Synthesis of new 1-substituted 4-perfluoroalkyl tetrazol-5-ones

Article abstract of DOI:10.1016/j.jfluchem.2008.06.019

1,3-Dipolar cycloaddition of perfluoroalkyl ethyle azides 1 with isocyanates 2 afforded 1-perfluoroalkyl-4-(n-Bu, phenyl or mesitylsulfonyl) tetrazol-5-ones 3 in good yields. The use of perfluoroalkyl ethyl azides extends the reaction to the less reactive

Full text of DOI:10.1016/j.jfluchem.2008.06.019

Journal of Fluorine Chemistry 129 (2008) 1073–1075
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis of new 1-substituted 4-perfluoroalkyl tetrazol-5-ones
*
Nejib Mekni , Ahmed Baklouti
Laboratory of Structural Organic Chemistry, Department of Chemistry, Faculty of Sciences of Tunis, Elmanar, 2092 Tunis, Tunisia
A R T I C L E I N F O
A B S T R A C T
Article history:
1,3-Dipolar cycloaddition of perfluoroalkyl ethyle azides 1 with isocyanates 2 afforded 1-perfluoroalkyl-
4-(n-Bu, phenyl or mesitylsulfonyl) tetrazol-5-ones 3 in good yields. The use of perfluoroalkyl ethyl
azides extends the reaction to the less reactive n-butyl isocyanate.
Received 18 March 2008
Received in revised form 19 June 2008
Accepted 19 June 2008
ß 2008 Elsevier B.V. All rights reserved.
Available online 27 June 2008
Keywords:
1,4-Tetrazol-5-one
1,3-Dipolar cycloaddition
Perfluoroalkyl azide
Isocyanate
1. Introduction
in pharmaceuticals and pesticides [26]. The development of an
efficient method for the synthesis of perfluoroalkylated hetero-
Tetrazoles are widely used due to their applications as
pesticides [1–4], antihypertensive, antialergic, antibiotic and
anticonvulsant agents [5–8]. They have also found use in cancer,
AIDS and obesity treatments [9–13]. These various applications are
presumably due to the metabolic stability of the tetrazole ring
which led to a wider use of their derivatives, including those
containing the 5-oxo-substituent (tetrazolones) [14].
1,4-Disubstituted tetrazolin-5-ones are indirectly synthesized
from reaction of azide ion [15] or trimethylsilylazide [16] with
isocyanates. The reaction yields initially monosubstituted tetrazol-
2-ones, which via an alkylation reaction, leads to the formation of a
mixture of N-alkylation and O-alkylation products [17] (Scheme 1).
Direct synthesis of 1,4-disubstituted tetrazol-5-ones [18] from
isocyanates and azides have been less reported due to the long
reaction time, poor yields and unreactivity of some alkyl
isocyanates [19]. Both alkyl and arylsulfonyl isocyanates were
used on several occasions [18–20], particularly in 1,3-dipolar
cycloaddition reactions [21]. Perfluoroalkyl azides have been, in
their turn, used as intermediates in the preparation of corre-
sponding perfluoroalkyl imines [22], amines [23] and triazoles
[24] as well as in the synthesis of compounds that have interesting
surface properties [25].
cycles is thus of growing interest due to their wide potential
bioactivities and commercial applications [27–29].
We have previously shown that isocyanates, aryl and alkox-
ysulfonyl isocyanates reacted with alcohols [30], thiols [31] and
amines [32] to give acyclic compounds.
Herein we report the direct synthesis of 1-substituted 4-
perfluoroalkyl tetrazol-5-ones 3 via the reaction of isocyanates 2
with fluorinated alkyl azides 1. These new fluoroheterocyclic
compounds were obtained in good to excellent yields.
2. Results and discussion
Perfluoroalkyl azides 1 react readily with isocyantes 2 to give
the 1-substituted 4-perfluoroalkyl tetrazol-5-ones in good yields
(Scheme 2).
The long reaction time known for this type of reactions [18,19]
is observed with n-butyl isocyanate. As expected, a significant
increase in the reaction rate occurs with the more reactive phenyl
and arylsulfonyl isocyanates, leading at the same time to better
reaction yields (see Table 1).
n-Butyl isocyanate was found to be unreactive toward azides
including the most reactive one, n-butyl azide [19]. In contrast, it is
shown in Table 1 that perfluoroalkyl azides do react with n-butyl
isocyanate to form products 3a and 3b. This can be expected since
the introduction of a perfluoroalkyl group in a molecule may
remarkably modify its chemical properties and biological activity
[33,34]. The better reactivity of the perfluoroalkyl azides as
compared to non-fluorinated analogs is thought to arise from the
electron withdrawing effects of the perfluoroalkyl group which
On the other hand, it has been shown that fluorine-containing
compounds, especially fluorinated heterocycles have good and
extensive biological activities allowing their possible applications
* Corresponding author.
E-mail address: mekninejib@yahoo.fr (N. Mekni).
0022-1139/$ – see front matter ß 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2008.06.019

1074
N. Mekni, A. Baklouti / Journal of Fluorine Chemistry 129 (2008) 1073–1075
Scheme 1.
heated at 70 8C for 14 days. Toluene was evaporated and the crude
product was purified by column chromatography, using initially
petroleum ether to eliminate impurities, then a petroleum ether/
diethyl ether mixture (90/10) to obtain tetrazol-5-one 3a as a
viscous oil; IR:
3JHH = 7.2), 1.37 (m, 2H, CH2–CH2–CH3), 1.51 (m, 2H, CH2), 2.46 (tt,
n d 0.94 (t, 3H, CH3–,
1720 cmÀ1 (C O); 1H NMR,
3
3
2H, CH2–CF2, JHH = 6.3, JHF = 17.9), 3.19 (m, 2H, CH2–N), 4.39 (t,
3
2H, CH2–N, JHH = 6.1); 13C NMR,
d 13.9 (s, 1C, CH3–) 20.1 (s, 1C,
Scheme 2.
2
CH2–CH3), 31.1 (t, 1C, CH2–CF2, JCF = 21.2), 31.6 (s, 1C, CH2CH2–
Table 1
CH2), 41.3 (s, 1C, CH2–N), 57.1 (s, 1C, CH2–N), 106–124 (m, 6CF),
Perfluoroalkylated tetrazol-5-ones 3
156.1 (s, 1C = O); 19F NMR,
d
À113.2 (m, CF2
,
3JFH = 18.39 Hz),
a
À121.8 (m, CF2 ), À123.7 (m, CF2 ), À123.1 (m, CF2 ), À127.2 (m,
R
RF
Tetrazol-5-one 3 Reaction time (day) Yield (%)
b
g
d
3
CF2 ), À82.1 (tt, CF3, JCF3 = 9.17 Hz); HRMS: calcd. for
v
n-Bu
C6F13 3a
C8F17 3b
14
15
77
80
C13H13F13N4O: 488.08828; found 488.08796.
C6H5
C6F13 3c
C8F17 3d
2
2
90
97
4.1.2. 1-Butyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10,-
heptadecfluorodecyl)-1H-tetrazol-5(4H)-one (3b)
C6F13 3e
C8F17 3f
1
1
95
97
A mixture of perfluoroalkyl azide 1b (3 mmol, 1.47 g) and n-
butylisocyanate 2a (3 mmol, 0.30 g) was reacted and the product
purified in the same manner as for 3a to obtain tetrazol-5-one 3b
as a white solid; m.p. = 48 8C; IR:
n d
1721 cmÀ1 (C O); 1H NMR,
3
0.93 (t, 3H, JHH = 7.1), 1.36 (m, 2H), 1.49 (m, 2H), 2.45 (m, 2H,
3
3
3JHH = 6.2, JHF = 18.4), 3.18 (m, 2H), 4.37 (t, 2H, JHH = 6.3); 13C
NMR,
d
13.5 (s, 1C) 19.8 (s, 1C), 30.9 (t, 1C, 2JCF = 21.5), 31.2 (s, 1C),
40.8 (s, 1C), 56.6 (s, 1C), 106–124 (m, 8CF), 155.9 (s, 1C O); 19F
would favor the canonical form, responsible for such cycloaddition
reactions.
NMR,
d
À114.9 (m, CF2 , 3JFH = 18.4 Hz), À123.0 (m, CF2 ), À124.9
a
b
(m, CF2 ), À124.1 (m, CF2 ), À123.2 (m, 2CF2 ), À127.5 (m, CF2 ),
g
d
e
v
3
À82.3 (tt, CF3, JCF3 = 9.2 Hz); HRMS: calcd. for C15H13F17N4O:
588.08189; found 588.08127.
3. Conclusion
4.1.3. 1-Phenyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1H-
tetrazol-5(4H)-one (3c)
A mixture of perfluoroalkyl azide 1a (3 mmol, 1.17 g) and
phenylisocyanate 2b (3 mmol, 0.36 g) in 15 mL of dry toluene was
heated at 100 8C for 2 days. The crude product was purified as
New 1-substituted 4-perfluoroalkyl tetrazol-5-ones were pre-
pared directly from isocyanates and perfluoroalkyl azides in good
to excellent yields. The use of perfluoroalkyl azide extends the
reaction of azides to n-butyl isocyanate. The possible biological
activity of these new fluorinated heterocyclic compounds is under
investigation.
described for 3a to obtain tetrazol-5-one 3c as a viscous oil; IR:
n
3
3
1722 cmÀ1 (C O); 1H NMR,
d 2.72 (tt, 2H, JHH = 6.2, JHF = 18.4),
4.48 (t, 2H, 3JHH = 6.2); 7.04–7.65 (m, 5H, arom); 13C NMR,
d
31.3 (s,
4. Experimental
2
1C, JCF = 21.8 Hz), 57.3 (s, 1C), 105–125 (m, 8CF), 119.2 (s, 1C),
IR spectra were recorded on PerkinElmer Paragon 1000 PC
spectrometer. 1H, 13C and 19F NMR spectra were recorded in CDCl3
on a Bruker AC 300 spectrometer at 300, 75 and 282 MHz,
respectively, for 1H (TMS), 13C (TMS) and 19F (CFCl3). HRMS spectra
in chemical ionization mode were carried out on a MAT 95 SBE
spectrometer. The silica gel used is of Merck 7734 type. The HRMS
spectra were performed at the ‘‘Institut National de Recherche et
d’Analyse Physico-chimique (INRAP), Laboratoire d’analyses, Pole
Technologique, Sidi Thabet-2020-Tunisia’’.
123.6 (s, 1C), 129.6 (s, 2C), 139.8 (s, 1C), 153.9 (s, 1C = O); 19F NMR,
d
À109.1 (m, CF2
,
3JFH = 16.0 Hz), À118.0 (m, CF2 ), À119.3 (m,
a
b
CF2 ), À118.3 (m, CF2 ), À117.4 (m, 2CF2 ), À121.36 (m, CF2 ),
g
d
e
v
3
À76.4 (tt, CF3, JCF3 = 9.3 Hz); HRMS: calcd. for C15H9F13N4O:
508.05698; found 508.05729.
4.1.4. 1-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10,-heptadecfluorodecyl)-4-
Phenyl-1H-tetrazol-5(4H)-one (3d)
A mixture of perfluoroalkyl azide 1b (3 mmol, 1.47 g) and
phenylisocyanate 2b (3 mmol, 0.36 g) was reacted and the product
purified inthe samemannerasfor3ctoobtain tetrazol-5-one 3dasa
Perfluoroalkyl ethyl azides 1 were prepared as previously
described in the literature [24].
white solid. m.p. = 50 8C; IR:
2H, 3JHH = 6.3, 3JHF = 18.3), 4.50 (t, 2H, 3JHH = 6.3); 7.05–7.60 (m, 5H,
arom); 13C NMR, 31.2 (s, 1C, 2JCF = 21.3 Hz), 57.3 (s, 1C), 105–125
n d 2.70 (tt,
1723 cmÀ1 (C O); 1H NMR,
4.1. Preparation of 4-substitueted 1-perfluoroalkyl tetrazol-5-ones
(3)
d
(m, 8CF), 119.2 (s, 1C), 123.6 (s, 1C), 129.5 (s, 2C), 139.8 (s, 1C), 153.8
4.1.1. 1-Butyl-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-1H-
tetrazol-5(4H)-one (3a)
A mixture of perfluoroalkyl azide 1a (3 mmol, 1.17 g) and n-
butyl isocyanate 2a (3 mmol, 0.30 g) in 15 mL of dry toluene was
(s, 1C = O); 19F NMR,
d
À109.8 (m, CF2 , 3JFH = 16.0 Hz), À118.0 (m,
a
CF2 ), À119.96 (m, CF2 ), À119.09 (m, CF2 ), À118.2 (m, 2CF2 ),
b
g
d
e
À122.56 (m, CF2 ), À77.48 (m, CF3, 3JCF3 = 10.0 Hz); HRMS: calcd. for
v
C17H9F17N4O: 608.05059; found 608.04988.

N. Mekni, A. Baklouti / Journal of Fluorine Chemistry 129 (2008) 1073–1075
1075
[7] (a) J.H. Toney, P.M.D. Fitzgerald, N. Grover-Sharma, S.H. Olson, W.J. May, J.G.
Sundelof, D.E. Vanderwall, K.A. Cleary, S.K. Grant, J.K. Wu, J.W. Kozarich, D.L.
Pompliano, G.G. Hammond, Chem. Biol. 5 (1998) 185–196;
4.2. Mesityl 5-oxo-4-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluororoctyl)-
4,5-dihydro-1H-tetrazole-1-sulfonate (3e)
(b) A. De Desarro, D. Ammendola, M. Zappala, S. Grasso, G.B. De Sarro, Antimicrob.
Agents Chemother. 39 (1995) 232–237.
[8] S. Berghmans, J. Hunt, A. Roach, P. Goldsmith, Epilepsy Res. 75 (2007) 18–28.
[9] Y. Tamura, F. Watanabe, T. Nakatani, K. Yasui, M. Fuji, T. Komurasaki, H. Tsuzuki, R.
Maekawa, T. Yoshioka, K. Kawada, K. Sugita, M. Ohtani, J. Med. Chem. 41 (1998)
640–649.
[10] (a) E. Muraglia, O.D. Kinzel, R. Laufer, M.D. Miller, G. Moyer, V. Munshi, F. Orvieto,
M.C. Palumbi, G. Pescatore, M. Rowley, P.D. Williams, V. Summa, Bioorg. Med.
Chem. Lett. 16 (2006) 2748–2752;
A mixture of perfluoroalkyl azide 1a (3 mmol, 1.17 g) and 2,4,6-
trimethylphenylsulfoxy isocyanate 2c (3 mmol, 0.72 g) was
reacted and the product purified in the same manner as for 3c
to obtain tetrazol-5-one 3e as a viscous oil; IR:
1H NMR,
: 2.28 (s, 3H, 1CH3–) 2.42 (s, 6H, 2CH3–), 2.75 (tt, 2H,
n
1722 cmÀ1 (C O);
d
3
3
3
CH2–CF2, JHH = 6.2, JHF = 18.1), 4.55 (t, 2H, CH2–N, JHH = 6.1);
7.03 (s, 2H, arom); 13C NMR,
d 20.8 (s, 1C, CH3–, arom), 22.1 (s, 2C,
(b) J.A. O’Meara, A. Jakalian, S. La Plante, P.R. Bonneau, R. Coulombe, A.-M.
Faucher, I. Guse, S. Landry, J. Racine, B. Simoneau, B. Thavonekham, C. Yoakim,
Bioorg. Med. Chem. Lett. 17 (2007) 3362–3366;
2CH3–, arom), 32.2 (s, 1C, 2JCF = 22.1 Hz) 58.1 (s, 1C), 101–125 (m,
6CF), 129.2 (s, 1C, arom), 132.1 (s, 2C, arom), 136.9 (s, 2C, arom),
(c) A. Savarino, Retrovirology 4 (2007), art. no. 21.
147.0 (s, 1C, arom), 155.1 (s, 1C = O); 19F NMR,
d
À108.7 (m, CF2
,
a
[11] T.L. Shih, M.R. Candelore, M.A. Cascieri, S.-H.L. Chiu, L.F. Colwell Jr., L. Deng, W.P.
Feeney, M.J. Forrest, G.J. Hom, D.E. MacIntyre, R.R. Miller, R.A. Stearns, C.D.
Strader, L. Tota, M.J. Wyvratt, M.H. Fisher, A.E. Weber, Bioorg. Med. Chem. Lett.
9 (1999) 1251.
[12] R.J. Mathvink, J.S. Tolman, D. Chitty, M.R. Candelore, M.A. Cascieri, L.F. Jr. Colwell,
L. Deng, W.P. Feeney, M.J. Forrest, G.J. Hom, D.E. MacIntyre, R.R. Miller, R.A.
Stearns, L. Tota, M.J. Wyvratt, H. Fisher, A.E. Weber, in: F. Ahmed, E.C. Breinlinger,
B.C. Follows, W.B. Geiss (Eds.), Potent, Selective and Orally Bioavailable 3-Pyr-
idylethanolamine-3 Adrenergic Receptor Agonists Possessing a Thiazole Benze-
nesulfonamide Pharmacophore, vol. 4, no., 48, Albany Molecular Research, Inc.
Technical Reports, 220th American Chemical Society National Meeting, Washing-
ton, D.C., August 20–24, 2000, Medicinal Chemistry Department, Albany Mole-
cular Research, Inc., Albany, NY, 28 pp.
3JFH = 16.0 Hz), À117.1 (m, CF2 ), À118.8 (m, CF2 ), À117.9 (m,
b
g
CF2 ), À116.8 (m, 2CF2 ), À121.5 (m, CF2 ), À76.2 (m, CF3,
d
e
v
3JCF3 = 9.1 Hz); HRMS: calcd. for C18H15F13N4O4S: 630.06075;
found 630.05994.
4.3. Mesityl 4-(3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-
heptadecafluorodecyl)-5-oxo-4,5-dihydro-1H-tetrazole-1-sulfonate
(3f)
[13] J.Y.L. Chung, G.-J. Ho, M. Chartrain, C. Roberge, D. Zhao, J. Leazer, R. Farr, M.
Robbins, K. Emerson, D.J. Mathre, J.M. McNamara, D.L. Hughes, E.J.J. Grabowski,
P.J. Reider, Tetrahedron Lett. 40 (1999) 6739–6743.
[14] R.J. Mathvink, J.S. Tolman, D. Chitty, M.R. Candelore, M.A. Cascieri, L.F. Colwell Jr.,
L. Deng, W.P. Feeney, M.J. Forrest, G.J. Hom, D.E. MacIntyre, R.R. Miller, R.A.
Stearns, L. Tota, M.J. Wyvratt, M.H. Fisher, A.E. Weber, Bioorg. Med. Chem. Lett. 10
(2000) 1971.
[15] (a) J.P. Horwitz, B.E. Fisher, A.J. Tomasewski, J. Org. Chem. 81 (1959) 3076–3079;
(b) A. Yanagi, Y. Watanabe, S. Narabu, JP Y7-97372-A (Nihon Bayer Agrochem
K.K.), 1995.
[16] O. Tsuge, S. Urano, K. Oe, J. Org. Chem. 45 (1980) 5130–5136.
[17] A.C. Rupert, J.F. Patricia, US Patent no. 4 618 365 (1986); applied from Uniroyal
Chem. Company, Inc.
[18] G. Denecker, G. Smets, G. L’Abbe´, Tetrahedron 31 (1975) 765–775.
[19] J.-M. Vandensavel, G. Smets, G. L’Abbe´, J. Org. Chem. 38 (1973) 675–678.
[20] (a) K. Laali, V. Gold, J. Org. Chem. 51 (1986) 2395–2397;
(b) A.G.M. Barrett, M.J. Betts, A. Fenwick, J. Org. Chem. 50 (1985) 169–175.
[21] S. Ozaki, Chem. Rev. 72 (1972) 457–496.
[22] (a) F. Guenouni, F. Szo¨nyi, A. Cambon, J. Fluorine Chem. 104 (2000) 143–148;
(b) Y. Wu, Q. Sun, J. Deng, W. Tian, J. Fluorine Chem. 127 (2006) 1152–1157.
[23] (a) F. Szo¨nyi, F. Guenouni, A. Cambon, J. Fluorine Chem. 55 (1991) 85;
(b) H. Trabelsi, F. Szo¨nyi, N. Michelangeli, A. Cambon, J. Fluorine Chem. 69 (1994)
115.
A mixture of perfluoroalkyl azide 1a (3 mmol, 1.47 g) and 2,4,6-
trimethylphenylsulfoxy isocyanate 2c (3 mmol, 0.72 g) was
reacted and the product purified in the same manner as for 3c
to obtain tetrazol-5-one 3f as a yellowish solid. m.p. = 96 8C; 3f: IR:
n
1721 cmÀ1 (C O); 1H NMR,
d
: 2.29 (s, 3H, 1CH3–) 2.40 (s, 6H,
2CH3–), 2.77 (tt, 2H, 3JHH = 6.1, 3JHF = 18.4), 4.51 (t, 2H, 3JHH = 6.1),
6.95 (s, 2H, arom.); 13C NMR,
d 20.9 (s, 1C, CH3–, arom), 21.9 (s, 2C,
2CH3–, arom), 31.7 (s, 1C, CF2–CH2–2JCF = 22.2 Hz), 57.9 (s, 1C,
CH2–N), 100–127 (m, 8CF), 129.8 (s, 1C, arom), 132.1 (s, 2C, arom),
136.8 (s, 2C, arom), 147.1 (s, 1C), 154.4 (s, 1C O); 19F NMR,
d
À107.8 (m, CF2
,
3JFH = 16.0 Hz), À116.0 (m, CF2 ), À117.9 (m,
a
b
CF2 ), À117.1 (m, CF2 ), À116.3 (m, 2CF2 ), À120.6 (m, CF2 ), À75.5
g
d
e
v
3
(m, CF3, JCF3 = 9.1 Hz); HRMS: calcd. for C20H15F17N4O4S:
730.05436; found 730.05366.
Acknowledgements
The authors wish to thank the Tunisian Ministry of High
Education and Scientific Research and Technology for financial
support (LR99ES14) of this research and Dr. M.A.K. Sanhoury,
MRSC from the Department of Chemistry, Faculty of Sciences of
Tunis for technical assistance.
[24] Y.-M. Wu, J. Deng, X. Fang, Q.-Y. Chen, J. Fluorine Chem. 125 (2004) 1415–
1423.
[25] E. Mayot, C. Ge´rardin-Charbonnier, C. Selve, J. Fluorine Chem. 126 (2005) 715–
720, and references therein.
[26] X. Qian, J. Tang, W. Chen, R. Zhang, Chem. J. Chin. Univ. 15 (1994) 224–227.
[27] (a) J.T. Kuethe, A. Wong, C. Qu, J. Smitrovich, I.W. Davies, D.L. Hughes, J. Org.
Chem. 70 (2005) 2555–2567;
(b) M.C. Van Zandt, M.L. Jones, D.E. Gunn, L.S. Geraci, J.H. Jones, D.R. Sawicki, J.
Sredy, J.L. Jacot, A.T. Dicioccio, T. Petrova, A. Mitschler, A.D. Podjarny, J. Med.
Chem. 48 (2005) 3141–3152;
References
[1] M.J. Schocken, R.W. Creekmore, G. Theodoridis, G.J. Nystrom, R.A. Robinson, Appl.
Environ. Microbiol. 55 (1989) 1220–2122.
[2] G.I. Sandmann, C. Schneider, P. Boger, Z. Naturforsch, C 51 (1996) 534.
[3] A. Yanagi, Pflanzenschutz Nachrichten Bayer 54 (2001) 1–11.
[4] S.J. Lim, Y. Sunohara, H. Matsumoto, J. Pestic. Sci. 32 (3) (2007) 249–254, and
references therein.
[5] (a) F. Janssens, J. Torremans, P.A.J. Janssen, J. Med. Chem. 29 (1986) 2290–2297;
(b) T. Mavromoustakos, A. Kolocouris, M. Zervou, P. Roumelioti, J. Matsoukas, R.
Weisemann, J. Med. Chem. 42 (1999) 1714–1722;
(c) Y. Hashimoto, R. Ohashi, Y. Kurosawa, K. Minami, H. Kaji, K. Hayashida, H.
Narita, S. Murata, J. Cardiovasc. Pharm. 31 (1998) 568–575.
[6] (a) H.D. Klaubert, J.H. Sellstedt, C.J. Guinosso, S.C. Bell, R.J. Capetola, J. Med. Chem.
24 (1981) 748–752;
(c) J.J. Li, G.W. Gribble, in: J. Baldwin, R.M. Williams (Eds.), Palladium in
Heterocyclic Chemistry, vol. 20, Pergamon Press, New York, 2000, pp. 73–181.
[28] V.A. Soloshonok, Enantiocontrolled Synthesis of Fluoro-Organic Compounds:
Stereochemical Challenges and Biomedical Targets, Wiley, New York, 1999.
[29] V.P. Kukhar, V.A. Soloshonok, Fluorine-Containing Amino Acids: Synthesis and
Applications, Wiley, New York, 1995.
[30] M. El Kateb, M. Beji, A. Baklouti, J. Fluorine Chem. 81 (1997) 139.
[31] M. Beji, H. Sbihi, A. Baklouti, J. Fluorine Chem. 99 (1999) 17.
[32] M. El Kateb, M. Beji, A. Baklouti, J. Fluorine Chem. 94 (1999) 119.
[33] C. Santaella, P. Vierling, J.G. Riess, T. Gulik-Krzywicki, A. Gulik, B. Monasse,
Biochim. Biophys. Acta (BBA) Biomembr. 1190 (1994) 25–39.
[34] (a) J.B. Nivet, M. le Blanc, J. Riess, Eur. J. Med. Chem. 26 (1991) 953–960;
(b) A.M. Mahe, J. Manoux, A. Valla, R. Follana, L. Zarif, J. Greiner, P. Vierling, J.G.
Riess, Biomater. Artif. Cells Immobil. Biotechnol. 19 (1991) 426.
(b) M. Anselmi, L. Bellussi, D. Passali, Acta Otorhinolaryngol. Ital. Suppl. 14 (1994)
95–103.