A Convenient Synthesis for Alkoxy Ethers as Olefin
Polymerization Agent
Balanarasimha Reddy Gonaa,b, Sukumar Nandiaand Bharathi Kumari Y.b
aDepartment of Chemical Research and Development,
Aurobindo Pharma Limited, Survey No. 71 & 72, Indrakaran Village, Sangareddy Mandal, Medak District, Telangana - 502 329, INDIA.
bDepartment of Chemistry,
Jawaharlal Nehru Technological University Hyderabad,
College of Engineering, Kukatpally, Hyderabad, Telangana-500 085, INDIA. email: [email protected]
.
(Received on: June 23, Accepted: June 27 , 2017)
ABSTRACT
A Novel cost effective, economical and commercially viable synthetic process was reported for manufacturing of alkoxy ethers, useful as olefin polymerization agent via alkylation of carbonyl compounds at α-position with desired alkoxymethyl chloride. Excellent yields of alkoxy ethers were observed by this approach as compared with other methods employed so far.
Keywords: Alkoxy ether, olefin polymerization, alkylation, alkoxy methylene chloride.
INTRODUCTION
Many proposals have been made on the process for the preparation of a catalyst component where a solid catalyst comprising magnesium, titanium and halogen compounds and an electron donor (i.e., an internal donor) as indispensable ingredient for olefin polymerization1-3. In most of these cases, an organic carboxylic acid ester is used as the
electron donor. However, these methods suffer from a common problem that an ester smell is left in the formed polymer unless the ester is removed by washing with an organic solvent or the like means. Methods using specific esters, that is, esters having an ether portion as electron donor have been proposed as means for overcoming these defects.
RESULTS AND DISCUSSION
Alkoxy ethers of follwoing general fomula (1), have gained interest as useful catalysts for polymerization of olefins.
1 O
O R1
O R3
R2
Ether group
Alkoxy group
Figure 1: Alkoxy ethers
Review of the literature revealed hardly any synthetic method for prepartion of this class of compound. Our initial approach of preparing this class of compound was not very succsessful while follwoing the below synthetic scheme 1. We tried reaction of alkyl formates (3) with alkyl alkanoates (2) employing sodium hydride as base as reported in the literature4.
This reaction resulted in very poor yields and involves pyrophoric reagent. The product obtained was subjected to redution to obtain corresponding alcohol compound (5) as per the reported method5. Finally alkylation of the resultant alcohol (5) was tried as per the literature
reported procedure using with iodoalkane (6) in the presence of sodium hydride in tetrahydrofuran6. The iodoalkane is an expensive reagent, causes very slow reaction rate and
also resulted in elimination product as major impurity.
R3 I /
O
O O
R1
R3
R2
O
O O
R1
H
R2
6
1
NaH / THF O
O
R1
R2
O
O
H R'
Alkyl Formate
NaH O
O
R1
R2
O H
Reduction
2
3
4 5
Scheme 1: Synthesis of Alkoxy ethers
We, report herein, a facile, high yielding process for preparation of alkoxy ethers as one of the important ingredients in olefin polymerization.
to required esterification to introduce the alkoxy group using appropriate alcohol. As a model study, we carried out esterification of 3-Methylbutanoic acid and 3,3-Dimethylbutanoic acid using ethanol in the presence of sulfuric acid. These reactions resulted in formation of Ethyl 3-Methylbutanoate (9) and Ethyl 3,3-dimethylbutanoate (10) with 97% and 95% isolated yields respectively.
Thereafter, our next attention was towards introduction of an ether functional group at α position of the resultant esters. It was envisaged that we can generate an anion at α to the carbonyl carbon followed by reaction with an appropriately substituted ether functional group, such as alkoxymethyl chlorides. As a model study, Ethoxymethyl chloride (11) was prepared as per similar the reported synthetic procedure7 by reacting ethanol with equimolar quantity
paraformaldehyde in the presence of dry hydrogen chloride gas. This was subsequently reacted with Ethyl 3-Methylbutanoate and Ethyl 3,3-dimethylbutanoate in the presence of various organic and inorganic bases to obtain the desired alkoxy ether. While optimizing the reaction parameters in terms of yield, it was found that the non-nucleophilic lithium diisopropylamide (LDA), generated in situ gives quantitative results. Thus, Ethyl 3-methylbutanoate when reacted with ethoxymethyl chloride in the presence of lithium diisopropylamide in tetrahydrofuran at -70°C to -75°C resulted in the formation of Ethyl 2-(ethoxymethyl)-3-methylbutanoate (12) in 90% isolated yield having 97.8% GC purity. Similarly, under similar reaction conditions, Ethyl 3,3-dimethylbutanoate resulted in the formation of Ethyl 2-(ethoxymethyl)-3,3-dimethylbutanoate (13) in 95% isolated yield having 98.22% GC purity. The detail of these reaction conditions along with characterization data of the compounds have been given in the experimental section.
R
O
O CH3
LDA / -78°C / THF
H3C O Cl
R
O
O CH3
O CH3
Ethoxymethylchloride Ethanol + Paraformaldehyde
Dry HCl
(1 mole) (1 mole)
R
O
OH Ethanol
H2SO4
Ethyl 2-(ethoxymethyl)-3,3-dimethylbutanoate O
O CH3
CH3
H3C
O CH3
Ethyl 2-(ethoxymethyl)-3-methylbutanoate
O
O CH3
CH3
H3C
O CH3
H3C
Yield: 90% Yield: 95%
(CH3)2CH - (7)
= (CH3)3C- (8)
R = (CH3)2CH - (9)
= (CH3)3C- (10)
R = (CH3)2CH - (12)
= (CH3)3C- (13)
(11)
(12) (13)
EXPERIMENTAL SECTION
Reagents
3-Methylbutanoic acid, 3,3-Dimethylbutanoic acid, N,N-Diisopropyl amine, n-Butyllithium, were purchased from Aldrich for using as raw materials. Commercial grade of Ethanol was used. Dichloromethane and tetrahydrofuran were used as solvents to carry out the reaction.
Instrumentation
The 1H NMR spectra was recorded in Varian 500 MHz and Bruker 300 MHz FT NMR
spectrometer in CDCl3. The chemical shifts were reported in ppm relative to TMS (δ 0.00
ppm) as internal standard. IR spectra were recorded as neat. Mass spectra were recorded using a API 2000-LC-MS/MS mass spectrometer. The solvents and reagents were used without further purification. Chromatographic purity of samples was analyzed qualitatively by GC analysis.
Preparation of Ethyl 3-Methylbutanoate (9): To the absolute ethanol (735 ml), 3-Methylbutanoic acid (4, 147 g, 1.44 mol) was added at 20-30°C. Concentrated Sulfuric acid (18.4 g, 12% w/w) was added in one lot at 20-30°C to the above 3-Methylbutanoic acid solution. Temperature of the reaction mass was raised to 75-80°C and reflux was continued at 75-80°C until the reaction was completed. The progress of the reaction is monitored by TLC (mobile phase: 10% ethyl acetate in hexanes; Rf: 0.8). After completion of the reaction, excess ethanol was distilled out at atmospheric pressure. The concentrated mass was dissolved in methylene chloride and water was added to it. It was stirred for 15-20 min and layers were separated. The lower methylene chloride layer was washed with ~7% w/w aqueous sodium bicarbonate followed by ~10% w/w aqueous sodium chloride solution. Organic layer was dried over anhydrous sodium sulfate. The methylene chloride layer was concentrated at atmospheric pressure. Finally, ethyl 3-methylbutanoate was distilled at 129-133°C under atmospheric pressure.
Yield: 175 g; Colourless Liquid; GC Purity: 99.8%; 1H NMR (500 MHz, CDCl
3): δ 0.96 (d,
J= 6.5 Hz, 6H, (CH3)2), 1.25 (t, J = 7 Hz, 3H, CH3), 2.1 (m, 1H, CH), 2.17 (d, J = 6.5 Hz, 2H,
CH2), 4.13 (q, J = 14, 7Hz, 2H, CH2).
organic layer was dried over anhydrous sodium sulfate. The methylene chloride layer was concentrated at atmospheric pressure. Finally, Ethyl 3,3-dimethylbutanoate was distilled at 100-105°C at 300 mm Hg.
Yield: 117 g (95%); Colourless Liquid; GC Purity: 100 %; 1H NMR (500 MHz, CDCl 3): δ
1.02 (s, 9H, (CH3)3), 1.25 (t, J = 7 Hz, 3H, CH3), 2.2 (s, 2H, CH2), 4.12 (q, J = 7 Hz, 2H, CH2).
Preparation of Ethoxymethyl Chloride (11): Paraformaldehyde (34.3 g) suspended in ethanol (50 g) was cooled to 15-20°C. Dry hydrogen chloride gas was passed for ~3 hours at 15-20°C until all the paraformaldehyde dissolves. Layers are allowed to separate. The organic layer was dried over anhydrous calcium chloride. Thereafter, the product was distilled at atmospheric pressure and the fraction distilling at 80-83°C was collected.
Yield: 65 g; Colourless Liquid; GC purity: 95.8%; 1,1-Diethoxymethane: 2.0%; Chloromethylether: 1.2%
1H NMR (500 MHz, CDCl
3): δ 1.25 (t, J= 7 Hz, 3H, CH3), 3.75 (q, J=14, 7Hz, 2H, CH2), 5.51
(s, 2H, CH2).
Preparation of Ethyl 2-(ethoxymethyl)-3-Methylbutanoate (12): Diisopropylamine (116.54 g, 1.153 mol) was added to a cold solution of n-BuLi (361 g, 15% solution in hexanes, 0.846 mol) at -20° to -10°C slowly over a period of 20 min. The reaction mass was stirred for 45 min at -20° to -10°C and thereafter, reaction mass was diluted with tetrahydrofuran (100 ml). It was cooled to -70°C to -75°C. Thereafter, a solution of ethyl 3-methylbutanoate (9)
(100 g in 100 ml of tetrahydrofuran, 0.769 mol) was added to the above reaction mass while maintaining the temperature of the reaction mass at -70°C to -75°C. Ethoxymethyl chloride (11) (79.96 g, 0.846 mol) was added slowly over a period of 30 min. The reaction temperature was raised to -20°C to -30°C and stirred at this temperature for completion of reaction. 1N Hydrochloric acid (1.0 Lt) was added slowly at -20°C to -30°C. The temperature was raised to 20-30°C and stirring was continued for 15 min. The tetrahydrofuran layer was separated, washed with aqueous sodium chloride (2 x 500 ml) at 20-30°C and dried over anhydrous sodium sulfate. The organic layer was concentrated and the product was isolated by fraction distillation at 63-65°C vapour temperature at 6-7 mm Hg.
Yield: 125 g; Colourless Liquid; GC Purity: 97.8%; 1H NMR (500 MHz, CDCl
3): δ 0.94 (d, J
= 6.5 Hz, 6H, (CH3)2), 0.96 (d, J = 6.5 Hz, 6H, (CH3)2), 1.16 (t, J = 7.5 Hz, 3H, CH3), 1.27 (t,
J = 7 Hz, 3H, CH3), 1.92 (m, 1H, CH), 2.46 (m, 1H, CH), 3.45 (m, 2H, CH2), 3.55 (m, 1H,
CH), 3.63 (m, 1H, CH), 4.19 (m, 2H, CH2); 13C NMR (500 MHz, CDCl3): δc 174.15, 70.07,
66.41, 59.99, 52.82, 28.24, 20.51, 20.31, 14.99, 14.27; Mass (PE SCIEX-API 2000) ESI in
+ve ion mode: m/z; 189 [M+H]+.
maintaining the temperature of the reaction mass at -70°C to -75°C. Ethoxymethyl chloride (11) (21.96 g, 0.0.232 mol) was added slowly over a period of 30 min. The reaction temperature was raised to -20°C to -30°C and stirred at this temperature for completion of reaction. 1N Hydrochloric acid (300 ml) was added slowly at -20°C to -30°C. The temperature was raised to 20-30°C and stirring was continued for 15 min. The tetrahydrofuran layer was separated, washed with aqueous sodium chloride (2 x 300 ml) at 20-30°C and dried over anhydrous sodium sulfate. The organic layer was concentrated and the product was isolated by fraction distillation at 66-68°C vapour temperature at 5-6 mm Hg.
Yield: 40 g; Colourless liquid; GC Purity: 98.22%; 1H NMR (500 MHz, CDCl
3): δ 0.97(s, 9H,
(CH3)3), 1.16 (t, J = 7.2 Hz, 3H, (CH3), 1.27 (t, J = 7.2 Hz, 3H, CH3), 1.49 (dd, J = 10.8, 3.9
Hz, 1H, CH), 3.48 (q, J = 7.2 Hz, 2H, CH2), 3.55-3.73 (m, 2H, CH2), 4.16 (q, J = 7.2 Hz, 2H,
CH2); 13C NMR (500 MHz, CDCl3): δc 174.15, 69.18, 66.50, 59.91, 56.13, 32.01, 28.20, 15.08,
14.33; Mass (PE SCIEX-API 2000) ESI in +ve ion mode: m/z; 203 [M+H]+.
CONCLUSION
The synergistic application of the basic principles of organic reactions, through development of novel reaction pathways for preparation of alkoxy ether class of compounds, useful for olefin polymerization, has been successfully demonstrated in the present paper. This methodology can be extended for preparation of a variety of alkoxy ethers using a wide range of acid components, introducing various alkoxy groups through esterification and using different alkoxy methyl chlorides.
ACKNOWLEDGEMENT
The authors are thankful to the management of Aurobindo Pharma Ltd., for supporting this work. Co-operation from colleagues of Analytical Research and Development is highly appreciated.
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