New hydrazyl derivatives with multiple properties

Article abstract of DOI:10.2174/157017810790796309

4-(N',N'-diphenylhydrazino)-3,5-dinitrobenzoic acid in reaction with 4-hydroxy-tempo, 4-aminobenzo-15- crown-5, and 1-bromoacetyl-pyrene, yielded the corresponding esters or amides, as yellow compounds. These hydrazines, by oxidation with lead dioxide, converted into the stable hydrazyl free radicals, with a purple-violet color. Same yellow hydrazines in reaction with alkali bases are converted into the corresponding salt of green color. The newly synthesized compounds were characterized by elemental analysis, IR, UV-Vis, ¹H- and ¹³C-NMR, and EPR (where applicable). Acid- base, redox, fluorescence and complexation properties were also studied and discussed.

Full text of DOI:10.2174/157017810790796309

182
Letters in Organic Chemistry, 2010, 7, 182-185
New Hydrazyl Derivatives with Multiple Properties
Madalina Tudose*,1, Daniel Angelescu1, Gabriela Ionita1, Miron T. Caproiu2 and Petre Ionita*,3
1Institute of Physical Chemistry, 202 Spl. Independentei, Bucharest 060021, Romania
2Center of Organic Chemistry, 202 Spl. Independentei, Bucharest 060023, Romania
3University of Bucharest, Organic Chemistry Department, 90 Panduri, Bucharest 050663, Romania
Received August 17, 2009: Revised December 10, 2009: Accepted December 31, 2009
Abstract: 4-(N’,N’-diphenylhydrazino)-3,5-dinitrobenzoic acid in reaction with 4-hydroxy-tempo, 4-aminobenzo-15-
crown-5, and 1-bromoacetyl-pyrene, yielded the corresponding esters or amides, as yellow compounds. These hydrazines,
by oxidation with lead dioxide, converted into the stable hydrazyl free radicals, with a purple-violet color. Same yellow
hydrazines in reaction with alkali bases are converted into the corresponding salt of green color. The newly synthesized
1
compounds were characterized by elemental analysis, IR, UV-Vis, H- and 13C-NMR, and EPR (where applicable). Acid-
base, redox, fluorescence and complexation properties were also studied and discussed.
Keywords: Hydrazyl, radical, tempo, crown, pyrene, EPR.
INTRODUCTION
RESULTS AND DISCUSSION
Hydrazyl radicals are one of the most known types of
stable free radicals under usual conditions [1]. Besides their
great stability, they have a range of different properties, such
as acid-base and redox behavior [2]. Because all these
properties are accompanied by color changes, hydrazyl
radicals have been employed as sensors and probes in
different physico-chemical processes, making them to be
followed very easily even with naked eyes [3, 4].
Synthesis of the Compounds 1-9 and their Main Physico-
Chemical Properties
Starting from the dinitrobenzoic acid derivative and using
simple coupling reactions, it was possible to obtain the
compounds 1-3, Fig. (1), with good yields. Thus, carboxylic
group easily reacts with the hydroxyl group from 4-hydroxy-
tempo in the presence of dicyclocarbodiimide (DCC), to
form the ester 1; with the amino-group from 4-aminobenzo-
15-crown-5, to form amide 2 (as well in the presence of
DCC), and, with 1-bromoacetyl-pyrene, to form ester 3, in
the presence of a base. General yields were around 40-60%,
and the new compounds 1-3 were separated and purified by
preparative TLC. Characterization of these compounds was
If such compounds are covalently bonded to other
materials of interest, such are crown ethers, nitroxide
radicals, fluorescent derivatives, and so on, multifunctional
derivatives are obtained. These derivatives represent a
challenge in the area of organic compounds with multiple
applications.
1
performed usually in the first instance by H-and 13C-NMR
(not suitable for the free radicals), elemental analysis and IR.
All these data confirm the chemical structure of the
compounds, as well as their purity. Multiple properties, such
as color, fluorescence, radical behavior, complexation, etc,
will be detailed as appropriate.
Nitroxide radicals are usually employed as probes in
different systems, from biological ones to polymer chemistry
[5]. Crown ethers derivatives are compounds, which exhibit
strong complexation properties, useful not only in analytical
chemistry, but also in membrane transport or in interphasic
catalysis [6]. Fluorescent derivatives are very important in
medicine, biology and biochemistry [7]. Hydrazyl or
hydrazine derivatives modified with such compounds will
have a great interest for many chemists.
As many other congeners, hydrazines [1-4], compounds
1-3 exhibit the same properties: i) by oxidation, they are
converted into the corresponding stable hydrazyl radicals 4-
6, (Scheme 1), and ii) in basic media, the acidic hydrazine
hydrogen atom is removed, with the formation of the
corresponding salts 7-9. All these acid-base and redox
processes are accompanied by color change, see (Scheme 1)
or Experimental part.
In our work we present the synthesis of some new
derivatives with multiple properties, such as acid-base,
redox, complexation and fluorescence. All the new
compounds were characterized by appropriate spectral and
physico-chemical means.
EPR Spectra of the Compounds 1, 4-6
Hydrazyl radicals are mainly characterized by their
hyperfine coupling constants, due to the interaction of the
unpaired electron with the two nitrogen atoms from the
hydrazine moiety. Due also to a ‘push-pull’ effect, they are
quite stable under usual condition, with no decomposition,
dimerization and no reaction with oxygen air being noticed
[1, 2].
*Address correspondence to these authors at the Institute of Physical
Chemistry, 202 Spl. Independentei, Bucharest 060021, Romania;
Tel: +40213167912; Fax: +40213121147;
E-mail: madalina_tudose2000@yahoo.com
University of Bucharest, Organic Chemistry Department, 90 Panduri,
Bucharest 050663, Romania; Tel: +40213121147; Fax: +40213121147;
E-mail: pionita@icf.ro
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

New Hydrazyl Derivatives
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
183
O2N
H
O
O
O
O2N
O2N
O
N
N
O
O
O
O
O
H
H
N
O•
N
N
N
N
O
O2N
HN
O
O2N
O2N
1
2
3
Fig. (1). Structure of the compounds 1-3.
505 nm
4
5
O
508 nm
N
N
.
O
N
O• for 1, 4 and 7
R
ox
500 nm
6
red
violet
O
383 nm
412 nm
1
2
O
O
O
H
red
N
N
where R is
ox
for
2, 5 and 8
O
R
HN
O
395 nm
3
yellow
+
O
-H
623 nm
628 nm
7
O
O
+
N
N-
3, 6 and 9
for
+H
8
R
9
593 nm
green
Scheme 1. Acid-base and redox behavior of the compounds 1-9, accompanied by color changes.
Compound 1 is in fact a nitroxide derivative, Fig. (1) and
its EPR spectrum consists of only 3 lines, Fig. (2a), with a
hyperfine coupling constant aN of 15.40 G (due to the
interaction of the unpaired electron with only one nitrogen
atom). By oxidation, compounds 1-3 are converted into the
corresponding hydrazyl radicals 4-6 (4 being now in fact a
diradical), see Scheme 1. The EPR spectrum of the diradical
4 is shown in Fig. (2b). It consists of a superposition of a
Fig. (2). Experimental (a-c) and simulated EPR spectra (d-e).

184 Letters in Organic Chemistry, 2010, Vol. 7, No. 2
Tudose et al.
O
O
O2N
N-
O2N
O2N
O
+
O
O
O
O
O
Na
H
NaOH
N
N
N
+
O
O
HN
HN
O
O
O2N
yellow
green
Fig. (3). Formation of a supramolecular complex.
nitroxide type spectrum and a hydrazyl type spectrum, in
which the hyperfine coupling constants are quite different
(aN1=15.4 G, aN2=12.6 G and aN3=4.3 G). Compounds 5 and
6 have a very similar spectrum, showed in Fig. (2c). All
these EPR spectra can be well simulated; Fig. (2d-e) shows
the simulated spectra obtained using WinSim software [8].
EXPERIMENTAL
Starting materials were archived from Sigma-Aldrich and
used as received. Solvents were purchased from Chimopar
and used as received. IR spectra were recorded on a Bruker
Vertex 70 spectrometer, NMR spectra were recorded on a
Bruker BB300 instrument, EPR spectra on Jeol JES-FA100
spectrometer, and UV-Vis spectra on
a UVD-3500
spectrometer. Simulations of the EPR spectra were
performed using the WinSim free software [8]. Typical
settings used for the EPR measurements are as follows:
concentration of the sample 10-4 M, number of scans 1,
centre field 3360 G, sweep field 100 G, frequency 9.42 GHz,
power 1mW, sweep time 60 s, time constant 0.1 s,
modulation frequency 100 kHz, gain 100, and modulation
width 1G.
Complexation Properties of Compound 2
Crown ethers have good complexation properties towards
alkali cations [3]. In order to test our compound 2 (which
contains a 15-crown-5 moiety) as a complexing agent for the
alkali cations lithium, sodium, and potassium, we used the
well known method of Job’s curve [9]. This is possible
because the formation of the complex is accompanied by a
colour change, Fig. (3). The ratio of the complexation
between these alkali cations and compound 2 has been
established (by Job’s curve, see Experimental) to be 1 to 1.
1. 394 mg (1 mmol) of 4-(N’,N’-diphenylhydrazino)-3,5-
dinitrobenzoic acid (synthesized as previously described
[10]), was dissolved into 50 mL dry DCM 172 mg of 4-
hydroxy-tempo (1 mmol) and 250 mg DCC (1.2 mmol) were
then added, and the mixture was left for 2 days at room
temperature. After the solvent removal, the residue has been
chromatographed on preparative TLC (silica gel) twice,
using DCM/MeOH 9/1 as eluent. Yields were about 40%.
Elemental analysis: Theoretical: C28H30N5O7 M=548,
C=61.31%, H=5.51%, N=12.77%; Found: C=61.01%,
H=5.59%, N=12.22%.
Fluorescence Properties of Compound 3
Pyrene derivatives are well known as fluorescence
precursors, so our derivative exhibited the expected
fluorescence property [7]. Thus, excitation at 330 nm leads
to the obtaining of fluorescence with a maximum intensity at
around 420 nm. The typical spectrum is shown in Fig. (4).
As usual in the case of free radicals linked to fluorescent
derivatives, for compound 6, the intensity of the fluorescence
is lower.
FT-IR (ATR in solid, ꢀ cm-1): 3295m; 3062w; 2928m;
2854m; 1703s; 1621vs; 1534vs; 1489vs; 1342m; 1264s;
1154m; 751m; 691m.
UV-Vis (DCM, ꢀnm): 383; by oxidation with lead
dioxide 505 (200 mg lead dioxide for 5 mg compound); in
basic media 623.
EPR (DCM): aN=15.4 G; by oxidation with lead dioxide
(200 mg lead dioxide for 5 mg compound) aN1=15.4 G,
aN2=12.6 G and aN3=4.3 G.
2. 394 mg (1 mmol) of 4-(N’,N’-diphenylhydrazino)-3,5-
dinitrobenzoic acid was dissolved into 100 mL DCM, 280
mg of 4-aminobenzo-15-crown-5 (1 mmol) and 230 mg
DCC (1.1 mmol) were added, and the mixture was left
overnight at room temperature. Next day the mixture was
washed with an aqueous solution of hydrochloric acid (0.1
M), sodium bicarbonate (3%) and water. After separation,
the organic phase was dried over anhydrous sodium sulfate,
and the solvent was removed. The residue was
chromatographed on preparative TLC (silica gel) twice,
using DCM/MeOH 9/1 as eluent. Yields were about 60%.
Elemental analysis: Theoretical: C33H33N5O10 M=659,
C=60.09%, H=5.04%, N=10.62%; found: C=60.27%,
H=5.14%, N=10.55%.
Fig. (4). Fluorescence spectrum of the compound 3.
In conclusion, all the new synthesized compounds exhibit
multiple properties; thus, they might be involved in acid-
base, redox, complexation and fluorescence studies. Most of
the changes that occur in such processes can be followed just
by naked eyes, due to the color changes that appear in such
processes.

New Hydrazyl Derivatives
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
185
1H-NMR (CDCl3, ꢀ ppm, J Hz): 9.82(s, 1H, NH,
deuterable); 9.39(bs, 1H, NHCO); 8.90(bs, 1H, H-5 or H-3);
8.49(bs, 1H, H-5 or H-3); 7.34(m, 1H, H-21); 7.32(dd, 4H-
meta, H-9, H-11, H-15, H-17, 8.4, 7.6); 7.14(tt, 2H-para, H-
10, H-16, 7.6, 1.2); 7.12(dd, 4H-ortho, H-8, H-12, H-14, H-
18, 8.4, 1.2); 7.12(m, 1H, H-25); 6.68(d, 1H, H-22, 8.4);
4.02(t, 4H, H-29, H-30, 6.1); 3.85÷3.70(m, 12H, H-26÷H-
28, H-30÷H-33).
13C-NMR (CDCl3, ꢀ ppm): 161.49(C-19); 156.87(Cq);
148.53(Cq); 146.55(C-7, C-9); 145.60(Cq); 139.94(Cq);
131.96(Cq); 129.37(C-meta, C-9, C-11, C-15, C-17); 125.30
(C-para, C-10, C-16); 124.43(Cq); 120.49(C-ortho, C-8, C-
12, C-14, C-18); 113.97(CH); 113.95(CH); 107.72(CH);
70.50(CH2); 70.41(CH2); 70.03(CH2); 69.94(CH2); 69.24
(CH2); 69.04(CH2); 68.91(CH2); 68.34(CH2).
FT-IR(ATR in solid, ꢁ cm-1): 3276m; 3104w; 3047w;
2937w; 1732vs; 1676s; 1622s; 1588s; 1564m; 1528vs;
1488vs; 1457m; 1415s; 1380m; 1357m; 1257vs; 1215s;
1185s; 1151s; 1116s; 982m; 953m; 931m; 850s; 761m;
749m; 719s; 695m; 621m; 568w.
UV-Vis(DCM, ꢀnm): 395; by oxidation with lead
dioxide 500 (200 mg lead dioxide for 5 mg compound); in
basic media 593.
EPR (DCM): after oxidation with lead dioxide (200 mg
lead dioxide for 5 mg compound), aN1=9.4 G, aN2=7.8 G
Determination of the Complexation Ratio by Job’s Curve
Equimolar solution of compound
2 and lithium
hydroxide, sodium hydroxide and potassium hydroxide in
dry methanol was prepared. As a typical procedure, 0.2, 0.4,
0.6, 0.8, 1.0, 1.2, 1.4, 1.6, and 1.8 mL of compound 2 was
mixed with 1.8, 1.6, 1.4, 1.2, 1.0, 0.8, 0.6, 0.4 and 0.2 mL of
the alkali solution, respectively, to achieve a total of 2 mL
mixture each time. For each mixture, the absorbance was
registered at 628 nm and plotted against concentration. The
maximum of the absorbance had been recorded in the case of
mixture formed by 1 mL compound 2 and 1 mL alkali
hydroxide (lithium hydroxide, sodium hydroxide and
potassium hydroxide), proving thus the ratio of 1 to 1
between the crown moiety and the cation.
FT-IR (ATR in solid, ꢁ cm-1): 3298m; 3064w; 2927m;
2870m; 1623s; 1533vs; 1510vs; 1491vs; 1454m; 1425m;
1345m; 1258s; 1194m; 1130s; 1057w; 993w; 909m; 727m;
696m; 646w.
UV-Vis (DCM, ꢀnm): 412; by oxidation with lead
dioxide 508 (200 mg lead dioxide for 5 mg compound); in
basic media 628.
EPR (DCM): after oxidation with lead dioxide (200 mg
lead dioxide for 5 mg compound), aN1=9.4 G, aN2=7.8 G.
3. 394 mg (1 mmol) of 4-(N’,N’-diphenylhydrazino)-3,5-
dinitrobenzoic acid was dissolved into 70 mL DMF 323 mg
of 1-bromoacetyl-pyrene (1 mmol) were added, and the
mixture was stirred overnight in the presence of 3 g of
sodium bicarbonate. Next day to the mixture was added
200mL of water, acidified at pH~5, and the solution
extracted with DCM. The organic phase was dried over
anhydrous sodium sulfate, and the solvent was removed. The
residue was chromatographed on preparative TLC (silica gel)
twice, using DCM/MeOH 9/1 as eluent. Yields were about
50%. Elemental analysis: Theoretical C37H24N4O7 M=636,
C=69.81%, H=3.80%, N=8.80%; found: C=69.44%,
H=3.80%, N=8.68%.
1H-NMR (CDCl3, ꢀ ppm, J Hz): 9.96(s, 1H, NH,
deuterable); 9.08(bs, 1H, H-3 or H-5); 9.01(d, 1H, H-34,
9.5); 8.42(bs, 1H, H-5 or H-3); 8.33(d, 1H, H-23, 8.1);
8.28÷8.25(m, 2H, H-5, H-7); 8.24(d, 1H, H-33, 9.5); 8.20(d,
1H, H-26 or H-27, 8.8); 8.19(d, 1H, H-24, 8.1); 8.08(d, 1H,
H-30, 9.0); 8.06(d, 1H, H-26 or H-27, 8.8); 8.24(d, 1H, H-
24, 9.4); 7.34(dd, 4H-meta, H-9, H-11, H-15, H-17, 8.4, 7.6);
7.18(tt, 2H-para, H-10, H-16, 7.6, 1.2); 7.14(dd, 4H-ortho,
H-8, H-12, H-14, H-18, 8.4, 1.2); 5.73(s, 2H, H-20).
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