Regioselective formation of novel functionalized 1-aza-9-oxafluorenes

Article abstract of DOI:10.3987/COM-00-9141

A small series of novel 1-aza-9-oxafluorenes have been prepared by regioselective cycloaddition reaction of p-benzoquinone to the sterically unhindered side of unsymmetrically substituted N-acyl-1,4-dihydropyridines (1). The stereochemistry of the product

Full text of DOI:10.3987/COM-00-9141

HETEROCYCLES, Vol. 55, No. 4, 2001, pp. 661 - 669, Received, 11th December, 2000
REGIOSELECTIVE
FORMATION
OF
NOVEL
FUNCTIONALIZED 1-AZA-9-OXAFLUORENES
Andreas Hilgeroth,*a Kristin Brachwitz, a and Ute Baumeister b
aInstitute of Pharmaceutical Chemistry, Department of Pharmacy, Martin-Luther-
University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle,
b
Germany Institute of Physical Chemistry, Martin-Luther-University, Mühlpforte
1, 06108 Halle, Germany
Abstract - A small series of novel 1-aza-9-oxafluorenes have been prepared by
regioselective cycloaddition reaction of p-benzoquinone to the sterically
unhindered side of unsymmetrically substituted N-acyl-1,4-dihydropyridines (1).
The stereochemistry of the products is discussed on the basis of X-Ray crystal
structure analysis of one starting structure (1a). The formation of pyridine
derivatives by possible redox reaction of the adducts was not observed. Rotameric
1
properties of the N-acyl-1,4-dihydropyridines are demonstrated by H and 13C
NMR spectroscopy, thus stabilizing the 1,4-dihydropyridine system towards
competing oxidation by the quinone.
Recent investigations in the redox behavior of symmetrically substituted NH and N-alkyl-4-phenyl-1,4-
dihydropyridines and p-benzoquinone showed that instead of being oxidized the dihydropyridine
derivatives undergoe cycloaddition reaction with the quinone to 1-aza-9-oxafluorenes.1 Steric hindrance
based on the pseudoaxial orientation of the phenyl moiety was discussed to prevent the formation of a CT
complex between oxidizing quinone and dihydropyridine thus preventing further redox reaction of the
compounds.1 As novel functionalized tricyclic systems, 1-aza-9-oxafluorenes are presently investigated as
potential cytostatic agents with DNA intercalating properties.2 However, with the phenyl substituent of
the first reported derivatives1 standing out of the molecular plane their potential intercalating properties
will be low. The current pharmacological interest in these substance class additionally as antiviral agents3
encouraged to create varied structures following the facile synthetic route of the reported cycloaddion
reaction between quinone and 1,4-dihydropyridine. We now report the regioselective formation of 1-aza-
9-oxafluorenes using unsymmetrically substituted 1,4-dihydropyridine derivatives. Surprisingly, also the

4-methyl substituted compounds were not oxidized by p-benzoquinone. The stereochemistry of the
cycloaddition products as well as the certain stability of the N-acyl-1,4-dihydropyridines towards
competing oxidations are discussed.
Results and Discussion
The N-acetyl 3-ethoxycarbonyl-1,4-dihydropyridines (1a, b) have been synthesized in two steps: First
ethyl nicotinate was N-acetylated at low temperatures (-8 °C). Then regioselective arylation or alkylation
at 4-position of the pyridinium ring was carried out using Grignard reagents and catalytic amounts of
copper(I) iodide.4,5 For preparation of corresponding 3-acetyl derivatives (1c, d) the temperature for
acetylation was lowered to -15 °C so that no attack of the 3-acetyl group of the pyridine took place. The
one-pot synthesis gave the 1,4-dihydropyridines (1a-d) in yields of about 85%.
O
2
R
O
O
1. CuI
2. R MgCl
O
2
1
R
1
R
1
R
CH CCl
3
+
N
THF
N
_
N
Cl
O
O
CH3
CH3
1
2
1a, R = OC H , R = Ph
2 5
1
2
b, R = OC H , R = CH
2 5
3
1
2
c, R = CH , R = Ph
3
1
2
d, R = CH , R = CH
Scheme 1
3
3
With two kinds of proton signals for 2-H and 6-H of the dihydropyridine the existance of two rotamers A
and B was proved (see EXPERIMENTAL). In the 13C NMR spectrum of selected derivative (1a)
corresponding double signals for both C-atoms, C-2 and C-6, were found. While the carbon-atom of the
N-acetyl group also gave two signals, the signal of the methyl-C was splitted.
Under acid conditions, 5% of perchloric acid in dioxane, treatment of equimolar mixtures of 1,4-
dihydropyridines (1a-d) with p-benzoquinone at room temperature yielded one single product monitored
by TLC. Within 24 hours the reactions were completed and following preparative TLC led to isolation of
1-aza-9-oxafluorene derivatives (2a-d) (Scheme 2).

The compounds show characterizing IR-absorptions of the N-acetyl group between < = 1628 - 1680 cm-1.
In comparison to the 1,4-dihydropyridine derivatives (1a, b) the almost unchanged absorptions of the
ester carbonyl groups at 1691 cm-1 (2a) and 1709 cm-1 (2b), respectively, indicated an unchanged
vinylogous carbamide ester partial structure in the reaction products, so that an exclusive attack of the p-
benzoquinone at the enamine side of the dihydropyridine as the sterically unhindered side was suggested.
1
In the H NMR spectra the 9a-protons with characteristic high field shift between 5.10 and 5.91 ppm
appear as doublets, so that the regioselective addition of the quinone at the enamine side of the
3
dihydropyridine was confirmed by coupling of 9a-H to 4a-H with coupling constants J9a,4a of about 7.3
Hz. Moreover, the resonances of the 2-protons were found unchanged compared to the dihydropyridines
due to the intact carbamide ester structure in 2a-d.
For characterization of the cycloaddition product formation X-Ray crystal structure of one starting 1,4-
dihydropyridine (1a) was determined.
R2
O
O
O
H
R1
+
N
O
CH3
1a-d
dioxane/HClO (5%)
4
HO
R2
N
R2
_
O
O
O
H
H
H
H
R1
R1
H
+
N
O
OH
CH3
O
O
CH3
2a-d
Scheme 2

O
3
H
OCH3
4
5
H
H
N CH3
N
O
CH3
OCH3
Figure 1. Molecular structure of N-acetyl-4-phenyl-1,4-dihydropyridine (1a) (left) and tetrakishomocu-
bane derivative (right), discussed in the text.
In the molecular structure of 1a the 4-phenyl substituent shows pseudoaxial orientation as has been repor-
ted for the symmetrically substituted 4-phenyldihydropyridines.6,7 In consequence, the attack of the p-
benzoquinone will take place from the back side of the dihydropyridine ring thus leading to a Michael
addition intermediate that undergoes a following ring closure to the tetrahydropyridine annelated
benzofuran product (Scheme 2). In order to decide, whether the ring junction in 2a-d would be cis or
trans the proton coupling constants of 9a-H and 4a-H were compared to those of cis-orientated 4-H and
5-H of the C2-symmetric tetrakishomocubane derivative5 shown in Figure 1 (right). These protons are
3
coupling with a constant of J4,5 = 9.4 Hz. Furthermore, the trans-coupling between 4-H and 3-H at C-3
3
with an axially standing phenyl substituent makes J4,3 = 1.9 Hz. Thus, the ring junction in compounds
3
(2a-d) will be cis and the coupling of 4a-H and 4-H with J4a,4 = 1-2 Hz results from the corresponding
pseudoaxial orientation of the phenyl ring as has been shown for the starting 1,4-dihydropyridine (1a).
Comparing to previous reports of N-alkyl-1,4-dihydropyridines as NADH or NAD model compounds8,9
that are being oxidized by quinone derivatives the N-acyl derivatives (1a-d) prove to be stable towards
possible competing oxidation by the quinone. However, manganese(IV) oxide treatment in boiling
toluene leads to corresponding pyridines (3a-d). TLC comparison with the reaction mixture of 1a-d and
p-benzoquinone showed that no pyridine derivative was formed during the cycloaddition reaction.
Obviously, the N-acyl substituted 1,4-dihydropyridines are stabilized towards quinone oxidation. The
stability may result from enhanced conjugation possibilities of the dihydropyridine double bonds with the
N-acyl group. This is supported by the observed rotameric properties of the dihydropyridines that reflect
enhanced conjugation over the N-acyl group.

In summary, the regioselectively controlled cycloaddition reaction between unsymmetrically substituted
1,4-dihydropyridines and p-benzoquinone leads to novel 1-aza-oxafluorenes that are exclusively yielded
by a uniform reaction without possible side products.
EXPERIMENTAL
1H NMR spectra were recorded with a Varian Gemini-400 and Varian Gemini-500 with tetramethylsilane
13
(TMS) as an internal standard. C NMR spectra were measured with the Varian Gemini-500. Chemical
shifts are given on the δ scale (ppm). The following abbreviations are used: s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, sh = shoulder, spl = splitted. MS was taken with a AMD 402
spectrometer. IR spectra were recorded on a Bruker IFS-28 spectrophotometer. Preparative TLC was
carried out with silica gel plates 60F254 with a layer thickness of 1 mm.
General Procedure for the Preparation of 1-Acetyldihydropyridines
1.0 g (6.62 mmol) of ethyl nicotinate or 0.8 g (6.62 mmol) of 3-acetylpyridine were solved in 60 mL of
anhydrous THF. After addition of copper(I) iodide 0.06 g (0.33 mmol) the solution was cooled down to
-8 °C for preparation of 1a, b and to -15 °C for preparation of 1c, d. Then 0.52 g (6.62 mmol) of acetyl
chloride were added dropwise to the solution. The reaction mixture was stirred for 15 min at the low
temperatures, Then 6.6 mL (6.6 mmol) of a 1 M solution of phenylmagnesium chloride or
methylmagnesium chloride were added. Stirring was continued for 15 min and for additional 30 min at rt.
Then 36 mL of an aqueous solution of ammonium chloride (20%, 7.2 g, 134. 6 mmol) were added,
followed by the extraction with ether (3 x 150 mL). The ether phase was then washed with 36 mL of a
20% solution mixture (1/1) of ammonia/ammonium chloride (3.6 g, 67.3 mmol), 36 mL of water, 36 mL
of 10% hydrochloride acid (2 x), 36 mL of water and 36 mL of a saturated solution of sodium chloride.
The ether phase was dried over sodium sulfate. After filtration the ether was removed under vacuum
leaving yellow oils of 1a, 1b and 1d and a yellow powder of 1d.
Ethyl 1-Acetyl-1,4-dihydro-4-phenylpyridine-3-carboxylate (1a)
Colorless needles from methanol, mp 55-57 °C (1.35 g, 75%). IR (KBr): 1693 (COOCH2CH3), 1680
(NCOCH3) cm-1. MS m/z: 271 (M+). 1H NMR (CDCl3): 8.37 (br s, 1 H, 2-H, B), 7.80 (br s, 1 H, 2-H, A),
7.30-7.16 (m, 11 H, aromat. H, A, B, 6-H, A), 6.60 (br "s", 1 H, 6-H, B), 5.24 (br m, 2 H, 5-H, A, B), 4.47
3
3
(d, J4,5 = 4.3 Hz, 2 H, 4-H, A, B), 4.05 (q, J = 7.2 Hz, 4 H, COOCH2CH3, A, B), 2.37 (br s, 6 H,
3
NCOCH3, A, B), 1.14 (t, J = 7.2 Hz, 6 H, COOCH2CH3, A, B). 13C NMR (CDCl3): 166.98, 166.63
(COCH3, A, B), 166.64 (COOCH2CH3, A, B), 144.66 (C1´, A, B), 132.13 (C2, B), 130.03 (C2, A),
128.55 (C3´, C5´, A, B), 128.12 (C4´, A, B), 126.91 (C2´, C6´, A, B), 121.05 (C6, A), 119.28 (C6, B),
113.55 (C5, A, B), 113.52 (C3, A, B), 60.49 (CH2CH3, A, B), 39.18 (C4, A, B), 21.33 (spl, COCH3, A, B),
13.93 (CH2CH3, A, B). Anal. Calcd for C16H17NO3: C, 70.83; H, 6.32; N 5.16. Found: C, 70.96; H 6.40;
N 5.09.
X-Ray Diffraction Analysis of 1a: A colourless crystal C16H17NO3 (from methanol), crystal size 0.38 x

0.29 x 0.23 mm, was measured at a temperature of 220 (2) K by using a Stoe-IPDS Diffractometer with
Mo-Kα radiation (λ = 0.71073 Å) and a graphite monochromator. 9186 Reflexions were collected in the
range 5.06° ≤ 2 Θ 51.82°; h,k,l range from –13, -9, -18 to 14, 9, 20. Crystal system: Monoclinic, space
group P21/c, Z = 4, a = 11.5025(15) Å, b = 7.4994(14) Å, c = 16.326(2) Å, β = 99.593(16)°; V =
1388.6(4) ∆3; Dx = 1.298 g cm-3; µ = 0.090 mm-1. The structure was solved by direct methods (SHELXS-
9710) using 2586 independent reflections. Structure refinement: Full matrix least-squares methods on F2
using SHELXL-97,11 all the non-hydrogen atoms with anisotropic displacement parameters. All hydrogen
atoms were taken from a difference fourier synthesis and isotropically refined. The refinement converged
to a final wR2 = 0.1285 for 2586 unique reflections and R1 = 0.0470 for 1923 observed reflections [I0 >
2.0Φ(I0)] and 249 refined parameters.
Ethyl 1-Acetyl-1,4-dihydro-4-methylpyridine-3-carboxylate (1b)
Yellow oil (1.12 g, 81%). IR (CHCl3): 1694 (COOCH2CH3), 1672 (NCOCH3) cm-1. MS m/z: 209 (M+).
1H NMR (CDCl3): 8.14 (br s, 1 H, 2-H, B), 7.61 (br s, 1 H, 2-H, A), 7.06 (br d, 3J6,5 = 6.4 Hz, 1 H, 6-H,
3
3
A), 6.49 (d, J6,5 = 9.8 Hz, 1 H, 6-H, B), 5.14 (br m, 2 H, 5-H, A, B), 4.19 (q, J = 7.0 Hz, 4 H,
COOCH2CH3, A, B), 3.30 (dq, 3J4,5 = 3.99 Hz, 3J = 6.84 Hz, 2 H, 4-H, A, B), 2.12 (s, 6 H, NCOCH3, A,
3
3
B), 1.27 (t, J = 7.0 Hz, 6 H, COOCH2CH3, A, B), 1.13 (d, J = 6.84 Hz, 6 H, C4-CH3, A, B). For
elemental analysis of the pyridine-picrate (3b) see below.
1,3-Diacetyl-1,4-dihydro-4-phenylpyridine (1c)
Yellow powder, mp 122-126 °C from methanol (1.40 g, 88%). IR (KBr): 1704 (COCH3), 1671
(NCOCH3). MS m/z: 241 (M+). 1H NMR (CDCl3): 8.33 (br s, 1 H, 2-H, B), 7.34-7.15 (m, 12 H, aromat. H,
A, B, 2-H, 6-H, A), 6.60 (br "s", 1 H, 6-H, B), 5.32-5.26 (br m, 2 H, 5-H, A, B), 4.58 (d, 3J4,5 = 3.78 Hz, 2
H, 4-H, A, B), 2.34 (s, 6 H, COCH3, A, B), 2.27 (s, 6 H, NCOCH3, A, B). Anal. Calcd for C15H15NO2: C,
74.69; H, 6.22; N, 5.81. Found: C, 74.38, H, 6.24, N, 5.73.
1,3-Diacetyl-1,4-dihydro-4-methylpyridine (1d)
Yellow oil (1.0 g, 84%). IR (CHCl3): 1704 (COCH3), 1659 (NCOCH3) cm-1. MS m/z: 179 (M+). 1H NMR
(CDCl3): 8.12 (br s, 1 H, 2-H, B), 7.50 (br s, 1 H, 2-H, A), 7.07 (br "s", 1 H, 6-H, A), 6.49 (br "s", 1 H, 6-
H, B), 5.16 (br m, 2 H, 5-H, A, B), 3.39 (dq, 3J4,5 = 5.08 Hz, 3J = 6.84 Hz, 2 H, 4-H, A, B), 2.31 (s, 6 H,
3
COCH3, A, B). 2.27 (s, 6 H, NCOCH3, A, B), 1.07 (d, J = 6.84 Hz, 6 H, C4-CH3, A, B). For elemental
analysis of the pyridine-picrate (3d) see below.
General Procedure for the Preparation of 1-Aza-9-oxafluorenes
A mixture of 1 g (3.7 mmol) of 1a or 0.77 g (3.7 mmol) of 1b, 0.89 g (3.7 mmol) of 1c or 0.66 g (3.7
mmol) of 1d with 0.4 g (3.7 mmol) of p-benzoquinone was solved in a minimum volume of dioxa-
ne/HClO4 (5%). The mixture was stirred at rt for 24 h and then poured into ice-water. Extraction with
ether (3 x 150 mL) followed and the organic phase was dried over sodium sulfate. After filtration ether
was removed in vaccum leaving a brownish oil. Preparative TLC of the oil in chloroform / ethyl acetate /

methanol (85/15/2) led to compounds (2a-d).
Ethyl 4(SR),4a(RS),9a(RS)-1-Acetyl-6-hydroxy-4-phenyl-1,4,4a,9a-tetrahydrobenzo[4,5]furo[2,3-b]-
pyridine-3-carboxylate (2a)
Yellow oil (0.77 g, 55%). IR (CHCl3): 3374 (OH), 1691 (COOCH2CH3), 1640 (NCOCH3). MS m/z: 379
(M+). 1H NMR (CDCl3): 8.40 (br s, 1 H, 2-H), 7.35-7.19 (m, 5 H, aromat. H), 6.73 (d, 4J5,7 = 1,4 Hz, 1 H,
5-H), 6.66 (d, 3J8,7 = 8.5 Hz, 1 H, 8-H), 6.61 (dd, 3J7,8 = 8.5 Hz, 4J7,5 = 1,4 Hz, 1 H, 7-H), 6.13 (br "s", 1 H,
9a-H), 5.10 (s, 1 H, OH, exchangable), 4.32 (d, 3J4,4a = 2.5 Hz, 1 H, 4-H), 4.21 (dd, 3J4a,9a = 7.5 Hz, 3J4a,4
=
2.5 Hz, 1 H, 4a-H), 4.08 (q, 3J = 7.5 Hz, 2 H, COOCH2CH3), 2.42 (s, 3 H, NCOCH3), 1.17 (t, 3J = 7.5 Hz,
3 H, COOCH2CH3). Anal. Calcd for C22H21NO5: C, 69.65; H, 5.58; N, 3.69. Found: C, 69.66; H, 5.46; N,
3.62.
Ethyl 4(RS),4a(RS),9a(RS)-1-Acetyl-6-hydroxy-4-methyl-1,4,4a,9a-tetrahydrobenzo[4,5]furo[2,3-b]-
pyridine-3-carboxylate (2b)
Brownish powder,12 mp > 360 °C from ether (0.76 g, 65%). IR (KBr): 3375 (OH), 1709 (COOCH2CH3),
1680 (NCOCH3). MS m/z: 317 (M+). 1H NMR (CDCl3): 8.15 (br s, 1 H, 2-H), 6.61-6.57 (m, 3 H, 5-H, 8-
3
H, 7-H), 5.91 (br "s", 1 H, 9a-H), 4.19 (s, 1 H, OH, exchangable), 4.13 (q, J = 7.0 Hz, 2 H,
3
3
COOCH2CH3), 3.93 ("d", J4a,9a = 7.8 Hz, 1 H, 4a-H), 4.32 (q, J = 6.4 Hz, 1 H, 4-H), 2.43 (br s, 3 H,
3
NCOCH3), 1.23 (d, J = 6.4 Hz, 3 H, C4-CH3), 1.22 (t, 3J = 7.0 Hz, 3 H, COOCH2CH3). Anal. Calcd for
C17H19NO5: C, 64.35; H, 5.99; N, 4.42. Found: C, 64.32; H, 5.67; N, 4.43.
4(SR),4a(RS),9a(RS)-1,3-Diacetyl-6-hydroxy-4-phenyl-,4,4a,9a-tetrahydrobenzo[4,5]furo[2,3-b]pyri-
dine (2c)
Yellow crystals, mp 135-139 °C from ether (1.14 g, 88%). IR (KBr): 3247 (OH), 1710 (COCH3), 1660
(NCOCH3). MS m/z: 349 (M+). 1H NMR (DMSO-D6): 8.96 (br, s, 1 H, OH, exchangable), 7.63 (s, 1 H, 2-
H), 7.31-7.29 (m, 5 H, aromat. H), 6.66 (d, 4J5,7 = 2.57 Hz, 1 H, 5-H), 6.59 (d, 3J8,7 = 9.52 Hz, 1 H, 8-H),
6.51 (dd, 3J7,8 = 9.52 Hz, 4J7,5 = 2.57 Hz, 1 H, 7-H), 5.65 (d, 3 J9a,4a = 7.32 Hz, 1 H, 9a-H), 4.34 ("s", 1 H,
4-H), 3.88 ("d", 3J4a,9a = 7.32 Hz, 1 H, 4a-H), 2.10 (s, 3 H, COCH3), 1.98 (s, 3 H, NCOCH3). Anal. Calcd
for C21H19NO4: C, 72.21; H, 5.44; N, 4.01. Found: C, 72.52; H, 5.68; N, 4.21.
4(RS),4a(RS),9a(RS)-1,3-Diacetyl-6-hydroxy-4-methyl--1,4,4a,9a-tetrahydrobenzo[4,5]furo[2,3-b]-
pyridine (2d)
Brownish powder, mp 249-252 °C from ether (0.80 g, 75%). IR (KBr): 3257 (OH), 1680 (COCH3), 1628
1
3
(NCOCH3). MS m/z: 287 (M+). H NMR (CDCl3): 7.66 (s, 1 H, 2-H), 6.64 (d, J8,7 = 8.4 Hz, 1 H, 8-H),
4
3
4
3
6.62 (d, J5,7 = 1.56 Hz, 1 H, 5-H), 6.59 (dd, J7,8 = 8.4 Hz, J7,5 = 1.56 Hz, 1 H, 7-H), 5.74 (d, J9a,4a
=
7.23 Hz, 1 H, 9a-H), 4.22 (br s, 1 H, OH, exchangable), 3.71 ("d", 3J4a,9a = 7.23 Hz, 1 H, 4a-H), 3.43 ("q",
spl, 3J = 6.05 Hz, 3J4,4a < 1 Hz, 1 H, 4-H), 2.72 (s, 3 H, COCH3), 2.43 (br s, 3 H, NCOCH3), 1.65 (d, 3J =
6.05 Hz, 3 H, C4-CH3). Anal. Calcd for C16H17NO4: C, 66.88; H, 5.96; N, 4.88. Found: C, 66.87; H, 5.82;
N, 4.82.

General Procedure for the Oxidation to Pyridines (3a-d)
1 g (3.7 mmol) of 1a, 0.77 g (3.7 mmol) of 1b, 0.89 g (3.7 mmol) of 1c and 0.66 g (3.7 mmol) of 1d were
stirred in boiling toluene (100 mL) with a 10-fold molar excess (3.22 g, 37 mmol) of manganese(II) oxide
for 72 h. Then the oxidizing reagent was filtered off and the solvent was removed in vaccum, leaving the
pyridine derivatives as brownish oils (3a-d).
Ethyl 4-Phenylnicotinate (3a)
Yellow oil (0.67 g, 80 %). IR (CHCl3): 1724 (COOCH2CH3) cm-1. MS m/z: 227 (M+). 1H NMR (CDCl3):
8.91 (s, 1 H, 2-H), 8.77 (d, 3J6,5 = 3.9 Hz, 1 H, 6-H), 7.42-7.29 (m, 6 H, aromat. H, 5-H), 4.14 (q, 3J = 7.03
Hz, 2 H, COOCH2CH3), 1.14 (t, 3J = 7.03 Hz, 3 H, COOCH2CH3). Anal. Calcd for C20H16N4O9 (picrate,
mp 126-129 °C from ethanol): C, 52.63; H, 3.53; N, 12.28. Found: C, 52.95; H, 3.51; N, 12.14.
Ethyl 4-Methylnicotinate (3b)
Yellow oil (0.54 g, 88%). IR (CHCl3): 1723 (COOCH2CH3) cm-1. MS m/z: 165 (M+). 1H NMR (CDCl3):
3
3
9.06 (s, 1 H, 2-H), 8.54 (br "s", 1 H, 6-H), 7,17 (d, J5,6 = 4.69 Hz, 1 H, 5-H), 4.37 (q, J = 7.0 Hz, 2 H,
3
COOCH2CH3), 2.60 (s, 3 H, C4-CH3), 1.39 (t, J = 7.0 Hz, 3 H, COOCH2CH3). Anal. Calcd for
C15H14N4O9 x 0.5 H2O (picrate, mp 128-134 °C from ethanol/water): C, 44.67; H, 3.75; N, 13.89. Found:
C, 44.88; H, 3.82; N, 13.51.
3-Acetyl-4-phenylpyridine (3c)
Yellow oil (0.61 g, 83 %). IR (CHCl3): 1692 (COCH3) cm-1. MS m/z: 197 (M+). 1H NMR (CDCl3): 8.80
(br "s", 2 H, 2-H, 6-H), 7.49-7.33 (m, 6 H, aromat. H, 5-H), 2.06 (s, 3 H, COCH3). Anal. Calcd for
C19H14N4O8 (picrate, mp 145-148 °C from ethanol): C, 53.52; H, 3.29; N, 13.15. Found: C, 53.38; H,
3.46; N, 12.81.
3-Acetyl-4-methylpyridine (3d)
Yellow oil (0.58 g, 79 %). IR (CHCl3): 1692 (COCH3) cm-1. MS m/z: 135 (M+). 1H NMR (CDCl3): 8.91
3
3
(s, 1 H, 2-H), 8.77 (d, J6,5 = 7.81, 1 H, 6-H), 7.48 (d, J5,6 = 7.81 Hz, 1 H, 5-H), 2.64 (s, 3 H, C4-CH3),
2.56 (s, 3 H, COCH3). Anal. Calcd for C14H12N4O8 (picrate, mp 137-140 °C from ethanol): C, 46.16; H,
3.32; N, 15.39. Found: C, 45.76; H, 3.32; N, 14.98.
ACKNOWLEDGEMENT
The authors gratefully acknowledge Prof. Dr. Merzweiler, Institute of Inorganic Chemistry of the Martin-
Luther-University, Halle Wittenberg, for the possibility of using the IPDS Diffractometer.
REFERENCES
1. A. Hilgeroth, K. Kuna, and U. Kuckländer, Heterocycles, 1998, 48, 1649.
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11. G. M. Sheldrick, SHELXL-97, Program for the Refinement of Crystal Structures, Univ. Göttingen,
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12. The brownish or yellow colors of compounds (2b-c) may be explained by the formation of
intermolecular charge-transfer complexes between the hydroquinone partial structures on one hand
and the nitrogen atoms of the enaminone partial structure that adopt positive charges in the system of
conjugated double bonds on the other hand.