9
588 J . Org. Chem., Vol. 63, No. 25, 1998
Ta ble 2. Rea ction of Su bstr a tes 2a -i w ith
Notes
Ta ble 3. Rea ction of Su bstr a tes 2a -d ,g-i w ith
+
-
a
+
-
a
Bu 4N F ‚n H2O (1) w ith ou t Solven t
products, %b
Bu 4N F ‚n H2O (1) in Aceton itr ile
products, %b
reaction
time, h
entry
2
n
time, h
RF
alkene
entry
2
n
RF
alkene
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
a
a
b
b
c
c
d
d
e
f
3.5
5
3.5
5
3.5
5
3.5
5
5
5
3.5
5
10
6
7
3 (95)
3 (96)
3 (91)
3 (94)
3 (70)
3 (76)
3 (100)
3 (100)
4 (88)
5 (86)
8 (5)
8 (4)
8 (9)
8 (6)
8 (30)
8 (24)
- -
1
2
3
4
5
6
7
8
9
10
11
12
13
2a
2a
2b
2b
2c
2c
2d
2d
2g
2h
2h
2i
3.5
5
3.5
5
3.5
5
3.5
5
3.5
5
10
5
5
12
16
1
3 (90)
3 (94)
3 (87)
3 (91)
3 (60)
3 (77)
3 (98)
3 (99)
6 (95)
7 (38)
7 (41)
7 (70)
7 (76)
8 (10)
8 (6)
8 (13)
8 (9)
8 (40)
8 (21)
8 (2)
0.5
0.5
0.25
0.25
0.25
0.25
0.5
0.5
0.5
1
6
0.5
2
0.25
0.25
0.5
0.5
0.5c
2
16
1
1
- -
8 (1)
d
9 (12)
10 (14)
- -
-
e
1
1
1
1
1
1
(62)
(59)
(30)
(24)
c
d
e
g
h
h
i
6 (90)
(68)e
(60)e
e
7 (32)
7 (40)
7 (72)
7 (78)
f
e
2i
e
5
5
(28)
a
Substrates 2a -d ,g-i 1 mol equiv; Bu4N F-.nH2O (1), 2 mol
equiv; 80 °C. GLC yields. c At 25 °C. d Together with 5% of benzyl
alcohol. e As a mixture of 1- and 2-octene. At 50 °C.
+
f
(22)e
i
4
b
a
+
-
f
Substrates 2a -i, 1 mol equiv; Bu4N F ‚nH2O (1), 2 mol equiv;
b
c
d
8
0 °C. GLC yields. At 25 °C. Together with 10% of benzyl
alcohol. As a mixture of 1- and 2-octenes. f At 50 °C.
e
external standards. The progress of the reaction was monitored
by GLC (50 cm × 1.6 mm OV 101-5% chrom WHP 100-120
mesh and capillary MP19091J -413 30m × 0.32 mm × 0.25 µm
columns with a temperature program from 30 °C to 240 °C) and
GC-MS (EI 70 eV, J &W 08-3MS 30 × 0.25 mm × 0.25 µm
column). The data were evaluated by an internal standard
method. In all cases the mass balance of the reaction mixture
was g 98% in the expected reaction products.
Compounds 2d , 2h , and 2i were prepared as described
elsewhere, whereas other substrates 2a -c,e-g are commercially
available and were distilled before use. Acetonitrile over molec-
ular sieves (Fluka) was used throughout the work.
molar excess of the fluorinating agent 1 or working at
5
0 °C instead of 80 °C (entries 12-17).
The results obtained for substrates 2a -i are reported
in Table 2. Under the better conditions found for 2b (n
)
(
5) or using commercial TBAF (n ) 3.5), octyl chloride
2a ) afforded octyl fluoride (3) in 95-96% (entries 1, 2),
whereas methanesulfonate 2d gave quantitative conver-
sion to 3 with both TBAF species (entries 7, 8). Lower
yields of 3 (76%) together with higher amounts of
-octene (8) (24%) were observed in the reaction of
-iodooctane (2c) (entries 5, 6). A reduced selectivity was
found increasing the number of carbon atoms in the alkyl
chain: 1-bromodecane (2e) and 1-bromohexadecane (2f)
gave the fluoro derivatives 4 in 88% and 5 in 86% yield,
respectively (entries 9, 10). Benzyl bromide (2g) quickly
reacted with commercial TBAF‚3.5H
affording benzyl fluoride (6) in excellent yields (90%) and
0% of benzyl alcohol (entry 11). The main reaction
product of 2-bromooctane (2h ) in the presence of TBAF‚
O (entry 12) was a mixture of 1- and 2-octene (68%)
together with only a minor quantity of 2-fluorooctane (7)
32%). A slight increase of 7 (40%) was obtained in the
reaction of 2h with TBAF‚10H O (1) (entry 13). Using
-octyl methanesulfonate (2i), the 2-fluoro derivative 7
8
9
8
TBAF 3.5‚H
tion).The final hydration state n of various TBAF nH
.5, 1.2, 5, 10) was confirmed by Karl Fischer titration of THF
solutions prepared in a dry box.
Typ ica l P r oced u r e for F lu or in a tion w ith TBAF ‚n H
(1) (n < 3.5). TBAF‚3.5H O 1 (2 mmol) was gently heated (<40
2
O was obtained by Aldrich (Karl Fischer titra-
1
1
.
2
O (1) (n )
0
2
O
2
-
4
°
C) under sonication and high vacuum (4 × 10 Torr) in a
round-bottomed flask equipped with an inlet. The loss of weight
was monitored at regular intervals after filling with nitrogen.
2
O (1) at 25 °C,
TBAF‚1.2H
necessary to prepare TBAF‚0.5H
2
O was obtained after 12 h, whereas 30 h were
1
6
2
O.
As soon as the desired hydration state was achieved, the
reactions were carried out in the same flask by adding 2-meth-
oxynaphthalene (0.2 mmol) as internal standard, the solvent (2
mL) (if necessary), and the substrate 2 (1 mmol). A reflux
condenser equipped with a calcium chloride drying tube was
connected and the reaction mixture heated under magnetic
stirring.
5
H
2
(
2
2
was obtained in 72% yield, which increased to 78% by
performing the reaction at 50 °C (entry 14, 15).
Generally, fluorinations in acetonitrile (Table 3) are
slower than those carried out without solvent, the fluoro
derivatives being generated in similar yields.
Typ ica l P r oced u r e for F lu or in a tion w ith TBAF ‚n H
(1) (n g 3.5). Meth od A (Nea t). A screw cap vial was charged
with TBAF‚3.5H O (1) (2 mmol), 2-methoxynaphthalene (0.2
mmol), and the water required to obtain the desired hydration
state (n ) 5, 10). After 1 min of stirring, the substrate 2 (1 mmol)
was added and the reaction mixture stirred at the specified
temperature until completion.
2
O
2
It is worth noting that, differently from that previously
5
reported by Cox et al., no detectable amounts of the
Samples were withdrawn at various times after cooling and
corresponding alcohols were produced in the fluorination
centrifuging the vial. The samples were further diluted with CH
3
-
CN and injected.10
reaction of the substrates 2a -f,h -i, using TBAF‚nH
in the hydration state range 0.5 < n < 10.
2
O
Meth od B (CH
3
CN). Standardized acetonitrile solutions of
TBAF‚nH O (n ) 5, 10) (2 M) were prepared by adding the
2
In conclusion, hydrated tetrabutylammonium fluoride
(
1), in particular the pentahydrate and the commercial
(
8) Williams, H. R.; Mosher, H. S. J . Am. Chem. Soc. 1954, 76, 2984.
(9) Hsueb, L. M.; Marvel, C. S. J . Am. Chem. Soc. 1928, 50, 855.
(10) When a chlorinated solvent (e.g., CH Cl ) was used instead of
CH CN, variable amounts of 1-chlorooctane (2a ) were detected in the
reaction mixture of 1-bromooctane (2b) with TBAF. As reported,
species, behaves as a powerful, nonbasic and nucleophilic
fluorinating agent, and it is particularly suitable for
converting alkyl chlorides, bromides, and methane-
sulfonates into the corresponding alkyl fluorides.
2
2
3
2
dichloromethane promotes metathesis of TBAF, producing tetrabutyl-
ammonium chloride, which is a good chlorinating reagent and reacts
with 2b, generating the less reactive 2a , thus reducing the overall
reaction rate. 2a , which we identified by GC-MS and C and H NMR
analyses, can be confused with 1-octanol because of the similar
chromatographic retention times and proton resonances. This behavior
could be responsible for the differences between the data reported by
Exp er im en ta l Section
13
1
Gen er a l Meth od s. The H NMR and 19F NMR were run in
1
CDCl
3 6
and acetone-d at 300 and 282 MHz. Chemical shifts are
1
19
5
reported in ppm relative to Me
4
Si ( H) and CFCl
3
( F) as
Cox et al. and our results (i.e., Cox found large amounts of 1-octanol).