AGENT FOR INITIATING A RADICAL ADDITION REACTION AND PROCESS USING IT

Abstract

An agent for initiating a radical addition reaction includes a persulfate and one or more transition metals, in elemental form or in an oxidized form, as well as a method for preparing a compound of formula (I)

##STR00001## in which X is selected from S, Se and O; by a radical addition reaction in the presence of such an agent.

Claims

1. A method for preparing a compound of formula (I) ##STR00007## in which X is selected from S, Se and O; R.sub.1 is selected from H, alkyl groups, aryl groups and alkylaryl groups; R.sub.2 is selected from H; OH; NR.sub.4R.sub.5; NHCOR.sub.4; OCOR.sub.4; where R.sub.4 and R.sub.5 are identical or different and are selected from H, alkyl groups, aryl groups, alkylaryl groups; and protecting groups; R.sub.3 is selected from OH, CH.sub.2OH, COOH, COOR.sub.6 where R.sub.6 is selected from alkyl, CN, CONR.sub.4R.sub.5 where R.sub.4 and R.sub.5 are as defined above, and COZ where Z represents a halide; which method comprising the reaction of a compound of formula (II) ##STR00008## in which X is selected from S, Se and O; R.sub.1′ is selected from H, alkyl, aryl, alkylaryl, thiol, thioalkyl, thioaryl, thioalkylaryl, selenol, selenoalkyl, selenoaryl and selenoalkylaryl groups, and R.sub.2′ is selected from H, alkyl, aryl and alkylaryl groups; with a compound of formula (III) ##STR00009## where R.sub.2 and R.sub.3 are as defined above for the compound of formula (I), in the presence of at least one agent for initiating a radical addition reaction comprising a persulfate and one or several transition metals, in elemental form or in oxidized form.

2. The method according to claim 1, wherein the persulfate is in the form of a salt of a cation.

3. The method according to claim 1, wherein the transition metal(s) are selected from Cu, Zn and Fe, in their elemental form or in an oxidized form selected from sulfates, phosphates, chlorides, carbonates, hydroxides, nitrites, nitrates, acetates, alcoholates, hydrogenphosphates and hydrogen sulfates, and their alloys such as brass.

4. The method according to claim 1, wherein the molar ratio of persulfate to the transition metal(s) ranges from 1 to 1000.

5. The method according to claim 1, wherein the persulfate is potassium persulfate or sodium persulfate.

6. The method according to claim 1, wherein the molar ratio of compound (II) or of compound (III) to the initiation agent ranges from 2 to 1000.

7. The method according to claim 1, wherein the molar ratio of compound (II) to compound (III) ranges from 0.9 to 20, preferably from 1.1 to 3.

8. The method according to claim 1, wherein the compound (II) is methylthiol or methylselenol.

9. The method according to claim 1, wherein the compound (III) is methyl vinyl glycolate.

10. The method according to claim 1, wherein the reaction is carried out at a temperature from −20° C. to 40° C.

11. A use of an agent for the initiation of a radical addition reaction for obtaining compounds of formula (I) as defined in claim 1, said agent comprising a persulfate and one or several transition metals, in elemental or oxidized form.

Description

DETAILED DESCRIPTION OF THE DISCLOSURE

[0028] Thus the disclosure concerns the application of an agent for the initiation, or initiator agent, or primer agent, in a radical addition reaction, said agent comprising or consisting of a persulfate and one or more transition metals, under elemental form or in an oxidized form.

[0029] The persulfate can be in the form of a salt of a cation, the associated cation preferably being selected from sodium, potassium, calcium, lithium and ammonium ions, although any counterion may be suitable.

[0030] As indicated above, according to the disclosure, the persulfates can be, in certain cases, advantageously replaced by organic peroxides.

[0031] The persulfate can be combined with one or more transition metals. When several metals are used, the mixtures may consist of the same metal in the elemental state and/or in different degrees of oxidation; different metals in elemental state and/or in the same degree of oxidation or in different degrees of oxidation, but also in the form of alloys such as for example brass, possibly in oxidized form.

[0032] The transition metal(s) are advantageously selected from Cu, Zn and Fe, in their elemental form or in an oxidized form as defined above.

[0033] Advantageously, the molar ratio of persulfate to the transition metal(s) ranges from 0.5 to 10,000. An excess of metal can lead to a drop in the selectivity of the reaction, but too low a content will slow down the reaction, affecting its industrializable interest. Preferably, this molar ratio ranges from 1 to 1000.

[0034] According to the disclosure, the aforementioned combination of a persulfate and one or more transition metals is applied to the initiation of a radical addition reaction involving an organic entity capable of forming a radical which reacts on a double bond. This double bond is unconjugated. It may or may not be terminal.

[0035] In the context of the disclosure, the initiator agent is used in very small proportions relative to the organic species involved in the reaction. Thus, the molar ratio of the organic species on which the initiator agent acts directly to said agent ranges from 2 to 1000. It is within the competence of one skilled in the art to adjust the value of this ratio as well as possible. The persulfate is preferably used in solution in an inert solvent. This can consist of water and any aqueous mixture containing a water soluble organic solvent such as an alcohol. According to a preferred variant of implementation of the initiator agent, the compound (III) is mixed with the metal, then the compound (II) is added, and finally the persulfate solution is slowly poured into this mixture.

[0036] The disclosure also concerns one of the applications of this initiator agent, and specifically its use for obtaining compounds of formula (I) cited above, namely,

##STR00004##

[0037] in which

[0038] X is selected from S, Se and O;

[0039] R.sub.1 is selected from H, alkyl groups, aryl groups and alkylaryl groups;

[0040] R.sub.2 is selected from H; OH; NR.sub.4R.sub.5; NHCOR.sub.4, OCOR.sub.4, where R.sub.4 and R.sub.5 are identical or different and are selected from H, alkyl groups, aryl groups, alkylaryl groups; and protecting groups;

[0041] R.sub.3 is selected from OH, CH.sub.2OH, COOH, COOR.sub.6 where R.sub.6 is selected from alkyl, CN, CONR.sub.4R.sub.5 where R.sub.4 and R.sub.5 are as defined above, and COZ where Z represents a halide;

[0042] said method comprising the reaction of a compound of formula (II)

##STR00005##

[0043] in which

[0044] X is selected from S, Se and O;

[0045] R.sub.1′ is selected from H, alkyl, aryl, alkylaryl, thiol, thioalkyl, thioaryl, thioalkylaryl, selenol, selenoalkyl, selenoaryl and selenoalkylaryl groups, and

[0046] R.sub.2′ is selected from H, alkyl groups, aryl groups and alkylaryl groups;

[0047] with a compound of formula (III)

##STR00006##

[0048] where R.sub.2 and R.sub.3 are as defined above for the compound of formula (I).

[0049] The initiator agent as described above, that is to say responding to any one or several of the mentioned characteristics, is suitable for this reaction.

[0050] The work carried out on this reaction has, however, made it possible to determine the preferred variants indicated below, which can be considered alone or in combination, according to which the method is the most efficient, in particular is the most selective.

[0051] Thus, the persulfate is preferably potassium persulfate or sodium persulfate.

[0052] The molar ratio of compound (II) or of compound (III) to the initiator agent advantageously ranges from 2 to 1000, and better still from 10 to 500.

[0053] The molar ratio of compound (II) to compound (III) ranges from 0.9 to 20, preferably from 1.1 to 3.

[0054] As said before, the use of an initiator agent of the disclosure allows the reaction temperature to be lowered; that can be carried out at a temperature of −20° C. to 60° C., preferably from −20 to 40° C., or even from 0° C. to 40° C., and even from 10° C. to 40° C. Such conditions are favorable for high selectivity, without affecting the reaction yield.

[0055] The initiator agent of the disclosure can be implemented for the radical addition of a compound (II) selected from methylthiol and methylselenol and of a compound (III) as defined above. It can also be used for the radical addition of a compound of formula (II) as generally defined above and of methyl vinyl glycolate, as compound (III).

[0056] According to a variant of the disclosure, the method is aimed at the preparation of HMTBA or its selenium analogue, hydroxymethyl selenobutyric acid (HMSeBA), as compound (I). HMTBA and HMSeBA can be obtained by the radical addition of methylthiol or methyl selenol, respectively, as compound (II), to methyl vinyl glycolate as compound (III) followed by hydrolysis of the formed correspondent ester.

EXAMPLES

[0057] The disclosure and its advantages are illustrated in the examples below.

Example 1: Preparation of methyl 2-hydroxy-4-(methylthio) butanoate by Radical Addition Reaction with an Initiator Agent According to the Disclosure

[0058] 26.0 g (0.22 mol) of methyl 2-hydroxybut-3-enoate and 0.17 g of metallic copper (0.00027 mol) are placed in a stirred reactor and cooled to −10° C. 12.1 g of methanethiol (0.25 mol) are then injected, then an aqueous solution of sodium persulfate (0.023 mol) is slowly added.

[0059] The temperature is increased to 0° C. and the mixture is left under stirring for one hour.

[0060] HPLC analysis of the mixture at the end of the reaction indicates an 81% yield of methyl 2-hydroxy-4-(methylthio) butanoate (selectivity of 81%).

Comparative Example 1: Preparation of methyl 2-hydroxy-4-(methylthio)butanoate by Radical Addition Reaction with a Persulfate Compound Alone at Elevated Temperature

[0061] 40.1 g (0.34 mol) of methyl 2-hydroxybut-3-enoate are placed in a stirred reactor and cooled to −15° C. 18.0 g of methanethiol (0.37 mol) are then injected, then an aqueous solution of sodium persulfate (0.034 mol) is slowly added.

[0062] The temperature is increased to 60° C. and the mixture is left under stirring for two hours.

[0063] HPLC analysis of the mixture at the end of the reaction indicates a 7.6% yield of methyl 2-hydroxy-4-(methylthio) butanoate (15% selectivity).

Example 2: Preparation of methyl 4-(butylsulfanyl)-2-hydroxybutanoate by Radical Addition Reaction with an Initiator Agent According to the Disclosure

[0064] 20.4 g (0.18 mol) of methyl 2-hydroxybut-3-enoate and 0.025 g of metallic copper (0.00040 mol) are placed in a stirred reactor and cooled to −10° C. 17.7 g of butanethiol (0.20 mol) are then injected, then an aqueous solution of sodium persulfate (0.0054 mol) is slowly added.

[0065] The temperature is increased to 25° C. and the mixture is left under stirring for one hour.

[0066] HPLC analysis of the mixture at the end of the reaction indicates a 16% yield of methyl 4-(butylsulfanyl)-2-hydroxybutanoate.

Example 3: Preparation of 3-(methylsulfanyl) propan-1-ol by Radical Addition Reaction with an Initiator Agent According to the Disclosure

[0067] 14.8 g (0.25 mol) of propen-3-ol and 0.015 g of metallic copper (0.00023 mol) are placed in a stirred reactor and cooled to −10° C. 13.5 g of methanethiol (0.28 mol) are then injected, then an aqueous solution of sodium persulfate (0.0077 mol) is slowly added.

[0068] The temperature is increased to 0° C. and the mixture is left under stirring for one hour.

[0069] HPLC analysis of the mixture at the end of the reaction indicates a quantitative yield of 3-(methylsulfanyl) propan-1-ol.

Example 4: Preparation of methyl 2-hydroxy-4-(methylthio) butanoate by Radical Addition Reaction with an Initiator Agent According to the Disclosure

[0070] 26.3 g (0.23 mol) of methyl 2-hydroxybut-3-enoate and 0.020 g of iron (II) and iron (III) oxide (0.00013 mol) are placed in a stirred reactor and cooled to −10° C. 13.2 g of methanethiol (0.27 mol) are then injected, then an aqueous solution of sodium persulfate (0.023 mol) is slowly added.

[0071] The temperature is increased to 0° C. and the mixture is left under stirring for one hour.

[0072] HPLC analysis of the mixture at the end of the reaction indicates a 79% yield of methyl 2-hydroxy-4-(methylthio) butanoate.

Example 5: Preparation of methyl 2-hydroxy-4-(methylthio) butanoate by Radical Addition Reaction with an Initiator Agent According to the Disclosure

[0073] 26.1 g (0.22 mol) of methyl 2-hydroxybut-3-enoate and 0.089 g of iron sulfate (0.00022 mol) are placed in a stirred reactor and cooled to −10° C. 12.0 g of methanethiol (0.25 mol) are then injected, then an aqueous solution of sodium persulfate (0.023 mol) is slowly added.

[0074] The temperature is increased to 0° C. and the mixture is left under stirring for one hour.

[0075] HPLC analysis of the mixture at the end of the reaction indicates a 70% yield of methyl 2-hydroxy-4-(methylthio) butanoate (selectivity of 84%).

[0076] These examples demonstrate the performance of an initiator agent according to the disclosure and of a method implementing it.