Simons electrochemical fluorination of substituted homopiperazines(hexahydro-1,4-diazepines) and piperazines

Article abstract of DOI:10.1016/S0022-1139(02)00247-6

Simons electrochemical fluorination (ECF) of 1,4-dimethyl-1,4-homopiperazine, methyl 4-ethylhomopiperazin-1-ylacetate and 1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine was studied. For comparison, ECF of three piperazines with a N-(methoxycarbonylmethyl) group(s) was also studied. ECF of 1,4-dimethyl-1,4-homopiperazine gave a low yield of corresponding perfluoro(1,4-dimethyl-1,4-homopiperazine) together with perfluoro(2,6-diaza-2,6-dimethylheptane) as the major product. Corresponding perfluoro(homopiperazines) with mono- and/or di-(fluorocarbonyldifluoromethyl) groups [-CF₂C(O)F] at the 1- and/or 4-position were formed in low yields from methyl 4-ethylhomopiperazin-1-ylacetate and 1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine, respectively. These new seven-membered perfluoro(1,4-dialkyl-1,4-homopiperazines) were accompanied by the formation of mono- and/or di-basic linear perfluoroacid fluorides resulting from the C-C bond scission at the 2- and 3-positions of the ring. From mono- and/or di-N-(methoxycarbonylmethyl)-substituted piperazines, corresponding perfluoropeperazines having the acid fluoride group(s) were formed in low yields.

Full text of DOI:10.1016/S0022-1139(02)00247-6

Journal of Fluorine Chemistry 119 (2003) 27±38
Simons electrochemical ¯uorination of substituted
homopiperazines(hexahydro-1,4-diazepines) and piperazines$
Takashi Abea,*, Hajime Babab, Haruhiko Fukayac,
Masanori Tamuraa, Akira Sekiyaa
aResearch Center for Fluorinated Greenhouse Gas Alternatives (F-Center), National Institute of Advanced Industrial
Science and Technology (AIST), AIST Central 5, 1-1-1 Higashi, Tukuba, Ibaraki 305-8565, Japan
bDepartment for New Refrigerants Research (c/o F-Center), Research Institute of Innovative Technology
for the Earth (RITE), AIST Central 5, 1-1-1 Higashi, Tukuba, Ibaraki 305-8565, Japan
cInstitute for Structure and Engineering Material, National Institute of Advanced Industrial Science
and Technology (AIST), Shimoshidami, Moriyama-ku, Nagoya 463-8560, Japan
Received 28 June 2002; received in revised form 3 September 2002; accepted 7 September 2002
Dedicate to Professor Tatlow on the occasion of his 80th birthday
Abstract
Simons electrochemical ¯uorination (ECF) of 1,4-dimethyl-1,4-homopiperazine, methyl 4-ethylhomopiperazin-1-ylacetate and 1,
4-bis(methoxycarbonylmethyl)-1,4-homopiperazine was studied. For comparison, ECF of three piperazines with a N-(methoxycarbo-
nylmethyl) group(s) was also studied. ECF of 1,4-dimethyl-1,4-homopiperazine gave a low yield of corresponding per¯uoro(1,4-
dimethyl-1,4-homopiperazine) together with per¯uoro(2,6-diaza-2,6-dimethylheptane) as the major product. Corresponding per¯uor-
o(homopiperazines) with mono- and/or di-(¯uorocarbonyldi¯uoromethyl) groups [±CF2C(O)F] at the 1- and/or 4-position were formed in
low yields from methyl 4-ethylhomopiperazin-1-ylacetate and 1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine, respectively. These
new seven-membered per¯uoro(1,4-dialkyl-1,4-homopiperazines) were accompanied by the formation of mono- and/or di-basic linear
per¯uoroacid ¯uorides resulting from the C±C bond scission at the 2- and 3-positions of the ring. From mono- and/or di-N-
(methoxycarbonylmethyl)-substituted piperazines, corresponding per¯uoropeperazines having the acid ¯uoride group(s) were formed
in low yields.
# 2002 Elsevier Science B.V. All rights reserved.
Keywords: Simons electrochemical ¯uorination; Organo¯uorine compound; 1-Alkyl-4-(methoxycarbonylalkyl)-1,4-homopiperazines; Per¯uoroacid
¯uorides; Per¯uoro(1,4-dialkyl-1,4-homopiperazines); Per¯uoro(1,4-dialkyl-1,4-piperazines)
1. Introduction
Concerning the preparation of per¯uoro(1,4-dialkyl-1,4-
homopiperazines), only scarce data have appeared [10]. To
the best of our knowledge, no report has described the
preparation of per¯uoro(1,4-dialkyl-1,4-homopiperazines)
containing a per¯uoroacid ¯uoride functional group. As
an extension of our work on the preparation of new N-
containing per¯uorocarboxylic acids by means of ECF [9],
we have investigated the ECF of several 1,4-homopipera-
zines having a methoxycarbonyl alkyl group, by comparing
with the ECF of several mono- and/or di-N-(methoxycarbo-
nylmethyl)-substituted 1,4-piperazines.
Recently, many N-containing per¯uorocarboxylic acids
including those having a heterocyclic ring such as per¯uor-
opyrrolidinyl-, per¯uoromorpholino-, per¯uoropiperidino-
and per¯uoro-4-alkylpiperazinyl group have been prepared
by the Simons electrochemical ¯uorination of corresponding
methyl esters of carboxylic acids having a N,N-dialkylamino
group [1±9].
Wehereinreport theresultsoftheECFof1,4-dimethyl-1,4-
homopiperazine (1) and the following two 1,4-homopiper-
azines having a (methoxycarbonylmethyl) group(s) (2, 3), and
three piperazines with one (4, 5) and/or two (methoxycarbo-
nylmethyl) groups (6) at the 1- and/or 4-positions (Scheme 1).
$ Electrochemical fluorination of N-containing carboxylic acids. Part 10.
The character of ``F-'' in schemes in this paper designates ``perfluoro-'' (all
C±H bonds are replaced by C±F bonds).
* Corresponding author. Fax: ‡81-298-61-4771.
E-mail address: t.abe@aist.go.jp (T. Abe).
0022-1139/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 2 ) 0 0 2 4 7 - 6

28
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
1-ylacetate (2) under almost comparable conditions to those
applied for the ECF of 1-alkyl-4-(methoxycarbonylalkyl)-
piperazine [7].
In the ¯uorination of 1, it was found that correspond-
ing per¯uoro(1,4-dimethyl-1,4-homopiperazine) (7) and per-
¯uoro(2,6-dimethyl-2,6-diazaheptane) (8) were formed as
the principal ¯uorination products in GC yields of 14 and
10.5%, respectively (Scheme 2).
Scheme 1. Samples subjected to ECF.
It is known that seven- and six-membered heterocyclic
compoundscontainingaheteroatomlikeoxygenandnitrogen
are apt to isomerize on ECF into smaller ring-sized com-
poundsduetothestabilizationofthethermodynamicallymore
stable molecular structure [11±14]. For example, from the
ECF of methyl hexahydroazepin-1-ylacetate, a considerable
amount of the formation of six-membered isomeric per¯uor-
opiperizine derivatives is observed together with the target
per¯uoro(hexahydroazepin-1-ylacetyl¯uoride)[6].However,
any isomer having a six-membered ring due to the ring
contraction could not be obtained from the ECF of 1.
When 2 was subjected to ECF, the target per¯uoro(4-
ethylhomopiperazin-1-ylacetyl ¯uoride) (9) was formed in
low yield (GC yield ˆ 8%) together with many cleaved by-
products (Scheme 3). Compound 9 is the ®rst example of the
per¯uoro(homopiperazine) having a functional group (per-
¯uoroacid ¯uoride group in this case).
2. Results and discussion
2.1. ECF products from substituted homopiperazines
and piperazines
We have previously studied the ECF of 4-methylpipera-
zine and 4-methylhomopiperazine [10]. While the former
compounds gave the corresponding per¯uoro(1-¯uoro-4-
methylpiperazine) (GC yield ˆ 6:8%) together with several
by-products such as per¯uoro(N,N-diethylmethylamine),
per¯uoro(1,3-dimethylimidazolidine) and per¯uoro[2-(N0,
N0-di¯uoroaminoethyl)-N-ethyl-N-methylamine)], the latter
compound gave only per¯uoro(N,N-diethylpropylamine) as
the main product as a result of the extensive cleavage of the
C±N bond between the 3±4 and 4±5 positions. The target
per¯uoro(1-¯uoro-4-methyl-1,4-homopiperazine) could not
be formed from 4-methyl-1,4-homopiperazine.
Among the products, per¯uoro(3,7-dimethyl-3,7-diaza-
nonanoyl ¯uoride) (10) was formed characteristically as
one of the principal products (3% yield), which resulted
from the C±C bond scission between the 2- and 3-positions
of the 1,4-homopiperazine ring. Another set of compounds
In order to compare the behavior of the ECF of the
derivatives of 1,4-piperazine and 1,4-homopiperazine in
more detail, we have examined the ECF of 1,4-dimethyl-
1,4-homopiperazine (1) and methyl 4-ethylhomopiperazin-
Scheme 2. Fluorination products from compound 1.
Scheme 3. Fluorination products from compound 2.

T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
29
Scheme 4. Fluorination products from compound 3.
consisting of per¯uoro(2,6-dimethyl-2,6-diazaoctane) (11)
and per¯uoro(1-ethyl-4-methyl-1,4-homopiperazine) (12),
which resulted from the a-bond scission of the carboxylic
acid group of 10 and 9, respectively, were formed in low
yields also.
When 1,4-bis(methoxycarbonylmethyl)-1,4-homopipera-
zine (3) was subjected to ECF, the target per¯uoro[1,4-
bis(¯uorocarbonylmethyl)-1,4-homopiperazine] (13) was
obtained successfully (GC yield ˆ 7%). A similar distribu-
tion pattern of the ¯uorinated products to those obtained from
2 was observed, which consisted of the ring-opened
type per¯uoro(2,6-dimethyl-2,6-diaza-1,7-heptanedioic acid
¯uoride) (14) as well as the target 13 as the major products
(Scheme 4).
Two sets of cleaved products consisting of 8 and 7, and
per¯uoro(3,7-dimethyl-3,7-diaza-octanoyl ¯uoride) (15)
and per¯uoro(4-methylhomopiperazine-1-ylacetyl ¯uoride)
(16) were also formed. The ratios of 8:7 and 15:16 were 1
and 0.6, respectively.
In order to compare the behavior on ECF between mono-
and/or di-(methoxycarbonylmethyl)-substituted 1,4-homo-
piperazines with those of 1,4-piperazines, ECF of methyl
4-alkylpiperazin-1-ylacetate [alkyl: methyl (4), ethyl (5)] and
1,4-bis(methoxycarbonylmethyl)-1,4-homopiperazine(6) was
conducted under the same conditions applied for 2. The
results of the ECF of 4 and 5 are shown in Scheme 5.
The target per¯uoro(4-methylpiperazin-1-ylacetyl ¯uor-
ide) (17) and per¯uoro(4-ethylpiperazin-1-ylacetyl ¯uoride)
(18) were formed from 4 and 5 in yields of 6 and 9%,
respectively. Per¯uoro(N,N-diethylmethylamine) (21) per-
¯uoro(N,N-diethylaminoacetyl ¯uoride) (22) and per¯uor-
otriethylamine (23) were formed as the major cleaved
products from them. In the ¯uorination of several methyl
esters of carboxylic acids (±CH2CH2C(O)OCH3, ±CH(CH3)
C(O)OCH3, ±CH(CH3)CH2C(O)OCH3, ±CH2CH(CH3)
C(O)OCH3) carrying a 4-alkylpiperazinyl group, it has been
reported that higher (almost double) 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 were ¯uorinated electrochemically
[7]. However, in the ECF of 4 and 5 (methyl ester of
carboxylic acid: ±CH2C(O)OCH3), a signi®cant difference
was not observed between the yields of the target products
(17 and 18). Although many cleaved by-products including
per¯uoro(1-methyl-4-alkylpiperazine) [alkyl: CF3 (19),
C2F5 (20)] were formed, the cleavage pattern of the ¯uori-
nated compounds was obviously different from those
Scheme 5. Fluorination products from compounds 4 and 5.

30
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
Scheme 6. Fluorination products from compound 6.
obtained from the ECF of 1,4-dialkyl-1,4-homopiperazines
(1 and 2); any ring-opened type cleaved products due to the
bond scission between the 2- and 3-positions of the piper-
azine ring were not formed in the case of 1,4-dialkyl-1,4-
piperazines.
Furthermore, for comparison with the results of the ECF
of 3, the ECF of 1,4-bis(methoxycarbonylmethyl)piperazine
(6) was conducted similarly. When compound 6 was sub-
jected to ECF, the target per¯uoro[1,4-bis(¯uorocarbonyl-
methyl)piperazine] (24) was obtained in a low yield (GC
yield ˆ 4%) together with cleaved by-products such as
per¯uoro(1,4-dimethylpiperazine) (19) and per¯uoro(4-
methylpiperazin-1-ylacetyl ¯uoride) (17) (Scheme 6). Pre-
viously, compound 24 has been prepared by the ECF of 1,4-
bis(2-hydroxyethyl)piperazine [15].
The apparent difference in the ECF products between 1,4-
dialkylhomopiperazine (1, 2 and 3) and 1,4-dialkylpipera-
zine (4, 5 and 6) was the formation of the ring-opened type
by-product (8, 10 and 14, respectively) from the former
arising from the C2±C3 bond scission of the homopipera-
zine ring. It is presumed that, in the case of the former
compounds when dissolved in AHF, the lengthening
(ˆweakening of the bond) of the C±C bond between the
2- and 3-positions of the ring is resulted from an intramo-
lecular repulsion of the two protonated ions formed in AHF,
which may lead to the easy C2±C3 bond scission at the very
early stage of the ¯uorination. However, the calculation for
the C2±C3 bond length of 1 and that of di-protonated ions of
1, which was done using semi-empirical molecular orbital
theory [18], showed that there was not any signi®cant
change in the C2±C3 bond length between 1 and di-proto-
nated ions of 1 (it changes only slightly from 1.530 to
Ê
1.525 A). Therefore, for the formation of the ring-opened
type by-product (8, 10 and 14, respectively) from 1,4-
dialkylhomopiperazine (1, 2 and 3), a number of factors
are combined in a complicated way.
When we consider the ECF of 1,4-dimethylhomopiper-
azine (1) and 1,4-dimethylpiperazine (25), the great variety
of ¯uorinated as well as of partially ¯uorinated products
(gases, dissolved liquids in HF-phase) are formed along with
the target compounds from them. During ¯uorination, the
C±C bond scission between 2- and 3-positions of the ring
both of 1 and 25 may take place to some extent yielding
partially ¯uorinated ring-opened type compounds (26 and 27
in Scheme 7).In this case, the number of bonds separating
two nitrogen atoms of the cleaved product is three in
compound 26 and two in 27. It is known that various
per¯uoro-tertiary-amines of the type R1(R2)N±(CF2)n±
NR1(R2) [n ˆ 2±3; R1(R2)N±: per¯uoro(N,N-dialkyla-
mino)- or per¯uoro(cyclic amino group)] can be obtained
by the ECF of corresponding di-amines [16,17]. However,
their yields were affected remarkably by the identity of
R1(R2)N± (cyclic or acyclic alkylamino group) and the
number of bonds [n ˆ 2±3; ±(CH2)n±] separating the two
nitrogen atoms. Generally, diamines consisting of n ˆ 3
gave corresponding per¯uorodiamines in better yields than
that where n ˆ 2. It is considered that this point is crucial for
the survival of the intermediate compounds (26 and 27)
during ECF. Compound 26 proceeded to 8 as the ®nal
¯uorination product. On the other hand, compound 27 will
Scheme 7.

T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
31
Scheme 8. Chemical shift of the CF2 group of the piperazine ring.
be subjected to severe C±C and C±N bond cleavage resulting
in yielding only degraded products.
one absorption peak due to the cyclic CF2 group is observed.
But, in the case where two N-per¯uoroalkyl groups are differ-
ent, two absorption peaks are separately observed; the bulkier
the N-per¯uoroalkyl group is, the more the deshielding of the
cyclic CF2 group linked to the same N-atom occurs, which
results in the difference of the chemical shifts (Scheme 8).
Therefore, it was suggested that this ®nding would be
applicable to the prediction of the chemical shifts of the
cyclic N-CF2 groups of the per¯uoro(1,4-dialkyl-1,4-homo-
piperazines) with short N-per¯uoroalkyl groups. The 19F
NMR shielding tensors were calculated by the GIAO-
B3LYP/6-31‡‡GÃÃ//B3LYP/6-31GÃà method using Gaus-
sian'98 program package [19]. For example, for per-
¯uoro(1,4-methyl-1,4-homopiperazine) (7), the calculation
gave the chemical shift of the geminal ¯uorines at the 2- and
3- positions and, that at the 5- and 7-positions of the ring was
À91.5 (À90.8 expl.) and À87.0 (À88.1 expl.), respectively,
which showed that the deshielding occurred more at the 5-
and 7-positions than at the 2- and 3-positions [20]. Similarly,
for per¯uoro(1-ethyl-4-methyl-1,4-homopiperazine) (12),
following chemical shifts of the cyclic N-CF2 groups were
obtained: À85.1 (À88.6 expl.) at the 2-position, À87.1
(À88.6 expl.) at the 3-position, À90.7 (À89.0 expl.) at
the 5-position, and À80.3 (À86.9 expl.) at the 7-position,
respectively.
2.2. DFT calculation for the determination
of 19F NMR chemical shifts
Many N-containing per¯uorocompounds including per-
¯uoro(1,4-dialkyl-1,4-homopiperazines) having a ±CF2-
C(O)F group(s) were formed as new compounds. They
were characterized by the measurement of IR, MS and
19F NMR and elemental analysis (carbon and ¯uorine) after
the puri®cation by use of semi-preparative GLC. However,
the assignment of 19F NMR chemical shifts to each of the
peaks of per¯uoro(1,4-dialkyl-1,4-homopiperazines), even
its N-alkyl group consists of a short alkyl chain such as CF3,
C2F5 and CF2C(O)F, could not be determined in a straight-
forward manner. For example, 19F NMR (dCFCl3 in ppm)
of per¯uoro(1,4-dimethyl-1,4-homopiperazine) (7), showed
four signals at À50.4 (17.2 Hz quintet), À87.0, À90.3 and
À123.1 (multiplets) of relative intensities 3:2:2:1 due to the
rapid interconversion of the ring at ambient temperature.
The ®rst peak was assigned to that of a CF3± group. Although
two peaks at À87.0 and À90.3 were easily assigned to those
of the cyclic N-CF2 groups due to the deshielding by the
adjacent nitrogen atom, the assignment of them to that of the
5- and 7-positions, and that of the 2- and 3-positions could
not be determined. In the case of per¯uoro(1-ethyl-4-
methyl-1,4-homopiperazine) (12), where two per¯uoroalkyl
groups linked to the nitrogen atom at the 1- and 4-positions
were different, absorption peaks due to the cyclic N-CF2
group appeared at À87.0, À89.0 and À89.6 (multiplets) of
relative intensities 1:2:1, which showed that chemical shifts
of the geminal ¯uorines at the 2-, 3-, 5- and 7-positions of the
ring were separated and two of them were overlapped. It is
known that the chemical shifts of cyclic CF2 group of
per¯uoro(1,4-dialkylpiperazines) show absorption peaks
(single multiplet) in the range of À88 to À93 when the
N-per¯uoroalkyl group consists of short alkyl chain such as
CF3±, C2F5± and n/iso-C3F7± and its values are affected by
the size (i.e. the electron-withdrawing effect by ¯uorine) of
the N-per¯uoroalkyl of the piperazine ring: in the case where
one of the N-per¯uoroalkyl group is such an asymmetric
alkyl chain such as ±CF(CF3)COF and CF2CF(CF3)COF, the
splitting into an AB quartet instead of showing a single
multiplet, is observed in the 19F NMR of cyclic N-CF2 group
due to the slow interconversion of the ring at ambient
temperature usually [7,8]. When the same N-per¯uoroalkyl
group is attached at the 1- and 4-positions of the ring, only
3. Conclusion
In summary, it was revealed that new per¯uoro(1,4-dia-
lkyl-1,4-homopiperazines) with or without ±CF2C(O)F
group(s) could be prepared by the ECF of 1,4-dimethyl-
1,4-homopiperazine (1), methyl 4-ethylhomopiperazin-1-
ylacetate (2) and 1,4-bis(methoxycarbonylmethyl)-hexahy-
dro-1,4-diazepine (3), which was accompanied by the
formation of the linearly ring-opened type compounds.
4. Experimental
Boiling points were uncorrected. 1,4-Dimethyl-1,4-
homopiperazine (1) was prepared by the reaction of homo-
piperazine(hexahydro-1,4-diazepine) (Tokyo Kasei Co.)
with the mixture of formaldehyde (37 wt.% solution in
water) and formic acid according to the method in the
literature [21]. 4-Ethyl-homopiperazine-1-ylacetate (2)
was prepared by the reaction of 1-ethyl-1,4-homopiperazine
with methyl chloroacetate in the presence of triethylamine

32
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
according to the method described by Moffett [22]. 1-Ethyl-
1,4-homopiperazine was purchased from Koei Kasei Co.,
Osaka, Japan, and was used as received. Methyl 4-methyl-
piperazin-1-ylacetate (4) and methyl 4-ethyl-piperazin-1-
ylacetate (5) were prepared by the reaction of corresponding
4-alkyl-1,4-piperazine with methyl chloroacetate in the
presence of triethylamine in a similar way. 1,4-Bis(methox-
ycarbonylmethyl)-1,4-homopiperazine (3) and 1,4-bis(-
methoxycarbonylmethyl)piperazine (6) were prepared by
the reaction of methyl chloroacetate with 1,4-homopiper-
azine and 1,4-piperazine in the presence of triethylamine,
respectively.
The substrates synthesized for ECF had the following
boiling points: 1,4-dimethyl-1,4-homopiperazine (1), bp
126±127 8C/281 mmHg (reported [21]: bp 158±161 8C/
738 mmHg); 4-ethylhomopiperazin-1-ylacetate (2), bp
119±120 8C/6 mmHg; 1,4-bis(methoxycarbonylmethyl)-1,4-
homopiperazine (3), bp 162±163 8C/5 mmHg; methyl 4-
methylpiperazin-1-ylacetate (4), bp 108±109 8C/10 mmHg;
methyl 4-ethylpiperazin-1-ylacetate (5), bp 126±127 8C/
14 mmHg; 1,4-bis(methoxycarbonylmethyl)piperazine (6),
mp 52.0±53.5 8C.
on GC, and components were calculated on the basis of
chromatographic peak areas assuming equal sensitivities
for all compounds). Cell drainings (35.8 g) consisted
of C2F5(CF3)NC3F7 (29) (2.3 g), per¯uoro(2,6-dimethyl-
2,6-diazaheptane) (8) (12.8 g), per¯uoro(1,4-dimethyl-1,4-
homopiperazine) (7) (15.4 g) and unidenti®ed products
(5.3 g).
The GC yields of 7 and 8 were 13.8 and 10.5%, respec-
tively. The physicochemical properties and spectral data (IR
and mass) of 7 are shown below.
Per¯uoro(1,4-dimethyl-1,4-homopiperazine) (7) (nc): bp
106.5±107.5 8C, nD20 1.2925 and d420 1.8726. IR (gas): 1350
(vs), 1300 (m), 1244 (s), 1144 (ms), 1084 (w), 945 (m), 876
‡
‡
‡
‡
(m), 721 (m). Mass: 397 [M-F] (0.3), 347 [M-CF3] (0.6),
‡
164 C3F6N (22.8), 150 C3F6 (19.4), 114 C2F4N (28.1),
‡
‡
100 C2F4 (58.1), 69 CF3 (100).
19F NMR data of 7 are shown in Table 1 together with
other new compounds synthesized in this experiment.
4.2. Methyl 4-ethylhomopiperazin-1-ylacetate (2)
Sample 2 (40.1 g, 0.200 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 6.1±6.6 V, 7±
8 8C, 641 min (237 Ah). The work-up gave the following
products in the À78 8C trap (11.2 g): a mixture of
(CF3)2NCF3 (28) and (CF3)2NCF2C(O)F (30) (1.5 g), a
mixture of (C2F5)2NCF3 (21) and C2F5(CF3)2NCF2C(O)F
(31) (5.2 g), C2F5(CF3)2NC3F7 (29) (2.9 g), (C2F5)2NC3F7
(32) (0.8), and unidenti®ed products (0.8 g).
The electrolytic ¯uorination apparatus, operating proce-
dures and work-up of products were similar to those
described previously [1]. Molecular orbital calculations
were conducted by a MOPAC program [18], and a CAChe
system (Sony Tektronix) was also used, DFT calculations
were carried out using Gaussian'98 [19].
4.1. Fluorination of 1,4-dimethyl-1,
4-homopiperazine (1)
Cell drainings (17.8 g) gave (C2F5)2NCF3 (21) (0.2 g),
C2F5(CF3)NC3F7 (29) (0.4 g), (C2F5)2NC3F7 (32) (0.8),
per¯uoro(2,6-dimethyl-2,6-diazaoctane) (11) (2.2), per-
¯uoro(1-ethyl-4-methyl-1,4-homopiperazine) (12) (1.8),
per¯uoro(3,7-dimethyl-3,7-diazanonanoyl ¯uoride) (10)
(2.8), per¯uoro(4-ethyl-homopiperazin-1-ylacetyl ¯uoride)
(9) (7.7 g) and unidenti®ed products (1.9 g).
The GC yields of 9, 10, 11 and 12 were 8, 3, 2 and 2%,
respectively.
The spectral data (IR and MS) of 9, 10 and 31 are
shown below. The spectral data (IR and MS) and physi-
cochemical properties of 11 and 12 are shown below
similarly.
Sample 1 (36.1 g, 0.282 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 5.6±5.9 V, and a cell
temperature of 7±8 8C over a period of 614 min (230 Ah).
The ef¯uent gases from the cell were passed over NaF
pellets and then condensed in a trap cooled to À78 8C. The
gaseous products which did not condense in the À78 8C 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).
Per¯uoro(4-ethylhomopiperazin-1-ylacetyl ¯uoride) (9)
(nc): IR (gas):1896 [n(C=O)] (ms), 1331 (s), 1246 (vs),
1217 (ms), 1151±1165 (ms), 1128 (m, sh), 1099 (w), 1055
(m), 945 (m), 932 (m), 735 (m), 700 (w). MS: 447 M-
‡
‡
‡
‡
‡
‡
C(O)F] (5.4), 309 C6F11N2 (4.9), 264 C5F10N (25.1), 214
‡
C4F8N (45.6), 169 C3F7 (12.7), 164 C3F6N (51.4), 150
‡
‡
C3F6 (26.5), 119 C2F5 (100), 114 C2F4N (74.2), 100
‡
‡
‡
C2F4 (75.4), 97 CF2C(O)F (22.4), 69 CF3 (98.0).
Per¯uoro(3,7-dimethyl-3,7-diazanonanoyl ¯uoride) (10)
(nc): IR (gas): 1896 [n(C=O)] (m), 1323 (s), 1246 (vs), 1225
(ms, sh), 1157 (m, sh), 1130 (w, sh), 739 (m). MS: 485 [M-
The products (16.5 g) condensed in the À78 8C trap
consisted of (CF3)2NC2F5 (28) (6.8 g), (C2F5)2NCF3 (21)
(4.0 g), C2F5(CF3)NC3F7 (29) (2.5 g), per¯uoro(2,6-diaza-
2,6-dimethylheptane) (8) [17] (0.5 g), per¯uoro(1,4-
dimethyl-1,4-hompiperazine) (7) (0.8 g) and unidenti®ed
products (1.9 g) (products are arranged in order of elution
‡
‡
‡
‡
C(O)F] (3.3), 309 C6F11N2 (6.2), 265 (17.1), 264
‡
C5F10N
C4F8N (54.3), 169 C3F7 (63.7), 164 C3F6N (72.5),
(24.1), 252 C2F5(CF3)NCF2
‡
(57.3), 214
‡

T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
33
Table 1
19F NMR spectral data of compounds 7, 9, 10, 11, 12, 13, 14, 15, 16, 18, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and 44
Compound
Formula
Chemical shifta,b
J (Hz)b
7
a ˆ À50.4 (quintet)
b ˆ À87.0 (m)
c ˆ À90.3 (m)
a±b ˆ a±c ˆ 17.2
d ˆ À123.1 (m)
9
a ˆ À85.5 (quintet)
b ˆ À92.7 (quintet)
c ˆ À87.1 (m)
a±c ˆ a±f ˆ 8.5
b±c ˆ b±f ˆ 27.7
d ˆ À121.6 (m)
e ˆ À87.1 (m)
f ˆ À86.8 (m)
g ˆ À88.6 (m)
h ˆ À83.7 (quintet)
i ˆ 13.2 (m)
h±e ˆ h±g ˆ 15.5±17.2
10
a ˆ À83.8 (m)
b ˆ À93.4 (m)
c ˆ À50.9 (m)
d ˆ À88.7 (m)
e ˆ À120.5 (m)
f ˆ À88.7 (m)
g ˆ À51.6 (m)
h ˆ À85.3 (m)
i ˆ 13.5 (s)
11
a ˆ À83.8 (m)
b ˆ À93.4 (m)
c ˆ À50.9 (m)
d ˆ À88.7 (m)
e ˆ À121.0 (m)
f ˆ À91.6 (heptet)
g ˆ À52.9 (m)
f±g ˆ 13.6±15.5
12
a ˆ À85.4 (quintet)
b ˆ À92.0 (quintet)
c ˆ À89.0 (m)
a±c ˆ a±f ˆ 8.5±8.8
b±c ˆ b±f ˆ 20.9±22.7
d ˆ À121.4 (m)
e ˆ À89.0 (m)
f ˆ À87.0 (m)
g ˆ À89.6 (m)
h ˆ À50.6 (quintet)
h±e ˆ h±g ˆ 11.9±12.1
b±c ˆ b±e ˆ 14.3±17.2
13
a ˆ 13.3 (s)
b ˆ À83.1 (quintet)
c ˆ À86.1 (m)
d ˆ À122.9 (m)
e ˆ À88.4 (m)
14
15
a ˆ 13.5 (s)
b ˆ À85.4 (m)
c ˆ À51.6 (m)
d ˆ À90.0 (m)
e ˆ À121.4 (m)
a ˆ À52.9 (t±t)
b ˆ À91.5 (m)
c ˆ À121.7 (m)
d ˆ À90.9 (m)
e ˆ À51.6 (m)
f ˆ À85.3 (m)
g ˆ 13.5 (s)
a±b ˆ 8.5±8.8, a±c ˆ 6.8±7.1

34
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
Table 1 (Continued )
Compound
Formula
Chemical shifta,b
J (Hz)b
16
a ˆ À50.3 (quintet)
b ˆ À90.5 (m)
c ˆ À123.0 (m)
d ˆ À85.8 (m)
e ˆ À88.3 (m)
f ˆ À87.2 (m)
g ˆ À83.2 (quintet)
h ˆ 13.3 (s)
a±b ˆ a±e ˆ 17.2
g±d ˆ g±f ˆ 17.2
18
a ˆ À85.8 (quintet)
b ˆ À95.4 (quintet)
c ˆ À90.9 (m)
a±c ˆ 6.8±8.8
b±c ˆ 18.9
d ˆ À91.8 (t)
d±e ˆ 12.1
e±d ˆ 13.8
e ˆ À85.9 (quintet)
f ˆ 14.2 (s)
33
34
a ˆ À84.1 (m)
b ˆ À94.9 (quartet±t)
c ˆ À51.8 (m)
d ˆ À86.0 (m)
e ˆ d 3.99 (s)
a ˆ À83.8 (m)
b ˆ À93.4 (m)
c ˆ À50.7 (m)
d ˆ À88.8 (m)
e ˆ À121.4 (m)
f ˆ À90.1 (m)
g ˆ À51.5 (m)
h ˆ À85.6 (m)
i ˆ d 3.99 (s)
b±c ˆ 14.7, b±d ˆ 14.1
35
a ˆ À85.5 (quintet)
b ˆ À92.5 (quintet)
c ˆ À86.8 (m)
a±c ˆ a±f ˆ 8.8±9.8
b±c ˆ b±f ˆ 15.9±27.7
d ˆ À121.6 (m)
e ˆ À86.6 (m)
f ˆ À87.1 (m)
g ˆ À88.6 (m)
h ˆ À84.3 (quintet)
h±e ˆ h±g ˆ 16.2±17.2
a±c ˆ 10.4±11.9
i ˆ d 3.99 (s)
36
37
a ˆ À81.6 (t)
b ˆ À125.7 (m)
c ˆ À90.3 (m)
d ˆ À51.6 (m)
e ˆ À82.9 (m)
f ˆ 13.6 (s)
a ˆ À81.6 (t)
b ˆ À123.7 (m)
c ˆ À87.1 (m)
d ˆ À82.8 (m)
e ˆ À91.2 (m)
f ˆ À83.1 (m)
g ˆ 13.5 (s)
a±c ˆ 10.2±12.1
38
a ˆ À81.6 (t)
b ˆ À125.4 (m)
c ˆ À85.7 (m)
d ˆ À51.6 (m)
e ˆ À90.3 (m)
f ˆ d 3.99
a±c ˆ 10.5±11.0

T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
35
Table 1 (Continued )
Compound
Formula
Chemical shifta,b
J (Hz)b
39
40
41
a ˆ À81.7 (t)
b ˆ À123.3 (m)
c ˆ À87.1 (m)
d ˆ À82.4 (m)
e ˆ À83.8 (m)
f ˆ À91.0 (m)
g ˆ d 3.98 (s)
a ˆ À52.8 (t±t)
b ˆ À91.5 (m)
c ˆ À121.5 (m)
d ˆ À90.2 (m)
e ˆ À51.5 (m)
f ˆ À85.7 (m)
g ˆ d 3.99 (s)
a±c ˆ 11.0
a±b ˆ 8.5, a±c ˆ 7.4
a ˆ À50.3 (quintet)
b ˆ À90.7 (m)
c ˆ À123.2 (m)
d ˆ À85.1 (m)
e ˆ À88.3 (m)
f ˆ À86.5 (m)
a±b ˆ a±e ˆ 17.5±17.8
g±d ˆ g±f ˆ 16.4±18.4
g ˆ À83.8 (quintet)
h ˆ d 3.99 (s)
42
43
a ˆ d 3.98 (s)
b ˆ À85.6 (m)
c ˆ À51.5 (m)
d ˆ À90.1 (m)
e ˆ À120.8 (m)
a ˆ d 3.99 (s)
b ˆ À83.8 (quintet)
c ˆ À84.9 (m)
d ˆ À123.3 (m)
e ˆ À88.7 (m)
b±c ˆ b±e ˆ 14.3±18.1
44
a ˆ À85.6 (quintet)
b ˆ À95.4 (quintet)
c ˆ À90.8 (m)
a±c ˆ 7.9±8.5
b±c ˆ 18.9
d ˆ À91.6 (t)
d±e ˆ 13.3
e ˆ À85.7 (quintet)
f ˆ d 4.00 (s)
e±d ˆ 13.3±13.6
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.
‡
‡
‡
‡
‡
‡
119 C2F5 (75.9), 114 C2F4N (74.8), 100 C2F4 (20.8), 97
‡
164 C3F6N (18.8), 119 C2F5 (20.8), 114 C2F4N (42.1),
‡
‡
CF2C(O)F (26.8), 69 CF3 (100).
69 CF3 (100). Analysis: calc. for C8F20N2: C, 19.05%; F,
75.4%. Found: C, 19.0%; F, 75.6%.
Per¯uoro(1-ethyl-4-methyl-1,4-homopiperazine) (12) (nc):
bp 117.0±117.5 8C, nD20 1.2951 and d420 1.8756. IR: 1348 (s),
1319 (m, sh), 1246 (vs), 1234 (ms, sh), 1198 (m), 1153 (m),
1030 (m), 1057 (m), 947 (m), 893 (w), 854 (m), 729 (m). MS:
Per¯uoro(N-ethyl-N-methylaminoacetyl ¯uoride) (31)
(nc): IR (gas): 1896 [n(C=O)] (ms), 1342 (s), 1313 (vs),
1244 (vs), 1213 (s), 1157 (ms), 1107 (ms), 1080 (m), 951
(m), 883 (m).
Per¯uoro(2,6-dimethyl-2,6-diazaoctane) (11) (nc): bp
118.0±118.5 8C, nD20 1.2813 and d420 1.8408. IR (gas):
1363 (s), 1340 (vs), 1246 (s), 1227 (s), 1200 (m), 995
‡
‡
‡
‡
397 [M-CF3] (1.0), 359 C7F13N2 (1.4), 347 [M-C2F5]
‡
‡
(4.7), 164 C3F6N (30.5), 150 C3F6 (26.6), 119 C2F5
‡
‡
‡
‡
‡
(m), 745 (m). MS: 397 [M-F] (0.3), 347 [M-C2F5]
‡
(63.5), 114 C2F4N (39.8), 100 C2F4 (72.7), 69 CF3 (100).
Further characterization of 9, 10 and 31 was conducted in
the form of the methyl ester.
‡
(0.3), 252 (CF3)2NCF2CF2 , C2F5(CF3)NCF2 (9.3), 214
‡
‡
‡
C4F8N (13.5), 202 (CF3)2NCF2 (12.1), 169 C3F7 (12.8),

36
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
Methylesterswerepreparedbythereactionofper¯uoroacid
¯uoride) (16) (3.3 g), per¯uoro(3,7-dimethyl-3,7-diazan-
onanedioicacid ¯uoride) (14) (2.1 g), per¯uoro[1,4-
bis(¯uorocarbonylmethyl)-1,4-homopiperazine] (13) (5.6 g)
and unidenti®ed products (1.3 g). The GC yields of 7, 8, 13,
14, 15 and 16 were 1, 1, 7, 3, 3 and 5%, respectively.
Spectral data (IR and mass) of 13, 14, 15, 16, 34 and 35
are shown below.
¯uorides with methanol. The procedure will be explained in
thecaseof10;intoa10 mlPFAresinbottle,wasplaced1.040 g
(1.61 mmol) of 10 which was isolated by preparative GC, and
methanol (0.48 g) was added dropwise while cooling in an ice
bath.Thereactiontookplaceimmediatelywithanevolutionof
heat giving a clear liquid. After shaking with an addition of
1 ml water into the reaction mixture, the lower phase [the
methyl ester of 10 (34)] was separated (1.10 g, 87% yield) and
puri®ed by semi-preparative GLC.
Per¯uoro[1,4-bis(¯uorocarbonylmethyl)-1,4-homopiper-
azine] (13) (nc): IR (gas): 1896 [n(C=O)] (s), 1333 (vs),
1265 (ms), 1240 (ms), 1217 (ms), 1167 (ms), 1060 (w), 934
‡ ‡
Methyl per¯uoro(N-ethyl-N-methylaminoacetate) (33)
(nc); bp.103.5±104.0 8C, n2D0 1.2983 and d420 1.6024. IR
(capillary ®lm): 1798 [n(C=O] (s). MS: 252 [M-
(ms). MS: 425 [M-C(O)F] (14.1), 264 C5F10N (11.2), 214
‡
‡
‡
‡
‡
C4F8N (33.5), 164 C3F6N (42.2), 150 C3F6 (12.2), 145
‡
‡
C3F5N (6.7), 119 C2F5 (24.1), 114 C2F4N (67.1), 100
‡
‡
‡
‡
‡
CF2C(O)OMe] (18.2), 164 C5F6N (18.7), 119 C2F5
‡
C2F4 (50.5), 97 CF2C(O)F (37.3), 69 CF3 (100).
Per¯uoro(3,7-dimethyl-3,7-diazanonanedioic acid ¯uoride)
{molecular formula: (c-FC(O)CF2N(CF3)CF2CF2CF2N(CF3)
CF2C(O)F} (14) (nc): IR (gas): 1896 [n(C=O)] (s), 1342 (vs),
‡
(22.8), 114 C2F4N (24.0), 109 CF2C(O)OMe (15.6), 81
‡
‡
‡
C2F3 (15.0), 69 CF3 (58.0), 65 CF2CH3 (8.1), 59
‡
C(O)OMe (100). Analysis: calc. for C6F10NO2H3: C,
23.15%; F, 61.1%. Found: C, 23.36%; F, 60.7%.
1221±1260 (sꢀms), 1155 (ms), 1086 (m), 932 (m), 789 (m).
‡
Methyl per¯uoro(3,7-dimethyl-3,7-diazanonanoate) (34)
(nc): bp.176±178 8C, nD20 1.3103 and d420 1.7779. IR (capillary
MS: 463 [M-C(O)F] (3.1), 330 CF2CF2CF2N(CF3)
CF2C(O)F (6.2), 230 CF2N(CF3)CF2C(O)F (18.5), 214
‡
‡
‡ ‡ ‡
®lm): 1798 [n(C=O] (s). MS: 485 [M-CF2C(O)OMe] (14.3),
C4F8N (19.4), 169 C3F7 (17.7), 114 C2F4N (48.9), 100
‡
‡
‡
‡
‡
‡
‡
342 CF2CF2CF2N(CF3)CF2C(O)OMe (4.5), 169 C3F7
‡
C2F4 (10.9), 97 CF2C(O)F (27.8), 69 CF3 (100).
Per¯uoro(3,7-methyl-3,7-diazaoctanoyl ¯uoride) (15)
(nc): IR (gas): 1896 [n(C=O)] (m), 1344 (vs), 1229 (vs),
1163 (w), 1130 (w), 1086 (w), 995 (m), 950 (w), 900 (w),
(20.6), 164 C5F6N (26.3), 119 C2F5 (29.0), 114 C2F4N
‡
‡
(22.5), 109 CF2C(O)OMe (37.1), 100 C2F4 (15.4), 81
‡
‡
‡
C2F3 (23.9), 69 CF3 (61.5), 65 CF2CH3 (10.6), 59
‡
‡
C(O)OMe (100). Analysis: calc. for C10F19N2O2H3: C,
22.06%; F, 66.4%. Found: C, 22.17%; F, 66.1%.
799 (w), 760 (w), 731 (w). MS: 435 [M-C(O)F] (1.9), 230
‡ ‡
CF2N(CF3)CF2C(O)F (8.8), 214 C4F8N (19.7), 202
‡
‡
‡
Methyl per¯uoro(4-ethylhomopiperazin-1-ylacetate) (35)
(nc): bp. 185±187 8C, nD20 1.3266and d420 1.8045. IR (capillary
(CF3)2NCF2 (20.2), 114 C2F4N (53.8), 97 CF2C(O)F
‡
(10.5), 69 CF3 (100).
‡
®lm): 1798 [n(C=O] (vs). MS: 487 [M-CF3] (12.5), 321
C7F11N2 (14.4), 309 C6F11N2 (13.3), 214 C4F8N (26.1),
Per¯uoro(4-methylhomopiperazin-1-ylacetyl¯uoride)(16)
(nc): IR (gas): 1896 [n(C=O)] (m), 1350 (vs), 1234 (s), 1209
(m), 1192 (m), 1157 (ms), 1157 (ms), 1092 (w), 1055 (m),
‡
‡
‡
‡
‡
‡
114 C2F4N (24.7), 109 CF2C(O)OCH3 (51.3), 100 C2F4
‡
‡
‡
‡
‡
‡
(27.4), 81 C2F3 (28.6), 69 CF3 (15.3), 65 CF2CH3 (16.9),
‡
1016 (w), 937 (m). MS: 397 [M-C(O)F] (5.0), 214 C4F8N
‡ ‡
(21.5), 164 C3F6N (33.8), 119 C2F5 (15.7), 114 C2F4N
59 C(O)OMe (100). Analysis: calc. for C10F17N2O2H3: C,
‡
‡
‡
23.72%; F, 63.8%. Found: C, 23.8%; F, 64.0%.
19F NMR data of 9, 10, 11, 12, 33, 34 and 35 are shown in
Table 1.
(45.7), 100 C2F4 (50.5), 97 CF2C(O)F (13.6), 69 CF3 (100).
Per¯uoro(N-methyl-N-propylaminoacetyl ¯uoride) (36)
(nc): IR (gas): 1894 [n(C=O)] (m), 1840 (s), 1319 (s),
1292 (s), 1210±1246 (sꢀvs), 1182 (m), 1155 (ms), 1138
(m), 1088 (m), 1070 (w), 1028 (w), 934 (m), 843 (m), 741
4.3. Fluorination of 1,4-bis(methoxycarbonylmethyl)-1,4-
homopiperazine (3)
‡ ‡
(m). Mass: 302 [M-C(O)F] (10.7), 280 [M-CF3] (2.7), 230
‡
‡
‡
CF2N(CF3)CF2C(O)F (2.7), 169 C3F7 (20.4), 119 C2F5
(28.4), 114 C2F4N (35.6), 100 C2F4 (16.7), 97
‡ ‡
Sample 3 (39.0 g, 0.160 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 5.8±6.3 V, 7±
8 8C, 583 min (213 Ah). The work-up gave the following
products in the À78 8C trap (8.4 g): a mixture of
(CF3)2NC2F5 (28) and (CF3)2NCF2C(O)F (30) (1.9 g),
C2F5(CF3)NCF2C(O)F (31) (3.4 g), C3F7(CF3)NCF2C(O)F
(36) (1.7 g), C3F7(C2F5)NCF2C(O)F (37) (0.5 g), per-
¯uoro(2,6-dimethyl-2,6-diazaheptane) (8) (0.3 g), per-
¯uoro(1,4-dimethyl-1,4-homopiperazine) (7) (0.1 g) and
unidenti®ed products (0.4 g). Cell drainings (17.6 g):
C3F7(CF3)NCF2C(O)F (36) (0.4 g), C3F7(C2F5)NCF2C(O)F
(37) (0.8 g), per¯uoro(2,6-dimethyl-2,6-diazaheptane) (8)
(0.8 g), per¯uoro(1,4-dimethyl-1,4-homopiperazine) (7)
(0.6 g), per¯uoro(3,7-dimethyl-3,7-diazaoctanoyl ¯uoride)
(15) (2.7 g), per¯uoro(4-methylhomopiperazin-1-ylacetyl-
‡
‡
CF2C(O)F (14.4), 69 CF3 (100).
Per¯uoro(N-ethyl-N-propylaminoacetyl ¯uoride) (37)
(nc): IR (gas): 1894 [n(C=O)] (m), 1350 (m, sh), 1310 (s,
sh), 1298 (s), 1244 (vs), 1177 (m), 1153 (m), 1136 (m), 739
‡
‡
‡
(m). Mass: 352 [M-C(O)F] (13.5), 280 [M-C2F5] (4.7),
‡
‡
169 C3F7 (59.4), 164 C3F6N (30.9), 119 C2F5 (48.7),
‡
‡
‡
114 C2F4N (23.0), 100 C2F4 (13.6), 97 CF2C(O)F
‡
(25.4), 69 CF3 (100).
Methyl esters of 37, 36, 16, 15, 14 and 13 were prepared in
a similar manner as explained for 10 and characterized
similarly.
Methyl per¯uoro(N-methyl-N-propylaminoacetate) (38)
(nc): bp 121.5±123.5 8C, n2D0 1.3003 and d420 1.6475. IR
‡
(capillary ®lm): 1798 [n(C=O)] (s). MS: 302 [M-C(O)OMe]

T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
37
‡
‡
(17.8), 169 C3F7 (22.4), 114 C2F4N (26.3), 109
‡
8 8C, 606 min (218 Ah). The work-up gave the following
products in the À78 8C trap (12.2 g): (CF3)2NCF2C(O)F
(30) (1.2 g), (C2F5)2NCF3 (21) (3.9 g), (C2F5)2NCF2C(O)F
(22) (2.5 g), per¯uoro(1,4-dimethylpiperazine) (19) (2.7 g),
per¯uoro(4-methylpiperazin-1-ylacetyl ¯uoride) (17) [15]
(0.8 g) and unidenti®ed products (1.1 g).
Cell drainings (7.6 g): (C2F5)2NCF3 (21) (0.2 g),
(C2F5)2NCF2C(O)F (22) (0.9 g), per¯uoro(1,4-dimethylpi-
perazine) (19) (2.0 g), per¯uoro(4-methylpiperazin-1-ylace-
tyl ¯uoride) (17) (4.2 g) and unidenti®ed products (0.3 g).
The GC yields of 17, 19, 21 and 22 were 6, 6, 6 and 5%,
respectively.
‡
‡
CF2C(O)OMe (20.7), 69 CF3 (61.7), 65 CF2CH3 (8.9),
59 C(O)OMe (100). Analysis: calc. for C7F12NO2H3: C,
23.27%; F, 63.2%. Found: C, 22.38%; F, 63.1%.
Methyl per¯uoro(N-ethyl-N-propylacetate) (39) (nc): bp
133±135 8C, n2D0 1.3046 and d420 1.6927. IR (capillary ®lm):
1796 [n(C=O)] (ms). MS: 352 [M-C(O)OMe] (23.0169
C3F7 (46.5), 164 C3F6N (25.1), 119 C2F5 (25.9), 114
C2F4N (12.3), 109 CF2C(O)OMe (22.0), 100 C2F4
‡
‡
‡
‡
‡
‡
‡
‡
‡
‡
(11.9), 69 CF3 (48.0), 59 C(O)OMe (100). Analysis:
calc. for C8F14NO2H3: C, 23.36%; F, 64.7%. Found: C,
23.29%; F, 64.5%.
Methyl per¯uoro(3,7-dimethyl-3,7-diazaoctanoate) (40)
(nc): bp 163±164 8C, nD20 1.3095 and d420 1.7401. IR (capil-
4.5. Fluorination of methyl 4-ethylpiperazin-1
-ylacetate (5)
‡
lary ®lm): 1798 [n(C=O)] (s). MS: 435 [M-CF2C(O)OMe]
(15.8), 342 CF2CF2CF2N(CF3)CF2C(O)OMe (6.6), 302
‡
‡
‡
(CF3)2CF2CF2CF2
‡
(6.3), 214 C4F8N
‡
(26.3), 202
‡
Sample 5 (39.1 g, 0.210 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 6.0±6.3 V, 7±
8 8C, 643 min (233 Ah). The work-up gave the following
products in the À78 8C trap (9.9 g):a mixture of (CF3)2NC2F5
(28) and (CF3)2NCF2C(O)F (30) (2.0 g), (C2F5)2NCF3 (21)
(1.3 g), (C2F5)3N (23) (4.5 g), per¯uoro(1-ethyl-4-methylpi-
perazine) (20) (1.2 g) and unidenti®ed products (0.9 g). Cell
drainings (16.7 g): (C2F5)3N (23) (1.7 g), 20 (5.9 g), per-
¯uoro(4-ethylpiperazin-1-ylacetyl ¯uoride) (18) (8.2 g) and
unidenti®ed products (0.9 g). The GC yields of 18, 20, 28 and
43 were 9, 8, 2 and 8%, respectively. Spectral data (IR and
mass) of 18 are shown below. Its 19F NMR data are shown in
Table 1.
(CF3)2NCF2 (9.3), 169 C3F7 (14.1), 131 C3F5 (4.1),
‡
‡
‡
114 C2F4N (47.1), 109 CF2C(O)OMe (33.4), 100 C2F4
‡
‡
‡
(13.0), 81 C2F3 (22.1), 69 CF3 (77.6), 65 CF2CH3 (8.7),
‡
59 C(O)OMe (100). Analysis: calc. for C9F17N2O2H3: C,
21.86%; F, 65.4%. Found: C, 21.95%; F, 65.1%.
Methylper¯uoro(4-methylhomopiperazin-1ylacetate)(41)
(nc): bp 170±172 8C, nD20 1.3279 and d420 1.7917. IR (gas):
‡
1798 [n(C=O)] (s). MS: 397 [M-C(O)OMe] (5.4), 309
C6F11N2 (2.9), 214 C4F8N (14.2), 164 C3F6N (14.8),
‡
‡
‡
‡
‡
‡
‡
‡
145 C3F5N (3.1), 119 C2F5 (6.2), 114 C2F4N (25.2), 109
‡
CF2C(O)OF (23.3), 100 C2F4 (16.5), 69 CF3 (31.4), 65
‡
‡
CF2CH3 (7.6), 59 CF2C(O)OMe (100). Analysis: calc. for
C9F16N2O4H6: C, 23.68%; F, 62.5%. Found: C, 23.78%; F,
62.3%.
Per¯uoro(4-ethylpiperazin-1-ylacetyl ¯uoride) (18) (nc):
IR (gas): 1894 [n(C=O)] (ms), 1342 (s), 1304 (vs), 1279 (s),
1250 (vs), 1196 (s), 1148 (m), 1080 (m), 1051 (ms), 957 (s),
Dimethyl ester of per¯uororo(3,7-dimethyl-3,7-diazano-
nanedioic acid) (42) (nc): bp 215±217 8C, n2D0 1.3374. IR
(capillary ®lm): 1794 [n(C=O)] (s). MS: 475 [M-
‡
822 (ms), 766 (w), 741 (m). MS: 425 [M-F] (2.7), 397 [M-
‡
‡
‡
C(O)F] (24.7), 309 C6F11N2 (9.0), 259 C5F9N2 (15.4),
171 C4F5N2 (8.4), 164 C3F6N (32.8), 119 C2F5 (100),
‡
‡
‡
‡
‡ ‡ ‡
C(O)OMe] (4.0), 342 CF2CF2CF2N(CF3)CF2C(O)OMe
‡
‡
‡
‡
(43.0), CH3OC(O)CF2CF2CF2CH3 (9.5), 214 C4F8N
‡
114 C2F4N (67.7), 100 C2F4 (45.9), 97 CF2C(O)F
(23.6), 69 CF3 (73.5), 50 CF2 (7.8).
‡
‡ ‡
(10.3), 169 C3F7 (4.2), 150 C3F6 (8.3), 131 C3F5
‡
‡
(6.1), 124 CH3OC(O)CF2CH3 (7.2), 114 C2F4N (14.7),
‡
The methyl ester of 18 was prepared for the further
characterization in a similar manner as explained for 10.
Methyl per¯uoro(4-ethylpiperazin-1-ylacetate) (44) (nc):
bp 166±168 8C, n2D0 1.3197 and d420 1.7475. IR (capillary
‡
‡
‡
109 CF2C(O)OMe (54.0), 100 C2F4 (14.6), 81 C2F3
‡
(41.1), 69 CF3 (27.5), 59 C(O)OMe (100).
1,4-Bis(methoxycarbonyldi¯uoromethyl)-per¯uoro(1,4-
‡
‡
homopiperazine) (43) (nc): bp. 235±238 8C, n2D0 1.3562 and
®lm): 1796 [n(C=O] (s). MS: 397 [M-C(O)OMe ] (6.7),
259 C5F9N2 (3.9), 195 C4F7N (2.7), 164 C3F6N (11.7),
‡
‡
d420 1.7297. IR (gas): 2968 n(CH) (w), 1793 [n(C=O] (s). MS:
437 [M-C(O)OMe] (15.8), 214 C4F8N (25.7), 114 C2F4N
‡
‡
‡
‡ ‡ ‡
145 C3F5N (3.0), 119 C2F5 (25.1), 114 C2F4N (23.9),
‡
‡
‡
‡
‡
(20.5), 109 CF2C(O)OMe (42.5), 100 C2F4 (21.8), 81
‡
109 CF2C(O)OMe (22.6), 69 CF3 (17.3), 59 C(O)OMe
(100). Analysis: calc. for C9F15N2O2H3: C, 23.68%; F,
62.5%. Found: C, 23.75%; F, 62.3%.
‡
‡
C2F3 (22.1), 69 CF3 (12.9), 65 CF2CH3 (15.2), 59
‡
C(O)OMe (100). Analysis: calc. for C11F14N2O4H6: C,
26.61%; F, 53.6%. Found: C, 26.74%; F, 53.8%.
19F NMR data of 13, 14, 15, 16, 36, 37, 38, 39, 40, 41, 42
and 43 are shown in Table 1.
19F NMR data of 18 and 44 are shown in Table 1.
4.6. Fluorination of 1,4-
bis(methoxycarbonylmethyl)piperazine (6)
4.4. Fluorination of methyl 4-methylpiperazin-
1-ylacetate (4)
Sample 6 (37.6 g, 0.154 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 6.0±6.5 V, 7±
8 8C, 614 min (255 Ah). The work-up gave the following
products in the À78 8C trap (8.5 g): (CF3)2NCF2C(O)F (30)
Sample 4 (29.2 g, 0.228 mol) was ¯uorinated similarly
under the following conditions; 3.2 A/dm2, 6.1±6.6 V, 7±

38
T. Abe et al. / Journal of Fluorine Chemistry 119 (2003) 27±38
[9] T. Abe, H. Baba, I. Soloshonok, J. Fluorine Chem. 111 (2001) 115±
128 (preceding paper of this series).
(1.2 g), (C2F5)2NCF3 (21) (2.2 g), (C2F5)2NCF2C(O)F (22)
(2.1 g), per¯uoro(1,4-dimethylpiperazine) (19) (1.3 g), per-
¯uoro(4-methylpiperazin-1-ylacetyl ¯uoride)(17) (0.8 g)
and unidenti®ed products (0.9 g). Cell drainings (7.7 g):
21 (trace), 22 (0.7 g), 19 (0.7 g), 17 (3.2 g), per¯uoro[1,4-
bis(¯uorocarbonylmethyl)-1,4-piperazine](24) [15] (2.8 g)
and unidenti®ed products (0.3 g). The GC yields of 17,
19, 24 and 22 were 6, 3, 4 and 5%, respectively.
[10] H. Baba, T. Abe, E. Hayashi, Nihon Kagaku Kaishi, J. Chem. Soc.
Jpn. Chem. Ind. Chem. (1986) 1249±1251.
[11] T. Abe, S. Nagase, J. Fluorine Chem. 13 (1979) 519±530.
[12] T. Abe, E. Hayashi, H. Baba, K. Kodaira, S. Nagase, J. Fluorine
Chem. 26 (1984) 417±434.
[13] E. Hayashi, T. Abe, H. Baba, S. Nagase, J. Fluorine Chem. 23 (1983)
371±381.
[14] E. Hayashi, T. Abe, H. Baba, S. Nagase, J. Fluorine Chem. 26 (1984)
417±434.
[15] T. Abe, I. Soloshonok, H. Baba, A. Sekiya, J. Fluorine Chem. 99
(1999) 51±57.
Acknowledgements
[16] P. Sartori, D. Velayutham, N. Ignat'ev, M. Noel, J. Fluorine Chem. 83
(1997) 1±8.
This investigation was supported by the New Energy and
Industrial Technology Development Organization (NEDO).
[17] E. Hayashi, T. Abe, H. Baba, S. Nagase, Chem. Express 3 (1989)
191±194.
[18] J.J.P. Stewart, MOPAC Version 6.00, QCPE Bull. 10, 86.
[19] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb,
J.R. Cheeseman, V.G. Zakrzewski, J.A. Montgomery, Jr., R.E.
Startmann, J.C. Burant, S. Dapprich, J.M. Millam, A.D. Daniels,
K.N. Kudin, M.C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi,
R. Cammi, B. Mennucci, C. Pomelli, C, Adamo, S. Clifford, J.
Ochterski, G.A. Petersson, P.Y. Ayala, Q. Cui, K. Morokuma, D.K.
Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J. Cioslows-
ki, J.V. Ortiz, A.G. Baboul, B.B. Stfanov, G. Liu, A. Liashenko, P.
Piskorz, I. Komaromi, R. Gomperts, R.L. Martin, D.J. Fox, T. Keith,
M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, C. Gonzalez, M.
Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, J.L.
Andres, M. Head-Gordon, E.S. Replogle, J.A. Pople, Gaussian'98,
Revision A.7, Gaussian Inc., Pittsburgh, PA, 1998.
[20] H. Fukaya, et al., in preparation.
References
[1] T. Abe, E. Hayashi, H. Baba, H. Fukaya, J. Fluorine Chem. 48 (1990)
257±279.
[2] T. Abe, E. Hayashi, H. Fukaya, H. Baba, J. Fluorine Chem. 50 (1990)
173±196.
[3] T. Abe, E. Hayashi, H. Fukaya, Y. Hayakawa, H. Baba, J. Fluorine
Chem. 57 (1992) 101±111.
[4] T. Abe, H. Fukaya, E. Hayashi, Y. Hayakawa, M. Nishida, H. Baba,
J. Fluorine Chem. 66 (1994) 193±201.
[5] T. Abe, H. Fukaya, T. Ono, E. Hayashi, I. Soloshonok, K. Okuhara, J.
Fluorine Chem. 87 (1998) 193±201.
[6] T. Abe, S.K. Pandey, H. Baba, J. Fluorine Chem. 105 (2000) 149±157.
[7] T. Abe, H. Baba, I. Soloshonok, J. Fluorine Chem. 108 (2001) 21±35.
[8] T. Abe, H. Baba, I. Soloshonok, J. Fluorine Chem. 111 (2001) 101±
104, , for the erratum of the 19F NMR data, see 111 (2002) 101±104.
[21] S.M. McElevain, L.W. Bannister, J. Am. Chem. Soc. 76 (1954)
1126±1137.
[22] R.B. Moffett, J. Org. Chem. 14 (1949) 862±867.