Lanthanide-Promoted Reactions of Aldehydes and Amine Hydrochlorides in Aqueous Solution. Synthesis of 2,3-Dihydropyridinium and Pyridinium Derivatives

Full text of DOI:10.1021/jo961175n

208
J . Org. Chem. 1997, 62, 208-211
Sch em e 1
La n th a n id e-P r om oted Rea ction s of
Ald eh yd es a n d Am in e Hyd r och lor id es in
Aqu eou s Solu tion . Syn th esis of
2,3-Dih yd r op yr id in iu m a n d P yr id in iu m
Der iva tives
Li-Bing Yu, Depu Chen, J un Li, J ohnny Ramirez, and
Peng George Wang*
Department of Chemistry, University of Miami, P.O. Box
249118, Coral Gables, Florida 33124
Ta ble 1. Rea ction of Hexa n a l a n d Ben zyla m in e
Hyd r och lor id e in th e P r esen ce of Differ en t La n th a n id esa
Ln(OTf)3
La
Pr
Nd
Gd
Dy
Er
Yb
Simon G. Bott†
4a + 4bb (%)
4a /4b
73
3.1
82
3.2
74
3.2
57
3.1
38
3.2
64
3.1
56
3.1
Department of Chemistry, University of North Texas,
P.O. Box 5068, Denton, Texas 76203
a
2 mmol of amine hydrochloride and 8 mmol of aldehydes in
4.0 mL of 0.25 M lanthanide triflate solution. b The yield was based
on benzylamine hydrochloride.
Received J une 21, 1996
flate)9 can promote reactions of aldehydes and amine
hydrochlorides in water to afford 2,3-dihydropyridiniums.
In tr od u ction
The chemistry of dihydropyridines has attracted con-
siderable research interest for decades.1 Dihydropy-
ridines perform important biological function. For ex-
ample, the reduced form of coenzyme â-nicotinamide
adenine dinucleotide (NADH) bears the 1,4-dihydropy-
ridine moiety.2 Metabolites of 2,3-dihydropyridine such
as N-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+)
display neurotoxicity.3 Moreover, dihydropyridines have
been shown to be versatile intermediates in the synthesis
of a variety of natural products such as alkaloids.4 The
general synthetic routes to dihydropyridines comprise (i)
cyclization of acyclic starting materials5 and (ii) reduction
of pyridines, pyridinium ions, or their derivatives.6 2,3-
Dihydropyridines are not stable unless an electron-
withdrawing group (e.g., acyl) is attached to the nitrogen.
Few synthetic methods are available for the formation
of 2,3-dihydropyridines or pyridiniums from acyclic start-
ing materials.7 In the course of our exploration on
applications of stable Lewis acids in protic solutions,8 we
found that lanthanide trifluoromethanesulfonate (tri-
Resu lts a n d Discu ssion
The reaction of hexanal and benzylamine hydrochloride
was studied as a model for our methodology (Scheme 1).
Hexanal and benzylamine hydrochloride were added to
a solution of lanthanide triflate in water. The hetero-
geneous reaction mixture was sealed in a vial and was
shaken vigorously for 24 h at room temperature. The
products 3,5-dibutyl-2-pentyl-N-benzyl-2,3-dihydropyri-
dinium (4a ) and 3,5-dibutyl-2-pentyl-N-benzylpyridinium
(4b) were isolated via flash chromatography over silica
gel in a combined yield of 82% based on benzylamine
hydrochloride. In addition, 2-butyl-2-octenal formed by
self-condensation of hexanal was isolated in small
amounts. The effect of different lanthanide triflates on
the reaction yield and product distribution is summarized
in Table 1. Of the seven lanthanide triflates tested, the
lighter lanthanide triflate salts such as praseodymium
and lanthanum triflates showed the best catalytic effects.
The ratio of 2,3-dihydropyridinium to pyridinium was
around 3:1. For these reactions, the yield of the reaction
was dependent on the amount of lanthanides used. The
combined yield of 4a and 4b was 14, 43, and 82% with
10, 25, and 50% equivalent of praseodymium triflate. We
also observed that the reaction did not proceed in either
methanol or ethanol solution even in the presence of
lanthanide triflates.
This lanthanide-promoted reaction was applied to
different aldehydes and amine hydrochlorides (Table 2).
Acetaldehyde did not afford the pyridine compounds due
in part to its tendency toward polymerization. Propi-
onaldehyde or butanal with benzylamine hydrochloride
(Table 2, entries 1 and 2) gave only 2,3-dihydropyri-
dinium 1a or 2a , and no corresponding pyridiniums were
isolated. In contrast, isovaleraldehyde produced both 2,3-
dihydropyridinium 3a and pyridinium 3b in a ratio of
8.6:1 (Table 2, entry 3). The reaction of hexanal with
benzylamine hydrochloride (Table 2, entry 4) gave the
best yield, while replacement of benzylamine hydrochlo-
ride with propylamine hydrochloride (Table 2, entry 5)
resulted in a lower yield of the products. It is noteworthy
* To whom correspondence should be addressed.
† To whom correspondence should be made regarding X-ray analysis.
(1) For reviews on dihydropyridines, see: (a) Eisner, U.; Kuthan,
J . Chem. Rev. 1972, 72, 1. (b) Stout, D.; Meyers, A. Chem. Rev. 1982,
82, 223. (c) Sausins, A.; Duburs, G. Heterocycles 1988, 27, 291. (d)
Comins, D.; O’Connor, S. Adv. Heterocycl. Chem. 1988, 44, 199.
(2) Yasui, S.; Ohno, A. Bioorg. Chem. 1986, 14, 70.
(3) (a) Peterson, L.; Caldera, P.; Trevor, A.; Chiba, K.; Castagnoli,
N., J r. J . Med. Chem. 1985, 28, 1432. (b) Arora, P.; Riachi, N.; Fiedler,
C.; Singh, M.; Abdallah, F.; Harik, S.; Sayre, L. Life Sci. 1990, 46,
379. (c) Wang, Y.-X.; Castagnoli, N., J r. J . Med. Chem. 1995, 38, 1904.
(4) (a) Harris, M.; Besselievere, R.; Grieson, D.; Husson, H.-P.
Tetrahedron Lett. 1981, 22, 331. (b) Tubery, F.; Grierson, D.; Husson,
H.-P. Tetrahedron Lett. 1990, 31, 523. (c) Nakano, H.; Tomisawa, H.;
Hongo, H. Heterocycles 1992, 33, 195. (d) Al-awar, R.; J oseph, S.;
Comins, D. J . Org. Chem. 1993, 58, 7732. (e) Tschamber, T.; Bachen-
strass, F.; Neuburger, M.; Zehnder, M.; Streith, J . Tetrahedron 1994,
50, 1135.
(5) (a) Hantzsch, A. Liebigs Ann. Chem. 1882, 215, 1. (b) Craig, D.;
Schaefgen, L.; Tyler, W. J . Am. Chem. Soc. 1948, 70, 1624. (c) Krow,
G.; Michener, E.; Ramey, K. Tetrahedron Lett. 1971, 12, 3653. (d)
Chennat, T.; Eisner, V. J . Chem. Soc., Perkin Trans. 1 1975, 926. (e)
Fuentes, L.; Marques, C.; Contreras, M.; Lorenzo, M. J . Heterocycl.
Chem. 1995, 32, 29.
(6) Pyridine and its derivatives. Supplement part one; Abramovitch,
R. A., Ed.; J ohn Wiley & Sons: New York, 1974.
(7) (a) Fuks, R.; Merenyi, R.; Viehe, H. Bull. Soc. Chem. Belg. 1976,
85, 147. (b) Charman, H. B.; Rowe, J . M. Chem. Commun. 1971, 476.
(c) Guillemin, J .-C.; Denis, J .-M.; Lasne, M.-C.; Ripoll, J .-L. Tetrahe-
dron 1988, 44, 4447.
(8) (a) Yu, L.-B.; Chen, D.-P.; Wang, P. G. Tetrahedron Lett. 1996,
37, 2169. (b) Chen, D.-P.; Yu, L.-B.; Wang, P. G. Tetrahedron Lett. 1996,
37, 4467.
(9) For lanthanide triflates in organic synthesis, see reviews: (a)
Marshman, R. Aldrichim. Acta 1995, 28, 77. (b) Kobayashi, S. Synlett
1994, 689.
S0022-3263(96)01175-9 CCC: $14.00 © 1997 American Chemical Society

Notes
J . Org. Chem., Vol. 62, No. 1, 1997 209
Ta ble 2. La n th a n id e-Ca ta lyzed Rea ction s of Ald eh yd es a n d Am in e Hyd r och lor id es in Aqu eou s Solu tion
Sch em e 2
that the reactions with phenylacetaldehyde and 4-decenal
only afforded pyridinium products 6b and 7b. The data
in Table 2 indicated that this lanthanide-promoted
condensation gave the best yield of 2,3-dihydropyridinium
for middle-size aldehydes (three to eight carbons). For
the amine part, the reaction of amino acid or aniline
hydrochlorides did not give the desired 2,3-dihydropyri-
diniums.
The structures of the products 1a -5a and 3b-7b were
elucidated through IR, UV, NMR, and MS. The counte-
rion could be triflate or chloride, depending on the
workup conditions. Generally, the organic phase was
washed with saturated NaCl solution during workup so
that the counterion was in the most cases chloride. In
entry 3 of Table 2, the reaction was washed with water
instead of the saturated NaCl solution, and consequently,
compounds 3a and 3b were triflate salts. Triflate ac-
counted for the peak 120.2 and 123.4 ppm in 13C NMR
of 3a and 120.3 and 123.6 ppm in 13C NMR of 3b,
respectively. For the dihydropyridiniums, the two down-
mation).10 NOE between 2-H and the 3-methyl group of
1a was observed via 2D NOESY experiment, which
suggested trans-2,3-substitution of 1a . Moreover, NOE
between 2-methylene and 3-H of 2a via 2D NOESY was
observed, which supported trans-2,3-substitution of 2a ,
1
after the assignment of each peak of H NMR spectrum
of 2a via 2D COSY (Table 2).
The lanthanide-promoted reaction reported here is a
novel extension of pyridine synthesis via condensation
of aldehydes and amines (Chichibabin reaction).11 This
condensation normally requires high-temperature, high-
pressure, or vapor-phase reaction conditions. Under
milder conditions, it was reported that butanal reacted
with ammonium acetate in acetic acid to give a 2,3-
dihydropyridine that in situ disproportionated to a
mixture of tetrahydropyridine and pyridinium.7b Amine
hydrochlorides or amino acids with aldehydes were
1
field H NMR peaks (one around 6.75 ppm and the other
ranging from 8.41 to 8.68 ppm) account for the two
hydrogens of the conjugated imine. For the correspond-
ing pyridiniums, the chemical shifts of the two hydrogens
both appear between 8.21 and 9.10 ppm. In addition,
the structures have been further verified by chemical
transformations and X-ray crystallography. 2,3-Dihy-
dropyridinium 4a was dehydrogenated to give pyridinium
4b by refluxing in toluene in the presence of triethy-
lamine. Compound 4b was debenzylated to produce
2,3,5-trialkyl-substituted pyridine 8 through hydrogenol-
ysis (Scheme 2). The X-ray structure of 3a salt showed
unambiguously the 2,3,5-trisubstituted, trans-2,3-dihy-
dropyridinium core structure (see the Supporting Infor-
(10) The X-ray data for 3a have been deposited with the Cambridge
Crystallographic Data Centre. The coordinates can be obtained, on
request, from the Director, Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge, CB2 1EZ, UK. C23H34F3NO3S; fw ) 461.59;
monoclinic space group P21/n; a ) 12.500(1) Å, b ) 13.261(1) Å, c )
16.220(2) Å; â ) 111.439 (8)°, V ) 2502.6(5) Å; R ) 0.0454, Rw ) 0.0585
based on 1418 observed reflections.
(11) (a) Frank, R.; Seven, R. J . Am. Chem. Soc. 1949, 71, 2629. (b)
Farley, C.; Eliel, E. J . Am. Chem. Soc. 1956, 78, 3477.

210 J . Org. Chem., Vol. 62, No. 1, 1997
Notes
J ) 7.2 Hz, 3 H), 1.15 (t, J ) 7.2 Hz, 3 H), 1.2-1.5 (m, 3 H),
1.73 (m, 2 H), 2.42 (q, J ) 7.2 Hz, 2 H), 2.52 (m, 1 H), 3.67 (t, J
) 6.5 Hz, 1 H), 4.99 (d, J ) 13.6 Hz, 1 H), 5.18 (d, J ) 13.6 Hz,
1 H), 6.76 (d, J ) 7.0 Hz, 1 H), 7.45 (m, 3 H), 7.53 (m, 2 H), 8.68
(s, 1 H); 13C NMR (CD3OD) δ 10.1, 12.9, 13.8, 19.7, 25.8, 25.9,
32.1, 39.6, 60.2, 63.8, 129.9, 130.2, 130.6, 131.1, 131.2, 132.2,
Sch em e 3
134.0, 146.4, 166.5; MS m/e 270 (M+); HRMS calcd for C19H28
N
270.2222, found 270.2217.
3,5-Diisop r op yl-2-(2′-m et h ylp r op yl)-N-b en zyl-2,3-d ih y-
d r op yr id in iu m (3a ) a n d 3,5-Diisop r op yl-2-(2′-m eth ylp r o-
p yl)-N-ben zylp yr id in iu m (3b). Prepared from isovaleralde-
hyde and benzylamine hydrochloride. 3a : mp 88-89 °C; UV
λmax 295 nm (ꢀ 4820); IR λ-1
(cm-1) 1602, 1480, 1458, 1352;
max
1H NMR (CD3OD) δ 0.25 (d, J ) 6.4 Hz, 3 H), 0.79 (d, J ) 6.8
Hz, 3 H), 0.92 (d, J ) 6.8 Hz, 3 H), 0.95 (d, J ) 6.8 Hz, 3 H),
1.12 (m, 1 H), 1.21 (d, J ) 6.0 Hz, 6 H), 1.33 (m, 1 H), 1.47 (m,
1 H), 1.63 (m, 1 H), 2.33 (d, J ) 7.8 Hz, 1 H), 2.75 (m, 1 H), 3.77
(dd, J ) 11, 2.6 Hz, 1 H), 5.04 (dd, J ) 13.6 Hz, 1 H), 5.23 (d, J
) 13.6 Hz, 1 H), 6.83 (d, J ) 6.4 Hz, 1 H), 7.45 (m, 5 H), 8.79 (s,
1 H); 13C NMR (CD3OD) δ 19.4, 19.7, 21.1, 21.5, 22.8, 23.6, 25.1,
32.1, 31.2, 37.9, 43.9, 57.5, 63.5, 130.6, 127.9, 130.7, 130.8, 131.3,
reported to form quaternary pyridinium salts without any
dihydropyridiniums observed.12 In this work, an aqueous
medium with the catalysis of lanthanide triflates allows
the Chichibabin reaction to proceed under milder condi-
tions and enables the isolation of 2,3-dihydropyridinium
intermediates.
The reaction apparently proceeds through sequential
condensations of three molecules of the Schiff base
formed between the aldehyde and the amine (Scheme 3).
Pyridinium products 3b-7b were presumed to result
from oxidation or disproportionation of their correspond-
ing precursors, 2,3-dihydropyridiniums. The lanthanide
triflates serve as stable Lewis acids and potentially can
catalyze several individual steps in the reaction sequence.
Work is currently underway to map the detailed mecha-
nistic picture.
138.8, 144.4, 166.1; MS m/e 312 (M+); HRMS calcd for C22H34
N
312.2691, found 310.2698. 3b: UV λmax 282 nm (ꢀ 3150); IR
λ-1max (cm-1) 1633, 1504, 1458; 1H NMR (CD3OD) δ 0.99 (d, J )
6.8 Hz, 6 H), 1.31 (m, 12 H), 2.10 (m, 1 H), 3.01 (d, J ) 7.6 Hz,
2 H), 3.16 (m, 1 H), 3.30 (m, 1 H), 5.90 (s, 2 H), 7.12, 7.39 (m, 5
H), 8.44 (s, 1 H), 8.67 (s, 1 H); 13C NMR (CD3OD) δ 22.4, 23.1,
23.5, 30.8, 31.1, 32.9, 37.3, 63.1, 127.8, 130.0, 130.2, 130.7, 143.4,
144.2, 147.5, 151.8; MS m/e 310 (M+); HRMS calcd for C22H32
N
310.2535, found 310.2524.
3,5-Dibu tyl-2-pen tyl-N-ben zyl-2,3-dih ydr opyr idin iu m (4a)
a n d 3,5-Dibu tyl-2-p en tyl-N-ben zylp yr id in iu m (4b). Pre-
pared from hexanal and benzylamine hydrochloride. 4a : UV
λmax 291 nm (ꢀ 2860); IR λ-1
(cm-1) 1663, 1587, 1504, 1458,
max
1
1378; H NMR (CD3OD) δ 0.64 (t, J ) 7.2 Hz, 3 H), 0.76 (m, 1
H), 0.90 (m, 6 H), 1.11 (m, 1 H), 1.35 (m, 12 H), 1.50 (m, 2 H),
1.76 (m, 2 H), 2.35 (m, 2 H), 2.58 (m, 1 H), 3.56 (t, J ) 7.0 Hz,
1 H), 4.94 (d, J ) 13.6 Hz, 1 H), 5.14 (d, J ) 13.6 Hz, 1 H), 6.71
(d, J ) 6.4 Hz, 1 H), 7.44 (m, 5 H), 8.67 (s, 1 H); 13C NMR (CD3-
OD) δ 14.0, 14.2, 23.0, 23.3, 23.4, 26.2, 28.6, 30.0, 31.7, 32.3,
32.4, 32.5, 38.1, 60.4, 63.7, 130.7, 131.1, 131.2, 147.7, 166.5; MS
m/e 354 (M+), 282, 91 (100); HRMS calcd for C25H40N 354.3161,
In summary, lanthanide-promoted condensation be-
tween aldehydes and amine hydrochlorides in aqueous
solution affords a simple approach for the preparation
of 2,3,5-trisubstituted 2,3-dihydropyridinium and pyri-
dinium derivatives.
found 354.3159. 4b: UV λmax 281 nm (ꢀ 2420); IR λ-1
(cm-1
)
max
1640, 1504, 1458, 1378; 1H NMR (CD3OD) δ 0.79 (t, J ) 7.2 Hz,
3 H), 0.90 (m, 6 H), 1.18-1.45 (m, 10 H), 1.59 (m, 4 H), 2.74 (t,
J ) 7.6 Hz, 4 H), 2.94 (m, 2 H), 5.80 (s, 2 H), 7.11 (d, J ) 4.0 Hz,
2 H), 7.39 (m, 3 H), 8.23 (s, 1 H), 8.63 (s, 1 H); 13C NMR (CD3-
OD) δ 14.0, 23.1, 23.5, 29.0, 30.3, 32.6, 32.7, 32.8, 33.5, 33.7,
62.8, 127.9, 130.2, 130.6, 135.3, 142.5, 144.6, 144.9, 147.9, 156.2;
MS m/e 352 (M+), 91 (100); HRMS calcd for C25H38N 352.3004,
found 352.3001.
Exp er im en ta l Section
Gen er a l Meth od s. All unspecified reagents were from
commercial resources. 1H and 13C NMR spectra were recorded
at 400 MHz. Mass spectra (CI, EI or FAB) were performed by
the mass spectrometry facility at the University of California,
Riverside. UV spectra were recorded in methanol.
Syn th esis of 1a -5a a n d 3b-7b. Gen er a l P r oced u r e. To
a vial containing 4 mL of 0.25 M lanthanide triflate aqueous
solution were added an aldehyde (8 mmol) and an amine
hydrochloride (2 mmol). The reaction vial was sealed tightly
and shaken for 24 h. The reaction mixture was extracted with
ethyl acetate (5 mL × 3), and the combined organic layers were
washed with brine (Table 2, entries 1-2, 5-7) or water (Table
2, entry 3) and dried over anhydrous MgSO4. After removal of
solvents in vacuo, the oil was chromatographed, eluting with
hexane, ethyl acetate, and methanol (4/1/0, 0/1/0, and 0/10/1)
sequentially, to give the products.
3,5-Dibu tyl-2-pen tyl-N-pr opyl-2,3-dih ydr opyr idin iu m (5a)
a n d 3,5-Dibu tyl-2-p en tyl-N-p r op ylp yr id in iu m (5b). Pre-
pared from hexanal and propylamine hydrochloride. 5a : UV
λmax 293 nm (ꢀ 2820); IR λ-1
(cm-1) 1663, 1504, 1458, 1397;
max
1H NMR (CD3OD) δ 0.92 (m, 9 H), 1.04 (t, J ) 7.6 Hz, 3 H),
1.20-1.58 (m, 16 H), 1.72 (m, 3 H), 1.91 (m, 1 H), 2.35 (t, J )
8.0 Hz, 2 H), 2.75 (m, 1 H), 3.84 (t, J ) 7.6 Hz, 2 H), 3.90 (t, J
) 6.8 Hz, 1 H), 6.81 (d, J ) 6.4 Hz, 1 H), 8.41 (s, 1 H); 13C NMR
(CD3OD) δ 10.9, 13.9, 14.0, 14.2, 22.7, 22.9, 23.3, 23.4, 26.7, 29.1,
30.9, 31.7, 32.4, 32.5, 33.1, 38.1, 61.7, 62.9, 132.4, 147.3, 166.3;
MS m/e 306 (M+); HRMS calcd for C21H40N 306.3161, found
306.3163. 5b: UV λmax 281 nm (ꢀ 2410); IR λ-1
1633, 1504,
3,5-Dim et h yl-2-et h yl-N-b en zyl-2,3-d ih yd r op yr id in iu m
(1a ). Prepared from propionaldehyde and benzylamine hydro-
max
1
1458, 1379; H NMR (CD3OD) δ 0.96 (m, 9 H), 1.08 (t, J ) 7.2
Hz, 3 H), 1.45 (m, 8 H), 1.67 (m, 6 H), 2.00 (m, 2 H), 2.79 (m, 4
H), 3.07 (m, 2 H), 4.52 (t, J ) 8.0 Hz, 2 H), 8.21 (s, 1 H), 8.60 (s,
1 H); 13C NMR (CD3OD) δ 10.9, 14.0, 14.1, 23.1, 23.5, 25.9, 29.4,
29.7, 32.7, 32.8, 33.4, 33.5, 60.7, 142.3, 143.8, 147.1, 155.3; MS
m/e 304 (M+); HRMS calcd for C21H38N 304.3004, found 304.3008.
3,5-Dip h en yl-2-ben zyl-N-ben zylp yr id in iu m (6b). Pre-
pared from benzylacetaldehyde and benzylamine hydrochlo-
ride: UV λmax 262 nm (ꢀ 5830); 1H NMR (CDCl3) δ 1.59 (s, 2 H),
6.10 (s, 2 H), 7.38, 7.55, 7.73 (m, 20 H), 8.55 (s, 1 H), 9.10 (s, 1
H); MS m/e 412 (M+), 322(100); HRMS calcd for C31H24N (M -
H) 411.1987, found 411.1981.
chloride: UV λmax 293 nm (ꢀ 2120); IR λ-1
(cm-1) 1602, 1458,
max
1378; 1H NMR (CD3OD) δ 0.59 (d, J ) 7.2 Hz, 3 H), 0.96 (t, J )
7.6 Hz, 3 H), 1.79 (m, 2 H), 2.05 (s, 3 H), 2.75 (m, 1 H), 3.53 (dd,
J ) 9.2, 4.8 Hz, 1 H), 4.98 (d, J ) 13.6 Hz, 1 H), 5.16 (d, J )
13.6 Hz, 1 H), 6.74 (d, J ) 6.4 Hz, 1 H), 7.45 (m, 3 H), 7.52 (m,
2 H), 8.60 (s, 1 H); 13C NMR (CD3OD) δ 10.3, 17.6, 17.7, 23.7,
32.6, 63.9, 64.7, 127.8, 130.5, 131.1, 132.2, 148.5, 166.7; MS m/e
228 (M+); HRMS calcd for C16H22N, 228.1752, found 228.1759.
3,5-Diet h yl-2-p r op yl-N-b en zyl-2,3-d ih yd r op yr id in iu m
(2a ). Prepared from butanal and benzylamine hydrochloride:
UV λmax 293 nm (ꢀ 2320); IR λ-1
(cm-1) 1663, 1458, 1378; 1H
NMR (CD3OD) δ 0.44 (t, J ) 7.2 Hz, 3 H), 0.68 (m, 1 H), 0.94 (t,
max
3,5-Di(2′-octen yl)-2-(3′-n on en yl)-N-ben zylpyr idin iu m (7b).
Prepared from 4-decenal and benzylamine hydrochloride: UV
(12) Suyama, K.; Adachi, S. J . Org. Chem. 1979, 44, 1417.
λ
max 286 nm (ꢀ 2580); IR λ-1max (cm-1) 1633, 1504, 1458; 1H NMR

Notes
J . Org. Chem., Vol. 62, No. 1, 1997 211
(CD3OD) δ 0.84 (m, 9 H), 1.22 (m, 18 H), 1.85 (m, 2 H), 2.10 (m,
4 H), 2.24 (m, 2 H), 3.10 (m, 2 H), 3.56 (d, J ) 7.6 Hz, 2 H), 3.62
(d, J ) 7.2 Hz, 2 H), 5.43-5.53 (m, 4 H), 5.68 (m, 2 H), 5.85 (s,
1H NMR (CDCl3) δ 0.94 (m, 9 H), 1.36 (m, 8 H), 1.53 (m, 4 H),
1.68 (m, 2 H), 2.55 (m, 4 H), 2.73 (t, J ) 8.0 Hz, 2 H), 7.21 (s, 1
H), 8.19 (d, J ) 2.0 Hz, 1 H); MS m/e 262 (M + 1), 190, 163.
2 H), 7.14 (m, 2 H), 7.39 (m, 3 H), 8.19 (s, 1 H), 8.62 (s, 1 H); 13
C
NMR (CD3OD) δ 14.3, 23.5, 26.6, 28.2, 28.3, 28.5, 30.1, 30.2, 30.3,
30.6, 31.1, 32.6, 32.7, 62.8,125.2, 125.3, 127.0, 128.0, 128.1, 130.4,
130.7, 133.9, 135.5, 135.6, 141.5, 143.5, 144.7, 147.4, 156.3; MS
m/e 514 (M+); HRMS calcd for C37H56N 514.4413, found 514.4405.
Tr a n sfor m a tion of 4a to 4b. To a solution of 4a (200 mg)
in toluene (5 mL) was added triethylamine (0.5 mL), and the
resulting solution was refluxed for 1 h or stirred at room
temperature overnight. After evaporation of the solvent in
vacuo, the oil was purified through a silica gel column eluting
with methanol and ethyl acetate (1/9) to give 4b (165 mg) in
83% yield.
Ack n ow led gm en t. This work was partially sup-
ported by a research grant (F95UM-2) from the Ameri-
can Cancer Society, Florida Division, Inc.; a research
grant (PRF# 30616-G1) from the Petroleum Research
Fund, administered by the American Chemical Society
(PGW), and the Robert A. Welch Foundation (SGB).
D.C. acknowledges financial support from Tsinghua
University, China.
Deben zyla tion of 4b To P r ep a r e 3,5-Dibu tyl-2-p en tylp y-
r id in e (8). To a solution of 4b (150 mg) in methanol (5 mL)
was added Pd/C (5%, 100 mg). Under a hydrogen pressure of
50 lb/in.2, the reaction mixture was shaken overnight. After
filtration to remove the catalyst, the filtrate was evaporated,
and the residue was purified by flash chromatography, eluting
with hexane and ethyl acetate (5/1). The pure compound 8 (71
mg) was obtained in 91% yield. 3,5-Dibutyl-2-pentylpyridine (8):
Su p p or tin g In for m a tion Ava ila ble: NMR spectra and
ORTEP presentation of the X-ray structure of 3a (37 pages).
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