Synthesis of N-benzoylamino-1,2,3,6-tetrahydropyridine derivatives as potential anti-inflammatory agents

Article abstract of DOI:10.1002/jhet.5570440622

(Chemical Equation Presented) N-Benzoylamino-1,2,3,6-tetrahydropyridines 9a-q were synthesized from 4-substituted pyridines in four steps. Amination of pyridines was carried out to prepare intermediate N-aminopyridinium mesylates using mesytelenesulfonyl hydroxmate (MSH) as aminating agent. N-aminopyridinium mestylates reacted with appropriately substituted acyl chlorides to form N-ylides as stable crystalline solids. Partial reduction of N-ylides with mild reducing agent afforded N-benzoylamino-1,2,3,6-tetrahydropyridines in fair to good yields.

Full text of DOI:10.1002/jhet.5570440622

Nov-Dec 2007
1383
Synthesis of N-Benzoylamino-1,2,3,6-tetrahydropyridine
Derivatives as Potential Anti-inflammatory Agents
Bereket Mochona1 and Kinfe K. Redda2
1Department of Chemistry, 2College of Pharmacy and Pharmaceutical Sciences,
Florida A&M University, Tallahassee, FL 32307
Received January 3, 2007
R1
O
O
+
N
N
R1
MSH
R2
Cl
R1
N
+
N
R2
CH2Cl2
Ms
NaHCO3/H2O
NH2
NaBH4, EtOH
O
S
O
H2NO
= MSH
N
N
R1
H
O
R2
9
N-Benzoylamino-1,2,3,6-tetrahydropyridines 9a-q were synthesized from 4-substituted pyridines in four
steps. Amination of pyridines was carried out to prepare intermediate N-aminopyridinium mesylates using
mesytelenesulfonyl hydroxmate (MSH) as aminating agent. N-aminopyridinium mestylates reacted with
appropriately substituted acyl chlorides to form N-ylides as stable crystalline solids. Partial reduction of
N-ylides with mild reducing agent afforded N-benzoylamino-1,2,3,6-tetrahydropyridines in fair to good
yields.
J. Heterocyclic Chem., 44, 1383 (2007).
tetrahydropyridine derivatives by partial reduction of N-
ylides constitute some of the most important methods for
preparing tetrahydropyridines.
INTRODUCTION
Tetrahydropyridine rings have attracted synthetic
interests for being essential structures in many
agrochemicals as well as medicinal agents (Figure 1). For
example, compound 1 is useful as a pesticide [1],
compounds 2-4 possess dopaminergic and antipsychotic
effects [2-7] and compounds 5 and 6 have anti-
inflammatory activities [8,9]. The electrophilic cyclization
of iminium ions (Mannich cyclization) to generate
unsaturated azacyclic systems [10] and the synthesis of
The synthesis of tetrahydropyridines via partial
reduction of N-ylides using mild reducing agents has been
extensively investigated by Redda et al., to prepare N-
benzoylamino-1,2,3,6-tetrahydropyridine derivatives as
anti-inflammatory agents [11-13].
In previous papers, we reported the synthesis and anti-
inflammatory activity profiles of
a
few 1,2,3,6-
tetrahydropyridines [14]. The results showed the
O
R
N
O
H3C
N
H3C
N
X
X = O, S
N
CH3
1
2
3
S
N
O
X
O
C
N
H
H
N
N
N
N
N
O(CH2)5CH3
N
CH3
6
X = C, S
4
5
Figure 1. Some Biologically Active Tetrahydropyridines.

1384
B. Mochona and K. Redda
Vol 44
petroleum ether. This is in sharp contrast to (15) which is
soluble in methanol and other polar solvents. Analytical
data of compounds 9a-q is presented in Table 1.
pharmacological activities of the derivatives of (6)
depended on the nature of the substitutents on the
tetrahydropyridine ring moiety. This investigation is a
continuation of the synthesis of 1,2,3,6-tetrahydropyridine
designed to modify the tetrahydropyridine ring and phenyl
moieties by introducing groups with various electronic
properties.
EXPERIMENTAL
Melting points (mp) were determined on Gallenkamp Melting
Point apparatus and are uncorrected. The structures of the
products described were confirmed by IR, 1H-NMR and
elemental analysis data. IR spectra were run with KBr pellets
on Perkin-Elmer 1430 FT spectrometer. 1H-NMR spectra
were recorded on a Bruker HX-300 spectrometer, using
CDCl3 as the solvent unless otherwise specified. Chemical
shifts (ꢀ) are reported in parts per million (ppm) downfield
from tetramethylsilane (Me4Si, 0.00ppm) as the internal
standard and coupling constants in Hertz (Hz). Elemental
analysis was performed in Galbraith Laboratories Inc.,
Knoxville, TN. Analysis indicated by the symbols of the
elements was within ± 0.4% of the theoretical values.
Analytical thin layer chromatography was performed on
precoated silica-gel using Whatman TLC plates (0.2mm,
GF254, E Merck). Spots were located by UV illumination.
Solvents were evaporated in vacuo. Anhydrous sodium
sulfate or phosphorus pentoxide was used as a drying agent.
Reaction products were purified, when necessary, by flash
chromatography on silica gel 60, (250-400 mesh), with the
solvent system indicated. All solvents and chemicals were
purchased from Fisher Scientific Company and Sigma-
Aldrich Chemical Company and used as received.
A series of 4-substituted 1,2,3,6-tetrahydropyridines,
9a-q, were prepared via partial reduction of N-ylides with
a mild reducing agent, as outlined in Scheme 1. The
ylides were prepared by coupling N-aminopyridinium salt
(14) with appropriate acyl chlorides. N-aminopyridinium
salts were prepared by aminating 4-substituted pyridines
under a basic condition. Several methods of aminating
pyridine derivatives are reported in literature. The use of
mesitylenesulfonyl hydroxmate (MSH) was found the
most versatile. MSH (13) was prepared by the method
reported by Tamura and Katritzky [15,16].
O
H
R1
N
N
C
R2
(9)
Treatment of the N-aminopyridinium derivatives with
appropriately substituted acylating agents like acyl
chlorides, followed by treatment with a base afforded N-
ylides (15) as stable crystalline solids. Partial reduction
of N-ylides using mild reducing conditions gave the
tetrahydropyridines in fair to good yields.
General Procedure for Sulfonylation. Powdered mesityl-
enesulfonyl chloride (1 mmol) was added to a solution of
ethylacetohydroxymate (1 mmol) and triethyl amine in dimethyl
formamide in small portions over a period of about 20 minutes
with stirring under ice cooling. (Precipitation of triethyl
ammonium mesitylenesulfonate was noted soon after the first
addition of the chloride). After addition was complete, triethyl
amine (1 ml) was added to keep the reaction mixture basic.
Stirring continued for additional 20 min at 5-10 °C and the
RESULTS AND DISCUSSION
Physical constants of the synthesized tetrahydro-
pyridines are summarized in Table 1. The tetrahydro-
pyridines are thermally stable and soluble in commonly
used organic solvents such as chloroform, dichloro-
methane, ethyl acetate but are insoluble in hexane and
reaction mixture was poured into ice/water.
A white
precipitated solid was collected and washed thoroughly with
cold water (yield 70-80%). The crude product was used for the
next step without further purification.
O
S
O
S
O
(i)
(ii)
(iii)
Cl
NOH
+
NO
H2NO
S
EtO
O
EtO
O
O
10
11
13
12
R1
O
O
+
(iv)
(v)
N
N
R1
N
N
R1
+
N
H
OMs
R2
R2
NH2
9a-q
15
14
Scheme -1 Reactions and conditions: (i) DMF, Et3N, 00C (ii) p-dioxane/H2O, 70% HClO4, 1h, 0OC
(iii) 4-substituted Py, CH2Cl2, 0oC, 1h (iv) 4-substituted acylchloride, THF, 70 - 75oC b) NaHCO3/H2O
(v) NaBH4, EtOH, 0oC, 4h.

Nov-Dec 2007
Synthesis of 1,2,3,6-Tetrahydropyridines
1385
Table 1
Physical and Analytical Data of 1,2,3,6-THPs
Compound
R1
R2
mp(°C)
Yield (%)
Molecular
Formula
Analysis %
Calcd./Found
C
H
N
9a
9b
9c
9d
9e
9f
Ph
H
128-130
156-157
189-190
141-142
131-133
182-183
132-133
146-148
123-125
132-134
178-179
166-167
141-142
142-143
131-133
160-161
138-140
56
65
46
51
56
72
58
62
54
46
42
72
74
68
46
56
61
C18H18N2O
C19H20N2O
C25H24N2O
C21H24N2O
C14H18N2O
C16H22N2O
C18H18N2O
C16H22N2O
C15H20N2O
C16H22N2O
C16H16N2O
C19H19N2OF
C19H19N2OCl
C20H22N2O
C20H24N2O
C20H22N2O2
C21H24N2O2
77.67 6.52 10.06
77.46 6.38 9.88
78.05 6.89 9.58
77.64 7.07 9.39
81.49 6.57 7.60
80.41 6.72 7.34
78.71 7.55 8.74
78.55 7.76 8.59
78.05 6.89 9.58
77.89 6.66 9.46
74.38 8.58 10.84
73.56 8.64 10.56
77.67 6.52 10.06
77.50 6.48 9.98
74.38 8.58 10.80
74.12 8.76 10.70
73.74 8.25 11.47
73.62 8.46 11.60
74.38 8.58 10.84
74.12 8.76 10.70
76.16 6.39 11.10
75.27 6.43 10.69
73.52 6.17 9.02
73.49 6.36 8.93
69.82 5.85 8.57
69.75 6.04 8.56
78.39 7.24 9.14
78.22 7.39 9.08
78.71 7.55 8.74
78.39 7.38 8.92
74.50 6.88 8.69
73.30 6.35 8.97
74.97 7.19 8.33
74.70 6.98 8.67
CH2Ph
CH(Ph)2
Ph-propyl
Et
H
H
H
H
t-Bu
H
9g
9h
9i
H
Ph
t-BU
n-Pr
n-Bu
C4H4
F
H
H
9j
H
*
9k
9l
H
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
9m
9n
9o
9p
9q
Cl
Me
Et
OMe
OEt
*9k is N-Naphtholylamino-1,2,3,6-tetrahydropyridine.
General Procedure for Hydrolysis. The crude product from
step 1 was dissolved in dioxane:water (4:1) and 70% perchloric
acid was added at 0 °C over 10 min. The reaction mixture
became pasty due to the precipitation of O-mesitylenesulfonyl
hydroxylamine perchlorate. After stirring was continued for
further 10 min, the reaction mixture was poured onto ice/water
to give a white solid, which was collected, and washed with cold
petroleum ether to give mesitylenesulfonyl hydroxmate (MSH)
(13) as an aminating agent (yield 62-70%).
General procedure for Amination. To an ice-cooled
solution of pyridine derivatives (1 mmol) in dichloromethane
was added drop-wise a solution of O-mesitylenesulfonyl-
hydroxyylamine (13) (1 mmol) in dichloromethane. The reaction
mixture was allowed to stand at room temperature for 10 min.
after addition of ether, the precipitated crystals were collected
and recrystalized from methanol/ethyl acetate to give N-amino-
pyridinum mesitylenesulfonate (14).
shaken repeatedly in separatory funnel and allowed to stand for
few minutes. Extraction with chloroform (4 x 30 ml), drying
over sodium sulfate and removal of the solvent in vacuo gave
the crude product, which was purified by elution with ethyl
acetate - methanol (4:1) in a short column. The initial 100 ml
eluate was discarded and further elution with 300 ml afforded
(15) in fair to good yields.
General Procedure for Reduction. A solution of (15) (5
mmol) in 20 ml of absolute ethanol was added drop-wise to a
solution of sodium borohydride (50 mmol) in 25 ml of absolute
ethanol pre-cooled to 0 °C. The reaction was allowed to proceed
for 5 h at 0 °C with stirring. Water (35 ml) was added, and
allowed to warm up to room temperature. Extraction with
chloroform (3x50 ml), drying over sodium sulfate, and removal
of the solvent in vacuo gave crude product of (9) which was
purified by column chromatography using ethyl acetate:hexane
(2:3) as eluent to afford a purified compound (9) in fair to good
yields.
General Procedure for Acylation. To an ice-cold solution of
(14) (8 mmol) in 25 ml of anhydrous tetrahydrofuran was added
an acid chloride (12 mmol) with stirring. The reaction was
allowed to proceed for 12 h at 70 °C. After cooling to room
temperature the reaction was quenched by adding 25 ml of a
saturated aqueous sodium bicarbonate solution. The mixture was
N-Benzoylamino-4-phenyl-1,2,3,6-tetrahydropyridine (9a).
This compound was obtained as white powder, yield 56%, mp
128-130°C. 1H NMR (CDCl3) ꢀ 2.38 (t, 2H, C3-H), 3.29 (t, 2H,
C2-H), 3.78 (d, 2H, C6-H), 5.70 (s, 1H, C5-H), 7.09-7.83 (m,
10H, phenyl protons), 7.18 (br, s, NH, deuterium oxide

1386
B. Mochona and K. Redda
Vol 44
exchanged). IR(potassium bromide): 3300 (NH), 1667 (CO)
cm-1. Anal. Calcd. For C18H18N2O: C, 77.67; H, 6.52; N, 10.06.
Found: C, 77.46, H, 6.38, N, 9.88.
oxide exchanged). IR (potassium bromide): 3300 (NH), 1667
(CO) cm-1 Anal. Calcd. For C16H22N2O: C, 74.38; H, 8.58; N,
10.84. Found: C, 74.12; H, 8.76; N, 10.70.
N-Benzoylamino-4-benzyl-1,2,3,6-tetrahydropyridine (9b).
This compound was obtained as white solid product, yield 65%,
mp 156-157°C. 1H NMR (CDCl3) ꢀ 2.38 (t, 2H, C3-H), 3.29 (t,
2H, C2-H), 3.43 (s, 2H, -H2C-C6H5), 3.78 (d, 2H, C6-H), 5.70 (s,
1H, C5-H), 7.08-7.15 (m, 5H, -C6H5), 7.44-7.48 (d, 1H, C4'-H),
7.48-7.50 (d, 2H, C3'-H and C5'-H), 7.79-7.82 (d, 2H, C2'-H and
C6'-H), 6.96 (br, s, NH, deuterium oxide exchanged). IR
(potassium bromide): 3300 (NH),1667 (CO) cm-1. Anal. Calcd.
For C19H20N2O: C, 78.05; H, 6.89; N, 9.58. Found: C, 77.64; H,
7.07; N, 9.39.
N-(4'-n-Propylbenzoylamino)-1,2,3,6-tetrahydropyridine
(9i). This compound was obtained as yellow powder, yield 54%,
mp 123-125°C. H NMR (CDCl3) ꢀ 0.94 (t, 3H, -CH2CH2CH3),
1.64 (m, 2H, -CH2CH2CH3), 2.36 (t, 2H, C3-H), 2.54 (t, 2H,
-CH2CH2CH3), 3.29 (t, 2H, C2-H), 3.58 (d, 2H, C6-H), 5.68 (s,
1H, C4-H), 6.20 (s, 1H, C5-H), 7.33 (d, 2H, C3'-H and C5'-H),
7.75 (d, 2H, C2'-H and C6'-H), 7.02 (br, s, NH, deuterium oxide
exchanged). IR (potassium bromide): 3300 (NH), 1667 (CO)
cm-1. Anal.Calcd. For C15H20N2O: C, 73.74; H, 8.25; N, 11.47.
Found: C, 73.62; H, 8.46; N, 11.60.
1
N-Benzoylamino-4-(diphenyl-4-pyridylmethane)-1,2,3,6-
tetrahydropyridine (9c). This compound was obtained as
yellow brown powder, yield 46%, mp 189-190°C. 1H NMR
(CDCl3) ꢀ 2.38 (t, 2H, C3-H), 3.29 (t, 2H, C2-H), 4.60 (s, 1H,
-HC-(C6H5)2, 3.78 (d, 2H, C6-H), 5.08 (s, 1H, C5-H), 6.83-7.09
(m, 10H, -HC-(C6H5)2), 7.42-7.83 (m, 5H, -C6H5), 7.08 (br, s,
NH, deuterium oxide exchanged). IR (potassium bromide): 3300
(NH),1667 (CO) cm-1. Anal. Calcd. For C25H24N2O: C, 81.49; H,
6.57; N, 7.60. Found: C, 80.41; H, 6.72; N, 7.34.
N-(4'-n-Butylbenzoylamino)-1,2,3,6-tetrahydropyridine
(9j). This compound was obtained as white powder, yield 46%,
mp 132-134°C. H NMR (CDCl3) ꢀ 0.92 (t, 3H, -CH2CH2CH2-
1
CH3), 1.46 (m, 2H, -CH2CH2CH2CH3), 1.57 (m, 2H, -CH2CH2-
CH2CH3) 2.38 (t, 2H, C3-H), 2.71 (t, 2H, -CH2CH2CH2CH3)
3.12 (t, 2H, C2-H), 3.78 (d, 2H, C6-H), 5.88 (s, 1H, C4-H), 5.92
(s, 1H, C5-H), 6.99 (d, 2H, C3'-H and C5'-H), 7.82 (d, 2H, C2'-H
and C6'-H), 7.08 (br, s, NH, deuterium oxide exchanged). IR
(potassium bromide): 3300 (NH), 1667 (CO) cm-1. Anal. Calcd.
For C16H22N2O: C, 74.38; H, 8.58; N, 10.84. Found: C, 74.12; H,
8.76; N, 10.70.
N-Benzoylamino-4-(3-phenylpropyl)-1,2,3,6-tetrahydro-
pyridine (9d). This compound was obtained as yellow powder,
1
yield 51%, mp 141-142°C. H NMR (CDCl3) ꢀ 0.93 (t, 3H,
N-Naphtholylamino-1,2,3,6-tetrahydropyridine (9k). This
compound was obtained as yellow brown, yield 42%, mp 178-
-CH2CH2CH3), 1.63 (m, 2H, -CH2CH2CH3), 2.38 (t, 2H, C3-H),
2.55 (t, 2H, -CH2CH2CH3), 3.29 (t, 2H, C2-H), 3.78 (d, 2H, C6-
H), 5.35 (s, 1H, C5-H), 7.14-7.83 (m, 9H, -phenyl protons), 7.0
(br, s, NH, deuterium oxide exchanged). IR (potassium
bromide): 3300 (NH),1667 (CO) cm-1. Anal. Calcd. For
C21H24N2O: C, 78.71; H, 7.55; N, 8.74. Found: C, 78.55; H,
7.76; N, 8.59.
1
179°C. H NMR (CDCl3) ꢀ 2.38 (t, 2H, C3-H), 3.29 (t, 2H, C2-
H), 3.78 (d, 2H, C6-H), 5.62 (s, 1H, C4-H), 5.68 (s, 1H, C4-H),
7.52-8.35 (m, 7H, -C10H7), 6.98 (br, s, NH, deuterium oxide
exchanged). IR (potassium bromide): 3300 (NH), 1667 (CO)
cm-1. Anal. Calcd. For C16H16N2O: C, 76.16; H, 6.39; N, 11.10.
Found: C, 74.27; H, 6.43; N, 10.69.
N-Benzoylamino-4-ethyl-1,2,3,6-tetrahydropyridine (9e).
This compound was obtained as yellow brown powder, yield
56%, mp 131-133°C. H NMR (CDCl3) ꢀ 2.38 (t, 2H, C3-H),
3.29 (t, 2H, C2-H), 3.78 (d, 2H, C6-H), 5.70 (s, 1H, C5-H), 7.08-
7.15 (m, 5H, -C6H5), 7.44-7.48 (d, 1H, C4'-H), 7.48-7.50 (d, 2H,
C3'-H and C5'-H), 7.79-7.82 (d, 2H, C2'-H and C6'-H), 7.22 (br, s,
NH, deuterium oxide exchanged). IR (potassium bromide): 3300
(NH), 1667 (CO) cm-1. Anal. Calcd. For C19H20N2O: C, 78.05;
H, 6.89; N, 9.58. Found: C, 77.89; H, 6.66; N, 9.46.
N-(4'-Fluorobenzoylamino)-4-benzyl-1,2,3,6-tetrahydro-
pyridine (9l). This compound was obtained as white crystalline
solid, yield 72%, mp 166-167°C. 1H NMR (CDCl3) ꢀ2.30 (t,
2H, C3-H), 3.29 (t, 2H, C2-H), 3.43 (s, 2H, -H2C-C6H5), 3.78 (d,
2H, C6-H), 5.96 (s, 1H, C5-H), 7.08-7.17 (m, 5H, -C6H5), 7.25-
7.31 (d, 2H, C3'-H and C5'-H), 7.70-7.73 (d, 2H, C2'-H and C6'-H)
8.22 (br, s, NH, deuterium oxide exchanged). IR (potassium
bromide): 3300 (NH),1665 (CO) cm-1 Anal. Calcd. For
C19H19N2OF: C, 73.52; H, 6.17; N, 9.02. Found: C, 73.49; H,
6.36; N, 8.93
N-(4'-Chlorobenzoylamino)-4-benzyl-1,2,3,6-tetrahydro-
pyridine (9m). This compound was obtained as light yellow
solid product, yield 74%, mp 141-142°C. 1H NMR (CDCl3)
ꢀ2.32 (t, 2H, C3-H), 3.31 (t, 2H, C2-H), 3.43 (s, 2H, -H2C-C6H5),
3.77 (d, 2H, C6-H), 5.96 (s, 1H, C5-H), 7.08-7.17 (m, 5H,
-C6H5), 7.40-7.43 (d, 2H, C3'-H and C5'-H), 7.72-7.75 (d, 2H,
C2'-H and C6'-H) 8.22 (br, s, NH, deuterium oxide exchanged).
IR (potassium bromide): 3300 (NH),1665 (CO) cm1 Anal. Calcd.
For C19H19N2OCl: C, 69.82; H, 5.85; N, 8.57. Found: C, 69.75;
H, 6.04; N, 8.56.
1
N-Benzoylamino-4-tert-butyl-1,2,3,6-tetrahydropyridine
(9f). This compound was obtained as brown powder, yield 72%,
1
mp 182-183°C. H NMR (CDCl3) ꢀ 1.06 (s, 9H, -C(CH3), 2.38
(t, 2H, C3-H), 3.29 (t, 2H, C2-H), 3.78 (d, 2H, C6-H), 5.70 (s,
1H, C5-H), 7.08-7.15 (m, 5H, -C6H5), 7.22 (br, s, NH, deuterium
oxide exchanged). IR (potassium bromide): 3300 (NH), 1667
(CO) cm-1 Anal. Calcd. For C16H22N2O: C, 74.38; H, 8.58; N,
10.84. Found: C, 73.56; H, 8.64; N, 10.56.
N-(4'-Biphenylcarbonylamino)-1,2,3,6-tetrahydropyridine
(9g). This compound was obtained as white powder, yield 58%,
1
mp 132-133°C. H NMR (CDCl3) ꢀ 2.38 (t, 2H, C3-H), 3.29 (t,
2H, C2-H), 3.78 (d, 2H, C6-H), 5.68 (s, 1H, C4-H), 5.70 (s, 1H,
C5-H), 7.36-7.87 (m, 9H, -C6H4-C6H5), 7.18 (br, s, NH,
deuterium oxide exchanged). IR 3300 (NH), 1667 (CO) cm-1.
Anal. Calcd. For C18H18N2O: C, 77.67; H, 6.52; N, 10.06. Found:
C, 77.50; H, 6.48; N, 9.98.
N-(4'-tert-Butylbenzoylamino)-1,2,3,6-tetrahydropyridine
(9h). This compound was obtained as white powder, yield 62%,
mp 146-148°C1H NMR (CDCl3) ꢀ 1.06 (s, 9H, -C(CH3), 2.38 (t,
2H, C3-H), 3.29 (t, 2H, C2-H), 3.78 (d, 2H, C6-H), 5.70 (s, 1H,
C5-H), 7.08-7.15 (m, 5H, -C6H5), 7.22 (br, s, NH, deuterium
N-(4'-Methylbenzoylamino)-4-benzyl-1,2,3,6-tetrahydro-
pyridine (9n). This compound was obtained as white solid
powder, yield 68%, mp 142-143°C. 1H NMR (CDCl3) ꢀ2.23 (s,
3H, -CH3), 2.32 (t, 2H, C3-H), 3.31 (t, 2H, C2-H), 3.43 (s, 2H,
-H2C-C6H5), 3.77 (d, 2H, C6-H), 5.96 (s, 1H, C5-H), 7.10-7.17
(m, 7H, -C6H5, C3'-H and C5'-H), 7.72-7.75 (d, 2H, C2'-H and C6'-
H) 8.22 (br, s, NH, deuterium oxide exchanged). IR (potassium
bromide): 3300 (NH), 1667 (CO) cm-1. Anal. Calcd. For
C20H22N2O: C, 78.39; H, 7.24; N, 9.14. Found: C, 78.22; H,
7.39; N, 9.08.

Nov-Dec 2007
Synthesis of 1,2,3,6-Tetrahydropyridines
1387
also grateful to the Chemistry Department, NMR Unit, Florida
State University, Tallahassee, Florida, for recording the NMR
spectra of our compounds.
N-(4'-Ethylbenzoylamino)-4-benzyl-1,2,3,6-tetrahydro-
pyridine (9o). This compound was obtained as white solid
product (46%), mp 131-133°C. 1H NMR (CDCl3) ꢀ1.24-1.27 (t,
3H, -CH2CH3), 2.23 (s, 3H, –CH3), 2.32 (t, 2H, C3-H), 2.82-2.84
(m, 2H, -CH2CH3), 3.31 (t, 2H, C2-H), 3.43 (s, 2H, -H2C-C6H5),
3.77 (d, 2H, C6-H), 5.96 (s, 1H, C5-H), 7.10-7.17 (m, 7H, -C6H5
C3'-H and C5'-H), 7.72-7.75 (d, 2H, C2'-H and C6'-H) 8.22 (br, s,
NH, deuterium oxide exchanged). IR (potassium bromide): 3300
(NH), 1667 (CO) cm-1. Anal. Calcd. For C21H24N2O: C, 78.71;
H, 7.55; N, 8.74. Found: C, 78.39; H, 7.38; N, 8.92.
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pyridine (9p).
This compound was obtained as white
crystalline solid, yield 56%, mp 160-161°C. 1H NMR (CDCl3),
2.38 (t, 2H, C3-H), 2.41 (t, 2H, C2-H), 3.43 (s, 2H, -H2C-C6H5),
3.62 (d, 2H, C6-H), 3.98 (s, 3H, -OCH3), 5.96 (s, 1H, C5-H),
7.08-7.17 (m, 5H, -C6H5), 6.97-7.00 (d, 2H, C3'-H and C5'-H),
7.98-8.01(d, 2H, C2'-H and C5'-H) 8.22 (br, s, NH, deuterium
oxide exchanged). IR (potassium bromide): 3300 (NH),1663
(CO) cm-1. Anal. Calcd. For C20H22N2O2: C, 74.50; H, 6.88; N,
8.69. Found: C, 73.30; H, 6.35; N, 8.97.
N-(4'-Ethoxybenzoylamino)-4-benzyl-1,2,3,6-tetrahydro-
pyridine (9q) This compound was obtained as yellow powder,
yield 61%, mp 138-140°C. 1H NMR (CDCl3) ꢀ1.35-1.38 (t, 3H,
-OCH2CH3), 2.38 (t, 2H, C3-H), 2.41 (t, 2H, C2-H), 3.43 (s, 2H, -
H2C-C6H5), 3.62 (d, 2H, C6-H), 3.98-4.02 (m, 2H, -OCH2CH3),
5.96 (s, 1H, C5-H), 7.08-7.17 (m, 5H, -C6H5), 6.97-7.00 (d, 2H,
C3'-H and C5'-H), 7.98-8.01(d, 2H, C2'-H and C5'-H) 8.22 (br, s,
NH, deuterium oxide exchanged). IR (potassium bromide): 3300
(NH), 1663 (CO) cm-1. Anal. Calcd. For C21H24N2O2: C, 74.97;
H, 7.19; N, 8.33. Found: C, 74.70; H, 6.98; N, 8.67.
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Acknowledgment. This research was supported by the
National Institutes of Health, the National Institute of General
Medical Sciences, MBRS Program, Grant Number GM 08111
and the National Center of Research Resources, Research Center
in Minority Institutions (RCMI) Program, NIH/NCRR grant 1
C06 RR12512-01 and NIH/NCRR grant G12 RR0 3020. We are
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