Catalysis in water: Aldol-type reaction of aldehydes and imines with ethyl diazoacetate catalyzed by highly basic magnesium/lanthanum mixed oxide

Article abstract of DOI:10.1002/adsc.200600597

Magnesium/lanthanum mixed oxide is an effective heterogeneous catalyst for aldol-type condensation of aldehydes and imines with ethyl diazoacetate (EDA) at room temperature in water to afford corresponding β-hydroxy-α-diazo carbonyl compounds and β-amino-α-diazo carbonyl compounds in good yields. The catalyst is recovered and reused for several cycles with consistent activity.

Full text of DOI:10.1002/adsc.200600597

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DOI: 10.1002/adsc.200600597
Catalysis in Water: Aldol-Type Reaction of Aldehydes and
Imines with Ethyl Diazoacetate Catalyzed by Highly Basic Mag-
nesium/Lanthanum Mixed Oxide
M. Lakshmi Kantam,a,* V. Balasubrahmanyam,a K. B. Shiva Kumar,a
G. T. Venkanna,a and F. Figuerasb
a
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology, Hyderabad – 500 007, India
Fax : (+91)-40-2716-0921; e-mail: mlakshmi@iict.res.in
Institut de Recherches sur la Catalyse, 2 Av. A. Einstein, 69626 Villeurbanne, France
b
Received: November 15, 2006; Revised: June 15, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Magnesium/lanthanum mixed oxide is an
effective heterogeneous catalyst for aldol-type con-
densation of aldehydes and imines with ethyl diazo-
acetate (EDA) at room temperature in water to
afford corresponding b-hydroxy-a-diazo carbonyl
compounds and b-amino-a-diazo carbonyl com-
pounds in good yields. The catalyst is recovered and
reused for several cycles with consistent activity.
catalysts to reduce the amount of toxic waste. The use
of a solid catalyst allows easy separation of catalyst
from the reaction mixture in large-scale production to
conform to the concept of green technology. In a
recent review, Sheldon[9] emphasized the point that
“the best solvent is no solvent and if a solvent (dil-
uent) is needed then water is preferred. Water is non-
toxic, non-flammable, abundantly available and inex-
pensive” therefore, reactions performed in water are
safer and cheaper.
We herein report the synthesis of b-hydroxy-a-
diazo carbonyl compounds and b-amino-a-diazo car-
bonyl compounds by condensation of a wide variety
of aldehydes and imines with ethyl diazoacetate using
the Mg/La mixed oxide catalyst in water (Scheme 1).
Keywords: b-amino-a-diazo carbonyl compounds;
b-hydroxy-a-diazo carbonyl compounds; heteroge-
neous catalyst; magnesium/lanthanum mixed oxide;
water as solvent
a-Diazo carbonyl compounds[1] are a potential source
of amino alcohols and acids. a-Diazo carbonyl com-
pounds are generally prepared by the azido transfer
reaction of carbonyl compounds.[2] Condensation of
acyldiazomethane to aldehydes and imines also yields
a-diazo carbonyl compounds but requires deprotona-
tion of the acyldiazomethane. This is usually carried
Scheme 1.
out by using strong bases, such as butyllithium,[3] lithi- To the best of our knowledge, there are no reports on
um diisopropylamide (LDA),[4] sodium hydride,[5] po- this condensation using a heterogeneous catalyst and
tassium hydroxide,[6] 1,8-diazabicyclo
[5.4.0]undec-7- water as solvent. The Mg/La mixed oxide catalyst was
G
ene (DBU)[7] and quarternary ammonium hydrox- prepared by the co-precipitation method described
ide.[8] However, some of the methods require low earlier.[10] Chemical analysis of the solid gave the
temperatures and absolutely anhydrous conditions, composition La2O3 29.5%, MgO: 30.1%, K2O: 3.4%,
moreover the use of such strong bases may not be H2O: 37%. The catalyst is well characterized by
compatible with functional groups in the substrates. XRD, DTA coupled with mass spectrometry, FTIR
Thus, the development of more improved synthetic and calorimetry. This mixed oxide is macroporous and
methods for the preparation of a-diazo carbonyl com- shows a surface area of 37.6 m2gÀ1 after calcination at
pounds remains an active research area.
923 K. Recently, we have efficiently performed trans-
In recent years, there has been increasing emphasis esterifications of diethyl carbonate by alcohols[11] and
on the use and design of environment-friendly solid Michael addition reactions[10] by using this highly
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M. Lakshmi Kantam et al.
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basicMg/La mixed oxide catalyst. We have also used
solvent has a pronounced effect in these reactions
the Mg/La mixed oxide as a support for palladium (Table 1, entries 8–10), in which water provided better
À
and performed various C C bond forming reactions yields. This high activity of a solid base in water as
with this palladium/Mg-La mixed oxide catalyst.[12]
solvent is rather surprising since it is well known that,
In an effort to develop a better catalytic system, for most solid bases, their catalytic properties appear
various reaction parameters were studied for the only after removal of water.[13] The controlled reac-
preparation of ethyl 3-hydroxy-2-diazo-3-(4-chloro- tion conducted under identical conditions devoid of
phenyl)-propionate by the reaction of 4-chlorobenzal- Mg/La mixed oxide catalyst gave no condensed prod-
dehyde with ethyl diazoacetate (EDA) at room tem- uct, despite prolonged reaction times. Mg/La mixed
perature and the results are summarized in Table 1. oxide was recovered quantitatively by simple centrifu-
gation and reused for four cycles with consistent ac-
tivity (Table 1, entry 1).
Table 1. Screening reaction parameters for the synthesis of
ethyl 3-hydroxy-2-diazo-3-(4-chlorophenyl)-propionate.[a]
We chose a variety of structurally divergent alde-
hydes and imines possessing a wide range of function-
al groups to understand the scope and the generality
of the Mg/La mixed oxide catalyzed aldol-type con-
densation reaction to form b-hydroxy-a-diazo carbon-
yl compounds and b-amino-a-diazo carbonyl com-
pounds and the results are summarized in Table 2.
Among the aromatic, aliphatic and heteroaromatic al-
dehydes tested, aromaticaldehydes with eletcron-
withdrawing substituents reacted faster than those
with electron-donating substituents (Table 2, en-
tries 2–5). Heteroaromaticaldehydes suhc as pyri-
dine-2-carboxaldehyde,
pyridine-4-carboxaldehyde
and furfuraldehyde gave good yields of corresponding
b-hydroxy-a-diazo-carbonyl compounds (Table 2, en-
tries 6–8), in contrast to quarternary ammonium hy-
droxide reported earlier which gave poor yields. On
the other hand, aliphaticaldehydes such as valeralde-
hyde, cinnamaldehyde and isovaleraldehyde gave
poor yields of the corresponding b-hydroxy-a-diazo
carbonyl compounds (Table 2, entries 9–11). It is also
worthwhile to note that only the monocondensation
product was obtained with a 1,4-dicarboxaldehyde
(Table 2, entry 12). Imines such as 2-chloroaldimine
and 4-methoxyaldimine were also successfully em-
ployed to give the corresponding b-amino-a-diazo
carbonyl compounds with moderate yields (Table 2,
entries 14 and 15). We have also carried out the re-
action with labile substrates like 6-bromopipernal
[a]
Reaction conditions: 4-chlorobenzaldehyde (1 mmol),
EDA (1.1 mmol), catalyst (0.025 g), solvent (2 mL), reac-
tion time (6 h), room temperature, stirring rate 1500 rpm.
Isolated yields.
Yield after fourth cycle.
[b]
or 6-bromobenzo[1,3]dioxole-5-carbaldehyde and
A
[c]
TBDMS-protected aldehyde [3-(tert-butyldimethylsi-
lanyloxy)-benzaldehyde]. We obtained good yields of
the corresponding b-hydroxy-a-diazo carbonyl com-
pounds and the acetal/TBDMS moieties remained
[d]
Stirring rate: 2500 rpm.
Various solid base catalysts such as Mg/La mixed intact (Table 2, entries 16 and 17). The plausible
oxide, fluorapatite(FAP), hydroxyapatite(HAP), KF/ mechanism for the present aldol-type reaction is de-
Al2O3, commercial MgO, layered double hydroxides- picted in Scheme 2.
A
ACHTREUNG
chloride (LDH-Cl) and layered double hydroxides-
In conclusion, we have developed a simple and effi-
carbonate (LDH-CO3) were screened in water and it cient method for the preparation of b-hydroxy-a-
was found that Mg/La mixed oxide is the most effi- diazo carbonyl compounds and b-amino-a-diazo car-
cient catalyst (Table 1, entry 1). FAP, LDH-Cl and bonyl compounds by the condensation of aldehydes
LDH-CO3 (Table 1, entries 2, 6 and 7) provided mod- and imines with ethyl diazoacetate using Mg/La
erate yields of ethyl 3-hydroxy-2-diazo-3-(4-chloro- mixed oxide as a heterogeneous catalyst in water at
phenyl)-propionate whereas HAP, KF/Al2O3 and room temperature. The catalyst can be readily recov-
commercial MgO showed poor catalytic activity. The ered and reused. This methodology illustrates the fact
1888
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Adv. Synth. Catal. 2007, 349, 1887 – 1890

Aldol-Type Reaction of Aldehydes and Imines with Ethyl Diazoacetate
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Scheme 2.
preparation of b-hydroxy-a-diazo carbonyl com-
pounds and b-amino-a-diazo carbonyl compounds.
Table 2. Mg/La mixed oxide catalyzed aldol-type reaction of
aldehydes and imines with EDA.[a]
Experimental Section
Typical Procedure for Preparation of Ethyl 3-
Hydroxy-2-diazo-3-(4-chlorophenyl)-propionate
Mg/La mixed oxide (0.025 g) was added to a mixture of 4-
chlorobenzaldehyde (1 mmol), EDA (1.1 mmol) in water
(2 mL) and stirred at room temperature. After completion
of reaction (as monitored by TLC), the catalyst was centri-
fuged, washed with ethyl acetate and the centrifugate was
treated with ethyl acetate (10 mL) and stirred vigorously.
The resultant organiclayer was separated and the aqueous
layer was again extracted with ethyl acetate (5 mL). The
combined organic layer was concentrated to give the crude
ethyl
3-hydroxy-2-diazo-3-(4-chlorophenyl)-propionate.
Column chromatography was performed using silica gel
(100–200 mesh) to afford pure ethyl-3-hydroxy-2-diazo-3-(4-
chlorophenyl)-propionate as an oil; 1H NMR (300 MHz,
CDCl3): d=1.29 (t, J=7.1 Hz, 3H), 3.73 (br s, 1H), 4.23 (q,
J=7.1 Hz, 2H), 5.82 (s, 1H), 7.25–7.36 (m, 4H); MS: m/z=
254 (M+).
Supporting-Information
Characterization of all compounds with scanned 1H NMR
spectra are available in the Supporting Information
Acknowledgements
K.B.S.K, V.B and G.T.V thank UGC and CSIR, India for
their fellowships.
[a]
Reaction conditions: aldehyde/imine (1 mmol), EDA
(1.1 mmol), Mg/La mixed oxide catalyst (0.025 g), water
(2 mL), room temperature.
Isolated yields.
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