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4.5.1. 2,2,6,6-Tetramethyl-4-(30,30,40,40,50,50,60,60,70,70,80,80,80-
tridecafluorooctylamino)piperidin-1-oxyl (10a)
C25H23F26N2O2 requires C, 34.22; H, 2.64; F, 56.30; N, 3.19; O, 3.65%
(sample was very difficult to dry, hence the slight discrepancy).
Prepared according to the general procedure using 4-oxo-2,2,6,6-
tetramethylpiperidin-1-oxyl (382 mg, 2.2 mmol), 3,3,4,4,5,5,6,6,7,7,-
8,8,8-tridecafluorooctylamine (1.06 g, 2.9 mmol), sodium borohydride
(128 mg, 3.4 mmol) and dry ethanol (10 ml) to afford the title com-
pound as an orange/red solid (610 mg, 1.2 mmol, 52%); Rf 0.53 (4:1
[CH2Cl2/ether] plus 1% TEA); mp 86–88 ꢀC (hexane); found [MþH]þ
518.1570; C17H22F13N2OþH requires 518.3617; nmax/cmꢁ1 (KBr) 3510 w
(N–H), 3054 m, 2987 m (C–H), 1626 w, 1422 m (N–O$), 1266 s (N–Oꢃ)
and 1145 w (N–Oꢃ); dH could not be obtained; dC (100 MHz; CDCl3) 55.3
C(2), 38.1 C(4), 32.2 C(1), 31.9 C(3), 29.9 C(5), 21.5 (CH3), 20.1 (CH3),10.8
(CH3) and 8.9 (CH3); dF (282 MHz; CDCl3) ꢁ81.07 (CF3), ꢁ113.2 (CF2),
ꢁ121.4 (CF2), ꢁ122.7 (CF2), ꢁ124.0 (CF2) and ꢁ126.5 (CF2); m/z (CI) 518
[(MH)þ, 31%], 517 [(M)þ, 100%]; 501 [(MꢁO)þ, 27%].
4.6.2. 2,2,6,6-Tetramethyl-4-(30,30,40,40,50,50,60,60,60-nonafluoro-
hexyl)-(300,300,400,400,500,500,600,600,600-nonafluorohexan)amide
piperidin-1-oxyl (4)
Prepared according to the general procedure using 2,2,6,6-tetra-
methyl-4-(3,3,4,4,5,5,6,6,6-nonafluorohexylamino)piperidin-1-oxyl
(900 mg, 2.16 mmol), 3,3,4,4,5,5,6,6,6-nonafluorohexanoyl chloride
(639.8 mg, 2.158 mmol), triethylamine (217.9 mg, 2.158 mmol) and
dry THF (15 ml) to afford title compound as an orange solid (802 mg,
1.29 mmol, 60%); Rf 0.63 (4:1 [DCM/ether] plus 1% TEA); mp 84 ꢀC;
dH could not be obtained; dC 162.7 (C10), 56.3 (C4), 36.1 (C20), 35.3
(C100), 30.9 and 30.5 (C3 and C5), 27.4 (C200), 21.8 (CH3), 19.5 (CH3),
12.1 (CH3), 11.8 (CH3); dF (282 MHz, CDCl3) ꢁ81.1 (CF3), ꢁ119.8 (CF2),
ꢁ124.3 (CF2), ꢁ125.4 (CF2); m/z (EI) 677.1 [(M)þ, 27%], 657.1
[(MꢁHF)þ, 48%]. Found C, 38.16; H, 3.30; N, 4.00; F, 48.71%.
C21H23F18N2O2 requires C, 37.23; H, 3.42; F, 50.48; N, 4.14% (sample
was very difficult to dry, hence the slight discrepancy).
4.5.2. 2,2,6,6-Tetramethyl-4-(30,30,40,40,50,50,60,60,60-
nonafluorohexylamino)piperidin-1-oxyl (10b)
Prepared according to the general procedure using 4-oxo-2,2,6,6-
tetramethylpiperidin-1-oxyl (1.24 g, 7.3 mmol), 3,3,4,4,5,5,6,6,6-non-
afluorohexylamine (2.5 g, 9.5 mmol), sodium borohydride (417 mg,
10.9 mmol) and dry ethanol (40 ml) to afford the title compound as
a red/orange solid (1.68 g, 4.0 mmol, 55%); Rf 0.55 (4:1 [DCM/ether] plus
1% TEA); mp 81–82 ꢀC (hexane); found [MþH]þ 418. 5613,
C15H22F9NOþH requires 418.3451; nmax/cmꢁ1 (KBr) 3296–3190 m (N–
H), 2976 s, 2936 s, 2876 s (C–H),1458 m (N–H),1379 s (NOꢃ),1358 s (NOꢃ),
1294 m (NOꢃ),1236 s (CF2), 1221 s (CF2) and 1134 s (CF2); dH and dC could
not be obtained; dF (282.4 MHz; CDCl3) ꢁ81.9 (CF3), ꢁ113.8 (CF2),
ꢁ125.0 (CF2) and ꢁ126.4 (CF2); m/z 418 [(MH)þ, 100%] and 401
[(MꢁO)þ, 65%].
4.7. General procedure for the determination of partition
coefficients
The fluorous-TEMPO reagent (25 mg) was dissolved in the or-
ganic solvent (1 ml) and the fluorous solvent (1 ml) added in
a small sample vial. The vial was placed in a thermostatic bath at
25 ꢀC and the mixture was stirred vigorously for 24 h. After this
time, the two layers were carefully separated and concentrated in
vacuo. The residue remaining in each flask was weighed to give the
amount of fluorous-TEMPO in each layer. Each system was repeated
twice for accuracy.
4.6. General procedure for the formation of di-fluorous-
tagged TEMPO derivatives
4.8. Typical experimental procedure for oxidation reaction
A solution of the mono-alkylated TEMPO derivative in dry THF
was cooled to 0 ꢀC under N2, treated with dry triethylamine and
stirred at 0 ꢀC for 15 min. The reaction mixture was treated with the
perfluorinated-acid chloride and stirred at 0 ꢀC for 3 h. The reaction
mixture was then warmed to room temperature and quenched
with water (25 ml) and diethyl ether (25 ml) and stirred vigorously
for 10 min. The aqueous mixture was separated and extracted with
diethyl ether (3ꢂ50 ml). The organic phases were combined,
washed with water (3ꢂ50 ml), dried over MgSO4, filtered and
concentrated in vacuo. The residue was purified by flash neutral
alumina column chromatography. The radical and also highly
fluorinated nature of these compounds meant obtaining accurate
NMR data was very difficult or impossible.
4.8.1. Method A: general procedure for the mild oxidation
of alcohols using fluorous-TEMPO and NaOCl
A solution of the alcohol (1 equiv, typically 0.5–1 mmol) in
CH2Cl2 was cooled to 0 ꢀC and treated with a solution of fluorous-
TEMPO (0.03 equiv) in CH2Cl2. The reaction mixture was stirred at
0 ꢀC for 5 min before being treated with a 0.5 M solution of KBr
(0.3 equiv) and NaOCl solution buffered with NaHCO3. The reaction
mixture was stirred at 0 ꢀC for 1 h before being allowed to warm to
room temperature over 20 min. The aqueous phase was separated
and extracted with CH2Cl2 (3ꢂ10 ml). The organic phases were
combined, dried over MgSO4, filtered and concentrated in vacuo.
The residue was purified by fluorous silica column chromatogra-
phy, eluting first with 10% water in methanol to remove the organic
reaction components, followed by 100% methanol to obtain the
recycled Rf-TEMPO.
4.6.1. 2,2,6,6-Tetramethyl-4-(30,30,40,40,50,50,60,60,70,70,80,80-
tridecafluorooctyl)-(300,300,400,400,500,500,600,600,700,700,800,800,800-
tridecafluorooctan)amide piperidin-1-oxyl (5)
Prepared according the general procedure using 2,2,6,6-tetra-
methyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctylamino)piperidin-
1-oxyl (600 mg,1.16 mmol), 3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctanoyl
chloride (460 mg, 1.16 mmol), triethylamine (117 mg, 1.16 mmol)
and dry THF (10 ml) to afford the title compound as an orange/red
solid (818 mg, 0.93 mmol, 55%); Rf 0.42 (4:1 [DCM/ether] plus 1%
TEA); mp 48–49 ꢀC (petrol); nmax/cmꢁ1 (KBr disc) 2979 w, 2899 w,
1702 m, 1639 s (amide), 1436 m, 1365 m, 1294 m (CF3), 1236 s (CF3),
1221–1159 br, s (8ꢂCF2),1144 s (CF2) and 1114 s (CF2); dH could not be
obtained; dC (100 MHz; CDCl3) 161.9 (CH2CON), 57.7 (CHN), 34.1
(CH2CO), 33.9 (CH2CH2N), 30.5 (CH2CHN), 30.3 (CH2CHN), 28.2
(CH2CH2N), 21.8 (CH3), 19.6 (CH3), 11.9 (CH3) and 11.8 (CH3); dF
(282.4 MHz; CDCl3) ꢁ81.1 (CF3), ꢁ112.7 (CF2), ꢁ118.6 (CF2), ꢁ121.5
(CF2), ꢁ124.3(CF2) and ꢁ126.5 (CF2); m/z (EI) 877(MþH)þ,100%) and
857 (MþH, ꢁF)þ, 58%). Found C 33.37, H 2.22, N 2.15, F 56.28%.
4.8.2. Method B: general procedure for the mild oxidation
of alcohols using fluorous-TEMPO and oxoneÒ
A solution of the alcohol (1.0 equiv, typically 0.5–1 mmol) and
Bu4NBr (0.4 equiv) in dry toluene was treated with a 0.1 M solution
of fluorous-TEMPO (0.1 equiv) in dry toluene and oxoneÒ
(2.2 equiv) and stirred at room temperature for 8–48 h. After TLC
showed complete conversion the solvent was removed in vacuo
and the residue was suspended between CH2Cl2 and water (10 ml,
1:1). The aqueous phase was separated and extracted with CH2Cl2
(3ꢂ10 ml). The organic phases were combined, washed with water
(15 ml), dried over MgSO4, filtered and concentrated in vacuo. The
residue was purified by fluorous silica column chromatography,
eluting first with 10% water in methanol to remove the organic
reaction components, followed by 100% methanol to obtain the
recycled Rf-TEMPO.