S. Perrin, K Monnier, B. Laude, M. Kubicki, O. Blacque
FULL PAPER
pyridone-4-carboxylate (18cC): Heating 4 hours, yield 25%, m.p.
272°C (EtOH). Ϫ C29H28N2O5 (484.5): calcd. C 71.89, H 5.82, N
5.78; found C 72.01, H 5.75, N 5.69. Ϫ IR (KBr): ν˜ ϭ 3352 cmϪ1
(NH), 3304 (NH), 1684 (CϭO), 1731 (CϭO). Ϫ 1H NMR
([D6]DMSO): δ ϭ 2.12 (s, 3 H, CH3), 2.87 (s, 2 H, CH2ϪCO), 3.52
H-4), 3.83 (q, 2 H, J ϭ 7.0 Hz, OCH2), 5.53 (dd, 1 H, 3J ϭ 6.2
Hz, 4J ϭ 1.0 Hz, H-5), 6.33 (broad s, 1 H, NH), 6.51 (d, 2 aromatic
H.), 6.76 (d, 2 aromatic H.), 7.25Ϫ7.70 (m, 10 aromatic H.), 9.77
(d, 1 H, J ϭ 1.0 Hz, NH). Ϫ 13C NMR ([D6]DMSO): δ ϭ 13.7 (q,
J ϭ 126.9 Hz, CH3), 20.1 (q, J ϭ 124.5 Hz, CH3), 54.5 (d, J ϭ
(s, 3 H, OCH3), 3.61 (s, 3 H, OCH3), 5.64 (broad s, 1 H, NH), 5.78 137.9 Hz, C-4), 60.4 (t, J ϭ 144.0 Hz, OCH2), 61.0 (s, C-3), 97.4
(d, 1 H, H-5), 6.32 (d, 2 aromatic H), 6.76 (d, 2 aromatic H),
(d, J ϭ 172.1 Hz, C-5), 115.6Ϫ142.9 (11 signals for 19 aromatic or
7.30Ϫ7.60 (m, 11 aromatic H and NH). Ϫ 13C NMR ([D6]DMSO): sp2 C), 168.0 (s, CϭO), 169.4 (s, CϭO).
δ ϭ 20.18 (q, J ϭ 129.2 Hz, CH3), 37.6 (t, J ϭ 135.4 Hz, CH2),
X-ray Crystal Structure of 18ЈcA: Solved by direct methods and
51.9 (q, J ϭ 147.7 Hz, OCH3), 52.1 (q, J ϭ 146.5 Hz, OCH3), 54.1
(s, C-3), 66.1 (s, C-4), 104.1 (d, J ϭ 172.1 Hz, C-5), 116.2Ϫ142.0
(10 signals for 17 aromatic or sp2 C), 165.7 (s, CϭO), 170.5 (s,
CϭO), 171.1 (s, CϭO).
refined by full-matrix least-squares (SHELXL-97). All non-hydro-
gen atoms were given anisotropic thermal parameters, whereas the
hydrogen atoms were included in a “riding” model with Biso fixed
at 1.3 times Beq of the heavy atoms bearing them. Crystallographic
data are given in Table 1. Selected bond lengths for 18ЈcA: N1ϪC2
1.375(12), N1ϪC6 1.408(12), C2ϪC3 1.550(13), C3ϪC4 1.568(13),
Reactions at 20 °C, General Procedure: To a solution of 0.01 mole
of the hydrofluoroborate salt 2c؊5c in 30 mL of anhydrous DMF,
4 mL of the α,β-ethylenic ester was added. The solution was kept
at 20°C for varying periods in order to obtain the best yield of
each product. The reaction medium was poured into ice-cold water,
then extracted three times with 30 mL of dichloromethane. The
extracts were collected, washed five times with 50 mL of water,
dried and evaporated off. The oily residue was dissolved into 50
mL of refluxing ethanol and each product was isolated by frac-
tional recrystallization.
˚
C4ϪC5 1.470(14), C5ϪC6 1.347(13) A.
Acidic treatment of 18cA or 18ЈcA gave the 2-pyridone 19. 200 mg
of compound 18cA or 18ЈcA were dissolved into 4 mL of AcOH.
A drop of 1 HCl was added, and the solution was heated at 50°C
for 45 min. and then poured into 50 mL of water. The mixture was
extracted three times with 30 mL of methylene chloride. The col-
lected extracts were washed several times with 30 mL of water, then
dried and evaporated off. The residual solid was recrystallized in
ethyl acetate to yield quantitatively the precedent 2-pyridone 19.
Reaction with Ethyl Acrylate (A) at 20 °C: Reaction time 150 h.
The first crop of crystals consisted of the 2-pyridone 19 (yield 15%).
The second were crystals of the (cis) ethyl 3,6-diphenyl-3-p-tolyl-
amino-3,4-dihydro-2-pyridone-4-carboxylate (18cA): This product
was identified by X ray analysis[24], yield 30%, m.p. 217°C. Ϫ IR
(KBr): ν˜ ϭ 3364 cmϪ1 (NH), 3313 (NH), 1695 (CϭO), 1720 (Cϭ
O). Ϫ 1H NMR ([D6]DMSO): δ ϭ 1.05 (t, 3 H, J ϭ 7.1 Hz, CH3),
2.12 (s, 3 H, CH3), 4.05 (q, 2 H, J ϭ 7.1 Hz, OCH2), 4.66 (d, 1 H,
Reaction with Methyl Methacrylate (B) at 20 °C: The reaction time
was 120 h. It lead to two products which were separated by frac-
tional recrystallization in ethanol. The first recrystallized product
was 18cB which has already been described (vide supra), yield 35%.
The second crop of crystals was the [3 ϩ 2] cycloadduct methyl 3-
imino-endo-5-methyl-1,4-diphenyl-7-p-tolyl-1,4-imino-2-oxacyclo-
3
4
J ϭ 6.6 Hz, H-4), 5.73 (dd, 1 H, J ϭ 6.6 Hz, J ϭ 1.3 Hz, H-5),
5.89 (broad s, 1 H, NH), 6.45 (d, 2 aromatic H), 6.76 (d, 2 aromatic
H), 7.15Ϫ7.65 (m, 10 aromatic H), 9.77 (broad s, 1 H, NH coupled
with H-5). Ϫ 13C NMR (CDCl3): δ ϭ 13.7 (q, J ϭ 128.2 Hz, CH3),
20.2 (q, J ϭ 117.2 Hz, CH3), 47.8 (d, J ϭ 136.7 Hz, C-4), 60.9 (t,
J ϭ 144.0 Hz, OCH2), 62.2 (s, C-3), 98.9 (d, J ϭ 176.6 Hz, C-5),
115.8Ϫ141.6 (11 signals for 19 aromatic or sp2 C), 170.3 (s, CϭO),
171 (s, CϭO).
Table 1. Crystallographic data of 3,4-dihydro-2-pyridone 18ЈcA[a]
Molecular formula
Formula weight [g]
Crystal system
C27H26N2O3
426.50
monoclinic
P21/n (n°14)
Space group
Cell dimensions:
˚
a [A]
10.023(2)
˚
b [A]
16.963(4)
˚
c [A]
13.665(3)
The third fraction was the ethyl 3-imino-1,4-diphenyl-7-p-tolyl-1,4-
imino-2-oxacyclohexane-exo-5-carboxylate or ethyl 7-aza-3-imino-
2-oxa-1,4-diphenyl-7-p-tolylbicyclo[2.2.1]heptane-exo-5-carboxy-
late (13cA), yield 8%, m.p. 204°C. Ϫ C27H26N2O3 (426.5): calcd. C
76.03, H 6.15, N 6.57; found C 76.19, H 6.04, N 6.49. Ϫ IR (KBr):
ν˜ ϭ 3320 cmϪ1 (NH), 1713 (CϭN), 1737 (CϭO). Ϫ 1H NMR
(CDCl3): δ ϭ 1.11 (t, 3 H, J ϭ 7.1 Hz, CH3), 2.08 (s, 3 H, CH3),
2.68 (dd, 1 H, 3J ϭ 4.4 Hz, 2J ϭ 11.7 Hz, H-6a), 3.19 (dd, 1 H,
3J ϭ 9.7 Hz, 2J ϭ 11.7 Hz, H-6b), 3.54 (dd, 1 H, 3J ϭ 4.4 Hz,
β [deg]
107.67(2)
3
˚
V [A ]
2213.7(8)
Z
4
ρcalc [g.cmϪ3
F(000)
Diffractometer
Radiation [A]
]
1.280
904
EnrafϪNonius CAD4
˚
λ(Mo-Kα) 0.71073
Crystal size [mm]
Scan type
0.25 ϫ 0.25 ϫ 0.15
ω
Reflections measd.
θ range [deg]
h: Ϫ11.0; k: Ϫ19.0; l: Ϫ15.16
2.23Ϫ24.64
0.084
2
3
3J ϭ 9.7 Hz, H-5), 4.06 (part AB of an ABX3, J ϭ 10.7 Hz, J ϭ
7.1 Hz, OCH2), 6.33 (d, 2 aromatic H.), 6.57 (broad s, 1 H, NH),
6.61 (d, 2 aromatic H), 7.15Ϫ7.83 (m, 10 aromatic H). Ϫ 13C NMR
(CDCl3): δ ϭ 13.9 (q, J ϭ 126.9 Hz, CH3), 20.6 (q, J ϭ 122.1 Hz,
CH3), 40.0 (t, J ϭ 133.0 Hz, C-6), 52.0 (d, J ϭ 144.0 Hz, C-5),
61.1 (t, J ϭ 147.7 Hz, OCH2), 76.4 (s, C-4), 84.0 (s, C-1),
126.9Ϫ138.2 (12 signals for 18 aromatic C), 171.0 (s, CϭO or Cϭ
N), 176.1 (s, CϭN or CϭO).
Linear abs., µ [mmϪ1
No. reflns measd.
No. reflns unique
Cut off for obsd.data
]
3921
3700
I Ն 2σ(I)
1562
No. of unique obsd.data
No. of parameters
R(F)
289
0.134
Rw(F2)
0.413
G.O.F.
1.403
3
˚
ρmax; ρmin, e/A
0.63; Ϫ0.45
The crystals of the fourth fraction were those of the (trans) ethyl
3,6-diphenyl-3-p-tolylamino-3,4-dihydro-2-pyridone-4-carboxylate
(18ЈcA) identified by X-ray analysis (vide infra), yield 10%, m.p.
169 °C. Ϫ IR (K Br): ν˜ ϭ 3371 cmϪ1 (N H ), 3313 (N H ), 1695
(CϭO), 1720 (CϭO). Ϫ H NMR ([D6]DMSO): δ ϭ 0.94 (t, 3 H,
J ϭ 7.0 Hz, CH3), 2.11 (s, 3 H, CH3), 3.66 (d, 1 H, J ϭ 6.2 Hz,
[a] Crystallographic data (excluding structure factors) for the struc-
ture reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication no.
CCDC-101489. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ,
UK [Fax: (ϩ44) 1223 336033; E-mail: deposit@ccdc.cam.ac.uk]
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Eur. J. Org. Chem. 1999, 297Ϫ303