(Hive Bee)
09-06-02 17:47
No 353513
      Selective hydrogen donor
(Rated as: excellent)

From JOC 1989, 54, 953-958

Chemoselective reductions with triethylammonium hypohosphite/Raney nickel and RuCl2(PPh)3

The triethylammonium hypophosphite x nH2O was prepared from equimolar amounts  of triethylamine and  50% aq hypophosphorous acid. It is liquid and stable in ambient conditions and soluble in some dry solvents such as THF, 1,4-dioxande, MeOH, EtOH and DMF. Its activity and selectivity have shown some differences from those of sodium hypophosphite. A great advantage is that a homogenous catalyst can be used with this reagent the RuCl2(PPh)3-Et3NH hypophosphite system selectively reduced ketones at room temperature, while RuCl2(PPh)3-NaH2PO2 failed to do so.

We have found that the quantity of water in the salt has an effect on the catalytic activity: there is good activity when this salt contains 1-2 molecules of water, whereas when there are more than three molecules of water, the reaction is erratic. When triethylammonium hypophosphite is dry the reaction is slow. But when one molecule of water is added to the dry salt, both Raney nickel and RuCl2(PPh)3 become more active and hydrogen is rapidly evolved.

Et3NH hypophosphite / Raney nickel system

The Et3NH hypophosphite reagent rapidly liberates hydrogen in the presence of Raney nickel, and it can be used as a good reductive hydrolytic reagent. Cyclohexanone oxime and 1-nitro-1-cyclohexene were converted to cyclohexanone (79% and 86% respectively) without cyclohexylamine; also aromatic and aliphatic nitriles were reduced to the corresponding aldehydes in excellent yields. Byproducts such as amines, imines, and alcohols were not detected.

The Et3NH hypophosphite reagent

50% aq H3PO2 (54.5 ml, 66 g) was placed in a flask immersed in an ice bath, then 69.7 ml (50.6 g) of Et3N was slowly added and the mixture was shaken after each addition until a homogenous solution was obtained, whereupon water was removed by distillation in two ways:

(a) At 40-50 deg C under 15 mmHg, after 30 min about 17 g of water was removed leaving 96.3 g  liquid; and after 1h, 21 g water was removed leaving 91 g liquid.

(b) At 65 deg C under 0.2 mmHg for 3h, not only water but also Et3N was removed (about 42 g),    leaving 69 g of dry Et3NH hypophosphite. 

Reduction of nitriles to aldehydes

Moist Raney-nickel (5 g) was placed into a flask containing 10 ml THF and 5 ml EtOH at 0 deg C, then 4 ml of the triethylammonium hypophosphite x 1.5H2O reagent was added all at once, and immediately an evolution of hydrogen was observed. The reaction temperature rose to 8-10 deg C. When the temperature began to fall, 0.01 mol of nitrile was added, and the solution was kept at 2-3 deg C for 2h. In the cases when the conversion was not complete, the solution was cooled to 0 deg C and 1 g Raney-nickel and 1 ml reagent was added. The addition of reagent can be repeated until conversion is complete.
The solution was then stirred for 4-5h at 2-3 deg C. Finally, the products were extracted three times with 20 ml ether, washed three times with 25 ml water, and dried over MgSO4. After solvent evaporation, the aldehydes were found from IR and NMR spectra to be sufficiently pure.

Reduction of ketones to alcohols

0.006 mol of the ketone and 4 ml triethylammonium hypophosphite x 1.5H2O were mixed in a flask under nitrogen at room temp and stirred until a homogenous solution was obtained. Then 6x10 -5 mol of RuCl2(PPh)3 was added to the solution, and immediately hydrogen was evolved. The solution was stirred overnight, then 20 ml  water was added, and the products was extracted with 20 ml ether or DCM. Finally the extract was washed with water and dried over MgSO4, and the solvent evaporated.

Nitrobenzene                           aniline                                  100%
Cyclohexanone oxime             cyclohexanone                          79%
1-Nitro-1-cyclohexene            cyclohexanone                          86%
p-Chloroacetophenone            no conversion
Benzaldehyde                          benzylalcohol                          15%
2-Furonitrile                            furfural                                   97%
2-Thiophenecarbonitrile         2-thiophenecarboxaldehyde          100%
Benzonitrile                            benzaldehyde                            96%
Phenylacetonitrile                   phenylacetaldehyde                    92%
Valeronitrile                           valeraldehyde                            90%
5-Chlorovaleronitrile              5-chlorovaleraldehyde                 98%