A PROCESS FOR THE PREPARATION OF POLYFLUOROALKYLAMINES FROM POLYFLUOROALKYLALCOHOLS

Abstract

A process for the preparation of polyfluoroalkylamines wherein polyfluoroalkylalcohols are reacted with an imide in the presence of SO.sub.2F.sub.2 and an acid scavenger in a first step and the compound obtained is then reacted with an acid, base or hydrazine in a second step.

Claims

1. Process for preparation of a polyfluoroalkylamine of formula (IV)
R.sub.FCH.sub.2NH.sub.2(IV) in which R.sub.F is defined as in (i) below comprising: (i): Reaction of polyfluoroalkylalcohols of formula (I)
R.sub.FCH.sub.2OH(I) in which R.sub.F=CHF.sub.2, CF.sub.3, C.sub.2F.sub.5 or HCF.sub.2CF.sub.2, with an imide of formula (II) ##STR00016## in the presence of SO.sub.2F.sub.2 and an acid scavenger to give a compound of formula (III) ##STR00017## in which, in the compounds of formulae (II) and (III), R.sup.1 and R.sup.2 are, each independently of one another, hydrogen or C.sub.1-C.sub.6-alkyl or R.sup.1 and R.sup.2 form, together with the carbon atoms to which they are bonded, a six-membered aromatic ring which is optionally substituted with halogen or C.sub.1-C.sub.12-alkyl; (ii): Reaction of the compound of formula (III) with an acid, base or hydrazine.

2. The Process according to claim 1, wherein the polyfluoroalkylamine of formula (IV) is 2,2-difluoroethyl-1-amine.

3. The Process according to claim 1, in which the compound of formula (II) is succinimide or phthalimide.

4. The Process according to claim 1, in which the compound of formula (II) is phthalimide.

5. The Process according to claim 1, in which the acid scavenger in (i) is a base chosen from tertiary amines, substituted or unsubstituted pyridines and substituted or unsubstituted quinolines, 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, quinoline, quinaldine, N,N,N,N-tetramethyl-ethylenediamine, 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 hydrogencarbonate, potassium hydrogencarbonate, sodium acetate, KF and CsF.

6. The Process according to claim 1, in which the acid scavenger in (i) is a base which is diazabicycloundecane, potassium carbonate, sodium carbonate, KF or CsF.

7. The Process according to claim 5, in which the molar ratio of the base to the imide of formula (II) used is in a range of from 1:1 to 5:1.

8. The Process according to claim 1, in which inorganic acids are used in (ii).

9. The Process according to claim 8, in which the inorganic acid is hydrochloric acid, hydrobromic acid, sulphuric acid or phosphoric acid.

10. The Process according to claim 1, in which hydrazine hydrate is used in (ii).

11. The Process according to claim 1, in which the molar ratio of acid or hydrazine hydrate to the compound of the formula (III) is in a range of from 0.8:1 to 10:1.

Description

PREPARATION EXAMPLES

Example 1

Preparation of 2-(2,2-difluoroethyl)-1H-isoindole-1,3(2H)-dione (step (i))

[0066] ##STR00005##

Example 1.1

[0067] 1.47 g (0.01 mmol) of phtalimide, 1.45 mL (0.02 mol) of 2,2-difluoroethanol and 6 g (0.04 mol) of diazabicycloundecane were placed in 25 mL of N,N-Dimethylacetamide. 2.2 g (0.02 mol) SO.sub.2F.sub.2 was slowly bubbled through the reaction mixture at 20 ? C. for 40 min. The solvent was removed under vacuum of 1 mbar. The concentrated solution was diluted with methyl tert-butyl ether and washed with water. The organic layer was collected, dried with magnesium sulfate and filtered. The removal of ether under vacuum yielded 1,97 g of a white solid with purity of 98%, yield 91%. M.p. 114-116? C.

[0068] .sup.1H NMR (DMSO): 7.95-7-87 (m, 4H), 6.25 (tt, 1H), 4.0 (td, 2H) ppm.

[0069] .sup.13C NMR (DMSO): 167.37, 134.93, 131.51, 123.54, 113.54 (t), 39.70 (t) ppm.

[0070] .sup.19F NMR (DMSO): 121.40 (dt) ppm.

Example 1.2

[0071] ##STR00006##

[0072] 1.47 g (0.01 mmol) of phtalimide, 1.45 mL (0.02 mol) of 2,2-difluoroethanol and 3.88 g (0.03 mol) of N-ethyldiisopropylamine were placed in 25 mL of N,N-Dimethylacetamide. 3.06 g (0.03 mol) SO.sub.2F.sub.2 was slowly bubbled through the reaction mixture at 40? C. for 3 h and the reaction mixture was stirred under SO.sub.2F.sub.2 atmosphere for 5 h at 40? C. The solvent was removed under vacuum and reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 1.81 g of a white solid with purity of 100%, yield 86%. M.p. 114-116? C.

[0073] .sup.1H NMR (DMSO): 7.95-7-87 (m, 4H), 6.25 (tt, 1H), 4.0 (td, 2H) ppm.

[0074] .sup.13C NMR (DMSO): 167.37, 134.93, 131.51, 123.54, 113.54 (t), 39.70 (t) ppm.

[0075] .sup.19F NMR (DMSO): 121.40 (dt) ppm.

Example 1.3

[0076] ##STR00007##

[0077] 1.47 g (0.01 mmol) of phtalimide, 1.45 mL (0.02 mol) of 2,2-difluoroethanol and 3.1 g (0.03 mol) of triethylamine were placed in 25 mL of N,N-Dimethylacetamide. 3.06 g (0.03 mol) SO.sub.2F.sub.2 was slowly bubbled through the reaction mixture at 40? C. for 3 h and the reaction mixture was stirred under SO2F2 atmosphere for 12 h. at 40? C. The solvent was removed under vacuum and reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 1.9 g of a white solid with purity of 100%, yield 84%. M.p. 114-116? C.

[0078] .sup.1NMR (DMSO): 7.95-7-87 (m, 4H), 6.25 (tt, 1H), 4.0 (td, 2H) ppm.

[0079] .sup.13C NMR (DMSO): 167.37, 134.93, 131.51, 123.54, 113.54 (t), 39.70 (t) ppm.

[0080] .sup.19F NMR (DMSO): 121.40 (dt) ppm.

Example 2

Preparation of 2-(2,2,2-trifluoroethyl)-1H-isoindole-1,3(2H)-dione (step (i))

Example 2.1

[0081] ##STR00008##

[0082] 1.47 g (0.01 mol) of phtalimide, 1.8 mL (0.02 mol) of 2,2,2-trifluoroethanol and 4.5 g (0.03 mol) of diazabicycloundecane were placed in 25 mL of N,N-Dimethylacetamide. 2.2 g (0.02 mol) SO.sub.2F.sub.2 was bubbled through the reaction mixture at 20 ? C. for 60 min. The solvent was removed under vacuum and reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 2,1 g. of a white solid with purity of 100%, yield 92%. M.p. 122-127? C.

[0083] .sup.1H NMR (DMSO): 7.99-7-90 (m, 4H), 4.43 (q, 2H) ppm.

[0084] .sup.13C NMR (DMSO): 166.86, 135.20, 131.30, 123.86 (q), 123.82, 38.89 (q) ppm.

[0085] .sup.19F NMR (DMSO): ?68.85 (t, 3F) ppm.

[0086] Example 2.2

##STR00009##

[0087] 1.47 g (0.01 mol) of phtalimide, 1.8 mL (0.02 mol) of 2,2,2-trifluoroethanol and 2.3 g (0.04 mol) of spray-dried KF were placed in 25 mL of N,N-dimethylacetamide. 2.2 g (0.02 mol) SO.sub.2F.sub.2 was bubbled through the reaction mixture at 30? C. for 40 min and the reaction mixture was stirred under SO2F2 atmosphere for 12 h. The solvent was removed under vacuum and reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 1.98 g of white solid with purity of 100%, yield 86%. M.p. 122-127? C.

[0088] .sup.1H NMR (DMSO): 7.99-7-90 (m, 4H), 4.43 (q, 2H) ppm.

[0089] .sup.13C NMR (DMSO): 166.86, 135.20, 131.30, 123.86 (q), 123.82, 38.89 (q) ppm.

[0090] .sup.19F NMR (DMSO): ?68.85 (t, 3F) ppm.

Example 3

Preparation of 2-(2,2,3,3,3-pentafluoropropyl)-1H-isoindole-1,3(2H)-dione (step (i))

[0091] ##STR00010##

[0092] 1.47 g (0.01 mol mmol) of phtalimide, 3 g (0.02 mol) of 2,2,3,3,3-pentafluopropanol and 4.5 g (0.03 mol) of diazabicycloundecane were placed in 25 mL of N,N-Dimethylacetamide. 2.55 g (0.025 mol) SO.sub.2F.sub.2 was bubbled through the reaction mixture at 20? C. for 60 min and the reaction mixture was stirred under SO2F2 atmosphere for 5 h. The solvent was removed under vacuum and the reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 2.53 g of a white solid with purity of 100%, yield 91%. M.p.134-135? C.

[0093] .sup.1H NMR (DMSO): 8.00-7-90 (m, 4H), 4.42 (t, 2H) ppm.

[0094] .sup.13C NMR (DMSO): 166.92, 135.30, 131.25, 123.89, 118.40 (tq), 112.60 (m), 37.00 (t) ppm.

[0095] .sup.19F NMR (DMSO): ?83.70 (s, 3F), ?118.86 (t, 2F) ppm.

Example 4

Preparation of 2-(2,2,3,3-tetrafluoropropyl)-1H-isoindole-1,3(2H)-dione (step (i))

[0096] ##STR00011##

[0097] 1.47 g (0.01 mol) of phtalimide, 3.3 g (0.02 mol) of 2,2,3,3-tetrafluopropanol and 4.5 g (0.03 mol) of diazabicycloundecane were placed in 25 mL of N,N-Dimethylacetamide. 2.55 g (0.025 mol) SO.sub.2F.sub.2 was bubbled through the reaction mixture at 20? C. for 60 min and the reaction mixture was stirred under SO2F2 atmosphere for 5 h. The solvent was removed under vacuum and the reaction mixture diluted with water. The precipitate was filtered off and dried. Obtained 2.3 g of a white solid with purity of 100%, yield 88%. M.p. 129-130? C.

[0098] .sup.1H NMR (DMSO): 7.97-7-90 (m, 4H), 6.64 (tt, 1H), 4.23 (t, 2H) ppm.

[0099] .sup.13C NMR (DMSO): 167.22, 135.08, 131.50, 123.75, 114.98 (tt), 109.54 (tt), 37.43 (t) ppm.

[0100] .sup.19F NMR (DMSO): ?120.95 (m, 2F), ?138.64 (dt, 2F) ppm.

Example 5

Preparation of 2,2-difluoroethylamine (step (ii))

[0101] ##STR00012##

[0102] 4.22 g (0.02 mol) of 2-(2,2-difluoroethyl)-1H-isoindole-1,3(2H)-dione was placed in 50 mL of ethanol and treated with 1.8 g (0.036 mol) of hydrazine hydrate. The reaction mixture was stirred 2 h at reflux. Subsequently, the reaction mixture was cooled to 20? C. and the solid was filtered off. The filtrate was adjusted to pH 2 with 10 mL of hydrochloric acid (2N) and concentrated to dryness to yield 2 g (85%) of hydrochloride salt of 2,2-difluoroethylamine.

[0103] .sup.19F NMR (DMSO): ?122.10 (dt, 2F) ppm.

[0104] .sup.13C NMR (DMSO): 132.77, 125.32, 113.51 (t) ppm.

[0105] .sup.1H NMR (DMSO): 6.39 (tt, 1H), 3.31 (m, 2H) ppm.

Example 6

Preparation of 2,2,3,3-tetrafluoropropan-1-amine (step (ii))

[0106] ##STR00013##

[0107] 5.22 g (0.02 mol) of 2-(2,2,3,3-tetrafluoropropyl)-1H-isoindole-1,3(2H)-dione was placed in 50 mL of ethanol and treated with 1.4 g (0.028 mol) of hydrazine hydrate. The reaction mixture was stirred 2 h at reflux. Subsequently, the reaction mixture was cooled to 20? C. and the solid was filtered off. The filtrate was adjusted to pH 2 with 10 mL of hydrochloric acid (2N) and concentrated to dryness to yield 3.1 g yield 92% of hydrochloride salt of 2,2,3,3-tetrafluoropropan-1-amine.

[0108] .sup.19F NMR (DMSO): ?121.08 (m, 2F), ?137.84 (dt, 2F) ppm.

[0109] .sup.13C NMR (DMSO): 114.93 (tt), 109.24 (tt), 38.23 ppm.

[0110] .sup.1H NMR (DMSO): 6.73 (tt, 1H), 3.62 (t, 2H) ppm.

Example 7

Preparation of 2,2,3,3,3-pentafluoropropan-1-amine (step (ii))

[0111] ##STR00014##

[0112] 5.58 g (0.02 mol) of 2-(2,2,3,3,3-pentafluoropropyl)-1H-isoindole-1,3(2H)-dione was placed in 50 mL of ethanol and treated with 1.4 g (0.028 mol) of hydrazine hydrate. The reaction mixture was stirred 2 h at reflux. Subsequently, the reaction mixture was cooled to 20? C. and the solid was filtered off. The filtrate was adjusted to pH 2 with 10 mL of hydrochloric acid (2N) and concentrated to dryness to yield 3.37 g. (91%) of hydrochloride salt of 2,2,3,3,3-pentafluoropropan-1-amine.

[0113] .sup.19F NMR (DMSO): ?83.37 (3F), ?119.01 (t, 2F) ppm.

[0114] .sup.1H NMR (DMSO): 3.91 (t, 2H) ppm.

Example 8

Preparation of 2,2,2-trifluoroethylamine (step (ii)

[0115] ##STR00015##

[0116] 4.58 g (0.02 mmol) of 2-(2,2,2-trifluoroethyl)-1H-isoindole-1,3(2H)-dione was placed in 50 mL of ethanol and treated with 1.6 g (0.032 mol) of hydrazine hydrate. The reaction mixture was stirred 2 h at reflux. Subsequently, the reaction mixture was cooled to 20? C. and the solid was filtered off. The filtrate was adjusted to pH 2 with 10 mL of hydrochloric acid (2N) and concentrated to dryness to yield 2.45 g (90%) of hydrochloride salt of 2,2-difluoroethylamine.

[0117] .sup.19F NMR (DMSO): -67.89 (t, 3F)

[0118] .sup.1H NMR (DMSO): 3.87 (q, 2H)