3,3,3-Trifluoro-N′-(3-trifluoromethylphenyl)-1,2-propanediamine and its N-mono- and N,N-dicarboxyethyl derivatives: Synthesis, protolytic and complexation properties

Article abstract of DOI:10.1007/s11172-006-0153-y

3,3,3-Trifluoro-N′-(3-trifluoromethylphenyl)-1,2-propanediamine (5) was synthesized by the reaction of 2-diazo-1,1,1-trifluoro-3-nitropropane or 3,3,3-trifluoro-1-nitropropene with 3-aminobenzotrifluoride followed by the reduction of the nitro group. The

Full text of DOI:10.1007/s11172-006-0153-y

Russian Chemical Bulletin, International Edition, Vol. 54, No. 11, pp. 2545—2549, November, 2005
2545
3,3,3ꢀТrif luoroꢀN´ꢀ(3ꢀtrif luoromethylphenyl)ꢀ1,2ꢀpropanediamine
and its Nꢀmonoꢀ and N,Nꢀdicarboxyethyl derivatives:
synthesis, protolytic and complexation properties
V. Yu. Korotaev,aꢀ Yu. A. Skorik,bꢀ A. Yu. Barkov,c M. I. Kodess,c and A. Ya. Zapevalovc
aA. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vladislav.Korotaev@usu.ru
bDepartment of Chemistry, University of Pittsburgh,
219 Parkman Avenue, Pittsburgh, PA 15260, USA.
Fax: +1 (412) 624 8611. Eꢀmail: skorik@pitt.edu; yury_skorik@mail.ru
cI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
20 ul. S. Kovalevskoi, 620219 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: nmr@ios.uran.ru
3,3,3ꢀTrifluoroꢀN´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropanediamine (5) was synthesized by
the reaction of 2ꢀdiazoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane or 3,3,3ꢀtrifluoroꢀ1ꢀnitropropene with
3ꢀaminobenzotrifluoride followed by the reduction of the nitro group. The Michael 1,4ꢀaddition
of diamine 5 to acrylic acid occurs only at the N(1) atom and affords Nꢀmonoꢀ or
N,Nꢀdicarboxyethyl derivatives 6 and 7, depending on the reactant ratio. Protolytic equilibria
5—7 in aqueous solutions were studied by pHꢀpotentiometry and UV spectroscopy. Only the
aliphatic amino group can be protonated in an aqueous solution, while the aromatic amino
group remains unprotonated even in 12 M HCl. The stability constants of transition metal
(Cu2+, Ni2+, Zn2+) complexes with ligands 5—7 were determined by pHꢀpotentiometric titraꢀ
tion. The stability of the complexes and selectivity of the ligands toward Cu2+ ions increase
with an increase in the number of Nꢀcarboxyethyl groups.
Key words: 3,3,3ꢀtrifluoroꢀN´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropanediamine, 3ꢀ[2ꢀ(3ꢀtriꢀ
fluoromethylphenylamino)ꢀ3,3,3ꢀtrifluoropropylamino]propionic acid, 3,3ꢀ[2ꢀ(3ꢀtrifluoroꢀ
methylphenylamino)ꢀ3,3,3ꢀtrifluoropropylamino]dipropionic acid, carboxyethylation, proꢀ
tolytic equilibria, complexation, transition metal ions, selectivity.
Structural fragments of 1,2ꢀethylenediamine and
βꢀalanine with aryl and alkyl substituents at the nitrogen
atoms are constituents of many compounds with a wide
spectrum of biological activity.1—3 For example, βꢀalaꢀ
nine derivatives can enhance inhibition processes in the
central nervous system, being agonists of γꢀaminobutyric
and glycine receptors and, thus, potential anticonvulsive
preparations in treating epilepsy.2 A pharmacophore based
on Nꢀsubstituted βꢀalanine containing the amine and
carboxylate acceptors and the lipophilic fragment was proꢀ
posed as a result of the simulation and pharmacological
studies.2 The introduction of an additional lipophilic
trifluoromethyl group into both the aromatic ring and
ethylene chain favors absorption and transport of the
medicine in biological systems and, therefore, improves
the pharmacological properties of a candidate molecule.4
In analytical chemistry, carboxymethylated derivatives
of 1,2ꢀethylenediamine are used as chelating agents. Howꢀ
ever, they are poorly selective toward metal ions with
similar properties. As shown previously,5—7 the ligands
containing the βꢀalaninate group are more selective toꢀ
ward Cu2+ ions than the glycinate analogs. For instance,
the high selectivity of Nꢀphenyliminobisꢀ3ꢀpropionic
acid6,7 and its derivatives7 toward Cu2+ ions is caused by
all the energy and spatial factors leading to a decrease in
the stability of the complexes with the metal ions and a
simultaneous increase in the differentiating ability toward
Cu2+ ions, which form the most stable complexes. Thereꢀ
fore, it can be expected that ligands containing simultaꢀ
neously the βꢀalaninate group, aromatic and aliphatic
amino groups, and trifluoromethyl substituent with unique
electronic and steric features would manifest interesting
complexation properties.
In the present work, we synthesized 3,3,3ꢀtrifluoroꢀ
N´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropanediamine and
its Nꢀmonoꢀ and N,Nꢀdicarboxyethyl derivatives containꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2465—2469, November, 2005.
1066ꢀ5285/05/5411ꢀ2545 © 2005 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Korotaev et al.
ing trifluoromethyl groups in both the ethylene fragment
and aryl substituent at the N(2) nitrogen atom and studꢀ
ied their protolytic and complexation properties.
the proton of the arylamino group (δNH = 6.83 ppm, 3J =
9.8 Hz), which indicates that only the N(1) nitrogen atom
is protonated.
The carboxyethylation of compound 5 with acrylic
acid affords Nꢀmonoꢀ or N,Nꢀdicarboxyethyl derivatives
6 or 7, depending on the ratio of reactants (Scheme 2).
No addition to the N(2) nitrogen atom occurs even in
excess carboxyethylating agent because of its low nucleoꢀ
philicity.
Results and Discussion
Synthesis of 3,3,3ꢀtrifluoroꢀN´ꢀ(3ꢀtrifluoromethylꢀ
phenyl)ꢀ1,2ꢀpropanediamine and its derivatives. The startꢀ
ing compounds for the synthesis of several fluoroꢀconꢀ
taining 1,2ꢀdiamines, including CF3ꢀsubstituted derivaꢀ
tives, can be the corresponding βꢀnitroenamines8 or
βꢀnitrodiazoalkanes,9 which are prepared from available
nitriles of fluorocarboxylic acids. A simple and conveꢀ
nient procedure for the synthesis of the ethylenediamine
derivatives is the method based on the Michael addition
of amines to nitroalkenes followed by the reduction of the
nitro group in the reaction products.10 At the same time,
no data were reported on the use of this method for the
synthesis of fluoroalkylꢀsubstituted 1,2ꢀdiamines. In the
present work, we studied two alternative methods for the
synthesis of 1ꢀtrifluoromethylꢀ1,2ꢀethylenediamines, usꢀ
ing compound 5 as an example, from 2ꢀdiazoꢀ1,1,1ꢀ
trifluoroꢀ3ꢀnitropropane11 (1) or Eꢀ3,3,3ꢀtrifluoroꢀ1ꢀ
nitropropene12 (2), which is a synthetic analog of diazo
compound 1 13,14 (Scheme 1).
Scheme 2
Protolytic equilibria. The completely deprotonated
forms of compounds 5—7 are organic bases of moderate
strength and capable of adding protons to the aliphatic
and aromatic amino groups and to one (compound 6)
or two (compound 7) carboxylate groups. The general
and stepwise protonation constants obtained from the
pHꢀpotentiomeric titration data are given in Table 1 in
comparison with the constants of the related compounds:
1,2ꢀethylenediamine (En),15 Nꢀphenylethylenediamine
(PhEn),16 and 3,3,3ꢀtrifluoropropaneꢀ1,2ꢀdiamine (8).
The protonation constants of the aromatic amino
group in compounds 5—7 were not determined from the
potentiometric data, because the condition necessary for
Scheme 1
Table 1. Protonation constants
and
for selected Nꢀ and Cꢀsubstituted ethyleneꢀ
diamines (T = 25 °C, I = 0.1 M KNO3)
Ligand L
n
logβ
logKH
H
5
6
1
1
2
1
2
3
1
2
1
2
1
2
7.69 0.02
7.76 0.02
11.05 0.02
7.33 0.02
11.18 0.03
13.95 0.05
7.91 0.01
9.87 0.02
9.59
7.69
7.76
3.29
7.33
3.85
2.77
7.91
1.96
9.59
–0.1
9.89
7.08
R = 3ꢀCF3C6H4
The reaction of compound 1 or 2 with 3ꢀaminobenzoꢀ
trifluoride in benzene at 60 °C affords βꢀnitroamine 3 in
82 and 84% yields, respectively. The reduction of the
nitro group in nitroamine 3 by the action of LiAlH4 in
THF followed by the treatment with dry HCl produces
diamine hydrochloride 4, from which diamine 5 was obꢀ
tained by the treatment with an aqueous solution of
NaOH. The 1H NMR spectrum of compound 4 contains
a singlet of the NH3+ group at 8.35 ppm and a doublet of
7
8
PhEn16
En15
9.5
9.89
16.97

Fluorinated 1,2ꢀpropanediamine
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2547
λ
max/nm
effect of the N´ꢀ(3ꢀtrifluoromethyl)phenyl and Cꢀtriꢀ
fluoromethyl substituents in the ethylenediamine fragꢀ
ment of compounds 5—7. This effect can be analyzed by
comparison of the protonation constants of the pairs of
compounds En—PhEn and En—8 (see Table 1), which
differ by the presence of the Nꢀphenyl or Cꢀtrifluoromethyl
substituent, respectively. The introduction of the phenyl
substituent into En only insignificantly decreases the first
constant of protonation of the aliphatic amino group
A
a
b
244
243
242
241
240
0.8
0.6
0.4
0.2
pH
5
6
7
8
9
pH
∆logK1H(En—PhEn) = 0.3 and decreases substantially the
basicity of the nitrogen atom, which is directly conjugated
with the benzene ring (∆logK2H(En—PhEn) = 7.2). By
contrast, the introduction of the Cꢀtrifluoromethyl subꢀ
stituent into En decreases the basicity of both amino
groups to a great extent: ∆logKH(En—8) = 2.0 and 5.1 for
N(1) and N(2), respectively. The summation of these two
effects enhanced by the presence of one more trifluoroꢀ
methyl substituent in the benzene ring results in a very
low basicity of the aromatic amino group.
250
300
λ/nm
Fig. 1. Electronic absorption spectra of an aqueous solution of
diamine 5 at different pH (C = 5•10–5 mol L–1).
Complexation with transition metal ions. The composiꢀ
tion and stability constants of the complexes formed by
ligands 5—7 with Cu2+, Ni2+, Zn2+, and Cd2+ ions were
determined by pHꢀpotentiometric titration of solutions
containing the ligand and metal nitrate in different mole
ratios, an equimolar amount of nitric acid, and a supportꢀ
ing electrolyte (0.1 M KNO3). In all cases, points of the
titration curves lying in the interval of pH 2—7 before the
onset of hydrolysis of cations were used to calculate the
stability constants of the complexes. Different models inꢀ
cluding the formation of complex species [MpHqLr] were
tested. The results that describe best of all the experimenꢀ
tal data are given in Table 2. For several systems including
Cd2+ and Zn2+ (see Table 2), the titration curves before
the onset of cation hydrolysis coincide with similar titraꢀ
this procedure CL > 1/KH (see Ref. 17) is not fulfilled due
to the low protonation constant and insufficient solubility
of the compounds in water.
Additional information on the protonation of the aroꢀ
matic amino group can be obtained from analysis of the
electronic spectra in the UV region where the benzene
chromophore absorbs. The absorption spectra of aqueous
solutions of compound 5 at different acidities of the soluꢀ
tion are presented in Fig. 1. The spectra of solutions of
compounds 6 and 7 are similar and differ insignificantly
by the position of maxima of the absorption bands. In
the whole studied acidity interval (from 12 M HCl to
1 M KOH), no protonation of the aromatic amino group
and related changes in the spectral curves (hypochromism
and hypsochromic shift of absorption bands)18 are obꢀ
served, which indicates a very low basicity of the N(2)
nitrogen atom (logKH < –1). Nevertheless, slight hypsoꢀ
Table 2. Stability constants
of 3,3,3ꢀtriꢀ
fluoroꢀN´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropanediamine and
its Nꢀmonoꢀ and N,Nꢀdicarboxyethyl derivatives (T = 25 °C,
I = 0.1 M KNO3)*
1
chromic shifts of the absorption bands of B1u 245 nm
and 1B2u 300 nm are observed in the region of protonation
of the aliphatic amino group (рH = 9—6, Fig. 1, b),
which is probably related to the cleavage of the intramoꢀ
lecular hydrogen bond (Scheme 3).
Ligand L
M
p
q
r
Complex
logβ
pqr
5
Cu
Ni
Zn
Cu
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
1
1
1
2
1
2
1
1
1
CuL
NiL
ZnL
CuL
CuL2
NiL
NiL2
CuL
NiL
3.77 0.12
1.9 0.2
1.7 0.2
5.84 0.02
10.36 0.03
3.07 0.03
5.15 0.10
7.60 0.04
4.42 0.04
2.90 0.03
Scheme 3
6
7
Ni
Cu
Ni
Zn
ZnL
R = H, (CH2)2COOH
* Since the stability constants of the Cd (L = 5, 6, 7) and Ni
(L = 6) complexes are low, they cannot be determined by
pHꢀmetry.
The low basicity of the aromatic amino group is unꢀ
ambiguously related to the strong electronꢀwithdrawing

2548
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Korotaev et al.
were measured on a Perkin—Elmer SpectrumꢀBX II FTꢀIR specꢀ
trometer in KBr pellets or in thin layer. UV spectra of aqueous
solutions of 5—7 were obtained on a Shimadzu UVꢀ3101PC
spectrophotometer at 25.0 0.1 °C with an increment of 0.1 nm.
pHꢀPotentiometric titration was carried out using an earlier
described procedure19 with a 0.1 M carbonateꢀfree solution of
KOH as titrant, ionic strength I = 0.1 M KNO3, and T =
25.0 0.1 °C. The acidic ionization constants of 5—7 were deterꢀ
mined by the titration of 10–3 M aqueous solutions containing
an equimolar amount of nitric acid; no additional acid was
introduced in the case of dihydrochloride 8. To determine comꢀ
plexation constants, 10–3 M solutions of 5—7 were titrated, varyꢀ
ing the concentration of M(NO3)2 (M = Cu, Ni, Zn, Cd) in the
range of metal to ligand ratios from 2 : 1 to 1 : 3. All calculations
were performed using the SUPERQUAD program.20
Diazo compound 1 (see Ref. 11) and nitroalkene 2 (see
Ref. 12) were synthesized according to earlier described methods.
3ꢀNitroꢀ2ꢀ(3ꢀtrifluoromethylphenyl)aminoꢀ1,1,1ꢀtrifluoroꢀ
propane (3). Method A. A solution of diazo compound 1 (2.62 g,
15.5 mmol) in benzene (20 mL) was added dropwise with stirꢀ
ring for 20 min to a solution of 3ꢀaminobenzotrifluoride (2.50 g,
15.5 mmol) in benzene (20 mL) heated to 60 °C. Then the
mixture was stirred for 6 h at 60 °C and cooled to ~20 °C. The
solvent was removed in vacuo, and the residue was recrystallized
from hexane. The yield was 3.84 g (82%).
tion curves of the ligands within the error of pH measureꢀ
ments ( 0.01), which does not allow one to calculate the
complexation constants from these potentiometric data.
The stability constants of the complexes formed by
diamine 5 are low (see Table 2). Since the basicity of the
N(2) nitrogen atom is very low, it seems probable that
compound 5 behaves as a monodentate ligand coordinatꢀ
ing the central metal ion through the aliphatic amino
group. Only the stability constants of the ML complexes
were calculated because of low stability, although the forꢀ
mation of other, less stable complexes MLn is quite
probable.
NꢀMonoꢀ or N,Nꢀdicarboxyethyl derivatives 6 and 7
form more stable complexes than the starting diamine 5
due to closure of one or two sixꢀmembered βꢀalaninate
chelate rings. Ligand 6 forms complexes ML and ML2,
whereas ligand 7 forms only complexes ML; no formation
of protonated complexes was observed.
For all the ligands under study, the stability series of
the complexes coincides with the Irwing—Williams seꢀ
ries: Cu2+ > Ni2+ > Zn2+ > Cd2+. The difference between
logarithms of constants of the complexes, which are most
similar in stability, can be used as a measure of selectivity
of the ligand toward a certain metal ion. For instance, the
selectivity of the ligands toward the Cu2+ ions compared
Method B. A mixture of nitroalkene 2 (2.68 g, 19.0 mmol)
and 3ꢀaminobenzotrifluoride (3.06 g, 19.0 mmol) in benzene
(40 mL) was stirred for 6 h at 60 °C and then treated according
to method A. The yield was 4.82 g (84%), m.p. 81—82 °C.
Found (%): C, 39.81; H, 2.65; N, 9.30. C10H8F6N2O2. Calcuꢀ
lated (%): C, 39.75; H, 2.67; N, 9.27. IR, ν/cm–1: 3393 (NH);
to the Ni2+ ions increases in the series 5, 6, 7 (∆logβCu/Ni
=
1.87 (5), 2.77 (6), and 3.18 (7)). Both the stability of the
complexes that formed and selectivity of the ligands toꢀ
ward the Cu2+ ions increase with an increase in the numꢀ
ber of the Nꢀcarboxyethyl groups.
1
1621, 1601 (Ar); 1569, 1385 (NO2). H NMR (CDCl3), δ: 4.11
(d, 1 H, NH, J = 10.7 Hz); 4.61, 4.81 (both dd, 1 H each,
CH2NO2, 2J = 13.5 Hz, 3J = 8.8, 4.4 Hz); 4.92 (ddqd, 1 H,
CH—CF3, 3J = 10.7, 8.8, 6.5, 4.4 Hz); 6.93 (dd, 1 H, H(6), J =
8.2, 2.4 Hz); 6.97 (dd, 1 H, H(2), J = 2.4, 1.7 Hz); 7.14 (ddq,
1 H, H(4), J = 7.8, 1.7, 1.8 Hz); 7.36 (dd, 1 H, H(5), J = 8.2,
Thus, the method for the synthesis of trifluoromethylꢀ
substituted 1,2ꢀethylenediamines was proposed and
demonstrated for 3,3,3ꢀtrifluoroꢀN´ꢀ(3ꢀtrifluoromethylꢀ
phenyl)ꢀ1,2ꢀpropanediamine (5). The introduction of
trifluoromethyl groups in both the ethylene chain and
N´ꢀphenyl substituent decreases the nucleophilicity of the
secondary amino group to such an extent that diamine 5
is carboxyethylated with acrylic acid only at the N(1)
nitrogen atom and, hence, monoꢀ or diaddition products
can be obtained depending on the ratio of reactants. The
study of protolytic equilibria in aqueous solutions of comꢀ
pounds 5—7 compared to the fluorinated and nonꢀfluoriꢀ
nated analogs showed that only the combined effect of
the Cꢀtrifluoromethyl and N´ꢀ(3ꢀtrifluoromethyl)phenyl
substituents in 1,2ꢀethylenediamine resulted in such a
low basicity of the N(2) amino group. Selectivity of
ligand 7 toward Cu2+ ions and sufficient stability of the
complexes that formed provide possibilities of using this
ligand as a copperꢀselective complexing agent.
7.8 Hz). 19F NMR (CDCl3), δ : 87.06 (d, CF3, J = 6.5 Hz);
F
98.76 (t, CF3—Ar, J = 0.8 Hz).
3,3,3ꢀTrifluoroꢀN´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropaneꢀ
diamine hydrochloride (4). A solution of βꢀnitroamine 3 (4.50 g,
14.9 mmol) in anhydrous THF (50 mL) was added dropwise
with stirring and cooling to 0 °C for 30 min to a suspension of
LiAlH4 (2.83 g, 74.5 mmol) in anhydrous THF (100 mL). Then
the mixture was refluxed with stirring for 4 h and cooled to 0 °C.
Water (2.83 g), a 10% solution of NaOH (2.83 g), and H2O
(8.49 g) were successively added. The mixture was stirred for
15 min and filtered. The solvent was removed in vacuo. The
residue was dissolved in anhydrous benzene (40 mL), and the
solution was cooled to 10 °C. Dry HCl was bubbled through the
solution to saturation. A precipitate that formed was filtered off,
dried in vacuo, and dissolved in ethyl acetate (15 mL). Hexane
(15 mL) was added, and a precipitate was filtered off and dried
in vacuo. The yield was 2.94 g (64%), m.p. 168—169 °C (subl.).
Found (%): C, 38.82; H, 3.69; N, 8.89. C10H11F6N2•HCl. Calꢀ
culated (%): C, 38.91; H, 3.59; N, 9.08. IR, ν/cm–1: 3312, 3257
(NH); 2987, 2911 (NH3+), 1619 (Ar). 1H NMR (DMSOꢀd6), δ:
3.07, 3.30 (both m, 1 H each, CH2); 4.81 (m, 1 H, CH—CF3);
6.83 (d, 1 H, NH—Ar, J = 9.8 Hz); 6.99 (dm, 1 H, H(4), J =
8.6 Hz); 7.06 (dd, 1 H, H(6), J = 8.6, 2.3 Hz); 7.08 (m, 1 H,
H(2)); 7.38 (dd, 1 H, H(5), J = 8.6, 7.8 Hz); 8.35 (br.s, 3 H,
Experimental
NMR spectra were recorded on a Bruker DRXꢀ400 specꢀ
1
trometer (400 and 376 MHz for H and 19F, respectively) using
Me4Si (1H) and C6F6 19F) as internal standards. IR spectra
(

Fluorinated 1,2ꢀpropanediamine
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2549
NH3+). 19F NMR (CDCl3), δ : 88.64 (d, CF3, J = 6.9 Hz);
101.19 (s, CF3—Ar).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 04ꢀ03ꢀ
32463).
F
3,3,3ꢀTrifluoroꢀN´ꢀ(3ꢀtrifluoromethylphenyl)ꢀ1,2ꢀpropaneꢀ
diamine (5). A solution of hydrochloride 4 (5.25 g, 17.0 mmol) in
H2O (35 mL) was treated with a 10% solution of NaOH to
alkaline pH and extracted with CH2Cl2 (2×20 mL). The solvent
was distilled off, and the residue was distilled in vacuo. The yield
was 4.21 g (91%), b.p. 98—99 °C (4 Torr). IR, ν/cm–1: 3308
(NH); 1618, 1601 (Ar). 1H NMR (CDCl3), δ: 1.26 (br.s, 2 H,
NH2); 3.04 (ddq, 1 H, CHH—CHCF3, 2J = 13.5 Hz, 3J =
References
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4
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13.5 Hz, 3J = 4.7 Hz); 3.89 (dqdd, 1 H, HC—CF3, J = 9.0, 7.3,
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3
J = 8.2, 7.7 Hz). 19F NMR (CDCl3), δ : 87.90 (dd, CF3, J =
F
7.3 Hz, 4JH,F = 1.0 Hz); 98.90 (t, CF3—Ar, J = 0.8 Hz).
3ꢀ[2ꢀ(3ꢀTrifluoromethylphenylamino)ꢀ3,3,3ꢀtrifluoropropylꢀ
amino]propionic acid (6). A mixture of diamine 5 (0.95 g,
3.5 mmol) and acrylic acid (0.25 g, 3.5 mmol) in 1,2ꢀdichloroꢀ
ethane (10 mL) was refluxed for 6 h and cooled to room temꢀ
perature. A precipitate that formed was filtered off and reꢀ
crystallized from acetonitrile. The yield was 0.50 g (43%),
m.p. 191—192 °C. Found (%): C, 45.39; H, 4.11; N, 8.01.
8. A. Ya. Aizikovich and V. Yu. Korotaev, Zh. Org. Khim.,
1999, 35, 226 [Russ. J. Org. Chem., 1999, 35, 207 (Engl.
Transl.)].
9. A. Ya. Aizikovich, M. V. Nikonov, M. I. Kodess, V. Yu.
Korotaev, V. N. Charushin, and O. N. Chupakhin, Tetraꢀ
hedron, 2000, 56, 1923.
10. N. Ono, The Nitro Group in Organic Synthesis, WileyꢀVCH,
New York, 2001, 392 pp.
11. A. Ya. Aizikovich and I. T. Bazyl´, Zh. Org. Khim., 1987, 23,
1330 [J. Org. Chem. USSR, 1987, 23 (Engl. Transl.)].
12. H. Shechter, D. E. Ley, and E. B. Roberson, J. Am. Chem.
Soc., 1956, 78, 4984.
C
13H14F6N2O2. Calculated (%): C, 45.36; H, 4.10; N, 8.14. IR,
ν/cm–1: 3340, 3332 (NH); 1649 (CO); 1619 (Ar). 1H NMR
(DMSOꢀd6), δ: 2.33 (t, 2 H, CH2CH2COOH, J = 6.7 Hz); 2.75
(td, 2 H, CH2CH2COOH, J = 6.7, 1.7 Hz); 2.82, 2.91 (both dd,
1 H each, CH2NH, 2J = 12.5 Hz, 3J = 8.7, 3.7 Hz); 4.47 (m,
1 H, HC—CF3); 6.43 (d, 1 H, NH—Ar, J = 9.0 Hz); 6.90 (d,
1 H, H(6), J = 7.6 Hz), 7.03 — 7.05 (m, 2 H, H(2), H(4)); 7.31
(t, 1 H, H(5), J = 7.9 Hz). 19F NMR (DMSOꢀd6), δ : 89.23 (d,
CF3, J = 7.4 Hz); 101.25 (s, CF3—Ar).
F
3
13. A. Ya. Aizikovich, V. Yu. Korotaev, and L. E. Yaroslavtseva,
Zh. Org. Khim., 1994, 30, 989 [Russ. J. Org. Chem., 1994, 30
(Engl. Transl.)].
14. A. Ya. Aizikovich, V. Yu. Korotaev, M. I. Kodess, and A. Yu.
Barkov, Zh. Org. Khim., 1998, 34, 1149 [Russ. J. Org. Chem.,
1998, 34, 1093 (Engl. Transl.)].
15. R. M. Smith and A. E. Martell, Critical Stability Constants,
Plenum Press, New York—London, 1975, Vol. 2, p. 36.
16. R. Chen, H. Lin, and J. Zhu, Wuji Huaxue Xuebao,
3,3ꢀ[2ꢀ(3ꢀTrifluoromethylphenylamino)ꢀ3,3,3ꢀtrifluoroproꢀ
pylimino]dipropionic acid (7). A mixture of diamine 5 (2.65 g,
9.7 mmol) and acrylic acid (1.75 g, 24.3 mmol) in 1,2ꢀdiꢀ
chloroethane (40 mL) was refluxed for 6 h and cooled to
room temperature. A precipitate was filtered off and recrystalꢀ
lized from 1,2ꢀdichloroethane. The yield was 2.25 g (67%),
m.p. 145—146 °C. Found (%): C, 46.02; H, 4.33; N, 6.66.
C
16H18F6N2O4. Calculated (%): C, 45.16; H, 4.36; N, 6.73. IR,
ν/cm–1: 3322 (NH); 1663 (CO); 1620, 1604 (Ar). 1H NMR
(DMSOꢀd6), δ: 2.24—2.29 (m, H, CH2CH2COOH);
1992, 8, 190.
4
17. M. Beck and I. Nagypal, Chemistry of Complex Equilibria,
Cop., Budapest, 1989.
18. E. Stern and C. Timmons, Introduction to Electronic Absorpꢀ
tion Spectroscopy in Organic Chemistry, Edward Arnold,
London, 1970.
2.66—2.89 (m, 6 H, CH2N, CH2CH2COOH); 4.48 (m, 1 H,
HC—CF3); 6.33 (d, 1 H, NH—Ar, J = 9.0 Hz); 6.89 (d, 1 H,
H(6), J = 7.8 Hz); 7.00—7.07 (m, 2 H, H(2), H(4)); 7.30 (t,
1 H, H(5), J = 7.8 Hz); 12.08 (br.s, 2 H, COOH). 19F NMR
(DMSOꢀd6), δ : 89.24 (d, CF3, 3J = 7.5 Hz); 101.31
F
19. Yu. A. Skorik, E. V. Osintseva, N. V. Podberezskaya, A. V.
Virovets, L. K. Neudachina, and A. A. Vshivkov, Izv. Akad.
Nauk, Ser. Khim., 2005, 1518 [Russ. Chem. Bull., Int. Ed.,
2005, 54, 1563].
20. P. Gans, A. Sabatini, and A. Vacca, J. Chem. Soc., Dalton
Trans., 1985, 1195.
(s, CF3—Ar).
3,3,3ꢀTrifluoropropaneꢀ1,2ꢀdiamine hydrochloride (8) was
obtained by the treatment of a benzene solution of the correꢀ
sponding diamine8 with anhydrous HCl followed by recrystalliꢀ
zation from an ethyl acetate—hexane (1 : 3) system. IR, ν/cm–1
:
2948 (NH3+). 1H NMR (DMSOꢀd6), δ: 3.38, 3.35 (both dd,
1 H each, CH2, 2J = 14.6 Hz, 3J = 6.6, 4.7 Hz); 4.65 (dqd, 1 H,
HC—CF3, 3J = 7.7, 6.6, 4.7 Hz); 9.13 (br.s, 6 H, 2 NH3+).
Received July 11, 2005;
in revised form October 3, 2005
19F NMR (DMSOꢀd6), δ : 91.04 (d, CF3, 3J = 7.7 Hz).
F