Title of Invention

PREPARATION OF NEW LAYERED DOUBLE HYDROXIDES EXCHANGED WITH DIISOPROPYLAMIDE FOR C-C BOND FORMING REACTIONS

Abstract The present invention relates to design and preparation of LDH- diisopropylamide through simple exchange process for the first time and its use in catalytic amounts for preparing aldols / α,β-unsaturated nitriles / α,β-unsaturated esters / transesterified products / P-nitroalkanols / Michael adducts and epoxide, resulting in higher yields.
Full Text Preparation of new Layered Double Hydroxides Exchanged with
Diisopropylamide for C-C Bond forming reactions
Field of the invention
The present invention relates to preparation of layered double hydroxides exchanged
with diisopropylamide (LDH-diisopropylamide) useful as recyclable catalysts for preparing
aldols / a,p-unsaturated nitriles / a,p-unsaturated esters / transesterified products / Pnitroalkanols
/ Michael adducts and epoxides. More particularly the present invention relates
to preparation of layered double hydroxides exchanged with diisopropylamide of the formula
[M1 and /or MII
(1.x) MIH
X (OH)2][NCH(CH3)2"]x/2.zH2O wherein M1 is a monovalent cation
(Li+, Na+, K+, Rb+ or Cs+), M11 is a divalent cation (Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+
or Ca2+); M111 is a trivalent ion (A13+, Cr3+, Mn3+, Fe3+, Co3+, Ni3+, or La3+); x has a value
ranging between 0.10 to 0.50 and more preferably 0.20 to 0.33; z is an integer whose values
depends on the ingredients and reactions conditions used and methods of preparation and use
thereof. The LDH-diisopropylamides of this invention are recyclable catalysts for preparing
aldols / cc,p-unsaturated nitriles / ot,p-unsaturated esters / transesterified products / pnitroalkanols
/ Michael adducts and epoxides.
This invention particularly relates to an eco-friendly process employing recyclable
LDH-diisopropylamide as an heterogeneous catalyst in place of soluble bases for preparing
aldols / a,p-unsaturated nitriles / cc,p-unsaturated esters / transesterified products / Pnitroalkanols
/ Michael adducts and epoxides by reacting with corresponding aldehydes with
acetone (Aldol condensation), aldehydes with activated nitriles or esters (Knoevenagel
condensation), alcohols with p-keto or simple esters (transesterification), aldehydes with
nitro alkanes (Henry reaction), activated methylenes with a,p-unsaturated compounds
(Michael addition), epoxidation of olefins. The obtained products are important intermediates
for the preparations of drugs, Pharmaceuticals, perfumes, cosmetics, oils, paint and fine
chemicals. For example the products of benzylidene derivatives prepared by Knoevenagel
condensation are used to inhibit tyrosine proteinase kinase, fine chemicals such as styrene
oxide, 1-decene oxide, 1-octene oxide, 1-hexene oxide, cyclohexene oxide, cyclopentene
oxide, epoxy chalcones by epoxidation of olefins, can be obtained by this method.
There are serious disadvantages in performing the reactions such as Aldol,
Knoevenagel condensation, transesterification, Henry reaction, Michael addition and
epoxidation of olefins with homogeneous system in the manufacture of aldols / a,punsaturated
nitriles / a,p-unsaturated esters / transesterified products / p-nitroalkanols /
Michael adducts and epoxides due to presence of toxic wastes remnants of neutralization of
soluble base with acid at the end of the reaction, lack of reusability and selectivity, tedious
work-up procedure, higher temperatures and longer reaction times. By employing the
heterogeneous catalytic system, the cost naturally comes down due to easy recovery and
recyclability of the catalyst for number of recycles and very insignificant loss of active
species, when compared with homogenous system. The products thus obtained using
heterogeneous catalyst system are benign in the sense that the presence of minor impurities
due to side reactions is also precluded.
Background and prior art references
Reference may be made to US patent US 4,458,026 wherein aldol condensation of
acetone is carried out by heat-treated synthetic anionic clay. The inherent disadvantages in
this process are higher temperatures and longer reaction times with lower yields.
Reference may be made to Choudary et al., Chem. Commun., 1998, 1033 wherein
aldol condensation of acetone is carried out by rehydrated hydrotalcite. The inherent
disadvantages in this process are higher temperatures, longer reaction times and lack of
selectivity.
Reference may be made to Choudary et al., Tetrahedron. Lett., 1998, 3555 wherein
aldol condensation of acetone is carried out by Mg-Al-O-t-Bu hydrotalcite. The inherent
disadvantage in this process is the catalyst is more sensitive to moisture and shelf life is
short.
Reference may be made to J. Otera Chem. Rev., 1993, 93, 1449 wherein
transesterification of alcohols are reviewed detailing many procedures under homogeneous
and heterogeneous routes. The inherent disadvantages in these processes are higher
temperatures, longer reaction times, and lack of selectivity and reusability.
Reference may be made to US patent US 5,350,879 wherein transesterification of
alcohols is carried by calcined hydrotalcites in heterogeneous way. The drawback of this
process is the reaction is carried at higher temperature.
Reference may be made to Choudary et al., J. Mol. Catal., 2000, 159, 411 wherein
transesterification is carried out by Mg-Al-O-t-Bu hydrotalcite. The inherent disadvantage
in this process is the catalyst is more sensitive to moisture and shelf life is short.
Reference may be made to Choudary et al., Tetrahedron. 2000, 56, 9357 wherein
Knoevenagel condensation and Michael addition is carried out by Mg-Al-O-t-Bu
hydrotalcite. The inherent disadvantage in this process is the catalyst is more sensitive to
moisture and shelf life is short.
Reference may be made to Choudary et al., Synlett, 1998, 1203 wherein
epoxidation of olefms is carried out by Mg-Al-O-t-Bu hydrotalcite. The inherent
disadvantage in this process is the catalyst is more sensitive to moisture and shelf life is
short.
Reference may be made to Choudary et al., J. Mol. Catal., 1999, 146, 279 wherein
Michael addition is carried out by Mg-Al rehydrated hydrotalcite. The inherent
disadvantages in this process are low yields, longer reaction times and require activation
for each catalytic cycle for reuse.
Reference may be made to Choudary et al., Green. Chem., 1999, 187 wherein
Henry reaction is carried out by Mg-Al rehydrated hydrotalcite. The inherent
disadvantages in this process are low yields, longer reaction times and require activation
for each catalytic cycle to reuse.
Objects of the invention
The main object of the present invention is to prepare a heterogeneous recyclable
LDH- diisopropylamide and use in catalytic amounts for preparing aldols / a,p-unsaturated
nitriles / a,p-unsaturated esters / transesterified products / p-nitroalkanols / Michael adducts
and epoxides which obviates the drawbacks as detailed above.
Another object of the present invention is that LDH as synthesized having
interstitial anions such as chloride, nitrate, carbonate, sulfate or calcination of LDH having
the said interstitial anions at temperatures in the range of 350 to 550°C is used as precursors
for the preparation of LDH-diisopropylamide.
Still another object of the present invention is to recover the heterogeneous LDHdiisopropylamide
used in C-C bond forming reactions comprising Aldol, Knoevenagel.
Michael,etc , transesterification and epoxidation by simple filtration and reuse for number of
cycles with consistent activity and selectivity.
Still another object of the present invention is the quantity of LDHdiisopropylamide
used in the reaction contains 1 to 10 mol % of diisopropylamide with
respect to the substrate.
Summary of the Invention:
The novelty of the present invention lies in the design and preparation of LDHdiisopropylamide
through simple exchange process for the first time and its use in catalytic
amounts for preparing aldols / a,p-unsaturated nitrites / oc,p-unsaturated esters /
transesterified products / p-nitroalkanols / Michael adducts and epoxides. Higher yields were
obtained when LDH-diisopropylamide catalysts are used in the C-C bond forming
epoxidation, and transesterification reactions in organic solvents. The products obtained by
various methods are important intermediates for the preparation of drugs, Pharmaceuticals,
perfumes, cosmetics, oils, paints and fine chemicals. The consistent activity for several
cycles in C-C bond formation reactions makes the processes economical and possible for
commercial realisation. Therefore, LDH-diisopropylamide is better option for the synthesis
of aldols / oc,p-unsaturated nitriles / a,p-unsaturated esters / transesterified products / Pnitroalkanols
/ Michael adducts and epoxides. Thus this invention offers the best technoeconomic
route for the synthesis of intermediates in the preparation of drugs,
Pharmaceuticals and fine chemicals. The use of different metals and in varied compositions
used in the preparation of LDH support has showed little impact on its final form of LDHdiisopropylamide
with respect to activity.
Detailed description of the invention:
Accordingly the present invention provides a process for the preparation of layered double hydroxide exchanged with diisopropylamide catalyst as represented herein below:
[M1 and/or M11(1-x)M111(x)(OH)2][NCH(CH3)2]x/2.zH20.
Wherein M1 is a monovalent cation
M11 is a bivalent cation
M111 is a trivalent cation
X=0.10to0.50
Z is an integer, whose value depends on the ingredients and the reaction conditions used,
the said process comprising steps of:
a) reacting layered double hydroxide of general formula represented as described herein
[M1 and/or M11(1-x)M111(x)(OH)2] [An]x/2.zH2O wherein An_ is selected from the group consisting of chloride, nitrate, carbonate or sulphate with lithium diisopropylamide in an organic solvent under an inert atmosphere of nitrogen at a temperature ranging between 20°-30°C for a period of 5 to 24 hours, and. b) filtering the reaction mixture of step (a) to obtain the required layered double hydroxide exchanged with diisopropylamide catalyst of general formala (1), referred to as LDH-diisopropylamide catalyst.
In an embodiment of the present invention, a process for the preparation of the catalyst LDH-diisopropylamide of the formula [M1 and/or M11(1-x)M111(x)(OH)2][NCH(CH3)2]x/2.zH20] wherein the said process comprises reacting lithium diisopropylamide of formula LiNCH(CH3)2 with a LDH of formula [M1 and/or M11(1-x)M111(x)(OH)2][NCH(CH3)2]x/2.zH20] wherein x has a value ranging between 0.10 to 0.50 and more preferably 0.20 to 0.33; z is an integer whose values depends on the ingredients and reactions conditions used; An" is an anion selected from nitrate, carbonate, sulphate or chloride; M1 is a monovalent cation selected from the group consisting of Li, Na, K, Rb, Cs, M11 is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2*, Cu2*, Zn2+, V2*, Cr2+, or Ca2+ and M111 is a trivalent ion selected from the group consisting Al3+, Cr3+, Mn3+, V3+, Fe3+, Co3+, Ru3+, Rh3+, Ga3+, ln3+, or La3* in an organic solvent selected from the group consisting of organic solvent selected from the group consisting of organic solvents selected from group consisting of methanol, ethanol, isopropanol, 1-propanol, 1-

butanol, 2-butanol and tert-butyl alcohol, acetonitrile, tetrahydrofuran, dichloromethane,
dichloroethane at a temperature ranging between 20 to 30°C for a period of 5 to 24 h under
the nitrogen atmosphere followed by filtration to obtain the desired catalyst.
In an embodiment of the present invention, a method for the preparation of aldols /
ct,p-unsaturated nitriles / a,p-unsaturated esters / transesterifled products / p-nitroalkanols
Michael adducts and epoxides using the recyclable catalyst LDH- diisopropylamide of the
formula [M1 and/or Mn(i.X) Mm
x (OH)2][NCH(CH3)2']x/2.zH2O wherein M1 is a monovalent
cation (Li, Na, K, Rb, Cs), M11 is a divalent cation (Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+
V2+, Cr2+, or Ca2+); M111 is a trivalent ion (A13+, Cr3+, Mn3+, V3+, Fe3+, Co3+, Ru3+, Rh3+, Ga3+,
In3"1", or La3+) as recyclable catalysts for Aldol condensation (aldehydes with acetone),
Knoevenagel condensation (aldehydes with activated nitriles or esters), transesterification
(alcohols with p-keto or simple esters), Henry reaction (aldehydes with nitro alkanes),
Michael addition (activated methylenes with a,p-unsaturated compounds), epoxidation of
olefms in a solvent selected from acetone, methanol, ethanol, dichloromethane, chloroform,
1-propanol, 2-propanol, toluene, nitromethane, acetonitrile and / or t-butanol at a temperature
in the range of 10 to 120°C for a period 0.15 to 24 h, and obtaining the pure product by
conventional method.
In an embodiment of the present invention, a catalyst having the diisopropylamide
contents ranges between 1 to 30 % of diisopropylamide.
In an embodiment of the present invention, LDH as synthesized having interstitial
anions such as chloride, nitrate, carbonate, sulfate or calcination of LDH having the said
interstitial anions at temperatures in the range of 350 to 550°C is used as precursors for the
preparation of LDH-diisopropylamide.
In an embodiment of the present invention, the quantity of LDH- diisopropylamide
used in the reactions contains 0.01 to 15mol% of diisopropylamide content with respect to
the substrate.
In an embodiment of the present invention, LDH-diisopropylamide is reused for
several cycles with consistent activity.
In another embodiment of the present invention, the solvent selected is acetone,
methanol, ethanol, dichloro methane, chloroform, 1-propanol, 2-propanol, toluene,
nitromethane, acetonitrile and / or t-butanol, etc.
In still another embodiment of the present invention, the reaction is, preferably,
effected at a known temperature, in the range of 10 to 120°C for a period of 0.15 to 24
In still another embodiment of the present invention, the products formed by
various methods are important intermediates for the preparations of drugs, Pharmaceuticals,
perfumes, cosmetics, oils, paints and fine chemicals. For example the products of
benzylidene derivatives prepared by Knoevenagel condensation are used to inhibit tyrosine
proteinase kinase, fine chemicals such as styrene oxide, 1-decene oxide, 1-octene oxide, 1-
hexene oxide, cyclohexene oxide, cyclopentene oxide, epoxy chalcones by epoxidation of
olefms, can be obtained by this method.
Scientific Explanation:
In the present invention, we prepared LDH-diisopropylamide for the first time and
used in catalytic amounts for the preparation of aldols / a,(3-unsaturated nitriles / a,(3-
unsaturated esters / transesterified products / p-nitroalkanols / Michael adducts and epoxides
in a heterogeneous way.
LDH-diisopropylamide is prepared by anion exchange method from the LDH
containing chloride, nitrate anions or their calcined forms. The diisopropylamide anions in
LDH are responsible for the Aldol and Knoevenagel condensations, transesterification,
Henry reactions, Michael addition and epoxidation reactions. The activity of LDHdiisopropylamide
is similar or higher than the homogeneous counter parts. The higher
activity is ascribed to the support effect. The basic LDH-NCH(CH3)i induces abstraction of
proton from the active methylene group to trigger C-C coupling in epoxidation and
transesterification reactions.
Higher yields are obtained with LDH- diisopropylamide catalysts and the products
are important intermediates for the preparation of drugs and pharmaceuticals, this invention
is timely and appropriate. Therefore, LDH-diisopropylamide is a better option. The LDHdiisopropylamide
catalysts prepared by various metals showed little variation in the catalytic
activity. Albeit, all the metals used in the preparation of LDH offered good to excellent
yields. Thus this invention offers the best techno-economic route for the preparation of
intermediates of drugs, pharmaceuticals, perfumes, cosmetics, oils, paints and fine chemicals.
LDH-diisopropylamides are prepared as exemplified and used in catalytic amounts
for preparing aldols / a,p-unsaturated nitriles / oc,p-unsaturated esters / transesterified
products / p-nitroalkanols / Michael adducts and epoxides in a heterogeneous way as
described in the examples.
The following examples are given by way of illustration of the present invention and
therefore should not be construed to limit the scope of the invention.
Preparation of Layered Double Hydroxides
Example 1
Preparation ofMg2+/Al3+/NO3~ -LDH (la)
The Mg2+/Al3+/NO3" LDH with a Mg/Al ratio of 3:1 was prepared from magnesium nitrate
hexahydrate (30.8 g, 0.12 mol) and aluminum nitrate nonahydrate (15.0 g, 0.04 mol) which
were dissolved in 100 ml of deionised and decarbonated water. The pH of the solution was
adjusted to -10 by the addition of NaOH (2M). The slurry was stirred for 2 h at room
temperature under nitrogen atmosphere and then filtered under nitrogen atmosphere, washed
thoroughly and dried under vacuum at 80°C.
Example 2
Preparation of Calcined Mg2+/Al3+'-LDH (Ib)
The Mg2+/Al3+/NO3~ LDH with a Mg/Al ratio of 3:1 was prepared from magnesium nitrate
hexahydrate (30.8 g, 0.12 mol) and aluminum nitrate nonahydrate (15.0 g, 0.04 mol) which
were dissolved in 100 ml of deionised and decarbonated water. The pH of the solution was
adjusted to -10 by the addition of NaOH (2M). The slurry was stirred for 2 h at room
temperature under nitrogen atmosphere and then filtered under nitrogen atmosphere, washed
thoroughly and dried under vacuum at 80°C. The solid was then dried and calcined at 450°C
for 6h in airflow.
Example 3
Preparation ofMg2+/A!3+/Cr -LDH (Ic)
A mixture of MgCl2.6H2O (30.49 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol)
was dissolved in 200 mL of deionised water. The resultant aqueous solution was slowly
added at 25°C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow.
The pH of the reaction mixture was maintained constantly (-10) by the continuous addition
of 2 M NaOH. The suspension thus obtained was stirred overnight under a nitrogen
atmosphere at 70°C. The solid product was isolated by filtration, washed thoroughly with
deionised water, and dried overnight at 80°C. Decarbonated water was used in all the
synthetic steps. Mg2+/Al3+/Cl~ hydrotalcites of the different Mg/Al ratios were also prepared
similarly, using appropriate amounts of magnesium chloride hexahydrate and aluminium
chloride hexahydrate.
Example 4
Preparation ofMg2+/Al3+/Cl~ -LDH (Id)
A mixture of MgCl2.6H2O (30.49 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was
dissolved in 200 mL of deionised water. The resultant aqueous solution was slowly added at
25 °C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH of
the reaction mixture was maintained constantly (-10) by the continuous addition of 2 M
NaOH. The suspension thus obtained was stirred overnight under a nitrogen atmosphere at
70°C. The solid product was isolated by filtration, washed thoroughly with deionised water,
and dried overnight at 80°C. Decarbonated water was used in all the synthetic steps.
Mg2+/Al3+/Cl" hydrotalcites of the different Mg/Al ratios were also prepared similarly, using
appropriate amounts of magnesium chloride hexahydrate and aluminium chloride
hexahydrate. The solid was then dried and calcined at 450°C for 6h in airflow.
Example 5
Preparation of Mg2+/Al3+/CO3
-LDH (Calcined, le)
A mixture of 60.09 g of Mg(NO3)2.6H20 (0.234 mol) and 29.31 g of A1(NO3)3.9H2O (0.078
mol) in 70 ml distilled water was added to a solution of 28.12 g, 50% aq. NaOH (0.703 mol)
and 22.08 g Na2CO3 (0.41 mol) in 100 ml distilled water. The addition was carried out slowly
in a 500 ml flask equipped with a mechanical stirrer and the resultant heavy slurry was
heated at 65 ± 5°C for about 18 h. The slurry was allowed to cool to room temperature,
filtered and washed. The solid was then dried and calcined at 450°C for 6h in airflow.
Example 6
Preparation ofNi2+/Al3+/Cr-LDH (If)
A mixture of NiCl2.6H2O (35.65 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was
dissolved in 200 mL of deionised water. The aqueous solution was slowly added at 25 °C to
100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH was
constantly maintained (-10) by the continuous addition of 2 M NaOH. The suspension was
stirred overnight under a nitrogen atmosphere at 70°C. The solid product was isolated by
filtration, washed thoroughly with deionised water, and dried overnight at 80°C. All
synthetic steps were carried out using decarbonated water.
Example 7
Preparation ofLi+/Al3+/Cr -IDE (Ig)
The Li+/Al3+/Cl" LDH with a Li/Al ratio of 1:2 was prepared as follows. Aluminum nitrate
nonahydrate (12.07 g, 0.05 mol) was dissolved in 100 ml of 2M (8.0 g) NaOH. Lithium
nitrate (1.025 g, 0.025 moles in 100ml) was dissolved in this solution, and mixture heated for
48 hours at 90 °C. The product was washed with deionised and decarbonated water followed
by 0.1 M sodium chloride solution and the resultant solid was dried at 80°C for 5h. Care was
taken to exclude the CO2 during the synthesis.
Example 8
Preparation of Calcined Li+/Al3+-LDH (Ih)
The Li+/Al3+/Cl" LDH with a Li/Al ratio of 1:2 was prepared as follows. Aluminum nitrate
nonahydrate (12.07g, 0.05 mol) was dissolved in 100 ml of 2M (8.0 g) NaOH. Lithium
nitrate (1.025 g, 0.025 moles in 100ml) was dissolved in this solution, and mixture was
heated for 48 hours at 90 °C. The product was washed with deionised and decarbonated
water followed by 0.1M sodium chloride solution and the resultant solid was dried at 80°C
for 5h. Care was taken to exclude the COi during the synthesis. The solid was calcined at
450°C for 6h in airflow.
Preparation of LDH-diisopropylamide
Example 9
Preparation of(Mg-Al)LDH-NCH(CH})2'(IIa) from Mg2+/Al3+/NO3'-LDH(Ia)
1.214g of la was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11% of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 10
Preparation of(Mg-Al)LDH-NCH(CH3)i(Hb)from Calcined Mg2+/Al3+--LDH (Ib)
1.214 g of Ib was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 11
Preparation of(Mg-Al)LDH-NCH(CH3)2~(IIc)from Mg2+/Al3+/Cr-LDH (Ic)
1.214 g of Ic was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under Na atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 12
Preparation of(Mg-Al)LDH-NCH(CH3)2~(IId)from Mg2+/Al3+/Cr-LDH (Id)
1.214 g of Id was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 13
Preparation of(Mg-Al)LDH-NCH(CH3)2(IIe)from Mg2+/A13+/CO/'-LDH (Calcined, le)
1.214 g of le was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 14
Preparation of(Ni-Al)LDH-NCH(CH3)i(IIf> Ni2+/Al3+/Cr-LDH (If)
1.214 g of If was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 15
Preparation of(Li-Al)LDH-NCH(CH3)2'(IIg)from Li+/Al3+/Cl' -IDE (Ig)
1.214 g of Ig was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under N2 atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11% of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
Example 16
Preparation of(Li-Al)LDH-NCH(CH3)2'(IIh)from Calcined Li+/Al3+-LDH (Ih)
1.214 g of Ih was suspended in 100 ml of lOmmol (1.0713g) solution of lithium diisopropyl
amide in dry THF and stirred at 25°C for 24 h under Na atmosphere. The solid product is
filtered, washed with dry THF (250ml) and vacuum dried. Chemical analysis showed that the
product contains 11 % of diisoproylamide. This means that 1.1 mmol of diisoproylamide per
1 gram of the product.
C-C Bond forming reactions
The C-C bond forming reactions were performed using LDH-NCH(CH3)2 catalysts to
evaluate of the present invention.
Example 17
Aldol reaction between benzaldehyde and acetone catalysed by LDH-NCH(CHi)2 (Ha)
A two-necked flask was charged with 0.2 ml (2 mmol) of benzaldehyde, 50 mg of
catalyst Ha , 5 ml of acetone and the contents were stirred at room temperature. After
completion of the reaction (followed by TLC), the catalyst was filtered off and washed with
acetone (2x5 ml). The filtrate was concentrated under reduced pressure. The product thus
obtained was purified by column chromatography to afford the corresponding aldol in 95%
yield.
Example 18
Aldol reaction between 4-nitrobenzaldehyde and acetone catalysed by LDH~NCH(CHi)2
catalyst (Ha)
A two-necked flask was charged with 0.24g (2 mmol) of 4-nitrobenzaldehyde, 50 mg of
catalyst Ha, 5 ml of acetone and the contents were stirred at room temperature. After
completion of the reaction (followed by TLC), the catalyst was filtered off and washed with
acetone (2x5 ml). The filtrate was concentrated under reduced pressure. The product thus
obtained was purified by column chromatography to afford the corresponding aldol in 93%
yield.
Example 19
Aldol reaction between 4-nitrobenzaldehyde and acetone catalysed by LDH-NCH(CH3)2
catalyst (lib): Recycle experiment.
A two-necked flask was charged with 0.24g (2 mmol) of 4-nitrobenzaldehyde, 50 mg
of used catalyst lib of example 15, 5 ml of acetone and the contents were stirred at room
temperature. After the completion of reaction, the catalyst was allowed to settle and the
supernatant solution was pumped out from the reaction flask. The catalyst was washed with
dry acetone four times ( 4 X 5 mL), allowed to settle and the supernatant acetone solution on
each wash was pumped out. Fresh quantities of 4-nitrobenzaldehyde and acetone were
introduced. The catalyst was thus recycled for six cycles with consistent activity and
selectivity. The filtrate was concentrated under reduced pressure. The product thus obtained
was purified by column chromatography to afford the corresponding aldol in 95% yield.
Examples 20-24
For recycle experiments the procedure was followed as in example 19 and the results
are presented in Table 1.
Examples 25-30
The procedure was followed as in example 18 with various catalysts Ilc-IIh and the
results are presented in Table 1.
Examples 31-36
A Idol reaction between substituted benzaldehydes and acetone catalysed by LDHNCH(
CH3)2 catalyst (lib)
The procedure was followed as in example 18 and the results are given in Table 2.
aReaction conditions as exemplified in Example 1 8
Knoevenagel condensation:
Knoevenagel condensation reactions involving various aromatic aldehydes compounds with
(a) malononitrile and (b) ethyl cyanoacetate (Scheme 2) as the active methylene compounds
were carried out with LDH-NCH(CH3)2 catalyst (lib) at room temperature (Table 3).
Example 37
General procedure for Knoevenagel condensation:
Aldehyde (2 mmol) and 0.05 g of Mg-Al-NCH(CH3)2 LDH (lib) were stirred in 5 ml of
dimethylformamide for 5 min. Then the active methylene compound (2 mmol) was added
and stirring was continued till the completion of the reaction, as monitored by thin layer
chromatography (TLC). The catalyst was filtered and the product was extracted with ethyl
acetate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The
crude product was purified by column chromatography.
Examples 38-49
The procedure was followed as in example 37 and the results are given in Table 3.
Henry reactions:
Henry reactions involving various aromatic aldehydes compounds with nitromethane
(Scheme 3) as the active methylene compound is carried out with LDH-NCH(CH3)2 catalyst
Scheme-3
Example 50
General procedure for Henry reactions:
To a mixture of nitroalkane (10 mmol) and benzaldehyde (2 mmol), 0.03 g of catalyst (lib)
was added at room temperature and stirred till completion of the reaction, as monitored by
TLC. The catalyst was filtered and washed with dichloromethane (10 ml x 3). Then, the
filtrate was concentrated under reduced pressure.
Examples 51-57
The procedure was followed as in example 50 and the results are given in Table 4.
Example 58
General procedure for transesterification reactions:
In a two-necked round bottomed flask, (Immol) of ester ,(lmmol) of alcohol and 25mg of
catalyst (lib) in 10ml dry toluene were stirred at 90-100 °C and reaction was monitored by
thin layer chromatography (TLC). Work-up comprises of simple filtration followed by
evaporation under reduced pressure and purified by column chromatography
(hexane/ethylacetate, 95/5, v/v) to afford the product. The product was analysed by NMR, IR
and Mass spectra, which were in accordance with those obtained by literature procedures.
Reaction conditions as exemplified in Example 58.
Isolated Yields
Examples 59-67
The procedure was followed as in example 58 and the results are given in Table 5.
Epoxidation of olefins:
Incorporation of diisopropylamide in the interlayers of LDH by anion-exchange
provided a simple methodology for the preparation of Mg-Al-NCH(CH3)2 LDH. In the
present endeavor, we describe a magnificent display of superactivity in the epoxidation of
unfunctionalised as well as electron deficient olefins employing lib and hydrogen peroxide
as an oxidant under a set of different conditions as described in Scheme 5 and 6.
LDH-LDA-Catalyst
Methanol, roomtemp
Scheme-5
Example 68
General procedure for the epoxidation offunctionalised olefins:
1 mmol of enone and 0.03 g of catalyst (lib) were taken inlO ml of methanol in a 50ml twonecked
round bottom flask. To this solution, 0.35ml (3mmol) of aqueous hydrogen peroxide
(30% w/w) was added slowly at room temperature under continuous stirring. The reaction
was monitored by thin layered chromatography (TLC) till the completion of reaction. After
the completion, the solid was separated by filtration and washed with diethyl ether. The
solution was evaporated and the residuum is re-dissolved in methylene choride, the solution
is then dried over sodium sulfate, the solvent was eliminated under reduced pressure and
subjected to a silica gel chromatography using a mixture of n-hexane-EtOAc (40:1, v/v) as
an eluent to afford pure product.
aReaction conditions as exemplified in Example 68.
b Isolated yields
Examples 69-74
The procedure was followed as in example 68 and the results are given in Table 6.
Example 75
General procedure for the epoxidation ofunfunctionalisedolefins:
Into a round-bottomed flask with a reflux condenser were successively placed 0.03g of
catalyst (lib), 10ml of methanol, 4mmol of alkene, 1.0ml of benzonitrile (10.5 mmol) and
2.4ml of 30% hydrogen peroxide. The resulting mixture was stirred at 60°C and monitored
by thin layered chromatography. After the completion of reaction, the hydrotalcite was
separated by filtration and filtrate was treated with MnC2 (0.03g) to decompose the
remaining HC. The filtrate was diluted with deionized water (20ml) and extracted with
CHCls (20ml X 3). The extract was concentrated under reduced pressure and subjected to a
silica gel chromatography using a mixture of n-Hexane-EtOAc (40:1, v/v) as a eluant to
afford the pure product.
Examples 76-82
The procedure was followed as in example 75 and the results are given in Table 7.
Michael addition:
The selective 1, 4 addition (Michael reaction) on acceptors (1) (a,(3-unsaturated compound)
e.g. simple or substituted chalcones and cyclohexanone by donors (2) (active methelene
compound) such as nitromethane, diethylmalonate and diethylmalonate catalysed by
Example 83
General procedure for Michael reaction:
Acceptor (2 mmol) and O.OSg of LDH-NCH(CH3)2 catalyst (Ilb)were stirred in 10 ml of
methanol for 5 min., then donor (2 mmol) was added and stirring was continued until the
completion of the reaction which was monitored by thin layer chromatography (TLC). The
catalyst was filtered and the filtrate was concentrated under reduced pressure. The crude
product was purified by column chromatography (Acme Synthetic Chemicals, 60-120 mesh,
silica gel using ethyl acetate/hexane). The products were well characterized by !H NMR,
Mass and IR spectrometry.
Examples 84-90
The procedure was followed as in example 83 and the results are given in Table 8.
aReaction conditions as exemplified in Example 83.
blsolated Yield, Cn-Hexane used as solvent.
The main advantages of the present invention are:
1. A novel and ecofriendly process for C-C bond forming reactions is presented.
2. The present process dispenses the use of soluble bases, or lithiumdiisopropylamide
instead a heterogeneous reusable LDH-diisopropylamide is used.
3. LDH-diisopropylamide is prepared and used for C-C bond forming reactions under
heterogeneous catalysis. The use of heterogeneous LDH-diisopropylamide precludes the
presence of by-products.
4. The process is accomplished in a short time to afford high productivity.
5. The work-up procedure is simple.
6. The catalyst is subjected to many recycles, which displayed consistent activity and
selectivity.
7. The present process is environmentally safe since there is no disposal problem.
8. The process is economical.



We Claim:
1. A process for the preparation of layered double hydroxide exchanged
with diisopropylamide catalyst as represented herein below:
[M1 and/or M11(1-x)M111(x)(OH)2][NCH(CH3)2]x/2.zH20.
Wherein M1 is a monovalent cation
M11 is a bivalent cation
M111 is a trivalent cation
X=0.10to0.50
Z is an integer, whose value depends on the ingredients and the
reaction conditions used,
the said process comprising steps of:
c) reacting layered double hydroxide of general formula represented as described herein [M1 and/or M11(1-x)M111(x)(OH)2] [An-]x/2.zH20 wherein An- is selected from the group consisting of chloride, nitrate, carbonate or sulphate with lithium diisopropylamide in an organic solvent under an inert atmosphere of nitrogen at a temperature ranging between 20°-30°C for a period of 5 to 24 hours, and. d) filtering the reaction mixture of step (a) to obtain the required layered double hydroxide exchanged with diisopropylamide catalyst of general formala (1), referred to as LDH-diisopropylamide catalyst.
2. A process as claimed in claim 1 wherein the monovalent cation is
selected from a group consisting of lithium (Li+), sodium (Na+),
potassium (K+), rubium (Rb+)or cesium (Cs+).

3. A process as claimed in claim 1 wherein the bivalent cation is selected from a group consisting of magnesium (Mg2+), manganese (Mn2+), iron (Fe2+), cobalt (Co2+), nickel (Ni2+), copper (Cu2+), zinc (Zn2+), vanadium (V2+), chromium (Cr2*) or calcium (Ca2+).
4. A process as claimed in claim 1 wherein the trivalent cation is selected from a group consisting of aluminium (Al3+), chromium (Cr3+), manganese (Mn3+), vanadium (V3+), iron (Fe3+), cobalt (Co3+), ruthenium (Ru3+), rhodium (Rh3+), gallium (Ga3+), indium (ln3+) or lanthanum (La3+).
5. A process as claimed in claim 1 wherein step (a) , the organic solvent used is selected from a group consisting of methanol, ethanol, isorpopenol, 1-propanol, 1-butanol, 2-butanol, t-butanol, acetonitrile, tetrahydrofuran, dichloromethane or dichloroethane.
6. A process as claimed in claim 1 wherein the value of x ranges between 0.1 to 0.5 and more preferably 0.20 to 0.33.
7. A process as claimed in claim 1, wherein in step (b) the said catalyst LDH-diisopropylamide has diisopropylamide content ranging between 5 to 30%.
8. A process as claimed in claim 1 wherein the said catalyst LDH-diisopropylamide is used in the LDH-diisopropylamide catalyst as claimed in claim 1 which can be used in the preparation of aldols, α,ß-unsaturated nitriles, ,α,ß-unsaturated esters, transesterified products, ß -nitroalkanols, Michael addition products and epoxides.

9. A process as claimed in claim 1, wherein the LDH-diisopropylamide catalyst used provides 0.01 to 15 mole% of disopropylamide content with respect to substrate used in the reaction.
10. A process for preparation of new layered double hydroxides exchanged with diisopropylamide for C-C bond forming reactions substantially as herein described with reference to the examples.

Documents:

124-del-2003-abstract.pdf

124-DEL-2003-Claims-(01-10-2008).pdf

124-del-2003-claims.pdf

124-DEL-2003-Correspondence-Others-(01-10-2008).pdf

124-del-2003-correspondence-others.pdf

124-del-2003-correspondence-po.pdf

124-DEL-2003-Description (Complete)-(01-10-2008).pdf

124-del-2003-description (complete).pdf

124-DEL-2003-Form-1-(03-10-2008).pdf

124-del-2003-form-1.pdf

124-del-2003-form-18.pdf

124-del-2003-form-2.pdf

124-DEL-2003-Form-3-(03-10-2008).pdf

124-del-2003-form-3.pdf

124-DEL-2003-Petition-137-(03-10-2008).pdf


Patent Number 227511
Indian Patent Application Number 124/DEL/2003
PG Journal Number 05/2009
Publication Date 30-Jan-2009
Grant Date 12-Jan-2009
Date of Filing 17-Feb-2003
Name of Patentee COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH
Applicant Address RAFI MARG, NEW DELHI-110001, INDIA.
Inventors:
# Inventor's Name Inventor's Address
1 BOYAPATI MANORANJAN CHOUDARY INDIA INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, ANDHRA PRADESH, INDIA.
2 ADURI RAVINDRA INDIA INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, ANDHRA PRADESH, INDIA.
3 MANNEPALLI LAKSHME KANTAM INDIA INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, ANDHRA PRADESH, INDIA.
4 CHINTA REDDY VANKAT REDDY INDIA INSTITUTE OF CHEMICAL TECHNOLOGY, HYDERABAD, ANDHRA PRADESH, INDIA.
PCT International Classification Number C07D 413/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA