WO2005023774A1 - Process for the preparation of a trifluoromethylthioether - Google Patents
Process for the preparation of a trifluoromethylthioether Download PDFInfo
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- WO2005023774A1 WO2005023774A1 PCT/DK2004/000582 DK2004000582W WO2005023774A1 WO 2005023774 A1 WO2005023774 A1 WO 2005023774A1 DK 2004000582 W DK2004000582 W DK 2004000582W WO 2005023774 A1 WO2005023774 A1 WO 2005023774A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/44—Oxygen and nitrogen or sulfur and nitrogen atoms
Definitions
- the present invention relates to a process for the preparation of a trifluoromethyl thioether of the formula (I)
- Yi and Y 2 which may be identical or different, each represent H or O-R, where R represents a hydrogen atom, a linear or branched alkyl chain of 1-5 carbon atoms or an alkali metal atom, with the provisio that at least one of Yj and Y 2 is other than a hydrogen atom.
- the reaction is very exothermic and when the reaction is performed on large scale it may result in a substantial pressure increase in the vessel and associated operator hazard.
- a metal is used as a reducing agent the reaction will also produce metal containing waste that need to be discharged, which may be considered an environmental hazard.
- the mixture of disulphide, sodium formate, sulphur dioxide and N,N-dimefhylformamide is unstable and may lead to the formation of unwanted by-products. Therefore it has been found necessary to add the trifluoromethyl bromide quickly, which is not favourable because of the exothermic nature of the reaction.
- the compound (I) is a well known compound, which is useful as the starting material in the preparation of the insecticide Fipronil and related compounds by known methods, e.g. as described in European patent no. 295117-A1.
- the present invention relates to a process for the preparation of a trifluoromethyl thioether of the formula (I)
- X represents O or S
- Yi and Y 2 which may be identical or different, each represent H or O-R, where R represents a hydrogen atom, a linear or branched alkyl chain of 1-5 carbon atoms or an alkali metal atom; with the provisio that at least one of Y ⁇ and Y 2 is other than a hydrogen atom.
- the trifluoromethylhalide may be chosen among CF 3 C1, CF 3 I and CF Br with CF I and CF 3 Br being the preferred choice and especially CF 3 Br.
- Preferred reagents of the formula (TTT) x Yi PH (III) Y 2 are those where X represent O. More preferred are those where Yi represents H or OH; and Y 2 represent OH or O-alkali metal, with sodium being the preferred alkali metal. Even more preferably the reagent(s) is selected among phosphorous acid (H 3 PO ), hypophosphorous acid (H 3 PO 2 ) and sodium hypophosphorous acid (NaH PO 2 ), with hypophosphorous acid and sodium hypophosphorous acid being the most preferred choice.
- the reagent(s) of formula (TTT) may be employed in one or more of its hydrated forms, preferably such as sodium hypophosphorous acid monohydrate (NaH 2 PO 2 , 1H 2 0) and sodium hypophosphorous acid hydrate (NaH 2 PO 2 , xH 2 O).
- the molar ratio of trifluoromethylhalide to disulphide of formula (TT) is prefera- bly higher than 1.
- Sulphur dioxide may be present in a catalytic quantity but amounts higher than 1 equivalent relative to the disulphide of formula (TT) is preferred, more preferably between 1 and 7, even more preferred between 1.5 and 4.5 although the upper limit is not critical.
- the amount of reagent(s) of formula (III) used is generally 1-15 molar equiva- lents relative to the disulphide of formula (TT), preferably 2-11 molar equivalents.
- the solvent for the reaction may in principle be any solvent that is inert and which is capable of dissolving the reactants under the reaction conditions.
- inert is intended to mean that the solvent does not in a substantial degree react with the components of the mixture.
- the sol- vent is a polar solvent such as formamide, pyridine, dimethylformamide (DMF), N,N-dimethylacetamide (DMA), Hexamethylphosphoric triamide (HMPT), N- methylpyrrolidone (NMP), dimethyl sulphoxide (DMSO), sulpholane and ethers such as dioxane, tetrahydrofuran and dimethoxyethane or mixtures thereof with HMPT, DMA and DMF being the preferred choice.
- Small amounts of water may advantageously be added to the solvent, e.g. a volume of up to 35% of the volume of solvent(s) used, and preferably in an amount of 5-25%.
- the reaction temperature is usually within the range of 20-140°C or at or below the boiling temperature of the solvent, preferably between 30-110°C. Due to the gaseous nature of the trifluoromethylhalide the reaction is performed under pres- sure in a suitable apparatus made of a non-reactive material e.g. a glass reactor or teflon coated reactor. A pressure of between 1 and 50 bars is preferred.
- the sulphur dioxide is added portion wise, continuously or prior to the reaction and one may introduce the sulphur dioxide as the last reagent to the reaction mixture.
- the sulphur dioxide is introduced to the reaction vessel either in gaseous form or dissolved in a solvent, preferably the same as the reaction solvent.
- Variation of the pH in the reaction mixture may be achieved by adding a buffer prior to or during the reaction.
- buffer can be of the organic or inorganic type and include pyridine, amines (e.g. aqueous ammonia, triethyl- amine), alkali metal hydroxides and salts of weak acids such as alkali metal salts of carbonates, phosphates, sulphites, citrates and acetates (e.g. NaHCO 3 , Na 2 CO 3 , NaH 2 PO 4 , Na 2 HPO 4 , NaHSO 3 ).
- the starting compound (TT) utilised in the process of the present invention may be prepared according to known methods e.g. as described in European patent no. 295117-A1 and International application WO 01/30760-A1.
- the compounds of formula (TTT) are commercially available or can be produced according to known methods.
- Teflon insert to a Berghof autoclave was added sodium hypophosphorous hydrate (7.15 mmol 0.89g), bis-[5-amino-3-cyano-l-(2,6-dichloro-4- trifluoromethyl-phenyl)-pyrazole-4-yl] disulphide (1.43 mmol l.Olg), N,N- dimethylacetamide (10 ml), water (2.07ml) and sulphur dioxide (2.81 mmol 0.18g). Then the Teflon insert was cooled to -60°C, CF 3 Br (39.0 mmol 5.82g) condensed into the insert and the autoclave closed and heated to 80°C for 2 hours.
- the autoclave was closed and with stirring for 5 minutes at room temperature, the autoclave was pressurized with CF 3 Br until a pressure of 13 bars.
- the autoclave was heated to 63°C. Additional sulphur dioxide (14.7 mmol 0.94g) dis- solved in 25 ml N,N-dimethylacetamide was pumped into the reactor over 45 minutes, and the temperature was maintained at 63°C. After 2 hours the autoclave was cooled to room temperature and opened after release of pressure. After washing with water and extracting the product with methyl-t-butylether the product was analyzed (GC internal standard method). Yield of 5-amino-3-cyano- l-(2,6-dichloro-4-trifluoromethyl-phenyl)-4-trifluoromethylthio-lH-pyrazole was 4.8g (79.3%).
- DMF Dimethylformamide
- DMA N,N-dimethylacetamide
- HMPT Hexamethylphosphoric triamide
- the amount of compound (TT) used was 7.15 mmol and the amount of solvent besides water added was 50 ml.
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
A process for the preparation of a trifluoromethyl thioether of the formula (I) by reaction of a disulphide with a trifluromethyl halide in the presence of sulphur dioxide and one or more compounds of the formula (III) wherein X represents O or S; Y1 and Y2, which may be identical or different, each represent H or O-R, where R represents a hydrogen atom, a linear or branched alkyl chain of 1-5 carbon atoms or an alkali metal atom; with the provisio that at least one of Y1 and Y2 is other than a hydrogen atom.
Description
Process for the preparation of a trifluoromethylthioether.
The present invention relates to a process for the preparation of a trifluoromethyl thioether of the formula (I)
by reaction of a disulphide with a trifluromethyl halide in the presence of sul- phur dioxide and one or more compounds of the formula (HI) x Yi PH (III) γ2 wherein X represents O or S;
Yi and Y2, which may be identical or different, each represent H or O-R, where R represents a hydrogen atom, a linear or branched alkyl chain of 1-5 carbon atoms or an alkali metal atom, with the provisio that at least one of Yj and Y2 is other than a hydrogen atom.
Background
Preparation of perfluoroalkylthioethers from perfluoroalkyl halides and disul- phides, including the compound (I), has been described previously:
In United States patent no. 5,082,945 a process is described using a perfluoroalkyl halide which is brought into contact with a disulphide in the presence of a reducing agent consisting of a metal chosen among zinc, cadmium, aluminium
and manganese, with sulphur dioxide or consisting of an alkali metal dithionite or of an alkali or alkali-earth metal or metal hydroxymethanesulphinate or consisting of a formate anion and sulphur dioxide. When employing sulphur dioxide it is introduced prior to the addition of the perfluoroalkyl halide. The reaction is very exothermic and when the reaction is performed on large scale it may result in a substantial pressure increase in the vessel and associated operator hazard. When a metal is used as a reducing agent the reaction will also produce metal containing waste that need to be discharged, which may be considered an environmental hazard. Further it has been found that the mixture of disulphide, sodium formate, sulphur dioxide and N,N-dimefhylformamide is unstable and may lead to the formation of unwanted by-products. Therefore it has been found necessary to add the trifluoromethyl bromide quickly, which is not favourable because of the exothermic nature of the reaction.
This problem was addressed in International patent application no. WO 01/30760-A1 describing that when using a formate anion/sulphur dioxide mixture as reducing agent one may advantageously introduce the sulphur dioxide as the last reagent to the reaction mixture. Even though this order of addition of the component of the reaction mixture significantly reduces the amount of formed by-products the reaction mixture still contains the disulphide, sodium formate, sulphur dioxide and N,N-dimethylformamide, with the possibility of formation of small amounts of by-products, in particular under less favourable conditions. European patent application no. 295117-A1 describes the use of sodium dithio- nite or sodium borohydride in an aqueous-organic solvent such as ethanol or a mixture of alcohol and water.
The previous mentioned methods are also described by Clavel et al. in Phosphorus, Sulfur and Silicon and the Related Elements (1991), 59(1-4), 423-6; Journal of the Chemical Society, Chemical Communications (1991), (15), 993-4 and Journal of the Chemical Society, Perkin Transactions 1 (1992), (24), 3371-5.
In International patent application no. WO 02/066423-A1 a process is described utilising hydrazine and/or a metal borohydride as the reducing agent. Despite of the recent progresses within the area there still exists a need for alternative processes for the manufacture of the compound having the formula (I).
The compound (I) is a well known compound, which is useful as the starting material in the preparation of the insecticide Fipronil and related compounds by known methods, e.g. as described in European patent no. 295117-A1.
Description of the invention
The present invention relates to a process for the preparation of a trifluoromethyl thioether of the formula (I)
Yi and Y2, which may be identical or different, each represent H or O-R, where R represents a hydrogen atom, a linear or branched alkyl chain of 1-5 carbon atoms or an alkali metal atom; with the provisio that at least one of Y\ and Y2 is other than a hydrogen atom.
The trifluoromethylhalide may be chosen among CF3C1, CF3I and CF Br with CF I and CF3Br being the preferred choice and especially CF3Br.
Preferred reagents of the formula (TTT) x Yi PH (III) Y2 are those where X represent O. More preferred are those where Yi represents H or OH; and Y2 represent OH or O-alkali metal, with sodium being the preferred alkali metal. Even more preferably the reagent(s) is selected among phosphorous acid (H3PO ), hypophosphorous acid (H3PO2) and sodium hypophosphorous acid (NaH PO2), with hypophosphorous acid and sodium hypophosphorous acid being the most preferred choice. It is to be understood that the reagent(s) of formula (TTT) may be employed in one or more of its hydrated forms, preferably such as sodium hypophosphorous acid monohydrate (NaH2PO2, 1H20) and sodium hypophosphorous acid hydrate (NaH2PO2, xH2O). The molar ratio of trifluoromethylhalide to disulphide of formula (TT) is prefera- bly higher than 1.
Sulphur dioxide may be present in a catalytic quantity but amounts higher than 1
equivalent relative to the disulphide of formula (TT) is preferred, more preferably between 1 and 7, even more preferred between 1.5 and 4.5 although the upper limit is not critical.
The amount of reagent(s) of formula (III) used is generally 1-15 molar equiva- lents relative to the disulphide of formula (TT), preferably 2-11 molar equivalents. The solvent for the reaction may in principle be any solvent that is inert and which is capable of dissolving the reactants under the reaction conditions. In this connection the term "inert" is intended to mean that the solvent does not in a substantial degree react with the components of the mixture. Preferably the sol- vent is a polar solvent such as formamide, pyridine, dimethylformamide (DMF), N,N-dimethylacetamide (DMA), Hexamethylphosphoric triamide (HMPT), N- methylpyrrolidone (NMP), dimethyl sulphoxide (DMSO), sulpholane and ethers such as dioxane, tetrahydrofuran and dimethoxyethane or mixtures thereof with HMPT, DMA and DMF being the preferred choice. Small amounts of water may advantageously be added to the solvent, e.g. a volume of up to 35% of the volume of solvent(s) used, and preferably in an amount of 5-25%. The reaction temperature is usually within the range of 20-140°C or at or below the boiling temperature of the solvent, preferably between 30-110°C. Due to the gaseous nature of the trifluoromethylhalide the reaction is performed under pres- sure in a suitable apparatus made of a non-reactive material e.g. a glass reactor or teflon coated reactor. A pressure of between 1 and 50 bars is preferred. The sulphur dioxide is added portion wise, continuously or prior to the reaction and one may introduce the sulphur dioxide as the last reagent to the reaction mixture. The sulphur dioxide is introduced to the reaction vessel either in gaseous form or dissolved in a solvent, preferably the same as the reaction solvent.
Variation of the pH in the reaction mixture may be achieved by adding a buffer prior to or during the reaction. Examples of such buffer can be of the organic or inorganic type and include pyridine, amines (e.g. aqueous ammonia, triethyl- amine), alkali metal hydroxides and salts of weak acids such as alkali metal salts of carbonates, phosphates, sulphites, citrates and acetates (e.g. NaHCO3,
Na2CO3, NaH2PO4, Na2HPO4, NaHSO3).
At the end of the reaction the solvent(s) and the reaction products are separated and the trifluoromethylthioether compound (I) purified prior to any subsequent synthesis sequence.
The starting compound (TT) utilised in the process of the present invention may be prepared according to known methods e.g. as described in European patent no. 295117-A1 and International application WO 01/30760-A1. The compounds of formula (TTT) are commercially available or can be produced according to known methods.
The invention is illustrated by the following examples:
Example 1
To a 50 ml Teflon insert to a Berghof autoclave was added sodium hypophosphorous hydrate (7.15 mmol 0.89g), bis-[5-amino-3-cyano-l-(2,6-dichloro-4- trifluoromethyl-phenyl)-pyrazole-4-yl] disulphide (1.43 mmol l.Olg), N,N- dimethylacetamide (10 ml), water (2.07ml) and sulphur dioxide (2.81 mmol 0.18g). Then the Teflon insert was cooled to -60°C, CF3Br (39.0 mmol 5.82g) condensed into the insert and the autoclave closed and heated to 80°C for 2 hours. The autoclave was cooled to room temperature and opened after release of pressure. After washing with water and extracting the product with methyl-t- butylether the product was analyzed (GC internal standard method). Yield of 5- amino-3-cyano- 1 -(2,6-dichloro-4-trifluoromethyl-phenyl)-4-trifluoromethylthio- lH-pyrazole was 1.06g (88.6%).
A series of experiments using the above method is provided in Table 1.
Example 2
To a 200 ml Teflon insert to a Berghof autoclave was added sodium hypophosphorous hydrate (21.3 mmol, 2.59g), bis-[5-amino-3-cyano-l-(2,6-dichloro-4- trifluoromethyl-phenyl)-pyrazole-4-yl] disulphide (7.15 mmol 5.05g), N,N- dimethylacetamide (50 ml), water (7.7 ml) and sulphur dioxide (10.5 mmol 0.67g).
The autoclave was closed and with stirring for 5 minutes at room temperature, the autoclave was pressurized with CF3Br until a pressure of 13 bars. The autoclave was heated to 63°C. Additional sulphur dioxide (14.7 mmol 0.94g) dis- solved in 25 ml N,N-dimethylacetamide was pumped into the reactor over 45 minutes, and the temperature was maintained at 63°C. After 2 hours the autoclave was cooled to room temperature and opened after release of pressure. After washing with water and extracting the product with methyl-t-butylether the product was analyzed (GC internal standard method). Yield of 5-amino-3-cyano- l-(2,6-dichloro-4-trifluoromethyl-phenyl)-4-trifluoromethylthio-lH-pyrazole was 4.8g (79.3%).
A series of experiments using the above method is provided in Table 2.
Table 1
Table 2
Claims
1. A process for the preparation of a compound of the formula (I)
2. A process according to claim 1, wherein the compound of formula (HI) is selected among those where X represent O.
3. A process according to claim 2 wherein the compound of formula (TTT) is selected among those where Y\ represents H or OH; and Y2 represents OH or O-alkali metal.
4. A process according to claim 3, wherein the compound of formula (JJI) is se- lected among phosphorous acid (H PO ), hypophosphorous acid (H3PO ) and sodium hypophosphorous acid (NaH2PO2).
5. A process according to claim 4, wherein the compound of formula (III) is sodium hypophosphorous acid (NaH2PO2).
6. A process according to claim 5, wherein the compound of formula (Iff) is sodium hypophosphorous acid in one of its hydrated forms.
7. A process according to claim 1, wherein the trifluoromethylhalide is CF3Br.
8. A process according to claim 1, wherein the reaction temperature is between 20-140°C.
9. A process according to claim 8, wherein the temperature is between 30- 110°C.
10. A process according to claim 1, wherein the solvent is chosen among dimethylacetamide (DMA), Hexamethylphosphoric triamide (HMPT) and dimethylformamide (DMF).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DKPA200301309 | 2003-09-11 | ||
| DKPA200301309 | 2003-09-11 |
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| Publication Number | Publication Date |
|---|---|
| WO2005023774A1 true WO2005023774A1 (en) | 2005-03-17 |
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| Application Number | Title | Priority Date | Filing Date |
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| PCT/DK2004/000582 WO2005023774A1 (en) | 2003-09-11 | 2004-09-02 | Process for the preparation of a trifluoromethylthioether |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112430213A (en) * | 2020-12-03 | 2021-03-02 | 江苏优普生物化学科技股份有限公司 | Synthesis process of trifluoromethylthio pyrazole |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5082945A (en) * | 1988-12-13 | 1992-01-21 | Rhone-Poulenc Agrochimie | Process for the preparation of perhaloalkylthioethers |
| WO2001030760A1 (en) * | 1999-10-22 | 2001-05-03 | Aventis Cropscience S.A. | Process for preparing 4-trifluoromethylsulphinylpyrazole derivative |
-
2004
- 2004-09-02 WO PCT/DK2004/000582 patent/WO2005023774A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5082945A (en) * | 1988-12-13 | 1992-01-21 | Rhone-Poulenc Agrochimie | Process for the preparation of perhaloalkylthioethers |
| WO2001030760A1 (en) * | 1999-10-22 | 2001-05-03 | Aventis Cropscience S.A. | Process for preparing 4-trifluoromethylsulphinylpyrazole derivative |
Non-Patent Citations (1)
| Title |
|---|
| WOLFGANG: "Hypophosphorous Acid", JOURNAL OF ORGANIC CHEMISTRY., vol. 31, 1966, AMERICAN CHEMICAL SOCIETY. EASTON., pages 1202 - 1205, XP002306107 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112430213A (en) * | 2020-12-03 | 2021-03-02 | 江苏优普生物化学科技股份有限公司 | Synthesis process of trifluoromethylthio pyrazole |
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