Investigation of rotations in isomerism forms of a ylide of theophylline: Dynamic 1H NMR study

Article abstract of DOI:10.13005/ojc/330316

The internal rotations around the some within a ylide involving theophylline has been studied using the dynamic ¹H NMR spectroscopic technique in different temperatures. The kinetic and activation quantities were calculated. Arrhenius, Eyring a

Full text of DOI:10.13005/ojc/330316

ISSN: 0970-020 X
CODEN: OJCHEG
017, Vol. 33, No. (3):
Pg.1182-1189
ORIENTAL JOURNAL OF CHEMISTRY
An International Open Free Access, Peer Reviewed Research Journal
2
www.orientjchem.org
Investigation of rotations in isomerism forms of a ylide of
1
theophylline: Dynamic H NMR study
1
,
1
SAYYED MOSTAFA HAbIbI-KHORASSANI *, MEHDI SHAHRAKI ,
1
2
EIDEH MOFARRAH and ELHAM MOFARRAH
1
Department of Chemistry, University of Sistan and Baluchestan, P. O. Box 98135-674, Zahedan, Iran.
2
Department of Chemical Engineering, Amirkabir University of Technology, Tehran, Iran.
*
Corresponding author E-mail: smhabibi@chem.usb.ac.ir
http://dx.doi.org/10.13005/ojc/330316
(Received: January 23, 2017; Accepted: March 03, 2017)
AbSTRACT
The internal rotations around the some within a ylide involving theophylline has been
1
studied using the dynamic H NMR spectroscopic technique in different temperatures. The kinetic
and activation quantities were calculated. Arrhenius, Eyring and classic methods were applied for
isomers. compared for carbon-carbon double, carbon-carbon single bond for Z isomer. The results
obtained by classic method was different with data calculated from Arrhenius and Eyring methods
while these methods were consistent together.
1
Keywords:Ylide, Isomerism, Dynamic H NMR, Activations Parameters
9
,14
9
INTRODUCTION
anti-Inflammatory , immunomodulatory , air
1
5-16
ways smooth muscle effects
sapnea . Theophylline is naturally in green and
black tea, coffee, and cocoa .
, effects infant
17, 18
Ylides are important compound in the
synthesis of plenty products with the various
applications in pharmacology and medicine
19
1
-7
.
Moreover, theophylline character ized
s1, 3-dimethylxanthine, is known as an impressive
bronchodilator drug . This compound has been
Theophylline in structure of ylides has
significant dynamic H NMR effects.So, these effects
1
8
afford important information regarding the rotational
2,20-25
used for over half a century in the treatment of
asthma and remains the most widely prescribed
isomers
.
9
1
anti-asthma treatment in the whole world .
In this work, the dynamic H NMR
This compound also used in treatment chronic
effects on the titled compound prepared of the
reaction between triphenylphosphine1 and
1
0-11-12-13
pulmonary obstructive disease (COPD)0
,

1183
KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
1
dimethylacetylendicarboxylaten 2 in the presence
H NMR spectra of the ylide4 showed two
of theophylline 3 has been described.The synthesis doublets for methine proton (H–C–C=P) and methyl
26
reaction has been previously reported . For these groups d = 5.493-5.510 and 3.69-3.72 ppm, for the
reasons, three methods for determining the activation minor and major geometrical isomers, respectively.
2
7
parameters are applied .
All interchangeable process of rotational isomers
for ylide 4 involving isomers I, II, III, IV, V and VI are
shown in Fig. 3
Chemicals and instruments
Tiphenylphosphine1,dimethyl acetylene
dicarboxylate 2 and theophylline 3 obtained from Dynamic effects for the Z-4 and E-4 rotational
Fluka (Buchs, Switzerland) are used in analytical isomers around the carꢀon–carꢀon douꢀle ꢀond
grade,. The extra pure solvents including ether and (Fig. 3, a, I and II)
1
acetone-d (supplied by Merk, Darmstadt Germany)
The H NMR spectrum for the 4-Z and the
6
1
are used in this work. The HNMR spectra were 4-E (Fig.3, a, I and II) at º0C (273.15 K) exhibited two
recorded on a FTNMR 400.22 MHz-BRUKER- sharp doublets for the methene proton (H–C–C=P,
3
Avance III.
JPH) in acetone. This spectrum is broadened
at 20ºC (293.15 K). The resonance coalescence
occurred at near 26 ºC (299.15 K) that they belong
to rotational process around carbon–carbon double
RESULTS AND DISCUSSION
The presence of two isomers Z nd E for bond.The methoxy proton resonance coalescence is
1
13
the synthesized ylide4 was confirmed by the H,
and P NMR spectra (Fig .1) .
C
accrued at near 32 ºC (305.15 K).The coalescence
3
1
26
temperature (T ) and isotropic chemical shift (∆ν) is
c
obtained for the maximum peak separation in the
27
The adjacent carbonyl group along with the low-temperature limit . Moreover, parameters and
three rotations around the restricted rotational bonds kinetic parameters are calculated by the classic
1
of the synthesized compunds is strongly conjugated method and tabulated in Table 1.
in the Z-4 and E-4 rotational isomers (Fig. 2).
Fig. 1: Synthesise of dimethyl-2-(Theophylline-1-yl)-3-(triphenylphosphoranylidene)
ꢀutandioate4 from the reaction ꢀetween triphenylphosphine1 and dimethyl
acetylene dicarꢀoxylate 2 with theophylline 3
Fig. 2: Three possiꢀle rotations for the interchangeaꢀle processes of the two isomers
Z- and E-) in ylide4
(

KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
1184
For completing analysis and reducing the
errors, the determining of activation parameters
are repeated by Eyring and Arrhenius methods.
from of Eyring equation has been employed to draw
‡
Fig.4B for determination of ∆H (activation enthalpy)
‡
28-30
and ∆S (activation energy)
:
‡
With using the average value of ∆G in various
‡
‡
temperature (Table 2), ln(k/T) and lnk can be drawed
Tln(k/T) = T(23.76 + ∆S /R - ∆H /RT)
1
2
27
according to the Eyring and Arrhenius equations .
The Eyring and Arrhenius plots are shown in Figs.4A
and 5, respectively. In addition, a different linearized
By using some correlation reported
previously by researchers, the standard errors
Taꢀle 1:The activation parameters forylide4 around the carꢀon-carꢀon douꢀle ꢀound
(
Entry a,Fig. 3)
Tc
K
d
∆ν
Hz
k
s
∆G‡
kcalmol
∆H‡
kcalmol
∆S‡
calmol K
Ea
kcalmol
c
-
1
-1
-1
-1 -1
-1
ppm
2
3
99.15
5.493-
6.8
15.10
15.90
15.88
5.510
16.58
2.28
17.17
05.15
3.699-
.729
12.01 26.66
3
‡
Taꢀle 2:Values of ∆G , lnk/T and lnk for rotation around carꢀon-carꢀon douꢀle ꢀond
(
Entry a, Fig. 3)
‡
T K
1/T
∆dppm
∆ νHz ∆G kcal/mol
Lnk/T
Lnk
T×Lnk/T
c
2
2
2
2
63.15
0.00380 5.479-5.494
0.00366 5.493-5.510
0.00353 5.508-5.529
0.00341 5.524-5.545
6.00
6.80
8.40
8.40
14.05
14.51
14.93
15.45
-4.41
-3.38
—2.42
-1.52
1.16
2.23
3.23
4.15
-1159.965
-922.154
-684.656
-477.053
73.15
83.15
93.15
Taꢀle 3: A comparing ꢀetween the results oꢀtained ꢀy the three methods for
the rotation around the carꢀon-carꢀondouꢀle ꢀond in the isomer
Z-4 and E-4 [entry a]
‡
-1
‡
-1
‡
-1 -1
-1
Methods
∆G (kcalmol ) ∆H (kcalmol ) ∆S ( calmol K ) E (kcalmol )
a
Classic
15.90
14.73
14.73
14.64
16.58
2.28
17.17
Eyring(A)
Eyring(B)
Arrhenius
14.68±0.033
14.73±0.033
14.59±0.033
-0.18±0.00011
0.004 ±0.00011
-0. 18±0.00011
15.27 ±0.033
15.32 ±0.033
15.18 ±0.033
Taꢀle 4: Activation parameters of ylide4 for the carꢀon- carꢀon single ꢀond in the Z-4
isomers, (I, III) ꢀy the classic method
Tc
K
d
∆ν
Hz
k
s
∆G‡
kcalmol
∆H‡
kcalmol
∆S‡
calmol K
Ea
kcalmol
c
-
1
-1
-1
-1 -1
-1
ppm
2
2
04.15
13.15
3.177- 3.194
5.295-5.355
6.80
15.106
53.316
10.69
11.70
4.97
12.11
24.013
1
10.55

1185
KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
of the Eyring and Arrehnius equations are also
An evaluation of the results obtained
1
28-30
calculated
.The values of activation energy and (Table 3) by using three methods shows the results
activation parameters obtained by three methods are from the Eyring and Arrhenius are consistent, but
reported in Table 3. are different from the classic method.
Fig. 3:The restricted rotational processes for ylide4
Taꢀle 5: Activation parameters of ylide4 for rotation around the nitrogen- carꢀon single ꢀond
in the Z-4 isomers, (I, V) oꢀatiend ꢀy the classic method
Tc
K
d
∆ν
Hz
k
s
∆G‡
kcalmol
∆H‡
kcalmol
∆S‡
calmol K
Ea
kcalmol
c
-
1
-1
-1
-1 -1
-1
ppm
2
2
43.15 8.336-8.345
47.15 5.447-5.462
4
8.881
13.08
11.63
-5.94
12.11
6.003 13.328
13.10
Taꢀle 6:The activation parameters derived from dynamic reviewylide 4 around the carꢀon-carꢀon
single ꢀound (Entry d,Fig. 3) according to classic method
Tc
K
08.15
d
∆ν
Hz
23.21
k
s
51.54
∆G‡
kcalmol
10.4
∆H‡
kcalmol
∆S‡
calmol K
Ea
kcalmol
c
-
1
-1
-1
-1 -1
-1
ppm
3.685-3.743
2
2
11.55
5.54
11.96
05.15
5.317-5.355
15.208
33.767
10.39

KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
1186
Dynamic effect (Fig. 3, ꢀ, I and III) for the carꢀon–
carꢀon single ꢀond and the nitrogen–carꢀon
(8.336-8.345ppm)around the carbon–nitrogen single
bond in acetone-d .Another resonance coalescence
6
(
N -C-CH) ꢀond (Fig. 3, c, I and IV) of the Z
is accrued at near -26 ºC (247.15 K) is belong
to the methine proton (H–C–C=P, JPH)) for the
3
isomer
With decreasing temperature lower than
30 ºC, a singlet from methyl proton begin to
broad spectrum for the 4-Z isomer. The resonance
coalescence can be observed at -69 ºC (204.15
K) and the spectrum for the 4-Z isomer (Fig. 3, b, I
and III) shows a resonance arising from
restricted rotational process around nitrogen–carbon
single bond. The activation parameters and kinetic
parameters are calculated by the classic method and
is shown in Table 5.
-
Dynamic effect (Fig. 3, d, II andV) for the carꢀon-
carꢀonsingleꢀondandthe4-Erotationalisomers
as a result of restricted rotational processes (Fig.
3, e, II andVI) around the nitrogen-carꢀon single
ꢀond
(
3.177-3.194ppm) in acetone-d around the carbon–
6
carbon single bond.Another resonance coalescence
observed at near -60ºC (213.15 K) is belong to the
3
methine proton (H–C–C=P, JPH)).For this process,
the activation parameters and kinetic parameters is
calculated by using the classic method and is shown
in Table 4.
With decreasing temperature in lower
than -30ºC, two singlet from methoxy protons begin
to broad at -50ºC. The resonance coalescence is
1
observed at -65 ºC (20815 K). Then the H NMR
Also, in lower temperature than -10 ºC
8.298 ppm) , a singlet from proton of nitrogen in
ring five-membered (N=CH )begin to broad at -50ºC.
spectrum for the 4-E isomer (Fig. 3, d, II and V)
shows a resonance arising from (3.685-3.743
ppm)around the carbon–nitrogen simple bond in
(
The resonance coalescence occurs at approximately
acetone-d . Another resonance coalescence is
6
1
-
(
30ºC (243.15 K) and then the H NMR spectrum
Fig. 3, c, I and IV) shows a resonance arising from
obsreved at near -68ºC (205.15 K) is belong to the
3
methine proton (H–C–C=P, JPH)) for rotational
process around carbon–nitrojen single bond. The
activation and kinetic parameters are calculated by
the classic method and are reported in Table 7.
The Eyring plot and Arrhenius plot are
shown in Figs. 5 and 6 and also the activation and
kinetic parameters are calculated by using the
classic method and also are presented in Table 8.
The results from Eyring and Arrhenius plots
are consistent together more than the classic method
(
Table 8). Moreover, when temperature is reduced
down lower than -10 ºC a singlet from proton of
nitrogen in ring five-membered (N=CH ) begin to
Fig. 4 A: An Eyring plot of ln (k/T) versus 1/T
Fig. 4 b: A different linearized form of Eyring
equation
Fig. 5: An Arrhenius plot of lnk versus 1

1187
KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
Fig. 6A: An Eyring plot of ln (k/T) versus 1
Fig. 6b: A different linearized form of Eyring equation
Taꢀle 7: Comparing the oꢀtained results from the two methods (Eyring and Arrhenius) for
the restricted rotation around the carꢀon-carꢀon single ꢀond in the isomers E-4 [entry d]
‡
-1
‡
1
‡
-1 -1
1
Methods
∆G (kcalmol ) ∆H (kcalmol- )
∆S (kcalmol K )
E (kcalmol- )
a
Classic
10.40
9.58
9.57
9.56
11.55
5.54
11.96
Eyring(A)
Eyring(B)
Arrhenius
9.52 ± 0.1
9.57± 0.1
9.49± 0.1
-0.30 ± 0.00034
-0.014 ± 0.00034
-0. 30± 0.00034
9.93 ±0.1
9.98 ±0.1
9.9.91 ±0.1
Taꢀle 8: Activation parameters of ylide4 for rotation around the nitrogen-carꢀon single
ond in the E-4 isomers, (II ,VI) ꢀy the classic method
ꢀ
Tc
K
d
∆ν
Hz
k
s
∆G‡
kcalmol
∆H‡
kcalmol
∆S‡
calmol K
Ea
kcalmol
c
-
1
-1
-1
-1 -1
-1
ppm
2
2
44.15
46.15
8.393-8.404
5.408-5.421
4.40
9.77
13.09
9
.49
-14.7
11.55
9.94
13.2
5.202

KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
1188
Fig. 7: An Arrhenius plot of ln (k) versus 1/T
broad at -25ºC.The resonance coalescence occurs
at -29 ºC (244.15 K). Then the H NMR spectrum
for the 4-E isomer (Fig. 3, e, II and VI) shows a
resonance arising from (8.393-8.404ppm)around
the carbon–nitrogen simple bond in acetone-d6.
Another resonance coalescence is accrued at near
Eyring and Arrhenius method did not use in these
rotation because required data were not available.
Because of the strong conjugation with the adjacent
carbonyl group, the value of activation barrier energy
1
‡
(∆G ) of the restricted rotation around the partial
carbon-carbon double bond (MeO C=CPPh ) was
2
3
-
(
27ºC (246.15 K) in relation to the methene proton
H–C–C=P, JPH)) which is relevant to restricted
larger than the nitrogen-carbon (N-C-CH) and
carbon-carbon (MeO CH-C-C=PPh ) single bonds.
3
2
3
rotational process around carbon–nitrogen single
bond. For this process, the activation parameters
and kinetic parameters obtained using the classic
method is tabulated in Table 9. Because of lone
pair inversion of nitrogen atom in hetero atom five-
membered ring, rotation around the carbon-carbon
single bond requires a barrier rotational energy more
than the carbon-carbon single bond (comparison
As a case study, because of the lone pair inversion
of nitrogen atom in hetero atom -membered ring,
rotation around the carbon-nitrogen single bond
needs a barrier rotational energy more than the
carbon-carbon single bond. Rotation around the
‡
carbon-carbon double bond ∆G has a more positive
‡
value. So high value of ∆G indicates the rate of
this process is slow at room temperature. At higher
temperature it is fast and spontaneous. Rotation
‡
between E and ∆G in Table 9).
a
‡
around the carbon-carbon single bond ∆G has low
CONCLUSION
value (less position value), so rotation around the
carbon-carbon single bond is a fast process and
spontaneous at room temperature, observation of
two conformers (I, II or III and IV) on the basis of
this rotation at low temperature is a good evidence
for the process that is not spontaneous under this
condition.
The three most common methods for
calculating the activation parameters of the restricted
rotational isomers are used. Results obtained from
the Eyring and Arrhenius methods were consistent,
however, were different with the classic method for
the carbon-carbon double bond.Results from Eyring
and Arrhenius plots agree more than the classic
method for carbon-carbon single bond in E isomer.
The activation parameters were calculated using the
classic method (single point) for nitrogen–carbon in
E and Z isomer and carbon-carbon Z isomer. The
ACKNOꢁLEDGEMENT
We gratefully acknowledge financial
support from the Research Council of the University
of Sistan and Baluchestan.

KHORASSANI et al., Orient. J. Chem., Vol. 33(3), 1182-1189 (2017)
1189
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