Process for the transesterification of dimethyl succinylsuccinate

A process for the transesterification of dimethyl succinylsuccinate with one or more aliphatic alcohols which in each case have at least 2 C atoms, in the presence of an acidic catalyst and in the presence or absence of a diluent which is inert under the reaction conditions, with exclusion of oxygen and under pressure, at least one of the two methoxy groups being replaced by the oxy group corresponding to the alcohol used.

Quinacridones have especially gained great importance as red or violet 
pigments in the dyestuffs industry. 
In GB Patent 891,640 the basic reaction scheme is disclosed by which 
quinacridones are in general prepared: 
1. Condensation of diethyl succinate to give the corresponding 
diethylsuccinyl succinate which 
2. is reacted with an aniline to give diethyl 
2,5-dianilino-3,6-dihydroterephthalate. This is 
3. oxidized to the diethyl 2,5-dianilinoterephthalate which 
4. is hydrolyzed to the 2,5-dianilinoterephthalic acid. This is finally 
5. ring-closed to the quinacridone. 
A number of processes follow the reaction scheme indicated, which are 
intended to furnish improvements with respect to one or more reaction 
stages in comparison with the process of GB Patent 891,640. In the known 
processes, however, solvents or reagents are used whose use appears 
questionable from the point of view of environmental protection. 
According to GB Patent 891,640 itself, the oxidation and hydrolysis in 
reaction stages 3. and 4. are carried out in pyridine, picolines or their 
homologs, the use and disposal of which, however, are unpleasant and not 
environmentally protective. According to the procedures described in U.S. 
Pat. No. 2,821,541 or U.S. Pat. No. 3,674,814 "Dowtherm A", a mixture of 
biphenyl and diphenyl oxide, and according to WO 92/09558 xylene, is 
employed as a solvent. Such solvents, however, have toxic properties. In 
U.S. Pat. No. 3,031,501, U.S. Pat. No. 3,388,149, GB Patent 1,228,727 or 
U.S. Pat. No. 4,124,768, the oxidation according to reaction stage 3. 
using highly toxic nitrobenzenes is described. 
In U.S. Pat. No. 4,981,997, the use of an oxygen-carrying agent such as 
anthraquinone-2-sulfonic acid and of a quaternary ammonium compound is 
described for the oxidation in reaction stage 3. Such compounds, however, 
can only be removed with difficulty, if at all, from the reaction product. 
In U.S. Pat. No. 4,435,589, a process according to the reaction scheme 
described starting from dimethyl succinate in methanol as a solvent is 
described, in which the oxidation according to stage 3 is carried out 
using air. The yields of the 2,5-dianilinoterephthalic acids prepared in 
this process, however, are only about 70%. The low yields are to be traced 
back according to EP-A1-0 536 083 to the low solubility of dimethyl 
succinate and its secondary products, which are formed according to the 
reaction scheme described, in a solvent. In EP-A1-0 536 083, it is 
therefore proposed to transesterify dimethyl succinate using aliphatic 
alcohols which have 2 to 6 C atoms, and to employ the transesterification 
products which, on account of the longer hydrophobic side chains, have a 
higher solubility in organic solvents, for the preparation of 
quinacridones according to the reaction scheme described. According to the 
examples, however, the reaction, which is carried out in the presence of 
metal alkoxide, in no case takes place completely, so that the reaction 
mixture always contains considerable amounts of unreacted dimethyl 
succinate. The solubility of the correspondingly prepared dialkyl 
succinate, methyl alkyl succinate and dimethyl succinate mixture does not 
appear to be very much improved in organic solvents compared with that of 
dimethyl succinate on its own, because according to the examples the toxic 
mixture of biphenyl and diphenyl oxide (Dowtherm A) already described also 
has to be used for the reaction of the transesterified succinates. 
It has now unexpectedly been found that dimethyl succinylsuccinate can be 
transesterified using an alcohol which has at least 2 C atoms, virtually 
no dimethyl succinylsuccinate remaining unreacted. This was completely 
unexpected, because from Helvetica Chimica Acta, Col. 62, Vol. 5 (1979), 
pp. 1682 to 1687, it is known that dimethyl succinylsuccinate cannot be 
transesterified, in contrast to diethyl succinylsuccinate, on account of 
the unusual stability of the methyl ester bonds. 
The succinylsuccinates transesterified according to the invention and their 
secondary products according to the above reaction scheme in this case 
have a better solubility than dimethyl succinylsuccinate and its secondary 
products in environmentally protective organic solvents, such as alcohols, 
and can therefore be employed in an environmentally protective process for 
the preparation of 2,5-dianilinoterephthalic acid in an alcoholic solvent, 
the yields being unexpectedly high. The 2,5-dianilinoterephthalic acids 
prepared in this manner in environmentally protective solvents according 
to the reaction scheme described are ring-closed to the quinacridones as 
usual. 
The invention therefore relates to a process for the transesterification of 
dimethyl succinylsuccinate, which is characterized in that dimethyl 
succinylsuccinate is reacted with one or more aliphatic, straight-chain, 
branched or cyclic monoalcohols which are unsubstituted or substituted by 
phenyl groups and in each case have 2 to 22 C atoms, in the presence of an 
acidic catalyst and in the presence or absence of a diluent which is inert 
under the reaction conditions, with exclusion of oxygen and under 
pressure, at least one of the two methoxy groups being replaced by the oxy 
group corresponding to the alcohol used. 
Dimethyl succinylsuccinate can be prepared as usual by condensation of 2 
mol of dimethyl succinate, which is an easily obtainable product produced 
on a large scale. 
Alcohol is to be understood as meaning a straight-chain, branched or cyclic 
aliphatic monoalcohol which has 2 to 22, preferably 2 to 16, particularly 
preferably 3 to 8 C atoms, for example ethanol, propanol, butanol, 
hexanol, octanol, dodecanol, eicosanol or their isomers such as 
isopropanol, isobutanol, 2-methylhexanol, cyclopentanol, cyclohexanol, 
cyclooctanol or a mixture of such alcohols, it being possible for the 
alcohol to be unsubstituted or substituted by aryl groups, preferably 
phenyl groups, such as, for example, benzyl alcohol. Preferably, an 
unsubstituted, aliphatic, straight-chain or branched alcohol having 3 to 8 
C atoms is employed. Preferably, only one alcohol is employed and not a 
plurality of alcohols. 
The acidic catalysts employed are mineral acids, for example sulfuric acid, 
hydrochloric acid, nitric acid, preferably sulfuric acid, strongly acidic 
cation exchangers or organic sulfonic acids, such as p-toluenesulfonic 
acid, preferably mineral acids. 
The reaction can take place directly in the desired alcohol if this is 
liquid under the reaction conditions, or a diluent which is inert under 
the reaction conditions is added. Suitable inert diluents are, for 
example, aliphatic hydrocarbons, such as pentane, hexane, cyclopentane or 
cyclohexane, ethers, such as tetrahydrofuran, or mixtures of such 
diluents. 
To carry out the reaction according to the invention, dimethyl 
succinylsuccinate is mixed with the desired alcohol, the acidic catalyst 
and, if desired, the diluent and heated under pressure with exclusion of 
oxygen. 
At least 2 mol of alcohol per mole of dimethyl succinylsuccinate are 
employed, but in general an excess of at least 5 mol of alcohol per mole 
of dimethyl succinyl-succinate. If the alcohol is liquid under the 
reaction conditions, the reaction can be carried out directly in the 
desired alcohol, in this case at least a four-fold molar amount of alcohol 
being employed relative to dimethyl succinylsuccinate. 
The optimum amount of the diluent is easy to determine by simple 
preliminary experiments using various amounts. The acidic catalyst is 
employed in catalytic amounts, i.e. in amounts of about 0.1 to 10 mol 
percent relative to dimethyl succinylsuccinate. 
The reaction mixture is heated in a pressure-tight vessel with exclusion of 
oxygen. For this purpose, an inert gas atmosphere is built up as usual, 
for example, using nitrogen, helium or argon. The reaction temperatures 
are from about 60.degree. to 220.degree. C., preferably from 80.degree. to 
210.degree. C., particularly preferably from 90.degree. to 160.degree. C. 
The reaction is in this case carried out under the resulting pressure, 
regulation using the inert gas pressure being possible. The pressure is in 
general from about 1 to 20 bar, preferably 2 to 6 bar. 
When carrying out the process according to the invention, at least one of 
the two methoxy groups of the dimethyl succinylsuccinate is replaced by 
the corresponding alkoxy group of the alcohol used, virtually no unreacted 
starting material remaining. In general, a mixture of dialkyl 
succinylsuccinate and alkyl methyl succinylsuccinate results, the alkyl 
moiety corresponding to the alkyl moiety of the alcohol employed for the 
reaction. The amount of dialkyl succinylsuccinate in the product mixture 
in this case is all the higher, the higher the reaction temperature and 
the longer the reaction time. If an alcohol mixture is used, mixtures of 
succinylsuccinates corresponding to the alcohols used result. 
The reaction course is monitored as usual, advantageously by 
chromatography. Depending on the amount of dialkyl succinylsuccinate 
desired in the product mixture, in any case at the earliest after 
consumption of the dimethyl succinylsuccinate in the reaction mixture, the 
reaction is terminated and the reaction mixture cooled. The reaction 
products here are in general precipitated in crystalline form. They are 
isolated as usual, for example by filtration or centrifuging off. In 
special cases a purification, for example by recrystallizing, can be 
added. 
The process according to the invention yields methyl alkyl 
succinylsuccinates and dialkyl succinylsuccinates in which the alkyl 
groups correspond to those alcohols used for the reaction. Succinates of 
this type can be employed in many different types of chemical syntheses. 
The products, however, are especially employed for the environmentally 
protective synthesis of 2,5-dianilinoterephthalic acids, which are a 
preliminary stage in quinacridone synthesis. In this synthesis, it does 
not matter whether in the process according to the invention mixtures of 
methyl alkyl succinylsuccinates and dialkyl succinylsuccinates in general 
result, as the esters are hydrolyzed to the acid in the later synthesis 
stage 4. of the above reaction Scheme, so that in any case homogeneous 
products result from the hydrolysis stage. 
The invention therefore also relates to a process for the preparation of 
2,5-dianilinoterephthalic acids of the formula 
##STR1## 
in which R.sub.1 and R.sub.2 are identical or different and in each case 
are a phenyl or naphthyl group which is unsubstituted or mono- or 
polysubstituted by halogen, nitro, alkyl, alkoxy, phenyl, phenoxy or 
trifluoromethyl or by alkyl-substituted carbamoyl groups, at least one of 
the alpha positions of the C atom to which the amino group is bonded being 
unsubstituted, which is characterized in that 
a) dimethyl succinylsuccinate is heated with one or more alcohols of the 
formula 
EQU R.sub.3 --OH II 
in which R.sub.3 is an alkyl group which is unsubstituted or substituted by 
phenyl and has 2 to 22 C atoms, in the presence of an acidic catalyst 
under pressure at temperatures from 60.degree. to 180.degree. C., a 
compound of the formula 
##STR2## 
in which R.sub.3 has the abovementioned meaning and R.sub.4 has the 
meaning of R.sub.3 or is additionally a methyl group, R.sub.3 and R.sub.4 
in the formula III being exchangeable, being obtained, 
b) the reaction product from stage a) is heated to temperatures of 
40.degree. to 150.degree. C. after or without isolation, optionally with 
addition of a diluent which is inert under the reaction conditions, with 
at least a two-fold molar amount of one or more amines of the formula 
EQU R.sub.1 --NH.sub.2 and/or R.sub.2 --NH.sub.2 IV 
in which R.sub.1 and R.sub.2 have the abovementioned meaning, in the 
presence of acid, a compound of the formula 
##STR3## 
in which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the abovementioned 
meanings, being obtained, 
c) the reaction product from stage b) is treated with acid until the 
reaction is acidic and heated to temperatures of 50.degree. to 100.degree. 
C. after or without isolation, optionally with addition of a diluent which 
is inert under the reaction conditions, after which air is blown into the 
reaction mixture, the terephthalate ester of the formula 
##STR4## 
in which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the abovementioned 
meaning, being obtained, which 
d) is converted with heating after or without isolation, optionally with 
addition of a diluent which is inert under the reaction conditions, by 
reaction with a compound of the formula M--OH, in which M is a metal, to a 
compound of the formula 
##STR5## 
which e) is treated with water and acid until the reaction is acidic and 
allowed to react after or without isolation, optionally with addition of a 
diluent which is inert under the reaction conditions to give the 
terephthalic acid of the formula I which is isolated from the reaction 
mixture. 
The process with the exception of stage a. is carried out in a manner 
disclosed in one of the cited literature references, but in an alcohol of 
the formula II as a diluent or in one of the inert diluents indicated for 
stage a. 
The reaction stage a) is carried out according to the invention, the 
alcohol of the formula R.sub.3 OH in which R.sub.3 has the abovementioned 
meaning preferably being employed simultaneously as a diluent. Preferably, 
R.sub.3 is a straight-chain or branched alkyl group having 3 to 8 C atoms. 
Preferably, only one alcohol is employed and not a plurality of alcohols. 
Reaction stage b) is preferably carried out according to U.S. Pat. No. 
4,435,589, but using a compound of the formula III as a starting material 
and in an alcohol of the formula II or in an inert diluent of stage a., 
preferably in an alcohol of the formula II as a diluent; reaction stages 
c) and d) are preferably carried out according to WO 92/09558, but using a 
compound of the formula III or of the formula V and without use of a 
molybdenum catalyst, without isolation of the terephthalate ester and in 
an alcohol of the formula II or in an inert diluent of stage a., 
preferably in an alcohol of the formula II as a diluent. Preferably, only 
one amine of the formula IV is employed, R.sub.1 preferably being a phenyl 
group which is unsubstituted or substituted by alkyl or alkoxy groups in 
each case containing 1 to 4 C atoms, halogen or nitro groups, at least one 
of the alpha positions of the C atom to which the amino group is bonded 
being unsubstituted. 
The reaction stage e) is preferably carried out by addition of water and of 
a mineral acid to the reaction mixture consisting of the terephthalate of 
the formula VII in an alcohol of the formula II or in an inert diluent of 
stage a., preferably in an alcohol of the formula II as a diluent. 
The reaction steps a. to d. can be carried out here with or without 
isolation of the individual reaction products, it having been shown that 
in a one-pot process without isolation of individual reaction products 
high yields of terephthalic acid of the formula VII of about 90% relative 
to dimethyl succinylsuccinate are nevertheless achieved. 
In a particularly preferred embodiment, dimethyl succinylsuccinate is 
heated to temperatures of 90.degree. to 160.degree. C. with an 
unsubstituted, aliphatic, straight-chain or branched alcohol which has 3-8 
C atoms and with a mineral acid in a pressure-tight vessel in an inert gas 
atmosphere. After reaction is complete, the pressure in the reactor is 
released and the reaction mixture is heated to temperatures of 60.degree. 
to 100.degree. C. with an amine of the formula R.sub.1 --NH.sub.2, in 
which R.sub.1 is a phenyl group substituted by one or more alkyl groups, 
at least one of the alpha positions of the C atom to which the amino group 
is bonded being unsubstituted, after which the reaction mixture is 
acidified and heated to temperatures of 60.degree. to 90.degree. C. Air is 
then blown into the reaction mixture until the reaction to give the 
terephthalate ester of the formula VI is terminated. An alkali metal 
hydroxide is then added to the reaction mixture until the reaction is 
alkaline and the mixture is heated to reflux. After cooling, water and a 
mineral acid are added to the reaction mixture until the reaction is 
acidic. If two phases are formed here as a result of the poor miscibility 
with water of the diluent used, the aqueous phase is separated off, after 
which the terephthalic acid of the formula I in general precipitates from 
the reaction mixture in crystalline form and is isolated by filtration. 
Also claimed is a process for the preparation of quinacridones of the 
formula 
##STR6## 
in which R.sub.5, R.sub.6, R.sub.7 and R.sub.8 are identical or different 
and in each case are one or more halogen atoms, nitro, alkyl, alkoxy, 
phenyl, phenoxy, or trifluormethyl- or alkyl- substituted carbamoyl groups 
and n is the number 0 or 1, which is characterized in that terephthalic 
acid of the formula I is prepared according to the invention and 
ring-closed as usual, for example according to U.S. Pat. No. 4,956,464, to 
give the quinacridone of the formula VIII. 
As in the process described no environmentally harmful substances have to 
be disposed of, the process for the preparation of dialkyl 
succinylsuccinates and alkyl methyl succinylsuccinate of terephthalic 
acids of the formula I and of quinacridones of the formula VIII represents 
an enrichment of the art.

EXAMPLE 
A 0.5 1 autoclave having a stirrer and gas inlet tube was filled with 46 g 
of dimethyl succinylsuccinate (0.2 mol), 250 ml of 1-butanol and 0.52 ml 
of concentrated sulfuric acid and closed. The reaction mixture was purged 
with nitrogen for 15 minutes and heated at 140.degree. C. for 2 hours. 
After cooling, a precipitate was deposited which was identified by 
thin-layer chromatography as a mixture of dibutyl succinylsuccinate and 
methyl butyl succinylsuccinate. Dimethyl succinylsuccinate was only still 
found in traces. 26 g of p-toluidine were added to the reaction mixture, 
it was purged with nitrogen and heated without pressure at about 
75.degree. C. for 1 hour with further nitrogen purging. 20 ml of acetic 
acid were then added and the mixture was heated to reflux. After reaching 
the reflux temperature, air was blown into the reaction mixture for 4 
hours using a dip tube. 70 g of solid potassium hydroxide were then added 
and the mixture was heated to reflux for a further 1 hour. After cooling, 
500 ml of water were added to the reaction mixture and the pH was adjusted 
to 2.5 to 3 by adding sulfuric acid. After separating off the aqueous 
phase and again adding about 400 ml of water, a dark-violet precipitate 
was deposited, which was filtered off and dried at about 100.degree. C. 
In this way, 67.6 g of pure 2,3-dimethyldianilinoterephthalic acid, i.e. 
90% of theory relative to dimethyl succinylsuccinate, were obtained. The 
purity was determined by means of HPLC (high pressure liquid 
chromatography) and was 98%.