Aryl-di-tert-butylfluorosilanes as Synthons for 18F Labeling
FULL PAPER
C20H37F32S28Si2: 384.2133; found 384.2146; elemental analysis calcd (%)
for C20H37FSSi2 (384.74): C 62.4, H 9.7; found C 62.3, H 9.4.
1.14 mL) in toluene (30 mL) at 08C.[13] The reaction mixture was then
heated at reflux for 4 h. After the solution had been cooled to room tem-
perature, the volatiles were removed in vacuo to afford 4a as a dark-
brown oil in quantitative yield (1.05 g). 1H NMR (300.13 MHz, CDCl3):
4-(Di-tert-butylfluorosilanyl)benzenethiol (3a): A solution of 2a (2.6 g,
6.75 mmol) in a mixture of dichloromethane (10 mL) and trifluoroacetic
acid (7.7 g, 5.2 mL, 67.5 mmol) was stirred for 24 h.[11] The volatiles were
then evaporated in vacuo (at 10À3 Torr) to afford 3a as a yellowish oil in
d=7.59 (d, 3J(1H,1H)=8 Hz, 2H; Hm), 7.23 (d, 3J(1H,1H)=8 Hz, 2H;
ACTHNUTRGENNUG CAHTUNGTRENNUGN
Ho), 1.04 ppm (s, 18H; CH3); 13C{1H} NMR (75.48 MHz, CDCl3): d=
136.1 (s; NCS), 135.1 (d, 3J(13C,19F)=4 Hz; Cm), 133.4 (d, 2J(13C,19F)=
14 Hz; Cp), 132.5 (s; Ci), 124.9 (s; Co), 27.2 (s; CH3), 20.3 ppm (d, 2J-
quantitative yield. 1H NMR (300.13 MHz, C6D6): d=7.47 (d, 3J
ACHTUNGTRENNUNG
(1H,1H)=
(1H,1H)=8 Hz, 2H; Harom), 3.12 (s, 1H; SH),
(1H,19F)=1 Hz, 18H; CH3); 13C{1H} NMR (75.48 MHz,
C6D6): d=134.5 (d, 3J(13C,19F)=4 Hz; Cm), 133.9 (s; Ci), 129.9 (d, 2J-
(13C,19F)=14 Hz; Cp), 128.2 (s; Co), 27.2 (s; CH3), 20.2 ppm (d, 2J-
A
ACHTUNGTRENNUNG
8 Hz, 2H; Harom), 7.07 (d, 3J
1.09 ppm (d, 4J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(13C,19F)=12 Hz; CCH3); 19F NMR (282.38 MHz, CDCl3): d=
ACHTUNGTRENNUNG
À191.1 ppm (s, 1J
(19F,29Si)=297 Hz); 29Si{1H} NMR (59.63 MHz, CDCl3):
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
1
d=14.2 ppm (d, J
N
ACHTUNGTRENNUNG
(CS); HR-MS: m/z: calcd for C15H22FN32S28Si: 295.1221; found 295.1227;
elemental analysis calcd (%) for C15H22FN32S28Si (295.49): C 60.9, H 7.5,
N 4.7; found C 61.1, H 7.4, N 4.5.
ACHTUNGTRENNUNG
(13C,19F)=12 Hz; CCH3); 19F NMR (282.38 MHz, CDCl3): d=
À190.7 ppm (s, 1J
ACHTUNGTRENNUNG
d=14.2 ppm (d, 1J
ACHTUNGTRENNUNG
HR-MS: m/z: calcd for C14H23F32S29Si: 270.1268; found 270.1269; elemen-
tal analysis calcd (%) for C14H23FSSi (270.48): C 62.2, H 8.6; found C
62.0, H 8.7.
Di-tert-butylfluoro(4-isocyanatophenyl)silane (4b): A solution of 4-(di-
tert-butylfluorosilanyl)phenylamine (1.44 g, 5.7 mmol) in toluene (20 mL)
was added dropwise to a 20% solution of phosgene in toluene (30 mL,
57 mmol) at 08C.[13] The reaction mixture was then heated at reflux for
4 h. After the solution had been cooled to room temperature, the
2-[4-(Di-tert-butylfluorosilanyl)phenyl]-1,1,1,3,3,3-hexamethyldisilazane
(2b): At À788C under magnetic stirring, a solution of tBuLi in pentane
(24 mL, 1.5 molLÀ1) was added to a solution of 2-(4-bromophenyl)-
1,1,1,3,3,3-hexamethyldisilazane[12] (5.50 g, 17 mmol) in diethyl ether
(60 mL). After the reaction mixture had been stirred for 30 min at
À788C, the suspension obtained was added dropwise over a period of
30 min to a cooled (À788C) solution of di-tert-butyldifluorosilane (3.67 g,
20.4 mmol) in diethyl ether (50 mL). The reaction mixture was allowed
to warm to room temperature over a period of 12 h and then hydrolyzed
with saturated aqueous NaCl solution. The organic layer was separated
and the aqueous layer was extracted with diethyl ether (3ꢆ100 mL). The
combined organic layers were dried over magnesium sulfate. After the
latter had been filtered off, the filtrate was concentrated in vacuo to give
2b (6.55 g, 16.5 mmol, 97%) as a colorless oil that solidified (m.p. 388C).
AHCTUNGTRENNUNG
3
3
7.56 (d, J
1.05 ppm (s, 18H; CH3); 13C{1H} NMR (75.48 MHz, CDCl3): d=135.2 (d,
3J(13C,19F)=4 Hz; Cm), 134.7 (s; Ci), 131.3 (d, 2J(13C,19F)=15 Hz; Cp),
(13C,19F)=12 Hz; CCH3);
(1H,1H)=7.5 Hz, 2H; Hm), 7.12 (d, J(1H,1H)=7.5 Hz, 2H; Ho),
ACHUTGTNRENNUG CAHTUNGTRENNUGN
G
ACHTUNGTRENNUNG
125.1 (s; Co), 27.3 (s; CH3), 20.2 ppm (d, 2J
ACHTUNGTRENNUNG
19F NMR (282.38 MHz, CDCl3): d=À191.2 ppm (s, 1J
ACHTUNGTRENNUNG
29Si{1H} NMR (59.63 MHz, CDCl3): d=14.2 ppm (d, 1J
ACHTUNGTRENNUNG
298 Hz); IR (KBr): n˜ =2263 (C=N), 1469 cmÀ1 (C=O); HR-MS: m/z:
calcd for C15H22OFN28Si: 279.1449; found 279.1423; elemental analysis
calcd (%) for C15H22FNOSi (279.43): C 64.5, H 7.9, N 5.0; found C 64.0,
H 7.9, N 4.7.
1H NMR (300.13 MHz, CDCl3): d=7.66 (d, 3J
7.01 (d, 3J(H,H)=8.1 Hz, 2H; Ho) 1.19 (d, 4J
CH3), 0.18 ppm (s, 18H; CH3); 13C{1H} NMR (100.63 MHz, CDCl3): d=
149.5 (s; Ci), 134.1 (d, 3J(13C-19F)=4 Hz; Cm), 129.3 (s; Co), 127.6 (d, 2J-
G
1-[4-(Di-tert-butylfluorosilanyl)phenyl]pyrrole-2,5-dione (5):
A
two-
A
U
necked flask fitted with a dropping funnel and a reflux condenser was
charged with maleic anhydride (0.47 g, 4.8 mmol) and diethyl ether
(20 mL).[14] The mixture was stirred magnetically until all of the maleic
anhydride had dissolved. A solution of 4-(di-tert-butylfluorosilanyl)phe-
nylamine (1.22 g, 4.8 mmol) in diethyl ether (5 mL) was then added by
means of a dropping funnel to give a viscous suspension. This was stirred
at room temperature for 1 h and then cooled to 108C. A cream-colored
powder was precipitated, which was collected by filtration and used for
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG ACHTUNGTRENNUGN
(13C,19F)=14 Hz; Cp), 27.3 (s; CH3), 20.3 (d, 2J(13C,19F)=12 Hz; CCH3),
1.9 ppm (s; SiCH3); 19F NMR (282.38 MHz, CDCl3): d=À191.5 ppm (s,
ACHTUNGTRENNUNG
1J(19F,29Si)=298 Hz); 29Si{1H} NMR (59.63 MHz, CDCl3): d=14.5 (d, 1J-
ACHTUNGTRENNUNG
(29Si,19F)=298 Hz; (tBu)2FSi), 4.8 ppm (s, 2Si; (CH3)3Si); HR-MS: m/z:
calcd for C20H40FN28Si3 397.2447; found 397.2450; elemental analysis
calcd (%) for C20H40FNSi3: (397.79): C 60.4, H 10.1, N 3.5; found C 60.2,
H 9.8, N 3.4.
1
subsequent reactions without further purification. H NMR (300.13 MHz,
CDCl3): d=7.78 (d, 3J
G
E
3
2H; Ho), 6.69 (d, J
A
(1H,1H)=13 Hz,
p-Aminophenyl-di-tert-butylfluorosilane (3b): Gaseous HCl (10 molar
equiv, freshly generated from NaCl and H2SO4) was slowly passed
through a solution of 2b (2.45 g, 6.16 mmol) in chloroform (50 mL) that
was maintained under reflux. After completion of the reaction, the
1H; CH), 1.05 ppm (s, 18H; CH3); 19F NMR (282.38 MHz, CDCl3): d=
À191.2 ppm (s, 1J
(19F,29Si)=297 Hz); 29Si{1H} NMR (59.63 MHz, CDCl3):
ACHTUNGTRENNUNG
1
d=14.2 ppm (d, J
N
A
E
were evaporated under reduced pressure to leave a residue that
A 50 mL flask was charged with acetic anhydride (5 mL) and anhydrous
sodium acetate (0.5 g).[14] The acid (1.48 g, 4.2 mmol), obtained as de-
scribed above, was added, and the resulting mixture was heated over a
steam bath for 30 min to dissolve the suspended solids. After the reaction
mixture had been cooled to room temperature, it was poured into iced
water (50 mL) to precipitate the product, which was separated by filtra-
tion and washed with ice-cold water (3ꢆ10 mL) and with petroleum
ether (20 mL, b.p. 30–608C). Recrystallization from n-hexane gave 5 as
yellow needles (1.05 g, 3.16 mmol, 75%). M.p. 125–1268C; 1H NMR
a
(1.78 g). This white powder was dissolved in diethyl ether and the result-
ing solution was washed with saturated aqueous NaHCO3 solution. The
aqueous phase was extracted three times with diethyl ether. The com-
bined organic layers were dried over MgSO4 and filtered. Concentration
of the filtrate in vacuo afforded 3b (1.56 g) as an orange oil in quantita-
tive yield. 1H NMR (300.13 MHz, CDCl3): d=7.57 (d, 3J
2H; Hm), 6.42 (d, 3J(1H,1H)=8 Hz, 2H; Ho), 2.97 (br, 2H; NH2),
1.19 ppm (d, 4J(1H,19F)=1 Hz, 18H; CH3); 13C{1H} NMR (75.48 MHz,
C6D6): d=148.2 (s; Ci), 135.2 (d, 3J(13C-19F)=4 Hz; Cm), 120.3 (d, 2J-
(13C,19F)=14 Hz; Cp), 114.4 (s; Co), 27.4 (s; CH3), 20.3 ppm (d, 2J-
(1H,1H)=8 Hz,
ACHTUNGTRENNUNG
T
(300.13 MHz, CDCl3): d=7.69 (d, 3J
3J(1H,1H)=7.5 Hz, 2H; Ho), 6.85 (s, 2H; CH), 1.05 ppm (s, 18H; CH3);
13C{1H} APT-NMR (75.48 MHz, CDCl3): d=169.5 (s; CO), 134.8 (d, 3J-
(13C,19F)=5 Hz; Cm), 134.4 (s; CH), 133.7 (d, 2J(13C,19F)=15 Hz; Cp),
(1H,1H)=7.5 Hz, 2H; Hm), 7.38 (d,
ACHTUNGTRENNUNG
T
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
A
ACHTUNGTRENNUNG
2
A
132.6 (s; Ci), 124.8 (s; Co), 27.4 (s; CH3), 20.4 ppm (d, JACHTNGUTERNNUG
(13C,19F)=12 Hz;
À190.7 ppm (s, 1J
R
CCH3); 19F NMR (282.38 MHz, CDCl3): d=À191.2 ppm (s, 1J
ACHTUNGTRENNUNG
(19F,29Si)=
d=14.2 ppm (d, 1J
C
299 Hz); 29Si{1H} NMR (59.63 MHz, CDCl3): d=14.2 ppm (d, 1J-
3475 cmÀ1 (ns NH2); HR-MS: m/z: calcd for C14H24FN28Si: 253.1657;
found 253.1659; elemental analysis calcd (%) for C14H24FNSi (253.43): C
66.4, H 9.6, N 5.5; found C 66.5, H 9.6, N 5.4.
(29Si,19F)=299 Hz); IR (KBr): n˜ =1709 cmÀ1 (C=O); HR-MS: m/z: calcd
ACHTUNGTRENNUNG
for C18H24O2FN28Si: 333.1555; found 333.1554; elemental analysis calcd
(%) for C18H24FNO2Si (279.43): C 64.8, H 7.3, N 4.2; found C 64.5, H 7.3,
N 4.0.
Di-tert-butylfluoro(4-isothiocyanatophenyl)silane (4a): A solution of 4-
(di-tert-butylfluorosilanyl)phenylamine (0.91 g, 3.6 mmol) in toluene
(20 mL) was added dropwise to a solution of thiophosgene (14.4 mmol,
Di-tert-butyl{4-[(tert-butyldimethylsilyloxy)methyl]phenyl}fluorosilane
(2c): At À788C under magnetic stirring, a solution of t-butyllithium in
Chem. Eur. J. 2009, 15, 2140 – 2147
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2145