, 2006, 16(2), 82–83
the reaction is also stereoselective.10 Here, we report a stereo-
selective reaction of 2-(4-phenylpiperidino)benzaldehyde 1†
and cyclic CH-active compounds 2a,b, which led to a single
isomer‡ with an axiality hydrogen in the 3- and 4a-positions of
benzo[c]quinolizine (Scheme 1). The structures of 3a,b were
determined by 2D correlation NMR spectroscopy (DEPT,
COSY, HETCOR) and ax-eq coupling constants.
In contrast to the cyclization of 1 with 2a,b, the reaction of 1
and malononitrile led to benzylidene malononitrile 5, similarly
to published data.9 The cyclization of 4§ led to a mixture¶ of
two isomers 5 and 6 in a ratio of 1:1 (Scheme 2).
References
1
2
3
4
5
6
7
8
9
O. Melh-Cohn and H. Suschitzky, Adv. Heterocycl. Chem., 1972, 14,
211.
W. Verboom and D. N. Reinhoudt, Recl. Trav. Chim. Pays-Bas, 1990,
109, 311.
O. Elias, L. Karolyhazy, G. Horvath, V. Harmat and P. Mtyus, J.
Molecular Structure (Theochem), 2003, 666–667, 625.
Our present results indicate that the cyclization of benzal-
dehyde 1 and CH-active compounds occurred stereoselectively
for reaction with cyclic CH-active compounds but not for one
of malononitrile.
†
4-Phenylpiperidine (0.160 mg, 0.988 mmol) and potassium carbonate
10 E. V. Deeva, T. V. Glukhareva, N. A. Zybina and Yu. Yu. Morzherin,
Izv. Akad. Nauk, Ser. Khim., 2005, 1492 (Russ. Chem Bull., Int. Ed.,
2005, 54, 1537).
(0.138 g, 0.988 mmol) were added to a solution of 2-fluorobenzaldehyde
(0.118 g, 0.949 mmol) in DMF (1.0 ml). The reaction mixture was refluxed
in a glycerol bath at 150 °C for 20 h. The completion of the reaction was
judged from TLC. The reaction mixture was cooled to ~20 °C, water
(15 ml) was added, and the product was extracted with ethyl acetate
(3×20 ml). The combined organic extract was washed with a solution of
ammonium chloride. The organic layer was dried with Na2SO4, and the
solvent was removed in vacuo. Data for 1: 2-(4-phenylpiperidino)-
benzaldehyde. Yield, 75%; mp 122 °C. 1H NMR ([2H6]DMSO) d:
10.26 (s, 1H, CHO), 7.70 (dd, 1H, HAr, J 7.7 and 1.7 Hz), 7.61 (ddd, 1H,
HAr, J 8.3, 8.5 and 1.7 Hz), 7.30–7.33 (m, 4H, HAr), 7.25 (d, 1H, HAr
J 8.3 Hz), 7.21 (ddd, 1H, HAr, J 7.7, 7.0 and 4.7 Hz), 7.14 (dd, 1H, HAr
,
,
J 7.7 and 8.5 Hz), 3.32–3.38 (m, 2H, 2NCH), 3.01 (ddd, 2H, 2NCH,
J 11.9, 11.8 and 2.9 Hz), 2.64–2.74 (m, 1H, CH), 1.87–1.99 (m, 4H,
2CH2). 13C NMR ([2H6]DMSO) d: 33.09 (CH2), 41.28 (CH2Ph), 54.64
(NCH2), 119.33 (ArH), 121.90 (ArH), 126.10 (Ph), 126.74 (Ph), 127.86
(Ph), 128.34 (Ph), 128.97 (ArH), 135.07 (ArH), 145.82 (Ar), 155.86
(Ar), 190.80 (CHO). MS, m/z: 265 (M+). Found (%): N, 5.15. Calc. for
C18H19NO (%): N, 5.28.
‡
Meldrum’s acid (or dimedone) (2.3 mmol) was added to a solution of
benzaldehyde 1 (0.608 g, 2.3 mmol) in toluene (20 ml). The reaction
mixture was refluxed for 3 h. The completion of the reaction was deter-
mined by TLC. The reaction mixture was cooled to ~20 °C and con-
centrated in vacuo. The residue was triturated with ethanol.
3-Phenyl-2',2'-dimethyl-2,3,4,4a,5,6-hexahydro-6H-spiro(benzo[c]-
quinolizine-5,5'-[1,3]dioxane)-4',6'-dione 3a. Yield, 80%; mp 240 °C.
1H NMR (CDCl3) d: 7.27 (dd, 2H, HPh, J 7.4 and 7.4 Hz), 7.19 (tt, 1H,
HPh, J 7.4 and 1.9 Hz), 7.15 (ddd, 1H, HAr, J 8.2, 6.9 and 1.3 Hz),
7.09–7.12 (m, 2H, HAr), 6.97 (d, 1H, HAr, J 7.3 Hz), 6.93 (d, 1H, HAr
,
J 8.3 Hz), 6.74 (ddd, 1H, HAr, J 7.4, 7.4 and 1.0 Hz), 4.10 [ddd, 1H,
CH(1), J 12.8, 4.6 and 2.6 Hz], 3.52 [d, 1H, CH(6), J 16.4 Hz], 3.43 [dd,
1H, CH(4a), J 11.8 and 2.4 Hz], 3.11 [d, 1H, CH(6), J 16.4 Hz], 2.72
[ddd, 1H, CH(1), J 12.8, 12.8 and 2.6 Hz], 2.60 [dd, 1H, CH(4), J 13.7
and 6.0 Hz], 2.50 [dd, 1H, CH(3), J 13.7 and 7.8 Hz], 1.76 (s, 3H, Me),
1.75 (s, 3H, Me), 1.72–1.78 [m, 1H, CH(4)], 1.36 [ddd, 1H, CH(2),
J 12.8, 12.8 and 4.6 Hz], 1.15 [ddd, 1H, H(2), J 12.8, 12.8 and 12.8 Hz].
13C NMR (CDCl3) d: 169.28 (CO), 164.78 (CO), 144.60 (Ar), 139.46
(Ar), 129.06 (ArH), 128.71 (ArH), 128.37 (ArH), 127.67 (ArH), 126.23
(ArH), 119.50 (Ar), 118.49 (ArH), 113.52 (ArH), 61.24 (C4a), 52.21
(OCO), 48.27 (C1), 43.00 (C5), 37.63 (C3), 34.72 (C6), 34.56 (C4), 30.62
(C2), 30.28 (Me), 28.20 (Me). MS, m/z: 391 (M+). Found (%): N, 3.58.
Calc. for C24H25NO4 (%): N, 3.58.
Received: 3rd October 2005; Com. 05/2585
§
2-[2-(4-Phenylpiperidino)benzylidene]malononitrile 4. Yield, 85%;
mp 116 °C. 1H NMR ([2H6]DMSO) d: 8.26 (s, 1H, CH=), 7.98 (dd, 1H,
HAr, J 8.1 and 1.2 Hz), 7.58 (ddd, 1H, HAr, J 8.4, 7.4 and 1.2 Hz),
7.00–7.30 (m, 7H, HAr), 3.20–3.26 (m, 2H, 2NCH), 2.94–3.06 (m, 2H,
2NCH), 2.60–2.70 (m, 1H, CH), 1.90–2.08 (m, 4H, 2CH2). 13C NMR
([2H6]DMSO) d: 33.07 (CH2), 41.26 (CH2Ph), 54.22 (NCH2), 81.10
(C=), 113.32 (CN), 114.51 (CN), 119.58 (ArH), 122.18 (ArH), 124.37
(Ph), 126.13 (Ph), 126.76 (Ph), 128.34 (Ph), 129.00 (ArH), 134.84 (ArH),
145.75 (Ar), 154.59 (Ar), 158.34 (C=). MS, m/z: 313 (M+). Found (%):
N, 13.51. Calc. for C21H19N3 (%): N, 13.41.
3-Phenyl-5',5'-dimethyl-2,3,4,4a,5,6-hexahydro-6H-spiro(benzo[c]-
quinolizine-5,2'-cyclohexane)-1',3'-dione 3b. Yield, 68%; mp 230 °C.
1H NMR ([2H6]DMSO) d: 7.23 (dd, 2H, HPh, J 7.6 and 7.6 Hz), 7.16 (tt,
1H, HPh, J 7.6 and 1.3 Hz), 7.07 (d, 1H, HAr, J 7.6 Hz), 7.05–7.10 (m,
¶
A solution of vinyl compound 4 (0.225 g, 0.72 mmol) in BuOH (10 ml)
was heated at 100 °C for 3 h and then filtered with charcoal. The solvent
was evaporated, and the residue was recrystallised from ethyl acetate.
A mixture of 3-phenyl-2,3,4,4a,5,6-hexahydro-6H-benzo[c]quinolizine-
5,5-dicarbonitriles 5, 6: Yield, 91%; mp 115 °C. 1H NMR ([2H6]DMSO)
d: two isomers 6.90–7.40 (m, 7H, HAr), 6.78 (d, 1H, HAr, J 7.0 Hz),
6.74 (dd, 1H, HAr, J 7.0 and 7.0 Hz), 4.18 (d, 0.5H, CH, J 12.5 Hz),
3.50–3.90 (m, 3.5H, CH), 3.35–3.40 (m, 1H, CH), 2.80–3.12 (m,
1H, CH), 2.58–2.65 (m, 1H, CH), 2.10–2.38 (m, 3H, CH). 13C NMR
([2H6]DMSO) d: 144.37, 142.39, 129.13, 128.58, 127.37, 126.62, 126.12,
118.75, 116.59, 115.21, 114.69, 113.89, 54.44, 43.52, 36.41, 35.34, 33.71,
32.99, 28.49, isomer 144.47, 143.78, 129.35, 129.12, 128.62, 128.40,
126.55, 118.89, 116.59, 115.18, 114.46, 114.03, 58.10, 47.45, 36.51,
35.78, 34.78, 34.13, 31.24. MS, m/z: 313 (M+). Found (%): N, 13.19.
Calc. for C21H19N3 (%): N, 13.41.
2H, HAr), 7.00 (ddd, 1H, HAr, J 7.9, 7.2 and 1.3 Hz), 6.86 (d, 1H, HAr
,
J 7.9 Hz), 6.66 (ddd, 1H, HAr, J 7.3, 7.4 and 1.0 Hz), 4.59 [dd, 1H,
CH(1), J 12.2 and 3.1 Hz], 4.13 [d, 1H, CH(4a), J 14.5 Hz], 3.48 [d, 1H,
CH(6), J 13.3 Hz], 3.11–3.32 (m, 3H, 3CH), 3.11 [d, 1H, CH(6),
J 13.3 Hz], 2.64 [d, 1H, CH(4'), J 16.9 Hz], 2.27 (dd, 1H, CH, J 13.8 and
2.1 Hz), 2.14 (dd, 1H, CH, J 13.8 and 2.1 Hz), 1.47–1.59 (m, 2H, 2CH),
1.18–1.23 (m, 2H, 2CH), 1.23 (s, 3H, Me), 0.68 (s, 3H, Me). 13C NMR
([2H6]DMSO) d: 205.99 (CO), 205.01 (CO), 145.22 (Ar), 141.67 (Ar),
129.32 (ArH), 128.37 (ArH), 126.45 (ArH), 125.37 (ArH), 126.15 (ArH),
122.32 (Ar), 117.66 (ArH), 113.22 (ArH), 67.32 (C4a), 60.09 (C1), 50.83
(C5), 49.09 (C4'), 48.09 (C6'), 42.11 (C5'), 31.14 (C3), 30.69 (C6), 29.46
(C4), 27.91 (C5), 26.18 (Me), 23.56 (Me). MS, m/z: 387 (M+). Found (%):
N, 3.47. Calc. for C26H29NO2 (%): N, 3.61.
Mendeleev Commun. 2006 83