WO2006031180A1 - Process for preparation of alkyl phosphinates - Google Patents

Process for preparation of alkyl phosphinates Download PDF

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Publication number
WO2006031180A1
WO2006031180A1 PCT/SE2005/001316 SE2005001316W WO2006031180A1 WO 2006031180 A1 WO2006031180 A1 WO 2006031180A1 SE 2005001316 W SE2005001316 W SE 2005001316W WO 2006031180 A1 WO2006031180 A1 WO 2006031180A1
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WO
WIPO (PCT)
Prior art keywords
process according
acid
ethyl
hypophosphite
mmol
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.)
Ceased
Application number
PCT/SE2005/001316
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English (en)
French (fr)
Inventor
Maths Nilsson
Mats Thelin
Johanna Wachtmeister
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.)
AstraZeneca AB
Original Assignee
AstraZeneca AB
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 AstraZeneca AB filed Critical AstraZeneca AB
Priority to EP05779058A priority Critical patent/EP1791851B1/en
Priority to DE602005025140T priority patent/DE602005025140D1/de
Priority to JP2007531131A priority patent/JP2008512451A/ja
Priority to AT05779058T priority patent/ATE490259T1/de
Priority to US11/575,082 priority patent/US7557234B2/en
Publication of WO2006031180A1 publication Critical patent/WO2006031180A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/48—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof
    • C07F9/4808—Phosphonous acids [RP(OH)2] including [RHP(=O)(OH)]; Thiophosphonous acids including [RP(SH)2], [RHP(=S)(SH)]; Derivatives thereof the acid moiety containing a substituent or structure which is considered as characteristic
    • C07F9/4816—Acyclic saturated acids or derivatices which can have further substituents on alkyl

Definitions

  • the present invention is directed to a new process for the production of alkyl dialkoxyalkylphosphinates.
  • ethyl (diethoxymethyl) phosphinate has been described in Gallagher, M. J. Honegger, H. Aust. J. Chem. 1980, 33, 287-294 (see below).
  • the phosphinic acid was obtained by evaporation of commercial aqueous solutions (50 wt% water).
  • EP 307362 A2 describes the production of aliphatylphosphinic acid derivatives from aqueous phosphinic acid.
  • One object of the present invention was to develop a process for the production of alkyl dialkoxyalkylphosphinates that is more suitable for large-scale production.
  • the present invention is directed to a new process for the production of alkyl dialkoxyalkylphosphinates of formula (I):
  • R 1 , R 2 , R 3 and R 4 are as defined above; in the presence of a solvent and an acid.
  • the process according to the present invention may be used for the synthesis of inter alia ethyl (diethoxymethyl) phosphinate.
  • This method the hazardous handling of neat phosphinic acid can be avoided. Further, the amount of by-products may be controlled.
  • the compound of formula (II) is charged to a stirred slurry of hypophosphite salt and a suitable solvent such as toluene-ethanol (20:1).
  • a suitable solvent such as toluene-ethanol (20:1).
  • the mixture is carefully inerted and acid is charged at a controlled speed.
  • the slurry is stirred at from O 0 C to 20 °C during 1 to 20 hours or until most of the intermediate alkyl ester is consumed.
  • the mixture is quenched by the addition of aqueous sodium hydrogen carbonate and the organic layer is concentrated.
  • the hypophosphite salt is selected from ammonium hypophosphite, sodium hypophosphite and potassium hypophosphite.
  • the compound of formula (II) is selected from trimethylorthoformate, triethylorthoformate, trimethylorthoacetate and triethylorthoacetate.
  • the acid used in the reaction is selected from methane sulphonic acid, sulphuric acid, boron trifluoride etherate and trifluoromethane sulphonic acid.
  • the acid is essentially water-free. In one embodiment, the acid contains up to 10% water, up to 5% water or up to 2% water.
  • the solvent used in the process according to the present invention is toluene, acetonitrile, tetrahydrofuran (THF), methylene chloride, benzene or a mixture of toluene and ethanol.
  • Triethylorthoformate (42.1 mL, 253 mmol, 2.1 eq) was added to a cold (0 0 C) mixture of finely ground ammonium hypophosphite (10 g, 120 mmol, 1.0 eq), toluene (50 mL) and ethanol (3.5 mL) under a nitrogen atmosphere. The slurry was inerted and cooled to about 0 0 C. Methane sulphonic acid (8.4 mL, 127 mmol, 1.05 eq) was charged (exotermic) during 4 minutes (T; was kept below 1O 0 C).
  • Triethylorthoformate (632 mL, 3.80 mol, 2.1 eq) was added to a cold (O 0 C) mixture of ammonium hypophosphite (150 g, 1.81 mol, 1.0 eq), toluene (750 mL) and ethanol (75 mL) under a nitrogen atmosphere. The slurry was inerted and cooled to ⁇ 0°C.
  • Triethylorthoformate (133.6 kg, 901.4 mol, 2.1 eq) was charged to a cold (0 0 C), vigorously stirred mixture of ammonium hypophosphite (35.6 kg, 429.2 mol, 1.0 eq), toluene (107 L) and ethanol (11 L) under a nitrogen atmosphere. The slurry was carefully inerted while cooled to -O 0 C. The slurry was then continuously purged with nitrogen in order to reduce the amount of oxidized by-products. Methane sulphonic acid (43.3 kg, 450.7 mol, 1.05 eq) was then charged (exotermic) during 30 minutes (T; was kept below 1O 0 C).
  • Trifluoromethane sulphonic acid (1.2 mL, 13.6 mmol, 1.1 eq) was charged during 3 minutes to a cold (O 0 C) mixture of ammonium hypophosphite (1 g, 12.0 mmol, 1 eq), toluene (10 mL) and triethylorthoformate (4.2 mL, 31.3 mmol, 2.6 eq).
  • the reaction was stirred at ambient temperature and after 2 hours GC-analysis showed good conversion to the desired product. The product was not isolated.
  • Triethylorthoacetate (4.6 mL, 25.1 mmol, 2.1 eq) was added to a cold (0°C) mixture of ammonium hypophosphite (1.0 g, 12.0 mmol, 1.0 eq) and toluene (5 mL). The slurry was cooled to -O 0 C and inerted. Methane sulphonic acid (0.84 mL, 12.7 mmol, 1.05 eq) was charged (exotermic) during 4 minutes (Tj was kept below 10°C). The reaction was stirred at 0°C and after 1 hour GC-analysis showed ⁇ 40% conversion to the desired product.
  • Trimethyiorthoacetate (3.2 mL, 25.1 mmol, 2.1 eq) was added to a cold (O 0 C) mixture of ammonium hypophosphite (1.0 g, 12.0 mmol, 1.0 eq) and toluene (5 mL). The slurry was cooled to ⁇ 0°C and inerted. Methane sulphonic acid (0.84 mL, 12.7 mmol, 1.05 eq) was charged (exotermic) during 4 minutes (Ti was kept below 10 0 C). The reaction was stirred at 0 0 C and after 1 hour GC-analysis showed ⁇ 50% conversion to the desired product.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/SE2005/001316 2004-09-13 2005-09-12 Process for preparation of alkyl phosphinates Ceased WO2006031180A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
EP05779058A EP1791851B1 (en) 2004-09-13 2005-09-12 Process for preparation of alkyl phosphinates
DE602005025140T DE602005025140D1 (de) 2004-09-13 2005-09-12 Verfahren zur herstellung von alkylphosphinaten
JP2007531131A JP2008512451A (ja) 2004-09-13 2005-09-12 ホスフィン酸アルキルの製造方法
AT05779058T ATE490259T1 (de) 2004-09-13 2005-09-12 Verfahren zur herstellung von alkylphosphinaten
US11/575,082 US7557234B2 (en) 2004-09-13 2005-09-12 Process for the preparation of alkyl phosphinates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE0402199A SE0402199D0 (sv) 2004-09-13 2004-09-13 New process I
SE0402199-4 2004-09-13

Publications (1)

Publication Number Publication Date
WO2006031180A1 true WO2006031180A1 (en) 2006-03-23

Family

ID=33157526

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2005/001316 Ceased WO2006031180A1 (en) 2004-09-13 2005-09-12 Process for preparation of alkyl phosphinates

Country Status (8)

Country Link
US (1) US7557234B2 (https=)
EP (1) EP1791851B1 (https=)
JP (1) JP2008512451A (https=)
CN (1) CN100575355C (https=)
AT (1) ATE490259T1 (https=)
DE (1) DE602005025140D1 (https=)
SE (1) SE0402199D0 (https=)
WO (1) WO2006031180A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11466041B2 (en) 2017-02-22 2022-10-11 Adama Agan Ltd. Process for preparing methyl phosphinic acid butyl ester

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103755605B (zh) * 2013-12-30 2016-08-17 中国科学院上海硅酸盐研究所 对己硫基苯甲醛的制备方法
CN103980306B (zh) * 2014-04-28 2017-02-15 湖南大学 一种以含p(o)‑oh类化合物制备次膦酸/亚膦酸/磷酸酯类化合物的方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0307362A2 (en) * 1987-09-11 1989-03-15 Ciba-Geigy Ag Process for the manufacture of aliphatylphosphinic acid derivatives
US20040167330A1 (en) * 2001-07-17 2004-08-26 Ivan Lukes Novel chelating agents and conjugates thereof, their synthesis and use as diagnois and therapeutic agents

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8728483D0 (en) * 1987-12-04 1988-01-13 Ciba Geigy Ag Chemical compounds
EP1773740B1 (en) * 2004-06-25 2009-02-18 The University Of Sydney Neurologically-active compounds

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0307362A2 (en) * 1987-09-11 1989-03-15 Ciba-Geigy Ag Process for the manufacture of aliphatylphosphinic acid derivatives
US20040167330A1 (en) * 2001-07-17 2004-08-26 Ivan Lukes Novel chelating agents and conjugates thereof, their synthesis and use as diagnois and therapeutic agents

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
DEPRELE S, MONTCHAMP J.: "A Novel and Convenient Preparation of Hypophosphite Esters.", J OF ORGANOMETALLIC CHEMISTRY., vol. 643-644, February 2002 (2002-02-01), pages 154 - 163, XP004339567 *
FICH SJ ET AL: "Synthesis of Hypophosphite Esters from Orthocarbonyl Compounds.", J AM CHEM SOC., vol. 86, 1964, pages 61 - 64, XP002993830 *
GALLAGHER MJ, HONEGGER H.: "Organophosphorus Intermediates. VI The Acid-CAtalysed Reaction of Triakyl Orthoformates with Phosphinic Acid.", AUST J CHEM., vol. 33, 1980, pages 287 - 294, XP009043408 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11466041B2 (en) 2017-02-22 2022-10-11 Adama Agan Ltd. Process for preparing methyl phosphinic acid butyl ester

Also Published As

Publication number Publication date
CN101018794A (zh) 2007-08-15
SE0402199D0 (sv) 2004-09-13
EP1791851A4 (en) 2010-03-10
DE602005025140D1 (de) 2011-01-13
EP1791851A1 (en) 2007-06-06
JP2008512451A (ja) 2008-04-24
US7557234B2 (en) 2009-07-07
EP1791851B1 (en) 2010-12-01
CN100575355C (zh) 2009-12-30
ATE490259T1 (de) 2010-12-15
US20080319231A1 (en) 2008-12-25

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