Synthesis of 2,3-disubstituted 4-pyridone from a β-aminocarboxylate derivative and acetoacetate

Article abstract of DOI:10.1080/00397910500278545

The reaction of diethyl aminomethylenemalonate with ethyl acetoacetate proceeded, when catalyzed by anhydrous hydrogen chloride, toward a respectively substituted α- instead of γ-pyridone derivative formation, contrary to the literature report. Additionally, it was found that the amine used as a starting component in this reaction showed a great tendency to autocondensation under the influence of anhydrous hydrogen chloride to yield 5-ethoxycarbonyl-2- pyridone. The most convenient method to prepare 4-pyridone 2,3-disubstituted derivative appeared to be a three-step synthesis, starting from a chain enamine formation, which was subjected to cyclization, followed by oxidation of the last intermediate. The usefulness of the stepwise synthesis was demonstrated on the 3-ethoxycarbonyl-2-methyl-4-pyridone preparation as an example. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1080/00397910500278545

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Synthesis of 2,3‐Disubstituted
4‐Pyridone From a
β‐Aminocarboxylate Derivative
and Acetoacetate
Adam Sobczak a b & Wiesław Z. Antkowiak a
a Faculty of Chemistry, Adam Mickiewicz University,
Poznań, Poland
b Department of Chemistry, August Cieszkowski
Agricultural University, ul. Wojska Polskiego 75,
Poznan, 60-625, Poland
Published online: 21 Aug 2006.
To cite this article: Adam Sobczak & Wiesław Z. Antkowiak (2005): Synthesis
of 2,3‐Disubstituted 4‐Pyridone From a β‐Aminocarboxylate Derivative and
Acetoacetate, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:23, 2993-3001
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Synthetic Communicationsw, 35: 2993–3001, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500278545
Synthesis of 2,3-Disubstituted 4-Pyridone
From a b-Aminocarboxylate Derivative and
Acetoacetate
Adam Sobczak‡ and Wiesław Z. Antkowiak
´
Faculty of Chemistry, Adam Mickiewicz University, Poznan, Poland
Abstract: The reaction of diethyl aminomethylenemalonate with ethyl acetoacetate
proceeded, when catalyzed by anhydrous hydrogen chloride, toward a respectively sub-
stituted a- instead of g-pyridone derivative formation, contrary to the literature report.
Additionally, it was found that the amine used as a starting component in this reaction
showed a great tendency to autocondensation under the influence of anhydrous
hydrogen chloride to yield 5-ethoxycarbonyl-2-pyridone. The most convenient
method to prepare 4-pyridone 2,3-disubstituted derivative appeared to be a three-
step synthesis, starting from a chain enamine formation, which was subjected to cycli-
zation, followed by oxidation of the last intermediate. The usefulness of the stepwise
synthesis was demonstrated on the 3-ethoxycarbonyl-2-methyl-4-pyridone preparation
as an example.
Keywords: Aminomethylenemalonate, autocondensation, g-pyridone, a-pyridone
Syntheses of specifically substituted pyridine derivatives, based on a
condensation of simple aliphatic amine and a carbonyl compound, have
attracted considerable attention, mainly because of the constant demand for
new methods applicable to total syntheses of many naturally occurring or bio-
logically active heterocycles. Our interest in such synthetic problems results
from the continuing studies carried out by us on a bipyridine mushroom
Received in Poland May 24, 2005.
‡Present affiliation: Department of Chemistry, August Cieszkowski Agricultural
University, ul. Wojska Polskiego 75, 60-625 Poznan, Poland.
Address correspondence to Wiesław Z. Antkowiak, Faculty of Chemistry, Adam
´
Mickiewicz University, ul. Grunwaldzka 6, 60-780, Poznan, Poland. Tel.: þ 48 (61)
8291-318; Fax: þ48 (61) 8658-008; E-mail: wzantk@amu.edu.pl
2993

2994
A. Sobczak and W. Z. Antkowiak
alkaloid, orellanine,[1a–d] the molecule of which is composed of 3,4-difunctio-
nalized 2-pyridyl N-oxide moieties.
According to the literature report,[2a,b] such a synthesis of the pyridine
derivative can be achieved by a condensation of diethyl aminomethylene-
malonate (1) with ethyl acetoacetate (2). When sodium metal is used as an
initiating agent, 3,5-diethoxycarbonyl-4-methyl-2-pyridone was obtained,
but the reaction catalyzed by anhydrous hydrogen chloride yielded a
derivative of an isomeric pyridone, 3-ethoxycarbonyl-2-methyl-4-pyridone
(3).[2a] The structure of the last product would correspond to the one
expected on the basis of the starting component structures and of their
generally known chemical properties.
Our attempts to accomplish a condensation of 1, or, in a separate exper-
iment, ethyl aminomethyleneacetoacetate (4), with 2 dissolved in a small
amount of ether in the presence of anhydrous hydrogen chloride actually
yielded pyridone derivatives that turned out to be identical in both cases.
However, the detailed analysis of the product’s spectral properties and their
comparison with the corresponding literature data[3a,b] showed the product
structure to be 3-ethoxycarbonyl-2-methyl-6-pyridone (5), an a- instead of
the expected g-pyridone derivative. Such a conclusion was additionally
proved by comparison of the product with an authentic sample, which had
been obtained by an intramolecular cyclization of diethyl a-acetylglutarate
in the presence of ammonium acetate, followed by an aromatization of the
annulated intermediate, 3-ethoxycarbonyl-2-methyl-4,5-dihydro-6-pyridone
(6).[4] When lead tetraacetate was used as an oxidizing agent, the final
product 5 was additionally accompanied by two minor derivatives, one of
the product and one of its dihydro ancestor, both acetoxylated at the a
methyl group (Scheme 1).
In experiments in which reagents other than 2 were used (e.g., diethyl
malonate, diethyl ketipinate, 2,4,5,7-octanetetraone), no condensation,
Scheme 1.

2,3-Disubstituted 4-Pyridone
2995
Scheme 2.
initiated by hydrogen chloride, with 1 was observed. Instead, when the
reaction mixture was kept at room temperature for a few days, 5-ethoxy-
carbonyl-2-pyridone (ethyl 6-hydroxynicotinate, 7) was obtained as a result
of the condensation of two molecules of 1. The tendency of 1 to undergo an
autocondensation when treated with anhydrous HCl was confirmed in a
separate experiment (Scheme 2).
To achieve the desired 4-pyridone derivative preparation, we chosen a
stepwise mode of synthesis with the formation, at the first step, of a linear
enamine intermediate 10, in the molecule of which the bridging nitrogen is
separated from an alkoxycarbonyl group by two carbon atoms. The use in
such a synthesis of a readily available 1 as a component in the reaction with
2 does not fulfil our requirements. This is because, as has already been
shown by Agui et al.,[2b] this set of reagents caused 3,5-diethoxycarbonyl-2-
methyl-4-pyridone (8) formation, a product bearing an additional substituent
at C-5, originating from the substituted malonate component. Because of
the difficulty in the b-aminoacrylic acid ester preparation, the synthesis was
started by a condensation of ethyl 3-aminopropionate (9) with 2. The
resulting enamine 10 was then subjected to cyclization (both processes
were carried out in basic conditions opposite those used in the case
already reported), yielding 3-ethoxycarbonyl-2-methyl-5,6-dihydro-4-pyridone
(11),[5a,b] which, when oxidized by lead tetraacetate, was transformed into 3
with a satisfactory yield. It follows from an X-ray study[6] and the spectral
data analysis that the final product 3 has mainly a keto tautomer’s structure
instead of a hydroxypyridine’s. With the aim of attaining a stabilized enol
structure in the form of its methyl ether by forcing a change of the keto–
enol equilibrium, 3 was treated with dimethyl sulfate in the presence of
potassium carbonate. However, this procedure led to N instead of O methyl-
ation, yielding 3-ethoxycarbonyl-1,2-dimethyl-4-pyridone (12) exclusively
(Scheme 3).
In conclusion, it has to be stated that the verification of the literature
report concerning the a- instead of g-pyridone structure of the product of 1
with 2 condensation carried out in the presence of hydrogen chloride
indicates that the direction of such a synthesis does not depend on the
acidic or basic reaction conditions, but on the sequence of the intermediate
steps. It appeared that, besides a singular case dealing with a synthesis

2996
A. Sobczak and W. Z. Antkowiak
Scheme 3.
carried out on a borane complex,[7a,b] the 4-pyridone derivative can only be
synthesized in a stepwise manner, which is initiated by the preparation of a
nitrogen-linked chain condensation product, composed of the starting amine
and carbonyl derivative. The nitrogen-bridged intermediate is then subjected
to cyclization. The use of 1 in this way leads to 3,5-disubstituted 4-pyridone
derivative 8 formation, whereas the synthesis of the monosubstituted system,
3-ethoxycarbonyl-2-methyl-4-pyridone (3), requires a condensation of
b-aminopropionate 9 with 2 followed by cyclization and, additionally,
oxidation of the cyclic intermediate 11 to the final 4-pyridone derivative 3.
EXPERIMENTAL
Combustion analyses were performed by using Elementar Vario EL III
apparatus (samples were predried under diminished pressure of 1 mmHg
within 30 min). Melting points were determined by a hot-plate method (only
occasionally a Bu¨chi 535 capillary apparatus was used) and are uncorrected.
NMR spectra were recorded on a Varian Gemini 300 and a Bruker DRX-
1
600 spectrometer using TMS (for H and 13C NMR) or nitromethane (for
15N NMR) as standards. Proton and carbon assignments were based on
HETCOR experiments, though occasionally double resonance, NOE and
HMBC were used. UV spectra were recorded on a Jasco V-550 spectrometer,
using 1-mm cell. IR spectra were measured on a FT-IR Bruker IFS 113v
instrument for KBr discs. MS spectral data were obtained on an AMD 402
mass spectrometer.
TLC analyses were carried out using Merck DC–Alufolien, Kieselgel 60
WF254s and AcOEt–MeOH (7:3 or 9:1, A or B, respectively) as a developing

2,3-Disubstituted 4-Pyridone
2997
system. Column chromatography was carried out using Merck Kieselgel 60,
(230–400 mesh) as the stationary phase, and hexane, benzene, AcOEt,
CH2Cl2, CHCl3, and 5% MeOH in CHCl3 were the eluting solvents.
3-Ethoxycarbonyl-2-methyl-4,5-dihydro-6-pyridone (6)[5]
Mp 161–1628C (AcOEt) [lit.[8] 1568C]; 1H NMR (CDCl3) d: 8.59 (b, NH, 1H),
4.20 (q, J 7.1, CH2CH3, 2H), 2.66 (m, H-4, 2H), 2.48 (m, H-5, 2H), 2.31 (t, J 1.6,
CH3, 3H), 1.30 (t, J 7.1, CH2CH3, 3H); 13C NMR (CDCl3) d: 172.43 (COOEt or
C-6), 167.02 (COOEt or C-6), 145.42 (C-2), 104.18 (C-3), 60.08 (CH2CH3),
30.20 (C-5), 21.43 (C-4), 18.70 (CH3), 14.41 (CH2CH3); Other spectroscopic
data were consistent with those already reported.[4,8,9]
3-Ethoxycarbonyl-2-methyl-6-pyridone (5)
The product was obtained according to the procedure for 4-pyridone deriva-
tive 3 preparation published by Ochiai and Ito.[2a] Mp 216–2188C [lit.[3b]
2228C]; 13C NMR (CDCl3) d: 165.40 (C-6), 164.71 (COOEt), 152.87 (C-2),
142.77 (C-4), 116.02 (C-5), 109.01 (C-3), 60.79 (CH2CH3), 19.76 (CH3),
14.41 (CH2CH3); 15N NMR (CDCl3) d: 2200.4; MS: 181 (84%, Mþ), 166
(5%), 153 (25%), 136 (100%), 125 (12%), 108 (15%), 107 (14%), 95 (8%),
80 (20%), 53 (20%), 42 (19%).
5-Ethoxycarbonyl-2-pyridone (7)
A solution of 1 (748 mg, 4 mmol) in Et2O (4 ml), after being saturated with
anhydrous HCl, was stirred at room temperature for 3 days. Next, the
volatile components were removed under diminished pressure and the oily
residue, when chromatographed on silica gel (AcOEt-PhH) and recrystallized
from CHCl3, gave pure 7 melting at 155–1568C [lit.[3b] 1508C]; IR (KBr,
cm21): 2991, 2873 (b), 2805, 2700, 1727, 1709, 1682, 1597, 1479, 1435,
1427, 1364, 1301, 1268, 1228, 1118, 1020, 846, 776, 660; 13C NMR
(CDCl3) d: 165.51 (C-6 or COOEt), 164.07 (C-6 or COOEt), 141.05 (C-4),
139.68 (C-2), 119.52 (C-5), 111.36 (C-3), 61.08 (CH2CH3), 14.22
(CH2CH3); MS: 167 (41%, Mþ), 139 (48%), 123 (13%), 122 (100%), 111
(9%), 99 (9%), 94 (26%), 82 (5%), 67 (9%), 66 (12%).
Ethyl 3-(2-Ethoxycarbonylethylamino)-2-butenoate (10)
A mixture of b-alanine ethyl ester hydrochloride (9, 462 mg, 3 mmol), ethyl
acetoacetate (2, 0.38 ml, 388 mg, 3 mmol) and anhydrous potassium

2998
A. Sobczak and W. Z. Antkowiak
carbonate (1 g) in 10 ml of benzene was refluxed under the Dean–Stark trap
for 3 h. The reaction mixture, when cooled and diluted with AcOEt and
CH2Cl2, was filtered, and the obtained solution was concentrated under dimin-
ished pressure, yielding pure enamine 10 (652 mg, 95%). Yellow oil. Rf 0.8
(B). HRMS for C11H19NO4 [M]þ: calcd. 229.13141, found 229.13061. IR
(KBr film, cm21): 3287, 2981, 2935, 2905, 1733, 1652, 1608, 1503, 1444,
1
1376, 1342, 1295, 1251, 1174, 1114, 1052, 1029, 785; H NMR (CDCl3) d:
8.66 (broad, NH, 1H), 4.47 (s, 55CH, 1H), 4.18 (q, J 7.1, CH2CH3, 2H),
4.09 (q, J 7.1, CH2CH3, 2H), 3.52 (q, J 6.6, NHCH2CH2CO, 2H), 2.56
(t, J 6.6, NHCH2CH2CO, 2H), 1.95 (s, CH3, 3H), 1.27 (t, J 7.1, CH2CH3,
3H), 1.24 (t, J 7.1, CH2CH3, 3H); 13C NMR (CDCl3) d: 171.29 (COOEt),
170.46 (COOEt), 161.20 (C-3), 83.02 (C-2), 60.81 (CH2CH3), 58.31
(CH2CH3) 38.55 (NHCH2CH2CO), 35.45 (NHCH2CH2CO), 19.23 (CH3),
14.56 (CH2CH3), 14.09 (CH2CH3); MS: 229 (43%, Mþ), 200 (2%), 184
(60%), 157 (44%), 156 (50%), 154 (12%), 142 (39%), 138 (21%), 136
(7%), 128 (7%), 110 (99%), 101 (30%), 96 (100%), 84 (60%), 82 (29%),
73 (28%), 70 (20%), 68 (38%), 55 (35%).
2-(2-Ethoxycarbonylethylamino)-2-penten-4-one (14)
The compound 14 was prepared from b-alanine ethyl ester hydrochloride (9,
4.62 g, 30 mmol) and acetylacetone (13, 3.0 g, 30 mmol) in the presence of
K2CO3 by using a procedure similar to that described in the preparation of
the enamine butenoate derivative 10. The crude product (3.86 g, 65%) was
subjected to a short-path distillation (80–1608C, 1 mm Hg), yielding 1.59 g
(27%) of a yellow liquid. Rf 0.6 (B, a bright yellow spot at l 366 nm).
1H NMR (CDCl3) d: 10.85 (b, NH, 1H), 4.98 (s, 55CH, 1H), 4.17
(q, J 7.1, CH2CH3, 2H), 3.55 (q, J 6.6, NHCH2CH2CO, 2H), 2.59 (t, J 6.6,
NHCH2CH2CO, 2H), 2.00 (s, CH3, 3H), 1.96 (s, CH3, 3H), 1.27 (t, J 7.1,
CH2CH3, 3H); MS: 199 (100%, Mþ), 184 (83%), 182 (31%), 170
(2%), 156 (19%), 154 (14%), 142 (6%), 138 (29%), 126 (51%), 112 (85%),
110 (32%), 108 (24%), 101 (24%), 97 (30%), 96 (51%), 94 (9%), 84 (30%),
82 (12%), 73 (12%), 70 (9%), 68 (13%), 55 (22%), 43 (57%), 42 (43%).
3-Ethoxycarbonyl-2-methyl-5,6-dihydro-4-pyridone (11)
A solution of ethyl 3-(2-ethoxycarbonylethylamino)-2-butenoate (10, 13.74 g,
60 mmol) in 350 ml of benzene was supplied with sodium hydride (4 g of a
50% dispersion in oil, 83 mmol; before use, the reagent was washed with
benzene) and the resulting yellow suspension, when stirred, was kept at
reflux for 3 h. Next, after the mixture had been cooled to room temperature,
the reaction was quenched with water (160 ml) and the organic solvent was
removed in vacuum. The obtained alkaline, aqueous solution was treated

2,3-Disubstituted 4-Pyridone
2999
with 15% hydrochloric acid (25 ml), then washed with Et2O (3 ꢀ 100 ml),
followed with making it alkaline again by means of NaHCO3 and taking up
the product into methylene chloride (3 ꢀ 100 ml). After being dried over
Na2SO4, the CH2Cl2 solution was concentrated to a pale yellow solid
residue (3.97 g, 36%, melting at 115–1218C), which was recrystallized
from AcOEt/hexane, yielding almost colorless crystals of mp 126–1278C.
Rf 0.15 (B), 0.5 (A). Anal. calcd. for C9H13NO3: C, 59.00; H, 7.15; N,
7.65; found: C, 58.96; H, 7.20; N, 7.59. HRMS: for [M]þ, C9H13NO3,
calcd. 183.08954, found 183.09004; for [M-C2H5O]þ, C7H8NO2, calcd.
138.05550, found 138.05568; IR (KBr, cm21): 3248, 3092, 2977, 2902,
1705, 1671, 1618, 1607, 1570, 1527, 1445, 1418, 1384, 1337, 1314, 1291,
1230, 1214, 1169, 1111, 1085, 1054, 1027, 958, 886, 740, 537; UV
1
(MeOH): 244 nm (1 8000), 301 nm (1 12600); H NMR (CDCl3) d: 7.27 (b,
NH, 1H), 4.22 (q, J 7.1, CH2CH3, 2H), 3.58 (td, J 7.7, 3.0, H-6, 2H), 2.47
(t, J 7.7, H-5, 2H), 2.32 (s, CH3, 3H), 1.31 (t, J 7.1, CH2CH3, 3H);
1H NMR (DMSO) d: 8.48 (b, NH, 1H), 4.03 (q, J 7.1, CH2CH3, 2H), 3.40
(td, J 7.7, 2.7, H-6, 2H), 2.22 (t, J 7.7, H-5, 2H), 2.12 (s, CH3, 3H), 1.17
(t, J 7.1, CH2CH3, 3H); 13C NMR (CDCl3) d: 188.66 (C-4), 167.27 (C-2),
166.78 (COOEt), 103.03 (C-3), 59.79 (CH2CH3), 40.44 (C-6), 35.51 (C-5),
21.68 (CH3), 14.33 (CH2CH3); 15N NMR (CDCl3) d: 2269.2; MS: 183
(31%, Mþ), 154 (1%), 138 (100%), 126 (2%), 111 (62%), 96 (4%), 94
(3%), 86 (13%), 84 (37%), 82 (20%), 80 (10%), 67 (42%), 55 (33%).
3-Ethoxycarbonyl-2-methyl-4-pyridone (3)
A mixture of 3-ethoxycarbonyl-2-methyl-5,6-dihydro-4-pyridone (11, 183 mg,
1 mmol) and lead tetraacetate (1.33 g, 3 mmol) in 2 ml of acetic acid was
stirred under reflux for 4 h. Next, the solvent was removed under diminished
pressure and the dark yellow, oily residue was digested with a 10% solution of
EtOH in CH2Cl2 (50 ml). The resulting suspension was filtered through a layer
of silica gel (2 g), and the filtrate was concentrated, yielding a colorless solid.
The crude product was chromatographied on a silica gel (1 g) column and the
solid (84 mg, 46%) eluted by a 10% solution of MeOH in CH2Cl2, when
recrystallized from AcOEt, gave needles of mp 148–1498C. Rf 0.1 (B),
0.35 (A). HRMS for [M]þ, C9H11NO3, calcd. 181.07390, found 181.07480;
IR (KBr, cm21): 3253, 3052, 2983, 2941, 2754 (b), 1722, 1633, 1617,
1535, 1512, 1397, 1299, 1220, 1106, 1096, 1041, 852, 604, 537; UV
1
(MeOH): 256 nm (1 12300); H NMR (DMSO) d: 11.56 (b, NH, 1H), 7.59
(d, J 7.1, H-6, 1H), 6.07 (d, J 7.1, H-5, 1H), 4.19 (q, J 7.1, CH2CH3, 2H),
1
2.18 (s, CH3, 3H), 1.24 (t, J 7.1, CH2CH3, 3H); H NMR (CDCl3, 258C) d:
12.91 (b, NH, 1H), 7.64 (b, H-6, 1H), 6.40 (d, J 6.6, H-5, 1H), 4.30 (q, J
7.1, CH2CH3, 2H), 2.46 (s, CH3, 3H), 1.33 (t, J 7.1, CH2CH3, 3H);
1H NMR (CDCl3, 2508C) d: 13.60 (b, NH, 1H), 7.67 (t, J 6.3, H-6, 1H),
6.43 (d, J 6.9, H-5, 1H), 4.30 (q, J 7.1, CH2CH3, 2H), 2.45 (s, CH3, 3H),

3000
A. Sobczak and W. Z. Antkowiak
1.35 (t, J 7.1, CH2CH3, 3H); 13C NMR (CDCl3, 2508C) d: 176.43(C-4), 166.67
(COOEt), 148.79 (C-2), 138.18 (C-6), 121.83 (C-3), 116.43 (C-5), 61.47
1
(CH2CH3), 17.94 (CH3), 13.97 (CH2CH3); H NMR (CDCl3 þ AcOH) d:
11.94 (b, NH, 1H), 7.67 (d, J 7.1, H-6, 1H), 6.46 (d, J 7.1, H-5, 1H), 4.29
(q, J 7.1, CH2CH3, 2H), 2.47 (s, CH3, 3H), 1.33 (t, J 7.1, CH2CH3, 3H);
1H NMR (CD3CN) d: 10.64 (b, NH, 1H), 7.51 (d, J 7.1, H-6, 1H), 6.23 (d, J
7.1, H-5, 1H), 4.25 (q, J 7.1, CH2CH3, 2H), 2.28 (s, CH3, 3H), 1.28 (t, J 7.1,
CH2CH3, 3H); 1H NMR (TFA) d: 8.37 (d, J 6.9, H-6, 1H), 7.38 (d, J
7.1, H-5, 1H), 4.72 (q, J 7.1, CH2CH3, 2H), 3.10 (s, CH3, 3H), 1.58 (t, J 7.1,
CH2CH3, 3H); MS: 181 (50%, Mþ), 166 (1%), 153 (1%), 135 (100%), 107
(47%), 94 (3%), 79 (17%), 67 (9%), 53 (23%), 42 (9%).
3-Ethoxycarbonyl-1,2-dimethyl-4-pyridone (12)
A stirred suspension of 3-ethoxycarbonyl-2-methyl-4-pyridone (3, 181 mg,
1 mmol) and anhydrous potassium carbonate (265 mg, 1.9 mmol) in 3 ml of
acetone was treated dropwise with dimethyl sulfate (0.25 g, 0.19 ml,
2 mmol) and the stirring at room temperature was continued overnight. To
complete the reaction (according to TLC), the mixture was then kept at
608C for a further 1.5 h. Next, the solvent was removed under diminished
pressure, and the crude product was isolated by extraction with CH2Cl2 of
the residue dissolved in water. Purification on a silica gel (4 g) column
gave, from an AcOEt fraction, a colorless solid (160 mg, 82%), which,
when recrystallized from PhH/CH2Cl2 (2:1) mixture, melted at 161.5–
1628C. Rf 0.3 (A). HRMS for [M]þ, C10H13NO3, calcd. 195.08954, found
195.08809; IR (KBr, cm21): 2990, 2964, 2927, 1719, 1644, 1576, 1534,
1492, 1311, 1280, 1227, 1193, 1150, 1081, 1059, 1021, 842, 787, 563, 471;
1H NMR (CDCl3) d: 7.25 (d, J 7.5, H-6, 1H), 6.32 (d, J 7.5, H-5, 1H), 4.38
(q, J 7.1, CH2CH3, 2H), 3.58 (s, NCH3, 3H), 2.30 (s, CH3, 3H), 1.36 (t, J
7.1, OCH2CH3, 3H); 13C NMR (CDCl3) d: 175.25 (C-4), 167.14 (COOEt),
146.32 (C-2), 141.62 (C-6), 125.46 (C-3), 118.18 (C-5), 61.49 (CH2CH3),
41.24 (NCH3), 17.31 (CH3), 14.16 (OCH2CH3); MS: 195 (Mþ, 8%), 151
(15%), 150 (37%), 138 (7%), 124 (8%), 123 (100%), 122 (18%), 95 (5%),
94 (11%), 84 (3%), 82 (6%), 67 (19%).
REFERENCES
1. (a) Antkowiak, W. Z.; Gessner, W. P. The structures of orellanine and orelline.
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decomposition of orellanine and orellinine, the fungal toxins of Cortinarius
orellanus Fries and Cortinarius speciossimus. Experientia 1985, 41, 769–771;
(c) Kubicki, M.; Borowiak, T.; Antkowiak, W. Z. Crystal structure of orellanine
hydrate. J. Cryst. Spectr. Res. 1991, 21, 401–405; (d) A biosynthesis of this

2,3-Disubstituted 4-Pyridone
3001
fungal toxin was recently reported by Steglich’s team after very interesting and
exceptional experiments were carried out on wild growing fruit bodies:
Spiteller, P.; Spiteller, M.; Steglich, W. Occurrence of the fungal toxin orellanine
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