1,1-Dihydroperfluoroalkylamines. Report (1)
 

A.F.Gontar, V.L.Don, E.V.Igoumnova, S.M. Igoumnov

 A.N.Nesmeyanov Institute of Organoelements Compounds RAS. 119991, Vavilova str.28, Moscow, Russia.
e-mail: gontar@ineos.ac.ru

The main method to produce 1,1-dihydrofluoroalkyl amines is reduction of amides or nitriles of corresponding acids with lithium alumohydride [1-3].

This method has a number of disadvantages, first it is difficult to work with LiAlH₄ and it is impossible to obtain the desired amines in a tangible quantity.

A more promising for the reduction is using diborane that may be obtained both separately or generated in situ directly in the reaction mixture in the presence of amide to be reducted, for example from NaBH₄ and BF₃*Et₂O.This method was used earlier in obtaining dihydrotrifluoroethylamine [4]. A possibility to synthesize 1,1-dihydrofluoroalkylamines with using NaBH₄ -BF₃*Et₂O system was studied in the present work. It has been found that amides of fluorocarbonic acids (I) in ether solvents ( diglyme, dioxane) react exothermally with  NaBH₄ at addition of BF₃*Et₂O.The amide reduction runs in two competitive directions- to form amine RFCH₂NH2 (II) and alcohol RFCH₂OH (III).

After completion of the interaction the reaction mass was treated with hydrochloric  acid, then the solvents and alcohol (III) were distilled, the latter was separated by pouring the strippant into water followed by rectification of the bottom layer. Amine (III) was isolated in treatment of dry residue with water solution of alkali and distillation with steam.The yields of fluoroalkylamines (II a-g) are from 32 to 65%, the yields of alcohols (IIIa-g) are from 18 to 32%.

Table 1.

We have also found that it is more easy to obtain higher dihydrofluoroalkylamines (R_f=C₅F₁₁, C₆F₁₃, C₇F₁₅, C₈F₁₇ )by the action of NaBH₄ on perfluoroalkylnitriles ( Method 2) because they are liquid products unlike lower homologues ( compare CF₃CN bp=-64^oC; C₄F₉CN bp=150^oC).See also [5].

Experimental

2,2-Difluoroethylamine(IIa)
A solution of amide of difluoroacetic acid (190 g, 2.00 mole) in 500 mL of abs. diglyme and NaBH₄ (83g, 2.19 mole) are fed in a three-neck flask ( 2 L) fitted with a mixer, dropping funnel and a backflow condenser (the outlet is connected with a Tischenko flask with concentrated H₂SO₄). BF₃*Et₂O (306g, 2.16 mole) is added dropwise under stirring resulted in heating.

After completion of addition the reaction mixture is stirred for an hour on a boiling water bath, then it is cooled with ice water and hydrochloric acid (1L) is added dropwise. The obtained mixture is evaporated to dryness on a water bath at 15 mm Hg. The strippant is collected in a cooled receiver, poured in water, the bottom layer is separated and distilled to yield 2,2-difluoroethanol (IIIa), its boiling temperature and yield are given in Table 1.

A solution of NaOH (480g, 12.0 mol) in a minimal quantity of water is added dropwise to the residue and the product with water is distilled to 100 ^oC. After rectification there is obtained 90 g ( 55%) of 2,2-difluoroethylamine,  purity 99% (BP 68-69^oC).

1,1-Dihydroperfluoroalkylamines II (b-k) and alcohols III(b-d) are obtained analogously to IIa and IIIa ( see Table 1).

1H,1H-Perfluorohexylamine (IIe), method 2
 Diglyme (1.5 L) and NaBH₄ (150 g. 3.95 mol) are placed and stirred in a four-neck flask (6L water capacity) fitted with a mechanical mixer, thermometer, dropping funnel and a backflow condenser, then perfluorohexanonitrile (570g, 1.93 mol) is added dropwise. The reaction mixture is heated up to 60^oC. After completion of nitrile addition the reaction mass is boiled for 2 hours and is kept overnight.

Then the reaction mass is poured cautiously in portions, as foaming occurs, into a mixture of NaOH solution ( 120g NaOH and 300 mL water) with ice (1.5 kg). The formed mass is placed in a 6L flask and distilled with steam. The lower layer of the strippant is separated to obtain 370g of the crude product that is then rectified to obtain 320 g of 1H,1H-perfluorohexylamine of 98% purity, BP 107^oC in 55% yield. Amines (II b-k) are obtained in a similar way.

References

1.D.R.Husted, S.Paul, A.H.Ahlbrecht; US patent 1954 2, 691,043

2. Z.B. Papanastassion, R.I. Brini I. Org. Chem 1965, v 29, 2870-2871

3. M. Sander; Monatsheftc fur. Chtme, 95, 1964, 608-616.

4. E.R. Bissele, M. Finger, I. Am. Chem, Sos., 24, 1959, 1256-1259.

5. S. E. Ellzer, I.S. Wittman, W.I. Connick., I. Org. Chem., 30, 1965, 3645-3950