47
Synthesis of p-alkoxy alkyl benzoates
Section A.
General introduction, literature survey and applications of p-
alkoxy alkyl benzoates.
Section B.
Synthesis of p- alkoxy alkyl benzoates by using organic sulphate.
Section C.
Synthesis of p-alkoxy alkyl benzoates by using alkyl halide.
Section D.
Solvents recycle and stability study of p-alkoxy alkyl benzoates
48
Section A
General introduction, literature survey and application of p-
alkoxy alkyl benzoates:
Introduction:
Polypropylene is a thermoplastics polymer, made by chemical
industry and used in a wide variety of applications. The global
market for polypropylene had a volume of 45, 1 million tons which
lead to a turnover of about 65 billion US dollar.
Polypropylene is most commonly used for plastic molding where it
is injected in to a mold while molten, forming complex shape at
relatively low cost and high volume, example includes bottle tops,
bottles and fitting. Recently it has been produced in sheet form and
this has been widely used for the production of stationary folders,
packaging and storage boxes. Polypropylene has been used in
hernia repair operations to protect the body from new hernias in the
same location; a small patch of the material is placed over the spot
of the hernia below the skin, and is painless and is rarely, if ever,
rejected by the body. The material has recently been introduced in
to the fashion industry through the work of designers such as
Anoush Waddington who have developed specialized techniques to
create jewellary and wearable items from polypropylene [1]. ZHU et
al. [2] suggested that internal electron donor such as various esters
of oxygenated organic or inorganic acids. Such an internal donor is
added to an aluminum trialkyl compound and a catalyst
composition containing magnesium, titanium, halogen and an
external electron donor selected from amines, ester, ketones, and
ether. The most preferred internal electron donors for the addition
49
to the aluminum trialkyl are ethyl benzoate, ethyl p- methoxy
benzoate.
Goodall et al. [3] suggested esters are suitable as selectivity control
agent such as ethyl and methyl benzoates, methyl p-
methoxybenzoate, these catalyst are extremely active and highly
stereo selective in propylene polymerization.
Rebhan et al. [4] have observed mono carboxylic acid ester, which
can be used in the Mg/Ti complex as the inside electron donor or as
a selectivity control agent(out side electron donor) such as methyl
and ethyl benzoate, p-methoxyethylbenzoate, p-
ethoxymethylbenzoate, p-ethoxyethyl benzoates, p-chloro
ethylbenzoate, p-amino hexyl benzoate and amyl toluate. The
advantages of these catalysts in polymerization process show higher
productivity resulting in reduced ash levels and lower xylene
soluble with higher isotacticity, extremly high polymer yield.
John A.Schofield et al. [5] reported synthesis of p- ethoxy methyl
benzoate cupric chloride dihydrate and 1, 10- phenanthroline
hydrate was added to a solution of Na in methanol. A stream of dry
oxygen was passed through the mixture 1-(4-ethoxyphenyl)-2,2,2-
trichloroethnol added and the mixture was stirred at 30 -35°C for 1
h. The reaction mixture was acidified with hydrochloric acid and
extracted with ether. The combined ether extracts were washed once
with water and twice with alkali. Further on distillation gaves
methyl 4-ethoxybenzoate with moderate yield [Fig.3.1] .
50
Cl
Cl
Cl
OH
CH3
O
CH3
O
CH3
O
O
1) CuCl22) 1,10 phenanthroline Hydrate
3) Sodium in methanol4) Dry O2 ,30-35 °C
5) H2SO4
Fig.3.1.
John A.Schofield and same team [6] reported synthesis of p- ethoxy
ethyl benzoate. Cupric chloride dihydrate and 1,10- phenanthroline
hydrate were added to a solution of Na in ethanol. A steam of dry
oxygen was passed through the mixture 1-(4-ethoxyphenyl)-2,2,2-
trichloroethnol added and the mixture stirred at 30 -35°C for 2 h.The
solution of Na in ethanol was then added and reaction was allowed
to continued for further 1h. The reaction mixture was acidified with
hydrochloric acid and extracted with ether. The combined ether
extract were washed with dilute aqueous sodium carbonate and
water. On distillation give ethyl 4-ethoxybenzoate yield 66%
[Fig.3.2].
CH3O
CH3
O
OCl
Cl
Cl
OH
CH3
O
1) CuCl22) 1,10 phenanthroline Hydrate
3) Sodium in ethanol4) Dry O2 ,30-35 °C
5) H2SO4
Fig.3.2.
Weidlich T et al. [7] reported synthesis of p-ethoxy ethyl benzoate
using diethyl carbonate and ethanol as alkylating agent in the
presence of N,N-dimethylacetamide solvent and sodium ethoxide
51
as the base at 90°C for 2.0 h and further at 137°C. Organic mass was
extracted by diethoxymethane gives moderate yield [Fig.3.3].
O
OH
OH
+N,N Dimethyl acetamide, NaOC2H5
C2H5OH , 45.5 hr / 137 °C(C2H5)2CO3
O
OC2H5
OC2H5
Fig.3.3
Chandrasekhar et al.[8] demonstrated synthesis of p-ethoxy ethyl
benzoate using diethylsulphate as alkylating agent in xylene media
and sodiumcarbonate base at 100-140°C over a period of 18 h and
further it was reacted with acetic acid for 4 h at 135-140 °C gave 80
%yield[Fig.4.4].
(C2H5)2SO4
O
OH
OH
Na2CO3 ,(C2H5)3N , C6H5CH2Cl
Xylene , CH3COOH22 hr / 135-140 °C
+
O
OC2H5
OC2H5
Fig3.4
Yin Guodong et al [9] synthesized p- ethoxy ethyl benzoate starting
from p-ethoxy acetophenone in the presence of copper oxide,
iodine, pyridine alcohol media and potassium carbonate at 65°C for
24 h reflux followed by treatment with K2CO3 for 8 h gave 72 %
yield. [Fig.3.5].
52
O
OC2H5
CH3
+
O
OC2H5
OC2H5
C2H5OHCuO , C5H5N,I2
K2CO3
Reflux / 24 h
Fig.3.5
Jaiprakash Brijlal sainani [10] reported p-hydroxy benzoic acid (1.0
mole) and diethyl sulphate (3.25 mole) reacted with aqueous
sodium hydroxide (3.13 mole) in the presence of xylene media at
90°C maintaining PH 8-10 gave p-ethoxy ethyl benzoates gave
moderate yield with 98.6 % purity by HPLC [Fig.3.6].
COOH
OH
+ 2 (C2H5)2SO4
COOC2H5
OC2H5
1) 2 NaOH
2) Xylene3) 90 °C4) pH = 8 - 10
[Fig.3.6]
Jaiprakash Brijlal and same team [10] reported p-hydroxy benzoic
acid (1.0 mole) and dimthyl sulphate (3.19 mole) reacted with
aqueous sodium hydroxide (3.13 mole in the presence of xylene
media at 85°C maintaining PH 8-10 gives p-ethoxy ethyl benzoates
gave moderate yield with 98.6 % purity by HPLC [Fig.3.7].
53
COOH
OH
+ 2 (CH3)2SO4
COOCH3
OCH3
1) 2 NaOH
2) Xylene3) 85°C4) pH = 8 - 10
Fig.3.7.
Kornblum et al.[11]reported p-nitro ethylbenzoate underwent
nucleophilic displacement of the nitro group at 25°Cin (Me2N)3PO.
Nucleophiles used were PhONa and PhSNa gave moderate yield
[Fig.3.8].
O
NO2
OC2H5 O
OC2H5
OC2H5
+ NaOC2H5
Fig.3.8.
Kabushiki Kaisha Ueno Oyo et al. [12] reported alkylation of p-
hydroxy benzoic acid using diethyl sulphate and sodium carbonate
in presence of tetra butyl ammonium bromide in Xylene at 120°C to
gave moderate yield [Fig.3.9].
O O H
O H
+ +2(C 2 H 5 ) 2 SO 4
C H 3O
C H 3
O
O
2 Na 2 CO 3
Xylene
Fig.3.9
54
Ciucanu et al. [13] reported 120 mL of methyl iodide and 112 gm
KOH and 138 gm p-hydroxyl benzoic acid reacted in the presence of
800 mL dimethyl formamide at 25°C with stirring to give 4-methoxy
methyl benzoate with 42% yield [Fig.3.10].
O O H
O H
+ +2 CH 3 I
C H 3
O
C H 3
O
O
2 KOHDMF
Fig.3.10.
Koltyar et al [14] demonstrated synthesis of p-ethoxy ethyl benzoate
using alkyl halide in aqueous potassium hydroxide in presence of
crown ether gave 62 %yield [Fig.3.11]
O
OC2H5
OC2H5O
OH
OH
+ C2H5IKOH , H2O
18-Crown-6 (catalyst)
Fig.3.11
55
Section B
Synthesis of p-alkoxy alkyl benzoates
Introduction
From the literature review it has been observed that p-
alkoxy alkyl benzoates was least studied for its synthesis. Although
few synthetic protocols are reported for the preparation of p-alkoxy
alkyl benzoates, most of these suffer from one or more
disadvantages such as harsh reaction condition, more time cycle,
low purity, unsatisfactory yield, costly solvent excessive quantity of
reactants and which hence may pollute waste water and generate
large quantity of effluent, tedious workup, hazardous reagents,
which is not viable on industrial scale.
Present work describes a novel, highly efficient synthetic pathway
for the preparation of p-alkoxy alkyl benzoates have been
synthesized by etherification using high purity p-hydroxy alkyl
benzoates prepared in chapter II section B . In this part we have
studied the synthesis of p- alkoxy alkyl benzoates reaction
extensively developed new synthesis path.
The synthesis was employed due to following merits.
1) It requires mild reaction conditions.
2) Selective phase transfer catalyst to enhance reaction rate.
3) Extremely high purity compound with good yield.
4) Less effluent.
5) Simple work up.
6) Easily availability of pure and safe solvent.
7) Solvent can be recycled as such, no further purification
required.
8) Safe process, economical and commercial viable.
56
Etherification of p-hydroxy alkyl benzoates by alkyl sulphate.
General methods of preparation [Fig.3.12]
p-Hydroxy alkyl benzoates and sodium hydroxide were mixed in
dry Toluene in the presence of suitable catalyst and etherification
was carried using alkyl sulphate such as diethyl sulphate/dimthyl
sulphate. Organic layer washed with sodium carbonate solution
followed by water wash. The solvent was evaporated and
concentrated mass on distillation gives pure compound.
O
OR'
OH
O
OR'
R''O
1)Organic sulphate 2) Catalyst 3) NaOH
Toluene
Fig.3.12.
Where,
R’ = methyl, ethyl, propyl, butyl, isobutyl.
R’’ = methyl, ethyl.
Mechanism:
General reaction mechanism of William ether synthesis is as
follows.[ 15-17]
COOR
OH
+
R
R
S
O
O
O
O
NaOH+ -
COOR
ONa
+
Na
R
S
O
O
O
O
OH2
+ -
+-
ROOC ONa+-
+ ROOC OR +
Fig.3.13
57
Etherification of p- alkoxy alkyl benzoates using different phase
transfer catalyst.
A phase transfer catalyst in chemistry is a catalyst which
facilitates the migration of a reactant in a heterogeneous system
from one phase in to another phase where reaction can take place.
Ionic reactants are often soluble in an aqueous phase but insoluble
in an organic phase unless the phase transfer catalyst is present [18]
.By using a phase transfer catalyst process, one can achieve faster
reactions, obtain higher conversions, make fewer byproducts and
eliminate the expensive raw materials and minimize waste
problems. Phase transfer catalysts are especially useful in green
chemistry [19,20].
To optimize the synthesis of p- alkoxy alkyl benzoates by
diethyl sulphate and dimethyl sulphate different phase transfer
catalysts were examined and it was observed tetra methyl
ammonium chloride, tetra butyl ammonium chloride and tetra butyl
ammonium bromide low or lack of reactivity and results also
showed concomitant decomposition of both reactants after
prolonged reaction time. Under similar conditions, methyl tri octyl
ammonium chloride proved to be a better catalyst and conversion
were obtained in 96-97%. Increasing the catalyst loading or
changing temperature above 60°C had little effect on yield, methyl
tri octyl ammonium chloride is found to be an excellent phase
transfer-catalyst for alkylation of p- hydroxy alkyl benzoates by
dimethyl sulphate and diethyl sulphate in toluene medium. The
reagent methyl tri octyl ammonium chloride is air stable and easy to
handle. The operation is quite simple; hence we have chosen this
catalyst. The results are included in Table 3.1 entry 1 and 6.
58
Table 3.1
Percentage conversion in etherification of p-hydroxy alkyl
benzoates using different Quaternary ammonium salts.
Entry Ester used
Alkylating
agent used
Catalyst used %
conversion
1 p- hydroxy
ethyl benzoate
Diethyl
sulphate
Methyltrioctyl
ammonium chloride 97.0
2 p- hydroxy
ethyl benzoate
Diethyl
sulphate
Tetrabutyl ammonium
bromide 88
3 p- hydroxy
ethyl benzoate
Diethyl
sulphate
Tetrabutyl ammonium
chloride 82
4 p- hydroxy
ethyl benzoate
Diethyl
sulphate
Tetramethyl
ammonium chloride 79
5 p- hydroxy
ethyl benzoate
Diethyl
sulphate Without catalyst 70
6 p- hydroxy
ethyl benzoate
Dimethyl
sulphate
Methyltrioctyl
ammonium chloride 96.0
7 p- hydroxy
ethyl benzoate
Dimethyl
sulphate
Tetrabutyl ammonium
bromide 86
8 p- hydroxy
ethyl benzoate
Dimethyl
sulphate
Tetrabutyl ammonium
chloride 84
9 p- hydroxy
ethyl benzoate
Dimethyl
sulphate
Tetramethyl
ammonium chloride 79
10 p- hydroxy
ethyl benzoate
Dimethyl
sulphate Without catalyst 68
59
EXPERIMENTAL
Reaction was monitored by TLC on aluminum sheet precoated with
silica gel 60F254.Wavelength (λ max.) was determined on UV
Spectrometer Model Shimadzu 1601.Purity of compound is checked
on GC. Model Shimadzu 2016. Diethyl sulphate, dimethyl sulphate,
toluene and caustic flakes were purchased from Merck, India.
Experimental procedure for the synthesis of p-ethoxy ethyl
benzoate.
A 250 mL 4- necked round bottom flask fitted with
overhead mechanical stirrer, equipped with a dropping funnel, a
thermometer, and condenser. Flask was charged with p-hydroxy
ethyl benzoate (25.0 gm, 0.15 mole), 75 mL dry Toluene, sodium
hydroxide (6.02 gm, 0.15 mole) in the presence of methyl tri octyl
ammonium chloride (0.5 gm, 0.0012 mole). Diethyl sulphate (23.19
gm, 0.15 mole) was added through dropping funnel and maintained
at 60-62°C for 10 h. The progress of reaction was monitored by TLC.
On cooling reaction mass was poured over crushed ice and
separated aqueous and organic layer. The obtained organic layer
was washed firstly with sodium carbonate solution and then with
water. Organic layer was distilled using Perkin triangle setup under
reduced pressure maintaining L/D ratio gave 91.0 % yield and
purity 99.9 % by Gas chromatography.
Same procedure was extended for etherification of p-hydroxy alkyl
benzoate (i.e. methyl, propyl, butyl and isobutyl benzoates) using
alkyl sulphate such as diethyl sulphate and dimethyl sulphate
respectively. The results of synthesized compound are given in
Table 3.2.
60
Table 3.2
Percentage yields and reaction Temperature in Etherification of
p- hydroxy alkyl benzoates using dimethyl/diethylsulphate.
Entry p-hydroxy alkyl
benzoate used Alkylating
agent
Reaction temp. (°C)
p-alkoxy alkyl benzoate obtained
% Yield
1
O O
C H 3
O H
Dimethyl
sulphate
60-62
O
OCH3
O
CH3
86.5
Diethyl
sulphate
60-62
O
OCH3
O
CH3
90.0
2
O O CH3
OH
Dimethyl
sulphate 60-62
O
O
O
CH3
H3C
86.7
Diethyl
sulphate
60-62
H3C
O
O
O
CH3
91.0
3
CH3
O O
OH
Dimethyl
sulphate 60-62
O
O
O
CH3
CH3
88.1
Diethyl
sulphate 60-62
O
O
O
CH3
CH3
88.5
61
Entry p-hydroxy alkyl
benzoate used
Alkylating agent
Reaction temp. (°C)
p-alkoxy alkyl benzoate obtained
% Yield
4
CH3O O
OH
Dimethyl
sulphate 60-62
H3C
O
O
O
CH3
87.0
Diethyl
sulphate
60-62
H3C
O
O
O
CH3
87.90
5
O O
OH
CH3
CH3
Dimethyl
sulphate 60-62
O
O
O
CH3
CH3CH3
86.90
Diethyl
sulphate
60-62
O
O
O
CH3
CH3CH3
86.20
Spectral discussion:[21-23]
IR-spectra [Fig. 3.14 – 3.15]
Synthesized compounds were scanneds for IR Spectra on Brucker
FT-IR (Alpha-P) using KBr. Spectral results are listed in Table 3.3
and spectra are included after table.
62
Table 3.3 IR Spectral data of p-alkoxy alkyl benzoates.
Sr. No.
Structure of Compounds υC-H arom cm-1
υC=O cm-1
υC=C cm-1
υC-H bend. cm-1
υC-O str. cm-1
υC-X p-
disub. cm-1
1. O
OCH3
O
CH3
3399 1713 1607 1433 1169 849
2. O
OCH3
O
CH3
2992 1715 1608 1435 1170 850
3.
O
O
O
CH3
H3C
2983 1714 1610 1435 1171 849
4.
H3C
O
O
O
CH3
2982 1713 1607 1510 1169 849
5.
O
O
O
CH3
CH3
2992 1715 1607 1440 1168 848
6.
O
O
O
CH3
CH3
2990 1716 1608 1436 1170 849
7.
H3C
O
O
O
CH3
2982 1713 1608 1436 1169 850
8.
H3C
O
O
O
CH3
2981 1715 1607 1435 1170 848
9. O
O
O
CH3
CH3CH3
2983 1717 1608 1434 1169 849
10.
O
O
O
CH3
CH3CH3
2982 1715 1607 1435 1170 849
63
64
65
1H NMR Spectra [Fig.3.16, 3.17&3.18]
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 3.4 and spectra are included after table.
Table 3.4 1H NMR – Chemical Shifts in p- alkoxy alkyl benzoates.
Sr. No.
Structure of Compounds
Chemical Shifts in D ppm
1. O
OCH3
O
CH3
3.87(s,3H,-OCH3) Protons
3.90(s,3H,-COOCH3 Protons
6.93(d,2H,3&5 Ar-H) Protons
8.01(d,2H,2&6 Ar-H) Protons
2. O
OCH3
O
CH3
1.33(t,3H,-OCH2CH3)Protons
3.88(s,3H,-COOCH3)Protons
3.98(q,2H,-OCH2CH3)
6.73(d,2H,3&5 Ar-H) Protons
7.85(d,2H,2&6 Ar-H) Protons
3.
O
O
O
CH3
H3C
1.29(t,3H,-COOCH2CH3) Protons
3.73(s,3H,-OCH3)Protons
4.01(q,2H,-COOCH2CH3)Protons
6.77(d,2H,3&5 Ar-H) Protons
7.89(d,2H,2&6 Ar-H) Protons
4.
H3C
O
O
O
CH3
1.25( t,3H,-OCH2CH3) Protons
1.27( t,3H,-COOCH2CH3) Protons
3.86(q,2H,-OCH2CH3) Protons
4.21(q,2H,-COOCH2CH3 )Protons
6.73(d,2H,3&5 Ar-H) Protons
7.85(d,2H,2&6 Ar-H) Protons
66
Sr. No.
Structure of compounds
Chemical Shifts in D ppm
5. O
O
O
CH3
CH3
0.96(t,3H,-COOCH2CH2CH3)Protons
1.78(sextet,2H,-COOCH2CH2CH3)Protons
3.73(s,3H,-OCH3)Protons
3.99(t,2H,-COOCH2CH2CH3)Protons
6.73(d,2H,3&5 Ar-H) Protons
7.85(d,2H,2&6 Ar-H) Protons
6. O
O
O
CH3
CH3
0.97(t,3H,-COOCH2CH2CH3)Protons
1.33(t,3H,-OCH2CH3)Protons
1.79(sextet,2H,-COOCH2CH2CH3)Protons
3.81(q,2H,-OCH2CH3)Protons
3.98(t,2H,-COOCH2CH2CH3)Protons
6.83(d,2H,3&5 Ar-H) Protons
7.93(d,2H,2&6 Ar-H) Protons
7.
H3C
O
O
O
CH3
0.94(t,3H,-COOCH2CH2CH2CH3)Protons
1.33(sextet,-COOCH2CH2CH2CH3)Protons
1.75(quintet,-COOCH2CH2CH2CH3)Protons
3.73(s,3H,-OCH3)Protons
3.91(t,2H,-COOCH2CH2CH2CH3)Protons
6.92(d,2H,3&5 Ar-H) Protons
8.01(d,2H,2&6 Ar-H) Protons
8.
H3C
O
O
O
CH3
0.93(t,3H,-COOCH2CH2CH2CH3)Protons
1.34(sextet, 2H,-COOCH2CH2CH2CH3)Protons
1.33(t,3H,-OCH2CH3)Protons
1.74(qui, 2H,-COOCH2CH2CH2CH3)Protons
3.82(quintet,2H,-OCH2CH3)Protons
3.90(t,2H,-COOCH2CH2CH2CH3)Protons
67
Sr. No.
Structure of
compounds Chemical Shifts in D ppm
6.79(d,2H,3&5 Ar-H) Protons
7.88(d,2H,2&6 Ar-H) Protons
9. O
O
O
CH3
CH3CH3
1.01(d,6H,-COOCH2CH(CH3)2Protons
2.43(m,1H,-COOCH2CH(CH3)2Protons
3.74(s,3H,-OCH3)Protons
4.20(d,2H,-COOCH2CH(CH3)2Protons
6.77(d,2H,3&5 Ar-H) Protons
7.89(d,2H,2&6 Ar-H) Protons
10.
O
O
O
CH3
CH3CH3
1.02(d,6H,-COOCH2CH(CH3)2Protons
1.34(t,3H,-OCH2CH3)Protons
2.44(m,1H,-COOCH2CH(CH3)2Protons
3.80(q,2H,-OCH2CH3)Protons
4.22(d,2H,-COOCH2CH(CH3)2)Protons
6.72(d,2H,3&5 Ar-H) Protons
7.85(d,2H,2&6 Ar-H) Protons
68
69
70
71
Mass spectrum [Fig.3.19 and 3.20]
Synthesized compounds of chapter-III section- B were scanned for
mass spectrum on Shimadzu GCMS QP 5050A make Shimadzu
Corporation Japan, mode EI. Spectral results are listed in Table 3.5
and spectra are included after table.
Table 3.5
Mass fragmentation values of p-alkoxy alkyl benzoates.
Sr. No.
Structure of the Compounds
Molecular weight (Calcd.)
M/Z Values
1.
O
OCH3
O
CH3
166 166,135,92,77,41.
2.
O
OCH3
O
CH3
180 180,138,121,93,76,65,41.
3.
O
O
O
CH3
H3C
180 180,138,121,93,65,41.
4. H3C
O
O
O
CH3
194 194,179,166,138,121,93,76,65.
5.
O
O
O
CH3
CH3
194 194,166,138,121,93,76,65,41.
72
Sr. No.
Structure of the compounds
Molecular weight (Calcd.)
M/Z Values
6.
O
O
O
CH3
CH3
208 208,166,138,121,93,65,40.
7. H3C
O
O
O
CH3
208 208,193,138,93,76,65,43,40.
8. H3C
O
O
O
CH3
222 222,191,179,135,121,65,41.
9.
O
O
O
CH3
CH3CH3
208 208,193,180,15,121,76,65,43,40
.
10.
O
O
O
CH3
CH3CH3
222 222,193,163,121,93,76,65,43,40
.
73
74
75
Mass fragmentation pattern: [24,25]
The mass fragmentation pattern of p-ethoxy ethyl benzoate is given
as a representative case [Fig.3.21].
CH2--CH3
CH2--CH2--HC
O
O
O
194
CH3
.
CH2
CH2--CH3C
O
O
O
179
+ .
-CHO.
CH2--CH3C
O
O
149
+ .
CH2--CH3
CH2C
O
O
O
CH2
H
CH2CH2
C
O
OH
O H
CH2=CH2
.
166
CH2=CH2
.
C
O
OH
O
H
H
C
O
OH
OH
138
--C
O
OH.
OH
+.
65
-- CO.
--OH.
C
O
OH
121
+
93
76
Section C:
General methods for preparation of p-alkoxy alkyl benzoates by
using alkyl halide. [Fig. 3.22]
p-Hydroxy alkyl benzoates and K2CO3 were mixed in dry
N,N dimethylformamide and then etherification was carried using
alkyl halide. After completion of reaction, organic layer were
washed by sodium carbonate solution followed by water wash.
Organic mass on distillation gives pure compound.
O
OR'
OH
O
OR'
R''O
1)Alkyl halide 2) K2CO3
DMF
Fig. 3.22
Where,
R’ = methyl, ethyl, propyl, butyl, isobutyl.
R’’ = propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl.
Experimental procedure for p- isopropoxy ethyl benzoate
synthesis.
A 250 mL 4- necked round bottom flask fitted with
overhead mechanical stirrer, equipped with a dropping funnel, a
thermometer, and double coil condenser. Flask was charged with p-
hydroxy ethyl benzoate (25.0 gm, 0.15 mole), 30 mL dry N,N-
dimethylformamide, potassium carbonate (21.0 gm,0.15 mole),
isopropyl bromide (18.52 gm,0.15 mole) was added through
dropping funnel under stirring and maintained at 58-60°C for 11 hr.
The progress of reaction was monitored by TLC. After completion
of reaction N, N-dimethylformamide was recovered.
77
On cooling reaction mass was added in water and
stirred further 30 min. and separated aqueous and organic layers.
The obtained organic layer was washed firstly with sodium
carbonate solution and then with water. Organic layer was distilled
using Perkin triangle setup under reduced pressure maintaining
L/D ratio gave 90.0 % yield and purity 99.78% by Gas
chromatography.
Color = clear colorless liquid.
Same procedure was extended for etherification of p-
hydroxy alkyl benzoate (i.e. methyl, ethyl, propyl, butyl & isobutyl
benzoates) using alkyl halide such as propyl, isopropyl, butyl,
isobutyl, pentyl and Isopentyl bromides. The results are included in
Table No. 3.6-3.10.
78
Table 3.6-3.10 Percentage yields and reaction temperature in etherification of p-
hydroxy alkyl benzoates using alkyl halide.
Entry
p-hydroxy
methyl benzoate
used
Alkylating
agent
Reaction
temp.
(°C)
p-alkoxy methyl
benzoate obtained
%
Yield
1
2
3
4
5
6
O O
CH3
OH
n-propyl
bromide
isopropyl
bromide
n-butyl
bromide
isobutyl
bromide
n-pentyl
bromide
isopentyl
bromide
58-60
58-60
65-67
65-67
65-67
65-67
O
OCH3
O
CH3
O
OCH3
O
CH3
CH3
O
OCH3
O
CH3
O
OCH3
O
CH3 CH3
O
OCH3
O
CH3
O
OCH3
O
CH3CH3
88.0
90.0
86.1
87.9
88.1
86.3
79
Table 3.7
Entry p-hydroxy ethyl
benzoate used Alkylating
agent
Reaction temp. (°C)
p-alkoxy ethyl benzoate obtained
% Yield
1
2
3
4
5
6
O O CH3
OH
n-propyl bromide
isopropyl bromide
n-butyl bromide
isobutyl bromide
n-pentyl bromide
isopentyl bromide
58-60
58-60
65-67
65-67
65-67
65-67
O
O
O
CH3H3C
O
O
O
CH3
CH3H3C
O
O
O
CH3
H3C
O
O
O
CH3 CH3H3C
O
O
O
CH3
H3C
O
O
O
CH3CH3
H3C
87.2
86.9
87.6
87.5
87.0
88.1
80
Table 3.8
Entry p-hydroxy
propyl benzoate used
Alkylating agent
Reaction temp (°c)
p-alkoxy propyl benzoate obtained
% Yield
1
2
3
4
5
6
CH3
O O
OH
n-propyl
bromide
isopropyl
bromide
n-butyl
bromide
isobutyl
bromide
n-pentyl
bromide
isopentyl
bromide
58-60
58-60
65-67
65-67
65-67
65-67
O
O
O
CH3
CH3
O
O
O
CH3
CH3
CH3
O
O
O
CH3CH3
O
O
O
CH3
CH3
CH3
O
O
O
CH3CH3
O
O
O
CH3CH3
CH3
87.5
86.4
88.0
87.1
85.1
87.0
81
Table 3.9
Entry p-hydroxy
butyl benzoate used
Alkylating agent
Reaction temp.
(°c)
p-alkoxy butyl benzoate obtained
% Yield
1
2
3
4
5
6
CH3O O
OH
n-propyl bromide
isopropyl bromide
n-butyl bromide
isobutyl bromide
n-pentyl bromide
isopentyl bromide
58-60
58-60
65-67
65-67
65-67
65-67
H3C
O
O
O
CH3
H3C
O
O
OCH3
CH3
O
O
O
CH3
H3C
O
O
O
CH3
CH3
H3C
O
O
O
CH3H3C
O
O
O
CH3
CH3H3C
86.0
87.9
88.0
87.1
85.1
88.4
82
Table 3.10
Entry p-hydroxy isobutyl
benzoate used
Alkylating agent
Reaction temp.
(°C)
p-alkoxy isobutyl benzoate obtained
%
Yield
1
2
3
4
5
6
O O
OH
CH3
CH3
n-propyl
bromide
isopropyl
bromide
n-butyl
bromide
isobutyl
bromide
n-pentyl
bromide
isopentyl
bromide
58-60
58-60
65-67
65-67
65-67
65-67
O
O
O
CH3
CH3CH3
O
O
O
CH3
CH3
CH3CH3
O
O
O
CH3CH3CH3
O
O
O
CH
CH
CH3CH3
O
O
O
CH3
CH3CH3
O
O
O
CH3
CH3CH3
CH3
89.0
87.9
85.6
85.8
88.2
84.8
83
Spectral discussion [Fig.3.23-3.27]
IR-Spectra
Synthesized compounds were scanned for IR Spectra on Brucker
FT-IR (Alpha-P) using KBr. (Fig.3.23-3.27). Spectral results are listed
in Table 3.11 and spectra are included after table.
Table 3.11
IR Spectral data of p- alkoxy alkyl benzoates.
Sr. No
.
Structure of Compounds
υC-H arom cm-1
υC=O
cm-1
υC=C cm-1
υC-H bend. cm-1
υC-O str. cm-1
υC-X p-
disub. cm-1
1. O
OCH3
O
CH3
2966 1716 1606 1578 1191 847
2.
O
OCH3
O
CH3
2953 1717 1606 1579 1159 846
3.
O
O
O
CH3
CH3H3C
2980 1713 1606 1508 1166 848
4. O
O
O
CH3
CH3
2967 1714 1607 1580 1168 847
5.
O
O
O
CH3CH3
2958 1714 1607 1580 1167 846
84
Sr. No
.
Structure of compounds
υC-H arom cm-1
υC=O
cm-1
υC=C cm-1
υC-H bend. cm-1
υC-O str. cm-1
υC-X p-
disub. cm-1
6. O
O
O
CH3
H3C
2935 1713 1606 1580 1167 848
7. O
O
O
CH3H3C
2958 1714 1607 1580 1168 846
8. O
O
O
CH3
CH3CH3
2964 1712 1606 1580 1167 846
9. O
O
O
CH3
CH3CH3
2958 1714 1606 1581 1167 846
85
86
87
88
89
90
1H NMR Spectra [Fig.3.28 – 3.33]
Synthesized compounds were scanned for 1H NMR using CDCl3
and DMSO as a solvent on Bruker “AVANCE 400 “ MHz
spectrometer using TMS as an standard. Spectral results are listed in
Table 3.12 and spectra are included after table.
Table 3.12
1H NMR – Chemical Shifts in p- alkoxy alkyl benzoates.
Sr. No.
Structure of Compounds
Chemical Shifts in D ppm
1.
O
OCH3
O
CH3
0.98 (t,3H,-OCH2CH2CH3) Protons. 1.74 (sextet,2H, ,-OCH2CH2CH3) Protons. 3.81 (s,3H,- COOCH3) Protons. 3.86 (t,2H,- OCH2CH2CH3) Protons. 6.92 (d,2H,3 & 5 Ar-H) Protons. 7.91 (d,2H,2 & 6 Ar-H) Protons.
2.
O
OCH3
O
CH3
0.89 (t,3H,-OCH2CH2CH2CH2CH3) Protons. 1.38 (quintet,2H,-OCH2CH2CH2CH2CH3) Protons 1.73 (quintet,2H,-OCH2CH2CH2CH2CH3) Protons 3.81 (s,3H,-COOCH3) Protons. 3.89 (t,2H,-OCH2CH2CH2CH2CH3) Protons 6.83 (d,2H,3 & 5 Ar-H) Protons. 7.93 (d,2H,2 & 6 Ar-H) Protons.
3.
O
O
O
CH3
CH3H3C
1.30 (d,6H,-OCH(CH3)2) Protons. 1.35 (t,3H,-COOCH2CH3) Protons. 4.30 (q,2H,- COOCH2CH3) Protons. 4.56 (sextet,1H ,- OCH(CH3)2) Protons 6.83 (d,2H, 3 & 5 Ar-H) Protons 7.94 (d,2H, 2 & 6 Ar-H) Protons
4. O
O
O
CH3
CH3
0.91 (t,3H,-OCH2CH2CH3) Protons. 0.94 (t,3H,-COOCH2CH2CH3) Protons. 1.66 (sextet,2H,-OCH2CH2CH3) Protons. 1.70 (sextet,2H,-COOCH2CH2CH3) Protons. 3.79 (t,2H,-OCH2CH2CH3) Protons 4.14 (t,2H,-COOCH2CH2CH3) Protons. 6.79 (d,2H,3 & 5 Ar-H) Protons. 7.89 (d,2H,2 & 6 Ar-H) Protons.
91
5.
O
O
O
CH3CH3
0.89 (t,3H,-OCH2CH2CH2CH2CH3) Protons. 0.98 (t,3H,-COOCH2CH2CH3) Protons. 1.35 (sextet,2H,-OCH2CH2CH2CH2CH3) Protons. 1.39 (quintet,2H,-OCH2CH2CH2CH2CH3) Protons 1.66 (quintet,2H,-OCH2CH2CH2CH2CH3) Protons 1.74 (sextet,2H,-COOCH2CH2CH3) Protons. 3.91 (t,2H,-OCH2CH2CH2CH2CH3) Protons. 4.20 (t,2H,-COOCH2CH2CH3) Protons 6.85 (d,2H,3 & 5 Ar-H) Protons. 7.96 (d,2H,2 & 6 Ar-H) Protons.
6.
O
O
O
CH3
H3C
0.93(t,3H,-OCH2CH2CH2CH3) Protons. 0.96 (t,3H,-COOCH2CH2CH2CH3) Protons. 1.43 (sextet,2H,-OCH2CH2CH2CH3) Protons. 1.47(sextet,2H,-COOCH2CH2CH2CH3) Protons 1.69 (quintet,2H,-OCH2CH2CH2CH3) Protons 1.73(quintet,2H,-COOCH2CH2CH2CH3) Protons. 3.93 (t,2H,-OCH2CH2CH2CH3) Protons. 4.25 (t,2H,-COOCH2CH2CH2CH3) Protons 6.86 (d,2H,3 & 5 Ar-H) Protons. 7.95(d,2H,2 & 6 Ar-H) Protons.
7.
O
O
O
CH3H3C
0.93(t,3H,-OCH2CH2CH2CH2CH3) Protons. 0.94 (t,3H,-COOCH2CH2CH2CH3) Protons. 1.39(sextet,2H,-OCH2CH2CH2CH2CH3)Protons 1.42(quintet,2H,-OCH2CH2CH2CH2CH3) Protons 1.45 (sextet,2H,-COOCH2CH2CH2CH3) Protons 1.72(quintet,2H,-OCH2CH2CH2CH2CH3) Protons. 1.77 (quintet,2H,-COOCH2CH2CH2CH3) Protons 3.96 (t,2H,-OCH2CH2CH2CH2CH3) Protons. 4.28 (t,2H,-COOCH2CH2CH2CH3) Protons. 6.89 (d,2H,3 & 5 Ar-H) Protons. 7.98(d,2H,2 & 6 Ar-H) Protons.
8.
O
O
O
CH3
CH3CH3
0.88 (d,6H,-COOCH2CH(CH3)2) Protons. 0.92 (t,3H, -OCH2CH2CH3) Protons. 1.96(m,1H,-COOCH2CH(CH3)2) Protons 3.78 (t,2H, -OCH2CH2CH3) Protons. 3.97(d,2H,-COOCH2CH(CH3)2) Protons. 6.79 (d,2H, 3 & 5 Ar-H) Protons. 7.90 (d,2H, 2 & 6 Ar-H) Protons.
9.
O
O
O
CH3
CH3CH3
0.94 (t,3H,-OCH2CH2CH2CH2CH3) Protons. 1.02(d,6H, -COOCH2CH(CH3)2 Protons. 1.37 (sextet,2H,-OCH2CH2CH2CH2CH3) Protons 1.45 (t,2H,-OCH2CH2CH2CH2CH3) Protons 1.79 (quintet,2H,-OCH2CH2CH2CH2CH3) Protons 2.07(m,1H, -COOCH2CH(CH3)2 Protons. 3.98 (t,2H,-OCH2CH2CH2CH2CH3) Protons 4.07(d,2H, -COOCH2CH(CH3)2 Protons. 6.91(d,2H, 3 & 5 Ar-H) Protons. 8.00 (d,2H, 2 & 6 Ar-H) Protons.
92
93
94
95
96
97
98
Mass spectrum [Fig. 3.34- 3.38]
Synthesized compounds of chapter-III section-C were scanned for
mass spectrum on Shimadzu GCMS QP 5050A make Shimadzu
Corporation Japan, mode - EI. Spectral results are listed in Table
3.13 and spectra are included after table.
Table 3.13
Mass fragmentation values of p-alkoxy alkyl benzoates.
Sr. No. Structure of the
Compounds
Molecular weight (Calcd.)
M/Z Values
1. O
OCH3
O
CH3
194
194,179,163,162,121,93,76
, 65, 43, 40.
2.
O
OCH3
O
CH3
222
222,191,179,165,152,135,
121,93,65,43.
3.
O
O
O
CH3
CH3H3C
208
208,193,166,138,121,93,65,
40.
4.
O
O
O
CH3
CH3
222
222,193,180,163,151,138,
121,93,76,65,43,40
5. O
O
O
CH3CH3
250
250,221,208,191,180,163,
151,138,121,93,65,43.
99
Sr. No.
Structure of the compounds
Molecular weight (Calcd.)
M/Z Values
6.
O
O
O
CH3
H3C
250
250,221,207,194,177,138,
121,93,65,41,40.
7.
O
O
O
CH3H3C
264
264,235,208,191,177,165,138,12
1,93,76,65,41
8.
O
O
O
CH3
CH3CH3
236
236, 207, 180, 163, 138, 121, 93,
76, 65, 41.
9.
O
O
O
CH3
CH3CH3
264
264,235,208,191,177,138,
121,93,65,41
100
101
102
103
Mass Fragmentation pattern:
104
105
Mass fragmentation pattern
The mass fragmentation pattern of p- pentoxy methyl benzoate is
given as a representative case [Fig.3.39].
1) p-pentoxy methyl benzoate:-
CH 2-CH 2-CH 2-CH 2-CH 3C
O
OCH3 O
CH 2-CH 3
CH 2C
O
OCH3 O
CH
HCH2
208
C
O
OCH3 O
HH
CH 2-CH 2-CH 3
CH2
CH
+ .
+ .
C
O
OCH3 OH
+ .
152
152
C
O
OH+
.
121
-CH 3-O
O H+
.
93
-CO
OH + O
+
+
65
C3H4
40
-CH=CH. .
.-CO
-
106
Section D
Solvents recycle and Stability study of p- alkoxy alkyl benzoates.
1) Solvent recycles study
Solvent disposal costs and volatile organic component emission
control are primary concern in industry. Another compelling reason
for recovering solvents is the increasing environmental legislation
against emission; such emission may be as a result of a process
design where solvent recovery was not incorporated at the outset,
or where venting has occurred as a result of plant problems. With
increasing commercial and regulatory pressure on chemical
industries, the recovery, reconditioning and reuse of solvents is an
important aspect of running chemical industry efficiently [26]. In
present study we have successfully demonstrated solvent recycle
study without hampering yield and compound purity.
Table 3.14
Toluene recycles study of p- ethoxy ethyl benzoate synthesis
Cycle Purity of
compound
Yield
Appearance
Fresh 99.9 91.5 Colorless liquid
1 99.94 90.8 Colorless liquid
2 99.91 91.2 Colorless liquid
3 99.9
91.6
Colorless liquid
107
Table 3.15
N, N-dimethylformamide recycles study of p- isopropoxy ethyl
benzoate.
Cycle Purity of
compound Yield Appearance
Fresh 99.8 91.0 Colorless liquid
1 99.79 90.7 Colorless liquid
2 99.82 91.3 Colorless liquid
3 99.78 90.2 Colorless liquid
Stability study of p-alkoxy alkyl benzoates:
Stability study is an important factor for organic compound.
Physical change which might affect the appearance, clarity and
color of solution and chemical changes which can be observed in an
increase in degradation products or decrease of purity. Stability
study gives information of storage, packing and shelf life of
compound [27,28] synthesized compound storage stability study
observed for two years and it was found quite stable with respect to
purity, color, smell and sedimentation. Some compound checked by
GC for purity, appearance and results are summarized in Table 3.16.
108
Table 3.16
Stability study of p- alkoxy alkyl benzoates.
Entry Compounds Initial After two years
color purity color purity
1 p-propoxy methyl benzoate Colorless
liquid 99.7
Colorless
liquid 99.69
2 p-pentoxy methyl benzoate Colorless
liquid 99.67
Colorless
liquid 99.66
3 p-ethoxy ethyl benzoate Colorless
liquid 99.88
Colorless
liquid 99.87
4 p-isopropoxy ethyl benzoate Colorless
liquid 99.75
Colorless
liquid 99.71
5 p-propoxy propyl benzoate Colorless
liquid 99.75
Colorless
liquid 99.70
6 p-pentoxy propyl benzoate Colorless
liquid 99.66
Colorless
liquid 99.65
7 p-butoxy butyl benzoate Colorless
liquid 99.78
Colorless
liquid 99.72
8 p-pentoxy butyl benzoate Colorless
liquid 99.60
Colorless
liquid 99.61
9 p-propoxy isobutyl benzoate Colorless
liquid 99.59
Colorless
liquid 99.55
10 p-pentoxy isobutyl benzoate Colorless
liquid 99.60
Colorless
liquid 99.55
109
Results and Discussion:-
p-Alkoxy alky benzoates were prepared by the reaction of alkyl
sulphate with different p-hydroxy alkyl benzoate in the presence of
suitable phase transfer catalyst and selective solvent. To optimize
the reaction conditions the etherification of p-hydroxy alkyl
benzoates was carried out with alkyl sulphate in the presence of
methyl tri octyl ammonium chloride using alkali hydroxide in
selective easily available inert solvent, similarly several p-hydroxy
alkyl benzoates underwent the etherification give p-alkoxy alkyl
benzoates (Fig 3.12) in excellent yield and purity(Table 3.2).
Methyl tri octyl ammonium chloride exhibited a powerful phase
transfer catalyst activity in an amt as low as 0.0012 mole. This was
enough to complete the reaction within a few hours. Toluene was
found to be the effective solvent for the excellent conversion, atom
economy, easily available with high purity.
Similarly series of p-alkoxy alkyl benzoate were prepared by the
reaction of alkyl halide with different p-hydroxy alkyl benzoate in a
polar solvent with mild reaction condition, short reaction time,
Simple workup and optmal use of solvent with extreamly high
purity and excellent yield.results are given in (Table 3.6-3.10).
N,N-dimethylformamide was found to be effective solvent for the
conversion and no need to use any catalyst for the reaction because
alkyl halide gets easily polarized in dimethylforamide solvent and
produce carbonium ion easily therefore this solvent found to be
effective solvent for the conversion of p-alkoxy alkyl benzoates
synthesis.
110
Macroscopic property such as dielectric constant, which is a
measure of the ability of the bulk material to increase the
capacitance of a condenser. In terms of structure, the dielectric
constant is a function of both the permanent dipole of the molecule
and its polarizability. Polarizability refers to the ease of distortion of
molecules electron distribution. Dielectric constants increase with
dipole moment and with polarizability because of the ability of both
the permanent and the induced molecular dipole to align with an
external electric field. An important property of solvent molecules is
the response of the solvent to changes in charge distribution as
reaction occurs [29]. The dielectric constant of a solvent is a good
indicator of the ability of the solvent to accommodate separation of
charge.
Solvent effects being a macroscopic property, it conveys little
information about the ability of the solvent molecules to interact
with the solute molecules at close range. These direct solute –
solvent interaction will depend on the specific structures of the
molecules.
Solvents that fall in the nonpolar aprotic class are much less
effective at stabilizing the development of charge separation. These
molecules have small dipole moments and do not have hydrogen’s
capable of forming hydrogen bonds. Reactions that involve charge
separation in the transition state therefore usually proceed much
more slowly in this class of solvents than in protic or polar aprotic
solvents. The reverse is true for reactions in which species having
opposite charges come together in the transition state. Because in
this case the transition state is less highly charged than the
individual reactants, it is favoured by weaker salvation, which
111
leaves the oppositely charged reactants in a more reactive state.
[30,31]
We have also tested the effect of reaction temperature. When
etherification is carried out by alkyl sulphat at 60-62°C the
maximum yield and high purity compound was obtained, we
choose to perform the reaction at 60-62°C in the presence of methyl
tri octyl ammonium chloride. Similarly we also optimized the
reaction temperature parameter for etherification by alkyl halide in
polar solvent at 58-60°C and 65-67 °C accordingly. The maximum
yield and high purity compound was obtained.The completion of
the reaction was monitored by TLC.
With increasing commercial and regulatory pressure on chemical
industries, the recovery, reconditioning and reuse of solvents is an
importants aspect of running production facilities efficiently.We
have successfully demonstrated solvent recovery and recycle study
as such without hampering yield and quality of compound and it
was resulted into atom economy and clean environment protocol
(Table-3.14 - 3.15)
Stability study of organic compound is an important parameter.
From this information, optimal storage, packaging condition and
shelf life can be assessed properly. Stability study of synthesized
compound was observed for two year with respect to physical
appearance, purity and sedimentation and results are found to be a
quite satisfactory at ambient temperature .The results are included
in (Table 3.16).
112
The synthesized compounds in this work have been obtained in
pure form only by vacuum distillation and it is seems to be good
commercial viable technique for chemical industries, no need to do
any additional purification.The purity of the compounds was
checked by Gas chromatography and structures of the compound
have been characterized by IR, 1H NMR and mass spectroscopy.The
results are included in (Table 3.3, 3.4, 3.5, 3.11, 3.12, 3.13.)
113
Conclusion
In conclusion, we have developed a novel and efficient
new synthetic pathway for the preparation of p-alkoxy alkyl
benzoates in excellent yield, high purity and extremely low isomer,
for the first time. The novel method offers several advantages
including mild reaction conditions, high conversions, short reaction
time, clean reaction profiles; ease of handling and ready availability
of the catalyst and solvent, minimum generation of waste from the
process and purification by vacuum distillation which makes it a
useful and attractive process for the synthesis of p-alkoxy alkyl
benzoates. Moreover, the extremely high purity, good storage
stability, excellent recyclability of solvent system makes this
procedure cleaner and economical, which is a good example of
green chemistry technology.
The main advantages of this methodology
1) It requires mild reaction conditions.
2) Extremely high purity compound with excellent yield.
3) Simple experimental operation.
4) Powerful and selective phase transfer catalyst for good
conversion.
5) Solvent can be recycled as such, no further purification required.
6) Safe process.
7) Atom economy and less energy consumption process.
8) Purified compound free from OH and COOH.
9) These procedure can be used for large scale production.
We believe that this synthetic procedure provides a valuable
addition for the synthesis of p-alkoxy alkyl benzoates as a catalyst
for making different grades of polypropylene.
114
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Gueckel Chen Wei Eric Fang, US Patent application,
2010/0144991A1, 2010
3. Goodall; Brian L. US Patent, 4, 520, 163, 1985.
4. Rebhan, David Merrill, Kanawha County, Andrea, Ronald Rene,
EP Patent, 0490 451 B1, 1991.
5. John A. Schofield, U.S. Patent, 4 249 015, 1981.
6. Johan A. Schofield and same team, U.S.Patent 4, 249, 015, 1981.
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