
ter t-Bu tyl N-(2-P yr id yl)ca r ba m a te, 3a .9a Di-tert-butyl
dicarbonate (2.4 g, 11 mmol) was added to 2-aminopyridine
(940 mg, 10 mmol) in tert-butyl alcohol. The mixture was
stirred overnight at 30-40 °C. The solvent was evaporated,
and the residue was filtered through silica gel with methylene
chloride as the eluant. The product was a white solid (with
THF as the solvent, the major product was N,N′-bis(2-pyridyl)-
urea, as described in the literature9a). Yield: 60%. mp 93-
94 °C (lit. 92-93 °C).9a Rf (methylene chloride) ) 0.59; 1H
NMR (500 MHz, CDCl3) δ 1.52 (s, 9 H), 6.95 (t, 1 H, J ) 6.5
Hz), 7.68 (t, 1 H, J ) 8.0 Hz), 7.98 (d, 1 H, J ) 5.5 Hz), 8.30
(d, 1 H, J ) 7.5 Hz), 8.72 (s, 1 H); 13C NMR (125 MHz, CDCl3)
δ 28.5, 80.8, 112.6, 118.1, 138.7, 147.7, 152.9, 153.2; FAB MS
m/z 195 (MH)+; FAB HRMS (calcd for C10H14N2O2) 195.1134,
found 195.1127. Anal. Calcd for C10H14N2O2: C, 61.84; H, 7.26;
N, 14.42. Found: C, 62.05; H, 7.50; N, 14.62.
Ch olester yl N-(2-P yr id yl)ca r ba m a te, 3b. 2-Aminopy-
ridine (0.50 g, 5.31 mmol) was added to solution of cholesteryl
chloroformate (2.38 g, 5.31 mmol) and K2CO3 (3.76 g, 26.5
mmol) in dry THF (22 mL). The reaction was allowed to reflux
for 3 h before the solvent was evaporated. The residue was
recrystalized from 1:1 hexane/methylene chloride. Yield: 32%.
mp 212-214 °C. Rf (ethyl acetate) 0.75. 1H NMR (300 MHz,
CDCl3) δ 0.68 (s, 6 H), 0.86 (d, 6 H, J ) 7.8 Hz), 0.92 (d, 3 H,
J ) 6.6 Hz), 0.93-2.43 (m, 22 H), 1.04 (s, 6 H), 4.64 (m, 1 H,
J ) 5.6 Hz), 5.41 (d, 1 H, J ) 5.4 Hz), 6.97 (t, 1 H, J ) 6.2
Hz), 7.49 (s, 1 H), 7.67 (t, 1 H, J ) 7.1 Hz), 7.95 (d, 1 H, J )
8.7 Hz), 8.24 (d, 1 H, J ) 7.3 Hz); 13C NMR (75 MHz, CDCl3)
δ 12.1, 18.9, 19.6, 21.3, 22.8, 23.0, 24.1, 24.5, 28.2, 28.3, 28.5,
28.6, 32.2, 36.0, 36.4, 36.8, 37.2, 38.7, 39.7, 40.0, 42.6, 50.3,
56.4, 56.9, 75.3, 81.0, 112.6, 118.4, 188.6, 123.0, 138.4, 138.6,
139.8, 147.9, 152.5, 152.6, 152.9, 153.2; FAB MS m/z 507 (M+);
FAB HRMS (calcd for C33H51N2O2) 507.3951, found 507.3974.
Anal. Calcd for C33H50N2O2: C, 78.21; H, 9.94; N, 5.53.
Found: C, 78.35; H, 10.03; N, 5.41.
Con clu sion
In CDCl3 solution, the double hydrogen bonding acetic
acid moderately stabilizes the syn rotamer of phenyl
carbamate 4 (Figure 2) but has no measurable effect on
the syn/anti ratio for 2-pyridyl carbamate 3 (Figure 8).
Conversely, the donor-acceptor-donor triad 1 strongly
stabilizes the syn rotamer of 3 (Figure 3), but has no
effect on the syn/anti ratio for 4, presumably because of
steric hindrance to the formation a hydrogen bonded
complex (Figure 4).
Exp er im en ta l Section
The low-temperature NMR studies were conducted on a
Varian 500 MHz instrument. The probe temperatures were
measured with a calibrated, digital thermocouple which is
accurate to (0.5 °C. Fresh bottles of CDCl3 (Aldrich) were
used to prepare the NMR samples.
2,6-Bis(octyla m id o)p yr id in e, 1. 2,6-Diaminopyridine (0.5
g, 4.58 mmol) was dissolved in ethyl acetate and added to an
aqueous solution of NaOH (5.7 M, 2 mL). The reaction flask
was cooled to 0 °C, and octanoyl chloride (2 mL, 11.5 mmol)
was added dropwise. The reaction mixture was stirred for
several hours and then washed five times with 0.2 M NaOH.
The organic layer was dried over MgSO4 and the solvent
evaporated. The product was recrystallized from chloroform/
hexane to give a white solid. Yield: 30%. mp 99-100 °C; 1H
NMR (300 MHz, CDCl3) δ 0.93 (t, 6 H, J ) 6.0 Hz), 1.31 (m,
16 H), 1.72 (quint, 4 H, J ) 7.0 Hz), 2.39 (t, 4 H, J ) 7.5 Hz),
ter t-Bu tyl N-P h en ylca r ba m a te, 4a .9b Di-tert-butyl di-
carbonate (2.4 g, 11 mmol) was added to aniline (911 µL, 10
mmol) in dry THF (25 mL), and the mixture was stirred at
room temperature for 12 h. The solvent was evaporated and
the residue taken up in hexane and filtered. The white solid
was recrystallized from hexane/methylene chloride. Yield:
90%. mp 136-137 °C (lit. 135-136 °C).9b Rf (4:1 hexane/ethyl
acetate) ) 0.61. 1H NMR (500 MHz, CDCl3) δ 1.51 (s, 9 H),
6.55 (s, 1 H), 7.02 (t, 1 H, J ) 7.5 Hz), 7.32 (t, 2 H, J ) 8.0
Hz), 7.39 (d, 2 H, J ) 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ
28.6, 80.7, 118.7, 123.3, 129.2, 138.5, 191.2; FAB MS m/z 193
(M)+; FAB HRMS (calcd for C11H15NO2) 193.1103, found
193.1103. Anal. Calcd for C11H15NO2: C, 68.37; H, 7.82; N,
7.25. Found: C, 68.50; H, 7.81; N, 7.47.
(12) Association constants for hydrogen bonded DAD-ADA pairs
are typically 102-103 M-1
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(14) Schneider, H.-J . Chem. Rev. 1994, 94, 7-234.
(15) Geall, A. J .; Taylor, R. J .; Earll, M. E.; Eaton, M. A. W.;
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(16) J ames, T. D.; Kawabata, H.; Ludwig, R.; Murata, K.; Shinkai,
S. Tetrahedron 1995, 51, 555-566.
(17) van Nunen, J . L. M.; Nolte, R. J . M. J . Chem. Soc., Perkin Trans.
2 1997, 1473-1478.
Ch olester yl N-P h en ylca r ba m a te, 4b. 2-Aniline (0.50 g,
5.36 mmol) was added to solution of cholesteryl chloroformate
(2.40 g, 5.36 mmol) and K2CO3 (3.80 g, 26.8 mmol) in dry THF