Successful thermal rearrangements of acrylenamides to give tetrahydro-2-pyridones under FVT conditions

Article abstract of DOI:10.1081/SCC-120002697

Enamides of α,β-unsaturated acids are theoretically capable of electrocyclisation to give tetrahydro-2-pyridones. The only successful method reported for this conversion involved photochemical activation. We would like to present new and effective method

Full text of DOI:10.1081/SCC-120002697

This article was downloaded by: [The University of British Columbia]
On: 06 June 2013, At: 12:13
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
SUCCESSFUL THERMAL REARRANGEMENTS OF
ACRYLENAMIDES TO GIVE TETRAHYDRO-2-PYRIDONES
UNDER FVT CONDITIONS
Stanislaw Lesniak a & Beata Pasternak a
a Department of Organic and Applied Chemistry, University of Lodz, ul. Narutowicza 68, 90
136, Lodz, Poland
Published online: 16 Aug 2006.
To cite this article: Stanislaw Lesniak & Beata Pasternak (2002): SUCCESSFUL THERMAL REARRANGEMENTS OF ACRYLENAMIDES
TO GIVE TETRAHYDRO-2-PYRIDONES UNDER FVT CONDITIONS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:6, 875-880
To link to this article: http://dx.doi.org/10.1081/SCC-120002697
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,
proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONS, 32(6), 875–880 (2002)
SUCCESSFUL THERMAL
REARRANGEMENTS OF
ACRYLENAMIDES TO GIVE
TETRAHYDRO-2-PYRIDONES
UNDER FVT CONDITIONS
*
Stanislaw Lesniak and Beata Pasternak
Department of Organic and Applied Chemistry,
University of Lodz, ul. Narutowicza
68, 90 136 Lodz, Poland
ABSTRACT
Enamides of a,b-unsaturated acids are theoretically capable
of electrocyclisation to give tetrahydro-2-pyridones. The only
successful method reported for this conversion involved
photochemical activation. We would like to present new and
effective method for this transformation using flash vacuum
thermolysis.
Nitrogen-containing six-membered ring systems, such as the piperi-
dines and decahydroquinolines have been popular synthetic targets due
to the array of potent biological activities of these compounds. From a
number of methods of synthesis our attention has been attracted to the
reaction of imines with activated acrylate derivatives. It was found
*Corresponding author. E-mail: slesniak@chemul.uni.lodz.pl
875
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

876
LESNIAK AND PASTERNAK
by Stille1a and earlier by Hicmott1b that 1,2,3,4-tetrahydro-2-pyridones
or 3,4,5,6,7,8-hexahydro-2(1H )-quinolinones can be prepared by the aza-
annulation of imines with acrylate derivatives. Generally, the reaction
of acryloyl chloride with imines in the presence of the base (Et3N) resulted
in the formation of acrylenamides, whereas in the absence of triethylamine
d-lactams were formed. However, the chemical cyclisation failed when it was
applied to synthesis of natural products.2 Although the transformation of
acrylenamides to tetrahydro-2-pyridones or hexahydro-2(1H )-quinolinones
has been attempted using a number of thermal, protic and Lewis acidic
conditions, the only successful method involved photolysis.3
In our work we wish to present a simple and efficient method for this
conversion, which seems to be general and revises existing opinion regarding
the exceptional thermal stability of acrylenamides. In our laboratory we
have investigated the behaviour of enamides of a,b-unsaturated acids
under FVT conditions, particularly their possibility to undergo, electro-
cyclisation.
The required compounds were prepared by N-acylation of imines. The
reaction of imines 1a–d with a,b-unsaturated acid chlorides in the presence
of triethylamine under standard conditions1a afforded corresponding enam-
ides 2a–g (Scheme 1).
Scheme 1.
All prepared compounds represents the wide range of starting
materials which could define the scope and limitations of the method, par-
ticularly the influence of substituents in acryloyl and vinyl moiety. The
enamides 2a–g were thermolysed in FVT conditions at 800ꢀC under pressure
1.5 ꢁ 10ꢂ3 Torr. The temperature 800ꢀC was chosen as the lowest possible at
which the starting material was not present in the reaction mixture after
thermolysis. We found that thermolyses of 2a–g resulted in the formation of
1,2,3,4-tetrahydro-2-pyridones 3a–c or 3,4,5,6,7,8-hexahydro-2(1H )-quino-
linones 3d–g, respectively, as the exclusive products of the reaction in high
yield (Scheme 2).

THERMAL REARRANGEMENTS OF ACRYLENAMIDES
877
Scheme 2.
None of products 3 contain two asymmetric carbon atoms, therefore
the formation of diastereoisomers is not possible.
The formation of 3 can be rationalised in terms of an initial formation
of 1,4-dipole 30 by electrocyclic rearrangement of 2. The resulting betaines
undergo a subsequent proton shift (probably as [1,5] shift4a) to generate 3.
The last reaction is well known4a,4b,3 for a variety cyclic betaines.
Compounds 3a–g were purified by flash chromatography on neutral
Al2O3 and identified by spectral methods. The yields of crude products
were excellent, but purification on Al2O3 caused their decomposition
and final yields were around 50% (use of silica gel resulted in a much
higher loss of the products). The rearrangement occurred easily and the
substituents in acryloyl and vinyl moiety were of insignificant consequence.
This makes our method more general in comparison with aza-annulation,
which is considerably affected by the substituents. Although, our results can
be rationalized by an electrocyclisation or the formation of the diradical, the
last is unlikely considering of the selectivity of the reaction and literature
data which showed that the photolytic reaction of N-(a,b-unsaturated
carbonyl)thioamides proceeded as a diradical process and led to different
products.5
In conclusion, we have found that enamides of a,b-unsaturated acids
can undergo electrocyclic cyclisations under FVT conditions at 800ꢀC. In
contrast to the aza-annulation pathway no effects of the substituents in the
starting enamides were observed.

878
LESNIAK AND PASTERNAK
EXPERIMENTAL
General
Infrared (IR) absorption spectra were performed on a Specord-75
1
spectrophotometer. The band frequencies are reported in cmꢂ1. H NMR
and 13C NMR spectra (CDCl3) were recorded on a Tesla 487 (80 MHz) or a
Varian Gemini 200 (200, 50.4 MHz for 13C) apparatus using TMS as an
internal standard.
Starting Materials
All starting materials were prepared according to described
procedures: butylidene-isopropylamine (1a),1a methyl-(1-phenyl-ethyli-
dene)-amine (1b),6a cyclohexylidene-methyl-amine (1c),6b N-cyclohexyli-
dene-aniline (1d)6c and N-isopropyl-N-vinyl-acrylamide (2a).1a
General Procedure for the Preparation of Enamides 2b–g1a
To 40 ml of dry THF were added the imine (8 mmol) and Et3N (1.21 g,
12.0 mmol) at 0ꢀC. The appropriate a,b-unsaturated acid chloride
(9.0 mmol) was added slowly to this solution at 0ꢀC. After the addition
was complete, the resulting mixture was stirred at rt. for 4 h. Solids were
removed from the mixture by filtration and were then washed thoroughly
with Et2O. The combined filtrate was concentrated, and the corresponding
enamide was isolated by column chromatography on neutral Al2O3
(hexane/AcOEt 9 : 1). Reported yields refer to isolated products.
1
2b: (90%) IR (film): 1665, 1605. H NMR: 3.08 (s, 3H), 5.16(bs, 1H),
5.40–5.65 (m, 1H), 5.67 (bs, 1H), 6.35–6.57 (m, 2H), 7.37 (bs, 5H).
1
2c: (87%) IR (film): 1670, 1610. H NMR: 1.73–1.83 (m, 3H), 3.12
(s, 3H), 4.95–5.05 (m, 1H), 5.08 (bs, 1H), 5.18–5.30 (m, 1H), 5.45 (bs,
1H), 7.30–7.50 (m, 5H).
2d: (93%) IR (film): 1665, 1605. 1H NMR: 1.45–1.76(m, 4H),
1.76–2.33 (m, 4H), 3.02 (s, 3H), 5.43–5.73 (m, 2H), 6.33–6.50 (m, 2H).
2e: (95%) IR (film): 1640, 1620. 1H NMR: 1.58–1.83 (m, 4H),
1.90–2.33 (m, 4H), 5.47–5.83 (m, 2H), 6.29–6.50 (m, 2H), 7.18–7.29 (m, 5H).
2f: (52%) IR (film): 1650, 1620. 1H NMR: 1.50–1.93 (m, 4H), 1.82 (dd,
J ¼ 1.5 and 7 Hz, 3H), 1.94–2.45 (m, 4H), 3.02 (s, 3H), 5.54–5.71 (m, 1H),
6.14 (dq, J ¼ 1.5 and 15 Hz, 1H), 6.98 (dq, J ¼ 7 and 15 Hz, 1H).

THERMAL REARRANGEMENTS OF ACRYLENAMIDES
879
2g: (91%) IR (film): 1670, 1625. 1H NMR: 1.50–1.83 (m, 4H),
2.00–2.27 (m, 4H), 3.07 (s, 3H), 5.58–5.75 (m, 1H), 6.76 (d, J ¼ 16Hz,
1H), 7.17–7.52 (m, 5H), 7.66 (d, J ¼ 16Hz, 1H).
General Procedure for Flash Vacuum Thermolysis
The Flash vacuum thermolyses were carried out in a 30 ꢁ 2 cm
horizontal quartz tube packed with quartz rings, electrically heated to
800ꢀC at 1.5 ꢁ 10ꢂ3 Torr. Compounds 2a–g were slowly distilled from a
flask held at 60ꢀC into the thermolysis tube. The products were collected
in a CO2/acetone trap. After thermolysis, the system was brought to atmos-
pheric pressure, allowing a slow warm up to room temperature and the
products were dissolved in CH2Cl2. The solvent was removed under reduced
pressure and the crude products, obtained in practically quantitative yield,
were purified by flash chromatography on neutral Al2O3 with hexane:
AcOEt (75 : 25) mixture.
Syntheses of compounds 3a,1a 3b,7a 3d,7b and 3e7c by other methods
were described earlier but no spectral data for 3b and 3d. Spectroscopic
details for 3a and 3e were identical to those reported.1a,7c For 3b and 3e
the authors didn’t submit the spectral data of these products, that’s why
they are presented below.
5-Ethyl-1-isopropyl-3,4-dihydro-1H-pyridin-2-one (3a).1a Yield: 55%.
1-Methyl-6-phenyl-3,4-dihydro-1H-pyridin-2-one (3b).7a Yield: 51%.
IR (film): 1680, 1610. 1H NMR: 2.10–2.75 (m, 4H). 2.90 (s, 3H), 5.29
(dd, J ¼ 4.5 and 9.5 Hz, 1H), 7.15–7.62 (m, 5H). 13C NMR: 19.88, 31.83,
32.01, 109.08, 127.99, 128.54, 128.72, 136.54, 143.71, 172.05. Anal. Calcd for
C12H13NO: C, 76.96; H, 6.99; N, 7.48. Found: C, 76.81; H, 7.02, N; 7.20.
1,3-Dimethyl-6-phenyl-3,4-dihydro-1H-pyridin-2-one (3c). Yield: 53%.
1
IR (film): 1670, 1625. H NMR: 1.25 (d, J ¼ 6Hz, 3H), 2.10–2.43 (m, 3H),
2.88 (s, 3H), 5.30 (dd, J ¼ 4.5 and 6.5 Hz, 1H), 7.18–7.50 (m, 5H). 13C NMR:
15.57, 28.00, 32.35, 35.63, 108.35, 127.93, 128.51, 128.75, 136.78, 143.35,
175.06. Anal. Calcd for C13H15NO: C, 77.58; H, 7.51; N, 6.96. Found:
C, 77.33; H, 7.46; N, 6.73.
1-Methyl-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one (3d).7b Yield: 49%.
IR (film): 1675, 1620. 1H NMR: 1.45–1.80 (m, 4H), 1.95–2.20 (m, 6H),
2.30–2.60 (m, 2H), 3.10 (s, 3H). 13C NMR: 22.22, 23.05, 25.48, 25.78,
28.06, 29.00, 31.61, 114.47. 132.04, 170.65. Anal. Calcd for C10H15NO:
C, 72.69; H, 9.15; N, 8.48. Found: C, 72.60; H, 8.98; N, 8.21.
1-Phenyl-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one (3e).7c Yield: 57%.
1,4-Dimethyl-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one(3f ). Yield:49%.
1
IR (film): 1665, 1610. H NMR: 0.93 (d, J ¼ 7 Hz, 3H), 1.53–1.75 (m, 4H),

880
LESNIAK AND PASTERNAK
1.95–2.15 (m, 5H), 2.35–2.45 (m, 2H), 3.00 (s, 3H). 13C NMR: 17.24, 22.38,
23.04, 24.84, 25.87, 27.12, 30.77, 39.10, 119.42, 139.63, 170.13. Anal. Calcd
for C11H17NO: C, 73.70; H, 9.56; N, 7.81. Found: C, 73.58; H, 9.63; N, 7.80.
1-Methyl-4-phenyl-3,4,5,6,7,8-hexahydro-1H-quinolin-2-one (3g). Yield:
54%. IR (film): 1670, 1610. 1H NMR: 1.33–2.40 (m, 9H), 2.58–2.87 (m, 2H),
3.05 (s, 3H), 7.10–7.30 (m, 5H). 13C NMR: 21.16, 21.86, 24.93, 2 ꢁ 26.91,
38.25, 41.23, 115.38, 125.99, 126.47, 127.87, 131.82, 140.95, 168.12. Anal.
Calcd for C16H19NO: C, 79.63; H, 7.93; N, 5.81. Found: C, 79.61; H, 7.82;
N, 5.53.
REFERENCES
1. (a) Paulvannan, K.; Stille, J.R. J. Org. Chem. 1992, 57, 5319;
(b) Hickmott, P.W.; Sheppard, G. J. Chem. Soc. (C), 1971, 1358.
2. Heathcock, C.H.; Norman, M.H.; Dickman, D.A. J. Org. Chem. 1990,
55, 798.
3. Ninomiya, I.; Naito, T. Heterocycles 1981, 15, 1433.
4. (a) Potts, K.T.; Rochanapruk, T. J. Org. Chem. 1995, 60, 3795 and
references cited therein; (b) Padwa, A.; Coats, S.J.; Hadjiarapoglou, L.
Heterocycles 1995, 41, 1631.
5. Sakamoto, M.; Yanase, T.; Fujita, T.; Watanabe, S.; Aoyama, H.;
Omote, Y. J. Chem. Soc. Perkin Trans. 1, 1991, 403.
6. (a) Cobas, A.; Guitian, E.; Castedo, L. J. Org. Chem. 1993, 58, 3113;
(b) Knorr, R.; Schnegg, A.; Lattke, E.; Rapple, E. Chem. Ber. 1979,
112, 3490; (c) Sell, M.S.; Klein, W.R.; Rieke, R.D. J. Org. Chem. 1995,
60, 1077.
7. (a) Schulte, K.E.; Mleinek, I.; Schar, K.H. Arch. Pharm. 1958, 291, 227;
(b) Horii, Z.; Iwata, C.; Ninomiya, I.; Imamura, N.; Ito, M.; Tamura, Y.
Chem. Pharm. Bull. 1964, 12, 1405; (c) Shabana, R.; Rasmussen, J.B.;
Olesen, S.O.; Lawesson, S.-O. Tetrahedron 1980, 36, 3047.
Received in the Netherlands April 6, 2001