Improved synthesis of perfluorooctylpropyl amine

Article abstract of DOI:10.1016/j.jfluchem.2004.02.006

Hydrazinolysis of N-perfluorooctylpropyl phthalimide is an easy route to scale up for the title compound. Both the alkylation of potassium phthalimide with perfluorooctylpropyl iodide and the hydrogenolysis of the adduct of perfluoroctyl iodide to N-allyl-phthalimide provide this amine precursor in good yields. The latter procedure, however, has a better atom economy, since it requires only three steps from perfluorooctyl iodide.

Full text of DOI:10.1016/j.jfluchem.2004.02.006

Journal of Fluorine Chemistry 125 (2004) 1143–1146
Improved synthesis of perfluorooctylpropyl amine
a
Abudurexiti Abulikemu , Gabor Halasz , Antal Csampai ,
a
b
´
´
¨ ¨
Agnes Gomory , Jozsef Rabai
´
c
a,*
´
´
´
a
¨ ¨
´
Department of Organic Chemistry, Eotvos Lorand University, P.O. Box 32, H-1518, Budapest 112, Hungary
´
b
¨
¨
Department of General and Inorganic Chemistry, Eotvos Lorand University, P.O. Box 32, H-1518, Budapest 112, Hungary
cInstitute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525, Budapest 112, Hungary
Received 14 January 2004; received in revised form 22 February 2004; accepted 24 February 2004
Available online 1 April 2004
Abstract
Hydrazinolysis of N-perfluorooctylpropyl phthalimide is an easy route to scale up for the title compound. Both the alkylation of potassium
phthalimide with perfluorooctylpropyl iodide and the hydrogenolysis of the adduct of perfluoroctyl iodide to N-allyl-phthalimide provide
this amine precursor in good yields. The latter procedure, however, has a better atom economy, since it requires only three steps from
perfluorooctyl iodide.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Perfluorooctylpropyl amine; Preparation; Dehalogenation
1. Introduction
2. Results and discussion
Perfluorooctylpropyl amine is a nucleophilic scavenger
and important fluorophilic compound, which can also be
used as a precursor for the synthesis of novel fluorous
reagents, ligands, catalysts, tags, scavengers and protect-
ing groups [1,2]. It is accessible by multistep syntheses
(Scheme 1) starting from perfluorooctylpropyl alcohol
[3]. According to a general protocol, developed by Gladysz
and co-workers [4], alcohol 1 first was oxidized to aldehyde
2, which then reacted with benzylamine in the presence of
sodium triacetoxy-hydridoborate to yield intermediate 3,
and its hydrogenolysis afforded amine 4 in excellent yield.
An alternative route to amine 4, involves the radical chain
addition of perfluorooctyl iodide 6 to protected allyl amine 7
and subsequent dehalogenation followed by deprotection
(Scheme 2). The strategy of using N-allyl-phthalimide 7 in
combination with perfluoroalkyl iodides was first introduced
by Commeyras and co-workers [8] and recently further
elaborated for the synthesis of amino terminated semifluori-
nated long-chain alkanethiols by Amato and Calas [9].
We have found that heating N-allyl-phthalimide 7 and
perfluorooctyl iodide 6 in iso-octane for 2 days with periodic
addition of azobisisobutyronitrile (AIBN) results in the
formation of the iodo-adduct 8 in excellent yield. Then,
compound 8 was hydrogenated in THF over an Pd/C catalyst
in the presence of a slight excess of triethyl amine to afford
N-perfluorooctylpropyl phthalimide 9. Finally, the protect-
ing group was removed by heating with hydrazine hydrate in
methanol and then with 6 N hydrochloric acid. Amine 4 was
obtained from the solid precipitate with ether/NaOH–H2O
partition and consecutive fractionation of the organic phase.
This three-step procedure resulted in a 60% overall yield of 4
from F-alkyliodide 6.
´
While in the method of Rabai and co-workers [5] perfluoro-
octylpropyl iodide 5 [6] on treatment with a pressurized
solution of ammonia in THF afforded a separable mixture
of the primary and the corresponding secondary amines.
Although this amine has recently become commercially
available [7], we aimed to develop more efficient methods
for the production of primary F-alkylpropyl amines, and as a
consequence, to facilitate the access to novel amine based
fluorous reagents.
Phthalimide 9 can also be prepared in excellent yield by
heating a DMF solution of potassium phthalimide and iodide
5 as partly disclosed by us [10] (Scheme 2).The efficacy of
different routes for the preparation of amine 4 depends on
* Corresponding author. Tel.: þ36-1209-0555x1416;
fax: þ36-1209-0602.
´
E-mail address: rabai@szerves.chem.elte.hu (J. Rabai).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.02.006

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A. Abulikemu et al. / Journal of Fluorine Chemistry 125 (2004) 1143–1146
1) PhCH2NH2,
Dess-Martin
oxidation
NaBH(OAc)3
C8F17
OH
C8F17
O
THF, r.t., 5 h
CH2Cl2
2) SiO2/chromat.
2, 96%
1
H2/Pd-C, 1 atm
ether-hexanes
C8F17
NHCH2Ph
C8F17
NH2
r.t., 12 h
4, 98%
3, 90%
NH3 (liq),THF
pressure
C8F17
I
4
C8F17
+ C8F17
N
H
25 oC, 24 h
5
68%
13%
Scheme 1. Synthesis of amine 4 from the precursor alcohol 1 or iodide 5.
O
O
I
AIBN, i-octane
+
N
C8F17I
N
C8F17
70 oC, 2 d
O
O
6
7
8, 92%
O
H2/Pd-C, 40 psi
N(C2H5)3 1 eq
1) N2H4/MeOH, then
HCl-H2O reflux
8
N
C8F17
4, 77%
THF, r.t.
2) 1N NaOH/Et2O
partition
O
9, 84%
KI/H3PO4
Ref. [6]
1) K-Phthalimide, DMF
100 oC, 7 h
OH
C8F17
C8F17
I
9, 80%
85%
2) Na2CO3-H2O/CH2Cl2
5
1
Bu3SnH
Triallyl borate
AIBN
H2O
AIBN
80 oC
C8F17I
1, 77%
overall yield
Ref. [3]
(C8F17
O)3B
(C8F17
O)3B
80 oC
80 oC
I
6
10
11
Scheme 2. An F-efficient sequence (6–8–9–4) for the synthesis of amine 4.

A. Abulikemu et al. / Journal of Fluorine Chemistry 125 (2004) 1143–1146
1145
Table 1
added with stirring, then the mixture was refluxed for 2 h.
It was poured to water (300 ml) and the precipitate formed
was filtered and dried in vacuo over KOH pellets. Recrys-
tallization from iso-octane afforded 14.0 g (75%) white
needles of mp ¼ 68–69 8C, literature mp ¼ 70 8C [11].
1H NMR d: 7.79 (m, A part of an AA0XX0 spin system,
2H) and 7.67 (m, X part of an AA0XX0 spin system, 2H,
Effectiveness of different synthetic sequences for the use of 6 or 1
Entry Sequence
of steps
No. of
steps
Yield (%)
from 6 (or 1)a
1
2
3
4
6 ! 10 ! 11 ! 1 ! 2 ! 3 ! 4
6 (3)
5 (2)
6 (3)
3
65 (85)
45 (58)
40 (52)
60
6 ! 10 ! 11 ! 1 ! 5 ! 4
6 ! 10 ! 11 ! 1 ! 5 ! 9 ! 4
6 ! 8 ! 9 ! 4
0
JAX ¼ 8:1, JAX ¼ 2:6 Hz); 5.84 (ddt, 1H, J ¼ 18:4, 10.2,
a Calculated by using yield data of Schemes 1 and 2.
1.5 Hz); 5.14 (dqa, 1H, J ¼ 10:2, 1.5 Hz); 5.2 (dqa, HX, 1H,
J ¼ 18:4, 1.5 Hz); 4.24 (dt, N–CH2, 2H, J ¼ 5:7, 1.5 Hz).
13C NMR d: 117.9 (C30) 131.8 (C20); 40.3 (C10); 168.0 (C1,
C3); 132.3 (C3a, C7a); 123.5 (C4, C7); 134.2 (C5, C6).
both the yields and the number of synthetic steps involved
(Table 1). Thus, methods displayed in Entries 1–3 are viable
for smaller scale syntheses, especially if they are started at a
later step using commercially available precursors, such as
alcohol 1 or iodide 5. On the other hand, Entry 4 provides an
easy to scale up and a more cost efficient procedure.
4.2. 2-(4,4,5,5,6,6,7,7,8,8,9,9,10,10, 11,11,11-
Heptadecafluoro-2-iodo-undecyl)-isoindole-1,3-dione (8)
A solution of 6 (68.2 g, 125 mmol) and 7 (23.4 g,
125 mmol) in iso-octane (30 ml) was stirred and heated to
70 8C under an argon atmosphere, then the reaction was
initiated with AIBN (0.15 g). The mixture was stirred and
heated at this temperature and in every 3rd h further portion
of AIBN (0.15 g) was added. After 46 h reaction, GC
analysis showed >95% conversion of 7. The resulted pre-
cipitate was filtered at ice-bath temperature and washed with
cold iso-octane (30 ml) to afford the crude product as
white crystals (84.3 g, 92%; GC purity: 92%). Recrystalli-
zation (3Â) from methanol (4 ml/g) yielded an analytically
pure sample (GC: 98%), mp ¼ 90–92 8C. (Literature
3. Conclusions
The three-step sequence (Entry 4, Table 1), involving the
radical chain addition of a perfluoroalkyl iodide to a pro-
tected allyl amine, followed by reductive dehalogenation
and deprotection, could be the method of choice for amine
synthesis, when the price of the F-precursors is a limiting
factor.
1
4. Experimental
mp ¼ 90 8C/MeOH [8].) H NMR d: 7.89 (m, A part of
an AA0XX0 spin system, 2H); 7.76 (m, X part of an AA0XX0
0
Meltingpointsweredeterminedona Boetiusmicromelting
point apparatus and are uncorrected. Reagents 1, 4–6 were
commercially available [7], while 7 was prepared as reported
spin system, 2H, JAX ¼ 8:1, JAX ¼ 2:6 Hz); 4.72 (ꢀqi,
CHI, 1H, J ¼ 7:2 Hz); 2.92 (2 Â m, CH2CF2, 2H);. 4.17,
3.98 (NCH2, 2 Â dd, 2 Â 1H, J ¼ 14:3, 8.6 Hz, J ¼ 14:3,
6.8 Hz). 13C NMR d: 46.1 (C10); 13.4 (C20); 39.8 (t,
J ¼ 21:1 Hz); 167.9 (C1, C3); 131.9 (C3a, C7a); 123.9
(C4, C7); 134.6 (C5, C6). 19F NMR d: À112.5, À114.2
(CH2CF2, m, A and B parts of an ABX2 spin system,
2JFF ¼ 271 Hz, 4JFF ¼ 13:8 Hz); À126.66 (br, 2F);
À123.93 (br, 2F); À123.24 (br, 2F); À122.41 (br, 4F);
À122.06 (br, 2F); À81.38 (CF3, t, 3F, J ¼ 9:9 Hz). 15N
NMR d: 162.6. MS (m/z, I%, M À X): 734, 6, M þ 1; 733,
6, M; 714, 6, M À F; 606, 100, M À I; 586, 15; 160, 45,
M À CH(I)CH2(CF2)7CF3. HRMS (m/z) calculated for
C19H9F17INO2, Mþ ¼ 732:9407, found Mþ ¼ 732:9390.
1
[11]. H and 13C NMR spectra were recorded on a Bruker
DRX 500 spectrometer at 500 (1H) and 125 (13C) MHz with
Me4Si as internal standard. 19F NMR spectra were obtained
on a Bruker (250 MHz) spectrometer in CDCl3 with CFCl3 as
external standard, downfield shifts being designated as nega-
tive. All chemical shifts (d) are expressed in ppm, coupling
constants (J) are given in Hz. The letters s, d, t, qa, qi and m
designate singlet, doublet, triplet, quartet, quintet and multi-
plet, respectively. Mass spectra were determined on a VG
ZAB-2SEQ tandem mass spectrometer using electron impact
(70 eV) for ionization and direct probe for sample introduc-
tion at a source temperature of 180 8C. Mass range (m/z) from
25 to 1500 was considered. The accuracy of the HRMS
measurements is described by the formula: ðMðfoundÞÀ
MðcalculatedÞÞ=MðcalculatedÞ < Æ5 Â 10À6. All reaction
steps were monitored by gas chromatography (Hewlett-Pack-
ard 5890 Series II, PONA 50 m to 0.2 mm, 0.5 mm column, H2
carrier gas, FID).
4.3. 2-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-Hepta-
decafluoroundecyl)-isoindole-1,3-dione (9)
4.3.1. Method A
In a 500 ml volume Pyrex bottle of a Parr hydrogenation
apparatus were placed the iodo-adduct
8 (33.0 g;
45.0 mmol) dissolved in THF (230 ml), triethyl amine
(7.0 ml; 50 mmol) and 10% Pd-C (0.90 g). After removal
of air with N2, this mixture was hydrogenated at room
temperature and at a pressure of 40–50 psi until higher than
98% conversion detected (GC). The mixture was then
4.1. 2-Allyl-isoindole-1,3-dione (7)
To a solution of allyl amine (5.70 g, 100 mmol) in acetic
acid (30 ml) phthalic anhydride (14.8 g, 100 mmol) was

1146
A. Abulikemu et al. / Journal of Fluorine Chemistry 125 (2004) 1143–1146
filtered through a Celite plug (30 g) which finally washed
with some THF. The combined filtrates were concentrated
in vacuum, and then diluted with water (250 ml). The solid
precipitate obtained was filtered, washed thoroughly with
water and dried. Recrystallization of the off-white crude
product from methanol (300 ml) in the presence of charcoal
yielded 22.9 g (84%) white product, mp ¼ 92–93.5 8C,
GC: 98%.
and ether (200 ml) for 3 h to afford a clear solution of
phthalylhydrazide in the water phase, and that of 4 in the
ether layer. After the separation of the phases the aqueous
solution was washed with more ether (2 Â 100 ml), then the
combined organic phase was dried (Na2SO4) and evaporated
to yield 13.8 g (77%) colorless liquid (GC: þ98%), with bp
140–41 8C/100 mmHg and spectral data agreeable to that
1
reported earlier [4,5]. H NMR d: 2.80 (t, 2H, J ¼ 6:9 Hz,
CH2CH2NH2); 2.15 (tt, 2H, J ¼ 18:9, 6.9 Hz, C8F17CH2);
1.74 (qi, 2H, J ¼ 6:9 Hz, CH2CH2NH2); 1.22 (s, br, 2H,
NH2). 13C NMR d: 41.6 (C1); 24.5 (t, J ¼ 3:2 Hz, C2); 28.7
(t, J ¼ 22:5 Hz, C3). 19F NMR d: À81.64 (br t, 3F,
J ¼ 9:9 Hz, CF3); À114.87 (ꢀt, 2F, J ¼ 13:8 Hz, CH2CF2);
À126.87 (br, 2F); À124.15 (br, 2F); À123.41 (br, 2F);
À122.56 (br, 4F); À122.40 (br, 2F). HRMS (m/z) calculated
for C11H7F17N, ½MÀHꢁþ ¼ 476:0307, found: ½MÀHꢁþ ¼
476:0302.
4.3.2. Method B
To a stirred suspension of potassium phthalimide (18.5 g,
100 mmol) in DMF (150 ml), iodide 5 (29.4 g, 50.0 mmol)
was added and the mixture heated at 100 8C for 7 h. It was
poured into 0.5 N Na2CO3 (600 ml), extracted with CH2Cl2
(3 Â 100 ml) and the combined organic phases were filtered
through Celite, washed with water (3 Â 300 ml) and dried
(Na2SO4). After evaporation of the solvent, the residue
was recrystallized from methanol (220 ml) to yield 24.3 g
(80%) of pure 3 as pale yellow needles, mp 93.0–93.8 8C
(GC: 99.4%).
Acknowledgements
1H NMR d: 7.84 (m, A part of an AA0XX0 spin system,
2H); 7.72 (m, X part of an AA0XX0 spin system, 2H, JAX
¼
Support from the Hungarian Scientific Research
Foundation (OTKA T 034871) and the European Contract
of Research Training Network (‘Fluorous Phase’ HPRN-CT-
2000-00002) is gratefully acknowledged.
0
8:1, JAX ¼ 2:6 Hz); 3.77 (t, 2H, J ¼ 7:0 Hz, N–CH2); 2.16
(m, 2H, CH2C8F17). 2.02 (qi, 2H, J ¼ 7:0 Hz, NCH2CH2).
19F NMR d: À114.72 (ꢀt, CH2CF2, 2F); À126.68 (br, 2F);
À123.87 (br, 2F); À123.27 (br, 2F); À122.01 to –122.69 (br,
6F); À81.43 (CF3, t, 3F, J ¼ 9:9 Hz). 13C NMR d: 37.2
(C10); 20.2 (C20); 28.9 (t, J ¼ 22:9 Hz); 168.4 (C1, C3);
132.2 (C3a, C7a); 123.6 (C4, C7); 134.3 (C5, C6). MS
(m/z, I%, M À X): 607, 25, M; 588, 10, M À F; 188, 8,
M À (CF2)7CF3; 160, 100, M À (CH2)2(CF2)7CF3. HRMS
(m/z) calculated for C19H10F17NO2, Mþ ¼ 607:0440, found:
Mþ ¼ 607:0449.
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