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of bromine placed in a copper reactor and held at temperatures
between 0 and +10 8C. Under these conditions, the higher
oxidation state of bromine, BrF5, will not be formed in any
appreciable amount [16]. The reagent can be stored in Teflon1
containers indefinitely. BrF3 is a strong oxidizer and tends to
react very exothermically with water and oxygenated organic
solvents such as acetone or THF. Alkanes, like petrol ether,
cannot serve as solvents either since they also react quickly
with BrF3. Solvents such as CHCl3, CH2Cl2, CFCl3 or, if
solubility is not an issue, any perfluoroalkane or perfluoroether
can be used. Any work using BrF3 should be conducted in a
well ventilated area and caution and common sense should be
exercised. It is recommended that face shield and comfortable,
yet heavy-duty, gloves should be worn when working with this
reagent.
Scheme 4. The proposed mechanism for acyl fluorides formation from t-butyl
esters.
two C–F bonds. The production of t-butyl fluoride that we were
able to detect and isolate (Scheme 4), was obviously
encouraged by the ability of the t-butyl group to stabilize a
partially positive charge on the central carbon, attracting one of
the naked nucleophilic fluorides bonded to the bromine atom.
The esters’ reactions are slower than the parallel ones with the
acyl chlorides as evident from competitive reactions between
these two families of compounds. When we reacted, for
example, one mole-equivalent of BrF3 with a 1:1 mixture of 1
mole-equivalent of 6 and 13 only the acyl chloride 6 was
consumed while the t-butyl ester 13 remained intact. The
slower reaction allowed more radical destructive processes to
take place resulting in somewhat lower yield of acyl fluorides
when t-butyl esters served as reactants.
3.1.2. General procedure for the preparation of the acyl
fluorides
The reactants (carboxylic acids, acyl chlorides or t-butyl
esters: 1–10 mmol) were dissolved in 10–20 ml of CFCl3 and
cooled to 0 8C. About 1.1 mole-equivalent of BrF3 dissolved in
the same solvent and cooled to the same temperature were drop-
wisely added. After the addition was completed, the reaction
was washed with Na2S2O3 solution till colorless. The aqueous
layer was extracted with CH2Cl2 and the organic layer dried
over MgSO4.
In conclusion, it is demonstrated once again that BrF3 can
become a useful reagent in organic chemistry and perform
under proper conditions selective reactions. This work shows
that bromine trifluoride can be an effective reagent in the
synthesis of the important acyl fluorides from either carboxylic
acids, acyl chlorides or t-butyl esters.
Cyclohexanoyl fluoride (1a) [12] was prepared from 1 as
described above in 65% yield: bp 23 8C(21 Torr) oil; IR
1
1831 cmÀ1; H NMR 2.51 ppm (1 H, tt, J1 = 10, J2 = 4 Hz);
19F NMR + 36.2 ppm (bs).
3. Experimental
Octanoyl fluoride (2a) [12] was prepared from either 2 or 12
as described above in 65 and 45% yield, respectively: bp
1
3.1. General
28 8C(2 Torr) oil; IR 1838 cmÀ1; H NMR 2.51 ppm (1 H, tt,
J1 = 7.5, J2 = 1 Hz); 19F NMR + 44.9 ppm (bs); 13C NMR
163.5 ppm (d, J = 360 Hz).
1H NMR spectra were recorded using a 200 MHz spectro-
meter with CDCl3 as a solvent and Me4Si as an internal
standard. The 19F NMR spectra were measured at 188.1 MHz
using CFCl3 as an internal standard. The proton broadband
decoupled 13C NMR spectra were recorded at 100.5 MHz. Here
too, CDCl3 served as a solvent and Me4Si as an internal
standard. For all NMR spectra, only relevant and characteristic
signals are reported. IR spectra were recorded in CCl4 solution
on a FTIR spectrophotometer. MS spectra were measured under
EI or CI conditions. In some cases, the molecular ion could not
be detected by standard MS and we resorted to Amirav’s
supersonic GC–MS which revealed the molecular ion without
any difficulties [15]. In such cases, an isotope abounded
analysis was performed in order to establish the composition of
the compound. The yields were determined by either
distillation, GC using an internal standard, but in most cases
they were determined by reacting the crude acyl fluorides with
methanol followed by isolation of the corresponding methyl
esters.
2,4-Dinitrobenzoyl fluoride (3a) was prepared from 3 as
described above in 70% yield. The yield was determined by
hydrolyzing the acyl fluoride to the acid itself. IR 1842 cmÀ1
;
1H NMR 8.09 ppm (1 H, d, J = 8.5 Hz), 8.92 (1 H, d, J = 2 Hz),
8.62 (1 H, dd, J1 = 8.5, J2 = 2 Hz); 19F NMR + 42.9 ppm (bs);
13C NMR 153.5 ppm (d, J = 350 Hz); HRMS m/z = 214.0032
(M)+, calcd. for C7H3FN2O5 = 214.0026.
Dehydrocholicoyl fluoride (5a) was prepared from 5 as
described above in 65% yield. The yield was determined by
treating the acyl fluoride with MeOH and isolating the methyl
dehydrocholate. IR 1839 cmÀ1 1H NMR 2.9 ppm (1 H, t,
;
J = 11 Hz), 19F NMR + 45.4 ppm (bs); HRMS m/z = 404.2371
(M)+, calcd. for C24H33FO4 = 404.2374.
2-Norbornaneacetyl fluoride (6a) was prepared from 6 or 13
as described above in 70 and 55% yield, respectively: bp
52 8C(2 Torr) oil. The yield was determined by treating the acyl
fluoride with MeOH and isolating the methyl dehydrocholate.
IR 1844 cmÀ1; 1H NMR 2.52 ppm (1 H, dd, J1 = 4, J2 = 2 Hz);
19F NMR + 46.2 ppm (bs); HRMS (CI) m/z = 155.0871
(M + 1)+, calcd. for C9H13FO = 155.0872.
3.1.1. Preparing and handling of BrF3
Although commercially available, we usually prepare our
own BrF3 simply by passing 0.6 mol fluorine through 0.2 mol
2-Ethylhexanoyl fluoride (7a) [12] was prepared from 7 or
14 as described above in 75 and 40% yield, respectively: bp