Microscale Preparation of Isotopically Enriched 37ClHC=CHF

Article abstract of DOI:10.1081/SCC-120030310

Chlorination of 1-bromo-2-fluoroethylene followed by reductive dehalogenation of the produced 1-bromo-1,2-dichloro-2-fluoroethane selectively affords 1-chloro-2-fluoroethylene. This process is suitable to produce ³⁷Cl isotopically enriched ClHC=CHF on a convenient scale (3.8 mmol).

Full text of DOI:10.1081/SCC-120030310

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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 7, pp. 1229–1235, 2004
Microscale Preparation of Isotopically
Enriched 37ClHC55CHF
*
Alessandro Baldan
`
Dipartimento di Chimica Fisica, Universita Ca’ Foscari di Venezia,
Venice, Italy
ABSTRACT
Chlorination of 1-bromo-2-fluoroethylene followed by reductive
dehalogenation of the produced 1-bromo-1,2-dichloro-2-fluoroethane
selectively affords 1-chloro-2-fluoroethylene. This process is suitable to
produce 37Cl isotopically enriched ClHC55CHF on a convenient scale
(3.8 mmol).
Key Words: Fluoroalkenes; Isotopic labeling; ClHC55CHF; Reductive
dehalogenation.
*
`
Correspondence: Alessandro Baldan, Dipartimento di Chimica Fisica, Universita Ca’
Foscari di Venezia, DD 2137, I-30123 Venice, Italy; Fax: þ39-041-2348594; E-mail:
abaldan@unive.it.
1229
DOI: 10.1081/SCC-120030310
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

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Baldan
INTRODUCTION
Natural chlorine exists as a mixture of the two stable isotopes 35Cl
and 37Cl, in abundance of 75.4% and 24.6%, respectively. These isotopes
are incorporated into molecules and equilibria among isotopically sub-
stituted molecules (isotopomers) reflect the background isotopic 35Cl/37Cl
ratio.
Recent literature contains some spectroscopic studies of gas-phase
high-resolution infrared spectra of the natural cis-1-chloro-2-fluoroethylene,
which are limited to the more abundant cis-35ClHC55CHF isotopomer
owing to the scarcity of the cis-37ClHC55CHF in an ordinary specimen.[1–3]
Therefore, isotopically enriched cis-37ClHC55CHF has been regarded as
necessary in order to obtain reliable spectroscopic parameters by measure-
ments.[1–3]
Previously, many methods have been used to synthesise ClHC55CHF,[1–8]
which are not suitable for the preparation of 37-chlorine isotopically enriched
samples. At variance, this method, involving the 37Cl-chlorination of 1-bromo-
2-fluoroethylene to 1-bromo-1,2-(dichloro-37Cl)-2-fluoroethane, followed by
reductive 1,2-elimination of Br37Cl, does afford a Z-E diastereoisomeric
mixture of 1-(chloro-37Cl)-2-fluoroethylene. Since the key intermediate reagent
BrHC55CHF is not commercially available, it was prepared with a slight
modification of the reported method (Sch. 1).[9,10]
Since hitherto, to the best of my knowledge, isotopically enriched
37ClHC55CHF preparation has not been reported, this work describes a simple
method able to afford this species on a convenient scale (3.8 mmol).
Scheme 1.

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Isotopically Enriched 37ClHC55CHF
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RESULTS
Fluorination of 1,1,2,2-tetrabromoethane (1) by SbF3–Br2 mixture
(“Swarts reagent”) gave a mixture of 1,1,2-tribromo-2-fluoroethane (2),
1,1-dibromo-2,2-difluoroethane (3) and unreacted 1,[9,10] which was some-
what difficult to separate into its components. During fluorination in a closed
reactor, the presence of the most volatile product 3 was periodically checked
by gas-phase IR spectroscopy.[11] After separation, the more abundant and
pure fluorinated ethane 3 was reacted with zinc in absolute ethanol to afford
a cis–trans mixture of BrHC55CHF (4). Traces of vinyl fluoride and acetylene
were identified by IR spectroscopy[12,13] in the raw 4 into the reaction vessel.
Vinyl fluoride formation may be attributed to the presence of BrCH2CHBrF in
the sample of 3 owing to the fluorination of traces of BrCH2CHBr2 likely con-
tained in the starting Br2CHCHBr2.
Since it has been reported that the trans-BrHC55CHF is quite sensitive
to polymerization even at room temperature,[14] 4 was stored under vacuum
at 2208C in the dark and checked by IR spectroscopy just before the
chlorination.[9,15]
At first, in order to perform exploratory syntheses with the most stable cis-
isomer and natural chlorine, the two isomers of 4 were separated. Later on, as
a cis-trans isomerization occurred during the first step of cis-BrHC55CHF
chlorination, the isomeric mixture 4 was used as reactant in the present
preparation and Br37ClCHCH37ClF (5) was obtained without olefin
polymerization.
As far as the cis-trans isomerization of cis-BrHC55CHF is concerned, its
nature is similar to iodine-catalyzed gas-phase isomerization reported for
other cis-1-2-dihaloethylenes.[16,17]
When, in a separated experiment, chlorination reaction of 4 was per-
formed in the presence of air and light, the olefin oxidation was observed.
This oxidation reaction should be similar to the chlorine-initiated photochemi-
cal oxidation previously reported for other halogenated ethylenes.[18,19] There-
fore, in order to obtain Br37ClCHCH37ClF (5), 37-Chlorine addition to
BrCH55CHF (4) was performed under vacuum and at minimized light level
conditions.
The sample of (5) obtained by chlorination of 4 is a threo and erythro
isomeric mixture of Br37ClCHCH37ClF. These diastereoisomers were charac-
terized by NMR spectroscopy.[20,21] Gas-phase infrared data for 5, not pub-
lished in the literature, are reported in Experimental section. Furthermore, it
was observed that 1,2-elimination reaction of 5 with zinc in absolute ethanol
is totally selective and affords, as the only product, the requested compound
37ClHC55CHF (6). It is known that the equilibrium composition of the
ClHC55CHF isomeric mixture is 70% cis- and 30% trans-isomer.[9]

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Baldan
In order to check 37Cl enrichment in 6, the 35/37Cl splitting was estimated
from the Q-branches (central part) of the n8 and n7 gas-phase IR bands for the cis-
isomer, where the isotope effect can be observed even with medium resolution
IR spectroscopy.[5] In the IR spectrum of the natural cis-ClHC55CHF n8 and n7
show two Q-branches and for every band the most intense peak is located at a
greater wavenumber. Q-branches of n8 and n7 for cis-35ClHC55CHF are located
at 655.7 and 811.6 cm21, while for cis-37ClHC55CHF they are at 651.8 and
808.7 cm21, respectively. In the IR of 6 both n8 and n7 for the cis-isomer exhibit
only one intense Q-branch at 651.8 and 808.7 cm21, respectively, which is
consistent with an 95% abundance of 37Cl incorporated into 6. In summary,
this convenient method for 37ClHC55CHF preparation should be useful in the
spectroscopic field.
EXPERIMENTAL
The expensive isotopically enriched Na37Cl salt (95% stated isotopic
enrichment) was obtained from Stable Isotopes Icon (Summit, NJ, USA). Br2-
CHCHBr2 (98%), SbF3 (99.8%), Br2 (99%) and zinc dust (98%) were obtained
by Sigma–Aldrich and used without further purification. Pure cis- and trans-
isomers of the natural ClHC55CHF were prepared, separated and purified as
reported previously.[7] All of the products prepared in the present research
are known compounds and were characterized by comparison of their
spectral data (NMR, IR) and Boiling Points with those reported in the
literature.[4,5,9–12,14,15,20–22] Gaseous compounds were handled in a mercury-
free vacuum line of known volume fitted with a manometer. Krytox (perfluoro-
polyether) LVP high-vacuum grease (E.I. Du Pont de Nemours) was used on
stopcocks and joints coming to contact with chlorine. Proton NMR spectra
were recorded on a Bruker AC 200 instrument. Survey midrange IR spectra
were taken as vapors in a 16-cm gas cell, equipped with KBr windows, on a
Bruker Vector 22 FT-IR spectrometer operating at 0.5 cm21 resolution.
Preparation of Z- and E-1-bromo-2-fluoroethylene (4). (1) 116 g
(0.336 mol) was treated with a mixture of SbF3 20 g (0.112 mol) and Br2
17.9 g (0.112 mol) in a closed steel reactor at 120–1258C for 23 hr. Into a
separating funnel, the raw product was washed successively with 20% HCl,
.
20% L-tartaric acid, 30% Na2S2O3 5H2O and water, to remove the SbBr3
and Br2. The reaction mixture is more dense than water and so it lies below
the aqueous layer. The separated organic phase was dried over anhydrous
MgSO4 and filtered. After fractionation, both 2 (10.6 g, 0.037 mol, 11%)
b.p.17: 74–848C [lit.[9] b.p.24: 74–788C] and 3 (14.4 g, 0.064 mol, 19%)
b.p.: 1078C [lit.[9,10] 1078C, 106.88C] were obtained. Compound 3 (14.4 g,
0.064 mol) was treated with zinc dust in absolute ethanol at room temperature.