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JP-7855601-B2 - Method for preparing polyfluoroalkylamines from polyfluoroalkyl alcohols

JP7855601B2JP 7855601 B2JP7855601 B2JP 7855601B2JP-7855601-B2

Inventors

  • パゼノク，セルギイ
  • ベルニエ，デビッド
  • ルルー，フレデリック
  • サントス，ローラ
  • パノシアン，アルメン
  • ドナード，モーガン

Assignees

  • バイエル・アクチエンゲゼルシヤフト
  • サントル・ナショナル・ドゥ・ラ・ルシェルシュ・シャンティフィク
  • ユニベルシテ・ドウ・ストラスブール

Dates

Publication Date
20260508
Application Date
20220208
Priority Date
20210217

Claims (11)

  1. Formula (IV) [In the formula, R F is defined as in step (i) below.] A method for preparing polyfluoroalkylamines, comprising the following steps: Step (i): Equation (I) [In the formula, R F = CHF 2 , CF 3 , C 2 F 5 or HCF 2 CF 2 ] Polyfluoroalkyl alcohols, Formula (II) Formula (III) with imide in the presence of SO₂F₂ and an acid scavenger [In the compounds of formulas (II) and (III), R1 and R2 are independently hydrogen or C1 - C6 -alkyl, or R1 and R2 , together with the carbon atoms to which they are bonded, form a six-membered aromatic ring which may be substituted with a halogen or C1 - C12 -alkyl.] Reaction to obtain the compound; Step (ii): The method comprising the reaction of a compound of formula (III) with an acid, a base, or hydrazine.
  2. The method according to claim 1, wherein the polyfluoroalkylamine of formula (IV) is 2,2-difluoroethyl-1-amine.
  3. The method according to claim 1 or 2, wherein the compound of formula (II) is succinimide or phthalimide.
  4. The method according to claim 1 or 2, wherein the compound of formula (II) is phthalimide.
  5. The acid scavenger in step (i) is a tertiary amine, a substituted or unsubstituted pyridine, a substituted or unsubstituted quinoline, triethylamine, trimethylamine, diisopropylethylamine, tri-n-propylamine, tri-n-butylamine, tri-n-hexylamine, tricyclohexylamine, N-methylcyclohexylamine, N-methylpyrrolidine, N-methylpiperidine, N-ethylpiperidine, N,N-dimethylaniline, N-methylmorpholine, pyridine, 2-,3- or 4-picoline, 2-methyl-5-ethylpyridine, 2,6-lutidine, 2,4,6-collidine, 4-dimethylaminopyridine, or quinoline. The method according to any one of claims 1 to 4, wherein the base is selected from quinaldine, N,N,N,N-tetramethylethylenediamine, N,N-dimethyl-1,4-diazacyclohexane, N,N-diethyl-1,4-diazacyclohexane, 1,8-bis(dimethylamino)naphthalene, diazabicyclooctane (DABCO), diazabicyclononane (DBN), diazabicycloundecane (DBU), butylimidazole, methylimidazole, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, sodium acetate, KF, and CsF.
  6. The method according to any one of claims 1 to 4, wherein the acid scavenger in step (i) is a base that is diazabicycloundecane, potassium carbonate, sodium carbonate, KF, or CsF.
  7. The method according to claim 5 or 6, wherein the molar ratio of the base used to the imide of formula (II) is in the range of 1:1 to 5:1.
  8. The method according to any one of claims 1 to 7, wherein an inorganic acid is used in step (ii).
  9. The method according to claim 8, wherein the inorganic acid is hydrochloric acid, hydrobromic acid, sulfuric acid, or phosphoric acid.
  10. The method according to any one of claims 1 to 7, wherein hydrazine hydrate is used in step (ii).
  11. The method according to any one of claims 1 to 10, wherein the molar ratio of the acid or hydrazine hydrate to the compound of formula (III) is in the range of 0.8:1 to 10:1.

Description

This invention relates to a method for producing polyfluoroalkylamines starting from polyfluoroalkyl alcohols using Gabriel synthesis. Polyfluoroalkylamines are important intermediates in the preparation of active substances. For example, 2,2-difluoroethylamine can be used as an intermediate in the preparation of flupyradiflon. Various methods are known for preparing fluoroalkylamines, for example: (a) reacting the corresponding polyfluoroalkyl halide with ammonia (e.g., Dickey et al., Industrial and Engineering Chemistry, 1956, No. 2, 209-213, US2002/0183557), or reacting the corresponding alcohol with ammonia (JP2005002031A); (b) hydrogenating the corresponding nitrile or azide compound (US3532755, Mecinovic et al., Green Chem, 2018, 20, 4418-4442); (c) reducing the corresponding polyfluoroalkylamide (Douglas et al., Chem. Commun., 2016, 52, 12195-12198 ( CF3CH2 )) . Regarding NH2 ), see Husted & Ahlbretcht, J. Am. Chem. Soc. 1953, 75 , 7 , 1605-1608 (Regarding CHF2CH2NH2 ), Soloshonok et al., Tetrahedron Letters, 2002, 43 , 5449-5452 (Regarding R F CH2NH2 , R F = -CF3 , -C2F5 , -C3F9 ), Papanastassiou & Bruni, J. Org. Chem. 1964, 29, 10 , 2870-2872 (Regarding FCH2CH2NH2 )). Furthermore, WO-A-2012/101044 discloses a method for preparing 2,2-difluoroethylamine, in which 2,2-difluoro-1-chloroethane is reacted with an imide in the presence of an acid scavenger such as a base to obtain 2,2-difluoroethylamine. WO-A-2011/012243 and WO-A-2012/095403 disclose a method for preparing 2,2-difluoroethylamine, in which 2,2-difluoro-1-chloroethane is reacted with ammonia to obtain 2,2-difluoroethylamine. WO-A-2011/042376 discloses a method for preparing 2,2-difluoroethylamine, in which 2,2-difluoro-1-nitroethane is hydrogenated in the presence of a catalyst to obtain 2,2-difluoroethylamine. WO-A2011/069994 discloses a method for preparing 2,2-difluoroethylamine, in which difluoroacetonitrile is catalytically hydrogenated, and the resulting difluoroethylamide is converted to 2,2-difluoroethylamine by adding an acid suitable for cleavage of the difluoroethylamide. WO-A2012/062702 discloses a method for preparing 2,2-difluoroethylamine, in which 2,2-difluoro-1-chloroethane is reacted with a benzylamine compound, and the resulting N-benzyl-2,2-difluoroethaneamine compound is catalytically hydrogenated to obtain 2,2-difluoroethylamine. WO-A-2012/062703 discloses a method for preparing 2,2-difluoroethylamine, in which 2,2-difluoro-1-chloroethane is reacted with prop-2-ene-1-amine, and the allyl group is removed (deallylated) from the resulting N-(2,2-difluoroethyl)prop-2-ene-1-amine. Known methods are disadvantageous because they require extremely long reaction times at high temperatures and pressures, have low yields, require expensive reagents or equipment, or produce highly corrosive reaction mixtures. Therefore, known methods are unsuitable for commercial use. US2012/0190867 (WO-A-2012/101044) describes the use of HCF2CH2Cl (CFC-142) by Gabriel synthesis. HCF2CH2Cl is environmentally unfriendly, belongs to the class of ozone-depleting substances (ODS), and its use is strictly restricted. The described method has a short reaction time but requires high temperatures (90–140°C). Furthermore, this method may require the use of a catalyst. M. Epifanov et al. described the process of SO₂F₂ - mediated alkylation of primary and secondary amines with polyfluoroalcohols in JACS 2018, 140, 16464-16468. The examples in this document only show amines bonded to one or two alkyl chains, alkyl- NH₂ or R₂NH , such as cyclohexylamine, morpholine, phenylalanine, and N-methylbenzylamine. These amines exhibit high nucleophilicity and basicity (pKb 3.5–4.5), and have been successfully alkylated with low-reactivity polyfluoroalcohols to date. However, the authors (JACS, p. 16466) also found that not only substrates with stereobulk alpha to amines such as cyclohexylamine, but also aniline, are insufficient substrates for this reaction, and alkylation using polyfluoroalcohols cannot be achieved at high reaction rates. Like other amines, aniline is nucleophilic with a base (pKb = 9.42), but it is a weaker base and less nucleophilic than structurally similar aliphatic amines. In this invention, a phthalimide having two carbonyl groups at the α-position relative to the amine group in the cyclic system is used, and therefore can be considered a bulky substrate. Due to the electron-withdrawing (-M) effect of the two carbonyl groups, phthalimide is known to have significant NH acidity and no basicity at all. The high acidity of imide-NH is a result of the adjacent pair of electrophilic carbonyl groups. Furthermore, amides (such as the phthalimide or succinimide used in the method according to this invention) are generally known to be less reactive with electrophiles than amines (similar to those used in the method of Epifanov et al.). Therefore, it is remarkable that the polyfluoroalkylation of phthalimide (which is acidic and not basic) in the method