Electrochemical fluorination of 1-ethylpiperazine and 4-methyl- and/or 4-ethylpiperazinyl substituted carboxylic acid methyl esters

Article abstract of DOI:10.1016/S0022-1139(00)00397-3

Electrochemical fluorination (ECF) of 1-ethylpiperazine and eight methyl esters of 4-methyl- and/or 4-ethylpiperazinyl substituted carboxylic acids were studied. Corresponding perfluoro(4-fluoro-1-ethylpiperazine) was obtained from 1-ethylpiperazine in a small yield along with perfluoro(1-methyl-3-ethylimidazolidine), perfluoro[2-(N′,N′-difluoroaminoethyl)-N,N-diethylamine)] and perfluorotriethylamine. The corresponding mono-basic perfluoroacid fluorides with a perfluoro(4-alkylpiperazinyl) group were obtained in fair to good yields from the fluorination of methyl esters of 4-alkylpiperazinyl-substituted carboxylic acids. Yields of the targeted perfluoro(4-alkylpiperazinyl) group containing perfluorocarboxylic acid fluorides varied depending on both the type of N-alkyl (alkyl=CH₃^- or C₂H₅^-) group at the 4-position and the (ω-methoxycarbonylalkyl) group at the 1-position of the piperazine ring of the substrate. Higher yields of perfluoroacid fluorides were obtained by the ECF of 4-ethyl substituted piperazine derivatives than of the 4-methyl substituted piperazine derivatives when 4-alkylpiperazines with the same carboxylic acid ester group were fluorinated electrochemically. Spectroscopic data as well as physical properties are described for new perfluoro(1,4-dialkylpiperazines) and N-containing perfluorocarboxylic acids with a perfluoropiperazinyl group.

Full text of DOI:10.1016/S0022-1139(00)00397-3

Journal of Fluorine Chemistry 108 (2001) 21±35
Electrochemical ¯uorination of 1-ethylpiperazine and
4-methyl- and/or 4-ethylpiperazinyl substituted
carboxylic acid methyl esters$
Takashi Abea,*, Hajime Babab, Irina Soloshonoka
aDepartment of Chemistry, National Industrial Research Institute of Nagoya, 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 14 March 2000; received in revised form 26 September 2000; accepted 7 November 2000
Abstract
Electrochemical ¯uorination (ECF) of 1-ethylpiperazine and eight methyl esters of 4-methyl- and/or 4-ethylpiperazinyl substituted
carboxylic acids were studied. Corresponding per¯uoro(4-¯uoro-1-ethylpiperazine) was obtained from 1-ethylpiperazine in a small yield
along with per¯uoro(1-methyl-3-ethylimidazolidine), per¯uoro[2-(N0,N0-di¯uoroaminoethyl)-N,N-diethylamine)] and per¯uorotriethyla-
mine. The corresponding mono-basic per¯uoroacid ¯uorides with a per¯uoro(4-alkylpiperazinyl) group were obtained in fair to good yields
from the ¯uorination of methyl esters of 4-alkylpiperazinyl-substituted carboxylic acids. Yields of the targeted per¯uoro(4-alkylpiperazinyl)
group containing per¯uorocarboxylic acid ¯uorides varied depending on both the type of N-alkyl (alkyl ˆ CH3 or C2H5 ) group at the 4-
position and the (o-methoxycarbonylalkyl) group at the 1-position of the piperazine ring of the substrate. Higher yields of per¯uoroacid
¯uorides were obtained by the ECF of 4-ethyl substituted piperazine derivatives than of the 4-methyl substituted piperazine derivatives
when 4-alkylpiperazines with the same carboxylic acid ester group were ¯uorinated electrochemically. Spectroscopic data as well as
physical properties are described for new per¯uoro(1,4-dialkylpiperazines) and N-containing per¯uorocarboxylic acids with a
per¯uoropiperazinyl group. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: Electrochemical ¯uorination; Per¯uoroacid ¯uorides; Per¯uoropiperazines; Per¯uoromono-basic acids
1. Introduction
We have previously shown that the ECF of two methyl
esters of 4-methylpiperazinyl substituted carboxylic acids
(methyl 2-(4-methylpiperazinyl)propionate, methyl 3-(4-
methylpiperazinyl)-2-methylpropionate) resulted in fair to
good yields of the corresponding per¯uoroacid ¯uorides
with a per¯uoropiperazine ring [8,9]. Furthermore, we have
shown in a previous paper that per¯uoro[1,4-bis(o-¯uoro-
carbonylmethyl)piperazine] could be obtained by the ECF
of 1,4-bis(2-hydroxyethyl)piperazine [10].
We have now embarked on the preparation of various
per¯uorocarboxylic acids with a per¯uoropiperazine ring by
ECF because little data are available on the ECF of piper-
azine derivatives with a functional group [11±14].2 Though
results of the ECF of methyl 2-(4-methylpiperazinyl)pro-
pionate (4) [8] and 3-(4-methylpiperazinyl)-2-methylpro-
Electrochemical ¯uorination (ECF) is a very important
method for the production of per¯uoro-compounds1 with a
hetero-atom [1±3]. Although the ECF of several per¯uoro(1,
4-dialkylpiperazines) including various per¯uoroheterocyc-
lic compounds were reported by Russian chemists in 1965
[4], it was not until 1975 that the synthesis of per¯uoro(1,4-
di¯uoropiperazine), a per¯uoroderivative of piperazine, was
done by the ECF of piperazine by Banks et al. [5].
However, a need still exists for developing new per¯uor-
ocarboxylic acids especially those with a hetero-atom such
as S, N, and O, because per¯uorocarboxylic acids are
important starting materials for products such as agrochem-
icals and pharmaceuticals [6,7].
$ Electrochemical fluorination of N-containing carboxylic acids. Part 7.
* 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).
2 It has been shown in brief by one of authors (TA) that F-[1,4-bis(1-
fluorocarbonylethyl)piperazine] was obtained by the ECF of 1,4-bis(1-
methoxycarbonylethyl)piperazine [13]. It was stated in brief that
F-[1,4-bis(2-fluorosulfonylethyl)piperazine] was prepared by the ECF of
1,4-bis(2-fluorosulfonylethyl)piperazine [14].
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 0 ) 0 0 3 9 7 - 3

22
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
pionate (6) [9] have already been reported, these two
samples were also examined in order to identify the by-
products in detail under the same conditions as those applied
for other samples for the purposes of comparison.
We herein report the results of the ECF of 1-ethylpiper-
azine (1) and the following eight derivatives of 4-methyl-
and/or 4-ethylpiperazines with a o-(methoxycarbonylalkyl)
group at the 1-position of the piperazine ring (2±9):
c-C2H5N(C2H4)2NH (1), c-CH3N(C2H4)2NCH2CH2C(O)-
OMe (2), c-C2H5N(C2H4)2NCH2CH2C(O)OMe (3),
c-CH3N(C2H4)2NCH(CH3)C(O)OMe (4), c-C2H5N(C2-
H4)2NCH(CH3)C(O)OMe (5), c-CH3N(C2H4)2NCH2CH-
(CH3)C(O)OMe (6), c-C2H5N(C2H4)2NCH2CH(CH3)C(O)-
OMe (7), c-CH3N(C2H4)2NCH(CH3)CH2C(O)OMe (8),
c-C2H5N(C2H4)2NCH(CH3)CH2C(O)OMe (9).
Scheme 1.
were different. The expected per¯uoro(4-¯uoro-1-ethylpi-
perazine) (10) was obtained at a small yield (GC yield ˆ
1:7%) together with per¯uoro(1-methyl-3-ethylimidazoli-
dine) (11) [16], per¯uoro[2-(N0,N0-di¯uoroaminoethyl)-
N,N-diethylamine)] [molecular formula: (C2F5)2NCF2-
CF2NF2] (12) and per¯uorotriethylamine (13) (major pro-
duct) through the ECF of 1, as shown in Scheme 2.
The second major product other than cleaved products
was the ring-contracted compound 11 instead of 10 which
was desired in this case. Though, an attempt to improve the
yield of the corresponding per¯uoro(4-¯uoro-1-methylpi-
perazine) by the ECF of 1-methylpiperazine was made
successfully by raising the initial substrate concentration
(from 5.1 to 8.2%) in anhydrous hydrogen ¯uoride (AHF)
[15] with the yield increasing from 0.8 to 6.8%, changing of
the solute concentration did not produce the same effect in
the case of 1 (see Section 3). Therefore, it was expected that
some correlation would be observed from the results of the
comparative ECF study where methyl esters of 4-alkylpi-
perazinyl substituted carboxylic acids were ¯uorinated by
changing the N-alkyl group (alkyl ˆ CH3 or C2H5 ) at
the 4-position of the piperazine ring, because it is known that
the ECF yield of the tertiary amines of the type of CH3-
NR1(R2) (R1 ˆ CnH2n‡1, R2 ˆ CmH2m‡1; n, m > 2) can be
raised considerably by replacing the N-CH3 group with other
higher N-alkyl groups of the starting material [17].
We have investigated the ECF of 1,4-dialkylpiperazine
derivatives which have a methyl and/or an ethyl group at the
4-position of the piperazine ring and a carboxylic acid
methyl ester group at the 1-position. The results of the
¯uorination of (4-alkylpiperazinyl) substituted n- and/or
iso-propionic acid methyl esters [alkyl ˆ CH3 (2, 4),
C2H5 (3, 5)], and those of methyl 3-(4-alkylpiperazinyl)-
2-methylpropionate [alkyl ˆ CH3 (6), C2H5 (7)] and methyl
2. Results and discussion
We have shown that the ECF of N-(2-hydroxylethyl)pi-
perazine does not produce per¯uoro(4-¯uoropiperazinyl-
acetyl ¯uoride) as the expected product due to the extensive
cleavage of the C±N bond of the secondary amine. Instead,
per¯uoro(N,N-diethylamino-acetyl ¯uoride) was formed as
the cleaved product (Scheme 1) [10].
However, it has been shown that the ECF of 1-methylpi-
perazine yielded the corresponding per¯uoro(4-¯uoro-1-
methylpiperazine) (GC yield ˆ 6:8%), which retained
its original structure, together with per¯uoro(N,N-diethyl-
methylamine) (14.8%), per¯uoro(1,3-dimethylimidazoli-
dine) (2.6%) and per¯uoro[2-(N0,N0-di¯uoroaminoethyl)-
N-methyl,N-ethylamine)] [molecular formula: C2F5(CF3)-
NCF2CF2NF2] (2.0%) [15]. Among these products,
per¯uoro(1,3-dimethylimidazolidine) was formed as a
result of the ring isomerization of the piperazine ring during
¯uorination.
In order to investigate the process of the ECF of 1-
alkylpiperazine in more detail, we have examined the
ECF of 1-ethylpiperazine (1) under almost comparable
conditions to those applied in the ECF of 1-methylpiper-
azine. It was found that almost the same types of products as
those obtained from 1-methylpiperazine were formed
through the ECF of 1, though their distribution patterns
Scheme 2.

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
23
Table 1
Results of the fluorination of 2, 3, 4 and 5
Run
1
Sample g
(mol)
Current
passed (A h)
Fluorinated
product (g)
Fluorinated productsc (yield %)
(2) 39.5 (0.212)
233
9.5a (19.9)b
(C2F5)2NCF3 (32) (5.0), (C2F5)3N (13) (3.5), CF3
CF3 (33) (3.8),
(C2F5)2NCF2CF2C(O)F (16) (4.0), CF3
(14) (8.0)
C2F5 (17) (5.8), CF3
CF2CF2C(O)F
2
3
4
(3) 39.7 (0.198)
(4) 39.7 (0.213)
(5) 39.2 (0.196)
233
211
209
6.5a (30.2)b
6.7a (16.0)b
5.1a (30.1)b
(CF3)2NC2F5 (31) (2.3), 32 (1.1), (CF3)2NCF2CF2C(O)F (36) (0.7), 13 (4.9), 16 (6.1), 17
(4.2), C2F5 C2F5 (18) (12.8), C2F5 CF2CF2C(O)F (15) (14.3)
31 (1.6), 32 (1.7), (CF3)2NCF(CF3)C(O)F (38) (1.6), 13 (3.2), 33 (0.4), 17 (6.4),
CF3
31 (2.9), 32 (0.7), 39 (1.2), 13 (2.7), 17 (1.0), 18 (12.4), C2F5
(15.7), C2F5 CF(CF3)C(O)OCF3 (22) (0.9)
CF(CF3)C(O)F (19) (7.5), CF3
CF(CF3)C(O)OCF3 (20) (0.5)
CF(CF3)C(O)F (21)
a Products obtained in a cold trap.
b Products obtained as cell drainings.
c Arranged in order of the elution time on GC.
3-(4-alkylpiperazinyl)butyrate [alkyl ˆ CH3 (8), C2H5 (9)]
are summarized in Tables 1 and 2, respectively.
obvious difference was observed in the yields of the targeted
per¯uoroacid ¯uorides between those with a per¯uoro(4-
methylpiperazinyl) group and those with a per¯uoro(4-
ethylpiperazinyl) group. Characteristically, the yields of
the per¯uoroacid ¯uorides were almost double that when
were obtained from the ECF of 4-ethylpiperazinyl substi-
tuted substrate as compared with those from 4-methylpiper-
azinyl substituted substrate.
It was found that the desired per¯uoro(4-alkylpiperazinyl)
substituted per¯uoro(carboxylic acid ¯uorides) could be
obtained in fair yields by the ECF of corresponding car-
boxylic acid methyl esters with a 4-alkylpiperazinyl group
[alkyl ˆ CH3 (2, 4, 6, 8), C2H5 (3, 5, 7, 9)]. Although
almost the same kind of the products and distribution pattern
of the cleaved by-products were obtained through ECF of 4-
alkylpiperazine derivatives in the case where an identical
carboxylic acid group was attached at the 1-position, an
For example, the corresponding per¯uoro[3-(4-methylpi-
perazinyl)propionyl ¯uoride] (14) and per¯uoro[3-(4-ethyl-
piperazinyl)propionyl ¯uoride] (15) were obtained together
Table 2
Results of the fluorination of 6, 7, 8 and 9
Run
1
Sample g
(mol)
Current
passed (A h)
Fluorinated
product (g)
Fluorinated productsc (yield %)
(6) 39.7 (0.199)
239
10.0a (40.2)b
iso-C3F7C(O)F (42) (7.2), (CF3)2NCF2CF(CF3)C(O)F (43) (4.3), 33 (0.8), 17 (1.3),
(C2F5)2NCF2CF(CF3)C(O)F (27) (14.5), CF3
CF3 CF2CF(CF3)C(O)F (23) (22.1)
42 (2.8), 31 (2.1), 38 (3.2), 27 (2.3), C2F5
C2F5 CF2CF(CF3)C(O)F (25) (37.5)
C3F7(n) (44) (3.4),
2
3
(7) 40.0 (0.187)
(8) 40.5 (0.203)
232
229
6.6a (53.1)b
C3F7(n) (46) (5.2),
12.0a (26.9)b
n-C3F7C(O)F (48) (4.7), 32 (4.4), 13 (3.7), 17 (3.5), CF3
CF3 CF(CF3)CF2C(O)F (24) (10.9), CF3
48 (trace), 32 (1.8), 13 (3.4), 18 (11.0), C2F5
C2F5 CF(CF3)CF2C(O)F (26) (20.2), C2F5
C3F7(i) (49) (3.8),
(30) (4.5)
4
(9) 40.3 (0.188)
237
7.1a (56.1)b
C3F7(i) (28) (9.5),
(29) (9.7)
a Products obtained in a cold trap.
b Products obtained as cell drainings.
c Arranged in order of the elution time on GC.

24
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
Scheme 3.
with cleaved products in yields as shown in Scheme 3 by the
¯uorination of 2 and 3.
Other major by-products obtained were per¯uoro[3-(N,N-
diethylamino)propionyl ¯uoride] (16) and per¯uoro(4-
methyl-1-ethylpiperazine) (17) from 2, and 16 and per-
¯uoro(1,4-diethylpiperazine) (18) from 3, respectively. In
the case of the ¯uorination of 3, it was found that not only the
yield of the targeted 15 but also that of 18, which resulted
from the a-bond scission of the carboxylic acid, also
increased as compared with that of the corresponding 17
from 2. Among the targeted compounds (14 and 15), com-
pound 15 is a known compound which has been ®led in the
patent literature [12]. Previously, compound 15 has been
isolated as a cleaved by-product from the ¯uorination of 1,4-
bis(b-propionyl chloride)piperazine dihydrochloride.
We have reported that various kinds of per¯uoro[2-(cyclic
amino)propionyl ¯uoride] could be obtained together with a
small amount of per¯uoro[methyl 2-(cyclic amino)propio-
nate] by the ECF of methyl esters of 2-(cyclic amino)pro-
pionic acid [8] (Scheme 4).
Scheme 4.
the cleavage of the a-bond to the carbonyl group is generally
observed. While, in the ECF of acyclic tertiary amines with
a branched alkyl group [alkyl ˆ N-CHR1(R2); R1 ˆ
CnH2n‡1, R2 ˆ CmH2m‡1; n, m > 2], the very easy cleavage
of the C±C bond at the site of either a C±R1 bond or a C±R2
bond (b-bond from the amine) is widely acknowledged [17].
Therefore, compound 18 from the ECF of 5, which is a
tertiary amine with a branched propionic acid methyl ester,
is thought to be formed due to a complex effect consisting of
the a-bond scission at the carboxylic acid site and the b-
bond scission at the amine site.
In accordance with these observations, a pair of the
targeted per¯uorocarboxylic acid derivatives, speci®cally,
per¯uoro[2-(4-methylpiperazinyl)propionyl ¯uoride] (19)
and per¯uoro[methyl 2-(4-methylpiperazinyl)propionate]
(20), and per¯uoro[2-(4-ethylpiperazinyl)propionyl ¯uor-
ide] (21) and per¯uoro[methyl 2-(4-ethylpiperazinyl)pro-
pionate] (22) were obtained by the ¯uorination of 4 and
5, respectively. For example, several products including 21
and 22 were obtained in the ¯uorination of 5 as shown in
Scheme 5.
The formation of per¯uoro(methyl esters) such as per-
¯uoro[methyl 2-(4-ethylpiperazinyl)propionate] (22) can be
easily identi®ed by studying spectroscopic data (19F NMR
and IR). The CF3O signal of the ester group was observed in
the 19F NMR spectra of 22 as a singlet at 59.4 ppm, and the
IR spectra exhibited characteristic n(C=O) bands which split
into two peaks at 1854 and 1840 cm 1. The values for
n(C=O) bands of the corresponding per¯uoroacid ¯uoride
(21), which similarly split into two peaks at 1898 and
1881 cm 1, are slightly higher than those of the per¯uor-
o(methyl ester) (22). The mass spectra of 22 were consider-
Among the products, considerable quantities of per-
¯uoro(1,4-diethylpiperazine) (18) was formed as a cleaved
product resulting from the C±C bond scission. In the ECF of
carboxylic acids (acid halides, methyl esters and amides),
‡
ably different from those of 21. The base peak was the CF3
‡
ion at m/e 69 for 19, while that of 20 was the C2F5 ion at m/
e 119.
Scheme 5.

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
25
Scheme 6.
Relatively good yields of per¯uoroacid ¯uorides were
obtained from the ECF of 4-alkylpiperazines with a n- and/
or an iso-butyric acid group at the 1-position of the piper-
azine ring as compared with those obtained from 4-alkylpi-
The targeted per¯uoro[3-(4-methylpiperazinyl)butyryl
¯uoride] (24) and per¯uoro[3-(4-ethylpiperazinyl)butyryl
¯uoride] (26) were obtained in fair yields together with
cleaved and cyclization products by the ¯uorination of
methyl 3-(4-methylpiperazinyl)butyrate (8) and methyl 3-
(N-ethylpiperazinyl)butyrate (9).
As a typical example, the reaction pathway for each of the
¯uorination products from the ECF of 9 can be explained as
shown in Scheme 7.
perazines with
a n- and/or an iso-propionic acid
group. Furthermore, the kinds of products obtained from
the ECF of 4-alkylpiperazines with an iso-butyric acid group
and/or a n-butyric acid one differed from each other. Rela-
tively simple kinds of ¯uorinated products were formed
from the ECF of the former substrates. In contrast, a com-
plex mixture of cleaved products and a cyclization product
as well as the targeted per¯uoroacid ¯uoride were obtained
from the ECF of the latter substrates. For example, the
per¯uoro[(4-ethylpiperazinyl)-2-methylpropionyl ¯uoride]
(25) was formed at a yield as high as 37.5% together with
cleaved products by the ECF of methyl 3-(4-ethylpiperazi-
nyl)-2-methypropionate (7) as is shown in Scheme 6. The
yield of 25 was almost doubled that of per¯uoro[(4-methyl-
piperazinyl)-2-methylpropionyl ¯uoride] (23) obtained from
the ECF of 4-methylpiperazinyl substituted substrate (6).
Per¯uoro[3-(N,N-diethylamino)-2-methylpropionyl
¯uoride] (27) was formed due to the C±N bond scission
between the 3- and 4-position of the piperazine ring in a
small yield (2.3%) as a cleaved product from 7. This
compound was also obtained from 6 as a common cleaved
product at a higher yield (yield ˆ 14:5%) than that obtained
from 7. Therefore, in the case of the ECF of 7 having a 4-
ethylpiperazinyl group, the degree of the C±N bond scission
at the 4-position of the piperazine ring was considerably
lower than the case of 6 with a 4-methylpiperazinyl group,
which resulted in an increased amount of the formation of
the corresponding per¯uoroacid ¯uoride.
Among them, per¯uoro(1,4-diethylpiperazine) (18) and
per¯uoro[4-ethyl-1-(iso-propyl)piperazine]
(28)
were
formed as major cleaved products. Compound 28 was
formed as a result of the a-bond scission of the carboxylic
acid skeleton. Compound 18 is thought to be formed due to
the b-bond scission (from the side of the amine) of the
butyric acid skeleton as is shown in Scheme 5 by looking at
the cleavage pattern of the products from ECF of 5 which
resulted in per¯uoro(1,4-diethylpiperazine) (18) as the main
cleaved product. Another major product obtained was the
per¯uoro[3-(4-ethylpiperazinyl)oxolane] (29) which is a
speci®c product from the ECF of the substrate with a ±
CH(CH3)CH2C(O)OMe group. We have shown that per-
¯uoroalkylamines bearing a per¯uorooxolane group are
formed in the ¯uorination of a series of methyl 3-(dialky-
lamino)butyrates as a result of the intramolecular cyclization
[9]. Corresponding per¯uoro[3-(4-methylpiperazinyl)oxo-
lane] (30) was similarly formed as the expected cyclization
product (Y ˆ 4:5%) by the ¯uorination of 8. The yields of
these cyclization products (29 and 30) amounted to almost
half of those of the corresponding per¯uoroacid ¯uorides (26
and 24), respectively. Accordingly, it can be concluded that
this cyclization is one of the major reasons for lowered yield
Scheme 7.

26
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
14 (A form) < 24 (C form) < 23 (D form). The comparison of
the ECF yields in a series of per¯uoro[4-ethylpiperazinyl]
group substituted per¯uoroacid ¯uorides showed the same
increasing order of the yield as was observed in that for
per¯uoro[4-methylpiperazyniyl] group substituted per¯uor-
oacid ¯uorides; 15 (A form) < 21 (B form) < 26 (C form) <
25 (D form).
Scheme 8.
Our study on the preparation of N-containing per¯uor-
oacid ¯uorides is in progress and the results of the ECF of
piperazines with bis(o-methoxycarbonylalkyl) groups at the
1- and 4-positions of the piperazine ring will be reported in a
subsequent paper.
of the targeted per¯uoroacid ¯uorides in the case of the
¯uorination of those substrates with a 4-alkylpiperazinyl
group.
It has been reported by Moore and co-workers at 3M Co.
that there is a relationship between the structure and the ECF
yield for substrates which have a dialkylamino-substituted
ether structure [18]. They found that good product yields
were obtained when an iso-propyl group was incorporated
into the ether linkage (I and II) compared with the case
where the N and O atoms are separated by three methylene
groups (III) (Scheme 8).
Similarly we have found that there is a correlation
between the yields of the desired per¯uoroacid ¯uoride
and the structure of the substrate consisting of (N,N-dialky-
lamino) substituted carboxylic acids with respect to both the
dialkylamino-group and the carboxylic acid skeleton [8,9].
The cyclic amino group substituted carboxylic acids result in
higher yields of per¯uoroacid ¯uoride than those from
acyclic amino group substituted carboxylic acids. Further-
more, good yields of the corresponding per¯uoro(N,N-dia-
lkylamino) substituted per¯uoroacid ¯uorides are obtained
in the case of iso-butyric acid (the precursor for D form in
Scheme 9) compared with those of n-/iso-propionic acid (the
precursor for A and B forms) and n-butyric acid (the
precursor for C form) as the substrate in regard to the
structure of the carboxylic acid bearing a N,N-dialkyla-
mino-group. Generally, the following order of increasing
yields was observed as shown in Scheme 9.
3. Experimental details
Boiling points were uncorrected. The 1-ethylpiperazine
(1) was used as commercial grade. Methyl esters of 2-(4-
alkylpiperazinyl)propionic acids were prepared by the reac-
tion of corresponding 4-alkylpiperazine with methyl 2-bro-
mopropionate in the presence of Na2CO3 and small
quantities of H2O according to the method described in
the literature [19]. Methyl esters of 3-(4-alkylpiperazinyl)-
propionic acids, methyl esters of 3-(4-alkylpiperazinyl)-2-
methylpropionic acids, and methyl esters of 3-(N-alkylpi-
perazinyl)butyric acids were prepared by the Michael
reaction of corresponding 1-alkylpiperazine with
methyl acrylate, methyl methacrylate and methyl crotonate,
respectively.
The substrates synthesized for ¯uorination had the fol-
lowing boiling points: methyl 3-(4-methylpiperazinyl)pro-
pionate (2), bp 103±1048C/5 mmHg; methyl 3-(4-
ethylpiperazinyl)propionate (3), bp 1078C/3 mmHg; methyl
2-(4-methylpiperazinyl)propionate (4), bp 798C/5 mmHg;
methyl 2-(4-ethylpiperazinyl)propionate (5), 868C/
3 mmHg; methyl 3-(4-methylpiperazinyl)-2-methylpropio-
nate (6), 267±1708C/15 mmHg; methyl 3-(4-ethylpiperazi-
nyl)-2-methylpropionate (7), 1428C/17 mmHg; methyl 3-(4-
methylpiperazinyl)butyrate (8), 1328C/19 mmHg; methyl 3-
(4-ethylpiperazinyl)butyrate (9), 1348C/17 mmHg.
So, it has become possible to determine the relationship
between the yields of corresponding per¯uoroacid ¯uorides
and the structure of the substrate by studying the data, in
which 4-methyl and/or ethylpiperazinyl groups bearing one
of four kinds of (methoxycarbonylalkyl) groups are ¯uori-
nated. It was found that, in accordance with the general rule
shown in Scheme 9, the following order of the increasing
yield was obtained for the series of per¯uoro[4-methylpi-
perazinyl] substituted per¯uoroacid ¯uorides; 19 (B form),
Purity of anhydrous hydrogen ¯uoride (AHF) (Daikin
Industries Co.) was more than 99.8%. The electrolytic
¯uorination apparatus and operating procedures were simi-
lar to those described previously [20]. Analytical GLC work
was carried out with a Shimadzu GC-14B gas chromato-
graph using stainless steel columns (3 mm diameter) packed
Scheme 9.

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
27
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 ft) 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 MHz for 19F
of 11, 10 and 12 are shown below. 19F NMR data of 10 are
shown in Table 3 together with those of other new com-
pounds isolated in this study.
Per¯uoro(3-methyl-1-ethylimidazolidine) (11): bp 76.0±
20
77.08C (reported bp 70±758C) [16], d4
nD < 1:28. IR (gas): 1366 (vs), 1340 (s), 1304 (ms),
1.7653,
20
1248 (vs), 1219 (s), 1188 (ms), 1077 (m), 1008 (w), 1922
‡
(m), 824 (w), 748 (w), 709 (w), 665 (w). MS: 347 [M F]
‡
‡
(15.8), 297 C5F11N2 (22.2), 259 C5F9N2 (6.6), 214
‡
‡
‡
‡
C4F8N (3.4), 209 C4F7N2 (13.5), 164 C3F6N (59.3),
‡
‡
119 C2F5 (33.6), 114 C2F4N (100), 100 C2F4 (13.4), 69
‡
‡
1
and 299.95 MHz for H, respectively). Chemical shifts for
CF3 (96.9), 50 CF2 (11.1).
Per¯uoro(4-¯uoro-1-ethylpiperazine) (10) (nc): bp 85.0±
19F and 1H NMR spectra were reported relative to CFCl3 and
TMS, respectively. Positive shifts are down®eld from the
reference (CFCl3 and TMS). MS spectra were measured on a
Shimadzu GC/MS-QP5000 and a Shimadzu GC/MS-
QP1100EX instruments ®tted with a capillary column (Neu-
tra Bond-1, 30 m long, 0.25 mm i.d., 1.5 mm thick) at 70 eV.
Elemental analyses were performed by Mikroanalytisches
20
20
85.58C, d4 1.8030, nD < 1:2835. IR (gas): 1381 (m),
1334 (s), 1287 (ms), 1247 (vs), 1229 (vs), 1183 (s), 1140 (w),
1120 (w), 1071 (s), 970 (m), 951 (ms), 824 (m), 734 (m), 706
‡
(w), 665 (w), 626 (w). MS: 347 [M F] (4.9), 297
‡
‡
‡
‡
C5F11N2 (4.2), 259 C5F9N2 (1.5), 209 C4F7N2 (16.8),
‡
‡
164 C3F6N (42.3), 159 C3F7 (4.1), 145 CF3N2 (11.0),
119 C2F5 (100), 114 C2F4N (99.6), 100 C2F4 (40.7), 95
‡ ‡ ‡
È
Laboratorium Beller in Gottingen, Germany.
‡
‡
‡
C2F3N (7.1), 69 CF3 (88.9), 50 CF2 (19.0). Analysis:
Calc. for C6F14N2: C, 19.67%; F, 72.7%. Found: C, 19.72; F,
72.4%.
Per¯uoro[2-(N0,N0-di¯uoroaminoethyl)-N,N-diethyla-
mine) (12) (nc): bp 95.0±95.58C, d4
nD < 1:2800. IR (gas): 1348 (w), 1816 (m), 1286 (vs),
1241 (vs), 1171 (m), 1158 (m), 1109 (ms), 1050 (w), 939
(w), 879 (m), 841 (w), 788 (w), 755 (w), 742 (w). MS: 302
3.1. Fluorination of 1-ethylpiperazine at a lower solute
concentration (1)
20
Sample 1 (28.6 g, 0.250 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 5.7±5.8 V, and a cell
temperature of 7±88C over a period of 690 min (261 A h). At
the ®nal stage of the ¯uorination, the voltage reached 6.2 V.
The ef¯uent gases from the cell were passed over NaF
pellets and then condensed in a trap cooled to 788C. The
gaseous products which did not condense in the 788C 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).
The products (21.1 g) condensed in the 788C trap con-
sisted of per¯uoro(N,N-dimethylethylamine) (31) (3.3 g),
per¯uoro(N,N-diethylmethylamine) (32) (5.6 g), per¯uoro-
triethylamine (13) (9.1 g), per¯uoro(3-methyl-1-ethylimida-
zolidine) (11) [16] (0.7 g), per¯uoro(4-¯uoro-1-ethyl-
piperazine) (10) (0.1 g) and unidenti®ed products (2.3 g)
(products are arranged in order of elution on GC). Cell
drainings (24.2 g) consisted of 32 (1.3 g), 13 (18.1 g), 11
(2.1 g), 10 (1.4 g), per¯uoro[2-(N0,N0-di¯uoroaminoethyl)-
N,N-diethylamine)] (12) (0.9 g) and unidenti®ed products
(0.4 g). The GC yield of 10 was 1.7%. 19F NMR data of 11
were the same as those of the reported one [16]. The
physicochemical properties and spectral data (IR and MS)
1.8075,
20
‡
‡
‡
‡
‡
[M CF2NF2] (1.1), 247 C4F9N2 (1.3), 214 C4F8N
‡
‡
‡
(8.9), 195 C2F5N2 (3.2), 164 C3F6N (15.3), 119 C2F5
‡
(100), 114 C2F4N (10.7), 100 C2F4 (11.4), 76 N2F2
‡
‡
(1.3), 69 CF3 (66.5), 50 CF2 (6.8). 19F NMR: d 18.1 (m,
2F, NF2), 81.8 (m, 6F, (CF3CF2)2NCF2 ), 86.2 (m, 2F,
(CF3CF2)2NCF2 ), 89.9 (m, 4F, (CF3CF2)2NCF2),
112.0 (m, 2F, ±CF2NF2). Analysis: Calc. for C6F16N2:
C, 17.82%; F, 75.3%. Found: C, 17.92; F, 75.0%.
3.2. Fluorination of 1-ethylpiperazine (1) at a higher
solute concentration
Sample 1 (40.2 g, 0.352 mol) was ¯uorinated similarly
under the following conditions: 3.2 A/dm2, 5.6±5.8 V, 7±
88C, 846 min (321 A h). The work-up gave the following
products in the 788C trap (18.1 g): 31 (3.3 g), 32 (5.8 g),
13 (6.7 g), 11 (0.4 g), and unidenti®ed products (1.9 g). Cell
drainings (29.2 g): 32 (1.3 g), 13 (21.4 g), 11 (3.3 g), 10
(1.6 g), 12 (1.2 g) and unidenti®ed products (0.4 g). The GC
yield of 11 was 1.3%.
3.3. Fluorination of methyl 3-(4-methylpipera-
zinyl)propionate (2)
Sample 2 (39.5 g, 0.212 mol) was ¯uorinated similarly
under the following conditions: 3.2 A/dm2, 5.8±6.4 V, 7±
88C, 638 min (233 A h). The work-up gave the following
products in the 788C trap (9.5 g): 32 (3.4 g), 13 (1.8 g),

28
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
Table 3
19F NMR of compounds 10, 14, 15, 21, 22, 24, 25, 26, 28, 29, 30, 34, 37, 40, 44, 45, 46, 47, 49, 50 and 51
Compound
Formula
Chemical shifta,b
J (Hz)b
10
a
b
c
d
e
87.1 (quintet)
97.2 (quintet)
89.6 (broad)
109.6
a±c ˆ 8.7
b±c ˆ 17.2
107.7 (s)
14
15
a
b
c
d
e
f
52.4 (quintet)
93.5 (quartet)
90.6 (m)
a±b ˆ 13.8
b±a ˆ 13.8
91.0 to 91.4 (m)
118.9 (double quintet)
26.0 (m)
e±f ˆ e±c ˆ 10.4
a
b
c
d
e
f
86.8 (quintet)
96.6 (quintet)
92.4 (m)
a±b ˆ 6.8
b±c ˆ 18.9
92.2 (m)
119.8 (double quintet)
26.3 (m)
f±d ˆ 8.8, f±g ˆ 8.5
g
21
22
24
25
a
b
c
d
e
f
86.1 (quintet)
93.8, 97.7
87.2, 95.4
87.1, 93.5
75.8 (m)
a±c ˆ 7.1
JAB ˆ 238
JAB ˆ 192
JAB ˆ 191
140.8 (m)
24.9 (m)
g
a
b
c
d
e
f
86.0 (m)
93.3, 98.0
86.3, 96.2
86.3, 94.0
75.8 (m)
JAB ˆ 238
JAB ˆ 189
JAB ˆ 190
142.3 (m)
59.1 (s)
g
a
b
c
d
e
f
52.9 (quintet)
89.8, 92.8
84.9, 87.6
76.1 (m)
a±b ˆ 11.9±13.8
JAB ˆ 191
JAB ˆ 189
158.2 (quintet)
112.0, 112.9
25.8
e±c ˆ 20.6±24.0
JAB ˆ 271
g
a
b
c
d
e
f
87.0 (m)
96.9 (quintet)
92.9
b±c ˆ 18.9
JAB ˆ 243
92.6
82.7, 86.6
73.3 (m)
177.2 (m)
33.8
g
h
26
a
b
c
d
e
f
85.2 (m)
94.9 (quintet)
88.0, 90.3
86.8, 88.9
75.9
b±c ˆ 18.9
JAB ˆ 193
JAB ˆ 179
158.1 (m)
112.3, 112.9
25.9
g
h
JAB ˆ 276

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
29
Table 3 (Continued )
Compound
Formula
Chemical shifta,b
J (Hz)b
28
a
b
c
d
e
f
85.2 (quintet)
95.0 (quintet)
89.4 (m)
a±c ˆ 8.5±8.8
b±c ˆ 18.9
88.0 (m)
77.3 (quintet)
160.5 (quintet)
e±d ˆ 8.6
f±d ˆ 24.1
29
a
86.1 (quintet)
95.6, 96.2
a±c ˆ 6.8
b
JAB ˆ 238 (F1±cˆ 18.9±
20.6; F2±cˆ 17.2±20.9)
JAB ˆ 200
c
d
e
f
90.4, 91.6
90.4 (m)
136.0 (m)
70.4, 83.5
117.2, 127.4
79.8, 91.3
JAB ˆ 135
JAB ˆ 250
JAB ˆ 127
g
h
30
a
b
c
d
e
f
52.8 (quintet)
91.7, 92.9
89.4, 90.1
135.4 (m)
a±b ˆ 13.0
JAB ˆ 189
JAB ˆ 192
117.2, 127.4
70.1, 83.3
80.0, 91.4
JAB ˆ 257
JAB ˆ 133
JAB ˆ 127
g
34
a
b
c
d
e
f
52.5 (quintet)
93.7 (quintet)
90.7 (m)
a±b ˆ 12.1
b±a ˆ 13.8
91.7 (quintet)
119.7 (quintet)
d 3.99 (s)
d±c ˆ 18.9
e±c ˆ 11.3
37
a
b
c
d
e
f
86.9 (quintet)
96.7 (quintet)
92.6
a±c ˆ 8.5
b±c ˆ 18.9
b±a ˆ 13.8
92.3
92.9 (quintet)
120.6 (quintet)
d 3.98 (s)
e±d ˆ 17.2±18.9
f±d ˆ 8.5
g
40
a
b
c
d
e
f
86.0 (m)
93.3, 98.2
86.3, 96.3
86.0, 94.5
76.7 (m)
JAB ˆ 238
JAB ˆ 206
JAB ˆ 197
142.4 (m)
d 4.00 (s)
g
44
45
a
b
c
d
e
f
52.4 (quintet)
93.7 (quintet)
90.8 (m)
a±b ˆ 13.8
b±a ˆ 13.8
91.1 (m, broad)
127.5 (quintet)
81.3 (triplet)
e±c ˆ 10.4±11.9
f±d ˆ 8.8±10.2
a
b
c
d
e
f
52.3 (quintet)
93.9, 94.8
90.7, 92.1
83.8, 84.7
73.6 (m)
a±b ˆ 13.8
JAB ˆ 195
JAB ˆ 190
JAB ˆ 239
178.7 (m)
g
d 3.97 (s)

30
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
Table 3 (Continued )
Compound
Formula
Chemical shifta,b
J (Hz)b
46
a
b
c
d
e
f
86.8 (quintet)
96.7 (quintet)
92.7 (m)
a±c ˆ 7.1
b±c ˆ 18.9
92.3 (m)
92.0 (m)
128.3 (quintet)
81.3 (triplet)
f±d ˆ 10.4
g
g±e ˆ 8.8±10.4
47
a
b
c
d
e
f
81.7 (quintet)
97.0 (quintet)
92.8 to 92.9 (m)
92.8 to 92.9 (m)
84.5, 85.7
73.6 (m)
a±c ˆ 7.1±8.5
b±c ˆ 17.2±20.6
JAB ˆ 237
g
h
178.9 (m)
d 3.96 (s)
49
50
a
b
c
d
e
52.4 (quintet)
91.5
a±b ˆ 12.1±13.8
87.7
77.4 (double quintet)
160.9 (heptet)
d±c ˆ 10.2, d±e ˆ 3.4
e±d ˆ 3.4
a±b ˆ 13.5
JAB ˆ 195
JAB ˆ 196
a
b
c
d
e
f
52.9 (quintet)
87.7, 95.3
85.0, 89.5
75.3 (m)
158.3 (triple triplet)
114.1 (m)
e±c ˆ 22.3±26.8
g
d 3.98 (s)
51
a
b
c
d
e
f
85.1 (quintet)
93.4 (F1), 96.5(F2)
86.7, 91.6
a±c ˆ 8.7
JAB ˆ 239, F2-c ˆ 18.9
JAB ˆ 190
85.1, 90.1
75.1 (m)
JAB ˆ 195
158.3 (quintet)
114.2 (double quartet)
d 3.98 (s)
f±d ˆ 20.6±27.9
g±e ˆ g±f ˆ 10.4
g
h
a
19F chemical shifts in ppm relative to internal CCl3F (negative shifts are upfield) and 1H chemical shifts in ppm relative to TMS.
b Only obvious chemical shifts and coupling constants are given.
‡
‡
‡
per¯uoro(1,4-dimethylpiperazine) (33) (1.2 g), per¯uoro[3-
(N,N-diethylamino)propionyl ¯uoride] (16) [21] (0.4 g),
per¯uoro(4-methyl-1-ethylpiperazine) (17) (0.6 g) and uni-
denti®ed products (2.1 g). Cell drainings (19.9 g): 13 (1.0 g),
33 (1.8), 16 (2.9 g), 17 (4.9 g), per¯uoro[3-(4-methylpiper-
azinyl)propionyl ¯uoride] (14) (7.5 g) and unidenti®ed pro-
ducts (1.8 g). The GC yield of 14 was 8.0%. Spectral data
(IR and MS) of 14 are shown below. 19F NMR data of 14 are
shown in Table 3.
(64.8), 114 C2F4N (39.3), 100 C2F4 (39.2), 95 C2F3N
‡
‡
‡
(2.5), 81 C3F3 (1.2), 76 C2F2N (2.3), 69 CF3 (100), 50
‡
CF2 (6.8).
Further characterization of 14 was conducted in a form of
the methyl ester. Methyl ester (34) of 14 were prepared by
mixing about 5 g of cell drainings with 2 ml of methanol.
The reaction was completed within a few minutes. The lower
layer of the reaction mixture was separated by means of
semi-preparative GC to give 34.
Per¯uoro[3-(4-methylpiperazinyl)propionyl
¯uoride]
Methyl
(34) (nc) had bp 171.0±171.78C, d4 1.7675 and nD
per¯uoro[3-(4-methylpiperazinyl)propionate]
20
20
(14) (nc): IR (gas): 1886 n(C=O) (ms), 1358 (vs), 1338
(m), 1311 (vs), 1268 (ms), 1230 (vs), 1180 (ms), 1121 (m),
1092 (w), 1077 (w), 986 (w), 959 (ms), 896 (w), 800 (w),
1.3223. IR (capillary ®lm): 2968 (w) n(CH), 1789 n(C=O)
(s), 1444 (w), 1351 (s), 1302 (vs), 1269 (s), 1217 (s), 1166
(vs), 1087 (m), 1071 (m), 1015 (m), 954 (s), 894 (m), 853
(w), 826 (w), 792 (m), 729 (m), 744 (m), 679 (w). MS: 437
‡
742 (w), 731 (w), 691 (w). MS: 425 [M F] (0.7), 347
‡
‡
‡
‡
‡
‡
‡
[M CF2C(O)F] (9.6), 259 C5F9N2 (7.7), 214 C4F8N
(0.9), 209 C4F9N2 (1.4), 171 C4F5N2 (3.1), 164 C3F6N
‡ ‡
[M F] (0.6), 347 [M CF2C(O)OCH3] (7.8), 259
‡
‡
‡ ‡ ‡
C5F9N2 (4.5), 171 C4F5N2 (1.8), 164 C3F6N (7.3),
(15.9), 147 C2F5N2 (3.4), 145 C3F5N (1.8), 119 C2F5

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
31
‡
‡
‡
159 C2F4C(O)CH3 , C3F5N2 (8.3), 145 C3F5N (2.4), 131
‡
Pe¯uoro[3-(4-ethylpiperazinyl)propionyl ¯uoride] (15)
[12]: IR (gas): 1885 n(C=O) (m), 1340 (s), 1304 (s), 1270
(ms), 1252 (vs), 1214 (m, sh), 1185 (s), 1121 (w), 1102 (w),
1068 (m), 987 (w), 956 (m), 824 (w), 796 (w), 731 (w), 662
‡
‡
C3F5 (14.0), 119 C2F5 (15.2), 114 C2F4N (19.5), 100
‡
‡
‡
‡
‡
C2F4 (27.8), 97 C2F3O (3.2), 95 C2F3N (1.3), 81 C2F3
‡
‡
(8.1), 76 C2F2N (1.2), 69 CF3 (43.7), 59 [C(O)OCH3]
‡
‡ ‡
(100), 50 CF2 (2.6). Analysis: Calc. for C9F15N2O2H3: C,
23.68%; F, 62.5%. Found: C, 23.80%; F, 62.3%. 19F NMR
data of 34 are shown in Table 3.
(w). MS: 475 [M F] (0.8), 425 [M CF3] (1.2), 397
‡
‡
[M CF2C(O)F] (10.8), 309 C6F11N2 (3.8), 259
‡
‡
‡
C5F9N2 (4.9), 214 C4F8N (1.4), 171 C4F5N2 (3.8),
‡ ‡
‡
‡
Compound 14 was derivatized into an amide of p-meth-
oxyaniline for further characterization also: into a 100 ml
polytetra¯uoroethylene beaker, was placed 0.23 g
(1.9 mmol) of p-methoxyaniline dissolved in 10 ml of
dichloromethane and 0.23 g (2 mmol) of triethylamine,
and compound 14 (1.01 g, 2 mmol) which was isolated
by preparative GC was added dropwise while shaking.
The mixture was left standing in the draft overnight. The
residue was dissolved in a mixture of hexane and acetonitrile
(1:1) and analyzed by TLC. The crude product was puri®ed
by column chromatography (hexane/acetonitrile as eluent)
to give per¯uoro[3-(4-methylpiperazinyl)propionyl]-p-
methoxyanilide (35) as white crystals (0.52 g, 46% yield).
Per¯uoro[3-(4-methylpiperazinyl)propionyl]-p-methoxya-
nilide (35) (nc) had mp 82.3±83.08C. IR (KBr): 1701
164 C3F6N (15.4), 147 C3F5O (2.8), 145 C3F5N
‡
‡
(1.6), 119 C2F5 (100), 114 C2F4N (33.4), 100 C2F4
‡
‡
‡
(32.6), 95 C2F3N (1.8), 76 C2F2N (1.9), 69 CF3 (45.8),
‡
50 CF2 (4.4).
Methyl ester (37) of 15 were prepared in a similar manner
as explained for 14.
Methyl per¯uoro[3-(4-ethylpiperazinyl)propionate] (37)
(nc) had bp 181.2±181.78C, d420 1.7712 and nD20 1.3193. IR
(capillary ®lm): 2968 n(CH) (w), 1788 n(C=O) (s), 1444 (w),
1333 (s), 1297 (vs), 1260±1227 (s±vs), 1200±1166 (s±vs),
1101 (w), 1063(s), 1015 (s), 951 (s), 821 (s), 756 (s), 739 (s),
726 (m), 696 (m), 676 (m), 656 (ms), 623 (m), 613 (w). MS:
‡
‡
‡
‡
‡
‡
447 [M C(O)OCH3] (0.5), 397 [M CF2C(O)OCH3]
‡
‡
(8.6), 309 C6F11N2 (2.1), 259 C5F9N2 (4.3), 214 C4F8N
‡
‡
(1.3), 171 C4F5N2 (2.9), 164 C3F6N (10.2), 159 C3F5N2
(11.9), 149 C3F5O (1.0), 145 C3F5N (2.7), 131 C3F5
‡
‡ ‡
n(C=O) (ms). MS: 547 [M ‡ 1] (0.9), 149 C(O)NHPh-
‡
‡
‡ ‡
(22.1), 119 C2F5 (52.8), 114 C2F4N (24.7), 100 C2F4
OCH3 (54.6), 134 C(O)NHPhO (22.5), 122 NHPhOCH3
‡
‡
‡
‡
‡
‡ ‡ ‡
(100), 119 C2F5 (17.2), 114 C2F4N (19.1), 100 C2F4
‡
(40.3), 97 C2F3O (5.4), 95 C2F3N (1.6), 81 C2F3 (12.0),
‡
‡
‡
(17.2), 95 C2F3N (18.3), 69 CF3 (54.1), 52 CF2H2
‡
76 C2F2N (1.4), 69 CF3 (32.3), 59 [C(O)OCH3] (100),
‡
‡
(23.3), 51 CF2H (11.9) 50 CF2 (8.4). 19F NMR (CDCl3):
50 CF2 (3.7). Analysis: Calc. for C10F17N2O2H3: C,
d
52.4 (quintet, 3F, JF ˆ 13:8 Hz, CF N), d 90.5 [m,
23.72%; F, 63.8%. Found: C, 23.80%; F, 63.7%. 19F
NMR data of 37 are shown in Table 3.
F
3
4F, c-CF3N(CF2CF2)2N], d 91.2 [quintet, 2F, JF
18:9 20:9 Hz, NCF2CF2C(O)O)], d 93.6 [quartet, 4F,
11.9±13.8 Hz, c-CF3N(CF2CF2)2N], d 120.8 (quintet,
ˆ
F
3.5. Fluorination of methyl 2-(4-methylpiperazinyl)-
propionate (4)
1
2F, JF ˆ 10:4 Hz, NCF CF C(O)O), H NMR (CDCl ):
F
2
2
3
d 7.90 (s, 1H, NH), d 7.45 (d, 2H), d 6.91 (d, 2H), d 3.81 (s,
3H, OCH3). Analysis: Calc. for C15F15N3O2H8: C, 32.91%;
F, 52.10%. Found: C, 33.04%; F, 51.9%.
Sample 4 (39.7 g, 0.213 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.6±6.7 V, 7±
88C, 575 min (211 A h). The work-up gave the following
products in the 788C trap (6.7 g): 31 (0.9 g), 32 (1.2 g),
per¯uoro[2-(N,N-dimethylamino)propionyl ¯uoride] (38)
[22] (1.0 g), 13 (1.7 g), 33 (0.3 g), 17 (0.5 g) and unidenti-
®ed products (1.1 g). Cell drainings (16.0 g): 13 (0.9 g),
per¯uoro(4-methyl-1-ethylpiperazine) (17) (5.2 g), per-
¯uoro[2-(4-methylpiperazinyl)propionyl ¯uoride] (19)
(7.1 g), per¯uoro[methyl 2-(4-methylpiperazinyl)propio-
nate] (20) (0.6 g) and unidenti®ed products (2.2 g). The
GC yields of 19 and 20 were 7.5 and 0.5%, respectively.
Spectral data (IR, Mass and 19F NMR) of 19 and 20, and
the methyl ester of per¯uoro[2-(4-methylpiperazinyl)pro-
pionic acid] have been reported in our previous paper [8].
Therefore, the physical property (mp) and spectral data (IR,
3.4. Fluorination of methyl 3-(4-ethylpiperazinyl)pro-
pionate (3)
Sample 3 (39.7 g, 0.198 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.8±6.1 V, 7±
88C, 638 min (233 A h). The work-up gave the following
products in the 788C trap (6.5 g): 31 (1.2 g), 32 (0.7 g),
per¯uoro[3-(N,N-dimethylamino)propionyl ¯uoride] (36)
[22] (0.4 g), 13 (2.4 g), 17 (0.4 g), per¯uoro(1,4-diethylpi-
perazine) (18) (0.5 g) and unidenti®ed products (0.9 g). Cell
drainings (31.8 g): 13 (1.2 g), 16 (0.5 g), 17 (3.1 g), 18
(11.3 g), per¯uoro[3-(4-ethylpiperazinyl)propionyl ¯uor-
ide] (15) (14.0 g) and unidenti®ed products (1.7 g). The
GC yield of 15 was 14.3%. Spectral data (IR and MS) of
15 will be shown below as no data except the bp (86±888C/
0.6 mmHg) and mp (56±598C) of per¯uoro[3-(4-ethylpiper-
azinyl)propionic acid] which was derived by a hydrolytic
reaction of 15 are described in the patent literature [12]. 19F
NMR data of 15 are shown in Table 3.
1
MS and 19F and H NMR) of p-methoxyanilide (39) of
per¯uoro[2-(4-methylpiperazinyl)propionic acid], which
was prepared in a similar manner as explained for 14, will
be reported.
Per¯uoro[2-(4-methylpiperazinyl)propionyl]-p-methox-
yanilide (39) (nc) had mp 124.0±124.58C (55% yield). IR
‡
(KBr disk): 1705 n(C=O) (s). MS: 547 [M ‡ 1] (0.7), 149

32
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
‡
‡
C(O)NHPhOCH3 (30.7), 134 C(O)NHPhO (9.7), 122
‡
Methyl per¯uoro[2-(4-ethylpiperazinyl)propionate] (40)
(nc) had bp 180.0±180.78C, nD20 1.3212 and d420 1.7808. IR
(capillary ®lm): 2968 n(CH) (w), 1789 (s) n(C=O), 1443 (m),
1408 (w), 1340±1225 (s±vs), 1175 (vs), 1125 (s), 1084 (ms),
1067 (ms), 1046 (s), 951 (s), 932 (w), 919 (w), 842 (w), 820
(ms), 841 (w), 820 (w), 792 (w), 776 (m, sh), 739 (s), 719
(w), 689 (w), 676 (w), 668 (w), 641 (w), 624 (w). MS: 487
‡
NHPhOCH3 (100), 119 C2F5 (22.1), 114 C2F4N (12.5),
‡
‡
‡
100 C2F4 (12.8), 95 C2F3N (15.7), 77 C2F2NH (11.4), 69
‡
‡
‡
CF3 (42.9), 53 ? (11.1), 52 CF2H2 (19.1), 51 CF2H
(10.3). 19F NMR (CDCl3): d 52.8 (triple triplet, 3F,
JF ˆ 8:8 and 10.2 Hz, CF N), d 85.6, 99.3 [4F,
F
3
JAB ˆ 192 Hz, c-C2F5N(CF2CF2)2N], d
83.4,
94.8
‡
‡
‡
[4F, JAB ˆ 189 Hz, c-C2F5N(CF2CF2)2N], d 73.7 [m,
[M F]
(0.5), 447 [M C(O)OCH3]
‡
‡ ‡
(0.9), 309
‡
1
3F, NCF(CF3)], d 133.6 [m, 1F, NCF(CF3)]. H NMR
C6F11N2 (2.2), 214 C4F8N (2.2), 195 C4F7N (2.8),
(CDCl3): d 7.88 (s, 1H, NH), d 7.43 (d, 2H), d 6.92 (d, 2H), d
3.82 (s, 3H, OCH3). Analysis: Calc. for C15F15N3O2H8: C,
32.91%; F, 52.1%. Found: C, 33.03%; F, 52.2%.
164 C3F6N (7.4), 159 [C2F4C(O)OCH3] (1.2), 145
‡
‡
‡
C3F5N (1.8), 131 C3F5 (12.9), 119 C2F5 (21.1), 114
‡
‡
‡
‡
‡
C2F4N (7.7), 100 C2F4 (13.9), 97 C2F3O (1.8), 81 C2F3
‡
‡
(3.9), 69 CF3 (14.5), 59 [C(O)OCH3] (100), 50 CF2
3.6. Fluorination of methyl 2-(4-ethylpiperazinyl)pro-
pionate (5)
(1.6). Analysis: Calc. for C10F17N2O2H3: C, 23.72%; F,
63.8%. Found: C, 23.85%; F, 63.6%.
Per¯uoro[2-(4-ethylpiperazinyl)propionyl]-p-methoxya-
nilide (41) (nc) had mp 105.5±106.08C (60% yield). IR (KBr
Sample 5 (39.2 g, 0.196 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.8±6.3 V, 7±
88C, 572 min (209 A h). The work-up gave the following
products in the 788C trap (5.1 g): 31 (1.5 g), 32 (0.4 g), 38
(0.7 g), 13 (1.6 g), 17 (0.3 g), 18 (0.2 g) and unidenti®ed
products (0.4 g). Cell drainings (30.1 g): 13 (0.4 g), 17
(0.5 g), 18 (11.2 g), per¯uoro[2-(4-ethylpiperazinyl)propio-
nyl ¯uoride] (21) (15.2 g), per¯uoro[methyl 2-(4-ethyl-
piperazinyl)propionate] (22) (1.0 g) and unidenti®ed
products (1.8 g). The GC yields of 21 and 22 were 15.7
and 0.9%, respectively.
‡
disk): 1712 n(C=O) (ms). MS: 597 [M ‡ 1] (0.5), 221 ?
‡
‡
‡
(0.9), 164 C3F6N (0.8), 150 C3F6 (1.0), 149 C8H7NO2
(32.8), 134 C2F5NH (8.9), 123 C7H9NO2 (7.9), 122
‡
‡
‡
‡
‡
C7H8NO2 (100), 119 C2F5 (35.7), 114 C2F4N (12.4),
‡
‡
‡
100 C2F4 (15.2), 95 C2F3N (16.0), 77 C2F2NH (10.6), 69
‡
‡
‡
CF3 (25.2), 53 ? (11.0), 52 CF2H2 (20.5), 51 CF2H
(10.5). 19F NMR (CDCl3): d 73.8 (m, 3F, NCF(CF3), d
84.2, 85.5 (2F, JAB ˆ 184 Hz, CF3CF2N) d 85.4,
97.5 [4F, JAB ˆ 203 Hz, c-C2F5N(CF2CF2)2N],
d
84.1, 94.4 [4F, JAB ˆ 195 Hz, c-C2F5N(CF2CF2)2N],
Spectral data (IR and Mass) of 21 and 22 including the
physicochemical properties for the former one are shown
below. 19F NMR data of 21 and 22 are shown in Table 3.
Per¯uoro[2-(4-ethylpiperazinyl)propionyl ¯uoride] (21)
d
85.7 [quintet, JF ˆ 8:8, CF CF N], d 134.3 [m,
F
3
2
1
1F, NCF(CF3)]. H NMR (CDCl3): d 7.86 (s, 1H, NH), d
7.43 (d, 2H), d 6.92 (d, 2H), d 3.82 (s, 3H, OCH3). Analysis:
Calc. for C16F17N3O2H8: C, 32.16%; F, 54.1%. Found: C,
32.12%; F, 54.2%.
20
20
(nc) had bp 138.5±139.58C, nD 1.3007 and d4 1.8386.
IR (gas): 1898 (m) and 1881 (ms) n(C=O), 1326 (s), 1302 (s),
1247 (vs, broad), 1185 (vs), 1135 (m), 1107 (w), 1186 (w),
1071 (w), 1053 (ms), 1044 (ms), 981 (m), 955 (m), 824 (w),
3.7. Fluorination of methyl 3-(4-methylpiperazinyl)-2-
methylpropionate (6)
‡
810 (w), 741 (ms), 697 (w). MS: 475 [M F] (0.7), 447
‡
‡
‡
‡
‡
[M COF] (4.0), 425 [M CF3] , 309 C6F11N2 (4.3),
‡
‡
259 C5F9N2 (1.2), 214 C4F8N (9.4), 171 C4F5N2 (1.6),
‡
Sample 6 (39.7 g, 0.199 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.8±6.1 V, 7±
88C, 656 min (239 A h). The work-up gave the following
products in the 788C trap (10.0 g): per¯uoro(iso-propionyl
¯uoride) (42) (3.1 g), per¯uoro[3-(N,N-dimethylamino)-2-
methylpropionyl ¯uoride] (43) [9] (2.2 g), 33 (0.5 g), 17
(1.0 g), per¯uoro[3-(N,N-diethylamino)-2-methylpropionyl
¯uoride] (27) [9] (0.9 g) and unidenti®ed products (2.3 g).
Cell drainings (40.2 g): 43 (0.9 g), 27 (12.1 g), per¯uoro[4-
methyl-1-(propyl)piperazine] (44) (3.1 g), per¯uoro[3-(4-
‡
164 C3F6N (19.7), 145 C3F5N (1.8), 126 C3F4N (0.5),
‡
‡
‡
119 C2F5 (100), 114 C2F4N (26.5), 100 C2F4 (31.9), 95
‡
‡
‡
‡
C2F3N (2.1), 76 C2F2N (2.8), 69 CF3 (50), 50 CF2
(5.6).
Per¯uoro[methyl 2-(4-ethylpiperazinyl)propionate] (22)
(nc): IR (gas): 1854 (m) and 1840 (m) n(C=O), 1324 (m),
1289 (ms), 1256 (vs), 1219 (m), 1185 (ms), 1153 (ms), 1107
(w), 1089 (w), 1054 (w), 1019 (w), 955 (w), 824 (w), 788
‡
(w), 741 (w). MS: 491 [M F]
‡
(0.2), 447
(0.5), 309
‡
[M C(O)OCF3]
‡
(2.0), 397 C7F15N2
‡
methylpiperazinyl)-2-methylpropionyl
¯uoride]
(23)
‡
C6F11N2 (6.3), 259 C5F9N2 (0.3), 214 C4F8N (3.0),
‡
(21.7 g) and unidenti®ed products (2.4 g). The GC yield
of 23 was 22.1%.
‡
‡
195 C4F7N (1.8), 164 C3F6N (6.3), 145 C3F5N (1.5),
‡
‡
‡
119 C2F5 (30.2), 114 C2F4N (7.7), 100 C2F4 (12.7), 76
‡
Spectral data (IR, MS and 19F NMR) of 23 have been
reported in our previous paper [9]. Therefore, physicochem-
ical properties and spectral data of 44 and methyl per-
¯uoro[3-(4-methylpiperazinyl)-2-methylpropionate] (45),
which had not been characterized yet, will be described.
19F NMR data of 44 and 45 are shown in Table 3.
‡
‡
C2F2N (1.1), 69 CF3 (100), 50 CF2 (5.3).
Methyl ester (40) and p-methoxyanilide (41) of per-
¯uoro[2-(4-methylpiperazinyl)propionic acid] were pre-
pared in a similar manner as explained for 16. 19F NMR
data of 40 are shown in Table 3.

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
33
‡
‡
‡
‡
Per¯uoro[4-methyl-1-(propyl)piperazine] (44) (nc) had
C2F4 (69.0), 95 C2F3N (2.1), 76 C2F2N (1.8), 69 CF3
‡
20
20
bp 121.2±121.88C, nD 1.2874 and d4 1.8386. IR (gas):
1359 (s), 1311 (s), 1273 (ms), 1233 (vs), 1179 (ms), 1151
(w), 1136 (w), 1102 (w), 1076 (w), 979 (m), 959 (ms), 895
(100), 50 CF2 (5.7).
Per¯uoro[4-ethyl-1-(propyl)piperazine] (46) (nc) had bp
137.0±137.68C, nD20 1.2883 and d420 1.8384. IR (gas): 1340
(s), 1307 (s), 1271 (s), 1252 (vs), 1235 (s), 1184 (s), 1137
(w), 1108 (w), 1070 (ms), 978 (ms), 956 (ms), 824 (w), 793
‡
(w), 796 (w), 739 (ms), 666 (w), 626 (w). MS: 447 [M F]
‡
‡
(2.1), 347 [M C2F5] (13.1), 259 C5F9N2 (11.1), 214
‡
‡
‡
‡
C4F8N (2.4), 209 C4F7N2 (1.3), 171 C4F5N2 (2.8), 169
‡
(w), 741 (ms), 665 (w), 647 (w). MS: 497 [M F] (1.8),
‡
‡
‡ ‡
‡
‡
‡
‡
‡
C3F7 (34.7), 164 C3F6N (13.3), 145 C3F5N (2.0), 121
‡
447 [M CF3] (2.8), 397 C7F13N2 (11.7), 359 C7F13N2
‡ ‡
(2.0), 309 C6F11N2 (9.5), 264 C5F10N (2.0), 259 C5F9N2
‡
‡
C3F3N2 (2.0), 119 C2F5 (16.3), 114 C2F4N (30.7), 100
‡
‡
‡
‡
‡ ‡
C2F4 (46.7), 95 C2F3N (2.2), 76 C2F2N (1.7), 69 CF3
‡
(7.7), 214 C4F8N (5.1), 171 C4F5N2 (6.1), 169 C3F7
‡ ‡
(65.9), 164 C3F6N (26.7), 145 C3F5N (3.2), 119 C2F5
(100), 50 CF2 (4.0). Analysis: Calc. for C8F18N2: C,
20.60%; F, 73.1%. Found: C, 20.58%; F, 73.0%.
Methyl per¯uoro[3-(4-methylpiperazinyl)-2-methylpro-
pionate] (45) had bp 179.5±180.08C, nD 1.2874 and
d4 1.8386. IR (capillary ®lm): 2969 n(CH) (w), 1793
‡
‡
(97.3), 114 C2F4N (55.4), 100 C2F4 (83.7), 95 C2F3N
‡
‡
‡
(3.1), 81 C2F3 (1.3), 76 C2F2N (2.8), 69 CF3 (100), 50
‡
20
CF2 (7.7). Analysis: Calc. for C9F20N2: C, 20.93%; F,
73.6%. Found: C, 20.83%; F, 73.3%.
20
(ms) and 1780 (m) n(C=O), 1443 (w), 1351 (s), 1301
(vs), 1262 (s), 1226 (vs), 1164 (s), 1090 (m), 1070 (w),
1045 (m), 1034 (m), 1019 (w), 968 (m), 953 (s), 892 (m), 852
(m), 808 (w), 780 (m), 743 (w), 729 (w), 701 (w), 620 (w).
For the further characterization of 25, it was derivatized
into the corresponding methyl ester (47) similarly. It was a
compound like sherbet at room temperature.
Methyl per¯uoro[3-(4-ethylpiperazinyl)-2-methylpropio-
nate] (47) (nc) had bp 192.0±192.58C. IR (capillary ®lm):
2969 n(CH) (w), 1792 and 1980 n(CO) (ms), 1443 (w), 1335
(s), 1295 (s), 1250±1245 (s±vs), 1226 (s), 1201 (m), 1165 (s),
1099 (w), 1065 (s), 1046 (m), 1034 (m), 967 (w), 951 (s),
823 (m), 807 (w), 780 (m), 755 (w), 739 (ms), 697 (w),
‡
‡
‡
MS: 347 [M CF(CF3)C(O)OCH3] (2.3), 259 C5F9N2
‡
‡
(2.2), 209 C3F6C(O)OCH3 , C4F7N2 (5.5), 197 C4F7N2
‡
‡
‡
(2.0), 169 C3F7 (2.8), 164 C3F6N (4.1), 150 C3F6 (9.1),
‡
‡
‡
145 C3F5N (1.1), 131 C3F5 (3.6), 119 C2F5 (4.8), 114
‡
‡
‡
‡
C2F4N (12.9), 100 C2F4 (10.8), 81 C2F3 (10.4), 69 CF3
‡
‡
‡
(31.5), 59 [C(O)OCH3] (100), 50 CF2 (1.4). Analysis:
Calc. for C10F17N2O2H3: C, 23.72%; F, 63.8%. Found: C,
23.70%; F, 63.8%.
674 (w), 642 (m). MS: 397 [M CF(CF3)C(O)OCH3]
‡
‡
(1.9), 309 C6F11N2 (0.8), 259 C5F9N2 (1.6), 209
‡
‡
‡
C3F7C(O)OCH3 , C4F7N2 (7.7), 197 C3F7N2 (2.4), 169
‡
‡
‡
C3F7 (3.3), 164 C3F6N (4.9), 159 C3F5N2 (1.1), 150
‡
‡
‡
C3F6 (10.5), 145 C3F5N (1.0), 131 C3F5 (4.1), 119
C2F5 (18.6), 114 C2F4N (14.7), 100 C2F4 (11.6), 81
‡ ‡ ‡
3.8. Fluorination of methyl 3-(4-ethylpiperazinyl)-2-
methylpropionate (7)
‡
‡
‡
C2F3 (11.9), 69 CF3 (21.3), 59 [C(O)OCH3] (100), 50
CF2 (1.4). Analysis: Calc. for C11F19N2O2H3: C, 23.74%;
F, 64.9%. Found: C, 23.90%; F, 65.2%.
‡
Sample 7 (40.0 g, 0.187 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.6±6.0 V, 7±
88C, 632 min (232 A h). The work-up gave the following
products in the 788C trap (6.6 g): 42 (1.2 g), 31 (1.1 g), 43
(2.1 g) and unidenti®ed products (2.2 g). Cell drainings
(53.1 g): 27 (1.9 g), per¯uoro[4-ethyl-1-(propyl)piperazine]
(46) (5.0 g), per¯uoro[3-(4-ethylpiperazinyl)-2-methyl-
propionyl ¯uoride] (25) (38.2 g) and unidenti®ed products
(8.0 g). The GC yield of 25 was 37.5%.
19F NMR data of 46 and 47 are shown in Table 3.
3.9. Fluorination of methyl 3-(4-methylpiperazinyl)buty-
rate (8)
Sample 8 (40.5 g, 0.203 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.9±6.1 V, 7±
88C, 619 min (229 A h). The work-up gave the following
products in the 788C trap (12.0 g): per¯uoro(propionyl
¯uoride) (48) (2.1 g), 32 (2.9 g), 13 (2.7 g), 17 (0.9 g) and
unidenti®ed products (3.4 g). Cell drainings (26.9 g): 17
(2.0 g), per¯uoro[4-methyl-1-(iso-propyl)piperazine] (49)
(3.2 g), per¯uoro[3-(4-methylpiperazinyl)butyryl ¯uoride]
(24) (10.9 g), per¯uoro[3-(4-methylpiperazinyl)oxolane]
(30) (4.6 g) and unidenti®ed products (6.2 g). The GC yield
of 24 was 10.9%.
Spectral data (IR and MS) of 24 and physicochemical
properties and spectral data (IR and Mass) of 30 and 49 are
shown below. 19F NMR data of 49 isolated by preparative
GC revealed that it contained small quantities of per-
¯uoro[4-methyl-1-(propyl)piperazine] (43). 19F NMR data
of 24, 49 and 30 are shown in Table 3.
Physicochemical properties and spectral data (IR and MS)
of 25 and 46 are shown below. 19F NMR data of 25 and 46
are shown in Table 3.
Per¯uoro[3-(4-ethylpiperazinyl)-2-methylpropionyl ¯uo-
20
20
ride] (25) had bp 138.5±139.58C, nD 1.3005 and d4
1.8512. IR (gas): 1890 (m) and 1875 (m) n(CO), 1340
(s), 1230 (s), 1271 (s), 1252 (vs), 1184 (ms), 1155 (w),
1069 (ms), 1011 (w), 988 (w), 970 (w), 955 (m), 824 (w),
789 (w), 756 (w), 741 (m), 692 (w), 630 (w). MS:
‡
‡
‡
525 [M F] (0.3), 475 [M CF3] (2.3), 397 [M
‡
‡
C2F4C(O)F] (4.3), 309 C6F11N2 (1.5), 259 C5F9N2
‡
‡
(3.9), 214 C4F8N (1.5), 197 C4F7N2 (22.3), 171
‡
‡
‡
C4F5N2 (1.8), 169 C3F7 (32.9), 164 C3F6N (14.2),
‡
‡
‡
150 C3F6 (3.2), 145 C3F5N (1.9), 131 C3F5 (2.3), 128
‡
‡
‡
C4F4N2 (2.4), 119 C2F5 (51.8), 114 C2F4N (33.8), 100

34
T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
Per¯uoro[3-(4-methylpiperazinyl)butyryl ¯uoride] (24)
C, 23.81%; F, 63.5%. 19F NMR data of 50 are shown in
Table 3.
(nc): IR (gas): 1886 n(CO) (ms), 1413 (w), 1360 (vs),
1296 (s), 1270 (s), 1227 (vs), 1199 (m), 1177 (ms), 1124
(w), 1092 (w), 1075 (w), 1031 (w), 960 (ms), 928 (w), 897
3.10. Fluorination of methyl 3-(4-ethylpiperazinyl)butyrate
(9)
‡
(m), 855 (w), 788 (w), 732 (m). MS: 425 [M F] (0.8),
‡
‡
397 [M C(O)F] (4.9), 359 C7F13N2 (0.4), 309
‡
‡
‡
‡
C6F11N2 (1.5), 264 C5F10N (3.2), 259 C5F9N2 (1.9),
‡
Sample 9 (40.3 g, 0.188 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.9±6.0 V, 7±
88C, 656 min (237 A h). The work-up gave the following
products in the 788C trap (7.1 g): 48 (trace), 32 (1.1 g), 13
(2.4 g), 18 (0.3 g) and unidenti®ed products (3.3 g). Cell
drainings (56.1 g): 18 (9.3 g), per¯uoro[4-ethyl-1-(iso-
propyl)piperazine] (28) (9.3 g), per¯uoro[3-(4-ethylpipera-
zinyl)butyryl ¯uoride] (26) (20.7 g), per¯uoro[3-(4-ethylpi-
perazinyl)oxolane] (29) (10.0 g) and unidenti®ed products
(6.8 g). The GC yield of 26 was 20.2%.
‡
214 C4F8N (5.7), 197 C3F7N2 (1.3), 171 C4F5N2 (1.3),
‡
‡
‡
169 C3F7 (6.6), 164 C3F6N (18.6), 145 C3F5N (2.2), 131
‡
‡
‡
C3F5 (1.5), 119 C2F5 (52.3), 114 C2F4N (18.1), 100
‡
‡
‡
‡
C2F4 (21.7), 95 C2F3N (2.1), 76 C2F2N (2.3), 69 CF3
‡
(100), 50 CF2 (4.7).
Per¯uoro[4-methyl-1-(iso-propyl)piperazine] (49) (nc)
20
20
had bp 121.0±121.68C, nD 1.2895 and d4 1.8564. IR
(gas):1413 (w), 1360 (vs), 1320±1272 (vs), 1245±1229 (vs),
1176 (m), 1149 (w), 1075 (w), 1060 (w), 978 (m), 959 (s),
897 (w), 857 (w), 796 (w), 740 (m), 730 (w), 629 (w), 546
Spectral data (IR and MS) of 26 and physicochemical
properties and spectral data (IR and Mass) of 28 and 29 are
shown below. 19F NMR of 26, 28 and 29 are shown in
Table 3.
‡
‡
(w). MS: 447 [M F] (3.2), 397 [M CF3] (19.9), 359
‡
‡
‡
C7F15N2 (3.6), 309 C6F11N2 (3.9), 264 C5F10N (12.7),
‡
‡
‡
259 C5F9N2 (3.3), 214 C4F8N (10.6), 171 C4F5N2 (1.8),
‡
‡
‡
169 C3F7 (4.4), 164 C3F6N (29.7), 145 C3F5N (3.1), 119
‡
Per¯uoro[3-(4-ethylpiperazinyl)butyryl ¯uoride] (26)
(nc): IR (gas): 1886 n(C=O) (m), 1323 (ms), 1292 (s),
1254 (vs), 1182 (ms), 1072 (w), 1030 (m), 955 (m), 928
‡
‡
C2F5 (66.2), 114 C2F4N (29.2), 100 C2F4 (47.7), 95
‡
‡
‡
‡
C2F3N (2.6), 81 C2F3 (1.2), 76 C2F2N (3.5), 69 CF3
‡
‡
‡
(100), 50 CF2 (5.8). Analysis: Calc. for C8F18N2: C,
20.60%; F, 73.4%. Found: C, 20.50%; F, 73.1%.
Per¯uoro[3-(4-methylpiperazinyl)oxolane] (30) (nc) had
(w), 826 (w), 741 (m). MS: 525 [M F] (0.4), 475
‡
[M CF3] (0.7), 447 [M CF2C(O)F] (4.2), 425
‡
‡
‡
C8F16N2O (0.2), 359 C7F13N2 (0.4), 309 C6F11N2
(2.8), 264 C5F10N (3.3), 214 C4F8N (6.4), 197
20
20
‡ ‡
bp 145.0±145.58C, nD 1.3055 and d4 1.8756. IR (gas):
1360 (s), 1316 (s), 1254 (s), 1227 (vs), 1186 (ms), 1124 (w),
1084 (m), 1073 (w), 1011 (w), 972 (m), 927 (w), 8976 (w),
‡
‡
‡
C3F7N2 (1.2), 171 C4F5N2 (1.5), 169 C3F7 (5.5), 164
‡
‡
‡
C3F6N (14.9), 150 C3F6 (1.3), 145 C3F5N (1.5), 131
C3F5 (1.5), 119 C2F5 (100), 114 C2F4N (20.3), 100
‡
‡
‡ ‡ ‡
764 (w), 732 (w). MS: 428 [M CF3] (3.7), 378 C7F14N2
‡
‡
‡
‡
‡
‡
(11.4), 321 C7F11N2 (1.1), 295 C6F11N (4.7), 264
‡
C2F4 (23.2), 95 C2F3N (1.6), 76 C2F2N (2.1), 69 CF3
‡
‡
‡
C5F10N (4.0), 245 C5F9N (7.3), 221 C5F7N2 (1.3),
‡
(57.8), 50 CF2 (4.4).
Per¯uoro[4-ethyl-1-(iso-propyl)piperazine] (28) (nc) had
‡
‡
214 C4F8N (4.6), 176 C4F6N (7.7), 169 C3F7 (2.4),
‡
‡
‡
20
20
164 C3F6N (9.9), 152 ? (1.8), 150 C3F6 (7.3), 145
‡
bp 137.3±137.98C, nD 1.2929 and d4 1.8734. IR (gas):
1324 (s), 1290 (vs), 1268 (vs), 1247 (vs), 1204 (ms), 1180
(s), 1147 (w), 1123 (w), 1086 (w), 1072 (w), 1041 (m), 978
(m), 956 (m), 826 (w), 796 (w), 741 (ms), 729 (m), 676 (w),
‡
C3F5N (21.9), 131 C3F5 (10.1), 119 C2F5 (35.6), 114
‡
‡
‡
C2F4N (21.0), 100 C2F4 (74.4), 95 C2F3N (3.2), 81
‡
‡
‡
‡
C2F3 (2.3), 76 C2F2N (4.2), 69 CF3 (100), 50 CF2
(6.1). Analysis: Calc. for C9F18N2O: C, 21.86%; F, 69.2%.
Found: C, 21.76%; F, 69.1%.
‡ ‡
621 (w). MS: 497 [M F] (0.7), 447 [M CF3] (5.9),
‡
‡
‡
‡
‡
‡
387 C7F15N2 (2.7), 309 C6F11N2 (4.4), 259 C5F9N2
(3.5), 214 C4F8N (5.0), 171 C4F5N2 (2.7), 169 C3F7
‡ ‡
For the further characterization of 24, it was derivatized
into the methyl ester (50) similarly.
Methyl per¯uoro[3-(4-methylpiperazinyl)butyrate] (50)
‡
‡
(23.0), 164 C3F6N (18.8), 145 C3F5N (1.9), 119 C2F5
(76.2), 114 C2F4N (33.1), 100 C2F4 (43.4), 95 C2F3N
(2.2), 76 C2F2N (2.3), 69 CF3 (100), 50 CF2 (4.8).
Analysis: Calc. for C9F20N2: C, 20.93%; F, 73.6%. Found:
C, 20.91%; F, 73.3%.
‡ ‡
20
20
‡
‡
‡
(nc) had bp 185.5±185.88C, nD 1.3262 and d4 1.7971.
IR (capillary ®lm): 2969 n(CH) (w), 1792 n(C=O) (s), 1444
(w), 1411 (w), 1352 (s), 1340±1171 (vs), 1070 (ms), 1050
(m), 1034 (m), 955 (s), 895 (ms), 881 (w), 853 (w), 817 (m),
776 (m), 729 (ms), 691 (w), 673 (w), 627 (m), 576 (w). MS:
Per¯uoro[3-(N-ethylpiperazinyl)oxolane] (29) (nc) had
20
20
bp 159.5±160.08C, nD 1.3065 and d4 1.8986. IR (gas):
1312 (m, broad), 1254 (vs), 1236 (s, sh), 1188 (ms), 1128
(w), 1190 (w), 1067 (w), 1011 (w), 968 (w), 923 (w), 826
‡
‡
‡
‡
447 [M C(O)OCH3] (0.3), 397 [M CF2C(O)OCH3]
‡
‡
(6.1), 309 C6F11N2 (1.1), 264 C5F10N (1.5), 259 C5F9N2
‡
‡
‡
(1.1), 214 C4F8N (2.7), 209 C3F6C(O)OCH3 , C4F7N2
‡
(w), 762 (w), 741 (w). Mass: 525 [M F] (1.2), 478
C9F18N2 (2.0), 428 C8F16N2 (6.7), 295 C6F11N (2.1),
‡
‡
‡ ‡ ‡
(8.0), 181 C4F7 (1.2), 164 C3F6N (6.7), 150 C3F6 (7.8),
‡
‡
‡
‡ ‡ ‡
264 C5F10N (5.1), 245 C5F9N (4.7), 214 C4F8N (4.3),
145 C3F5N (2.1), 131 C3F5 (2.9), 119 C2F5 (15.8), 114
‡
‡
‡
‡ ‡ ‡
C2F4N (13.1), 100 C2F4 (10.9), 95 C2F3N (1.1), 81
‡
195 C4F7N (16.0), 176 C4F6N (5.4), 169 C3F7 (2,5), 164
‡
‡
‡ ‡ ‡
C3F6N (14.6), 150 C3F6 (8.3), 145 C3F5N (13.8), 131
C2F3 (2.1), 76 C2F2N (1.1), 69 CF3 (36.3), 59
‡
‡
‡ ‡ ‡
[C(O)OCH3] (100), 50 CF2 (1.6). Analysis: Calc.
for C10F17N2O2H3: C, 23.72%; F, 63.8%. Found:
C3F3 (10.3), 119 C2F5 (100), 114 C2F4N (34.5), 100
‡
‡
‡
‡
C2F4 (86.7), 81 C3F3 (2.7), 76 C2F2N (5.0), 69 CF3

T. Abe et al. / Journal of Fluorine Chemistry 108 (2001) 21±35
35
‡
[3] F.G. Drakesmith, in: R.D. Chambers (Ed.), Organofluorine Chem-
istry, Technique and Synthons, Topics in Current Chemistry,
Springer, Berlin, 1997, pp. 197±242.
(85), 50 CF2 (7.7). Analysis: Calc. for C10F20N2O: C,
22.06%; F, 69.9%. Found: C, 22.03%; F, 69.8%.
For the further characterization of 26, it was derivatized
into the methyl ester (51) similarly.
[4] S.A. Mazalov, S.I. Gerasimov, S.V. Sokolov, V.L. Zolatavin, Zh.
Obshch. Khim. 35 (1965) 485.
Methyl per¯uoro[3-(4-ethylpiperazinyl)butyrate] (51)
[5] R.E. Banks, P.A. Carson, R.N. Haszeldine, J. Chem. Soc., Perkin I
(1973) 1111.
20
20
(nc) had bp 199.0±199.58C, nD 1.3253 and d4 1.8216.
IR (capillary ®lm): 2968 n(CH) (w), 1792 n(C=O) (s), 1444
(w), 1350±1230 (s±vs), 1173 (vs), 1111 (m, sh), 1068 (ms),
1034 (ms), 951 (s), 917 (w), 855 (w), 825 (ms), 817 (ms),
776 (m), 740 (ms), 675 (w), 691 (w), 675 (w), 620 (w), 567
[6] R.E. Banks, Fluorocarbons and Their Derivatives, MacDonald & Co.
Ltd, London, 1970.
[7] Organofluorine Chemistry. Principles and Commercial Applications,
R.E. Banks, B.E. Smart, J.C. Tatlow (Eds.), Plenum Press, New York,
1994.
‡
[8] T. Abe, E. Hayashi, H. Fukaya, H. Baba, J. Fluorine Chem. 50 (1990)
173.
(w), 541 (w). MS: 447 [M CF2C(O)OCH3] (3.3), 309
‡
‡
‡
C6F12N2 (1.8), 264 C5F10N (1.5), 214 C4F8N (2.2), 209
‡
[9] T. Abe, H. Fukaya, E. Hayashi, Y. Hayakawa, M. Nishida, H. Baba, J.
Fluorine Chem. 66 (1994) 193.
‡
‡
C3F6C(O)OCH3 (6.9), 164 C3F6N (7.9), 150 C3F6 (7.2),
‡
‡
‡
‡
145 C3F5N (2.4), 131 C3F5 (2.5), 119 C2F5 (31.2), 114
‡
[10] T. Abe, I. Soloshonok, H. Baba, A. Sekiya, J. Fluorine Chem. 99
(1999) 51.
‡
C2F4N (16.0), 100 C2F4 (12.7), 81 C2F3 (1.7), 76
‡
‡
‡
[11] 3M Co., Britain Patent 1,146,312 (1966).
[12] R.A. Guenthner, US Patent 3,471,484 (1969).
[13] T. Abe, JP Patent 1,451,067 (1988).
C2F2N (1.0), 69 CF3 (20.8), 59 [C(O)OCH3] (100),
‡
50 CF2 (3.4). Analysis: Calc. for C11F19N2O2H3: C,
23.74%; F, 64.9%. Found: C, 23.85%; F, 64.5%. 19F
NMR data of 51 are shown in Table 3.
[14] W.M. Grootaert, US Patent 5,285,002 (1994).
[15] H. Baba, T. Abe, E. Hayashi, Nihon Kagaku Kaishi J. Chem. Soc.
Jpn. (1986) 1249.
Â
[16] P. Sartori, D. Velayutham, N. Ignatev, M. Noel, J. Fluorine Chem. 83
(1997) 1.
Acknowledgements
[17] T. Abe, E. Hayashi, H. Baba, S. Nagase, Nihon Kagaku Kaishi J.
Chem. Soc. Jpn. (1985) 1980.
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.
[18] G.G.I. Moore, J.C. Hansen, T.M. Barrett, J.E. Waddell, K.M. Jewell,
T.A. Kestner, R.M. Payfer, J. Fluorine Chem. 32 (1986) 41.
[19] T.C. Moore, M. Boyle, V.M. Thorn, J. Chem. Soc. (1929) 39.
[20] T. Abe, S.K. Pandey, H. Baba, Electrochemical fluorination of N-
containing carboxylic acids. Part 6, J. Fluorine Chem. 105 (2000)
149.
References
[1] S. Nagase, in: P. Tarrant (Ed.), Fluorine Chemistry Reviews, Vol. 1,
Marcel Dekker, New York, 1967, p. 77.
[21] T. Abe, E. Hayashi, H. Fukaya, Y. Hayakawa, H. Baba, J. Fluorine
Chem. 57 (1992) 101.
[2] N.L. Weinberg (Ed.), Technique of Electroorganic Synthesis. Part II,
Techniques of Chemistry. Vol. V, Wiley, New York, 1995, pp. 1±82.
[22] T. Abe, E. Hayashi, H. Baba, H. Fukaya, J. Fluorine Chem. 48 (1990)
257.