Process for the preparation of 1,1-cyclopropanedicarboxylic...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters

Reexamination Certificate

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C560S127000, C560S203000

Reexamination Certificate

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06462224

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a process for the preparation of 1,1-cyclopropanedicarboxylic diesters from malonic diesters, 1,2-dihaloethane and alkali metal carbonate in the presence of a mixture of a phase transfer catalyst and polyalkylene glycol or a capped derivative thereof.
2. Discussion of the Background
A solvent-free process for the cycloalkylation of malonic dialkyl esters, in which a 2-to 5-fold, most preferably 2.2- to 4-fold, molar excess of sodium carbonate or potassium carbonate is used, is described by Katsuro et al. in Japanese patent JP 06 234 705.
A large carbonate excess of this type results in a high salt loading, which prevents industrial realization of the process because of cost and ecological aspects.
Furthermore, water is added to the reaction and water which forms during the reaction is not removed. Accordingly, the water present in the reaction mixture causes partial hydrolysis of the used malonic ester, thus reducing the yield of the target product.
In the above process a quartenary alkylammonium halide is initially introduced at room temperature.
However, experimental results show that this practice leads to partial deactivation of the phase transfer catalyst, and accordingly a large amount of the costly phase transfer catalyst is required. For example, Katsuro et al. used 30 mol % of the phase transfer catalyst tetrabutylammonium bromide (TBAB), based on the malonic diester.
Furthermore, the target product is worked up and isolated via phase separation with subsequent extraction of the aqueous phase which is economically not very attractive. Work-up of this type results in a 1,2-dichloroethane-contaminated waste water stream, the disposal of which is problematical.
SUMMARY OF THE INVENTION
An object of the present invention was therefore to provide a process which does not have the disadvantages as described above.
This and other objects are achieved according to the invention, the first embodiment of which includes a process for the preparation of 1,1-cyclopropanedicarboxylic diesters, comprising:
a) reacting malonic diester, 1,2-dihaloethane and alkali metal carbonate in the presence of available or in-situ-produced phase transfer catalyst and polyalkylene glycol or at least one derivative of polyalkylene glycol which is capped at one or both ends;
wherein a molar ratio of malonic diester: 1,2-dihaloethane: alkali metal carbonate is 1:(1 to 7):(1 to 1.4);
wherein a reaction temperature is ≧70° C.;
b) azeotropically distilling off water produced during the reaction with 1,2-dihaloethane;
c) separating off the reaction salt by a mechanical separation operation;
d) distilling off an excess of 1,2-dihaloethane; and
e) fractionally distilling off said 1,1-cyclopropanedicarboxylic diester;
wherein said reacting proceeds according to the schematic reaction equation
wherein R and R
1
independently are an unbranched or branched alkyl group having from 1 to 6 carbon atoms;
Z is nitrogen or phosphorus; and
R
2
, R
3
, R
4
and R
5
independently are an unbranched or branched alkyl group having from 1 to 16 carbon atoms, an aryl, alkylaryl or arylalkyl radical having from 6 to 12 carbon atoms or a 1,2-dihaloethyl group;
n is an integer or a fraction from 1 to 30;
R
6
is an ethylene radical, a propylene radical, or a mixed compound with ethylene and propylene radicals, and
R
7
and R
8
independently are a hydrogen radical, an unbranched or branched alkyl group having from 1 to 6 carbon atoms or an acyl group having from 2 to 7 carbon atoms;
Y and Y′ independently are chlorine, bromine or iodine;
Y″ is chloride, bromide, iodide or hydrogen sulfate; and
X is Na or K.
Another embodiment of the invention includes a 1,1-cyclopropanedicarboxylic diester prepared by the above process.
DETAILED DESCRIPTION OF THE INVENTION
We have now found that the addition of a mixture of phase transfer catalyst leads to significantly improved space-time yields during the synthesis of 1,1 -cyclopropanedicarboxylic diesters. Preferred phase transfer catalysts are quaternary ammonium halide, polyalkylene glycol or derivatives thereof which are capped at one or both ends, in particular those with ether end groups.
The invention therefore provides a process for the preparation of 1,1-cyclopropanedicarboxylic diesters according to the schematic reaction equation
which comprises
a) allowing malonic diester, 1,2-dihaloethane and alkali metal carbonate to react in the presence of available or in-situ-produced phase transfer catalyst and polyalkylene glycol or derivatives thereof which are capped at one or both ends, in particular those with ether end groups, where the molar ratio of malonic diester: 1,2-dihaloethane: alkali metal carbonate is 1:(1 to 7):(1 to 1.4), preferably 1:(2.5 to 3.8):(1.1 to 1.4),
b) carrying out the reaction essentially at a reaction temperature of ≧70° C. on account of the quantitative ratios,
c) distilling off the water of reaction azeotropically with the 1,2-dihaloethane,
d) separating off the reaction salt by means of a mechanical separation operation,
e) distilling off the excess 1,2-dihaloethane, and
f) fractionally distilling off the 1,1-cyclopropanedicarboxylic diester.
R and R
1
independently of one another are each an unbranched or branched alkyl group having from 1 to 6 carbon atoms, preferably from 1 to 4 carbon atoms, in particular the methyl, ethyl, n-propyl or n-butyl group. Z is nitrogen or phosphorus as the central atom of the phase transfer catalyst.
R
2
, R
3
, R
4
and R
5
independently of one another are each an unbranched or branched alkyl group having from 1 to 16 carbon atoms, an aryl or alkylaryl radical having from 6 to 12 carbon atoms, preferably the phenyl radical, an aralkyl radical having from 6 to 12 carbon atoms, preferably the benzyl radical, or 1,2-dihaloethane used. In a preferred embodiment, R
2
, R
3
, R
4
and R
5
are identical and are each a butyl group.
R
6
is an ethylene or propylene radical, mixed compounds with ethylene and propylene radicals also being included.
R
7
and R
8
independently of one another are a hydrogen radical, an unbranched or branched alkyl group having from 1 to 6 carbon atoms, preferably a methyl or ethyl group, or an unbranched or branched acyl group having from 2 to 7 carbon atoms.
n is a mean number from 1 to 30, preferably from 2 to 20, and can also be a fraction. n is preferably chosen such that the polyalkylene or polyalkylene glycol derivative is liquid at room temperature.
Y and Y′ independently of one another are chlorine, bromine or iodine,
Y″ is chloride, bromide, iodide or hydrogen sulfate, and
X is Na or K.
Preferred malonic diesters are dimethyl malonate (DMM) or diethyl malonate (DEM). It is also possible to use mixed esters, such as methylethyl malonate, or mixtures of the esters.
The 1,2-dihaloethane is preferably 1,2-dichloroethane (EDC). It is also possible to use mixed 1,2-dihaloethanes with different halogen atoms such as chloride, bromide or iodide.
Preferred alkali metal carbonates are sodium carbonate, potassium carbonate, or mixtures of the two carbonates. Preference is given to using potassium carbonate. The potassium carbonate preferably has a fines content of 85% <0.1 mm and 70% <0.05 mm.
Tetrasubstituted ammonium or phosphonium compounds (quaternary salts) can be used as phase transfer catalysts. The radicals on the nitrogen or phosphorus atom can in principle be different, but are preferably identical. The anion is preferably a halogen ion such as chloride, bromide or iodide. Preferred are tetraalkylammonium salts, more preferred are tetrabutylammonium halide (tetrabutylammonium bromide, TBAB), benzyltrimethylammonium salts or tetrabutylphosphonium salts.
The phase transfer catalyst can also be generated in situ from, for example, trialkylamine and 1,2-dihaloethane.
The polyalkylene glycol used is preferably polyethylene glycol. The same is true for the derivatives which are capped at one or both ends, in particular those with ether end groups, the end groups preferably being

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