Efficient microscale preparation of isotopically enriched 1-[ 79Br]bromo-2-fluoroethylene, [79Br]BrHC=CHF

Article abstract of DOI:10.1081/SCC-200057980

An efficient preparation of 1-[⁷⁹Br]bromo-2-fliioroethylene, [⁷⁹Br]BrHC= CHF, was carried out by a three-step procedure: (a) natural 1-bromo-2-fluoroethylene, BrHC=CHF, was iodinated to 1-fluoro-2-iodoethylene, FHC=CHI; (b) 1-fluoro-2-iodoethylene was ⁷⁹Br₂-brominated to 1,2-di[⁷⁹Br]bromo-1-fluoro- 2-iodoethane, [⁷⁹Br]BrFCHCH[⁷⁹Br]BrI; and (c) 1,2-di[ ⁷⁹Br]bromo-1-fluoro-2-iodoethane was dehalogenated to 1-[ ⁷⁹Br]bromo-2-fluoroethylene, [⁷⁹Br]BrHC=CHF. The yield of isolated product, on a 2-mmol scale, was 62% with respect to ⁷⁹Br₂. Copyright Taylor & Francis, Inc.

Full text of DOI:10.1081/SCC-200057980

Synthetic Communicationsw, 35: 1447–1453, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200057980
Efficient Microscale Preparation of
Isotopically Enriched 1-[79Br]Bromo-2-
Fluoroethylene, [79Br]BrHC55CHF
Alessandro Baldan
`
Dipartimento di Chimica Fisica, Universita Ca’ Foscari di Venezia,
Venezia, Italy
Augusto Tassan
Dipartimento di Processi Chimici dell’Ingegneria, Universita degli Studi
di Padova, Padova, Italy
`
Abstract: An efficient preparation of 1-[79Br]bromo-2-fluoroethylene, [79Br]BrHC55
CHF, was carried out by a three-step procedure: (a) natural 1-bromo-2-fluoroethylene,
BrHC55CHF, was iodinated to 1-fluoro-2-iodoethylene, FHC55CHI; (b) 1-fluoro-2-
iodoethylene was 79Br2-brominated to 1,2-di[79Br]bromo-1-fluoro-2-iodoethane,
[79Br]BrFCHCH[79Br]BrI; and (c) 1,2-di[79Br]bromo-1-fluoro-2-iodoethane was deha-
logenated to 1-[79Br]bromo-2-fluoroethylene, [79Br]BrHC55CHF. The yield of isolated
product, on a 2-mmol scale, was 62% with respect to 79Br2.
Keywords: 1-[79Br]Bromo-2-fluoroethylene, 1-bromo-2-fluoroethene, fluoroalkenes,
infrared spectroscopy, isotopic labeling, reductive dehalogenation
INTRODUCTION
Because the bromine atom has two different isotopes, 79Br (abundance
50.69%) and 81Br (49.31%),[1] two different isotopic forms of BrHC55CHF
exist: [79Br]BrHC55CHF and [81Br]BrHC55CHF. Recent literature contains
the first microwave and infrared studies on BrHC55CHF.[2,3] Because the
Received in Poland January 10, 2005
Address correspondence to Alessandro Baldan, Dipartimento di Chimica Fisica,
`
Universita Ca’ Foscari di Venezia, DD 2137, I-30123, Venezia, Italy. Fax: þ 39 041
2348594; E-mail: abaldan@unive.it
1447

1448
A. Baldan and A. Tassan
studies of high-resolution IR spectra of cis- and trans-BrHC55CHF are
complicated, because of overlap of [79Br] and [81Br] isotopic species,[3] prep-
aration of Br-labeled product is desired. The primary objective of the present
research is the production of inexpensive samples of [79Br]BrHC55CHF
suitable for infrared high-resolution measurements. The available methods
to obtain the unlabeled product[4–9] are not suitable for our scope;
therefore, we have prepared bromine-79 isotopically enriched [79Br]
BrHC55CHF by a new method. Introduction of this method is useful in the
molecular spectroscopy field because preparation of [79Br]BrHC55CHF has
not been reported in the literature.
RESULTS AND DISCUSSION
Isotopically enriched [79Br]BrHC55CHF was synthesised by the following
three-step process: (a) natural 1-bromo-2-fluoroethylene (1) was iodinated to
1-fluoro-2-iodoethylene (2), (b) 79Br2-bromination of 2 to 1,2-di[79Br]bromo-
1-fluoro-2-iodoethane ([79Br]3), (c) followed by reductive 1,2-elimination of
79BrI afforded 1-[79Br]bromo-2-fluoroethylene ([79Br]4) (Scheme 1).
Scheme 1.

1-[79Br]Bromo-2-Fluoroethylene
1449
The key intermediate reagent, FHC55CHI (2), is not commercially
available.
The cis:trans ratio observed on BrHC55CHF (1) is 80:20. The calculated
approximate composition of 1 is cis-[79Br] 40.55%, cis-[81Br] 39.45%,
trans-[79Br] 10.14%, and trans-[81Br] 9.86%. Iodination of 1 was performed
by halogen-exchange reaction with NaI (the molar ratio NaI:1 was of 3.1)
and with a slight modification of the reported method.[10] The cis- and
trans-configuration of FHC55CHI (2) was assigned on the basis of the
3
3
magnitude of the JHF and JHH coupling constants. Pure compound 2
consisted of 81:19 cis/trans configurations. Because the compounds [79Br]3
and [79Br]4 are expensive, only the corresponding natural compounds 3 and
4, prepared with the same method, were characterized. Bromination of neat
2 with a slight excess of enriched molecular bromine-79 (79Br2) was
performed in partially liquid phase, at room temperature and under vacuum.
Product 3 consisted of two isomers having abundance ratio 73:27, whereas
in the product obtained brominating 90% pure cis-2 the isomeric ratio was
85:15. This result is interpreted in terms of an electrophilic bromination,
trans-stereospecific like most alkenes, where erythro- and threo-3 arise
predominantly from anti-addition of bromine to cis- and trans-2, respectively.
Consequently, the erythro- form was assigned to the most abundant diaster-
eoisomer of 3. The new compound 3 was characterized by MS and
(1H, 19F, 13C) NMR spectroscopy. In the zinc-promoted dehalogenation of
[79Br]3, the exclusive 1,2-elimination of 79BrI is consistent with the
tendency of the halogens to be eliminated by reductants in the order
I . Br . Cl ꢀ F.[12] The trans:cis ratio in crude BrHC55CHF (4) was
found to be 63:37. This product distribution is interpreted in terms of a
prevalent anti-stereochemistry of the dehalogenation reaction where trans-
and cis-4 arise predominantly from elimination of erythro- and threo-3,
respectively.[12,13] IR and NMR spectral data of trans- and cis-4 are in good
agreement with those reported in the literature.[3,10,11,14] Isotopic enrichment
level of [79Br]4 was checked by employing the splitting of bromine isotopes
observed in the gas-phase IR spectrum in the n8 band region (C–Br stretching)
of the cis-isomer where the Q branches (central parts) of the isotopic species
cis-[79Br] and cis- [81Br] are located at 568.2 cm21 and 567.0 cm21, respect-
ively.[3] By comparison of the spectral intensities of [79Br]4 and 4 in the
reported spectral region, the isotopic enrichment of [79Br]4 was found to be
close to 90%. Therefore, the approximate composition of [79Br] BrHC55CHF
([79Br]4) calculated from the data is the following: trans-[79Br] 57%,
cis-[79Br] 33%, trans-[81Br] 6%, and cis-[81Br] 4%.
EXPERIMENTAL
The starting material BrHC55CHF (1) was synthesized, separated, and
purified as previously reported.[15] The isotopically enriched NH749Br (90%

1450
A. Baldan and A. Tassan
stated enrichment) was obtained from Cambridge Isotope Laboratories, Inc.
(Andover, MA, USA). 79Br2 was prepared from NH749Br as previously
reported.[16] The products NaI (99.5%), I2 (99.8%), and Zn dust (98%) were
obtained from Aldrich, natural Br2 (99.5%) was obtained from Fluka, and
all were used as received. The volatile compounds were manipulated in a
vacuum line equipped as previously reported.[15] NMR spectra were
recorded at room temperature using a Bruker AC 200 (1H at 200.13, 13C at
1
50.32, and 19F at 188.31 MHz) spectrometer. The 13C NMR spectra are H
coupled. The chemical shifts (d) are referred to Me4Si (1H and 13C) and to
CFCl3 (19F). Chemical shifts are reported in ppm and the coupling constant
in Hz. CDCl3 was used as the NMR lock solvent. Survey midrange FTIR
spectra were taken as CS2 solution or vapor on a Bruker Vector 22 FTIR spec-
trometer, operating at 0.5 cm21 resolution using KBr windows. IR bands
that showed a resolved structure (r.s.) are indicated. All the products
prepared in the present research are known compounds (except 3) and have
been characterized by comparison of their spectral data (IR, NMR) and
boiling points with those reported in the literature.[3,10,11,14] GC analyses
were performed employing a Hewlett Packard 5890 gas chromatograph
with a 10-ft Supelco column (5% Fluorcol on 60/80 Carbopack) and/or a
Agilent 6890 with a 30-m HP5 column (5% phenyl–95% methylsilicone).
GC/MS (70 eV) analyses were run on a Agilent 5973 using HP5 column.
The isomeric ratios reported in the present work for the products 1, 2, 3,
and 4 were determined by both GC and 19F NMR spectroscopic analysis.
Preparation of cis- and trans-1-fluoro-2-iodoethylene (2): Iodination was
performed into a modified Carius tube (ca. 0.40 l vol.) that consisted of a
thick-walled Pyrex tube provided with a sealing screw tread for the introduc-
tion of the solid chemicals and a fused Rotaflow stopcock for both gas evacua-
tion and admission. Compound 1 (6.44 g, 51.6 mmol) was treated with a
mixture of finely ground NaI (25.76 g, 162.8 mmol) and I2 (0.96 g, 4.0 mmol)
in the temperature range from 2508C to 2788C. During iodination the
presence into the reactor of 1 and 2 was monitored by FTIR spec-
troscopy.[3,10,11] After 44 h the reactor was first brought to room temperature
and then connected to a system for vacuum-line manipulations. Synthesis
product was first scavenged using metallic mercury, later vacuum-transferred
in a coil of Pyrex tubing merged into a 21598C isopentane/liquid nitrogen
slush bath, and then carefully trap-to-trap fractionated under dynamic
vacuum in the temperature range from 21598C to 2898C. The following
side products, identified by IR analysis,[17–20] were separated: C2H6,
H2C55CHF, and CH3CHF2.
Product 2 (6.75 g, 39.2 mmol, 76%) bp: 63–678C [lit.[11] bp 64–658C].
Cis-2: [lit.[10] bp 74–758C]. FTIR (gas) ncentral: 3262.5 (vw), 3107.5 (m),
3082.0 (m, r.s.), 2661.1 (vw), 2231.3 (vw), 2058.9 (vw), 1722.2 (w), 1637.3
(s, r.s.), 1587.5 (m), 1313.1 (s), 1204.6 (s), 1180.2 (m), 1031.0 (s, r.s.)
(C-F), 862.9 (m), 754.8 (vw), 728.7 (vs, r.s.), 507.0 (m), 386.9 (s) cm21
.
3
2
1H NMR (CDCl3): dHA 6.9 (dd, JHH ¼ 3.7, JHF ¼ 83.6), dHB 5.5

1-[79Br]Bromo-2-Fluoroethylene
1451
3
(dd, JHF ¼ 38.8); 19F NMR (CDCl3): d –101.9; 13C NMR (CDCl3): dCA
1
1
2
154.9 (ddd, JCH ¼ 205.4, JCF ¼ 263.6, JCH ¼ 14.0), dCB 59.5 (ddd,
2
2
1JCH ¼ 192.3, JCF ¼ 16.6, JCH ¼ 22.9). Trans-2: [lit.[10] bp 59–608C].
FTIR (gas) ncentral: 3095.8 (m), 1626.8 (s), 1097.6 (s) (C–F), 900.4 (m, r.s.)
cm21. H NMR (CDCl3): dHA 6.7 (dd, JHH ¼ 11.6, JHF ¼ 83.7), dHB 5.8
1
3
2
(dd, JHF ¼ 15.8); 19F NMR (CDCl3): d –94.3; 13C NMR (CDCl3): dCA
3
1
1
2
154.1 (ddd, JCH ¼ 207.3, JCF ¼ 275.9, JCH ¼ 4.0), dCB 60.5 (ddd,
2
2
1JCH ¼ 188.3, JCF ¼ 22.2, JCH ¼ 11.8). A part of 2 was repeatedly trap-
to-trap fractioned under vacuum, from 2758C to 2688C, to give a micro-
sample cis-2 (isomeric purity 90%) employed for analytical purposes.
Preparation of erythro- and threo-1,2-di[79Br]bromo-1-fluoro-2-
iodoethane ([79Br]3): Bromination was accomplished in partially liquid
phase, with a minimized light level in the laboratory, into an evacuated
flask wrapped in aluminium foil. 2 (0.375 g, 2.18 mmol) and dry 79Br2
(0.347 g, 2.20 mmol) were vacuum-transferred into the flask using liquid
nitrogen. The mixture was brought to room temperature and after 2 h the
reaction was completed. [79Br]3: brown little volatile liquid. 3: brown little
volatile liquid; mp 239/ 2 418C. FTIR (CS2) nmax: 2998.9 (m), 2967.4
(w), 1327.4 (s), 1244.7 (m), 1206.0 (m), 1148.9 (m), 1108.6 (s), 1096.1 (s),
1085.4 (s), 1075.8 (vs), 1042.9 (m), 1014.2 (s), 941.4 (m), 935.1 (s), 752.3
(m), 738.5 (m-s), 726.8 (s), 717.1 (m), 685.0 (m), 668.4 (m), 658.4 (m),
624.6 (s), 574.0 (s), 471.0 (m) cm21. GC/MS: m/z 334 (Mþ þ 2, 17%),
332 (Mþ, 34), 330 (Mþ-1, 18), 253 (Mþ-Br, 16), 251 (Mþ-Br, 17), 208
(11), 207 (50), 206 (16), 205 (Mþ-I, 100), 172 (12), 127 (34), 126 (38), 124
(39), 45 (14), (the two isomers erythro and threo showed almost identical
1
3
GC/MS spectra). erythro-3; H NMR (CDCl3): dHA 6.3 (dd, JHH ¼ 3.6,
3
2JHF ¼ 49.5), dHB 5.7 (dd, JHF ¼ 16.5); 19F NMR (CDCl3): d –128.4; 13C
1
1
NMR (CDCl3): dCA 93.2 (dd, JCH ¼ 190.1, JCF ¼ 261.2), dCB 10.7 (ddd,
2
2
1JCH ¼ 175.7, JCF ¼ 25.6, JCH ¼ 4.1). threo-3; 1H NMR (CDCl3): dHA
6.7 (dd, JHH ¼ 3.5, JHF ¼ 83.7), dHB 5.8 (dd, JHF ¼ 16.2); 19F NMR
3
2
3
(CDCl3): d –120.7; 13C NMR (CDCl3): dCA 93.6 (dd, JCH ¼ 189.4,
1
1JCF ¼ 261.2), dCB 9.9 (ddd, JCH ¼ 175.5, JCF ¼ 24.7, JCH ¼ 5.3).
Preparation of trans- and cis-1-[79Br]bromo-2-fluoroethylene ([79Br]4):
The flask containing [79Br]3 was, in sequence, merged in liquid nitrogen,
opened to the atmosphere, loaded with the zinc powder (0.72 g, 11 mmol)/
cold ethanol mixture, closed, and finally connected to the vacuum line for
the evacuation. Reaction mixture was brought to room temperature and after
1 h the dehalogenation was completed. Finally, the reaction mixture was
repeatedly trap-to-trap distilled in the temperature range from 2988C to
2868C to obtain spectroscopically pure [79Br]4. The yield of isolated pure
product, based on 79Br2, was estimated to be 62%, assuming ideal behavior
1
2
2
for the gas. [79Br]4: colorless vapor. trans-[79Br]4; FTIR (gas) ncentral
3104.5 (m), 2216.7 (w), 1734.9 (w), 1645.2 (s), 1327.2 (w), 1299.7 (w),
1172.9 (w), 1114.0 (vs) (C–F), 892.3 (s, r.s.), 795.4 (s), 774.9 (w, r.s) cm21
cis-[79Br]4; FTIR (gas) ncentral: 3118.1 (m), 3091.8 (w), 1651.8 (s, r.s),
:
.

1452
A. Baldan and A. Tassan
1327.5 (s), 1222.0 (s), 1045.4 (vs, r.s) (C–F), 750.1 (w), 730.1 (s, r.s), 568.2
(m-s) (C–79Br), 567.0 (w) (C–81Br), 416.1 (m) cm21. 4: colorless vapor.
trans-4: FTIR (gas) ncentral: 3104.5 (m), 2216.7 (w), 1734.9 (w), 1645.2 (s),
1327.2 (w), 1299.7 (w), 1172.9 (w), 1114.0 (vs) (C–F), 892.3 (s, r.s), 795.4
(s), 774.9 (w, r.s.) cm21
3
.
1H NMR (CDCl3): dHA 6.8 (dd, JHH ¼ 10.9,
2JHF ¼ 80.8), dHB 6.0 (dd, JHF ¼ 11.5); 19F NMR (CDCl3): d –117.4; 13C
3
1
1
NMR (CDCl3): dCA 152.0 (dd, JCH ¼ 206.1, JCF ¼ 268.7), dCB 93.7 (ddd,
1JCH ¼ 193.5, JCF ¼ 32.5, JCH ¼ 10.1). cis-4: FTIR (gas) ncentral: 3118.1
(m), 3091.8 (w), 1651.8 (s, r.s.), 1327.5 (s), 1222.0 (s), 1045.4 (vs, r.s) (C–
F), 750.1 (w), 730.1 (s, r.s.), 568.2 (m) (C–79Br), 567.0 (m) (C–81Br), 416.1
2
2
(m) cm21. H NMR (CDCl3): dHA 7.0 (dd, JHH ¼ 3.5, JHF ¼ 79.8), dHB
1
3
2
5.5 (dd, 3JHF ¼ 31.6); 19F NMR (CDCl3): d –119.3; 13C NMR (CDCl3): dCA
1
1
2
150.9 (ddd, JCH ¼ 205.4, JCF ¼ 264.2, JCH ¼ 16.2), dCB 90.0 (ddd,
1JCH ¼ 197.5, 2JCF ¼ 12.8, 2JCH ¼ 24.7).
ACKNOWLEDGMENTS
The authors thank Lucio Ronchin and Francesco Pinna (Dipartimento di
`
Chimica, Universita Ca’ Foscari di Venezia) for their help with GC and
`
Maurizio Selva (Dipartimento di Scienze Ambientali, Universita Ca’
Foscari di Venezia) for his help with GC/MS spectra. Daniela Baldan is
also acknowledged for her valuable aid in the article preparation.
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