New and Efficient Syntheses of α-Iodo-α,α-Difluoro- and β-Iodo-α,α,β,β-Tetrafluorocarboxylic Acid Derivatives as Useful Building Blocks for Making Functional Fluoro Compounds

Article abstract of DOI:10.1021/jo035170j

Perfluoroolefins reacted with I-Cl and ClSO₃H under mild conditions to give R_FCFICF₂OSO₂Cl, which could be readily converted into various α-iodo-perfluorocarboxylic acid derivatives or telomerized with tetrafluo

Full text of DOI:10.1021/jo035170j

difluoroacetate6 and the Lewis-acid-catalyzed reaction of
difluoroketene silyl acetates7 with carbonyl substrates
have been applied to synthesize compounds bearing the
carboalkoxydifluoromethyl group. The coupling reaction
of selected organic iodides with (carbomethoxydifluoro)-
methylcopper, prepared from methyl iododifluoroacetate
and copper, produces R,R-difluoroesters.8 The atom trans-
fer reactions of methyl iododifluoroacetate with alkenes
to make R,R-difluoroesters have been reported by Kisel-
eva,9 Burton,10 Taguchi, and others.11 However, iododi-
fluoroacetate and its derivatives are difficult and expen-
sive to make. R,R,â,â-Tetrafluoro functional compounds
have been found to be almost inaccessible previously, and
their chemistry and properties are virtually unknown.
In this note, we report facile and cost-effective prepara-
tions of various types of R-iodo-R,R-difluoro- and R,R,â,â-
tetrafluorocarboxylic acid derivatives that are expected
to be useful building blocks for making selectively
fluorinated compounds.
R-Iodo-R,R-difluoroacetates were previously made from
costly bromodifluoroacetates through iodination of di-
fluoro Reformatsky agents10 or from hydrolysis of highly
toxic ICF2CF2I with oleum.12 We used tetrafluoroethylene
(TFE) as a starting material and directly reacted it with
ClSO3H and I-Cl under mild conditions to give ICF2CF2-
OSO2Cl in high yields. Although a similar reaction was
reported previously, it required use of the expensive
FSO3H and only moderate yields were obtained.13 This
reaction could be extended to other fluoroolefins such as
hexafluoropropylene (HFP), and the corresponding sul-
fate 2 was formed in high yield.
New a n d Efficien t Syn th eses of
r-Iod o-r,r-Diflu or o- a n d
â-Iod o-r,r,â,â-Tetr a flu or oca r boxylic Acid
Der iva tives a s Usefu l Bu ild in g Block s for
Ma k in g F u n ction a l F lu or o Com p ou n d s†
Ming-H. Hung,*,‡ Lu Long,§ and Zhen-Yu Yang*,|
DuPont Dow Elastomers, L.L.C., and DuPont Central
Research and Development, Experimental Station,
Wilmington, Delaware 19880
zhenyu.yang-1@usa.dupont.com
Received August 8, 2003
Abstr a ct: Perfluoroolefins reacted with I-Cl and ClSO3H
under mild conditions to give RFCFICF2OSO2Cl, which could
be readily converted into various R-iodo-perfluorocarboxylic
acid derivatives or telomerized with tetrafluoroethylene to
I(CF2CF2)nOSO2Cl. Ring-opening reaction of perfluoroalkoxy-
pentafluorocyclopropane with iodine at 240 °C produced
ICF2CF2COF, which was quenched by alcohol, water, or NH3
to give â-iodo-R,R,â,â-tetrafluorocarboxylic acid derivatives.
These functional fluorinated iodides can be used as building
blocks for making selectively fluorinated compounds.
Partially fluorinated functional compounds have gained
attention since it was found that the introduction of
fluorine into organic molecules can lead to significant
changes in biological activities.1 Fluorinated alkyl iodides
are one of the most important starting materials for the
introduction of F-alkyl groups into organic molecules.2
The introduction of the difluoromethylene functionality
into organic compounds has been a very active field.3
Difluoromethylene-containing molecules have been found
to inhibit various enzymes, and some can be partially
metabolized into more active substances.4 It has been
argued that the difluoromethylene group is regarded as
an isopolar-isosteric replacement for oxygen.5 R-Halo-
R,R-difluoroacetates have been most widely used as a
synthon for making R,R-difluoromethylene-containing
compounds.3 The Reformatsky reaction of R-halo-R,R-
In these reactions, temperature control was found to
be critical to obtain high yields. The initial stage of the
(6) (a) Hallinan, E. A.; Fried, J . Tetrahedron Lett. 1984, 25, 2301.
(b) Gelb, M. H.; Svaren, J . P.; Abeles, R. H. Biochemistry 1986, 24,
1813. (c) Thaisrivongs, S.; Pals, D. T.; Kati, w. M.; Turner, S. R.;
Thomasco, L. M. J . Med. Chem. 1985, 28, 1553. (d) Thaisrivongs, S.;
Pale, D. T.; Kati, W. M.; Turner, S. R.; Thomasco, L. M.; Watt, W. J .
Med. Chem. 1986, 29, 2080. (e) Burton, D. J .; Eaadon, J . C. J . Fluorine
Chem. 1988, 38, 125. (f) Lang, R. W.; Schaub, B. Tetrahedron Lett.
1988, 29, 2943. (g) Takahashi, L. R.; Radhakrishnan, R.; Roeenfield,
R. E., J r.; Meyer, E. F., J r.; Trainor, D. A. J . Am. Chem. Soc. 1989,
111, 3368. (h) Braun, M.; Vonderhagen, A.; Waldmuller, D. Liebigs
Ann. 1995, 1447. (i) Vidal, A.; Nefzi, A.. Houghten, R. A. J . Org. Chem.
2001, 66, 8268. (j) Marcotte, S.; Pannecoucke, X.; Feasson, C.; Quirion,
J . J . Org. Chem. 1999, 64, 8461.
(7) (a) Kitagawa, O.; Taguchi, T.; Kobayashi, Y. Tetrahedron Lett.
1988, 29, 1803. (b) Taguchi, T.; Kitagawa, O.; Suda, Y.; Ohkawa, S.;
Hashimoto, A.; Iitaka, Y.; Kobayashi, Y. Tetrahedron Lett. 1988, 29,
5291. (c) Kitagawa, O.; Hashimoto, A.; Kobayashi, Y.; Taguchi, T.
Chem. Lett. 1990, 1307. (d) Weigel, J . A. J . Org. Chem. 1997, 62, 6108.
(8) Taguchi, T.; Kitagawa, 0.; Morikawa, T.; Nishiwaki, T.; Uehara,
H.; Endo, H.; Kobayashi, Y. Tetrahedron Lett. 1986, 27, 6103.
(9) Kieeleva, L. N.; Dostovalova, V. I.; Velichko, F. K.; Cherstkov,
V. F.; Sterlin, S. R.; Savicheva, G. I.; Kurykin, M. A.; Germen, L. C.
Zzu. Akad. Nauk. SSSR Ser. Khim. 1988, 2132.
† Publication no. 8440.
‡ DuPont-Dow Elastomers.
§ Current address: Shanghai Institute of Organic Chemistry,
Shanghai, China.
| DuPont Central Research and Development.
(1) (a) Biochemical Aspects of Fluorine Chemistry; Filler, R., Koba-
yashi, Y., Eds.; Elsevier Biomedical Press: Amsterdam, Kodansha,
LTD: New York, 1982. (b) Welch, J . T. Tetrahedron 1987, 43, 3123.
(c) Welch, J . T.; Ekwarakrishnan, S. Fluorine in Bioorganic Chemistry;
J ohn Wiley and Sons: New York, 1991.
(2) Organofluorine Chemistry, Principles and Commercial Applica-
tions; Banks, R. E., Smart, B. E., Tatlow, J . C., Eds.; Plenum Press:
New York, 1994.
(3) Tozer, M. J .; Herpin, T. F. Tetrahedron 1996, 52, 8619.
(4) (a) Ando, K.; Koike, F.; Kondo, F.; Takayama, H. Chem. Pharm.
Bull. 1995, 43, 189. (b) Hertel, L. W.; Kroin, J . S.; Misner, J . W.; Tustin,
J . M. J . Org. Chem. 1988, 53, 2406. (c) Chou, T. S.; Heath, P. C.;
Patterson, L. E.; Poteet, L. M.; Lakin, R. E.; Hunt, A. H. Synthesis
1992, 565.
(5) (a) Blackburn, G. M.; England, D. A.; Kolkmann, F. J . Chem.
Soc., Chem. Commun. 1981, 930. (b) Blackburn, G. M.; Kent, D. E.;
Kolkmann, F. J . Chem. Soc., Perkin Trans. 1 1984, 1119.
(10) (a) Yang, Z. Y.; Burton, D. J . J . Org. Chem. 1991, 56, 5125. (b)
Yang, Z. Y.; Burton, D. J . J . Org. Chem. 1992, 57, 5144. (c) Yang, Z.
Y.; Burton, D. J . J . Fluorine Chem. 1989, 45, 435.
10.1021/jo035170j CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/10/2003
198
J . Org. Chem. 2004, 69, 198-201

reaction is exothermic, and temperature must be con-
trolled by the addition rate of TFE (caution: TFE is
explosive and extremely hazardous; the reaction needs to
be done in a barricade). We found the optimal tempera-
ture to be around 0-10 °C, and the yields of product
isolated were between 70 and 95%. As a typical example,
into a 1 L pressure reactor was charged a mixture of
iodine monochloride (390 g, 2.4 mol) and chlorosulfonic
acid (490 g, 4.206 mol). The reactor was cooled and kept
at 0-10 °C while 300 g of tetrafluoroethylene (3.0 mol)
were added. After the addition of TFE was complete, the
reaction mixture was held at 0-10 °C for 6 h, at 25 °C
for 2 h, and at 50 °C for 2 h. The reaction mixture was
then slowly poured into a large amount of ice water with
stirring. The lower layer was separated, washed with
dilute aqueous NaHSO3 and water, and dried over
MgSO4. Distillation afforded 610 g (74% yield) of 1 as a
clear, colorless liquid.
Although the exact mechanism for this useful conver-
sion is still unclear, we propose that an iodinium of I-Cl
first electrophilically adds to the double bond of TFE to
form intermediate A, which is trapped by chlorosulfonic
acid. The regiochemistry of the addition also supports this
mechanism. When I-Cl and ClSO3H react with HFP,
only isomer 2 is obtained; the iodinium adds favorably
to the central carbon of HFP due to electronic effects.
Fluorine atoms are well-known to stabilize the carbon
cation, whereas CF3 groups destabilize the adjacent
carbocation.14
proponyl fluoride 8 in quantitative yield along with
formation of the perfluoroalkyl iodides.15b
The ring-opening reaction can be quenched without
purification of the corrosive ICF2CF2COF since the
byproduct RFI does not react with the quenching re-
agents. The reaction mixture was added to ethanol to
form the ester 10 in 76% yield from 8. KF is usually used
to trap the HF formed. Hydrolysis of 9 produced the acid
11 in high yields. When NH3 gas was bubbled into the
reaction mixture, the corresponding amide 12 was ob-
tained. The use of ether or other inert solvents is
recommended to control the rate of the highly exothermic
reaction. After the amide 12 was ground into a fine
powder and mixed with finely powdered P2O5, the solid
mixture was heated directly to 180-200 °C to give a clear
liquid ICF2CF2CN in 90% yield.16
1 and 2 are versatile compounds and can be readily
converted into other R-iodo-difluoro functional com-
pounds. 1 can be quenched with alcohols such as ethanol
in the presence of NaF to give R-iodo-R,R-difluoroacetate
3 in 90% yield. When reacted with aqueous ammonium
hydroxide in ether, the corresponding R-iododifluoro-
acetamide 4 was formed in high yield. Similarly, 2 could
be readily converted into the corresponding amide 6.
When the amides, 4 and 6, were treated with P2O5, the
corresponding R-iodofluoronitriles, 5 and 7, were ob-
tained, respectively.
Longer chain iodofluorocarboxylic acid derivatives
I(CF2)2nCO2R (n > 1) can be obtained by telomerization
of TFE and ICF2CF2OSO2X (X ) Cl, F), prepared by
reaction of TFE, I-Cl, and XSO3H (X ) Cl, F). The
telomerizations are usually carried out in sealed stainless
steel tubes. When a 1-1.25 molar ratio of ICF2CF2OSO2F
and TFE was heated at 250 °C for 4 h, oligomers I(CF2-
CF2)nOSO2F were formed in 60% yields and 38% of ICF2-
CF2OSO2F was recovered. The major oligomers were
I(CF2CF2)2OSO2F and I(CF2CF2)3OSO2F along with higher
homologues. These oligomers can be readily converted
into longer chain I(CF2)2nCO2R (n > 1) by treatment of
I(CF2CF2)nOSO2F with alcohols and NaF or KF.
In summary, we have developed new and cost-effective
methods for the preparation of various iodofluorocar-
(11) (a) Kitagawa, O.; Miura, A.; Kobayashi, Y.; Taguchi, T. Chem.
Lett. 1990, 1011. (b) Barth, F.; O-Yang, C. Tetrahedron Lett. 1990,
31, 1121. (c) Sato, K.; Nakazato, S.; Enko, H.; Tsujita, H.; Fujita, K.;
Yamamoto, T.; Omote, M.; Ando, A.; Kumadaki, I. J . Fluorine Chem.
2003, 121, 105.
(12) Hauptschein, M, Braid, M. J . Am. Chem. Soc. 1961, 83, 2500.
(13) (a) Fokin, A. V. Izv. Akad. Nauk. SSSR. Ser. Khim. 1985, 2298.
(b). Fokin, A. V.; et al. Izv. Akad. Nauk. SSSR. Ser. Khim. 1984, 1572.
(14) (a) Tian, F.; Battiste, M. A.; Dolbier, W. R., J r. Org. Lett. 1999,
1, 193. (b) Battiste, M. A.; Tian, F.; Baker, J . M.; Bautista, O.;
Villalobos, J .; Dolbier, W. R. J r. J . Fluorine Chem. 2003, 119, 39.
(15) (a) Yang, Z. Y.; Krusic, P. J .; Smart, B. E. J . Am. Chem. Soc.
1995, 117, 5397. (b) Yang, Z. Y. J . Org. Chem. 2003, 68, 4410.
(16) Krespan, C. G. J . Org Chem. 1986, 51, 326.
â-Iodo-R,R,â,â-tetrafluorocarboxylic acid derivatives
were obtained by ring-opening reaction of fluorinated
cyclopropanes with iodine.15 When perfluoroalkoxylcy-
clopropane was treated with iodine neat at 240 °C, the
ring-opening product B decomposed to iodotetrafluoro-
J . Org. Chem, Vol. 69, No. 1, 2004 199

distilled off. Redistillation gave pure ICF2CN (115 g, 81% yield),
bp 52-54 °C. 19F NMR (CDCl3): δ -46.5. MS: calcd for [M+],
202.9116; found, 202.9116.
boxylic acid derivatives, which are versatile reagents and
can participate in numerous reactions. These compounds
are useful building blocks for making other interesting
compounds such as bioactive molecules or specialty
materials. For example, we have demonstrated that
I(CF2)nCN may be used to make iododifluorinated tria-
zines 14 by catalysis with NH3 gas at 40-130 °C. The
triazine 14, containing an extremely thermally stable
triazine core and multiple reactive sites (C-I bond), is
useful in building networks for highly thermally stable
specialty materials. Other applications of the iodofluo-
rocarboxylic acid derivatives will be reported in the
future.
P r ep a r a tion of 2-Iod o-h exa flu or op r op yl F lu or osu lfa te
(2). Into a 1.3 L stainless steel tube was charged a mixture of
iodine monochloride (130 g, 0.80 mol) and fluorosulfonic acid (88
g, 0.88 mol). The tube was sealed and cooled, and then hexafluo-
ropropylene (144 g, 0.96 mol) was transferred into the tube. The
reaction mixture was kept at 25 °C for 2 h, 50 °C for 2 h, and 80
°C for 4 h. The product unloaded from the shaker tube was
poured into ice-water, and the bottom organic layer separated
was washed with water and distilled to afford the title product
(120 g, 40% yield) as a clear liquid, bp 47 °C/50 mm. 19F NMR
(CDCl3): δ -74.5 (m, 3F), -77.0 (m, AB-pattern, 2F), -148.2 (m,
1F), +49.7 (m, 1F).
P r ep a r a tion of Eth yl 2-Iod o-tetr a flu or op r op ion a te. The
starting material (112.8 g, 0.30 mol) was added dropwise into a
mixture solution of potassium fluoride (17.5 g, 0.31 mol) and
absolute ethanol (110 mL). The pot temperature was controlled
at 20-25 °C with external cold water cooling during the addition
process. After the addition was completed, the reaction mixture
was heated at 70 °C for 4 h. The mixture was then dumped into
ice-water. The bottom organic layer was separated, and the top
layer was extracted with ether. The ether phase was combined
with the bottom layer material, washed with brine, and dried
over magnesium sulfate. The ether was removed in vacuo, and
the residue was distilled to afford the title product (50 g, 55.6%
yield) as a clear, light-pink-colored liquid, bp 50-54 °C at 25
Exp er im en ta l Section
1
Compound 8 was prepared according to the literature.15b
P r ep a r a tion of 2-iod o-1,1,2,2-tetr a flu or oeth yl ch lor o-
su lfa te (1). Into a 1 L pressure reactor was charged a mixture
of iodine monochloride (390 g, 2.4 mol) and chlorosulfonic acid
(490 g, 4.206 mol). The reactor was cooled and kept at 0-10 °C
until 300 g of tetrafluoroethylene (3.0 mol) was added. After the
addition of TFE was complete, the reaction mixture was held at
0-10 °C for 6 h, at 25 °C for 2 h, and at 50 °C for 2 h. The
reaction mixture was then slowly poured into a large amount of
ice with stirring and worked up as described above, affording
610 g of the desired product (74%), bp 62-64 °C/50 mmHg. 19F
NMR (CDCl3): δ -85.6 (t, J ) 4.5 Hz, 2F), -65.3 (t, J ) 4.5 Hz,
2F). Anal. Calcd for C2F4IClSO3: C: 7.02, F: 22.19. Found: C:
7.19, F: 22.73.
P r ep a r a tion of Eth yl Iod od iflu or oa ceta te (3). A 500 mL
flask was charged with sodium fluoride (18.9 g, 0.45 mol) and
ethanol (200 mL) and cooled in an ice-water bath. 2-Iodo-1,1,2,2-
tetrafluoro-ethyl chlorosulfate (103 g, 0.3 mol) was added slowly.
The reaction was exothermic, and the reaction temperature was
controlled at 20-30 °C. After addition, the reaction mixture was
stirred at room temperature for 10 h and then poured into cold
water. Ether was added to extract the product. The organic layer
was washed with saturated NaCl solution and dried over MgSO4.
Evaporation of the solvent in vacuo followed by distillation gave
68.1 g (91%) of ethyl iododifluoroacetate, bp 57-58 °C/30 mmHg.
1H NMR (CDCl3): δ 1.35 (t, J ) 7.0 Hz, 3H), 4.37 (q, J ) 7.0
Hz, 2H).19F NMR (CDCl3): δ -57.9 (s, 2F).
mmHg. H NMR (300 MHz, CDCl3): δ 4.40 (q, J ) 7.2 Hz, 2H),
1.36 (t, J ) 7.2 Hz, 3H). 19F NMR (188.235 MHz, CDCl3): δ -76.2
(d, J ) 12.4 Hz, 3F); -140.5 (q, J ) 12.8 Hz, 1F). IR (KBr): 1761
cm-1. Mass [M] for C5H5F4IO2: calcd, 299.9270; found, 299.9285.
Anal. Calcd for C5H5F4IO2: C, 20.02; H, 1.68; F, 25.33. Found:
C, 20.24; H, 1.75; F, 24.68.
P r ep a r a tion of 2-Iod o-tetr a flu or op r op ion a m id e (6). Into
a glass flask was placed a mixture of aqueous ammonium
hydroxide (28 wt %, 40.5 mL, 0.6 mol) and methylene chloride
(80 mL), and the mixture was cooled at 10-15 °C. 2-Iodo-
hexafluoropropyl fluorosulfate (37.6 g, 0.1 mol) was added slowly
with vigorous stirring, while the reaction temperature was
controlled at <15 °C. After the addition was completed, the
mixture was warmed to ambient temperature, and the bottom
organic layer was separated, washed with aqueous sodium
bisulfite solution, and dried over MgSO4. The solvent was
removed in vacuo to give the title product as a white solid (18.5
1
g, 68.3% yield), mp 75-77 °C. H NMR (CDCl3): δ 6.98, 6.53 (2
broad singlets). 19F NMR (CDCl3): δ -76.3 (2 singlets, 3F),
-138.5 (m, 1F). IR: 1690 cm-1 (CdO). Anal. Calcd for C3H2F4-
INO: C, 13.30; H, 0.74; F, 28.05; N, 5.17. Found: C, 13.68; H,
0.83; F, 28.43; N, 5.21. Mass: calcd for [M+], 270.9117; found,
270.9093.
P r epar ation of 2-Iodo-tetr aflu or opr opion itr ile (7). 2-Iodo-
tetrafluoropropionamide prepared from experiment 7 (16.3 g,
0.06 mol) was thoroughly mixed with P2O5 (16.3 g, 0.115 mol)
in a flask under a nitrogen atmosphere. The mixture was heated
slowly to 95-100 °C, the volatile product started to form and
was collected in a cold trap (dry ice-acetone bath). The title
product was obtained as a slightly pink liquid after purified by
distillation, yield 12.5 g (82.5%), bp 68-70 °C. 19F NMR (188.24
MHz, CDCl3): δ -78.7 (2 singlets, 3F), -137.9 (q, J ) 16 Hz,
1F). IR: 2288 cm-1. Mass: calcd for [M+], 252.9382; found,
252.9012.
P r ep a r a tion of I-(CF 2CF 2)n -OSO2F Oligom er . 2-Iodo-
1,1,2,2-tetrafluoroethyl fluorosulfate (65.2 g, 0.2 mol) was mixed
with TFE (25 g, 0.25 mol) in a sealed stainless tube. The mixture
was heated at 250 °C for 4 h. The product unloaded was
subjected to fractional distillation. About 25 g (38.3%) of the
starting was recovered. Other oligomer products (ca. 50 g)
obtained were I-(CF2CF2)2-OSO2F (bp 42 °C/25 mm), I-(CF2CF2)3-
OSO2F (bp 54 °C/5 mm), and higher boiling I-(CF2CF2)n-OSO2F
(n > 3). I-(CF 2CF 2)2-OSO2F . 19F NMR (188.24 MHz, CDCl3): δ
-60.3 (t, J ) 13.8 Hz, 2F), -83.7 (d, J ) 7.2 Hz, 2F), -113.7 (s,
2F), -124.1 (t, J ) 12.4 Hz, 2F), +50 9 (m, br, 1F). Mass: calcd
for [M+], 425.8471; found, 425.8381. I-(CF2CF2)3-OSO2F: 19F
P r epar ation of Iododiflu or oacetam ide (4). Into the stirred
solution of ammonium hydroxide (150 mL, 28-30% in aqueous)
and ether (150 mL) was added dropwise ICF2CF2OSO2Cl (102.8
g, 0.3 mol) with external cooling. The temperature was main-
tained at 10-20 °C during the addition. After that, the mixture
was warmed to room temperature and stirred for 30 min. The
ethereal layer was separated, and the aqueous layer was
extracted with ether. The combined organic layer was washed
with brine and dried over MgSO4. Evaporation of the solvent
followed by recrystallization from hexane/ether gave 61.5 g,
1
(92%) of ICF2CONH2 as a white solid, mp. 96-98 °C. H NMR
(300 MHz, acetone-d6): δ 7.35 (br, 1H), 7.81 (br, 1H). 19F NMR
(acetone-d6): δ -57.5.
P r ep a r a tion of Iod od iflu or oa ceton itr ile (5). Iododifluo-
roacetamide (155 g, 0.7 mol) was well mixed with P2O5 (100 g,
0.704 mol) and heated at 150 °C in vacuo (about 150 mmHg).
The volatile was collected in a cold trap (dry ice-acetone bath).
The heating oil bath temperature was increased slowly to 200
°C, and the reaction was stopped until no more product was
200 J . Org. Chem., Vol. 69, No. 1, 2004

NMR (188.24 MHz, CDCl3): δ -59.7 (m, 2F), -83.5 (m, 2F),
-113.5 (m, 2F), -121.4 (m, 2F), -122.3 (m, 2F), -125.0 (m, 2F),
+50 6 (t, J ) 8.2 Hz, 1F). Mass: calcd for [M+], 525.8407; found,
525.8345.
137 °C. 19F NMR: δ -62.3 (t, J ) 5 Hz, 2F), -112.1 (t, J ) 5
Hz, 2F). 1H NMR (acetone-d6): δ 7.99 (br, 1H), 7.69 (br, 1H). IR
(neat): 3375, 3267 (m), 3193 (m), 1708 (s), 1416 (s), 1180 (s),
1080 (s), 647 (s). Anal. Calcd for C3H2F4NOI: C, 13.30; H, 0.74;
F, 28.05; N, 5.17; I, 46.84. Found: C, 13.35; H, 0.78; F, 27.10;
N, 4.81; I, 46.87.
P r ep a r a tion of Iod otetr a flu or op r op a n on itr ile (13). A
mixture of 150 g of fine powder of ICF2CF2CONH2 and 235 g of
P2O5 was heated at 130 to 150 °C, during which volatiles were
distilled out. Final volatiles were collected in a -78 °C trap at
200 mmHg. A total 125.3 g of crude product was obtained, 95%
GC pure. Redistillation gave pure product, bp 60-61 °C. 19F
NMR: δ -63.3 (t, J ) 10.4 Hz, 2F), -100.5 (t, J ) 10.4 Hz, 2F).
IR (neat): 2264 (w), 1235 (s), 1196 (s), 1172 (s), 1146 (s), 1089
(s), 1065 (s), 893 (s). (See ref 16.)
P r epar ation of Eth yl 2-Iododtetr aflu or opr opan oate (10).
A 300 mL shaker tube was charged with 50.8 g of iodine and 50
g of trifluoromethoxylpentafluorocyclopropane and heated at 150
°C for 4 h and 240 °C for 8 h. After the tube was cooled to room
temperature, 57.6 g of crude products was obtained, which was
treated with 75 mL of EtOH and 11.g of KF at 10 °C for 4 h.
The reaction mixture was poured into water. The lower layer
was separated, washed with Na2SO3 solution, and dried over
molecular sieves to give 51.2 g of crude ester. Distillation gave
45.3 g of pure product, bp 72-73 °C/30 mmHg. 1H NMR: δ 4.43
(q, J ) 7.0 Hz, 2H), 1.39 (t, J ) 7.2 Hz, 3H). 19F NMR: δ -60.6
(t, J ) 7.0 Hz, 2F), -111.9 (t, J ) 7.0 Hz, 2F). IR (neat): 2995
(w), 1778 (s), 1374 (m), 1709 (s), 1185 (s), 1141 (s), 1076 (s). Anal.
Calcd for C5H5F4IO2: C, 20.02; H, 1.68; F, 25.33; I, 42.30.
Found: C, 19.83; H, 1.52; F, 27.74; I, 43.46.
P r ep a r a tion of 2,4,6-Iod od iflu or om eth yl-1,3,5-tr ia zin e
(14a ). A mixture of ICF2CN (8.1 g, 40 mmol) and ammonia (ca.
0.1 g) was stirred in a sealed tube at 40 °C for 40 h and then
purified on a silica gel column using hexane and ethyl acetate
as an eluant to give the triazine (2.7 g, 33% yield), bp 100 °C/
P r ep a r a tion of ICF 2CF 2CO2H (11). To a stirred solution
of 11.6 g of KF and 40 mL of H2O was added 67.3 g of ICF2CF2-
COF at 5 °C. After the addition was complete, the mixture was
stirred for 2 h, then neutralized with HCl, and extracted with
ether. The ether layer was dried over MgSO4. After removal of
the ether, residue was distilled to give 52.0 g (84%) of ICF2CF2-
0.5 mmHg. 19F NMR (acetone-d6): δ -57.9. IR (KBr): 1540 cm-1
.
Mass: calcd for [M+], 608.7131; found, 608.7123.
P r ep a r a tion of 2,4,6-Iod otetr a flu or oeth yl-1,3,5-tr ia zin e
(14b). A mixture of ICF2CF2CN (13.3 g, 52.6 mmol) and
ammonia (0.15 g) was stirred in a sealed tube at 130 °C for 12
h and then purified on silica gel column using hexane and ethyl
acetate (9:1) as an eluant to give the triazine (6.8 g, 51% yield).
19F NMR (acetone-d6): δ -62.8 (t, J ) 6 Hz, 6F), -109.3 (t, J )
6 Hz, 6F). IR (KBr): 1540 cm-1. Anal. Calcd for C9F12N3I3: C,
14.25; F, 30.04; N, 5.54. Found: C, 14.33; F, 29.94; N, 5.33.
1
CO2H as an ether complex, bp 80-81 °C/15 mmHg. HNMR: δ
10.85 (s). 19F NMR: δ -61.0 (t, J ) 7.7 Hz, 2F), -112.1 (t, J )
7.7 Hz, 2F). IR: 3200 (br), 1769 (s), 1187 (s), 1151 (s), 1077 (s).
P r ep a r a tion of 2-Iod otetr a flu or op r op a n oa m id e (12). A
1 L autoclave was charged with 353 g of iodine and 285 g of
trifluoromethoxylpentafluorocyclopropane and heated at 150 °C
for 3 h and 240 °C for 12 h. After the autoclave was cooled to
room temperature, the reaction mixture was diluted with 1 L of
ether and cooled to -78 °C. NH3 gas was added until the solution
was basic. The reaction mixture was warmed to room temper-
ature over 1.5 h. The mixture was poured into 1 L of ether,
washed with water, and dried over MgSO4. After removal of the
ether, 203.5 g of product was obtained. An analytic sample was
obtained by recrystallization from hexane and ether, mp 136-
Ack n ow led gm en t. The authors thank the late
Professor Chang-Ming Hu at Shanghai Institute of
Organic Chemistry for helpful discussion, Mr. R. E.
Smith J r. for technical assistance, and DuPont Pressure
Research Lab for conducting high-pressure reactions.
J O035170J
J . Org. Chem, Vol. 69, No. 1, 2004 201