(20672446 - Acta Chemica Iasi) Aldol Condensation Reactions Effectively Catalysed by Lewis Acid
(20672446 - Acta Chemica Iasi) Aldol Condensation Reactions Effectively Catalysed by Lewis Acid
(20672446 - Acta Chemica Iasi) Aldol Condensation Reactions Effectively Catalysed by Lewis Acid
DOI: 10.1515/achi-2017-0007
Introduction
Aldol condensation reaction as C-C bond formation reaction
continued to provide opportunity for the synthesis of valuable intermediates,
natural products, and biologically important compounds.1-3 One of the major
concern with some of the reported methodologies has always been the issue
of atom economy.4,5 Although a number of attempts which employ catalysts
was made to improve the condition, it however usually incorporates the use
of harsh temperature.6‐10 In this work, a new organic-metal complex based
*
Yusuf, Hassan, e-mail: [email protected]
64 Y. Hassan et al.
1. KOH(aq)
2. Mn(OAc)2.4H2O
CH3CO2H 3. Satd. NaCl(aq) N
N N N
HO O
Mn
HO2C CHCl3, 36h, EtOH, 12h, reflux
O OH O O Cl O
reflux
O O
1 R,R-3 R,R-4
H 2N NH2
2
Ph H +
Solvent, room temperature
5 6 7
Aliphatic ketone
a 2-Methylcyclohexanone
b 4-Methylcyclohexanone
c 2-Hexanone
d Pinacolone
Aldol condensation reactions effectively catalysed by lewis acid 67
Table 2. Continued
Aldol products, 9b Time (h) Yield (%)c
O
4.2 99
a
O
4.4 99
b
O
c 4.7 99
5 99
O
d
a
Benzaldehyde (1.5 mmol), Ketone (15 mmol);
b
Geometrical assignment for 9a and 9b was determined using
DFT calculation of the lowest-energy isomers;
c
Determined by the 1H NMR spectroscopic analysis of the reaction mixture.
Experimental
Reagent-grade ethanol was used as received from commercial
source, tetrahydrofuran was distilled from benzophenone/ketyl solutions and
chloroform was passed through a column of basic alumina. Analytical thin-
layer chromatography was performed on ALUGRAM XTRA silica gel 0.2
mm (containing a fluorescent indicator at 254 nm). Flash chromatography
was carried out on MN Kieselgel 60 0.063-0.2 mm/ 70-230 mesh. All other
reagents were purchased from Aldrich and used as received. NMR spectra
were recorded on Bruker Avance III HD spectrometer (400 and 600 MHz).
All signals were expressed as ppm down field from TMS, referenced to the
residual protonated solvent signals in 1H NMR (7.26 ppm) and to the
deuterated carbon signals in 13C NMR (77.36 ppm). IR spectral
measurements were carried out on a Perkin Elmer spectrum 400 FT-IR
spectrometer (ATR). Elemental analyses were conducted using an
68 Y. Hassan et al.
2,2'-(1R,2R)-cyclohexane-1,2-diylbis(azan-1-yl-1-ylidene)bis(7,7-
dimethylbicyclo[2.2.1]heptane-1-carboxylic acid) R,R-3
2,2'-(1R,2R)-cyclohexane-1,2-diylbis(azan-1-yl-1-ylidene)bis(7,7-
dimethylbicyclo[2.2.1]heptane-1-carboxylato) manganese (III) chloride
R,R-4
Solution of the ligand R,R-3 (119 mg, 0.268 mmol) containing KOH
(0.5M, 8 mL) in ethanol was allowed to reflux under nitrogen atmosphere
with Mn(OAc)2 4H2O (138 mg, 0.563 mmol) for 12 h. The reaction
mixture was cooled to room temperature and brine (8 mL) was added to
give a biphasic solution. The resulting solution was filtered, concentrated in
vacuo and redissolved in dichloromethane. After concentration, the water
layer was removed using a separating funnel and the solution was again
concentrated till dryness. The complex was recrystallized from acetonitrile
Aldol condensation reactions effectively catalysed by lewis acid 69
and obtained as brown amorphous powder (71 mg, 50% yield). Anal. Calcd
for C26H36ClMnN2O4 % : C, 60.75; H, 8.50; N, 4.72. Found: C, 60.75; H,
8.51; N, 4.74. IR (neat, cm-1): 1738 (C=O), 1687 (C=N).
(Z)-2-benzylidenecyclohexanone 7
Yellow oil; 99% yield, H (600 MHz; CDCl3) 1.50 (q, J = 2.0 Hz,
CH2), 1.55 (q, J = 2.3 Hz, CH2), 1.57 (t, J = 3.1 Hz, CH2), 1.63 (t, J = 3.1
Hz, CH2), 6.88 (s, 2H), 7.32-7.33 (m, 2H), 7.40 (s, 1H), 7.61 (s, 1H), C
(100 MHz; CDCl3) 22.2, 24.3, 35.0, 128.2, 128.3, 128.4, 133.1, 134.0,
139.5, 198.3. IR (neat, cm-1) 3038, 1671, 1638, 1450.
(E)-2-benzylidene-6-methylcyclohexanone 9a
Yellow oil; 99% yield; H (600 MHz; CDCl3) 1.22 (d, J = 1.2 Hz,
CH3), 1.23-1.24 (m, 2H), 1.32-1.36 (m, 2H), 2.10-2.12 (m, 2H), 2.22-2.32
(m, 2H), 6.89 (s, 2H), 7.41-7.43 (m, 2H), 7.54 (s, 1H), 7.81 (s, 1H). C (100
MHz; CDCl3) 16.2, 26.3, 29.2, 30.6, 40.6, 133.2, 136.3, 136.7, 134.2, 134.8,
140.1, 199.3. IR (neat, cm-1) 3045, 1674, 1632, 1447.
(E)-2-benzylidene-4-methylcyclohexanone 9b
Yellow oil; 99% yield, H (600 MHz; CDCl3) 0.99 (d, J = 0.5 Hz,
CH3), 1.62-1.68 (m, 2H), 1.85-1.93 (m, 2H), 2.33-2.80 (m, 2H), 2.86-2.93
70 Y. Hassan et al.
(m, 1H), 3.20-3.52 (m, 1H), 3.62-3.72 (m, 1H), 7.02 (s, CH), 7.61-7.68 (m,
2H), 7.72 (s, 1H), 7.84 (s, 1H). C (100 MHz; CDCl3) 16.2, 26.3, 29.2, 30.6,
40.3, 133.2, 136.3, 136.7, 134.2, 134.8, 140.1, 199.5. IR (neat, cm-1) 3044,
1675, 1632, 1447.
trans-1-phenylhept-1-en-3-one 9c
Yellow oil; 99% yield, H (600 MHz; CDCl3) 0.96 (t, J = 0.9 Hz,
3H), 1.52-1.59 (m, 4H), 3.20 (t, J = 3.1 Hz, 2H), 6.53 (d, J = 12.0 Hz, 1H),
6.66 (d, J = 12.0 Hz, 1H), 6.83 (d, J = 6.5, 2H), 7.66-7.68 (m, 3H). C (100
MHz; CDCl3) 12.3, 23.4, 28.6, 40.2, 128.3, 129.0, 131.1, 135.1, 140.1,
147.2, 199.5. IR (neat, cm-1) 3051, 1668, 1646, 1510.
Cis-4,4-dimethyl-1-phenylpent-1-en-3-one 9d
Yellow oil ; 99% yield, H (600 MHz; CDCl3) 1.51 (s, 9H), 6.93 (d,
J = 6.0 Hz, 1H), 7.43 (d, J = 6.0 Hz, 1H), 7.66-7.68 (m, 2H), 7.72-7.75 (m,
3H). C (100 MHz; CDCl3) 33.2, 43.1, 127.3, 129.1, 129.8, 133.10, 138.0,
140.2, 198.5. IR (neat, cm-1) 3055, 1671, 1644, 1525.
Conclusions
The synthesis of a complex based on the scaffold of ketopinic acid
was successfully achieved, and its subsequent application in the catalytic
aldol condensation reactions of benzaldehyde with various aliphatic
ketones. It is quite remarkable that irrespective of the structure of the
aliphatic ketone, the yield of the products was apparently excellent within
short duration.
Acknowledgements
The authors gratefully acknowledge the financial support of the National Research
Foundation and the Tertiary Education Trust Fund, Nigeria for granting fellowship to
Yusuf Hassan.
Aldol condensation reactions effectively catalysed by lewis acid 71
References
1. Heathcock, C. H.; Ellis, J. E.; McMurry, J. E.; Coppolino, A. Acid-
catalyzed Robinson annelations. Tetrahedron Letters. 1971, 12,
4995-4996.
11. Yang, K.-S.; Lee, W. -D.; Pan, J. -F.; Chen, K. Chiral Lewis acid-
catalyzed asymmetric Baylis-Hillman reactions. J. Org. Chem.
2003, 68, 915-919.
12. Kureshy, R. I.; Khan, N.; Abdi, S.; Iyer, P.; Bhatt, A.
Enantioselective catalytic epoxidation of nonfunctionalized prochiral
olefins by dissymmetric chiral Schiff base complexes of Mn (III)
and Ru (III) metal ions. J. Mol. Cat. A: Chemical. 1997, 120, 101-
108.
13. Biswas, S.; Kar, T.; Sarkar, S.; Dey, K. Synthesis, characterization,
and density functional study of some manganese (III) Schiff-base
complexes. J. Coord. Chem. 2012, 65, 980-993.
14. Dunning Jr, T. H.; Hay, P. J. Modern Theoretical Chemistry;
Plenum: New York, 1978; Vol. 3.
15. Hay, P. J.; Wadt, W. R. Ab initio effective core potentials for
molecular calculations. Potentials for the transition metal atoms Sc
to Hg. J. Chem. Phys. 1985, 82, 270-283