Use of C,N-chelated di-n-butyltin(IV) fluoride for the synthesis of acyl fluorides, fluoroformates and fluorophosgene

Article abstract of DOI:10.1016/j.tetlet.2008.08.060

{2-[(CH₃)₂NCH₂]C₆H₄}(n-Bu)₂SnF (1) reacts with various chloroformates, acyl chlorides, methanesulfonyl chloride, 4,4′-dimethoxytrityl chloride and phosgene precursors or derivatives to form fluorinated analogues. All reactions proceed rapidly and under mild conditions. The use of a catalytic amount of 1 and KF in toluene led to a relatively high yield of a selected fluoroformate.

Full text of DOI:10.1016/j.tetlet.2008.08.060

Tetrahedron Letters 49 (2008) 6320–6323
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Use of C,N-chelated di-n-butyltin(IV) fluoride for the synthesis
of acyl fluorides, fluoroformates and fluorophosgene
a
b
b
c
d
a,
*
ˇ
ˇ ˇ
Petr Švec , Aleš Eisner , Lenka Kolárová , Tomáš Weidlich , Vladimír Pejchal , Aleš Ru˚ zicka
a
ˇ
Department of General and Inorganic Chemistry, Faculty of Chemical Technology, University of Pardubice, nám. Cs. legií 565, CZ-532 10 Pardubice, Czech Republic
Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, nám. Cs. legií 565, CZ-532 10 Pardubice, Czech Republic
Institute of Environment Protection, Faculty of Chemical Technology, University of Pardubice, nám. Cs. legií 565, CZ-532 10 Pardubice, Czech Republic
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, nám. Cs. legií 565, CZ-532 10 Pardubice, Czech Republic
b
c
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ˇ
d
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a r t i c l e i n f o
a b s t r a c t
Article history:
{2-[(CH3)2NCH2]C6H4}(n-Bu)2SnF (1) reacts with various chloroformates, acyl chlorides, methanesulfonyl
chloride, 4,40-dimethoxytrityl chloride and phosgene precursors or derivatives to form fluorinated ana-
logues. All reactions proceed rapidly and under mild conditions. The use of a catalytic amount of 1 and
KF in toluene led to a relatively high yield of a selected fluoroformate.
Received 30 June 2008
Revised 13 August 2008
Accepted 19 August 2008
Available online 22 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Dedicated to Prof. Dr. Rudolph Willem on
the occasion of his 60th birthday in
recognition of his outstanding contributions
to the area of organometallic chemistry and
NMR spectroscopy
Acyl fluorides, fluoroformates and fluorinated phosgene are
more stable than their chloro or bromo analogues and are useful,
for example, in peptide or natural products synthesis.1,2 Several
methods have been developed for acyl fluoride synthesis. Acyl
chlorides or bromides were converted to the corresponding fluo-
rides using (CF3)2Cd,3 Ishikawa’s reagent (CF3CF2CHFN(C2H5)2),4
aerosol fluorination,5 SF4 or DAST6 and various forms of HF and
other fluorides serving as fluorine sources.7 Cyclic ketones,8 alco-
hols, aldehydes,9 carboxylic acids, acyl chlorides or t-Bu esters (in
BrF3)10 can also be converted into the respective acyl fluorides.
Unfortunately, most of the reagents used for these purposes
must be stored in TeflonÒ or copper containers, or under pressure,
react very exothermically with water and also the selection of sol-
vents which can be used with them is rather limited.
Figure 1. Structure of LCN(n-Bu)2SnF (1).
highly sensitive carriers for fluoride ion recognition.15 In our more
recent papers, we reported the structure and fluorination ability of
C,N-chelated di-n-butyltin(IV) fluoride (1, Fig. 1)16 towards various
organochlorosilanes, dichlorophenylphosphine, antimony and bis-
muth complexes,17 and some metal halides.
Recently, we have reported triorganotin(IV) fluorides of general
formula LCNR2SnF, where LCN is {2-[(CH3)2NCH2]C6H4}ꢀ and R is al-
kyl (Me, n-Bu (1), t-Bu) or aryl (Ph) groups of different steric bulk
and electronic properties.11 These compounds are able to fluori-
nate titanocene dichloride essentially quantitatively. In our recent
reports in this field, we described the ability of LCN(n-Bu)2SnF (1,
Fig. 1) to form di-12 and monoorganotin(IV)13 fluorides bearing
the same or a similar ligand.14 These compounds are presumably
tri-, tetranuclear or polymeric species with rather low solubility
in common organic solvents, and we used them as selective and
Here we communicate the high potential of C,N-chelated di-n-
butyltin(IV) fluoride for preparing acyl fluorides, fluoroformates
and other fluorides.
{2-[(CH3)2NCH2]C6H4}(n-Bu)2SnF (1) reacts (Table 1, Fig. 2) with
various chloroformates to form exclusively fluoroformates (runs
1–4), with acyl chlorides to give acyl fluorides (runs 6–13), with
methanesulfonyl chloride to give its fluoride (run 14) and various
phosgene precursors or derivatives to form fluorinated phosgene
or thiophosgene. Di- and triphosgene gave, in the presence of
moisture, fluorinated phosgene; when the reaction of triphosgene
was carried out in a sealed tube, a complex composed of two {2-
[(CH3)2NCH2]C6H4}(n-Bu)2SnCl units and ClF6 was observed.18
ꢀ
* Corresponding author. Fax: +420 466037068.
The reaction of 4,40-dimethoxytrityl chloride yielded the corre-
ˇ ˇ
E-mail address: ales.ruzicka@upce.cz (A. Ru˚ zicka).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.060

P. Švec et al. / Tetrahedron Letters 49 (2008) 6320–6323
6321
Table 1
Fluorination experiments
Run
1
Substrate
Conditions
Product
Conversiona (%)
100
O
O
Et2O, rt, 1 equiv of 1, 10 min
Cl
O
F
O
O
O
O
O
2
3
Et2O, rt, 1 equiv of 1, 10 min
100
100
n-Bu
n-Bu
Cl
Cl
O
O
F
F
O
O
Et2O, rt, 1 equiv of 1, 10 min
O
O
O
O
O
O
O
O
O
O
O
Cl
O
F
O
O
4
5
Et2O, rt, 2 equiv of 1, 3 h
100
30
O
O
N
O
Cl
Cl
O
N
F
F
O
O
Toluene, reflux, 1 equiv of 1, 12 h
6
7
8
Benzene, rt, 1 equiv of 1, 1 h
Et2O, rt, 1 equiv of 1, 1 h
100
100
100
Me2N
N
N
COCl
Me2N
N
N
COF
COCl
COF
COF
COCl
Et2O, rt, 2 equiv of 1, 10 min
ClOC
FOC
9
10
11
CH3COCl
CH3CH2COCl
ClCH2CH2CH2COCl
Et2O, 0 °C, 1 equiv of 1, 3 h
Et2O, 0 °C, 1 equiv of 1, 3 h
Et2O, rt, 1 equiv of 1, 1 h
CH3COF
CH3CH2COF
ClCH2CH2CH2COF
100
100
100
Cl
F
12
Et2O, rt, 1 equiv of 1, 1 h
100
Cl
Cl
O
O
13
14
15
16
CH3(CH2)7CH@CH(CH2)7COCl
CH3SO2Cl
CSCl2
Et2O, rt, 1 equiv of 1, 10 min
Et2O, rt, 1 equiv of 1, 10 min
tol.-d8, rt, 2 equiv of 1, 10 min
tol.-d8, rt, 2 equiv of 1, 10 min
CH3(CH2)7CH@CH(CH2)7COF
CH3SO2F
A mixture of fluorinated compounds
COF2
100
100
100
100
COCl2
O
17
18
tol.-d8, rt, 4 equiv of 1, 10 min, H2O
tol.-d8, rt, 6 equiv of 1, 10 min, H2O
COF2
100
100
CCl3
Cl
O
O
COF2
Cl3C
CCl3
Cl
O
O
F
O
O
O
O
19
Et2O, rt, 1 equiv of 1, 30 min
100
a
Directly after the reaction, based on multinuclear NMR measurements.

6322
P. Švec et al. / Tetrahedron Letters 49 (2008) 6320–6323
CH). 19F{1H} NMR (CDCl3, 295 K, ppm): ꢀ17.7 (s). Elemental
Anal. Calcd for C5H5O5F (164.09): C, 36.6; H, 3.1. Found: C, 36.4;
H, 3.0.
Tri(ethyleneglycol) bis(fluoroformate) (4): 1H NMR (CDCl3, 295 K,
ppm): 4.41–4.37 (m, 4H, OCH2CH2O), 3.64–3.60 (m, 4H, OCH2-
CH2O), 3.45 (s, 4H, OCH2). 19F{1H} NMR (CDCl3, 295 K, ppm):
ꢀ16.8 (s). Elemental Anal. Calcd for C8H12O6F2 (242.18): C, 39.7;
H, 5.0. Found: C, 40.0; H, 5.2.
Figure 2. Reactivity of 1.
N-Cyclohexyl-N-ethyl carbamoyl fluoride (5): 1H NMR (CDCl3,
295 K, ppm): 3.97 (t, 2H, cyclohexyl H, 3J = 9.1 Hz), 3.86 (t, 2H,
cyclohexyl H, 3J = 9.2 Hz), 3.27 (q, 2H, ethyl CH2, 3J = 7.0Hz),
1.76–1.68 (m, 2H, cyclohexyl H), 1.59–1.55 (m, 2H, cyclohexyl
H), 1.41–0.99 (m, 6H, cyclohexyl H and ethyl CH3). 19F{1H} NMR
(CDCl3, 295 K, ppm): 20.2 (s). Elemental Anal. Calcd for C9H16ONF
(173.23): C, 62.4; H, 9.3; N, 8.1. Found: C, 62.7; H, 9.0; N, 8.2.
4-(4-Dimethylaminophenylazo)benzoyl fluoride (6): Mp 188–
191 °C. 1H NMR (C6D6, 295 K, ppm): 8.15 (d, 2H, benzoyl H,
3J = 7.4 Hz), 7.94 (d, 2H, phenylazo H, 3J = 5.5 Hz), 7.84 (d, 2H, ben-
zoyl H, 3J = 3.6 Hz), 6.39 (d, 2H, phenylazo H, 3J = 9.0 Hz), 2.28 (s,
6H, N(CH3)2). 19F{1H} NMR (CDCl3, 295 K, ppm): 21.0 (s). Elemental
Anal. Calcd for C15H14ON3F (271.30): C, 66.4; H, 5.2; N, 15.5. Found:
C, 66.6; H, 5.0; N, 15.8.
sponding fluorinated product almost quantitatively. All these reac-
tions proceed rapidly under very mild conditions, and an equimo-
lar amount of 1 is used. The process developed is selective, and
chlorine atoms bonded to alkyl groups remain unchanged as dem-
onstrated in runs 11 and 12. N-Cyclohexyl-N-ethyl carbamoyl fluo-
ride is rather unreactive under the conditions used (run 5).
To test for a possible catalytic procedure, fluorination of
tri(ethylene glycol) bis(chloroformate) was selected because of
the relatively high thermal stability and boiling points of both reac-
tant and suggested product. Ten molar equivalents of KF (530 mg),
1 M equiv of tri(ethyleneglycol) bis(chloroformate) (250 mg) and
one molar percent of 1 were suspended in a reaction tube equipped
with a TeflonÒ Young valve, in toluene. The closed tube was heated
under ultrasound activation at 85 °C for one hour. The KF was fil-
tered off and the solvent evaporated. The multinuclear NMR spectra
of the yellowish oily product proved ca. 42% conversion to tri(eth-
yleneglycol) bis(fluoroformate). Under the same conditions but
without 1, no conversion to fluorinated product was observed.
When we tried to expand the series of compounds to different
types of organic halides, we found that tert-butyl chloride,
1-bromooctane, benzyl bromide, 4-nitrobenzyl chloride, 2,6-di-
4-Chlorobutyryl fluoride (11): 1H NMR (C6D6, 295 K, ppm): 2.97
(t, 2H, ClCH2, 3J = 6.2 Hz), 1.95 (t, 2H, CH2C(O)F, 3J = 6.6 Hz), 1.48–
1.44 (m, 2H, CH2). 19F{1H} NMR (C6D6, 295 K, ppm): 45.7 (s).
4-Chloro-2-methylbutyryl fluoride (12): 1H NMR (CDCl3, 295 K,
ppm): 3.40 (t, 2H, ClCH2, 3J = 6.3 Hz), 2.95–2.82 (m, 1H, CH),
2.19–2.11 and 1.90–1.80 anisochronous protons (m, 2H, CH2),
1.23 (d, 3H, CH3, 3J = 7.1 Hz). 19F{1H} NMR (CDCl3, 295 K, ppm):
38.7 (s). Elemental Anal. Calcd for C5H8OClF (138.57): C, 43.3; H,
5.8. Found: C, 43.1; H, 6.0.
Thiocarbonyl difluoride (15): Bp 54 °C (760 Torr). 19F{1H} NMR
(tol.-d8, 295 K, ppm): a mixture of products was observed with
d(19F) at 35.7, 9.3, ꢀ27.7, ꢀ45.5, ꢀ46.7 and ꢀ50.7 ppm and five
other minor signals.
chlorobenzonitrile, 2-chlorobenzonitrile,
a,a,a-trichlorotoluene,
cyclohexyl and tert-butyl acetates did not react with 1. Only phenyl
acetate gave acetyl fluoride in 25% yield when refluxed in toluene
for 20 h.
Carbonyl difluoride (16): 19F{1H} NMR (tol.-d8, 295 K, ppm):
ꢀ19.3 (s).
In conclusion, the advantage of reagent 1 over other systems,
compounds and methods is that it has a very short reaction time
and compound 1 is not volatile, is less toxic, and normal glassware
can be used. Additionally, compound 1 is extremely soluble in all
organic solvents, is stable in air for years, and can be recycled
directly after distilling the product off by reaction with excess KF
(in water/diethyl ether mixture) in very high yields (usually more
than 90%).
Fluorination of diphosgene (17): 19F{1H} NMR (tol.-d8, 295 K,
ppm): ꢀ18.7 (s).
Fluorination of triphosgene (18): 19F{1H} NMR (tol.-d8, 295 K,
ppm): ꢀ19.7 (s).
4,40-Dimethoxytrityl fluoride (19): 1H NMR (CDCl3, 295 K, ppm):
7.24 (t, 1H, phenyl H, 3J = 6.3 Hz), 7.11 (d, 6H, phenyl H,
3J = 8.9 Hz), 6.80–6.76 (m, 6H, phenyl H), 3.77 (s, 6H, OCH3).
19F{1H} NMR (CDCl3, 275 K, ppm): ꢀ121.3 (s).
General description of the fluorinating method: The starting sub-
strates were dissolved in various solvents (see Table 1), and com-
pound 1 (equimolar amount) was added in one portion. The
products were separated from the reaction mixture by distillation
or by trap-to-trap distillation and identified by multinuclear NMR
spectroscopy and by GC/MS and ESI/MS techniques. Chromatogra-
phy can also be used as a separating method, but in these cases dis-
tillation, trap-to-trap distillation and crystallization are the easiest
procedures to obtain pure products. During the reaction, the com-
position of each reaction mixture was determined by ESI/MS tech-
niques and the reaction was stopped when no peak for ‘{2-
[(CH3)2NCH2]C6H4}(n-Bu)2SnF+H’ at m/z 388 in positive ion mode
was observed. The reaction progress was also monitored by 1H
and 119Sn NMR spectroscopy.11 The NMR spectra were recorded
as solutions in C6D6, CDCl3 or toluene-d8 on a spectrometer
(equipped with Z-gradient 5 mm probe) at 300 K, 1H (500.13
MHz), 19F{1H} (470.53 MHz) and 119Sn{1H} (186.50 MHz).
Data for the known products are given in the Supplementary
data (available online).
Examples of synthesis and product separation
Benzoyl fluoride (run 1): Benzoyl chloride (0.90 g, 6.40 mmol)
was dissolved in diethyl ether (30 ml) and compound 1 (2.47 g,
6.40 mmol) was added. The reaction mixture was stirred for one
hour at room temperature. Afterwards, the solvent was evaporated
in vacuo at 20 Torr. Pure benzoyl fluoride was distilled off (bp 159–
161 °C at 760 Torr). Yield 0.72 g (91%). In the distillation residue,
pure {2-[(CH3)2NCH2]C6H4}(n-Bu)2SnCl (2.45 g, 6.1 mmol) was
identified by multinuclear NMR spectroscopy.
4-(4-Dimethylaminophenylazo)benzoylfluoride (run 6): 4-(4-Di-
methylaminophenylazo)benzoyl chloride (0.50 g, 1.74 mmol) was
suspended (only partially soluble) in benzene (30 ml) and com-
pound 1 was added (0.67 g, 1.74 mmol). The reaction mixture was
stirred for 1 h at room temperature, then filtered and the solid part
was washed with 10 ml of hexane yielding 0.39 g (82%) of pure 4-
(4-dimethyl-aminophenylazo)benzoyl fluoride. In the filtrate, after
evaporation of the solvent in vacuo, essentially quantitative conver-
sion of 1 to {2-[(CH3)2NCH2]C6H4}(n-Bu)2SnCl had occurred and the
remainder of the 4-(4-dimethylaminophenylazo)benzoyl fluoride
was observed by multinuclear NMR spectroscopy.
(2-Oxo-1,3-dioxolan-4-yl)methyl fluoroformate (3): 1H NMR
(CDCl3, 295 K, ppm): 5.02–4.99 (m, 1H, CH), 4.65–4.58 (m, 2H,
CH2), 4.48–4.45 and 4.34–4.32 anisochronous protons (m, 2H,

P. Švec et al. / Tetrahedron Letters 49 (2008) 6320–6323
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General experimental details, data for known compounds, and
19F NMR spectra of some products are available. Supplementary
data associated with this article can be found, in the online version,
at doi:10.1016/j.tetlet.2008.08.060.
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