________________________________________
*author for correspondence e-mail: aadreab22@yahoo.com
int. j. chem. sci.: 14(2), 2016, 513-528
issn 0972-768x
www.sadgurupublications.com
investigation study of transition state for
synthesis new schiff base ligands of
isatin derivatives
ebtihal k. kareema, abbas a-ali drea* and
sajid m. lateefb
achemistry department, college of science, babylon university, hilla, iraq
bchemistry department, college of iben a-lhythem, baghdad university, hilla, iraq
abstract
quantum calculation methods have been used to estimate the real transition states of synthesis
new schiff base ligands derivative from isatin using semiemperical calculation methods. optimized
structures and vibration spectrum have been calculated to the prepared compounds, that’s compared with
their practical data. theoretical study of transition states have been done to investigate the real transition
state of reaction through zero point energy, total binding energy and first imaginary frequency. three
suggested transition states have been proposed into the reaction of 4-dmia with 2-hydroxy amine. they
found the second transition state is real transition state than other proposed, due their energetic values.
suggestion of six transition states to the reaction of dmaa with isatin. good agreements has been found
between the experimental and theoretical data for the synthetic products, likes[(3e)-3-[3-(2-hydroxy
phenylimino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1h-pyrazol-4-ylimino]indolin-2-one] and [(3e)-3-[3-
(3-amino phenylimino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1h-pyrazol-4-ylimino]indolin-2-one] as final
products.
key words: quantum calculation methods, transition states, isatin, schiff base, semi-empirical and
pm3.
introduction
biological activities are released by schiff bases derivatives from isatin such as
antifungal, antiviral, and anticancer, due to cis-?-dicarbonyle moiety of isatin1-4. schiff bases
specially poly dentate with deferent donor atoms such as (n2o2, nnnn, ono)5-7, which
made these compounds good substrate for the synthesis of metal complexes either alone or
e. k. kareem et a 514 l.: investigation study of transition….
mixed with different other ligands8. schiff base ligands have wide range of application9. in
analytical chemistry along record of use as chromogenic reagent for determination of many
metals including ni(ii) in some natural food samples10. importance of these compounds is
come out by presence of azomethine group, which plays an important role in coordination11.
the tools of computational chemistry have been used to investigate the chemical
behavior and different reactivity parameterized of synthetic derivatives12,13. chemical
synthesis reactions required optimized structures of their chemical species and their
transition states of synthesis reaction. the structural properties are elementary keys to
understand the chemical reactivity during the potential energy surface calculations14,15.
in present work, the transition state of synthesis reaction for schiff s base compound
using different conditions and reactant species has been carried out. simulation studies are
taken in several stages of calculation. to estimate at the last spectroscopic comparative
study, that’s made and suggested the real transition state for the reaction.
experimental
materials and methods
all chemicals used were supplied from bdh, fluka, and merck companies and used
without any further purification absorption spectra were recorded using shimadzu uv-vis
1700 spectrophotometer, for solution of the complexes in aqueous ethanol at room
temperature. using 1 cm quartz cell. ir spectra were recorded with ft-ir-8000 shimadzu,
in the range of (4000-400) cm-1 using kbr discand melting points were obtained using an
electro thermal apparatus stuart melting point.
calculation details
semi-empirical methods according to molecular orbital theory have been used to
find the optimized structures of (4-dmia) and (dmaa) and their schiff base derivatives
structural configuration interaction (2x 2) of microstate. the transition state for the reaction
path techniques have been studied using quadratic synchronous transit method (qst) of
hyperchem 8.0216. it searches for a maximum along a parabola connecting reactants and
products, and for a minimum in all directions perpendicular to the parabola. vibration
frequencies of the proposed transition state structures have been calculated at uhf/pm3 for
characterization of the nature of zero point energy (zpe) calculations to compute the
quantum energies of these reactions.
int. j. chem. sci.: 14(2), 2016 515
preparation of schiff base (3e)-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1hpyrazol-
4-yl)imino]-1,3-dihydro-2h-indol-2-one (4-dmia)
in a round bottom flask, 4-aminoantipyrine (0.01 mol, 2.03 g) in (15 ml) ethanol and
isatin (0.01 mol, 1.47 g) in (15 ml) ethanol added few dropings of glacial acetic acid to
solution the mixture was refluxed for (6 hr), the product precipitate was obtained by
filtration and recrystallized from hot ethanol, and dried over anhydrous cacl2.17
preparation of schiff base n-(4-amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3hpyrazol-
3-ylidene)-n-(3-aminophenyl)amine (dmaa)
in a round bottom flask, 4-aminoantipyrine (0.01 mol, 2.03 g) in (15 ml) ethanol
and (0.01 mol, 1.08 g) of 3-phenylene di amine in (15 ml) ethanol added few dropings of glacial
acetic acid to solution the mixture was refluxed for (10 hr), the product precipitate was
obtained by filtration and recrystallized from hot ethanol and dried over anhydrous cacl2.
preparation of new schiff base ligand (2-hdmia)
the schiff base ligand (2-hdmia) was prepared by condensation of compound
(4-dmia) (0.01 mol, 3.32 g), which was dissolved in (50 ml) ethanol and refluxed with
(0.01 mol, 1.09 g) of 2-hydroxy amine for (16 hr)18. adding three dropings from glacial acetic
acid, a clear colored solution was obtained. the schiff base ligand was isolated after the
volume of mixture was reduction to half by evaporation and recrystallized by hot ethanol
and dried over anhydrous cacl2.
preparation of new schiff base ligand (3-admia)
the schiff base ligand (3-admia) was prepared by condensation of compound
(dmaa) (0.01 mol, 2.933 g), which was dissolved in (50 ml) ethanol and refluxed with
isatin (0.01 mol, 1.47 g) in (15 ml) for (30 hr)19. adding three dropings from glacial acetic acid,
a clear colored solution was obtained. the schiff base ligand was isolated after the volume
of mixture was reduction to half by evaporation and recrystallized by hot ethanol and dried
over anhydrous cacl2.
results and discussion
fig. 1 shows the geometries of the only possible three proposed transition state
structures. these have been optimized and (4-dmia) was ir-tested. the probable transition
state of prepared compounds comes out through confirmation table 1. it shows the
e. k. kareem et a 516 l.: investigation study of transition….
interaction of (4-dmia) with (2-hydroxy amine) in transition state, which are expected to
yield ts2 is the real transition state and second transition state is the most probable state to
give up the reaction products than other states due to the highest value of zero point energy
216.243 kcal mol-1 and highest energy stability -93552.470 kcal mol-1.
ts1 ts2
ts3
fig. 1: geometrical wire form view of proposed transitions states calculated at
uhf/mp3 of 2-hdmia
int. j. chem. sci.: 14(2), 2016 517
table 1: energy properties of probable transition states for 4-dmia with
2-hydroxyamine calculated at uhf/pm3
transition
state
total
energy
(kcal/mol)
binding
energy
(kcal/mol)
zero point
energy
(kcal/mol)
ir-frequency
(imaginary)
heat of
formation
(kcal/mol)
s1 -93499.664 -4780.168 213.804 - 35.254
s2 -93552.470 -4832.975 216.243 - -17.552
s3 -93449.4 -4729.9 209.833 - 85.52
fig. 2 shows the geometries of the six proposed transition state structures. these
have been optimized and (dmaa) was ir-tested. the probable transition state of prepared
compounds comes out through confirmation table 2. it shows the interaction of (dmaa)
with isatin in transition state, which are expected to yield ts1 is the real transition state and
first transition state is the most probable state to give up the reaction products than other
states due to the highest value of zero point energy 283.923 kcal mol-1 and highest energy
stability -112774.114 kcalmol-1.16
ts1 ts2
cont…
e. k. kareem et a 518 l.: investigation study of transition….
ts3 ts4
ts5 ts6
fig. 2: geometrical wire form view of proposed transitions states calculated at
uhf/mp3 of 3-admia
int. j. chem. sci.: 14(2), 2016 519
table 2: energy properties of probable transition states for dmaa with isatin
calculated at uhf/pm3
transition
state
total energy
(kcal/mol)
binding
energy
(kcal/mol)
zero point
energy
(kcal/mol)
ir-frequency
(imaginary)
heat of
formation
(kcal/mol)
s1 -112774.114 -6258.353 283.923 - 61.462
s2 -112773.114 -6257.353 283.563 - 62.462
s3 -112773.392 -6257.631 283.252 - 62.184
s4 -112768.693 -6252.932 277.751 - 66.883
s5 -112772.911 -6257.150 279.350 - 62.665
s6 -112771.304 -6255.543 277.519 - 64.272
table 3 shows comparison between the experimental and theoretical vibration
spectrum of the synthetic compounds.
table 3: comparative of experimental and theoretical vibration spectrum analysis of
synthetic compounds
compound experimental
cm-1
theoretical
pm3/cm-1 intensity description
(3-admia)
3394 3487 90586.860 n-h asymmetric
3364 3344 12055.210 n-h symmetric
1653 1643 4163.225 c=n1
1618 1569 4315.949 c=n2
1718 1763 9732.004 c=o
3064 3100 9307.601 c-h ar
2922 2999 10704.170 n-ch3
1492 1497 1593.685 c=c
(2-hdmia)
3402 3642 235 o-h
1663 1665 57 c=n2
1616 1647 34 c=n1
1718 1819 111 c=o
3064 3014 2297 c-h ar
1595 1512 662.067 c=c
e. k. kareem et a 520 l.: investigation study of transition….
the compound (3-admia) was confirmed according to data. they found in good
agreement by two bands at 3394 cm-1 and 3364 cm-1 due to asymmetric and symmetric
stretching vibrations of ? nh2 group, respectively. absorption bands at 2922 cm-1was
attributed to n-ch3 group. bond absorption at 1653 cm-1 and 1618 cm-1 was due to ? c=n
stretching. the sharp bands at 1591 is due to the ? c=c stretching vibration. the compound
(2-hdmia) was confirmed according to data, they found in good agreement20. absorption
band of o-h group found at 3402 cm-1. bond absorption at 1663 cm-1 and 1616 cm-1 was
due to ? c=n stretching. the sharp bands at 1595 is due to the ? c=c stretching vibration as
showed in figs. 2, 3, 4 and 5.
%t
1/cm
105
90
75
60
45
30
15
0
3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
fig. 2: experimental ftir vibration spectra of 3-admia
fig. 3: theoretical ftir vibration spectra of 3-admia
int. j. chem. sci.: 14(2), 2016 521
%t
1/cm
120
105
90
75
60
45
30
15
3750 3500 3250 3000 2750 2500 2250 2000 1750 1500 1250 1000 750 500
fig. 4: experimental ftir vibration spectra of 2-hdmia
fig. 5: theoretical ftir vibration spectra of 2-hdmia
electronic spectra
the electronic spectra of ligand (3-admia) (fig. 6) and (2-hdmia) (fig. 7) were
studied and the spectral data were listed in table 4. the uv-vis spectrum of the schiff base
ligand (3-admia) was characterized mainly by four absorption peaks at (278 and 345) nm
assigned to (? ? ?*) and at (362 and 440) nm assigned to (n ? ?*). while the uv-vis
spectrum of the schiff base ligand (2-hdmia) was characterized mainly by two absorption
peaks at (291) nm assigned to (? ? ?*) and at (460) nm assigned to (n ? ?*)10.
e. k. kareem et a 522 l.: investigation study of transition….
+2.50 a
0.500
+0.00 a
200.0 100.0 (nm/div.) 1000.0
nm
(a/div.)
fig. 6: electronic spectra of (3-admia)
+2.50 a
0.500
+0.00 a
200.0 100.0 (nm/div.) 1000.0
nm
(a/div.)
fig. 7: electronic spectra of (2-hdmia)
table 4: experimental uv/visible spectra of synthetic compounds
compounds ?max (nm) ? (cm-1) ?max transition
3-admia
278 35971 1957 ? ? ?*
345 28986 1275 ? ? ?*
362 27624 888 n ? ?*
440 22727 744 n ? ?*
2-hdmia
291 34364 2317 ? ? ?*
460 21739 2141 n ? ?*
int. j. chem. sci.: 14(2), 2016 523
the chemical formula and physical properties of prepared compounds have been
listed in table 5.
table 5: the chemical formula and physical properties of prepared compounds
compounds chemical
formula m. wt. yield
(%) color melting point
(oc)
3-admia c25h22n6o 422.489 72 brown 170
2-hdmia c25h21n5o2 423.474 69 reddish-brown 168
scheme 1 and 2, shows the diagrams of the consecutive reaction to synthesis
different chemical compounds that may be useful as new ligands in order to coordinate with
different transition metals.
+
4-amino-1,5-dimethyl-2
-phenyl-1,2-dihydro-3hpyrazol-
3-one
3-aminophenylamine n-(4-amino-1,5-dimethyl-2-phenyl-1,2-dihydro-3h-py
razol-3-ylidene)-n-(3-aminophenyl)amine
n
n o
h3c nh2
h3c
nh2
h2n
n
n n
h3c nh2
h3c
nh2
+
3-admia 1h-indole-2,3-dione
n h
o
o
n
n n
h3c n
h3c
nh2
n h
o
scheme 1: diagrammatic pathways of the synthesis reactions for the
new schiff base 3-admia
e. k. kareem et a 524 l.: investigation study of transition….
1h-indole-2,3-dione (3e)-3-[(1,5-dimethyl-3-oxo-2-phenyl-2,3
-dihydro-1h-pyrazol-4-yl)imino]-1,3-
dihydro-2h-indol-2-one
+
4-amino-1,5-dimethyl-2-phenyl-
1,2-dihydro-3h-pyrazol-3-one
n h
o
o
n
n o
h3c nh2
h3c n
n o
h3c n
h3c
n h
o
+
nh2
oh
n
n n
h3c n
h3c
n h
o
oh
2-hdmia 2-aminophenol
scheme 2: diagrammatic pathways of the synthesis reactions for the
new schiff base 2-hdmia
scheme 3 and 4, shows the physical and energy properties of schiff bases compounds.
long of bond with tube shape total charge density (3d)
int. j. chem. sci.: 14(2), 2016 525
electrostatic potential (3d) electrostatic potential (2d)
homo (2d) lumo (2d)
scheme 3: physical and energy properties of schiff base 3-admia
long of bond with tube shape total charge density (3d)
e. k. kareem et a 526 l.: investigation study of transition….
electrostatic potential (3d) electrostatic potential (2d)
homo (2d) lumo (2d)
scheme 4: physical and energy properties of schiff base 2-hdmia
application
new schiff bases ligands can be synthesized according to the estimation study
and performing through the comparative study between the experimental and theoretical
results.
conclusion
(i) second transition state is the most probable state to give up the reaction
products than other transition states of 2- hdmia.
int. j. chem. sci.: 14(2), 2016 527
(ii) first transition state is the most probable state to give up the reaction products
than other transition states of 3-admia.
(iii) they found a good agreement between the experimental and theoretical values
of vibration spectrums of synthetic compounds.
references
1. w. rehman, m. k. baloch, b. muhammad, a. badshah and k. m. khan, chin. sci.
bull., 49(8), 119-122 (2004).
2. c. silva da, d. silva da, l. modolo and r. alves, j. adv. res., 2(1), 1-8 (2011).
3. m. jesmin, m. h. ali and j. a. khanam, pharm. sci., 34, 20-31 (2010).
4. r. h. ahmad, s. moagtoof mahmood and m. a. abid allah, j. kufa for chem. sci.,
1(1), 35-44 (2010).
5. a. a. ahmed, s. a. benguzzi and a. o. agoob, rasayan j. chem., 2(2), 271-275 (2009).
6. r. amit, k. ashish and s. rupa, vsrd-tnt j., 2(8), 352-357 (2011).
7. omer b. ibrahim, m. a. mohamed and moamen s. refat, canadian chemical
transactions, 2(2), 108-121 (2014).
8. c. leelavathy and s. arul antony, int. j. basic appl. chem. sci., 3(4), 88-95 (2013).
9. k. rishu, k. harpreet and k. k. brij, sci. revs. chem. commun., 3(1), 1-15 (2013).
10. a. fakhari, khorrami, r. afshin and h. naeim, talanta, 66, 813-817 (2005).
11. n. al-shareefi abbas, h. k. salih and a. j. waleed, j. applicable chem., 2(3), 438-
446 (2013).
12. a. dearing, computer-aided molecular modelling: research study or research tool,
j. computer-aided molecular design, 2, 179-189 (1988).
13. p. gund, d. c. barry, j. m. blaney and n. c. cohen, guidelines for publications in
molecular modeling related to medicinal chemistry, j. med. chem., 31, 2230-2234
(1988).
14. a. r. katritzky, z. wang and r. j. offerman, j. heterocyclic chem., 27, 139 (1990).
15. c. h. zhengming and y. itan, j. agr. food chem., 48, 5312 (2000).
16. s. a. bahadur, k. goel and r. s. nerva, j. chem. soc., l.3, 590 (1976).
17. m. a. hadi, acta. chim. pharm. indica, 3(2), 127-134 (2013).
e. k. kareem et a 528 l.: investigation study of transition….
18. y. bogale zemede and s. ananda kumar, int. j. chem. tech. res., 7(1), 279-286
(2014).
19. v. prakash and m. s. suresh, rjpbcs, 4(4), 1536-1550 (2013).
20. e. o. fadhel, j. k. kadhum and a-ali drea abbas, j. applicable chem., 1(3), 344-
351 (2012).
revised : 25.01.2016 accepted : 27.01.2016