EP3177590A1 - Low temperature free radical initiated process for the preparation of 3-((3,3,3-trifluoropropyl)thio)propionic acid and esters thereof - Google Patents

Low temperature free radical initiated process for the preparation of 3-((3,3,3-trifluoropropyl)thio)propionic acid and esters thereof

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Publication number
EP3177590A1
EP3177590A1 EP14899236.5A EP14899236A EP3177590A1 EP 3177590 A1 EP3177590 A1 EP 3177590A1 EP 14899236 A EP14899236 A EP 14899236A EP 3177590 A1 EP3177590 A1 EP 3177590A1
Authority
EP
European Patent Office
Prior art keywords
esters
thio
trifluoropropyl
free radical
propionic acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP14899236.5A
Other languages
German (de)
French (fr)
Other versions
EP3177590A4 (en
Inventor
Kaitlyn Gray
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Corteva Agriscience LLC
Original Assignee
Dow AgroSciences LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dow AgroSciences LLC filed Critical Dow AgroSciences LLC
Publication of EP3177590A1 publication Critical patent/EP3177590A1/en
Publication of EP3177590A4 publication Critical patent/EP3177590A4/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/18—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by addition of thiols to unsaturated compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/26—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
    • C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated

Definitions

  • the present invention concerns a process for the preparation of 3-((3,3,3-trifluoro- propyl)thio)propionic acid and esters thereof. More particularly, the present invention concerns a process for the preparation of 3-((3,3,3-trifluoropropyl)thio)-propionic acid and esters thereof by the free radical coupling of 3-mercaptopropionic acid and esters thereof with 3,3,3- trifluoropropene .
  • 3-((3,3,3-Trifluoropropyl)thio)propionic acid and methyl 3-((3,3,3-trifluoropropyl)- thio)propionate are useful to produce pesticidal thioether and pesticidal sulfoxides such as N-(3- chloro- l-(pyridin-3-yl)- lH- razol-4-yl)-N-ethyl-3-((3,3,3-trifluoro ropyl)thio)-propanamide.
  • Methyl 3-((3,3,3-trifluoropropyl)thio)propionate has typically been produced by the free radical addition of methyl 3-mercaptopropionate to 3,3,3-trifluoropropene in the presence of a free radical initiator such as a-azobisisobutyronitrile (AIBN) at high temperatures.
  • a free radical initiator such as a-azobisisobutyronitrile (AIBN) at high temperatures.
  • AIBN a-azobisisobutyronitrile
  • the present invention concerns a process for the preparation of 3-((3,3,3-trifluoro- propyl)thio)propionic acid or esters thereof by the low temperature free radical initiated coupling of 3-mercaptopropionic acid or esters thereof with 3,3,3-trifluoropropene. More particularly, the present invention concerns a process for the preparation of 3-((3,3,3- trifluoropropyl)thio)propionic acid or esters thereof (Formula I)
  • R represents H or (C C 4 ) alkyl
  • V-70 2,2'-azobis(4-methoxy-2,4-dimethyl) valeronitrile
  • alkyl denotes branched or unbranched hydrocarbon chains.
  • the low temperature free radical initiated coupling of the present invention more selectively prepares 3-((3,3,3-trifluoropropyl)thio)propionic acid or esters thereof.
  • the ratio of linear to branched isomer is enhanced from about 10: 1 to about 40: 1 or greater for the acid and is enhanced from about 10: 1 to about 20: 1 or greater for the esters.
  • V-70 From about 1 to about 10 mole percent initiator, V-70, is typically used, with about 5 mole percent being preferred.
  • the low temperature free radical initiated coupling is conducted in an inert organic solvent.
  • Typical inert organic solvents must remain liquid to -50 °C, must remain relatively inert to the free radical conditions and must dissolve the reactants at reaction temperatures.
  • Preferred inert organic solvents are solvents such as toluene, ethyl acetate, and methanol.
  • the temperature at which the reaction is conducted is from about 0 °C to about 40 °C.
  • the 3-mercaptopropionic acid or esters thereof and V-70 are added to an inert organic solvent.
  • the solution is cooled to less than about -50 °C and the 3,3,3- trifluoropropene is transferred into the reaction mixture.
  • the reaction mixture is heated to about 50 °C for about 1 hour to decompose any remaining V-70 initiator followed by cooling and solvent removal.
  • octanophenone 526.2 mg as an internal standard and was purged and pressure checked with nitrogen.
  • the reactor was cooled with dry ice and the 3,3,3-trifluoropropene (3.10 g, 32.3 mmol) was condensed into the reactor.
  • the ice bath was removed and the reactor heated to 60 °C and stirred for 27 hours.
  • the internal yield of the reaction was determined to be 80% by use of the octanophenone internal standard (12.2: 1 lineanbranched isomer by GC).
  • the pressure was released and the crude mixture removed from the reactor.
  • the mixture was concentrated by rotary evaporation and sodium hydroxide (10 wt%, 50 mL) was added.
  • a 2 L autoclave reactor was charged with toluene (716.45 g), methyl 3-mercapto- propionate (187.78 g, 1562.6 mmol), and a-azobisisobutyronitrile (12.890 g, 78.500 mmol).
  • the reactor was sealed and pressurized with nitrogen (-100 psig) three times to purge the system of air.
  • 3,3,3-Trifluoropropene (153.20 g, 1595.0 mmol) was added via transfer cylinder at 12 °C (cold water bath). The reaction was heated to 80 °C and stirred for 21 hours. The reaction was allowed to cool to room temperature and vacuum transferred out of the reactor.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

3-((3,3,3-Trifluoropropyl)thio)propionic acid and esters thereof are prepared by a low temperature free radical process involving the free radical coupling of 3-mercaptopropionic acid and esters thereof with 3,3,3-trifluoropropene. The ratio of linear to branched isomer is enhanced.

Description

LOW TEMPERATURE FREE RADICAL INITIATED PROCESS FOR THE
PREPARATION OF 3-((3,3,3-TRIFLUOROPROPYL)THIO)PROPIONIC ACID AND
ESTERS THEREOF CROSS REFERENCE TO RELATED APPLICATIONS
This Application claims the benefit of U.S. Provisional Application Serial No.
62/034,452, filed August 7, 2014, the entire disclosure of which is hereby expressly
incorporated by reference into this Application. TECHNICAL FIELD
The present invention concerns a process for the preparation of 3-((3,3,3-trifluoro- propyl)thio)propionic acid and esters thereof. More particularly, the present invention concerns a process for the preparation of 3-((3,3,3-trifluoropropyl)thio)-propionic acid and esters thereof by the free radical coupling of 3-mercaptopropionic acid and esters thereof with 3,3,3- trifluoropropene .
BACKGROUND
3-((3,3,3-Trifluoropropyl)thio)propionic acid and methyl 3-((3,3,3-trifluoropropyl)- thio)propionate are useful to produce pesticidal thioether and pesticidal sulfoxides such as N-(3- chloro- l-(pyridin-3-yl)- lH- razol-4-yl)-N-ethyl-3-((3,3,3-trifluoro ropyl)thio)-propanamide.
Methyl 3-((3,3,3-trifluoropropyl)thio)propionate has typically been produced by the free radical addition of methyl 3-mercaptopropionate to 3,3,3-trifluoropropene in the presence of a free radical initiator such as a-azobisisobutyronitrile (AIBN) at high temperatures. The ratio of the desired linear isomer to the undesired branched isomer is approximately 10: 1.
Linear Branched
It would be desirable to more selectively prepare methyl 3-((3,3,3-trifluoropropyl)thio)- propionate or 3-((3,3,3-trifluoropropyl)thio)propionic acid with less of the branched isomer.
SUMMARY
The present invention concerns a process for the preparation of 3-((3,3,3-trifluoro- propyl)thio)propionic acid or esters thereof by the low temperature free radical initiated coupling of 3-mercaptopropionic acid or esters thereof with 3,3,3-trifluoropropene. More particularly, the present invention concerns a process for the preparation of 3-((3,3,3- trifluoropropyl)thio)propionic acid or esters thereof (Formula I)
wherein R represents H or (C C4) alkyl
which comprises coupling 3-mercaptopropionic acid or esters thereof (Formula II)
O R "0' ^ ^SH (ii)
wherein R is as previously defined
with 3,3,3-trifluoropropene (Formula III)
in the presence of 2,2'-azobis(4-methoxy-2,4-dimethyl) valeronitrile (V-70) initiator at temperatures of about -50 °C to about 40 °C in an inert organic solvent.
DETAILED DESCRIPTION As used herein, the term "alkyl" denotes branched or unbranched hydrocarbon chains.
The low temperature free radical initiated coupling of the present invention more selectively prepares 3-((3,3,3-trifluoropropyl)thio)propionic acid or esters thereof. The ratio of linear to branched isomer is enhanced from about 10: 1 to about 40: 1 or greater for the acid and is enhanced from about 10: 1 to about 20: 1 or greater for the esters.
While stoichiometric amounts of 3-mercaptopropionic acid or esters thereof and 3,3,3- trifluoropropene are required, because of its low boiling point, excess 3,3,3-trifluoropropene is usually employed to compensate for routine losses.
From about 1 to about 10 mole percent initiator, V-70, is typically used, with about 5 mole percent being preferred.
The low temperature free radical initiated coupling is conducted in an inert organic solvent. Typical inert organic solvents must remain liquid to -50 °C, must remain relatively inert to the free radical conditions and must dissolve the reactants at reaction temperatures. Preferred inert organic solvents are solvents such as toluene, ethyl acetate, and methanol.
The temperature at which the reaction is conducted is from about 0 °C to about 40 °C.
After the reaction is complete it is necessary to heat the mixture to about 50 °C to decompose any remaining V-70.
In a typical reaction, the 3-mercaptopropionic acid or esters thereof and V-70 are added to an inert organic solvent. The solution is cooled to less than about -50 °C and the 3,3,3- trifluoropropene is transferred into the reaction mixture. After stirring at room temperature for 24 hours, the reaction mixture is heated to about 50 °C for about 1 hour to decompose any remaining V-70 initiator followed by cooling and solvent removal.
The following examples are presented to illustrate the invention.
Examples
Weight percent purities were determined using a GC internal standard assay with octanophenone as the internal standard. Linear/branched ratios are based on GC area percent of the respective linear and branched products. GC Method Details: Agilent DB-5MS (122-5532) column 30m x 0.25 mm x 0.25 um; heater: 250 °C; control mode, flow: 2 mL/min; oven program: 50 °C for 2 min then 20 °C/min to 280 °C for 8 min.
1. Low temperature free radical initiated synthesis of 3-((3,3,3-trifluoropropyl)thio)- propanoic acid A 100 mL stainless steel Parr reactor was charged with 3-mercaptopropionic acid (3.67 g, 34.6 mmol), toluene (30.26 g), and 2,2'-azobis(4-methoxy-2,4-dimethyl) valeronitrile (V-70, 0.543 g, 1.76 mmol) and the reactor was cooled with a dry ice/acetone bath, purged with nitrogen, and pressure checked. 3,3,3-Trifluoropropene (3.20 g, 33.3 mmol) was added via transfer cylinder and the reaction was allowed to warm to 20 °C. After 24 hours, the reaction was heated to 50 °C for 1 hour to decompose any remaining V-70 initiator. The reaction was allowed to cool to room temperature. The solution was concentrated by rotary evaporation to provide the title compound (6.80 g, 77.5 wt% linear isomer by GC internal standard assay, 5.27 g active, 76%, 200: 1 lineanbranched by GC, 40: 1 lineanbranched by fluorine NMR): 1H NMR (400 MHz, CDC13) δ 2.83 (td, J = 7.1, 0.9 Hz, 2H), 2.76 - 2.64 (m, 4H), 2.47 - 2.30 (m, 2H); 13C NMR (101 MHz, CDC13) δ 177.68, 125.91 (q, J = 277.1 Hz), 34.58 (q, J = 28.8 Hz), 34.39, 26.63, 24.09 (q, J = 3.3 Hz); 19F NMR (376 MHz, CDC13) δ -66.49.
2. High temperature free radical initiator synthesis of 3-((3,3 -trifluoropropyl)thio)- propanoic acid: A 100 mL stainless steel Parr reactor was charged with azobisisobutyronitrile (AIBN, 0.231 g, 1.41 mmol), toluene (45 mL), 3-mercaptopropionic acid (3.40 g, 32.0 mmol), and
octanophenone (526.2 mg) as an internal standard and was purged and pressure checked with nitrogen. The reactor was cooled with dry ice and the 3,3,3-trifluoropropene (3.10 g, 32.3 mmol) was condensed into the reactor. The ice bath was removed and the reactor heated to 60 °C and stirred for 27 hours. The internal yield of the reaction was determined to be 80% by use of the octanophenone internal standard (12.2: 1 lineanbranched isomer by GC). The pressure was released and the crude mixture removed from the reactor. The mixture was concentrated by rotary evaporation and sodium hydroxide (10 wt%, 50 mL) was added. The solution was washed with methyl tert- butyl ether (50 mL) then acidified to pH ~1 with hydrochloric acid (6 N). The product was extracted with 100 mL methyl iert-butyl ether, dried over magnesium sulfate, filtered, and concentrated to give the crude titled compound as an oil (5.34 g, 11.9: 1 lineanbranched isomer by GC, 88 area% pure linear isomer by GC): 1H NMR (400 MHz, CDCI3) δ 3.71 (s, 3H), 2.82, (td, J= 7.3, 0.7 Hz, 2H), 2.75-2.68 (m, 2H), 2.63 (td, J= 7.2, 0.6 Hz, 2H), 2.47-2.31 (m, 2H); 13C NMR (101 MHz, CDC13) δ 172.04 , 125.93 (q, J = 2112 Hz), 51.86 , 34.68 (q, J = 28.6 Hz), 34.39 , 27.06 , 24.11 (q, J = 3.3 Hz); 19F NMR (376 MHz,
3. Low temperature free radical initiated synthesis of methyl 3-((3 ,3-trifluoropropyl)- thio)propionate A 100 mL stainless steel Parr reactor was charged with methyl 3-mercaptopropionate (4.15 g, 34.5 mmol), toluene (30.3 g), and 2,2'-azobis(4-methoxy-2,4-dimethyl) valeronitrile (V-70, 0.531 g, 1.72 mmol) and the reactor was cooled with a dry ice/acetone bath, purged with nitrogen, and pressure checked. 3,3,3-Trifluoropropene (3.40 g, 35.4 mmol) was added via transfer cylinder and the reaction was allowed to warm to 20 °C. After 23 hours the reaction was heated to 50 °C for 1 hour to decompose any remaining V-70 initiator. The reaction was allowed to cool to room temperature. The solution was concentrated to provide the title compound (7.01 g, 66%, 70.3 wt% linear isomer by GC internal standard assay, 4.93 g active, 66%, 24: 1 lineanbranched by GC, 18: 1 lineanbranched by fluorine NMR): 1H NMR (400 MHz, CDC13) δ 3.71 (s, 3H), 2.82, (td, J= 7.3, 0.7 Hz, 2H), 2.75-2.68 (m, 2H), 2.63 (td, J= 7.2, 0.6 Hz, 2H), 2.47-2.31 (m, 2H); 13C NMR (101 MHz, CDC13) δ 172.04 , 125.93 (q, J = 277.2 Hz), 51.86 , 34.68 (q, J = 28.6 Hz), 34.39 , 27.06 , 24.11 (q, J = 3.3 Hz); 19F NMR (376 MHz,
4. High temperature free radical initiator synthesis of methyl 3-((3 ,3-trifluoropropyl)- thio)propionate
A 2 L autoclave reactor was charged with toluene (716.45 g), methyl 3-mercapto- propionate (187.78 g, 1562.6 mmol), and a-azobisisobutyronitrile (12.890 g, 78.500 mmol). The reactor was sealed and pressurized with nitrogen (-100 psig) three times to purge the system of air. 3,3,3-Trifluoropropene (153.20 g, 1595.0 mmol) was added via transfer cylinder at 12 °C (cold water bath). The reaction was heated to 80 °C and stirred for 21 hours. The reaction was allowed to cool to room temperature and vacuum transferred out of the reactor. The crude solution was concentrated by rotary evaporation (bath: 40 °C, 12 mm Hg) to provide a clear yellow liquid (371.95 g, 9.8: 1 linear : branched isomer by GC, 69 wt% pure linear isomer determined by a GC internal standard assay, 257.39 g active, 76% in pot yield).

Claims

WHAT IS CLAIMED IS:
1. A process for the preparation of 3-((3,3,3-trifluoropropyl)thio)propionic acid or esters thereof (Formula I)
O F
R -O^^^S^^CF (l)
wherein R represents H or (CrC4) alkyl
which comprises coupling 3-mercaptopropionic acid or esters thereof (Formula II)
wherein R is as previously defined
with 3,3,3-trifluoropropene (Formula III)
F
H2C
F F (III)
in the presence of 2,2'-azobis(4-methoxy-2,4-dimethyl) valeronitrile (V-70) initiator at temperatures of about 0 °C to about 40 °C in an inert organic solvent.
2. The process of Claim 1 in which R represents H or CH3.
3. The process of Claims 1 or 2 in which the inert organic solvent is toluene.
EP14899236.5A 2014-08-07 2014-10-17 Low temperature free radical initiated process for the preparation of 3-((3,3,3-trifluoropropyl)thio)propionic acid and esters thereof Withdrawn EP3177590A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201462034452P 2014-08-07 2014-08-07
PCT/US2014/061022 WO2016022162A1 (en) 2014-08-07 2014-10-17 Low temperature free radical initiated process for the preparation of 3-((3,3,3-trifluoropropyl)thio)propionic acid and esters thereof

Publications (2)

Publication Number Publication Date
EP3177590A1 true EP3177590A1 (en) 2017-06-14
EP3177590A4 EP3177590A4 (en) 2018-03-14

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Country Status (10)

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EP (1) EP3177590A4 (en)
JP (1) JP2017524001A (en)
KR (1) KR20170039268A (en)
CN (1) CN107074756A (en)
AR (1) AR098111A1 (en)
BR (1) BR112017001996A2 (en)
CA (1) CA2957164A1 (en)
IL (1) IL250361A0 (en)
TW (1) TW201612155A (en)
WO (1) WO2016022162A1 (en)

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Publication number Priority date Publication date Assignee Title
JP5495799B2 (en) * 2008-02-15 2014-05-21 旭化成イーマテリアルズ株式会社 Resin composition
TW201113243A (en) * 2009-08-10 2011-04-16 Sumitomo Chemical Co Process for preparation of (fluoroalkylthio)acetic acid esters
US8937083B2 (en) * 2011-10-26 2015-01-20 DowAgroSciences, LLC Pesticidal compositions and processes related thereto

Also Published As

Publication number Publication date
WO2016022162A1 (en) 2016-02-11
CA2957164A1 (en) 2016-02-11
CN107074756A (en) 2017-08-18
AR098111A1 (en) 2016-05-04
BR112017001996A2 (en) 2017-12-12
IL250361A0 (en) 2017-03-30
KR20170039268A (en) 2017-04-10
JP2017524001A (en) 2017-08-24
EP3177590A4 (en) 2018-03-14
TW201612155A (en) 2016-04-01

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