Convenient synthetic methods for the preparation of N-fluoroalkylhydroxamic acids

Article abstract of DOI:10.1081/SCC-120015396

Polyhydroxamate chelators containing fluoro substituents are of interest as potential extractants for actinides in separations involving supercritical carbon dioxide. In this context, we have developed three new reagents 1, 2, and 3, that allow the efficient incorporation of an N-fluoroalkyl hydroxamate moiety onto a variety of substrates using acylation, alkylation, and Michael addition strategies.

Full text of DOI:10.1081/SCC-120015396

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CONVENIENT SYNTHETIC METHODS FOR THE
PREPARATION OF N-FLUOROALKYLHYDROXAMIC ACIDS
Nirmal Koshti a , Gantla Vidyasagar Reddy a , Hollie Jacobs a & Aravamudan Gopalan b
a Department of Chemistry and Biochemistry , New Mexico State University , Las Cruces, NM,
88003-8001, U.S.A.
b Department of Chemistry and Biochemistry , New Mexico State University , Las Cruces,
NM, 88003-8001, U.S.A.
Published online: 23 Aug 2006.
To cite this article: Nirmal Koshti , Gantla Vidyasagar Reddy , Hollie Jacobs & Aravamudan Gopalan (2002) CONVENIENT
SYNTHETIC METHODS FOR THE PREPARATION OF N-FLUOROALKYLHYDROXAMIC ACIDS, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:24, 3779-3790, DOI: 10.1081/
SCC-120015396
To link to this article: http://dx.doi.org/10.1081/SCC-120015396
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 24, pp. 3779–3790, 2002
CONVENIENT SYNTHETIC METHODS
FOR THE PREPARATION OF
N-FLUOROALKYLHYDROXAMIC ACIDS
Nirmal Koshti, Gantla Vidyasagar Reddy,
*
Hollie Jacobs, and Aravamudan Gopalan
Department of Chemistry and Biochemistry,
New Mexico State University, Las Cruces,
NM 88003-8001, USA
ABSTRACT
Polyhydroxamate chelators containing fluoro substituents are
of interest as potential extractants for actinides in separations
involving supercritical carbon dioxide. In this context, we
have developed three new reagents 1, 2, and 3, that allow
the efficient incorporation of an N-fluoroalkyl hydroxamate
moiety onto a variety of substrates using acylation, alkyla-
tion, and Michael addition strategies.
Key Words: Hydroxamic acids; Fluorinated chelators;
Supercritical carbon dioxide; Extractants
*Corresponding author. E-mail: agopalan@nmsu.edu
3779
DOI: 10.1081/SCC-120015396
Copyright & 2002 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
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3780
KOSHTI ET AL.
An attractive strategy in the area of remediation of toxic and radio-
active metal ions involves the use of supercritical fluid extraction (SFE) for
achieving selective separations.[1] Using SFE, it is possible to chelate and
then extract target metal ions from solid radioactive wastes into supercritical
carbon dioxide.[2] This technology avoids the use of hazardous organic
solvents but a limiting factor is often the solubility of the chelator in super-
critical carbon dioxide. The addition of fluorine in the chelating structure
has been shown to greatly improve its solubility in supercritical carbon
dioxide. Many of the chelators investigated so far have been fluorinated
and unfluorinated derivatives of dithiocarbamates, b-diketones, and
organophosphorous reagents. Such extractants have limited use for the
extraction of hard metal ions such as Fe(III) or An(IV) ions.
Hydroxamic acids are well known to bind hard metal ions like Fe(III)
or An(IV).[3] As part of our ongoing program on the synthesis of hydro-
xamic acids,[4] we have been interested in the synthesis of N-fluoroalkyl-
hydroxamic acid ligands with the aim of developing chelating systems that
have applications for the extraction of actinides into supercritical carbon
dioxide. To our surprise, methodology to access N-fluoroalkylhydroxamates
has not been documented in the literature. Some reports on the synthesis of
hydroxamic acids with fluorinated acyl groups have been reported.[5–8] In
this paper, we report the synthesis of three new reagents 1, 2, and 3 and their
application to prepare a variety of N-fluoroalkylhydroxamic acids, a new
class of extractants.
For this project, it was important to develop both electrophilic and
nucleophilic reagents that allow the incorporation of N-fluoroalkylhydroxa-
mic acids onto a variety of platforms (alcohols, amines and carboxylic
acids). Treatment of commercially available 3,3,4,4,5,5,6,6,7,7,8,8,8-trideca-
fluoro-1-octanol with trifluoromethanesulfonic anhydride and triethylamine
in dichloromethane afforded the corresponding triflate which was reacted
with benzyloxyamine to furnish N-fluoroalkyl benzyloxyamine 1 in 43%
overall yield after chromatographic purification (Sch. 1). Numerous
attempts to react benzyloxyamine with the corresponding mesylates or
iodides in the presence of various bases in different solvent systems gave
only very low yields of the desired product. Treatment of amine 1 with
acryloyl chloride and triethylamine in THF at 60ꢀC gave the Michael accep-
tor 2 in excellent yields. The electrophilic a-bromohydroxamic acid 3, was
conveniently prepared by reaction of 1 with bromoacetyl bromide in THF in
the presence of triethylamine.
We have prepared a variety of N-fluoroalkylhydroxamic acids by use
of reagents 1–3 in good yields (Table 1). The hydroxylamine 1 was coupled
with a number of acid chlorides in THF in the presence of triethylamine at
room temperature to afford O-benzylhydroxamic acids in good yields

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N-FLUOROALKYLHYDROXAMIC ACIDS
3781
Scheme 1.
Table 1. Preparation of N-Fluoroalkyl Hydroxamic Acids
Starting Material Reagent
Product
Yield (%)
O
O
OR
1
7a R¼Bn, 82
7b R¼H, 99
CH3(CH2)6
N
CH3(CH2)6
Cl
C6F13
O
O
1
2
OR
8a R¼Bn, 88
8b R¼H, 99
CF3(CF2)2
N
CF3(CF2)2
C6F13
Cl
O
O
NH2ðCH2Þ3NH2
RO
OR
9a R¼Bn, 79
9b R¼H, 86
N
N
N(CH2)3N
C6F13
C6F13
2
2
O
O
O
O
RO
OR
2
10a R¼Bn, 66
10b R¼H, 85
N
N
N
C
6F13
C
6F13
N
N
N
NH HN
NH HN
C6F13
C6F13
N
N
N
RO
OR
O
CH3ðCH2Þ4OH
OR
OR
3
11a R¼Bn, 87
11b R¼H, 93
CH3(CH2)4O
C6F13
C6F13
C6F13
O
OH
3
12a R¼Bn, 98
O
N
O
ClðCH2Þ4OH
3
13a R¼Bn, 44
13b R¼H, 91
OR
Cl(CH2)4O
N
3a
14a R¼Bn, 53
14b R¼H, 87
O
C8F17ðCH2Þ3OH
OR
C8F17(CH2)3O
N
C6F13
arxn conditions: 2 eq. fluoroalcohol in ether.

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3782
KOSHTI ET AL.
(Eq. (1), Table 1) after chromatographic purification. Subsequent hydro-
genolysis of the O-benzylhydroxamic acids using a catalytic amount of
5% Pd/C in ethanol gave the desired hydroxamic acids in excellent yields.
ð1Þ
The N-fluoroalkylhydroxamic acid moiety can be readily introduced
into a variety of commercially available amine platforms by use of reagent 2.
The reagent 2, reacted cleanly with a number of amines (1.1 eq. of reagent 2
per amine equivalent) in refluxing acetonitrile to give the benzyl protected
Michael adducts in good yields (Eq. (2), Table 1) after purification. As
before, hydrogenolysis of the benzyl protected products using a catalytic
amount of 5% Pd/C in ethanol gave the desired hydroxamic acids in excel-
lent yields. Compound 5b (Eq. (2)) is a fluorinated analog of the well known
siderophore rhodotorulic acid.[9] Also, it is noteworthy that this method-
ology works very well for the preparation of tetra-N-fluoroalkylhydroxamic
acids such as the cyclam derivative 10b.
ð2Þ
The electrophilic a-bromohydroxamic acid 3 has been reacted with a
number of simple and bifunctional alcohols to give the benzyl protected
hydroxamic acids in good yields after purification (Eq. (3), Table 1).
Among the reaction conditions examined, biphasic conditions using
sodium hydroxide and t-butylammonium bromide or bisulfate as the
phase transfer catalyst was found best for this alkylation.[10] In the case of
inexpensive alcohols, it was preferable to use a large excess of the alcohol in
this alkylation to obtain a high yield of the desired product. Some hydrolysis
of the reagent 3 was observed in its coupling to the less nucleophilic fluoro-
alcohol (preparation of 14a). Hydrogenolysis of the benzyl protected prod-
ucts using a catalytic amount of 5% Pd/C in ethanol gave the desired
hydroxamic acids in excellent yields. It should also be possible to react
the a-bromohydroxamic acid 3 with amines, phenols, thiols and even

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N-FLUOROALKYLHYDROXAMIC ACIDS
3783
carbon nucleophiles to provide access to a wide range of N-fluoroalkyl-
hydroxamic acids further enhancing its synthetic utility.
ð3Þ
In summary, we have prepared three new reagents 1, 2, and 3 and
utilized them for the synthesis of a diverse array of N-fluoroalkylhydrox-
amic acid ligands in good yields. All of the N-fluoroalkylhydroxamic acids
prepared in this study exhibit good solubility in methanol, an important
additive used in supercritical carbon dioxide extractions. Further applica-
tions of these reagents for the synthesis of other fluorinated polyhydroxamic
acids including some polymers is under investigation.
EXPERIMENTAL
General
Melting points were obtained on an Electrothermal melting point appa-
ratus and are uncorrected. Infrared spectra were recorded on a Perkin Elmer
Series 1720X Spectrophotometer. 1H and 13C NMR spectra were obtained on
a Varian XL 200 MHz operating at 200 MHz and 50 MHz, respectively, in
CDCl3 using TMS as an internal standard unless otherwise noted. Elemental
analyses were performed by Desert Analytics, Tucson, AZ. Column chroma-
tography was performed on silica gel 60 (70–230 mesh) obtained from EM
Science. All solvents for chromatography were HPLC grade and were
obtained from either Fisher Scientific Co. or VWR Scientific Co. THF was
freshly distilled from sodium/benzophenone. Reagents obtained from
Aldrich Chemical Co., were used without purification unless otherwise noted.
O-Benzyl-N-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-octyl)-
hydroxylamine (1)
Trifluoromethanesulfonic anhydride (1.01 g, 3.6 mmol) was added
to a solution of 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol (1.09 g,
3.0 mmol) and triethylamine (0.36 g, 3.6 mmol) in dry dichloromethane
(25 mL) at 0ꢀC under N2. The reaction mixture was stirred at 0ꢀC for 2 h
and then at r.t. for 12 h. The reaction mixture was again cooled to 0ꢀC and

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3784
KOSHTI ET AL.
ice cold water (2 mL) was added slowly. The product was extracted into
dichloromethane (20 mL) and then washed with 1 M HCl (10 mL) and satu-
rated NaHCO3 (10 mL). The organic layer was dried (MgSO4), filtered and
the solvent removed in vacuo to give the triflate (1.21 g, 81%) which was used
in the next step without purification. The crude triflate (1.21 g, 2.43mmol) was
added to a suspension of O-benzylhydroxylamine hydrochloride (0.48 g,
3.0 mmol) and triethylamine (0.61 g, 6.0 mmol) in dry THF (25 mL) under
N2. The mixture was stirred at 0ꢀC for 2 h and then at r.t. for 12 h. The solvent
was removed in vacuo and the residue was extracted with ethyl acetate
(20 mL). The organic layer was dried (Na2SO4), filtered and the solvent
removed under reduced pressure. The crude product was purified by silica
gel chromatography to give 1 (0.49 g, 43%) as a colorless liquid. IR (neat)
3418, 2926 cmꢁ1; 1H NMR (CDCl3) ꢀ 2.20–2.50 (m, 2H), 3.20 (t, 2H), 4.69 (s,
2H), 5.6 (s, 1H), 7.30–7.38 (br s, 5H); 13C NMR (CDCl3) ꢀ 29.8 (t, JC–F
18.0 Hz), 44.3, 76.8, 102–124 (m), 121.1, 128.0, 125.8, 137.6; Anal. calcd. for
C15H12F13NO: C, 38.37; H, 2.55; N, 2.98. Found: C, 38.37; H, 2.44; N, 3.00.
¼
N-Benzyloxy-N-(3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluoro-octyl)-acrylamide (2)
A solution of acryloyl chloride (0.348 g, 3.85 mmol) in dry THF (5 mL)
was added to a solution of 1 (1.51 g, 3.21 mmol) and triethylamine (0.389 g,
3.21 mmol) in dry THF (15 mL) at 0ꢀC under N2. The mixture was then
stirred at r.t. for 1 h and heated at 60ꢀC for 12 h. The reaction mixture was
cooled and the salt filtered off. After removal of the solvent, the residue was
dissolved in dichloromethane (30 mL) and washed with saturated NaHCO3
(10 mL), 1 N HCl (10 mL) and water (10 mL). The organic layer was dried
(MgSO4), filtered, and the solvent removed in vacuo. The crude product was
purified by silica gel chromatography to give 2 (1.39 g, 83.5%) as a colorless
1
liquid. IR (neat) 1671 cmꢁ1; H NMR (CDCl3) ꢀ 2.30–2.58 (m, 2H), 3.93
(t, 2H), 4.87 (s, 2H), 5.77 (dd, 1H), 6.44 (dd, 1H), 6.71 (dd, 1H), 7.39 (br s,
5H); 13C NMR (CDCl3) ꢀ 28.4 (t, JC–F ¼ 20.0 Hz), 39.2, 78.1, 102–124 (m),
123.0, 126.3, 129.4, 129.8, 130.4, 134.3, 167.8; Anal. calcd. for C18H14
F13NO2: C, 41.30; H, 2.67; N, 2.67. Found: C, 41.43; H, 2.58; N, 2.69.
N-Benzyloxy-2-bromo-N-(3,3,4,4,5,5,6,6,7,7,8,8,8-
tridecafluoro-octyl)-acetamide (3)
A solution of bromoacetyl bromide (0.44 g, 2.2 mmol) in THF (5 mL)
was added to a solution of 1 (0.94 g, 2.0 mmol) and triethylamine (0.22 g,

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N-FLUOROALKYLHYDROXAMIC ACIDS
3785
2.2 mmol) in THF (5 mL) at 0ꢀC and then stirred at r.t. for 12 h. The solvent
was removed in vacuo. The residue was dissolved in ethyl acetate (30 mL)
and washed with saturated NaHCO3 (10 mL), 2 N HCl (10 mL) and water
(10 mL), dried (MgSO4), filtered and the solvent removed in vacuo. The
crude product was purified by silica gel chromatography to give 3 as a
1
colorless liquid (0.81 g, 68%). IR (neat) 1686 cmꢁ1; H NMR (CDCl3) ꢀ
2.26–2.58 (m, 2H), 3.89 (s, 2H), 3.91 (t, 2H), 4.94 (s, 2H); 13C NMR
(CDCl3) ꢀ 25.8, 28.0 (t, JC–F ¼ 22.0 Hz), 39.3, 77.5, 102–124 (m), 129.3,
129.6, 129.9, 134.0, 169.2; Anal. calcd. for C17H13BrF13NO2: C, 34.57; H,
2.20; N, 2.37. Found: C, 34.80; H, 2.12; N, 2.35.
Representative Procedure for Coupling Reagent 1
with Acid Chlorides
Preparation of 4a: A solution of benzoyl chloride (0.10 g, 0.76 mmol) in
dry THF (2 mL) was added to a solution of 1 (0.30 g, 0.63 mmol) and
triethylamine (0.077 g, 0.76 mmol) in THF (2 mL) under N2 at r.t. After
stirring for 1 h at r.t., the reaction mixture was heated at 60ꢀC for 12 h.
The reaction mixture was cooled, the salt filtered off, and the solvent
removed in vacuo. The remaining residue was dissolved in dichloromethane
(20 mL) and washed with saturated NaHCO3 solution (10 mL), 2 N HCl
(10 mL) and water (10 mL). The organic layer was dried (MgSO4) and the
solvent removed in vacuo. The crude product was purified by silica gel
chromatography to give 4a (0.28 g, 76.4%) as a colorless liquid. IR (neat)
1
1666 cmꢁ1; H NMR (CDCl3) ꢀ 2.35–2.65 (m, 2H), 3.92 (t, J ¼ 8.0 Hz, 2H),
4.64 (s, 2H), 7.00–7.64 (m, 10H); 13C NMR (CDCl3) ꢀ 27.9 (t JC–F
22.0 Hz), 39.3, 76.3, 102–124 (m), 127.5, 128.2, 128.6, 129.0, 130.4, 133.4,
169.9; Anal. calcd. for C22H16F13NO2: C, 46.07; H, 2.79; N, 2.44. Found:
C, 45.99; H, 2.61; N, 2.49.
¼
7a: Colorless oil (82%). IR (neat) 1675 cmꢁ1; 1H NMR (CDCl3) ꢀ 0.85
(t, J ¼ 7.0 Hz, 3H), 1.15–1.40 (m, 8H), 1.50–1.70 (m, 2H), 2.20–2.55 (m, 4H),
3.85 (t, J ¼ 6.6 Hz, 2H), 4.80 (s, 2H), 7.30–7.45 (m, 5H); 13C NMR (CDCl3) ꢀ
13.9, 22.5, 24.2, 27.8 (t, JC–F ¼ 21.6 Hz), 29.0, 31.6, 32.3, 38.5, 76.9, 102–124
(m), 128.8, 129.2, 134.2, 175.9; Anal. calcd. for C23H26F13NO2: C, 46.39;
H, 4.40; N, 2.35. Found: C, 46.72; H, 4.48; N, 2.42.
1
8a: Pale yellow oil (88%). IR (neat) 1706 cmꢁ1; H NMR (CDCl3) ꢀ
2.25–2.60 (m, 2H), 3.80–4.00 (m, 2H), 4.90 (s, 2H), 7.30–7.50 (m,
5H).13C NMR (CDCl3) ꢀ 24–28 (m), 38.7, 76.8, 102–126 (m), 127.0, 127.4,
127.9, 131.6, 157–159 (m); Anal. calcd. for C19H11F20NO2: C, 34.30; H, 1.67;
N, 2.11. Found: C, 34.30; H, 1.56; N, 2.18.

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3786
KOSHTI ET AL.
Representative Procedure for Reaction of Reagent 2 with Amines
Preparation of 5a: A solution of 2 (0.5 g, 0.95 mmol) and piperazine
(0.041 g, 0.47 mmol) in acetonitrile (5 mL) was stirred under N2 at reflux for
24 h. The reaction mixture was cooled and the acetonitrile removed under
reduced pressure. The crude product was purified by silica gel chromatog-
raphy to give 5a (0.366 g, 68.8%) as a pale yellow liquid. IR (neat)
1681 cmꢁ1
;
1H NMR (CDCl3) ꢀ 2.22–2.60 (m, 20H), 3.80 (t, J ¼ 7.6 Hz,
4H), 4.78 (s, 4H), 7.31 (br s, 10H); 13C NMR (CDCl3) ꢀ 28.3(t, JC–F
¼
22.0 Hz), 30.6, 30.9, 53.3, 53.6, 77.3, 102–124 (m), 118.1, 129.2, 129.5,
134.6, 175.1; Anal. calcd. for C40H38F26N4O4: C, 42.40; H, 3.35; N, 4.94.
Found: C, 42.72; H, 3.70; N, 4.71.
9a: Pale yellow oil (79%). IR (neat) 1676 cmꢁ1; H NMR (CDCl3) ꢀ
1
1.52–1.63(m, 2H), 2.20–2.80 (m, 28H), 3.81 (t, J ¼ 8.0 Hz, 8H), 4.82 (s, 8H),
7.36 (br s, 20H); 13C NMR (CDCl3) ꢀ 25.2, 28.3(t, JC–F ¼ 21.0 Hz), 30.5,
39.0, 48.9, 52.6, 77.5, 102–124 (m), 121.1, 129.2, 129.8, 134.7, 175.1; Anal.
calcd. for C75H66F52N6O8: C, 41.55; H, 3.04; N, 3.87. Found: C, 41.52;
H, 3.01; N, 3.89.
1
10a: Pale yellow oil (66%). H NMR (CDCl3) ꢀ 1.48–1.51 (m, 4H),
2.21–2.55 (m, 32H), 2.58–2.80 (m, 8H), 3.83 (t, J ¼ 8.0 Hz, 8H), 4.83(s, 8H),
7.35 (br s, 20H); 13C NMR (CDCl3) ꢀ 24.2, 28.1 (t JC–F ¼ 22.0 Hz), 30.4,
38.8, 50.2, 51.2, 51.4, 77.2, 102–124 (m), 118.0, 129.0, 129.5, 134.4, 175.1;
Anal. calcd. for C82H80F52N8O8: C, 42.93; H, 3.49; N, 4.88. Found: C,
42.89; H, 3.38; N, 4.99.
Representative Procedure for Reaction of Reagent 3 with Alcohols
Preparation of 6a: To a solution of 2 (0.300 g, 0.50 mmol) and
2-ethoxyethanol (0.178 g, 1 mmol) in benzene (5 mL) at 10ꢀC was added
aqueous 30% NaOH solution (0.5 mL) and a catalytic amount of tetra-
butylammonium bromide (0.010 g). The mixture was stirred vigorously at
10ꢀC for 1 h and at r.t. for 12 h. The reaction mixture was diluted with ethyl
acetate (10 mL) and washed with water (5 mL). The organic layer was dried
(Na2SO4), filtered and the solvent removed in vacuo. The crude product was
purified by silica gel chromatography (5–15% ethyl acetate/hexane) to give
6a as a colorless oil (0.263g, 87%). IR (neat) 1694 cm ꢁ1; 1H NMR (CDCl3)
ꢀ 1.20 (t, J ¼ 7.0 Hz, 3H), 2.31–2.51 (m, 2H), 3.50 (q, J ¼ 7.0 Hz, 2H),
3.60–3.68 (m, 4H), 3.88 (t, J ¼ 7.8 Hz, 2H), 4.25 (s, 2H), 4.83(s, 2H),
7.33–7.43 (m, 5H); 13C NMR (CDCl3) ꢀ 14.8, 27.6 (t, JC–F ¼ 21.8 Hz),
38.5, 66.5, 69.0, 69.8, 70.7, 76.9, 102–126 (m), 128.7, 129.3, 133.8, 172.4;

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N-FLUOROALKYLHYDROXAMIC ACIDS
3787
Anal. calcd. for C21H22F13NO4: C, 42.08; H, 3.70; N, 2.34. Found: C, 42.02;
H, 3.70; N, 2.38.
11a: Colorless oil (89%). IR (neat) 1694 cmꢁ1; 1H NMR (CDCl3) 0.88
(t, J ¼ 7.0 Hz, 3H), 1.27–1.37 (m, 4H), 1.50–1.70 (m, 2H), 2.30–2.60 (m, 2H),
3.45 (t, J ¼ 6.6 Hz, 2H), 3.88 (t, J ¼ 7.4 Hz, 2H), 4.14 (s, 2H), 4.83(s, 2H),
7.37–7.43 (m, 5H); 13C NMR (CDCl3) ꢀ 13.1, 21.7, 26.9 (t, JC–F ¼ 21.6 Hz),
27.3, 28.5, 39.0, 67.9, 71.2, 76.2, 102–122 (m), 128.1, 128.3, 133.2, 171.9.;
Anal. calcd. for C22H24F13NO3: C, 44.23; H, 4.05; N, 2.34. Found: C, 44.49;
H, 4.23; N, 2.37.
1
12a: Colorless oil (98%). IR (neat) 1695 cmꢁ1; H NMR (CDCl3) ꢀ
2.30–2.55 (m, 2H), 3.85–3.95 (m, 2H), 4.02–4.08 (m, 2H), 4.15 (s, 2H),
4.69 (s, 2H), 5.20–5.32 (m, 2H), 5.80–6.00 (m, 1H), 7.30–7.48 (m, 5H);
13C NMR (CDCl3) ꢀ 27.6 (t, JC–F ¼ 21.8 Hz), 38.5, 67.4, 72.2, 76.0,
102–124 (m), 128.7, 129.3, 133.8, 172.2; Anal. calcd. for C23H26NO2F13:
C, 42.34; H, 3.20; N, 2.47. Found: C, 42.47; H, 3.32; N, 2.56.
1
13a: Colorless oil, (44%). IR (neat) 1701 cmꢁ1; H NMR (CDCl3) ꢀ
1.75–1.92 (m, 2H), 2.27–2.58 (m, 2H), 3.46 (t, J ¼ 5.7 Hz, 2H), 3.56 (t, J ¼
6.3 Hz, 2H), 3.84–3.91 (m, 2H), 4.11 (s, 2H), 4.80 (s, 2H), 7.37 (m, 5H);
13C NMR (CDCl3) ꢀ 26.8, 27.7 (t, JC–F ¼ 21.7 Hz), 29.1, 38.6, 44.6, 68.5,
70.7,106–122(m),128.7,129.3,133.8,172.3;Anal.calcd.forC21H21ClF13NO3:
C, 40.83; H, 3.43; N, 2.27. Found: C, 41.14; H, 3.74; N, 2.6.
1
14a: Colorless oil, (53%). IR (neat) 1696 cmꢁ1; H NMR (CDCl3) ꢀ
1.63–1.92 (m, 4H), 2.07–2.58 (m, 4H), 3.51 (t, J ¼ 7.0 Hz, 2H), 3.90 (t,
J ¼ 8.0 Hz, 2H), 4.11 (s, 2H), 4.82 (s, 2H), 7.40 (m, 5H).; 13C NMR
(CDCl3) ꢀ 20.7, 27.8 (t, JC–F ¼ 22.0 Hz), 27.9 (t, JC–F ¼ 21.7 Hz), 38.7,
68.5, 70.1,106–122 (m), 128.8, 129.1, 129.4,133.8, 172.2.
Representative Procedure for Hydrogenolysis of
O-Benzyl Protecting Group
Preparation of 4b: Palladium on carbon (5%, 50 mg) was added to 4a
(0.36 g, 0.62 mmol) in absolute ethanol (20 mL) and stirred under H2 at r.t.
for 18 h. The catalyst was removed by centrifugation and filtration followed
by removal of the solvent in vacuo to give 4b (0.29 g, 96%) as a white solid:
m.p. 63–64ꢀC; IR (KBr) 3176, 1631 cmꢁ1; 1H NMR (CDCl3) ꢀ 2.45–2.75 (m,
2H), .398 (t, 2H), 7.26–7.53(m, 5H), 8.87–9.13(br s, 1H);
13C NMR
(CDCl3) ꢀ 28.0 (t, JC–F ¼ 22.0 Hz), 42.8, 102–124 (m), 127.3, 128.2, 130.8,
131.7, 173.7; Anal. calcd. for C15H10F13NO2: C, 37.26; H, 2.0; N, 2.89.
Found: C, 37.23; H, 1.98; N, 2.90.
5b: Pale yellow solid (86%). M.p. 139–140ꢀC; 1H NMR (CDCl3)
ꢀ
2.20–2.90 (m, 20H), 3.97 (t, 4H); 13C NMR (CDCl3)
ꢀ 28.3

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3788
KOSHTI ET AL.
(t, JC–F ¼ 22.0 Hz), 32.6, 40.1, 53.1, 56.5, 102–124 (m), 171.6; Anal. calcd.
for C26H26F26N4O4ꢂH2O: C, 32.18; H, 2.91; N, 5.77. Found: C, 32.19;
H, 2.79; N, 5.71.
6b: Colorless solid (93%). M.p. 33–34ꢀC; 1H NMR (CDCl3): ꢀ 1.22 (t,
3H), 2.30–2.65 (m, 2H), 3.45–3.75 (m, 6H), 3.85–4.00 (m, 2H), 4.32 (s, 2H);
13C NMR (CDCl3) ꢀ 14.7, 27.8 (t, JC–F ¼ 21.8 Hz), 40.4, 66.7, 69.4, 69.8,
70.3, 104–124 (m), 170.9; Anal. calcd. for C14H16F13NO4: C, 33.02;
H, 3.17; N, 2.75. Found: C, 32.78; H, 3.09; N, 2.79.
7b: Pale yellow solid (99%). M.p. 56–58ꢀC; IR (KBr) 1613cm ꢁ1
;
1H NMR (CDCl3) ꢀ 0.80–0.95 (m, 3H), 1.20–1.45 (m, 8H), 1.55–1.75
(m, 2H), 2.25–2.70 (m, 4H), 3.85 (t, J ¼ 6.6 Hz, 2H); 13C NMR (CDCl3) ꢀ
13.8, 22.4, 24.6, 28.0, 28.8, 29.1, 31.6 (overlapped with triplet), 40.9, 102–124
(m), 175.6; Anal. calcd. for C16H20F13NO2: C, 38.03; H, 3.99; N, 2.77.
Found: C, 37.89; H, 3.90; N, 2.80.
8b: Pale yellow solid (99%). M.p. 42–44ꢀC; IR (KBr) 1678 cmꢁ1
;
1H NMR (CDCl3) ꢀ 2.40–2.80 (br s, 2H), 4.00–4.25 (br s, 2H); 13C NMR
(CDCl3) ꢀ 26–30 (m), 42.8, 102–108 (m), 157–160 (m); Anal. calcd. for
C12H5F20NO2: C, 25.06; H, 0.88; N, 2.44. Found: C, 24.84; H, 0.87; N, 2.84.
9b: Colorless oil (86%). IR (CDCl3) 1631, 3196 cmꢁ1 1H NMR
;
(CDCl3) ꢀ 1.52–1.64 (m, 2H), 2.30–2.95 (m, 28H), 3.92 (t, J ¼ 8.0 Hz, 8H);
13C NMR (CDCl3) ꢀ 22.3, 28.1 (t, JC–F ¼ 22.0 Hz), 29.8, 40.5, 50.0, 51.1,
102–124 (m), 173.2; Anal. calcd. for C47H42F52N6O8: C, 31.22; H, 2.32;
N, 4.65. Found: C, 30.98; H, 2.16; N, 4.72.
10b: Pale yellow solid (84%). M.p. 54–56ꢀC; IR (CDCl3) 1641 cmꢁ1
;
1H NMR (CDCl3) ꢀ 1.53–1.7 (m, 4H), 2.3–2.99 (m, 40H), 3.81–4.02 (m, 8H);
13C NMR (CDCl3) ꢀ 23.1, 28.2 (t, JC–F ¼ 22.0 Hz), 29.8, 40.9, 49.4, 50.0,
102–124 (m), 172.8; Anal. calcd. for C54H56F52N8O8: C, 33.54; H, 2.89;
N, 5.79. Found: C, 33.16; H, 2.74; N, 6.09.
11b: Pink colored solid (95%). M.p. 57–59ꢀC; IR (KBr) 1652 cmꢁ1
;
1H NMR (CDCl3) ꢀ 0.89 (t, J ¼ 7.0 Hz, 3H), 1.22–1.34 (m, 4H), 1.50–1.75
(m, 2H), 2.30–2.70 (m, 2H), 3.50 (t, J ¼ 6.6 Hz, 2H), 3.90–4.40 (m, 4H);
13C NMR (CDCl3) ꢀ 13.6, 22.3, 27.9, 28.9, 40.4, 41.5, 68.6, 72.0, 102–124
(m), 171.2; Anal. calcd. for C15H18F13NO3: C, 35.52; H, 3.58; N, 2.76.
Found: C, 35.07; H, 3.33; N, 2.78.
13b: Colorless solid (91%). M.p. 69.5–71ꢀC; IR (KBr) 1636 cmꢁ1
;
1H NMR (CDCl3) ꢀ 1.70–1.92 (m, 4H), 2.32–2.65 (m, 2H), 3.50–3.60
(m, 4H), 3.88–4.00 (m, 2H), 4.35 (s, 2H); 13C NMR (CDCl3) ꢀ 26.7, 27.8
(t, JC–F ¼ 22.0 Hz), 29.1, 40.6, 68.2, 70.9, 102–124 (m), 171.4; Anal. calcd.
for C14H15F13ClNO3: C, 31.87; H, 2.87; N, 2.65. Found: C, 32.26; H, 2.91;
N, 2.63.
14b: Pale yellow solid (87%). M.p. 41–43ꢀC; IR (KBr) 1656 cmꢁ1
1H NMR (CDCl3) ꢀ 1.83–2.02 (m, 2H), 2.05–2.56 (m, 4H), 3.55–3.73
;

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N-FLUOROALKYLHYDROXAMIC ACIDS
3789
(m, 4H), 3.98 (s, 2H); 13C NMR (CDCl3 with 2 drops CD3OD) ꢀ 20.4, 28.1
(m), 30.4 (m), 31.1, 67.7, 69.7, 102–126 (m), 170.0; Anal. calcd. for
C21H13F30NO3: C, 28.11; H, 1.46; N, 1.56. Found: C, 27.96; H, 1.48; N, 1.82.
ACKNOWLEDGMENTS
We thank WERC, New Mexico for their support of our program in
the actinide remediation area. This work was also supported in part by a
grant from the National Institutes of Health under PHS Grant No. SO6
GM08136-27.
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Received in the USA December 7, 2001