Solvent-free robinson annelation reaction

Article abstract of DOI:10.1246/cl.2000.888

Solvent-free Robinson annelation reaction proceeded at room temperature to give corresponding cyclohexenones.

Full text of DOI:10.1246/cl.2000.888

888
Chemistry Letters 2000
Solvent-Free Robinson Annelation Reaction
Hisakazu Miyamoto, Shotaro Kanetaka, Koichi Tanaka, Kazuhiro Yoshizawa,† Shinji Toyota,† and Fumio Toda*†
Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama, Ehime 790-8577
†Department of Chemistry, Faculty of Science, Okayama University of Science, Okayama, Okayama 700-0005
(Received May 10, 2000; CL-000460)
Solvent-free Robinson annelation reaction proceeded at
room temperature to give corresponding cyclohexenones.
Base-catalyzed annelation reaction of cyclic ketones with
α,β-unsaturated ketones which gives cyclohexenones in
15–20% yield had been reported by Robinson.1 This reaction is
known as Robinson annelation reaction.2–4 An acid-catalyzed
Robinson annelation reaction which proceeds by heating in
solution for a long time has also been known.5 We found that
solvent-free Robinson annelation reaction proceeds efficiently
at room temperature. We now report ecologically and econom-
ically valuable solvent-free annelation reactions.
For example, 2-methylcyclohexanone 1 (2.24 g, 20 mmol),
methyl vinyl ketone 2 (4.50 g, 40 mmol), and sodium methox-
ide (1.2 g, 24 mmol) were well mixed with agate mortar and
pestle and the mixture was kept at room temperature for 3 h.
The reaction product was mixed with 3M HCl (20 mL), extract-
ed with ether, and the dried ether solution was evaporated.
Distillation of the residue in vacuo gave 4,4a,5,6,7,8-hexahy-
dro-4a-methyl-2(3H)-naphthalenone 31 as colorless oil (1.05 g,
25% yield).6 The reaction can also be carried out by using
potassium hydroxide, sodium ethoxide, sodium t-butoxide, and
potassium t-butoxide instead of sodium methoxide (Table 1).
The solvent-free Robinson annelation reaction in one-pot
process has some advantages. Namely, procedure is much sim-
pler and yield of product is higher than that of solution reaction.
In order to isolate the product without using solvent, the reac-
tion mixture was neutralized by addition of p-toluenesulfonic
acid and distilled in vacuo. However, this method gave only
decomposed material.
We also found that the reaction of acyclic ketone 4 and
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
889
methyl vinyl ketone 2 with base in the absence of solvent gives
corresponding cyclohexenones 5. For example, benzyl phenyl
ketone 4d (2.0 g, 10 mmol), methyl vinyl ketone 2 (2.1 g, 30
mmol), and sodium methoxide (0.6 g, 12 mmol) were well
mixed with agate mortar and pestle and the mixture was kept at
room temperature for 3 h. The reaction product was mixed
with 3M HCl (20 mL), extracted with ether, and the dried ether
solution was evaporated. Distillation of the residue in vacuo
gave 3,4-diphenyl-2-cyclohexen-1-one 5d as colorless crystals
(1.13 g, 45% yield). When the reaction was carried out in
methyl alcohol (60 mL) by heating for 12 h, 3,4-diphenyl-2-
cyclohexen-1-one 5d was obtained in 29% yield. The reaction
of benzyl phenyl ketone 4d and methyl vinyl ketone 2 with
sodium methoxide proceeded more efficiently in the absence of
solvent than in solution. By a similar procedure using 4b–c,
4e–f, and 4h in the absence of solvent and in methyl alcohol,
cyclohexenones 5b–c, 5e–f, and 5h were obtained in the yield
indicated in Table 2. In most cases, the reaction of acyclic
ketone 4 and methyl vinyl ketone 2 with sodium methoxide
proceeded more efficiently in the absence of solvent than in
solution. In the case of 4a and 4g, reaction occurred neither in
the absence of solvent nor in methyl alcohol (Table 2).
References and Notes
1
2
3
4
5
6
E. C. du Feu, F. J. McQuillin, and R. Robinson, J. Chem.
Soc., 1937, 53.
F. D. Gunstone and R. M. Heggie, J. Chem. Soc., 1952,
1437.
E. D. Bergmann, D. Ginsburg, and R. Pappo, Org.
Reactions, 10, 179 (1959).
J. A. Marshall and W. I. Fanta, J. Org. Chem., 29, 2501
(1964).
C. H. Heathcock and J. E. Ellis, Tetrahedron Lett., 1971,
4995.
A typical procedure follows: Commercially available 2-
methylcyclohexanone 1, methyl vinyl ketone 2, and acyclic
ketone 3 were used for annelation reactions. IR spectra
were measured with an IR spectrometer, JASCO FT/IR-
350. 1H NMR spectra were recorded in CDCl3 on a JEOL
JNM-LA300 (300 MHz) spectrometer. 2-Methylcyclo-
hexanone 1 (2.21 g, 20 mmol), methyl vinyl ketone 2 (4.50 g,
40 mmol), and sodium methoxide (1.2 g, 24 mmol) were well
mixed with agate mortar and pestle and the mixture was kept
at room temperature for 3 h. The reaction product was
combined with 3M HCl (20 mL), extracted with ether (20
mL × 4), and the ether solution was washed with water and
dried over MgSO4. The dried ether solution was evaporat-
ed. Distillation of the residue in vacuo (150–170 °C / 25
mmHg) gave 4,4a,5,6,7,8-hexahydro-4a-methyl-2(3H)-
naphthalenone 31 as colorless oil (1.05 g, 25% yield). IR
Various organic reactions have been found to proceed effi-
ciently in the solid state.7 Although various simple organic
reactions have been established to proceed in the absence of
solvent,7 it is interesting to know the two-step reaction such as
Robinson condensation proceeds efficiently in the absence of
solvent and in one-pot.
(Neat) νmax 1698 cm–1; H NMR δ 1.25 (s, 3H), 1.25–2.50
1
(m, 12H), 5.73 (s, 1H). Similar treatment of 1 and 2 with
other base, and 4 and 2 with sodium methoxide gave 3 and
5 in the yields shown in Table 1 and 2, respectively.
F. Toda, Acc. Chem. Res., 28, 480 (1995); K. Tanaka and
F. Toda, Chem. Rev., 100, 1025 (2000).
This work was supported by Grant-in-aid for Scientific
Research from the Ministry of Education, Science, Sports and
Culture, Japanese Government, and by Mitsubishi Chemical
Corporation Fund (to H.M.).
7