9250 J . Org. Chem., Vol. 63, No. 25, 1998
Smith and Macartney
R ) i-P r : 1H NMR (D2O) δ 8.46 (d, 2H, J ) 6.2 Hz), 7.46 (d,
2H, J ) 6.2 Hz), 2.03 (m, 1H, J ) 6.8 Hz), 1.51 (s, 3H), 0.86,
(d, 3H, J ) 6.8 Hz), 0.76 (d, 3H, J ) 6.8 Hz) ppm. Anal. Calcd
for C10H15NO‚1/8H2O: C, 72.69; H, 9.15; N, 8.48. Found: C,
71.59; H, 9.08; N, 8.30.
the Fe(CN)5L3- complex splits into two resonances, one
shifting downfield (yielding KCD ) 1000 ( 200 M-1) and
the other upfield (KCD ) 400 ( 100 M-1). The preferen-
tial â-CD binding of one guest enantiomer over the other
has been observed for a number of guests, such as (R)-
and (S)-2-phenylpropanoic acids, for which KCD values
of 1090 ( 30 and 1010 ( 40 M-1, respectively, have been
measured.28 Further kinetic and binding studies on the
effects of guest chirality are ongoing in this laboratory.
R ) P h : mp 137-138 °C (lit.23 142-143 °C); 1H NMR (D2O)
δ 8.48 (d, 2H, J ) 6.0 Hz), 7.60 (d, 2H, J ) 6.2 Hz), 7.57-7.46
(m, 5H), 1.97 (s, 3H) ppm. Anal. Calcd for C13H13NO: C,
78.36; H, 6.94; N, 7.02. Found: C, 77.75; H, 6.54; N, 7.15.
Gen er a l P r oced u r e for th e Syn th esis of th e N-Meth yl-
4-(R-a lk yl-R-m eth ylm eth a n ol)p yr id in iu m Iod id es. The
N-methyl-4-(R-alkyl-R-methylmethanol)pyridinium iodides were
prepared according to the method of Toma et al.24 by adding
methyl iodide (12.1 mmol, Aldrich) to a solution of the
appropriate 4-(R-alkyl-R-methylmethanol)pyridine compound
in carbon tetrachloride (when using 4-(R,R-dimethylmethanol)-
pyridine, methanol was used as the solvent25). After the
reaction was maintained in the dark for several days, it was
combined with approximately 100 mL of diethyl ether to
precipitate the product as an orange oil. The crude product
was dissolved in warm ethanol and precipitated again with
diethyl ether. Several iterations of this step afforded the pure
hygroscopic solid in 60-95% yields.
Exp er im en ta l Section
Ma ter ia ls. The R-, â-, and γ-cyclodextrins (Aldrich) were
dried at 80 °C under reduced pressure for at least 8 h prior to
use.
Gen er a l P r oced u r e for th e Syn th esis of th e 4-(R-Alk yl/
a r yl-R-m eth ylm eth a n ol)p yr id in es. The racemic 4-(R-alkyl-
R-methylmethanol)pyridine compounds were prepared accord-
ing to the method of Weber and Seebach.20 To a stirred
solution of 4-acetylpyridine (40 mmol, Aldrich) in diethyl ether
(100 mL) under N2 at -20 °C was added the appropriate
alkylmagnesium bromide (48 mmol, Aldrich). Isopropylmag-
nesium bromide was prepared from Mg turnings and isopropyl
bromide in ether.21 The reaction mixture was allowed to warm
to room temperature. After 1 h, saturated NH4Cl solution was
added, and the organic layer was separated, washed with
brine, dried over Na2SO4, and freed from the solvent under
reduced pressure. The product was further purified by flash
chromatography (90% ether, 10% methanol, silica gel 60 with
particle size 0.040-0.063 mm (230-400 mesh ASTM, EM
Separations Technology)), recrystallization from H2O, and/or
distillation, with yields ranging from 10% to 80%.
1
R ) Me: mp 133-135 °C (lit.25 mp 135-136 °C); H NMR
(D2O) δ 8.71 (d, 2H, J ) 6.6 Hz), 8.09 (d, 2H, J ) 6.6 Hz), 4.35
(s, 3H), 1.62 (s, 6H) ppm.
R ) Et: mp 126-127 °C; 1H NMR (D2O) δ 8.70 (d, 2H, J )
6.7 Hz), 8.05 (d, 2H, J ) 6.7 Hz), 4.35 (s, 3H), 1.91 (q, 2H, J )
7.5 Hz), 1.60 (s, 3H), 0.79 (t, 3H, J ) 7.5 Hz) ppm; 13C{1H}
NMR (D2O) δ 167.26, 144.72, 124.54, 75.09, 47.63, 35.19, 27.58,
7.33 ppm. Anal. Calcd for C10H16NOI: C, 40.97; H, 5.51; N,
4.78. Found: C, 40.88; H, 5.49; N, 4.77.
1
R ) P r : H NMR (D2O) δ 8.70 (d, 2H, J ) 6.8 Hz), 8.06 (d,
2H, J ) 6.8 Hz), 4.35 (s, 3H), 1.88 (t, 2H, J ) 8.3 Hz), 1.61 (s,
3H), 1.36 (m, 1H), 1.06 (m, 1H), 0.85 (t, 3H, J ) 7.3 Hz) ppm.
Anal. Calcd for C11H18NOI: C, 43.01; H, 5.91; N, 4.56.
Found: C, 42.65; H, 5.97; N, 4.61.
1
R ) Me: mp 136-138 °C (lit.22 mp 139-140 °C); H NMR
(D2O) δ 8.49 (d, 2H, J ) 6.1 Hz), 7.52 (d, 2H, J ) 6.1 Hz), 1.56
(s, 6H) ppm.
1
R ) Et: mp 101-103 °C (lit.22 mp 102-104 °C); H NMR
R ) Bu : 1H NMR (D2O) δ 8.75 (d, 2H, J ) 6.9 Hz), 8.11 (d,
2H, J ) 6.9 Hz), 4.40 (s, 3H), 1.95 (t, 2H, J ) 6.9 Hz), 1.66 (s,
3H), 1.31 (m, 2H), 1.35 (m, 1H), 1.04 (m, 1H), 0.87 (t, 3H, J )
7.2 Hz) ppm. Anal. Calcd for C12H20NOI‚1/2H2O: C, 43.65;
H, 6.41; N, 4.24. Found: C, 44.04; H, 6.12; N, 4.16.
(D2O) δ 8.49 (d, 2H, H2, J ) 5.3 Hz), 7.48 (d, 2H, J ) 5.3 Hz),
1.85 (q, 2H, J ) 7.4 Hz), 1.53 (s, 3H), 0.76 (t, 3H, J ) 7.4 Hz)
ppm. Anal. Calcd for C9H13NO‚1/8H2O: C, 70.44; H, 8.70; N,
9.13. Found: C, 70.53; H, 8.57; N, 9.21.
1
R ) P r : mp 68-69 °C; H NMR (D2O) δ 8.45 (d, 2H, J )
1
R ) a llyl: H NMR (D2O) δ 8.72 (d, 2H, J ) 6.0 Hz), 8.06
5.0 Hz), 7.45 (d, 2H, J ) 5.0 Hz), 1.78 (t, 2H, J ) 8.4 Hz), 1.51
(s, 3H), 1.24 (m, 1H), 1.04 (m, 1H ), 0.80 (t, 3H, J ) 7.3 Hz)
ppm. Anal. Calcd for C10H15NO: C, 72.67; H, 9.17; N, 8.48.
Found: C, 72.45; H, 9.22; N, 8.39.
(d, 2H, J ) 6.0 Hz), 5.70 (m, 1H), 5.11 (m, 2H), 4.36 (s, 3H),
2.68 (d, 2H, J a,b ) 7.1 Hz), 1.64 (s, 3H) ppm. Anal. Calcd for
C
11H16NOI‚1/2H2O: C, 42.05; H, 5.45; N, 4.46. Found: C,
42.35; H, 5.24; N, 4.37.
1
R ) Bu : mp 69-71 °C; H NMR (D2O) δ 8.48 (d, 2H, J )
1
R ) 4-bu ten yl: H NMR (D2O) δ 8.73 (d, 2H, J ) 6.1 Hz),
4.7 Hz), 7.48 (d, 2H, J ) 4.7 Hz), 1.83 (m, 2H), 1.54 (s, 3H),
1.23 (m, 2H), 1.22 (m, 1H), 1.02 (m, 2H), 0.80 (t, 3H, J ) 7.4
Hz) ppm. Anal. Calcd for C11H17NO: C, 73.70; H, 9.56; N,
7.81. Found: C, 73.43; H, 9.25; N, 7.72.
8.09 (d, 2H, J ) 6.1 Hz), 5.82 (m, 1H), 5.04 (m, 2H), 4.37 (s,
3H), 2.02 (t, 2H, J ) 5.8 Hz), 2.15 (m, 1H), 1.87 (m, 1H), 1.65
(s, 3H) ppm. Anal. Calcd for C12H18NOI: C, 45.16; H, 5.68;
N, 4.39. Found: C, 45.08; H, 5.66; N, 4.31.
R ) i-P r : 1H NMR (D2O) δ 8.69 (d, 2H, J ) 6.7 Hz), 8.05 (d,
2H, J ) 6.7 Hz), 4.35 (s, 3H), 2.12 (m, 1H, J ) 6.8 Hz), 1.60 (s,
3H), 0.95 (d, 3H, J ) 6.8 Hz), 0.75 (d, 3H, J ) 6.8 Hz) ppm.
Anal. Calcd for C11H18NOI‚1/2H2O: C, 41.79; H, 6.06; N, 4.43.
Found: C, 42.09; H, 5.89; N, 4.27.
1
R ) a llyl: H NMR (D2O) δ 8.49 (d, 2H, J ) 4.8 Hz), 7.48
(d, 2H, J ) 4.8 Hz), 5.65 (m, 1H), 5.08 (m, 2H), 2.61 (m, 2H),
1.56 (s, 3H) ppm. Anal. Calcd for C10H13NO‚1/2H2O: C, 69.74;
H, 8.19; N, 9.13. Found: C, 70.53; H, 7.58; N, 8.22.
1
R ) 4-bu ten yl: H NMR (D2O) δ 8.47 (d, 2H, J ) 4.7 Hz),
7.47 (d, 2H), 5.80 (m, 1H), 4.97 (m, 2H), 2.02 (m, 1H), 1.84 (m,
Gen er a l P r oced u r e for th e Syn th esis of th e 1,12-Bis-
(4-(R-a lk yl-R-m eth ylm eth a n ol)p yr id in iu m )d od eca n e Di-
br om id es. The 1,12-bis(4-(R-alkyl-R-methylmethanol)pyri-
dinium)dodecane dibromides were prepared by a modification
of the method of Attalla et al.26 The appropriate 4-(R-alkyl-
R-methylmethanol)pyridine compound (2.5 mmol) was dis-
solved in DMF (5 mL), and 1,12-dibromododecane (0.5 mmol,
Aldrich) was then added to the solution. After being stirred
at 50 °C for 8 h, the reaction was cooled and combined with
approximately 100 mL of diethyl ether to precipitate the
product as an orange oil. The crude product was dissolved in
warm ethanol and precipitated again with diethyl ether.
Several iterations of this step afforded the pure hygroscopic
solid in 60-80% yields.
1H), 1.91 (m, 2H), 1.54 (s, 3H) ppm. Anal. Calcd for C11H15
NO: C, 74.54; H, 8.53; N, 7.90. Found: C, 74.30; H, 8.42; N,
7.73.
-
(20) Weber, B.; Seebach, D. Tetrahedron 1994, 50, 6117.
(21) Fieser, L. F.; Fieser, M. Reagents for Organic Synthesis; J ohn
Wiley and Sons: New York, 1967; Vol. 1, p 415.
(22) Zymalkowski, F.; Reimann, E. Liebigs Ann. Chem. 1968, 715,
98.
(23) Zeng, X.; J iaqiang, C.; Gu, Y. Tetrahedron Lett. 1995, 36, 7275.
(24) Toma, H. E. Can. J . Chem. 1973, 57, 2079.
(25) Ferles, M.; Stern, P.; Vysata, F. Collect. Czech. Chem. Commun.
1973, 38, 1979.
(26) Attalla, M. I.; McAlpine, N. S.; Summers, L. A. Z. Naturforsch.
1984, 39B, 74.
(27) Chu, C.; Teague, P. C. J . Org. Chem. 1958, 23, 1578.
(28) Brown, S. E.; Coates, J . H.; Duckworth, P. A.; Lincoln, S. F.;
Easton, C. F.; May, B. L. J . Chem. Soc., Faraday Trans. 1993, 89, 1035.
R ) Me: 1H NMR (D2O) δ 8.74 (d, 4H, J ) 6.5 Hz), 8.09 (d,
4H, J ) 6.5 Hz), 4.55 (t, 4H, J ) 7.1 Hz), 1.97 (m, 4H), 1.60 (s,
12H), 1.29-1.21 (m, 16H) ppm. Anal. Calcd for C28H46N2O2-