Electrochemical fluorination of several 1,4-bis[(methoxycarbonyl)alkyl] substituted piperazines

Article abstract of DOI:10.1016/S0022-1139(01)00357-8

Four piperazines, having bis[(methoxycarbonyl)alkyl] groups (-CH₂CH₂C(O)OMe (1), -CH(CH₃)C(O)OMe (2), -CH₂CH(CH₃)C(O)OMe (3) and -CH(CH₃)CH₂C(O)OMe (4) at the 1- and 4-positions of the piperazine ring), were subjected to electrochemical fluorination (ECF). Two bis[(methoxycarbonyl)alkyl] derivatives of N,N′-dimethylethylenediamine (molecular formulae: MeO(O)CH₂CH₂N(CH₃)CH₂CH₂N (CH₃)CH₂CH₂C(O)OMe (5) and MeO(O)CH(CH₃)CH₂N(CH₃)CH₂CH₂N(CH₃)CH₂CH(CH₃)C(O)OMe] (6)) were also similarly fluorinated for a comparative study. On ECF of piperazine derivatives (1-4), the corresponding perfluoropiperazines having bis[(fluorocarbonyl)perfluoroalkyl] groups were formed, while the ECF of the substrates 5 and 6 afforded degraded products only. Yields of the targeted di-basic perfluoroacid fluorides containing a perfluoropiperazinyl group varied, depending on the type of bis[(methoxycarbonyl)alkyl] groups at the 1- and 4-positions. The best yield of the di-basic perfluoroacid fluorides was obtained from the ECF of 1,4-bis[2-(methoxycarbonyl)propyl]piperazine (3). Spectroscopic data as well as physicochemical properties are described for new perfluoroacid fluorides and perfluoro(1,4-dialkylpiperazines).

Full text of DOI:10.1016/S0022-1139(01)00357-8

Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
Electrochemical ¯uorination of several 1,4-bis[ꢀmethoxycarbonyl)alkyl]
substituted piperazines$
Takashi Abea,*, Hajime Babab, Irina Soloshonoka
aDepartment of Chemistry, National Industrial Research Institute of Nagoya ꢀNIRIN), Hirate-cho 1-1, Kita-ku, Nagoya 462-8510, Japan
bDepartment for New Refrigerants Research, Research Institute of Innovative Technology for the Earth ꢀRITE), c/o NIRIN, Hirate-cho 1-1,
Kita-ku, Nagoya 462-8510, Japan
Received 11 October 2000; received in revised form 10 January 2001; accepted 29 January 2001
Abstract
Four piperazines, having bis[ꢀmethoxycarbonyl)alkyl] groups ꢀ±CH2CH2CꢀO)OMe ꢀ1), ±CHꢀCH3)CꢀO)OMe ꢀ2), ±CH2CHꢀCH3)CꢀO)-
OMe ꢀ3) and ±CHꢀCH3)CH2CꢀO)OMe ꢀ4) at the 1- and 4-positions of the piperazine ring), were subjected to electrochemical ¯uorination
ꢀECF). Two bis[ꢀmethoxycarbonyl)alkyl] derivatives of N,N0-dimethylethylenediamine ꢀmolecular formulae: MeOꢀO)CH2CH2NꢀCH3)-
CH2CH2NꢀCH3)CH2CH2CꢀO)OMe ꢀ5) and MeOꢀO)CHꢀCH3)CH2NꢀCH3)CH2CH2NꢀCH3)CH2CHꢀCH3)CꢀO)OMe] ꢀ6)) were also similarly
¯uorinated for a comparative study. On ECF of piperazine derivatives ꢀ1±4), the corresponding per¯uoropiperazines having bis-
[ꢀ¯uorocarbonyl)per¯uoroalkyl] groups were formed, while the ECF of the substrates 5 and 6 afforded degraded products only. Yields of the
targeted di-basic per¯uoroacid ¯uorides containing a per¯uoropiperazinyl group varied, depending on the type of bis[ꢀmethoxycarbo-
nyl)alkyl] groups at the 1- and 4-positions. The best yield of the di-basic per¯uoroacid ¯uorides was obtained from the ECF of 1,4-bis-
[2-ꢀmethoxycarbonyl)propyl]piperazine ꢀ3). Spectroscopic data as well as physicochemical properties are described for new per¯uoroacid
¯uorides and per¯uoroꢀ1,4-dialkylpiperazines). # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Electrochemical ¯uorination; Di-basic carboxylic acids; Per¯uoroacid ¯uorides; Per¯uoroꢀ1,4-dialkylpiperazines)
1. Introduction
of corresponding methyl esters of 4-alkylpiperazinyl-sub-
stituted carboxylic acids [8]. Furthermore, in our previous
paper, it was shown that per¯uoro{1,4-bis[ꢀ¯uorocarbonyl)-
methyl]piperazine} could be obtained by the ECF of
1,4-bis[2-ꢀhydroxy)ethyl]piperazine [9]. As far as the
preparation of di-basic per¯uoroacid ¯uorides having a
per¯uoropiperazine ring is concerned, only two compounds,
per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)ethyl]piperazine} [10]
and per¯uoro{1,4-bis[1-ꢀ¯uorocarbonyl)ethyl]piperazine}
[11], have been ®led in the patent literature other than
per¯uoro{1,4-bis[ꢀ¯uorocarbonyl)methyl]piperazine}.
As a continuing study on the preparation of various kinds
of N-containing per¯uorocarboxylic acids by ECF, we have
conducted detailed work on the preparation of di-basic
per¯uoroacid ¯uorides having a per¯uoropiperazinyl group.
We report the results of the ECF of the four piperazine
derivatives ꢀ1±4) which contain bis[ꢀmethoxycarbony-
l)alkyl] groups at the 1- and 4-positions of the piperazine
ring, and two derivatives ꢀ5, 6) of N,N0-dimethylethylene-
diamine having N,N0-bis[ꢀmethoxycarbonyl)alkyl] groups.
The ECF of 5 and 6 was carried out for a comparative
study with the results obtained from those of piperazine
derivatives ꢀ1±4). c-MeOꢀO)CH2CH2±NꢀC2H4)2N±CH2-
CH2CꢀO)OMe ꢀ1), c-MeOꢀO)CHꢀCH3)±NꢀC2H4)2N±CH-
Per¯uorocarboxylic acids1 are very important, versatile,
starting materials for the synthesis of organo¯uorine che-
micals [1,2]. Though electrochemical ¯uorination ꢀECF) is a
useful means for the preparation of per¯uoroacid ¯uorides,
its synthetic effort has been applied mainly to mono-basic
per¯uoroacid ¯uorides rather than di-basic ones [3±5]. Only
a few reports, limited to those compounds having a short
alkyl chain length, have therefore appeared concerning the
preparation by means of ECF of di-basic per¯uoroacid
¯uorides [6,7]. ECF of di-basic acid derivatives suffers from
extensive cleavage of the bond and an intramolecular cycli-
zation during ¯uorination compared with mono-basic deri-
vatives.
In a previous paper, we have shown that various per¯uor-
oacid ¯uorides bearing a per¯uoroꢀ4-alkylpiperazinyl)
group can be obtained in fair to good yield by the ECF
$ Electrochemical fluorination of N-containing carboxylic acids Part 8.
* Corresponding author. Tel.: ‡81-52-911-2998; fax: ‡81-52-916-2802.
E-mail address: abe@nirin.go.jp ꢀT. Abe).
1 The prefix of ``F-'' in this paper designates ``perfluoro-'' ꢀall C±H
bonds are replaced by C±F bonds).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 3 5 7 - 8

216
T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
ꢀCH3)CꢀO)OMe ꢀ2), c-MeOꢀO)CHꢀCH3)CH2±NꢀC2H4)2-
N±CH2CHꢀCH3)CꢀO)OMe ꢀ3), c-MeOꢀO)CHꢀCH3)CH2±
NꢀC2H4)2N±CH2CHꢀCH3)CꢀO)OMe ꢀ4), MeOꢀO)CH2-
CH2NꢀCH3)CH2CH2NꢀCH3)CH2CH2CꢀO)OMe ꢀ5), MeO-
ꢀO)CHꢀCH3)CH2NꢀCH3)CH2CH2NꢀCH3)CH2CHꢀCH3)C-
ꢀO)OMe ꢀ6).
Scheme 1.
2. Results and discussion
The targeted per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)ethyl]-
piperazine} ꢀ13) was formed in fair yield by the ECF of 1,
which is a methyl ester of di-basic acid incorporated with a
piperazine ring, along with several cleaved products result-
ing from C±C bond scission ꢀScheme 2). As expected, no
cyclization products were found among the products.
A considerable amount of per¯uoro[3-ꢀ4-ethylpiperazi-
nyl)propionyl ¯uoride] [10] ꢀ14) was formed as a result of
the a-scission of one of the two carboxylic acid groups of 1.
Previously, compound 13 has been prepared by the ¯uorina-
tion of the corresponding carboxylic acid chlorideÁHCl salt
ꢀmolecular formula: c-ClCꢀO)CH2CH2±NꢀCH2CH2)2N±
CH2CH2CꢀO)ClÁ2HCl [10]). Instead of using the carboxylic
acid chlorideÁHCl salts of the mono-basic carboxylic acids
as the substrate, we have shown that the corresponding
methyl esters can be used as suitable substitutes [16]. Thus,
in the case of the preparation of di-basic per¯uoroacid
¯uorides by ECF, it was con®rmed that compound 1, which
can be prepared by the Michael addition of piperazine and
methyl acrylate, served as a good substrate for the prepara-
tion of 13.
It is known that the intramolecular cyclization of car-
boxylic acids on ECF occurs as an inevitable side-reaction
when the chain length of the alkyl group of the starting
carboxylic acid is long enough to form a 5- and/or a 6-
membered cyclic ether [12,13]. It is expected that such a
cyclization occurs more readily in the case of a di-basic
carboxylic acid having a linear alkyl group where two
carboxyl groups are separated by a suf®cient number of
bonds ꢀ>4), as compared with that of the mono-basic one
having the same number of carbon atoms in the alkyl
group.
An effective way to improve the yield of per¯uoroacid
¯uoride is to strategically suppress the unfavorable side-
reaction ꢀcyclization) by the incorporation of either a
di¯uoromethylene group or a hetero-atom like a nitrogen
at the g-position of the alkyl group of the carboxylic acid to
be ¯uorinated electrochemically [12,13]. For example, the
¯uorination products are quite different from methyl 3-
cyclo-hexylpropionate ꢀ7) [14] and from methyl 3-morpho-
linopropionate ꢀ8) [15], as shown in Scheme 1.
While the ECF of 7 yielded per¯uoroꢀ1-oxaspiro[4,5]-
decane) ꢀ9) as the principal product instead of the desired
per¯uoroacid ¯uoride ꢀ10), the ECF of 8 afforded the
corresponding per¯uoro[3-ꢀpiperidino)propionyl ¯uoride]
ꢀ11) as the principal product in good yield without the
formation of any cyclization by-products, such as the
expected cyclized compound 12 shown in Scheme 1. The
intramolecular cyclization of 8 on ECF was therefore effec-
tively blocked due to the presence of the nitrogen atom at the
g-position of the carboxylic acid. From the view point of the
preparation of di-basic per¯uoroacid ¯uorides by means of
ECF, it is considered that the piperazine skeleton can be used
as a group for the improvement of the yield of the di-basic
per¯uoroacid ¯uoride when it is introduced into the proper
position of the bond between the methylene groups of the di-
basic acid of the substrate.
When 1,4-bis[1-ꢀmethoxycarbonyl)ethyl]piperazine ꢀ2),
which is an isomer of 1, was subjected to ECF, the expected
per¯uoro{1,4-bis[1-ꢀ¯uorocarbonyl)ethyl]piperazine} ꢀ15)
[11] was obtained at almost comparative yield ꢀGC
yield ˆ 9:0%) to that obtained from compound 1. Per-
¯uoroꢀ1,4-diethylpiperazine)ꢀ16) and per¯uoro[2-ꢀ4-ethyl-
piperazinyl)propionyl ¯uoride] ꢀ17) [8] ꢀresulting from the
a-bond scission of the carboxylic acid group) were obtained
as the major products ꢀScheme 3).
It has been reported that the formation of not only
per¯uoroacid ¯uorides but also per¯uoroꢀmethyl esters) is
observed when methyl esters of 2-ꢀcyclic amino)-substituted
propionic acids are ¯uorinated electrochemically [17]. In the
¯uorination of 2, it was found that small quantities of
per¯uoro{1-[1-ꢀ¯uorocarbonyl)ethyl]-4-[1-ꢀmethoxycarbo-
nyl)ethyl]piperazine}ꢀ18), which retains the structure of one
Scheme 2.

T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
217
Scheme 3.
of the two methyl ester linkages, was formed in small yield
ꢀGC yield ˆ 1:4%), together with the targeted per-
¯uoro{1,4-bis[1-ꢀ¯uorocarbonyl)ethyl]piperazine} ꢀ15). The
structure of 18, which was isolated from other products by
means of preparative GC, was elucidated on the basis of
spectral data ꢀIR, MS and 19F NMR). For example, IR
spectra of 18 show two sets of medium-strong characteristic
peaks at 1894 and 1878 cmÀ1 for ±CꢀO)F, and at 1851 and
1835 cmÀ1 for ±CꢀO)OCF3. In the 19F NMR spectra, absorp-
tion peaks due to ±CꢀO)F were found at 25.5 and 24.4
ꢀratio ˆ 1:1.3) and a peak centered at À59.1 ppm for the ±
CꢀO)OCF3. The separation of the absorption peak, due to ±
CꢀO)F, into two peaks, is considered to be caused by the
presence of diastereomers. The ratio of the integration of
the peaks due to ±CꢀO)F and ±CꢀO)OCF3 was 1:3. Per-
¯uoro-{1,4-bis[1-ꢀmethoxycarbonyl)ethyl]piperazine},
which is an expected compound retaining two methyl ester
linkages, could not be found among the products in this
investigation.
By the ¯uorination of 1,4-bis[2-ꢀmethoxycarbonyl)pro-
pyl]piperazine ꢀ3), corresponding per¯uoro{1,4-bis[2-
ꢀ¯uorocarbonyl)propyl]piperazine} ꢀ19) was obtained in
relatively good yield ꢀGC yield ˆ 36:3%). The other by-
products were rather simple compounds, showing a typical
pattern of bond scission of the piperazinyl-substituted car-
boxylic acid methyl esters on ECF, as shown in Scheme 4.
Though the formation of an appreciable amount of per-
¯uoro[1,4-bisꢀpropyl)piperazine] was expected as the
cleaved product due to the a-bond scission of the two
carboxylic acid groups, per¯uoro[1,4-bisꢀpropyl)pipera-
zine] was not found among the product.
Compared with the ECF products obtained from 1±3,
those obtained from 1,4-bis[1-methyl-2-ꢀmethoxycarbony-
l)ethyl)]piperazine ꢀ4) were rather complex, consisting of a
mixture of many cleaved products and cyclized products as
well as the targeted per¯uoro{1,4-bis[1-methyl-2-ꢀ¯uoro-
carbonyl)ethyl]piperazine} ꢀ20) ꢀGC yield ˆ 4:7%). The
formation of a considerable quantity of tarry materials in
AHF was also observed in the cell after completion of the
ECF.
It has been known that the ECF of the type of tertiary
amines with a N-CHꢀCH3)CH2CꢀO)OMe group gives a
cyclization product bearing
a per¯uorooxolane ring
[8,18]. In the case of the ECF of 4, this side-reaction took
place intramolecularly, using two carboxylic acid methyl
ester groups at the 1- and 4-positions of the piperazine ring,
giving two cyclization products, consisting of per¯uoro{3-
[4-ꢀ3-oxacyclopentyl)piperazinyl]butyryl ¯uoride} ꢀ21) and
per¯uoro[1,4-bisꢀ3-oxacyclopentyl)piperazine] ꢀ22) from
one side and both sides' cyclization, respectively
ꢀScheme 5).
Compounds such as 20±22 are a mixture of diastreomeric
isomers due to the presence of two asymmetric carbons in
their molecules. Compound 21 showed 19F NMR spectra too
complex for resolution, therefore all coupling constants
could not be determined and an assignment of the NMR
to the respective erythro and threo isomers was not
attempted ꢀTable 1).
Scheme 4.

Scheme 5.
Table 1
19F NMR of compounds 13, 15, 18±24, 27, 28, 35, 38, 39±42, and 44±46
Compound
Formula
Chemical shifta,b
J ꢀHz)b
13
a
b
c
d
26.3
À119.8
À92.3
À92.1
15
a
b
c
d
a
b
c
d
24.4 ꢀdl-form)
À76.1
b±a ˆ 13.8
JAB ˆ 190
À141.7
À80.9, À97.0
25.3 ꢀmeso-form)
À75.3
À139.0
À88.6, À89.4
JAB ˆ 195
18
a
b
c
d
25.5, 24.4 ꢀratio ˆ 1:1.4)
À75.2, À76.1
À138.7, À141.9 ꢀratio ˆ 1:1.3)
À88.6, À89.3
JAB ˆ 195
JAB ˆ 195
JAB ˆ 195
JAB ˆ 192
À88.4, À89.4
e
À80.4, À97.6
À80.7, À97.3
f
À76.1, À75.3
g
h
À140.9, À143.1 ꢀratio ˆ 1:1.3)
À59.10, À59.13
33.9 ꢀd)
19
20
a
b
c
d
e
a±c ˆ 17.2
JAB ˆ 248
À73.3 ꢀm)
À177.3 ꢀm)
À82.9, À86.7
À92.7 ꢀm)
a
b
c
d
e
25.9, 25.8
À112.3 to À112.8 ꢀm)
À76.1 ꢀm)
À158.5 ꢀm)
À86.4 ꢀmeso-form)
À84.1, À88.6 ꢀdl-form)
26.1, 25.9
JAB ˆ 191
21
a
b
c
d
e
f
À112.5 to À113.2 ꢀm)
À75.0, À76.2
À158.5 ꢀm)
À85.2 to À90.9 ꢀm)
À85.2 to À90.9 ꢀm)
À135.3 ꢀm)
g
h
À70.4, À83.1
JAB ˆ 128
JAB ˆ 134
JAB ˆ 248
JAB ˆ 240
JAB ˆ 124
JAB ˆ 129
À70.6, À83.6
i
j
À117.1, À127.3
À117.2, À122.8
À80.0, À91.3
À80.0, À91.7

Table 1 ꢀContinued )
Compound
Formula
Chemical shifta,b
J ꢀHz)b
22
a
b
c
d
e
À79.9, À91.2
JAB ˆ 124
JAB ˆ 124
JAB ˆ 248
JAB ˆ 253
JAB ˆ 127
JAB ˆ 130
À79.9, À91.7
À117.2, À127.2
À117.2, À127.9
À70.5, À82.8 ꢀdl-form)
À70.5, À83.6 ꢀmeso-form)
À135.2 ꢀdl-form)
À135.5 ꢀmeso-form)
À88.7, À90.0 ꢀmeso-form)
À87.7, À91.0 ꢀdl-form)
JAB ˆ 192
JAB ˆ 186
23
a
b
c
d
e
f
À77.4 to À77.5 ꢀm)
À161.2 ꢀm)
À85.2 to À90.5 ꢀm)
À85.2 to À90.5 ꢀm)
À76.1
À158.6 ꢀm)
g
h
À112.4 to À112.7 ꢀm)
25.8
24
a
b
c
d
e
f
À83.2
À83.6
À161.2 ꢀquintet)
À86.0 to À91.1 ꢀm)
À86.0 to À91.1 ꢀm)
À135.4 ꢀm)
c±d ˆ 20.6±24.3
g
h
i
À70.5, À83.4
À117.2, À127.6
À80.0, À91.5
JAB ˆ 135
JAB ˆ 245
JAB ˆ 124
27
a
b
c
d
a
b
c
d
À75.9 ꢀdl-form)
À140.3
À80.2, À98.5
d 4.00 ꢀm)
JAB ˆ 189
À76.2 ꢀmeso-form)
À141.5
À88.7, À89.6
d 4.00 ꢀm)
JAB ˆ 195
a±c ˆ 17.2
28
a
b
c
À73.5 to À73.6 ꢀm)
À179.0
À84.7, À85.9
À84.9, À86.2
À92.9 ꢀm)
JAB ˆ 233
JAB ˆ 239
d
e
d 3.97
35
38
a
b
c
d
À120.7
À93.1 ꢀquintet)
À92.3
b±c ˆ 17.2
d À3.94
a
b
c
d
e
f
À81.3 ꢀt)
a±c ˆ 10.2
À128.5 ꢀquintet)
À92.2 ꢀm)
À92.6 ꢀm)
À92.6 ꢀm)
À82.8, À86.6
À73.3 ꢀm)
À177.3 ꢀm)
33.9 ꢀm)
b±d ˆ 8.8±10.4
JAB ˆ 237
g
h
I
39
a
b
c
d
e
f
À81.4 ꢀt)
a±c ˆ 8.8±10.2
b±d ˆ 10.2±10.4
À128.5 ꢀquintet)
À92.4 ꢀm)
À92.7 ꢀm)
À92.7 ꢀm)
À84.5, À85.8
À73.6
JAB ˆ 239
g
h
i
À179.0 ꢀm)
d 3.97

220
T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
Table 1 ꢀContinued )
Compound
Formula
Chemical shifta,b
J ꢀHz)b
40
a
À113.5 ꢀmeso-form)
À114.8 ꢀdl-form)
À75.9 ꢀmeso-form)
À74.9 ꢀdl-form)
b
c
À158.7 to À158.9 ꢀm)
À86.4 ꢀmeso-form)
À82.4, À90.5 ꢀdl-form)
d 3.97±3.99
d
JAB ˆ 19.1
e
41
a
b
c
d
e
f
À114.1, À114.4
À75.0, À75.3
À158.6 to À159.0 ꢀm)
À82.7 to À92.0 ꢀm)
À82.7 to À92.0 ꢀm)
À134.9, À135.6
À70.2, À82.0
g
JAB ˆ 136
JAB ˆ 151
JAB ˆ 250
JAB ˆ 250
JAB ˆ 130
JAB ˆ 131
À70.7, À84.5
h
i
À117.0, À126.4
À117.3, À128.6
À79.9, À90.8
À80.0, À92.2
j
d 3.98
42
a
b
c
d
e
f
À76.9, À78.0
À161.4 ꢀquintet)
À83.9 to À90.0 ꢀm)
À83.9 to À90.0 ꢀm)
À75.4 ꢀm)
b±c ˆ 22.3±22.6
À158.8 ꢀquintet)
À114.1 to À114.2 ꢀm)
d 3.97
f±d ˆ 23±24
g
h
44
45
a
b
c
d
e
f
À83.8 ꢀtriple quartet)
À89.3 ꢀm)
a±d ˆ a±c ˆ 6.8
À50.8 ꢀm)
À93.4 ꢀm)
À117.3 ꢀtriple quartet)
d 3.98
e±b ˆ e±c ˆ 8.5±10.4
a
b
c
d
e
f
À83.4 ꢀtriple-quartet)
À92.9 ꢀm)
a±d ˆ 13
a±c ˆ 13
À50.7 ꢀm)
À80.6, À82.7
À73.3 ꢀdouble-quartet)
À172.6
JAB ˆ 286
e±f ˆ 15.5
e±c ˆ 7.1
g
33.1
46
a
b
c
d
e
f
À83.2 ꢀtriple-quartet)
À93.0 ꢀm)
a±d ˆ 9
a±c ˆ 9
À50.7 ꢀm)
À80.7, À83.8
À73.6 ꢀdouble-quartet)
À175.3 ꢀm)
JAB ˆ 238
e±f ˆ 6.8±8.5
e±c ˆ 6.8±8.5
g
d 3.98
a
19F chemical shift in ppm relative to internal CFCl3 ꢀnegative shifts are upfield) and 1H chemical shifts in ppm relative to TMS.
b Only obvious chemical shifts and coupling constants are given.
Small quantities of the degradation compounds, such as
per¯uoro{3-[4-ꢀiso-propyl)piperazinyl]butyryl ¯uoride}
ꢀ23), per¯uoro[1-ꢀiso-propyl)-4-ꢀ3-oxacyclopentyl)pipera-
zine] ꢀ24), per¯uoro[3-ꢀ4-ethylpiperazinyl)butyryl ¯uoride]
ꢀ25) [8] and per¯uoro[1-ethyl-4-ꢀ3-oxacyclopentyl)pipera-
zine] ꢀ26) [8] were found among the products. It is con-
sidered that the cyclization of carboxylic acids occurs at
the initial stage of the ¯uorination. Accordingly, a-bond
scission followed by b-bond scission, which occurs step-
by-step at one side of the N-alkyl group of the piperazine
ring of the intermediate compounds ꢀI and II) with the
same molecular structures as those of 20 and 21, leads to

T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
221
Scheme 6.
the formation of 23 and 25 ꢀfrom 20) and 24 and 26 ꢀfrom
21) ꢀScheme 6).
In order to determine the con®guration of 15, which has a
relatively simple structure, 19F NMR study was achieved
successfully in the form of the methyl ester ꢀ27) at various
temperatures from 25 to 1508C using 1,2-dichlorobenzene-
d4 as the solvent ꢀFigs. 1 and 2).
Two peaks at 90.6 and 90.3 ppm and two at 26.2 and
25.1 ppm {solvent: 1,2-dichlorobenzene-d4, standard ꢀexter-
nal): hexa¯uorobenzene} were assigned to CF3± and CF±,
respectively ꢀFig. 1). Two sets of AB quartets in the region of
67.8±87.0 ppm were assigned to the peaks of CF2± groups of
the piperazine ring. On raising the temperature, the absorp-
tion peaks due to the CF2± group ꢀwhich ®rst showed
two sets of well-resolved AB type quartets) behaved in a
Among four targeted di-basic per¯uoroacid ¯uorides ꢀ13,
15, 19 and 20), per¯uoro{1,4-bis[1-ꢀ¯uorocarbonyl)ethyl]-
piperazine} ꢀ15), per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)pro-
pyl]piperazine} ꢀ19) and per¯uoro{1,4-bis[1-methyl-2-
ꢀ¯uorocarbonyl)ethyl]piperazine} ꢀ20) are a mixture of
two diastereoisomers ꢀdl- and meso-forms), having two
identical N-alkyl group with an asymmetric carbon ꢀN-
CÃFꢀCF3)CꢀO)F for 15, N-CF2CÃFꢀCF3)CꢀO)F for 19 and
N-CÃFꢀCF3)CF2CꢀO)F for 20, respectively, where CÃ is an
asymmetric carbon) at the 1- and 4-positions of the piper-
azine ring.
Fig. 1. 19F NMR of 1,4-bis[1-ꢀmethoxycarbonyl)tetrafluoroethyl]octafluoropiperazine ꢀ27); ꢀsolvent: 1,2-dichlorobenzene-d4, standard: hexafluorobenzene
ꢀexternal)).

222
T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
different manner ꢀFig. 2). The inner part of the AB quartet
converged gradually into one peak due to the rapid chair-to-
chair inversion of the ring at temperatures higher than 608C,
becoming a single peak at a temperature of 1508C. The outer
part of the AB quartet still remained the same state as that of
the original AB quartet at this temperature. The outer AB
system is considered to be caused by the asymmetry of the
structure of 27. Hence, the outer AB quartet was assigned to
that of the dl-form which had no symmetric plane, and the
inner one, which had a symmetric plane, to that of the meso-
form. The mixing ratio of dl- and meso-form for 27 was
determined to be 1:1.1.
In a similar way, by taking into consideration the simi-
larity of the structures of 15 and 20, the ratio of dl- and meso-
form of 20 was determined to be 1:1.1 by the integration of
the peaks of CF2± of the piperazine ring ꢀconsisting of the
outer AB quartet and the inner one, respectively).
In the case of 19, the peak of CF2± groups of the
piperazine ring showed a slightly converged and collapsed
AB quartet centered at À92.7 ppm {solvent: CDCl3, stan-
dard ꢀinternal): CFCl3}; the absorption peaks due to ±CF2 of
N-CF2CÃFꢀCF3)CꢀO)F showed an AB quartet ꢀÀ82.9 and
À86.7 ppm, JAB ˆ 248 Hz). When 19F NMR was taken, in a
form of the methyl ester ꢀ28), it showed almost the same
spectrum as that of 19. However, the latter AB quartet split
into two sets of AB quartets, which may be ascribed to the
presence of diastereoisomers. An assignment of their peaks
to the dl- and meso-forms could not be achieved ꢀTable 1).
In a preceding paper, we have shown that there is a
correlation between the yield of mono-basic per¯uoroacid
¯uorides having a per¯uoroꢀ4-alkylpiperazinyl) group and
the substrate of the structure of the carboxylic acid skeleton
having a 4-alkylpiperazinyl group as shown in Scheme 7 [8].
Another interest of this investigation was to check
whether the correlation, between the yield of di-basic per-
¯uoroacid ¯uoride formed and the structure of several 1,4-
bis[ꢀmethoxycarbonyl)alkyl] groups on the piperazine ring
of 1±4, would be still be kept.
Among the results obtained from the ECF of 1±4, it was
found that the ECF yield of the corresponding di-basic
per¯uoroacid ¯uorides ꢀ19) ꢀform D) was optimal in the
case of the ¯uorination of 3 having two ±CH2CHꢀCH3)-
CꢀO)OMe groups at the 1- and 4-positions of the piperazine
ring. Comparison of the yields of other di-basic per¯uor-
oacid ¯uorides obtained from 1, 2, and 4 showed that the
order of increasing yield was different from that observed for
a series of 4-alkylpiperazinyl-substituted carboxylic acids.
Fig. 2. Variable-temperature 19F NMR of 27 in the region of À66 to
À88 ppm at the temperatures of 25±1508C.
Scheme 7.

T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
223
Scheme 8.
Their yields decreased in the order of 13 ꢀForm A)
ꢀyield ˆ 10:6%) obtained from 1; 15 ꢀForm B) ꢀ9.0%)
obtained from 2; and per¯uoro{1,4-[1-methyl-2-ꢀ¯uorocar-
bonyl)ethyl]piperazine} ꢀ20) ꢀForm D) ꢀ4.7%) obtained
from 4.
In order to compare the behavior between the two types
of the substrate on ECF ꢀone of which is di-basic acid
methyl esters having a piperazine ring and the other being
a N,N-dimethylethylenediamino group), we investigated
the ¯uorination of two methyl ester derivatives ꢀ5 and 6),
which were prepared by the Michael reaction of N,N0-
dimethylethylenediamine and methyl acrylate and methyl
methacrylate, respectively. It was revealed that the degrada-
tion involving the cleavage of the C±C and C±N bonds
occurred extensively in the case of the ECF of both 5 and 6,
resulting in the formation of cleaved products only
ꢀScheme 8).
[2-ꢀmethoxycarbonyl)propyl]piperazine] ꢀ3) and 1,4-bis-
[1-methyl-2-ꢀmethoxycarbonyl)ethyl]piperazine] ꢀ4) were
prepared by the reaction ꢀMichael reaction) of anhydrous
piperazine with methyl acrylate, methyl methacrylate and
methyl crotonate, respectively. 3,6-Diaza-3,6,-dimethyl-1,8-
octanedicarboxylic acid dimethyl ester ꢀ5) and 4,7-diaza-
4,7-dimethyl-2,9-decanedicarboxylic acid dimethyl ester ꢀ6)
were prepared by the reaction ꢀMichael reaction) of N,N0-
dimethylethylenediamine with methyl acrylate, and methyl
methacrylate similarly.
The substrates synthesized for ¯uorination had the fol-
lowing boiling points: 1,4-bis[2-ꢀmethoxycarbonyl)ethyl]-
piperazine] ꢀ1), mp: 55.0±55.58C ꢀsolid); 1,4-bis[1-
ꢀmethoxycarbonyl)ethyl]piperazine] ꢀ2), bp 145±1468C/
3 mmHg; 1,4-bis[2-ꢀmethoxycarbonyl)propyl]piperazine]
ꢀ3), bp 1408C/2 mmHg; 1,4-bis[1-methyl-2-ꢀmethoxycarbo-
nyl)ethyl]piperazine] ꢀ4), bp 134±1358C/3 mmHg; 3,6-
diaza-3,6-dimethyl-1,8-octanedicarboxylic acid dimethyl
ester ꢀ5), bp 105±1078C/2 mmHg and 4,7-diaza-4,7-
dimethyl-2,9-decanedicarboxylic acid dimethyl ester ꢀ6),
bp 140±1428C/2 mmHg.
Purity of anhydrous hydrogen ¯uoride ꢀAHF) ꢀDaikin
Industries Co.) was more than 99.9%. The electrolytic
¯uorination apparatus and operating procedures were simi-
lar to those described previously [21]. Analytical GLC work
was carried out with a Shimadzu GC-14B gas chromato-
graph using stainless steel columns ꢀ3 mm diameter) packed
with 25% Fomblin YR on Chromosorb PAW ꢀ6.4 m). For a
semi-preparative work, a GASUKURO LL-75 modi®ed gas
chromatograph using stainless steel columns ꢀ10 mm dia-
meter) packed with 30% KelF wax on Chromosorb PAW
ꢀ4.9 m), and a Varian model 920 GC using an aluminum
column ꢀ3/8 in. diameter) packed with 20% Fomblin YR on
Chromosorb PAW ꢀ20 feet) were used. The carrier gas was
helium in all cases. Infrared spectra were measured on a
Shimadzu FTIR-8000PC spectrometer using a 6 cm gas cell
with KBr windows. 19F NMR spectra were measured on a
Varian Unity Inova 300 spectrometer ꢀ282.238 MHzfor 19F
and 299.95 MHzfor 1H, respectively). Chemical shifts for
19F and 1H NMR spectra were reported relative to CFCl3 and
TMS, respectively. Variable-temperature 19F NMR spectra
were taken at the temperature higher than 258C using o-
dichlorobenzene-d4 as a solvent and hexa¯uorobenzene as
an external standard. Positive shifts are down®eld from the
reference ꢀCFCl3, hexa¯uorobenzene and TMS). Mass spec-
tra were measured on a Shimadzu GC/MS-QP5000 and a
Shimadzu GC/MS-QP1100EX instruments ®tted with a
capillary column ꢀNeutra Bond-1, 30 m long, 0.25 mm
i.d., 1.5 mm thick) at 70 eV. Elemental analyses were
From the ECF of 3,6-diaza-3,6-dimethyl-1,8-octanedicar-
boxylic acid dimethyl ester ꢀ5), per¯uoroꢀN,N-dimethy-
lethylamine), per¯uoro[3-ꢀN,N-dimethylamino)propionyl
¯uoride] and per¯uoro[3-ꢀN-methyl,N-ethylamino)propio-
nyl ¯uoride] were formed as the major cleaved products.
Similarly, per¯uoroꢀiso-butyryl ¯uoride), per¯uoro[3-ꢀN,N-
dimethylamino)-2-methylpropionyl ¯uoride] and per-
¯uoro[3-ꢀN-methyl,N-ethylamino)-2-methylpropionyl
¯uoride] were obtained from ECF of 4,7-diaza-4,7-
dimethyl-2,9-decanedicarboxylic acid dimethyl ester ꢀ6).
The targeted di-basic per¯uoroacid ¯uorides could not be
found among the products obtained. It is known that the b-
scission of the alkyl groups ꢀR1 and R2) of tertiary amines
occurs extensively in the ECF of those of the type CH3±
NR1ꢀR2) ꢀR1 ˆ CnH2n‡1, R2 ˆ CmH2m‡1; n, m > 2), afford-
ing CF3±NR3ꢀR4) ꢀR3 ˆ CnF2n‡1
,
R4 ˆ CmH2m‡1
; n,
m > 2) [19,20]. Therefore, it is considered that compounds
5 and 6, both of which have two CH3-N groups in their
molecules, were subjected to severe C±C bond cleavage ꢀb-
scission from the site of the nitrogen atom) during ECF,
resulting in the formation of many, but only cleaved, pro-
ducts.
3. Experimental details
Boiling points were uncorrected. Methyl ester of 1,4-
bis[1-ꢀmethoxycarbonyl)ethyl]piperazine] ꢀ2) was prepared
by the reaction of piperazineÁhexahydrate with methyl 2-
bromopropionate in the presence of anhydrous Na2CO3
according to the method described in the literature [22].
1,4-bis[2-ꢀmethoxycarbonyl)ethyl]piperazine] ꢀ1), 1,4-bis-

224
T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
È
performed by Mikroanalytisches Labor Beller in Gottingen,
Germany.
Compounds 13 was derivatized into the di-methyl ester
ꢀ35) for further characterization; into a 10 ml PFA resin
bottle, was placed 0.915 g ꢀ1.75 mmol) of 13 which was
isolated by preparative GC, and methanol ꢀ0.69 g) was
added drop-wise while cooling in an ice bath. The reaction
took place immediately with an evolution of heat giving a
white solid. The addition of 2 ml of FC721 ꢀper¯uorohex-
ane) did not dissolve it, but further addition of 5 ml of 1,1,2-
trichlorotri¯uoroethane to it could dissolve it resulting in a
formation of two layers. After shaking the reaction mixture
with an addition of 1 ml water, the lower phase was sepa-
rated, and the removal of the solvent afforded white solid
ꢀ0.91 g, 95% yield).
3.1. Fluorination of 1,4-bis[2-
ꢀmethoxycarbonyl)ethyl]piperazine ꢀ1)
Sample 1 ꢀ39.5 g, 0.153 mol) was charged into a cell
containing 420 ml electrolytically puri®ed AHF, and the
solution was subjected to ¯uorination with an anodic current
density of 3.2 A/dm2, a cell voltage of 5.8±6.2 V, and a cell
temperature of 7±88C over a period of 229 min ꢀ628 Ah). At
the ®nal stage of the ¯uorination, the voltage reached 6.7 V.
The ef¯uent gases from the cell were passed over NaF
pellets and then condensed in a trap cooled to À788C. The
gaseous products which did not condense in the À788C trap
were then bubbled through a ¯uoropolymer bottle contain-
ing water and a gas washing bottle containing an aqueous
solution of a mixture of K2CO3, KOH and KI. All products
except new ones were identi®ed by comparison of their
infrared spectra and GLC retention times with those of
authenticated samples. New compounds were separated
from the other products by use of semi-preparative GLC,
and their structures were determined on the basis of their
spectral data ꢀIR, 19F NMR and MS) and elemental analysis
ꢀcarbon and ¯uorine).
1,4-Bis[2-ꢀmethoxycarbonyl)tetra¯uoroethyl]octa¯uoro-
piperazine ꢀ35) ꢀnc): mp 69.0±69.88C and bp 257.0±
257.58C. IR ꢀnujol): 1790 [nꢀC=O)] ꢀs). MS ꢀDI): 437
‡
‡
[M À CF2CꢀO†OCH3] ꢀ8.2), 252 C4F12N ꢀ7.0), 138
‡
‡
‡
‡
‡
C2F6 ꢀ4.9), 164 C3F6N ꢀ11.7), 159 CF2CF2CꢀO)OCH3
ꢀ31.3), 149 C2F3O ꢀ3.6), 131 C3F5 ꢀ42.0), 119 C2F5
‡
‡
‡
‡
ꢀ19.1), 114 C2F4N ꢀ25.2), 100 C2F4 ꢀ49.0), 97 C2F3O
‡
‡
ꢀ12.1), 81 C2F3 ꢀ22.5), 69 CF3 ꢀ22.5), 60 ? ꢀ82.1), 59
‡
CꢀO)OCH3 ꢀ100). Analysis: Calc. for C12F16N2O4H6: C,
26.37%; F, 55.7%. Found: C, 26.16%; F, 55.6%.
19F NMR data of 13 and 35 are shown in Table 1
together with other new compounds synthesized in this
experiment.
The products ꢀ5.8 g) condensed in the À788C trap con-
sisted of per¯uoroꢀN,N-dimethylethylamine) ꢀ29) ꢀ0.5 g),
of per¯uoroꢀN,N-diethylmethylamine) ꢀ30) ꢀ0.7 g), per-
3.2. Fluorination of 1,4-bis[1-
ꢀmethoxycarbonyl)ethyl]piperazine ꢀ2)
¯uoro[3-ꢀN,N-dimethylamino)propionyl
¯uoride
ꢀ31)
ꢀ0.8 g), per¯uorotriethylamine ꢀ32) ꢀ1.5 g), per¯uoroꢀ1,4-
dimethylpiperazine) ꢀ33) ꢀ0.2 g), per¯uoroꢀ4-methyl-1-
ethylpiperazine) ꢀ34) ꢀ0.4 g), per¯uoroꢀ1,4-diethylpipera-
zine) ꢀ16) ꢀ0.4 g) and unidenti®ed products ꢀ1.3 g) ꢀproducts
are arranged in order of elution on GC). Cell drainings
ꢀ25.1 g) consisted of 32 ꢀ0.4 g), 34 ꢀ2.4 g), 16 ꢀ2.5 g),
pe¯uoro[3-ꢀ4-methylpiperazinyl)propionyl ¯uoride] [8]
ꢀ1.7 g), per¯uoro[3-ꢀ4-ethylpiperazinyl)propionyl ¯uoride]
ꢀ14) ꢀ7.7 g), per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)ethyl]pi-
perazine} ꢀ13) ꢀ8.5 g) and unidenti®ed products ꢀ1.9 g).
The GC yield of 13 was 10.6%. The physicochemical
properties of 14 [8] which has not yet been reported in a
preceding paper, and physicochemical properties and spec-
tral data ꢀIR and Mass) of 13 are shown below.
Sample 2 ꢀ34.7 g, 0.134 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm, 6.0±6.3 V, 7±88C,
553 min ꢀ205 Ah). The work-up gave the following products
in the À788C trap ꢀ5.2 g): 29 ꢀ1.2 g), per¯uoro[2-ꢀN,N-
dimethylamino)propionyl ¯uoride] [21] ꢀ1.5 g), 32 ꢀ1.6 g),
34 ꢀ0.1 g), 16 ꢀ0.2 g) and unidenti®ed products ꢀ0.7 g). Cell
drainings ꢀ29.8 g): 16 ꢀ7.7 g), per¯uoro[2-ꢀ4-ethylpiperazi-
nyl)propionyl ¯uoride] ꢀ17) ꢀ10.2 g), per¯uoro[methyl 2-
ꢀ4-ethylpiperazinyl)propionate] [8] ꢀ0.3 g), per¯uoro{1,4-
bis[1-ꢀ¯uorocarbonyl)ethyl]piperazine} ꢀ15) [11] ꢀ6.3 g),
per¯uoro{1-[1-ꢀ¯uorocarbonyl)ethyl]-4-[1-ꢀmethoxycarbo-
nyl)ethyl]piperazine} ꢀ18) ꢀ1.1 g) and unidenti®ed products
ꢀ4.2 g). The GC yield of 15 was 9.0%. The physicochemical
properties and spectral data ꢀIR and MS) of 15 and 18 are
shown below.
Per¯uoro[3-ꢀ4-ethylpiperazinyl)propionyl ¯uoride] ꢀ14):
bp 141.0±141.58C, d420 1.8290, nD20 1.2998.
Per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)ethyl]piperazine}
ꢀ13): bp 165.2±165.88C, d420 1.8438, nD20 1.3121. IR ꢀcapil-
lary ®lm): 1881 [nꢀC=O)] ꢀvs), 1334 ꢀvs), 1300 ꢀvs), 1265
ꢀvs), 1235 ꢀvs), 1208 ꢀvs), 1171 ꢀvs), 1117 ꢀs), 1088 ꢀm), 979
ꢀm), 952 ꢀs), 793 ꢀms), 767 ꢀw), 710 ꢀw), 691 ꢀw), 663 ꢀw),
Per¯uoro{1,4-bis[1-ꢀ¯uorocarbonyl)ethyl]piperazine}
ꢀ15): bp 162.0±162.58C, d420 1.8593, nD20 1.3146. IR ꢀcapil-
lary ®lm): 1894 and 1878 [nꢀC=O)] ꢀs), 1302 ꢀs), 1228±1250
ꢀbroad, vs), 1177 ꢀs), 1105 ꢀw), 1070 ꢀw), 1047 ꢀw), 977 ꢀm),
930 ꢀw), 948ꢀw), 930 ꢀw), 917 ꢀw), 802 ꢀw), 769 ꢀw), 702
‡
‡
‡
‡
‡
655 ꢀw). Mass: 503 [M À F] ꢀ0.3), 425 [M À CF2CꢀO†F]
ꢀw), 674 ꢀw). Mass: 503 [M À F] ꢀ1.0), 475 [M À CꢀO†F]
‡
‡
‡
‡
‡
ꢀ12.1), 309 C6F11N2 ꢀ0.8), 259 C5F9N2 ꢀ2.5), 214 C4F8N
ꢀ8.5), 453 [M À CF3] ꢀ4.5), 309 C6F11N ꢀ1.5), 214
‡
‡ ‡ ‡
ꢀ0.5), 171 C4F5N ꢀ2.1), 164 C3F6N ꢀ13.4), 147
‡
C4F8N ꢀ17.7), 164 C3F6N ꢀ29.4), 145 C3F5N ꢀ1.5),
119 C2F5 ꢀ100), 114 C2F4N ꢀ22.6), 100 C2F4 ꢀ23.3),
‡
‡
‡ ‡ ‡
C2F4CꢀO)F ꢀ4.6), 145 C3F5N ꢀ1.3), 119 C2F5 ꢀ100),
‡
‡
‡
‡
‡
‡
‡
114 C2F4N ꢀ29.8), 100 C2F4 ꢀ23.3), 76 C2F2N ꢀ1.3), 69
‡
95 C2F3N ꢀ2.6), 81 C2F3 ꢀ1.2), 76 C2F2N ꢀ3.0), 69 CF3
‡
‡
CF3 ꢀ34.6), 50 CF2 ꢀ3.1).
ꢀ34.2), 50 CF2 ꢀ4.1).

T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
225
Per¯uoro{1-[1-ꢀ¯uorocarbonyl)ethyl]-4-[1-ꢀmethoxycar-
bonyl)ethyl]piperazine} ꢀ18) ꢀnc): bp 170.5±171.08C, d420
1.8527, n2D0 1.3143. IR ꢀcapillary ®lm): 1894 ꢀm) and 1878
ꢀms) [nꢀC=O)F], 1851 ꢀm) and 1835 ꢀms) [nꢀC=O)OCF3],
1200±1300 ꢀbroad, vs), 1177 ꢀvs), 1143 ꢀvs), 1169 ꢀm),
1048 ꢀm), 1016 ꢀm), 977 ꢀm), 930±949 ꢀm), 785 ꢀw), 702
products ꢀ2.2 g). Cell drainings ꢀ51.0 g): per¯uoro[3-ꢀ4-
propylpiperazinyl)-2-methylpropionyl ¯uoride] ꢀ38) ꢀ6.9 g),
per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)propyl]piperazine]}
ꢀ19) ꢀ31.5 g) and unidenti®ed products ꢀ12.6 g). The GC
yield of 19 and 38 were 36.3 and 8.3%, respectively. Spectral
data ꢀIR and Mass) and physicochemical properties of 19
and 38 are shown below.
‡
ꢀw), 676 ꢀw). Mass: 541 [M À CꢀO†F] ꢀ0.7), 475
‡
‡
[M À CꢀO†OCF3] ꢀ8.2), 425 C8F15N2O ꢀ1.0), 309
Per¯uoro{1,4-bis[2-ꢀ¯uorocarbonyl)propyl]piperazine]}
ꢀ19) ꢀnc): mp 58.0±61.08C and bp 192.0±192.58C. IR
ꢀcapillary ®lm): 1885 and 1870 [nꢀC=O)] ꢀs), 1335 ꢀs),
1300 ꢀms), 1237±1250 ꢀvs±s), 1160 ꢀs), 1090 ꢀm), 1008
ꢀms), 985 ꢀms), 950 ꢀs), 786 ꢀs), 757 ꢀw), 715 ꢀw), 702 ꢀw),
‡
‡
‡
C6F11N ꢀ2.2), 214 C4F8N ꢀ9.3), 195 C4F7N ꢀ2.5), 164
C3F6N ꢀ16.0), 145 C3F5N ꢀ1.5), 119 C2F5 ꢀ49.0), 114
‡
‡
‡
‡
‡
‡
C2F4N ꢀ12.0), 113 C2F3O2 ꢀ3.6), 100 C2F4 ꢀ19.9), 97
‡
‡
‡
‡
C2F3O ꢀ1.4), 81 C2F3 ꢀ1.2), 76 C2F2N ꢀ1.6), 69 CF3
‡
‡
ꢀ100), 50 CF2 ꢀ2.1).
688 ꢀw), 623 ꢀw). MS: 475 [M À CFꢀCF3†CꢀO†F] ꢀ28.1),
‡ ‡
‡
‡
‡
Corresponding methyl ester ꢀ27) of 15 was prepared in a
similar manner as explained for the case of 13 $89% yield).
1,4-Bis[1-ꢀmethoxycarbonyl)tetra¯uoroethyl]octa¯uoro-
piperazine ꢀ27) ꢀnc): bp 243.0±243.58C, d420 1.7364, nD20
1.3492. IR ꢀcapillary ®lm): 1784 [nꢀC=O)] ꢀs). MS: 487
197 CFꢀCF3)CꢀO)F ꢀ43.4), 169 C3F7 ꢀ100), 164 C3F6N
ꢀ20.0), 150 C3F6 ꢀ12.7), 131 C3F5 ꢀ9.0), 119 C2F5
‡
‡
‡
‡
ꢀ13.7), 114 C2F4N ꢀ35.5), 100 C2F4 ꢀ63.7), 69 CF3
‡
ꢀ74.3), 50 CF2 ꢀ2.0).
Per¯uoro[3-ꢀ4-propylpiperazinyl)-2-methylpropionyl
¯uoride] ꢀ38) ꢀnc): bp 173.5±174.08C, d420 1.8697, nD20
1.3045. IR ꢀcapillary ®lm): 1886 and 1871 [nꢀC=O)]
ꢀms), 1336 ꢀvs), 1304 ꢀvs), 1232±1270 ꢀvs±s), 1166 ꢀvs),
1134 ꢀm), 1096 ꢀm), 1010 ꢀm), 986 ꢀm), 961 ꢀs), 952 ꢀvs),
791 ꢀs), 756 ꢀw), 746 ꢀw), 737 ꢀs), 693 ꢀw), 670 ꢀw), 632 ꢀw).
‡
‡
‡
‡
[M À CF2CꢀO†OMe] ꢀ0.9), 288 C7F10N ꢀ6.4), 207
‡
‡
C5F7N ꢀ6.5), 174 C5F6 ꢀ6.6), 164 C3F6N ꢀ6.9), 131
C3F5 ꢀ8.7), 119 C2F5 ꢀ10.9), 114 C2F4N ꢀ6.2), 100
‡
‡
‡
‡
‡
‡
C2F4 ꢀ15.2), 81 C2F3 ꢀ8.5), 69 CF3 ꢀ8.6), 59 CꢀO)OMe
ꢀ100). Analysis: Calc. for C12F16N2O4H6: C, 26.37%; F,
55.7%. Found: C, 26.25%; F, 55.5%.
‡
‡
MS: 575 [M À F] ꢀ0.3), 475 [M À C2F5] ꢀ10.9), 447
‡ ‡
‡
‡
‡
19F NMR data of 15, 18 and 27 {solvent: CDCl3, standard
ꢀinternal): CFCl3} are shown in Table 1.
C5F9O ꢀ6.2), 214 C4F8N ꢀ3.3), 197 CF2CFꢀCF3)CꢀO)F
ꢀ29.6), 169 C3F7 ꢀ100), 164 C3F6N ꢀ20.3), 150 C3F6
‡
‡
‡ ‡
Compound 15 was derivatized into an amide of p-meth-
oxyaniline for further characterization also: into a 100 ml
polytetra¯uoroethylene beaker, was placed 0.25 g
ꢀ2.0 mmol) of p-methoxyaniline dissolved in 10 ml of
dichloromethane and 2.02 g ꢀ20 mmol) of triethylamine,
and compound 15 ꢀ0.5 g, 1 mmol) which was isolated by
preparative GC was added drop-wise while shaking. The
mixture was left standing in the draft overnight. The residue
was dissolved in a mixture of hexane and ethyl acetate ꢀ4:1)
and analyzed by TLC. The crude product was puri®ed by
column chromatography ꢀhexane/ethyl acetate as an eluent)
to give corresponding diꢀp-methoxyanilide) of 15 as white
yellow solid ꢀ0.29 g, 41% yield).
Diꢀp-methoxyanilides) of 15 ꢀnc): mp 173.0±173.58C. IR
ꢀNujor): 1701 nꢀC=O) ꢀms). 19F NMR ꢀCDCl3): d À73.9 [6F,
CFꢀCF3)N], d À87.0, À90.0 [8F, JAB ˆ 195 Hz, ±NꢀCF2-
CF2)2N±], d À134.4 [2F, CFꢀCF3)N], 1H NMR ꢀCDCl3): d
7.90 ꢀs, 2H, NH), d 7.44 ꢀd, 4H), d 6.92 ꢀd, 4H), d 3.81 ꢀs, 6H,
OCH3). Analysis: Calc. for C24F16N4O4H16: C, 39.56%; F,
41.8%. Found: C, 39.48; F, 41.9%.
ꢀ4.3), 131 C3F5 ꢀ3.6), 119 C2F5 ꢀ18.9), 114 C2F4N
‡
‡
‡
ꢀ36.6), 100 C2F4 ꢀ48.9), 69 CF3 ꢀ73.7), 50 CF2 ꢀ1.9).
Methyl esters ꢀ28 from 19 and 39 from 38, respectively) of
19 and 38 were prepared in a similar manner as explained
for 13.
1,4-Bis[2-ꢀmethoxycarbonyl)hexa¯uoropropyl]octa¯uor-
opiperazine ꢀ28) ꢀnc): mp: 58.5±59.08C and bp 258.0±
258.58C. IR ꢀNujol): 1790 and 1771 [nꢀC=O)] ꢀms). Ana-
lysis: Calc. for C14F20N2O4H6: C, 26.01%; F, 58.8%. Found:
C, 25.99%; F, 59.0%.
Methyl per¯uoro[3-ꢀ4-propylpiperazinyl)-2-methylpro-
pionate] ꢀ39) ꢀnc): bp 257.0±257.58C, n2D0 1.3208 and d420
1.7949. IR ꢀcapillary ®lm): 1792 and 1779 [nꢀC=O] ꢀs). MS:
‡
‡
525 [M À C2F3]
ꢀ3.3), 281 C5F9
‡
ꢀ3.3), 209
‡
‡
[C3F6CꢀO)OMe] ꢀ10.2), 169 C3F7 ꢀ5.1), 164 C3F6N
‡
‡
‡
‡
ꢀ8.0), 150 C3F6 ꢀ9.7), 131 C3F5 ꢀ6.8), 119 C2F5
‡
‡
ꢀ20.7), 114 C2F4N ꢀ10.2), 100 C2F4 ꢀ15.3), 85 CF3O
‡
‡
‡
ꢀ5.9), 81 C2F3 ꢀ7.1), 69 CF3 ꢀ22.5), 59 CꢀO)OMe ꢀ100).
Analysis: Calc. for C12F21N2O2H3: C, 23.76%; F, 65.8%.
Found: C, 23.80%; F, 65.6%. 19F NMR data of 19, 28, 38
and 39 are shown in Table 1.
3.3. Fluorination of 1,4-bis[2-
ꢀmethoxycarbonyl)propyl]piperazine ꢀ3)
p-Methoxyanilides of 19 and 38 were prepared for
further characterization in a similar manner as explained
for 15.
Sample 3 ꢀ39.9 g, 0.140 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.5±5.6 V, 7±
88C, 628 min ꢀ229 Ah). The work-up gave the following
products in the À788C trap ꢀ6.0 g): per¯uoroꢀiso-butyryl
¯uoride) ꢀ36) ꢀ2.4 g), per¯uoro[3-ꢀN,N-dimethylamino)-2-
methylpropionyl ¯uoride] ꢀ37) [18] ꢀ1.4 g) and unidenti®ed
Diꢀp-methoxyanilide) of 19 ꢀnc): white brown solid
ꢀyield: 56%), mp 169.5±170.08C. IR ꢀNujor): 1693
[nꢀC=O)] ꢀms). 19F NMR ꢀCDCl3): d À73.1 [6F, CFꢀCF3)-
CF2N], d À84.7 [4F, CFꢀCF3)CF2N], d À93.0 [broad, 8F, ±
1
NꢀCF2CF2)2N±], d À177.5 [2F, CFꢀCF3)CF2N], H NMR
ꢀCDCl3): d 7.86 ꢀd, 2H, NH), d 7.40 ꢀd, 4H), d 6.90 ꢀd, 4H), d

226
T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
‡
‡
‡
‡
3.81 ꢀs, 6H, OCH3). Analysis: Calc. for C26F20N4O4H16: C,
37.68%; F, 45.9%. Found: C, 37.7%; F, 46.0%.
p-Methoxyanilide of 38 ꢀnc): white yellow solid ꢀyield:
62%), mp 109.5±109.88C. IR ꢀNujor): 1701 [nꢀC=O)] ꢀms).
C2FNO ꢀ4.7), 69 CF3 ꢀ53.0), 57 C2FN ꢀ3.6), 50 CF2
‡
ꢀ2.7), 47 COF ꢀ5.4).
Per¯uoro[1,4-bisꢀ3-oxacyclopentyl)piperazine] ꢀ22) ꢀnc):
‡
bp 163.5±164.08C. MS: 603 [M À F]
ꢀ9.0), 556
ꢀ9.6), 506
‡
‡
19F NMR ꢀCDCl3):
d
À73.2 ꢀtriple doublet, 2F,
[M À CF2O]
ꢀ4.7), 553 [M À CF3]
‡
‡
‡
JFÀF ˆ 10:4 Hz, 6.8 Hz, NCF2CFꢀCF3)CꢀO)), d À81.2 ꢀtri-
plet, 3F, JFÀF ˆ 8:8 À 10:2 Hz ,CF3CF2CF2N), d À84.4 ꢀm,
2F, NCF2CFꢀCF3)CꢀO)), d À92.3 ꢀm, 2F, CF3CF2CF2N), d
À92.7 [m, 8F, c-NꢀCF2CF2)2N], d À128.4 ꢀm, 2F,
[M À C2F4O] ꢀ36.2), 440 C9F16N2 ꢀ4.5), 295 C6F11N
‡
‡
‡
‡
‡
‡
‡
ꢀ8.7), 273 C5F9NO ꢀ9.6), 264 C5F10N ꢀ17.2), 245 C5F9N
ꢀ20.1), 226 C5F8N ꢀ5.4), 214 C4F8N ꢀ10.8), 207 C5F7N
‡
‡
‡
‡
ꢀ10.7), 195 C4F7N ꢀ10.6), 176 C4F6 ꢀ14.8), 169 C3F7
ꢀ10.0), 164 C3F6N ꢀ12.4), 150 C3F6 ꢀ22.4), 145 C3F5N
‡ ‡
ꢀ24.8), 131 C3F5 ꢀ22.9), 119 C2F5 ꢀ85.4), 114 C2F4N
‡ ‡
1
CF3CF2CF2N), d À177.5 ꢀm, 1F, NCF2CFꢀCF3)CꢀO)), H
NMR ꢀCDCl3): d 7.88 ꢀs, 1H, NH), d 7.42 ꢀd, 2H), d 6.91 ꢀd,
‡ ‡ ‡
2H),
d
3.82 ꢀs, 3H, OCH3). Analysis: Calc. for
C18F21N3O2H8: C, 30.99%; F, 57.3%. Found: C, 30.75; F,
ꢀ19.8), 100 C2F4 ꢀ100), 81 C2F3 ꢀ4.9), 73 C2FNO ꢀ7.2),
‡
‡
‡
69 CF3 ꢀ62.1), 57 C2FN ꢀ10.6), 50 CF2 ꢀ4.8). Analysis:
Calc. for C12F22N2O2: C, 23.15%; F, 67.2%. Found: C,
23.00%; F, 67.1%.
57.0%.
3.4. Fluorination of 1,4-bis[1-methyl-2-
ꢀmethoxycarbonyl)ethyl]piperazine ꢀ4)
Per¯uoro{[3-ꢀ4-iso-propylpiperazinyl)]butyryl ¯uoride}
ꢀ23) ꢀnc): bp 173.5±174.08C. IR ꢀcapillary ®lm): 1882.4
‡
‡
‡
‡
‡
‡
[nꢀC=O)] ꢀms). Mass: 575 [M À F] ꢀ4.6), 425 [M À CF3]
‡
Sample 4 ꢀ39.6 g, 0.138 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.5±5.6 V, 7±
88C, 611 min ꢀ223 Ah). The work-up gave the following
products in the À788C trap ꢀ10.8 g): per¯uoroꢀpropionyl
¯uoride) ꢀ4.9 g), 30 ꢀ1.6 g), 32 ꢀ2.7 g) and unidenti®ed
products ꢀ1.6 g). Cell drainings ꢀ32.9 g): 30 ꢀ1.0 g), 32
ꢀ2.0 g), 34 ꢀ1.9 g), 16 ꢀ6.2 g), per¯uoroꢀ4-ethyl-1-iso-pro-
pylpiperazine) [8] ꢀ3.1 g), per¯uoro{[3-ꢀ4-ethylpiperazi-
nyl)]butyryl ¯uoride} ꢀ25) [8] ꢀ3.2 g), per¯uoro[1-ethyl-4-
ꢀ3-oxacyclopentyl)piperazine] ꢀ26) [8] ꢀ1.7 g), per¯uoro{[3-
ꢀ4-iso-propylpiperazinyl)]butyryl ¯uoride} ꢀ23) ꢀ2.0 g),
per¯uoro[1-ꢀiso-propyl)-4-ꢀ3-oxacyclopentyl)piperazine]
ꢀ24) ꢀ1.4 g), per¯uoro{1,4-bis[1-methyl-2-ꢀ¯uorocarbony-
l)ethyl]piperazine} ꢀ20) ꢀ4.0 g), per¯uoro{3[4-ꢀ3-oxacyclo-
pentyl)piperazinyl]butyryl ¯uoride} ꢀ21) ꢀ2.7 g), per-
¯uoro[1,4-bisꢀ3-oxacyclopentyl)piperazine] ꢀ22) ꢀ0.5 g)
and unidenti®ed products ꢀ3.2 g). The GC yield of
the targeted per¯uoro{1,4-bis[1-methyl-2-ꢀ¯uorocarbonyl)-
ethyl]piperazine} ꢀ20) was only 4.7%.
ꢀ25.4), 497 [M À CF2CꢀO†F] ꢀ4.5), 478 [M À C2F4O]
‡
‡
ꢀ8.8), 281 C5F9 ꢀ4.4), 264 C5F10N ꢀ16.7), 245 C5F9N
ꢀ9.1), 214 C4F8N ꢀ18.3), 207 C5F7N ꢀ6.3), 195 C4F7N
‡
‡
‡
‡
ꢀ3.4), 169 C3F7 ꢀ14.1), 164 C3F6N ꢀ34.6), 150 C3F6
‡
‡
‡
ꢀ8.1), 145 C3F5N ꢀ10.1), 131 C3F5 ꢀ7.2), 119 C2F5 ꢀ100),
‡
‡
‡
114 C2F4N ꢀ21.0), 100 C2F4 ꢀ53.4), 73 C2FNO ꢀ10.7),
‡
‡
69 CF3 ꢀ55.8), 50 CF2 ꢀ2.7).
Per¯uoro{[3-ꢀ4-iso-propylpiperazinyl)]oxolane} ꢀ24)
‡
ꢀnc): bp 192.5±193.08C. Mass: 603 [M À F] ꢀ1.8), 525
‡
‡
‡
‡
‡
[M À CF2CꢀO†F] ꢀ16.0), 264 C5F10N ꢀ8.0), 214 C4F8N
‡
‡
ꢀ15.2), 207 C5F7N ꢀ3.8), 197 C4F7O ꢀ4.2), 195 C4F7N
ꢀ3.0), 169 C3F7 ꢀ21.2), 164 C3F6N ꢀ33.3), 150 C3F6
‡
‡
‡
‡
‡
ꢀ8.6), 145 C3F5N ꢀ8.0), 131 C3F5 ꢀ7.7), 119 C2F5 ꢀ100),
‡
‡
‡
114 C2F4N ꢀ19.2), 100 C2F4 ꢀ40.8), 73 C2FNO ꢀ4.7), 69
‡
‡
CF3 ꢀ53.0), 50 CF2 ꢀ2.7). Analysis: Calc. for C11F22N2O:
C, 22.22%; F, 70.4%. Found: C, 22.20%; F, 70.2%.
Methyl esters ꢀ40 from 20, 41 from 21 and 42 from 23,
respectively) of 20, 21 and 23 were prepared in a similar
manner as explained for 13.
Spectral data ꢀIR and Mass) and boiling points of 20±24
are shown below.
1,4-bis[1-tri¯uoromethyl-2-ꢀmethoxycarbonyl)tri¯uor-
oethyl]octa¯uoropiperazine ꢀ40) ꢀnc): bp 254.5±255.08C,
n2D0 1.3492, d420 1.7364. IR ꢀcapillary ®lm): 1881 [nꢀC=O)]
Per¯uoro{1,4-bis[1-methyl-2-ꢀ¯uorocarbonyl)ethyl]pi-
perazine} ꢀ20) ꢀnc): bp 199.5±199.88C. IR ꢀcapillary ®lm):
‡
‡
‡
ꢀms). MS: 537 [M À CF2CꢀO†OMe] ꢀ5.5), 224 C4F8N
‡
‡
1881.4 [nꢀC=O)] ꢀms). Mass: 603 [M À F] ꢀ1.5), 553
ꢀ8.8), 214 C4F8N ꢀ3.9), 209 CFꢀCF3)CF2CꢀO)OMe
‡
‡
‡ ‡
[M À CF3] ꢀ6.6), 525 [M À CF2CꢀO†F] ꢀ23.4), 264
ꢀ19.9), 207 C5F7N ꢀ10.4), 164 C3F6N ꢀ10.3), 150
‡
‡
‡
‡ ‡ ‡
C3F6 ꢀ10.4), 131 C3F5 ꢀ6.1), 119 C2F5 ꢀ13.0), 114
C5F10N ꢀ7.7), 214 C4F8N ꢀ14.6), 207 C5F7N ꢀ6.0),
197 CFꢀCF3)CꢀO)F ꢀ5.0), 169 C3F7 ꢀ26.2), 164
‡
‡
‡
‡
‡
C2F4N ꢀ10.8), 100 C2F4 ꢀ9.7), 69 CF3 ꢀ13.8), 59
‡
‡
‡
‡
C3F6N ꢀ46.1), 150 C3F6 ꢀ4.8), 145 C3F5N ꢀ3.5), 131
‡
CꢀO)OMe ꢀ100). Analysis: Calc. for C14F20N2O4H6: C,
‡
‡
C3F5 ꢀ4.0), 119 C2F5 ꢀ100), 114 C2F4N ꢀ22.8), 100
‡
26.01%; F, 58.82%. Found: C, 25.85%; F, 59.1%.
Methyl per¯uoro{3[4-ꢀ3-oxacyclopenty)piperazinyl]bu-
tyrate} ꢀ41) ꢀnc): bp 225.0±225.58C. IR ꢀcapillary ®lm):
‡
‡
‡
C2F4 ꢀ23.6), 73 C2FNO ꢀ8.5), 69 CF3 ꢀ54.3), 47 COF
ꢀ6.3).
Per¯uoro{3[4-ꢀ3-oxacyclopenty)piperazinyl]butyryl
‡
1792 [nꢀC=O)] ꢀms). MS: 525 [M À CF2CꢀO†OMe] ꢀ2.2),
‡ ‡
¯uoride} ꢀ21) ꢀnc): bp 218.0±218.58C. IR ꢀcapillary ®lm):
214 C4F8N ꢀ3.9), 209 CFꢀCF3)CF2CꢀO)OMe ꢀ9.2), 164
C3F6N ꢀ9.7), 150 C3F6 ꢀ10.7), 145 C3F5N ꢀ5.1), 131
‡
‡ ‡ ‡
1882.4 [nꢀC=O)] ꢀms). MS: 603 [M À F] ꢀ1.8), 525
‡
‡
‡ ‡ ‡
C3F5 ꢀ5.8), 119 C2F5 ꢀ27.8), 114 C2F4N ꢀ10.5), 100
[M À CF2CꢀO†F]
ꢀ16.0), 264 C5F10N
ꢀ8.0), 214
‡
‡
‡
‡
‡
‡
C4F8N ꢀ15.2), 169 C3F7 ꢀ21.2), 164 C3F6N ꢀ33.3),
‡
C2F4 ꢀ15.2), 69 CF3 ꢀ21.0), 59 CꢀO)OMe ꢀ100). Ana-
lysis: Calc. for C13F21N2O3H3: C, 24.61%; F, 62.9%. Found:
C, 24.75%; F, 63.0%.
‡
‡
‡
150 C3F6 ꢀ8.6), 145 C3F5N ꢀ8.0), 131 C3F5 ꢀ7.7), 119
‡
‡
C2F5 ꢀ100), 114 C2F4N ꢀ19.2), 100 C2F4 ꢀ40.8), 73

T. Abe et al. / Journal of Fluorine Chemistry 108 ꢀ2001) 215±228
227
Methyl per¯uoro{[3-ꢀ4-iso-propylpiperazinyl)]butyrate}
ꢀ42) ꢀnc): bp 202.5±203.08C. IR ꢀcapillary ®lm): 1792
Per¯uoro[3-ꢀN-methyl,N-ethylamino)-2-methylpropionyl
¯uoride] ꢀ45) was new compound. The characterization of
45 was conducted in a form of methyl ester ꢀ46). IR data of
45 and spectroscopic data ꢀIR and MS) and physicochemical
properties of 46 are shown below. 19F NMR data of 45 and
46 are shown in Table 1.
Per¯uoro[3-ꢀN-methyl,N-ethylamino)-2-methylpropionyl
¯uoride] ꢀ45) ꢀnc): IR ꢀgas): 1890, 1877 [nꢀC=O)] ꢀms),
1324 ꢀvs), 1249 ꢀvs), 1232 ꢀs), 1152 ꢀm), 1097 ꢀms), 1010
ꢀw), 985 ꢀw), 931 ꢀm), 843 ꢀms), 755 ꢀm), 738 ꢀm), 712 ꢀw),
689 ꢀw), 664 ꢀw).
‡
[nꢀC=O)] ꢀms). MS: 497 [M À CF2CꢀO†OMe] ꢀ15.2),
‡
‡
‡
209 CFꢀCF3)CF2CꢀO)OMe ꢀ18.1), 164 C3F6N ꢀ17.1),
150 C3F6 ꢀ13.4), 145 C3F5N ꢀ24.8), 131 C3F5 ꢀ5.2),
‡
‡
‡
‡
‡
119 C2F5 ꢀ33.3), 114 C2F4N ꢀ15.0), 100 C2F4 ꢀ14.3), 69
‡
‡
CF3 ꢀ23.8), 59 CꢀO)OMe ꢀ100). Analysis: Calc. for
C12F21N2O2H3: C, 23.76%. Found: C, 23.50%.
19F NMR data of 20±24 and 40±42 are shown in
Table 1.
3.5. Fluorination of 3,6-diaza-3,6-dimethyl-1,8-octane-
dicarboxylic acid dimethyl ester ꢀ5)
Methyl per¯uoro[3-ꢀN-methyl,N-ethylamino)-2-methyl-
propionate] ꢀ46) ꢀnc): bp. 138.0±138.58C, d420 1.7151, nD20
1.3049. IR ꢀcapillary ®lm): 1790 [nꢀC=O)] ꢀs), 1443 ꢀm),
1308±1350 ꢀvs±s), 1222±1240 ꢀvs), 1120 ꢀs, sh), 1161 ꢀm),
1092 ꢀs), 1045 ꢀm), 1034 ꢀm), 999 ꢀw), 926 ꢀms), 943 ꢀms),
802 ꢀw), 758 ꢀm), 735 ꢀms), 673 ꢀm). MS: 352
Sample 5 ꢀ40.8 g, 0.157 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.8±6.5 V, 7±
88C, 626 min ꢀ229 Ah). The work-up gave the following
products in the À788C trap ꢀ19.5 g): 29 ꢀ2.8 g), 31 ꢀ7.5 g),
‡
‡
[M À CF2CꢀO†OMe] ꢀ0.9), 324 C6F12N ꢀ2.5), 315
‡
‡
‡
per¯uoro[3-ꢀN-methyl,N-ethylamino)propionyl
¯uoride]
C6F12NH ꢀ4.4), 252 C4F12N ꢀ16.6), 234 C4F11NH
‡ ‡
ꢀ43) ꢀ2.7 g) and unidenti®ed products ꢀ6.5 g). Cell drainings
ꢀ6.4 g): all unidenti®ed.
ꢀ2.7), 191 HC3F5CꢀO)OMe ꢀ11.3), 169 C3F7 ꢀ3.7), 164
‡
‡
‡
‡
‡
‡
C3F6N ꢀ20.0), 159 CF2CF2CꢀO)OMe ꢀ4.2), 132 C3F5H
‡ ‡
Per¯uoro[3-ꢀN-methyl,N-ethylamino)propionyl ¯uoride]
ꢀ43) was new compound. The characterization of 43 was
conducted in a form of methyl ester ꢀ44). IR data of 43 and
spectroscopic data ꢀIR and MS) and physicochemical prop-
erties of methyl per¯uoro[3-ꢀN-methyl,N-ethylamino)pro-
pionate] ꢀ44) are shown below. 19F NMR data of 44 are
shown in Table 1.
Per¯uoro[3-ꢀN-methyl,N-ethylamino)propionyl ¯uoride]
ꢀ43) ꢀnc): IR ꢀgas): 1888 [nꢀC=O)] ꢀms), 1321±1340 ꢀvs±
s), 1246 ꢀvs), 1213 ꢀms), 1157 ꢀm), 1123 ꢀms), 1096 ꢀms),
1024 ꢀw), 935 ꢀm), 854 ꢀm), 760 ꢀw), 737 ꢀm).
ꢀ7.4), 131 C3F5 ꢀ2.7), 119 C2F5 ꢀ25.5), 114 C2F4N
‡
‡
ꢀ16.7), 113 C3F4H ꢀ10.9), 100 C2F4 ꢀ4.8), 82 C2F3H
‡
‡
ꢀ4.2), 81 C2F3 ꢀ43.2), 69 CF3 ꢀ52.9), 59 CꢀO)OMe
ꢀ100). Analysis: Calc. for C8F14NO2H3: C, 23.36%; F,
64.7%. Found: C, 23.40%; F, 65.0%.
Acknowledgements
This investigation was supported by the New Energy and
Industrial Technology Development Organization ꢀNEDO).
Authors wish also thank to Ms. J. Tachibana for taking
NMR, Mass and IR spectra.
Methyl per¯uoro[3-ꢀN-methyl,N-ethylamino)propionate]
ꢀ44) ꢀnc): bp 129.5±130.08C, d420 1.6742, nD20 1.3053. IR
ꢀcapillary ®lm): 1790 [nꢀC=O)] ꢀs), 1445 ꢀm), 1310±1350
ꢀvs±s), 1229 ꢀvs), 1198 ꢀvs), 1151 ꢀs), 1094 ꢀs), 1034 ꢀm),
957 ꢀm), 930 ꢀms), 860 ꢀms), 812 ꢀms), 760 ꢀm), 735 ꢀms),
References
‡
665 ꢀw). MS: 252 C4F12N ꢀ11.4), 209 CFꢀCF3)CF2-
‡
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‡
‡
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‡
‡
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