Download Synthesis of p-hydroxy alkyl benzoates

Synthesis of p-hydroxy alkyl benzoates
Section A.
General introduction and literature survey of p-hydroxy alkyl
benzoates.
Section B.
Synthesis of p-hydroxy alkyl benzoates.
18
Section A:
General introduction and literature survey p-hydroxy
alkyl benzoates:
Introduction:
Parabens [Fig.2.1, 2.2, 2.3 and 2.4] have been attracting great
interest because of their importance in synthetic organic chemistry.
Parabens have been widely used as antimicrobial preservative
agents in foods, beverages, drugs and cosmetics for more than fifty
years due to their broad antimicrobial spectrum, [1]. Parabens are
very versatile in terms of food preservatives, differing from the
other preservatives such as benzoates, propionates and sorbates;
because they are not weak acid compounds but have a wide pH
range. The antimicrobial activity of parabens is directly dependent
on the chain length [2, 3].
In the plant world, 4-hydroxybenzoic acid and
its
derivatives are commonly found in various vegetable foods, such as
barley, strawberries, black currants, peaches, carrots, onions, cocoabeans, vanilla; further in foods prepared from fruit plants such as
grapes and fruit juices, yeast extract, wine vinegar and also in
cheeses [4].
Methyl paraben found application in the synthesis of
dimethyl 4, 4 - (tetraphaioyldioxy) dibenzoates as a reactant for
monomer preparation [5]. Methyl and propyl p-hydroxybenzoate
are used in Rhamnolipid based formulation for fire suppression and
chemical and biological hazards [6] Methyl and propyl p-hydroxy
19
benzoates are used in collagen or gelatin based crumble as a
preservatives [7].Polyester is a manufactured fiber in which the
fiber-forming substance is any long-chain, synthetic polymer
composed of at least 85% of an ester of a substituted aromatic
carboxylic acid [8].
Paraben are esters of p-hydroxybenzoic acid, from which the name
is derived common parabens include methylparaben[Fig.2.1],
ethylparaben [Fig.2.2], propylparaben [Fig. 2.3] and butylparaben
[Fig. 2.4]
O
OCH3
O
OH
OCH2CH3
O
OH
Fig. 2.1.
Fig. 2.2.
OCH2CH2CH3
O
OCH2CH2CH2CH3
OH
OH
Fig.2.3.
Fig.2.4.
Phukan et al. [9] reported a synthesis of parabens using
montmorillonite K10 clay as heterogeneous catalyst. Methyl, ethyl,
and propyl parabens were synthesized by esterification of phydroxy benzoic acid with corresponding alcohols [Fig. 2.5].
O
O
OH
+
ROH
OR
Montmorillonite K10 Clay
+
Reflux
OH
OH
Fig. 2.5.
20
H2O
Theodor et al. [10] reported an improved method for the
synthesis of 4-hydroxy methyl benzoate using p-hydroxy benzoic
acid through dipotasium salt of p-hydroxy benzoic acid and
esterification was carried out by dimethyl sulphate and adjusting
pH of reaction mass by sulphuric acid, NaOH, and ammonia.
Thereafter the crude product was purified by charcoal and sodium
dithionate to give p-hydroxy methyl benzoates [Fig.2.6].
O
OH
O
O
OK
OCH3
Purification
1. charcoal
2.filter
Conc H2 SO4 (pH=5)
Dimethyl sulphate
KOH
33% NaOH(pH=6)
Water,Liq NH3
OH
3.Sodium dithionate
4.H2 SO4 (pH=8.5)
OH
OK
OCH3
O
OH
Fig. 2.6.
John et al. [11] reported that a stream of dry oxygen was
passed through a solution of 1-(4-hydroxy phenyl)–2, 2, 2-trichloro
ethanol in methanol and a solution of sodium in methanol
containing cupric chloride dihydrate and 1,10 phenanthroline
hydrate was added and the reaction was allowed to continue for a
further 2h at room temperature and the reaction mixture was then
poured into dilute hydrochloric acid, extracted with ether and the
combined extracts washed with water. The dried MgSO4 extracts
was evaporated to dryness and the residue crystallized from
aqueous ethanol to give methyl 4-hydroxy benzoate (yield 66%)
[Fig. 2.7].
Cl
Cl
Cl
HO
OH
O
Dry O2
Sodium in methanol
CuCl2.2H2O
1,10 phenanthroline Hydrate
25-30°C,Dil.HCl
Fig. 2.7.
21
CH3
O
HO
Hosangadi et al. [12] reported treatment of variety of aromatic
carboxylic acids with alcohols in the presence of thionyl chloride
results in excellent yields of corresponding esters. This esterification
system is compatible with a wide assortment of functional groups
[Fig. 2.8].
O
O
OH
X
SOCl 2, ROH
OR
X
Fig. 2.8.
Schlater et al. [13] demostrated esterification of 4-hydroxy
benzoic acid under microwave irradiation with 42 % yield [Fig. 2.9].
O
O
OH
+
H2SO4
OCH3
CH3OH
MW
HO
HO
Fig. 2.9.
Desmurs et al. [14] reported esterification of p-hydroxy benzoic acid
using N, N-diisopropyl ethyl amine with isopropyl bromide gives
isopropyl p-hydroxy benzoate with moderate yield [Fig. 2.10].
H3C
O
OH
O
H3C
+
CH3
O
N,N diisopropyl ethyl amine
+
Br
H3C
OH
OH
Fig. 2.10.
22
CH3CH2N(C3H7)2.HBr
Shi Xiaobo Li Chungen [15] reported esterification of buty paraben
using Dodecatungstophosphoric acid gave moderate yield
[Fig. 2.11].
O
OH
O
O
Dodecatungstophosphoric
acid
HO
OH
OH
Fig. 2.11.
Raghaven et al. [16] reported efficient synthesis method of n-butyl
parabens under microwave irradiation in the presence of an
inorganic salt Zinc chloride as a catalyst. The main advantages of
this methodology are better selectivity, rate enhancement and
reduction of thermal degradation and higher energy consumption
efficiency when compared to traditional heating. Yield is 43%
[Fig. 2.12].
O
O
OH
+
CH3CH2CH2CH2OH
OCH2CH2CH2CH3
ZnCl2
+
MW
H2O
OH
OH
Fig. 2.12.
M.Gorsd et al. [17] investigate that trifluoro methane sulphonic acid
immobilized on zirconium was found to be on effective catalyst for
esterification of 4-hydroxy benzoic acid with propyl alcohol gives
moderate yield [Fig. 2.13].
23
O
O
OH
+
CH3CH2CH2OH
OCH2CH2CH3
trifluoromethanesulphonic acid
immobilised on Zirconium oxide
+
H2O
OH
OH
Fig. 2.13.
Lin Qi et al. [18] reported the synthesis
of n-butyl
p –hydroxy
benzoate with n-butanol and p-hydroxybenzoic acid as reactants
and solid super acid ZrO2/SO42- as catalysts has been studied. The
yield of butyl p-hydroxybenzoate was around 87% [Fig. 2.14].
O
O
OH
+
CH3CH2CH2CH2OH
OCH2CH2CH2CH3
solid superacid supported
ZrO2/SO 4
+
2-
H2O
OH
OH
Fig. 2.14.
GAO Wen-yi et al. [19] The ethyl p-hydroxybenzoate was
synthesized by esterification of p-hydroxybenzoic acid with ethanol
using solid super acid S_2O~ (2-)_8/ZrO_2-Al_2O_3 as catalyst. The
yield of product reaches to 79.0% [Fig. 2.15].
O
O
OH
+
HO
OCH 2CH 3
Solid Superacid
CH3CH 2OH
-
S-2O~(2 )-8 /ZrO- 2 -Al-2O-3
HO
Fig. 2.15.
Alireza R. Sardarian et al. [20] reported aromatic carboxylic
acid esterification in the presence of triphenylphosphin dibromide
or triphenylphosphinediiodide and N,N-dimethylaminopyridine in
24
dichloromethane with 81% yield [Fig. 2.16].
O
O
O
R'OH
Ph3PX3
R
OH
- HX
R
O PPh3
R = Alkyl, Aryl
- Ph3PO
- HX
R
O R'
X
Fig. 2.16.
Jeum Jong kim et al. [21] reported esterification of carboxylic acid
with
alcohol
using
4,5-dichloro-2-[(4-nitrophenyl)
sulphonyl]pyridazine-3(2H)-one
in
the
presence
of
4-(N,N-
dimethylamino)pyridine in refluxing tetrahydrofuran gave the
corresponding ester in good yield. [Fig. 2.17].
Cl
Cl
O
R C OH
+ R'
OH
O
O
N S
N O
Pyridine
Fig.2.17
25
NO 2
RCOOR'
Section B
Synthesis of p-hydroxy alkyl benzoates
Introduction
Azeotropic distillation is an essential unit operation in
today’s processes. Applications using azeotropic distillation are
readily apparent in the chemical process industry, specialty
chemicals and food industries.
The main advantages of azeotropic distillation are in allowing
the separation of chemicals that cannot feasibly be separated by
conventional distillation, such as systems containing azeotrope or
pinch points, and improving the economics of the separation by
saving energy and increasing recovery.
A minimum-boiling azeotrope can be formed by the
introduction of an azeotrope-forming compound (entrainer) to an
existing azeotropic mixture or close boiling mixture for which
separation by conventional distillation is not feasible. One example
is alcohol dehydration. Ethanol and water form a minimum-boiling
azeotrope with ethanol as the major component and therefore
ethanol
cannot
be
completely
dehydrated
by
conventional
distillation. Benzene forms a ternary azeotrope with ethanol and
water, which boils at a lower temperature and will therefore remove
the water with some ethanol overhead, leaving dry ethanol as a
bottoms product.
Similarly esters are produced by reacting alcohols with
organic acids. The reaction is reversible and therefore unless one of
the products is removed, the ester yield is limited. Assuming the
reaction is equilibrium-limited and not rate-limited, higher
conversions can be obtained by removing one of the products. For
instance, if during the reaction the water is removed, the reaction
26
will be driven by equilibrium to produce more ester product. High
purity esters can be produced with azeotropic distillation to
simultaneously remove water and alcohol from the esters using
aromatic and aliphatic hydrocarbons as entrainers.
There are distinct advantages to using azeotropic distillation,
including energy savings, increased recovery and ability to separate
components contained in close boiling, pinch point and azeotropic
mixtures. Azeotropic distillation will undoubtedly remains a viable
alternative for simplifying difficult separations found in industry
[22]. Parabens have synthetically important skeleton and possess
very potent pharmacological activities. Although many synthetic
protocols are reported for the preparation of parabens, most of these
suffer from one or more disadvantages such as harsh reaction
conditions, long reaction time, unsatisfactory yield, low purity,
multistep purification, hazardous catalyst, large quantity of effluent
and tedious workup.
Herein, we report the simple and efficient and economical
method of synthesis to get highly pure compound with short
reaction time and easy workup procedure for the synthesis of phydroxybenzoic acid esters by azeotropic distillation technique
using toluene as azeotropic agent in presence of minimum amount
of concentrated sulphuric acid
with corresponding
alcohol
[Fig. 2.18].
O
O
R
OH
HO
+
H2SO4/Toluene
O
ROH
Azeotropic distillation
HO
Fig. 2.18.
27
The mechanism of esterification involves the following steps
1) Protonation of carboxyl group by H + of the acid catalyst.This makes the carbonyl carbon
more strongly electropositive
O
HO
HO
+
OH
H
+
HO
C
+
OH
2) Attack By nucleophile
H
HO
HO
C
+
+
:O
OH H
HO
R
O
OH
+
R
OH
3) Transfer of proton to one of the -OH groups
H
OH H
H
O
+
+
HO
O R
O R
HO
OH
OH
4) The -OH group leaves as water molecule gives protonated ester
H
+
O H
HO
O R
HO
C
-H 2 O
OH
+
O R
O
H
5) Elimination of Proton
HO
C
+
O
R
-H
O
+
O
H
H
+
+
HSO 4
-
H 2 SO 4
Fig. 2.19.
28
O R
HO
Experimental
Melting point was determined in open glass capillaries and is
uncorrected. 1H NMR spectra were recorded at room temperature
on Brucker “AVANCE 400” MHz spectrometer in CDCl3 using TMS
as an internal standard. Reaction was monitored by TLC on
aluminum sheet precoated with silica gel 60F254. p -hydroxybenzoic
acid and alcohols were purchased from Merck, India. Alcohols were
purified by distillation before use. Wave length was determined on
UV Spectrometer model Shimadzu 1601
Experimental procedure for the synthesis of p-hydroxy ethyl
benzoates
A 500 mL 4-necked round bottom flask fitted with overhead
mechanical stirrer, a dropping funnel, a thermometer and deanstark with condenser. Flask was charged with 100 mL Toluene, 2 mL
concentrated Sulphuric acid, p-hydroxybenzoic acid (50 gm, 0.362
mole) and ethanol (16.5 gm, 0.35 mole) and heated the reaction
mixture at 95-98°C and continuously added ethanol (28.0 gm, 0.6
mole) through dropping funnel within 5 h then performed
azeotropic distillation with continuous removal of water formed in
reaction mixture. The progress of reaction was monitored by TLC.
After completion of reaction, reaction mixture was cooled to 5°C.
Filtered the reaction mixture and washed with water (25mL x 3) and
dried in vacuo to afford the pure product. The purity of compound
was checked by HPLC [23,24] .The structures of compounds were
confirmed on the basis of IR, 1H NMR and mass spectra. Similarly
the compounds of the series shown in the Table-2.1 were
synthesized by using above procedure and characterization data is
given in Table 2.2.
29
Table 2.1
Efficient synthesis of p-hydroxy alkyl benzoates
Entery
No.
Alcohol
used
Temp.
range
(°C)
Reaction
Time
(h)
1
Methanol
90-95
5
2
Ethanol
95-98
5
Product obtained
p-hydroxy methyl
benzoate
p-hydroxy ethyl
benzoate
Yield
(%)
Purity
(%)
94
99.96
95
99.90
95
99.90
93
99.89
90
99.97
88
99.80
p-hydroxy
3
n-Propanol
90-105
6
n-propyl benzoate
p-hydroxy
4
n-Butanol
90-105
6
n-butyl benzoate
5
iso butanol
90-107
6
p-hydroxy
isobutyl benzoate
p-hydroxy
6
n-Pentanol
90-107
6
n-pentyl benzoate
30
Table 2.2
Characterization data of p-hydroxy alkyl benzoates
Sr.
Substituents
M.P./ B.P.
Molecular
Molecular
λ Max.
No.
‘R’
(°C)
formula
weights
(nm)
1
Methanol
121 – 123
C8H8O3
152
256
2
Ethanol
114 – 115
C9H10O3
166
256
3
n-Propanol
93 - 95
C10H12O3
180
256
4
n-Butanol
68 - 70
C11H14O3
194
257
5
Iso Butanol
68.5-69
C11H14O3
194
257
6
n-Pentanol
28-30
C12H16O3
208
258
Melting points of synthesized compounds were taken by open
capillary method and are uncorrected.
Spectral discussion [25, 26]
IR-Spectra
Synthesized compound were scanned for IR Spectra on Brucker FTIR (Alpha-P) using KBr. (Fig.2.20 and 2.21). Spectral results are
listed in Table 2.3 and spectra are included after table.
31
Table 2.3
IR Spectral data of p-hydroxy alkyl benzoates.
Sr.
No.
1.
Structure of
Compounds
O
OCH
υO-H
cm-1
υCalkyl
cm-1
υC=O
cm-1
υC-H
aromatic
cm-1
3
3294
28503000
1682
15141432
HO
2.
O
OCH
υC-O
str.
cm-1
υC-X
para
disub.
cm-1
1165
-
850
1118
2 CH 3
3222
28503000
1672
15921449
1169
-
849
1168
HO
3.
O
OCH 2 CH 2 CH 3
3274
2980
1676
15181440
HO
O
1163
-
849
1125
OCH2CH2CH2CH3
4.
3383
2956
1678
15101467
1165
-
852
1127
HO
CH3
5.
O C
O CH2 CH
CH3
3367
2962
OH
32
1680
1513-
116-
1479
1127
846
33
34
1H
NMR Spectra [Fig.2.22, 2.23 and 2.24]
Synthesized compounds were scanned for 1H NMR using CDCl3
and DMSO as a solvent on Bruker “AVANCE 400 “ MHz
spectrometer using TMS as an internal standard. Spectral results are
listed in Table 2.4 and spectra are included after table.
Table 2.4 1H NMR – Chemical Shifts in p- hydroxy alkyl
benzoates.
Sr.
No.
Structure of
Compounds
O
OCH
Chemical Shifts in B ppm
3
3.78(s,3H,-COOCH3) Protons
6.86(d,2H,3&5 Ar-H) Protons
7.82(d,2H,2&6 Ar-H) Protons
10.33(s,1H,Phenolic –OH) Proton
1.
HO
O
OCH 2 CH 3
1.28(t,3H,-COOCH2CH3) Protons
4.24(q,3H,-COOCH2CH3) Protons
6.85(d,2H,3&5 Ar-H) Protons
7.81(d,2H,2&6 Ar-H) Protons
10.33(s,1H,Phenolic –OH) Proton
2.
HO
O
OCH 2 CH 2 CH 3
3.
HO
O
OCH2CH2CH2CH3
4.
HO
0.93(t,3H,-COOCH2CH2CH3) Protons
1.67(sextet,2H,-CH2CH2CH3) Protons
4.14(t,2H,-COOCH2CH2CH3) Protons
6.86(d,2H,3&5 Ar-H) Protons
7.82(d,2H,2&6 Ar-H) Protons
10.31(s,1H,Phenolic –OH) Proton
0.91(t,3H,-COOCH2CH2CH2CH3) Protons
1.39(sextet,2H,-CH2CH2CH2CH3) Protons
1.64(quint,2H,- CH2CH2CH2CH3) Protons
4.19(t,2H,-CH2CH2CH2CH3) Protons
6.85(d,2H,3&5 Ar-H) Protons
7.82(d,2H,2&6 Ar-H) Protons
10.31(s,1H,Phenolic –OH) Proton
CH3
O
C
O
CH
2
CH
CH3
5.
OH
0.94(d,6H,-CH-(CH3)2)Protons
1.97(m,,1H ,-CH-(CH3)2) Protons
3.98(d,2H,-CH2,-CH-(CH3)2) Protons
6.87(d,2H,3&5 Ar-H) Protons
7.82(d,2H,2&6 Ar-H) Protons
10.32(s,1H,Phenolic –OH) Proton
35
36
37
38
Mass spectrum [24, 25]
Synthesized compounds were scanned for mass spectrum on
Shimadzu GCMS QP 5050A make Shimadzu Corporation Japan,
mode EI. Spectral results are listed in Table 2.5 and spectra are
included after table [Fig.2.25, 2.26].
Table 2.5
Mass fragmentation values of p-hydroxy alkyl benzoates.
Sr.
No.
Structure of the
Compounds
O
OCH
Molecular
weight
(Calcd.)
M/Z Values
152
152,121,93,65,53,40.
166
166,138,121,93,65,53,40.
180
180,151,138,121,93,65,53,40
3
1.
HO
O
OCH 2 CH 3
2.
HO
O
OCH 2 CH 2 CH 3
3.
HO
O
OCH 2 CH 2 CH 2 CH 3
194,165,138,121,177,93,65,
4.
194
53,40
HO
CH 3
O
C
O CH 2
CH
CH 3
5.
194
OH
39
194,177,138,121,93,65,43,41
.
40
41
Mass fragmentation pattern:
The mass fragmentation patterns of some p-hydroxy alkyl benzoate
are given the representative cases [Fig.2.27].
Mass fragmentation pattern of p-hydroxy butyl benzoate
O-CH 2 -CH 2 -CH 2 -CH 3
O
C
OH
e
+
O
O-CH 2 -CH 2
O
70 ev
O-CH 2 -CH 2 -CH 2 -CH 3
C
C
+.
.
O
O-CH 2 -CH 2 -CH 2 -CH 3
C
.
- OH
-CH 2 -CH 3
+
OH
OH
m/z = 177
m/z = 165
Molecular ion
m/z = 194
+
O
.
C
CH 2 -CH 3
CH
-O-CH 2 -CH 2 -CH 2 -CH 3
H
CH 2
+
O
O
C
+
OH
m/z = 121
.
.
- CO
HO
+
.
CH 2
O
HO
H
m/z = 93
O
C
+
.
- CO
.
-CH
+
C 4H 5
.
-CH
+
HO
C 3H 4
m/z = 138
+
m/z = 65
CH
m/z = 53
m/z = 40
Fig. 2.27
42
.
CH 2
CH 2
Results and discussion:
The development of environment friendly technologies is a
major goal of present research in chemistry. Synthetic esters are
generally prepared by reaction of alcohol with organic carboxylic
acid in presence of catalyst such as sulphuric acid, the reaction is
known as Fischer esterification. The Fischer esterification is a
reversible reaction. The equilibrium is pushed to the product side by
taking excess of a reactant by continuously removing the water
formed in the reaction.
We achieved simple and effective method for the synthesis
of p-hydroxybenzoic acid esters by azeotropic distillation technique
using Toluene as azeotropic agent in presence of minimum amount
of concentrated sulphuric acid with corresponding alcohol. This
method helps to avoid the etherification of free hydroxyl group and
polycondensation of phenol containing carboxylic acid as an
impurity. The product produced by this technique gives extremely
pure and further purification is not required.
Esterification of p-hydroxybenzoic acid with common
alcohols was carried out under similar conditions. Good to excellent
yields and perfect selectivity were obtained in all cases.
Azeotropic technique seems to be more effective, efficient and
economical to get highly pure compound with short reaction time
and easy workup procedure. Reaction and azeotropic distillation
can be carried out in same reaction vessel and as water formed in
the reaction, it can be removed continuously by ternary azeotropic
distillation and aqueous bottom phase separates out via phase
separator. Reaction will complete within 5-6 h with minimum
43
amount of alcohol. Recovered toluene can be used as such for next
batch and corresponding alcohol can be used after distillation.
CONCLUSION
In summary, a novel method for the synthesis of p-hydroxy alkyl
benzoates by azeotropic distillation technique using toluene as
azeotropic agent in presence of minimum amount of concentrated
sulphuric acid with corresponding alcohol was developed on high
yield with extremely high purity for the first time.
The main advantages of this methodology are
1) This novel method helps to avoid the etherification of free
hydroxy group and polycondensation of phenol containing
carboxylic acid as an impurity.
2) Extremely high purity product obtained with good yield
3) Easy synthetic procedure
4) For commercial point of view, process is economical
5) Toluene and excess alcohol can be recycled
6) Low energy consumption
(7) No additional purification required.
8) One pot synthesis.
44
References
1. Soni M. G., Burdock G. A., Taylor S. L.; Greenberg N. A., Food
Chem.Toxicol, 2001,39, 513.
2. Robach M. C., Food Technol. 1980, 34, 81.
3. Dziezak J. D., Food Technol, 1986, 40,104.
4. Anthony C.Dweek Natural Parabens, (site visited) on
September 2010
5. Luigi Abis, Riccardo Po, Giuliana Schimperna, Edoardo
Merlo. Micromol. Chem. Phys, 1994, 195,181-193.
6. KeithDeSantowww.faqs.org/patents/app/20090126948, 2008.
(Site visited on September 14, 2010)
7. Richard M. Herreid, Austin, Minn., U.S.Patent, 6, 090, 915,
2000.
8. Market data compiled by the Fibers Economics Bureau,
www.fibersource.com. ( site visited on September 14, 2010)
9. Prodeep Phukan, Mridulkumar Hazarika, Raghav Paraguli,
Indian Journal of Chemical Tech., 2007, 14, 104-106.
10. Theodor Papenfuhs, Frankfurt am Main, U.S.Patent 4,052,438,
1977.
11. John A. Schofield, John E. Haws, US Patent 4, 492, 015, 1981.
12. Bhaskar D.Hosangadi, Rajesh S.Dave, Tetrahedron llet. 1996,
37, 6375-6378.
13. Lisa Schalater, David Ziemnik, www.heidelberg.edu/depts./
chem./fisher .html.1995. (Site visited on September 14, 2010)
14. Jean-Roger Demurs, Dozon, Serge Ratton, U.S.Patent, 5, 260,
475, 1993.
15. Shi Xiaobo Li Chungen, Natural science edition, 1998,
45
16. Raghavan, G. S., Liao X., Yaylayan V. A., Tetrahedron Lett,
2002, 43,104.
17. Blanco’s, M.; Gorsd, M.; Pizzio, L.; 3 rd IUPAC conference on
green chemistry, Argentina, abstract.icg2010.ca /vdv00013,
2010.
18. Qi L,Huilong Z, Zhicheng L, Jiqing L, Journal of Fuzhou,1999.
19. Gao wean-yi, Ren Li-guo, Zhang Xiao-li, Journal of Liaoning
University of petroleum and chemical Technology, 2006.
20. Alireza R.Sardarian, Maryam Zandi and Soghra Motevally.
Acta Chim.Slov. 2006, 56,729-733.
21. Jeum-Jong Kim, Yong-Dae Park, Deok-Heon Kweon, YoungJin Kong, Ho-Kyun Kim, Bull. Koream Chem.Soc. 2004,
25(4),501
22. Lee F.M., Wytcherley R.W., GTC Technology Corporation
Houston Taxas, USA, 1990.
23. Marvin C. Mc Master, HPLC A practical users Guide second
Edition Wiley interscience, A John willey and sons, inc.,
Publication, 2007.
24. Ewing’s Analytical instrumentation Handbook. Third Edition,
Edited by Jacks Cazes, Florida Atantic University Boca
Ration, Florida USA, 2009.
25. Schbimann F., Nuclear Magnetic Resonance and Infrared
Spectroscopy, 1970, 1, 41.
26. Bellamy L.J., The Infrared spectra of complex Molecule, II
Ed.Methuen London, 1964.
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