6
Tetrahedron
4
.3.2. 2,6-Dichloro-4-(perfluorobutyl)benzoyl
167 (26), 150(100), 121 (15), 120 (15), 104 (23); HRMS (EI) m/z
ACCEPTED MANUSCRIPT
chloride (1b)
calcd for C H F NO 527.0402, found 527.0389.
16 10 13 4
The synthetic procedure for 1a was repeated using compound
9
b (1.05 g, 2.56 mmol) to give 1b (1.09 g, 99%) as a colourless
liquid, which was used in the next reaction without further
4.5. A typical procedure for macrolactonization using FY reagent
1a (Table 2, Entry 1)
1
13
5a
purification; H NMR (400 MHz, CDCl ) δ 7.62 (s, 2H);
C
=
3
NMR (100 MHz, CDCl ) δ 108-118, 127.0, 131.0, 132.8 (t, J
3
C-F
19
To a mixture of 12-hydroxyoctadecanoic acid (154 mg, 0.51
mmol) and N,N-diisopropylethylamine (71 mg, 0.55 mmol) in
THF (5 mL), was added FY reagent 1a (268 mg, 0.51 mmol), and
this was stirred at 25 °C for 1 h. The mixture was then added to a
solution of DMAP (369 mg, 3.0 mmol) in toluene (250 mL)
being heated under reflux over a period of 3 h. The resulting
mixture was concentrated, after which brine (10 mL) was added
to the residue, and the mixture was cooled to 0 °C to afford a
while precipitate. The cooled mixture was filtered and the filtrate
was extracted with diethyl ether (3 × 15 mL). The combined
organic extract was dried over Na SO (5 g) and concentrated in
2
1
4.9 Hz), 140.0, 164.2; F NMR (378 MHz, CDCl ) δ -80.89, -
3
-1
11.44, -122.15, -125.46; IR (KBr) 1796 cm ; LRMS (EI) m/z
+
(relative intensity) 426 (M , 0.54), 410 (27), 408 (41), 393 (40),
3
91 (65), 241 (64), 239 (100), 211 (21), 150 (25%); HRMS (EI)
35
m/z calcd for C H Cl F O 425.9028, found 425.9008.
11
2
3 9
4
.3.3. 2,6-Dichloro-4-(perfluorodecyl)benzoyl
chloride (1c)
The synthetic procedure for 1a was repeated using compound
2
4
9
c (909 mg, 1.28 mmol) to give 1c (918 mg, 99%) as a white
vacuo. The crude residue was purified by silica gel (10 g)
chromatography using hexane/chloroform = 1/1 as the eluent to
solid, which was used in the next reaction without further
1
purification; mp 83.4-85.0 ºC; H NMR (400 MHz, CDCl ) δ
3
13
give 12-hexyl-12-dodecanolide (123 mg, 86%) as a white solid;
7
1
.62 (s, 2H); C NMR (100 MHz, CDCl ) δ 127.0, 131.0, 132.7,
40.0, 164.3 (signals corresponding to the perfluorinated alkyl
carbons were not observed); F NMR (378 MHz, CDCl ) δ -
1
3
H NMR (400 MHz, CDCl ) δ 0.87 (t, J = 6.8 Hz, 3H), 1.25-1.70
3
19
(m, 26H), 2.22-2.28 (m, 2H), 2.40-2.45 (m, 2H), 4.91-4.93 (m,
3
13
1
H); C NMR (100 MHz, CDCl ) δ 14.0, 22.6, 24.4, 24.5, 24.7,
3
8
0.70, -111.16, -121.11, -121.70, -121.85, -122.67, -126.07; IR
-
1
+
24.9, 25.4, 25.9, 26.3, 26.7, 29.2, 31.7, 33.3, 34.8, 35.0, 74.4,
73.8. The white precipitate obtained by the filtration was
(
0
KBr) 1795 cm ; LRMS (EI) m/z (relative intensity) 726 (M ,
.24), 693 (66), 691 (100), 222 (14); HRMS (EI) m/z calcd for
1
35
poured into a 2 M HCl solution (10 mL) and the mixture was
extracted with diethyl ether (3 × 10 mL). The combined organic
layer was washed with brine (2 × 15 mL) and dried over Na SO
C H Cl F O 725.8836 found 725.8850.
17
2
3 21
2
4
(
9
5 g) and concentrated in vacuo to recover fluorous benzoic acid
a (230 mg, 83%) as a pale yellow solid.
5a
4
.4. A typical procedure for esterification using FY reagent 1a
(Table 1, Entry 1)
A mixture of benzoic acid (60 mg, 0.49 mmol), N,N-
4
.6. A typical procedure for monitoring of an esterification with
diisopropylethylamine (78mg, 0.60 mmol), FY reagent 1a (290
mg, 0.55 mmol) and N,N-dimethylaminopyridine (DMAP, 72
mg, 0.59 mmol) in benzene (3 mL) was stirred at 25 °C for 15
min. 1-Octanol (77 mg, 0.59 mmol) was added, and the mixture
was stirred at room temperature for 1 h. Brine (10 mL) was then
added to the mixture, which was poured into iced water (20 mL)
to precipitate a white solid. The precipitate was separated, and
FY reagent 1a
A mixture of benzoic acid (60 mg, 0.49 mmol), N,N-
diisopropylethylamine (186 mg, 1.4 mmol), and 1a (288 mg, 0.55
mmol) in benzene (3 mL) was stirred at 30 °C for 20 min.
DMAP (12 mg, 0.10 mmol) was added to the mixture and stirring
was continued for another 10 min at the same temperature.
Phenol (56 mg, 0.59 mmol) was then added to the mixture with
stirring and the mixture was monitored by GC using tetradecane
as an internal standard. GC analysis was repeated three times for
each reaction.
the filtrate was washed with brine (2 × 5 mL), dried over Na SO4
2
(
3 g) and concentrated in vacuo. The crude residue was purified
by silica gel (10 g) chromatography with hexane/chloroform =
/1 as the eluent to give n-octyl benzoate (109 mg, 95%) as a
1
1
colourless liquid; H NMR (500 MHz, CDCl ) δ 0.88 (t, J = 7.3
3
Hz, 3H), 1.25-1.45 (m, 10H), 1.77 (quint, J = 6.9 Hz, 2H), 4.32
Acknowledgments
(
t, J = 6.9 Hz, 2H), 7.44 (t, J = 7.8 Hz, 2H), 7.56 (t, J = 7.4 Hz,
13
1
1
1
H), 8.05 (d, J = 6.9 Hz, 2H); C NMR (100 MHz, CDCl ) δ
3
This work was partially supported by a Grant-in-Aid for
Scientific Research (C) (no. 24550213) from the Japan Society
for the Promotion of Science (JSPS).
4.1, 22.6, 26.0, 28.7, 29.2 (2C), 31.8, 65.1, 128.3, 129.5, 130.5,
32.8, 166.7. The white precipitate obtained by the filtration was
poured into a 2 M HCl solution (10 mL) and the mixture was
extracted with diethyl ether (3 × 10 mL). The combined organic
References and notes
layer was washed with brine (2 × 15 mL) and dried over Na SO4
2
(
9
5 g) and concentrated in vacuo to recover fluorous-benzoic acid
a (247 mg, 89%) as a pale yellow solid.
1
2
.
.
For a general review on fluorous chemistry, see: (a) Gladysz, J.
A.; Curran, D. P.; Horváth, I. T., Eds. Handbook of Fluorous
Chemistry; Wiley-VCH: Weinheim, 2004.
For reviews on fluorous biphasic reaction, see: (a) Carreira, M.;
Contel, M. Topics in Current Chemistry 2012, 308, 247-273. (b)
Cai, C.; Yi, W.-B.; Zhang, W.; Shen, M.-G.; Hong, M.; Zeng, L.-
Y. Molecular Diversity 2009, 13, 209-239. (c) Yoshida, A.; Hao,
X.; Yamazaki, O.; Nishikido, J. Molecules 2006, 11, 627-640. (d)
Mathison C. R.; Cole-Hamilton, D. J. Catalysis by Metal
Complexes 2006, 30, 145-181.
4
4
.4.1. 4,4,5,5,6,6,7,7,8,8,9,9,9-Tridecafluorononyl
-nitrobenzoate (Table 1, Entry 13)
1
Light yellow crystalline solid; mp 55.0-56.0 °C, H NMR (400
MHz, CDCl ) δ 2.15-2.29 (m, 4H), 4.47 (t, J = 6.0 Hz, 2H), 8.21
3
13
(d, J = 8.8 Hz, 2H), 8.31 (d, J = 9.2 Hz, 2H); C NMR (100
3
.
Papers utilising electron-withdrawing effect of a perfluoroalkyl
group: (a) Huang, Y.-B.; Yi, W.-B.; Cai, C. J. Fluorine Chem.
MHz, CDCl ) δ 20.0, 27.9 (t, J = 22.9 Hz), 64.4, 108-121,
1
3
C-F
1
9
23.6, 130.7, 135.1, 150.7, 164.5; F NMR (378 MHz, CDCl ) δ
3
-1
2
010, 131, 879-882. (b) Dordonne, S.; Crousse, B.; Bonnet-
-80.9, -114.3, -121.9, -122.9, -123.4, -126.2; IR (KBr) 1718 cm ;
Crousse, D.; Bonnet-Delpon, D.; Legros, J. Chem. Commun. 2011,
47, 5855-5857. (c) Shen, M.-G.; Cai, C.; Yi, W.-B. J. Fluorine
LRMS (EI) m/z (relative intensity) 527 (9), 295 (4), 168 (50),