Process for the synthesis of 3-mercaptopropionic acid

This process for the synthesis of 3-mercaptopropionic acid by an addition reaction of H.sub.2 S with acrylic acid is carried out in the presence of a solid support having basic guanidine functional groups, provided that the latter do not contain hydrogen bonded directly to a nitrogen atom.

FIELD OF THE INVENTION 
The present invention relates to the preparation of 3-mercaptopropionic 
acid (MPA) by addition of hydrogen sulphide to acrylic acid (AA) according 
to the reaction (1): 
EQU H.sub.2 S+CH.sub.2 =CH--COOH.fwdarw.HS--CH.sub.2 --CH.sub.2 --COOH(1) 
The MPA formed can react with the AA present in the reaction mixture to 
give 3,3'-thiodipropionic acid (TDPA) according to the reaction (2): 
EQU HS--CH.sub.2 --CH.sub.2 --COOH+CH.sub.2 .dbd.CH--COOH.fwdarw.S(CH.sub.2 
--CH.sub.2 --COOH).sub.2 ( 2) 
BACKGROUND OF THE INVENTION 
U.S. Pat. No. 5,008,432 describes the addition of H.sub.2 S to unsaturated 
compounds, such as methyl acrylate or acrylic acid. 
This addition is carried out in the presence of a basic catalyst chosen 
from magnesium oxide and basic anion-exchange resins. These resins are 
chosen from those having tertiary amines or quaternary ammonium hydroxides 
as functional group. 
The reaction takes place in the absence or in the presence of solvents. The 
latter are chosen from lower alcohols, saturated aliphatic or 
cycloaliphatic hydrocarbons and aromatic hydrocarbons. 
If an anion-exchange resin is used, the reaction pressure is generally from 
3037.5 to 6750 kPa. 
Example VII describes the addition of H.sub.2 S to acrylic acid, without 
solvent, at a reaction pressure of 3037.5 kPa, in the presence of 
Amberlyst A-21 resin (Rohm and Haas). This resin has dimethylamino 
functional groups. During the reaction, a solid separate from the liquid 
medium is formed. This solid contains mercaptans, sulphides, acrylic acid 
and dimers and trimers. Test No. 4 of this example would result, for an 
H.sub.2 S/AA molar ratio of 10.4, in a conversion of 89% and a selectivity 
of 100% for MPA. 
Test No. 3 would result, for an H.sub.2 S/AA molar ratio of 5.4, in a 
conversion of 90% for a selectivity of 98% for MPA. 
Patent application J07-228568 also relates to the synthesis of MPA by 
addition of H.sub.2 S to acrylic acid. According to the process of this 
application, the addition is carried out in the presence of an 
anion-exchange resin and of a solvent chosen from water or amide, ester, 
ether or ketone compounds. 
The amide, ester, ether or ketone solvent must not have a hydrogen bonded 
to an oxygen, sulphur, nitrogen and similar atom. Among the solvents which 
may be used in this process, dimethylformamide (DMF), dimethylacetamide, 
N-methylpyrrolidone and dimethylimidazolidinone are recorded among the 
amide solvents, DMF being preferred as it results in a high MPA yield. 
Dioxane, dioxolane and diethylene glycol dimethyl ether are recorded among 
the ether solvents, dioxane being preferred as it results in a high MPA 
yield. 
Acetone, diethyl ketone, methyl ethyl ketone and methyl isobutyl ketone are 
recorded among the ketones. 
The anion-exchange resin described can have, as functional group, a 
tertiary amine (weakly basic resins) or a quaternary ammonium hydroxide 
(strongly basic resins). The weakly basic anion-exchange resins are 
indicated as ideal in practice because they do not form salts with the 
compounds of the reaction mixture. 
The polymer of these resins, rendered insoluble by crosslinking, can be 
polystyrene, polyacrylamide or an epoxy resin. 
In J07-228568, the examples of the synthesis of MPA employ the following 
resins manufactured by the company Rohm & Haas: 
Amberlite IRA 93 (groups: tertiary amine) 
Amberlite IRA 94 (groups: tertiary amine) 
Amberlite IRA 900 (groups: quaternary ammonium) 
Example 2 (Amberlite IRA 94 resin) and Example 12 (Amberlite IRA 900 
resin), carried out under identical conditions as regards the molar ratio 
(H.sub.2 S/AA=3) and the reaction temperature of 60.degree. C., would 
result virtually identical MPA yields (90.0% and 89.7%) and selectivities 
(90.6% and 90.8%). 
Example 3, carried out in DMF in the presence of Amberlite IRA-94 resin, 
would result in a conversion of the AA of 98.9% and an MPA yield of 91.5% 
with a selectivity of 92.5%, for an H.sub.2 S/AA molar ratio of 6.0, a 
reaction temperature of 60.degree. C., a pressure of 30 atm (3039 kPa) and 
a maximum pressure of 44 atm (4458 kPa). 
DESCRIPTION OF THE INVENTION 
The aim of the present invention is to find conditions for the 
implementation of the reaction (1) such that, while retaining a very high 
degree of conversion, the selectivity for MPA is markedly better than that 
of the prior art, in particular that which could be obtained from the 
technical teaching of the document J07-228568. 
This aim is achieved in the above reaction (1) by replacing the resins of 
the prior art by a solid support having guanidine functional groups, 
provided that the latter do not contain hydrogen bonded directly to a 
nitrogen atom. 
The subject of the present invention is thus a process for the preparation 
of 3-mercaptopropionic acid by an addition reaction of H.sub.2 S with 
acrylic acid in the presence of a solid support having basic functional 
groups, characterized in that the functional groups are guanidine groups, 
provided that the latter do not contain hydrogen bonded directly to a 
nitrogen atom. 
The solid support can be any support which is insoluble in the reaction 
mixture. Mention may be made, as examples of such supports, of silica and 
alumina but it is preferable to use a polymeric support of any kind. 
When the reaction (1) is carried out in the presence of a solvent, the 
polymeric support must additionally be substantially insoluble in the 
solvent. This insolubility is generally obtained by crosslinking the 
polymer or polymers constituting the polymeric support. 
The present invention more specifically provides a process for the 
synthesis of 3-mercaptopropionic acid by an addition reaction of H.sub.2 S 
with acrylic acid in the presence of a solid support having basic 
functional groups, characterized in that these functional groups are 
chosen from: 
1) a guanidine radical of general formula (C): 
##STR1## 
in which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, independently of one 
another, hydrocarbon groups such as methyl, ethyl, propyl or butyl, the 
imine nitrogen being bonded to the solid support via a chemical bond or a 
sequence of chemical bonds, 
2) a bicyclic guanidine radical of formula (D): 
##STR2## 
in which n has the value 2 or 3 and m has the value 2, 3 or 4, provided 
that n is less than or equal to m, this radical (D) being bonded to the 
solid support via a chemical bond or a sequence of chemical bonds starting 
from the initially N--H nitrogen of the corresponding bicyclic guanidine. 
The radical (D) can advantageously be chosen from the .DELTA..sup.8 
-hexahydro-1,4,8-pyrimidazolyl (m=3, n=2), .DELTA..sup.9 
-1,5,9-triazabicyclo4.4.0!decenyl (m=3, n=3), .DELTA..sup.9 
-1,4,9-triazabicyclo5.3.0!decenyl (m=4, n=2) and 
2,3,5,6-tetrahydro-1H-imidazo1,2-a !-imidazolyl (m=2, n=2) radicals. 
This process makes it possible to obtain, with an excellent degree of 
conversion of the AA, a better selectivity for MPA than the processes of 
the prior art, with in particular a concomitant decrease in the content of 
TDPA in the reaction mixture. 
Thus, surprisingly, everything takes place as if the guanidine functional 
groups selectively increased the kinetics of the reaction (1) with respect 
to the kinetics of the reaction (2). 
The increase in the selectivity for MPA of the process according to the 
present invention is based hereinbelow on the presentation of comparative 
examples including a quantitative calibration of chromatograms (see the 
experimental part). 
The functionalized resin based on polystyrene-divinylbenzene (PS-DVB) 
preferably has the general formula (I): 
##STR3## 
B being a group chosen from the radicals of general formula (c) or (D), L 
being a linear organic radical having a length equal to or greater than 
that of the methylene radical --(CH.sub.2)-- or the radical, 
##STR4## 
being the PS-DVB resin support. 
Preferably, in the general formula (I): 
the radical (C) is substituted by L, the latter then representing a 
--CH.sub.2 -- radical and R.sub.1, R.sub.2, R.sub.3 and R.sub.4 each 
representing a methyl group, 
the radical (D) is substituted by L on the nitrogen which, in the related 
bicyclic compound, carries a hydrogen, provided that L then represents a 
--(CH.sub.2).sub.p -- radical, p being an integer having a value from 1 to 
9. 
The functionalized polymeric resin advantageously has the general formula 
(II): 
##STR5## 
in which X represents an oxygen or sulphur atom, q has the value 1 or 2 
and R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, independently of one 
another, chosen from the methyl, ethyl, propyl and butyl groups. 
Advantageously, in the general formula (II), R.sub.1, R.sub.2, R.sub.3 and 
R.sub.4 each represent a methyl group and q has the value 1. 
Preferably, the addition reaction (1) takes place in the presence of a 
solvent, the latter not having a mobile hydrogen. 
In general, the said solvent is an amide, ester, ether or ketone solvent or 
one of their mixtures. The said solvent is advantageously chosen from 
dimethylformamide (DMF), diethylene glycol dimethyl ether or dioxane. The 
most preferred solvent is DMF. 
The H.sub.2 S/AA molar ratio should preferably be high in order to promote 
the reaction (1) even more with respect to the reaction (2). This molar 
ratio is generally between 3 and 10. 
It is preferable, in order to increase this molar ratio in the liquid 
mixture in contact with the solid resin acting as basic catalyst, to 
subject the reaction mixture to an H.sub.2 S pressure which is greater 
than atmospheric pressure. The pressure is generally greater than 15 bar 
(1500 kPa) and can reach 35 bar (3500 kPa) when the reaction is carried 
out at high temperatures. 
The reaction is advantageously carried out at a temperature of 20.degree. 
C. to 150.degree. C. The temperature of the reaction mixture preferably 
ranges from 30.degree. C. to 110.degree. C. 
The amount by weight of resin used with respect to the amount by weight of 
acrylic acid employed is advantageously from 1 to 100% and preferably from 
10 to 70%. 
The catalysts containing a guanidine functional group of the invention 
exhibit high chemical and thermal stability with respect to the reaction 
mixture and can thus be used continuously or reused without reactivation. 
The reaction can be carried out in a stirred or tubular reactor, according 
to a non-continuous process, either by charging the reactants before they 
react or by gradual addition of acrylic acid after the addition of the 
hydrogen sulphide or alternatively by simultaneous addition of the 
reactants to the reactor, and, finally, according to a continuous process 
with controlled addition of the reactants. 
The resins of general formula (I) can be obtained or prepared in the 
following way: 
1) The group B is a radical of general formula (C). 
A process is known, from U.S. Pat. No. 5,340,380, which consists in 
substituting the chlorine of a chloromethylated polystyrene-divinylbenzene 
resin with a substituted or unsubstituted guanidine and which makes it 
possible to obtain resins of general formula (I.C): 
##STR6## 
representing the starting polystyrenedivinylbenzene resin solid support 
and it being possible for the symbols R.sub.1, R.sub.2, R.sub.3 and 
R.sub.4 each to be a hydrogen, an alkyl group or an aromatic group. 
U.S. Pat. No. 3,346,516 also describes this reaction of a chloromethylated 
polystyrenedivinylbenzene resin with guanidine or tetramethylguanidine in 
the presence of a lower alcohol and a solvent for swelling the PS-DVB 
copolymer, such as tetrahydrofuran, dioxane or diglyme. 
In U.S. Pat. No. 5,028,259, tetramethylguanidine is brought into contact 
with a chloromethylated polystyrene-divinylbenzene resin in a mixture of 
toluene and tetrahydrofuran. 
In U.S. Pat. No. 5,340,380, guanidines are reacted with this same type of 
chloromethylated resins in the presence of sodium hydroxide in a solvent 
composed of ethanol or of water. 
However, this technique for functionalizing a chloromethylated PS-DVB resin 
with a guanidine is very limited in practice for the production of resins 
of formulae (I.C) in which the guanidine radicals carry R.sub.1, to 
R.sub.4 substituents which are other than four methyls, insofar as only 
1,1,3,3-tetramethylguanidine is currently available commercially. 
Such resins (I.C), in which the R.sub.1 to R.sub.4 groups are all other 
than hydrogen, can be obtained by using tetrasubstituted ureas, which are 
often available commercially, under the following preparation conditions: 
a) The starting point is the preparation of a PS-DVB resin functionalized 
by primary amine groups having the general formula (A) 
##STR7## 
These can be obtained by different techniques: 
1) It is possible, for example, to start from a resin of general formula 
(J): 
##STR8## 
X being a leaving group, in particular halogen or tosylate, obtained from 
a hydroxyl group --OH, and L representing in particular a 
--(CH.sub.2).sub.p -- radical with p being an integer having a value from 
1 to 9. 
Preferably, when L represents a single methylene, X is a chlorine atom. In 
this case, one method, described by D. H. Rich and S. K. Gurwara, J. Am. 
Chem. Soc., 1975, 97, 1575-1579, consists in reacting a chloromethylated 
PS-DVB resin with an excess of ammonia. Another route is based on 
obtaining phthalimidomethylated PS-DVB resin, which is converted by 
hydrazinolysis into a resin containing a primary amine functional group. 
The two methods of access to such phthalimidomethylated resins are 
described in the publication by A. R. Mitchell, S. B. H. Kent, B. W. 
Erickson and R. E. Merrifield, Tetrahedron Letters, No. 42, 1976, 
3795-3798. One consists in starting from a PS-DVB resin which, by reaction 
with N-(chloromethyl)phthalimide, is directly converted into 
phthalimidomethylated resin. The other method starts from a 
chloromethylated PS-DVB resin, which is treated with potassium phthalimide 
in order to give the corresponding phthalimidomethylated resin. 
A few PS-DVB resins containing a primary amine functional group of formula 
(A) in which L represents a methylene are commercially available. 
Thus, the Company Purolite provides two macroporous resins, A-107 and 
A-109, while the Company Fluka has, in its 1995-1996 catalogue, two 
gel-type resins: the resin 08564 PS, crosslinked with 2%. DVB and 
containing 1.1 mmol of --NH.sub.2 groups per gram of resin, and the resin 
08566 PS, crosslinked with 1% DVB and containing 0.6 mmol of --NH.sub.2 
per gram of resin. 
The potassium phthalimide method is also applicable to the resins of 
formula (J) in the case where L is a linear organic radical with a length 
greater than that of the methylene radical, in particular 
--(CH.sub.2).sub.r -- with r having the value of an integer greater than 
1. 
2) It is also possible to start from a PS-DVB resin of formula (J) in 
which L represents a methylene and X has the above meaning and preferably 
represents a chlorine atom. Applicant has found that this chloromethylated 
resin can be reacted with an alkanolamine or a mercaptoalkylamine, in the 
form of an alkali metal alkoxide or thiolate, under the conditions of the 
Williamson reaction. 
If ethanolamine is employed, PS-DVB resins containing a primary amine 
functional group are obtained with --CH.sub.2 --O--CH.sub.2 --CH.sub.2 
--NH.sub.2 functional groups attached to the PS-DVB resin supports. 
Analogously, starting from 2-aminoethanethiol hydrochloride, --CH.sub.2 
--S--CH.sub.2 --CH.sub.2 --NH.sub.2 functional groups are obtained. 
If 2-(2-aminoethoxy)ethanol is used, PS-DVB resins containing a primary 
amine functional group are obtained with --CH.sub.2 (--O--CH.sub.2 
--CH.sub.2).sub.2 --NH.sub.2 functional groups. 
Finally, by using 2-(2-aminoethyl)thio!-ethanethiol, the functional groups 
obtained are: 
EQU --CH.sub.2 --(S--C.sub.2 --CH.sub.2).sub.2 --NH.sub.2. 
This starting mercaptoalkylamine can be prepared according to Iwakura et 
al., J. Polym. Sci., Part A, 2, 1964, 881-883, or according to Voronkov, 
M. G. et al., Chem. Heterocycl. Compd. (Engl. Transl.), 15, 1979, 
1183-1185. 
The general conditions of the Williamson reaction are as follows: 
The alkanolamine or the mercaptoalkylamine, diluted in anhydrous 
tetrahydrofuran (THF) or anhydrous N-methylpyrrolidone, is reacted with 
sodium hydride in suspension in the same anhydrous solvent. After 
formation of the sodium alkoxide or sodium thiolate, the chloromethylated 
resin is introduced into the liquid reaction mixture. 
b) After obtaining the resin possessing primary amine groups of general 
formula (A), these primary amine groups are reacted with 
chloroformamidinium chloride (Vilsmeier salt) of general formula (H): 
##STR9## 
in which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are, independently of one 
another, chosen from the methyl, ethyl, propyl and butyl groups, 
in order to obtain a PS-DVB resin functionalized by a guanidine group and 
with the general formula (I.C): 
##STR10## 
L and R.sub.1 to R.sub.4 having the same meanings as above. 
The chloroformamidinium chlorides (H) are generally obtained from 
tetrasubstituted ureas by reaction with electrophilic compounds, such as 
phosgene, thionyl chloride, oxalyl chloride or phosphorus oxychloride, 
according to methods described in the literature, in particular: 
COCl.sub.2 H. Eilingsfeld, M. Seefelder, Angew. Chem., 72, 1960, 836. 
SOCl.sub.2 H. Ulrich, A. A. R. Sayigh, Angew. Chem. Intern. Ed. Engl., 5, 
1966, 704. 
(COCl.sub.2 T. Fujisawa et al., Chem. Lett., 1982, 1891. 
POCl.sub.3 H. Bredereck, K. Bredereck, Chem. Ber., 94, 1961, 2278. 
The starting point is generally stoichiometric amounts of tetrasubstituted 
ureas and of electrophilic chlorinated compounds and the reaction is 
carried out in the presence of a solvent, such as carbon tetrachloride, in 
the case of oxalyl chloride, or without a solvent, with phosgene or 
thionyl chloride, at a temperature generally of 0.degree. C. to 40.degree. 
C. and in an anhydrous atmosphere, in order to avoid any hydrolysis. 
The tetrasubstituted ureas are advantageously chosen from tetramethylurea, 
tetraethylurea, tetra(n-propyl)urea and tetra(n-butyl)urea. 
The chloroformamidinium chlorides (H) are generally placed in a solvent, 
such as toluene or acetonitrile. Their reactions with the resins 
containing a primary amine functional group (A) are carried out in the 
presence of a base, preferably in the presence of an excess of base. 
If the base is triethylamine (TEA), the reaction is generally carried out 
with a molar excess of TEA of 10 to 50% with respect to the 
chloroformamidinium chlorides (H). The latter are generally in a molar 
excess of 10 to 100% with respect to the number of moles of primary amine 
functional group, in order to convert all of the latter into a guanidine 
functional group. 
2) In the general formula (I), the group B is a radical of formula (D) 
(a) The starting point is the preparation of a resin of general formula 
(J), as in part 1 a) above, L representing a --(CH.sub.2).sub.p -- 
radical, p being an integer having a value from 1 to 9, and X being a 
chlorine or a bromine. 
(b) The above halogenated resin is reacted with a bicyclic guanidine chosen 
in particular from .DELTA..sup.8 -hexahydro-1,4,8-pyrimidazole (m=3, n=2), 
.DELTA..sup.9 - 1,5,9-triazabicyclo4.4.0!decene (TBD) (m=3, n=3), 
.DELTA..sup.9 -1,4,9-triazabicyclo5.3.0!decene (m=4, n=2) and 
2,3,5,6-tetrahydro-1H-imidazo1,2-a!imidazole (m=2, n=2). 
The preparation of these bicyclic guanidines is described in Patents GB 
826,837 and EP 0,198,680. 
The reaction is carried out in a way analogous to the process of M. Tomoi 
et al., J. M. S. Pure Appl. Chem., A29(3), 1992, 249-261, in particular 
page 251 ("Preparation of Polystyrene-Supported TBD"). 
A PS-DVB resin functionalized by a bicyclic guanidine group is thus 
obtained of general formula (I.D): 
##STR11## 
L representing a --(CH.sub.2).sub.p -- radical with p being an integer 
having a value from 1 to 9. 
The process of Tomoi et al., J. Macromol. Sci. Pure Appl. Chem., A29(3), 
1992, 249-261, consists in reacting the lithium salt of TBD with a 
chloromethylated resin. A simplified procedure was studied in the context 
of the present invention in order to prepare larger amounts of resins 
containing a -TBD functional group, by reacting excess 
1,5,7-triazabicyclo4.4.0!dec-5-ene directly with chloromethylated PS-DVB 
resin in anhydrous THF as solvent. 
The catalytic effectiveness of the resins used in the present invention is 
found to be improved when they are used dry.

EXAMPLES 
The present invention will be better understood by virtue of the 
experimental part hereinbelow which in particular comprises a description 
of the equipment used, the latter being represented diagrammatically in 
the single appended figure. 
Experimental Part 
I. Preparation of polystyrene-divinylbenzene resins containing a guanidine 
functional group. 
The chloromethylated PS-DVB base resin which is used is of macroporous 
type. It has the following characteristics: 
Specific surface: 22.5 m.sup.2 /g of resin 
Mean pore diameter: 20 .ANG. 
Volume of the pores: 69% 
chloromethylated with a degree of chlorine of 19.32% by weight with respect 
to the total weight. 
This resin thus contains 5.44 meq of Cl/g of resin. 
I.1 Production of PS-DVB resins of formula (I.C) containing a 
1,1,3,3-tetramethylguanidine (TMG) functional group, 
EQU (L=--CH.sub.2 --, R.sub.1 =R.sub.2 =R.sub.3 =R.sub.4 =CH.sub.3 --) 
The technique used consists in incorporating the TMG directly in a 
chloromethylated PS-DVB resin, according to the method described in U.S. 
Pat. Nos. 3,346,516 and 5,028,259. 
Procedure: 
20 g of dry chloromethylated resin (5.44 meq of Cl/g of resin) are weighed 
out. It contains 0.109 mol of Cl. It is brought into contact, under a 
nitrogen atmosphere, with 50 g (0.435 mol) of TMG diluted in 210 g of 
tetrahydrofuran (THF) dried beforehand over a molecular sieve. The 
reaction mixture thus obtained is stirred mechanically for 48 hours at a 
temperature of 60.degree. C. After cooling to 20.degree. C., the resin is 
filtered off and is washed with 500 ml of water and then with 250 ml of 
water at 60.degree. C. It is then treated with 300 ml of a 10% aqueous 
sodium hydroxide solution and washed with water to neutrality. The resin 
is washed with methanol (300 ml) and then dried under vacuum at 60.degree. 
C. to constant weight. 
The elemental analysis of the resin thus obtained was carried out. For this 
resin, N=9.3% by weight, i.e. 2.2 mmol of TMG functional group/g of resin. 
Resin subsequently indicated: PS-DVB-TMG 
I.2 Production of PS-DVB resins of formula (I.D) containing a 
1,5,7-triazabicyclo4.4.0!dec-5-ene (TBD) functional group with 
L=--CH.sub.2 --. 
Procedure: 
20 g of dry chloromethylated resin (5.44 meq of Cl/g of resin) are weighed 
out. The resin charge contains 0.109 mol of Cl. It is brought into 
contact, under a nitrogen atmosphere, with 30 g (0.216 mol) of TBD diluted 
in 285 g of THF dried beforehand over a molecular sieve. The reaction 
mixture thus obtained is stirred mechanically for 48 hours at a 
temperature of 60.degree. C. After cooling to 20.degree. C., the resin is 
filtered off and is washed with 500 ml of water and then 250 ml of water 
at 60.degree. C. It is then treated with 300 ml of a 10% aqueous sodium 
hydroxide solution and washed with water to neutrality. The resin is 
washed with methanol (300 ml) and then dried under vacuum at 60.degree. C. 
to constant weight. 
The elemental analysis of the resin thus obtained was carried out. For this 
resin, N=13.26% by weight, i.e. 3.15 mmol of TBD functional group/g of 
resin. 
Resin subsequently indicated: PS-DVB-TBD 
II. Examples of the synthesis of 3-mercaptopropionic acid 
II.1. General points 
The tests were carried out in equipment which makes it possible to study, 
under pressure, the formation reaction of 3-mercaptopropionic acid from 
acrylic acid and hydrogen sulphide in a solvent (dimethylformamide or 
diglyme) with different basic resins as catalysts. 
The introduction of the reactants and of the solvent before the start of 
the reaction makes it possible to carry out the reaction according to a 
batch process (the progress of the reaction is equivalent to continuous 
plug-flow operating conditions). 
The design of the equipment (description of the equipment: paragraph II.2) 
makes it possible to study the reaction under stirred batch conditions 
(closed reactor) by means of a tubular reactor (resin in a stationary 
bed), through which recirculates, at a high flow rate, the liquid reaction 
mixture via a pump on the circuit of a circulation loop which is connected 
to the two ends of the reactor. 
This operating technique of stirred batch type makes it possible to study 
the kinetics of the reaction under conditions which are equivalent to 
continuous plug-flow operating conditions (open reactor), given that all 
the reactants (H.sub.2 S and acrylic acid) are introduced, as well as the 
solvent, into the equipment before the start of the reaction, the reactor 
being isolated (no contact with the resin) (operating protocol: paragraph 
II.3). 
The progress of the reaction with time is monitored by withdrawing samples 
which are analysed by gas chromatography in order to determine the 
conversion of the acrylic acid and the corresponding selectivities for 
3-mercaptopropionic acid and for 3,3'-thiodipropionic acid as a function 
of time. 
BRIEF DESCRIPTION OF THE DRAWING 
II.2. Equipment 
As represented in the single figure, the stainless steel equipment is 
composed of the following elements: 
a vertical tubular reactor 1, in which the functionalized resin charge 2 is 
contained, 
a recirculation loop 3 which emerges at the upper end 4 and at the lower 
end 5 of the reactor 1, this loop comprising pipes successively 
connecting, from the lower end 5, a closing valve 6, a by-pass 7 equipped 
with a valve 8, a jacketed exchanger 9, a gear pump 10 (maximum throughput 
40 l/h), a temperature recorder 11, a ball flowmeter 12 and a jacketed 
cylindrical tank 13 equipped with a window 14 made of thick transparent 
glass. This tank 13 is connected to the upper end 4 of the reactor via a 
pipe which passes through a closing valve 15. The tank 13 is placed above 
the reactor 1. 
This circulation loop 3 itself contains a bypass loop 16 equipped with 2 
valves 17 and 18. 
This loop 16 makes it possible to isolate the reactor 1 from the 
circulation stream by virtue of the interaction of the valves 6, 15, 17 
and 18. 
The tank 13 is equipped, at its upper part, with a pipe 19 for introducing 
acrylic acid and the various solvents. This pipe 19 containes a valve 20. 
The tank 13 is also equipped with a pipe 21 equipped with a pressure valve 
22. The pipe 21 is connected to a flare. 
The tank 13 is equipped, at its lower part, with a pipe 23 equipped with a 
valve 24, which pipe is intended for the introduction of pressurized 
H.sub.2 S into the tank. 
The lower part of the tank is connected, via a pipe 25 equipped with a 
valve 26, to a receiver 27. The latter is equipped, at its lower part, 
with a pipe 28 equipped with a valve 29. The pipe 28 makes it possible to 
recover samples during reaction. 
II.3. Operating protocol 
The operations of charging resin and of introducing acrylic acid and the 
solvent are carried out in a nitrogen atmosphere. 
II.3.1 Preparation of the Reaction Mixtures 
The reactor 1, containing the resin 2 (charges of the order of 20 g), is 
isolated from the rest of the equipment by closing the valves 6 and 15. 
The acrylic acid and the solvent are introduced via the pipe 19 into the 
cylindrical tank 13 which is in direct communication with the 
recirculation loop. The equipment is pressurized to a pressure of 3 bar of 
nitrogen. The cylindrical tank 13, in which the starting reaction mixture 
will be prepared, is cooled by circulating oil at 12.degree. C. 
(originating from a cryostat) which also passes through the external 
jacket of the exchanger 9 of the recirculation loop. The circulation pump 
10 is started and the liquid contained in the cylindrical tank circulates 
in the loop 3 and the loop 16 by being directed from the tank 13 towards 
the valve 17 before passing through the valve 18. 
The hydrogen sulphide, supplied under a pressure of 16 bar, is injected via 
the pipe 23 into the tank 13 by means of a diffuser and dissolves in the 
cooled liquid mixture (at the start: acrylic acid+solvent) . At the end of 
the injection of the H.sub.2 S, the pressure is 15 bar and the temperature 
of the liquid mixture (acrylic acid+H.sub.2 S+solvent) is 20.degree. C. 
The charging volume can be controlled via the window 14. 
II.3.2 Performing the Tests 
The cryostat set point is placed at the value corresponding to the 
temperature at which the reaction has to be carried out and, while the oil 
rapidly rises to the set temperature, the circulating reaction mixture is 
introduced, by opening the valves 15 and 6 and closing the valves 17 and 
18, into the reactor 1, through which it recirculates at a high flow rate 
(maximum: 40 l/h). The reaction temperature programmed for the test is 
maintained throughout the duration of the reaction, i.e. generally 6 
hours. The pressure of the gas phase in the plant, which is connected to 
the pressure valve 22, becomes established between 19 bar and 24 bar, 
depending on the test conditions. 
During testing, samples of the reaction mixture are withdrawn at 
predetermined times via the receiver 27 and recovered at atmospheric 
pressure and are then analysed by gas chromatography. At the end of the 
test, the plant is decompressed and the final reaction product is 
recovered. 
II.4. Analysis of the reaction products 
Analysis by gas chromatography (GC) required a specific development in 
order to solve the problems posed by the analysis of 3,3'-thiodipropionic 
acid and by the separation of acrylic acid and dimethylformamide. 
3,3'-Thiodipropionic acid, because of its physical properties and its polar 
functional groups, can only be analysed at high temperature with a 
chromatographic column of high thermal stability (greater than 300.degree. 
C.) and of very low polarity. The chromatography columns which may be 
suitable are capillary columns containing polysiloxane-based phases; the 
non-polar crosslinked dimethylpolysiloxane phase is very well suited. This 
type of phase is not appropriate for the separation of acrylic acid and 
dimethylformamide with columns commonly used in laboratories, that is to 
say 25-meter or 50-meter columns. The separation of these two compounds 
could be obtained by connecting two, respectively 50 m and 25 m, Hewlett 
Packard Ultra-1 capillary columns in series, the chromatography device 
being a Hewlett Packard 5890 FID. 
The results of the chromatographic analyses of the reaction samples were 
controlled by analyses of reference samples of known compositions by 
weight, prepared from acrylic acid (AA), 3-mercaptopropionic acid (MPA), 
3,3'-thiodipropionic acid (TDPA) and solvent (DMF or diglyme). These 
control analyses have made it possible to determine the response factors 
relating to the various constituents. In the case of the evaluation of the 
content of 3,3'-thiodipropionic acid, its true content in the samples is 
greatly reduced when analysed by GC and a specific correction is essential 
in order to determine quantitatively the 3,3'-thiodipropionic acid 
produced in the reaction. 
II.5. Experimental tests 
II.5.1 General Points 
The tests were carried out according to the operating protocol which has 
been employed by us and which has been described in a preceding paragraph. 
Withdrawals from the reaction mixture were carried out at predetermined 
times in each test: after 2 hours, 4 hours and 6 hours. 
The samples withdrawn were analysed by gas chromatography with the method 
which has been developed. These analyses give the value of the conversion 
of the acrylic acid (AA) at the predetermined times (2 h, 4 h and 6 h) and 
the selectivity by weight for 3-mercaptopropionic acid (MPA) and for 
3,3'-thiodipropionic acid (TDPA). 
II.5.2 Comparative Tests with the IRA 94 Resin and DMF 
Comparative Test No. 1 
The operating conditions taken for this test correspond to Example 2 of 
J07,228,568: 
______________________________________ 
Charge of IRA 94 resin 
24 g 
DMF 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 142 g (4.2 mol) 
Molar ratio H.sub.2 S/AA = 3/1 
Temperature 60.degree. C. 
______________________________________ 
At the reaction temperature of 60.degree. C., the pressure in the equipment 
is 20 bar (relative). 
Comparative Test No. 2 
The operating conditions taken for this test correspond to Example 3 of 
J07,228,568: 
______________________________________ 
Charge of IRA 94 resin 
24 g 
DMF 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 284 g (8.34 mol) 
Molar ratio H.sub.2 S/AA = 6/1 
Temperature 60.degree. C. 
______________________________________ 
At the reaction temperature of 60.degree. C., the pressure in the equipment 
is 24 bar. 
II.5.3 Tests with the PS-DVB-TMG and DMF 
Test No. 3 
With the exception of the resin employed, the operating conditions of this 
test are identical to those used for Test No. 1: 
______________________________________ 
Charge of PS-DVB-TMG resin 
19 g 
DMF 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 142 g (4.2 mol) 
Molar ratio H.sub.2 S/AA = 3/1 
Temperature 60.degree. C. 
______________________________________ 
At the reaction temperature of 60.degree. C., the pressure in the equipment 
is 19-20 bar (relative). 
Test No. 4 
With the exception of the resin employed, the operating conditions of this 
test are identical to those used for Test No. 2: 
______________________________________ 
Charge of PS-DVB-TMG resin 
19 g 
DMF 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 284 g (8.34 mol) 
Molar ratio H.sub.2 S/AA = 6/1 
Temperature 60.degree. C. 
______________________________________ 
At the reaction temperature of 60.degree. C., the pressure in the equipment 
is 23-24 bar. 
II.5.4 Tests with the PS-DVB-TMG Resin with Diglyme as Solvent 
Test No. 5 
This test was carried out under conditions identical to those of Test No. 
3, with the sole difference that diglyme replaces DMF as solvent: 
______________________________________ 
PS-DVB-TMG resin 19 g 
Diglyme 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 142 g (4.2 mol) 
Molar ratio H.sub.2 S/AA = 3/1 
Reaction temperature 60.degree. C. 
______________________________________ 
At the temperature of 60.degree. C., the pressure in the equipment is 20 
bar (relative). 
Test No. 6 
This test was carried out under conditions identical to those of Test No. 
4, with the sole difference that diglyme replaces DMF as solvent: 
______________________________________ 
PS-DVB-TMG resin 19 g 
Diglyme 150 g 
Acrylic acid 100 g (1.39 mol) 
H.sub.2 S 284 g (8.34 mol) 
Molar ratio H.sub.2 S/AA = 6/1 
Reaction temperature 60.degree. C. 
______________________________________ 
At the temperature of 60.degree. C., the pressure in the equipment is 24 
bar (relative). 
The results of Tests No. 3 and No. 4 (resin containing TMG guanidine 
functional group), compared with the results of Tests No. 1 and No. 2 (IRA 
94 resin containing a tertiary amine functional group), show that the 
PS-DVB-TMG resin is markedly more selective than the IRA 94 resin for the 
production of 3-mercaptopropionic acid. 
After 6 hours, with a charge of PS-DVB-TMG resin (19 g) which is lower than 
with the IRA 94 resin, comparable levels of conversion of the acrylic acid 
(AA) are obtained. 
The same effects on the selectivity for 3-mercaptopropionic acid are 
encountered as a function of the H.sub.2 S/AA ratio, that is to say, from 
a 3/1 ratio to a 6/1 
ratio, the gain in selectivity for MPA is comparable. 
The results with the PS-DVB-TMG resin on using diglyme as solvent (Tests 
No. 5 and No. 6) are markedly poorer than with dimethylformamide (Tests 
No. 3 and No. 4). In diglyme, the conversion of the acrylic acid is much 
slower and the selectivity for 3-mercaptopropionic acid is significantly 
lower than in DMF. 
DMF is a remarkable solvent which has the effect of greatly increasing the 
activity and the selectivity of the PS-DVB-TMG resin for the above 
reaction (1). 
The conversion and selectivity values in the above Tests 1 to 6 and in the 
following tests are quantitative because they have been calibrated by 
reference mixtures. 
If chromatographic response factors are not taken into account, an apparent 
selectivity for MPA of 80.4% (instead of the true 68.4%) and for TPDA of 
19.3% (instead of the true 31.2%) are obtained for Test No. 1. 
Likewise, Test No. 2 results in an apparent selectivity for MPA of 90.9% 
(instead of 84.1%) and an apparent selectivity for TDPA of 9.9% (instead 
of 15.8%). 
The results obtained for the above tests are presented in the following 
Table I. 
TABLE I 
__________________________________________________________________________ 
2 Hours 4 Hours 6 Hours 
AA MPA 
TDPA 
AA MPA 
TDPA 
AA MPA 
TDPA 
Test H.sub.2 S 
Conv. 
Sel. 
Sel. 
Conv. 
Sel. 
Sel. 
Conv. 
Sel. 
Sel. 
No. 
Solvent 
AA (%) (%) 
(%) (%) (%) 
(%) (%) (%) 
(%) 
__________________________________________________________________________ 
1* DMF 3 89.8 
70.9 
28.8 
95.7 
70.4 
29.3 
98.6 
68.4 
31.2 
1 
2* DMF 6 95.5 
84.5 
15.3 
97.6 
84.2 
15.6 
99.0 
84.1 
15.8 
1 
3 DMF 3 79.1 
89.7 
10.1 
89.0 
86.6 
13.3 
97.7 
86.5 
13.4 
1 
4 DMF 6 85.5 
94.7 
5.2 94.6 
92.9 
7.0 98.2 
92.5 
7.4 
1 
5 Diglyme 
3 41.3 
92.6 
7.2 58.3 
78.9 
20.9 
76.9 
77.3 
22.5 
1 
6 Diglyme 
6 61.6 
88.3 
11.5 
78.3 
86.9 
12.9 
89.3 
85.8 
14.0 
1 
__________________________________________________________________________ 
*Comparative Test 
II.5.5 Comparative Tests in DMF as Solvent, at a Temperature 40.degree. C., 
of Resins Containing Guanidine Functional Groups (Invention) and of Resins 
Containing a Tertiary Amine Functional Group. 
These tests were carried out at a lower temperature with the aim of 
comparing the catalytic activities of the resins containing a guanidine 
functional group and of the resins containing an amine functional group 
under kinetic conditions which are more favourable for the production of 
3-mercaptopropionic acid. 
Two series of tests were carried out under identical operating conditions, 
with H.sub.2 S/acrylic acid molar ratios of 3/1 and 6/1, from 100 g (1.39 
mol) of acrylic acid and 150 g of DMF (solvent). 
Two resins containing a tertiary amine functional group were tested: 
*IRA 94 (24 g), Rohm and Haas resin given as example in J07,228,568 and 
used as reference resin in our preceding tests. 
*A-21 (22.5 g), Rohm and Haas resin given as example in U.S. Pat. No. 
5,008,432 (or EP 208,323). 
Two resins containing a guanidine functional group of the invention were 
tested: 
*PS-DVB-TBD (21.6 g), resin containing our 
1,5,7-triazabicyclo4.4.0!dec-5-ene functional group, prepared according 
to the procedure described above. 
*PS-DVB-TMG (19 g), resin containing a 1,1,3,3-tetramethylguanidine 
functional group, prepared according to the procedure described above. 
Tests No. 7, 8, 9 and 10 with a molar ratio 
##EQU1## 
Conditions: DMF: 150 g 
Acrylic acid: 100 g (1.39 mol) 
H.sub.2 S: 142 g (4.2 mol) 
At the reaction temperature of 40.degree. C., the pressure in the equipment 
is 17 bar (relative). 
Tests No. 11, 12, 13 and 14 with a molar ratio 
##EQU2## 
Conditions: DMF: 150 g 
Acrylic acid: 100 g (1.39 mol) 
H.sub.2 S: 284 g (8.34 mol) 
At the reaction temperature of 40.degree. C., the pressure in the equipment 
is 20 bar (relative). 
The results obtained at 40.degree. C. confirm the results of the preceding 
tests at 60.degree. C. with the solvent DMF, namely: 
*The resins containing a guanidine functional group are more selective for 
3-mercaptopropionic acid than the resins containing a tertiary amine 
functional group. 
In the case of the resins containing a guanidine functional group: 
*The decrease in temperature from 60.degree. C. to 40.degree. C. slightly 
improves the selectivity for 3-mercaptopropionic acid. In contrast, the 
decrease in temperature affects the rate of conversion of the acrylic 
acid. 
In the case of the resins containing a tertiary amine functional group: 
*The decrease in temperature from 60.degree. C. to 40.degree. C. has the 
same effects as for the guanidine resins (slight gain in selectivity for 
MPA and fall in the conversion of the acrylic acid). 
*The A-21 resin, which is more active than the IRA 94 resin, has the same 
selectivity for 3-mercaptopropionic acid as the IRA 94 resin. 
The results obtained for the 8 resins tested under these conditions are 
recorded in Table II. 
TABLE II 
__________________________________________________________________________ 
2 Hours 4 Hours 6 Hours 
AA MPA 
TDPA 
AA MPA 
TDPA 
AA MPA 
TDPA 
Test Conv. 
Sel. 
Sel. 
Conv. 
Sel. 
Sel. 
Conv. 
Sel. 
Sel. 
No. 
Resin (%) (%) 
(%) (%) (%) 
(%) (%) (%) 
(%) 
__________________________________________________________________________ 
7* 
IRA 94 66.9 
78.2 
21.6 
82.5 
77.8 
22.0 
92.5 
76.9 
22.9 
8* 
A-21 81.5 
78.6 
21.2 
93.7 
77.9 
21.9 
97.6 
75.9 
23.9 
9 PS-DVB-TBD 
80.6 
88.7 
11.2 
90.9 
87.2 
12.7 
96.2 
86.8 
13.1 
10 PS-DVB-TMG 
61.1 
93.6 
6.3 78.5 
91.3 
8.6 88.3 
89.2 
10.7 
11* 
IRA 94 68.1 
87.0 
12.8 
85.6 
85.0 
14.8 
95.1 
84.2 
15.6 
12* 
A-21 84.1 
85.6 
14.2 
90.5 
84.5 
15.3 
97.4 
84.1 
15.7 
13 PS-DVB-TBD 
86.0 
94.5 
5.4 93.8 
93.8 
6.1 96.8 
92.8 
7.1 
14 PS-DVB-TMG 
65.1 
96.4 
3.5 86.2 
96.2 
3.7 94.1 
93.7 
6.2 
__________________________________________________________________________ 
*Comparative Test 
Although the invention has been described in conjunction with specific 
embodiments, it is evident that many alternatives and variations will be 
apparent to those skilled in the art in light of the foregoing 
description. Accordingly, the invention is intended to embrace all of the 
alternatives and variations that fall within the spirit and scope of the 
appended claims. The above references are hereby incorporated by 
reference.