Process for the preparation of keto compounds

Keto compounds are prepared by a condensation reaction in which an enolate is formed, and then a protonation in which the free keto compound is produced. In accordance with the invention, both condensation and protonation are carried out in one step by electrodialysis. Transesterification can also be carried out in the same step.

BACKGROUND OF THE INVENTION 
The present invention relates to a novel process for the preparation of 
keto compounds by condensation reactions. 
DISCUSSION OF THE BACKGROUND 
Keto compounds are valuable intermediates in the preparation of, for 
example, heterocycles, pharmaceuticals, plant protection agents and aroma 
substances. 
It is possible, by ester condensation reactions, to convert carboxylic 
esters to dicarbonyl compounds. In accordance with this method, for 
example, acetoacetic esters can be prepared from acetic esters. Similarly, 
using acetic esters, lactones can also be converted into the corresponding 
acetyl derivatives. In this case the reaction takes place in two steps. In 
step 1, a condensation is carried out under alkaline conditions, and then 
the enolate formed is protonated in step 2. The reaction is illustrated by 
the following scheme, taking as an example the preparation of methyl 
acetoacetate from methyl acetate: 
1. Condensation 
##STR1## 
2. Protonation 
##STR2## 
In accordance with the process in step 2 of the German Patent Application P 
44 33 823.6, protonation is carried out by electrodialysis. In this case, 
for the protonation, use is preferably made of an alcohol which is 
converted into an alkali metal alcoholate. The alcohol therefore acts as a 
proton donor which simultaneously traps alkali metal ions. 
OBJECTS OF THE INVENTION 
One object of the present invention is to simplify the process of German 
Patent Application (DE) P 44 33 823.6 while retaining its advantages: the 
recovery of the condensing agent, the avoidance of an acid foreign to the 
system, and the avoidance of a salt product. 
This and other objects will become apparent as the invention becomes better 
understood by reference to the following detailed description and attached 
Figure, wherein:

DETAILED DESCRIPTION OF THE INVENTION 
In accordance with the above objects a process is provided wherein both 
condensation and protonation are carried out in one step by 
electrodialysis. 
Keto compounds which can be prepared in accordance with the present 
invention are not limited and may be any of simple ketones, diketones, 
keto esters, keto halides, keto amino acids, keto nitro compounds, etc. 
They are preferably keto esters, and especially .beta.-keto esters. 
Condensation is generally carried out in the presence of alkali metal 
alcoholates. In this context, suitable alkali metal ions are the sodium 
and the potassium ion. These alcoholates are generally derived from an 
alcohol which is also used as a solvent. Suitable examples are alcohols 
having 1 to 5 carbon atoms, such as methanol, ethanol, isopropanol or 
tert-butanol, diols such as glycol and butanediol, or triols, such as 
glycerol. It is also possible to employ alcohol mixtures. The alcohols can 
contain up to 5% water. They may also contain starting material or 
product. 
Electrodialysis is preferably carried out in the present invention in an 
electrodialysis cell having 2n+2 chambers, where n is a number from 1 to 
60. In particularly preferred cases, n is a number from 1 to 10. 
Electrodialysis is preferably carried out at from -20.degree. to 
+90.degree. C., with particular preference being given to temperatures 
from 10.degree. to 50.degree. C. 
One benefit of the present invention process is that by the combination of 
condensation and protonation in one process step, the alcoholate consumed 
in the condensation is recovered during the protonation. Alcoholate can, 
in this case, be circulated. The process of DE P 44 33 823.6 is simplified 
further, while retaining the advantages specified therein, in that in the 
present invention the condensation too is included in the electrodialysis 
process. 
The process of the present invention is illustrated below taking as an 
example the condensation of methyl acetate to methyl acetoacetate. Of 
course, the present process is not restricted to this reaction. It is 
provided only for purposes of illustration. 
The present invention process can be elucidated using as an example an 
electrodialysis cell consisting of 6 chambers, as in FIG. 1: the chambers 
are each bounded by a cation exchange membrane K and a bipolar membrane B. 
Instead of the bipolar membrane it is also possible to use a pair of 
membranes consisting of one anion and one cation exchange membrane. 
Into the anode chamber III is fed a methanolic solution of the sodium 
enolate of methyl acetoacetate. This anolyte forms a separate circuit. 
Into the chambers I is fed a mixture of methyl acetate and methanol. This 
mixture is hereafter termed "concentrate". The chambers II are fed with a 
methanolic solution of the sodium enolate of methyl acetoacetate. This 
mixture is hereafter termed "diluate". 
When an electrical field is applied, the alkali metal ions migrate from the 
anode chamber and from the chambers II through the cation exchange 
membranes K, in the direction of the cathode, into the chambers I, where 
they form the alcoholate. The production of the condensing agent leads to 
the condensation of the carboxylic ester in these chambers. The chambers I 
therefore represent reactor chambers in which the methyl acetoacetate is 
produced in the enolate form. Protons pass through the bipolar membranes 
B. Therefore, the protonation of the enolate takes place in the chambers 
II, thereby producing the free methyl acetoacetate. 
The condensation is an equilibrium reaction and requires continuous removal 
of the alcohol produced. For example, the concentrate is subjected to 
electrodialytic treatment until the condensation has almost reached 
equilibrium. It is subsequently led into an external tank (not indicated 
in FIG. 1) which acts as reactor. The reaction can be carried out at any 
suitable temperature, even higher than 90.degree. C. The reaction is then 
followed by distillative removal of the alcohol optionally by means of an 
entraining agent. The unreacted acetic ester which remains is employed as 
starting material for the next batch. 
In a preferred embodiment of the process according to the invention, the 
concentrate tank is maintained at an elevated temperature in order to 
accelerate the condensation. The abovementioned distillation can then take 
place directly from the concentrate tank with a column mounted on it. By 
means of such an embodiment it is possible for condensation and 
protonation to be carried out rapidly and be harmonized with one another. 
Following a batchwise electrodialysis, the product solution is run off from 
the diluate tank and the tank is filled with the freshly produced 
condensation product (still in the from of the Na enolate) from the 
concentrate tank. The spent anolyte is replaced by the corresponding 
amount of the diluate which has been run off. In this way, the sodium ions 
are retained in the system. The net equation of the above process is: 
EQU 2 CH.sub.3 COOCH.sub.3 .fwdarw.CH.sub.3 COCH.sub.2 COOCH.sub.3 +CH.sub.3 OH 
The larger remainder of the diluate is passed to a distillation stage in 
order to free the acetoacetic ester from methanol, in so far as this has 
not already been done in the concentration tank. After the concentration 
tank has been filled with fresh methyl acetate solution, the next 
batchwise reaction can be commenced. 
Since the condensation is an equilibrium reaction, the attempt may be made 
to continually remove the products formed from the system to increase 
yield. In a further preferred embodiment of the process according to the 
invention, after just a slight conversion in the electrodialysis unit, the 
concentrate stream is introduced into the diluate chambers II. Here, the 
protonation of the small quantity of enolate which has just been produced 
takes place. In this way, the enolate is taken out of the chemical 
equilibrium with the condensation. The diluate stream is then subjected to 
distillation in order to remove the alcohol produced as well. 
Subsequently, the solution is passed back into the concentrate tank in 
order to continue the reaction. In this embodiment, continual condensation 
and protonation take place in a circuit. 
Furthermore, the process according to the invention can also be used to 
carry out condensation and transesterification simultaneously. This is 
possible when the alcohol of the concentrate is different from the alcohol 
of the diluate. Thus, for example, from methyl acetate it is possible to 
prepare the ethyl acetoacetate. 
The example which follows is intended to further illustrate the invention. 
EXAMPLE 1 
In accordance with the description which has already been given, a stack is 
used which is equipped with four circuits, namely two electrode circuits, 
a diluate circuit and a concentrate circuit. The membranes come from 
TOKUYAMA SODA Corp. Instead of a bipolar membrane, a membrane pair 
consisting of one anion and one cation exchange membrane is employed. The 
sequence of membranes, from the anode to the cathode, is as follows: a 
cation exchange membrane (type C66-10F), a membrane pair (type AM 1 and CM 
1) and another cation exchange membrane (type C66-10F), followed by the 
cathode. The effective membrane area per membrane is 100 cm.sup.2. The 
experiment takes place at room temperature. Only the concentrate circuit, 
in which condensation takes place, is maintained at 45.degree. C. 
The initial anolyte charge comprises 1,388 g of a 6 percent by weight 
solution of sodium methanolate in methanol. The catholyte consists 
initially of a 1.23 percent by weight solution of sodium methanolate in 
methanol. The diluate used (protonation circuit) comprises 1,282 g of a 10 
percent by weight solution of the sodium enolate of methyl acetoacetate in 
methanol. The concentrate employed (reaction circuit) comprises 1,450 g of 
a 15.78 percent by weight solution of methyl acetate. The solution 
additionally contains 0.5 percent by weight of sodium methanolate as 
conductive salt. 
The solutions are pumped continuously around appropriate circuits. Between 
the electrodes, a voltage of 120 V is applied. The experiment is 
terminated after 26 hours and 40 minutes, at which point the samples from 
the circuits are analyzed. In the concentrate circuit, 12.4 g of the Na 
enolate of the acetoacetic ester are produced. in the same period, in the 
diluate circuit, 11.7 g of free acetoacetic ester are prepared. From the 
results it is evident that simultaneous condensation and protonation 
according to the invention has occurred. 
This application is based on German Patent Application 195 05 957.3 filed 
Feb. 21, 1995, incorporated herein by reference.